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Biomedical subjects

S Banerjee

Publications and source records attributed to S Banerjee.

At least 307 records · Page 17Linked to original sources
PubMed1997

Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production.

Interferon-gamma-inducing factor (IGIF, interleukin-18) is a recently described cytokine that shares structural features with the interleukin-1 (IL-1) family of proteins and functional properties with IL-12. Like IL-12, IGIF is a potent inducer of interferon (IFN)-gamma from T cells and natural killer cells. IGIF is synthesized as a biologically inactive precursor molecule (proIGIF). The cellular production of IL-1beta, a cytokine implicated in a variety of inflammatory diseases, requires cleavage of its precursor (proIL-1beta) at an Asp-X site by interleukin-1beta-converting enzyme (ICE, recently termed caspase-1). The Asp-X sequence at the putative processing site in proIGIF suggests that a protease such as caspase-1 might be involved in the maturation of IGIF. Here we demonstrate that caspase-1 processes proIGIF and proIL-1beta with equivalent efficiencies in vitro. A selective caspase-1 inhibitor blocks both lipopolysaccharide-induced IL-1beta and IFN-gamma production from human mononuclear cells. Furthermore, caspase-1-deficient mice are defective in lipopolysaccharide-induced IFN-gamma production. Our results thus implicate caspase-1 in the physiological production of IGIF and demonstrate that it plays a critical role in the regulation of multiple proinflammatory cytokines. Specific caspase-1 inhibitors would provide a new class of anti-inflammatory drugs with multipotent action.

Animals↗
PubMed1997

Characterization of mice deficient in interleukin-1 beta converting enzyme.

Interleukin-1 beta converting enzyme (ICE) processes the inactive prolL-1 beta to the proinflammatory mature IL-1 beta. ICE belongs to a family of cysteine proteases that have been implicated in apoptosis. To address the biological functions of ICE, we generated ICE-deficient mice through gene targeting technology. ICE-deficient mice developed normally, appeared healthy, and were fertile. Peritoneal macrophages from ICE-deficient mice underwent apoptosis normally upon ATP treatment. Thymocytes from young ICE-deficient mice also underwent apoptosis when triggered by dexamethasone, gamma irradiation, or aging. ICE-deficient mice had a major defect in the production of mature IL-1 beta and had impaired IL-1 alpha production on LPS stimulation in vitro and in vivo. ICE-deficient mice were resistant to LPS-induced endotoxic shock.

Adenosine Triphosphate↗
PubMed1997

The effect of denaturants on protein structure.

Virtually all studies of the protein-folding reaction add either heat, acid, or a chemical denaturant to an aqueous protein solution in order to perturb the protein structure. When chemical denaturants are used, very high concentrations are usually necessary to observe any change in protein structure. In a solution with such high denaturant concentrations, both the structure of the protein and the structure of the solvent around the protein can be altered. X-ray crystallography is the obvious experimental technique to probe both types of changes. In this paper, we report the crystal structures of dihydrofolate reductase with urea and of ribonuclease A with guanidinium chloride. These two classic denaturants have similar effects on the native structure of the protein. The most important change that occurs is a reduction in the overall thermal factor. These structures offer a molecular explanation for the reduction in mobility. Although the reduction is observed only with the native enzyme in the crystal, a similar decrease in mobility has also been observed in the unfolded state in solution (Makhatadze G, Privalov PL. 1992. Protein interactions with urea and guanidinium chloride: A calorimetric study.

Crystallography, X-Ray↗
PubMed1997

Pulmonary agenesis with intrathoracic upper limb.

A 10-week-old boy was referred because of respiratory distress, absence of right upper limb, and a mass in the right upper chest and shoulder region. Investigations showed agenesis of the right lung; the right hemithorax was filled by a mass that was mainly cystic but also contained a deformed right upper limb. When surgery was performed at the age of 13 weeks, the mass was delivered out of the chest and removed together with the deformed limb. The upper 5 cm of the shaft of the humerus could be preserved, and the chest wall could be repaired satisfactorily. Recovery was uneventful. The embryology of the malformation is briefly discussed.

Arm↗
PubMed1997

Acute mercury vapour poisoning in an infant.

Mercury vapour inhalation is a rare cause of acute toxic injury to the lungs and is often fatal in infants. A 5 month-old girl with mercury vapour poisoning who developed chemical pneumonitis with bilateral pneumothoraces is reported. She was managed successfully in an intensive care unit with respiratory support, without chelation therapy.

Female↗
PubMed1997

Patient density, nurse-to-patient ratio and nosocomial infection risk in a pediatric cardiac intensive care unit.

