Search PubMed⌕ Search

Biomedical subjects

A Chandra

Publications and source records attributed to A Chandra.

At least 73 records · Page 4Linked to original sources
PubMed2000

Structure of a mixed dipolar liquid near a metal surface: A combined approach of weighted density and perturbative approximations

We study the interfacial structure of a mixed dipolar liquid in contact with a metal surface by using a combined approach of the weighted density and the perturbative approximations. Both the molecular size and the dipole moment of various species can be unequal. The metal surface is treated by using the jellium model. Explicit numerical results are obtained for the interfacial structure of a binary dipolar liquid in contact with a metal surface of varying electron density. The theoretical predictions are compared with the results of Monte Carlo simulations and a good agreement is found for the inhomogeneous density, mole fraction, and polarization profiles of both the species in the interfacial region.

Journal Article↗
PubMed1999

Detection of distinct patterns of anti-tat antibodies in HIV-infected individuals with or without Kaposi's sarcoma.

Patterns of antibody response to recombinant transactivator protein (HIV-1 tat) in serum samples from HIV-1-negative persons (n = 60), HIV-1-infected asymptomatic persons (n = 20), HIV-1-infected people with Kaposi's sarcoma (n = 25) and of people with Kaposi's sarcoma without HIV-1 infection have been analyzed. None of the healthy people had anti-tat IgG in their serum. All asymptomatic patients with HIV-1 infection were anti-tat IgG-positive. Epitope mapping revealed that these sera have anti-tat IgG to all the functional domains of tat protein. Four of the 25 HIV-1-infected patients with Kaposi's sarcoma were anti-tat IgG-positive; however, epitope analysis revealed that IgG to functional domains of tat protein, in particular to TAR-binding site, were absent. All patients with Kaposi's sarcoma without HIV-1 infection were anti-tat IgG-negative. Presence or absence of anti-tat IgG, and prevalence of different antibody profiles in different groups of patients suggest the pathophysiologic role of tat protein. Thus, a passive immunization with anti-tat IgG could be a useful strategy to influence the pathophysiologic state of the disease.

AIDS-Related Opportunistic Infections↗
PubMed1999

Amino acid substitution in alpha-helix 7 of Cry1Ac delta-endotoxin of Bacillus thuringiensis leads to enhanced toxicity to Helicoverpa armigera Hubner.

Insecticidal proteins or delta-endotoxins of Bacillus thuringiensis are highly toxic to a wide range of agronomically important pests. The toxins are formed of three structural domains. The N-terminal domain is a bundle of eight alpha-helices and is implicated in pore formation in insect midgut epithelial membranes. All the delta-endotoxins share a common hydrophobic motif of eight amino acids in alpha-helix 7. A similar motif is also present in fragment B of diphtheria toxin (DT). Site-directed mutagenesis of Cry1Ac delta-endotoxin of B. thuringiensis was carried out to substitute its hydrophobic motif with that of DT fragment B. The mutant toxin was shown to be more toxic to the larvae of Helicoverpa armigera (cotton bollworm) than the wild-type toxin. Voltage clamp analysis with planar lipid bilayers revealed that the mutant toxin opens larger ion channels and induces higher levels of conductance than the wild-type toxin.

Amino Acid Substitution↗
PubMed1999

Adoption, adoption seeking, and relinquishment for adoption in the United States.

OBJECTIVES: This report presents national data on adoption and adoption-related behaviors among ever-married women 18-44 years of age in the United States, according to selected characteristics of the women. Trends are shown in the prevalence of adoption and relinquishment of children for adoption. For 1995, the report shows demand for adoption and women's preferences for characteristics of the child. METHODS: Data are based on nationally representative samples of women 15-44 years of age from the 1973, 1982, 1988, and 1995 National Surveys of Family Growth (NSFG). RESULTS: The percent of ever-married women 18-44 years of age who have ever adopted a child declined from 2.1 percent in 1973 to 1.3 percent in 1995. Of the 9.9 million women who had ever considered adoption, 16 percent had taken steps toward adoption, and 31 percent of these had actually adopted a child. Older women, nulliparous women, women with fecundity impairment, and women who have used infertility services were more likely to have considered adoption, to have taken concrete steps toward adoption, and to have actually adopted a child. In response to the questions about preferred characteristics of an adopted child, women expressed strong preferences with respect to age, sex, race, and disability level of the child, but were willing to accept children with the less-desired traits. Between 1989 and 1995, about 1 percent of babies born to never-married women were relinquished for adoption, down from 9 percent among such babies born before 1979. CONCLUSIONS: Federally supported adoption data collection sources corroborate the decline in adoption shown by the NSFG over the past 25 years. Demand for adoption in the United States varies, depending on whether demand is conceptualized liberally as "ever having considered adoption" or more narrowly, as "currently taking concrete steps toward adoption." The narrow definition was fulfilled by 232,000 ever-married women in 1995.

