Immortalisation of human urothelial cells

A cell line derived from the urothelium lining the ureter of a 12-year-old girl was immortalised using a temperature-sensitive SV40 large T-antigen gene construct, and designated UROtsa. Following immortalisation, UROtsa cells expressed SV40 large T-antigen, but did not acquire characteristics of neoplastic transformation, including growth in soft agar or the development of tumours in nude mice. Metaphase spreads had a normal chromosomal appearance and number. UROtsa cells remained permissive for cell growth at 39°C, indicating that they did not retain temperature sensitivity. UROtsa provides an in vitro model of normal urothelium.     

Polyvinylpyrrolidone dermatoses. Clinical aspects and ultrastructural morphology

High-molecular polyvinylpyrrolidone (PVP) is used in order to induce a depot of subcutaneously or intramuscularly applied drugs. Deposits of PVP in skin plaques persisting for years and distant from the injection site have been demonstrated by the use of a modified fixation and embedding method for electron microscopy. The storage of PVP did not only occur in macrophages but also in other dermal cells whose pinocytotic activity seems to have been underestimated so far. PVP was found in mucinous and serous cells of sweat glands, in myoepithelial cells, endothelial cells, mast cells, and in the perineurium as well as in Schwann cells.     

SO2-induced enhancement of inhalative allergic sensitization: inhibition by anti-inflammatory treatment.

Epidemiological studies have shown a relationship between air pollution and allergic airway disease. In a previous study we have found that exposure to SO2 enhances allergic sensitization to inhaled ovalbumin (OA) in the guinea pig. We have now investigated the influence of pre-treatment with anti-inflammatory drugs on SO2-induced enhancement of allergic sensitization in this model. Four groups of 6 guinea pigs each were exposed to 5 ppm SO2 on 5 consecutive days over 8 h per day with intermittent inhalation of OA, while the air-control group was exposed to clean air and OA. During the period of SO2 exposure and sensitization three experimental groups were treated with indomethacin (group I), methylprednisolone (group M) and nebulized nedocromil sodium (group N), while the control group remained untreated. Guinea pigs were investigated for sensitization to OA by specific bronchial provocation tests using body plethysmographic measurement of compressed air (CA) and by measurement of specific antibody response in serum. While in the SO2-exposed control group 5 of 6 animals reacted to specific bronchial provocation testing (CA median 0.15 ml, range 0-0.175 ml), only 1 animal was sensitized in group M (CA 0 ml, 0-0.125, p < 0.05), whereas no bronchial reactions were seen in groups I and N (CA 0 ml, 0-0.05, p < 0.025). Specific IgG antibody titres increased in the control group (median 43 EU-->85 EU), but not in the treatment groups (medians group I 35 EU-->35 EU, group M 30-->35 EU, group N 64-->50 EU).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cellular changes in the bronchoalveolar lavage (BAL) of pigs, following immunization by the enteral or respiratory route.

Normal young pigs were immunized by the oral or aerogenic route with the viable or inactivated lung-pathogenic bacterium Actinobacillus (Haemophilus) pleuropneumoniae. Three weeks later the cellular composition as well as the lymphocyte subset composition of the bronchoalveolar space were examined by BAL. Lymphocytes in the lavage increased significantly, including CD4+ and CD8+ T cells. After oral immunization a dramatic increase of plasma cells and lymphoid blasts was found. Among immunoglobulin-positive lymphocytes IgG+ cells showed the most pronounced increase. For most lymphocyte subsets there was no difference between viable and inactivated bacteria. Oral immunization with a lung-pathogenic bacterium results in increased numbers of lymphocytes in the bronchoalveolar space and might play a critical role in protection against lower respiratory tract infections.     

Acanthosis nigricans maligna Fallbeschreibung und Literaturübersicht

Zusammenfassung Insgesamt wurden bis 1995 23 F?lle mit „florider kutaner Papillomatose” (FCP) und über 400 F?lle mit Acanthosis nigricans maligna (ANM) publiziert. Die ANM gilt als obligate Paraneoplasie. Wir berichten über eine 28j?hrige Patientin, bei der zun?chst warzige Hautver?nderungen an den Armen und kurze Zeit sp?ter eine AN auftraten. In der apparativen Diagnostik wurde ein Adenokarzinom des Magens diagnostiziert. Die Zusammenstellung der bisher publizierten F?lle gibt eine übersicht über Art und H?ufigkeit der assoziierten Malignome bei ANM. In der überwiegenden Mehrzahl wurde ein Adenokarzinom des Magen-Darm-Traktes diagnostiziert. Eine kritische Auswertung der Literatur zeigt, da? die „FCP” keine eigenst?ndige Entit?t ist, sondern unter die ANM zu subsumieren ist. Eingegangen am 20. Juni 1996 Angenommen am 12. Februar 1997     

Detection of Epstein-Barr virus-DNA in tongue epithelium of human immunodeficiency virus-infected patients.

