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Biomedical subjects

S Carpenter

Publications and source records attributed to S Carpenter.

At least 19 recordsLinked to original sources

Loss and renewal of thick myofilaments in glucocorticoid-treated rat soleus after denervation and reinnervation.

Denervation of rat soleus muscle and simultaneous administration of high doses of corticosteroids for 7 days caused marked muscle fiber atrophy and selective loss of thick myofilaments from many muscle fibers by light and electron microscopy. Myosin heavy chain/actin ratios were greatly reduced on polyacrylamide gel electrophoresis. Nerve crush instead of cut permitted reinnervation after 2 weeks and demonstrated the reversibility of the muscle changes within a week after reinnervation. There was formation of new thick filaments and their reintegration into myofibrils without further breakdown, although large areas of Z-disc streaming appeared. The mechanism of A-band breakdown remains obscure, but it presumably starts with limited proteolysis and continues with disaggregation of myosin molecules. This is consistent with our observation that the muscle fibers retain a relatively good reactivity to antibodies against myosin heavy chain 1 week after denervation and corticosteroid administration. A syndrome recalling these experiments is seen in severely asthmatic patients receiving corticosteroids and pharmacologically paralyzed for mechanical respiration.

Actin Cytoskeleton

Vancomycin-associated linear IgA dermatosis. A report of three cases.

BACKGROUND: Linear IgA dermatosis is an autoantibody-mediated, subepidermal blistering disease that is rarely associated with drug exposure. OBJECTIVE: We report the development of linear IgA dermatosis in three patients associated with the administration of vancomycin and further characterize the immunopathology. METHODS: Direct and indirect immunofluorescence assays were performed to characterize the immunoreactants, determine the subclass of the IgA deposits, and map the site of antibody deposition. RESULTS: A subepidermal blistering disease developed in all patients shortly after vancomycin was initiated, which resolved on discontinuation of the drug. Immunofluorescence studies revealed linear deposits of IgA1 only at the basement membrane zone, below the lamina lucida. Circulating IgA anti-basement membrane zone antibodies were not detected. CONCLUSION: Three patients had linear IgA dermatosis in association with the administration of vancomycin. All patients had linear deposits of IgA1 localized to the sublamina densa zone. Immunophenotypically, the disease in these patients mimics the pattern of IgA deposits seen in the majority of patients with idiopathic linear IgA dermatosis.

Aged

A chronic myopathy with coated vesicles and tubular masses.

Two muscle biopsies from a 38-yr-old man with a lifelong mild chronic nonprogressive myopathy, showed accumulations of randomly oriented tubules of T-tubular origin, some of which had become greatly dilated and had accumulated osmiophilic material. The tubular masses lacked oxidative enzyme activity but during their evolution acquired esterase and acid phosphatase activity. Tubular areas appeared to break down and lead to intrusions of extracellular space into the center of fibers. Coated vesicles were numerous and often appeared to arise from the tubules. No abnormality could be detected on SDS PAGE electrophoresis of fractions from sucrose gradients.

Adult

Interlaboratory comparison of different alpha-particle and radon sources: cell survival and relative biological effectiveness.

Alpha radiation-induced cell killing was determined in four different laboratories in order to: 1) measure interlaboratory variability and 2) compare the effects of radon and radon daughter exposures with the effects of 238Pu (an often-used model for radon exposure). The results suggest that differences in handling from laboratory to laboratory can affect both low and high linear energy transfer responses and should be considered when comparing results from different laboratories.

Alpha Particles

Staff anxieties about death in residential settings for elderly people.

This study examined the relationship between death anxiety, the anxiety surrounding dealing practically with dying, and the level of experience of care assistants in residential settings for the elderly. It also examined the perception of the officer in charge of the establishment of the care assistants' level of anxiety. Age was the best predictor of both death anxiety and practical anxiety, the two being correlated. There was also a difference in perception of staff anxiety as a consequence of ethnic-group membership. The implications of this for training and practice are discussed.

Adult

Characterization of early pathogenic effects after experimental infection of calves with bovine immunodeficiency-like virus.