Adolescent↗
PubMed1999

Intercellular traffic of human immunodeficiency virus type 1 transactivator protein defined by monoclonal antibodies.

Monoclonal antibodies (mAbs) directed against the amino-terminal region (N-terminal sequence 2-19) of transactivator protein (tat) of HIV-1 have been shown to inhibit intercellular transactivation mediated by the extracellular tat protein. The intracellular transactivation was not significantly affected by anti-tat mAbs. The specificity of anti-tat mAbs in abolishing the transactivating potential of extracellular tat is documented by studies with mAbs to HIV-1 reverse transcriptase, or to a human mammary cancer protein. None of these antibodies showed any inhibitory effect on intercellular transactivation. Specific interaction of anti-tat IgG with tat protein expressed in Jurkat cells is further supported by experiments on immunoblotting. Extracellular tat is responsible for signals which induce a variety of biological responses in HIV-infected cells, as well as in uninfected cells. The fact that anti-tat mAbs can abolish the intercellular traffic of tat protein offers a unique strategy in the development of vaccines against AIDS.

Animals↗
PubMed1999

Health insurance coverage of the unemployed: COBRA and the potential effects of Kassebaum-Kennedy.

We use the April 1993 Current Population Survey to examine the health insurance coverage decisions of the unemployed and to simulate the potential effects of the new Kassebaum-Kennedy legislation. After controlling for demographic characteristics, COBRA eligibility raises the probability of health insurance coverage by 0.095, while eligibility for spouse employer insurance increases the likelihood of coverage by 0.318, and eligibility for both increases the likelihood of coverage by 0.341. In our simulations, we find that had Kassebaum-Kennedy been in effect in April 1993, 9.0 percent of the unemployed would be eligible to take up coverage, and the coverage rate of the unemployed would have been increased by 0.85 percent to 1.5 percent from 41.6 percent. Our estimates of the effect of Kassebaum-Kennedy on health insurance coverage are much lower than those reported by the Government Accounting Office prior to the passage of the legislation.

Eligibility Determination↗
PubMed1999

Induction of glutathione S-transferase hGST 5.8 is an early response to oxidative stress in RPE cells.

PURPOSE: To delineate the role of the glutathione S-transferase (GST) isozyme hGST 5.8 in protection mechanisms against oxidative stress, the effect of low-level transient exposure of H2O2 to retinal pigmented epithelial (RPE) cells on hGST 5.8 and other enzymes involved in defense against oxidative stress was examined. METHODS: Cultured human RPE cells were exposed to 50 microM H2O2 for 20 minutes. Subsequently, the cells were washed and resuspended in the culture media. The cells were pelleted and lysed, and the levels of lipid peroxidation products including thiobarbituric acid-reactive substances (TBARS), glutathione (GSH), glutathione peroxidase (GPX), glucose 6-phosphate dehydrogenase, glutathione reductase, GST, catalase (CAT), and superoxide dismutase (SOD) were determined and compared with levels in control cells. Total GSTs were purified by GSH-affinity chromatography, and the isozymes were separated by isoelectric focusing, characterized, and quantitated. hGST 5.8 was quantitated by an immunologic method as well as by determining activity toward its preferred substrate, 4-hydroxynonenal (4-HNE). Kinetic constants of hGST 5.8 purified from H2O2-treated cells were also determined and compared with those of control cells. RESULTS: Exposure of RPE cells to 50 microM H2O2 for 20 minutes showed a significant increase in TBARS (1.8-fold) and gamma-glutamyl cysteine synthetase (gamma-GCS) activity (1.6-fold). A significant increase (1.2-fold) was also observed in GPX activity toward cumene hydroperoxide, but CAT and SOD activities remained unchanged. There was no significant increase in GST activity toward 1-chloro-2, 4-dinitrobenzene but GST activity toward 4-HNE was increased by 1.4- to 1.8-fold. The increase in GST activity toward 4-HNE was associated with a 2.8-fold increase in protein of the isozyme hGST 5.8, which uses 4-HNE as the preferred substrate. CONCLUSIONS: Results of these studies show that the induction of hGST 5.8, which is involved in the detoxification of the lipid peroxidation products 4-HNE and hydroperoxides, may be an early adaptive response of RPE cells exposed to low levels of transient oxidative stress. It is suggested that this isozyme may be crucial for protecting the RPE from low levels of chronic oxidative stress. Observed increases in GPX and gamma-GCS activities are consistent with this idea, because GPX activity is also expressed by hGST 5.8, and gamma-GCS is the rate-limiting enzyme in biosynthesis of GSH, the substrate for hGST 5.8.

Benzene Derivatives↗
PubMed1998

Kinetic studies of FR-1, a growth factor-inducible aldo-keto reductase.

