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Prognostic validity of self-report and interview measures of personality disorder in depressed inpatients.

Presence of personality disorders was assessed with the Structured Interview for the DSM-III Personality Disorders (SIDP) in a series of 78 nonpsychotic inpatients with major depression. Measures of severity of depression were administered at admission, at discharge, and 6 months after admission. Outcome for the depression was especially poor in patients meeting criteria for multiple personality disorders from multiple DSM-III clusters. A subgroup of 38 patients received both the SIDP interview and a self-report measure of personality disorder, the Personality Diagnostic Questionnaire. Depressed inpatients who met more than the median number of personality disorder criteria by either measure were approximately half as likely to show improvement at discharge and at 6-month follow-up than were patients with less than the median number of criteria.

Adult↗

A common region of homozygous deletion in malignant human gliomas lies between the IFN alpha/omega gene cluster and the D9S171 locus.

Deletions of the 9p-localized type-I interferon (IFN) genes and adjacent loci often occur during the development of malignant glioma. We have applied restriction fragment length polymorphism and microsatellite analysis to 12 loci covering this region of 9p and 3 loci on 9q in 74 human glial tumor tissues to define and further localize the smallest region of hemizygous or homozygous deletion common to the tumors. Three regions of homozygous deletion were evident among the panel of tumors; only one of these, however, residing between D9S171 and the IFN alpha/omega gene cluster, was involved in multiple cases (13 glioblastomas). Hemizygous deletion of this same region was observed in an additional 27 tumors. In total these data indicate the frequent inactivation of a novel tumor suppressor gene residing adjacent to and centromeric of the type-I IFN genes in malignant gliomas.

Alleles↗

Pattern of echocardiographic abnormalities with acute cardiac allograft rejection in adults: correlation with endomyocardial biopsy.

In patients who have undergone successful orthotopic heart transplantation, a noninvasive method for rejection surveillance would reduce the frequency of endomyocardial biopsy, guide the timing of biopsies, and allow for more frequent monitoring. This study identified the pattern of change in echocardiographically determined indexes of left ventricular mass, volume, and function that characterized biopsy-positive acute rejection in adult heart transplant patients receiving triple-drug immunosuppressive therapy and describes a simple computer-driven algorithm capable of identifying rejection with high sensitivity and specificity. Two-dimensional and M-mode echocardiography and Doppler color flow analyses were performed within 24 hours of endomyocardial biopsy. M-mode echocardiograms of the left ventricle were digitized and analyzed blinded to the biopsy interpretation, using a computer-assisted measurement format, for size, mass, and wall motion in systole and diastole. Twenty-nine studies were retrospectively analyzed to define the echocardiographic pattern characteristic for rejection. Left ventricular chamber size decreased, and indexes of diastolic function were significantly depressed in patients with biopsy evidence of moderate or severe rejection. However, no single parameter was sufficiently sensitive to detect all episodes of rejection partly because of differences between patients in the echocardiographic manifestations of acute rejection. To accommodate this patient variability, multiple echocardiographic parameters were clustered into a unique scoring algorithm (ECHO score). When applied prospectively to 49 studies, the likelihood that a patient would have an ECHO score not indicative of rejection but with moderate/severe rejection on biopsy was low (less than 3%) or a negative predictive value of 97.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Structure of the murine Mac-2 gene. Splice variants encode proteins lacking functional signal peptides.

The murine Mac-2 gene is composed of six exons dispersed over 10.5 kilobases. S1 nuclease mapping showed multiple transcription initiation sites, clustered within a 30-base pair region. Sequence analysis revealed that a consensus initiator sequence is located in this area which lacks a TATA motif. The untranslated first exon contains an alternative splice donor site, confirming the existence of two cDNA species with the potential to encode proteins differing at their NH2 termini. In vitro expression and translocation experiments demonstrate that both of the alternatively spliced variants of Mac-2 encode proteins which lack a functional signal peptide. Subcellular fractionation studies indicate that most of the Mac-2 protein is present in the cytosol. These results support the view that Mac-2 is exported from the cell by an unusual mechanism which does not depend on the presence of a signal peptide.

Alternative Splicing↗

Trends toward a national health care marketplace.