BACKGROUND: An investigation of a Serratia marcescens outbreak in a pediatric cardiac intensive care unit (CICU) suggested that understaffing or overcrowding might have been underlying risk factors. OBJECTIVE: To assess the effect of fluctuations in CICU nurse staffing levels and patient census on CICU nosocomial infection rate (NIR). METHODS: The monthly CICU nursing hours, patient days and nosocomial infections were obtained from retrospective review of administrative, patient and microbiology records during December, 1994, through December, 1995 (study period). The NIR and nursing hours:patient day ratio were then calculated. The correlations between NIR vs. nursing hours, patient days and nursing hours:patient day ratio were determined. RESULTS: The median monthly CICU NIR was 6.9 (range, 0 to 15.2) infections per 1000 patient days; the median number of hours worked per month by CICU registered nurses was 7754 (range, 7133 to 8452) hours; the median number of patient days treated per month was 507 (range, 381 to 590) patient days; and the median monthly nursing hours:patient day ratio was 15.2:1 (range, 13.2:1 to 19.9:1). The strongest linear correlation was observed between the monthly NIR and patient days (r = 0.89, P = 0.0001). There was an inverse correlation between the monthly NIR and nursing hours:patient day ratio (r = -0.77, P = 0.003). CONCLUSIONS: The NIR was most strongly correlated with patient census but also was strongly associated with the nursing hours:patient day ratio. These factors may influence the infection rate because of breaks in health care worker aseptic technique or decreased hand washing. Increased patient census alone may increase the risk of cross-transmission of nosocomial infections. As hospitals proceed with cost containment efforts the effect of fluctuations in patient census and nurse staffing on patient outcomes needs evaluation.

Child↗
PubMed1997

Fat accretion and the regulation of insulin-mediated glycogen synthesis after puberty in rats.

Peripheral insulin sensitivity decreases after puberty in both humans and rodents and can be explained mostly by a reduction in insulin-mediated glycogen synthesis. We tested the hypothesis that the increase in postpubertal fat mass (FM), reflecting an alternative energy store, regulates a decrease in the capacity to store muscle glycogen. We studied Sprague-Dawley rats (n = 21) before puberty (Pre) or after puberty (at 4 mo of age) in groups that were either ad libitum fed (Post) or moderately caloric restricted (CR). FM (by 3H2O isotope dilution technique) was decreased by >40% in CR compared with Post. Glucose uptake (Rd, by 18 mU x kg(-1) x min(-1) hyperinsulinemic clamp) was 63 +/- 8 mg x kg(-1) x min(-1) in Pre and decreased to 39 +/- 2 mg x kg(-1) x min(-1) in Post (P < 0.001). However, it increased in CR to 53 +/- 2 mg x kg(-1) x min(-1) (P < 0.001 vs. Post). This increase in Rd was mainly accounted for by an increase in glycogen synthesis (Rd glycolysis determined by the rate of conversion of 3H-labeled glucose to 3H2O) from 23 +/- 2 in Post to 33 +/- 2 mg x kg(-1) x min(-1) in CR (P < 0.001; 38 +/- 7 mg x kg(-1) x min(-1) in Pre). Correction of glycogen synthesis in CR to near-prepubertal levels was further supported by directly assayed muscle glycogen content after insulin stimulation that was 45% higher and by a 35% enhanced accumulation of [3H]glucose into glycogen. No changes in the enzyme kinetics of glycogen synthase or phosphorylase were observed. An additional group of 2-mo-old postpubertal ad libitum-fed rats was matched with CR for lean body mass but had more FM. This group demonstrated 25% lower rates of insulin-mediated glycogen synthesis compared with CR, further supporting the notion that a moderate reduction of FM prevents the decline in insulin responsiveness and glycogen synthesis occurring after puberty. These data suggest a cause-effect relationship between the increased deposition of fat and the reduced ability to store glucose in skeletal muscle after puberty.

Adipose Tissue↗
PubMed1997

Personality disorder and psychopathology in Tourette's syndrome: a controlled study.

BACKGROUND: Some specialists associate a wide variety of psychopathologies with Tourette's syndrome (TS), while others suggest that there is no psychopathology specifically associated. Few controlled studies have been conducted to address this issue, and none has investigated personality disorder in TS. METHOD: Adults with TS and controls were evaluated using standardised psychiatric rating scales, including self-rated (STPCD) and clinician-rated (SCID-II) assessments of personality disorder, to investigate associations between personality disorder, other psychopathology and TS. RESULTS: Significantly more TS patients (25/39 (64%)) than controls (2/34 (6%)) had one or more personality disorders. TS subjects were also more likely to have more personality disorders. TS patients had significantly more depression, anxiety and obsessionality than controls. The SCID-II and STCPD were moderately well correlated. CONCLUSIONS: TS patients have a high prevalence of personality disorder and psychopathology when compared with controls. These results are the first to suggest a high level of personality disorder in a TS clinic population.

