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Biomedical subjects

S Kaur

Publications and source records attributed to S Kaur.

At least 109 records · Page 6Linked to original sources

Transformation-mediated developmental mutants of Glomerella graminicola.

Glomerella graminicola transformants were generated by insertional plasmid mutagenesis. Five transformants with developmental mutant phenotypes that segregated in crosses as single-gene mutations were selected. In four transformants, the mutant phenotype cosegregated with the inserted plasmid DNA. At least three of the mutants result from gene disruption, as demonstrated by recovery of the mutant phenotypes after transformation of wild type with "rescued" plasmid DNA. Whereas the wild type produces uninucleate, salmon-colored conidia, the tagged mutant M26 has white conidia. After exposure to either UV light or singlet oxygen, the percentage germination of M26 conidia is reduced compared to that of the wild-type conidia, indicating that the spore pigment confers protection from UV light and singlet oxygen. The tagged mutant T30 has weakened walls; falcate conidia rupture and hyphae have swollen regions unless the medium is amended with an osmoticum. The tagged mutant T29 has falcate conidia with one to four nuclei; wild-type falcate conidia are uninucleate. Two other mutants, one which grows slowly and one having conidia with increased curvature, are also described.

Ascomycota↗

Immunohistochemical expression of c-erbB-2 oncoprotein and EGF-R in pre- and postmenopausal breast cancer.

Tissues from 40 cases each of premenopausal and postmenopausal breast cancer were studied immunohistochemically for epidermal growth factor receptor (EGF-R) and c-erbB-2 oncoprotein. In the premenopausal group, immunopositivity for c-erbB-2 was 15% and for EGF-R 22.5%, whereas in the postmenopausal group, 45% of cases were positive for c-erbB-2 and 42.5% for EGF-R. The difference in immunoexpression of c-erbB-2 between the two groups was significant. A significant correlation was observed between the concomitant expression of c-erbB-2 as well as EGF-R and lymph node involvement. Furthermore, an association was found between c-erbB-2 positivity and histological grading of the tumour. It is interesting that the pattern of the investigated parameters indicates the difference in the pathological events of pre- and postmenopausal breast cancer.

Adult↗

An easy method for detection of rheumatic antigen(s) in rheumatic fever/rheumatic heart disease patients by dot-ELISA.

BACKGROUND: Various monoclonal antibodies developed against human B cell alloantigen have different positivity in different population groups around the world. Thus, monoclonal antibody D8/17, found to be 100% specific for rheumatic fever/rheumatic heart disease (RF/RHD) patients from New York, identified only 62% to 68% in the north Indian population. PATIENTS AND METHODS: A battery of monoclonal antibodies against B cell alloantigen was developed in Indian RF/RHD patients. A total of 50 patients and 25 controls were studied. RESULTS: These antibodies, named PG-12A, -13A and -20A, demonstrate more specificity in north Indian patients. In dot-ELISA, these antibodies correctly show the presence of the marker in 84% of RHD and 90% of recurrence of rheumatic activity patients. CONCLUSIONS: It is suggested that different alloantigens are expressed in the north Indian population. This standardized dot-ELISA is low cost and simple to use, and has a very high percentage of sensitivity, specificity and positive predictive value for this population.

Antibodies, Monoclonal↗

MK 801 reverses haloperidol-induced catalepsy from both striatal and extrastriatal sites in the rat brain.

The present study investigated whether the anticataleptic effect of (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine (MK 801) is due to a blockade of N-methyl-D-aspartate (NMDA) receptors in striatal output pathways as well as in the striatum. Catalepsy induced by haloperidol (1 mg/kg i.p.) was more effectively reversed by MK 801 (0.2 mg/kg i.p.) given 10 min prior to rather than 45 min after the neuroleptic. Catalepsy evoked by intrastriatal haloperidol (7 micrograms/side) was also strongly attenuated by systemic MK 801 (0.2 mg/kg i.p.). We also found that the cataleptic rigidity induced by systemic haloperidol (1 mg/kg i.p.) could be prevented by prior injection of MK 801 into the striatum (10 micrograms), subthalamic nucleus (5 micrograms), entopeduncular nucleus (5 micrograms) or substantia nigra pars reticulata (1 microgram). These results suggest that the anticataleptic action of systemic MK 801 versus haloperidol, is due to the blockade of NMDA receptors in the striatum as well as in striatal output circuits through the subthalamus. However, systemic MK 801 (0.2 mg/kg i.p.) was without effect on the catalepsy elicited by injecting muscimol into the globus pallidus (25 ng) or ventromedial thalamus (50 ng). These findings suggest that MK 801 has little influence over thalamic excitatory feedback to the cortex, and that hypoactivity of the pallidum may not be a prerequisite for hyperactivity in the subthalamus.

