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Biomedical subjects

M L Martin

Publications and source records attributed to M L Martin.

At least 19 recordsLinked to original sources

Baculovirus expression of the glycoprotein gene of Lassa virus and characterization of the recombinant protein.

A recombinant baculovirus was constructed that expresses the glycoprotein gene of Lassa virus (Josiah strain) under the transcriptional control of the polyhedrin promoter. The expressed protein (B-LSGPC) comigrated with the authentic viral glycoprotein as observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), was reactive with monoclonal antibodies (MAbs) in Western blots, and was glycosylated. Although the recombinant protein was not processed into the mature glycoproteins, G1 and G2, it demonstrated reactivity with all known epitopes as measured by indirect immunofluorescence (IFA), and it was immunogenic, eliciting antisera in rabbits that recognized whole virus in IFAs. Regarding future applications to diagnostic assays, the recombinant glycoprotein proved to be an effective substitute for Lassa virus-infected mammalian cells in IFAs and it was able to distinguish sera from several human cases of Lassa fever, against a panel of known negative sera of African origin, in an enzyme immunoassay (EIA).

Animals

Trends in rates of multiple vascular disruption defects, Atlanta, 1968-1989: is there evidence of a cocaine teratogenic epidemic?

Research suggests that, perhaps through mechanisms initiated by vasoconstriction and leading to vessel thrombosis or embolism, cocaine causes vascular disruption defects, and that frequent cocaine use during early pregnancy could disrupt multiple organ systems in the fetus. We hypothesized that if cocaine is an important cause of multiple vascular disruption defects, a rising prevalence of cocaine use by mothers during pregnancy should be accompanied by rising rates of these defects in their offspring. Using data from the Metropolitan Atlanta Congenital Defects Program, we identified all infants born in Atlanta from 1968 through 1989 who had nonsyndromic, provisional vascular disruption defects affecting more than one organ system: 61 infants (78%) had gastrointestinal and genitourinary defects, 7 (9%) had gastrointestinal and abdominal wall defects, 2 (3%) had gastrointestinal and limb reduction defects, 2 (3%) had limb reduction and abdominal wall defects, 2 (3%) had central nervous system and gastrointestinal defects, 2 (3%) had genitourinary and limb reduction defects, 1 (1%) had genitourinary and abdominal wall defects, and 1 (1%) had central nervous system and genitourinary defects. The prevalence of Atlanta infants with more than one vascular disruption defect is 0.13 per 1,000 live births. Chi-square analysis for trends showed no increase in prevalence during the study period. Our data are from one of the first population-based studies in which trends for defects potentially caused by maternal cocaine use are examined; the results of our study show no significant change in the prevalence of multiple vascular disruption defects over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced

Cocaine and single ventricle: a population study.

A recent case report by Shepard et al. (Teratology 43:113-117, 1991) suggested that single ventricle may result from maternal cocaine ingestion by inducing coronary occlusion in the developing fetal heart. We used data from the Atlanta Birth Defects Case-Control Study and the Metropolitan Atlanta Congenital Defects Program (MACDP) to investigate the role of maternal cocaine ingestion in the induction of single ventricles. We identified through the MACDP 58 case infants with a single ventricle, 27 who were study subjects in the Atlanta Birth Defects Case-Control Study, and 31 who were not. We conducted a case-control study with the 27 Atlanta Birth Defects Case Control Study infants, frequency-matched to control infants by race, hospital of birth, and calendar quarter of birth. None of the 27 case infants were exposed to cocaine during early pregnancy, but 7 (0.43%) of the control infants were exposed during early pregnancy. Using MACDP data, we conducted an analysis of trends for prevalence of single ventricle in the metropolitan area. No upward trend in single ventricle was detected for 1968 through 1990. Our data suggest that even if maternal cocaine ingestion during pregnancy is a cause of single ventricle, most cases appear to be unrelated to this exposure.

Abnormalities, Drug-Induced

Alternative approaches to nursing practice: application of Peplau, Rogers, and Parse.

This article demonstrates three major nursing theories in practice. The uniqueness of each theory is clarified through the presentation of nursing formulations and practice implications. The discussion provides a metaperspective of how practice based in nursing theory is different from traditional practice and how nursing theory can guide practice.

Humans

Determination of site-specific carbon isotope ratios at natural abundance by carbon-13 nuclear magnetic resonance spectroscopy.

