Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

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Patterns of health-compromising behaviors among Minnesota adolescents: sociodemographic variations.

OBJECTIVES: This study compared prevalence rates of health-compromising behaviors among boys and girls from different ethnic backgrounds in early, middle, and late adolescence and compared co-occurrences of such behaviors across gender and ethnic groups. METHODS: The study population included 123 132 adolescents in grades 6, 9, and 12. Adolescents completed a classroom-administered statewide survey focusing on high-risk behaviors, including unhealthy weight loss, substance abuse, suicide risk, delinquency, and sexual activity. RESULTS: Prevalence rates of most health-compromising behaviors differed by gender, increased with age, and tended to be highest among American Indian youth and lowest among Asian Americans. Strong associations were found between substance abuse and delinquency across all ethnic groups. Substance abuse and delinquency were associated with suicide risk across most ethnic groups. Covariations with sexual activity and unhealthy weight loss behaviors showed more ethnic variation. CONCLUSIONS: Prevention interventions should take into account the tendency for health-compromising behaviors to co-occur and should be sensitive to demographic and socioeconomic differences in behavior patterns.     

Use of photodynamic therapy in the palliation of massive advanced rectal cancer

Photodynamic therapy (PDT) is a relatively new form of cancer therapy utilizing a photosensitizer such as hematoporphyrin derivative. We conducted a pilot study to determine the efficacy of its use in palliating advanced rectal cancer, to determine toxicity, and to establish objective outcome criteria. Six patients with very advanced, usually recurrent rectal cancer were treated with PDT after being photosensitized with Photofrin II^®. A protocol was established to measure clinical and radiologic response to therapy. A new intraluminal delivery system was incorporated. Five patients had both clinical and radiologic responses to therapy. In two patients we observed such significant responses that they cannot be accounted for on a photobiologic basis alone. One patient developed a significant sunburn after discharge. There was no major toxicity of bleeding or sepsis even at maximum doses (200 J/cm²). We are confident that PDT has a role to play in rectal cancer and speculate as to future applications.     

Factors associated with liver biopsy performance in HCV-HIV coinfected injecting drug users with HCV viremia: Results from a five-year longitudinal assessment

The last international consensus conference about hepatitis C virus (HCV) treatment emphasized the importance of treatment for persons coinfected with HCV and human immunodeficiency virus (HIV). As liver biopsy precedes treatment, we aimed to identify factors associated with the performance of liver biopsy among HIV-HCV coinfected drug users during a 5-year follow-up to study their access to HCV treatment. Of the 296 patients followed in the HIV hospital departments of Nice and Marseilles and with retrievable records about HCV diagnosis and care, 166 were eligible for analysis having had detectable HCV RNA at least once during the study period. Overall, 45.2% of patients underwent liver biopsy during follow-up. Using proportional hazard models, predictors of having had a liver biopsy were high social support, complete abstinence from drug injection, and lack of immunosuppression as well as male gender, no history of multiple incarcerations, more recent onset of drug use, and an increase of liver enzyme levels. These results suggest that specific efforts should be devoted to HIV-HCV coinfected drug users to assist with stabilizing these patients to optimize their access to HCV care whenever possible. The MANIF 2000 study group includes C. Boirot, A. D. Bouhnik, M. P. Carrieri, J. P. Cassuto, M. Chesney, P. Dellamonica, P. Dujardin, S. Duran, J. G. Fuzibet, H. Gallais, J. A. Gastaut, G. Lepeu, D. A. Loundou, C. Marimoutou, D. Mechali, J. P. Moatti, J. Moreau, M. Nègre, Y. Obadia, I. Poizot-Martin, C. Pradier, D. Rey, C. Rouzioux, A. Sobel, B. Spire, F. Trémolières, and D. Vlahov.     

Chronic α1-Na/K-ATPase inhibition reverses the elongation of the axon initial segment of the hippocampal CA1 pyramidal neurons in Angelman syndrome model mice

Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of function of the maternal UBE3A gene. The hippocampus is one of the most prominently affected brain regions in AS model mice, manifesting in severe hippocampal-dependent memory and plasticity deficits. Previous studies in AS mice reported an elongated axon initial segment (AIS) in pyramidal neurons (PNs) of the hippocampal CA1 region. These were the first reports in mammals to show AIS elongation in vivo. Correspondingly, this AIS elongation was linked to enhanced expression of the α1 subunit of Na⁺/K⁺-ATPase (α1-NaKA). Recently, it was shown that selective pharmacological inhibition of α1-NaKA by marinobufagenin (MBG) in adult AS mice rescued the hippocampal-dependent deficits via normalizing their compromised activity-dependent calcium (Ca⁺²) dynamics. In the herein study, we showed that a chronic selective α1-NaKA inhibition reversed the AIS elongation in hippocampal CA1 PNs of adult AS mice, and differentially altered their excitability and intrinsic properties. Taken together, our study is the first to demonstrate in vivo structural plasticity of the AIS in a mammalian model, and further elaborates on the modulatory effects of elevated α1-NaKA levels in the hippocampus of AS mice.Subject terms: Cellular neuroscience, Autism spectrum disorders, Developmental disorders     

Influence of conduction disturbances on clinical outcome in patients with acute myocardial infarction receiving thrombolysis (results from the ARGAMI-2 study)

Right bundle branch block and complete atrioventricular (AV) block are conduction disorders (CDs) that have been observed in 14% of patients admitted with ST-elevation acute myocardial infarction. CDs carry a poor prognosis, with a threefold increase in the mortality rate, mainly due to cardiogenic shock and recurrent fatal myocardial infarction at 1-year follow-up. According to multivariable analysis, CD was the second strongest predictor of death, after high Killip class. Compared with patients without CD, the 1-year outcome of patients with CD was identically worse, irrespective of whether CD appeared during admission, disappeared, or remained constant. Similar adverse outcomes were seen in patients with complete AV block and right bundle branch block.     

