N-Methyl-D-aspartate receptor participation in Parkinson's disease, a neurodegenerative disorder.
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Biomedical subjects
Publications and source records attributed to A Verma.
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We describe a clinical picture similar to Parkinson's disease in a patient with midbrain encephalitis due to cysticercosis. The clinical, radiographic, and cerebrospinal fluid findings suggested an inflammatory reaction to a dying cyst that involved midbrain structures. The encephalopathy appeared to worsen temporarily after the institution of anticysticercus therapy. A discordance between worsening parkinsonian symptoms and improving pyramidal features was noted. Virtually a complete clinical recovery eventually ensued.
Chronic treatment with the dopamine (DA) agonist B-HT 920 (0.25-1 mg/kg) or bromocriptine (1 mg/kg) followed by morphine (10 mg/kg) on days 1-9 prevented the development of tolerance to the antinociceptive effect of morphine as measured by the tail-flick test in mice, but failed to suppress the development of morphine dependence as assessed by naloxone (2 mg/kg)-precipitated withdrawal jumps on day 10 of testing. Repeated administration of SKF 38393 (5 mg/kg) followed by morphine for 9 days significantly reduced naloxone-precipitated jumps on day 10 but failed to produce any significant change in tail-flick latency from the saline-pretreated group of mice on days 9 and 10 of testing. Repeated administration of B-HT 920 or bromocriptine enhanced the ability of MK-801 to attenuate the development of morphine tolerance and dependence while SKF 38393 failed to do so. The above data suggest a preferential role of D2 DA receptors in morphine tolerance and D1 receptors in the development of morphine dependence. D2 DA receptor stimulation may also play an important role in enhancing the effectiveness of MK-801 in the treatment of opiate tolerance and dependence.
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One hundred and seventy two strains of beta haemolytic streptococci were isolated from various clinical specimens over a period of one year. Group A was isolated in 69.70% and group C in 16.80 percent. Majority of the strains were isolated during winter season and only 21.00 percent in summer 93.30 percent strains were bacitracin sensitive and all were sensitive to penicillin. The most common T pattern among group A was found to be 5/11/12/27/44 followed by 3/13/B 3264.
A functional analysis of Mycobacterium tuberculosis 16S ribosomal RNA (rRNA) transcription and processing was undertaken in this study. RNA:DNA hybridizations indicated that the maximum transcriptional activity of rRNA-encoding genes (rDNA) corresponded to the earliest period of exponential growth. Transcription start points (tsp) were mapped by primer extension analysis of RNA from M. tuberculosis H37Rv and M. tuberculosis H37Ra. An identical pattern of rRNA transcription and processing was exhibited in laboratory-grown cultures of M. tuberculosis H37Rv and H37Ra. One promoter represents the structural equivalent of the Escherichia coli rrn P2 promoter. The precursor transcripts are processed into mature 16S rRNA through a pathway that includes recognition of RNA secondary structure by ribonuclease III (RNase III) in the stem structure surrounding the 16S rRNA indicating that at least this RNA processing step is conserved in mycobacteria and E. coli. The 16S rDNA promoter region from H37Rv was cloned upstream from the promoterless chloramphenicol (Cm) acetyltransferase (CAT)-encoding gene (cat) in a shuttle plasmid vector, pSD7. The promoter-fusion construct, pSD7.16S, was characterized by CAT assays, measurement of percent survival in Cm-containing medium and in vivo transcription analysis in M. smegmatis. The M. smegmatis transformant exhibited a CAT activity of 16,669 nmol/min per mg protein, suggesting that the 16S promoter was of exceptionally high strength. Two tsp utilized in M. tuberculosis were also employed in M. smegmatis. The cat mRNA synthesized under the direction of the ribosomal promoter was less stable, as compared to genome-derived rRNA.
