Expression pattern of the CCAAT/enhancer-binding protein C/EBP-beta in gestational trophoblastic disease.

The CCAAT/enhancer-binding protein (C/EBP) family consists of several factors that are important regulators of intracellular processes and hormone action. C/EBP-beta, the most important member of the C/EBP family, was shown recently to be expressed in the normal human placenta where it is localized in villous syncytiotrophoblast and in the extravillous (intermediate) trophoblast but not the villous cytotrophoblast. The purpose of this study was to investigate the expression pattern of C/EBP-beta in gestational trophoblastic disease (GTD) which has not been studied so far. We used immunohistochemistry on a total of 15 cases of GTD including nine complete hydatidiform moles, one placental site nodule (PSN), one placental site trophoblastic tumor (PSTT), and four choriocarcinomas. All our tested specimens showed positivity for C/EBP-beta. The strongest C/EBP-beta expression could be observed in villous syncytiotrophoblast and in the trophoblast proliferations on the villous surface of hydatidiform moles; villous cytotrophoblast was negative. The PSN also showed positive nuclear staining but the expression was not as strong as it was in the hydatidiform moles and the total amount of stained cells was the lowest of all GTD. The PSTT also showed immunoreactivity but with a weaker and more heterogeneous staining than in the choriocarcinomas. The specific expression pattern of C/EBP-beta in GTD indicate that C/EBP-beta could potentially be an additional marker of such lesions.     

The mitochondrial genome of the fission yeast Schizosaccharomyces pombe

Summary The three mutator strains ana ^r-8, ana ^r-14, and diu ^r-301 were shown to produce respiratory deficient mutants at different rates. The frequency of respiratory deficient mutants in a culture could be increased by adding ethidium bromide. According to their cytochrome spectra and enzymatic activities they form three classes, namely mutants defective in cytochrome oxidase, in cytochrome b, and in both cytochromes. By restriction enzyme analysis of mitochondrial DNA from about 100 mutants, 22 deletion mutants were identified. The deletions, ranging from 50 to 1,500 base pairs were physically mapped. Deletions were localized in the genes coding for subunit 1 of cytochrome oxidase with its two introns, within the cytochrome b gene and its intron, and within the genes for subunits 2 and 3 of cytochrome oxidase. In several cases, where the physical mapping yielded ambiguous results, pairwise genetic crosses ruled out an overlap between two neighbouring deletions.Using these mitochondrial deletion mutants as tester strains, it was shown that only tetrad analysis and chemical haploidization, but not mitotic segregation analysis, allows a decision between chromosomal and mitochondrial inheritance of respiratory deficiency in Schizosaccharomyces pombe. Abbreviations. MtDNA = mitochondrial DNA; S. pombe = Schizosaccharomyces pombe; cox1, cox2, and cox3 refer to the mt genes coding for the three subunits of cytochrome oxidase; ATPase 6 (oli2), ATPase 8 (aapl in Saccharomyces cerevisiae, urf a61 in HeLa) and ATPase 9 (olil) refer to the three respective subunits of ATP synthase; cob is thegene for apocytochrome b; urf a is the single intergenic unassigned reading frame in S. pombe; 1 rRNA and s rRNA refer to the large and small ribosomal RNA, respectively. Mut^– is a cytoplasmic mutator (the corresponding wild type allele is mut⁺). Mit^– are mitochondrially inherited respiratory deficient mutants with mitochondrial protein synthesis; RC = respiratory competent, RD = respiratory deficient.     

Expression pattern of the cell cycle promoter cyclin e in benign extravillous trophoblast and gestational trophoblastic lesions: correlation with expression of Ki-67.

In this study, a specific monoclonal antibody was used to immunohistochemically investigate correlated expression of the cell cycle promoter cyclin E and the proliferation marker Ki-67 in benign extravillous trophoblast and gestational trophoblastic lesions. Our data show that cyclin E is expressed in the normal extravillous trophoblast, with strongest levels of expression in the cell columns of anchoring villi. Differences could be observed in expression of Ki-67 in both normal extravillous trophoblast and gestational trophoblastic lesions. In the extravillous trophoblast of the cell columns, expression of cyclin E started more distal compared with Ki-67 and was maintained (with less intensity) into the deeper layers of interstitial trophoblast. In the benign trophoblastic lesions (exaggerated placental site [EPS] and placental site nodule [PSN]) and in the trophoblast proliferations on the surface of hydropic villi of hydatidiform moles (HM), the percentage of cells expressing cyclin E was higher than of those expressing Ki-67. The same observation could be made for a case of placental site trophoblastic tumor (PSTT). In contrast, choriocarcinomas (N=8), which are definitely malignant tumors, showed an opposite pattern, with a much higher percentage of strongly Ki-67-positive cells compared with cyclin E-positive cells. We conclude that cyclin E is expressed in benign extravillous trophoblast and gestational trophoblastic lesions, where a ratio cyclin E/Ki-67<1 characterizes choriocarcinomas, whereas PSTT and the benign lesions (HM, EPS, PSN) show expression of cyclin E in a higher percentage of cells than Ki-67 (cyclin E/Ki-67 ratio >1).     

