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Biomedical subjects

W R Markesbery

Publications and source records attributed to W R Markesbery.

At least 181 records · Page 10Linked to original sources
PubMed1981

Instrumental neutron activation analysis of brain aluminum in Alzheimer disease and aging.

Instrumental neutron activation analysis procedures were used to determine the aluminum content of various brain regions in histologically verified Alzheimer disease (AD) and in controls. The grand mean aluminum level for 74 AD specimens was 0.372 +/- 0.058 microgram/gm and for 137 adult controls, 0.467 +/- 0.033 microgram/gm, both on a wet weight basis. No difference was found at the bulk sample level between AD and adult controls, corrected for age and sex, or when frontal, temporal, and hippocampal specimens were compared. Control specimens (infancy to 85 years) showed an increase in brain aluminum concentration with age. Comparison of freeze-dried to wet weight ratios of AD and controls revealed a small increase in water content in AD brains.

Adolescent↗
PubMed1981

Ultrastructure of pineal parenchymal neoplasms.

The fine structures of two pineal parenchymal neoplasms has been described. The tumors contained a predominance of small, poorly differentiated cells with prominent nuclei and scanty cytoplasm. These cells were similar to those found in medulloblastomas, primitive cerebral neuroectodermal tumors, and fetal cerebellum and cerebrum. Some cells contained 9 + 0 cilia, dense core vesicles, and processes containing microtubules and numerous dense core and clear vesicles, suggesting neuronal differentiation. Astrocytic elements were also present. This study suggests that the predominant cells of these tumors are primitive neuroectodermal elements which have the potential to differentiate along several different lines.

Adult↗
PubMed1981

Lymphocyte subpopulations and responsiveness in rats bearing intracranial tumors induced by avian sarcoma virus.

The mitogenic responsiveness of peripheral blood lymphocytes obtained from Fischer 344 rats inoculated with avian sarcoma virus was studied. In addition, quantitative alterations in lymphocyte subpopulations were determined in these animals. Only peripheral blood lymphocytes from rats bearing astrocytomas had significantly diminished responses to concanavalin A when compared to control responses. The percentage of lymphocyte subpopulations detected in either the peripheral blood or spleen of tumor-bearing rats did not differ from values obtained with control rats. However, rats bearing astrocytomas had a marked decrease in the absolute number of the various lymphocyte subpopulations as a result of lymphopenia. Neither the sarcoma-bearing rats nor the virus-inoculated rats that did not develop tumors exhibited this lymphopenia. In addition, sera from rats bearing astrocytomas diminished the concanavalin A reactivity of spleen cells obtained from normal rats. The results of this study establish the avian sarcoma virus-induced rat astrocytoma model as a useful immunological parallel for the human disease.

Animals↗
PubMed1981

Reoperation for glioblastoma.

The results of a second operation for tumor removal in 24 adult patients with supratentorial glioblastoma multiforme or anaplastic astrocytoma were analyzed. The median survival time after reoperation was 14 weeks. Five of the 24 patients lived 6 months or longer after reoperation. Only three of these patients maintained a Karnofsky rating (KR) of at least 60 for 6 months or longer after reoperation. Preoperative neurological status (KR) is the most significant determinant of survival after reoperation (p = 0.02). When the KR is at least 60, median survival after reoperation is 22 weeks. When the KR prior to reoperation is less than 60, median survival is 9 weeks. Only one of 13 patients with a KR of less than 60 prior to reoperation survived longer than 6 months after the second operation. The interval between first and second operation is significantly related to survival (p = 0.03), but when adjustment is made for the KR the interoperative interval is no longer significantly related to survival after the second operation (p = 0.39). Age, sex, and location of tumor were not significantly related to duration of survival. This study suggests that reoperation is most likely to produce the best result when the KR is at least 60 and the interval between operations is longer than 6 months. Using these criteria, one-third of the patients could be expected to survive with a KR of at least 60 for 6 months. The study indicates that reoperation should not be carried out when the KR is less than 60.

Adult↗
PubMed1980

Hypothalamic-immune interactions. I. The acute effect of anterior hypothalamic lesions on the immune response.

Rats with electrolytic anterior hypothalamic lesions show changes in lymphoid tissue cellularity and a decrease in the response to concanavalin A (Con A). This effect manifests itself maximally 4 days after lesioning, with a return to normal by day 14. The changes are not mediated through the release of corticosteroids. These data indicate the presence of a neuroendocrine pathway that is capable of modulating immune function.

Animals↗
PubMed1980

Mucopolysaccharidoses: ultrastructure of leukocyte inclusions.

