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Biomedical subjects

S Kaur

Publications and source records attributed to S Kaur.

At least 19 recordsLinked to original sources
PubMed1999

Colorectal liver metastasis thymidylate synthase staining correlates with response to hepatic arterial floxuridine.

We assessed whether intensity of colorectal liver metastasis staining with the thymidylate synthase (TS) antibody TS106 predicted response to hepatic arterial infusion (HAI) of floxuridine chemotherapy. Liver metastasis biopsies were taken during laparotomy for hepatic arterial cannulation and stained using the TS106 monoclonal antibody. Staining intensity was designated at histological examination by two independent assessors as either "high" or "low." Patients were treated by HAI, and liver metastasis response was assessed by comparison of computed tomography scan tumor volume before and after 4 months of treatment. A significant correlation (Fisher's exact test, P = 0.01) was noted between partial response to HAI and TS106 staining intensity in patients with colorectal liver metastases. Seventy-five percent of patients with evidence of a partial response had low TS staining compared with 29% of nonresponders. There was a significant difference (Fisher's exact test, P = 0.01) in the proportion of low (9 of 16) compared with high (3 of 20) TS staining tumors in which a partial response occurred. There was no significant difference (logrank test, P = 0.4) in survival from hepatic cannulation and HAI treatment of high (median, 322 days; interquartile range, 236-411) compared with low (median, 335 days; interquartile range, 301-547) TS staining patients. This study demonstrates an inverse correlation between TS immunohistochemical staining intensity in colorectal liver metastases and response to HAI. The results suggest that a prospective assessment of TS staining intensity in colorectal liver metastases would be useful to determine whether this method can be used to define patients who will benefit from HAI chemotherapy.

Aged↗
PubMed1998

Antimutagenicity of hydrolyzable tannins from Terminalia chebula in Salmonella typhimurium.

A tannin fraction (TC-E) from the dried fruit pulp of Terminalia chebula was obtained by successfully extracting with 95% ethyl alcohol and ethyl acetate. TC-E was subjected to silica gel chromatography which yielded four fractions, viz., TC-EI, TC-EII, TC-EIII and TC-EIV. Thin layer chromatography (TLC) and 13C-NMR revealed that TC-EI was gallic acid (GA) derivative while the other fractions were tannin in nature. TC-E and its fractions were evaluated for their antimutagenic potential against two direct-acting mutagens, 4-nitro-o-phenylenediamine (NPD) and 4-nitroquinoline-N-oxide (4NQNO), and S9-dependent mutagen, 2-aminofluorene (2AF) in TA98 and TA100 strains of Salmonella typhimurium. The study revealed that the extract (TC-E) and its fractions were highly significant against S9-dependent mutagen, 2AF. The effect was found to be more or less corresponding with the nature of the fractions, as the monomeric TC-EI (a GA derivative) was least effective as compared to other fractions which were oligomeric, and the order of their effectiveness as per their IbD50 value being TC-EIV (8.9 micrograms)>TC-EIII (17.8 micrograms)>TC-EII (45 micrograms)>TC-EI (320 micrograms) in TA98; TC-EIV being 40 times more effective than TC-EI in inhibiting his+ revertants. A similar effect was noticed in TA100 too, where TC-EI was the least effective and TC-EII had the maximum effect. A similar result was noticed when the antimutagenicity of GA (a monomeric) was compared with tannic acid (TA, an oligomeric). However, chebula tannins were found to be partly effective against NPD but not at all effective against 4NQNO.

Antimutagenic Agents↗
PubMed1998

The granulin/epithelin precursor abrogates the requirement for the insulin-like growth factor 1 receptor for growth in vitro.

3T3 cells null for the type 1 insulin-like growth factor receptor are refractory to stimulation by a variety of purified growth factors that are known to be required for the stimulation of other 3T3 cells. However, these cells, known as R- cells, grow in serum-supplemented medium and also in media conditioned by certain cell lines. We report here the purification of a growth factor that stimulates DNA synthesis (and growth) of R- cells. The growth factor, purified to homogeneity by SDS-polyacrylamide gel electrophoresis, was identified as the granulin/epithelin precursor by an accurate determination of the masses of endoproteinase Lys-C peptides using matrix-assisted laser desorption ionization mass spectrometry, followed by a data base search. The granulin/epithelin precursor is a little known growth factor, secreted by a variety of epithelial and hemopoietic cells. It is at present the only purified growth factor that can stimulate the growth of mouse embryo fibroblasts null for the type 1 insulin-like growth factor receptor.

3T3 Cells↗
PubMed1998

Ethnic differences in expression of susceptibility marker(s) in rheumatic fever/rheumatic heart disease patients.

The ability of monoclonal antibodies (MAb) against a human B lymphocyte alloantigen has been suggested to discriminate between rheumatic fever "susceptible" individuals and persons with a lower risk of developing RF. However, while such MAb have been reported to identify a majority of RF/RHD patients in some populations, a reduced discriminatory ability has been observed in others. Antigenic variation in the RF marker(s) may exist among ethnic groups which reduce the discriminatory ability of these monoclonal antibodies. We developed MAb using B lymphocytes from RF patients of North Indian ethnic origin. In this same population we compared the new MAb (PGI/MN II) with a previously described MAb of Caucasian ethnic origin (D8/17). In three groups: acute rheumatic fever patients (no evidence of previous attacks of rheumatic fever), patients with chronic rheumatic heart disease and normal controls from the same population, we found a greater discriminating ability of PGI/MNII MAb to identify Indian RF/RHD patients than with the D8/17 MAb. Further, sixty percent of 142 siblings of the RF/RHD patients were "positive" when tested with PGI/MN II. The data from these studies suggest that before such MAb can be used for identification of RF "susceptibles" in public health programs, variation among ethnic populations must be assessed.

Adolescent↗
PubMed1998

Alterations in early biochemical events following T cell activation in leprosy patients.

The early events of activation and cytokine profiles (IL-2, 4, and 6) were studied in lymphocytes of paucibacillary (TT/BT) and multibacillary (BL/LL) leprosy patients after stimulation with PMA/A23187 and Mycobacterium leprae antigen (PGL-1). Lymphocytes from BT/TT patients showed proliferation in response to both PMA/A23187 and PGL-1 compared to BL/LL. The levels of early activation signaling molecules such as IP3, calcium, and protein kinase C (PKC) in the particulate fraction were found to be elevated in BT/TT and BL/LL patients and showed a further significant increase after stimulation with PMA/A23187 in BT/TT patients. PGL-1 marginally increased the IP3 levels in BT/TT patients, whereas in BL/LL patients, it had no effect. The levels of IL-2 were enhanced in lymphocytes of BT/TT leprosy patients and were further augmented by PPD and PGL-1, while the levels of IL-4 and IL-6 were increased in LL/BL lymphocytes and further augmented by PGL-1. Thus PGL-1 seems to be a major culprit in inducing the TH2-type cytokine response observed in lepromatous leprosy patients.

Antigens, Bacterial↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