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1.
BACKGROUND: Neutral lipases are ubiquitous and diverse enzymes. The molecular architecture of the structurally characterized lipases is similar, often despite a lack of detectable homology at the sequence level. Some of the microbial lipases are evolutionarily related to physiologically important mammalian enzymes. For example, limited sequence similarities were recently noted for the Streptomyces exfoliatus lipase (SeL) and two mammalian platelet-activating factor acetylhydrolases (PAF-AHs). The determination of the crystal structure of SeL allowed us to explore the structure-function relationships in this novel family of homologous hydrolases. RESULTS: The crystal structure of SeL was determined by multiple isomorphous replacement and refined using data to 1.9 A resolution. The molecule exhibits the canonical tertiary fold of an alpha/beta hydrolase. The putative nucleophilic residue, Ser131, is located within a nucleophilic elbow and is hydrogen bonded to His209, which in turn interacts with Asp177. These three residues create a triad that closely resembles the catalytic triads found in the active sites of other neutral lipases. The mainchain amides of Met132 and Phe63 are perfectly positioned to create an oxyanion hole. Unexpectedly, there are no secondary structure elements that could render the active site inaccessible to solvent, like the lids that are commonly found in neutral lipases. CONCLUSIONS: The crystal structure of SeL reinforces the notion that it is a homologue of the mammalian PAF-AHs. We have used the catalytic triad in SeL to model the active site of the PAF-AHs. Our model is consistent with the site-directed mutagenesis studies of plasma PAF-AH, which implicate Ser273, His351 and Asp296 in the active site. Our study therefore provides direct support for the hypothesis that the plasma and isoform II PAF-AHs are triad-containing alpha/beta hydrolases.  相似文献   

2.
Associations of cardiovascular risk factors, including several measures of adiposity, with hyperinsulinemia were assessed in 3562 elderly (71 to 93 years of age) Japanese American men from the Honolulu Heart Program who were examined between 1991 and 1993. In addition, cardiovascular risk factors measured 25 years earlier were also examined in relation to hyperinsulinemia. Hyperinsulinemia was defined as fasting insulin > or = 95th percentile (20 microU/mL) among the subset of subjects (n = 504) who were nonobese and free of clinical diabetes and glucose intolerance. When this definition was applied to the entire population, the prevalence of hyperinsulinemia declined cross-sectionally with age (P < 0.001) from 24.2% in men aged 71 to 74 years to 16.4% in men aged 85 to 93 years. Factors having a positive and independent association with hyperinsulinemia included body mass index (BMI), triglycerides, glucose, hematocrit, use of diabetic medication, heart rate, and hypertension. The association with physical activity was negative. Triglycerides, BMI, diabetic medication, hypertension, and smoking levels measured 25 years earlier were also associated independently with hyperinsulinemia. Associations were similar in nondiabetic subjects. Three measures of adiposity (BMI, waist circumference, and subscapular skinfold thickness) were independently related to hyperinsulinemia cross-sectionally. However, associations involving a difference between the 80th and 20th percentiles in each adiposity measure appeared strongest for BMI (odds ratio (OR) = 4.5, 95% confidence interval (CI) = 3.7 to 5.6) and waist circumference (OR = 4.1, 95% CI = 3.3-5.1) and slightly weaker for subscapular skinfold thickness (OR = 2.1, 95% CI = 1.8-2.5). These findings suggest that features of an insulin resistance syndrome including dyslipidemia, glucose intolerance, hypertension, and obesity, assessed both cross-sectionally and 25 years previously, are associated independently with hyperinsulinemia in elderly Japanese American men.  相似文献   

3.
A comparative analysis is given of the gastric cancer incidence in the Tjumen Province for a period of 1959--1973. There was noted a direct dependence between the rate and number of risk factors (the complexes of unfavourable factors) in males and females. A conclusion is made that a higher incidence rate (1.7 times more) of gastric cancer among males may be attributed to the complexes of infavourable factors to which they are subject to a greater extent, 1.7 times as often as females, (mainly to bad habits) but not to biological features of the organism. Elimination of these harmful effects on the body would lessen the risk of this affection.  相似文献   

