Biomedical subjects

N Gupta

Publications and source records attributed to N Gupta.

At least 181 records · Page 10Linked to original sources

PubMed1998

Defect in IgV gene somatic hypermutation in common variable immuno-deficiency syndrome.

Common Variable Immuno-Deficiency (CVID) is the most common symptomatic primary antibody-deficiency syndrome, but the basic immunologic defects underlying this syndrome are not well defined. We report here that among eight patients studied (six CVID and two hypogammaglobulinemic patients with recurrent infections), there is in two CVID patients a dramatic reduction in Ig V gene somatic hypermutation with 40-75% of IgG transcripts totally devoid of mutations in the circulating memory B cell compartment. Functional assays of the T cell compartment point to an intrinsic B cell defect in the process of antibody affinity maturation in these two cases.

Adult↗

PubMed1998

Hypoxia-reoxygenation potentiates zymosan activated plasma-induced endothelial injury.

The pathophysiology of ischemia-reperfusion injury and the role played by the interaction of plasma proteins, including complement, with reperfused endothelium remains incompletely understood. Venular endothelial changes due to hypoxia followed by reoxygenation (H-R) are vital because venules are the primary site of fluid accumulation and polymorphonuclear leukocyte deposition due to inflammation. This investigation focused on whether H-R potentiates the response to permeability inducing agents found in activated plasma. Activated complement was studied by using zymosan activated plasma (ZAP). Permeability changes were assessed by quantitating rate of clearance of albumin across the monolayers. H-R alone did not change permeability relative to the normoxic condition. ZAP at 2% in normoxic cells increased albumin clearance from 2 +/- 0.2 to 9 +/- 1. 0 microL/h, which increased significantly to 13.5 +/- 2.0 microL/h when given to hypoxia-reoxygenation challenged monolayers. The permeability response to ZAP was dose related and not present with heat inactivated ZAP. ZAP at 2% altered the structure of the cytoskeleton of the human umbilical vein endothelial cells (HUVEC). However, addition of monoclonal anti-complement antibodies or addition of soluble complement receptor-1 did not attenuate ZAP-induced HUVEC permeability. Addition of zymosan-activated serum did not alter the permeability and addition of heparin inhibited the ZAP-induced changes in permeability, suggesting that these changes were mediated via thrombin and not complement. The increase in monolayer permeability due to ZAP was prevented by increasing intracellular adenosine-3',5'-cyclic monophosphate. These findings suggest that HUVEC monolayers challenged with H-R are more susceptible to increases in permeability induced by activated plasma components.

Actins↗

PubMed1998

Kinetic mechanism of glutathione conjugation to leukotriene A4 by leukotriene C4 synthase.

The kinetic mechanism for human leukotriene (LT) C4 synthase, a membrane-bound glutathione S-transferase, which catalyzes the conjugation of glutathione (GSH) to 5,6-oxido-7,9,11, 14-eicosatetraenoic acid (LTA4), to form 5(S)-hydroxy-6(R)-S-glutathionyl-7,9,trans-11, 14-cis-eicosatetraenoic acid (LTC4) was investigated by initial rate kinetic studies in which concentrations of both substrates and the reversible dead-end inhibitor, 2-[2-[1-(4-chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)- methoxy]- 4,5-dihydro-1H-thiopyrano[2,3,4-c,d]indol-2-yl]ethoxy]butanoic acid (L-699,333) were varied. Analysis of the initial velocities of LTC4 formation in the absence of the inhibitor using non-linear regression fits of various models to the data favoured a random, rapid equilibrium mechanism, with strong substrate inhibition by LTA4, over both a compulsory ordered mechanism and a ping-pong mechanism. The estimated parameters were calculated to be Vmax = 14 +/- 4 microM/min, KLTA4 = 40 +/- 18 microM, KGSH = 0.4 +/- 0.2 mM, and a KiLTA4 = 2.3 +/- 1.7 microM for the rapid equilibrium random model. Inhibition of enzymatic activity by L-699,333 was found to be reversible as assessed by the ability of the enzyme to restore its activity by 95% upon dilution. L-699,333 was found to be a competitive inhibitor against GSH and non-competitive against LTA4. Non-linear least squares regression analysis yielded estimated parameters of Km = 0.7 +/- 0.1 mM, Vmax = 2.5 +/- 0.1 microM/min, and Ki = 0.7 +/- 0.1 microM for GSH at a fixed LTA4 concentration of 20 microM, and Km = 45 +/- 3 microM, Vmax = 4.9 +/- 0.2 microM/min, and a Ki = 5.8+/-0.4 microM for LTA4 at a fixed GSH concentration of 2 mM. The rate equation for the random equilibrium mechanism accommodates the inhibition patterns observed for L-699,333 against both substrates as revealed by kinetic fits of the inhibition data to the overall rate equation.

