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Biomedical subjects

A Kaul

Publications and source records attributed to A Kaul.

At least 55 records · Page 3Linked to original sources
PubMed1996

Early signaling events by endotoxin in PC12 cells: involvement of tyrosine kinase, constitutive nitric oxide synthase, cGMP-dependent protein kinase, and Ca2+ channels.

We studied the effects of endotoxin from Escherichia coli (E. coli) on Ca2+ channel activity in PC12 cells using the cell-attached patch clamp technique. Endotoxin (1-100 ng/ml) decreased channel availability (n x Po) to about one third of control values, an effect that required 3.5 +/- 1 min (mean +/- SD; n = 13) to reach steady state. The biophysical properties of the channel, including slope conductance (22 pS; 40 mM Ba2+), voltage dependence of n x Po, and open times (tau 1 = 0.78 ms, tau 2 = 8.9 ms) for the two open states at 0 mV, were not altered. The effect of endotoxin was blocked by polymyxin-B, indicating involvement of the lipid-A moiety of lipopolysaccharide, and by the tyrosine kinase (tk) inhibitor, tyrphostin. The effect of endotoxin was mimicked by 8-bromo-cGMP (100 microM), and was blocked by the inhibitor of cGMP-dependent protein kinase (PKG), H-8, suggesting involvement of the cGMP/PKG pathway. The effect of endotoxin also was blocked by the nitric oxide (NO) synthase inhibitor, NG-monomethyl-L-arginine monoacetate, suggesting involvement of nitric oxide synthase (NOS). The rapidity of the effect of endotoxin on Ca2+ channel activity suggested that constitutive NOS (cNOS) was involved, in accordance with our finding that endotoxin-induced transcriptional induction of NOS, as measured by nitrite production, required > 6 hr. We conclude that early signaling events by endotoxin in PC12 cells involve tk, cNOS, cGMP/PKG, and Ca2+ channels.

Animals↗
PubMed1996

Cytomegalovirus infection in human immunodeficiency virus type 1-infected children.

BACKGROUND: Cytomegalovirus (CMV) is a frequent opportunistic infection in human immunodeficiency virus type 1 (HIV-1)-infected children. The interactions of CMV and HIV-1 in coinfected children are not well-characterized. OBJECTIVE: To evaluate the prevalence of asymptomatic CMV infection and symptomatic CMV disease and to assess the influence of CMV on clinical and laboratory markers of HIV disease progression in CMV-coinfected children. METHODS: Serial urine CMV cultures were performed on 500 children (131 HIV-1-infected (HIV+), 129 seroreverters born to HIV-infected mothers, and 240 HIV-uninfected (HIV-)). The clinical, immunologic and virologic data of 131 HIV+ children were analyzed. RESULTS: CMV was recovered in 40 of 131 HIV+ (31%), 22 of 129 seroreverters (17%) and 30 of 240 HIV- (13%) children. Of the 40 HIV+ children with CMV coinfection, 7 developed symptomatic CMV disease (17.5%) including chorioretinitis (3), colitis (2) and pneumonitis (2). The HIV+ children with symptomatic CMV disease had significantly lower mean CD4+ T lymphocyte proportions (17% vs. 26%; age-adjusted P = 0.013) and greater HIV p24 antigen concentrations (329 pg/ml vs. 57 pg/ml; age-adjusted P = 0.13) than HIV+ children with asymptomatic CMV infection. In a subset of children coinfected with CMV before 6 months of age (n = 11), 5 (45%) developed symptomatic CMV disease, and 4 of these 5 children died within 10 months of diagnosis of CMV disease. At the time of the first positive CMV culture in these children, mean CD4+ T lymphocyte proportions did not differ according to the presence or absence of CMV-related symptoms (symptomatic CMV+, 21% vs. asymptomatic CMV = 38%; P = 0.14). In HIV+ children with symptomatic CMV disease, p24 antigen concentrations were greater than in those with asymptomatic CMV infection (461 vs. 190 pg/ml, P = 0.06). CONCLUSIONS: Symptomatic CMV disease occurred in young CMV-coinfected children with low CD4+ lymphocytes and elevated HIV p24 antigen concentrations. Whether progressive immunodeficiency allows the emergence of CMV disease or CMV infection causes more rapidly progressive HIV-1 disease or whether there is a more complex relationship remains to be determined.

