Dramatic loss of human muscle fibre size after leg fracture and immobilization in plaster casts

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Initiated and written by Professor Anthony J Sargeant while working at the Joint Services Medical Rehabilitation Centre at Chessington, Surrey, UK this was the first research paper in the scientific literature that showed the massive loss in muscle fibre size in otherwise healthy young male patients who following leg fracture had been immobilized in plaster casts. Although gross measurement of leg muscle size suggested a modest loss of about 12% after an average of 6 weeks in plaster cast needle biopsy of the vastus lateralis muscle revealed a reduction in cross sectional area of muscle fibres of nearly 50%. Furthermore recovery appeared very slow and many subjects seemed never to fully recover in terms of muscle fibre size and strength – deficits being identified in later studies many years later after the injury.
Clinical Science and Molecular Medicine
Clin Sci Mol Med. 1977 Apr;52(4):337-42

1. Seven patients who had suffered unilateral leg fracture were studied after removal of immobilizing plaster casts. 2.

Leg volume measured anthropometrically was reduced by 12% in the injured leg (5-68 +/- 1-05 litres) compared with the uninjured (6-43 +/- 0-87 litres). Associated with this loss was a similar reduction in the net maximum oxygen uptake achieved in one-leg cycling, from 1-89 +/- 0-21 1/min in the uninjured leg to 1-57 +/- 0-18 1/min in the injured. 3. Measured by a percutaneous needle biopsy technique, a reduction of 42% was found in the cross-sectional area of the muscle fibres sampled from the vastus lateralis of the injured compared with the uninjured leg. 4. Staining for myosin adenosine triphosphatase activity showed that both type I and II fibres were affected, being reduced respectively from 3410 to 1840 micronm2 and from 3810 to 2390 micronm2 cross-sectional area. 5. Possible reasons and implications are discussed for the discrepancy between the magnitude of the difference observed in the gross measurement of leg function (maximum oxygen uptake) and structure (leg volume) as compared with the cellular level (cross-sectional fibre area).

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Journal of Physiology – preliminary research report

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A preliminary report to The Physiological Society of research seeking to understand the limitations to maximum exercise. This paper was part of the groundwork for Anthony J Sargeant‘s PhD thesis.

School Sports Teams – Participation of West Indian boys

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This research published by Anthony J Sargeant in 1972 was based on data he collected as part of a Bachelor’s degree dissertation while studying at The University of London. At the time their were no black footballers or cricketers playing for England and there were many racial stereotypes being bandied about. The logical conclusion of the level of participation and success of West Indian boys in school teams was that they would soon be represented in national teams: A point picked up and given publicity by the media including the national press. The consequence was anonymous poison pen letters to the author from racists. The only time in his career that research by Professor Sargeant generated such a reaction.
Educational Research
Educational Research 1972: 14 (3), 225-230

This paper reports the results of an investigation into the proportional participation of West Indian boys in secondary school sports teams. Information on participation in the first two years was obtained by questionnaire from 969 third‐year boys of whom 13 per cent were West Indian, and analysed in two groupings, the top and botton half streams. An overwhelming predominance of West Indian boys proportionate to their numbers were found in soccer, cricket and athletics.

A secondary finding was a high correlation between academic ability and participation; both West Indian and white English participation was proportionally higher in the top streams.

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The first research paper published by Professor Anthony J Sargeant

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European Journal of Applied Physiology (International Zeitschrift fur angewandte physiology)
Int Z Angew Physiol. 1971;30(1):10-9

Anthony J Sargeant completed this research for his Bachelor degree research dissertation. It shows how endurance exercise training results in heat acclimatisation.

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London School of Hygiene and Tropical Medicine

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The London School of Hygiene and Tropical Medicine is a wonderful Art-deco building faced in Portland Stone. It was where Professor Anthony J Sargeant worked from 1970 until 1977 as a research scientist in the Medical Research Council’s Environmental Physiology Research Unit and where he completed the research for his PhD (part-time) which was awarded by the Board of Studies in Physiology of The University of London for a thesis on the effects of disuse atrophy of human muscle. The School which is a postgraduate school of The University of London is in Keppel Street with side facades on Malet Street and Gower Street. Tony’s office and basement laboratory were on the Malet Street side of the building facing the imposing Senate House building of The University of London.

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Characterization of single human skeletal muscle fibres – Research supervised by Professor Anthony J Sargeant

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Professor Anthony J Sargeant was the Head of Department and supervisor of Jose Sant’ana Pereira (very sadly now deceased) who carried out this meticulous work under his supervision in the early 1990s.
Journal of Muscle Research and Cell Motility
J Muscle Res Cell Motil. 1995 Feb;16(1):21-34

In the present study we have developed a method which, by combining histochemical, immunohistochemical, electrophoretic and immunoblotting analyses on a single fibre, enables a sensitive characterization of human skeletal muscle fibres dissected from freeze-dried biopsy samples. For histochemical (and immunohistochemical) analysis fibre fragments (500 microns) of individual fibres were mounted in an embedding medium to allow cryostat sections of normalized thickness to be reproducibly obtained. The specificity of the myofibrillar Ca2+ ATPase (mATPase) staining profiles in gelatin-embedded single fibre sections was tested by immunohistochemical reactions with anti-myosin heavy chain (MyHC) monoclonal antibodies specific to human MyHC I, IIA, IIB and IIA + IIB and by gel electrophoresis.

The combined methodologies demonstrated the specificity of the mATPase staining patterns which correlated to the expression of distinct MyHC isoforms. In addition the results provide evidence that many fibres co-expressed different MyHC isoforms in variable relative amounts, forming a continuum. Staining intensities for mATPase, converted into optical density values by image analysis revealed that a relationship between mATPase and MyHC expression holds for hybrid fibres even when displaying one MyHC type with overwhelming dominance. The results also revealed that three MyHC isoforms I, IIA and IIB can be co-expressed on a single muscle fibre. In such a case mATPase alone, with the current protocols, does not allow an accurate characterization of the specific MyHC-based fibre type(s). Although some hybrid fibres may have displayed a non-uniform expression of myosins along their lengths, most fibres from the IIA/B group (type) remained very stable with respect to the relative amounts of the MyHCs expressed. Finally, a second slow MyHC isoform was recognized on immunoblots of a mixed muscle samples

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Research by Jose Sant’Ana Pereira (now sadly deceased)- PhD student of Professor Anthony J Sargeant

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In the present study we report a novel histochemical method which, by sequential pre-incubations in alkaline and acidic media, selectively differentiates muscle fibres expressing myosin heavy chain IIX, on the basis of a specific profile for myofibrillar actomyosin ATPase (mATPase) activity. The enzyme reactions were tested for specificity by means of anti-myosin heavy chain monoclonal antibodies, which were characterized on Western blots of muscle homogenates. Enzyme histochemical reactions with the traditional pH buffers were compared to those of the new method and, in conjunction with the immunoreactions, used to confirm the relationship between MyHC expression and the distinct profiles for mATPase.

Immunohistochemical reactions demonstrated that the new method only differentiates those fibres expressing myosin heavy chain IIX. The method revealed a continuum in which the intermediate staining intensities corresponded to hybrid fibres expressing myosin heavy chain IIX in combination with either the IIA or IIB forms. Quantitative histochemistry and immunohistochemistry (by image analysis), used to examine the relationship between staining intensities for mATPase and amounts of myosin heavy chain IIX expression, revealed that the new method discriminates well between hybrid fibres expressing variable amounts of the IIX isoform (r2 = 0.93)

http://www.pubfacts.com/author/Anthony+J+Sargeant