In recent years, the health care industry has experienced considerable growth in organizations that are national in focus-organizations that operate in multiple markets not all clustered in one geographic region. This study summarizes information on trends in ownership of various types of health care organizations (i.e., HMOs, PPOs, hospitals, physician practices) for purposes of assessing the growth rate of national companies and the overall significance of this phenomenon. This is followed by a synthesis of factors that encourage or impede the growth of national managed care companies, the sector that has exhibited the most pronounced growth of national companies. We discuss likely future directions and the degree to which national companies may enjoy long-term competitive advantages.

Economic Competition↗

The prevalence and clustering of four major lifestyle risk factors in an English adult population.

BACKGROUND: The aim of this study was to examine the clustering of four major lifestyle risk factors (smoking, heavy drinking, lack of fruit and vegetables consumption, and lack of physical activity), and to examine the variation across different socio-demographic groups in the English adult population. METHODS: The study population was derived from the 2003 Health Survey for England (n=11,492). Clustering was examined by comparing the observed and expected prevalence of the different possible combinations. A multinomial multilevel regression model was conducted to examine the socio-demographic variation in the clustering of the four risk factors. RESULTS: The study found that, when using British health recommendations, a majority of the English population have multiple lifestyle risk factors at the same time. Clustering was found at both ends of the lifestyle spectrum and was more pronounced for women than for men. Overall, multiple risk factors were more prevalent among men, lower social class households, singles, and people who are economically inactive, but less prevalent among home owners and older age groups. CONCLUSIONS: The clustering of multiple risk factors provides support for multiple-behavior interventions as opposed to single-behavior interventions.

Adolescent↗

Experts outline ways to decrease the decade-long yearly rate of 40,000 new HIV infections in the US.

This paper presents data from a brief, anonymous, open-ended survey of 50 behavioral research experts in HIV prevention. Responses were received from 31 participants who provided input regarding the primary reasons they believe the rate of the HIV epidemic in the United States has persisted in recent years, and how they believe we can most efficiently decrease the current rate of new HIV infections in the United States. Four clusters of reasons suggested for the persistent rate of new infections: Intervention level reasons, Society level reasons, Person level reasons, and Multiple Risk Factor reasons. Three clusters of strategies suggested for decreasing the current rate: Improved Targeting of HIV Prevention efforts, Larg-Scale Changes to HIV prevention, and Integrating HIV Prevention into more aspects of society. Results are reviewed with the objective of providing a fresh perspective on the potential means for addressing the current HIV epidemic.

Adolescent↗

Multiple-race mortality data for California, 2000-2001.

OBJECTIVES: To examine mortality rates and quality of race reporting for multiple-race individuals in California using the new multiple-race data available on the death certificate. METHODS: Death date were drawn from California vital statistics for 2000 and 2001. Denominator data were drawn from the 2000 census Modified Race Data Summary File. The authors calculated mortality rates and relative standard errors for multiple-race individuals as a whole and by county, and for the three largest reported multiple-race groups (African American and white, American Indian/Alaska Native and white, and Asian and white). RESULTS: Decedents reported to be of more than one race were disproportionately young, Hispanic, male, and never-married. Age-adjusted mortality rates for multiple-race groups were approximately one-sixth as high as rates for single-race individuals. There was substantial variability in rates for multiple-race decedents according to county of residence. CONCLUSIONS: Mortality rates for multiple-race people were implausibly low, and death certificates for multiple-race individuals were geographically clustered. Race reporting on death certificates will need to be improved before accurate death rates can be calculated for those of multiple races.

Adolescent↗

Surveillance of Pseudomonas aeruginosa in intensive care units: clusters of nosocomial cross-infection and encounter of a multiple-antibiotic resistant strain.

