Biomedical subjects

D L Groves

Publications and source records attributed to D L Groves.

12 recordsLinked to original sources

PubMed1989

Adipsin and complement factor D activity: an immune-related defect in obesity.

Adipsin is a serine protease that is secreted by adipocytes into the bloodstream; it is deficient in several animal models of obesity, representing a striking example of defective gene expression in this disorder. Recombinant mouse adipsin was purified and its biochemical and enzymatic properties were studied in order to elucidate the function of this protein. Activated adipsin has little or no proteolytic activity toward most substrates but has the same activity as human complement factor D, cleaving complement factor B when it is complexed with activated complement component C3. Like authentic factor D, adipsin can activate the alternative pathway of complement, resulting in red blood cell lysis. Decreased (58 to 80 percent) complement factor D activity, relative to lean controls, was observed as a common feature of several experimental models of obesity, including the ob/ob, db/db, and monosodium glutamate (MSG)-injected mouse and the fa/fa rat. These results suggest that adipsin and the alternative pathway of complement may play an unexpected but important role in the regulation of systemic energy balance in vivo.

Adipose Tissue↗

PubMed1989

Adrenal glucocorticoids regulate adipsin gene expression in genetically obese mice.

Adipsin expression at the protein and mRNA levels is greatly reduced in several distinct syndromes of obesity in the mouse: genetic obesity due to the db/db and ob/ob genes, and a chemically induced model secondary to neonatal exposure to monosodium glutamate. We considered first the possibility that the adipsin gene might be identical to the db or ob locus and the lowered expression of this protein might result from a mutation in this gene. We show here that the adipsin structural gene is located on chromosome 10 and hence is physically distinct from any obesity genes so far identified in the mouse. A major role for the adrenal gland and adrenal glucocorticoids in the aberrant regulation of adipsin in these models of obesity is indicated by several experiments. Adrenalectomy of the ob/ob mouse raises the circulating levels of adipsin protein and the amount of this mRNA in epididymal fat pads (5-fold), although neither is increased to the levels seen in lean controls. Exogenous administration of corticosterone completely blocks the effects of adrenalectomy on adipsin, suggesting that the effect of this endocrine ablation is through reduction of adrenal glucocorticoids. Corticosterone administration also causes suppression in the levels of adipsin mRNA and protein in lean mice, although this decrease is never as severe as that seen in obese mice. The effect of exogenous corticosterone in lean mice occurs within 2 days and hence is not secondary to the obesity which these hormones eventually elicit. These results indicate that glucocorticoids can regulate adipsin expression in vivo and strongly suggest that the hyperglucocorticoid state seen in certain obese models plays a significant role in lowering adipsin mRNA and protein levels. Quantitative analysis of these experiments suggests that other as yet unknown neuroendocrine factors also function to suppress adipsin in obesity.

Adipose Tissue↗

PubMed1989

Sports competition and its influence on self-esteem development.

Competition and its influence upon the adolescent is the primary concern of many recreational agencies. In the past ten years, many youth agencies have de-emphasized competition in their programs because of its negative influence upon self-esteem. There is a need to examine the relationship between competition and self-esteem so that recreational programs can be better designed to utilize competition as a positive factor. A study was undertaken to examine self-esteem in relation to competition in a basketball program. It was found that the coach's assessments of ability and intention of participation are important factors in positive self-esteem development. The social aspects of peer interaction and parent influence also contribute to positive self-esteem. These are minor elements, however, in comparison to the impact of the coach. There needs to be intensive training for coaches on how to develop positive self-esteem and how to deal with the range of participation styles.

Achievement↗

PubMed1987

Nucleoprotein complexes that regulate gene expression in adipocyte differentiation: direct participation of c-fos.

