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Elevated serum leptin concentrations in women with components of multiple risk factor clustering syndrome.

This cross sectional study was undertaken to determine whether serum leptin levels were associated with multiple risk factor (MRF) clustering syndrome. We examined the relationship between serum leptin concentrations and blood pressure (BP), serum lipids levels, calculated insulin resistance (HOMA-ratio) and adiposity among 581 Japanese adult women. The serum leptin was increased in female subjects with systolic (> or =160 mmHg) and diastolic > or =90 mmHg) hypertension compared with the normotensive females (mean+/-SE; 9.3+/-0.5 vs 7.7+/-0.3; 10.2+/-0.6 vs 7.1+/-0.3 ng/ml, both p<0.001). Serum leptin was elevated in those with hyper-cholesterolemia (C; > or =220 mg/dl) and triglyceridemia (TG; > or =150 mg/dl) compared with the normolipidemia (9.4+/-0.4 vs 7.8+/-0.3; 11.7+/-0.6 vs 7.5+/-0.2 ng/ml, both p <0.001). Serum leptin was also elevated in those with adiposity (BMI > or =26.4 kg/m2) and insulin resistance (HOMA-ratio > or =2.5) compared with the normal females (14.8+/-0.7 vs 5.2+/-0.2; 11.3+/-1.1 vs 7.1+/-0.4ng/ml, both p<0.001). Even after adjusting for BMI or percent body fat mass (BFM), leptin levels remained to be elevated significantly in all these diseases. There was a positive correlation between serum leptin and systolic, diastolic BP, TC, TG, BMI, BFM, IRI and HOMA-ratio (r=0.12, p=0.005; r=0.24, p<0.0001; r=0.19, p<0.0001; r=0.35, p<0.0001; r=0.72, p<0.0001; r=0.73, p<0.0001; r=0.47, p< 0.0001; r=0.44, p<0.0001), and a negative correlation with HDL-C levels (r= -0.20, p< 0.0001). These correlations were also observed in leptin levels after adjusting for the BMI or BFM. Multiple regression analysis showed that BFM, HOMA-ratio and TG were significant determinants of leptin concentration before (t=12.6, p<0.0001; t=3.33, p=0.001; t=3.22, p=0.001) and after adjusting for BMI or BFM. These results suggest that because serum leptin levels were elevated in components of MRF clustering syndrome, leptin may have a pathophysiological role in MRF clustering syndrome.

Adolescent↗

Application of a multiple-trait herd cluster model for genetic evaluation of dairy sires from seventeen countries.

The multiple-trait across country evaluation method is currently used for international genetic evaluation of dairy sires. This method simultaneously combines national estimated breeding value (EBV) of sires in all countries and produces a separate breeding value to be used in each of the 24 countries that participate in the service. The major drawbacks to this method are the large number of genetic parameters that must be estimated and the large number of EBV produced for each sire. In the current method, each sire receives an EBV for each separate environment, and environments change at the country borders. It is unreasonable to assume that each country contains only one homogeneous environment and that every country has a distinctly different environment from all others. In the present study, an alternative method for international sire evaluation was utilized. Herds were grouped according to important management, climatic, and genetic factors rather than country borders. Data consisted of 16,403,413 first lactation cows in Australia, Austria, Belgium, Canada, Czech Republic, Estonia, Finland, Germany, Hungary, Ireland, Israel, Italy, The Netherlands, New Zealand, South Africa, Switzerland, and the United States. Herds were grouped according to 13 descriptive herd variables, including temperature, rainfall, peak yield, persistency, herd-size, age at calving, seasonality of calving, standard deviation of milk yield, culling percentage, fat-to-protein ratio, days to peak yield, percent of North American Holstein genes, and average PTA milk of sires. Variables were weighted by their relative importance in explaining genotype by environment interactions between herds. Herds were grouped into seven clusters; clusters ranged in size from 4805 to 59,272 herds and 1,414,966 to 3,966,431 cows. The proposed model predicts EBV for dairy sires based on the production environment in which their progeny wili perform, rather than the country where they will be located.

