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Biomedical subjects

S K Shankar

Publications and source records attributed to S K Shankar.

At least 19 recordsLinked to original sources
PubMed1992

Microsomal cytochrome P450 in human brain regions.

Cytochrome P450 (P450) levels were quantitated in microsomes from human brain regions obtained at autopsy. The reduced carbon monoxide binding spectra of cortical microsomes showed two absorption maxima at 449 and 425 nm. On solubilization of the microsomes, essentially a single peak was observed at 449 nm. The P450 levels in human brain cortical microsomes varied from 0.03 to 0.12 nmol/mg protein among the seven samples examined. The concentration of the hemeprotein present as nmol/g tissue was highest in the brain stem and cerebellum and lowest in the striatum and hippocampus.

Adult↗
PubMed1992

Neuroanatomy of Cysticercus cellulosae (Cestoda) as revealed by acetylcholinesterase and nonspecific esterase histochemistry.

The nervous system of Cysticercus cellulosae, the metacestode stage of the tapeworm Taenia solium, was delineated using histochemical methods for the localization of the enzyme markers; nonspecific esterase and acetylcholinesterase. The main features of the nervous system include a pair of cerebral ganglia, a circumcerebral nerve ring, a rostellar nerve ring, and anterior and posterior nerves and their branches. The posterior nerves form a subtegumental network in the strobila and the bladder wall. A nerve network around excretory tubules could also be demonstrated, suggesting neuronal control of excretion in the metacestode. No sheath was observed around the nervous system. The morphological features described suggest "cephalization" of the nervous system in this parasite.

Acetylcholinesterase↗
PubMed1991

Effect of chronic ethanol ingestion on phosphate content of neurofilament proteins and neurofilament associated protein phosphatase in rat spinal cord.

Rats were trained to drink alcohol solution by gradually increasing the ethanol content [2.5-15% (v/v)] in drinking water. After 11 months of alcohol (15% v/v) ingestion, animals were guillotined and the spinal cords were used for the preparation of neurofilaments (NF). NF triplet proteins were separated by SDS-PAGE and the phosphate contents of individual components were estimated. Results indicated a significant increase in phosphate content of 200 KD protein in alcohol fed rats (30.19 +/- 4.12 mol of phosphate/mole of protein: p less than 0.001) compared to control group (18.42 +/- 3.91 mol of phosphate/mole of protein). No significant change in the phosphate content of 150KD and 68KD components of NF were seen in experimental group. Further, the studies on NF associated protein phosphatase activity indicated a significant decrease in phosphatase activity among the alcohol fed rats (14.10 +/- 2.5 mU; p less than 0.001) against NF rich fraction as a substrate, as compared to control (20.15 +/- 2.15 mU). While the observed decrease in NF associated protein phosphatase would possibly explain the increase in phosphate content of NF proteins in alcohol fed rats, the precise mechanism of decrease in enzyme activity remains to be elucidated. Nevertheless, the change seen in phosphate content and NF associated protein phosphatase activity as a result of ethanol ingestion would possibly form the biochemical basis of some of the neuropathological changes seen in alcoholics.

Alcoholism↗
PubMed1991

A simple and inexpensive slicer for preparation of brain slices.

A simple and inexpensive slicer has been developed for the preparation of slices of mouse or rat brain. The instrument consists of razor blades, separated by an 0.5 mm thick polyethylene sheet (1 x 1 cm), mounted on metal screws through a hole in the center of the polyethylene sheet. Using this slicer, 6-8 uniform slices of 500 microns thickness were obtained from mouse or rat brain. These brain slices were incubated in a medium consisting of artificial cerebrospinal fluid for 1 h at 37 degrees C under an oxygen atmosphere and the activities of various subcellular marker enzymes were assayed. The slice weights and the activities of the enzymes did not vary significantly in different batches of slices. Morphological evaluation of the slices revealed well-preserved neurons. Histochemical staining for mitochondrial enzymes revealed intense staining of neuronal cells and lighter staining of the white matter in all the regions examined. These slices could serve as a useful in vitro model for studying brain function and the effect of various toxicants on the brain.