Ultrastructural study of leukocytes from 7 patients with mucopolysaccharidosis (MPS) I, II, or III demonstrated a variety of membrane-bound inclusions in 34 to 68% of lymphocytes and larger mononuclear cells. The most common inclusions were membrane-bound vacuoles containing faintly osmiophilic material, but a variety of clear vacuoles, dense granular inclusions and myelin figures were also seen. Fingerprint profiles were present in small percentages in MPS II and III, indicating that they are not as specific as previously considered. Granulocytes, lymphocytes, and larger mononuclear cells from a patient with MPS VII showed many small and large membrane-bound vacuolated inclusions, some of which contained large dense granules. The presence of alterations in a readily accessible tissue such as blood indicates that ultrastructural study of leukocytes may be a useful adjunct in guiding further biochemical studies in MPS, especially in early or obscure cases.

Adolescent↗
PubMed1980

Review of 38 cases of subacute sclerosing panencephalitis: effect of amantadine on the natural course of the disease.

Thirty-eight cases of subacute sclerosing panencephalitis (SSPE) were reviewed. Deterioration in school performance, personality changes, and seizures were common early symptoms. Initial examination frequently showed myoclonus, spasticity, and extrapyramidal dysfunction, and in two-thirds of patients these findings were asymmetrical or focal. Retinitis or papilledema was present on initial examination in 50% of the patients. At last follow-up 24 children had died, with a mean survival of 42 months. Most patients reached a state of severe neurological impairment within 13 months. Subsequent evidence of improvement was noted in 10 children and was sustained in 4. Fifteen patients received antiviral treatment. Ten treated patients died from 5 to 133 months (mean, 58) from onset of their illness, while 15 untreated patients survived a mean of 33 months. Duration of survival appeared to be affected most by treatment with amantadine. Three patients treated with the drug were alive 97 to 139 months after onset of SSPE, and 5 died with a mean survival of 78 months. Five of 6 individuals treated with rifampin died after a mean survival of 27 months. Prolonged remissions occurred only in patients treated with amantadine. Although the number of treated individuals was small, our data suggest that amantadine may affect the natural course of SSPE.

Amantadine↗
PubMed1980

Specificity of biophysical and biochemical alterations in erythrocyte membranes in neurological disorders--Huntington's disease, Friedreich's ataxia, Alzheimer's disease, amyotrophic lateral sclerosis, and myotonic and duchenne muscular dystrophy.

Previous studies in our laboratory had demonstrated alterations in the physical state of membrane proteins in erythrocytes in Huntington's disease. In order to assess the specificity of our findings, the results of electron spin resonance studies of protein and lipid components, scanning electron-microscopic studies, enzymatic analyses of membrane-bound sodium plus potassium stimulated, magnesium-dependent adenosine triphosphatase and protein kinase, and cell deformability studies of erythrocyte membranes have been performed in the neurological disorders, Huntington's disease, Friedreich's ataxia, Alzheimer's disease, amyotrophic lateral sclerosis, and myotonic and Duchenne muscular dystrophy. Comparison of the results revealed that alterations in the biophysical and biochemical states of erythrocyte membranes in each disorder are specific to the particular disease state with the exception of those in Friedreich's ataxia and Alzheimer's disease. In the latter instance, the clinical and pathological alterations suggest that these two diseases have different primary defects. Our studies suggest that the molecular basis of each disease is different. In addition, the results suggest that biophysical and biochemical investigations of extraneural tissue in Huntington's disease and other neurological disordes have the potential of clarifying the molecular mechanisms by which these diseases arise.

Alzheimer Disease↗
PubMed1980

Spin label and biochemical studies of erythrocyte membranes in Alzheimer's disease.

Electron spin resonance, enzymatic, and SDS-polyacrylamide gel electrophoretic investigations of erythrocyte membranes from patients with Alzheimer's disease were performed. Alterations in the physical state of membrane proteins in Alzheimer's disease erythrocytes were found by spin labeling studies. However, no alterations in membrane lipid fluidity or in the activities of membrane-bound sodium plus potassium-stimulated, magnesium-dependent adenosine triphosphatase or acetylcholinesterase could be demonstrated. Also, no changes in staining profiles of AD erythrocyte membrane proteins subjected to electrophoresis were observed. The altered conformation and/or organization of extraneural membrane proteins in Alzheimer's disease suggests the possibility that this disorder may have more widespread membrane involvement than was originally thought.

Acetylcholinesterase↗
PubMed1980

Ultrastructural study of the medulloblastoma in tissue culture.

