Familial and metabolic factors related to blood pressure in Pima Indian children

High blood pressure, abnormal glucose tolerance, and obesity are frequently associated with each other, but the mechanism of these associations is poorly understood. Studying them in children may help in understanding the pathogenesis of hypertension. Blood pressure, height, weight, and plasma glucose and serum insulin concentrations during a 75-g oral glucose tolerance test were measured in 1,698 Pima Indian children aged 6-17 years who participated in an ongoing epidemiologic study. Weight relative to height was used as an index of obesity. The parents of many of the children were also examined. Fasting and 2-hour glucose and insulin concentrations, adjusted for age, sex, and relative weight, were positively related to systolic blood pressure but not to diastolic blood pressure. Relative weight, 2-hour glucose, and fasting insulin concentrations were independently and significantly associated with systolic blood pressure in a stepwise regression analysis that included age and sex. After parental hypertension was taken into account, maternal but not paternal non-insulin-dependent diabetes mellitus, controlled for the child's relative weight and glucose and insulin concentrations, was significantly associated with higher blood pressure in children. The stronger association with maternal diabetes suggests a greater sharing of environmental factors between mother and child than between father and child, but familial similarities in obesity and glucose and insulin concentrations, the diabetic intrauterine milieu, and shared environmental factors probably all contribute to this association.     

Maternal diabetes status does not influence energy expenditure or physical activity in 5-year-old Pima Indian children

A novel series of matrix metalloproteinase (MMP) inhibitors is described. Incorporation of a terminal alpha-mercaptoketone or alpha-mercaptoalcohol in the zinc binding domain of a series of inhibitors led to compounds exhibiting low nanomolar activity against collagenase-1 (MMP-1), stromelysin (MMP-3), and gelatinase-B (MMP-9).     

Reduced beta-adrenergic sensitivity in patients with type 1 diabetes and hypoglycemia unawareness

OBJECTIVE: We tested the hypothesis that impaired tissue sensitivity to catecholamines contributes to hypoglycemia unawareness in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 21 subjects with type 1 diabetes underwent a standardized insulin infusion protocol to produce a stepwise decrease in plasma glucose to 45-min plateaus of 4.3, 3.6, 3.0, and 2.3 mmol/l. Glycemic thresholds, maximum responses for adrenergic and neuroglycopenic symptoms, and counterregulatory hormones were determined. Patients were classified as hypoglycemia unaware if the initiation of adrenergic symptoms occurred at a plasma glucose level 2 SD below that of nondiabetic volunteers. beta-Adrenergic sensitivity was measured as the dose of isoproterenol required to produce an increment in heart rate of 25 beats per minute above baseline (I25) in resting subjects. RESULTS: Subjects with type 1 diabetes and hypoglycemia unawareness experienced the onset of adrenergic symptoms at a lower plasma glucose level than did those with awareness (2.5+/-0.1 vs. 3.7+/-0.1 mmol/l, P < 0.001), whereas neuroglycopenic symptoms occurred at similar glucose levels (2.7+/-0.2 vs. 2.8+/- 0.1 mmol/l). The plasma glucose levels for counterregulatory hormone secretion (epinephrine 2.9+/-0.2 vs. 4.1+/-0.2 mmol/l; norepinephrine 2.7+/-0.1 vs. 3.2+/-0.2 mmol/l; cortisol 2.5+/-0.2 vs. 3.3+/-0.2 mmol/l, P < 0.01) were also lower in subjects with unawareness. The maximal epinephrine (1,954+/-486 vs. 5,332+/- 1,059 pmol/l, P < 0.01), norepinephrine (0.73 +/- 0.14 vs. 1.47+/-0.21 nmol/l, P = 0.04), and cortisol (276+/-110 vs. 579+/-83 nmol/l, P < 0.01) responses were reduced in the unaware group. I25 was greater in unaware subjects than in subjects without unawareness (1.5+/-0.3 vs. 0.8+/-0.2 microg), where I25 was not different from that of controls (0.8 +/-0.2 microg). CONCLUSIONS: We conclude that subjects with type 1 diabetes and hypoglycemia unawareness have reduced beta-adrenergic sensitivity, which may contribute to their impaired adrenergic warning symptoms during hypoglycemia.     

