Search PubMed⌕ Search

Biomedical subjects

A Gupta

Publications and source records attributed to A Gupta.

At least 289 records · Page 16Linked to original sources
PubMed2000

Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 kinase.

BACKGROUND: The p35-Cdk5 kinase has been implicated in a variety of functions in the central nervous system (CNS), including axon outgrowth, axon guidance, fasciculation, and neuronal migration during cortical development. In p35(-/-) mice, embryonic cortical neurons are unable to migrate past their predecessors, leading to an inversion of cortical layers in the adult cortex. RESULTS: In order to identify molecules important for p35-Cdk5-dependent function in the cortex, we screened for p35-interacting proteins using the two-hybrid system. In this study, we report the identification of a novel interaction between p35 and the versatile cell adhesion signaling molecule beta-catenin. The p35 and beta-catenin proteins interacted in vitro and colocalized in transfected COS cells. In addition, the p35-Cdk5 kinase was associated with a beta-catenin-N-cadherin complex in the cortex. In N-cadherin-mediated aggregation assays, inhibition of Cdk5 kinase activity using the Cdk5 inhibitor roscovitine led to the formation of larger aggregates of embryonic cortical neurons. This finding was recapitulated in p35(-/-) cortical neurons, which aggregated to a greater degree than wild-type neurons. In addition, introduction of active p35-Cdk5 kinase into COS cells led to a decreased beta-catenin-N-cadherin interaction and loss of cell adhesion. CONCLUSIONS: The association between p35-Cdk5 and an N-cadherin adhesion complex in cortical neurons and the modulation of N-cadherin-mediated aggregation by p35-Cdk5 suggests that the p35-Cdk5 kinase is involved in the regulation of N-cadherin-mediated adhesion in cortical neurons.

Cadherins↗
PubMed2000

Analysis of Contact Interactions between a Rough Deformable Colloid and a Smooth Substrate.

A model was developed for the effect of van der Waals interactions between a rough, deformable, spherical colloid and a flat, smooth, hard surface in contact. The model demonstrates the significant effect of colloid roughness on removal force. Small changes in colloid roughness produce large changes in the predicted removal force. Several authors attribute discrepancies in the observed interaction force between particles and surfaces to colloid roughness, and our model supports their hypotheses. Experimental data documenting the force required to remove colloids of polystyrene latex from silica substrates in aqueous solution were collected during AFM studies of this system. When colloid roughness exists, as is the case in this work, our model bounds the observed removal force. The predicted range of removal forces is in better quantitative agreement with our removal force data than are forces predicted by classical DLVO theory. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex.

A puzzling feature of the neocortex is the rich array of inhibitory interneurons. Multiple neuron recordings revealed numerous electrophysiological-anatomical subclasses of neocortical gamma-aminobutyric acid-ergic (GABAergic) interneurons and three types of GABAergic synapses. The type of synapse used by each interneuron to influence its neighbors follows three functional organizing principles. These principles suggest that inhibitory synapses could shape the impact of different interneurons according to their specific spatiotemporal patterns of activity and that GABAergic interneuron and synapse diversity may enable combinatorial inhibitory effects in the neocortex.

Action Potentials↗
PubMed2000

Effect of quinalphos and cypermethrin exposure on developing blood-brain barrier: role of nitric oxide.