Age Factors↗
PubMed1996

Rapid oral desensitization to trimethoprim-sulfamethoxazole in infants and children.

BACKGROUND: Although trimethoprim-sulfamethoxazole is the preferred chemoprophylaxis against Pneumocystis carinii pneumonia, there are frequent IgE-mediated reactions among children infected with the human immunodeficiency virus (HIV). Oral desensitization allows more patients to receive chemoprophylaxis, but it has been studied in only a limited number of children. METHODS: We desensitized five children infected with the HIV using a rapid, 4-h oral protocol. RESULTS: Three children (including two infants) successfully completed desensitization and started maintenance therapy, but the other two experienced reactions that precluded further administration of trimethoprim-sulfamethoxazole. CONCLUSIONS: We conclude that a rapid, oral trimethoprim-sulfamethoxazole desensitization protocol is safe and, in some instances, effective among HIV-infected children and infants with a history of non-life-threatening, IgE-mediated reactions to trimethoprim-sulfamethoxazole.

AIDS-Related Opportunistic Infections↗
PubMed1996

Estrogen regulation of lactoferrin expression in human endometrium.

PROBLEM: Lactoferrin is an iron-binding glycoprotein that has been shown to be overexpressed in human endometrial carcinomas. The purpose of our present study is to investigate the possible role of estradiol in the expression of lactoferrin. METHOD OF STUDY: We investigated 1) serum levels of lactoferrin in five women during normal ovulatory cycles, 2) serum levels of lactoferrin during ten human menopausal gonadotropin induced cycles when estradiol levels are high, and 3) lactoferrin expression in five proliferative and five secretory phase endometrium by immunohistochemical studies. The serum concentrations of lactoferrin were measured by a peroxidase-based enzyme-linked immunosorbent assay. RESULTS: In normal ovulatory cycles, the mean serum lactoferrin concentration during the proliferative phase (0.4013 +/- 0.0242 micrograms/mL) was significantly higher (P < 0.02) than in the secretory phase (0.3468 +/- 0.0209 micrograms/mL). In induced cycles, there was gradual increase in lactoferrin levels with increasing estradiol concentrations. Peak lactoferrin levels in induced cycles (0.7495 +/- 0.1148 micrograms/mL) were significantly higher (P < 0.003) than the midcycle levels (0.423 +/- 0.0424 micrograms/mL) in normal cycles. Immunohistochemical analysis of the endometrium revealed greater expression of lactoferrin in proliferative endometrium (50.7 +/- 13%, range 28-72%) than in secretory endometrium (19.2 +/- 4%, range 7-31%). CONCLUSION: These results indicate that estradiol may play a role in the regulation of lactoferrin expression in human endometrium.

Adult↗
PubMed1995

Association of colony variation in Serratia marcescens with the differential expression of protease and type 1 fimbriae.

Several clinical isolates of Serratia marcescens were found to dissociate on peptone glycerol agar into colonies with red and pink or white and gray phenotypes that differ in the expression of proteolytic activity and mannose-sensitive type of hemagglutination. Colonies of red and white type were proteolytically active but did not express hemagglutination, whereas pink and gray colonies were protease-deficient but agglutinated guinea pig erythrocytes. Site-directed mutagenesis of a red laboratory strain S. marcescens SM6 resulted in selection of protease negative derivative prt::G7 which expressed the pink phenotype with hemagglutinating activity. It is suggested that a DNA-regulatory element may be involved in this type of colony variation.

Animals↗
PubMed1995

Comparison of methods of estimating the mother-to-child transmission rate of human immunodeficiency virus type 1 (HIV-1). New York City Perinatal HIV Transmission Collaborative Study Group.

Four methods of estimating mother-to-child transmission rates of human immunodeficiency virus type 1 (HIV-1), based on the 1992 Ghent workshop, were compared in a multicenter New York City prospective cohort study in 1986-1992. Of 833 infants born to women at risk of HIV-1 infection, 388 were born HIV-1 seropositive and 445 were HIV-1 seronegative. The four methods, the Antibody Only, Indirect, Direct, and Virologic Methods, yielded transmission rate estimates of 19-25%, classifying 59-89% of the cohort. Estimation based on persistence of HIV-1 antibody and clinical assessment yielded transmission rates similar to those methods that incorporated virologic testing.

