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Biomedical subjects

S S Martin

Publications and source records attributed to S S Martin.

At least 37 records · Page 2Linked to original sources
PubMed1997

The small guanosine triphosphate-binding protein Rab4 is involved in insulin-induced GLUT4 translocation and actin filament rearrangement in 3T3-L1 cells.

Insulin's stimulation of glucose transport involves the translocation of vesicles containing the glucose transporter GLUT4 to the plasma membrane. Small GTP-binding proteins have been implicated in the regulation of vesicular traffic. We studied the effects of microinjection of wild-type Rab4 glutathione S-transferase fusion protein (WT Rab4), a GTP-binding defective mutant (Rab4 N121I), a guanosine triphosphatase-defective mutant (Rab4 Q67L), and a Rab4 antibody on insulin-induced GLUT4 translocation in 3T3-L1 adipocytes. Microinjection of Rab4 N121I and Rab4 antibodies had no effect on basal GLUT4 staining, but inhibited insulin-induced GLUT4 translocation by 50% compared with that in control IgG-injected cells. WT Rab4 and Rab4 Q67L microinjection had no effect on either basal or insulin-induced GLUT4 translocation. Premixing and coinjection of the Rab4 antibody with WT Rab4 almost completely abolished its inhibitory effect on insulin-induced GLUT4 translocation. In contrast, microinjection of an antibody directed against the highly conserved region of Rab3 proteins had no effect on insulin-induced GLUT4. These results point to a direct role of Rab4 in insulin-induced GLUT4 translocation, and that this effect is dependent on nucleotide binding to the protein. We also studied the effect of microinjection of the same proteins on insulin-induced actin filament rearrangement (membrane ruffling) in the same cell line. Microinjection of Rab4 N121I and Rab4 antibodies inhibited insulin-induced membrane ruffling by 40%, whereas WT Rab4 or a Rab3 antibody injection had no effect on cytoskeletal rearrangement. In summary, 1) Rab4 is a necessary component of the insulin/GLUT4 translocation signaling pathway; 2) the function of Rab4 in this pathway requires GTP binding; 3) Rab4 also participates in the process of insulin-induced membrane ruffling; and 4) Rab3 proteins do not seem to be involved in these processes.

3T3 Cells↗
PubMed1996

Evidence for an insulin receptor substrate 1 independent insulin signaling pathway that mediates insulin-responsive glucose transporter (GLUT4) translocation.

Interaction of the activated insulin receptor (IR) with its substrate, insulin receptor substrate 1 (IRS-1), via the phosphotyrosine binding domain of IRS-1 and the NPXY motif centered at phosphotyrosine 960 of the IR, is important for IRS-1 phosphorylation. We investigated the role of this interaction in the insulin signaling pathway that stimulates glucose transport. Utilizing microinjection of competitive inhibitory reagents in 3T3-L1 adipocytes, we have found that disruption of the IR/IRS-1 interaction has no effect upon translocation of the insulin-responsive glucose transporter (GLUT4). The activity of these reagents was demonstrated by their ability to block insulin stimulation of two distinct insulin bioeffects, membrane ruffling and mitogenesis, in 3T3-L1 adipocytes and insulin-responsive rat 1 fibroblasts. These data suggest that phosphorylated IRS-1 is not an essential component of the metabolic insulin signaling pathway that leads to GLUT4 translocation, yet it appears to be required for other insulin bioeffects.

3T3 Cells↗
PubMed1996

Activated phosphatidylinositol 3-kinase is sufficient to mediate actin rearrangement and GLUT4 translocation in 3T3-L1 adipocytes.

Insulin stimulation of 3T3-L1 adipocytes causes rapid translocation of actin and the GLUT4 glucose transporter to the plasma membrane. Both processes depend on the activity of phosphatidylinositol 3-kinase. Using single cell microinjection, we have transiently expressed a constitutively activated mutant of phosphatidylinositol 3-kinase, p110*, in 3T3-L1 adipocytes. Fluorescent detection of GLUT4 protein and actin within these cells demonstrates that expression of p110* is sufficient to cause translocation of GLUT4 to the plasma membrane and the formation of actin membrane ruffles. These effects are inhibited by wortmannin in the p110*-expressing cells, indicating that the phosphatidylinositol 3-kinase activity of the protein is required. Overexpression of an identical protein containing a point mutation in the kinase domain, p110*Deltakin, was incapable of mediating either action, confirming that neither the microinjection process nor a nonspecific effect of the protein was responsible for the observed effects. These data suggest that although insulin is capable of inducing numerous signaling pathways, the isolated activation of phosphatidylinositol 3-kinase can initiate the signaling cascade leading to both actin rearrangement and GLUT4 translocation in the absence of insulin stimulation.

3T3 Cells↗
PubMed1996

Selection of RNA-binding peptides in vivo.

Many priniciples of sequence-specific DNA recognition have been established over the past decade, largely from structural studies of protein-DNA and drug-DNA complexes. On the basis of these principles, it has been possible to design or select variants of known structural motifs, including zinc-fingers and minor groove-binding drugs, that bind desired sequences. Here we describe a strategy, based on transcriptional termination in bacteria, to identify specific RNA-binding peptides using the arginine-rich RNA-binding motif as a framework. Peptides were isolated from two combinatorial libraries that bind tightly and specifically to the Rev response element of HIV. It appears that alpha-helical peptides resembling Rev were selected from one library whereas new peptides that probably do not form helices were selected from the other, suggesting that the arginine-rich motif may be a particularly versatile framework for recognizing RNA structures.

