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WHAT'S NEW IN MUSCLE REGENERATION:

THE 1995-1996 LITERATURE

A MEDLINE search compiled at Indiana University, Bloomington, Indiana
and presented with the permission and through the generosity of SilverPlatter

MEDLINE EXPRESS (R) 1/96-6/96 1 of 80*

TI: Capillary supply during development of individual regenerating muscle fibers.

AU: Luque-E; Pena-J; Martin-P; Jimena-I; Vaamonde-R

AD: Department of Morphological Sciences (Section of Histology), Faculty of Medicine, University of Cordoba, Spain.

SO: Anat-Histol-Embryol. 1995 Jun; 24(2): 87-9

ISSN: 0340-2096

PY: 1995

LA: ENGLISH

CP: GERMANY

AB: This study describes the capillary supply of individual regenerating muscle fiber during three stages of its development. Regeneration was induced by the injection of mepivacaine in the anterior tibial muscle of rats. Muscle fiber capillarization during regeneration was analysed in semithin sections, employing the following parameters: the number of capillaries around a fiber and the number of capillaries per fiber cross-sectional area. The results revealed that during development of regenerating fibers, the fiber cross-sectional area increased, the number of capillaries around each fiber increased and the number of capillaries per fiber cross-sectional area decreased. These data indicated a greater capillary supply of the individual regenerating muscle fiber during its early stage of maturation.

MESH: Capillaries-; Muscle,-Skeletal-physiology; Rats-; Rats,-Wistar

MESH: *Muscle-Fibers-physiology; *Muscle,-Skeletal-blood-supply; *Regeneration-

TG: Animal

PT: JOURNAL-ARTICLE

AN: 96173015

UD: 9605

MEDLINE EXPRESS (R) 1/96-6/96 2 of 80

TI: "Bystander" damage of host muscle caused by implantation of MHC-compatible myogenic cells.

AU: Wernig-A; Irintchev-A

AD: Department of Physiology, Neurophysiology, University of Bonn, Germany.

SO: J-Neurol-Sci. 1995 Jun; 130(2): 190-6

ISSN: 0022-510X

PY: 1995

LA: ENGLISH

CP: NETHERLANDS

AB: Transplantation of normal myoblasts has been considered a potential therapy for muscle dystrophies. While survival of implanted cells has been described in animal experiments and in human trials, functional effects remained unclear. Here we report on survival of progenors of implanted C2nlsBAG cells in regenerating muscles but irreversible net loss in muscle tissue and contractile force. This is caused by immune rejection of implanted myoblasts despite MHC-compatibility and "bystander" damage of host muscle tissue.

MESH: beta-Galactosidase-biosynthesis; Antigens,-CD4-analysis; Antigens,-CD8-analysis; Cell-Survival-physiology; Fluorescent-Antibody-Technique; Immunohistochemistry-; Isometric-Contraction-physiology; Mice-; Mice,-Inbred-CBA; Muscle-Contraction-physiology; Muscle,-Skeletal-pathology; Muscle,-Skeletal-physiology; Organ-Weight-physiology; Stem-Cells-physiology; T-Lymphocytes,-Cytotoxic-immunology

MESH: *Cell-Transplantation-physiology; *Major-Histocompatibility-Complex-immunology; *Muscle,-Skeletal-transplantation; *Regeneration-physiology

TG: Animal; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: EC 3.2.1.23; 0; 0

NM: beta-Galactosidase; Antigens,-CD4; Antigens,-CD8

AN: 96172598

UD: 9605

MEDLINE EXPRESS (R) 1/96-6/96 5 of 80

TI: The cellular events of injured muscle regeneration depend on the nature of the injury.

AU: Lefaucheur-JP; Sebille-A

AD: Laboratoire de Physiologie, Atelier de Regeneration Neuromusculaire, Faculte de Medecine Saint-Antoine, Paris, France.

SO: Neuromuscul-Disord. 1995 Nov; 5(6): 501-9

ISSN: 0960-8966

PY: 1995

LA: ENGLISH

CP: ENGLAND

AB: The cellular events of muscle degeneration and regeneration and their time course were studied in two experimental models of muscle injury mice; (i) the denervation-devascularization (DD) of the extensor digitorum longus (EDL) muscle, which is an ischaemic lesion; (ii) the injection of notexin (NOT), a snake venom, in the tibialis anterior (TA) muscle, resulting in a toxic lesion. Compared to the ischaemic lesion, the toxic lesion was characterized by a more extensive inflammatory infiltrate and a shortened phase of phagocytosis of the damaged myofibres. This allowed the proliferation and differentiation of muscle precursor cells (mpc) to take place earlier and may be further promoted by growth factors released by inflammatory cells. Compared to DD-EDL, NOT-TA showed also a greater conservation of the basement membranes of the necrotic myofibres, that can support the fusion of mpc into myotubes, and a better microvascularization. The onset of muscle regeneration is tightly related to the events which occur during the phase of degeneration.

MESH: Elapid-Venoms-toxicity; Immunohistochemistry-; Ischemia-pathology; Mice-; Muscle-Denervation; Muscle-Fibers-physiology; Muscle,-Skeletal-blood-supply; Muscle,-Skeletal-pathology; Muscular-Diseases-chemically-induced; Neurotoxins-toxicity; Phagocytosis-; Regeneration-physiology; Regional-Blood-Flow-physiology; Time-Factors

MESH: *Muscle,-Skeletal-injuries; *Muscular-Diseases-pathology

TG: Animal; Male; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 0; 37223-96-4

NM: Elapid-Venoms; Neurotoxins; notexin

AN: 96156454

UD: 9605

MEDLINE EXPRESS (R) 1/96-6/96 6 of 80

TI: Morphological and functional study of extensor digitorum longus muscle regeneration after iterative crush lesions in mdx mouse.

AU: Louboutin-JP; Fichter-Gagnepain-V; Pastoret-C; Thaon-E; Noireaud-J; Sebille-A; Fardeau-M

AD: Unite CNRS 1340. Hopital GR Laennec-BP 1005 Nantes, France.

SO: Neuromuscul-Disord. 1995 Nov; 5(6): 489-500

ISSN: 0960-8966

PY: 1995

LA: ENGLISH

CP: ENGLAND

AB: The regenerative capacity of mdx Extensor Digitorum Longus (EDL) muscle after iterative muscle crush injuries was examined and compared with that of age-matched control C57BL/10 mice. Muscle crush injuries were performed at 8 weeks and repeated at 12 and 16 weeks. Contralateral non-crushed EDLs from mdx and C57BL/10 mice were used as internal controls for histopathology, histoenzymology, morphometry and for the study of the contractile properties. Morphological examinations were performed at 12, 16 and 20 weeks, respectively one month after a single, a second or a third crush. Contractile properties were studied at 12 to 20 weeks. By 20 weeks, no difference in the number of fibres with internal nuclei could be observed between crushed EDL from both strains, and non-crushed mdx EDL; the area and the diameter of crushed EDL from mdx mice were, respectively, 1.5- and 1.2-fold higher than the ones from crushed EDL from C57BL/10 strain. By 20 weeks, diameter distribution of crushed EDL muscles from C57BL/10 mice were shifted towards smaller fibre diameter, whereas in mdx mice, diameter distribution of crushed EDL muscles paralleled that of non-crushed EDL muscles. By 20 weeks, crushed mdx and C57BL/10 EDL muscles produced 77 and 47% of normalized tetanus tension respectively of non-crushed mdx and C57BL/10 EDL muscles. Following crush injury, both 12- and 20-week mdx and C57BL/10 EDL exhibited a slowed time to peak (TTP) and half-relaxation time (H1/2R) of twitch. There was no difference in posttetanic potentiation between the different groups. Crushed EDL of both strains showed an increased resistance to fatigue, compared to the non-crushed controls. The present study provides morphological and functional evidence for the greater recovery of mdx muscle compared to C57BL/10 muscle following iterative crush injury; however, the recovery does not completely prevent the appearance of necrosis/regeneration features.

MESH: Isometric-Contraction-physiology; Mice-; Mice,-Inbred-mdx; Mice,-Inbred-C57BL; Muscle-Contraction-physiology; Muscle-Denervation; Muscle-Fibers-physiology; Muscle,-Skeletal-innervation; Regeneration-physiology

MESH: *Muscle,-Skeletal-injuries; *Muscle,-Skeletal-pathology; *Muscular-Dystrophy,-Animal-pathology

TG: Animal; Male; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

AN: 96156453

UD: 9605

MEDLINE EXPRESS (R) 1/96-6/96 9 of 80

TI: Effects of age on aneural regeneration of soleus muscle in rat.

AU: Lewis-DM; Schmalbruch-H

AD: Department of Physiology, Medical School, Bristol, UK.

SO: J-Physiol-Lond. 1995 Oct 15; 488 ( Pt 2): 483-92

ISSN: 0022-3751

PY: 1995

LA: ENGLISH

CP: ENGLAND

AB: 1. The ability of autografted soleus muscles to regenerate without innervation was investigated in young (two groups: 17 days or 35 g and 5 weeks or 100 g) and old (10 weeks or 300 g and 19 months or 700 g) rats. 2. Tetanic force and fibre area of the regenerated muscles were followed in 35, 100 and 300 g rats and found to reach a maximum 10-15 days after the operation and then declined. 3. Maximal tetanic force and fibre area were greater in old than in young rats; the largest increase was seen between 100 and 300 g rats. The relaxation phase of the twitch became shorter in the 700 g animals. The force per cross-sectional area appeared to fall with age. The length of the new fibres, inferred from the width of the length-force curve, increased only slightly with age. 4. Ten days after grafting, autophagocytosis of necrotic fibres was completed in young but not in old rats. The new fibres in young rats had one central nucleus per cross-section and fibre size was unimodally distributed; fibres in old rats had multiple internal nuclei and the size distribution was bimodal due to the presence of large fibres. 5. Previous results indicating greater muscle regeneration in young than in old rats may reflect more vigorous reinnervation in young animals rather than a greater myogenic potential. Increased fibre size of regenerated muscles of old compared with young rats may be attributed to the larger amount of necrotic material which is mitogenic for satellite cells, or to age-dependent changes of the expression of cell adhesion molecules. Enhanced lateral fusion of myotubes would give rise to large fibres with multiple internal nuclei.

MESH: Autophagocytosis-physiology; Body-Weight-physiology; Muscle-Contraction-physiology; Muscle-Fibers-physiology; Muscle-Fibers-ultrastructure; Muscle,-Skeletal-cytology; Muscle,-Skeletal-innervation; Necrosis-pathology; Rats-; Rats,-Wistar; Transplantation,-Autologous

MESH: *Aging-physiology; *Muscle,-Skeletal-physiology; *Regeneration-physiology

TG: Animal; Female; Male; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

AN: 96141129

UD: 9605

MEDLINE EXPRESS (R) 1/96-6/96 10 of 80

TI: Expression of c-fos and c-myc in satellite cell cultures from dystrophic mdx and control mouse muscle.

AU: Veal-EA; Jackson-MJ

AD: Department of Medicine, University of Liverpool, U.K.

SO: Biochem-Soc-Trans. 1995 Aug; 23(3): 456S

ISSN: 0300-5127

PY: 1995

LA: ENGLISH

CP: ENGLAND

MESH: Cell-Differentiation; Cell-Division; Cells,-Cultured; Gene-Expression; Mice-; Mice,-Inbred-mdx; Muscle,-Skeletal-pathology; Muscle,-Skeletal-physiopathology; Muscular-Dystrophy,-Animal-pathology; Muscular-Dystrophy,-Animal-physiopathology; Regeneration-genetics; RNA,-Messenger-genetics; RNA,-Messenger-metabolism

MESH: *Genes,-fos; *Genes,-myc; *Muscle,-Skeletal-metabolism; *Muscular-Dystrophy,-Animal-genetics

TG: Animal; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0

NM: RNA,-Messenger

AN: 96077317

UD: 9605

MEDLINE EXPRESS (R) 1/96-6/96 12 of 80

TI: [Effects of substituted dextran on reinnervation of a skeletal muscle in adult rats during regeneration]

TO: Effets d'un dextrane substitue sur la reinnervation du muscle squelettique du rat adulte au cours de la regeneration.

AU: Aamiri-A; Mobarek-A; Carpentier-G; Barritault-D; Gautron-J

AD: Laboratoire CREET, URA-CNRS 1813, UFR des sciences, universite Paris XII Val-de-Marne, Creteil, France.

SO: C-R-Acad-Sci-III. 1995 Oct; 318(10): 1037-43

ISSN: 0764-4469

PY: 1995

LA: FRENCH; NON-ENGLISH

CP: FRANCE

AB: RGTA11 is a chemically substituted dextran that mimics some of the properties of heparin or heparan sulphates towards heparin binding growth factors as well as inhibits some heparin binding proteases. In vivo RGTA11 has been shown to enhance muscle regeneration after crush. We now present evidence that RGTA11 can alos favour reinnervation of fast (EDL) as well as slow (soleus) crushed muscles. Both types of muscles were injected with RGTA11 after crushing and nerve cutting. In EDL muscles, after 16 days, motor end plates were more rapidly reformed and choline acetyl-transferase activity was 2 fold higher than in controls. In soleus muscles, after 16 days, motor end plates were reformed at normal size while controls were on average 30% smaller, the 16S form of acetyl-cholinesterase and choline acetyl-transferase activity were twice those of non injected regenerating controls. In conclusion, RGTA11 favours axonal growth and synaptic differentiation, allowing a more rapid reinnervation and maturation of the regenerated fibers. RGTA may present a new family of drugs against neuromuscular degenerescence.

MESH: Acetylcholinesterase-chemistry; Acetylcholinesterase-metabolism; Choline-Acetyltransferase-metabolism; English-Abstract; Muscle,-Skeletal-cytology; Muscle,-Skeletal-enzymology; Rats-; Rats,-Wistar

MESH: *Anticoagulants-pharmacology; *Dextrans-pharmacology; *Muscle,-Skeletal-innervation; *Nerve-Regeneration-drug-effects

TG: Animal; Male

PT: JOURNAL-ARTICLE

RN: EC 2.3.1.6; EC 3.1.1.7; 0; 9004-54-0

NM: Choline-Acetyltransferase; Acetylcholinesterase; Anticoagulants; Dextrans

AN: 96146772

UD: 9605

MEDLINE EXPRESS (R) 1/96-6/96 13 of 80

TI: Use of plasmid DNA for direct gene transfer and immunization.

AU: Davis-HL; Michel-ML; Whalen-RG

AD: Loeb Medical Research Institute, Ottawa Civic Hospital, Canada.