4.
The association between plasma fibrinogen, factor VII, factor X, activated partial thromboplastin time, antithrombin III and the lifestyle factors cigarette smoking, alcohol use, fat intake and physical activity was assessed in 802 men aged 70-90 years in Zutphen (The Netherlands), Montegiorgio and Crevalcore (Italy). Smoking was positively associated with fibrinogen, also after adjustment for other lifestyle factors, age, use of anticoagulants and aspirin like drugs, body mass index, and history of myocardial infarction. Alcohol use was associated with increased levels of factor X and decreased levels of antithrombin III. Fat intake was positively associated with antithrombin III. Between cohorts, considerable differences were observed in levels of haemostatic parameters and the lifestyle factors. Compared to the mediterranean cohorts the Zutphen cohort showed the highest levels of fibrinogen and factor VII. Differences in lifestyle factors could, however, not explain differences between cohorts in levels of any of the haemostatic parameters, despite the observed associations between lifestyle factors and haemostatic parameters.  相似文献   

5.
OBJECTIVE: To examine the relationship between hyperinsulinemia and clusters of cardiovascular risk factors in middle-aged hypertensive patients. DESIGN: A population-based study. SETTING: Pieks?m?ki District Health Center, and the Community health Center of the city of Tampere, in central Finland. SUBJECTS: Hypertensive men and women aged 36, 41, 46, and 51 years (n = 18) in the town of Pieks?m?ki, and a normotensive control population of 177 subjects aged 40 and 45 years in the city of Tampere. MAIN OUTCOME MEASURES: Clusters of obesity (body mass index > 30.0 kg/m2), abdominal adiposity (waist:hip ratio > 1.00 for men and > 0.88 for women), hypertriglyceridemia (> 1.70 mmol/l), a low level of high-density lipoprotein cholesterol (< 1.0 mmol/l in men and < 1.20 mmol/l in women) and abnormal glucose metabolism (impaired glucose tolerance or noninsulin-dependent diabetes as defined by World Health Organization criteria) according to statistical quartiles of the fasting plasma insulin concentration. RESULTS: Among the hypertensives, there was a 2.0- to 3.6-fold higher risk of having a clustering of the insulin-resistance associated cardiovascular risk factors compared with that of the normotensives. Among the hypertensive subjects in the highest quartile of fasting plasma insulin there was a six- to 12-fold increase in risk associated with having two or more insulin resistance-associated cardiovascular risk factors compared with the subjects in the lowest quartile. There was a positive correlation between a high number of ascertained risk factors and high levels of fasting plasma insulin. CONCLUSION: In clinical practice, knowledge of the close relationship between risk-factor cluster status and fasting plasma insulin levels offers a tool to evaluate the occurrence of hyperinsulinemia in middle-aged hypertensive men and women.  相似文献   

6.
Although a number of risk factors for cardiovascular morbidity and mortality have been identified in young and middle-aged adults, their prevalence and importance are less known in the elderly. Elderly people have a risk profile different from that of younger subjects, but representative data on risk factors for cardiovascular disease in the elderly are difficult to find in the literature. Some typical 'major' risk factors, like blood pressure (BP), total cholesterol or left ventricular hypertrophy, do not have a clear predictive role for cardiovascular mortality in the elderly, especially in the extreme ages, while risk indicators usually labelled as 'minor' (serum uric acid, ventilatory function or proteinuria), do have a strong predictive value in these individuals. This must be taken into account when evaluating the cumulative risk of the elderly, in order to avoid overtreatment of subjects with mildly elevated BP or cholesterol.  相似文献   