Adult↗
PubMed1997

Evidence based health care in old age psychiatry.

OBJECTIVE: The purpose of this article is to present the current status and future needs of old age psychiatry in relation to evidence-based health care. METHOD: The opportunities and difficulties of evidence-based medicine as applied to old age psychiatry are described. Depression is used as a specific example. The role of the Cochrane Collaboration and of clinical guidelines in dealing with these difficulties are discussed. RESULTS: There has been a tendency for drug studies to focus on younger age groups and to exclude patients with comorbidity or polypharmacy. Aspects of clinical management separate from drugs are given insufficient attention. The generalizability of current studies is a problem in old age psychiatry. CONCLUSIONS: Psychiatry is no less part of medicine than any other specialty. Increased attention to studies of effectiveness, as opposed to efficacy, is indicated. The Cochrane Collaboration is an international network which promotes and conducts systematic reviews of the effectiveness of health care. Systematic reviews can increase the generalizability of the current knowledge base and better define the needs for future research.

Aged↗
PubMed1997

Fine needle aspiration cytology in the diagnosis of mediastinal seminomas.

Fine needle aspiration cytology (FNAC) was employed to diagnose 117 cases of mediastinal tumours from January, 1985 till December, 1994. Six cases were diagnosed as mediastinal seminomas which are rare mediastinal malignant neoplasms. All patients had complete resolution of the mediastinal masses after external beam radiotherapy. Diagnosis of mediastinal masses by FNAC can spare the patients from more invasive diagnostic procedures and help the thoracic surgeons to plan immediate treatment.

Biopsy, Needle↗
PubMed1997

Immunity to cartilage link protein in patients with juvenile rheumatoid arthritis.

OBJECTIVE: To determine whether children with juvenile rheumatoid arthritis (JRA) express cellular immunity to cartilage link protein. METHODS: Link protein was purified from human fetal epiphyseal and bovine adult nasal cartilage. It was used in proliferation assays with the peripheral blood lymphocytes isolated from 54 children with JRA and 22 nonarthritic controls. RESULTS: Patients with JRA expressed a significantly higher prevalence of cellular proliferation to human link protein compared with the control group, independent of whether they had pauciarticular, polyarticular, or systemic disease. In the case of bovine link protein, significant differences were only noted for the polyarticular group. There was significant correlation between the immunity to bovine and to human link proteins. Furthermore, immune responses to both molecules correlated with measures of joint disease activity. CONCLUSION: These results suggest that immunity to link protein may play a role in the pathogenesis of JRA.

Adolescent↗
PubMed1997

The role of Helicobacter pylori in the pathophysiology of duodenal ulcer disease and gastric cancer.

Helicobacter pylori infection is now recognized to be an important acquired factor in the pathogenesis of duodenal ulcer disease. There is also an association between H pylori and the subsequent development of gastric cancer. The mechanism of the association between the infection and those disorders is incompletely understood but there is increasing evidence that H pylori-induced disturbances of gastric function play a pivotal role. In this article we review the role of H pylori infection in the pathophysiology of these important upper gastrointestinal diseases.

Ascorbic Acid↗
PubMed1997

Benign pleomorphic adenoma of the larynx: report of a case and review and analysis of 20 additional cases in the literature.

Among the benign pleomorphic adenomas of the minor salivary glands, those that develop in the larynx are very rare. One such case of benign pleomorphic adenoma of the larynx in an adult female is described. The patient was treated with epiglottectomy with a lateral pharyngotomy approach. Review of the literature showed an additional 20 well-described cases of benign pleomorphic adenoma of the larynx. These patients usually present with hoarseness, dyspnea or dysphagia, or any combination of these depending on the site of origin and the size of the tumor. Occasionally the tumor may be discovered incidentally. The tumor can occur in any part of the larynx with the epiglottis being the most common site. Clinically they are indistinguishable from other benign laryngeal neoplasms, as surface mucosal lining remains intact. Histopathological examination is used to make the definitive diagnosis, but rarely, misinterpretation may occur. Conservative surgery provides a lasting cure.

Adenoma, Pleomorphic↗
PubMed1997

Differential effects of taxol on two human cancer cell lines.