Animals↗

GABA in locus coeruleus regulates spontaneous rapid eye movement sleep by acting on GABAA receptors in freely moving rats.

The aminergic neurons in the locus coeruleus are known to cease firing during rapid eye movement sleep. Since electrical stimulation of locus coeruleus reduced, while carbachol stimulation increased rapid eye movement sleep and gamma-aminobutyric acid (GABA) neurons as well as terminals are present in the locus coeruleus, we hypothesized that GABA may be involved for cessation of locus coeruleus neuronal firing during rapid eye movement sleep. Under surgical anaesthesia male Wistar rats (250-300 g) with bilateral guide cannulae targeting locus coeruleus were prepared for chronic sleep-wakefulness recording. Electroencephalogram (EEG), electrooculogram (EOG), electromyogram (EMG) were recorded in normal, after 250 nl saline and after picrotoxin (250 ng in 250 nl) injection bilaterally into the locus coeruleus. The results showed that mean duration per episode of rapid eye movement sleep was significantly reduced, although its frequency of generation/h was not significantly affected. This study suggests that GABA in locus coeruleus is involved in tonic regulation of rapid eye movement sleep and the action is mediated through GABAA receptor.

Animals↗

Stimulation of basal and L-DOPA-induced motor activity by glutamate antagonists in animal models of Parkinson's disease.

In parkinsonism, glutamate pathways within the basal ganglia become overactive, leading to the suggestion that glutamate antagonists might possess antiparkinsonian qualities. This report examines the motor properties of antagonists of NMDA and AMPA-type glutamate receptors, as well as some inhibitors of glutamate release, in animal models of idiopathic Parkinson's disease. High affinity NMDA open-channel blockers (e.g. MK 801, phencyclidine), are highly potent antagonists with inconsistent antiakinetic and strong myorelaxant activity. Other compounds are better tolerated and are capable of relieving immobility and muscular rigidity by themselves (e.g. 1-aminoadamantanes, polyamine site antagonists, kappa agonists, riluzole). Yet others do not restore movements alone (e.g. dextromethorphan, ketamine), but may interact with and strengthen the antiparkinsonian action of L-DOPA (e.g. competitive NMDA and AMPA antagonists, lamotrigine). They may do this by potentiating dopaminergic behaviours mediated by D1 or D2 receptors, or by some other mechanism.

Animals↗

Differential effects of intrastriatal and intranigral injections of glutamate antagonists on motor behaviour in the reserpine-treated rat.

A variety of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonists, and the antiepileptic drug lamotrigine, were examined for their ability to restore locomotion and other behaviours when injected stereotaxically via indwelling cannulae into the striatum or substantia nigra pars reticulata of rats rendered akinetic with reserpine (5 mg/kg i.p. 24 h beforehand). Only the competitive N-methyl-D-aspartate antagonists 3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate and R-DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoate stimulated locomotion from the striatum, whereas 2-amino-phosphonopentanoic acid, the N-methyl-D-aspartate channel blockers dizocilpine maleate and phencyclidine, and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid antagonist 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(f)-quinoxaline-dione, were additionally effective in the substantia nigra pars reticulata. The N-methyl-D-aspartate glycine site antagonist (RS)-3-amino-1-hydroxypyrrolidin-2-one and the glutamate release inhibitor lamotrigine failed to restore locomotion at these sites, and the N-methyl-D-aspartate polyamine site antagonist eliprodil was ineffective in the substantia nigra pars reticulata, although all compounds tested (except lamotrigine) induced orofacial, head and/or limb movements to some degree. Except for 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(f)-quinoxaline-dione, locomotion was accompanied dose-dependently by increasingly pronounced ataxia and postural abnormalities. These results show that the monoamine-depleted substantia nigra pars reticulata has a broader spectrum of responsitivity to the antiparkinsonian actions of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid antagonists than does the striatum, and that the harmful as well as the beneficial effects of these compounds on locomotion arise from these two structures.

Animals↗

Diminution in parietal cell number in experimental portal hypertensive gastropathy.