Site-specific natural isotope fractionation of hydrogen studied by deuterium NMR (SNIF-NMR) spectroscopy is a powerful source of information on hydrogen pathways occurring in biosyntheses in natural conditions. The potential of the carbon counterpart of this method has been investigated and compared. Three typical molecular species, ethanol, acetic acid, and vanillin, have been considered. Taking into account the requirements of quantitative 13C NMR, appropriate experimental procedures have been defined and the repeatability and reproducibility of the isotope ratio determinations have been checked in different conditions. It is shown that the carbon version of the SNIF-NMR method is capable of detecting small differences in the carbon-13 content of the ethyl fragment of ethanols from different botanical or synthetic origins. These results are in agreement with mass spectrometry determinations of the overall carbon isotope ratios. Deviations with respect to a statistical distribution of 13C have been detected in the case of acetic acid and vanillin. However, since the method is very sensitive to several kinds of systematic error, only a relative significance can be attached at present to the internal parameters directly accessible. Isotope dilution experiments have also been carried out in order to check the consistency of the results. In the present state of experimental accuracy, the 13C NMR method is of more limited potential than 2H SNIF-NMR spectroscopy. However it may provide complementary information. Moreover it is particularly efficient for detecting and quantifying adulterations that aim to mimic the overall carbon-13 content of a natural compound by adding a selectivity enriched species to a less expensive substrate from a different origin.

Acetates

The anticonvulsant valproate teratogen restricts the glial cell cycle at a defined point in the mid-G1 phase.

Direct cell counting and extent of [3H]thymidine incorporation demonstrated valproate to inhibit C6 glioma proliferation rate in a dose-dependent manner with a 1 mM concentration achieving 50% inhibition. The antiproliferative effect was reversible and could not be attributed to cytotoxicity at the valproate concentrations employed. The site of valproate action within the cell cycle was determined to be in the G1 phase, at a point 6-6.5 h prior to S phase, by estimating the time to increased [3H]thymidine incorporation following release from a 70% proliferative arrest. Synchronised cells obtained by a mitotic selection procedure required 11-12 h to enter S phase and demonstrated the valproate restriction point to be 5 h into the G1 phase of the C6 cell cycle. Exposure of valproate to the part of the G1 period which follows the restriction point was without effect on cell entry into S phase.

Animals

Are offspring of women with hereditary hematologic disorders at increased risk of congenital cardiovascular malformations?

Hereditary hematologic disorders (HHD) have been reported in excess among infants and families of infants with congenital cardiovascular malformations (CCM) compared with controls, suggesting possible common pathogenetic mechanisms. It is plausible that hemodynamic changes during pregnancy associated with HHD could affect cardiac morphogenesis. To investigate whether offspring of women with selected HHD have an excess risk of CCM, the authors examined data from a nationwide birth defects monitoring program (BDMP) covering about 2.9 million births in the United States between 1982 and 1988. The system ascertains major birth defects diagnosed in the newborn period. An anonymous linkage procedure linked maternal obstetric records with newborn records using demographic, diagnostic, and geographic variables. A total of 1,239 mothers were identified with selected HHD (47 hereditary spherocytosis, 575 thalassemias, 310 sickle cell anemia, 88 other hereditary hemolytic anemias, 159 von Willebrand disease, and 60 other congenital coagulopathies). In all, 14 infants received a newborn discharge diagnosis of CCM (expected number based on population rates of CCM from the same hospitals and time period is 7.74; P = 0.0268). No single CCM entity accounted for this excess. In contrast, 8 infants had major non-CCM defects (expected number 7.46; P = 0.466). These data suggest an excess risk of CCM among offspring of women with selected HHD. Further studies are needed to explore these findings and to evaluate the pathogenetic significance of this association.

Epidemiologic Methods

Transient heat shock in mid-G1-phase of the C6 glioma cell cycle impairs entry into S-phase.

Synchronous populations of rat C6 glioma cells have been obtained by a mitotic selection procedure and used to establish the effect of transient temperature elevation on their progression through the cell cycle. A transient 3-h exposure to a 42 degree C heat shock within defined area in the mid-G1-phase of the cell cycle has been demonstrated to impair progression to S-phase. This anti-proliferative heat shock effect was not apparent in asynchronous cell populations. A small, but significant, decrease in 3H-thymidine incorporation was observed (approximately 5%) following an 8-h exposure to heat shock.

Animals

Participation of older adults in health programs and research: a critical review of the literature.