Animals↗
PubMed1991

Acute ataxic neuropathy: a clinical, electrophysiological and morphological study.

Sensory ataxia as the chief manifestation of acute neuropathy is rather rare. Of the 224 cases of acute polyneuropathy seen over 6 years (1984-1990) only 10 patients (M:F 3:7) had disabling ataxia as the presenting feature. Their ages ranged from 14-61 years. Antecedent febrile illness was present in 6 patients and the peak deficit evolved over 2-25 days. Severe ataxia, paresthesia, distal areflexia and predominant joint sense loss were common to all, motor weakness was either absent or insignificant. CSF was acellular and revealed elevated protein in 3 subjects. All patients had electrophysiological evidence of severe sensory neuropathy with mild or no motor neuropathy. Sural nerve biopsy in one patient showed loss of large, as well as small, diameter myelinated fibres, secondary demyelination, but no evidence of inflammation. At follow up marginal to moderate improvement in ataxia was noted in only 5 patients. Absence of ophthalmoplegia and motor weakness, poor prognosis and characteristic electrophysiological and histopathological observations suggest that acute ataxic neuropathy may be a distinct entity.

Adolescent↗
PubMed1991

Creutzfeldt-Jakob disease in India (1971-1990).

Thirty cases including 20 definite and 10 probable cases of Creutzfeldt-Jakob disease (CJD) seen in India between 1971 and 1990 are reported. Demographic analysis has shown similarities to the previously published reports from other parts of the world. Though 21 (70%) of cases were from two centers--Bombay and Bangalore-, suggesting clustering, this seems to be more apparent than real. One subject worked in the medical field, where possibility of iatrogenic transmission could not be ruled out. None of the cases had positive family history of CJD. There is no epidemiological data of CJD from India so far and hence this report is one such pilot study.

Adult↗
PubMed1990

Rat brain cytochromes P-450: catalytic, immunochemical properties and inducibility of multiple forms.

Cytochrome P-450 (P-450) and associated mono-oxygenase activities were estimated in male and female rat brain microsomes. The P-450 concentration in male rat brain was one-tenth the corresponding hepatic levels, which is considerably higher than earlier reports. A distinct sex-related difference was observed in the levels of total P-450 and mono-oxygenase activities known to be mediated by P-450b,e; the female brain levels were 60% of those in the males. Immunoinhibition and immunoblot studies using antisera to P-450b,e and P-450c,d indicated the presence of multiple forms of P-450, immunologically similar to P-450b,e, P-450c and P-450d in the rat brain. Prior treatment with phenobarbital resulted in two-fold increase of total P-450 and selective induction of aminopyrine N-demethylase (APD) and morphine N-demethylase (MND) activities. Administration of 3-methylcholanthrene, selectively induced the levels of ethoxycoumarin O-deethylase (ECD) and arylhydrocarbon hydroxylase, although the levels of total P-450 were not increased. 3-Methylcholanthrene induction was also accompanied by a shift in the absorption maximum of the reduced carbon monoxide difference spectrum from 452 to 448 nm. Immunocytochemical localization using antibodies to P-450b,e indicated the presence of P-450 predominantly in the neuronal cell bodies and to a lesser extent in the fibre tracts in cerebral cortex, cerebellum, thalamus, hypothalamus, hippocampus and brainstem. These studies indicate that the brain contains significant amounts of P-450, which exists in multiple forms and can be selectively induced by prior exposure to phenobarbital or 3-methylcholanthrene.

Animals↗
PubMed1990

NADPH cytochrome P-450 reductase in rat, mouse and human brain.

