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Biomedical subjects

A Mino

Publications and source records attributed to A Mino.

33 records · Page 2Linked to original sources
PubMed1998

Rho1p-Bni1p-Spa2p interactions: implication in localization of Bni1p at the bud site and regulation of the actin cytoskeleton in Saccharomyces cerevisiae.

Rho1p is a yeast homolog of mammalian RhoA small GTP-binding protein. Rho1p is localized at the growth sites and required for bud formation. We have recently shown that Bni1p is a potential target of Rho1p and that Bni1p regulates reorganization of the actin cytoskeleton through interactions with profilin, an actin monomer-binding protein. Using the yeast two-hybrid screening system, we cloned a gene encoding a protein that interacted with Bni1p. This protein, Spa2p, was known to be localized at the bud tip and to be implicated in the establishment of cell polarity. The C-terminal 254 amino acid region of Spa2p, Spa2p(1213-1466), directly bound to a 162-amino acid region of Bni1p, Bni1p(826-987). Genetic analyses revealed that both the bni1 and spa2 mutations showed synthetic lethal interactions with mutations in the genes encoding components of the Pkc1p-mitogen-activated protein kinase pathway, in which Pkc1p is another target of Rho1p. Immunofluorescence microscopic analysis showed that Bni1p was localized at the bud tip in wild-type cells. However, in the spa2 mutant, Bni1p was not localized at the bud tip and instead localized diffusely in the cytoplasm. A mutant Bni1p, which lacked the Rho1p-binding region, also failed to be localized at the bud tip. These results indicate that both Rho1p and Spa2p are involved in the localization of Bni1p at the growth sites where Rho1p regulates reorganization of the actin cytoskeleton through Bni1p.

Actins↗
PubMed1997

The effects of high altitude trekking on body composition and resting metabolic rate.

Resting metabolic rate (RMR) and body composition were evaluated in 12 healthy volunteers before and after 16 days of high altitude trekking and climbing. RMR was measured by indirect calorimetry and body composition by electrical impedance. A 29% reduction in energy intake during high altitude exposure was observed. Fat mass loss averaged about 2.2 kg (p < 0.05) and lean body mass about 1.1 kg, which was almost significant (p = 0.07). As expected, estimated RMR at the end of the expedition--calculated by predictive formulae including body fat and lean body mass as covariates--was significantly reduced by 119 kcal/day as a consequence of the reduction in body weight. Measured RMR values, on the contrary, did not show any significant decline. In conclusion our study showed that high altitude trekking induced a weight loss due approximately 2/3rds to fat mass and 1/3rd to lean body mass. Decreased energy efficiency, which was still present several days after returning to sea level, may have helped contribute to weight loss due to reduced energy intake.

Adult↗
PubMed1997

Predictors of patient retention in a newly established methadone maintenance treatment programme.

AIMS: To identify predictors of patient retention in methadone maintenance. DESIGN: Prospective study. SETTING: Methadone maintenance treatment programme newly established in Geneva, Switzerland. PARTICIPANTS: All patients who initiated treatment between February 1991 and January 1995. MEASUREMENTS: Baseline patient characteristics, dose of methadone, year of enrollment and retention in treatment. FINDINGS: Overall, 111 patients contributed 164.4 person-years of follow-up. The retention rate was 84% after 12 months. In multivariate analysis, the risk of dropping out was significantly higher for patients who had been using opioids for < or = 7 years (relative hazard (RH) 3.0, 95% confidence interval (CI) 1.2-7.4), and for patients who had no stable income at baseline (RH 3.3, 95% CI 1.2-9.1). Dropouts were less frequent at the highest doses of methadone (65-110 mg/day, RH 1.0) than at middle doses (45-60 mg/day, RH 2.0, 95% CI 0.7-5.5) but, quite unexpectedly, dropouts were least likely at the lowest doses (15-40 mg/day, RH 0.5, 95% CI 0.1-1.8). Dropouts were more likely among patients who enrolled in the first (RH 6.2, 95% CI 2.3-16.7) and second (RH 1.9, 95% CI 0.6-5.6) years of the programme, compared with subsequent years (RH 1.0). CONCLUSIONS: Patients who have a long history of drug use and who have a stable income were more likely to stay in methadone maintenance treatment. Independent of patient characteristics, retention improved dramatically in the first years of programme functioning, suggesting that patient retention is a sensitive indicator of programme performance.

