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Biomedical subjects

K S Brown

Publications and source records attributed to K S Brown.

At least 37 records · Page 2Linked to original sources

Glucolipsin A and B, two new glucokinase activators produced by Streptomyces purpurogeniscleroticus and Nocardia vaccinii.

During the screening of the natural products for their ability to increase the activity of glucokinase by relieving inhibition by long chain fatty acyl CoA esters (FAC), two novel compounds, glucolipsin A (1) and B (2) were isolated from the butanol extracts of Streptomyces purpurogeniscleroticus WC71634 and Nocardia vaccinii WC65712, respectively. The structures of these two compounds were established by spectroscopic methods and chemical degradation. Glucolipsin A (1) and B (2) relieved the inhibition of glucokinase by FAC with RC50 values of 5.4 and 4.6 microM.

Disaccharides↗

Central injection in rats of alpha-melanocyte-stimulating hormone analog: effects on food intake and brain Fos.

Lateral cerebroventricular (LCVT) administration of the alpha-MSH agonist analog Nle4DPhe7alpha-MSH (NDP-MSH) inhibited food intake in food-deprived rats, but did not inhibit water intake in water-deprived rats. When NDP-MSH was administered into the fourth ventricle (4CVT), comparable suppressions of food intake were observed. LCVT and 4CVT administration of NDP-MSH also reduced spontaneous 24 h food intake. LCVT injection of NDP-MSH greatly attenuated food intake stimulated in sated rats by acute CVT administration of neuropeptide Y (NPY). These and other data suggest that alpha-MSH is an important endogenous regulator of food intake, possibly acting downstream of NPY. In an attempt to assess further the sites of action of NDP-MSH, a qualitative mapping study of Fos-like immunoreactive (Fos-ir) neurons was performed following LCVT administration of NDP-MSH. LCVT injection of NDP-MSH induced Fos-ir in several forebrain regions including cortex, striatum, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus and arcuate nucleus. The combination of NPY and NDP-MSH did not produce obvious antagonism or cancellation of effects in any region examined. Thus, the site(s) of action of NDP-MSH on food intake remain to be clarified.

Animals↗

Joining forces for children's health.

From airborne particulatesto pesticide-laden fruit, children probably encounter more pollutants than adults. Because their bodies are rapidly developing, children may react more strongly to these toxins, too. The NIEHS hopes to learn more about how several hazardous agents specifically affect kids. Together, the NIEHS and the EPA are spending $10 million to establish up to six Centers for Children's Environmental Health and Disease Prevention Research. The CDC, a third partner,will later help apply center research to public health.

Adult↗

Southern synergy.

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National Institutes of Health (U.S.)↗

Sequence analysis of the Chlamydomonas reinhardtii flagellar alpha dynein gene.

Flagellar outer row dynein ATPases have been used extensively as model systems for studies of microtubule-based motility. Previously full-length sequences were only available for two of the three catalytic heavy-chain subunits (DHCs) of this enzyme. We have completed the sequence of an 18-kb genomic region encoding the Chlamydomonas reinhardtii flagellar outer row dynein alpha heavy chain. Unlike the beta- and gamma-subunits, DHC alpha is not required for assembly of other outer row dynein proteins, except for a tightly associated light chain, and thus occupies a unique position within this enzyme complex. The predicted 4,499 residue protein retains sequence homology to other dynein heavy chains throughout its central and C-terminal regions but lacks homology to any other dyneins in the first 1,000 amino acids, which may account for its unusual assembly properties. This N-terminal domain of DHC alpha contains a repetitive sequence rich in alanines, prolines, and glutamic acids. Within the more homologous C-terminal region, which includes the catalytic domain, three short sequences unique to DHC alpha may account for its specific catalytic properties and in vivo phosphorylation pattern.

Amino Acid Sequence↗

Global health: what's in it for us?

A new report, America's Vital Interest in Global Health, released in June by the Institute of Medicine's (IOM) Board on International Health, calls for increased U.S. foreign health care spending to fund research and education about diseases of the developing world, a global surveillance system to spot environmental changes and emerging disease conditions, public and private sector partnerships to distribute vaccines and drugs overseas, and a new government body to help coordinate these efforts. The report argues that, in an increasingly global society, the United States can't afford to ignore its neighbors' problems, for economic as well as social reasons.

Global Health↗

Glucokinase regulatory protein may interact with glucokinase in the hepatocyte nucleus.

Glucokinase (GK) plays a central role in the sensing of glucose in pancreatic beta-cells and parenchymal cells of the liver. Glucokinase regulatory protein is a physiological inhibitor of GK in the liver. To understand the role of the interaction of these two proteins in glucose sensing, we carried out a series of experiments to localize the protein in the liver cell. The regulatory protein was found to be present mainly in the nucleus of the cell under a variety of conditions that mimicked the glucose status of the fed and fasted state. GK was localized in the nucleus when the cells were exposed to low glucose concentrations. At higher glucose concentrations or in the presence of low concentrations of fructose, GK translocated to the cytoplasm. The effect of fructose was more robust and rapid than the effect of high glucose concentrations. Furthermore, the effect of fructose and high glucose on the translocation of GK from the nucleus could be partially reversed by glucagon. This unusual localization and behavior suggests a role for GK and its regulatory protein in hepatic energy metabolism that may be broader than glucose phosphorylation.

