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Biomedical subjects

N Moss

Publications and source records attributed to N Moss.

At least 37 records · Page 2Linked to original sources
PubMed1998

The effect of WIC and Medicaid on infant mortality in the United States.

OBJECTIVES: This study examine the impact of participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and Medicaid on risk of infant death in the United States. METHODS: The 1988 National Maternal and Infant Health Survey was used to consider the risk of endogenous and exogenous death among infants of women participating in WIC and Medicaid during pregnancy and the infant's first year. RESULTS: Participation in the WIC program during pregnancy and infancy was associated with a reduced risk of endogenous and exogenous infant deaths (odds ratios [ORs] = 0.68 and 0.62, respectively). The risk of endogenous death among infants whose mothers participated in Medicaid during pregnancy was equal to that of the privately insured (OR = 1.04). Uninsured infants faced higher risks of endogenous death (OR = 1.42). CONCLUSIONS: These results show that it is important to consider the net effect of WIC and Medicaid participation and to differentiate both the timing of program receipt and cause of death. Evidence suggests that WIC and Medicaid programs have beneficial effects for poor women and their infants.

Adult↗
PubMed1997

Effect of California's proposition 187 on the use of primary care clinics.

California's ballot proposition 187, passed by the voters in November 1994, threatened to discontinue undocumented immigrants' eligibility for most health services while mandating that health care professionals report suspected undocumented patients to authorities. Although the proposition has not been put into practice, reports suggest that its passage was associated with a decline in the use of health services by some groups. To assess the effects of the passage of Proposition 187 on the use of primary care services, we surveyed a representative sample of California clinics serving low-income groups (n = 129). Using a mailed questionnaire and phone interviews with clinic directors, we obtained qualitative and quantitative data regarding the effects of the passage of the proposition on clinic use. Among primary care clinics statewide and clinics serving predominantly Latino patients, we detected no significant decline in total monthly visits following the election. Nevertheless, half of clinic directors (51%) thought that the number of clinic visits declined after the passage of Proposition 187, and many directors thought that the deterrent effects of the election persisted for weeks to months after the election. Whereas the number of visits probably declined at some clinics, only a small minority of patients at most primary care clinics could have been deterred from seeking care after the passage of Proposition 187.

California↗
PubMed1996

Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase with improved in vivo antiviral activity.

We have been investigating the potential of a new class of antiviral compounds. These peptidomimetic derivatives prevent association of the two subunits of herpes simplex virus (HSV) ribonucleotide reductase (RR), an enzyme necessary for efficient replication of viral DNA. The compounds disclosed in this paper build on our previously published work. Structure-activity studies reveal beneficial modifications that result in improved antiviral potency in cell culture in a murine ocular model of HSV-induced keratitis. These modifications include a stereochemically defined (2,6-dimethylcyclohexyl)amino N-terminus, two ketomethylene amide bond isosteres, and a (1-ethylneopentyl)amino C-terminus. These three modifications led to the preparation of BILD 1351, our most potent antiherpetic agent containing a ureido N-terminus. Incorporation of the C-terminal modification into our inhibitor series based on a (phenylpropionyl)valine N-terminus provided BILD 1357, a significantly more potent antiviral compound than our previously published best compound, BILD 1263.

Animals↗
PubMed1996

Ureido-based peptidomimetic inhibitor of herpes simplex virus ribonucleotide reductase: an investigation of inhibitor bioactive conformation.

We have been investigating peptidomimetic inhibitors of herpes simplex virus (HSV) ribonucleotide reductase (RR). These inhibitors bind to the HSV RR large subunit and consequently prevent subunit association and subsequent enzymatic activity. This report introduces a new series of compounds that contain an extra nitrogen (a ureido function) at the inhibitor N-terminus. This nitrogen improves inhibitor binding potency 50-fold over our first published inhibitor series. Evidence supports that this improvement in potency results from a new hydrogen-bonding contact between the inhibitor and the RR large subunit. This report also provides evidence for the bioactive conformation around two important amino acid residues contained in our inhibitors. A tert-butyl group, which contributes 100-fold to inhibitor potency but does not directly bind to the large subunit, favors an extended beta-strand conformation that is prevalent in solution and in the bound state. More significantly, the bioactive conformation around a pyrrolidine-modified asparagine residue, which contributes over 30 000-fold to inhibitor potency, is elucidated through a series of conformationally restricted analogues.