Enzyme Inhibitors↗

PubMed1998

Response of postmitotic neurons to X-irradiation: implications for the role of DNA damage in neuronal apoptosis.

The molecular changes responsible for inducing neuronal apoptosis are unknown. Rat cortical neurons were treated with x-irradiation 7 d after isolation to test for the role of DNA damage in neuronal death. The response of neurons to x-irradiation was compared with that of astrocytes that had been isolated 3 weeks earlier from newborn rats. At the time of irradiation, the neurons appeared well differentiated morphologically and were predominantly (90-95%) noncycling, based on flow cytometric analysis. There was a similar, linear increase in DNA double-strand breaks with increasing radiation dose in neurons and astrocytes. However, whereas doses as low as 2 Gy induced typical apoptotic changes in neurons, including nuclear fragmentation and/or internucleosomal DNA fragmentation, doses as high as 32 Gy caused little or no apoptosis in astrocytes. Radiation-induced apoptosis of neurons started 4-8 hr after irradiation, was maximal at 12 hr, and was dependent on dose up to 16 Gy. It was prevented when cycloheximide, a protein synthesis inhibitor, was added up to 6 hr after irradiation. In addition to their distinct apoptotic response, neurons rejoined radiation-induced DNA double-strand breaks more slowly than astrocytes. Treatment with benzamide to inhibit ADP-ribosylation and strand break repair increased apoptosis; splitting the dose of radiation to allow increased time for DNA repair decreased apoptosis. These data suggest that DNA damage may induce neuronal apoptosis, that the extent of damage may determine the degree of apoptosis induced, and that slow repair of damage may play a role in the susceptibility of neurons to apoptosis.

Adenosine Diphosphate Ribose↗

PubMed1998

Relationship of optic disc topography to optic nerve fiber number in glaucoma.

OBJECTIVE: To assess the relationship between in vivo measurements of optic disc topography and histomorphometric measurements of optic nerve fiber number in glaucoma. METHODS: Both eyes of 10 monkeys (Macaca fascicularis) with laser-induced glaucoma in the right eye were studied. Optic disc topography was measured in vivo with a confocal scanning laser ophthalmoscope. Histomorphometry was performed on optic nerve cross sections using bright-field microscopy with camera lucida. Nerve fiber density was estimated by unbiased random sampling. Nerve fiber number was estimated for each sector by multiplying nerve fiber density with neuroglial area. Nerve fiber count was compared with each of 13 global optic disc topographic parameters. RESULTS: For neuroretinal measurements in the glaucomatous eyes, rim area, retinal nerve fiber layer (RNFL) cross-sectional area, rim volume, and RNFL thickness correlated significantly with optic nerve fiber number. Differences in nerve fiber count between control and glaucomatous optic nerves showed the strongest correlation with differences in mean height contour; this was followed by RNFL cross-sectional area, RNFL thickness, rim volume, and differences in rim area. For cup measurements in the glaucomatous eyes, cup volume below reference, cup area, mean cup depth, the ratio of cup area to disc area, and cup shape correlated significantly with nerve fiber number. Differences in nerve fiber number between control and glaucomatous optic nerves showed the strongest correlation with differences in cup shape; this was followed by mean cup depth, cup volume below reference, the ratio of cup area to disc area, cup area, and differences in cup volume below surface. No association was found between optic nerve fiber number and optic disc area in glaucomatous eyes. CONCLUSIONS: In experimental glaucoma, most optic disc topography measures correlated significantly with optic nerve fiber number. The results of this histomorphometric study support the use of confocal scanning laser ophthalmoscopy to evaluate optic nerve damage in glaucoma.

Animals↗

PubMed1998

Motion automated perimetry identifies early glaucomatous field defects.

