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Biomedical subjects

K S Brown

Publications and source records attributed to K S Brown.

At least 19 recordsLinked to original sources
PubMed2000

Regulation of Fc epsilonRI expression on human monocytic cells by ligand and IL-4.

BACKGROUND: The Fc epsilonRI subunit composition and kinetic of expression differ between antigen-presenting cells and mast cells. Up to now, there has been no human in vitro model available that mimics the characteristics on monocytes. OBJECTIVE: The characterization of a natural human monocytic cell line (THP1), which expresses Fc epsilonRI, and the comparison to primary human monocytes and other monocytic cell lines, which only express Fc epsilonRI after transfection with the human Fc epsilonRI alpha-chain gene. METHODS: Surface receptor expression was characterized by flow cytometry, the human Fc epsilonRI alpha-chain gene was introduced by electroporation, and induction of Fc epsilonRI alpha-chain message was detected by semiquantitative RT PCR. RESULTS: Here we show that the parental human cell line THP1, but none of the other cell lines tested, displays surface Fc epsilonRI in response to IL-4 or incubation with receptor ligand (IgE, antibody). Transfection of Fc epsilonRI alpha-chain resulted in receptor expression on all cell lines, all of which increased surface Fc epsilonRI in the presence of IgE. Only the THP1-alpha transfectant, however, further increased receptor levels in response to IL-4, resulting from mRNA induction for the Fc epsilonRI-alpha, but not the beta- or gamma-subunit. CONCLUSION: Based on THP1, U937 and HL60 and their alpha-chain transfectants we present a model system for the study of Fc epsilonRI regulation and signalling on human cells. THP1 in particular, due to its responsiveness to both ligand and IL-4, even without prior manipulation, is ideally suited to address questions on Fc epsilonRI modulation in an 'allergic environment'.

Electroporation↗
PubMed1999

Mice mutant for glucokinase regulatory protein exhibit decreased liver glucokinase: a sequestration mechanism in metabolic regulation.

The importance of glucokinase (GK; EC 2.7.1.12) in glucose homeostasis has been demonstrated by the association of GK mutations with diabetes mellitus in humans and by alterations in glucose metabolism in transgenic and gene knockout mice. Liver GK activity in humans and rodents is allosterically inhibited by GK regulatory protein (GKRP). To further understand the role of GKRP in GK regulation, the mouse GKRP gene was inactivated. With the knockout of the GKRP gene, there was a parallel loss of GK protein and activity in mutant mouse liver. The loss was primarily because of posttranscriptional regulation of GK, indicating a positive regulatory role for GKRP in maintaining GK levels and activity. As in rat hepatocytes, both GK and GKRP were localized in the nuclei of mouse hepatocytes cultured in low-glucose-containing medium. In the presence of fructose or high concentrations of glucose, conditions known to relieve GK inhibition by GKRP in vitro, only GK was translocated into the cytoplasm. In the GKRP-mutant hepatocytes, GK was not found in the nucleus under any tested conditions. We propose that GKRP functions as an anchor to sequester and inhibit GK in the hepatocyte nucleus, where it is protected from degradation. This ensures that glucose phosphorylation is minimal when the liver is in the fasting, glucose-producing phase. This also enables the hepatocytes to rapidly mobilize GK into the cytoplasm to phosphorylate and store or metabolize glucose after the ingestion of dietary glucose. In GKRP-mutant mice, the disruption of this regulation and the subsequent decrease in GK activity leads to altered glucose metabolism and impaired glycemic control.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Effectiveness of a social influences smoking prevention program as a function of provider type, training method, and school risk.

OBJECTIVES: This study determined the effect of provider (nurse or teacher) and training method (workshop or self-preparation) on outcomes of a social influences smoking prevention program. METHODS: One hundred elementary schools were stratified by school risk score (high risk = high smoking rate among senior students) and assigned randomly to conditions: (1) teacher/self-preparation, (2) teacher/workshop, (3) nurse/self-preparation, (4) nurse/workshop, and (5) control. Intervention occurred in grades 6 to 8. Smoking status at the end of grade 8 was the primary endpoint variable. RESULTS: Intervention reduced grade 8 smoking rates in high-risk schools (smoking rates of 26.9% in control vs 16.0% in intervention schools) but not in low-risk schools. There were no significant differences in outcome as a function of training method and no significant differences in outcome between teacher-provided and nurse-provided interventions in high- and medium-risk schools. Although nurses achieved better outcomes than did teachers in low-risk schools, neither provider type achieved outcomes superior to the control condition in those schools. CONCLUSIONS: Workshop training did not affect outcomes. Teachers and nurses were equally effective providers. Results suggest that programming should target high-risk schools.

Adolescent↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Southern synergy.

Explore the source record for details and available documents.

National Institutes of Health (U.S.)↗
PubMed1997

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↗
PubMed1997

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↗