Enzyme Inhibitors↗
PubMed1996

Accounting for the public's health: an introduction to selected papers from a U.S. conference on "measuring social inequalities in health".

Accounting for, and being accountable to, the public's health requires carefully documenting and analyzing social inequalities in health. Controversies abound over which measures of socioeconomic position to use, at which points in time, and at what level-e.g., individual, household, and neighborhood. Important debates also concern how to analyze these data and relate them to inequalities involving race/ethnicity and gender. Addressing these complex issues is particularly timely in the light of persistent- and even widening- social inequalities in health. To improve tools for evaluating socioeconomic gradients in health, in 1994 the U.S. Public Health Service and National Institutes of Health sponsored a conference on Measuring Social Inequalities in Health. This introduction to the Section on Social Inequalities in Health introduces five articles presented by participants at the conference. Topics include: a historical review of efforts to measure socioeconomic inequalities in health in the U.S. between 1990 and 1950; income dynamics and health; measuring inequalities in health among nonemployed persons; analyzing links between racial/ethnic and socioeconomic disparities in health; and using neighborhood-based socioeconomic data in public health research. Together, these five articles point to a new emphasis on refining methodologies to assess relationships between social position and health and their expression in population patterns of social inequalities in health.

Ethnicity↗
PubMed1995

Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase: a new class of antiviral agents.

We have been investigating a new class of antiviral compounds effective against herpes simplex virus (HSV) in vitro and in vivo. Antiviral activity results from inhibition of HSV ribonucleotide reductase (RR). The inhibitors are designed as mimics of the RR small subunit C-terminus, a region essential for RR subunit association and consequently enzymatic activity. Inhibition results from specific binding of the inhibitor to the HSV RR large subunit thereby preventing subunit association. This report details the structure--activity studies that lead to the indentification of BILD 1263, a potent inhibitor of HSV RR subunit association (IC50, 0.2 nM) that also inhibits the replication of HSV types 1 and 2 in cell culture (EC50, 3 and 4 microM) and reduces the severity of HSV-1-induced keratitis in a murine ocular model. The discovery of inhibitors with in vitro antiviral results from a combination of improving inhibitor potency in a RR binding assay and modifying inhibitor physicochemical properties. The importance and possible role of the new structural modifications introduced into this inhibitor series is discussed.

Animals↗
PubMed1994

A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo.

Herpes simplex viruses (HSV) types 1 and 2 encode their own ribonucleotide reductases (RNRs) (EC 1.17.4.1) to convert ribonucleoside diphosphates into the corresponding deoxyribonucleotides. Like other iron-dependent RNRs, the viral enzyme is formed by the reversible association of two distinct homodimeric subunits. The carboxy terminus of the RNR small subunit (R2) is critical for subunit association and synthetic peptides containing these amino-acid sequences selectively inhibit the viral enzyme by preventing subunit association. Increasing evidence indicates that the HSV RNR is important for virulence and reactivation from latency. Previously, we reported on the design of HSV RNR inhibitors with enhanced inhibitory potency in vitro. We now report on BILD 1263, which to our knowledge is the first HSV RNR subunit-association inhibitor with antiviral activity in vivo. This compound suppresses the replication of HSV-1, HSV-2 and acyclovir-resistant HSV strains in cell culture, and also strongly potentiates the antiviral activity of acyclovir. Most importantly, its anti-herpetic activity is shown in a murine ocular model of HSV-1-induced keratitis, providing an example of potent nonsubstrate-based antiviral agents that prevent protein-protein interactions. The unique antiviral properties of BILD 1263 may lead to the design of new strategies to treat herpesvirus infections in humans.