7.
The cardiovascular responses to postural change, and how they are affected by aging, are inadequately described in women. Therefore, the authors examined the influence of age and sex on the responses of blood pressure, cardiac output, heart rate, and other variables to change in posture. Measurements were made after 10 minutes each in the supine, seated, and standing positions in 22 men and 25 women who ranged in age from 21 to 59 years. Several variables differed, both by sex and by age, when subjects were supine. On rising, subjects' diastolic and mean arterial pressures, heart rate, total peripheral resistance (TPR), and thoracic impedance increased; cardiac output, stroke volume, and mean stroke ejection rate decreased; and changes in all variables, except heart rate, were greater from supine to sitting than sitting to standing. The increase in heart rate was greater in the younger subjects, and increases in TPR and thoracic impedance were greater in the older subjects. Stroke volume decreased less, and TPR and thoracic impedance increased more, in the women than in the men. The increase in TPR was particularly pronounced in the older women. These studies show that the cardiovascular responses to standing differ, in some respects, between the sexes and with age. The authors suggest that the sex differences are, in part, related to greater decrease of thoracic blood volume with standing in women than in men, and that the age differences result, in part, from decreased responsiveness of the high-pressure baroreceptor system.  相似文献   

8.
BACKGROUND: Ornithine decarboxylase (ODC; EC 4.1.1.17) is the first rate-limiting enzyme in the biosynthesis of polyamines. ODC protein has a characteristic amino acid sequence, the PEST sequence, which is related to the enzyme's rapid degradation. ODC cDNA prepared from human hepatoma tissues has been reported to show nonsense or missense mutations. METHODS: We examined somatic mutations of ODC cDNA by RT-PCR-SSCP analysis and mRNA expressions by RT-PCR in 50 colorectal cancer tissues to investigate the involvement of ODC gene alterations in colorectal cancers. RESULTS: Increased expression of the ODC gene was observed in 36 cases (86%) out of the 42 examined by RT-PCR. In one case, a missense mutation was found in the cancer tissue but not in normal mucosa. The missense mutation from Asp to Asn at codon 424, in the PEST region, possibly stabilizes the ODC protein. In colorectal cancer, replication error and a germline mutation in hMSH2 gene were observed. CONCLUSIONS: The missense mutation at codon 424 is speculated to be a cause of stabilization and a passenger mutation owing to the mutator phenotype. Since only one of 50 colorectal cancers exhibited a missense mutation of the ODC gene, mutations in ODC gene are not frequent in colorectal cancer. The increased expression of the ODC gene was noted in 86% of colorectal cancer tissues by RT-PCR, however, it was not due to point mutations in ODC coding exons.  相似文献   

9.
Between 1992-1994 nutrition and nutritional status of 2259 persons (1173 men, 1386 women) were examined in Hungary. The average of dietary fat intake was 38.0 (5.7) in %, the median of P/S ratio 0.26-0.27, showing the dominance of saturated fatty acids. According to TC, 34.4% of the examined persons could be ranked to moderate and 27.4% to high risk groups. Regarding LDL-C levels, 27.2-27.2% belonged to both groups. TG indicated risk in 19.5% and 2.4%, respectively and HDL-C values were under the lower limit of normal range in 7.6% Sodium intake is three- to fourfold of the desirable quantity, that of potassium just reaches or remains under the recommended level. As a result, the value of Na/K ratio (mmol/mmol) is over 4. Borderline and/or define hypertension was found according to systolic pressure in 27.4 and 7.9% of men and in 18.1 and 5.2% in women. Diastolic pressure was in this domain in the case of men in 16.9 and 21.9%, in women in 12.7 and 16.1%. Hypertension is frequent both in middle-aged and old men and women. The high CVD mortality in Hungary may be in considerable part explained by the outlined risk factors.  相似文献   

10.
Muscle mass decreases with age, leading to "sarcopenia," or low relative muscle mass, in elderly people. Sarcopenia is believed to be associated with metabolic, physiologic, and functional impairments and disability. Methods of estimating the prevalence of sarcopenia and its associated risks in elderly populations are lacking. Data from a population-based survey of 883 elderly Hispanic and non-Hispanic white men and women living in New Mexico (the New Mexico Elder Health Survey, 1993-1995) were analyzed to develop a method for estimating the prevalence of sarcopenia. An anthropometric equation for predicting appendicular skeletal muscle mass was developed from a random subsample (n = 199) of participants and was extended to the total sample. Sarcopenia was defined as appendicular skeletal muscle mass (kg)/height2 (m2) being less than two standard deviations below the mean of a young reference group. Prevalences increased from 13-24% in persons under 70 years of age to >50% in persons over 80 years of age, and were slightly greater in Hispanics than in non-Hispanic whites. Sarcopenia was significantly associated with self-reported physical disability in both men and women, independent of ethnicity, age, morbidity, obesity, income, and health behaviors. This study provides some of the first estimates of the extent of the public health problem posed by sarcopenia.  相似文献   

