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Biomedical subjects

S Carpenter

Publications and source records attributed to S Carpenter.

At least 163 records · Page 9Linked to original sources
PubMed1988

Small-caliber skeletal muscle fibers do not suffer necrosis in mdx mouse dystrophy.

The prevalence of internal nuclei in muscle fibers (centronucleation), which is a reliable cumulative index of all prior muscle fiber necrosis, was measured at different ages in different muscles of mdx mice and was correlated with muscle fiber diameter. The prevalence of centronucleated fibers (as percentage of total number of fibers) rose gradually after age 20 days until it reached a peak level of 80% at age 60 days. No significant centronucleation (or necrosis) was observed in the following circumstances: in 4 different limb muscles before age 15 days, in leg muscles that were denervated by peripheral nerve section or rendered immobile by high thoracic cordotomy at 15 days, or in rotator extraocular muscles throughout the animals' life span. In these situations, muscle fiber diameter remained below approximately 20 micron. The mechanism by which small-diameter fibers are resistant to necrosis in mdx dystrophy is unknown, but a similar situation exists in hamster and Duchenne muscular dystrophy.

Animals↗
PubMed1988

Adult onset motor neuronopathy in the juvenile type of hexosaminidase A and B deficiency.

Two sisters presented with progressive muscle cramps, as well as wasting and weakness of the legs with onset after age 20. They also showed intention tremor of the upper extremities and dysarthria starting during the first decade. The older patient also had fasciculations; the younger, hyperreflexia. Total plasma beta-hexosaminidase (Hex) activity with 4-methylumbelliferyl-acetyl-glucosamine as substrate was reduced to 1.4% and 2.7% of the control in the 2 patients, respectively. Hex A activity measured by 4-methylumbelliferyl-N-acetylglucosamine-6-O-sulphate as substrate was 9.9% and 12.8% of the mean control value in the 2 patients, respectively. Hex B activity was undetectable in both patients. Leukocyte total Hex activity was 7-8% of normal; residual Hex A activity in the 2 patients was 17.8% and 16.3% of normal controls, respectively. Fibroblastic residual Hex A activity in the 2 patients was 9.6% and 22% of normal mean value, respectively. Appendiceal ganglion cells contained membranous cytoplasmic bodies in the younger patient. Thin layer chromatography of the appendiceal extract from one patient (III/2) showed a marked increase of GM2 ganglioside, and some increase of GM3 ganglioside. Northern blots performed on fibroblast cell lines from both patients for the demonstration of alpha and beta locus messenger RNA showed no difference between patients and control. These patients have a rare form of adult-onset progressive motor neuron disease presumably due to abnormal beta subunits, causing severe deficiency of both Hex A and Hex B. The phenotypic expression of this disease is similar to motor neuron disease due to alpha locus mutations, which suggests that the Hex A deficiency, even though only a partial one, may be the important pathogenic factor.

Adult↗
PubMed1988

Kufs' disease: a critical reappraisal.

A review of 118 cases published as Kufs' disease revealed only 50 cases, including 2 patients described herein, that fulfilled our criteria for this diagnosis. Of the other 68 cases, 16 had inadequate data for analysis, 21 had evidence of a storage disease other than Kufs' disease, 10 did not have clear evidence of any neuronal storage, and 21 had atypical clinical features considered outside the spectrum of Kufs' disease. The 50 cases accepted as Kufs' disease comprised two clinical phenotypes; progressive myoclonus epilepsy (Type A) and dementia with motor disturbances (Type B). Marked photosensitivity was a striking feature of some Type A cases, and facial dyskinesias were common amongst Type B patients. Onset was typically at around the age of 30 years. A few cases began in adolescence; these differ from the protracted juvenile form of neuronal ceroid-lipofuscinosis by the absence of visual failure. Demonstration of fingerprint profiles or granular osmiophilic deposits by electron microscopy is mandatory for definitive diagnosis. Urinary sediment dolichol levels were markedly elevated in our 2 cases. This biochemical finding confirms the relationship of Kufs' disease to the early forms of neuronal ceroid-lipofuscinosis and is consistent with our hypothesis that these diseases are due to defects in the intracellular processing of lysosomal and related membranes.

Adult↗
PubMed1988

Familial myopathy with changes resembling inclusion body myositis and periventricular leucoencephalopathy. A new syndrome.

