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Biomedical subjects

S K Gupta

Publications and source records attributed to S K Gupta.

At least 343 records · Page 19Linked to original sources

Comparative evaluation of two indigenously developed tests for rapid detection of group-A streptococci directly from throat swabs.

The efficacy of two indigenously developed rapid tests, latex agglutination and antibody capture assay (a colour immunochromatographic assay) to detect group A Streptococcus pyogenes (GAS) was evaluated in comparison with the traditional culture method ('Gold Standard') in both asymptomatic children (1500) and symptomatic patients (233). Throat swabs were taken in duplicate and rapid tests performed on one swab and culture on the other. Both latex agglutination and antibody capture assays showed a sensitivity of 100 per cent and specificity of > 98 per cent as compared to culture and isolation in symptomatic patients. However, among asymptomatic carriers sensitivity of 100 per cent and 87.5 per cent and specificity > 95 per cent were observed for latex agglutination and antibody capture assays respectively. Latex agglutination showed no false negative results and sensitivity was not affected by low beta-haemolytic counts in asymptomatic children. The rapid tests described here will help in the detection and thereby the management of GAS infection.

Adolescent↗

Mammalian retinal pigment epithelial cells in vitro respond to the neurokines ciliary neurotrophic factor and leukemia inhibitory factor.

We examined whether primary cultures of rat retinal pigment epithelial (RPE) cells and RPE cells of an immortalized rat cell line, BPEI-1, would be responsive to the neurokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF), which are known to be potent trophic factors for neuronal cells. Primary RPE cell cultures were characterized by indirect immunofluorescence and exhibited positive immunoreactivity for RET-PE2, a monoclonal antibody that recognizes RPE cells, and for the intermediate filaments cytokeratin and vimentin. The survival of cultured RPE cells in serum-free defined medium in the presence of CNTF or LIF was investigated during a 0- to 5-day period. Both CNTF and LIF, at concentrations of 1-50 ng/mL (4-200 pM), markedly enhanced RPE cell survival. Bromodeoxyuridine labelling of RPE cells revealed an increased mitotic activity in cell cultures treated with either CNTF or LIF in comparison to untreated serum-free cultures. Increases in cell survival and proliferation after neurokine treatment were also observed with the BPEI-1 cell line. However, in comparison to the primary RPE cultures, LIF was more effective than CNTF in promoting survival of the cell line over a 5-day treatment period. These studies demonstrate that the neurokines CNTF and LIF are potent trophic factors for mammalian RPE cells in vitro and may serve as candidate therapeutic agents in degenerative conditions that affect the retina and RPE.

Animals↗

Dose-dependent response of central dopaminergic systems to metoclopramide in mice.

Metoclopramide (5 to 40 mg/kg, i.p.) induces catalepsy and antagonised apomorphine induced cage climbing behaviour in mice. This further indicate its postsynaptic striatal and mesolimbic D 2 dopamine (DA) receptor blocking activity. Metoclopramide at 1.25 and 2.5 mg/kg, i.p. induced stereotyped cage climbing behaviour in mice. Pretreatment with haloperidol and alpha-methyl-p-tyrosine significantly antagonised metoclopramide (1.25 and 2.5 mg/kg)-induced stereotyped cage climbing behaviour. Metoclopramide at these doses induces stereotyped cage climbing behaviour by releasing DA from the mesolimbic dopaminergic neurons with resultant activation of the postsynaptic mesolimbic D 2 DA receptors by the released DA. DA releasing action of metoclopramide (1.25 and 2.5 mg/kg, i.p.) and the subsequent induction of the stereotyped cage climbing behaviour by these doses of metoclopramide is explained on the basis of selective blockade of the presynaptic D 2 DA autoreceptors by these doses of metoclopramide.

Animals↗

Cataract related blindness in India & its social implications.

The prevalence of blindness in India is 14.9 per 1000. Eighty per cent of this blindness is due to cataract alone. Most of the cataract blinds in the country are in the rural areas while the surgical service delivery network is concentrated in the urban areas. Thus a large proportion of patients in the rural areas continue to remain blind. This situation has many social implications. There is loss of productivity, breakdown of interpersonal relationships, depressive manifestations, loss of self esteem and most patients lead an isolated humiliating life. Patients lack information on the available services and continue to remain blind for years even after being diagnosed as operable. This is unfortunate because cataract surgery is one of the most cost effective health interventions known and most operated patients, irrespective of the surgical technique, are immensely satisfied with the level of visual rehabilitation after surgery.