Adult↗
PubMed1995

Application of thin-section low-dose chest CT (TSCT) in the management of pediatric AIDS.

The aim of this study was to evaluate the usefulness of thin-section low-dose computed tomography (TSCT) in the management of children with AIDS, as chest radiographs (CXR) often fail to adequately explain the patients' clinical status. We performed 54 noncontrast TSCTs on 32 children. The patients aged from 3 months to 14.6 years, were diagnosed as having bacterial pneumonia, lumphocytic interstitial pneumonitis (LIP), Pneumocystis carinii pneumonia (PCP), or Mycobacterium avium-intracellulare infection (MAI). The scans were correlated with the clinical diagnosis, T-lymphocyte-subset percentages, and p24-antigen levels. Subsegmental consolidations were seen in patients with LIP, PCP, and MAI, and as an isolated finding in those with only bacterial pneumonia. Ground-glass haziness was seen exclusively with acute PCP. Reticulonodular thickening was identified only in patients with LIP. Mosaic perfusion was seen with MAI, LIP, and pneumonia. The presence of adenopathy correlated with CD4+ T-cell subset percentages. The greatest value of CT in this study was in detecting new disease when chest films failed to correlate with a patient's clinical state, and in demonstrating acute/subacute disease in patients with severe baseline chest-film changes. Recurrent pneumonias may represent progression of "smoldering" disease, rather than true recurrent disease following complete clearing. Adenopathy with low CD4+ levels should suggest lymphoma or infection with MAI.

AIDS-Related Opportunistic Infections↗
PubMed1995

Shortened survival in infants vertically infected with human immunodeficiency virus with elevated p24 antigenemia.

OBJECTIVE: To determine whether the amount of p24 antigenemia in the first 6 months of life is a predictor of survival in children infected vertically with human immunodeficiency virus type 1. METHODS: A retrospective study of vertically infected infants and children who were followed prospectively from early infancy and who had quantitation of plasma p24 antigen concentration in the first 6 months of life. Infants were first stratified by duration of survival as infants who died before 2 years of age (short-term survivors) and infants who survived to 2 years of age (intermediate-term survivors). The median p24 antigen concentration and the proportion of infants in each group with high concentrations of antigen were compared. Analyses with and excluding all p24 determinations made after the use of antiretroviral agents were compared Kaplan-Meier product limit analysis was used to compare survival in infants with low and high antigenemia during the first 6 months of life. RESULTS: The median p24 antigen concentration in 15 short-term survivors was 228 pg/ml, compared with 14 pg/ml in 26 intermediate-term survivors (p < 0.05). The proportion of children with > 100 pg/ml of p24 was higher in short-term than in intermediate-term survivors (p = 0.01). Survival to 2 years of age in infants in whom all p24 antigen values during the first 6 months of life were 100 pg/ml or less was 91%, in comparison with 39% in infants with values greater than 100 pg/ml (p = 0.0017). CONCLUSIONS: Elevated p24 antigenemia in the first 6 months of life is associated with shorter survival and may be a useful predictor of outcome.

Antigens, Viral↗
PubMed1995

Decreased expression of endometrial decay accelerating factor (DAF), a complement regulatory protein, in patients with luteal phase defect.

PROBLEM: We investigated the level of decay accelerating factor (DAF) in the endometrium of luteal phase defect (LPD) patients, before and after treatment with progesterone. METHODS: Endometrial samples from fourteen normal-cycling controls and six samples from infertility patients with LPD before and four samples after progesterone treatment were stained by anti-DAF IgG using immunohistochemistry. RESULTS: Mean DAF OD in LPD patients was 15% compared to 60% in the control group. The mean DAF OD was 88% after treatment with progesterone. CONCLUSION: Results support interpretation that progesterone upregulates DAF while decreased progesterone may be associated with reduced expression of the DAF in LPD patients.

Adult↗
PubMed1995

dra-related X adhesins of gestational pyelonephritis-associated Escherichia coli recognize SCR-3 and SCR-4 domains of recombinant decay-accelerating factor.