Portal hypertensive gastropathy is a well-established clinical entity. Although stimulated acid secretion has been found to be decreased in portal hypertensive rats, the parietal cell mass has not been studied. Portal hypertension was produced in Wistar rats either by partial portal vein ligation (N = 16) or by common bile duct ligation (N = 23) and confirmed by intrasplenic pulp pressure measurement. The parietal cells were isolated and counted in a Neubaur hemacytometer. The parietal cell count was also done in microscopic sections at direct histopathological examination. The viable, isolated parietal cell count and parietal cell count on histopathological examination were significantly decreased in partial portal vein ligated rats. Similarly, in common bile duct ligated rats, the parietal cell count was decreased as compared to sham-operated rats. In experimental portal hypertensive gastropathy there is a decrease in parietal cell number.

Animals↗

Affinity selection and mass spectrometry-based strategies to identify lead compounds in combinatorial libraries.

The screening of diverse libraries of small molecules created by combinatorial synthetic methods is a recent development which has the potential to accelerate the identification of lead compounds in drug discovery. We have developed a direct and rapid method to identify lead compounds in libraries involving affinity selection and mass spectrometry. In our strategy, the receptor or target molecule of interest is used to isolate the active components from the library physically, followed by direct structural identification of the active compounds bound to the target molecule by mass spectrometry. In a drug design strategy, structurally diverse libraries can be used for the initial identification of lead compounds. Once lead compounds have been identified, libraries containing compounds chemically similar to the lead compound can be generated and used to optimize the binding characteristics. These strategies have also been adopted for more detailed studies of protein-ligand interactions.

Binding, Competitive↗

alpha-Glucosidase activity in the rat epididymis under different physiological conditions.

The estimation of alpha-glucosidase activity in semen is widely used as a marker of epididymal function. In the present studies, glucosidase activity was evaluated in the different segments of the rat epididymis under various physiological conditions. In addition, the effect of two known male antifertility agents, gossypol and alpha-chlorohydrin, on enzyme activity was evaluated. Enzyme activity was absent from the epididymis of rats aged 10 and 20 days but became detectable at 30 days of age when the adult pattern of distribution (highest activity in the caput epididymis) was established. Enzyme activity was reduced significantly in all segments of the epididymis at 7 days after castration and a significant decrease in activity was also observed following the administration of either gossypol or alpha-chlorohydrin. These findings are consistent with a role for alpha-glucosidase in sperm maturation in the epididymis.

Aging↗

Confidentiality and death.

The duty of confidentiality in the normal doctor-patient relationship is well recognized. However, the duty of confidentiality between the pathologist who performs the autopsy and the requesting authorities and the next-of-kin is not as clearly spelt out. This article discusses the problems faced by the pathologist with regards to hospital and medico-legal autopsies in Malaysia. A proposed ethical guideline is included on how to deal with peculiar issues regarding confidentiality and the pathologist.

Autopsy↗

Antimutagenic potential of ellagic acid isolated from Terminalia arjuna.

Antimutagenic potential of a fraction isolated from Terminalia arjuna has been evaluated in TA98 and TA100 strains of Salmonella typhimurium against direct and indirect-acting mutagens. The fraction was quite effective against S9-dependent 2AF while it showed moderate effect against NPD. The fraction was analyzed to be ellagic acid.

Antimutagenic Agents↗

Y-chromosome polymorphism in species B and C of Anopheles culicifacies complex.

Isofemale cultures of wild-caught Anopheles culicifacies collected from 11 localities representing different ecoepidemiological zones on the mainland of India were identified by examining both F1 male larval mitotic karyotypes and polytene chromosomes of half-gravid F1 adult females. All cultures identified as species A by polytene chromosome examination had submetacentric Y chromosomes. In species B and C, some isofemale cultures had acrocentric Y chromosomes, whereas others were submetacentric. The study revealed the existence of a Y chromosome polymorphism in species B and C; consequently, male mitotic karyotypes are of limited use for differentiating members of the An. culicifacies complex.

Animals↗

Motor effects of lamotrigine in naive and dopamine-depleted mice.