Animals↗

Cluster analysis on multiple drugs susceptibility supplements genotyping of methicillin-resistant Staphylococcus aureus.

OBJECTIVE: To evaluate the typing power of cluster analysis of antimicrobial susceptibility. METHODS: Results of pulsed-field gel electrophoresis in 71 strains of methicillin-resistant Staphylococcus aureus were compared with cluster analysis of the diameter of growth inhibition in 11 drugs. Subjects were a consecutive series of patients (n = 71) from the wards and outpatient units of a community teaching hospital. RESULTS: The cluster analysis took 2 to 3 seconds once the data were entered into a computer. The sensitivity, specificity, and accuracy of the cluster analysis were 76.3%, 58.3%, and 73.2%, respectively, using genotyping as the reference. CONCLUSIONS: The cluster analysis offered real-time epidemiologic data at minimal cost and labor, warranting its cost-effective role.

Bacterial Typing Techniques↗

Visceral fat is a major contributor for multiple risk factor clustering in Japanese men with impaired glucose tolerance.

OBJECTIVE: The significance of abdominal visceral fat accumulation was evaluated in Japanese men with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: The IGT subjects (n = 123) were aged 55 +/- 9 years with a BMI of 24 +/- 3 kg/m(2). The 148 control subjects with normal glucose tolerance (NGT) were matched for age and BMI. IGT and NGT were classified according to the 1985 World Health Organization criteria. Abdominal fat distribution was analyzed by computed tomography at umbilical level. Plasma lipid, glucose, and insulin concentrations and blood pressure (BP) were measured. RESULTS: In subjects with IGT, the average visceral fat area (VFA) was significantly greater than in subjects with NGT. Fasting insulin, the sum of insulin concentrations during an oral glucose tolerance test, insulin resistance according to a homeostasis model assessment for insulin resistance (HOMA-IR), systolic BP, and serum triglyceride were significantly higher, whereas the DeltaI(30-0)/DeltaG(30-0) was significantly lower, in subjects with IGT. Subjects with IGT and NGT were then divided into three subgroups according to the number of risk factors they possessed (dyslipidemia, hypertension, neither, or both). In both IGT and NGT subjects, BMI, VFA, subcutaneous fat area, fasting insulin, HOMA-IR, and insulin secretion of the homeostasis model assessment were significantly higher in the double-risk factor subgroup than in the no-risk factor subgroup, and VFA was a potent and independent variable in association with the presence of a double risk factor. CONCLUSIONS: Visceral fat accumulation is a major contributor for multiple risk factor clustering in Japanese men with IGT and NGT.

Adipose Tissue↗

A cluster-focus of multiple sclerosis at Henribourg, Saskatchewan.

This study presents the clinical characteristics of 8 victims of multiple sclerosis from the hamlet of Henribourg, Saskatchewan with a population of less than 75 people. A diligent victim of the disease had observed that six female classmates from the early 1940's had later developed multiple sclerosis. Two male military personnel who had also resided briefly in close proximity, during the same common exposure time, also later developed multiple sclerosis. The mean onset time of developing the disease after leaving the area was 20 years. This cluster-focus suggests a common exposure to an environmental factor or a common infective agent in the etiology of multiple sclerosis.

Adult↗

Polymorphisms in the human haptoglobin gene cluster: chromosomes with multiple haptoglobin-related (Hpr) genes.