OBJECTIVE: To determine if motion automated perimetry can identify early glaucomatous visual field defects in patients with suspected glaucoma (by disc), those with ocular hypertension, and those with primary open-angle glaucoma. METHODS: Motion automated perimetry, a foveally centered motion test, and standard visual field tests were conducted on one randomly selected eye of normal patients (n = 38), patients with suspected glaucoma (by disc) (n = 28), patients with ocular hypertension (n = 18), and patients with primary open-angle glaucoma (n = 21). Subjects' performance on both motion tests were compared with their performance on standard perimetry. RESULTS: Perimetric motion thresholds significantly distinguished the groups (P< or =.001), while the foveally centered motion test was unable to separate them (P< or =.32). Of the total patients, 90.5% of those with glaucoma, 39.3% of those with suspected glaucoma, 27.8% of those with ocular hypertension, and 5.3% of the normal subjects had abnormal results on motion automated perimetry testing. Perimetric motion thresholds were significantly correlated with standard visual field thresholds (P< or =.001). CONCLUSION: Motion automated perimetry identifies visual field defects in patients who already show standard visual field loss as well as in a moderate percentage of those with suspected glaucoma and ocular hypertension, indicating that the testing of discrete locations might be necessary for increased diagnostic utility.

Aged↗

PubMed1998

Management and outcome of patients with combined bile duct and hepatic artery injuries.

BACKGROUND: Major bile duct injury is an important therapeutic problem that can be associated with simultaneous injury to the hepatic artery. Limited information exists regarding the course of patients who have combined bile duct and arterial injuries. OBJECTIVE: To compare the management and outcome of isolated bile duct injuries with bile duct and hepatic artery injuries. PATIENTS AND METHODS: Since 1991, 13 patients have undergone reconstruction of right and left hepatic confluence or proximal bile duct injuries. At the time of bile duct injury, 4 of these patients had simultaneous occlusion or extirpation of the right hepatic or common hepatic artery. All patients underwent reconstruction of the biliary tract with hepaticojejunostomies. The immediate and long-term outcomes of the patients with and without hepatic artery injury were compared. RESULTS: In the immediate postoperative period, 3 of 4 patients with combined injuries had hepatic necrosis and/or abscesses with 2 patients requiring transcutaneous or operative drainage. This problem was not diagnosed in patients with isolated bile duct injuries. None of the biliary anastomoses have failed in the patients with isolated bile duct injuries while 50% of the anastomoses in patients with combined injuries have caused recurrent problems following reconstruction. CONCLUSION: Patients with major bile duct injuries should be evaluated for concomitant hepatic arterial injury as management and outcome may be influenced by the absence of arterial blood flow to the injured bile ducts and to the liver.

Adult↗

PubMed1998

Heterogeneity in the organization of the CTX genetic element in strains of Vibrio cholerae O139 Bengal isolated from Calcutta, India and Dhaka, Bangladesh and its possible link to the dissimilar incidence of O139 cholera in the two locales.

After a lapse of 33 months, Vibrio cholerae O139, the new serogroup associated with cholera, has re-emerged in Calcutta, India and has become the dominant serogroup causing cholera from September 1996. In neighbouring Bangladesh, V. cholerae O1 biotype El Tor continues to be the dominant cause of cholera with the O139 serogroup accounting for only a small proportion of cases. Comparison of the phenotypic traits of representative O139 strains from Calcutta and Dhaka isolated between December 1996 and April 1997 showed similar phenotypic traits with the exception that Dhaka O139 strains were susceptible to streptomycin whilst Calcutta O139 strains were resistant. The Dhaka and Calcutta O139 strains displayed identical ribotypes but showed remarkable differences in the structure and organization of the CTX genetic element. In the Dhaka O139 strains, two copies of the CTX element were arranged in tandem and this resembled the pattern displayed by the 1992 epidemic strains of O139. The Calcutta O139 strains, in contrast, carried three copies of the CTX genetic element arranged in tandem with the loss of a conserved BglII restriction site in the RS1 element and the appearance of a new HindIII site in the same region. While there may be other factors, it appears that the reorganization of the CTX genetic element in the Calcutta O139 strains may have contributed to the resurgence of this serogroup in Calcutta.