Serogrouping (determination of O antigens) and bacteriocin typing (based on susceptibility to one or more of 18 bacteriocins) were employed to survey 210 isolates of Pseudomonas aeruginosa from 201 patients in 8 intensive care units (ICU) during an observation period of 18 months. Eighty-eight isolates (41.9%) were nonserogroupable (NT); most common were serogroups O1, O9, O11, and O3. All except 5 isolates (97.6%) were bacteriocin-typable. However, phenotypic variation of bacteriocin susceptibility, in particular the receptor for bacteriocin No. 13, rendered this typing method presumptive as well. Bacteriocin susceptibility profiles were not predictive of serogroup and vice versa. Workup of 19 isolates from 9 patients disclosed phenotypic variation of antibiotic susceptibility in 3 patients, superinfection by a different strain in 4 patients, and persistence (3 months) of the same strain in 2 patients, respectively. Serotyping and bacteriocin susceptibility test data revealed 15 clusters of putative cross-infection of 2 patients each, 8 clusters involving 3 patients each, one outbreak (serogroup NT, bacteriocin profile 777736) involving 4 patients in the pediatric ICU, one outbreak due to a multiple-antibiotic resistant (MAR) strain in the surgical ICU (4 patients, serogroup O12, bacteriocin profile 30400), and two putative outbreaks in the pneumonology ICU involving 6 patients (serogroup NT, bacteriocin profile 777726) and 9 patients (serogroup NT, bacteriocin profile 777736). Pulsed-field gel electrophoresis (PFGE) macrorestriction analysis (SpeI, XbaI) confirmed the pediatric and surgical ICU strains as singular strains. However, the two putative outbreaks in the pneumonology ICU were due to one particular strain which had infected 13 of the 15 patients as determined with the PFGE genotypic method. Isolates comprising the MAR strain of P. aeruginosa were susceptible only to amikacin, fosfomycin, and polymyxin B; the isolates varied in susceptibility to aztreonam and ceftazidime. This MAR strain was susceptible to the bactericidal activity of 65 vol% of fresh defibrinated human blood from donors B, L, and T. Either amikacin (16 micrograms/ ml) or fosfomycin (8 micrograms/ml) plus blood and amikacin (8 micrograms/ml) combined with fosfomycin (8 micrograms/ml) with and without blood consistently killed isolates of the MAR strain, which thus was amenable to antibiotic therapy.

Anti-Bacterial Agents↗

The serine/threonine kinase Akt Promotes Fc gamma receptor-mediated phagocytosis in murine macrophages through the activation of p70S6 kinase.

Fc gamma receptor (Fc gamma R) clustering by immune complexes activates multiple signaling pathways leading to phagocytosis. We and others have previously reported that Akt is phosphorylated in response to Fc gamma R clustering. However, the functional consequence of Akt activation by Fc gamma R is not known. Using Raw 264.7 macrophage cells transfected to overexpress either constitutively active myristoylated (Myr)-Akt or a dominant-negative CAAX-Akt and bone marrow macrophages (BMMs) from wild-type and transgenic mice expressing macrophage-specific Myr-Akt, we analyzed the function of Akt in phagocytosis. We report that overexpression of Myr-Akt resulted in significant increase in phagocytic efficiency, whereas CAAX-Akt down-regulated phagocytosis in Raw 264.7 cells. Likewise BMMs expressing Myr-Akt displayed enhanced phagocytic ability. Analyzing the downstream effectors of Akt, we demonstrate that p70S6 kinase is constitutively phosphorylated in Myr-Akt-expressing BMMs. p70S6 kinase is reported to influence actin cytoskeleton and cell migration, suggesting that Akt may influence phagocytosis through the activation of p70S6 kinase. Consistent with this, overexpression of either wild-type or constitutively active but not a kinase-inactive p70S6 kinase in Raw 264.7 cells significantly enhanced phagocytosis. Likewise suppression of p70S6 kinase with rapamycin down-regulated phagocytic efficiency conferred by the expression of constitutively active Akt. These findings demonstrate a novel role for Akt in phagocytosis through the activation of p70S6 kinase.

Animals↗

Microvascular dysfunction: causative role in the association between hypertension, insulin resistance and the metabolic syndrome?

The metabolic syndrome defines a clustering of metabolic risk factors that confers an increased risk for type 2 diabetes and cardiovascular disease. The metabolic syndrome seems to have multiple etiological factors and microvascular dysfunction may be one potential factor explaining the clustering of multiple metabolic risk factors including hypertension, obesity, insulin resistance and glucose intolerance. Microvascular dysfunction may increase not only peripheral vascular resistance and blood pressure, but may also decrease insulin-mediated glucose uptake in muscle. The present article summarizes some of the data concerning the role of microvascular dysfunction in the metabolic syndrome.

Capillary Permeability↗

Estimation of x ray overexposure in a childhood leukaemia cluster by means of chromosome aberration analysis.