This collection of five papers evaluates the participation of older adults in clinical trials, health promotion/disease prevention initiatives, and health programs designed to maintain or improve the functioning of chronically ill older adults. Understanding the willingness or unwillingness of older adults to participate in these programs is critical to the development and implementation of health programs and policies for this population. In this introductory paper we briefly review illustrative literature to provide both an overview of the participation of older adults in health programs as well as background information relevant to the symposium papers.

Aged

A collaborative model for the clinical education of baccalaureate nursing students.

Quality clinical supervision is fundamental for the consolidation of knowledge and the development of a professional identity for baccalaureate nursing students. Problems in providing high-quality clinical supervision range from a lack of practitioner role models to inadequate or unsupportive learning environments. Collaboration between the education and service sectors allows for the development of enriched clinical learning experiences for students. This paper describes an innovative collaborative educational process developed by McMaster University School of Nursing and the Nursing and Education Departments at Hamilton Psychiatric Hospital, Hamilton, Ontario, Canada. Front-line nursing staff are the clinical supervisors, with support from clinical nurse specialists, the hospital educator and the university faculty member. When compared to more traditional approaches, this model ensures that the students receive more variety in placements and access to expert human resources.

Education Department, Hospital

Isolation of Escherichia coli serotype O157:H7 and other Shiga-like-toxin-producing E. coli from dairy cattle.

We examined 1,266 fecal specimens from healthy cattle during the investigations of two sporadic cases of hemolytic uremic syndrome associated with raw milk consumption and an outbreak of gastroenteritis and hemolytic uremic syndrome caused by Escherichia coli serotype O157:H7. We collected specimens from heifers, calves, and adult cows on 22 farms, in a stockyard, and in a packing house. We also collected 3 raw hamburger specimens from a restaurant and 23 raw milk samples from two farms. All specimens were examined for E. coli O157:H7 by using sorbitol-MacConkey agar, H immobilization, O157 agglutination, and tissue culture cytotoxicity. E. coli O157:H7 was isolated from 16 heifers or calves and 1 adult cow on 22 farms, 1 stockyard calf, 2 beef specimens, and 1 raw milk sample. Selected fecal specimens were also examined for the presence of other Shiga-like-toxin-producing E. coli (SLTEC) by testing polymyxin B extracts of colony sweeps and then testing individual colonies for toxin production. SLTEC other than O157 was isolated from 8 of 10 farms investigated and from the stockyard; 8% of adult cows and 19% of heifers and calves were positive for SLTEC. Several animals were positive for SLTEC by colony sweep only. This investigation demonstrates that dairy cattle are a reservoir of E. coli O157:H7 and other SLTEC.

Animals

Effects of body fat distribution on regional lipolysis in obesity.

UNLABELLED: To determine the contribution of the major body fat depots to systemic free fatty acid (FFA) availability, palmitate ([1-14C]-palmitate) release was measured from leg (lower body) and non-leg (upper body) fat in eight upper body obese (UB Ob), six lower body obese (LB Ob), and six nonobese (Non Ob) age-matched premenopausal women in the overnight postabsorptive state. Splanchnic palmitate release was determined in 16 of these subjects. RESULTS: total palmitate release was greater in UB Ob (P less than 0.005) than LB Ob or Non Ob women (161 +/- 16 vs. 111 +/- 9 vs. 92 +/- 9 mumol/min, respectively). Despite increased leg fat mass in obese women, leg palmitate release was similar in each group. Therefore, leg fat palmitate release was greater in Non Ob women than LB Ob (P less than 0.01) or UB Ob (P = 0.06) women (3.7 +/- 0.3 vs. 2.4 +/- 0.2 vs. 2.7 +/- 0.2 mumol.kg fat-1.min-1, respectively). Upper body fat palmitate release was less (P less than 0.01) in LB Ob than Non Ob or UB Ob women (3.0 +/- 0.4 vs. 5.0 +/- 0.3 vs. 4.9 +/- 0.4 mumol.kg fat-1.min-1, respectively). Splanchnic palmitate release accounted for 20-32% of upper body fat palmitate release in each group (P = NS between groups). Leg fat palmitate release was significantly less than upper body fat palmitate release. We conclude that the major difference in resting FFA metabolism between UB Ob and LB Ob women is the ability of the later to down-regulate upper body fat lipolysis to maintain normal FFA availability.

Adipose Tissue

Use of birth defects monitoring programs for assessing the effects of maternal substance abuse on pregnancy outcomes.

