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Biomedical subjects

S Singh

Publications and source records attributed to S Singh.

At least 379 records · Page 21Linked to original sources

Biliary lipid peroxidation products in gallbladder cancer: increased peroxidation or biliary stasis?

Gallbladder cancer is a common malignancy among women in India. The aetiology of gallbladder carcinoma is still obscure and although numerous factors have been implicated, none has stood the test of time. This study was carried out to evaluate the role of lipid peroxidation product 4-hydroxynonenal (HNE) in gallbladder carcinogenesis. High-performance liquid chromatography (HPLC) analysis was carried out in 30 bile samples obtained during laparotomy from patients with gallbladder cancer (n = 10), cholelithiasis (n = 10) and age- and sex-matched controls (n = 10). A significantly high concentration of HNE and lower concentration of biliary pH and electrolyte was observed in patients with carcinoma of the gallbladder compared with controls and patients with cholelithiasis. A significant correlation was also observed between biliary Na+ and K+ (r = 0.72), biliary Ca2+ and Na+ (r = 0.69) among controls. However, there was no correlation between HNE, electrolytes and pH among cancer patients. An increased concentration of biliary HNE and decreased concentration of electrolytes suggest biliary stasis rather then increased peroxidation in cancer patients.

Aldehydes↗

Identification of epididymis-specific antigens using neonatal tolerization.

PROBLEM: Conventional immunization using whole sperm containing multiple antigens as the immunogen followed by hybridoma technology usually gives antibodies to antigens invariably of testicular origin, probably because of the strong immunogenic nature of these antigens. Therefore, an alternate approach of neonatal tolerization or subtractive immunization has been utilized to raise antibodies specific to epididymis by suppressing immune response to testicular antigens. METHOD OF STUDY: Neonatal mice were tolerized with testicular sperm proteins on days 0 and 5. These animals were then immunized with epididymal sperm proteins on day 21, followed by two boosters at biweekly intervals. Sera from these mice were used to localize epididymis-specific antigens. RESULTS: Sera from mice that were tolerized to testicular sperm proteins and later immunized with epididymal sperm proteins reacted only with epididymal proteins. CONCLUSION: The results of this study demonstrate that neonatal tolerization with testicular sperm proteins, followed by immunization with epididymal sperm proteins, enhances the production of antibodies to proteins exclusively of epididymal origin.

Animals↗

Antibodies against ribosomal phosphoprotein P0 of Plasmodium falciparum protect mice against challenge with Plasmodium yoelii.

Antibodies against the Plasmodium falciparum P0 ribosomal phosphoprotein (PfP0) have been detected exclusively but extensively in malaria-immune persons. Polyclonal rabbit and mice sera were raised against two recombinant polypeptides of P. falciparum P0 protein, PfP0N and PfP0C, covering amino acids 17 to 61 and the remaining amino acids 61 to 316, respectively. Sera against both these domains detected a 35-kDa protein from Plasmodium yoelii subsp. yoelii, a rodent malarial parasite, and stained the surface of merozoites in immunofluorescence assays. Total immunoglobulin G (IgG) purified from rabbit and mouse anti-PfP0 sera by ammonium sulfate and DEAE-cellulose chromatography was used for passive transfer experiments in mice. Mice passively immunized with both anti-PfP0N and anti-PfP0C showed distinctly lower levels of parasitemia than control mice. With immunizations on days -1, 0, 1, 3, and 5, about 50% of both sets of mice receiving anti-PfP0N and anti-PfP0C cleared the lethal 17XL strain of P. yoelii and revived by day 25. All the control mice died by day 10. By extending the immunization schedule, the survival period of the mice could be extended for every mouse that received anti-PfP0 IgG. These data demonstrate the cross-protection of the anti-PfP0 IgG and establish parasite P0 protein as a target for invasion-blocking antibodies.

Animals↗

Amylase hyper-producing haploid recombinant strains of Thermomyces lanuginosus obtained by intraspecific protoplast fusion.