Reduced adipocyte insulin sensitivity in Caucasian and Asian subjects with coronary heart disease

The association between insulin resistance and coronary heart disease (CHD) is strong in the British Indian-Asian population. Adipocyte metabolism may contribute to both insulin resistance and CHD. We examined insulin-stimulated glucose uptake in adipocytes and in vivo insulin sensitivity using the fasting insulin resistance index (FIRI) in 60 subjects (45 Caucasian and 15 Asian) with CHD and 30 Caucasian subjects without CHD. In 25 CHD subjects (18 Caucasian and 7 Asian), the relationship between adipocyte insulin sensitivity and non-esterified fatty acid (NEFA) suppression to oral glucose was examined. Compared with controls, the CHD subjects had higher values of fasting insulin [51 (46 to 54) pmol l(-1) vs 36 (31 to 41) pmol l(-1) p< 0.01] and FIRI [1.65 (1.5 to 1.79) vs 1.06 (0.89 to 1.23), p < 0.01]. Among the CHD subjects, the Asians had higher values than Caucasian [insulin 58 (48 to 67) pmol l(-1) vs 48 (44 to 53) pmol l(-1) p < 0.01, FIRI 1.89 (1.44 to 2.13) vs 1.62 (1.4 to 1.79), p< 0.01)]. Insulin-stimulated glucose uptake in adipocytes was lower in the CHD than control subjects [56 (50 to 62) vs 115 (75 to 132) attomol min(-1).mm2, p < 0.05], being most reduced among the Asians. It was positively correlated with postprandial NEFA suppression and negatively with insulin release. In conclusion, abnormalities of adipocyte function and insulin sensitivity occur in CHD and may contribute to its aetiology.     

Greater preference among females than males for dyadic interaction in early childhood

The present study was designed to examine sex differences in children's preferences for dyadic and group interaction in early childhood. In Study 1, a professional puppeteer interacted with 21 females and 20 males 4 and 5 years of age using 1 (dyad) and 3 (group) puppets in a within-subjects design. Enjoyment of the 2 conditions was assessed through frequency of smiling and eye contact. In addition, sociometric techniques were used to measure the size of children's play networks, and observations of naturally occurring dyadic and group interaction were conducted. Study 2 was a replication of the puppet play procedure used in Study 1 with 38 females and 37 males 3 and 4 years of age. In both studies, females were found to enjoy dyadic interaction more than males. In addition, some evidence suggests that males may enjoy group interaction more than females. Results are discussed in terms of theoretical explanations for sex differences in preferences for interaction with differing numbers of peers.     

Effect of hypoglycemia on beta-adrenergic sensitivity in normal and type 1 diabetic subjects

OBJECTIVE: The purpose of this study was to assess the potential role of reduced tissue sensitivity to catecholamines in the pathogenesis of hypoglycemia unawareness in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: The effect of a single episode of hypoglycemia on beta-adrenergic sensitivity was studied in 10 type 1 diabetic patients with apparently normal awareness of hypoglycemia (age 29 +/- 5 years, diabetes duration 13 +/- 8 years, HbA1c 7.3 +/- 0.9%) and 10 age-matched healthy control subjects. Beta-adrenergic sensitivity was measured with the isoproterenol test after a hyperinsulinemic euglycemic clamp and after a hyperinsulinemic hypoglycemic clamp. Beta-adrenergic sensitivity was expressed as the dose of intravenous isoproterenol that increased the heart rate by 25 beats/min (IC25). RESULTS: During hypoglycemia, diabetic subjects had an impaired plasma epinephrine response compared with that of the control subjects (16.7 +/- 5.0 vs. 40.1 +/- 6.8 ng/ml, P = 0.02). In control subjects, the IC25 was lower after hypoglycemia than after euglycemia (0.83 +/- 0.22 vs. 1.13 +/- 0.21 microg, P = 0.02) indicating an increase in beta-adrenergic sensitivity. In diabetic subjects, on the other hand, the IC25 was greater after hypoglycemia than after euglycemia (1.00 +/- 0.26 vs. 0.65 +/- 0.14 microg, P = 0.04), indicating a decrease in beta-adrenergic sensitivity. CONCLUSIONS: In normal subjects, a single episode of hypoglycemia increases beta-adrenergic sensitivity. In diabetic subjects, in contrast, hypoglycemia reduces beta-adrenergic sensitivity. These results provide evidence that in type 1 diabetic patients, some maladaptation of tissue sensitivity to catecholamines contributes to the development of hypoglycemia unawareness. A unifying hypothesis is presented for the pathogenesis of hypoglycemia unawareness in type 1 diabetic patients incorporating the concepts of both a reduced catecholamine response and reduced adrenergic sensitivity     

投标报价不低于成本价的探讨

在论述建设工程成本概念的基础上侧重阐述了招投标活动中界定投标报价是否低于成本价的几种方法。     

American Indian and Caucasian students' preferences for counselors: Effects of counselor dress and sex.