We have attempted to demonstrate that birth defects surveillance systems are a unique adjunct to clinical research data on maternal exposures, including substances of abuse. Surveillance system data reflect the experiences of the populations from which they are drawn and the characteristics of the people in those populations. Sensitive systems may reveal trends in health status and changes in behavioral, cultural, social, or environmental exposures. They can be used to monitor changing trends, to identify clusters for investigation, to generate and test hypotheses, and to conduct epidemiological studies. For researchers to interpret data derived from surveillance systems appropriately and wisely, they need a thorough knowledge of the data sources, the data-collection procedures, and the intent of the surveillance systems. Researchers using surveillance data should have a thorough understanding of the quality of their data and the methodologic subtleties that bear on its interpretation; researchers reviewing scientific literature based on surveillance data should be aware of the strengths and limitations inherent in the data.

Abnormalities, Drug-Induced

Arrhythmias in patients with CHF. Should they be treated?

Ventricular arrhythmias are a major cause of death in patients with congestive heart failure. Dr Ellenbogen and his associates discuss the current thinking, based on recent studies, concerning use of antiarrhythmic agents to prevent sudden cardiac death in these patients. As they point out, the proper antiarrhythmic therapy may be crucial to long-term survival.

Adult

2H-NMR resolution of the methylenic isotopomers of ethanol applied to the study of stereospecific enzyme-catalysed exchange.

We have shown that site-specific natural isotope fractionation of hydrogen studied by NMR (SNIF-NMR) is an important source of information on the mechanistic and environmental effects which govern the photosynthesis of sugars and their fermentation into ethanol. Three isotope ratios associated with the methyl, methylene, and hydroxyl sites of ethanol are determined in achiral media. In this study we show that complementary information about possible stereospecific mechanisms involving the methylenic hydrogens is also rendered accessible by 2H-NMR enantiomeric resolution. The synthesis of mandelate esters enables exchange between the pro-R site of ethanol and water to be investigated. Simultaneous access to the three site-specific isotope ratios of the ethyl group is obtained at isotopic dilutions close to the natural ones. Mediation of the exchange by the enzymic system alcohol dehydrogenase-alpha-lipoyldehydrogenase and by the yeast Saccharomyces cerevisiae are compared. The progress of the reaction can be followed quantitatively as a function of time and the occurrence of glycolytic metabolism of endogeneous materials by yeast can be substantiated in a one-pot experiment.

Alcohol Dehydrogenase

Descriptive epidemiology of selected malformations of the aorta, Atlanta, 1970-1983.

To augment available population-based epidemiologic data for obstructive malformations of the aorta, we studied the descriptive epidemiology of coarctation, hypoplasia, and interruption of the aortic arch in Atlanta from 1970 through 1983. The study used data from the Metropolitan Atlanta Congenital Defects Program, a population-based birth defects registry. One hundred seventy infants were identified as having either interruption of the aortic arch (18), coarctation (131), or hypoplasia (21) of the aorta. The prevalence per 10,000 live births was as follows: interruption of the aortic arch, 0.50; coarctation, 3.62; and hypoplasia of the aorta, 0.58. Despite the differences in rates, the descriptive epidemiology for the three malformations was similar. None of the malformations was associated with gender or maternal age. Birth prevalence for whites was higher than that for other races; the increase, however, was statistically significant only for coarctation. Birth prevalence of these malformations increased during the period of observation, with the greatest increase (threefold) seen with interruption of the aortic arch. The rates for all malformation groups also showed a strong inverse association with birthweight.

Adult

In vitro screening for anticonvulsant-induced teratogenesis in neural primary cultures and cell lines.

To establish inherent potential for the induction of neural tube defects the ability of selected anticonvulsant agents to interfere with cell division has been established in vitro using an antiproliferative assay in clonal cell lines and a cytotoxicity assay using primary cultures of cerebral cortex neurons at different stages of development. In order to evaluate the relative toxicities of these agents their in vitro effects were determined at 2-3 times the plasma therapeutic level. By these procedures valproate and the benzodiazepines, diazepam and clonazepam, exerted a potent antiproliferative action which could not be attributed to increased cytotoxicity. In contrast phenytoin was markedly cytotoxic but was without an antiproliferative action. This cytotoxicity was most pronounced during the periods of extensive fibre outgrowth. When compared to epidemiological and animal study data, agents which inhibited cell proliferation within twice therapeutic concentration were consistently associated with major neural tube malformations. However phenytoin, found to be positive in the cell cytotoxicity assay, is not associated with neural tube malformations but rather is primarily associated with mental retardation. Thus assessment of antiproliferative activity of anticonvulsant drugs may be one criterion for identification of teratogenic potential during neurulation.

Animals