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Biomedical subjects

W Baldwin

Publications and source records attributed to W Baldwin.

At least 19 recordsLinked to original sources

The oncostatic action of melatonin in an ovarian carcinoma cell line.

Melatonin is reported to reduce proliferation in many cell types, but the effect is small and the results are inconsistent. Information on the mechanism by which melatonin exerts its antiproliferative effects might provide insight into the variability of the response. In an ovarian adenocarcinoma cell line (BG-1), we find that melatonin at concentrations of 10(-9)-10(-7) M caused a 20-25% reduction in cell number. Melatonin also resulted in a similar reduction in [3H]-thymidine incorporation with no significant increase in cell death as measured by trypan blue incorporation. The Kd for melatonin reduction in cell number was approximately 5 x 10(-10) M. Melatonin ML2 receptors have a Kd for melatonin binding in the low nM range and are linked to the production of the calcium mobilizing agent inositol-1,4,5-trisphosphate (IP3). To investigate whether melatonin signaling involves an increase in cytosolic-free calcium. BG-1 cells were loaded with the calcium sensitive indicator, fura-2. Acute addition of melatonin (10(-5)-10(-9) M) did not alter cytosolic calcium. Addition of the putative nuclear receptor agonist CGP52608 caused a dose-dependent inhibition of cell number with a Kd of approximately 2 x 10(-9) M. Addition of CGP52608 caused a similar reduction in [3H]-thymidine incorporation. Neither melatonin (10(-8) M-10(-5) M) nor CGP52608 at concentrations below 10(-7) M induced cell death associated with the inhibition of cell proliferation; however, addition of CGP52608 at a high dose (10(-7) M) caused an increase in cell death, consistent with apoptosis. Growth inhibition by melatonin or CGP52608 did not alter the percentage of cells in G1 versus S/G2/M.

Adenocarcinoma↗

The Onchocerciasis Elimination Program for the Americas: a history of partnership.

The decision in 1987 by the pharmaceutical firm Merck & Co. to provide Mectizan (ivermectin) free of charge to river blindness control programs has challenged the international public health community to find effective ways to distribute the drug to rural populations most affected by onchocerciasis. In the Americas, PAHO responded to that challenge by calling for the elimination of all morbidity from onchocerciasis from the Region by the year 2007 through mass distribution of ivermectin. Since 1991, a multinational, multiagency partnership (consisting of PAHO, the endemic countries, nongovernmental development organizations, the Centers for Disease Control and Prevention in Atlanta, Georgia, as well as academic institutions and funding agencies) has developed the political, financial, and technical support needed to move toward the realization of that goal. This partnership is embodied in the Onchocerciasis Elimination Program for the Americas (OEPA), which is supported by the River Blindness Foundation (RBF) and now by the Carter Center. OEPA was conceived as a means of maintaining a regional initiative to eliminate what is otherwise a low priority disease. Since its inception in 1993, the OEPA has provided more than US$ 2 million in financial, managerial, and technical assistance to stimulate and/or support programs in Brazil, Colombia, Ecuador, Guatemala, Mexico, and Venezuela, so as to take full advantage of the Merck donation. Now halfway into a five-year, US$ 4 million grant provided through the Inter-American Development Bank, the OEPA's capacity to support the regional initiative is assured through 1999.

Americas↗

Immunohistochemical manifestations of unilateral kidney ischemia.

Events in the early post-transplant period have been correlated with increased renal allograft loss. Immunologic reactions and ischemic injury have been implicated in this process. While the immunologic aspects of allograft injury have been studied extensively, ischemic effects remain less well understood. To study the effects of ischemia in rats with different genetic backgrounds without the introduction of an alloimmune response, a clamp was placed on the vascular pedicle of the left kidney for 60 min. The short-term effects (1 wk) of ischemia were studied in groups of PVG (RT1c), LEW (RT1), DA (RT1a) and WR (RT1u) rats, Immunoperoxidase staining demonstrated limited infiltration of monocytes, macrophages, and T-cells accompanied by upregulation of low levels of MHC class II antigens on tubular epithelial cells, peritubular capillaries, and interstitial cells in kidneys of PVG and WF rats. Kidneys of LEW and DA rats had greater influxes of monocytes, macrophages, and T cells in addition to higher amounts of MHC class II antigens upregulation on tubular epithelium and interstitial cells. The long-term effects of ischemia were studied in kidneys of WF rats. These kidneys had a progressive increase in infiltrating T cells, monocytes, macrophages and MHC class II expression on the tubular epithelium and the interstitial cells at 14, 30, and 90 d after the ischemic insult. The differences in MHC class II expression between ischemic kidneys of PVG and LEW rats were not associated with differences in production of mRNA for IL-2, IFN-gamma, and TNF-alpha. In summary, transient renal ischemia in the absence of an allogeneic immune response triggers a progression of inflammatory responses, including leukocyte infiltration, cytokine production and MHC class II antigen upregulation which appears to be strain-dependent.