SO: Ann-N-Y-Acad-Sci. 1995 Nov 27; 772: 21-9

ISSN: 0077-8923

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: Direct gene transfer by intramuscular injection of plasmid DNA encoding an antigenic protein may be used for the purpose of immunization. Several factors influence the uptake and expression of plasmid DNA in skeletal muscle, which in turn influence the immune response to the expressed protein. Physical barriers and other factors may impede the diffusion of the DNA within the muscle tissue or its entry into the muscle fibers. Although the efficiency of gene transfer in normal mouse muscle is low (< 100 fibers per injection site), both humoral and cell-mediated immune responses to the hepatitis B surface antigen (HBsAg) are obtained after the expression of a transferred gene, and these are dose dependent. The efficacy of the immune response can be improved by injection of the DNA in or following pretreatment with a hypertonic solution or with the local anesthetic bupivacaine, and even more so by injecting the DNA into regenerating muscle.

MESH: Bupivacaine-administration-and-dosage; DNA,-Recombinant-administration-and-dosage; DNA,-Recombinant-genetics; Hepatitis-B-Antibodies-biosynthesis; Hepatitis-B-Surface-Antigens-genetics; Hepatitis-B-Surface-Antigens-immunology; Hepatitis-B-Vaccines-administration-and-dosage; Hypertonic-Solutions-administration-and-dosage; Injections,-Intramuscular; Mice-; Muscle,-Skeletal-physiology; Plasmids-administration-and-dosage; Plasmids-genetics; Recombinant-Proteins-genetics; Recombinant-Proteins-immunology; Regeneration-

MESH: *DNA,-Recombinant; *Immunization-methods; *Plasmids-; *Transfection-methods

TG: Animal; Human

PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL

RN: 0; 0; 0; 0; 0; 0; 0; 2180-92-9

NM: DNA,-Recombinant; Hepatitis-B-Antibodies; Hepatitis-B-Surface-Antigens; Hepatitis-B-Vaccines; Hypertonic-Solutions; Plasmids; Recombinant-Proteins; Bupivacaine

AN: 96135343

UD: 9604

MEDLINE EXPRESS (R) 1/96-6/96 17 of 80

TI: [An experimental study on recovery of lacerated skeletal muscle: correlation between separation gap and the potential for recovery]

AU: Terada-N

AD: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo.

SO: Nippon-Seikeigeka-Gakkai-Zasshi. 1995 Sep; 69(9): 754-66

ISSN: 0021-5325

PY: 1995

LA: JAPANESE; NON-ENGLISH

CP: JAPAN

AB: Skeletal muscle has a potential for recovery with muscle tissue when the lacerated stumps are maintained in contact. However, when there is no contact, this potential for recovery is unknown. Here we report our studies on the correlation between the recovery and the separation distance between the stumps in partially lacerated muscles in Wistar rat. The gastrocnemius muscle was subjected to a partial wedge-shaped laceration which allowed the surrounding tissue to hold a constant separation distance between the stumps throughout the duration of the study. Groups each of 7 rats were examined at 1, 2, and at 4 days, and at 1, 2, 2, and at 6 weeks after the laceration was performed. In each group, 5 rats underwent histological and immunohistological examinations, while the other 2 underwent electronmicroscopic examination. The muscle stumps initially degenerated, and then began to regenerate at 4 days after the laceration. During this period, local basement membranes remained intact allowing regeneration of muscle fibers. However, the absence of basement membrane between the stumps led to a random regeneration pattern of myotubes growing into the granulation tissue in the wedge-shaped gap. The electronmicroscopic findings showed that these growing myotubes had no basement membrane. The maximum growth of these myotubes was found to be 1.20 +/- 0.31 mm reached at 3 weeks after the laceration, suggesting that the maximum gap was approximately 1.0 mm across which there is a potential for recovery through regeneration.

MESH: Cytoskeletal-Proteins-analysis; English-Abstract; Immunohistochemistry-; Microscopy,-Electron; Muscle,-Skeletal-metabolism; Muscle,-Skeletal-ultrastructure; Rats-; Rats,-Wistar

MESH: *Muscle,-Skeletal-physiology; *Regeneration-

TG: Animal; Male

PT: JOURNAL-ARTICLE

RN: 0

NM: Cytoskeletal-Proteins

AN: 96020745

UD: 9604

MEDLINE EXPRESS (R) 1/96-6/96 18 of 80

TI: Effects of proanthocyanidin on normal and reinnervated rat muscle.

AU: Ambrogini-P; Cuppini-R; Bruno-C; Bombardelli-E

AD: Institute of Anatomy and Physiology, University of Urbino.

SO: Boll-Soc-Ital-Biol-Sper. 1995 Jul-Aug; 71(7-8): 227-34

ISSN: 0037-8771

PY: 1995

LA: ENGLISH

CP: ITALY

AB: Proanthocyanidin-A2, a catechic dimer extracted from the bark of Aesculus hippocastanum L., was tested on peripheral nerve regeneration. Reinnervation of EDL and soleus muscles following traumatic nerve damage was investigated in rats by using "in vivo" tension recording technique. Muscle contraction force (twitch and tetanus), the number of motor units and the time course of twitch (time to peak and half relaxation time), were observed. The results obtained do not show that the time course of EDL and soleus muscles reinnervation is different in Proanthocyanidin-A2-treated rats in comparison to control animals. On the contrary, results point out an increase in EDL and soleus muscle mass, both in denervated and in undenervated treated rats compared to corresponding controls. Moreover, consistently with this finding, an increase in their contraction force was found. These data show that Proanthocyanidin-A2 exerts a trophic effect on muscle.

MESH: Muscle-Contraction-drug-effects; Muscle-Fibers,-Fast-Twitch-drug-effects; Muscle-Fibers,-Slow-Twitch-drug-effects; Muscle,-Skeletal-physiology; Rats-; Rats,-Sprague-Dawley; Synaptic-Transmission-drug-effects

MESH: *Anthocyanins-pharmacology; *Antioxidants-pharmacology; *Muscle-Denervation; *Muscle,-Skeletal-drug-effects; *Nerve-Regeneration-drug-effects

TG: Animal; Comparative-Study; Male

PT: JOURNAL-ARTICLE

RN: 0; 0; 18206-61-6

NM: Anthocyanins; Antioxidants; proanthocyanidin

AN: 96058851

UD: 9603

MEDLINE EXPRESS (R) 1/96-6/96 19 of 80

TI: Preliminary histoenzymatic muscular evaluations after ischemia-reperfusion damage.

AU: Capelli-S; Rocca-M; Orienti-L; Giavaresi-G; Giardino-R

AD: Servizio di Chirurgia Sperimentale, Istituto di Ricerca Codivilla-Putti, Istituti Ortopedici Rizzoli, Bologna.

SO: Boll-Soc-Ital-Biol-Sper. 1995 May-Jun; 71(5-6): 149-55

ISSN: 0037-8771

PY: 1995

LA: ENGLISH

CP: ITALY

AB: The aim of this study was to evaluate the muscular regenerative properties after an induced ischemia/reperfusion injury of 4 hours and 30 min. of the left hind limb of the rat and to evaluate and compare the efficacy of native and modified polyethylene glycol superoxide dismutase (SOD and mPEG-SOD). In particular, we try to find a suitable method to study the histological and histoenzymatic properties of muscular fibres, focusing also the technical procedure employed to evaluate the new activated motor end-plates. Biopsies from flexor digitorum superficialis were collected immediately after the ischemia/reperfusion damage and also at 4th, 6th and 10th days. The adopted protocol showed a good reliability both for the necrosis and the regenerative process evaluations. However the assessment of regenerative and reinnervative processes will be completed by histomorphometric analysis.

MESH: Combined-Modality-Therapy; Femoral-Artery-surgery; Hindlimb-blood-supply; Hindlimb-surgery; Ischemia-enzymology; Ischemia-pathology; Motor-Endplate-physiology; Motor-Endplate-ultrastructure; Muscle,-Skeletal-enzymology; Necrosis-; Polyethylene-Glycols-administration-and-dosage; Rats-; Rats,-Wistar; Reactive-Oxygen-Species; Regeneration-; Reperfusion-Injury-enzymology; Reperfusion-Injury-pathology; Superoxide-Dismutase-administration-and-dosage

MESH: *Ischemia-drug-therapy; *Muscle,-Skeletal-pathology; *Reperfusion-Injury-prevention-and-control; *Superoxide-Dismutase-therapeutic-use

TG: Animal

PT: JOURNAL-ARTICLE

RN: EC 1.15.1.1; 0; 0

NM: Superoxide-Dismutase; Polyethylene-Glycols; Reactive-Oxygen-Species

AN: 96050307

UD: 9603

MEDLINE EXPRESS (R) 1/96-6/96 20 of 80

TI: [Ultrasound follow-up of experimental muscle injuries]

TO: Sonographische Verlaufskontrolle von experimentellen Muskelverletzungen.

AU: Kullmer-K; Rompe-JD; Eysel-P; Harland-U

AD: Orthopadische Klinik, Johannes-Gutenberg-Universitat Mainz.

SO: Sportverletz-Sportschaden. 1995 Sep; 9(3): 69-71

ISSN: 0932-0555

PY: 1995

LA: GERMAN; NON-ENGLISH

CP: GERMANY

AB: Experimental muscle lesions were produced in 28 rabbits by stab incision, thus creating a lesion of known extent and site. The changes in the course of healing were followed up and documented at short intervals for a period of two months via sonography. The changes take place in regular course and can be explained by fine tissue changes, taking into consideration the fundamentals of theoretical ultrasound physics. Sonography renders both valuable assistance in diagnosing muscular lesions and in following up the healing process--the latter, however, with some reservations due to the clinical terminology defining the extent of muscular lesions.

MESH: English-Abstract; Follow-Up-Studies; Muscle,-Skeletal-ultrasonography; Rabbits-; Reference-Values

MESH: *Muscle,-Skeletal-injuries; *Soft-Tissue-Injuries-ultrasonography; *Wound-Healing-physiology; *Wounds,-Stab-ultrasonography

TG: Animal; Male

PT: JOURNAL-ARTICLE

AN: 96060162

UD: 9603

MEDLINE EXPRESS (R) 1/96-6/96 22 of 80

TI: Fast and slow rat muscles degenerate and regenerate differently after whole crush injury.

AU: Bassaglia-Y; Gautron-J

AD: MYREM/CRRET, URA 1813, Universite Paris-Val de Marne, Creteil, France.

SO: J-Muscle-Res-Cell-Motil. 1995 Aug; 16(4): 420-9

ISSN: 0142-4319

PY: 1995

LA: ENGLISH

CP: ENGLAND

AB: The whole-crush injured rat skeletal muscle was used as a model to explore the regenerating potentialities of fast and slow muscles. Laminin was chosen to follow changes in basal lamina and desmin to visualize new muscular elements; they were revealed by immunofluorescence on cryostat sections of either fast (extensor digitorum longus) or slow (soleus) regenerating muscle. Soleus myolysis was rapid, extensive and heterogeneous. Basal laminae were nearly destroyed. In contrast, extensor digitorum longus maintained its basal lamina framework during myolysis. Soleus reconstruction began early, following the pattern of remaining basal laminae as closely as possible, but regeneration stagnated from day 16 and the regenerated muscle was fibrotic. In extensor digitorum longus, reconstruction progressed slower than in soleus, but regularly from the periphery toward the centre of the muscle. The regenerated extensor digitorum longus showed a quasi-normal structure from day 16. At the end of the process, the elimination of old basal lamina was completed in extensor digitorum longus, but was not achieved in soleus. We propose that the old basal lamina should help the initiation of reconstruction. This new model also underlines the importance of the turnover of basal laminae in muscular regeneration, and will be useful to understand the background of the different regenerative response of both muscles.

MESH: Basement-Membrane-metabolism; Desmin-analysis; Immunohistochemistry-; Laminin-analysis; Microscopy,-Electron; Muscle-Fibers,-Fast-Twitch-chemistry; Muscle-Fibers,-Fast-Twitch-cytology; Muscle-Fibers,-Slow-Twitch-chemistry; Muscle-Fibers,-Slow-Twitch-cytology; Muscle,-Skeletal-cytology; Muscle,-Skeletal-ultrastructure; Rats-; Rats,-Wistar; Time-Factors

MESH: *Muscle-Fibers,-Fast-Twitch-physiology; *Muscle-Fibers,-Slow-Twitch-physiology; *Muscle,-Skeletal-injuries; *Regeneration-physiology

TG: Animal; Comparative-Study

PT: JOURNAL-ARTICLE

RN: 0; 0

NM: Desmin; Laminin

AN: 96025311

UD: 9603

MEDLINE EXPRESS (R) 1/96-6/96 23 of 80

TI: Effect of dietary restriction on protein synthesis and wound healing after surgery in the rat.

AU: Emery-PW; Sanderson-P

AD: Department of Nutrition and Dietetics, King's College London, U.K.

SO: Clin-Sci-Colch. 1995 Oct; 89(4): 383-8

ISSN: 0143-5221

PY: 1995

LA: ENGLISH

CP: ENGLAND

AB: 1. The healing of an abdominal muscle wound after surgery is associated with a considerable increase in the rate of protein synthesis. We have investigated whether this increase in protein synthesis is affected by chronic undernutrition, and whether this causes a delay in wound healing. 2. A group of rats was fed 58% of the voluntary food intake of a matched control group. After 7 days half the rats in each group underwent abdominal surgery. Forty-eight hours later all the rats were killed and muscle protein synthesis rate was measured by the flooding dose technique. 3. In a second experiment using the same dietary regimen rats were placed in metabolic cages after surgery and killed 7 days later. In addition to measurements of muscle protein synthesis, wound breaking strength was measured with a tensiometer and collagen content was also measured at the wound site. 4. Dietary restriction caused a loss of body weight, a decrease in nitrogen balance and a deficit in muscle protein mass. It also caused a decrease in protein synthesis rate in gastrocnemius muscle and in parts of the abdominal muscle distant from the site of the wound. However, it had no effect on the rate of muscle protein synthesis at the site of the wound either 2 or 7 days after surgery. The tensile strength and the collagen content of the wound were also unaffected by food restriction. 5. It is concluded that the wound healing process is uniquely protected from the effects of moderate undernutrition such as might be experienced by a chronically ill patient.

MESH: Abdominal-Muscles-surgery; Postoperative-Period; Rats-; Rats,-Sprague-Dawley

MESH: *Abdominal-Muscles-metabolism; *Diet,-Protein-Restricted; *Muscle-Proteins-metabolism; *Wound-Healing-physiology

TG: Animal; Female; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0

NM: Muscle-Proteins

AN: 96097857

UD: 9603

MEDLINE EXPRESS (R) 1/96-6/96 27 of 80

TI: Anti-inflammatory medication after muscle injury. A treatment resulting in short-term improvement but subsequent loss of muscle function.