Anti-Bacterial Agents↗

PubMed1998

Boron neutron capture therapy: principles and potential.

This book on the therapeutic applications of neutrons and high-LET radiations in cancer therapy would not have been complete without a review of the present situation of boron neutron capture therapy (BNCT) and a discussion of its future perspectives. BNCT is a special type of high-LET radiation therapy that attempts to achieve a selectivity at the cellular level. The rationale is to incorporate boron atoms selectively in the cancer cells and then bombard those atoms with thermal neutrons to produce a neutron capture reaction and subsequent decay that emits alpha and lithium particles. The efficiency of the technique depends upon achieving selective incorporation of the boron atoms in the cancer cells and not (or to a lesser extent) in the normal cells. The present status and future directions are described, with emphasis on boron carriers (drugs) and their delivery, as well as physical and treatment planning aspects.

Boron Neutron Capture Therapy↗

PubMed1998

Evaluation of benzalkonium chloride chemoneurolytic proximal gastric vagotomy.

BACKGROUND: Transmucosal chemoneurolytic injection of benzalkonium chloride (BAC) has previously been shown to duplicate operative proximal gastric vagotomy (PGV) in controlling gastric acid secretion. In this study, BAC was evaluated as to efficacious dose, methods of delivery, and systemic toxicities. METHODS: Sham celiotomy, operative PGV controls, transmucosal injections through a gastrotomy, and transserosal injections of BAC (saline controls, 0. 625, 1.25, 2.5, 5.0, 10 mg BAC/kg body wt) were administered to Sprague-Dawley rats. After 3 months the rats underwent Congo red testing (CRT), horseradish peroxidase (HRP) neuronal staining, and necropsy. The color density change of the gastric mucosa from basic to acidic demonstrated by the CRT at the time of necropsy was used to calculate the residual anatomic acid-secreting area. Prior to necropsy, subserosal HRP injections into the anterior and posterior stomach walls assayed vagal neuronal viability via retrograde axonal flow. Results were compared by an ANOVA. RESULTS: The results demonstrated that 1.25-10 mg/kg transmucosal BAC replicated the results of operative PGV; 2.5 mg/kg was found to be the most effective dose. All injection groups including saline controls demonstrated similar diminished vagal retrograde axonal flow by HRP testing consistent with local BAC chemoneurolytic effects. No systemic toxic symptoms were observed after tail vein intravenous BAC 1.25, 2.5, and 5.0 mg/kg. CONCLUSIONS: These efficacy studies have demonstrated BAC's potential utility in the performance of endoscopic transmucosal chemoneurolytic PGV.

Animals↗

PubMed1998

Protective effect of Picroliv from Picrorhiza kurroa against Leishmania donovani infections in Mesocricetus auratus.

The prevalent drugs for treatment of kala azar viz. sodium stibogluconate (SSG) and pentamidine cause severe toxic side effects and acute immunosuppression in the treated individuals. Picroliv, a standardized mixture of iridoid glycosides, prepared from the alcoholic extract of the root and rhizome of Picrorhiza kurroa has shown strong hepatoprotective activity against several models of hepatotoxicity. Therefore, the present study was undertaken with an objective to study the effects of Picroliv (12.5 mg/kg x 7 days oral) alone and in combination with SSG on parasitemia, lipid peroxidation and hepatic marker enzymes of golden hamsters during Leishmania donovani infection. The results indicated a marked hepatoprotective effect of Picroliv in terms of biochemical markers, and a significant antileishmanial activity implying that it can be utilized as an adjunct to chemotherapy or in combination therapy of kala azar along with sodium stibogluconate, thus enhancing the efficacy of antileishmanials.

Administration, Oral↗

PubMed1998

Novel trabecular meshwork inducible glucocorticoid response mutation in an eight-generation juvenile-onset primary open-angle glaucoma pedigree.