Platinum-resistance in ovarian cancer cells is mediated by IL-6 secretion via the increased expression of its target cIAP-2

Ovarian carcinoma patients are initially responsive to platinum-based therapy, but eventually become refractory to treatment due to the development of platinum chemoresistance. Elevated levels of interleukin-6 (IL-6) in the sera and ascites of these patients predict poor clinical outcome. Our goal was to analyze the interaction between cisplatin and cisplatin-resistant ovarian cancer cells, and to identify means of circumventing platinum resistance. We studied ovarian carcinoma cell lines and cells drawn from ovarian carcinoma patients. Gene array analyses were performed on ovarian carcinoma cells upon treatment with cisplatin, and the results were validated by ELISA and Western blotting (WB). Cytotoxicity assays were performed on anti-IL-6 Ab-, IL-6-, and cellular inhibitor of apoptosis 2 (cIAP-2) siRNA-treated cells, following cisplatin addition. Our results revealed a highly significant increase in IL-6 and cIAP-2 mRNA and protein levels upon treatment with cisplatin. WB analysis of cisplatin-treated cells exhibited decreased cIAP-2 expression level following anti-IL-6 Ab addition. Furthermore, IL-6 by itself, significantly increased cIAP-2 levels in ovarian carcinoma cells. Finally, cytotoxicity assays showed sensitization to cisplatin following the addition of IL-6 and cIAP-2 inhibitors. In conclusion, cisplatin treatment of ovarian carcinoma cells upregulates IL-6 and cIAP-2 levels while their inhibition significantly sensitizes them to cisplatin. Here, we present cIAP-2 as a novel inducer of platinum resistance in ovarian carcinoma cells, and suggest an axis beginning with an encounter between cisplatin and these cells, mediated sequentially by IL-6 and cIAP-2, resulting in cisplatin resistance. Consequently, we propose that combining IL-6/cIAP-2 inhibitors with cisplatin will provide new hope for ovarian carcinoma patients by improving the current treatment.     

recA protein promotes homologous-pairing and strand-exchange reactions between duplex DNA molecules.

Purified recA protein, product of the recA+ gene, promotes homologous pairing between intact covalent circular duplex DNA and circular single-stranded DNA carrying a short hybridized fragment [West, S. C., Cassuto, E. & Howard-Flanders, P. (1981) Nature (London) 290, 29-33.]. In this paper we investigate the interaction of duplex fragments with circular single-stranded DNA carrying the hybridized fragment and find that recA protein promotes an efficient strand-exchange reaction between interacting DNA molecules. The exchange is dependent upon linear duplex DNA fragments that are homologous to, but extend beyond, the short fragment present on the hybridized DNA substrate. The reactions require stoichiometric amounts of recA protein and the presence of ATP.     

Management and outcomes of elderly women and men with acute coronary syndromes in 2000 and 2002

BACKGROUND: Previous studies have suggested that women with myocardial infarction are treated less aggressively and have worse outcomes compared with men. The objective of this study was to evaluate sex differences in the management and outcomes of elderly (age > or = 70 years) women and men with acute coronary syndromes (ACSs) in the new millennium. METHODS: This study includes 1331 consecutive elderly patients with ACSs admitted to all intensive coronary care units and cardiology departments in Israel from 2 prospective nationwide ACS surveys conducted in 2000 and 2002. RESULTS: The mean age of women vs men was comparable (79 vs 78 years). Comorbidities were more frequent in women, whereas previous coronary disease and typical anginal pain on admission were more frequent in men. Medical treatments and revascularization procedures during the index hospitalization were comparable in both groups. Crude and covariate-adjusted mortality rates were higher in women at 7 days (12% vs 7%; P = .007; adjusted odds ratio [OR], 1.83; 95% confidence interval [CI], 1.15-2.91) but not at 6 months (21% vs 19%; adjusted OR, 1.10; 95% CI, 0.79-1.52). This difference was attributed to ST elevation (STE)-ACS in women vs men (19% vs 12%; P = .007; adjusted OR, 1.97; 95% CI, 1.14-3.46). Seven-day mortality rates were highest in patients with STE-ACS denied coronary angiography, especially women (23% vs 15%; P = .06). CONCLUSIONS: In the 2000s, elderly women and men with ACSs are receiving similar medical and invasive management during the index hospitalization; however, women with STE-ACS have higher mortality rates at 7 days but not at 6 months. Mortality rates are highest in patients with STE-ACS denied coronary angiography. The benefit of invasive procedures on mortality rates in elderly patients with STE-ACS needs further investigation.