AU: Mishra-DK; Friden-J; Schmitz-MC; Lieber-RL

AD: Department of Orthopaedics, Veterans Administration Medical Center, San Diego, California, USA.

SO: J-Bone-Joint-Surg-Am. 1995 Oct; 77(10): 1510-9

ISSN: 0021-9355

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: We studied the effect of flurbiprofen, a non-steroidal anti-inflammatory drug, on muscles that had been subjected to exercise-induced injury. The muscles of the anterior compartment in the limbs of rabbits were cyclically activated as the ankle was simultaneously moved through passive plantar flexion every two seconds for thirty minutes. This treatment imposed acute passive lengthening (eccentric contractions) of the maximally contracted muscles of the anterior compartment. After the eccentric contraction-induced muscle injury, one group of rabbits was treated with oral administration of flurbiprofen, two times a day for six days, while the other group of rabbits served as untreated controls. The contractile, histological, and ultrastructural properties of the muscles were measured before the initial exercise and at three, seven, and twenty-eight days afterward. The group that was treated with flurbiprofen demonstrated a more complete functional recovery than the untreated controls at three and seven days but had a deficit in torque and force generation at twenty-eight days. The administration of flurbiprofen also resulted in a dramatic preservation of the intermediate filament protein desmin. After three days, the proportion of fibers of the extensor digitorum longus that lost desmin-staining was significantly greater in the untreated controls than in the treated animals (34 +/- 4.1 compared with 2.9 +/- 1.7 per cent) (p < 0.001), a finding that supports the concept of a short-term protective effect. However, the muscles in the treated animals still mounted a dramatic regenerative response, as indicated by the expression of embryonic myosin. Early in the recovery period (at three days), significantly fewer fibers of the extensor digitorum longus (2.2 +/- 1.4 per cent) expressed embryonic myosin in the treated animals than in the untreated controls (11.8 +/- 1.9 per cent) (p < 0.001). However, at seven days, the expression of embryonic myosin by the muscles from the treated animals (19.5 +/- 11.9 per cent) actually exceeded that of the muscles from the untreated controls (16.2 +/- 4.1 per cent). This finding suggests either a delayed or an ineffectual regenerative response by the muscles in the treated animals.

MESH: Analgesics-pharmacology; Analgesics-therapeutic-use; Anti-Inflammatory-Agents,-Non-Steroidal-pharmacology; Desmin-drug-effects; Desmin-metabolism; Flurbiprofen-pharmacology; Isometric-Contraction; Muscle-Contraction; Muscle-Fibers-drug-effects; Muscle-Fibers-metabolism; Muscle-Fibers-ultrastructure; Muscle,-Skeletal-physiopathology; Muscle,-Skeletal-ultrastructure; Myofibrils-drug-effects; Myofibrils-ultrastructure; Myosin-drug-effects; Myosin-metabolism; Rabbits-; Regeneration-drug-effects; Time-Factors

MESH: *Anti-Inflammatory-Agents,-Non-Steroidal-therapeutic-use; *Exertion-physiology; *Flurbiprofen-therapeutic-use; *Muscle,-Skeletal-drug-effects

TG: Animal; Comparative-Study; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.

PT: JOURNAL-ARTICLE

CN: AR40050ARNIAMS

RN: 0; 0; 0; 0; 5104-49-4

NM: Analgesics; Anti-Inflammatory-Agents,-Non-Steroidal; Desmin; Myosin; Flurbiprofen

AN: 96027815

UD: 9602

SB: AIM

MEDLINE EXPRESS (R) 1/96-6/96 28 of 80

TI: Cell death induced by gamma irradiation of developing skeletal muscle.

AU: Olive-M; Blanco-R; Rivera-R; Cinos-C; Ferrer-I

AD: Unidad de Neuropatologia, Hospital Principes de Espana, Universidad de Barcelona, Spain.

SO: J-Anat. 1995 Aug; 187 ( Pt 1): 127-32

ISSN: 0021-8782

PY: 1995

LA: ENGLISH

CP: ENGLAND

AB: Newborn Sprague-Dawley rats were exposed to a single dose of 2 Gy gamma rays and killed from 6 h to 5 d later. Increased numbers of dying cells, characterised by their extreme chromatin condensation and often nuclear fragmentation were seen in skeletal muscle 6 h after irradiation. Dying cells decreased to nearly normal values 48 h later. In situ labelling of nuclear DNA fragmentation identified individual cells bearing fragmented DNA. The effects of gamma rays were suppressed following cycloheximide i.p. at a dose of 1 microgram/g body weight given at the time of irradiation. Taken together, the present morphological and pharmacological results suggest that gamma ray induced cell death in skeletal muscle is apoptotic, and that the process is associated with protein synthesis. Finally, proliferating cell nuclear antigen-immunoreactive cells, which were abundant in control rats, decreased in number 48 h after irradiation. However, a marked increase significantly above normal age values was observed at the 5th day, thus suggesting that regeneration occurs following irradiation-induced cell death in developing muscle.

MESH: Animals,-Newborn; Apoptosis-radiation-effects; Cycloheximide-pharmacology; Immunohistochemistry-; Muscle,-Skeletal-growth-and-development; Muscle,-Skeletal-pathology; Proliferating-Cell-Nuclear-Antigen-analysis; Rats-; Rats,-Sprague-Dawley; Regeneration-; Time-Factors

MESH: *Cell-Death; *DNA-Damage; *Gamma-Rays-adverse-effects; *Muscle,-Skeletal-radiation-effects

TG: Animal; Female; Male; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 66-81-9

NM: Proliferating-Cell-Nuclear-Antigen; Cycloheximide

AN: 96083285

UD: 9602

MEDLINE EXPRESS (R) 1/96-6/96 29 of 80

TI: Association of an unusual form of a Pax7-like gene with increased efficiency of skeletal muscle regeneration.

AU: Kay-PH; Mitchell-CA; Akkari-A; Papadimitriou-JM

AD: Department of Pathology, University of Western Australia, Nedlands.

SO: Gene. 1995 Oct 3; 163(2): 171-7

ISSN: 0378-1119

PY: 1995

LA: ENGLISH

CP: NETHERLANDS

AB: Efficiency of regeneration of mechanically injured skeletal muscle is more pronounced in SJL/J mice, as compared to other laboratory strains in which regenerative properties of skeletal muscle are uniformly poor. Previously, we postulated that a small number of genes might differ between SJL/J and other mouse strains, and would be responsible for this variation in the efficiency of skeletal muscle regeneration. The results of initial experiments demonstrated that SJL/J mice have a unique form of the myogenic gene, Myo-D1, which partly influences efficiency of skeletal muscle repair, and that other genes were also involved. To identify other candidate genes, differences were sought within the myogenic paired box/homeobox-containing gene Pax7 between SJL/J and other laboratory mouse strains. Southern blotting indicated that SJL/J, Quackenbush and DDO mice share a Pax7/TaqI RFLP which differs from all other laboratory strains tested. This RFLP is most likely due to sequence differences within the homeobox of a Pax7-like gene. In vivo studies revealed that Quackenbush and DDO mice also share the same regenerative properties of mechanically damaged skeletal muscle as SJL/J mice. Since Quackenbush and DDO mice lack the SJL/J type of Myo-D1, and DDO belong to a different mouse sub-species, these studies suggest that structural alterations in the homeobox of a Pax7-like gene may be implicated in the effectiveness of renewal of damaged skeletal muscle of the limb in the mature animal.

MESH: Base-Sequence; Mice-; Mice,-Inbred-Strains; Molecular-Sequence-Data; Muscle,-Skeletal-pathology; Sequence-Analysis

MESH: *Genes,-Homeobox; *Muscle,-Skeletal-physiology; *Regeneration-genetics

TG: Animal; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

AN: 96011629

UD: 9602

MEDLINE EXPRESS (R) 1/96-6/96 30 of 80

TI: Ischaemia-induced expression of bFGF in normal skeletal muscle: a potential paracrine mechanism for mediating angiogenesis in ischaemic skeletal muscle.

AU: Walgenbach-KJ; Gratas-C; Shestak-KC; Becker-D

AD: Department of Surgery, University of Pittsburgh, Pennsylvania 15213, USA.

SO: Nat-Med. 1995 May; 1(5): 453-9

ISSN: 1078-8956

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: To test the hypothesis that induction of endogenous bFGF can lead to angiogenesis in ischaemic skeletal muscle, we studied the expression of bFGF after transposition of a well-vascularized muscle flap onto an ischaemic hindlimb in the rabbit. The results indicated a marked induction of bFGF mRNA throughout the myoblasts of the well-perfused muscle flap but not the myoblasts of the ischaemic muscle. bFGF protein was detected in the muscle flap, particularly in the myoblasts located closest to a newly formed, adjacent interface, and in the interface itself. In contrast, bFGF expression was not induced after transposition of a well-perfused muscle flap onto healthy muscle tissue. These data provide evidence that the juxtaposition of ischaemic skeletal muscle with healthy mesenchymal tissue triggers an increased expression of bFGF in the myoblasts of the well-perfused muscle. This paracrine induction of bFGF, in turn, leads to increased angiogenesis and regeneration of the ischaemic skeletal muscle.

MESH: Base-Sequence; Cell-Communication; Endothelium,-Vascular-cytology; Fibroblast-Growth-Factor,-Basic-genetics; Molecular-Sequence-Data; Pulmonary-Artery-cytology; Rabbits-; Regeneration-physiology; RNA,-Messenger-analysis; RNA,-Messenger-biosynthesis; Sheep-

MESH: *Fibroblast-Growth-Factor,-Basic-biosynthesis; *Ischemia-physiopathology; *Muscle,-Skeletal-blood-supply; *Muscle,-Skeletal-metabolism; *Neovascularization,-Physiologic-physiology

TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.

PT: JOURNAL-ARTICLE

RN: 0; 0

NM: Fibroblast-Growth-Factor,-Basic; RNA,-Messenger

AN: 96071474

UD: 9602

MEDLINE EXPRESS (R) 1/96-6/96 31 of 80

TI: Efficiency and functional consequences of adenovirus-mediated in vivo gene transfer to normal and dystrophic (mdx) mouse diaphragm.

AU: Petrof-BJ; Acsadi-G; Jani-A; Massie-B; Bourdon-J; Matusiewicz-N; Yang-L; Lochmuller-H; Karpati-G

AD: Department of Medicine, Royal Victoria Hospital, Montreal, Quebec, Canada.

SO: Am-J-Respir-Cell-Mol-Biol. 1995 Nov; 13(5): 508-17

ISSN: 1044-1549

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: The protein dystrophin is absent in muscles of patients with Duchenne muscular dystrophy (DMD) as well as in mdx mice. The mdx mouse diaphragm closely resembles the human DMD phenotype and should serve as an appropriate model for future studies of dystrophin gene replacement. In this regard, recombinant adenovirus (AV) holds great promise as a vector for delivering a functional dystrophin gene to muscle. However, the use of AV is hampered by the development of an immune response against transduced cells, resulting in short-lived transgene expression as well as possible adverse effects on organ function. In the present study, sensitive reporter genes were employed to determine the efficiency and functional consequences of AV-mediated gene transfer to the diaphragm in both normal and mdx adult mice. One week after direct intramuscular injection of AV into the diaphragm, the level of transgene expression was significantly increased in mdx compared with normal diaphragms. In addition, small-caliber fibers (< 500 microns2) demonstrated preferential transduction in both groups of mice. Normal diaphragms receiving AV exhibited a substantial reduction in maximal twitch and tetanic force generation, whereas no significant effect on diaphragm contractility was found in the mdx group at 1 wk after injection. At 1 mo after AV administration, however, there was a significant decrease in force production by both normal and mdx diaphragms. Immunosuppression with cyclosporine A over 1 mo did not augment the level of transgene expression, but a beneficial effect on diaphragm force-generating capacity was observed in both groups of animals. We conclude the following: (1) short-term transduction of the diaphragm is more efficient in mdx than in normal mice; (2) AV leads to reduced force production by the diaphragm, with this effect being more pronounced in normal than in mdx in the early (but not the late) postinjection period; and (3) immunosuppressive therapy with cyclosporine has a partially protective effect on muscle function after AV administration, which is apparently unrelated to sparing of transduced fibers from elimination by the host immune system. These findings have important implications for the application of AV-mediated dystrophin gene transfer to the treatment of DMD.

MESH: Adenoviruses,-Human-pathogenicity; Cyclosporine-pharmacology; Diaphragm-; Gene-Expression; Gene-Expression-Regulation,-Viral-drug-effects; Genetic-Vectors; Immunosuppressive-Agents-pharmacology; Mice-; Mice,-Inbred-C57BL; Mice,-Mutant-Strains; Muscle-Contraction; Myosin-Heavy-Chains-metabolism; Regeneration-; Time-Factors; Transgenes-genetics

MESH: *Adenoviruses,-Human-genetics; *Dystrophin-genetics; *Gene-Therapy-methods; *Gene-Transfer; *Muscular-Dystrophy,-Animal-therapy

TG: Animal; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 0; 0; 0; 59865-13-3

NM: Dystrophin; Genetic-Vectors; Immunosuppressive-Agents; Myosin-Heavy-Chains; Cyclosporine

AN: 96054915

UD: 9602

MEDLINE EXPRESS (R) 1/96-6/96 32 of 80

TI: Hypothyroidism prolongs and increases mdx muscle precursor proliferation and delays myotube formation in normal and dystrophic limb muscle.

AU: McIntosh-LM; Anderson-JE

AD: Department of Anatomy, University of Manitoba, Winnipeg, Canada.

SO: Biochem-Cell-Biol. 1995 Mar-Apr; 73(3-4): 181-90

ISSN: 0829-8211

PY: 1995

LA: ENGLISH

CP: CANADA

AB: Hypothyroidism (induced by 8 weeks of oral 0.05% propylthiouracil) heightened the phenotype of mdx mouse dystrophin-deficient myopathy to more closely resemble human Duchenne muscular dystrophy. Muscle repair after crush injury to the tibialis anterior muscle (TA) in hypothyroid mdx mice showed decreased myotube formation and delayed debris removal. To investigate whether reduced muscle precursor cell proliferation can account for the effects of hypothyroidism on repair from injury, immunocytochemistry for neural cell adhesion molecule (NCAM) on muscle precursor cells and autoradiography to detect DNA synthesis were performed in control and mdx TA. The proportions of labelled polymorphonuclear leukocyte nuclei (PMN), myotube nuclei (MN), and total mononuclear cell nuclei (TLN, the majority being muscle precursors) were counted in defined areas of regenerating TA after 2 and 4 days recovery. MN and the numbers of activated satellite cell nuclei on intact fibers were counted in surviving areas. In the same muscle, earlier phases of regeneration were observed in areas distal than proximal to the injury. At 2 days of regeneration, labelled PMN were increased in treated compared with untreated mdx TA. In distal areas at 4 days, fewer muscle precursors had recently fused to myotubes in treated than in untreated mdx. In proximal areas 4 days (relatively late in repair), TLN data suggested that muscle precursor proliferation was greater in hypothyroid compared with untreated mdx TA. NCAM immunostaining was consistent with proliferation data and confirmed that there were more muscle precursors in mdx than in control regenerating muscle. These results suggest that hypothyroidism prolongs and increases the phase of replication by mdx muscle precursors and delays precursor fusion into myotubes in regeneration.