Lamotrigine (3,5-diamino-6-[2,3-dichlorphenyl]-1,2,4-triazine) has been hypothesised to possess antiparkinsonian activity, by inhibiting the release of glutamate from basal ganglia neurones. This study therefore examined the motor effects of lamotrigine in naive and reserpine-treated mice and its interactions with dopaminergic agonists. In normal mice, lamotrigine (5-80 mg/kg i.p.) decreased spontaneous locomotor activity with high doses (> or = 40 mg/kg) causing moderately severe impairment to posture and gait. In mice treated 24 h beforehand with reserpine (5 mg/kg i.p.), lamotrigine (5-40 mg/kg i.p.) had no effect on akinesia by itself and did not alter the locomotion induced with the selective dopamine D1 receptor agonist 2,3,4, 5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepine hydrochloride (SKF 38393, 30 mg/kg i.p.). By contrast, motor responses to the dopamine D2 receptor-selective agonist N-n-propyl-N-phenylethyl-p-(3-hydroxyphenyl)ethylamine (RU 24213, 5 mg/kg s.c.) and to the dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA, 150 mg/kg i.p. in the presence of benserazide, 100 mg/kg i.p.), were significantly potentiated by 10 and 40 mg/kg i.p. lamotrigine respectively. It is suggested that lamotrigine may enhance the antiakinetic action of L-DOPA in parkinson-like mice by increasing motor responding mediated by dopamine D2 but not dopamine D1 receptors. This interaction profile of lamotrigine with dopamine D1 and D2 receptor mechanisms is opposite to what one sees with antagonists of glutamate receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Urinary excretion of renal brush border membrane enzymes in leprosy patients--effect of multidrug therapy.

Renal function at the brush border membrane level has been studied using characteristic enzymes, such as alkaline phosphatase, leucine-aminopeptidase and gamma-glutamyl transpeptidase. Urinary enzyme studies were performed using leprosy patients, classified on the basis of bacteriological index (BI>3; n=20, BI<3; n=12, BI-ve; n=10) and compared with control subjects (n=10). The role of enzymuria in monitoring WHO-recommended multidrug therapy (MDT) has been evaluated in these patients. A significant increase in the enzyme activities (p<0.01), as well as significant (p<0.01) proteinurea in 24-hour urine samples of both the smear positive groups (BI>3, BI<3) prior to therapy compared to control subjects, indicates proximal tubular functional impairment at brush border membrane level. In the smear negative (BI-ve) group, no significant difference was observed in enzyme activities as compared with the control group. In a follow-up study (BI>3;n=13, BI<3; n=4) the activities of all the enzymes decreased significantly in all the groups when compared to a corresponding untreated group. The follow-up study was not carried out on the smear negative group. The surprising finding was the differential behaviour of r-glutamyl transpeptidase, whose activity increased significantly (p<0.01) even after therapy in BI>3 group when compared with untreated patients. However in a detailed work-up including hepatic and renal function tests, the serum biochemistry was found to be normal both before and after therapy. Urinary excretion of brush border enzymes seems to be related to bacterial load, and their potential in studying the effect of MDT remains unclear.

Alkaline Phosphatase↗

Performance characteristics and results of a large-scale screening program for viral hepatitis and risk factors associated with exposure to viral hepatitis B and C: results of the National Hepatitis Screening Survey. National Hepatitis Surveillance Group.

Chronic viral hepatitis frequently goes undetected until cirrhosis develops. Although the effect of interferon on the natural history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in asymptomatic persons is unknown, treatment may modify the course of the infection, producing cures in some. In September 1992, screening for HBV and HCV was offered in 40 centers throughout the United States. Demographic features, potential risk factors, and symptoms were studied. Blood samples were obtained for the determination of serum alanine aminotransferase levels and for markers of HBV and HCV infection. Thirteen thousand nine hundred ninety seven subjects were screened. The prevalence of infection with HBV or HCV was 24.8% (HBV 17.8%; HCV 7.0%; and both 2.8%). Hepatitis B and C disease was present in 0.7% and 4.4% of the population, respectively. Risk factors for HBV and HCV infection were similar in: blood transfusions, hemodialysis, IV drug use, and sex with an IV drug user. For HBV infection, sex with multiple partners, increasing age, and birth in South East Asia or Africa were additional risk factors. The cost to find a case of HCV infection is less than the costs for finding many other treatable diseases. Screening for HBV, though more costly, is reasonably efficient, and simultaneous screening for HBV and HCV provides greater efficiency. It is practical to consider screening for HBV and HCV in the United States, particularly if any risk factor is present. Improved treatment strategies will make screening even more cost effective.

Adult↗