Adipocyte differentiation is accompanied by the transcriptional activation of many new genes, including a putative lipid-binding protein termed adipocyte P2 (aP2). The aP2 gene contains a regulatory element (FSE2) 124 bases 5' to its start of transcription. This element binds nuclear factors in sequence-specific and differentiation-dependent fashion as determined by altered mobility in gel retardation assays. Deletion analysis of promoter-linked transfection assays and competition of these constructions in cells with a synthetic FSE2 element suggest that trans-acting factors bind to this region and act as negative regulators of aP2 gene activity in preadipocytes. c-fos appears to participate directly in this nucleoprotein complex, as demonstrated by the ability of antibodies to c-fos to disrupt specific binding of factors to the FSE2 sequence but not to factor-binding sequences from several other genes. Antibodies to c-fos specifically immunoprecipitate protein complexes covalently bound to FSE2 DNA via UV cross-linking.

Adipose Tissue↗

PubMed1987

Nucleotide sequence and hormonal regulation of mouse glycerophosphate dehydrogenase mRNA during adipocyte and muscle cell differentiation.

We have studied the structure and regulation of glycerophosphate dehydrogenase (GPD) mRNA during mouse adipocyte and muscle cell differentiation. This message has a size of 2.8 kilobases that includes a coding segment of 1050 bases and a large untranslated 3' end of about 1700 bases. There is a high degree of amino acid homology (91%) between the mouse adipocyte and rabbit muscle GPD proteins. GPD mRNA is not detected in myoblasts, but, as in adipogenesis, it is expressed upon differentiation into myotubes. The modulation of GPD mRNA by cyclic AMP analogues and tumor necrosis factor has been examined in both adipocytes and myotubes. Dibutyryl cAMP or 8-bromo-cAMP causes a large reduction of GPD mRNA levels in both cell types, with less than 20% remaining after 18 h of treatment. Tumor necrosis factor effects a dramatic and rapid reduction in GPD mRNA in fat cells and a slower but significant decrease in the level of this mRNA in muscle cells. These results indicate that GPD gene expression is linked to cell differentiation in both fat and muscle cells, and suggest certain similarities in hormonal modulation in both cell types.

Adipose Tissue↗

PubMed1985

A developmentally regulated mRNA from 3T3 adipocytes encodes a novel serine protease homologue.

We previously have isolated cDNA clones for several mRNAs that increase in abundance during the differentiation of 3T3 adipocytes but whose physiological role is unknown. We show here that a mRNA that is complementary to one of these clones and encodes a protein of 28 kDa is expressed abundantly in mouse fat pads but not in several other mouse tissues. Sequence analysis of the corresponding cDNA clone indicated that the encoded protein shows 30% overall amino acid homology to several serine proteases including trypsin, chymotrypsin, and elastase. Homology is much higher (64%) between the 28-kDa protein and regions that are strongly conserved among the members of the serine protease family. The derived protein also has key features characteristic of active serine proteases, including the histidine, aspartic acid, and serine residues, which comprise the charge relay system, and a potential cleavage site for activation of the zymogen. Primer extension analysis performed to obtain the sequence of the 5' end of mRNA that encodes the 28-kDa protein indicates that two forms of this mRNA exist and probably arise through alternative splicing. The two mRNAs encode signal sequences that differ by the deletion of one amino acid near the predicted cleavage site of the signal peptide. These results demonstrate that adipocyte differentiation is accompanied by the expression of mRNA encoding a serine protease homologue that can be synthesized with two different signal peptides.

Adipose Tissue↗

PubMed1980

Music as a vehicle for life enrichment and expanded content for special audiences.

Music for special audiences has been a neglected part of most programs. The primary problem has been lack of understanding of the advantages of music and where it fits into a curriculum. Another problem has been the lack of skill to execute an effective program. Most musical events have been isolated with little continuity from one activity to another. Another programming difficulty has been where to find resources and how to use them. The purpose of this article is to briefly discuss programming for special audiences. An illustrative exercise has been provided to point out a programming format, especially the sequencing among activities and the resource utilization dimensions.

Adolescent↗

PubMed1974