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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 379 records · Page 21Linked to original sources

Hepatic polyploidy and liver growth control.

The onset of cellular polyploidy is recognized in all differentiated mammalian tissues. Polyploidy has been noted frequently in the normal liver, as well as in pathophysiological states of the liver. As insights into the significance of polyploidy accumulate gradually, it is becoming clear that cells belonging to high ploidy classes exhibit advancement toward terminal differentiation and cellular senescence with greater probabilities of apoptosis. Involvement of specific genetic abnormalities, such as impaired DNA repair, may lead to hepatocellular polyploidy. Working models indicate that extensive polyploidy could lead to organ failure, as well as to oncogenesis with activation of precancerous cell clones.

Animals↗

Detection of subdural placement of epidural catheter using nerve stimulation.

PURPOSE: To report the detection of a subdural catheter placement using nerve stimulation through an epidural catheter. CLINICAL FEATURES: An 85-yr-old gentleman was scheduled for radical cystectomy and creation of an ileal conduit. Combined general anesthesia and regional technqiue was selected. An epidural catheter (19 G Arrow Flextip Plus) was inserted prior to induction of general anesthesia. Intra-operatively, the patient received 5 mg morphine and 10 ml bupivacane 0.5% via the epidural catheter. The patient remained hemodynamically stable throughout the operation and did not require intravenous opioids. The patient was discharged to the ward with an order for epidural morphine for pain control. The next day, the patient remained comfortable. As an ongoing quality assessment to survey the success rate of epidural catheters at our institution, all patients are invited to have their catheter assessed using an electrical epidural stimulation test. Electrical stimulation (1-10 mA) with a segmental motor response (truncal or extremities movement) indicates that the catheter is in the epidural space. No motor response indicates that it is not. In this case, subdural catheter placement was suspected because a diffuse motor response including right anterior chest wall, back muscle, and bilateral lower extremities was observed using only 0.3 mA. Subdural catheter placement was subsequently confirmed by a radiograph showing a very thin film of dye spreading cephalad and caudad over many segments. CONCLUSION: This new electrical test helps to detect subdural placement objectively.

Aged↗

Image-guided percutaneous drainage of thoracic empyema: can sonography predict the outcome?

The aim of this study was to assess the safety and efficacy of image-guided percutaneous catheter drainage (IGPCD) of thoracic empyemas, and to correlate the outcome of IGPCD with the pre-procedural sonographic appearance. One hundred three patients (74 males and 29 females) with thoracic empyema (age range 1 month to 70 years, median age 28 years) underwent IGPCD. In 63 (61.17%) patients, IGPCD was the primary treatment modality; in 40 (38.84%) patients it was used after unsuccessful intercostal chest tube drainage (ICTD). Ultrasound was the main modality used for guidance; CT guidance was used in only 7 patients (6.8%). Eight- to 12-F pigtail catheters or 10- to 14-F Malecot catheters were used. The outcome was correlated with the pre-procedural US appearance (anechoic, complex non-septated or complex septated) of the empyema. The IGPCD technique was successful in 80 of 102 patients. Based on the US appearance, IGPCD was successful in 12 of 13 (92.3%) patients with anechoic empyemas; 53 of 65 (81.54%) patients with complex non-septated empyemas, and in 15 of 24 (62.5%) patients with complex septated empyemas. A statistically significant difference (p < 0.01) was seen in the outcome of IGPCD in the three categories. Twenty-two patients required further treatment: ICTD (n = 9; 2 of them later also underwent surgery); and surgery (n = 15). The duration of catheter drainage ranged from 2-60 days. No major complications were encountered. Percutaneous catheter drainage of thoracic empyemas with imaging guidance ensures accurate catheter placement with a high success and a low complication rate. Pre-procedural US can predict the likelihood of success of IGPCD.

Adolescent↗

Myocyte contractile function is intact in the post-infarct remodeled rat heart despite molecular alterations.