Effect of low-level exposure of quinalphos (QP) and cypermethrin (CP) on the blood-brain barrier (BBB) permeability to macromolecular tracers, Evans blue (EB) and horseradish peroxidase (HRP) was studied in developing rat pups. Ten-day-old rat pups were daily exposed to QP and CP at a dose of approximately 1/50th of adult LD50 through oral intubation, upto postnatal day 17 (PND). Functional integrity of the BBB was assessed by measuring the brain uptake index (BUI) of HRP and by visually grading the brains of control and treated rat pups for the staining of EB. Our results have demonstrated a significant increase in the BUI for HRP (204 and 254%) and have also shown a significant amount of EB staining in QP and CP exposed brains, respectively, as compared to the age-matched controls. Studies carried out with the nitric oxide synthase (NOS) inhibitor L-NAME (30 mg/kg, i.p., on alternate days from PND 10-17) have provided significant protection against the QP-induced increase in the BBB permeability, suggesting the possible involvement of NO in the barrier disruption. Microvessel acetylcholinesterase activity was also inhibited (53%, P<0.001) in QP-exposed rat pups only, with no change observed in CP-exposed microvessels. However, membrane fluidity was found to be decreased in both QP (18%, P<0.05) and CP (15%, P<0.05) exposed microvessels compared to controls. It is evident from the study that QP and CP exposure during early postnatal period causes significant impairment in the development and maturation of the BBB that may have adverse consequences on the normal brain functioning with long-term neurotoxic effects.

Journal Article↗
PubMed2000

Carotid stenting in patients older than 65 years with inoperable carotid artery disease: a single-center experience.

Carotid angioplasty and stenting to treat extracranial carotid stenosis is an alternative (as yet not widely accepted) to high-risk surgery, but its safety and efficacy are little known, especially in elderly patients. We reviewed our 3-year experience of treating 100 elderly patients (> 65 years old) considered to be inoperable (76 men, 24 women, mean age 76+/-10 years, mean follow-up 18+/-9.2 months) and present two case histories. Most (85%) were symptomatic (transient ischemic attacks in 60, stroke in 25); 80 had concomitant coronary artery disease (severe in 30 [defined by > 70% stenosis in two or more epicardial coronary arteries or the left main coronary artery]) and 25 had severe left ventricular dysfunction (ejection fraction < or =20%). The procedure was technically successful in all patients; there was one major stroke and no patient died. Postprocedure, 15% had minor complications: reversible neurological deficit (5%), pulmonary edema (3%), prolonged hypotension (3%), vascular access complications (3%), and neck hematoma (1%). Over 90% of patients were discharged home within 24 hr.

Age Factors↗
PubMed2000

omega-3 fatty acids decrease endothelial adhesion of human colorectal carcinoma cells.

BACKGROUND: Diets rich in omega-3 fatty acids have been shown to decrease both the initiation and promotion of colon carcinogenesis although their effect on hepatic metastasis formation is less well understood. Since adhesion of human colorectal carcinoma (HCRC) cells to hepatic endothelial cells is an important step in the metastatic cascade, the effect of membrane omega-3 fatty acid alterations on endothelial cell adhesion was studied. MATERIALS AND METHODS: CX-1 cells, a moderately differentiated HCRC cell line known to produce hepatic metastases in an athymic mouse intrasplenic injection model, were used. Cells were grown in omega-3 fatty acid-enriched medium and membrane-free fatty acid modifications confirmed with gas chromatography. Both human umbilical vein and hepatic sinusoidal endothelial cells were used in the binding assays. Adhesion assays were performed in a standard fashion using (51)Cr-labeled cells to tumor necrosis factor (TNF)-stimulated endothelial cell monolayers. Immunohistochemical analysis was performed for sialyl-Lewis(x), the receptor involved in endothelial adhesion on the surface of control and fatty acid-modified cells. RESULTS: Gas chromatographic analysis confirmed membrane fatty acid modification of CX-1 cells by growth in docosahexanoic acid (omega-3) (4.761 nmol/10(6) cells vs 0.057 nmol/10(6) cells for controls). Binding of CX-1 to both human umbilical vein and hepatic sinusoidal endothelial cells decreased from 38.4 +/- 0.44 to 11.58 +/- 0.87% (P < 0.01). Immunocytochemical analysis showed a decrease in sialyl-Lewis(x) expression with omega-3 treatment. CONCLUSIONS: These data indicate that omega-3 fatty acids may also be protective against the formation of hepatic metastases. The mechanism for this may be decreased endothelial cell adhesion which in turn may be due to decreased expression of the endothelial receptor sialyl-Lewis(x).