Amino Acid Sequence↗
PubMed1994

Herpes simplex virus ribonucleotide reductase subunit association inhibitors: the effect and conformation of beta-alkylated aspartic acid derivatives.

Incorporating beta-alkylated aspartic acid derivatives into herpes simplex virus ribonucleotide reductase subunit association inhibitors can improve inhibitor potency up to 50 times over the corresponding inhibitors containing an unsubstituted aspartic acid. A combination of NMR studies, conformational analysis, and molecular mechanics calculations suggests that the beta-alkyl group improves inhibitor potency by favoring the bioactive conformation of the critical aspartic acid carboxyl group. Further support for this hypothesis is provided by a potent conformationally restricted aspartic acid derivative in which the carboxyl group is locked in the putative bioactive conformation.

Alkylation↗
PubMed1994

The critical C-terminus of the small subunit of herpes simplex virus ribonucleotide reductase is mobile and conformationally similar to C-terminal peptides.

The C-terminus of the small subunit of class I ribonucleotide reductases is essential for subunit association and enzymatic activity. 1H NMR analysis of the small subunit (2 x 38 kDa as a homodimer) of herpes simplex virus ribonucleotide reductase shows that this critical binding site is mobile and exposed in relation to the rest of the protein. Assignments of six C-terminal amino acids are made by comparing the TOCSY and NOESY spectra of the small subunit with the spectra of an identical protein truncated by seven amino acids at the C-terminus and the spectra of an analogous 15 amino acid peptide. The mobility of the C-terminus may be important for subunit recognition and could be general for other ribonucleotide reductases. The spectral comparisons also suggest that the six C-terminal amino acids of the small subunit and peptide are conformationally similar. This observation may be important for the design of inhibitors of ribonucleotide reductase subunit association.

Binding Sites↗
PubMed1994

Behavioral risks for HIV in adolescents.

A psychosocial perspective on adolescent risk behavior is used to highlight aspects of psychological development and social environment that are relevant to sexual activity and substance use. Differences in behavior are also related to factors such as age and gender that have biological, developmental, and demographic implications. Sexual activity and substance use increase during adolescence, and are often interrelated. In the USA in 1992, 69% of 8th graders and 88% of 12th graders had drunk alcohol. In 1990, 54% of high school students had had sexual intercourse. Age of sexual initiation has decreased in recent cohorts, but condom use by adolescents has increased, with 35% of 15-19-year-old women reporting using condoms. Interventions that successfully change adolescent risk behavior take account of the teen's level of development and social context.

Adolescent↗
PubMed1993

Inhibition of herpes simplex virus type 1 ribonucleotide reductase by substituted tetrapeptide derivatives.

It is known that peptides corresponding to the C-terminus of the small subunit of herpes simplex virus type 1 and 2 ribonucleotide reductase can inhibit enzymatic activity by preventing the association of the enzyme's two subunits. In a quest for smaller, more potent inhibitors, we have conducted a structure activity investigation based on the pentapeptide H-Val-Val-Asn-Asp-Leu-OH. Potency increases of up to 4000 times (IC50 0.18 microM) have been achieved in an enzymatic assay by a combination of modifying the N-terminal valine to a diethylacetyl group, adding a methyl group to the beta-carbon of the adjacent valine, dialkylating the asparagine side-chain nitrogen and dimethylating the beta-carbon of the aspartic acid residue. In addition the relative contribution of various inhibitor functionalities to inhibitor potency has been investigated.

Amino Acid Sequence↗
PubMed1993

Pregnant women at work: sociodemographic perspectives.