Five of 6 male siblings were affected by a progressive myopathy beginning in early childhood. Muscle biopsies in all patients showed the characteristic changes of inclusion body myositis. Computerized tomography and magnetic resonance imaging revealed a markedly abnormal appearance of cerebral white matter in the 4 affected patients tested, but clinical and other laboratory examinations failed to demonstrate evidence of central white matter dysfunction. Muscle biopsies and brain imaging were normal in all clinically unaffected family members. On the basis of the genetics, muscle biopsy findings and cerebral white matter changes, we conclude that this constellation represents a hitherto undescribed syndrome.

Adult↗
PubMed1988

Vacuolation of muscle fibers near sarcolemmal breaks represents T-tubule dilatation secondary to enhanced sodium pump activity.

Transsected rat soleus muscles incubated in oxygenated Krebs solution in vitro at 37 degrees C develop prominent vacuolation in the vicinity of the cut ends of muscle fibers which extends further along the fiber with increasing time of incubation. Electron microscopy shows that the vacuoles represent dilated segments of T-tubules. Their formation is prevented if the muscle is not cut, or in the following situations: omission of Na+ from the medium, incubation at 10 degrees C, or in media containing either 2,4-dinitrophenol or ouabain. Vacuole formation is considerably reduced by substituting Cl- with organic anions or by adding 9-anthracene carboxylic acid to the medium. These results suggest that a massive influx of sodium into the muscle fibers through their cut ends results in maximal stimulation of the Na+-K+-ATPase of the T-tubular membrane leading to increasing Na+ concentration in the lumen of T-tubules followed by influx of Cl- to maintain the electrical gradient. The accumulation of these ions leads to the entry of water from either the extracellular space or the sarcoplasm and consequent dilatation of T-tubules. Rapid incorporation of lipids into T-tubular membrane to increase its surface is presumably necessary for this to occur. Similar T-tubular dilatation appears to occur in vivo in surviving portions of muscle fibers adjacent to segmental necrosis.

Animals↗
PubMed1988

A hypothesis for the pathogenesis of amyotrophic lateral sclerosis.

The microscopic pathology of spinal cord and brain in ALS has suggested that the earliest abnormality is a progressive depletion of dendritic neurofilaments leading to dendritic atrophy, vulnerability to breakage and attrition. We hypothesize that this in turn will lead to shrinkage and eventual death of the perikaryon. This hypothesis could explain the preferential vulnerability of the spinal, corticospinal and cortico-bulbar neurons to damage and death in ALS because only these neurons contain conspicuous bundles of neurofilaments in dendrites. Agents or factors that could subvert the transport or the integrity of dendritic neurofilaments should be sought in ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1987

Progressive dystonia with bilateral putaminal hypodensities.

Three unrelated patients, aged 4, 18, and 47 years, had generalized dystonia associated with bilateral striatal hypodensities on computed tomography. Mitochondrial encephalopathy was considered to be the most likely diagnosis, but this could not be proved. These patients confirm previous reports linking acquired generalized dystonia with bilateral putaminal lesions and they highlight the problem in differential diagnosis of this clinicoradiologic syndrome.

Adolescent↗
PubMed1987

Glucocorticoid excess induces preferential depletion of myosin in denervated skeletal muscle fibers.

The combined effects of dexamethasone treatment (1 mg/Kg/day) plus denervation (DEX-DEN), were studied at 7, 13, and 28 days by microscopic, biochemical, and physiological techniques in plantaris and soleus muscles of adult rats. The results were compared with corresponding dexamethasone-treated (DEX) and denervated (DEN) muscles and appropriate controls. There was a significantly more marked atrophy of all fiber types in the DEX-DEN plantares at 7 and 13 days than in either DEX or DEN muscles. The degree of atrophy was greatest in type 2B fibers in DEX-DEN plantares. Electron microscopy revealed a severe preferential depletion of thick myofilaments in DEX-DEN plantares and solei but not in DEX or DEN muscles. The thick myofilament depletion in DEX-DEN muscles occurred in addition to a severe overall reduction of myofibrillar caliber. Gel electrophoresis showed a marked preferential decrease of myosin heavy chain in DEX-DEN plantares and solei, but not in either DEX or DEN muscles. Myosin light chains were also markedly reduced in DEX-DEN plantares and solei. In vitro physiological studies showed a marked reduction of the denervation-induced twitch potentiation in DEX-DEN solei. Maximal tetanic tension (20 Hz stimulation) per gram weight of muscle as well as the twitch-tetanus ratio was significantly reduced only in DEX-DEN solei in relation to controls. Myosin depletion in DEX-DEN muscles may be due to a severe preferential inhibition of its synthesis coupled with an accelerated catabolism.