Animals↗
PubMed2000

Gag-derived proteins of HIV-1 isolates from Indian patients: cloning, expression, and purification of p24 of B- and C-subtypes.

A simple and efficient method for hyperexpression in Escherichia coli and purification of capsid protein, p24, of human immunodeficiency virus type 1 (HIV-1) of both B- and C-subtypes is described. DNA-encoding p24 of C-subtype was cloned from C-subtype gag sequence which was obtained by PCR amplification using DNA extracted from peripheral blood mononuclear lymphocytes (PBMLs) of an HIV-1-infected patient from India. DNA-encoding p24B protein was amplified directly by two-step PCR using genomic DNA obtained from PBMLs of an HIV-infected individual. A T7 promoter-based expression system was optimized for hyperexpression of p24 in the soluble form. Both p24 (B- and C-subtype) were purified to near homogeneity using conventional chromatographic techniques. Purification of p24 (C subtype) was described for the first time with yield of 53 mg from 1 liter of culture. The yield of p24 (B-subtype) was 67 mg from 1 liter of culture, which was severalfold better than reported earlier. The immunoreactivity of both types of p24 to sera from HIV-infected individuals was comparable. This report describes a simple, highly efficient, and reproducible method for obtaining large quantities of highly pure p24 of both B- and C-subtype, which can be used for structural, biochemical, and immunological characterization and, eventually, for diagnostic and prognostic applications.

Amino Acid Sequence↗
PubMed2000

Early versus late-onset idiopathic focal segmental glomerulosclerosis.

Glomerular diseases in children, although similar in histological appearance to those in adults, may have a better prognosis. There is much controversy regarding the prognostic factors in idiopathic focal segmental glomerulosclerosis (FSGS), especially the comparative prognosis of children and adults. A comparative analysis was carried out of 36 consecutive biopsy-proven cases of idiopathic FSGS presenting early in life ['early onset' as seen in children < or =12 years (group I)] and 36 cases presenting later ['late-onset' as seen in older children >12 years and adults (group II)]. Patients were compared for clinical, biochemical, and histopathological features, as well as disease outcome. A significantly higher prevalence of hypertension (P=0.002) and microscopic hematuria was seen in group II (P=0.02). There were no differences between the two groups in glomerular filtration rates corrected for body surface area at initial presentation (92+/-11 ml/min/1.73 m2 vs. 94+/-14 ml/min/1.73 m2). Patients with 'late-onset' FSGS had a significantly higher number of glomeruli with segmental sclerosis (P=0.007), more mesangial matrix expansion (P=0.009), greater mesangial cellularity (P=0.003), and significantly higher blood vessel involvement (P=0.03) than those with 'early onset' FSGS. There was a significantly higher response to steroids in group I (82.3%) than group II (36.4%) (P<0.02). At the end of the study period, 2 patients in group I and 11 in group II had developed persistent renal failure (P=0.01). Thus 'early onset' FSGS is more common in males, has significantly lower prevalence of hypertension and microscopic hematuria, with less-severe histopathological involvement, is more often steroid responsive, and has a better prognosis than 'late-onset' FSGS.

Adolescent↗
PubMed2000

Reliability of the sentinel node procedure in melanoma patients: analysis of failures after long-term follow-up.

BACKGROUND: The sentinel node (SN) concept assumes that early lymphatic metastases, if present, always are found first in the SN. The aim of this study was to determine the reliability of this procedure by establishing the success rate and number of failed procedures during a follow-up period of at least 2 years. METHODS: From August 1993 to November 1996, 204 consecutive patients with stage I and II cutaneous melanoma underwent SN biopsy by a triple technique. Preoperatively, all patients underwent (dynamic) lymphoscintigraphy. A gamma probe and blue dye helped localize the SN(s) during surgery, and these nodes subsequently were excised. These lymph nodes were step-sectioned and examined by routine and immunohistochemical staining. If the SN contained tumor cells, a lymphadenectomy was performed at a later date. RESULTS: The median follow-up time was 42 months. The success rate was 99%. Three patients developed a recurrence in the negative SN basin during follow-up, without simultaneous appearance of (locoregional) metastases. CONCLUSIONS: With a 99% success rate and a 1.5% rate of failed SN procedures (7% false-negative rate) after a median follow-up of 3.5 years, we concluded that the combined triple technique approach of detecting the SN was a reliable method to accurately identify and retrieve the SN.

