Felix Jerusalem

Human muscle fiber fine structure Morphometric data on controls

Muscle fiber fine structure was quantitatively analyzed in 70 longitudinally and 65 transversely sectioned fibers from 10 control subjects without weakness. The average mitochondrial fraction of the fiber volume is close to 4 percent and the mean size of a mitochondrion is about 0.1 μm2. The sarcotubular surface area per unit fiber volume is close to 1.5 μm2/μm3 in transverse sections and 0.65 times this value in longitudinal sections. Only one-third of all fibers contain lipid droplets in the sectioned plane, and for all fibers the droplets account for approximately 0.12 percent of the fiber volume. Variations with the age and sex of the subjects and with different muscles were analyzed and the feasibility of typing human muscle fibers at the ultrastructural level was evaluated.

A dominantly inherited myopathy with excessive tubular aggregates

We studied a family in which seven individuals in three generations had slowly progressive weakness without atrophy, myalgia, cramps, or episodic weakness. Creatine kinase was normal, and EMG showed only slight “Inyopathic” changes. Neuromuscular transmission was undisturbed. Muscle biopsies were performed in three patients. About 60 to 90% of all fibers contained tubular aggregates. There was a marked variation in fiber size and a marked type I1 fiber atrophy. Biopsy of an asymptomatic family member was normal. The nature of the underlying disease was obscure.

Exogenous coenzyme Q (CoQ) fails to increase CoQ in skeletal muscle of two patients with mitochondrial myopathies

Recently, several studies were published on therapy with coenzyme Q (CoQ) in patients with mitochondrial myopathies without biochemically established muscular deficiency of CoQ. Two patients with mitochondrial myopathies presenting as oculocraniosomatic syndromes were treated with coenzyme Q (CoQ). The muscle biopsy of both patients showed ragged-red fibers and single muscle fibers without histochemical reaction for cytochrome c oxidase. Biochemical analysis revealed normal activities of the respiratory chain complexes in muscle and normal levels of CoQ in serum and muscle. After one year of treatment CoQ in serum of both patients had increased 1.4-fold and 2.0-fold, respectively. In muscle, however, there was no increase of CoQ in either patient. In both patients the activities of citrate synthase and of the respiratory chain complexes I + III and IV, and in 1 patient also of complex II + III, were lower in the second biopsy compared with the first biopsy. In both patients there was no improvement of maximal isometric muscle strength assessed by a quantitative electronic strain gauge. The exercise-induced pathological rise of lactate in 1 patient remained essentially unchanged during therapy. The data indicate that orally administered CoQ fails to increase total CoQ in muscle of patients with mitochondrial myopathies but without muscular CoQ deficiency.

Cytochrome c oxidase in Alzheimer's disease

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Abnormal dystrophin expression in patients with limb girdle syndromes

Clinical differential diagnosis between Becker muscular dystrophy (BMD) and limb gridle muscular dystrophy (LGMD) may be difficult because the BMD clinical phenotype tends to overlap with other limb girdle syndromes, especially with LGMD. Therefore we studied the expression of dystrophin, the protein product of the Becker and Duchenne muscular dystrophy gene, in muscle biopsy specimens of 30 patients (18 males, of whom 15 represented spradic cases, and 12 females) diagnosed as having LGMD according to traditional clinical, electrophysiological and histological criteria. For dystrophin analysis, six different monoclonal antibodies directed against different epitopes of the dystrophin molecule were used. Immunocytochemically, five of the 30 LGMD patients (17%) showed abnormal dystrophin staining patterns diagnostic of BMD. Western blotting in these five patients, all sporadic cases, showed dystrophin of reduced size and/or abundance. Analysis of blood or muscle DNA using multiplex polymerase chain reaction revealed deletions in the dystrophin gene in three of the five. Thus, 5 of 15 (33%) sporadic male patients previously thought to have LGMD were identified as having BMD.

Sporadic adult-onset distal myopathy with rimmed vacuoles, 15–18 nm tubulofilaments and extensive rod formation

Starting after the age of 35 years this German man had a slowly progressive distal myopathy greater in the legs than in the arms. First he realized gait difficulties with reduced ankle dorsiflexion. Serum creatine kinase activity was normal. Muscle biopsy studies showed myopathic changes, rimmed vacuoles and the presence of rods in 66% of the type 1 muscle fibers. Ultrastructural examination revealed cytoplasmatic aggregates of tubulofilaments measuring 15-18 nm in diameter, myeloid bodies and rod formation. The nosological situation of this distal myopathy with tubulofilamentous inclusions is discussed.