MESH: Autoradiography-; Cell-Differentiation; Cell-Division; Cell-Nucleus-pathology; Dystrophin-analysis; Hypothyroidism-metabolism; Mice-; Mice,-Inbred-C57BL; Mice,-Mutant-Strains; Muscle,-Skeletal-physiopathology; NCAM-analysis; Regeneration-

MESH: *Dystrophin-deficiency; *Hypothyroidism-physiopathology; *Muscle,-Skeletal-injuries

TG: Animal; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 0

NM: Dystrophin; NCAM

AN: 96001928

UD: 9602

MEDLINE EXPRESS (R) 1991-1995 33 of 80

TI: Comparison of contractile properties between developing and regenerating soleus muscle: influence of external calcium concentration upon the contractility.

AU: Louboutin-JP; Fichter-Gagnepain-V; Noireaud-J

AD: URA CNRS 1340, CHR G.R. Laennec, Nantes, France.

SO: Muscle-Nerve. 1995 Nov; 18(11): 1292-9

ISSN: 0148-639X

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: In newborn rat skeletal extensor digitorum longus (EDL) muscle, it has been found that an influx of calcium from the extracellular medium is necessary for contraction, in contrast to the situation observed in adult EDL muscle. The aim of the present study was to determine the influence of the extracellular calcium concentration ([Ca]o) upon the contractile responses elicited in developing as well as in regenerating (notexin-injected) soleus (SOL) muscle. A morphological study was performed to follow the steps of postnatal development and regeneration in SOL muscle. In nominally calcium-free solution, the amplitudes of the twitch and tetanic tensions were greatly reduced in 1-14-day-old developing SOL muscles, as well as in notexin-injected SOL muscles. With longer times after birth, twitch and tetanic tensions of SOL muscle were less affected by the absence of calcium. This contrasts with notexin-injected SOL muscle in which the amplitudes of the contractions remained strongly dependent on [Ca]o. The present finding suggests that some functional characteristics are different in regenerating muscle fibers and may be of interest in the evaluation of the contractile properties of muscles in which injections of genetically engineered or not autologous myoblasts or viral vector have been performed.

MESH: Animals,-Newborn; Calcium-Channel-Blockers-pharmacology; Elapid-Venoms-pharmacology; Hindlimb-; Muscle-Relaxation-drug-effects; Muscle,-Skeletal-drug-effects; Muscle,-Skeletal-growth-and-development; Neurotoxins-pharmacology; Osmolar-Concentration; Rats-; Rats,-Wistar

MESH: *Aging-physiology; *Calcium-pharmacology; *Muscle-Contraction-drug-effects; *Muscle,-Skeletal-physiology; *Regeneration-

TG: Animal; Comparative-Study; Male; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 0; 0; 37223-96-4; 7440-70-2

NM: Calcium-Channel-Blockers; Elapid-Venoms; Neurotoxins; notexin; Calcium

AN: 96006310

UD: 9601

MEDLINE EXPRESS (R) 1991-1995 35 of 80

TI: Skeletal muscle necrosis and regeneration after injection of BaH1, a hemorrhagic metalloproteinase isolated from the venom of the snake Bothrops asper (Terciopelo).

AU: Gutierrez-JM; Romero-M; Nunez-J; Chaves-F; Borkow-G; Ovadia-M

AD: Instituto Clodomiro Picado, Facultad de Microbiologia, Universidad de Costa Rica, San Jose.

SO: Exp-Mol-Pathol. 1995 Feb; 62(1): 28-41

ISSN: 0014-4800

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: The effects of BaH1, a hemorrhagic metalloproteinase isolated from Bothrops asper venom, on mouse gastrocnemius muscle was investigated. The toxin induced severe hemorrhage within minutes after injection. Groups of necrotic muscle fibers were observed after the sixth hour, with evident disorganization of myofibrillar material. At the ultrastructural level myofibrils in these cells lost their regular arrangement, Z lines were absent, and sarcomeres were disoriented, although there was no evidence of myofilament clumping or hypercontraction. Plasma membrane was interrupted in many portions. Mitochondrial alterations included swelling and the formation of flocculent densities and dense intracristal plates. At 12, 24, and 48 hr necrotic cells had amorphous masses of myofilaments and abundant phagocytic cells were observed both within necrotic fibers and in the interstitial space. Fraction D-1, which contains the three hemorrhagic metalloproteinases BaH1, BH2, and BH3, did not cause direct muscle damage when incubated with gastrocnemius muscle in vitro. Upon intramuscular injection in mice this fraction induced a small but significant increment in muscle lactic acid levels. Observations carried out 7 and 14 days after BaH1 injection revealed some regenerating muscle fibers with centrally located nuclei. However, other areas had few regenerating fibers of reduced diameter, surrounded by abundant fibroblasts, fibrosis, calcification, and remnants of necrotic muscle cells. When BaH1 was injected together with B. asper myotoxin III, a myotoxic phospholipase A2 that induces myonecrosis but does not affect blood vessels, a poor muscle regeneration was observed. In contrast, if B. asper myotoxin III was injected alone, regeneration proceeded normally and successfully.

MESH: Bothrops-; Hemoglobins-analysis; Lactates-analysis; Mice-; Muscle,-Skeletal-drug-effects; Muscle,-Skeletal-ultrastructure; Necrosis-; Regeneration-

MESH: *Crotalid-Venoms-toxicity; *Muscle,-Skeletal-pathology; *Peptide-Peptidohydrolases-toxicity

TG: Animal; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: EC 3.4.-; EC 3.4.-; 0; 0; 0; 50-21-5

NM: hemorrhagic-proteinase-IV; Peptide-Peptidohydrolases; Crotalid-Venoms; Hemoglobins; Lactates; lactic-acid

AN: 96003647

UD: 9601

MEDLINE EXPRESS (R) 1991-1995 37 of 80

TI: [Acceleration of the regeneration of skeletal muscles in adult rats by dextran derivatives]

TO: Acceleration de la regeneration d'un muscle squelettique de rat adulte par des derives de dextranes.

AU: Gautron-J; Kedzia-C; Husmann-I; Barritault-D

AD: Laboratoires CRRET, URA-CNRS, Universite de Paris-XII, Creteil, France.

SO: C-R-Acad-Sci-III. 1995 Jun; 318(6): 671-6

ISSN: 0764-4469

PY: 1995

LA: FRENCH; NON-ENGLISH

CP: FRANCE

AB: Dextran derivatives were obtained by controlled successive substitutions of carboxymethyl, carbomethyl-benzylamide and carboxymethyl-benzylamide sulfonate groups on glucose residues. Among these derivatives, RGT11 was selected since it mimicked some properties of heparin or heparan sulfate to stabilise and protect heparin binding growth factors such as FGFs and TGF-beta. Furthermore RGT11 inhibited plasmine and leukocyte elastase. In previous works, we have explained the healing effects of RGT obtained in skin or bone repair models by these protecting and inhibiting properties. We now present the results obtained after a single injection of RGT11 in a regenerating crushed extensor digitorum longus (EDL) muscle. After 8 days, RGT11 injected muscles contained 10 times the number of fibers than controlled injected muscles. Fibers were organized in bundles of normal size. Histological analysis indicated that regeneration was comparable to that observed after 3 weeks without RGT. Hence in vivo, RGT11 could act by protecting the heparin binding growth factors involved in the natural process of muscle regeneration and therefore favour their actions. This family of polymers should offer a new pharmaceutical potential for treating muscle atrophy and destruction and is worth studying further.

MESH: Dextran-Sulfate-pharmacology; English-Abstract; Muscle,-Skeletal-cytology; Plasma-Substitutes-pharmacology; Rats-; Rats,-Wistar

MESH: *Dextrans-pharmacology; *Muscle,-Skeletal-physiology; *Regeneration-drug-effects

TG: Animal; Male; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 9004-54-0; 9042-14-2

NM: Plasma-Substitutes; Dextrans; Dextran-Sulfate

AN: 95400906

UD: 9512

MEDLINE EXPRESS (R) 1991-1995 41 of 80

TI: Ultrastructural and morphometric analysis of capillaries surrounding regenerating muscle fibers in rats.

AU: Luque-E; Pena-J; Martin-P; Jimena-I; Vaamonde-R

AD: Department of Morphological Sciences (Section of Histology), Faculty of Medicine, University of Cordoba, Spain.

SO: J-Submicrosc-Cytol-Pathol. 1995 Jul; 27(3): 367-74

ISSN: 0022-4782

PY: 1995

LA: ENGLISH

CP: ITALY

AB: A study was made of the characteristics of the capillaries surrounding regenerating muscle fibers at three different stages of their development. Mepivacaine was injected in the anterior tibial muscles of Wistar rats in order to obtain muscle and capillary degeneration which was followed by muscle and capillary regeneration. Muscles were examined at 4, 8 and 30 days post-injection. Capillaries were subjected to quantitative and qualitative examination using electron microscopy. Results showed the morphological and morphometrical variations taking place in capillaries as the regenerative fiber matures. Changes were most evident in the capillaries surrounding the most immature fibers. It was concluded that although capillary morphology suggests that the supply of blood to regenerative fibers may be hindered, morphometric data appear to indicate no such obstacle.

MESH: Cell-Nucleus-ultrastructure; Endothelium,-Vascular-ultrastructure; Microscopy,-Electron; Muscle,-Skeletal-ultrastructure; Rats-; Rats,-Wistar

MESH: *Capillaries-ultrastructure; *Muscle,-Skeletal-blood-supply; *Muscle,-Skeletal-physiology; *Regeneration-

TG: Animal; Male

PT: JOURNAL-ARTICLE

AN: 95401171

UD: 9512

MEDLINE EXPRESS (R) 1991-1995 42 of 80

TI: Regeneration pattern of cardiac and skeletal muscle after transplantation into a skeletal muscle bed in rats.

AU: Gulati-AK

AD: Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 30912-2000, USA.

SO: Anat-Rec. 1995 Jun; 242(2): 188-94

ISSN: 0003-276X

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: BACKGROUND: The ability of skeletal muscle to regenerate after injury is well established. In contrast, cardiac muscle is incapable of regeneration and recovery after injury. The aim of the present study was to evaluate and compare the regeneration pattern of cardiac and skeletal muscle after transplantation into a skeletal muscle bed in rats. METHODS: The following group of transplants were performed at the site prepared by removing the host extensor digitorum longus (EDL) muscle. The first group consisted of cardiac muscle transplanted as one piece or after mincing into 1-mm pieces. The second group included cotransplants of cardiac and skeletal muscle minces that were intermixed. Entire EDL muscle or minced EDL muscle were also transplanted for comparison. Rats were sacrificed 3-30 days after transplantation for morphological analysis. RESULTS: The results demonstrated that skeletal muscle transplants underwent rapid regeneration, and by 30 days the entire muscle was filled with regenerated myofibers. In transplants of cardiac muscle significant inflammation, myocardial degeneration and necrosis were observed. In spite of the necrosis and fibrosis, the presence of a few regenerated myotubes in the outer region was observed. In cardiac and skeletal muscle cotransplants, the inflammation was restricted to cardiac tissue; however, by 30 days the entire cotransplant was filled with regenerated myotubes and myofibers. CONCLUSIONS: These results show that skeletal muscle is capable of growth, regeneration, and integration with the cardiac muscle after cotransplantation. Combination of skeletal and cardiac muscle may prove useful in defining the cellular processes necessary for enhancing cardiac repair after injury.

MESH: Heart-physiology; Heart-Transplantation-pathology; Microscopy,-Electron; Muscle,-Skeletal-anatomy-and-histology; Myocardium-ultrastructure; Rats-; Rats,-Inbred-F344; Time-Factors

MESH: *Heart-Transplantation-physiology; *Muscle,-Skeletal-physiology; *Muscle,-Skeletal-transplantation; *Regeneration-

TG: Animal

PT: JOURNAL-ARTICLE

AN: 95397963

UD: 9512

MEDLINE EXPRESS (R) 1991-1995 43 of 80

TI: Age-related differences in regeneration of dystrophic (mdx) and normal muscle in the mouse.

AU: Pastoret-C; Sebille-A

AD: Laboratoire de Physiologie, Faculte de Medecine, Paris, France.

SO: Muscle-Nerve. 1995 Oct; 18(10): 1147-54

ISSN: 0148-639X

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: The mdx mouse, a genetic homologue of human Duchenne muscular dystrophy (DMD), has been attributed with a greater regenerative capacity of its skeletal muscles. Here, we have tested the hypothesis that muscles of mdx mice regenerate better than those of nondystrophic animals. We studied muscle regeneration resulting from a denervation-devascularization injury (DD) of extensor digitorum longus muscle (EDL) at 3 weeks and 2 months in mdx and wild-type (C57BL/10) mice. Histological and morphometrical studies of muscle regeneration were made from 3 to 180 days later. When DD was performed in 3-week-old C57BL/10 mice, the percentages of nonperipheral nuclei in regenerated fibers decreased progressively over 3 months. This decrease did not occur in animals where DDs were performed at 2 months, suggesting that two different populations of muscle precursor cells are mobilized in muscle regeneration in mice at these two ages. Moreover, mdx EDL muscle regenerated similarly to the controls for up to 60 postoperative days, as shown by distribution of mean diameters and percentage of nonperipheral nuclei of muscle fibers. After 60 postoperative days, necrosis/regeneration characteristics of mdx muscles recurred, suggesting that mdx-regenerated muscle fibers remain susceptible to degeneration.

MESH: Mice-; Mice,-Inbred-C57BL; Muscle-Denervation; Muscle-Fibers-cytology; Muscle-Fibers-pathology; Muscle-Fibers-physiology; Muscle,-Skeletal-cytology; Muscle,-Skeletal-pathology; Muscular-Dystrophy,-Animal-genetics; Muscular-Dystrophy,-Animal-pathology; Mutation-; Time-Factors

MESH: *Aging-physiology; *Muscle,-Skeletal-physiology; *Muscular-Dystrophy,-Animal-physiopathology; *Regeneration-physiology

TG: Animal; Male; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

AN: 95388085

UD: 9512

MEDLINE EXPRESS (R) 1991-1995 45 of 80

TI: Myocardial regeneration. Transplanting satellite cells into damaged myocardium.