Actins↗
PubMed1987

The clinical consequences of X-chromosome inactivation: Duchenne muscular dystrophy in one of monozygotic twins.

We have ascertained retrospectively a female patient, one of identical twins, who was diagnosed at age 23 years as having Duchenne muscular dystrophy (DMD). A muscle biopsy at that time showed a pattern in which large areas of destroyed muscle fibers replaced with adipose tissue were interspersed with normal-appearing muscle fascicles. The visualization of Barr bodies in the muscle biopsy, plus the patient's normal menstrual history served to rule out Turner's syndrome. The clinical expression of DMD in only one of monozygotic twins is strongly suggestive of uneven lyonization, with an excess of paternally derived X-chromosomes being inactivated in the patient. This view is supported by the appearance of the muscle biopsy. Twinning may conceivably predispose to uneven lyonization by reducing the size of the muscle cell anlage at the time of X-chromosome inactivation. Alternatively, lyonization may occur before the splitting of the embryonic mass, and by chance, the two embryonic centers could end up with a significantly different proportion of active maternal and paternal X-chromosomes.

Adult↗
PubMed1987

Randomized trial of ceftazidime versus placebo in the management of acute respiratory exacerbations in patients with cystic fibrosis.

A randomized trial of ceftazidime versus placebo was conducted in patients with cystic fibrosis hospitalized for acute respiratory exacerbations. Patients 12 years of age or older were included if they had mild to moderately severe illness according to the following criteria: erythrocyte sedimentation rate less than or equal to 50 mm/hr and less than three other abnormalities (leukocyte count greater than or equal to 15,000/microliter, pulse greater than or equal to 100 beats/min, respirations greater than or equal to 30/min, or temperature greater than or equal to 38.5 degrees C). In all 16 episodes treated with ceftazidime, the patients were rated improved in comparison with 10 of 12 patients treated with placebo. Three placebo-treated patients dropped out of the study within 3 to 5 days because they wanted antibiotic therapy. None of the 15 placebo-treated patients showed clinical deterioration. There were no significant differences in rate of improvement of symptom score, weight gain, or pulmonary function between the two treatment groups. There was no difference in the course during the 6 to 24 months after the study period. Intravenous antibiotics are not essential in the management of all acute respiratory exacerbations of mild to moderate severity in patients with cystic fibrosis.

Adolescent↗
PubMed1987

Role of the host immune response in selection of equine infectious anemia virus variants.

Equine infectious anemia virus was isolated from peripheral blood leukocytes collected during two early febrile cycles of an experimentally infected horse. RNase T1-resistant oligonucleotide fingerprint analyses indicated that the nucleotide sequences of the isolates differed by approximately 0.25% and that the differences appeared randomly distributed throughout the genome. Serum collected in the interval between virus isolations was able to distinguish the isolates by membrane immunofluorescence on live cells. However, no neutralizing antibody was detected in the interval between virus isolations. In fact, multiple clinical cycles occurred before the development of a neutralizing antibody response, indicating that viral neutralization might not be the mechanism for selection of antigenic variants. The ability of early immune sera to recognize variant specific antigens on the surface of infected cells suggested that immune selection occurs through recognition and elimination of certain virus-infected cells. Alternately, the random distribution of the genomic differences observed between the two isolates may indicate that equine infectious anemia virus variants emerge as a result of nonimmunological selection processes.

Animals↗
PubMed1987

Combined central and peripheral myelinopathy.

We studied clinical, electrophysiologic, and nerve biopsy findings in two men with evidence of severe central and peripheral demyelinating disease. These patients may be rare examples of MS with associated severe, chronic, clinically evident peripheral demyelinating neuropathy. Alternatively, they may be cases of some other form of combined central-peripheral myelinopathy or fortuitous coincidence of MS with idiopathic inflammatory-demyelinating neuropathy. There have been only five other reports of clinically evident combined central-peripheral myelinopathy, but there have also been reports of only electrophysiologic or nerve biopsy evidence (without clinical manifestation) of peripheral neuropathy in MS patients.

