Search PubMed⌕ Search

Biomedical subjects

S C Patel

Publications and source records attributed to S C Patel.

At least 73 records · Page 4Linked to original sources

25-Hydroxycholesterol induces reorganization of lysosomes in normal but not Niemann-Pick disease type C astrocytes.

25-hydroxycholesterol (25-OHC), an oxysterol that potently regulates cellular cholesterol metabolism, induced formation of novel fibrillar structures in normal mouse astrocytes as observed by fluorescence microscopy with the cholesterol probe, filipin. These fibrils were identified as lysosomes by their immunoreactivity for the lysosome associated membrane glycoprotein (LAMP). In contrast, astrocytes derived from the Niemann-Pick disease type C (NPC) mutant mouse were resistant to this oxysterol-induced lysosomal reorganization. NPC astrocytes have abnormal intracellular cholesterol storage as observed by brightly positive filipin staining of their lysosomes. These results show that lysosomal cholesterol storage in NPC astrocytes is associated with a block in oxysterol-mediated fibrillar reorganization of lysosomes.

Animals↗

Quinolinic acid stimulates somatostatin gene expression in cultured rat cortical neurons.

Striatal atrophy in Huntington's disease (HD) is characterized by selective preservation of a subclass of neurons colocalizing NADPH-diaphorase (NADPH-d), somatostatin (SS), and neuropeptide Y (NPY), which have been reported to show three- to fivefold increases in SS-like immunoreactivity (SSLI) and NPY content. Since HD brain is capable of producing excessive quantities of the excitotoxin quinolinic acid (Quin), an N-methyl-D-aspartate (NMDA) receptor agonist, and since experimental Quin lesions show neuronal loss with sparing of NADPH-d/SS/NPY neurons, it has been suggested that Quin may be important in the pathogenesis of HD. In the present study we determined whether Quin stimulates SS gene function in cultured cortical cells known to be rich in NADPH-d/SS/NPY neurons. Cultures of dispersed fetal rat cortical cells were exposed to Quin (1 and 10 mM) with or without (-)-2-amino-5-phosphonovaleric acid (APV; 0.5 mM), an NMDA receptor antagonist, NMDA (0.2 and 0.5 mM), and glutamate (Glu; 0.5 mM). Medium and cellular SSLI was determined by radioimmunoassay and SS mRNA by Northern analysis with a cRNA probe. Quin induced significant (p less than 0.01) 1.6- and 2.5-4 fold increases in SSLI and SS mRNA accumulation, respectively, which were abolished by APV. Release of SSLI into the culture medium was stimulated two- to fivefold by Quin over a 2- to 20-h period. The increase in SS mRNA produced by Quin was time and dose dependent. A similar dose-dependent increase in SS mRNA comparable with that observed with Quin was induced by NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Genetic defects of lysosomal function in animals.

In this article we have described studies using animals with genetic lysosomal defects with particular emphasis on mutant disorders that have contributed toward understanding of pathogenesis and/or management of analogous human conditions. The development of newer strategies in the production and use of animal models will greatly expand the contribution of this resource to biology and medicine.

Animals↗

Epidural lipomatosis.

The authors report six new cases of epidural lipomatosis--a rarely described entity characterized by increased extradural fat within the spinal canal causing compression of the spinal cord and neurologic deficits. Five of the six patients had a history of chronic steroid use. Myelography of the thoracic spine, followed by computed tomography (CT), was performed in five patients, and magnetic resonance (MR) imaging was done in three. Myelographic findings were abnormal in three patients and normal in two, compared with those of postmyelography CT, which revealed increased accumulation of extradural fat in all five patients. In the three patients in whom it was performed, MR imaging also showed the increased spinal canal fat. Four patients underwent surgery, which revealed an increased amount of histologically normal, unencapsulated fat in all cases. The diagnosis of epidural lipomatosis should be based on a combination of clinical, imaging, surgical, and histologic findings. If the clinical suspicion is high, even if results of myelography are normal, further evaluation with post-myelography CT or MR imaging should be considered.

Adult↗

Impaired cholesterol esterification in primary brain cultures of the lysosomal cholesterol storage disorder (LCSD) mouse mutant.

Esterification of cholesterol was investigated in primary neuroglial cultures obtained from newborn lysosomal cholesterol storage disorder (LCSD) mouse mutants. An impairment in 3H-oleic acid incorporation into cholesteryl esters was demonstrated in cultures of homozygous LCSD brain. Primary cultures derived from other phenotypically normal pups of the carrier breeders esterified cholesterol at normal levels or at levels which were intermediary between normal and deficient indicating a phenotypic expression of the LCSD heterozygote genotype. These observations on LCSD mutant brain cells indicate that the defect in cholesterol esterification is closely related to the primary genetic defect and is expressed in neuroglial cells in culture.