Adolescent↗
PubMed1996

Bni1p implicated in cytoskeletal control is a putative target of Rho1p small GTP binding protein in Saccharomyces cerevisiae.

The RHO1 gene encodes a homolog of mammalian RhoA small GTP binding protein in the yeast Saccharomyces cerevisiae. Rho1p is localized at the growth sites, including the bud tip and the cytokinesis site, and is required for bud formation. We have recently shown that Pkc1p, a yeast homolog of mammalian protein kinase C, and glucan synthase are targets of Rho1p. Using the two-hybrid screening system, we cloned a gene encoding a protein which interacted with the GTP-bound form of Rho1p. This gene was identified as BNI1, known to be implicated in cytokinesis or establishment of cell polarity in S.cerevisiae. Bni1p shares homologous domains (FH1 and FH2 domains) with proteins involved in cytokinesis or establishment of cell polarity, including formin of mouse, capu and dia of Drosophila and FigA of Aspergillus. A temperature-sensitive mutation in which the RHO1 gene was replaced by the mammalian RhoA gene showed a synthetically lethal interaction with the bni1 mutation and the RhoA bni1 mutant accumulated cells with a deficiency in cytokinesis. Furthermore, this synthetic lethality was caused by the incapability of RhoA to activate Pkc1p, but not glucan synthase. These results suggest that Rho1p regulates cytoskeletal reorganization at least through Bni1p and Pkc1p.

Base Sequence↗
PubMed1996

Interaction of the Rho family small G proteins with kinectin, an anchoring protein of kinesin motor.

The Rho family small G proteins are implicated in various cell functions, such as cell morphological change, cell motility, and cytokinesis. However, their modes of action in regulating these cell functions remain to be clarified. In the present study, we have isolated a cDNA encoding a protein which interacts with the GTP-bound form, but not with the GDP-bound form, of the Rho family members, including RhoA, Racl, and Cdc42, by the yeast two-hybrid method. This protein is kinectin, known to be a vesicle membrane anchoring protein of kinesin, which is an ATPase motor transporting vesicles along microtubules.

Binding Sites↗
PubMed1996

Relationship between hydration of lean body mass and visceral adipose tissue. A clinical study of women.

OBJECT: To study the relationship between hydration of lean body mass and adipose tissue location. DESIGN: Cross-sectional, clinical study of visceral adipose tissue area and total body water as a percentage of lean body mass. PATIENTS: Seventy-two adult, overweight, women, 52 pre- and 20 post-menopausal (age: 18-72 years, body mass index: 26-52). MEASUREMENTS: Total body water was obtained by electrical impedance measurement; visceral adipose tissue and lean body mass were obtained by computed tomography measurement of visceral adipose tissue area at the level of the 4th-5th lumbar vertebra. RESULTS: Visceral adipose tissue was found, by multiple regression analysis, to be the only predictor of the hydration of the lean body mass. The other independent variables: age, menopausal status, body mass index, glucose and insulin both fasting and after glucose load were not able to significantly improve the predictive power. CONCLUSION: Results of this study confirm the existence of a relationship between visceral adipose tissue content and hydration of the lean body mass.

Abdomen↗
PubMed1995

A downstream target of RHO1 small GTP-binding protein is PKC1, a homolog of protein kinase C, which leads to activation of the MAP kinase cascade in Saccharomyces cerevisiae.