The electron microscopic features of the early phases of growth of the medulloblastoma maintained in vitro are described. The predominant early growth is comprised of small migrating cells with large nucleocytoplasmic ratio, few organelles and prominent neuritic processes containing abundant microtubules. These cells compare favorably with the cells of the primitive external granular layer of the cerebellum and cells cultivated in vitro from the fetal cerebellar cortex previously described. In addition astrocytes containing 70 to 90 A cytoplasmic filaments were commonly found in these cultures. Undifferentiated cells and cells with cilia were present in the explant proper. Cells with processes containing large dense core vesicles were also present in the explant proper suggesting the presence of neuronal differentiation. Our studies support the concept that the medulloblastoma is derived from primitive neuroectodermal cells. In addition it also suggests that astrocytic and neuronal differentiation may occur in this neoplasm in vitro.

Adult↗
PubMed1980

Histological features of congenital lipomas of the lower spinal canal.

A study of 20 children with lipomyelomeningocele and two with intradural lipoma who underwent surgery revealed that five children had unusual and previously unreported histological findings. In each, the characteristic densely fibrous lipoma was present. One patient with an intradural lipoma had an ependymal-lined canal resembling a terminal ventricle. The subependymal layer was neuroglial and striated muscle fibers were scattered throughout adjacent connective tissue and lipoma. Three other children presented with lipomyelomeningoceles. In each case, the lipoma tapered to a firm fibrous tract which blended into conus medullaris. Microscopic examination of this fibrous tract showed it to contain not only a relatively acellular connective tissue stroma, but, in one case, sheets or islands of neuroglia and scattered nerve cells, in another, an epithelial cyst with a smooth muscle and fibrous tissue wall, and in a third case, a fragment of embryonic bone. These findings support the theory that there is a secondary phase to caudal neural tube development, and that congenital lipomas are formed by persistence and differentiation of ordinarily vestigial pluripotential embryonic cells. The fifth case, with extradural lipoma, diastematomyelia, and congenital dermal sinus, had a cyst at the junction of these structures. The cyst was lined by ciliated respiratory-like epithelium, and had mucous and serous glands in its wall. This finding supports the concept that formation of diastematomyelia depends on the prior existence of an accessory neurenteric canal.

Adolescent↗
PubMed1979

Electron spin resonance, hematological, and deformability studies of erythrocytes from patients with Huntington's disease.

Electron spin resonance, hematologic, and deformability studies of erythrocytes from patients with Huntington's disease have been performed A decreased deformability of Huntington's disease erythrocytes compared to normal controls was demonstrated. No difference in erythrocyte hematologic indices, osmotic fragility, reticulocyte counts, or intracellular Na+ concentration was found. Huntington's disease serum had no demonstrable effect on electron spin resonance parameters of a protein-specific spin label attached to membrane proteins in control erythrocytes compared to the effect of control serum. This finding suggests that under the conditions employed no serum component or circulating factor is responsible for the changes in the physical state of membrane proteins in Huntington's disease erythrocytes (Butterfield, D.A., Oeswein, J.Q. and Markesbery, W.R. (1977) Nature 267, 453--455). No alteration in lipid fluidity of Huntington's disease erythrocyte membranes could be discerned suggesting that the underlying molecular defect in Huntington's disease involves a membrane protein. The results of the present studies on erythrocytes strongly support the concept that Huntington's disease is associated with a generalized membrane abnormality.

Electron Spin Resonance Spectroscopy↗
PubMed1979

Electron microscopic findings in primitive neuroectodermal tumors of the cerebrum.

The fine structure of 3 primitive neuroectodermal neoplasms of the cerebral hemispheres was studied. The predominant tumor cells were undifferentiated cells with prominent nuclei and scanty cytoplasm containing few organelles. Ultrastructural evidence suggesting differentiation into ependymal, neuronal and possibly astrocytic elements was also present. This study suggests that the cell of origin of this tumor is a primitive multipotential cell of the cerebrum.

Adolescent↗
PubMed1979

Fatal neonatal nemaline myopathy with multiple congenital anomalies.

The clinical course and autopsy findings in a patient with fatal neonatal nemaline myopathy are described. A hypotonic infant required mechanical ventilatory support immediately following delivery and developed progressive congestive heart failure. He had mild facial dysmorphism, a high-arched palate, clinodactyly, short first metacarpals, abnormal dermatoglyphics, simian creases, and bilateral talipes varus. Light and electron microscopic study of a muscle biopsy was diagnostic of nemaline myopathy. Autopsy revealed a papillary muscle anomaly, myocardial scarring, and hepatic fibrosis. The severe clinical impairment in this infant and the unusual associated anomalies are compared with other examples of nemaline myopathy. Nemaline myopathy is a cause of respiratory insufficiency in the neonatal period.

Abnormalities, Multiple↗