OBJECTIVE: To investigate the cellular mechanisms underlying global and regional LV dysfunction in the post-infarct (MI) remodeled rat hearts. METHODS: LV remodeling and function were quantified by echocardiography, morphometry, in vivo hemodynamics, and isolated perfused heart studies in 6 weeks post-MI and sham-operated rats. LV myocytes from sham and MI hearts were used for morphometric and functional studies. Myocyte contractile function and intracellular calcium kinetics were measured at different stimulation frequencies (0.2-2 Hz), temperatures (30 and 37 degrees C), and external viscous load (1, 15, 200 and 300 centipoise). Myocyte apoptosis was measured by DNA laddering; BCL-2, BAX, Na(+)-Ca(2+) exchanger, and SERCA-2 proteins by western blot; and brain natriuretic peptide (BNP), SERCA-2 mRNA by RT-PCR. RESULTS: MI hearts were remodeled (Echo LV diameter 7.3+/-0.38 vs. 5.9+/-0.16 mm, P<0.03), and showed global (Echo % fractional shortening 30+/-2.4 vs. 58+/-3, P<0.001), and regional contractile dysfunction of non-infarcted myocardium (Echo % systolic posterior wall thickening 36+/-2 vs. 57+/-1.7, P<0.001). In vivo hemodynamic and isolated heart function studies confirmed depressed LV systolic and diastolic function and increased volumes. Whereas, myocytes isolated from infarcted hearts were remodeled (40% longer and 10% wider), their contractile function and calcium kinetics under basal conditions and at high stimulation frequency, temperature and viscous load were similar to sham myocytes. The mRNA for BNP was increased whereas that for SERCA-2 decreased, but the SERCA-2 protein was normal. Despite myocyte hypertrophy, ventricular septal thickness was reduced in infarcted hearts (2.2+/-0.1 vs. 2. 6+/-0.07 mm, P<0.01), and showed increased apoptosis. CONCLUSIONS: Myocytes from remote non-infarcted myocardium of the remodeled hearts have normal contractile function, despite structural remodeling and altered gene expression. Non-myocyte factors may be more important in genesis of contractile dysfunction in the remodeled heart, for up to 6 weeks after MI.

Analysis of Variance↗

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Journal Article↗

Characterization of fertilin beta-disintegrin binding specificity in sperm-egg adhesion.

An essential step leading to fertilization is the binding of a sperm to the egg plasma membrane. Fertilin beta, a membrane bound protein on the extracellular surface of sperm, partially mediates this binding via the alpha6beta1 integrin. Fertilin beta is a member of the still expanding family of ADAM proteins (a disintegrin and metalloprotease) that are implicated in many cellular functions ranging from neurogenesis to myoblast fusion and cytokine processing. Fertilin beta contains a highly conserved motif (D/E)ECD in the disintegrin domain. This suggests that (D/E)ECD could be the consensus sequence for recognition of disintegrins by alpha6beta1 integrins. Previously, it has been demonstrated that small peptides containing different moieties of this consensus sequence are inhibitors of in vitro fertilization. In the present study, we sought to determine whether a four amino acid peptide sequence with two adjacent acidic residues improved inhibition, and investigated the importance for inhibition of a cysteine versus a cystine. A series of linear and cyclic peptides were synthesized, in which either one or both adjacent acidic residues in the sequence DECD were mutated to their corresponding amides (N or Q). To explore the required oxidation state of the cysteine in the (D/E)ECD sequence, it was protected as a mixed disulfide. Our results indicate that only one acidic residue is required for inhibition of fertilization and a reduced C is required.

ADAM Proteins↗

Connective eccentricity index: a novel topological descriptor for predicting biological activity.

A simple, adjacency-cum-path length based, topological descriptor termed the connective eccentricity index has been conceptualized and its discriminating power investigated with regard to antihypertensive activity. A data set consisting of 81 derivatives of N-benzylimidazole was selected for the present investigation. These derivatives are potent, competitive, and nonpeptide angiotensin II receptor antagonists. The value of connective eccentricity index for each derivative was computed and active range identified. Subsequently, each derivative was assigned a biological activity that was compared with the reported antihypertensive activity. The results obtained using connective eccentricity index were better than the corresponding values obtained using Balaban's mean square distance index. The accuracy of prediction was found to be about 80% in the active range using connective eccentricity index.

Angiotensin Receptor Antagonists↗

A severe and explosive outbreak of hepatitis B in a rural population in Sirsa district, Haryana, India: unnecessary therapeutic injections were a major risk factor.