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13.
Physical activity and risk of colorectal cancer in men and women   总被引:1,自引:0,他引:1  
We examined the association between self-reported occupational and recreational physical activity and the subsequent risk of colorectal cancer in a population-based cohort in Norway. During a mean follow-up time of 16.3 years for males and 15.5 years for females, 236 and 99 colon cancers and 170 and 58 rectal cancers were observed in males and females, respectively, among 53,242 males and 28,274 females who attended the screening between 1972 and 1978. Physical activity at a level equivalent to walking or bicycling for at least four hours a week during leisure-time was associated with decreased risk of colon cancer among females when compared with the sedentary group (RR = 0.62, 95% CI 0.40-0.97). Reduced risk of colon cancer was particularly marked in the proximal colon (RR = 0.51, 95% CI 0.28-0.93). This effect was not observed for occupational physical activity alone, probably due to a narrow range of self-reported physical activity at work among females. However, by combining occupational and recreational physical activity we observed an inverse dose-response effect as increasing total activity significantly reduced colon cancer risk (P for trend = 0.04). Among males 45 years or older at entry to the study, an inverse dose-response effect was observed between total physical activity and colon cancer risk (P for trend = 0.04). We also found in males a stronger preventive effect for physical activity in the proximal as compared to distal colon. In addition, we found a borderline significant decrease in colon cancer risk for occupational physical activity in males 45 years or older when compared to the sedentary group (RR = 0.74, 95% CI 0.53-1.04). All results were adjusted for age, body mass index, serum cholesterol and geographic region. No association between physical activity and rectal cancer was observed in males or females. The protective effect of physical activity on colon cancer risk is discussed in regard to energy balance, dietary factors, age, social class, body mass index and gastrointestinal transit time.  相似文献   

14.
This study reports on standard coronary risk factors (plasma lipids and lipoproteins, blood pressure, heart rate, age, body mass index) and psychosocial variables (job strain, Type A behavior, hostility, illnesses, medical and psychological symptoms, health-damaging behavior) in a community sample of 324 employed men, 203 employed women, and 155 female homemakers. Employed women reported less hostility and fewer illnesses than homemakers and had lower cholesterol levels than homemakers and men. Job characteristics were unrelated to standard coronary risk factor levels in both sexes, but predicted medical symptoms and health-damaging behavior in men. These findings suggest that employment is associated with enhanced medical and physical well-being among women and point to possible behavioral and psychological pathways by which job strain may adversely influence men's health. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

15.
The relationship between mammographic patterns and reproductive and menstrual factors was examined in 3640 Norwegian women, aged 40-56 years, participating in the Third Troms? study conducted in 1986-87. Epidemiological data were obtained from questionnaires. The mammograms were categorised into five groups. This categorisation is based on anatomic-mammographic correlations, following three-dimensional (thick slice technique) histopathologic-mammographic comparisons, rather than simple pattern reading. Patterns 1-3 were combined into a low-risk group and patterns 4 and 5 into a high-risk group for analysis. Women who had more than four children were 90% less likely to have a high-risk pattern than nulliparous women (OR = 0.09, 95% CI 0.04-0.16) controlling for age, weight, height and menopausal status. Furthermore, those who first gave birth over 34 years of age were more than twice as likely to have a high-risk pattern than those giving birth in their teens (OR = 2.37, 95% CI 1.23-4.56) adjusting for parity. Among post-menopausal women, age at menarche was negatively (P for trend = 0.015) and late age at menopause positively (P for trend = 0.072) related to high-risk patterns. Among premenopausal women, age at menarche was positively related to high-risk patterns (P for trend = 0.001). Also, menopausal status rather than age was associated with high-risk patterns. These findings support the opinion that reproductive and menstrual factors are involved in determining the mammographic parenchymal pattern among perimenopausal women.  相似文献   