Examined the effects of 2 nonverbal cues, the counselor's dress and sex, on students' preferences for counselors. 140 Native Americans from a reservation high school and 226 students from a primarily Caucasian, urban high school rated their preferences for discussing personal, academic, and vocational concerns with a counselor. The independent variables were race and sex of student, and form of dress and sex of counselor. The results of the 2?×?2?×?6?×?2 MANOVA showed that the Ss' preferences for counselors varied with the counselors' sex and dress, the type of concern, and the race of the S. Same-sex preferences for counselors were not influenced by counselor dress. Preference for a counselor of the same sex was strongest for female Native Americans. Cultural and methodological aspects of these results are discussed. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Endoproteases other than furin have a role in hepatic proprotein processing

The enzyme or enzymes responsible for dibasic-directed proprotein processing in the liver have not yet been unequivocally identified, although there are a number of potential candidates. We have compared a Kex2-like proalbumin convertase activity present in rat liver ER/Golgi membranes with recombinant furin, a candidate hepatic convertase. Using a series of mutant recombinant proalbumins as substrates the biochemically identified convertase and furin had very similar specificities with both preferring a substrate with an ArgXaaArgArg processing motif. Kinetic studies with normal and -4R proalbumin suggested however that the proalbumin convertase was not identical to furin. This was confirmed in immunoabsorption studies which demonstrated that furin only accounts for approximately half of the convertase activity. Therefore at least two proprotein convertases with overlapping specificities are involved in hepatic proprotein processing.     

Mechanisms of thyroid hormone control over sensitivity and maximal contractile responsiveness to beta-adrenergic agonists in atria

This paper discusses the mechanisms of two basic effects of thyroid hormones on atrial responses to beta-adrenergic agonists, i.e. increased inotropic sensitivity and decreased maximal contractile responsiveness. The increased sensitivity of atria to beta-adrenergic agonists under thyroid hormones appears to be related to increases in beta-adrenoceptor density and Gs/Gi protein ratio, leading to activation of Gs-mediated pathway, but suppression of Gi-mediated pathway of adenylate cyclase regulation. Therefore, the i/c concentrations of cAMP and corresponding inotropic responses achieve their maximums at lower doses of beta-adrenergic agonist. Thyroid hormones also decrease the expression of phospholamban, but increase the expression of sarcoplasmic reticulum Ca2+-pump. As a result, the basal activity of sarcoplasmic reticulum Ca2+-pump increases, but its beta-adrenergic activation through phosphorylation of phospholamban decreases. It is suggested that these changes are causal for decreased maximal inotropic and lusitropic responses of atria to beta-adrenergic agonists.     

Computed tomography-determined body composition in relation to cardiovascular risk factors in Indian and matched Swedish males

Relationships between cardiovascular risk factors, body composition, and tissue distributions were examined in 10 Indian and 10 Swedish males matched by age, height, and weight. The body was divided into 29 compartments by means of a multiscan computed tomography (CT) technique. Fasting glucose, insulin, and triglycerides (TG) were higher in Indians than in Swedes. During the oral glucose tolerance test (OGTT), the glucose area was similar in both groups, whereas the insulin area was 80% larger in Indians. Adipose tissue (AT) and skin volumes were larger and remaining lean tissues were smaller in Indians. Indians had proportionally less muscle and more skeleton in the legs, but no ethnic difference could be demonstrated with respect to AT distribution. The visceral AT to total AT volume ratio was positively related to insulin and TG, and with higher risk factors for Indians at any given ratio. TG and glucose were negatively related to the leg muscle to total muscle volume ratio, and this ratio was smaller in Indians. It is concluded that the metabolic disturbances of Indians are not necessarily dependent on a preponderance of visceral AT, and also that an upper-body muscle distribution-recognized as a new phenotypic companion to the metabolic syndrome-is statistically related to cardiovascular risk factors.     

Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls.

Fifty-six heroin addicts and 60 age-matched controls were offered choices between monetary rewards ($11–$80) available immediately and larger rewards ($25–$85) available after delays ranging from 1 week to 6 months. Participants had a 1-in-6 chance of winning a reward that they chose on one randomly selected trial. Delay-discounting rates were estimated from the pattern of participants' choices. The discounting model of impulsiveness (G. Ainslie, 1975) implies that delay-discounting rates are positively correlated with impulsiveness. On average, heroin addicts' discount rates were twice those of controls (p?=?.004), and discount rates were positively correlated with impulsivity as measured by self-report questionnaires (p?     