Most outbreaks of viral hepatitis in India are caused by hepatitis E. This report describes an outbreak of hepatitis B in a rural population in Haryana state in 1997. At least 54 cases of jaundice occurred in Dhottar village (population 3096) during a period of 8 months; 18 (33.3%) of them died. Virtually all fatal cases were adults and tested positive for HBsAg (other markers not done). About 88% (21/24) of surviving cases had acute or persistent HBV/HCV infections; 54% (13/24) had acute hepatitis B. Many other villages reported sporadic cases and deaths. Data were pooled from these villages for analysis of risk factors. Acute hepatitis B cases had received injections before illness more frequently (11/19) than those found negative for acute or persistent HBV/HCV infections (3/17) (P = 0.01). Although a few cases had other risk factors, these were equally prevalent in two groups. The results linked the outbreak to the use of unnecessary therapeutic injections.

Adolescent↗

Immunological treatments for autism.

Several investigators, including ourselves, have reported significant changes in various immune responses in children with autism. These changes demonstrate dysregulation of the immune system (deficiency in some components of the immune system and excesses in others). In addition, certain genes in the major histocompatibility complex (that regulates immune responses) appear to be involved in autism. Based upon immunological abnormalities, various treatment modalities have been applied to children with autism. In this brief review, these immunological changes and various biological therapies are analyzed and summarized.

Autistic Disorder↗

Molecular steps of cell suicide: an insight into immune senescence.

The cellular and molecular basis of immune senescence is unclear. A number of mechanisms have been proposed. In this issue of the Journal of Clinical Immunology, some of the mechanisms for various immunologic abnormalities in aging are presented. In this article, various molecular steps of both death receptor and mitochondrial pathways of apoptosis in general are reviewed. In particular, the role of apoptosis in T-cell immune senescence is discussed.

Adult↗

Intestinal mucins: the binding sites for Salmonella typhimurium.

Mucus-bacterial interactions in the gastrointestinal tract and their impact on subsequent enteric infections are poorly delineated. In the present study, we have examined the binding of Salmonella typhimurium to rat intestinal mucus and characterized a mucus protein (Mucus-Rs) which specifically binds to S. typhimurium. Both virulent (1402/84), and avirulent (SF 1835) S. typhimurium were observed to bind to crude mucus, however, the virulent strain showed 6 fold more binding as compared to avirulent strain. Fractionation of crude mucus on sepharose CL-6B resolved it into three major peaks. Maximal bacterial binding was observed with a high mol. wt. glycoprotein corresponding to neutral mucin. SDS-PAGE of purified protein (termed Mucus-Rs) under non reducing conditions showed it to be a homogenous glycoprotein (mol. wt. 250 kDa), while under reducing conditions, three bands corresponding to mol. wt. of 118,75 and 60 kDa were observed. Pretreatment of Mucus-Rs with pronase, trypsin and sodium metaperiodate markedly inhibited bacterial binding. GLC analysis of Mucus-Rs showed it to contain Mannose, Glucose, Galactose, Glucosamine, Galactosamine and Sialic acid as main sugars. Competitive binding in the presence of various sugars and lectins indicated the involvement of mannose in the mucus-bacterial interactions. The Mucus-Rs binding was highly specific for S. typhimurium; no significant binding was seen with E. coli and V. cholerae. Thus, we conclude that S. typhimurium specifically binds to a 250 kDa neutral mucin of intestinal tract. This binding appears to occur via specific adhesin-receptor interactions involving bacterial pili and mannose of neutral mucin.

Animals↗

Receptor mediated endocytosis by mesangial cells modulates transmigration of macrophages.