We have found polymorphisms for the number of tandemly arranged haptoglobin-related (Hpr) genes in the haptoglobin gene cluster of Blacks. Genomic mapping and nucleotide sequence analysis indicate that two copies of the Hpr gene first resulted from unequal but homologous crossing-over in a region 3' to the haptoglobin (Hp) and the haptoglobin-related genes. Subsequent increases in the number of Hpr loci have occurred in some chromosomes. Among 25 American Blacks studied (15 were unrelated), 2 related individuals have one extra copy of the Hpr gene and 5 unrelated individuals have more than two extra Hpr genes. None of 26 Whites and one Oriental studied have extra copies. In one of the Blacks, six tandemly arranged Hpr genes were demonstrated in one chromosome by pulsed field gradient electrophoresis. His other chromosome had one Hpr gene. The tandem Hpr genes were found in individuals with the haptoglobin genotypes Hp2/Hp2 (3 of 3 tested) and Hp2/Hp1 (4 of 11 tested), but none were found in the Hp1/Hp1 individuals (11 tested). Fibroblast cell cultures from two Hp2/Hp1 heterozygotes were fused to mouse cells to obtain cell lines retaining a human chromosome 16 on which the haptoglobin gene cluster is located. DNA analysis of the hybrid cells showed that in both individuals the tandemly arranged Hpr genes are linked to the Hp2 allele. These results suggest that the multiple copies are associated with the Hp2 gene.

Base Sequence↗

Single- and double-cubane clusters in the multiple oxidation states [VFe(3)S(4)](3+,2+,1+).

A new series of cubane-type [VFe(3)S(4)](z)() clusters (z = 1+, 2+, 3+) has been prepared as possible precursor species for clusters related to those present in vanadium-containing nitrogenase. Treatment of [(HBpz(3))VFe(3)S(4)Cl(3)](2)(-) (2, z = 2+), protected from further reaction at the vanadium site by the tris(pyrazolyl)hydroborate ligand, with ferrocenium ion affords the oxidized cluster [(HBpz(3))VFe(3)S(4)Cl(3)](1)(-) (3, z = 3+). Reaction of 2 with Et(3)P results in chloride substitution to give [(HBpz(3))VFe(3)S(4)(PEt(3))(3)](1+) (4, z = 2+). Reaction of 4 with cobaltocene reduced the cluster with formation of the edge-bridged double-cubane [(HBpz(3))(2)V(2)Fe(6)S(8)(PEt(3))(4)] (5, z = 1+, 1+), which with excess chloride underwent ligand substitution to afford [(HBpz(3))(2)V(2)Fe(6)S(8)Cl(4)](4)(-) (6, z = 1+, 1+). X-ray structures of (Me(4)N)[3], [4](PF(6)), 5, and (Et(4)N)(4)[6] x 2MeCN are described. Cluster 5 is isostructural with previously reported [(Cl(4)cat)(2)(Et(3)P)(2)Mo(2)Fe(6)S(8)(PEt(3))(4)] and contains two VFe(3)S(4) cubanes connected across edges by a Fe(2)S(2) rhomb in which the bridging Fe-S distances are shorter than intracubane Fe-S distances. Mössbauer (2-5), magnetic (2-5), and EPR (2, 4) data are reported and demonstrate an S = 3/2 ground state for 2 and 4 and a diamagnetic ground state for 3. Analysis of (57)Fe isomer shifts based on an empirical correlation between shift and oxidation state and appropriate reference shifts results in two conclusions. (i) The oxidation 2 --> 3 + e(-) results in a change in electron density localized largely or completely on the Fe(3) subcluster and associated sulfur atoms. (ii) The most appropriate charge distributions are [V(3+)Fe(3+)Fe(2+)(2)S(4)](2+) (Fe(2.33+)) for 1, 2, and 4 and [V(3+)Fe(3+)(2)Fe(2+)S(4)](3+) (Fe(2.67+)) for 3 and [V(2)Fe(6)S(8)(SEt)(9)](3+). Conclusion i applies to every MFe(3)S(4) cubane-type cluster thus far examined in different redox states at parity of cluster ligation. The formalistic charge distributions are regarded as the best current approximations to electron distributions in these delocalized species. The isomer shifts require that iron atoms are mixed-valence in each cluster.