Bacterial adhesins are important virulence factors that allow colonization of the human urogenital tract by Escherichia coli. Adhesins of the Dr family have been found to be more frequently expressed in strains associated with symptomatic urinary tract infections. Because of the high frequency of symptomatic urinary tract infections during pregnancy, we screened E. coli isolates from 64 gestational pyelonephritis patients for the expression of Dr and X adhesins to address their potential virulence roles in this population. Using PCR and primers for the afaB gene, we detected dra-related operons in 17 isolates (27%). On the basis of the lack of hemagglutination of Dr(a-) erythrocytes containing a point mutation in the decay-accelerating factor (DAF) short consensus repeat-3 (SCR-3) domain, 12 of these strains were categorized as classical Dr adhesins. The hemagglutination of O erythrocytes by Dr+ strains was blocked or reduced by a monoclonal antibody to the DAF SCR-3 domain. The remaining five dra-positive strains agglutinated Dr(a-) erythrocytes. Monoclonal antibody to the DAF SCR-3 domain failed to block O-erythrocyte hemagglutination. Adhesins in these strains did not fulfill criteria for Dr hemagglutinins because of the undefined receptor specificities and were categorized as X. E. coli strains bearing dra-related X adhesins bound to DAF cDNA-transfected Chinese hamster ovary cells. Three of these dra-related X-adhesin-bearing E. coli strains failed to attach to the SCR-3 delta deletion transfectant, which suggested that binding sites were located in the SCR-3 domain but outside the region blocked by the monoclonal anti-SCR-3 immunoglobulin G. The binding sites of the remaining two dra-related X adhesin strains were localized to the SCR-4 domain, as the attachment was shown to be abolished on an SCR-4 delta mutant but unaffected by an SCR-3 delta deletion. The heterogeneity in the binding sites of E. coli DAF (Dr) family adhesins from gestational pyelonephritis isolates may reflect the ability of the adhesins to evolve to recognize alternate peptide epitopes for efficient colonization.

Adhesins, Escherichia coli↗
PubMed1995

An audit of fatal acute pancreatitis.

Acute pancreatitis has a mortality of about 10%: this figure has not changed over the last 20 years. A retrospective audit of fatal acute pancreatitis was performed in a teaching hospital with a catchment population of about 750,000 patients to examine patient characteristics. Using Hospital Activity Analysis code 577.0, all fatal cases of acute pancreatitis were studied in a six-year period 1987-93. Additionally, all post mortem diagnoses of acute pancreatitis were traced. The overall post mortem rate in Nottingham at the time of the study was about 35%. All available records, X-ray and biochemical data were studied and appropriate information recorded and analysed for 65 fatal cases. Only 15% were post mortem diagnoses, lower than in previous series; 72% had respiratory and 67% had renal complications. Only 34% had been admitted to the intensive care unit. A third of patients had had surgery; 67% of these was some form of external drainage. Of the 14 patients with proven gallstone pancreatitis only three had endoscopic retrograde cholangiopancreatography; 42% of patients had idiopathic disease. Not all the patients diagnosed ante mortem had the full biochemical predicted severity criteria analysed: pO2 and calcium analysis was performed in about 80%. Pre-mortem diagnoses of pancreatitis was achieved more frequently than in other comparable series.

Acute Disease↗
PubMed1994

Separation and purification of recombinant proteins from Escherichia coli with aqueous two-phase systems.

The partition of the protein thaumatin in the presence of Escherichia coli contaminant proteins has been studied. Extraction of thaumatin was followed by back-extraction of the product into a new phosphate phase and also back extraction combined with recycle of the top polyethylene glycol (PEG) phase. When partitioned in the absence or presence of insoluble cell debris (whole cell homogenate) little effect on the partitioning of thaumatin or the soluble E. coli protein was observed. A back extraction step that allowed for dilution of the NaCl was successful in extracting thaumatin back into a heavy phosphate phase. The PEG top phase was recycled to the first extraction stage. The stability ratio (tie-line length) had an effect on the average partition coefficient (Kapp) of E. coli soluble proteins in PEG-phosphate systems but in PEG sulphate systems Kapp was independent of this ratio. An increase in NaCl resulted in an increase in Kapp but this was always below 1. A mathematical model that describes the continuous steady-state operation of extraction and back extraction has been developed; it is based on steady state mass balances of the main components and phase equilibrium data and was successfully used to simulate the extraction and back extraction processes.

Bacterial Proteins↗