Animals↗

Demographics of adolescent sexual behavior, contraception, pregnancy, and STDs.

The demographics of fertility-related behavior of youth ages 10-18 are reviewed. Data were collected from U.S. vital statistics, and birth rates, contraceptive use, sexual behavior, number and types of sexual partners, patterns of sexual initiation and sexual intercourse, and sexually transmitted diseases were examined. Despite data limitations, the demographic profile of adolescent sexual intercourse is striking. Age clearly is the single most important predictor of sexual debut.

Adolescent↗

The response of American women to the threat of AIDS and other sexually transmitted diseases.

Using data from the National Survey of Family Growth, we observe that large numbers of American women say that they are responding to the rising danger of AIDS and other sexually transmitted diseases. Among the changes reported in the 1988 National Survey of Family Growth are use of condoms, sexual relations with fewer partners, reduced frequency of sexual intercourse, changes in specific sexual activities, and avoidance of sex with unknown men, bisexual men, and intravenous drug users. Interviews with a sample of the 51 million sexually active women aged 15-44 in the United States show that 28% report either that they have adopted less hazardous sexual practices or that their partners have used condoms to prevent disease. Among women exposed to higher risk of disease, the response is even greater: among unmarried women with five or more lifetime partners, 65% report modified behavior or condom use. Most of these changes occurred after the women heard of AIDS. However, there are still many women who report doing nothing to protect themselves against infection despite sexual and contraceptive behavior that appears to put them at high risk.

Acquired Immunodeficiency Syndrome↗

Scientist-administrators at the National Institute of Child Health and Human Development as contributors to the scientific enterprise.

At the National Institute of Child Health and Human Development (NICHD), as in other government research supporting agencies, scientist-administrators who are "program staff" work to accomplish their organization's set of research priorities using established mechanisms for supporting research. At the same time, the definition of their work is given to their interpretation, which, in turn, is guided by their understanding of their scientific discipline and their commitment to it. The tension that may arise between the organization-guided role and the science-guided role is more apparent than real because the major responsibility of "program staff" within the Institute is to cultivate a grant portfolio addressing scientific issues relevant to the mission of the Institute and exemplifying the most advanced research concepts and methodologies. When the overlap between the mission of the Institute and the direction of science is small, the push to increase it leads to new and imaginative solutions that benefit both the Institute and the science.

Administrative Personnel↗

HIV risk difference between condom users and nonusers among U.S. heterosexual women.

Using data from the National Survey of Family Growth, we estimate that among 3,498,060 U.S. reproductive-age women least likely to be protected from HIV, 12% rely on condoms for birth control. We have modeled the risk difference between condom users and nonusers and projected the number of preventable and nonpreventable HIV infections likely to occur among the 419,201 condom users as a function of 50 HIV-incidence/relative risk assumptions. Results of the attributable-risk model suggest that at the current low HIV-incidence level in U.S. women, condom-user failure rates will be less than 1% per year, substantially lower than the 10% condom-user failure rate for pregnancy. As few as 1% but up to 11% of all new HIV cases may be prevented by the current low level of condom use, depending on the exact degree of condom effectiveness in this population at risk. However, the model further projects that up to 45% of all new HIV cases may be prevented if condoms are maximally effective and far more widely used. Women with seropositive partners may enjoy the same protective benefits of condoms, but the costs in terms of condom-user failures will be much higher than in the remainder of the population at risk. Among serious and reliable users, condom-user failure rates for HIV may approach those for pregnancy, but only in women who have known seropositive partners.

Adolescent↗

Older maternal age and infant mortality in the United States.

We used data from the National Infant Mortality Surveillance project to examine the effect of older maternal age on infant mortality for the 1980 United States birth cohort. The 1,579,854 births and 14,591 deaths of singletons who were black or white and whose mothers were 25-49 years of age were included. Direct standardization was used to calculate birth-weight-adjusted relative risks of neonatal and postneonatal mortality, using the birth weights of infants with maternal age 25-29 as the standard. We found that the risk of infant mortality was nearly equal for infants born to mothers 25-29 and 30-34 years of age; infants born to mothers 35-39 years of age were at a slightly elevated (18% higher) risk, and those born to mothers 40-49 years of age were at a much more elevated (69% higher) risk. Among whites, the higher neonatal mortality associated with a maternal age of 35-39 was mostly due to an increased prevalence of low birth weight; among blacks, it was due to higher birth-weight-specific risks. Neither white nor black postneonatal mortality risks were much elevated until a maternal age of 40-49, and this last elevation was mostly due to higher birth-weight-specific risks. These findings suggest that infertility and fetal mortality aside, and considering only the effect on infant mortality, it is relatively safe for women to postpone childbearing into their middle, and perhaps late, thirties.

Adult↗