Adolescent↗
PubMed2000

Stability studies on (99m)technetium(III) complexes with tridentate/monodentate thiol ligands and phosphine ('3 + 1 + 1' complexes).

The preparation and characterisation of 3 + 1 + 1 technetium complexes of the general formula [Tc(SES)(RS)(PMe2Ph)] (SES = tridentate dithiol ligand, E = S, O, NMe; RSH = monothiol ligand) at the n.c.a. level is described. The Tc(III) complexes are prepared in a one-step procedure starting from pertechnetate in yields of 85-95% of radiochemical purity. A comparison of their chromatographic data with the fully characterised 99Tc complexes indicate the identity of the investigated compounds. Stability studies show that the 99mTc complexes undergo some alteration in solution. They are oxidised to the 3 + 1 oxotechnetium (V) complexes and/or decompose in aqueous solution. In challenge experiments performed with glutathione, exchange of the monothiolato ligand occurs in the same manner as known for the 3 + 1 complexes.

Chromatography, High Pressure Liquid↗
PubMed2000

Cerebral antioxidant status and free radical generation following glutathione depletion and subsequent recovery.

This study was aimed to evaluate the oxidative damage, production of reactive oxygen species and the status of antioxidative defenses following cerebral GSH depletion induced by two classical depletors, diethylmaleate (DEM, 3 mmol/kg, i.p.) and phorone (PHO, 4 mmol/kg, i.p.). The treatment decreased (40-43%) brain glutathione levels at 2 h, followed by a partial recovery at 24 h. Cerebral glutathione depletion by these agents increased the levels of superoxide anion and hydroxyl radical at both the time intervals; however, hydrogen peroxide was high at 24 h only. It also produced a dramatic increase in the protein carbonyls at 2 h but not at 24h, without any significant effect on lipid peroxidation and conjugated diene levels. These rats showed a significantly lowered superoxide dismutase activity both at 2 h and 24 h of exposure, as compared to controls. Glutathione depletion enhanced catalase activity markedly at 2 h, followed by some recovery at 24 h. While Se-independent glutathione peroxidase (GPx) and glutathione S-transferase activities were increased at both 2 and 24 h time intervals, Se-dependent GPx and glucose-6-phosphate dehydrogenase were induced at 2 h only. Glutathione depletion decreased ceruloplasmin and vitamin E levels significantly at 2 h. However, ascorbic acid remained unaffected. It may be concluded that an acute cerebral glutathione depletion generates higher levels of reactive oxygen species, which may be responsible for oxidative modification of proteins. Some of these changes appear to recover soon after an activation of a variety of cellular antioxidant defense mechanisms and glutathione restoration. It appears that central nervous system is highly vulnerable to oxidative damage following a moderate glutathione depletion that may result from certain diseases or xenobiotic exposures.

Animals↗
PubMed2000

Supraglottic activity: evidence of vocal hyperfunction or laryngeal articulation?