Amino Acid Sequence↗
PubMed1996

Phosphatidylinositol 3-kinase is necessary and sufficient for insulin-stimulated stress fiber breakdown.

Rat-1 fibroblasts overexpressing the human insulin receptor undergo rapid actin rearrangement in response to insulin. Breakdown of stress fibers present in quiescent cells is followed by transient membrane ruffling and a return of stress fibers. We investigated the signaling pathways that mediate this insulin-stimulated reorganization of the actin cytoskeleton, which was visualized with rhodamine-phalloidin. Treatment of cells with the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor wortmannin prevented insulin action at the preliminary step of stress fiber breakdown. Cellular microinjection of a polyclonal antibody directed against the p85 subunit of PI3-kinase as well as a purified recombinant p85-SH2 domain protein also inhibited actin reorganization. Transient expression of a constitutively active form of PI3-kinase (p110*) was sufficient to cause both stress fiber breakdown and membrane ruffling in the absence of insulin. Microinjection of a polyclonal anti-Shc antibody or dominant negative N17-Ras protein did not affect actin dynamics, and although constitutively active V12-Ras caused modest cytoskeletal reorganization, this effect was blocked by pretreatment with wortmannin. In summary, activation of PI3-kinase is necessary and sufficient to stimulate actin rearrangement, indicating that PI3-kinase may initiate the only signaling cascade required for insulin to induce cytoskeletal restructuring.

Actins↗
PubMed1995

Psychoactive medication, alcohol use, and falls among older adults.

The purposes of this study were to determine: (1) the prevalence of psychoactive medication and alcohol use and (2) the relationship among psychoactive medications, alcohol use, and falls in a sample of 1028 independently living women and men, aged 55 and older. Twenty-six percent of the sample reported falling, 28% were taking one or more psychoactive drugs, and 38% drank alcohol during the past year. Analyses with logistic regression indicate that predictors of falls were psychoactive drug use, age, and number of illnesses. Living alone, frequency of alcohol use, and gender were not significant predictors.

Accidental Falls↗
PubMed1994

Appropriateness of assertive case management for drug-involved prison releasees.

Assertive case management models have been used successfully in both social work and mental health settings and, most recently, in the substance abuse field. This article reports on the application of an assertive case management model with drug-involved parolees in Delaware. Because of a variety of factors, the evaluation proved to be less than an ideal test of the effectiveness of the case management approach. Although there were some modest effects on reducing relapse to drug use, it appears that assertive case management is of limited value for clients who are not merely unable to access services, but who are often quite assertive in their unwillingness to make use of these services.

Assertiveness↗
PubMed1993

Gender, styles of deviance, and drinking problems.

The analyses reported here draw on recent work on gender and deviance to derive hypotheses concerning sex differences in drinking behavior, reactions of significant others to male and female intoxication, and the psychological consequences of drinking experiences. The hypotheses are evaluated in structural equation models with recent national data on drinking behavior and consequences. Consistent with the gendered deviance perspective, the results suggest that sex differences in style as well as frequency of intoxication mitigate the adverse consequences of female drinking commonly presumed on the basis of biological vulnerability or societal disapproval of female drunkenness. Compared to males, females become intoxicated less frequently and are less likely to abandon personal control while drinking (as indicated by aggression, blackouts, and rapid ingestion). As expected, these sex differences in drinking behavior are smaller among adolescents than among adults. Partly as a result of this different drinking style, significant others are no more likely to criticize girls or women for their drinking than they are to criticize boys or men. Two hypotheses concerning the greater psychological vulnerability of females to depression as a result of drinking or criticism of drinking by significant others are supported among youths but not among adults.

Adolescent↗
PubMed1992

Postoperative inflammation following cataract extraction caused by bacterial contamination of the cleaning bath detergent.

Five of 16 patients who had uncomplicated cataract extraction with intraocular lens (IOL) implantation within a 2.5 day period experienced increased anterior segment inflammation on their first postoperative day. Four of these five patients had phacoemulsification and one a planned extracapsular cataract extraction. All had posterior chamber IOL implantation in the capsular bag. In all patients, this anterior segment inflammation cleared with topical steroids over two to three weeks with no evident residual ocular effects. A careful search for the possible cause of the inflammation showed that the ultrasonic cleaning bath and Weck liquid detergent used to clean the instruments contained Klebsiella pneumoniae bacteria. Further investigation demonstrated the presence of a heat-stable endotoxin produced by the bacteria. We postulate that endotoxin remaining on the instruments after cleaning and sterilization caused this postoperative anterior segment inflammation. To the best of our knowledge, these are the first reported cases caused by contaminated liquid detergent.

Aged↗
PubMed1992

The benefits and costs of caregiving and care receiving for daughters and mothers.

In accordance with social exchange theory (Thibaut and Kelley, 1959), this study examined the outcomes of caregiving for elderly mothers and their caregiving daughters (N = 141 pairs). Data were gathered through face-to-face interviews. Principal components factor analyses revealed three factors for mothers: Helplessness, Feeling Loved, and Anger; and three factors for daughters: Insufficient Time, Frustration, and Anxiety. Block regressions with an initial block of demographic variables and a second block of situational variables were performed to determine the relative influence of these two sets of independent variables on caregiving outcomes. The regressions revealed limited influence of demographic variables and significant influence of situational variables. Of particular importance for daughters is the role of perceived intimacy with the mother: Daughters with better relationships experience fewer caregiving costs. Mothers' health plays a critical role in the outcomes of care receiving: Mothers in poorer health experience greater helplessness and are less likely to feel loved.

Aged↗