1-Methyl-3-isobutylxanthine↗

School-based smoking control: a research agenda.

Within the context of a framework for cancer control, this article reviews evidence and suggests research directions for 3 types of school-based smoking interventions: elementary school prevention, secondary school interventions and interventions linking community and school. Directions for smoking research in elementary schools include improving adoption through the provision of effectiveness criteria, tailoring interventions to schools and training. Monitoring at micro and macro levels may help planning and implementation, but clearer evidence is required of its feasibility. Fundamental research should explore new options to understand why youth do not start smoking. Smoking intervention research at the secondary school level is less well established, with only 1 effectiveness trial reported. We recommend testing models that involve youth in developing their own solutions and examining the interaction of various control measures. Sustainability issues have led researchers to embed school-based smoking interventions in community-wide activities. Intervention research of this sort still needs to determine how to apply approaches (e.g., comprehensive school health) and what the appropriate roles are (such as technical assistance) for community agencies. All research using these school-community approaches needs to include process measures to explain potential failures to obtain significant differences between components. In addition, we call for research on the training of educators and health personnel, to increase the priority given to smoking prevention and improve the implementation of existing programs. Research on policy initiatives that lead to effective training needs to be explored. Finally, we argue that application of the principles incorporated into the cancer control framework (e.g., through participatory research methods) strengthens the research process and results.

Adolescent↗

Critique of the National Cancer Institute of Canada's framework for cancer control.

This paper offers a critique of the National Cancer Institute of Canada's (NCIC) framework for cancer control. The critique has been prepared by researchers who used the framework to review the literature in 5 substantive areas. These reviews, published in the current and previous issues of CPC, were designed to begin to outline a research agenda for the Sociobehavioural Cancer Research Network. In this paper, the authors reflect on the strengths and limitations of the framework. Perceived strengths are that the framework (a) facilitates systematic thinking about research options and priorities, (b) helps foster clear communication, (c) links science and practice, (d) may assist grant review panels to place proposed studies in context and (e) emphasizes important values. Perceived concerns include the following: (a) potential users are not familiar with the framework, (b) lack of clarity of definitions and classification criteria, (c) the utility of the framework is not immediately self-evident to potential users, (d) the framework lacks emphasis on environmental and policy interventions and (e) it is not clear how the values espoused are to be integrated with other dimensions of the framework. The concerns were seen as remediable. In short, the framework was seen to be valuable in its current form; refinement may enhance its value.

Canada↗

Sick days at work.

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Air Pollution, Indoor↗

Heterologous expression and characterization of rat liver glucokinase regulatory protein.

Glucokinase is a critical component of the physiological glucose sensor found in cell types that are responsive to changes in plasma glucose levels. The acute regulation of glucokinase activity has been shown to occur via a regulatory protein found in liver parenchymal cells (Van Schaftingen E, Detheux M, Da Cunha MV. Faseb J 8:414-419, 1994). The action of this protein is modulated by phosphate esters of fructose. In the presence of fructose-6-phosphate, the protein inhibits glucokinase in an allosteric competitive manner, while fructose-1-phosphate reverses this inhibition. A cDNA potentially encoding the rat liver regulatory protein has been cloned, but its identity is uncertain because of the small amounts of soluble protein obtained by expression in bacteria. We report the heterologous expression of the regulatory protein in Escherichia coli and its purification to homogeneity and high specific activity in a single chromatographic step. The properties of this recombinant protein are very similar to those of the liver protein. Direct demonstration of the binding of the recombinant protein to glucokinase has been obtained in vitro using coprecipitation experiments and in vivo, using the yeast two-hybrid system. These studies establish that the protein encoded by the cDNA is identical to the glucokinase regulatory protein and also validate tools with which to carry out structure-function studies on the interaction of the regulatory protein with glucokinase.

Adaptor Proteins, Signal Transducing↗

Anticonvulsant teratogenesis: I. A study design for newborn infants.

The basis for the apparent teratogenicity of maternal epilepsy is controversial. Is the critical factor the anticonvulsant drugs taken by the pregnant woman, or the genes which cause the mother's epilepsy? We describe a study design developed to assess these competing theories in a cohort study of newborn infants. We show the feasibility of ascertaining exposed and unexposed infants at several birthing hospitals in one urban area. Between 1986 and 1988, we identified 180 drug-exposed and 218 epilepsy-history infants among 49,403 infants. The rate of exposure to seizure medication was 0.36% and of maternal history of epilepsy was 0.44%. A significant number of infants could not be evaluated because they were missed, ineligible, or either the doctor, nurse or parent refused to participate. Overall, there was a significant increase in major malformations, microcephaly or growth retardation among the drug-exposed infants in comparison to both the epilepsy-history and the unexposed infants. The types of epilepsy and the apparent etiology were the same among women who took anticonvulsants and women with a history of epilepsy but no anti-convulsants during pregnancy. This study must be extended to include a sufficient number of infants exposed to each commonly used drug as monotherapy to allow for a comparison of the effect of each drug on pregnancy outcomes; to provide a comparison of infants whose mothers had a strong family history of epilepsy with infants whose mothers had trauma-induced epilepsy; and to assess the possible impact of the severity of the mothers' disease on the infants.

Abnormalities, Drug-Induced↗