Oral hairy leukoplakia is a lesion on the lateral part of the tongue that contains replicating Epstein-Barr virus (EBV) and presages progression from human immunodeficiency virus (HIV) infection to AIDS. To clarify the role of EBV in the development of the lesions, we used filter in situ DNA hybridization to determine the prevalence of EBV and of human papillomavirus (HPV) in epithelial cells obtained on swabs from the tongue of HIV-infected patients who had hairy leukoplakia, HIV-infected patients who did not have hairy leukoplakia, and healthy uninfected control persons. In samples collected from the 35 uninfected control persons, EBV DNA could not be detected except at low concentrations in three people. In contrast, all but one of the samples from 11 HIV-infected patients who had hairy leukoplakia contained EBV DNA. Of greatest interest, in 19 of 32 HIV-infected patients who had no signs of hairy leukoplakia, EBV DNA was also detected on the epithelium of the tongue. DNA filter in situ hybridization for the detection of HPV serotypes 6, 11, 16, and 18 in all cases yielded negative results. Statistical analysis showed that the presence of EBV DNA was significantly correlated with the clinical status of the HIV-infected persons, as determined by Walter Reed staging classification, whereas hairy leukoplakia was not. It is concluded that detection of EBV DNA in oral epithelium may be an earlier and more powerful predictor of progression to AIDS than is hairy leukoplakia.     

Perioperative medikamentöse Kardioprotektion

Patients with major cardiac risk factors have been suggested to benefit from perioperative beta-blockade. However, the scientific literature on perioperative beta-blockade needs to be interpreted carefully. So far treatment recommendations for millions of patients are based on heterogeneous data from randomized trials with divergent study results. The evidence for a beneficial effect of perioperative beta-blockers is sufficient only for a limited subpopulation of high cardiac risk patients undergoing vascular surgery. Perioperative beta-blocker treatment is not useful in patients with intermediate risk and may even be harmful in patients with low cardiac risk. Therefore, an individualized risk-benefit analysis is an important prerequisite for a rational therapy that may be based on a standardized protocol including the Revised Cardiac Risk Index. Such a protocol is presented in this article. A recently reported trial (POISE) demonstrated that perioperative treatment with high doses of oral metoprolol efficiently reduces the incidence of cardiovascular events. However, due to severe adverse effects (hypotension, bradycardia, stroke) the total mortality was increased. Thus, dose adjustments, safety aspects, and monitoring of beta-blocker therapy seem to be mandatory. So far evidence from relevant trials about how to best implement perioperative beta-blockade is lacking. This article offers a simple clinical concept for this purpose.     

Cardiac transplantation in patients with insulin-treated diabetes mellitus.

BACKGROUND AND METHODS: As documented earlier the incidence of cardiac mortality in diabetic patients due to coronary artery disease is high. Cardiac transplantation for congestive heart failure due to coronary artery disease, cardiomyopathy, and valvular diseases is obviously a therapeutic option in patients suffering from insulin-treated diabetes mellitus. To shed more light on this problem we performed a retrospective analysis of 40 patients with insulin-treated diabetes mellitus (three type-1; 37 type-2: insulin-treated for at least three months before cardiac transplantation) referred to our transplant unit for cardiac transplantation between March 1989 and December 1996. RESULTS: Orthotopic cardiac transplantation was performed in 40 patients (4 women, 36 men) aged 32-73 years (mean 56 years) with an insulin-treated diabetes mellitus preexisting for 3-348 months (mean 65.1 months). Donor age ranged from 15 to 72 years (mean 35.5 years) matched for body weight and blood group. Overall mortality in this group was 40.0% with an early mortality of 12.5%. CONCLUSIONS: Our results show that type-1/2 insulin-treated diabetes mellitus preoperative to heart transplantation is not a contraindication in patients suffering from end-stage heart failure. Adequate therapy of diabetes mellitus as well as individual immunosuppressive therapy are important in order to minimize additional organ damage caused by the drugs themselves or resulting infectious complications.