NADPH cytochrome P-450 reductase (P-450 reductase), an essential component of the cytochrome P-450 mono-oxygenase system, has been estimated in rat and mouse brain, and seven human brains obtained at autopsy. The ratio of cytochrome P-450 to P-450 reductase is lower in the rat and mouse brains (2.5-4.0) as compared to the respective livers (10.0-11.0). The rat and mouse brain P-450 reductase were immunologically similar to the rat liver P-450 reductase as examined by immunochemical inhibition, Ouchterlony double diffusion and immunoblot. The antisera to rat liver P-450 reductase inhibited rat brain aminopyrine N-demethylase activity to the same extent as NADPH cytochrome c reductase, suggesting that the level of P-450 reductase controls the rate of this cytochrome P-450 mediated activity. The human brain NADPH cytochrome c reductase exhibited regional variation, maximal activity being observed in the brain stem region. Immunochemical inhibition and immunoblot studies revealed immunological cross-reactivity between rat liver reductase and human brain medulla, while none was observed in cortex or cerebellum. Immunocytochemical studies on human brain medulla using antisera to rat liver P-450 reductase indicated localization of the P-450 reductase in neuronal cell body.

Adolescent↗
PubMed1990

Vertebro-basilar insufficiency due to carotid stenosis.

Two patients with internal carotid disease and normal/hypoplastic vertebro-basilar system presenting with symptoms of vertebrobasilar insufficiency are presented. The role of associated anomalies of the circle of Willis or major vessels in the pathogenesis of symptoms is highlighted.

Carotid Artery Diseases↗
PubMed1990

Simultaneous cerebral arterial and venous thrombosis.

Simultaneous thrombotic occlusion of cerebral arterial and venous systems in the same individual is rare. Three patients of stroke in whom autopsy revealed co-existing arterial and venous infarctions, major arterial occlusion (vertebral 1, internal carotid 1) and dural sinus and cortical vein thrombosis are reported. Role of infarcted brain, haemorrheological factors and alcohol in the pathogenesis of this rare event is highlighted.

Adult↗
PubMed1989

Xenobiotic metabolism in human brain--presence of cytochrome P-450 and associated mono-oxygenases.

The cytochromes P-450, a family of heme proteins, play an important role in the oxidation of drugs and carcinogens, as well as endogenous substrates. We report the presence of cytochrome P-450 and associated mono-oxygenase activity in human brain regions and their selective enrichment in the brainstem. Immunocytochemical studies on human medulla with antibodies raised to phenobarbital-inducible rat liver cytochrome P-450 indicate that the enzyme is primarily localized in the neuronal cell bodies and to a lesser extent in the axons. These observations indicate that the human brain could be involved in metabolism of xenobiotics and endogenous compounds, mediated through cytochrome P-450.

Adult↗
PubMed1989

Neuronal degeneration and neurofilament accumulation in the trigeminal ganglia in Creutzfeldt-Jakob disease.

We report the pathological and immunohistochemical changes in the first-order neurons in the trigeminal ganglia in Creutzfeldt-Jakob disease (CJD). Degenerative changes consisted of cytoplasmic vacuolation and fenestration, abundant satellite cells, neurofilament accumulation in neurons, and axonal dystrophy with spheroid formation and torpedolike structures arising from the neuronal cytoplasm. Dystrophic axons, axonal spheroids, and some ganglion cells were labeled with monoclonal antibodies to a phosphorylated epitope of neurofilaments (200 kDa). Polyclonal antibodies to purified scrapie-associated fibril/prion protein (molecular weight 27-30 kDa) extracted from scrapie-infected hamster brains, as well as polyclonal and monoclonal antibodies to a synthetic 15-amino acid polypeptide of the 27- to 30-kDa protein, demonstrated variable immunoreactivity with degenerating neurons in the CJD cases, but not in the controls. Furthermore, some of the satellite cells and dystrophic axons were stained by the antibodies to the synthetic peptide. These data indicate that the first-order neurons of the trigeminal ganglia may form a route by which the CJD agent may travel from the brain to the periphery or vice versa. As in other chronic neurodegenerative diseases, disturbances of neuroaxonal transport seem to occur in CJD.

Adult↗
PubMed1989

Immunocytochemical characterization of neurofibrillary tangles in amyotrophic lateral sclerosis and parkinsonism-dementia of Guam.

