A role for Rac1 activity in malignant progression of sebaceous skin tumors.

The small GTPase Rac1 is crucial for maintaining stem cells (SCs) in mammalian epidermis, and Rac1 activation leads to SC expansion. Loss or inhibition of Rac1 correlates with decreased frequency of skin cancer formation in a chemical carcinogenesis model. Here, we have addressed whether Rac1 activation would enhance carcinogenesis and result in tumor progression. We used K14ΔNLef1 mice, a model for differentiated sebaceous adenomas (SAs), and activated Rac1 in an epidermis-specific manner (K14L61Rac1). Surprisingly, Rac1 activation did not change the incidence and frequency of sebaceous tumors. However, tumors, which occurred exclusively in K14ΔNLef1/K14L61Rac1 double-transgenic mice, were poorly differentiated resembling malignant sebaceous tumors and were termed sebaceous carcinoma-like tumors (SCLTs). Compared with SAs, SCLTs showed an aberrant pattern of cell proliferation, invasive growth and less abundant expression of sebocyte differentiation markers, including stearoyl-CoA desaturase-1 and adipophilin. Interestingly, the adnexal SC marker Lrig1 was upregulated in SCLTs, showing that active Rac1 leads to the accumulation of sebocyte precursors in the context of K14ΔNLef1-induced skin tumors. In a search for targets of Rac1, we found cancer progression-related proteins, Dhcr24/Seladin1 and Nuclear protein 1/P8, to be strongly regulated in SCLTs. At last, Rac1 and Dhcr24/Seladin1 were detected in human sebaceous tumors demonstrating a potential high impact of our findings for human skin disease. This is the first study showing that Rac1 activity can lead to malignant progression of skin tumors.

[Relevance of MRI for endometriosis diagnosis]. / Stellenwert der Magnetresonanztomografie in der Diagnostik der Endometriose.

Endometriosis is a disease of the uterus with displacement of endometrium-like tissue outside the endometrium. Endometriosis is a common benign chronic often debilitating disease that primarily affects young woman. The estimated prevalence is about 10 %. In addition to the uterus and ovaries, clinically important localisations are the rectovaginal space, rectum, sigmoid colon, urinary bladder, ureter and peritoneum. The most common localisation outside the pelvis is the abdominal wall. Today, MRI is one of the most important tools in the diagnosis of endometriosis. The detection of peritoneal manifestations and the exact definition of the depth of infiltration in the rectum, sigmoid colon and bladder walls are limitations of MRI.

Enhanced contact allergen- and UVB-induced keratinocyte apoptosis in the absence of CD95/Fas/Apo-1.

FAS/CD95/Apo-1 is a ubiquitously expressed cell-surface receptor involved in the initiation of programmed cell death. Its function in epidermal keratinocytes has been incompletely defined. Available evidence from in vitro studies points to important roles of Fas in the pathogenesis of contact dermatitis and in keratinocyte apoptosis induced by ultraviolet light. To define functions of Fas in the epidermis in vivo, we have generated mice with epidermis-specific deletion of the fas gene and tested its requirement for 2,4-dinitrofluorobenzene-induced contact dermatitis and for ultraviolet light B (UVB)-induced keratinocyte apoptosis. We report here our unexpected finding that keratinocyte apoptosis induced by both a contact allergen and UVB irradiation was significantly enhanced in Fas-negative epidermis. Expression of Fas by epidermal keratinocytes was neither necessary for the normal development of contact hypersensitivity of the skin, nor required for keratinocyte apoptosis following UVB irradiation. Our study results thus show that in the epidermis in vivo Fas exerts antiapoptotic effects that outweigh its proapoptotic role in contact hypersensitivity responses of the skin and in the tissue response of the epidermis to UVB irradiation.

[Opiate dependent patients in inpatient detoxification. Prevalence of somatic diseases in hospital admissions]. / Opiatabhängige in der stationären Entgiftung. Prävalenz somatischer Erkrankungen bei stationären Patienten.

AIM: To investigate whether the impression that prevalence rates of diseases in drug addicts undergoing detoxification could be verified empirically. In addition, to make an attempt to identify possible relationships responsible for this development. METHOD: Between 1989 and 1993, within the framework of a detoxification program, 1041 opiate addicts were investigated for the presence of somatic diseases. For this purpose, the overall sample was divided up into 3 groups corresponding to the following time periods: 1989/1990, 1991/1992, 1993. The baseline data comprised the standardised history at the time of admission, the results of the initial clinical examination, and the serological and clinico-chemical findings during the further course. RESULTS AND INTERPRETATION: A deterioration in the general state of health associated with more risky drug consumption patterns and social isolation was established. Apparently, low-threshold treatment programs and prophylactic strategies made available to almost two-thirds of the addicts in Hamburg have proved unable to prevent the deterioration of the situation of a subpopulation of addicts.

[Drug substitution treatment of heroin dependent patients with codeine preparations--treatment effects from the viewpoint of the physicians and patients]. / Substitutionsbehandlung von Heroinabhängigen mit codeinhaltigen Präparaten--Behandlungseffekte aus Sicht der Arzte und Patienten.

The controversy caused by the debate on treatment and substitution strategies in drug addiction is unchanged. This is particularly true concerning the use of codein-based drugs in the substitution of heroin abusers. However, only a few studies on the effects of this old and widely used method of substitution have been carried out. This article presents one retrospective and prospective study on the effects of the codein-based substitution in heroin abusers (n = 416). With respect to the issues addressed by this study such as somatic and psychic health, social integration, delinquincy and consumption patterns, patients as well as clinicians report an improvement in general health and fewer of the problems usually associated with heroin abuse, similar to the results from substitution treatment elsewhere.