OBJECTIVE: This study aimed to update a large kindred with juvenile-onset primary open-angle glaucoma (POAG) first described in 1940 and to identify the underlying genetic cause of the disease. DESIGN: Molecular genetic study of a single kindred, including clinical examination, retrospective review of clinical and family history records, linkage analysis, and mutation screening. PARTICIPANTS: The retrospective review included 957 members of a single large family. The linkage study included 40 members of 1 branch of the family in which juvenile-onset POAG is segregating in an autosomal-dominant pattern. Mutation screening included 15 at-risk family members with juvenile-onset POAG, probands of 40 families with adult-onset POAG, probands of 11 additional unrelated juvenile-onset POAG families, and 43 unrelated normal control subjects. INTERVENTION: Clinical and family history records were obtained, ophthalmologic examinations were performed, and blood samples were drawn for use in genotyping. MAIN OUTCOME MEASURES: Allele sizes of microsatellite repeat genetic markers from the vicinity of the GLC1A glaucoma gene on chromosome 1q were assigned based on size fractionation of DNA fragments generated by polymerase chain reaction (PCR). Linkage was established by the method of lod scores. Mutations were identified by determination of the DNA sequence of PCR products amplified from the trabecular meshwork inducible glucocorticoid response (TIGR) gene. Glaucoma status for purposes of linkage and mutation analysis was based on a combination of ophthalmologic examination, clinical records, family history, and previously published information. For some individuals reported in the pedigree, but not included in the genotyping studies, less information was available as presented in the text and tables. RESULTS: Autosomal-dominant POAG was confirmed or reported for 78 members of an 8-generation family. Linkage analysis showed significant evidence for linkage of juvenile-onset POAG in one branch of the family to D1S452 (maximum lod score of 6.42 at a recombination fraction of 0.00) and other markers in the vicinity of the GLC1A gene on chromosome 1q. Screening of the TIGR gene identified a mutation that results in substitution of asparagine for isoleucine at codon 477 near the carboxyterminal end of the protein. CONCLUSIONS: The authors' findings strongly suggest that the juvenile-onset POAG locus in this family is the GLC1A locus and that the underlying cause of the disease is the IIe477Asn TIGR mutation that cosegregates with juvenile-onset POAG in one branch of this large family. Lack of samples from deceased individuals prevented the authors from determining whether reported adult-onset cases in this family could also be attributed to the IIe477Asn TIGR mutation. Absence of the IIe477Asn TIGR mutation from other juvenile- and adult-onset POAG families implies that this TIGR mutation is not a common cause of glaucoma.

Adolescent↗

PubMed1998

Simplified non-looping functional loop technique for HDR brachytherapy.

The loop technique has been employed in interstitial implantation of head and neck cancers for decades. However, cable-driven afterloading sources may be unable to negotiate the curve of the loop. The technique allows separate afterloading of each catheter ensuring a good dose distribution to the surface of the implanted structure.

Brachytherapy↗

PubMed1998

Decreased phosphorylation of a low molecular weight protein by cGMP-dependent protein kinase in variant HL-60 cells resistant to nitric oxide- and cGMP-induced differentiation.

We previously described the isolation of a variant subline of HL-60 cells that does not differentiate in response to nitric oxide (NO)-generating agents or to cGMP analogs. The variant cells have normal guanylate cyclase activity and normal NO-induced increases in the intracellular cGMP concentration. We now show that the variant cells have normal cGMP-dependent protein kinase (G-kinase) activity, both by an in vitro and in vivo assay, and using two-dimensional gel electrophoresis we have identified six G-kinase substrates in the parental cells. Of these six proteins, we found considerably less phosphorylation of one of the proteins in the variant cells than in parental cells, both in vitro and in intact cells, and by 35S-methionine/35S-cysteine incorporation we found much less of this protein in the variant cells than in parental cells. The protein is a shared substrate of cAMP-dependent protein kinase (A-kinase); since cAMP analogs still induce differentiation of the variant cells, it appears that the NO/cGMP/G-kinase and cAMP/A-kinase signal transduction pathways share some but not all of the same target proteins in inducing differentiation of HL-60 cells.

Cell Differentiation↗

PubMed1998

Seat belt-related injury to the common iliac artery: case report and review of the literature.

Blunt trauma to the common iliac artery is a rare phenomenon. Although seat belt injuries to the abdominal aorta and the carotid artery have been reported, there is only one previous report in the literature of seat belt injury to the common iliac artery. We report a case of common iliac arterial injury directly related to use of the lap belt and not associated with pelvic or lumbar fractures. The literature related to blunt trauma of the common iliac artery is reviewed.