Only multiple X ray diagnostics could be identified as a common risk factor in a leukaemia cluster that appeared between 1985-1989 in the municipality of Sittensen in northern Germany. In order to judge if the effect could be explained by irradiation dose, estimates were done in two of the leukaemia cases and seven former patients of a practice where some of the leukaemia cases had been treated for orthopaedic reasons. The methods used for the reconstruction of doses were physical simulation and biological dosimetry by dicentric chromosomes in peripheral lymphocytes. Compared to the Bremen laboratory control the mean frequency of dicentric chromosomes in the lymphocytes of the seven volunteers was significantly elevated. An overexposure of about 12-fold could be derived compared to state of the art X raying. At least two cases of the leukaemia cluster in Sittensen can therefore be correlated to an overexposure by diagnostic X rays.

Acute Disease↗

Extended spectrum of HIV-1 reverse transcriptase mutations in patients receiving multiple nucleoside analog inhibitors.

OBJECTIVE: To characterize reverse transcriptase (RT) mutations by their association with extent of nucleoside RT inhibitor (NRTI) therapy. To identify mutational clusters in RT sequences from persons receiving multiple NRTI. DESIGN: A total of 1210 RT sequences from persons with known antiretroviral therapy were analyzed: 641 new sequences were performed at Stanford University Hospital; 569 were previously published. METHODS: Chi-square tests and logistic regression were done to identify associations between mutations and NRTI therapy. Correlation studies were done to identify mutational clusters. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. RESULTS: Mutations at 26 positions were significantly associated with NRTI including 17 known resistance mutations (positions 41, 44, 62, 65, 67, 69, 70, 74, 75, 77, 116, 118, 151, 184, 210, 215, 219) and nine previously unreported mutations (positions 20, 39, 43, 203, 208, 218, 221, 223, 228). The nine new mutations correlated linearly with number of NRTI; 777 out of 817 (95%) instances occurred with known drug resistance mutations. Positions 203, 208, 218, 221, 223, and 228 were conserved in untreated persons; positions 20, 39, and 43 were polymorphic. Most NRTI-associated mutations clustered into three groups: (i) 62, 65, 75, 77, 115, 116, 151; (ii) 41, 43, 44, 118, 208, 210, 215, 223; (iii) 67, 69, 70, 218, 219, 228. CONCLUSIONS: Mutations at nine previously unreported positions are associated with NRTI therapy. These mutations are probably accessory because they occur almost exclusively with known drug resistance mutations. Most NRTI mutations group into one of three clusters, although several (e.g., M184V) occur in multiple mutational contexts.

Base Sequence↗

Dietary patterns and nutrient intakes of 7-year-old children taking part in an atherosclerosis prevention project in Finland.

OBJECTIVE: To evaluate the dietary patterns of 7-year-old children participating in an atherosclerosis prevention project and the relationship of those dietary patterns to nutrient intakes and serum cholesterol values. DESIGN: In the randomized, prospective Special Turku Coronary Risk Factor Intervention Project (STRIP) 1,062 children were randomly assigned to an intervention group (n=540; low-saturated fat, low-cholesterol diet) or to a control group (n=522; unrestricted diet) at 7 months of age. SUBJECTS/SETTINGS: The intervention families received, at 6-month intervals, individualized counseling that focused on the known environmental atherosclerosis risk factors and aimed at reducing children's saturated fat and cholesterol intake. Nutrition counseling was targeted at the child but, because of the young age of the children, was given to the parents. When children were 7 years old, food and nutrient intakes of 307 intervention and 323 control children were studied using 4-day food records. STATISTICAL ANALYSES PERFORMED: K-means cluster analysis was used to classify children into 4 groups on the basis of similarity of food intake. Differences in nutrient intakes and serum lipid concentrations between children in the 4 food intake clusters were evaluated using Tukey's multiple comparison test. RESULTS: Intervention children dominated the bread, skim milk, and margarine cluster and the cereals, rice, and pasta cluster whereas the 1.5%-fat milk and butter cluster included mainly control children. Saturated fat intake was nearest to the recommendations, that is 11.7% and 11.9% of energy, in the bread, skim milk, and margarine cluster and the cereals, rice, and pasta cluster, respectively. Children in the bread, skim milk, and margarine cluster had 20% to 27% higher fiber intakes (P<.001) whereas children in the sugar and sweets cluster had markedly higher sugar intakes than children in other clusters (P<.001). Serum cholesterol concentrations were lower in those clusters with high dietary ratios of polyunsaturated to saturated fat. CONCLUSION: Detailed and repeated dietary counseling of parents, starting when children are aged 7 months, that aims at decreasing children's exposure to known nutrition risk factors for coronary heart disease modifies children's food patterns and nutrient intakes toward expected values.