Catalysis↗

Multivariate methods for clustered binary data with multiple subclasses, with application to binary longitudinal data.

Clustered binary data occur frequently in biostatistical work. Several approaches have been proposed for the analysis of clustered binary data. In Rosner (1984, Biometrics 40, 1025-1035), a polychotomous logistic regression model was proposed that is a generalization of the beta-binomial distribution and allows for unit- and subunit-specific covariates, while controlling for clustering effects. One assumption of this model is that all pairs of subunits within a cluster are equally correlated. This is appropriate for ophthalmologic work where clusters are generally of size 2, but may be inappropriate for larger cluster sizes. A beta-binomial mixture model is introduced to allow for multiple subclasses within a cluster and to estimate odds ratios relating outcomes for pairs of subunits within a subclass as well as in different subclasses. To include covariates, an extension of the polychotomous logistic regression model is proposed, which allows one to estimate effects of unit-, class-, and subunit-specific covariates, while controlling for clustering using the beta-binomial mixture model. This model is applied to the analysis of respiratory symptom data in children collected over a 14-year period in East Boston, Massachusetts, in relation to maternal and child smoking, where the unit is the child and symptom history is divided into early-adolescent and late-adolescent symptom experience.

Adolescent↗

A multiple-trait herd cluster model for international dairy sire evaluation.

International dairy sire evaluations have traditionally been calculated using a two-step process. Lactation records within each country are used to predict national estimated breeding values, then these national breeding values are transformed to the genetic base, scale, and units of measurement of other countries by using conversion formulae or the multiple-trait, across-country evaluation method. A major limitation of this approach is the need to define environments (traits) according to country borders. Herds located in small, neighboring countries may be much more similar in management, climate, and genetic background than herds located far apart within a single large country. In the present study, international genetic evaluation with herd clusters is proposed. Data consisted of 4.6 million lactation records from 46,000 herds in Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, Israel, Switzerland, and five regions of the US (Midwest, Northeast, Northwest, Southeast, and Southwest). Herds were grouped into clusters based on data of 13 descriptive variables: herd size, calving interval, milking frequency, age at first calving, milk yield, month of calving, predicted transmitting ability of sire for milk, percentage North American genes of sire, latitude, altitude, temperature, rainfall, and percentage of arable land used for pasture. Five clusters were formed; each cluster contained herds from 5 to 11 countries or regions. Genetic correlations between herd clusters ranged from 0.81 to 0.97. The herd cluster model is intuitively appealing, because genetic merit of an animal is predicted for each unique environment or management system, regardless of country borders. This model is parsimonious (the number of traits was reduced from 13 to 5) and is computationally feasible for large data sets.

Animals↗

Toward an empirical taxonomy of suicide ideation: a cluster analysis of the youth risk behavior survey.

In this study we examined adolescent risk behaviors, giving special attention to suicide ideation. Cluster analysis was used to classify adolescents (N = 2,730) on the Youth Risk Behavior Survey. Six clusters of adolescent risk behavior were identified. Although each risk cluster was distinct, some clusters shared overlapping risk behaviors. Suicide ideation was central to two clusters: the Silent Suicide cluster and the Multiple Risk cluster. The findings demonstrate that suicide ideation is both a unique risk behavior for some adolescents and part of a generalized risk syndrome for other adolescents. A multiple subgroup framework is recommended for understanding adolescent risk behaviors.

Adolescent↗

Impact of multiple risk factor clustering on the elevation of blood pressure.