The early pathogenic effects of bovine immunodeficiency-like virus (BIV) were studied in calves experimentally inoculated with BIV. All animals inoculated with BIV R29-infected cells seroconverted by 6 weeks postinoculation, and BIV was recoverable from each animal at 2 weeks postinoculation. However, levels of BIV replication in vivo appeared to be low. In situ hybridization studies indicated that during peak periods of viral replication in vivo, less than 0.03% of peripheral blood mononuclear cells were expressing detectable levels of viral RNA. Moreover, the levels of viral RNA in these cells in vivo were less than 1/10 the levels observed in persistently infected cells in vitro. BIV-inoculated calves had significantly higher numbers of circulating lymphocytes, and follicular hyperplasia was observed in lymph nodes, hemal nodes, and spleen. The histopathological changes observed in BIV-infected calves were similar to changes found early after infection with the immunosuppressive lentiviruses, including human immunodeficiency virus type 1.

Animals

Time course of cerebral blood flow and histological outcome after focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: The relation between time-dependent changes in cerebral blood flow and the appearance of infarction after focal cerebral ischemia is still a matter for debate. The aim of this study was to measure perfusion after simultaneous occlusions of the left middle cerebral artery and ipsilateral common carotid artery in rats and correlate it with the timing and distribution of histological changes. METHODS: We studied histological and cerebral blood flow changes 5 minutes and 4, 24, and 48 hours after the onset of focal ischemia. Blood flow was determined autoradiographically using [14C]iodoantipyrine. A coronal template subdivided into regions of interest was applied to the autoradiographs and the histological data. RESULTS: In some regions of the nonoccluded hemisphere, cerebral blood flow 5 minutes after occlusion fell below 50% of normal. Many ischemic structures showed stable blood flow for 48 hours after occlusion, confirming that in this model reperfusion is minimal. Infarction occurred eventually in all areas in which blood flow at 5 minutes fell below 10% of that in control rats, but infarction appeared earlier in regions in which blood flow at 5 minutes was below 5% of that in control rats. When blood flow at 5 minutes rose above 12% of that in control rats, the occurrence of infarction became unpredictable. CONCLUSIONS: Despite the general dependence of infarction on perfusion levels, blood flow was not a reliable indicator of those regions committed to infarction.

Animals

The pathological diagnosis of specific inflammatory myopathies.

Pathological diagnosis of dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM) should be possible in almost all cases when an appropriately involved muscle is biopsied. DM shows characteristic patterns of muscle fiber damage and capillary damage. Lymphocytes and macrophages are seen in PM and IBM partially invading non-necrotic fibers. IBM is also characterized by rimmed vacuoles with membranous whorls, characteristic masses of filaments in cytoplasm and sometimes in nuclei, and grouped atrophic fibers. Muscle fiber damage in PM is more variable. Inflammatory myopathy can be associated with HTLV-1 and HIV infection. In the latter a strong resemblance to PM is reported. Separate, still less well characterized forms of inflammatory myopathy occur in young children.

Atrophy

Hydrocephalus and prominence of the choroid plexus: an unusual computed tomographic presentation of cerebral toxoplasmosis in AIDS.

Toxoplasmosis is a frequent cause of infection of the central nervous system (CNS) in patients with acquired immunodeficiency syndrome. Computed tomography (CT) usually shows solitary or multiple parenchymal lesions, which are most often located in the cortex, the juxtacortical white matter and the basal ganglia. The authors describe a 30-year-old immunocompromised Haitian woman with pathologically proven CNS toxoplasmosis who presented with hydrocephalus and prominence of the choroid plexus; there was no evidence of focal parenchymal lesions in contrast-enhanced CT scans. An autopsy revealed diffuse destruction of the ependyma of the lateral, the third and the fourth ventricles. Necrosis was evident, and the periventricular tissues and the choroid plexus were infiltrated with neutrophils and macrophages. Pseudocysts of Toxoplasma were identified near the ventricular surface.

Acquired Immunodeficiency Syndrome

Mucolipidosis type IV: clinical manifestations and natural history.

The clinical manifestations and psychomotor development of five patients with mucolipidosis IV (MLIV) from three Ashkenazi-Jewish families are reported. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus and none progressed beyond a developmental age of 15 months. One patient died of aspiration at 17 years while the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and is now 32 years old. Histopathological studies in four patients showed storage changes characteristic of MLIV.