Taxol is the prototype of a new class of drugs with promise in the treatment of various cancers. Its mechanism of action is not fully understood. We have investigated the effects of taxol on two human cancer cell lines, HT-29, derived from a colon carcinoma, and SK-MEL-28, from a melanoma. Immunofluorescence staining for microtubules, cell cycle analysis by flow cytometry, cytotoxicity assays, and DNA fragmentation studies by agarose gel electrophoresis were performed. The two cell lines responded quite differently to taxol. HT-29 cells, when treated with taxol for 24 h, showed an abundance of multiple microtubule asters and the cells were arrested in mitosis. Flow cytometry also showed arrest in mitosis and development of a hypodiploid region with increasing taxol incubation times. These cells were more sensitive to taxol exposure, which caused internucleosomal DNA fragmentation, indicative of apoptosis. The SK-MEL-28 cells, on the other hand, were less sensitive to taxol. Significant cytotoxic effects were only visible after 72 h. These cells exhibited a predominance of microtubule bundles and multinuclei, and only a few cells were arrested in mitosis. Flow cytometry revealed that the SK-MEL-28 cells became polyploid, as a result of exit from mitosis without cell division. These results suggest that the mechanism involved in taxol-induced cell death is different in these two cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Pre-labour rupture of membrane: the histological study of membrane and bacteriological profile.

One hundred two (102) cases of pre-labour rupture of membrane (PROM) were studied and special attention was given to the histological study of the amniotic membrane as well as to the bacteriological study of high vaginal flora, cervical flora and flora of amniotic fluid, in search of probable causes or factors leading to PROM. The incidence was found to be 3.16% in the age group of 20-25 years without any relation to parity; and the duration of gestation was 38 to 40 weeks in most of the cases. The histological study revealed: (a) Focally denuded amniotic epithelium, focally separated amniotic epithelium from chorion layer, lesser density of focal squamoid change of the epithelium and thicker chorion layer probably indicating focal immaturity of the chorio-amnion, (b) lesser thickness of collagen layer, focal hydropic degeneration and mild cellular infiltrate, (c) presence of focal hyaline degeneration and focal calcification of chorio-amnion. Microbial culture revealed: (a) Higher rate of positive culture in high vaginal swab, cervical swab and amniotic fluid showing presence predominantly of Esch coli, Strept haemolyticus, klebseilla species, Staph aureus, Strept non-haemolyticus, proteus species and pseudomonas species against that of positive cultures in the control cases, (b) no anaerobic bacteria from high vaginal swab, cervical swab or from amniotic fluid. It was presumed that focal immaturity of chorio-amnion or focal irregularity in the chorio-amnion at the microscopical level, focal degeneration of collagen superadded with bacterial infection, however mild, could be the factors leading to weakness in the tensile strength of chorio-amnion, again leading to PROM, in the face of stress factors of foetal origin.

Adult↗
PubMed1996

Elimination of the hydrolytic water molecule in a class A beta-lactamase mutant: crystal structure and kinetics.

Two site-directed mutant enzymes of the class A beta-lactamase from Staphylococcus aureus PC1 were produced with the goal of blocking the site that in the native enzyme is occupied by the proposed hydrolytic water molecule. The crystal structures of these two mutant enzymes, N170Q and N170M, have been determined and refined at 2.2 and 2.0 A, respectively. They reveal that the side chain of Gln 170 displaces the water molecule, whereas that of Met170 does not. In both cases, the catalytic rates with benzylpenicillin are reduced by 10(4) compared with the native enzyme. With nitrocefin, the N170Q mutant enzyme exhibits an approximately 800-fold reduced rate compared with the native enzyme and in addition, a fast initial burst with stoichiometry of 1 mol of degraded nitrocefin/mol of enzyme. Stopped-flow kinetic experiments establish that the rate constant of the burst is 250 s-1, a value comparable with the rate of acylation of the native enzyme. Two structurally based mechanisms that explain the kinetic properties of the N170Q beta-lactamase are proposed, both invoking a deacylation-impaired enzyme due to the elimination of the hydrolytic water molecule. The catalytic rate of the N170M mutant enzyme with nitrocefin is reduced by approximately 50-fold compared with the native enzyme, and the slow progressive inhibition that is revealed indicates that the hydrolysis proceeds via a branched pathway mechanism. This is consistent with the structural data that show that the water site is preserved and that Met170 occupies part of the space that is required for substrate binding. The short contacts between the substrate and the enzyme may lead to structure perturbation and inactivation.

Base Sequence↗