BACKGROUND: Accumulation of immune complexes in the mesangium is a common finding. Since migration of macrophages (Mphi) in the mesangium has been demonstrated to be an important event in the development of glomerular lesions, we studied the role of immune complexes and mesangial cell (MC) interaction in the transmigration (Tm) of Mphi. METHODS: To determine the effect of MC and immune complexes (aggregated IgG, IgGAg) on transmigration of Mphi. MC were incubated with or without IgGAg in the lower compartment of a modified Boyden Chamber. To determine the effects of the secretory products (as a result of endocytosis of IgGAg by mesangial cells), MC-IgAg conditioned media was prepared and placed in the lower compartment of the Boyden chamber. We evaluated the effects of MC alone, MC + IgGAg, or MC-IgGAg conditioned media on the transmigration of macrophages across a filter. To determine the effect of free radicals on MC-IgAg endocytosis-induced Mphi migration we evaluated the effect of free radical scavengers such as dimethyl thiourea (DMTU) and tetramethylthiourea (TMTU) in MC-IgAg endocytosis-induced Mphi migration. To determine the role of chemokines in MC-IgAs endocytosis-induced Mphi migration we evaluated the effect of ani-MCP-1 antibodies on MC-IgAg endocytosis-induced Mphi migration, and also studied the effects of IgAg on MC mRNA expression of MCP-1 and RANTES. In addition, we evaluated the role of Fc receptors and actin cytoskeleton of MC in transmigration of Mphi. RESULTS: Mesangial cell endocytosis of IgG aggregates (IgGAg) is associated with enhanced (P < 0.001) transmigration of Mphi (control, 11.2 +/- 0.2 vs. MC + IgGAg, 22.1 +/- 0.9 migrated Mphi/field). IgGAg also induced MC mRNA expression for RANTES and MCP-1 on MC. DMTU and TMTU attenuated (P < 0.001) the MC + IgGAg-induced migration of Mphi as well as IgGAg-induced mRNA expression for RANTES and MCP-1. MC and IgGAg interaction products (MC-IgGAg conditioned media) also increased (P < 0.01) transmigration of Mphi (control, 18.3 +/- 1.7 vs. MC-IgGAg conditioned media, 30.7 +/- 0.6 Mphi/field). This effect of MC-IgGAg conditioned media on the migration of macrophages was dose dependent. Anti-MCP-1 antibody partially inhibited MC-IgGAg-induced migration of macrophages. MC and monomeric IgG (MIgG) interaction (MC-MIgG conditioned media) showed a lower (P < 0.05) migration of Mphi, when compared to the MC-IgGAg conditioned media. MC-IgGAg conditioned media prepared from cytochalasin B pretreated MCs also showed a lower (P < 0.001) migration of Mphi when compared with MC-IgGAg conditioned media-induced migration. CONCLUSIONS: These results indicate that MC-IgGAg conditioned media-induced transmigration of macrophages may be mediated through the generation of RANTES and MCP-1 by MC.

Animals↗

The changing epidemiological pattern of hepatitis A in an urban population of India: emergence of a trend similar to the European countries.

The present study was undertaken to determine the seroprevalence of the antibody against hepatitis A virus (IgG anti-HAV) in an urban population sample from Delhi (India) and to assess any change in the epidemiological pattern of HAV infection in this part of the world. A total of 500 healthy subjects were enrolled and divided into groups on the basis of age, sex and per capita income and evaluated for the presence of IgG anti HAV antibodies using a commercially available kit. The mean age of all the subjects was 32.6 +/- 13.2 yr. and the male:female ratio was 1.5:1. The overall prevalence of IgG anti-HAV in all subjects was 71.2% (356/500). The prevalence in subjects >35 years (92.1% [186/202]) was significantly higher than that in subjects <35 years (92.1% [186/202]) was significantly higher than in subjects <35 years (57% [170/298]). No statistically significant difference was observed between male and female subjects (71.4% [217/304] vs. 70.9% [139/196]) or between subjects belonging to middle and low socioeconomic groups (68.9% [135/196] vs. 72.7% [221/304]). These findings when compared with the results that were obtained in 1982, showed a decreasing prevalence of IgG anti-HAV, most significantly in younger age groups (16-35 years). Thus, we may conclude that the seroepidemiology of hepatitis A virus infection in urban population of India seems to be changing with seroprevalence in the younger population approaching a figure similar to that of the more developed European countries.

Adolescent↗

Neuroleptic malignant syndrome associated with amoxapine and lithium in an older adult.

This report describes the presentation of neuroleptic malignant syndrome (NMS) in the primary care setting in an older adult with major depression with psychosis. This patient had been stable on a regimen of amoxapine, lithium carbonate, lorazepam, and benztropine. The patient had rigidity, altered sensorium, diaphoresis, autonomic instability, elevated WBC count and urine myoglobin, and creatine phosphokinase (CPK) reaching 1331 U/I. He was successfully treated with bromocriptine.

Amoxapine↗