Amylase hyper-producing, catabolite-repression-resistant, recombinant strains were produced by intraspecific protoplast fusion of thermophilic fungus Thermomyces lanuginosus strains, using well-characterized, morphological, and 2-deoxy-D-glucose resistant markers. The fusant heterokaryons exhibited enhanced amylase activities as compared to the amylase hyper-producing parental strain (T2). Diploids derived from heterokaryons segregated to stable haploid recombinant strains. In the haploid strain (Tlh 4q), approximately 5-fold higher specific activities of alpha-amylase and glucoamylase in the culture filtrate were observed as compared to the wild-type strain (W0).

Amylases↗

Dexamethasone and cyclosporin A affect the maturation of monocyte-derived dendritic cells differently.

In contrast to the confirmed effects of glucocorticoids (GCs) and cyclosporin A (CyA) on T cells, the effects of both agents on antigen-presenting cells (APCs), especially on dendritic cells (DCs), are still poorly understood. In this study, we cultured monocyte-derived DCs (MoDCs) under a variety of stimulations in the presence or absence of these immunosuppressants and compared their effects on the activation of MoDCs by these stimulations. The stimulations used were the following: three bacterial toxins, including lipopolysaccharide (LPS), staphylococcal enterotoxin A (SEA) and streptococcal pyrogenic exotoxin A (SPEA), the combination of IL-1beta and TNF-alpha, and an agonistic anti-CD40 antibody. All of these stimulations increased the expression of CD54, CD83, CD86, and HLA-DR antigen, and the production of TNF-alpha in MoDCs. When MoDCs were treated with dexamethasone (Dex) during the stimulation, Dex significantly suppressed the augmentation of CD86 expression and TNF-alpha production induced by all of these stimulations. In contrast, when MoDCs were treated with CyA, it inhibited only the effects induced by the superantigens, SEA and SPEA, but not that induced by LPS, the combination of cytokines, or anti-CD40 antibody. The augmentation of CD54 or HLA-DR antigen expression was not significantly suppressed by either Dex or by CyA. When we used MoDCs pretreated with each of these stimulations + Dex or + CyA as APCs, however, significant suppression of T cell proliferation was observed only in the case of the pretreatment with IL-1beta/TNF-alpha + Dex. The allogeneic T cell stimulation by MoDCs pretreated with the other combinations did not significantly differ from that treated with the stimulation alone. Our present study succeeded in demonstrating a clear difference between Dex and CyA in the activation of MoDCs. These differences may induce a significant difference in their final immunological responses.

Antigens, CD↗

Stress and vulnerability to posttraumatic stress disorder in children and adolescents.

OBJECTIVE: This study examined the experiential factors and interacting vulnerabilities that contribute to the development of posttraumatic stress disorder (PTSD) in children and adolescents. METHOD: Of 100 consecutive referrals to an inner-city child and adolescent psychiatry clinic, 59 had experienced a trauma that qualified as a precipitant of PTSD. For those with trauma, ages ranged from 3 to 18 years (mean=9.9, SD=4.10); 39 (66%) were males. The authors used a series of multiple regression analyses to examine the contribution of demographic characteristics, the nature of the stressor(s), and the role of preexisting clinical signs in the development of PTSD. RESULTS: Twenty-two percent of the 59 children who had been traumatized met full criteria for PTSD, 32% had some symptoms of PTSD but did not meet full criteria, and 46% had no symptoms of PTSD. Witnessing domestic violence or being physically abused predicted severity of PTSD. Children with preexisting aggressive behavior were more likely to be victims of physical abuse. CONCLUSIONS: Traumatic experience interacts with factors in the child and family to contribute to the development of PTSD. Trauma that threatens family integrity appears to make a strong contribution to the development of PTSD. Increased understanding of the factors contributing to PTSD may provide additional opportunities for developing effective interventions.

Adolescent↗

Non-fatal ethylene dibromide ingestion.

Ethylene dibromide (1,2-dibromoethane) is widely used to fumigate grain and fruit in India. However, acute poisoning due to it has rarely been reported in the literature and most of these patients had an fatal outcome. We describe the suicide attempt of a young male who ingested an ampoule (3 ml) of it, developed acute hepatic and renal failure, metabolic acidosis and coagulopathy but survived following supportive measures.

Acute Kidney Injury↗

Frequency- and time-dependent effects of fendiline on action potentials of guinea pig papillary muscle.