AU: Yoon-PD; Kao-RL; Magovern-GJ

AD: Cardiothoracic Surgical Research, Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania, USA.

SO: Tex-Heart-Inst-J. 1995; 22(2): 119-25

ISSN: 0730-2347

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: Millions of Americans suffer from chronic heart failure. Despite treatments with heart transplantation, cardiomyoplasty, and artificial assist devices, an ideal therapy is yet to be found. Since 1988, we have studied the transplantation of myogenic stem cells from skeletal muscle into injured myocardium in the hope that these cells would multiply and differentiate, thereby improving the function of the failing heart. We have achieved 2 goals thus far: the 1st was improving the culture technique to obtain high yield and purity of the satellite cells; the 2nd was successfully implanting cultured satellite cells in dog hearts and later identifying them as new myocardium. We share our findings here to encourage more study in this promising area.

MESH: Cell-Differentiation-physiology; Cell-Survival-physiology; Cells,-Cultured; Dogs-; Heart-Failure,-Congestive-pathology; Heart-Failure,-Congestive-surgery; Muscle,-Skeletal-pathology; Stem-Cells-pathology

MESH: *Heart-Transplantation-pathology; *Muscle,-Skeletal-transplantation; *Myocardium-pathology; *Regeneration-physiology; *Stem-Cells-transplantation

TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.

PT: JOURNAL-ARTICLE

CN: HL54286HLNHLBI

AN: 95375573

UD: 9512

MEDLINE EXPRESS (R) 1991-1995 46 of 80

TI: Cellular and molecular reactions in mouse muscles after myoblast implantation.

AU: Irintchev-A; Zweyer-M; Wernig-A

AD: Department of Physiology, University of Bonn, Germany.

SO: J-Neurocytol. 1995 Apr; 24(4): 319-31

ISSN: 0300-4864

PY: 1995

LA: ENGLISH

CP: ENGLAND

AB: Implantation of skeletal muscle precursor cells is a potential means of cell-mediated gene therapy. One unresolved question is the degree of immunogenicity of such myoblasts. We designed the extreme situation of implanting cells of a non-histocompatible myoblast cell line into cryodamaged, but regeneration-capable, muscles of adult mice. Without immunosuppression donor cells are rejected within the first weeks. Immunosuppression with Cyclosporin A prevented invasion of T-lymphocytes and allowed differentiation of implanted myoblasts into myofibres as well as down-regulation of MHC expression. Still, withdrawal of Cyclosporin A after 4 weeks triggered lymphocyte invasion and cytotoxic cell reactions with rejection of donor tissue. Although the vast majority of muscle fibres was MHC-negative 1-4 days after Cyclosporin A withdrawal, single small desmin-positive profiles were weakly positive for donor MHC. Parallel with the increase in the number of lymphocytes, larger numbers of small and large muscle fibres expressed high levels of either donor, host or both, class I--but not class II--molecules. Surprisingly, immune reactions continued over several months, causing gradual loss of muscle tissue. Donor class I molecules persisted for more than 6 months after Cyclosporin A withdrawal, clearly indicating survival of donor muscle fibres despite ongoing rejection. Indirect evidence on the other hand suggests additional loss of host fibres, possibly caused by cytokine release from the immune cells (bystander damage). We conclude that transient treatment with Cyclosporin A induced a kind of tolerance related to the maturation and down-regulation of class I antigens in donor muscle fibres. It is suggested that the start of immune reaction following Cyclosporin A withdrawal is initiated by remaining small amounts of donor MHC molecules, possibly related to the continuous proliferation of the cell-lined-derived donor myoblasts.

MESH: Cell-Count-drug-effects; Cyclosporine-pharmacology; Histocompatibility-Antigens-Class-I; Histocompatibility-Antigens-Class-II; Mice-; Mice,-Inbred-BALB-C; Mice,-Inbred-CBA; Muscle,-Skeletal-drug-effects; Muscle,-Skeletal-immunology; Regeneration-immunology

MESH: *Cell-Transplantation; *Graft-Rejection-immunology; *Major-Histocompatibility-Complex-immunology; *Muscle,-Skeletal-cytology

TG: Animal; Female; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 0; 59865-13-3

NM: Histocompatibility-Antigens-Class-I; Histocompatibility-Antigens-Class-II; Cyclosporine

AN: 95370847

UD: 9511

MEDLINE EXPRESS (R) 1991-1995 47 of 80

TI: Up-regulation of PKA RI alpha subunit mRNA in rat skeletal muscle after nerve injury.

AU: Morita-N; Namikawa-K; Kiyama-H

AD: Department of Neuroanatomy, Osaka University Medical School, Japan.

SO: Neuroreport. 1995 May 9; 6(7): 1050-2

ISSN: 0959-4965

PY: 1995

LA: ENGLISH

CP: ENGLAND

AB: Localization of all subunits of cAMP dependent protein kinase (PKA) mRNAs and their changes of expression after denervation were examined in rat tongue skeletal muscle by in situ hybridization histochemistry. Among all PKA subunits only RI alpha subunit mRNA was detected in the skeletal muscle, whereas positive signal of all subunits mRNA were observed in some haematocytes or lymphocytes within the tongue tissue. The RI alpha mRNA was distributed in a restricted area near the endplate. The mRNA level was substantially induced by the hypoglossal nerve transection, suggesting that the up-regulation of RI alpha mRNA leading to the down-regulation of PKA activity may contribute to some intracellular signalling modulation or to muscle specific gene transcription after the denervation.

MESH: Acetylcholinesterase-biosynthesis; Motor-Endplate-enzymology; Motor-Endplate-physiology; Nerve-Regeneration-physiology; Rats-; Rats,-Wistar; Tongue-innervation; Tongue-metabolism; Transcription,-Genetic

MESH: *Cyclic-AMP-Dependent-Protein-Kinases-biosynthesis; *Hypoglossal-Nerve-injuries; *Muscle,-Skeletal-enzymology; *RNA,-Messenger-biosynthesis; *Up-Regulation-Physiology-physiology

TG: Animal; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: EC 2.7.10.-; EC 3.1.1.7; 0

NM: Cyclic-AMP-Dependent-Protein-Kinases; Acetylcholinesterase; RNA,-Messenger

AN: 95359379

UD: 9511

MEDLINE EXPRESS (R) 1991-1995 49 of 80

TI: Effects of denervation on antioxidant enzymes in nerve and muscles of rats.

AU: Ninfali-P; Cuppini-C; Marinoni-S

AD: Istituto di Chimica Biologica G. Fornaini, Universita di Urbino.

SO: Boll-Soc-Ital-Biol-Sper. 1995 Jan-Feb; 71(1-2): 1-6

ISSN: 0037-8771

PY: 1995

LA: ENGLISH

CP: ITALY

MESH: Denervation-; Muscle,-Skeletal-innervation; Oxidative-Stress; Rats-; Rats,-Sprague-Dawley; Regeneration-; Sciatic-Nerve-physiopathology

MESH: *Catalase-analysis; *Glucosephosphate-Dehydrogenase-analysis; *Glutathione-Peroxidase-analysis; *Glutathione-Reductase-analysis; *Muscle,-Skeletal-enzymology; *Sciatic-Nerve-enzymology; *Superoxide-Dismutase-analysis

TG: Animal; Male

PT: JOURNAL-ARTICLE

RN: EC 1.1.1.49; EC 1.11.1.6; EC 1.11.1.9; EC 1.15.1.1; EC 1.6.4.2

NM: Glucosephosphate-Dehydrogenase; Catalase; Glutathione-Peroxidase; Superoxide-Dismutase; Glutathione-Reductase

AN: 95352255

UD: 9511

MEDLINE EXPRESS (R) 1991-1995 50 of 80

TI: Regenerative capacity of mdx mouse muscles after repeated applications of myo-necrotic bupivacaine.

AU: Itagaki-Y; Saida-K; Iwamura-K

AD: Department of Pediatrics, Utano National Hospital, Kyoto, Japan.

SO: Acta-Neuropathol-Berl. 1995; 89(4): 380-4

ISSN: 0001-6322

PY: 1995

LA: ENGLISH

CP: GERMANY

AB: We injected bupivacaine (BPVC), which produces muscle fiber necrosis, repeatedly into the soleus muscles of mdx mice, which represent a model of human Duchenne muscular dystrophy, over a 12-month period. Cytological and morphometric analysis revealed that the regenerative capacity of repeatedly BPVC-injected mdx muscles was almost equal to that of the saline-injected mdx muscles. At 9 months of age the endomysial collagen content of mdx muscles was 4.6 times that of control mice muscles, and was 7.2 times that of control mice muscle at 12 months. These results suggest that the regenerative capacity of the mdx muscle is quite large and that myo-necrosis induced by an extrinsic cause, such as BPVC, may not be an important factor in the disease progress. However, endomysial collagen, for which the mechanism of increase may be related to the defect of dystrophin, may play an important role in gradual decline of regeneration.

MESH: Age-Factors; Antibodies-immunology; Collagen-; Mice-; Mice,-Inbred-C57BL; Muscle-Fibers; Muscular-Dystrophy,-Animal; Regeneration-drug-effects

MESH: *Bupivacaine-pharmacology; *Muscle,-Skeletal-drug-effects

TG: Animal; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 2180-92-9; 9007-34-5

NM: Antibodies; Bupivacaine; Collagen

AN: 95335146

UD: 9510

MEDLINE EXPRESS (R) 1991-1995 51 of 80

TI: mdx mice show progressive weakness and muscle deterioration with age.

AU: Pastoret-C; Sebille-A

AD: Laboratoire de Physiologie, Faculte de Medicine Saint-Antoine, Paris, France.

SO: J-Neurol-Sci. 1995 Apr; 129(2): 97-105

ISSN: 0022-510X

PY: 1995

LA: ENGLISH

CP: NETHERLANDS

AB: The time-course of degeneration/regeneration was investigated in leg muscles throughout the life of the mdx mutant mouse, which is a biochemical homologue of Duchenne muscular dystrophy (DMD). In young and adult mice (up to 52 weeks old), muscle fibre necrosis was compensated by a vigorous regeneration, but in old mdx mice (65-104 weeks) this regeneration slightly declined, while the necrotic process persisted. Body and muscles weights declined strikingly after 52 weeks. Life span of mdx mutants was reduced in comparison with the control C57BL/10 animals. Immunostaining of old mdx muscles showed clusters of dystrophin-positive fibres. Muscle fibres in old mdx mice showed great variation in size, many being atrophied or split. Endomysial fibrosis became increasingly conspicuous, and there was some accumulation of adipose tissue. These progressive degenerative changes of old mdx mice resemble those found in DMD and imply that basic pathological similarities between the murine and human diseases previously observed in diaphragm of mdx mice may be extended to other skeletal muscles.

MESH: Mice-; Mice,-Inbred-C57BL; Mice,-Mutant-Strains; Muscle,-Skeletal-physiology; Regeneration-physiology

MESH: *Aging-pathology; *Muscular-Dystrophy,-Animal-genetics

TG: Animal; Support,-Non-U.S.-Gov't

GS: mdx

PT: JOURNAL-ARTICLE

AN: 95332930

UD: 9510

MEDLINE EXPRESS (R) 1991-1995 52 of 80

TI: M-cadherin localization in developing adult and regenerating mouse skeletal muscle: possible involvement in secondary myogenesis.

AU: Cifuentes-Diaz-C; Nicolet-M; Alameddine-H; Goudou-D; Dehaupas-M; Rieger-F; Mege-RM

AD: INSERM U. 153, CNRS ERS 64, Paris, France.

SO: Mech-Dev. 1995 Mar; 50(1): 85-97

ISSN: 0925-4773

PY: 1995

LA: ENGLISH

CP: IRELAND

AB: In this work, we investigated the distribution of the Ca(2+)-dependent cell adhesion molecule, M-cadherin, in mouse limb muscle during normal development and regeneration. Using two unrelated anti-M-cadherin peptide antibodies, we found scarce M-cadherin immunostaining during primary myogenesis (E12-E14) with no accumulation at areas of cell-cell contact. In contrast, the staining sharply increased in intensity at E16, remained high during secondary myogenesis (E16-P0) but disappeared soon after birth. During secondary myogenesis, M-cadherin was specifically accumulated at the characteristic sites of insertion of secondary myotubes in neighbouring primary myotubes. M-cadherin was also accumulated at the areas of contact between fusing secondary myoblasts and myotubes in vitro. In the adult normal and regenerating muscle, we did not detect M-cadherin accumulations at the surface of myofibres. All together, these observations suggest that M-cadherin is specifically involved in secondary myogenesis.

MESH: Amino-Acid-Sequence; Cell-Communication-physiology; Cells,-Cultured; Fetal-Development-physiology; Hindlimb-embryology; Mice-; Mice,-Inbred-Strains; Molecular-Sequence-Data; Muscle,-Skeletal-growth-and-development; Muscle,-Skeletal-physiology

MESH: *Cadherins-analysis; *Muscle-Proteins-analysis; *Muscle,-Skeletal-chemistry; *Regeneration-physiology

TG: Animal; Male; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 0; 142845-03-2

NM: Cadherins; Muscle-Proteins; M-cadherin

AN: 95329431

UD: 9510

MEDLINE EXPRESS (R) 1991-1995 53 of 80

TI: Increase of skeletal muscle relaxation speed by direct injection of parvalbumin cDNA.

AU: Muntener-M; Kaser-L; Weber-J; Berchtold-MW

AD: Institute of Anatomy, University of Zurich-Irchel, Switzerland.

SO: Proc-Natl-Acad-Sci-U-S-A. 1995 Jul 3; 92(14): 6504-8

ISSN: 0027-8424

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: Parvalbumin (PV) is a high affinity Ca(2+)-binding protein found at high concentration in fast-contracting/relaxing skeletal muscle fibers of vertebrates. It has been proposed that PV acts in the process of muscle relaxation by facilitating Ca2+ transport from the myofibrils to the sarcoplasmic reticulum. However, on the basis of metal-binding kinetics of PV in vitro, this hypothesis has been challenged. To investigate the function of PV in skeletal muscle fibers, direct gene transfer was applied in normal and regenerating rat soleus muscles which do not synthesize detectable amounts of PV. Two weeks after in vivo transfection with PV cDNA, considerable levels of PV mRNA and protein were detected in normal muscle, and even higher amounts were detected in regenerating muscle. Twitch half-relaxation time was significantly shortened in a dose-dependent way in transfected muscles, while contraction time remained unaltered. The observed shortening of half-relaxation time is due to PV and its ability to bind Ca2+, because a mutant protein lacking Ca(2+)-binding capacity did not promote any change in physiology. These results directly demonstrate the physiological function of PV as a relaxing factor in mammalian skeletal muscle.