Stroke although rare in children, is an important cause of morbidity in the paediatric age group. Over a period of 8 years, 43 children (17 boys and 26 girls) in the age groups of 1-16 years (mean 8.02 yrs) presented with stroke which constituted 10% of all strokes in the young and 0.7% of all paediatric admissions. The chief clinical features were hemiplegia (86%), convulsions (27%), fever (23%), dysphasia (23%), headache (11%) and altered level of consciousness (11%). Routine laboratory tests were non-contributory. Cranial computerized tomography (CCT) on 21 patients was abnormal in 95% and was useful in revealing the extent of infarction. Infarction was confined to middle cerebral artery territory, often involving basal ganglionic structures and was associated with focal or diffuse atrophy. Angiograms were abnormal in 78% of the patients (18/23) and were complimentary to the CCT. Etiological factors identified were: Moya-moya disease 6, arteritis 5, fibromuscular dysplasia 2, scorpion sting 2, and venous sinus thrombosis and small vessel occlusion one each. Though 23% of the patients had fever at onset, no obvious evidence of systemic or CNS infection was noticed. Stroke in children continues to pose a diagnostic challenge.
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Previous reports of primary lumbosacral plexopathy (LSP) have stressed the benign nature of the syndrome. No effective treatment is known for the occasional patients who do not recover or who have relapses. We report two patients presenting with a progressive form of idiopathic LSP. Both patients showed remarkable improvement on high-dose intravenous immunoglobulin therapy. We suggest that these patients represent a treatable subgroup of LSP.
Brainstem auditory evoked responses (BAER) were longitudinally recorded prospectively in 18 term infants with neonatal hyperbilirubinemia (NHB) (total serum bilirubin > 15 mg/dl). Seven neonates had abnormal BAER. Wave complex IV-V was absent in eight recordings in NHB group while they were normal in the control group (p < 0.001). Prolongation of latency of waves I and V and interwave conduction time (wave I-V) occurred in jaundiced infants especially when unconjugated serum bilirubin level rose above 22 mg/dl. The abnormalities in BAER reversed to normal in all seven neonates after exchange blood transfusion indicating transient nature of bilirubin toxicity to the brain. All seven neonates in the study and control group had normal hearing, development quotient and were free of neurological sequelae on follow up for one year.
Growth of exclusively breastfed 126 normal newborns in urban slums and those delivered at Nehru Hospital, Medical College, Gorakhpur were studied upto six months of age. The average weight of both boys and girls was almost equivalent to the 25th percentile of NCHS standard upto 3 months but fell below these standards thereafter. The average length in both boys and girls was between 25th and 50th percentile of NCHS data. The average head circumference in girls was between 25th and 50th percentile of NCHS data at all ages but in boys it was between 10th and 25th percentile at 4, 5 and 6 months of age. The average weight, length, head and chest circumference in both boys and girls were comparable to ICMR standards. The observations indicate that exclusive breastfeeding should be promoted for adequate growth of infants during first six months of life.
The partial nucleotide sequence of a recombinant plasmid containing the 23S rRNA gene of Mycobacterium tuberculosis was determined and an assay was developed for amplifying 23S rRNA gene sequences of mycobacteria. The PCR-based non-radioactive test enabled us to distinguish Mycobacterium from other closely related genera and was sensitive enough to detect 2 bacterial genome equivalents. The assay was extended to the detection of mycobacterial DNA in uncultured clinical specimens; 23S rRNA sequences were detected in thirty four of forty eight (70.8%) sputum and cerebrospinal fluid (CSF) specimens by the PCR assay, whereas direct smear examination and culture methods demonstrated a positivity rate of 29.2% and 16.7% respectively for the same specimens. A RNA-based PCR assay with a detection limit of 1 genome equivalent was also developed. These PCR assays should prove useful for the early and rapid detection of mycobacterial infection in uncultured clinical specimens.
