SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite

Yp-specific sequences, including the testicular determinant gene SRY, have been detected and located in a 46,XX true hermaphrodite individual, using PCR amplification and fluorescent in situ hybridization (FISH). Among different Y chromosome loci tested, it was only possible to detect Yp sequences. The Y-centromere and Yq sequences were absent. Unexpectedly, the Y fragment was translocated to the long arm of one of the X chromosomes, at the Xq28 level, and the derivative (X) chromosome of the patient lacked q-telomeric sequences. To our knowledge, this is the first Yp/Xq translocation reported. The coexistence of testicular and ovarian tissue in the patient may have arisen by differential inactivation of the Y-bearing X chromosome, in which Xq telomeric sequences are missing. The possible origin of the Yp/Xq translocation, during paternal meiosis or in somatic paternal cells, is discussed.     

Liver transplantation in HIV-HCV coinfected patients: a case-control study

Liver transplantation (LT) for hepatitis C virus (HCV)-associated cirrhosis in human immunodeficiency virus (HIV)-infected patients was compared with non-HIV patients. Nine patients with HIV-HCV coinfection were compared with patients transplanted before and after each HIV patient (control group). Immunosuppression consisted in tacrolimus with steroids or mycophenolate mofetil. Acute cellular rejection and three-year actuarial patient survival were respectively 44% and 87.5% in HIV group and 22% and 93.7% in the control group (P=NS). Acute hepatitis C virus occurred earlier (2.3 vs. 4.3 months) and was more cholestatic (mean bilirubin: 10.8 vs. 1.6 mg/dL) in the HIV group. Eight (100%) HIV and nine (64.3%) control patients received antiviral treatment with pegylated interferon and ribavirin. One patient (11.1%) of the control group and one patient (20%) of the HIV group presented a sustained virologic response (P=NS). Short- to midterm results of LT in HIV-HCV co-infected patients were excellent and similar to non-HIV patients.     

Self-reported differences on measures of executive function in a patient sample of pathological gamblers

Patients seeking help for pathological gambling often exhibit features of impulsivity, cognitive rigidity, poor judgment, deficits in emotion regulation, and excessive preoccupation with gambling. Some of these characteristics are also common among patients presenting with neurological pathology associated with executive deficits. Evidence of executive deficits have been confirmed in pathological gamblers using objective neurocognitive tests, however, it remains to be seen if such findings will emerge in self-report measures of executive control. These observations led to the current investigation of differences between a group of pathological gamblers (n = 62) and a comparison group (n = 64) using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). Significant differences between the groups emerged over all nine subscales of executive functioning with the most dramatic differences on BRIEF-A subscales Inhibit, Plan/Organize, Shift, Emotion Control, Self-Monitor, and Initiate among the pathological gamblers. These results provide evidence that support findings among pathological gamblers using objective neuropsychological measures and suggest that the BRIEF-A may be an appropriate instrument to assess possible problems with executive control in this population.     

Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome"

The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for approximately 80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.     

Sequence type 1 group B Streptococcus,an emerging cause of invasive disease in adults,evolves by small genetic changes

The molecular mechanisms underlying pathogen emergence in humans is a critical but poorly understood area of microbiologic investigation. Serotype V group B Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive serotype V GBS disease significantly increased starting in the early 1990s. We found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream of nonpregnant adults in the United States and Canada between 1992 and 2013 were multilocus sequence type (ST) 1. Elucidation of the complete genome of a 1992 ST-1 strain revealed that this strain had the highest homology with a GBS strain causing cow mastitis and that the 1992 ST-1 strain differed from serotype V strains isolated in the late 1970s by acquisition of cell surface proteins and antimicrobial resistance determinants. Whole-genome comparison of 202 invasive ST-1 strains detected significant recombination in only eight strains. The remaining 194 strains differed by an average of 97 SNPs. Phylogenetic analysis revealed a temporally dependent mode of genetic diversification consistent with the emergence in the 1990s of ST-1 GBS as major agents of human disease. Thirty-one loci were identified as being under positive selective pressure, and mutations at loci encoding polysaccharide capsule production proteins, regulators of pilus expression, and two-component gene regulatory systems were shown to affect the bacterial phenotype. These data reveal that phenotypic diversity among ST-1 GBS is mainly driven by small genetic changes rather than extensive recombination, thereby extending knowledge into how pathogens adapt to humans.The recent increase in large-scale DNA sequencing feasibility has allowed for significant advances in understanding the population genetics of bacteria that cause disease in humans (1, 2). A major outcome of the rapid expansion of available bacterial genomes has been the appreciation of the marked intraspecies genetic variability present in a wide variety of human bacterial pathogens (3, 4). This genetic variation can have profound impact on host–pathogen interaction by affecting transmissibility, infection severity, and antimicrobial resistance (2, 5, 6). The observed genetic intraspecies variability can arise via many distinct mechanisms including large-scale events such as recombination and bacteriophage-mediated horizontal gene transfer as well as small-scale genetic changes such as short insertions, deletions, and/or single nucleotide changes (2, 3, 5).Group B Streptococcus (GBS) is a common colonizer of humans that emerged in the 1970s as the leading cause of invasive bacterial disease in neonates and infants less than 3 mo of age (7). GBS is divided into 10 serotypes based on the carbohydrate composition of its sialic acid containing capsule, but gene content at the genomic level does not necessarily correlate with capsular serotype (8, 9). A seven-gene multilocus sequence typing (MLST) allows for the classification of the majority of GBS strains isolated from humans into five major clonal complexes (CCs) with a recent study by Da Cunha et al. showing that the major GBS CCs are primarily derived from a limited number of tetracycline-resistant clones, suggesting a key role of tetracycline resistance in GBS strain emergence (10, 11). CC-17 GBS strains have been particularly well studied given their role as the major cause of severe, invasive infant disease (10, 12). In contrast, serotype V strains cause a larger percentage of invasive disease in nonpregnant adults compared with neonates (13–15). Importantly, rates of invasive GBS disease have been increasing during the past 25 y in nonpregnant adults, with a significant part of the rise resulting from serotype V GBS strains (15–17).Despite the clear and increasing impact of serotype V strains, data are limited regarding molecular epidemiology of serotype V GBS causing invasive disease in nonpregnant adults (14, 15, 18). Only a few studies of serotype V strains have investigated the noncapsular genetic makeup of the strains, and those that have done so have included colonizing and invasive GBS strains isolated from infants or have not described the clinical origin of the tested strains (18, 19). Thus, we sought to analyze a large cohort of clinically well-defined, geographically distinct, and temporally disparate GBS isolates by using a whole-genome approach to elucidate the population structure of serotype V GBS causing invasive disease in nonpregnant adults. Data using non–genome-wide level approaches found that many serotype V strains were closely related, suggesting that a particular clone, rather than a genetically diverse array of strains arising from large-scale recombination, might be responsible for the majority of serotype V disease (18). Thus, we specifically sought to test the hypothesis that genetic diversity among invasive serotype V GBS strains is driven by small genetic changes at loci that are critical to GBS host–pathogen interaction.     