T-cell-rich large-B-cell lymphomas contain non-activated CD8+ cytolytic T cells, show increased tumor cell apoptosis, and have lower Bcl-2 expression than diffuse large-B-cell lymphomas

The factor(s) responsible for the reduced B cell number and increased T cell infiltrate in T-cell-rich large-B-cell lymphomas (TCRBCLs) have not been well characterized. We studied 18 TCRBCLs and 12 diffuse large-B-cell lymphomas (DLBCLs) to compare the 1) predominant T cell subpopulation(s), 2) expression of cytotoxic granule proteins (TIA-1 and granzyme B), 3) level of tumor cell apoptosis (Apoptag system, Oncor, Gaithersburg, MD), and 4) expression of Ki-67 (Mib-1) and apoptosis-related proteins (fas (CD95), bcl-2, and p53). T cells in TCRBCLs and DLBCLs were predominantly CD8+ T cells expressing alphabeta T-cell receptors and TIA-1 (16 of 18 TCRBCLs with >50% TIA-1+ small lymphocytes) but lacking granzyme B (16 of 18 TCRBCLs with <25% granzyme B+ small lymphocytes). Scattered apoptotic tumor cells (confirmed with CD20 co-labeling) were present in 15 of 18 TCRBCLs, with 14 of 15 cases having <10% apoptotic cells. No apoptotic cells were seen in 12 of 12 DLBCLs. In 16 of 16 immunoreactive TCRBCLs, <25% tumor cells were bcl-2+, whereas 6 of 12 DLBCLs had >50% bcl-2+ tumor cells. CD95 (fas) expression was also lower, with 3 of 18 (16.7%) TCRBCLs versus 4 of 12 (33%) DLBCLs having >25% CD95+ tumor cells. TCRBCLs and DLBCLs had similar levels of p53 and Ki-67 (Mib-1) expression. Thus, T cells in TCRBCLs are non-activated cytotoxic T lymphocytes (TIA-1+, granzyme B-). Tumor cell apoptosis (perhaps cytotoxic T cell mediated) may partly account for the decreased number of large (neoplastic) B cells in TCRBCLs, but other factors (ie, decreased bcl-2 expression) may also be needed.     

Serum inhibin levels are lower in ectopic than intrauterine spontaneously conceived pregnancies

OBJECTIVE: To determine if serum inhibin concentrations are lower in ectopic (EP) versus intrauterine pregnancies (IUPs) that are conceived spontaneously. DESIGN: Case-control study. SETTING: Academic clinical practice. PATIENTS: Serum samples were obtained from 19 women who had EP confirmed at surgery and by pathology. For comparison, serum samples were collected from 24 women of similar chronological and gestational age with sonographic evidence of an IUP. MAIN OUTCOME MEASURE: Serum dimeric inhibin-A, total inhibin, P, and hCG. RESULTS: Serum total and dimeric inhibin concentrations in women with EP were < 60% of the concentrations for women with single IUPs. Total inhibin, but not dimeric inhibin-A, was elevated in maternal serum before week 8 of gestation relative to normal menstrual cycle levels. CONCLUSIONS: Serum inhibin concentrations are lower in EP as compared with IUPs that are spontaneously conceived and the relative amounts of dimeric inhibin-A, B, and alpha inhibin subunit in maternal serum may change throughout gestation.     

Patients treated by cardiologists have a lower in-hospital mortality for acute myocardial infarction

Local anesthetics suppress excitability by interfering with ion channel function. Ensheathment of peripheral nerve fibers, however, impedes diffusion of drugs to the ion channels and may influence the evaluation of local anesthetic potencies. Investigating ion channels in excised membrane patches avoids these diffusion barriers. We investigated the effect of local anesthetics with voltage-dependent Na+ and K+ channels in enzymatically dissociated sciatic nerve fibers of Xenopus laevis using the patch clamp method. The outside-out configuration was chosen to apply drugs to the external face of the membrane. Local anesthetics reversibly blocked the transient Na+ inward current, as well as the steady-state K+ outward current. Half-maximal tonic inhibiting concentrations (IC50), as obtained from concentration-effect curves for Na+ current block were: tetracaine 0.7 microM, etidocaine 18 microM, bupivacaine 27 microM, procaine 60 microM, mepivacaine 149 microM, and lidocaine 204 microM. The values for voltage-dependent K+ current block were: bupivacaine 92 microM, etidocaine 176 microM, tetracaine 946 microM, lidocaine 1118 microM, mepivacaine 2305 microM, and procaine 6302 microM. Correlation of potencies with octanol:buffer partition coefficients (logP0) revealed that ester-bound local anesthetics were more potent in blocking Na+ channels than amide drugs. Within these groups, lipophilicity governed local anesthetic potency. We conclude that local anesthetic action on peripheral nerve ion channels is mediated via lipophilic drug-channel interactions. IMPLICATIONS: Half-maximal blocking concentrations of commonly used local anesthetics for Na+ and K+ channel block were determined on small membrane patches of peripheral nerve fibers. Because drugs can directly diffuse to the ion channel in this model, these data result from direct interactions of the drugs with ion channels.     