Epidemiology of Travelers— Diarrhea: Details of a Global Survey

Background Recent epidemiologic data on travelers— diarrhea (TD) are essential for the evaluation of conventional and future prophylactic and therapeutic measures.
Methods To determine the epidemiology, including risk factors, impact and quality-of-life evaluation of TD, a cross-sectional survey was conducted over 12 months at the airports of Mombasa (Kenya), Goa (India), Montego Bay (Jamaica) and Fortaleza (Brazil) by distributing questionnaires to visitors just prior to their flying home. The study period was March 1996 to July 1998.
Results Overall, 73,630 short-term visitors completed a questionnaire. The total diarrhea attack rate varied between a high of 54.6% in Mombasa and a low of 13.6% in Fortaleza, but only between 31.5% and 5.4% of all travelers had classic TD. The 14-day incidence rates varied between 19.5% and 65.7%. Few travelers meticulously avoided potentially dangerous food items, although in India and Kenya most travelers avoided those considered most dangerous. Risk factors were stays exceeding 1 week, age between 15 and 30 years, and residence in the UK. The impact, measured as incapacity or quality-of-life scores, was very considerable.
Conclusions TD continues to affect vacationers and business travelers as frequently as it did some 20 years ago. Compliance with recommendations to reduce exposure to pathogens by avoiding dangerous food items is poor among travelers from all countries. Implementation of food safety education programs may be difficult to achieve.     

Natural Course of Nonmalignant Partial Portal Vein Thrombosis in Cirrhotic Patients

Background/Aim:

Portal vein thrombosis (PVT) has a high incidence in patients with liver cirrhosis and determines a poor prognosis of hepatic disease. The aim of our study was to define the natural course of partial PVT in cirrhotic patients, including survival and decompensation rates.

Patients and Methods:

We performed a prospective, cohort study, in a tertiary referral center. There were 22 cirrhotic patients with partial nonmalignant PVT, without anticoagulant treatment, who were followed-up between January 2011 and October 2013. All patients were evaluated by Doppler abdominal ultrasound and computed tomography. Kaplan–Meier method was used to determine the difference in clinical events between the study subgroups.

Results:

After a mean follow-up period of 20.22 months, partial PVT improved in 5 (22.73%), was stable in 11 (50%), and worsened in 6 (27.27%) patients. Hepatic decompensation rate at 6 and 18 months was higher in patients with worsened PVT than in those with stable/improved PVT (50% vs. 25%, P < 0.0001 and 100% vs. 56.25%, P < 0.0001, respectively). The survival rate at 6 months was 66.66% in worsened PVT group vs. 81.25% (P = 0.005) in stable/improved group, and 16.66% vs. 81.25% (P < 0.0001) at 18 months, respectively. Multivariate analysis showed that Model of End-Life Disease was the independent predictor of hepatic decompensation [hazard ratio (HR) 1.42; 95% confidence interval (CI): 1.08−1.87, P = 0.012] and survival (HR 1.76; 95% CI: 1.06−2.92, P = 0.028).

Conclusions:

Nonmalignant partial PVT remained stable/improved in over half of cirrhotic patients and aggravated in more than one fourth in whom it negatively influenced the survival and decompensation rates.     

Macrophage LRP1 contributes to the clearance of von Willebrand factor

The relationship between low-density lipoprotein receptor-related protein-1 (LRP1) and von Willebrand factor (VWF) has remained elusive for years. Indeed, despite a reported absence of interaction between both proteins, liver-specific deletion of LRP1 results in increased VWF levels. To investigate this discrepancy, we used mice with a macrophage-specific deficiency of LRP1 (macLRP1(-)) because we previously found that macrophages dominate VWF clearance. Basal VWF levels were increased in macLRP1(-) mice compared with control mice (1.6 ± 0.4 vs 1.0 ± 0.4 U/mL). Clearance experiments revealed that half-life of human VWF was significantly increased in macLRP1(-) mice. Ubiquitous blocking of LRP1 or additional lipoprotein receptors by overexpressing receptor-associated protein in macLRP1(-) mice did not result in further rise of VWF levels (0.1 ± 0.2 U/mL), in contrast to macLRP1(+) mice (rise in VWF, 0.8 ± 0.4 U/mL). This points to macLRP1 being the only lipoprotein receptor regulating VWF levels. When testing the mechanism(s) involved, we observed that VWF-coated beads adhered efficiently to LRP1 but only when exposed to shear forces exceeding 2.5 dyne/cm(2), implying the existence of shear stress-dependent interactions. Furthermore, a mechanism involving β2-integrins that binds both VWF and LRP1 also is implicated because inhibition of β2-integrins led to increased VWF levels in control (rise, 0.19 ± 0.16 U/mL) but not in macLRP1(-) mice (0.08 ± 0.15 U/mL).