Adolescent

Familial inclusion body myositis among Kurdish-Iranian Jews.

We report two cases of adult-onset, slowly progressive limb-girdle muscle weakness with a remarkable sparing of quadriceps muscles that developed in patients from different families of Iranian-Kurdish-Jewish origin. Each patient had a similarly affected sibling. The findings by means of muscle biopsies showed abnormalities typical of inclusion body myositis, including abundant lined vacuoles and characteristic cytoplasmic inclusions of 15- to 18-nm filaments. Remarkably, many vacuolated muscle fibers showed immunoreactivity to neural cell adhesion molecule, a fetal muscle antigen. The common origin of these patients from an isolated ethnic group with frequent consanguinity and the familial incidence is indicative of a genetic causation or predisposition, probably with an autosomal recessive inheritance. This familial myopathy is one of several clinical syndromes that share the typical pathological findings of inclusion body myositis. The pathogenic relationship between these different familial forms and the more common sporadic form of inclusion body myositis is not known.

Adult

In vivo magnetic resonance spectroscopy of brain and muscle in a type of mitochondrial encephalomyopathy (MERRF).

Phosphorus magnetic resonance spectroscopy allows noninvasive measurement of the intracellular phosphate-containing metabolites and intracellular pH in localized volumes of human muscle and brain in vivo. This technique was used to study 8 patients with a mitochondrial cytopathy (myoclonus epilepsy with ragged red fibers). Phosphorus magnetic resonance spectroscopy of resting gastrocnemius muscle demonstrated significantly increased relative intracellular inorganic phosphate concentrations (p less than 0.0005) and decreased phosphocreatine to inorganic phosphate concentration ratios (p less than 0.01) in the patients, although only 3 had myopathic signs or symptoms. We propose, therefore, that phosphorus magnetic resonance spectroscopy of resting skeletal muscle is a useful clinical test in evaluation of progressive myoclonus epilepsy. In contrast to results from muscle, however, the relative phosphate metabolite concentrations and intracellular pH in central volumes of the brains of these patients were normal, despite evidence from our previous positron emission tomography studies suggesting that there is diffuse impairment of cerebral oxidative metabolism.

Brain

Mitochondrial dysfunction in multiple symmetrical lipomatosis.

Multiple symmetrical lipomatosis is a striking clinical finding associated with a variety of peripheral and central nervous system abnormalities. We describe 4 unrelated patients with evidence of mitochondrial dysfunction in skeletal muscle. Multiple symmetrical lipomatosis is an additional, albeit unusual, manifestation of the expanding clinical spectrum of mitochondrial diseases.

Adult

Glucocorticoids and immunosuppressants do not change the prevalence of necrosis and regeneration in mdx skeletal muscles.

Therapeutic doses of methylprednisolone, azathioprine, cyclosporin A, and cyclophosphamide administered to mdx mice between 15 and 45 days of age failed to significantly influence the time course and prevalence of necrosis and regeneration or serum creatine kinase activity. This finding contrasts with previously reported findings of beneficial effects of glucocorticoids in Duchenne muscular dystrophy (DMD). This may indicate that, mechanisms upon which beneficial effects of glucocorticoids depend in DMD, do not operate (sufficiently) in mdx mice.

Animals

Myopathy with thick filament (myosin) loss following prolonged paralysis with vecuronium during steroid treatment.

A 20-year-old female hospitalized with status asthmaticus was treated with bronchodilators, antibiotics, and high-dose corticosteroids, and was paralyzed with vecuronium for 10 days to facilitate mechanical ventilation. When this was discontinued, she was found to have a flaccid quadriplegia with areflexia and 4-fold elevation in serum creatine kinase. A muscle biopsy showed extensive loss of thick (myosin) myofilaments, sometimes in core-like distribution, with relative preservation of thin (actin) filaments and Z-discs. Muscle strength returned to normal after 2 months. The pathological lesion in this patient's muscle fibers resemble those in rats treated with high doses of corticosteroids following denervation.

Adult