Animals↗

Gaucher's disease in a patient with chronic active hepatitis.

Gaucher's disease, an inherited metabolic disorder, may cause hepatic fibrosis, but hepatic inflammation does not occur as part of the disorder. The case of an 18-year-old girl of Ashkenazic Jewish ancestry with chronic active hepatitis and coexistent Gaucher's disease is presented. The clinical course of remissions and exacerbations of the disease activity was typical of "autoimmune" chronic active hepatitis and seemed unaffected by the coexistence of Gaucher's disease. Steroid and immunosuppressive treatment resulted in prompt resolution of the chronic hepatitis. Gaucher's disease results in B cell stimulation and polyclonal gammopathy, which may have contributed to the hypergammaglobulinemia associated with idiopathic ("autoimmune") chronic hepatitis in this case.

Adolescent↗

Radiologic evaluation of extracranial to Sylvian middle cerebral artery bypass.

At this institution a new procedure has been developed that involves anastomosing one of the branches of the superficial temporal artery to one of the major trunks of the middle cerebral artery in the Sylvian fissure. This procedure has been performed in 22 cases to date. Clinical indications for this procedure have fallen into four major categories. This new type of anastomosis produces greater bypass flow than conventional cortical middle cerebral artery anastomoses, and may be a better therapeutic alternative in certain clinical situations. The preoperative and postoperative angiographic evaluation of these patients is discussed. The radiologic results in this series of patients are reviewed.

Adult↗

Blepharospasm associated with brainstem lesions.

We studied six patients with clinical and radiographic evidence of rostral brainstem lesion and bilateral blepharospasm. Two patients also had other facial dystonic movements. Four patients suffered rostral brainstem strokes, and two had multiple sclerosis. None had been treated with antipsychotic drugs prior to the onset of blepharospasm. Medical treatment was helpful in two patients, and bilateral selective facial nerve section was used in another patient. Possible pathogenic mechanisms are discussed.

Adult↗

Comparison of centrifugation and filtration assays of ligand binding: do multiple GABA receptive sites exist?

Filtration and microcentrifugation procedures for the separation of bound and free ligand are compared for the assay of GABA receptors. The 3H-GABA and 3H-muscimol are employed as ligands in saturation analyses of SPM and JC preparations. A direct comparison of the two methods, applied to two membrane preparations and two ligands, reveals that nonspecific binding is consistently higher with the microcentrifugation procedure. Analysis of the binding data yields essentially the same constants in either case; however, the filtration assay provides a better estimate in all cases.

Animals↗

Successful evacuation of a pontine hematoma secondary to rupture of a venous angioma.

A middle-aged woman presented with progressive brainstem neurological deficits. Clinical manifestations and preoperative radiological examination were indicative of an expanding intrapontine mass. At operation, an intrapontine hematoma and a venous angioma adherent to the floor of the fourth ventricle were discovered. Successful evacuation of the hematoma was followed by an excellent recovery. Postoperative angiography demonstrated the venous angioma. To our knowledge, this is the first case of angiographically proved ruptured venous angioma of the pons treated successfully by an operation.

Adult↗

A prospective randomized trial of the selective distal splenorenal shunt.

Distal splenorenal shunt has been compared in a prospective randomized way with end-to-side portacaval shunt in patients who have survived a major hemorrhage from esophageal varices. The operative mortality was higher after the elective shunt than after the portacaval shunt. However, most of these deaths occurred in the early phases of the study. Postoperative encephalopathy was significantly lower after the selective shunt than after the portacaval shunt. Follow-up studies to date show no significant difference in late survival.

Adult↗

Selection of operation in patients with bleeding esophageal varices.

The results of surgical treatment of bleeding esophageal varices over an 8-year period in 155 patients are reviewed. Primary treatment of bleeding was conservative, with intravenous administration of vasopressin and balloon tamponade. Emergency operations were carried out after 48 hours in persons with persistent bleeding who were surgical candidates. Operative mortality was higher in this group (40%) than in those undergoing elective or urgent operations (each 10%). Postoperative encephalopathy occurred in 35% of patients and was correlated closely to late death after establishment of a shunt. The mesocaval shunt is no better than the portacaval but appears to be a good alternative in an emergency. In a controlled trial the distal splenorenal shunt was found to be associated with a lower rate of postoperative encephalopathy than the portacaval shunt, but thus far the long-term survival rates have not differed.

Blood Vessel Prosthesis↗