MESH: Chloramphenicol-Acetyltransferase-analysis; Chloramphenicol-Acetyltransferase-biosynthesis; Cloning,-Molecular; DNA,-Complementary-administration-and-dosage; DNA,-Complementary-metabolism; Immunohistochemistry-; Mammary-Tumor-Viruses,-Mouse; Parvalbumins-analysis; Polymerase-Chain-Reaction; Promoter-Regions-Genetics; Rats-; Reference-Values; Regeneration-; RNA,-Messenger-analysis; Time-Factors

MESH: *DNA,-Complementary-pharmacology; *Isometric-Contraction; *Muscle-Relaxation; *Muscle,-Skeletal-physiology; *Parvalbumins-biosynthesis; *RNA,-Messenger-biosynthesis; *Transfection-

TG: Animal; Comparative-Study; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: EC 2.3.1.28; 0; 0; 0

NM: Chloramphenicol-Acetyltransferase; DNA,-Complementary; Parvalbumins; RNA,-Messenger

AN: 95327675

UD: 9510

MEDLINE EXPRESS (R) 1991-1995 54 of 80

TI: Functional effects of myoblast implantation into histoincompatible mice with or without immunosuppression.

AU: Wernig-A; Irintchev-A; Lange-G

AD: Department of Physiology, University of Bonn, Germany.

SO: J-Physiol-Lond. 1995 Apr 15; 484 ( Pt 2): 493-504

ISSN: 0022-3751

PY: 1995

LA: ENGLISH

CP: ENGLAND

AB: 1. The goals of this study were to evaluate the immunogenicity of myogenic cells (MCs) (1) immediately after implantation into regenerating muscles, and (2) following their maturation under initial immunosuppression. Implanted mouse soleus muscles were evaluated by isometric tension recordings in vitro followed by histological investigations on frozen sections. 2. Implantation of non-histocompatible myoblasts into cryodamaged soleus muscles of CBA/J mice induced immune rejection which caused large and permanent deficits in muscle force: 4-42 weeks postimplantation maximal tetanic tension was 50-60% that of intact or regenerated cryodamaged control muscles without tendency for recovery or histological signs of muscle regeneration. Specific tension (force per unit muscle weight) was also significantly reduced. 3. On frozen sections, only 62 +/- 12% of the total area was desmin-positive, that is, occupied by muscle fibres, versus 90 +/- 4% in regenerated and 92 +/- 3% in intact muscles. Also, the total number of muscle fibre profiles was significantly reduced. 4. Under immune suppression with cyclosporin A (CsA), large muscles developed within 4 weeks. Following CsA withdrawal, muscle weight and force, in addition to desmin-positive areas on cross-sections, gradually declined over several months despite continual regeneration, indicating retarded immune rejection. 5. Initial application of CsA for 8 weeks after implantation, instead of 4 weeks, did not result in better survival of the implants, nor did a higher initial dose of CsA (100 instead of 50 mg kg-1 day-1). Prolonged continuous application of a reduced dose (25 mg kg-1 day-1) did not prevent muscle wasting but caused an additional delay. 6. It is concluded that histoincompatible myoblasts are highly immunogenic and that immune rejection causes large and permanent muscle deficits indicating elimination of host muscle tissue. Initial transient immunosuppression protects the incompatible cells, but after withdrawal, prolonged immune rejection and retarded muscle wasting occur.

MESH: Cell-Count; Cell-Transplantation; Cyclosporine-pharmacology; Fibrosis-; Graft-Rejection; Immunohistochemistry-; Mice-; Mice,-Inbred-CBA; Muscle-Contraction; Muscle,-Skeletal-cytology; Regeneration-; Time-Factors

MESH: *Immunosuppression-; *Muscle,-Skeletal-immunology; *Muscle,-Skeletal-transplantation

TG: Animal; Female; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 59865-13-3

NM: Cyclosporine

AN: 95326090

UD: 9510

MEDLINE EXPRESS (R) 1991-1995 55 of 80

TI: Phenotypic and pathologic evaluation of the myd mouse. A candidate model for facioscapulohumeral dystrophy.

AU: Mathews-KD; Rapisarda-D; Bailey-HL; Murray-JC; Schelper-RL; Smith-R

AD: University of Iowa College of Medicine, Department of Pediatrics, Iowa City, USA.

SO: J-Neuropathol-Exp-Neurol. 1995 Jul; 54(4): 601-6

ISSN: 0022-3069

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant disease of unknown pathogenesis which is characterized by weakness of the face and shoulder girdle. It is associated with a sensorineural hearing loss which may be subclinical. FSHD has been mapped to the distal most portion of 4q35, although the gene has not yet been identified. Distal 4q has homology with a region of mouse chromosome 8 to which a mouse mutant, myodystrophy (myd), has been mapped. Muscle from homozygotes for the myd mutation appears dystrophic, showing degenerating and regenerating fibers, inflammatory infiltrates, central nuclei, and variation in fiber size. Brainstem auditory evoked potentials reveal a sensorineural hearing loss in myd homozygotes. Based on the homologous genetic map locations, and the phenotypic syndrome of dystrophic muscle with sensorineural hearing loss, we suggest that myd represents an animal model for the human disease FSHD.

MESH: Chromosome-Mapping; Chromosomes,-Human,-Pair-4; Evoked-Potentials,-Auditory,-Brain-Stem; Facial-Muscles-pathology; Genotype-; Mice-; Mice,-Mutant-Strains-genetics; Muscle-Fibers-pathology; Muscular-Dystrophy,-Animal-genetics; Necrosis-; Phenotype-; Regeneration-; Shoulder-pathology; Syndrome-

MESH: *Disease-Models,-Animal; *Hearing-Loss,-Sensorineural-genetics; *Mice,-Mutant-Strains; *Muscular-Dystrophy-genetics; *Muscular-Dystrophy,-Animal-pathology

TG: Animal; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.

GS: myd

PT: JOURNAL-ARTICLE

CN: 1P30HD27748HDNICHD

AN: 95325859

UD: 9510

MEDLINE EXPRESS (R) 1991-1995 56 of 80

TI: The expression of dystrophin-associated glycoproteins during skeletal muscle degeneration and regeneration. An immunofluorescence study.

AU: Vater-R; Harris-JB; Anderson-VB; Roberds-SL; Campbell-KP; Cullen-MJ

AD: Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, Newcastle upon Tyne, United Kingdom.

SO: J-Neuropathol-Exp-Neurol. 1995 Jul; 54(4): 557-69

ISSN: 0022-3069

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: The distribution and expression of dystrophin and three of the dystrophin-associated glycoproteins (DAG), alpha-dystroglycan (156 kDa DAG), beta-dystroglycan (43 kDa DAG) and adhalin (50 kDa DAG) in rat skeletal muscle were studied during a controlled cycle of degeneration and regeneration induced by the injection of a snake venom. Cryosections of muscle at various stages of degeneration and regeneration were labeled using monoclonal antibodies to the three glycoproteins and examined at fixed time points after venom injection. Adhalin and alpha-dystroglycan remained present at the sarcolemma throughout the entire cycle of degeneration and regeneration. beta-Dystroglycan, on the other hand, was lost from the sarcolemma by 12 hours and reappeared 2 days after venom injection when new muscle fibers were being formed. Dystrophin was not lost from the sarcolemma until 24 hours after venom injection and did not reappear at the membrane until 4 days. It is suggested that dystrophin and the glycoprotein complex are synthesized separately, both temporally and spatially, and only become associated at the plasma membrane during the later stages of regeneration. The expression of beta-dystroglycan in the regenerating muscle fibers was first seen at sites of newly forming plasma membrane that were closely associated with the old basal lamina tube. The basal lamina may therefore have a regulatory or modulatory role in the expression of the DAG.

MESH: Antibodies,-Monoclonal-immunology; Basement-Membrane-drug-effects; Blotting,-Western; Cytoskeletal-Proteins-genetics; Elapid-Venoms-toxicity; Fluorescent-Antibody-Technique; Gene-Expression; Membrane-Glycoproteins-genetics; Muscle,-Skeletal-drug-effects; Muscle,-Skeletal-pathology; Rats-; Rats,-Wistar; Sarcolemma-drug-effects; Sarcolemma-pathology

MESH: *Cytoskeletal-Proteins-biosynthesis; *Dystrophin-metabolism; *Membrane-Glycoproteins-biosynthesis; *Muscle,-Skeletal-physiology; *Regeneration-

TG: Animal; Female; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 0; 0; 0; 0; 0; 146888-27-9

NM: adhalin; Antibodies,-Monoclonal; Cytoskeletal-Proteins; Dystrophin; Elapid-Venoms; Membrane-Glycoproteins; 43-156K-dystrophin-associated-glycoprotein

AN: 95325855

UD: 9510

MEDLINE EXPRESS (R) 1991-1995 58 of 80

TI: Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation.

AU: Chiu-RC; Zibaitis-A; Kao-RL

AD: McGill University, Montreal, Quebec, Canada.

SO: Ann-Thorac-Surg. 1995 Jul; 60(1): 12-8

ISSN: 0003-4975

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: BACKGROUND. Damaged skeletal muscle is able to regenerate because of the presence of satellite cells, which are undifferentiated myoblasts. In contrast, destruction of cardiac myocytes is associated with an irreversible loss of myocardium and replacement with scar tissue, because it lacks stem cells. We tested the hypothesis that skeletal muscle satellite cells implanted into injured myocardium can differentiate into cardiac muscle fibers and thus repair damaged heart muscle. METHODS. Two series of canine studies were performed. In the first series (n = 26), satellite cells were isolated from skeletal muscle, cultured, and labeled with tritiated thymidine. The cells were implanted into acutely cryoinjured myocardium and the specimens harvested 4 to 18 weeks later. In the second series (n = 20), satellite cells in culture were labeled with lacZ reporter gene, which encodes production of Escherichia coli beta-galactosidase. Four to 6 weeks later, beta-galactosidase activity was studied using X-Gal stain. RESULTS. New striated muscles were found in the first series of experiments at the site of implantation, within a dense scar created by cryoinjury. These muscles showed histologic evidence of intercalated discs and centrally located nuclei, similar to those seen in cardiac muscle fibers. Tritiated thymidine radioactivity was not identified clearly, presumably due to dilutional effect as the stem cells replicated repeatedly. In the second series, histochemical studies of reporter gene-labeled and implanted satellite cells revealed the presence of beta-galactosidase within the cells at the implant site, which confirmed the survival of implanted cells. CONCLUSIONS. Our data are consistent with the hypothesis of milieu-influenced differentiation of satellite cells into cardiac-like muscle cells. Confirmation of these findings and its functional capabilities could have important clinical implications.

MESH: Cell-Differentiation; Cells,-Cultured; Dogs-; Heart-Surgery; Myocardium-pathology

MESH: *Heart-physiology; *Muscle-Fibers-cytology; *Muscle,-Skeletal-cytology; *Myocardium-cytology; *Regeneration-

TG: Animal; Female; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.

PT: JOURNAL-ARTICLE

CN: HL54286HLNHLBI

AN: 95321798

UD: 9510

SB: AIM

MEDLINE EXPRESS (R) 1991-1995 59 of 80

TI: The hyper-reinnervation of rat skeletal muscle.

AU: Kuiken-TA; Childress-DS; Rymer-WZ

AD: Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.

SO: Brain-Res. 1995 Apr 3; 676(1): 113-23

ISSN: 0006-8993

PY: 1995

LA: ENGLISH

CP: NETHERLANDS

AB: This study examines muscle recovery and related changes in the motor unit population of 'hyper-reinnervated' rat skeletal muscle. Medial gastrocnemius (MG) muscles were hyper-reinnervated by either cutting the MG nerve and implanting it on the MG muscle together with additional hind limb nerves, or by crushing the MG nerve and excising the medial portion (50-70%) of the MG muscle. Our findings were that muscles hyper-reinnervated with multiple nerves recovered muscle mass and strength more fully than did the self-reinnervated muscles, more motor units were formed (up to three times the normal number were found), and the mean motor unit size was significantly smaller. A relatively small percentage of muscle fibers became polyneuronally innervated. In contrast, the number of motor units that were formed in the muscle reduction experiments were not significantly larger than was expected considering the mass of the muscles. We conclude that hyper-reinnervation improves muscle recovery, it may be a useful technique for improving function in denervated muscle, and may serve to provide added sources of EMG control signals in some amputees.

MESH: Amputees-; Motor-Neurons-physiology; Muscle-Denervation; Muscles-physiopathology; Rats-; Rats,-Sprague-Dawley

MESH: *Muscle,-Skeletal-innervation; *Nerve-Regeneration-physiology

TG: Animal; Female; Support,-U.S.-Gov't,-Non-P.H.S.

PT: JOURNAL-ARTICLE

AN: 95316551

UD: 9510

MEDLINE EXPRESS (R) 1991-1995 60 of 80

TI: [Reconstruction of the diaphragm with various materials. An animal experiment study]

TO: Zwerchfellrekonstruktion mit verschiedenen Materialien. Eine tierexperimentelle Studie.

AU: Steinau-G; Hauptmann-G; Schindler-A; Schleef-J; Schumpelick-V

AD: Chirurgische Klinik, RWTH Aachen.

SO: Langenbecks-Arch-Chir. 1995; 380(3): 154-7

ISSN: 0023-8236

PY: 1995

LA: GERMAN; NON-ENGLISH

CP: GERMANY

AB: The relative merits of three methods of diaphragmatic hernia repair were evaluated in animals. Eighty Sprague-Dawley rats underwent laparotomy. The control group had an incision in the diaphragm with primary repair. The other three groups underwent partial resection of the left hemidiaphragm. The defects were repaired in 20 rats with lyophilized Dura, in 20 with polytetrafluoroethylene (PTFE) and in another 20 with absorbable serosa from a cow. Seventy-two animals survived the operation; they were followed up by electromyography (EMG) and post-mortem physical and histological examinations after 3 and 6 months. The EMG showed normal function for the absorbable material. Only scanty physiological waves were registered in the PTFE group. The examination for stretching and stress showed good results for all materials tested. The histological examinations amount to strong foreign body reactions with Dura and PTFE groups. The absorbable bovine serosa had vanished after 3 months postoperatively. It is concluded that bovine serosa can be recommended for diaphragmatic hernia.