Arteriosclerosis↗

Immune complex binding efficiency of erythrocyte complement receptor 1 (CR1).

C3b-coated immune complexes adhere to the complement receptor 1 (CR1, CD35) on human erythrocytes. This multi-valent binding might be favoured by the known clustering of CR1 and by the multiple C3b-binding sites on each CR1. The size of the CR1 clusters correlates directly with the number of CR1/erythrocytes, and the different structural CR1 alleles bear between two and five C3b-binding sites. Using radiolabelled hepatitis B surface antigen-antibody complexes, we investigated whether CR1 numbers and structural alleles modulate the ability of erythrocytes to bind immune complexes, and assessed if any reorganization of immune complexes takes place at the erythrocyte surface after the initial binding reaction. The binding efficiency (immune complexes/CR1) correlated with CR1 number as determined by the maximal binding at 4 degrees C, the kinetics of binding at 37 degrees C, and the binding in the presence of excess immune complexes and of immune complexes of small size. Binding efficiencies were similar for erythrocytes with low CR1 from normal subjects and patients with AIDS or SLE. A monoclonal antibody blocking the C3b-binding sites (3D9) of CR1 interfered with binding efficiency at a lower concentration on cells bearing low CR1 numbers, suggesting that CR1 clustering is essential. The larger alleles of CR1 (DD and BB) were more efficient than AA alleles. The distribution of immune complexes, visualized by immunofluorescence, was heterogeneous on erythrocytes: about two out of three cells bore between one and 12 immune complexes. No visible immune complex reorganization took place after initial binding, as prefixed erythrocytes displayed the same immune complex distribution and number/erythrocytes as unfixed erythrocytes. The contribution of CR1 alleles in immune complex binding efficiency was confirmed by morphological analysis. These results demonstrate that immune adherence efficiency is the resultant of the CR1 clustering, as well as the particular alleles carried by erythrocytes. Moreover, there is little or no immune complexes surface reorganization after the initial binding reaction.

Antibodies, Monoclonal↗

Clusters of identical new mutation in the evolutionary landscape.

In contrast to the common assumption that each new mutant results from a unique, independent mutation event, clusters of identical premeiotic mutant alleles are common. Clusters can produce large numbers of related individuals carrying identical copies of the same new genetic change. By entering the gene pool in multiple copies at one time, clusters can influence fundamental processes of population genetics. Here we report evidence that clusters can increase the arrival and fixation probabilities and can lengthen the average time to extinction of new mutations. We also suggest it may be necessary to reconsider other fundamental elements of population genetic theory.

Animals↗

Drosophila virilis histone gene clusters lacking H1 coding segments.

Approximately 30-40% of Drosophila virilis DNA complementary to cloned Drosophila histone genes is reduced to 3.4-kilobase-pair (kbp) segments by Bgl I or Bgl II digestion. The core histone genes of a 3.4-kbp Bgl II segment cloned in the plasmid pDv3/3.4 have the same order as the D. melanogaster core histone genes in the plasmid cDm500: H2B H3 H4 H2A. Nonetheless, pDv3/3.4 and cDm500 have different histone gene configurations: In pDv3/3.4, the region between the H2B and H3 genes contains 0.35 kbp and cannot encode histone H1; in cDm500, the region contains 2.0 kbp and encodes histone H1. The lack of an H1 gene between the H2B and H3 genes in 30-40% of D. virilis histone gene clusters suggests that changes in histone gene arrays have occurred during the evolution of Drosophila. The ancestors of modern Drosophila may have possessed multiple varieties of histone gene clusters, which were subsequently lost differentially in the virilis and melanogaster lineages. Alternatively, they may have possessed a single variety, which was rearranged during evolution. The H1 genes of D. virilis and D. melanogaster did not cross-hybridize in vitro under conditions that maintain stable duplexes between DNAs that are 75% homologous. Consequently, D. virilis H1 genes could not be visualized by hybridization to an H1-specific probe and thus remain unidentified. Our observations suggest that the coding segments in the H1 genes of D. virilis and D. melanogaster are greater than 25% divergent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