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.     

Hypergammaglobulinemia and autoantibody induction mechanisms in viral infections

Polyclonal hypergammaglobulinemia is a characteristic of chronic inflammatory conditions, including persisting viral infections and autoimmune diseases. Here we have studied hypergammaglobulinemia in mice infected with lymphocytic choriomeningitis virus (LCMV), which induces nonspecific immunoglobulins as a result of switching natural IgM specificities to IgG. The process is dependent on help from CD4+ T cells that specifically recognize LCMV peptides presented by B cells on major histocompatibility complex class II molecules. Thus, hypergammaglobulinemia may arise when specific helper T cells recognize B cells that have processed viral antigens irrespective of the B cell receptor specificity. This nonspecific B cell activation may contribute to antibody-mediated autoimmunity.     

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.     

Persistence of lymphocytic choriomeningitis virus at very low levels in immune mice

Lymphocytic choriomeningitis virus (LCMV), strain WE, is a non-cytopathic RNA virus that is highly adapted to its natural host, the mouse. Acute infection of adult mice leads to generalized virus spread, followed by cytotoxic T lymphocyte-mediated virus clearance below the detection levels of conventional assays within 2-3 weeks. Indirect evidence had suggested that virus or viral antigen might persist in the immune mouse. Here we demonstrate LCMV-WE persistence at low levels after infection with 10(2) or 10(6) plaque-forming units, shown as viral genome, viral antigen, and replicative virus using sensitive in vitro and in vivo assays. The finding that LCMV-WE persists in the face of apparently intact immune responses resembles the situation in some viral (hepatitis B and C, HIV) and bacterial (tuberculosis, leprosy) infections in humans; the results are relevant to the understanding not only of other murine and human persistent viral infections but also of protective immunological memory by "infection immunity."