MESH: Diaphragm-pathology; Diaphragm-physiopathology; Elasticity-; Electromyography-; English-Abstract; Foreign-Body-Reaction-pathology; Rats-; Rats,-Sprague-Dawley; Tensile-Strength; Wound-Healing-physiology

MESH: *Biological-Dressings; *Collagen-; *Diaphragm-surgery; *Polytetrafluoroethylene-

TG: Animal

PT: JOURNAL-ARTICLE

RN: 0; 9002-84-0; 9007-34-5

NM: lyodura; Polytetrafluoroethylene; Collagen

AN: 95311600

UD: 9509

MEDLINE EXPRESS (R) 1991-1995 63 of 80

TI: MyoD protein accumulates in satellite cells and is neurally regulated in regenerating myotubes and skeletal muscle fibers.

AU: Koishi-K; Zhang-M; McLennan-IS; Harris-AJ

AD: Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand.

SO: Dev-Dyn. 1995 Mar; 202(3): 244-54

ISSN: 1058-8388

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: MyoD belongs to a family of helix-loop-helix proteins that control myogenic differentiation. Transfection of various non-myogenic cell lines with MyoD transforms them into myogenic cells. In normal embryonic development MyoD is upregulated at the time when the hypaxial musculature begins to form, but its role in the function of adult muscle remains to be elucidated. In this study we examined the cellular locations of MyoD protein in normal and abnormal muscles to see whether the presence of MyoD protein is correlated with a particular cellular behaviour and to assess the usefulness of MyoD as a marker for satellite cells. Adult rats were anaesthetised and their tibialis anterior or soleus muscles either denervated, tenotomised, freeze lesioned, lesioned and denervated, or lesioned and tenotomised. At various intervals after the operations the rats were killed and their muscles removed, snap frozen, and sectioned with a cryostat along with muscles from unoperated neonatal and adult rats. The sections were processed for immunohistochemistry using a rabbit affinity-purified antibody to recombinant MyoD. MyoD proved to be an excellent marker for active satellite cells; satellite cells in neonatal and regenerating muscles contained high levels of MyoD protein. MyoD positive cells were not observed in the muscles of old adults, in which the satellite cells are fully quiescent. MyoD immunoreactivity was rapidly lost from satellite cell nuclei after they fused into myotubes and was not detected in either sub-synaptic or non-synaptic nuclei of mature fibers. Denervation, and to a lesser extent tenotomy, of lesioned muscles induced expression of MyoD in myotubal nuclei. Denervation of normal muscles also upregulated MyoD in muscle fiber nuclei, an effect which was maximal after 3 days. We conclude that MyoD protein is neurally regulated in both myotubes and muscle fibers.

MESH: Age-Factors; Biological-Markers; Cell-Differentiation-physiology; Cell-Nucleus-metabolism; Gene-Expression-Regulation,-Developmental-physiology; Muscle-Contraction-physiology; Muscle-Denervation; Muscle-Fibers,-Fast-Twitch-cytology; MyoD-Protein-genetics; Rats-; Rats,-Wistar; Receptors,-Cholinergic-genetics

MESH: *Muscle-Fibers,-Fast-Twitch-metabolism; *Muscle,-Skeletal-cytology; *MyoD-Protein-metabolism; *Nerve-Fibers-physiology; *Regeneration-physiology

TG: Animal; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 0; 0

NM: Biological-Markers; MyoD-Protein; Receptors,-Cholinergic

AN: 95299185

UD: 9509

MEDLINE EXPRESS (R) 1991-1995 64 of 80

TI: [MRI results in experimental muscle injuries]

TO: MRT-Ergebnisse bei experimentellen Muskelverletzungen.

AU: Kullmer-K; Harland-U; Sievers-KW; Kock-HJ; Schmit-Neuerburg-KP

AD: Abteilung fur Unfallchirurgie, Universitatsklinikum GHS Essen.

SO: Unfallchirurgie. 1995 Apr; 21(2): 59-63

ISSN: 0340-2649

PY: 1995

LA: GERMAN; NON-ENGLISH

CP: GERMANY

AB: We performed an incision of standardized size and location on the suprascapularic muscle of 18 rabbits by a stab with a scalpel and measured the signal intensity of the muscle 2, 5, 11, 21, 35 and 64 days after injury (3 rabbits on each day). We did not find any detectable changes in the MRI pictures but a characteristic graph of the calculated T2-times (a mathematical procedure of the MRI software). The MRI changes correlate with the histopathological changes after muscle injury. The MRI method allows the evaluation of minor muscle trauma by the detection of a changed liquid content by using calculated T2 times.

MESH: English-Abstract; Muscle,-Skeletal-pathology; Rabbits-; Wound-Healing-physiology

MESH: *Muscle,-Skeletal-injuries; *Soft-Tissue-Injuries-diagnosis; *Wounds,-Stab-diagnosis

TG: Animal; Male

PT: JOURNAL-ARTICLE

AN: 95288863

UD: 9509

MEDLINE EXPRESS (R) 1991-1995 65 of 80

TI: Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation.

AU: Fu-SY; Gordon-T

AD: Department of Pharmacology, University of Alberta, Edmonton, Canada.

SO: J-Neurosci. 1995 May; 15(5 Pt 2): 3886-95

ISSN: 0270-6474

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: The effects of prolonged denervation, independent from those of prolonged axotomy, on the recovery of muscle function were examined in a nerve cross-anastomosis paradigm. The tibialis anterior muscle was denervated for various durations by cutting the common peroneal nerve before a freshly cut tibial nerve was cross-sutured to its distal stump. Nerve regeneration and muscle reinnervation were quantified by means of electrophysiological and histochemical methods. Progressively fewer axons reinnervated the muscle with prolonged denervation; for example, beyond 6 months the mean (+/- SE) motor unit number was 15 +/- 4, which was far fewer than that after immediate nerve suture (137 +/- 21). The poor regeneration after prolonged denervation is not due to inability of the long-term denervated muscle to accept reinnervation because each regenerated axon reinnervated three- to fivefold more muscle fibers than normal. Rather, it is due to progressive deterioration of the intramuscular nerve sheaths because the effects of prolonged denervation were simulated by forcing regenerating axons to grow outside the sheaths. Fewer regenerated axons account for reinnervation of less than 50% of the muscle fibers in each muscle and contribute to the progressive decline in muscle force. Reinnervated muscle fibers failed to fully recover from denervation atrophy: muscle fiber cross-sectional area being 1171 +/- 84 microns2 as compared to 2700 +/- 47 microns2 after immediate nerve suture. Thus, the primary cause of the poor recovery after long-term denervation is a profound reduction in the number of axons that successfully regenerate through the deteriorating intramuscular nerve sheaths. Muscle force capacity is further compromised by the incomplete recovery of muscle fibers from denervation atrophy.

MESH: Anastomosis,-Surgical; Electrophysiology-methods; Glycogen-metabolism; Muscle-Fibers-physiology; Muscle-Fibers-ultrastructure; Muscle,-Skeletal-cytology; Muscle,-Skeletal-innervation; Peroneal-Nerve-surgery; Rats-; Rats,-Sprague-Dawley; Regression-Analysis; Tibial-Nerve-surgery; Time-Factors

MESH: *Axons-physiology; *Muscle-Contraction; *Muscle-Denervation; *Muscle,-Skeletal-physiology; *Nerve-Regeneration; *Peroneal-Nerve-physiology; *Tibial-Nerve-physiology

TG: Animal; Female; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 9005-79-2

NM: Glycogen

AN: 95271340

UD: 9508

MEDLINE EXPRESS (R) 1991-1995 67 of 80

TI: Localization of myogenin, c-fos, c-jun, and muscle-specific gene mRNAs in regenerating rat skeletal muscle.

AU: Kami-K; Noguchi-K; Senba-E

AD: Department of Health Science, Osaka University of Health and Sport Sciences, Japan.

SO: Cell-Tissue-Res. 1995 Apr; 280(1): 11-9

ISSN: 0302-766X

PY: 1995

LA: ENGLISH

CP: GERMANY

AB: It has been suggested that myogenin is an important factor for the differentiation of myoblasts and that its function in myogenesis is regulated by proto-oncogenes in in vitro experiments. We have characterized the spatial and temporal expression patterns of myogenin, c-fos, c-jun, and muscle creatine kinase mRNAs during the skeletal muscle regeneration process using in situ hybridization histochemistry. Myogenin transcripts are first detected in the myonuclei/nuclei of satellite cells at 6 h after induction of regeneration. Myogenin mRNA is expressed in desmin-positive myoblasts, yet no muscle creatine kinase mRNA is detected in this cell type. Both the muscle creatine kinase and myogenin mRNAs are expressed in the newly formed myotubes, but not at earlier stages. Transcripts for c-fos and c-jun mRNAs are expressed first in the myonuclei/nuclei of satellite cells at 3 h post-trauma. c-jun mRNA is expressed in both myoblasts and myotubes, while c-fos mRNA was not detected in these cells. These results suggest that myogenin plays important role in the regeneration of injured muscle and that c-jun and c-fos may have different roles in this process.

MESH: Biological-Markers; Creatine-Kinase-Isoenzymes-biosynthesis; Creatine-Kinase-Isoenzymes-genetics; Desmin-biosynthesis; Desmin-genetics; Gene-Expression-Regulation; Laminin-biosynthesis; Laminin-genetics; Muscle-Proteins-biosynthesis; Muscles-chemistry; Muscles-injuries; Muscles-pathology; Myogenin-biosynthesis; Rats-; Rats,-Wistar; RNA,-Messenger-biosynthesis; Time-Factors

MESH: *Genes,-fos; *Genes,-jun; *Muscle-Proteins-genetics; *Muscles-physiology; *Myogenin-genetics; *Regeneration-; *RNA,-Messenger-analysis

TG: Animal; Male; Support,-Non-U.S.-Gov't

GS: c-fos; c-jun

PT: JOURNAL-ARTICLE

RN: EC 2.7.3.-; 0; 0; 0; 0; 0; 0

NM: Creatine-Kinase-Isoenzymes; Biological-Markers; Desmin; Laminin; Muscle-Proteins; Myogenin; RNA,-Messenger

AN: 95269288

UD: 9508

MEDLINE EXPRESS (R) 1991-1995 71 of 80

TI: Expression and activity of the newt Msx-1 gene in relation to limb regeneration.

AU: Crews-L; Gates-PB; Brown-R; Joliot-A; Foley-C; Brockes-JP; Gann-AA

AD: Ludwig Institute for Cancer Research, University College London, U.K.

SO: Proc-R-Soc-Lond-B-Biol-Sci. 1995 Feb 22; 259(1355): 161-71

ISSN: 0962-8452

PY: 1995

LA: ENGLISH

CP: ENGLAND

AB: The Msx-1 homeobox gene is expressed in various contexts during vertebrate development, including the progress zone of the avian and mouse limb bud. Expression of mouse Msx-1 in a cultured myogenic cell line conferred a transformed phenotype and inhibited fusion into myotubes. It has been proposed that Msx-1 expression is required to maintain certain cells in a proliferating and undifferentiated state and may be associated with the ability to regenerate limbs. Urodele amphibians such as the newt regenerate their limbs by formation of a growth zone or blastema, and we have isolated and sequenced newt Msx-1 (NvMsx-1) from a limb blastemal cDNA library. NvMsx-1 expression was detectable in RNA preparations from both limb and tail and their regeneration blastemas, although cultured cells established from limb blastemal mesenchyme gave negative results. When either COS cells or cultured newt blastemal cells were cotransfected with an expression vector for NvMsx-1 and reporter plasmids containing multiple homeobox protein binding sites, NvMsx-1 repressed reporter expression. If NvMsx-1 was expressed together with a marker enzyme in cultured newt blastemal cells, no significant difference in DNA synthesis was observed relative to control transfectants. When myogenic mononucleate cells were transfected with NvMsx-1 and subsequently exposed to low serum to promote fusion, the fraction of Msx-1 positive cells in myotubes was comparable to a control transfected population analysed in the same culture. These results indicate that although Msx-1 expression could be important for limb regeneration, it does not exert a cell-autonomous effect on proliferation or myogenic differentiation of cultured blastemal cells.

MESH: Amino-Acid-Sequence; Base-Sequence; Cell-Differentiation-genetics; Cell-Division-genetics; Cell-Line; Cloning,-Molecular; DNA-genetics; Extremities-growth-and-development; Gene-Expression-Regulation,-Developmental; Homeodomain-Proteins-genetics; Homeodomain-Proteins-physiology; Mice-; Molecular-Sequence-Data; Notophthalmus-viridescens-growth-and-development; Plasmids-genetics; Sequence-Homology,-Amino-Acid; Sequence-Homology,-Nucleic-Acid; Species-Specificity; Transfection-

MESH: *Extremities-physiology; *Genes,-Homeobox; *Notophthalmus-viridescens-genetics; *Notophthalmus-viridescens-physiology; *Regeneration-genetics

TG: Animal; Comparative-Study; Support,-Non-U.S.-Gov't

GS: NvMsx-1; Msx-1

PT: JOURNAL-ARTICLE

RN: 0; 0; 0; 9007-49-2

NM: hox-7.1-protein; Homeodomain-Proteins; Plasmids; DNA

AN: 95249617

UD: 9508

MEDLINE EXPRESS (R) 1991-1995 72 of 80

TI: [Muscle-specific changes in free latissimus dorsi transplantation in the rat model]

TO: Muskelspezifische Veranderungen bei der freien Latissimus dorsi-Transplantation im Rattenmodell.

AU: Becker-MH; Lassner-F; Dagtekin-F; Walter-GF; Berger-A

AD: Klinik fur Plastische, Hand- und Wiederherstellungschirurgie, Medizinischen Hochschule Hannover am Krankenhaus Oststad.

SO: Handchir-Mikrochir-Plast-Chir. 1995 Mar; 27(2): 93-7

ISSN: 0722-1819

PY: 1995

LA: GERMAN; NON-ENGLISH

CP: GERMANY

AB: The aim of this study is to gain further knowledge concerning the regeneration of reinnervated, freely transplanted muscles. Therefore, we used a rat model, consisting of eight rats per group, in which the latissimus dorsi muscle was transplanted orthotopically, after a period of time of two and twelve weeks harvested, then evaluated histologically and enzyme-histochemically. As controls we used a group of non-operated muscles. At date of removal, the patency of the vascular anastomoses was checked clinically and histologically. Additionally, electrophysiological measurements and conventional and enzyme-histochemical histologies were performed. Two weeks after the free neurovascular flap transplantation, the muscle was not innervated yet, histologically a dissolved pattern of type 1 and type 2 muscle fibers was found. After twelve weeks of time, the muscles were reinnervated again, muscle contraction was positive after electrical stimulation and the typical pattern of fibers was reestablished.