Adult↗
PubMed1986

Small-caliber skeletal muscle fibers do not suffer deleterious consequences of dystrophic gene expression.

In Duchenne dystrophy and in the genetic dystrophies of CHF-147 hamsters and MDX mice, the fundamental deleterious consequence of dystrophic gene expression is segmental necrosis of skeletal muscle fibers. The nature of the gene defects and the pathogenesis of muscle fiber damage are not known. However, clinical and experimental evidence indicates that muscle fibers, whose girth is below a certain level (estimated at approximately 20-25 microns in diameter in dystrophic hamsters and MDX mice) are not susceptible to necrosis. This apparent "immunity" has been observed in muscle fibers that are naturally of small girth (such as those in extraocular muscles), and in fibers that were prevented from growing normally by experimental procedures (hamsters and mice) or by pathological processes (Duchenne patients). The cellular or molecular basis by which small-caliber muscle fibers are resistant to the necrotizing effect of the dystrophic gene expression remains unknown. In small-caliber muscle fibers, the normal contraction-related mechanical strains per unit surface area are relatively less than in larger fibers; this could explain their relative resistance to necrosis in some dystrophies.

Animals↗
PubMed1986

Myopathy caused by a deficiency of Ca2+-adenosine triphosphatase in sarcoplasmic reticulum (Brody's disease).

Four male patients from two families were first seen with impaired skeletal muscle relaxation that rapidly worsened during exercise. Muscle biopsies from 2 patients were examined by appropriate biochemical and microscopic immunocytochemical techniques. The adenosine triphosphate (ATP)-dependent Ca2+ transport rate was extremely low in a particulate membrane fraction of skeletal muscle, and there was also a marked reduction of the concentration of 100-kD phosphoprotein, corresponding to Ca2+-ATPase of sarcoplasmic reticulum, in muscle microsomes. The concentration of immunoreactive Ca2+-ATPase of sarcoplasmic reticulum was markedly reduced on immunoblots. Evaluation by microscopic immunocytochemical techniques, using one polyclonal and two monoclonal antibodies against sarcoplasmic reticulum Ca2+ transport protein, revealed that the severe reduction of immunoreactive Ca2+-ATPase was limited to the histochemical type 2 fibers. The deficiency of the Ca2+ transport protein in the sarcoplasmic reticulum of type 2 fibers, which may be the primary expression of a presumed gene defect, can explain the impaired muscle relaxation of the patients. This disease appears to be a clinically, electromyographically, and biochemically distinct metabolic myopathy.

Adult↗
PubMed1986

Calcium-induced damage of skeletal muscle fibers is markedly reduced by calcium channel blockers.

Vascular perfusion of rat hind limbs with a Ca2+-free physiological solution containing ethylenediaminetetraacetate, when followed by a physiological solution with normal concentration of Ca2+, caused a marked rise of creatine kinase (CK) in the venous effluent. When calcium channel blockers were present in the perfusing solutions, no rise of CK occurred. On histological sampling of perfused muscles, CK rise was roughly correlated with muscle fiber damage of the appropriate muscles. Removal of calcium from the plasmalemma of muscle fibers appears to prevent closure of calcium channels, making the muscle fibers susceptible to a deleterious influx of extracellular calcium. This influx can be prevented by the presence of calcium channel blockers in the perfusates.

Animals↗
PubMed1986

Lysosomal storage in human skeletal muscle.

Skeletal muscle is involved symptomatically in two lysosomal storage diseases, acid maltase deficiency and a similar condition in which enzyme levels are normal. Asymptomatic storage in skeletal muscle cells is found in Batten-Kufs' disease (ceroid lipofuscinosis), Fabry's disease, and mannosidosis, as well as in rare patients with an unidentified storage disease. Other cell types (vascular endothelium, smooth muscle, fibroblasts, satellite cells) within the confines of the biopsy specimen may reveal storage in other diseases. The differential diagnosis involves predominantly both normal and abnormal conditions in which acid phosphatase activity is prominent in cells.

Biopsy↗