Aged↗

Similarities inferred from the studies of long range correlations among mitochondrial DNA sequences.

Existence of long range correlations within the DNA sequences of living organism has immense importance in understanding the language of DNA sequences. Recently it has been reported that long range correlations occur in DNA sequences. Some investigators claimed that these type of correlations occur only on intron containing DNA sequences. Some observers, however, have the opinion that long range correlations do not distinguish between the intron containing DNA sequences and intronless DNA sequences. The biological origin of long range correlations in the DNA sequences is not clearly known. In this paper we have demonstrated that long range correlations also occur on intronless mitochondrial DNA sequences, indicating that these special type of correlations are not the unique features for intron containing DNA sequences. We have also demonstrated that long range correlations simply originate in the region around which there is a large variation of pyrimidine and purine ratios. The similarities among the mitochondrial DNA sequences can be inferred by computing the fractal exponents in the region where there is a large variation of pyrimidine and purine ratio, as well as in the region where the ratio of pyrimidine and purine fluctuates in a nearly constant manner. In other words the similarities among the mitochondrial DNA sequences cannot be inferred by calculating the fractral exponents for the whole sequence.

Animals↗

Topical aspirin provides protection against galactosemic cataract.

Effect of twice daily administration of aspirin eyedrops on the onset and progression of cataract induced by 30% galactose diet was studied. On the 30th day of galactose feeding while all control group rats showed complete stage IV opacity, those receiving aspirin eyedrops showed only mild cataractous changes of stage I. In vitro studies showed that addition of aspirin to the medium significantly decreased dulcitol formation (p < 0.01) and maintained glutathione levels (p < 0.02). Intraocular penetration studies using isolated goat cornea showed excellent penetration by salicylate indicating feasibility of topical administration. The results of the present study demonstrate that topical aspirin possesses significant anticataract activity in galactosemic cataract.

Administration, Topical↗

A receptor in pituitary and hypothalamus that functions in growth hormone release.

Small synthetic molecules termed growth hormone secretagogues (GHSs) act on the pituitary gland and the hypothalamus to stimulate and amplify pulsatile growth hormone (GH) release. A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. On the basis of its pharmacological and molecular characterization, this GPC-R defines a neuroendocrine pathway for the control of pulsatile GH release and supports the notion that the GHSs mimic an undiscovered hormone.

Amino Acid Sequence↗

Molecular cloning of the human fertilin beta subunit.

Fertilin, a heterodimeric sperm surface protein, first identified in guinea pig, has been shown to play an important role in sperm-egg interactions. We report here the complementary DNA and deduced amino acid sequence of human fertilin beta. The human fertilin beta shares significant sequence homology with mouse, guinea pig and monkey fertilin beta and also exhibits similar structural organization. Of particular interest, the mature guinea pig fertilin beta contains an amino-terminal 90 amino acid disintegrin domain. It has been suggested that the integrin recognition sequence (TDE) of the guinea pig fertilin beta disintegrin domain mediates sperm-egg binding. The amino acid sequence at this position in human fertilin beta differs from the mouse, guinea pig and monkey sequence (mouse-QDE; human-FEE; monkey-FDE).

ADAM Proteins↗

Determination of alosetron in human plasma or serum by high-performance liquid chromatography with robotic sample preparation.

A method of analysis for the determination of alosetron in human plasma or serum has been developed. The method was fully automated using a laboratory robot in order to improve analytical precision, efficiency and safety. The assay involved solid-phase extraction with reversed-phase HPLC separation and fluorescence detection. A validation exercise over the concentration range of 0.1 to 20 ng/ml demonstrated the selectivity, linearity, sensitivity, accuracy, precision, extraction efficiency, ruggedness and stability of the method. The method has been applied in support of numerous human pharmacokinetic/biopharmaceutic studies over the last five years.

Carbolines↗

On heavy metals in soil; rationalization of extractions by dilute salt solutions, comparison of the extracted concentrations with uptake by ryegrass and lettuce, and the possible influence of pyrophosphate on plant uptake.

Extractions of Cu, Zn, Cd and Pb from soils by dilute salt solutions have been rationalized by a simple chemical equilibrium relation which includes the total load of metals, soil pH, soil cation exchange capacity (CEC), and extractant ionic strength. Correlations between metal uptakes by ryegrass and lettuce with calculated concentrations of Cu, Zn, or Cd in a fictitious soil solution at zero ionic strength are comparable to those obtained with the weakest salt solutions, 0.1 mol.l-1 NaNO3 and 0.05 mol.l-1 CaCl2. The other salt solutions correlate slightly less well. Uptake of Pb is not represented well.