The action of fendiline on cardiac electrical activity was investigated in guinea pig papillary muscle by monitoring frequency- and time-dependent changes in membrane potential, action potential (AP) configuration and conduction velocity. Isolated guinea pig papillary muscles driven at 0.1 to 3 Hz showed a concentration-dependent reduction of +Vmax, overshoot, and AP duration at -20mV (APD20) in the presence of fendiline (1-320 microM), reflecting inhibition of Na+ and L-type Ca2+ channels, respectively. No significant change in resting potential and AP duration at 90% repolarization (APD90) were observed. Inhibition of +Vmax and APD20 was more prominent at higher frequency of stimulation (2 Hz) than at lower ones (0.2 Hz), demonstrating frequency-dependent block of Na+ and Ca2+ channels including an open channel block. A good relationship between changes in +Vmax and APD20 suggested some commonality in the mechanism of inhibition of Na+ and Ca2+ channels by fendiline. Time-dependence of effects of fendiline, observed in presence of bolus dose (200 microM), showed an earlier onset of inhibition of +Vmax and APD20, particularly at higher frequencies. Missed beats and conduction block also appeared earlier in preparations driven at higher frequency. These findings suggest a frequency-dependent (and open channel) block of Na+ and Ca2+ channels by fendiline, leading to inhibition of fast and slow conduction in addition to its reported inactivated Ca2+ channel block.

Action Potentials↗

Mutations affecting the delayed rectifier potassium current in Drosophila.

Mutations and pharmacological agents have been used to resolve and analyze several K(+) currents in Drosophila. Mutations that affect channels carrying the voltage-activated I(A) and the Ca(2+) -activated I(CF) have helped greatly in analyzing the structure, function and regulation of these channels. We now report mutations that selectively affect the delayed rectifier current, I(K). Flies mutagenized with ethylmethanesulfonate were screened for temperature-induced paralysis. Paralytic mutants identified in the screen were examined for K(+) currents in the larval body-wall muscles. The z66 mutant larvae showed a significant reduction in I(K). The mutation did not affect other K(+) currents (I(A), I(CF), or I(CS) ) or the Ca(2+) channel current in the muscles. Another mutation, z4, which showed reduced I(K), failed to complement z66. Genetic analysis localized the gene disrupted by z66 and z4 to the left arm of chromosome 3, in the 63A1-63B6 region on polytene chromosomes. The z66 and the z4 mutations, which lie in the Shab K(+) channel gene, provide an opportunity to undertake analysis of the functioning of these channels and to study the role of these channels in membrane excitability.

Action Potentials↗

Aspirin esterases in North-West Indians: the influence of age and nutrition.

OBJECTIVE: To determine the activity of aspirin esterases in North-West Indian population and to find the effect of age and nutrition on it. SUBJECTS, MATERIAL AND METHODS: The serum albumin, plasma cholinesterase (PChE), aspirin esterase (ASPES) and phenyl acetate esterase (PAE) were determined in 175 subjects: young (< 40 years) and healthy (BMI > 19) = 74; elderly (> 50 years) and healthy (BMI > 19) = 32; young (< 40 years) and emaciated (BMI < 19) = 44; elderly (> 50 years) and emaciated (BMI < 19) = 25). RESULTS: The serum albumin levels significantly decreased with increase in age (r = -0.384, p < 0.01) and with decrease in body mass index (r = 0.457, p < 0.01). When the activity of esterases in four groups was compared, the PAE activity was not found to be affected by age or nutrition and the ASPES and PChE activity were significantly lower only in elderly emaciated (p < 0.01). CONCLUSION: As elderly emaciated have decreased serum albumin, ASPES and PChE activity, they may need a lower dose of aspirin to achieve the desired antiplatelet and analgesic effect. The young emaciated subjects, in spite of their lower serum albumin levels, may not require a lower dose of aspirin.

Adult↗

Acute alcoholic myopathy, rhabdomyolysis and acute renal failure: a case report.

A case of middle aged male who developed swelling and weakness of muscles in the lower limbs following a heavy binge of alcohol is being reported. He had myoglobinuria and developed acute renal failure for which he was dialyzed. Acute alcoholic myopathy is not a well recognized condition and should be considered in any intoxicated patient who presents with muscle tenderness and weakness.