Premenopausal black women have more risk factors for coronary heart disease than white women

Premenopausal black women have a 2- to 3-fold greater rate of coronary heart disease (CHD) than premenopausal white women. The purpose of this study was to provide greater insight into the reasons for this difference, which are currently unclear. We compared CHD risk factors in 99 black and 100 white, healthy premenopausal women, aged 18 to 45 years, and of relatively advantaged socioeconomic status. Compared with white women, black women had a higher body mass index (32.0 +/- 9.2 vs 29.0 +/- 9.4 kg/m2, p = 0.021), and higher systolic (124 +/- 17 vs 115 +/- 14 mm Hg, p <0.0001) and diastolic (79 +/- 14 vs 75 +/- 11 mm Hg, p = 0.048) blood pressures. The mean plasma lipoprotein(a) concentration was markedly higher in the black women (40.2 +/- 31.3 mg/dl) than in the white women (19.2 +/- 23.7 mg/dl, p <0.0001). The plasma total homocysteine level was also higher in the black women (8.80 +/- 3.38 vs 7.81 +/- 2.58 micromol/L, p = 0.013). The black women, however, had lower plasma triglyceride levels (0.91 +/- 0.46 vs 1.22 +/- 0.60 mmol/L, p <0.0001), and a trend toward higher high-density lipoprotein (HDL) cholesterol levels (1.37 +/- 0.34 vs 1.29 +/- 0.31 mmol/L, p = 0.064) than the white women. Plasma total and low-density lipoprotein (LDL) cholesterol levels were similar, despite a greater consumption of saturated fat and cholesterol by the black women. Rates of cigarette smoking and alcohol intake were low and similar between the races. In summary, premenopausal black women had a higher mean body mass index, blood pressure, lipoprotein(a), and plasma total homocysteine level, and a greater consumption of saturated fat and cholesterol than white women. These differences in coronary risk factors may place the black women in our study at increased risk for CHD compared with the white women.     

Effect of a controlled high-fat versus low-fat diet on insulin sensitivity and leptin levels in African-American and Caucasian women

Subjective interpretation of dobutamine echocardiograms provides only moderate interinstitutional observer agreement if nonunified data acquisition and assessment criteria are applied. The present study was undertaken to evaluate parameters associated with low interinstitutional observer agreement in the interpretation of dobutamine echocardiograms and to analyze whether standardized interpretation criteria improve interinstitutional observer agreement. One hundred fifty dobutamine echocardiograms (dobutamine up to 40 microg/kg/min body weight and atropine up to 1 mg) were evaluated at 5 centers. Clinical, procedural, and echocardiographic parameters were included in the analysis of variables with significant impact on interinstitutional agreement. Standardized interpretative criteria were established, and 90 dobutamine echocardiograms were reanalyzed by 3 observers using a standardized image display. Multivariate analysis demonstrated low image quality (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.08 to 0.45, p=0.0002), low severity of induced wall motion abnormality (OR 0.17, 95% CI 0.07 to 0.40, p <0.0001), and a low peak rate-pressure product (OR 0.93, 95% CI 0.43 to 2.27, p=0.0382) to result in a low interinstitutional agreement. Standardization of image display in cine loop format and of dobutamine stress echo interpretation criteria resulted in improvement in test result categorization as normal or abnormal, with a kappa value of 0.50, compared with 0.39 using the original subjective interpretation. In conclusion, image quality, the severity of induced wall motion abnormalities, and the obtained rate-pressure product have a significant impact on the interpretation homogeneity of dobutamine echocardiograms. Standardization of image display in cine loop format and of reading criteria results in improved interinstitutional agreement in interpretation of stress echocardiograms.