Diphosphates↗

Simultaneous first-order and capacity-limited elimination kinetics after oral administration of verapamil.

In this study of the relationship between dose and plasma concentration of verapamil, controlled-release verapamil in doses of 120 mg, 180 mg, 360 mg, and 540 mg were examined. The 48 study subjects received verapamil daily during each of the 4 sequential 5-day dosing segments. Blood samples were collected frequently to obtain first-dose and steady-state (fifth dose) concentration profiles of verapamil. Plasma concentrations of R- and S-verapamil and R- and S-norverapamil were measured by stereospecific assay. Statistical comparisons of pharmacokinetic parameters and mean differences between doses were performed with analysis of variance models. At steady state, area under the concentration-time curve (AUC) values for R- and S-verapamil at both the 120-mg and 180-mg doses were about 1.5 times higher than the corresponding first-dose values. After both first and fifth doses, pharmacokinetic parameters for all four analytes were dose proportional between the 120-mg and 180-mg doses. A dose-proportional relationship also was found between the 360-mg and 540-mg dose levels. However, nonlinearity was found between the 180-mg dose and higher doses, suggesting saturable metabolic pathways. The dose-proportional relationship between the 360-mg and 540-mg doses suggests that other first-order metabolic pathways become dominant. Although results from this study are partially consistent with previously reported nonlinear verapamil kinetics, this is the first clinical study to demonstrate a dose-proportional relationship for verapamil at both low and high input rates (mg/hr). In addition, first-order disposition pathways of verapamil are probably nonexistent at medium input rates and become dominant at higher input rates.

Administration, Oral↗

Bacterial proteases and adherence of Pseudomonas aeruginosa to mouse cornea.

The goal of this study was to test whether bacterial exoproducts, such as elastase or alkaline protease contribute to the initial binding of Pseudomonas aeruginosa to mouse corneal epithelium. Each protease, purified from P. aeruginosa, when applied exogenously at concentrations of either 25 or 50 ng ml-1, elevated binding of Pseudomonas to mouse cornea in organ culture. Polyclonal antibodies against bacterial alkaline protease, but not elastase, interfered with bacterial binding and reduced significantly the number of organisms bound to cornea in an organ culture binding inhibition assay. Zymographic analysis of conditioned media from additional organ culture experiments showed that the P. aeruginosa strain used, which is highly virulent in cornea in vivo, secretes detectable levels of alkaline protease, but not elastase in vitro and that secretion was enhanced if the corneal epithelium was wounded. Lastly, how alkaline protease enhanced bacterial binding to the corneal epithelium of the organ cultured eye was examined. Data from this study suggest that exposure of lipase-sensitivity epithelial receptors represents at least one mechanism.

Animals↗

Anti-inflammatory activity of topical nimesulide gel in various experimental models.

OBJECTIVE AND DESIGN: The anti-inflammatory activity of topically applied nimesulide gel was compared in different experimental models with that of diclofenac and piroxicam gels. MATERIAL: Wistar albino rats of either sex were used. TREATMENT: In acute models, 50 mg of nimesulide or diclofenac were applied to right hind paws 1 h (carrageenan) or immediately before (formalin) irritant injection (sub-plantar). In adjuvant arthritis, 50 mg of nimesulide, diclofenac or piroxicam were applied daily to injected paws for 14 days. METHODS: Paw volume was measured by plethysmograph. Statistical significance was tested with Student's t-test. RESULTS: In the carrageenan paw odema, topical nimesulide gel exhibited similar anti-inflammatory activity to diclofenac gel, and was more effective than diclofenac gel in formalin-paw odema. In both acute (18 h) and chronic (14 d) phases of adjuvant arthritis, nimesulide gel was more effective than diclofenac or piroxicam gels. CONCLUSION: Topical nimesulide gel possesses higher anti-inflammatory activity than that of diclofenac or piroxicam gels.

Administration, Topical↗

Anti-receptor antibodies inhibit Pseudomonas aeruginosa binding to the cornea and prevent corneal perforation.