Accidents, Traffic↗

PubMed1998

Pregnancy and congenital heart disease--maternal and fetal outcome.

Two hundred and seventy five pregnancies in patients with congenital heart disease during 1980-1996 were analyzed retrospectively. Maternal and perinatal outcome was compared in 251 pregnancies of women with acyanotic and 24 pregnancies of women with cyanotic heart disease. Congenital heart disease was diagnosed during the index pregnancy in 26.1% of patients and the majority (88.4%) were in NYHA classes 1 and 2. Atrial septal defect (27.7%) was the most common lesion in women with acyanotic heart disease and the majority with cyanotic heart disease had Eisenmenger syndrome, 13 of 21 (61.9%). Sixty pregnancies occurred in patients with surgically corrected lesions (acyanotic, 56; cyanotic, 4). The incidences of abortions (8.3%), stillbirths (13.6%) and small for gestational age (SGA) (36.4%) were higher in cyanotic heart disease compared to acyanotic heart disease (stillbirth, 0.8%; SGA, 6.9%). There was a statistically significant difference in mean maternal age, mean gestational age and mean birth-weight in the surgically corrected and noncorrected lesions in both acyanotic and cyanotic heart disease. There was 1 maternal death in a woman with Eisenmenger syndrome.

Adult↗

PubMed1998

Dynamic positron emission tomography with F-18 fluorodeoxyglucose imaging in differentiation of benign from malignant lung/mediastinal lesions.

PURPOSE: This study was done to evaluate the diagnostic utility of dynamic positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) imaging in patients with suspected malignant pulmonary lesions. We wanted to test the hypothesis that the rate of FDG uptake (FDG influx constant values) would differentiate malignant from benign lung or mediastinal lesions. MATERIALS AND METHODS: We performed segmental dynamic PET imaging studies following administration of FDG in 19 patients with indeterminate pulmonary lesions based on chest radiograph and/or CT scans. Patlak analysis was done to compute Ki (FDG influx constant) values and compared with FDG standardized uptake values (SUVs) and histology. RESULTS: FDG Ki values (mean+/-SD) were significantly greater (p < 0.01) in all 12 malignant lesions (0.029+/-0.02) as compared with 7 benign lesions (0.0024+/-0.0011) with good correlation to the SUV values. Distinct time activity curve patterns were identified in malignant and benign lesions with continued uptake in malignant lesions. CONCLUSION: Dynamic PET-FDG imaging accurately differentiates malignant from benign pulmonary lesions. In certain cases with equivocal findings on visual analysis and SUV values, dynamic imaging may be further helpful in differentiating benign and malignant lesions.

Adenocarcinoma↗

PubMed1998

Changing definition of glaucoma.

OBJECTIVE: The authors assess whether there has been a change in the definition of open-angle glaucoma (OAG) in peer-reviewed articles during the past 15 years. METHODS: A literature review was conducted (via Medline) to identify all articles on OAG from the American Journal of Ophthalmology, Ophthalmology, and Archives of Ophthalmology for the years 1980, 1985, 1990, and 1995. One hundred eighty-two articles were reviewed to identify optic nerve, visual field, and intraocular pressure (IOP) criteria used to define glaucoma. Articles were classified and analyzed by study design, severity, and type of glaucoma. RESULTS: Of the 182 articles, 120 (66%) included a definition of OAG. Among these, approximately 36% used both optic disc and visual field criteria, 13% used optic disc or visual field criteria, 26% used only visual field criteria, 20% used only IOP, and 5% used only optic disc criteria. In the 1980s, when both disc and/or field parameters were used in the definition, 74% of the publications used general qualitative statements such as "characteristic glaucomatous changes." In the 1990s, 34% of articles provided specific descriptions of the optic disc and 61% provided specific visual field criteria. A similar proportion of reviewed articles published in the 1980s (20.4%) and 1990s (19.7%) used IOP as its sole criterion for defining glaucoma. A significantly larger proportion of prospective studies (38/46; 83%) provided specific criteria to define glaucoma compared to cross-sectional (67/111; 60%) and retrospective studies (15/25; 60%). CONCLUSION: There is a lack of consistency in how glaucoma is defined in current clinical research. Although recent studies provide more specific criteria, there is a need to obtain a consensus definition.

Glaucoma, Open-Angle↗