Murine fibroblasts cultured in the presence of fibroblast growth factor-1 express relatively high levels of FR-1, a approximately 36 kDa protein related to the aldo-keto reductase superfamily [Donohue, P. J., Alberts, G. F., Hampton, B. S., Winkles, J. A. (1994) J. Biol. Chem. 269, 8604-8609]. While the crystal structure of FR-1 shows striking homology with human aldose reductase [Wilson, D. K., Nakano, T., Petrash, J. M., Quiocho, F. A. (1995) Biochemistry 34, 14323-14330], an enzyme linked to the pathogenesis of diabetic complications, the physiological role of FR-1 is not known. We show that FR-1 is capable of reducing a broad range of aromatic and aliphatic aldehydes, including the abundant and highly reactive lipid-derived aldehyde 4-hydroxy-2-nonenal (HNE; Km approximately 9 microM). However, in the absence of coenzyme, HNE caused a time-dependent inactivation of FR-1. Results from electrospray ionization-mass spectrometry and Edman-degradation of peptides derived from HNE-modified FR-1 were consistent with formation of a Michael adduct at Cys298. This was confirmed with a C298S mutant, which was resistant to HNE-induced inactivation. Since steady-state Km values determined with alkanals, alpha,beta-unsaturated alkenals, alkadienals, and 4-hydroxyalkenals fall within their physiological concentrations, lipid-derived aldehydes appear to be potential in vivo substrates for FR-1.

Aldehyde Reductase↗
PubMed1998

Metabolism of the lipid peroxidation product, 4-hydroxy-trans-2-nonenal, in isolated perfused rat heart.

The metabolism of 4-hydroxy-trans-2-nonenal (HNE), an alpha, beta-unsaturated aldehyde generated during lipid peroxidation, was studied in isolated perfused rat hearts. High performance liquid chromatography separation of radioactive metabolites recovered from [3H]HNE-treated hearts revealed four major peaks. Based on the retention times of synthesized standards, peak I, which accounted for 20% radioactivity administered to the heart, was identified to be due to glutathione conjugates of HNE. Peaks II and III, containing 2 and 37% radioactivity, were assigned to 1, 4-dihydroxy-2-nonene (DHN) and 4-hydroxy-2-nonenoic acid, respectively. Peak IV was due to unmetabolized HNE. The electrospray ionization mass spectrum of peak I revealed two prominent metabolites with m/z values corresponding to [M + H]+ of HNE and DHN conjugates with glutathione. The presence of 4-hydroxy-2-nonenoic acid in peak III was substantiated using gas chromatography-chemical ionization mass spectroscopy. When exposed to sorbinil, an inhibitor of aldose reductase, no GS-DHN was recovered in the coronary effluent, and treatment with cyanamide, an inhibitor of aldehyde dehydrogenase, attenuated 4-hydroxy-2-nonenoic acid formation. These results show that the major metabolic transformations of HNE in rat heart involve conjugation with glutathione and oxidation to 4-hydroxy-2-nonenoic acid. Further metabolism of the GS-HNE conjugate involves aldose reductase-mediated reduction, a reaction catalyzed in vitro by homogenous cardiac aldose reductase.

Aldehydes↗
PubMed1998

Identification of cardiac oxidoreductase(s) involved in the metabolism of the lipid peroxidation-derived aldehyde-4-hydroxynonenal.

The aim of this study was to identify the cardiac oxidoreductases involved in the metabolism of 4-hydroxy-2-trans-nonenal (HNE), an alpha,beta unsaturated aldehyde generated during the peroxidation of omega-6 polyunsaturated fatty acids. In homogenates of bovine, human and rat ventricles the primary pyridine coenzyme-linked metabolism of HNE was associated with NADPH oxidation. The NADPH-dependent enzyme catalysing HNE reduction was purified to homogeneity from bovine heart. The purified enzyme displayed kinetic and immunological properties identical with the polyol pathway enzyme aldose reductase (AR), and catalysed the reduction of HNE to its alcohol 1,4-dihydroxynonene (DHN), with a Km of 7+/-2 microM. In the presence of NADP the enzyme did not catalyse the oxidation of DHN. During catalysis, HNE did not cause inactivation of AR. Nevertheless when the apoenzyme was incubated with HNE a dissociable complex was formed between the enzyme and HNE, followed by irreversible loss of activity. Inactivation of the enzyme by HNE was prevented by NADP. Partial modification of the enzyme with HNE led to a 17-fold increase in the KHNEm and Kglyceraldehydem, and the HNE-modified enzyme had a 500-fold higher IC50 for sorbinil than for the reduced enzyme, whereas the IC50 for tolrestat increased 25-fold. Incubation of the enzyme with radiolabelled HNE resulted in the incorporation of 2 mol of the aldehyde per mol of the enzyme. Sequence analysis of the radiolabelled peptides revealed modification of Cys-298 and Cys-187. The amino acid sequence of the HNE-modified peptides confirmed that the HNE-reducing cardiac enzyme is AR and not a related protein such as the fibroblast-growth-factor-regulated protein FR-1 or the mouse vas deferens protein MVDP. These results indicate that AR represents the only major oxidoreductase in the heart capable of utilizing HNE. The high affinity of the enzyme for HNE, the lack of inactivation during catalysis, and the lack of significant alcohol dehydrogenase activity of the protein suggests that AR-mediated catalysis of HNE is unlikely to be limited by substrate/product inhibition. Thus AR might constitute an antioxidative enzyme involved in myocardial protection against endogenous and exogenous cytotoxic aldehydes and against oxidative stress.