False vocal fold (FVF) adduction and compression of the arytenoid cartilages to the petiole of the epiglottis in an anterior to posterior (A-P) direction have been thought to characterize voice disorders with abnormally increased muscle tension or effort, often termed hyperfunctional voice disorders. To further evaluate the association between hyperfunctional voice disorders and supraglottic activity, we compared the incidence of static and dynamic supraglottic activity in individuals with normal laryngeal mucosa, normal voice quality, and no voice complaints to two populations: subjects with vocal fold nodules and subjects with complaints of dysphonia without visible vocal fold lesions, glottal incompetence, or impairment of arytenoid cartilage motion ("hyperfunctional" group). Thirty-two subjects were assigned to one of these three groups (10 control, 12 nodule, and 10 hyperfunctional). Laryngeal movements were recorded using flexible videoendoscopy while a subject was performing speech tasks such as sustained phonation, syllable repetitions, sentence imitations, and conversation. Samples were randomized by subject and task and rated for presence or absence of A-P and FVF compression. Statistically significant group differences were found for FVF compression across speech tasks (chi-square, p<0.001). The control group had the smallest incidence (45%), nodule patients the next larger incidence (68%), and hyperfunctional patients the largest incidence (80%). Statistically significant group differences were found for A-P compression across speech tasks (chi-square, p<.05). The control group had the smallest incidence (74%), nodule patients the next larger incidence (78%), and hyperfunctional patients the largest incidence (92%). Statistically significant task differences were found for the presence of FVF compression in control subjects (chi-square, p<.005), hyperfunctional patients (chi-square, p<.025), and nodule patients (chi-square, p<.001), but not for A-P compression for any of the groups. A higher incidence of FVF compression was present for the speech tasks that included glottal stops. This context-specific variation in supraglottic activity suggested a dynamic component to FVF compression and also explained the high proportion of FVF compression in the control group. Each video sample was also rated for consistency of FVF or A-P compression to explore the static and dynamic nature of supraglottic activity. For samples on which raters agreed, A-P compression was typically present consistently, suggesting a static component, and FVF compression inconsistently, suggesting a dynamic component, for all three groups (chi-square, p<.001). These findings do not support previous suggestions that supraglottic activity may be a precursor to developing vocal fold nodules, as the nodule patients did not exhibit a higher incidence or consistency of A-P or FVF compression than patients with hyperfunctional voicing patterns in this study. Subjects in the hyperfunctional voice group were found to have static components of FVF and A-P compression. The presence of FVF compression in speech tasks that included glottal stops in the control group suggests an articulatory function at the laryngeal level.

Adolescent↗
PubMed2000

Association of human leucocyte-DR and DQ antigens in coeliac disease: a family study.

BACKGROUND AND AIMS: No family studies regarding the association of coeliac disease with the human leucocyte antigen (HLA)-DQ locus are available. Moreover, no HLA studies have been carried out in coeliac disease patients from India. The aim of this study was to study the HLA class II (DR and DQ) antigens in children with coeliac disease and in their first-degree relatives. METHODS: Fifteen children with coeliac disease and their first-degree relatives (birth parents of all the coeliac disease patients and fifteen siblings) were studied. A group of 123 healthy unrelated and ethnically matched subjects were used as controls. The HLA-DR and -DQ typing was carried out by a complement-dependent microlymphocytotoxicity assay. The transmission disequilibrium test was used for analysis of results. RESULTS: There was no association of coeliac disease with DR phenotypes. Ninety-three per cent of patients (14/15) carried the DQ2 allele. DQ2 was transmitted in 15 of 19 informative cases (transmission probability of 79%, chi2 6.368 with 1 df, nominal P=0.012 and P value corrected for multiple test=0.035). The haplotype relative risk associated with DQ2 was 5.71 (95% confidence interval 1.71-16.28). CONCLUSION: Coeliac disease in Indian children is predominantly associated with HLA-DQ2.

Adolescent↗
PubMed2000

Bipartite scaphoid with proximal pole osteonecrosis in a patient with Holt-Oram syndrome.

The Holt-Oram syndrome features a spectrum of upper limb abnormalities, including an abnormal shape of the scaphoid. Our report concerns a 19-year-old man with Holt-Oram syndrome and flattening and sclerosis of the proximal pole of a bipartite scaphoid. The initial ossification centre in the scaphoid was located distally at 8 years of age. By age 13, a pair of ossific centres were present. After an automobile accident at age 18, the proximal pole became sclerotic and then began to fragment over a 22-month period. Computed tomography confirmed the presence of two poles of the scaphoid and sclerosis and fragmentation of the proximal pole.

Adult↗