The RHO1 gene in Saccharomyces cerevisiae encodes a homolog of the mammalian RhoA small GTP-binding protein, which is implicated in various actin cytoskeleton-dependent cell functions. In yeast, Rho1p is involved in bud formation. A yeast strain in which RHO1 is replaced with RhoA shows a recessive temperature-sensitive growth phenotype. A dominant suppressor mutant was isolated from this strain. Molecular cloning of the suppressor gene revealed that the mutation occurred at the pseuodosubstrate site of PKC1, a yeast homolog of mammalian protein kinase C. Two-hybrid analysis demonstrated that GTP-Rho1p, but not GDP-Rho1p, interacted with the region of Pkc1p containing the pseudosubstrate site and the C1 domain. MKK1 and MPK1 encode MAP kinase kinase and MAP kinase homologs, respectively, and function downstream of PKC1. A dominant active MKK1-6 mutation or overexpression of MPK1 suppressed the temperature sensitivity of the RhoA mutant. The dominant activating mutation of PKC1 suppressed the temperature sensitivity of the RhoA mutant. The dominant activating mutation of PKC1 suppressed the temperature sensitivity of two effector mutants of RHO1, rho1(F44Y) and rho1(E451), but not that of rho1(V43T). These results indicate that there are at least two signaling pathways regulated by Rho1p and that one of the downstream targets is Pkc1p, leading to the activation of the MAP kinase cascade.

Amino Acid Sequence↗
PubMed1994

[Current drug policies: the Geneva example].

During the last few years, drug policies have been at the center of passionate debates and have been developed in different ways, according to the country or, in Switzerland, the canton. The concept of risk reduction strategy emerged. This article reviews the international literature on the development of this concept and of the prevention and treatment strategies derived from it. The implementation of such a concept is illustrated by the recent developments of drug policy in the canton of Geneva.

Health Policy↗
PubMed1994

Interrelationships between intraabdominal fat and total serum testosterone levels in obese women.

Thirty-six women aged 18 to 52 years with body mass indexes (BMIs) between 27 and 52 were studied. Visceral and subcutaneous fat areas and body fat were evaluated by computerized tomography with a single scan at the IV-V lumbar vertebra level. Glucose, insulin, and C-peptide levels were measured before and after a glucose load. Total and free serum testosterone and 24-hour urinary cortisol excretion were measured. A stepwise multiple regression equation showed the visceral to subcutaneous fat area ratio to be the most powerful predictor for glucose alterations both during fasting and after a glucose load, and showed BMI to be the most powerful predictor for insulin and C-peptide levels. Total serum testosterone, after matching for age and BMI, demonstrates a significant negative correlation with visceral fat area. We conclude that in obese women, as in men, intraabdominal fat negatively correlates with serum testosterone levels.

Abdomen↗
PubMed1994

Measured and predicted total and visceral adipose tissue in women. Correlations with metabolic parameters.

The aim of this study was the verification of the clinical utility of predictive equations for total and intra-abdominal adipose tissue areas. Formulas were calculated using computed tomography (CT) as the gold standard. Ninety-three females were randomly divided into two groups. The predictive equation group was used to calculate the predictive equations for computed tomography adipose tissue areas at the L4-L5 level. These equations were then used to predict total and intra-abdominal adipose tissue area in the validation group. Correlations were made between metabolic parameters and both measured and calculated areas and single predictors. The following measurements were carried out: age, weight/height ratio, body mass index, waist, hip, waist/hip ratio, ultrasound measurement of intra-abdominal distance between abdominal muscle and aorta, sagittal abdominal diameter by CT, adipose tissue intra-abdominal area by CT, total abdominal adipose tissue area by CT. Blood glucose and insulin both fasting and after glucose load. Fasting cholesterol and triglycerides. The best predictors of total and visceral adipose tissue areas were, respectively: weight/height ratio and ultrasound intra-abdominal measurement. Correlations between metabolic parameters and adipose tissue areas both as measured and as calculated by predictive equations were quite similar. Correlations between metabolic parameters and single best predictors of measured adipose tissue areas also gave the same results. Some simple and safe anthropometric measurements can be used, instead of total and visceral adipose tissue area as assessed by CT, when studying associations between adipose tissue and metabolic parameters on sufficiently large groups of patients.

Adipose Tissue↗
PubMed1994

[New drug policies: the Geneva example].

As a consequence of the negative medical social effects of illicit drug use a certain number of countries, during the eighties, have chosen to rethink their therapeutical strategies which were mainly aimed at instoring rapid abstinence. Risk-reduction strategies are varied, including distribution of syringes, substitutive strategies and cultural modification of the drug-addicted representations. Such substantial modifications lead to reflections on both national and international legal systems.

Acquired Immunodeficiency Syndrome↗