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The purified mitochondrial benzodiazepine receptor (mBzR) is a complex comprising the voltage-dependent anion channel (VDAC), adenine nucleotide carrier, and an 18-kDa protein that binds isoquinoline carboxamide ligands (McEnery, M. W., Snowman, A. M., Trifiletti, R. R., and Snyder, S. H. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 3170-3174). An antiserum raised against the mBzR complex reacts selectively with VDAC and is used, along with purification, electrophysiological and immunohistochemical techniques, to characterize the properties and distribution of rat brain VDAC. Although purified VDAC displays biochemical and electrical conductance properties similar to VDAC from other sources, the immunohistochemical distribution of VDAC in rat brain is heterogeneous with pronounced regional variations; the pontine nuclei, the supraoptic nucleus, Purkinje cells of the cerebellum, and the caudate putamen evidence the highest density. The distribution of VDAC is inclusive of the more discretely localized 18-kDa mBzR protein, suggesting that only a portion of the total VDAC participates in the mBzR. The histochemical localizations of the mitochondrial marker enzymes glutamate dehydrogenase and cytochrome c oxidase also indicate marked regional variability in both mitochondrial content and composition. The discrete expression of VDAC reflects a striking heterogeneity of rat brain mitochondria and underlying differences in the utilization of mitochondrial outer membrane ion channels.
Carbon monoxide, an activator of guanylyl cyclase, is formed by the action of the enzyme heme oxygenase. By in situ hybridization in brain slices, discrete neuronal localization of messenger RNA for the constitutive form of heme oxygenase throughout the brain has been demonstrated. This localization is essentially the same as that for soluble guanylyl cyclase messenger RNA. In primary cultures of olfactory neurons, zinc protoporphyrin-9, a potent selective inhibitor of heme oxygenase, depletes endogenous guanosine 3',5'-monophosphate (cGMP). Thus, carbon monoxide, like nitric oxide, may be a physiologic regulator of cGMP. These findings, together with the neuronal localizations of heme oxygenase, suggest that carbon monoxide may function as a neurotransmitter.
The time of first stool was studied in 144 infants with a birth weight of 1000 gm or less. Median age at passage of the first stool was 3 days, and 90% of the infants passed stool by 12 days after birth. There was no relationship between the time of passage of the first stool and either birth weight or gestational age. Of the 114 infants, 88 (77%) passed stool before the initiation of any enteral feeding. The passage of the first stool was delayed in male compared with female infants (p = 0.03).
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The effect of selective D1- and D2-dopamine (DA) receptor stimulation on neocortical and hippocampal electroencephalographic (EEG) activity of rat brain was studied. The modulation of the effect of rimcazole, a sigma receptor antagonist, by D1- and D2-DA receptor agonists was also investigated. B-HT 920 (0.5 mg/kg), a D2 DA agonist, produced significant inhibition of EEG activity in neocortex and hippocampus. The lower doses of B-HT 920 (0.1 and 0.25 mg/kg) either enhanced the frequency and amplitude of cortical and hippocampal firing or lacked any significant effect. The inhibitory effect of B-HT 920 was blocked by haloperidol (0.5 mg/kg), a D2-receptor antagonist and enhanced by idazoxan (1.0 mg/kg), an alpha 2-adrenoceptor antagonist. SKF 38393 (5.0 mg/kg), a D1-DA receptor agonist and dopamine (10 mcg/rat) or apomorphine (0.5 mg/kg), a mixed D1-/D2-agonist, also inhibited the frequency and amplitude of cortical and hippocampal EEG. A significantly higher inhibition of electrical activity was observed following concomitant administration of B-HT 920 (0.1 mg/kg) and SKF 38393 (5.0 mg/kg) in comparison with the effect of each drug alone. Rimcazole (6.0 mg/kg) increased the frequency of cortical and hippocampal firing. Amplitude of cortical firing was enhanced but not of hippocampal EEG following administration of rimcazole. Rimcazole blocked the effect of SKF 38393 (5.0 mg/kg) and apomorphine (0.5 mg/kg) but not of B-HT 920 (0.5 mg/kg) on cortical and hippocampal EEG, respectively. The above data suggests a modulatory effect of D1-receptor activation on the inhibitory effect of D2-receptor stimulation in cortex as well as hippocampus and the blockade by rimcazole of the effect of D1-DA receptor agonist in these areas.