Cryostat-cut sections of formalin-fixed and unfixed hippocampus from 23 Guamanian Chamorros with clinically and neuropathologically verified amyotrophic lateral sclerosis (ALS) (8 cases) and parkinsonism-dementia (PD) (15 cases) and from 12 neurologically normal Guamanians (5 with and 7 without neurofibrillary degeneration) were evaluated by the immunoperoxidase technique, using monoclonal antibodies against phosphorylated neurofilament, human fetal microtubule-associated protein tau, and paired helical filaments. On immunostaining, all three antibodies showed intracellular tangles in the hippocampal neurons of patients with ALS, patients with PD, and in neurologically normal Guamanians with neurofibrillary pathology, but the correlation of immunostaining between these antibodies was not absolute. Extracellular or ghost tangles were immunostained only with the antibody against paired helical filaments. Our immunocytochemical data indicate that the antigenic composition of neurofibrillary tangles in Guamanian ALS and PD is similar to that of Alzheimer's disease, suggesting a common pathogenetic pathway for neurofibrillary tangle formation in these neurodegenerative disorders.

Adult↗
PubMed1989

Low-calcium, high-aluminum diet-induced motor neuron pathology in cynomolgus monkeys.

Long-term epidemiological studies indicate that environmental factors play a causative role in high-incidence amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) in the western Pacific. An increased risk for disease is acquired in youth and remains for life. The low concentrations of calcium and magnesium and high levels of aluminum in the soil and drinking water, along with the relative isolation of these populations, constitute an unusual environmental feature common to all three high-incidence foci. Studies of mineral deposition in brain tissue of Guamanian ALS and PD patients, as well as of neurologically normal Guamanians with neurofibrillary degeneration, demonstrate accumulations of calcium, aluminum and silicon in neurofibrillary tangle-bearing neurons. In an attempt to duplicate the low calcium and high aluminum and manganese in soil and drinking water in these foci, we maintained juvenile cynomolgus monkeys for 41 to 46 months on a low-calcium diet with or without supplemental aluminum and manganese. Experimental animals exhibited mild calcium and aluminum deposition and degenerative changes, compatible with those of early ALS and PD, in motor neurons of the spinal cord, brain stem, substantia nigra and cerebrum. Neuropathological findings included chromatolysis, aberrant perikaryal accumulation of phosphorylated neurofilament, neurofibrillary tangles, axonal spheroids, and basophilic and hyaline-like inclusions consisting of abnormal cytoskeletal elements by electron microscopy. The magnitude and extent of these lesions far exceeded those found in normal aged monkeys.

Aluminum↗
PubMed1989

Role of squash-smear technique for rapid diagnosis of neurosurgical biopsies--a cytomorphological evaluation.

The biopsy material obtained from lesions of CNS are subjected to squash smear technique for rapid diagnosis as it is easier to make and the cytological features of cells are well preserved. During the year 1982-1983 one hundred and seventy eight squash smears were made to offer rapid diagnosis to the operating surgeon. The diagnosis was verified on paraffin sections. Correct diagnosis was made in 87% of cases. Various lesions have distinct cytomorphological features on smears. These distinct characters and efficacy of the method are discussed.

Biopsy↗
PubMed1987

Localization of amyloid beta protein messenger RNA in brains from patients with Alzheimer's disease.

The distribution of cells containing messenger RNA that encodes amyloid beta protein was determined in hippocampi and in various cortical regions from cynomolgus monkeys, normal humans, and patients with Alzheimer's disease by in situ hybridization. Both 35S-labeled RNA antisense and sense probes to amyloid beta protein messenger RNA were used to ensure specific hybridization. Messenger RNA for amyloid beta protein was expressed in a subset of neurons in the prefrontal cortex from monkeys, normal humans, and patients with Alzheimer's disease. This messenger RNA was also present in the neurons of all the hippocampal fields from monkeys, normal humans and, although to a lesser extent in cornu ammonis 1, patients with Alzheimer's disease. The distribution of amyloid beta protein messenger RNA was similar to that of the neurofibrillary tangles of Alzheimer's disease in some regions, but the messenger RNA was also expressed in other neurons that are not usually involved in the pathology of Alzheimer's disease.

Alzheimer Disease↗