FK506 in the maturation of dendritic cells

BACKGROUND AND OBJECTIVES: FK506 (tacrolimus) is a potent immunosuppressive agent that inhibits interleukin-2 (IL-2) and interferon-g production by CD4+ cells. The effect of this agent on dendritic cells (DCs), the highly professional antigen-presenting cells for T-cells, has not been completely defined. We investigated the effect of FK506 on DC differentiation from monocytes, and on the shift from immature to mature immunophenotypes. DESIGN AND METHODS: DCs were generated in vitro from monocytes of healthy donors. Cells were exposed to lipopolysaccharide (LPS) and two doses of FK506, with variations in time of exposure and sequence of FK506 and LPS addition. Immunophenotype analysis in immature and mature DCs under FK506 treatment was performed by flow cytometry at the end of cell culture. The Student's t-test was used for statistical analyses. RESULTS: FK506 did not affect dendritic cell generation or viability. There were no changes in cell surface markers with addition of FK506 at physiologic concentrations (10 ng/mL). We found a decrease in CD1a median fluorescence intensity (MFI) and an increase in percentage of CD86-positive cells with lengthy exposure (6 days) to FK506 at 5000 ng/mL. In the sequential study, 5000 ng/mL FK506 before LPS addition resulted in a significant decrease in CD1a MFI and in the percentage of cells co-expressing CD83 and CD86. INTERPRETATION AND CONCLUSIONS: Our results indicate that lengthy exposure to 5000 ng/mL FK506 modified the expression of some DC-cell surface markers, maintaining DCs in a low maturity stage.     

DNA ploidy study of resected hepatocellular carcinoma in cirrhotic liver

Background/Aims: Results of several studies on DNA ploidy as a prognostic indicator in hepatocellular carcinoma are contradictory. The present study analysed the correlations between DNA ploidy of resected hepatocellular carcinoma and tumour characteristics, tumour recurrence, risk factors and survival.Methods: Tumoural DNA ploidy of hepatocellular carcinomas from 37 patients with cirrhosis who underwent curative tumour resection was studied by flow cytometry.Results: A diploid pattern was found in 23 hepatocellular carcinomas (62.2%) and an aneuploid pattern in 14 (37.8%). The tumour recurrence rate did not differ statistically between diploid (69.6%) and aneuploid (50%) hepatocellular carcinomas. The only prognostic variable with significant difference in DNA pattern was the histologic tumour type; the majority of non-trabecular tumours were aneuploid while most trabecular hepatocellular carcinomas had a diploid DNA pattern. Actuarial survival at 1, 2, 3 and 4 years of patients with diploid and aneuploid tumours was 69.6%, 40.6%, 16.2% and 0%, and 69.3%, 59.4%, 49.5% and 32.9%, respectively (log rank p=0.1927).Conclusion: These results indicate that DNA ploidy has no prognostic value in hepatocellular carcinoma.     

Functional activity of maternal and cord antibodies elicited by an investigational group B Streptococcus trivalent glycoconjugate vaccine in pregnant women

Objectives

The main aim of this exploratory study was to evaluate functional activity of antibodies elicited by a maternal Group B Streptococcus (GBS) investigational vaccine composed of capsular polysaccharides Ia, Ib, and III conjugated to genetically detoxified Diphtheria toxin CRM₁₉₇. The second objective was to investigate the relationship between serotype-specific IgG concentrations and functional activity in maternal and cord sera.