A polyclonal antibody (pAb) against gangliotetraosylceramide (asialo GM1), a glycolipid to which bacterial pili and LPS bind, and a mAb against a 66 kDa pilus-binding protein purified from adult mouse corneal epithelium were used to determine if antibodies against host receptors for bacterial adhesins could inhibit bacterial binding to wounded corneal epithelium and protect ocularly challenged mice from corneal perforation when topically applied. Bacteria were mixed with anti-66 kDa mAb, a mixture of anti-asialo GM1 pAb and anti-66 kDa mAb, an irrelevant control mAb (anti-human histocompatibility Ag HLA-DR5) or PBS prior to application to scarified corneas in organ culture. The combination of the two antibodies or the anti-66 kDa mAb alone was effective in reducing bacterial adherence compared with either PBS or the antibody control. To determine if these antibodies were protective in vivo, corneas of C57BL/6J mice were scarified and inoculated with Pseudomonas aeruginosa. Eyes were treated topically with anti-asialo GM1 pAb, anti-66 kDa mAb, a mixture of the two or control mouse serum. More serum-treated corneas perforated compared to corneas from any other group (P < or = 0.005) by 30 days postinfection. Treatment with a combination of the two antibodies resulted in significantly less corneal pathology 30 days p.i. when compared to any other treatment (P < or = 0.005). These data provide evidence that antibodies against host corneal receptors significantly inhibit bacterial binding in vitro and when applied topically in vivo, lessen the severity of ocular disease characteristic of P. aeruginosa keratitis.

Animals↗

A critical appraisal of six modern classifications of ductal carcinoma in situ of the breast (DCIS): correlation with grade of associated invasive carcinoma.

The in-situ component of 180 cases of screen detected infiltrating duct carcinoma of the breast was classified according to six published classifications for ductal carcinoma in situ based on architecture, necrosis and cytology. All cases were assessed independently by two experienced observers to assess inter-observer variation. The differentiation of ductal carcinoma in situ as assessed by all the classification systems correlated with the grade of the associated invasive carcinoma (chi-squared between 50 and 107: P < 0.0001). Disagreements were commonest in the assessment of architecture and least common in the assessment of necrosis. For cytonuclear grade most disagreements (62.2%) involved the distinction between low and intermediate as against 33.9% disagreements for intermediate vs. high. Nuclear grade alone and necrosis alone were correlated with the grade of invasive carcinoma associated with the ductal carcinoma in situ and the Nottingham prognostic index of the patient. The Van Nuys classification of ductal carcinoma in situ is commended because it has a low inter-observer disagreement, is significantly correlated with the grade of the infiltrating carcinoma, uses simple well-defined criteria (with no requirement for percentage estimations), is applicable to small numbers of ducts and, most importantly, appears to correlate with disease-free survival.

Breast Neoplasms↗

A follow-up study on visual outcome after camp-based intracapsular cataract extraction.

The visual outcome of 164 intracapsular cataract extractions (ICCE) performed in 158 patients at an eye-camp was evaluated. 93.3% had a preoperative visual acuity of less than 3/60. On the 4th/5th post-operative day, 39.3% had a visual acuity between 6/18 and 6/36; 84.7% had vision better than 3/60. Six weeks post-operatively, 44.1% had visual acuity better than 6/18 and a total of 84.1% better than 3/60. The vision of 40.7% improved between the 4th/5th post-operative day and the follow-up visit at 6 weeks. 46.4% of patients had post-operative corrected visual acuity better than 6/18, 24.3% had vision between 6/18 and 6/36, and a total of 84.3% had vision better than 3/60. The patients' satisfaction in terms of improvement in mobility and ability to do housework at 6 weeks after the operation correlated better with the improvement in vision in terms of the number of Snellen's lines than with the actual post-operative visual acuity.

Aged↗

Molecular cloning of a gene from 'chromosome 3 specific' genomic library that encodes a novel CC-chemokine receptor like isotype.

CC-chemokine receptors form a closely linked locus in the p21-23 region on the short arm of human chromosome 3. We report the isolation of a novel chemokine receptor like gene from a 'human chromosome 3 specific' genomic library, screened by cross-hybridization with cDNA probes derived from known chemokine receptors. The gene, CKR-SKG2 contains an open reading frame that encodes a 359-377 amino acid protein, with two potential in frame start codons. However, comparative Southern blot analysis of human, mouse and hamster genomic DNA, revealed that CKR-SKG2 is the hamster ortholog of a novel chemokine receptor. This presumably occurred because chromosome 3 used for construction of the genomic library were purified from a human-hamster somatic cell hybrid. Further studies are underway to identify and clone the putative human homolog of this novel chemokine receptor.

Amino Acid Sequence↗