Muscles, mitochondria and myalgia.
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Biomedical subjects
Publications and source records attributed to W M Behan.
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AIM: To examine peripheral blood and skeletal muscle from patients with chronic fatigue syndrome for exogenous retrovirus. METHODS: Blood samples from 30 patients and muscle biopsy specimens of 15 patients were examined for retroviral sequences by DNA extraction, polymerase chain reaction (PCR), and Southern blotting hybridisation. Sera were examined for human foamy virus by western immunoblotting and indirect immunofluorescence techniques. RESULTS: No differences between the patient and control populations was found for any of the PCR primer sets used (gag, pol, env, and tax regions of HTLV I/II). An endogenous gag band was observed in both the patient and control groups. All sera were negative for antibody to human foamy virus. CONCLUSION: The results indicate that there is no evidence of retroviral involvement in the chronic fatigue syndrome.
We have examined the muscle biopsies of 50 patients who had postviral fatigue syndrome (PFS) for from 1 to 17 years. We found mild to severe atrophy of type II fibres in 39 biopsies, with a mild to moderate excess of lipid. On ultrastructural examination, 35 of these specimens showed branching and fusion of mitochondrial cristae. Mitochondrial degeneration was obvious in 40 of the biopsies with swelling, vacuolation, myelin figures and secondary lysosomes. These abnormalities were in obvious contrast to control biopsies, where even mild changes were rarely detected. The findings described here provide the first evidence that PFS may be due to a mitochondrial disorder precipitated by a virus infection.
Evidence from several sources has long suggested that enteroviruses might play a role in the postviral fatigue syndrome (PVFS). We used the most sensitive molecular virological method available at present, the polymerase chain reaction (PCR) amplification technique, to look for enteroviral copies in peripheral blood leucocytes and muscle from a well-defined group of patients. We demonstrated that our PCR method amplified a sequence common to a wide range of enteroviral serotypes. A highly significant number of the muscle biopsies (53%: P = less than 0.001) from the patients were positive for enteroviral sequences. With regard to the leucocyte samples, 16% in both patient and control were positive. The PCR results on the peripheral blood leucocytes were in keeping with serological findings, in showing that the level of exposure to enteroviruses seemed to be the same in patients and controls: it was therefore of the greatest interest that patients were 6.7 times more likely to have enteroviral genome in their muscle. We conclude that persistent enteroviral infection plays a role in the pathogenesis of PVFS, also providing preliminary evidence that severe mitochondrial injury is one of the mechanisms involved.
We describe a simple, sensitive and reproducible ELISA assay for complement activation in mouse serum, based on measurement of the opsonization of purified, heat-aggregated mouse gamma-globulin bound to the solid phase. This assay measures mainly classical pathway activation, and we used it to show significant differences in complement activation in sera from mice of various autoimmune, immunodeficient and immunologically normal strains. This assay has the advantage over existing methods of requiring minimal volumes of serum, and of avoiding problems of species incompatibility.
Complement components were measured and immune complexes were sought in 75 patients with myasthenia gravis. Thirty-four per cent had decreased concentrations of complement component C4, and 29% had circulating immune complexes. The greatest immunological abnormalities were found in patients with mild disease which supports recent immunoelectronmicroscopic findings.
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Patients with and without adverse reactions on practolol therapy showed altered immune responses. There was cutaneous anergy to Candida albicans and streptokinase/streptodornase antigens and depression of lymphocyte function in vitro. Anticomplementary activity and a wide range of autoantibodies were found in patients who had received practolol.
Although five patients with severe pre-eclamptic toxaemia (PET) had increased anticomplementary activity in their serum, there was no evidence of complement activation in the plasma of four of the five patients. These results are not implicated in the pathogenesis of PET. No significant correlation was found between anticomplementary activity and pregnancy-associated alpha2-glycoprotein.
The effect of transfer factor prepared from relatives of patients with multiple sclerosis (M.S.) and from unrelated donors on the clinical course of M.S. has been studied in fifteen male and fifteen female patients. Some patients were given transfer factor and some placebo (physiological saline). Results of three independent clinical examinations by different neurologists and subjective assessments by the patients showed no difference between those given transfer factor and those given placebo.
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Humoral antibodies to skeletal muscle and its components and to thymus have been demonstrated in the sera of patients with myasthenia gravis. A role for cellular hypersensitivity to similar antigens in the pathogenesis of the disease has been suggested by some reports of the presence of cellular immunity. A detailed immunological study using muscle and thymic antigens, including those prepared from the patients' own tissues, failed to confirm these findings. It is suggested that previous reports of cellular hypersensitivity represent the demonstration of an epiphenomenon.