16.
17.
The relations between incidence and prognosis of postoperative fistulas after gastrectomy and some different variables were analysed in the present retrospective study. Thirteen digestive fistulas of 113 patients (11.9%) submitted to gastrectomy during the period 1989-1994 represent the study population. The incidence of postoperative fistulas was compared to the kind of gastric pathology, to the extension of gastrectomy, to different nutritional (serum haemoglobin, albumin and transferrin level, weight loss) and immunological factors (serum lymphocytes) and, for oncological patients, to the stage of the disease. Incidence was directly related to the extension of gastrectomy, to serum albumin and haemoglobin level, and to weight loss rate. The results were not statistically significant at Kruskal-Wallis and ANOVA tests. No relation was found between incidence of fistulas and serum transferrin level, number of lymphocytes and adoption of early postoperative enteral nutrition. Six patients had spontaneous closure of the fistula with conservative therapy. Seven patients required reoperation because of abdominal sepsis (53.8%). Three patients died (23%). Although spontaneous closure, reoperation and mortality were related to nutritional and immunological state, no examined variables showed a statistically significative relation. The adoption of early postoperative enteral nutrition was not related to the prognosis, unlike the stage of the disease: patients submitted to reoperation had a TNM III or IV stage; dead patients had a TNM IV stage. Treatment of metabolic-nutritional unbalance can prevent anastomotic failure and fistula after gastrectomy and improve the prognosis. The relation between early postoperative enteral nutrition and incidence and prognosis of postoperative fistulas remains unclear.  相似文献   

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19.
The aim of this study was to describe the sexual behaviour of men who had sex with both men and women in the preceding five years (behaviourally bisexual men), specifically to examine their needs in relation to HIV prevention. Anonymous telephone interviews were carried out with respondents recruited though advertisements in UK newspapers and magazines with (sexual) 'personal' or 'contact' sections. Data are reported from 745 respondents. Respondents report relatively high and approximately equal numbers of male and female sexual partners in the year preceding interview. There is a clear patterning of sexual activity by type of partner (regular or casual). A high proportion report anal intercourse with female and male partners. A third disclose their homosexual practices to regular female partners. Although self-reported HIV seroprevalence is low (less than 1%), the levels of unprotected sex with multiple sexual partners indicate substantial potential for transmission of sexually transmitted infections, including HIV. While low seroprevalence suggests that there is little overlap with existing core groups of HIV infection, the study provides information to judge the priority of targeting HIV prevention initiatives and suggests ways in which initiatives could be undertaken.  相似文献   

20.
The association between hypertension and insulin resistance might be explained by increased activity of the principal glucocorticoid, cortisol. Recent data show that the intensity of dermal vasoconstriction after topical application of glucocorticoids is increased in patients with essential hypertension. In this report, we examine whether increased glucocorticoid sensitivity or secretion is associated with insulin resistance and is a cause or consequence of hypertension. We studied 32 men (aged 47 to 56 years) from a cross-sectional study and 105 men (aged 23 to 33 years) in whom predisposition to high blood pressure has been defined by their own blood pressure and the blood pressures of their parents. In both populations, increased dermal glucocorticoid sensitivity was associated with relative hypertension, insulin resistance, and hyperglycemia. In young men with higher blood pressure whose parents also had high blood pressure, enhanced glucocorticoid sensitivity was accompanied by enhanced secretion of cortisol, enhanced ligand-binding affinities for dexamethasone in leukocytes, and impaired conversion of cortisol to inactive metabolites (cortisone and 5beta-dihydrocortisol). Increased tissue sensitivity to cortisol, amplified by enhanced secretion of cortisol, is a feature of the familial predisposition to high blood pressure rather than a secondary effect of high blood pressure. It may be mediated by an abnormal glucocorticoid receptor, and it may contribute to the association between hypertension and insulin resistance.  相似文献   

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