The 1988 National Maternal and Infant Health Survey, a stratified random sample of 9,953 live births, shows that women who work during pregnancy are more likely to be non-Hispanic white, married, of higher income and education, to have medical insurance, and of lower parity than nonemployed pregnant women (p < .0001). They begin prenatal care earlier, are less likely to smoke, and are more likely to state that the birth was wanted (p < .0001). Similar trends are seen for full-time as compared to part-time workers. Women employed as precision production workers, operators/fabricators, or in service occupations are disadvantaged with regard to sociodemographic and behavioral risks for pregnancy outcomes relative to women in professional and managerial occupations. Black race, parity, body mass index, and smoking, but not employment, are associated with low birth weight when gestational age is controlled. The effects of stress and its buffers, paternal characteristics, physical activity, and toxic exposures, both in and out of the workplace, should be considered, as should the normative and social policy context.

Adolescent↗
PubMed1992

Child health outcomes among Central American refugees and immigrants in Belize.

The purpose of this study was to investigate the effect of international migration, including refugee status, upon child health outcomes. Data were drawn from a survey conducted in 1989 in three settlements in Belize, Central America, that have a high proportion of refugees and economic immigrants living side-by-side with the local population. In two of the settlements, the entire population of mothers with children under 6 was interviewed; in the third settlement a two-thirds random sample was interviewed. Health history data were obtained for 255 children of 134 mothers, from whom sociodemographic data were also collected. The majority of children were born to Salvadoran or Guatemalan mothers, but native and naturalized Belizeans in the survey communities were included for comparison purposes. Migration, the exposure variable, was characterized by mother's residency/refugee legal status, nationality, and duration of time in country. Socioeconomic and proximate control variables were included as suggested by the Mosley-Chen framework. Despite normal birthweight averaging 3374 g, a large proportion of children are at the lowest percentiles of the weight-for-age curves (44% below the tenth percentile for the international reference population). A high incidence of diarrheal and respiratory illnesses (30% and 47% of children, respectively, having frequent episodes), and 50% of children with measles vaccination appropriate for age, indicate a population with high potential morbidity. Logistic regression was used to model the effects of migration on weight-for-age and frequency of diarrheal and respiratory tract episodes independent of socioeconomic and proximate factors, as suggested by the Mosley-Chen framework.(ABSTRACT TRUNCATED AT 250 WORDS)

Belize↗
PubMed1992

Morphological and contractile characteristics of rat aortae perfused for 3 or 6 days in vitro.

We studied the morphological and contractile characteristics of rat thoracic aortic segments perfused for 3 or 6 days under pulsatile conditions. Light microscopic examination of the segments revealed the presence of an unchanged tunica media. However, the intimal surface was mostly devoid of endothelial cells. The perfused aortic segments showed a dramatic increase in spontaneous tone when compared to fresh and sham-treated aortic segments. Maximum responses to potassium and norepinephrine were reduced after 3 days of perfusion (20-40% reduction), while maximum responses to 5-hydroxytryptamine and angiotensin II were not significantly different. After 6 days of perfusion, maximum responses to all agonist were reduced (50-60%). Sensitivity to norepinephrine was not affected by the treatment, while sensitivity to 5-hydroxytryptamine was reduced. The perfused aortic segments relaxed well in response to isoproterenol. Our system provides a useful experimental model for short-term studies of hypertension- and atherosclerosis-related vascular changes. Further refinement and characterization could improve the performance of the system for longer-term studies.

Acetylcholine↗
PubMed1991

The psychology of the aging athlete.

Athletes, like other patients, will adhere to their treatment more readily if they believe the physician really understands their needs and cares about them as individuals. The guidelines provided in this article are intended to help the practitioner respond more effectively to each individual patient because effective physician/patient interactions are the very heart of healing.

Aged↗
PubMed1985

Fatal coxsackievirus B4 infection in a neonate.

We reported a fatal coxsackievirus B4 infection in a neonate. The CSF WBC was elevated, with polymorphonuclear leukocytes predominating initially and lymphocytes predominating later in the illness. Autopsy findings included inflammation of the heart and liver. Coxsackievirus B4 was isolated from the heart and quantitated as 10(3) 50% tissue culture infectious doses (TCID50) per gram of myocardium.

Coxsackievirus Infections↗