Acute Kidney Injury↗

Mitral regurgitation following percutaneous transvenous mitral commissurotomy: a single-center experience.

BACKGROUND AND AIM OF THE STUDY: Percutaneous transvenous mitral commissurotomy (PTMC) has revolutionized the treatment of patients with symptomatic mitral stenosis and is now established as the procedure of choice. Despite high technical expertise in PTMC using the Inoue balloon, mitral regurgitation (MR) remains a major procedure-related complication. We retrospectively analyzed our data of PTMC using the Inoue balloon with regard to the incidence of MR, its likely causative mechanism, and follow up of these patients. METHODS: During the past ten years, PTMC was performed in 3,650 patients (median age 26 years; range: 8-76 years), of whom 910 (24.9%) were juveniles. Preprocedure mitral valve area (MVA) was 0.9 +/- 0.4 cm2 (range: 0.3-1.3 cm2); MR was mild in 1,396 cases (38.2%), moderate in 394 (10.8%) and severe in 22 (0.6%). None of the patients was rejected on the basis of echocardiographic score. RESULTS: The procedure was successful in 3,276 (89.8%), with post-procedure MVA of 1.7 +/- 0.6 cm2 (range: 1.4-2.6 cm2), and without development of any major complication. Severe MR was seen in 120 patients (3.3%), of whom 66 (1.8%) required urgent mitral valve replacement (MVR). Echocardiography in these latter patients showed leaflet rupture in 48 (72.7%), chordal rupture in 12 (18.2%) and excessive commissural tear in six (9.1%). Fifty-four patients (1.5%) with severe MR post PTMC were followed with medical treatment; echocardiography in these patients revealed chordal rupture in 40 (74.1%) and excessive commissural tear in 14 (25.9%). Follow up data were available in 49 patients (1.3%); 30 (0.8%) required MVR and 19 (0.5%) were in NYHA class II at a median follow up of 24 months. Moderate MR was seen in 188 cases (5.1%), with predominant causative mechanisms of excessive commissural tear in 120 (63.8%) and chordal rupture in 68 (36.2%). Severity of MR worsened in 30 cases (0.8%), of which 20 (0.6%) required elective MVR on follow up. MR decreased in 58 patients (1.6%), in whom excessive commissural tear was the causative mechanism. CONCLUSION: Significant MR (moderate or severe) after PTMC was seen in 308 patients (8.4%), of whom 116 (3.2%) required MVR urgently or on follow up. All patients with leaflet rupture during PTMC developed severe MR and required urgent MVR. There was a tendency for the severity of MR to decrease with time in cases where excessive commissural tear was the causative mechanism.

Adolescent↗

Imaging of mucormycosis skull base osteomyelitis.

Skull base osteomyelitis (SBO) is typically bacterial in origin and caused by Pseudomonas, although the fungus Aspergillus has also rarely been implicated. SBO generally arises from ear infections and infrequently complicates sinonasal infection. Rhinocerebral Mucor infection is characteristically an acute, fulminant, and deadly infection also affecting the orbits and deep face and is associated with intracranial complications. Bony involvement is uncommon because of the angioinvasive nature of the fungus. More recently, chronic invasive Mucor sinusitis has been described. We report the unusual clinical and imaging features of a patient with biopsy-proven invasive mucormycosis arising from chronic isolated sphenoid sinus disease, who presented with extensive SBO and a paucity of deep facial, orbital, or intracranial involvement.

Biopsy↗

Reconstruction of the superior vena cava with the aid of an extraluminal venovenous jugulo-atrial shunt.

A 57-year-old woman had chronic benign superior vena cava syndrome related to the long-term use of multiple central venous catheters for chemotherapy. Treatment included resection of the obstructed segment and repair of the superior vena cava with an autologous pericardial patch. Intraoperatively, return venous flow was maintained with an extraluminal venovenous jugulo-atrial shunt. The shunt relieved upper-body hypertension and congestion, resulting in early extubation and a short, smooth postoperative course.

Catheterization, Central Venous↗