A family history of hypertension, obesity, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia have all been associated with risk of hypertension. We retrospectively conducted a longitudinal study in a large screened cohort to explore the effect of the clustering of these five risk factors on the elevation of blood pressure (BP) in normotensive subjects at baseline. The study group comprised 4,857 normotensive subjects not treated with antihypertensive drugs (systolic BP < 140 mmHg, diastolic BP < 90 mmHg, 3,111 men and 1,746 women) who were followed up from 1997 to 1999. By 1999, 360 subjects had BP at the hypertensive level (systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg). The incidence of subjects whose BP became hypertensive was 37 per 1,000 person-years. After adjusting for age, sex, systolic BP and other clinical factors, multiple logistic analysis showed that the relative risk of BP elevation was 1.49 (95% Cl: 1.09 to 2.05) in subjects with one risk factor; 1.65 (95% Cl: 1.15 to 2.27) in those with two risk factors; 1.42 (95% Cl: 0.91 to 2.32) in those with three; and 4.86 (95% Cl: 2.58 to 9.16) in those with four or more when compared with subjects with no risk factors. Multiple regression analysis showed that the number of risk factors was positively correlated with an increase in BP from 1997 to 1999; the regression coefficient was 0.51 (p = 0.001) for increase in systolic BP, and 0.31 (p = 0.008) for increase in diastolic BP after adjusting for age and sex. In conclusion, clustering of risk factors significantly predicted the development of hypertension.

Adult↗

Cluster analysis of multiple experimental pain modalities.

Identifying individual differences in pain is an important topic; however, little is known regarding patterns of responses across various experimental pain modalities. This study evaluated subgroups emerging from multiple experimental pain measures. One hundred and eighty-eight individuals (59.0% female) completed several psychological instruments and underwent ischemic, pressure, and thermal pain assessments. Thirteen separate pain measures were obtained by using three experimental pain modalities with several parameters tested within each modality. The pain ratings and scores were submitted to factor analysis that identified four pain factors from which Pain Sensitivity Index (PSI) scores were computed: heat pain (HP), pressure pain (PP), ischemic pain (IP), and temporal summation of heat pain (TS). Cluster analyses of PSI scores revealed four distinct clusters. The first cluster demonstrated high overall pain sensitivity, the second cluster revealed high TS, the third cluster showed particular insensitivity to IP and low sensitivity across pain modalities except PP, and the fourth cluster demonstrated low sensitivity to PP. Significant correlations were found between psychological measures and Index scores and those differed by sex. Cluster membership was associated with demographic variables of ethnicity and sex as well as specific psychosocial variables, although cluster differences were only partially explained by such factors. These analyses revealed that groups respond differently across varied pain stimuli, and this was not related solely to demographic or psychosocial factors. These findings highlight the need for future investigation to identify patterns of responses across different pain modalities in order to more accurately characterize individual differences in responses to experimental pain.

Adolescent↗

Monocytoid B-cell reaction associated with peripheral T-cell lymphomas.

Benign monocytoid B-cells (MBCs) proliferation was reported to occur in various lymphoproliferative disorders, but not in peripheral T-cell lymphomas (PTCL). In our review of fifty three nodal-based, low and high grade PTCL, MBCs were identified histologically and immunohistochemically in eight of the cases. They included: chronic lymphocytic leukaemia of T-cell type (n = 1) with multiple MBCs clusters, large cell anaplastic lymphoma (n = 1) showing lymphoma cells within multiple MBCs foci, and PTCL of angioimmunoblastic lymphadenopathy (AILD) type (n = 6) with solitary (n = 4) or multifocal (n = 2) MBCs reaction. Progression from AILD-hyperimmune reaction to PTCL of AILD type could be observed in one case by three consecutive follow-up biopsies. While MBCs proliferation associated with hyperimmune reaction was prominent, in PTCL of AILD type only isolated or small multiple clusters of MBCs were present. In PTCL of AILD type, MBCs seemed to be a residual component of a prior hyperimmune reaction diminishing with progress of the disease. Therefore we assume that the development of PTCL of AILD type from preceding hyperimmune reaction is more common than previously considered. Cytologically, MBCs proliferation associated with PTCL shows two cell types, as described in reactive lymphadenopathies: the common type and the large cell type MBCs.

Adult↗