MESH: Back-; English-Abstract; Histocytochemistry-; Muscle-Contraction; Muscle,-Skeletal-blood-supply; Muscle,-Skeletal-enzymology; Muscle,-Skeletal-innervation; Rats-; Rats,-Inbred-Lew; Regeneration-; Vascular-Patency

MESH: *Muscle,-Skeletal-transplantation; *Surgical-Flaps

TG: Animal

PT: JOURNAL-ARTICLE

AN: 95247104

UD: 9508

MEDLINE EXPRESS (R) 1991-1995 73 of 80

TI: Mechanical load affects growth and maturation of skeletal muscle grafts.

AU: Esser-KA; White-TP

AD: School of Kinesiology, University of Illinois, Chicago 60608-1516.

SO: J-Appl-Physiol. 1995 Jan; 78(1): 30-7

ISSN: 8750-7587

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: The purpose of our study was to determine whether the early patterns of growth and maturation of regenerating soleus muscle grafts are sensitive to alterations in mechanical load. We hypothesized that decreased and increased mechanical loading of grafts would reduce and accelerate, respectively, the rate and magnitude of growth and impair and enhance, respectively, the pattern of maturation. On day 0, soleus muscles were grafted and rats were assigned to one of three groups: cage sedentary (normal load), hindlimb suspension (decreased load), or ablation of synergist muscle (increased load). From days 7 to 35, graft mass in cage-sedentary rats increased at a rate of 1.85 mg mass/day. Rates were less for grafts of suspended rats and greater in grafts of ablated rats (-1.06 and 3.89 mg mass/day, respectively; P < 0.01). Neonatal myosin heavy chain (MHC) in grafts reached 10 +/- 1.6% of total MHC at day 7 for cage-sedentary rats, whereas in the suspended animals it reached 11 +/- 2.4% of total MHC at day 14. At days 21 and 35, grafts from the suspended animals had a lower proportion of slow MHC (45 +/- 2.4%) than did grafts from the control and ablated groups (95 +/- 1.5%; P < 0.05). Decreased mechanical load impaired the rate and degree of growth and maturation during regeneration, whereas increased mechanical load enhanced growth characteristics but not maturation.

MESH: Body-Weight-physiology; Electrophoresis,-Polyacrylamide-Gel; Exertion-physiology; Hindlimb-physiology; Immunoblotting-; Isomerism-; Muscle-Contraction-physiology; Muscle-Proteins-metabolism; Muscle,-Skeletal-metabolism; Myosin-Subfragments-analysis; Myosin-Subfragments-metabolism; Organ-Weight-physiology; Rats-; Rats,-Wistar; Regeneration-

MESH: *Gravitation-; *Muscle,-Skeletal-physiology; *Muscle,-Skeletal-transplantation

TG: Animal; Female; Support,-U.S.-Gov't,-P.H.S.

PT: JOURNAL-ARTICLE

CN: DE07687DENIDR

RN: 0; 0

NM: Muscle-Proteins; Myosin-Subfragments

AN: 95229520

UD: 9507

MEDLINE EXPRESS (R) 1991-1995 74 of 80

TI: Magnetic resonance imaging and magnetization transfer in experimental myonecrosis in the rat.

AU: Mattila-KT; Lukka-R; Hurme-T; Komu-M; Alanen-A; Kalimo-H

AD: Department of Diagnostic Radiology, University of Turku, Finland.

SO: Magn-Reson-Med. 1995 Feb; 33(2): 185-92

ISSN: 0740-3194

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: Experimental myonecrosis--induced by injection of notexin into rat tibialis anterior muscle--and subsequent regeneration were studied from 1 h to 20 days postinjury with magnetic resonance imaging using conventional and magnetization transfer sequences, and these findings were correlated with histopathology. MR images revealed necrosis within 1 h postinjection. Histopathologically, necrotized fibers enlarged and intercellular spaces widened, indicating intracellular and extracellular edema, which began to decrease after 48 h, whereafter the formation of new myofibers predominated. T2 increased progressively until 7.5 h, while T1 increased until 24 h. Magnetization transfer contrast (MTC) and magnetization transfer rate (Rwm) decreased rapidly postinjection; the decrease in Rwm lasted longer than in MTC (96 h versus 48 h, respectively). Spin echo, inversion recovery and magnetization transfer sequences revealed the lesions equally effectively. MR images and relaxation parameters reflect well the extent of histopathological injury and edema in the acute phase, whereas specific tissue changes in the regenerative phase were not detectable by MRI. MT imaging and especially magnetization transfer rate are as sensitive as conventional T2 contrast to alterations in water imbalance.

MESH: Cell-Nucleus-ultrastructure; Edema-pathology; Elapid-Venoms-adverse-effects; Extracellular-Space; Image-Enhancement; Intracellular-Fluid; Macrophages-pathology; Muscle-Fibers-pathology; Muscle,-Skeletal-drug-effects; Necrosis-; Neurotoxins-adverse-effects; Neutrophils-pathology; Phagocytosis-; Rats-; Rats,-Sprague-Dawley; Regeneration-; Time-Factors

MESH: *Magnetic-Resonance-Imaging; *Muscle,-Skeletal-pathology

TG: Animal; Male

PT: JOURNAL-ARTICLE

RN: 0; 0; 37223-96-4

NM: Elapid-Venoms; Neurotoxins; notexin

AN: 95223153

UD: 9507

MEDLINE EXPRESS (R) 1991-1995 75 of 80

TI: Muscle regeneration following injury can be modified in vivo by immune neutralization of basic fibroblast growth factor, transforming growth factor beta 1 or insulin-like growth factor I.

AU: Lefaucheur-JP; Sebille-A

AD: Laboratoire de Physiologie, Faculte de Medecine Saint-Antoine, Paris, France.

SO: J-Neuroimmunol. 1995 Mar; 57(1-2): 85-91

ISSN: 0165-5728

PY: 1995

LA: ENGLISH

CP: NETHERLANDS

AB: Previous in vitro studies pointed out the role played by several growth factors (basic fibroblast growth factor or bFGF, transforming growth factor beta-1 or TGF beta 1, insulin-like growth factor-I or IGF-I) on the proliferation, the differentiation and the fusion of myogenic precursor cells. We attempted to modify the muscle regeneration which follows the denervation-devascularization of extensor digitorum longus in mice, by acting on the growth factors which are possibly involved in this process. The injection of neutralizing antibodies against either bFGF or IGF-I into the muscle at the time of lesion reduced the number and diameter of regenerating myofibres, suggesting a delay in proliferation and/or fusion of activated satellite cells. The neutralization of TGF beta 1 led to an increased number of small regenerating myofibres, which would be due to the promoting effects of the remaining growth factors (i.e. bFGF and IGF-I) on myoblast proliferation. These contrasted results strongly suggest that the growth factors regulate in vivo muscle regeneration and would be accessible tools for future therapy of muscular disorders.

MESH: Fibroblast-Growth-Factor,-Basic-physiology; Insulin-Like-Growth-Factor-I-physiology; Mice-; Muscles-pathology; Transforming-Growth-Factor-beta-physiology

MESH: *Antibodies-immunology; *Fibroblast-Growth-Factor,-Basic-immunology; *Insulin-Like-Growth-Factor-I-immunology; *Muscles-physiology; *Regeneration-; *Transforming-Growth-Factor-beta-immunology

TG: Animal; Male; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 0; 0; 67763-96-6

NM: Antibodies; Fibroblast-Growth-Factor,-Basic; Transforming-Growth-Factor-beta; Insulin-Like-Growth-Factor-I

AN: 95221583

UD: 9507

MEDLINE EXPRESS (R) 1991-1995 76 of 80

TI: Satellite cell proliferation and the expression of myogenin and desmin in regenerating skeletal muscle: evidence for two different populations of satellite cells.

AU: Rantanen-J; Hurme-T; Lukka-R; Heino-J; Kalimo-H

AD: Department of Pathology, Paavo Nurmi Center, University of Turku, Finland.

SO: Lab-Invest. 1995 Mar; 72(3): 341-7

ISSN: 0023-6837

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: BACKGROUND: Regeneration of mature skeletal muscle recapitulates closely fetal myogenesis. It is initiated by activation of the reserve myogenic precursor cells, the satellite cells, which proliferate, differentiate into myoblasts expressing muscle-specific proteins, fuse into myotubes, and finally mature into myofibers. The MyoD family of transcription factors participates in the regulation of the complex phenomenon of myogenic differentiation during development and in vitro. The function of these transcription factors in the regeneration of injured mature skeletal muscle in vivo is, however, still unclear. EXPERIMENTAL DESIGN: To clarify the primary events in myogenic precursor cell activation, the expression of myogenin was examined in rats 1 to 48 hours after either a contusion injury to the gastrocnemius or after toxic injury to the soleus muscle. Myogenin mRNA expression was studied by Northern blot hybridizations, and the results were correlated with the onsets of the mitotic activity (i.e., incorporation of bromodeoxyuridine) of the satellite cells and of the production of the myogenin and MyoD1 proteins, as well as muscle-specific intermediate filament protein, desmin. RESULTS: Both forms of muscle injury produced myofiber necrosis, followed by the activation of the satellite cells. The first sign of myogenic differentiation, an increase in myogenin mRNA expression, occurred between 4 and 8 hours after injury. The first desmin-, MyoD1- and myogenin-positive myoblasts were seen after 12 hours, but satellite cell proliferation was not seen until 24 hours after the injury. CONCLUSIONS: The schedule of the events in our study contradicts the general concept that differentiation should follow proliferation. To explain this discrepancy, we propose that there are two populations of precursor cells: committed satellite cells, which are ready for immediate differentiation without preceding cell division, and stem satellite cells, which undergo mitosis before providing one daughter cell for differentiation and another for future proliferation.

MESH: Cell-Differentiation-physiology; Cell-Division-physiology; Immunoenzyme-Techniques; Muscle,-Skeletal-pathology; Myogenin-genetics; Rats-; Rats,-Sprague-Dawley; RNA,-Messenger-biosynthesis

MESH: *Desmin-biosynthesis; *Muscle,-Skeletal-chemistry; *Muscle,-Skeletal-cytology; *Myogenin-biosynthesis; *Regeneration-physiology

TG: Animal; Male; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0; 0; 0

NM: Desmin; Myogenin; RNA,-Messenger

AN: 95205827

UD: 9506

MEDLINE EXPRESS (R) 1991-1995 78 of 80

TI: The time course of basic fibroblast growth factor expression in crush-injured skeletal muscles of SJL/J and BALB/c mice.

AU: Anderson-JE; Mitchell-CM; McGeachie-JK; Grounds-MD

AD: Department of Anatomy, University of Manitoba, Winnipeg, Canada.

SO: Exp-Cell-Res. 1995 Feb; 216(2): 325-34

ISSN: 0014-4827

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: Staining for basic fibroblast growth factor (bFGF), a potent mitogen, was examined in muscle recovering from a crush injury and compared between two mouse strains with distinctly different capacities for muscle regeneration to determine if bFGF staining and the steps and outcome of repair were related. Immunofluorescence studies on intact and crushed tibialis anterior muscle were carried out at 0, 1, 3, 6, and 12 h postcrush in SJL/J mice, and at 1, 2, 3, 5, 7, and 11 days after injury in both SJL/J and BALB/c mice (n = 2-4). Disrupted fibers showed increased sarcoplasmic staining for bFGF as little as 3-6 h after injury prior to infiltration with intensely fluorescent mononuclear cells (at 12-24 h). Fiber bFGF was maintained in SJL/J muscles for 2 days, but was lower in most damaged fibers of BALB/c muscles at the same time. Surviving stumps of crushed fibers, once sealed, exhibited sarcoplasmic extensions, some of which stained intensely for bFGF. These processes appeared to connect adjacent fiber stumps, and many were noted in association with aligned mononuclear cells (presumptive myoblasts) at the site of new myotube formation. In representative sections there were more bFGF-positive mononuclear cells present in SJL/J than BALB/c muscles. Intense bFGF localization marked newly regenerating myotubes in both SJL/J and BALB/c muscles, and such myotubes were more frequent and larger in SJL/J muscles. More bFGF was present in regenerating muscles of SJL/J compared with BALB/c mice (with respect to damaged myofibers, mononuclear cells, and myotubes) and this correlates with the superior new muscle formation seen in SJL/J mice. These studies support the idea of a positive relation between bFGF in damaged fibers, the bFGF-positive mononuclear cells, and the speed and success of muscle regeneration.

MESH: Kinetics-; Mice-; Mice,-Inbred-BALB-C; Mice,-Inbred-Strains; Muscle,-Skeletal-injuries; Muscle,-Skeletal-physiology

MESH: *Fibroblast-Growth-Factor,-Basic-biosynthesis; *Muscle-Fibers-physiology; *Muscle,-Skeletal-metabolism; *Regeneration-

TG: Animal; Comparative-Study; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

RN: 0

NM: Fibroblast-Growth-Factor,-Basic

AN: 95145580

UD: 9505

MEDLINE EXPRESS (R) 1991-1995 79 of 80

TI: Radiation inhibition of mdx mouse muscle regeneration: dose and age factors.

AU: Quinlan-JG; Lyden-SP; Cambier-DM; Johnson-SR; Michaels-SE; Denman-DL

AD: Department of Neurology, University of Cincinnati, Ohio.

SO: Muscle-Nerve. 1995 Feb; 18(2): 201-6

ISSN: 0148-639X

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: A single hind limb was irradiated with 12, 18, 24, or 30 Gy in mdx and C57 mice aged 12, 21, or 42 days to determine regeneration inhibition dose-response curves in different aged dystrophic mice and to characterize radiation side-effects in normal mice. The anterior tibial muscle mass (8 weeks postirradiation) and percent central nucleated (i.e., regenerated) muscle fibers were measures of regeneration inhibition. Twenty-one-day-old mdx mice irradiated with 18 Gy had complete inhibition of muscle regeneration, but 30 Gy only partially blocked regeneration in mdx mice irradiated at 12 and 42 days in age. In working to produce a clinically relevant model for Duchenne dystrophy, it is crucial to regard mouse age as a major factor in determining radiation effects on mdx muscle regeneration.

MESH: Dose-Response-Relationship,-Radiation; Hindlimb-; Mice-; Mice,-Inbred-mdx; Mice,-Inbred-C57BL; Muscle,-Skeletal-pathology; Muscle,-Skeletal-physiology; Muscular-Dystrophy,-Animal-pathology; Radiation-Dosage; Regression-Analysis

MESH: *Aging-physiology; *Muscle,-Skeletal-radiation-effects; *Muscular-Dystrophy,-Animal-physiopathology; *Regeneration-radiation-effects

TG: Animal; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.

PT: JOURNAL-ARTICLE

AN: 95124387

UD: 9504


*Irrelevant items have been dropped from the compilation; thus the reader will find fewer than 80 items.
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