Aldehyde Reductase↗
PubMed1998

Updated projections of infertility in the United States: 1995-2025.

OBJECTIVE: To project the number of infertile women aged 15-44 every 5 years from 2000 to 2025. DESIGN: Data are used from Cycle 5 of the National Survey of Family Growth conducted by the National Center for Health Statistics. Population projections prepared by the U.S. Bureau of the Census are used as the base population for 2000-2025. Prospective demographic projections are used to estimate the number of infertile women. PARTICIPANTS: The National Survey of Family Growth (Cycle 5) interviewed 10,847 women aged 15-44 in 1995. MAIN OUTCOME MEASURE(S): Number of infertile women. RESULT(S): The number of women experiencing infertility will range from 5.4-7.7 million in 2025, with the most likely number to be just under 6.5 million. CONCLUSION(S): This is a substantial revision (upward) in the number of infertile women, largely a result of the increase in the observed percentage of infertile women in 1995. This is the base population of concern to providers; of particular interest is the percentage of infertile women who seek medical treatment.

Adolescent↗
PubMed1998

Novel bioactivities of Curcuma longa constituents.

Bioassay-directed fractionation of ethyl acetate extract from Curcuma longa Linn. rhizomes yielded three curcuminoids, which displayed topoisomerase I and II enzyme inhibition activity. Curcumin III (3) was the most active curcuminoid, inhibiting topoisomerase at 25 micrograms mL-1. Curcumin I (1) and curcumin II (2) inhibited the topoisomerases at 50 micrograms mL-1. Fractionation of the volatile oil from the rhizomes afforded ar-turmerone (4), which displayed mosquitocidal activity with an LD100 of 50 micrograms mL-1 on Aedes aegyptii larvae. Bioassay-directed fractionation of hexane extract from the turmeric leaves yielded labda-8(17),12-diene-15,16 dial (5) with antifungal activity against Candida albicans at 1 micrograms mL-1 and inhibited the growth of Candida kruseii and Candida parapsilosis at 25 micrograms mL-1. In addition, 5 displayed 100% mosquitocidal activity on A. aegyptii larvae at 10 micrograms mL-1.

Antifungal Agents↗
PubMed1998

Germ cell tumour of testis.

Germ cell tumour, though rare, represents most common malignancy among young men aged between 15 to 35 years. In 1990's dramatic improvement has taken place in survival rate of testicular tumours (from 10% in 1970's and 90% in 1990's). This has been possible because of effective diagnostic techniques, accurate monitoring with biological markers and use of effective platinum based combination chemotherapy in its management. The most significant improvement in survival rate has occurred in advanced stage germ-cell tumours. Seminomas are sensitive to radiation therapy and NSGCT (Non Seminomatous Germ Cell Tumours). are effectively treated by combination chemotherapy of 3 drugs of which Bleomycin is most expensive and many patient can not afford it and so compliance is poor. In the present series we have tried only 2 drug regimen consisting of Platinum and Etoposide (PE). Since January 1992 to December 1994, 40 cases of testicular tumours were treated. 16 cases received PEB regimen and 24 cases were treated by PE regimen of which only 6 cases in the former and 20 cases in the later group completed the scheduled course. Patients were given 6 cycles of PE regimen (inj. Platinum 20 mg/m2 D1-D5, VP-16 (ETOPOSIDE), 100 MG/M2 1.V. D1-D5) repeated every three weeks. Final evaluation was done in June 1996. 17/20 (85%) patients on PE regiment exhibited complete regression of the disease by the end of June 1996, I was lost to follow up, and 2 of them had the disease in progressive stage and were considered for another regimen. 18 months disease free survival was 85%. Table I. Royal Marsden Staging System Stage I: Disease econfined to testes Stage II: Intradiaphragmatic node involvement A: Less than 2 cm B: 2-5 cm C: Greater than 5 cm Stage III: Supradiaphragmatic node involvement Stage IV: Extralymphatic disease Lung, Liver, Bone etc.

Adolescent↗