Mechanism of antithrombin III inhibition of factor VIIa/tissue factor activity on cell surfaces. Comparison with tissue factor pathway inhibitor/factor Xa-induced inhibition of factor VIIa/tissue factor activity

Recent studies have shown that antithrombin III (AT III)/heparin is capable of inhibiting the catalytic activity of factor VIIa bound either to relipidated tissue factor (TF) in suspension or to TF expressed on cell surfaces. We report studies of the mechanism of which by AT III inhibits factor VIIa bound to cell surface TF and compare this inhibitory mechanism with that of tissue factor pathway inhibitor (TFPI)-induced inhibition of factor VIIa/TF. AT III alone and AT III/heparin to a greater extent reduced factor VIIa bound to cell surface TF. Our data show that the decrease in the amount of factor VIIa associated with cell surface TF in the presence of AT III was the result of (1) accelerated dissociation of factor VIIa from cell surface TF after the binding of AT III to factor VIIa/TF complexes and (2) the inability of the resultant free factor VIIa-AT III complexes to bind effectively to a new cell surface TF site. Binding of TFPI/factor Xa to cell surface factor VIIa/TF complexes markedly decreased the dissociation of factor VIIa from the resultant quaternary complex of factor VIIa/TF/TFPI/factor Xa. Addition of high concentrations of factor VIIa could reverse the AT III-induced inhibition of cell surface factor VIIa/TF activity but not TFPI/factor Xa-induced inhibition of factor VIIa/TF activity.     

Nearly identical strains of human herpesvirus 8 in couples discordant for Kaposi's sarcoma

Transmission of human herpesvirus 8 (HHV-8) may occur through various routes including breastfeeding and sexual intercourse. We attempted to detect HHV-8 infection in nine HIV-positive couples discordant for Kaposi's sarcoma who maintained a monogamous sexual relationship for at least one year. By quantitative real-time polymerase chain reaction and HHV-8 genotyping we provide strong evidence for the sexual transmission of HHV-8 in this unique cohort.     

Neurosyphilis in Verbindung mit Sekundärsyphilis bei HIV-Infektion

A 37-year-old patient presented with a generalized maculopapular rash, white oral plaques, and blurred vision of the left eye. Laboratory tests revealed the diagnosis of syphilis II and neurosyphilis in the context of HIV infection.     

Erstmanifestation eines Morbus Wegener an der Haut

Wir präsentieren den Fall eines 51-jährigen Patienten, bei dem sich ein Morbus Wegener zuerst an der Haut manifestierte und erst später eine Mitbeteiligung des Respirationstraktes festgestellt wurde. Anhand histopathologischer und bildgebendender Verfahren sowie dem positiven Nachweis von PR3-ANCA konnte die Diagnose gesichert werden. In interdisziplinärer Zusammenarbeit führte die topische Applikation von Tacrolimus, die orale Gabe von Glukokortikosteroiden und eine intravenöse Cyclophosphamidstoßtherapie zu einer Abheilung der Ulzera sowie zu einer Verbesserung des Lungenbefundes.     

Erfolgreicher Einsatz einer allogenen Stammzelltransplantation bei therapierefraktärer Mycosis fungoides

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma and characterized by a chronic progressive course spanning decades. The choice of treatment options should be tailored to the stage depending on the extent and aggressiveness of the disease and taking the individual situation of the patient into consideration. Long-term complete remissions can only be achieved in the early phase of the disease, while there is no therapy that results in a cure or long-term remission in advanced stages. In young patients with a treatment-refractory course of mycosis fungoides, allogeneic stem cell transplantation represents an important alternative option to manage the disease since complete clinical remission can be obtained even in advanced stages.     

Epithelial stem cells in the skin: definition, markers, localization and functions

In recent years, cutaneous epithelial stem cells have attained a genuine celebrity status. They are considered the key resource for epidermal and skin appendage regeneration, and are proposed as a preferential target of cutaneous gene therapy. Follicular epithelial stem cells may also give rise to a large variety of epithelial tumors, and cutaneous epithelial stem cells likely are crucial targets for physical or chemical agents (including carcinogens) that damage the skin and its appendages. However, as this Controversies feature illustrates, few experts can agree on how exactly to define and identify these elusive cells, or on where precisely in the skin they are localized. Given their potential importance in skin biology, pathology and future dermatological therapy, it is, therefore, timely to carefully reconsider the basic questions: What exactly is a stem cell, and how can we reliably identify epithelial stem cells? How many different kinds are there, and how do they differ functionally? Where exactly in the skin epithelium is each of the putative stem cell subpopulations located, and can we selectively manipulate any of them?     

Painful bruising syndrome

A 54-year old anorectic patient with painful bruising syndrome (Gardner-Diamond syndrome) suffered from various gastrointestinal and psychologic complaints. The episodes of painful bruising could be provoked following intradermal injection of washed red blood cells within 96 h. The pathogenesis of this rare entity is more likely due to a psychiatric alteration rather than to the immunological mechanisms, as had been postulated two decades ago. Nevertheless, the Gardner-Diamond-syndrome should be included in the differential diagnosis of ecchymotic bleeding.     

ERK1/2 is highly phosphorylated in melanoma metastases and protects melanoma cells from cisplatin-mediated apoptosis

Activation (phosphorylation) of mitogen-activated protein kinase (MAPK) signal transduction through BRAF and RAS causes a variety of functional effects including cell survival and cell death. In this study, we observed high extracellular signal-regulated kinase (ERK)1/2 phosphorylation levels in clinical melanoma metastases and various melanoma cell lines. Treatment of melanoma cell lines with cisplatin, a potent antitumor agent, increased the level of phosphorylated-ERK (P-ERK)1/2 and enhanced chemoresistance through activation of the cell survival protein 90-kDa ribosomal S6 kinase (RSK)1. The mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) was able to block this effect and reduced cell viability and sensitized cells to cisplatin-induced apoptosis, as shown by PARP cleavage, caspase 3 expression, and annexin-V staining. In conclusion, the MAP kinase-ERK pathway is activated in melanoma and reduces the sensitivity of melanoma to cisplatin. Thus, inhibition of ERK1/2 in combination with selected chemotherapeutic agents may hold promise for more effective therapy of melanoma.     

Very early cytological and DNA-cytometric diagnosis of in situ carcinoma in an immunosuppressed liver transplant recipient

BACKGROUND: We describe a patient with an in situ carcinoma with the clinical presentation of an erythroplakia of the tongue in an area where DNA-aneuploidy was detected by means of exfoliative cytology (EC) and DNA-image-cytometry 32 months before. METHODS: Brush- and scalpel biopsies were obtained from a suspicious lesion of the right border of the tongue prior to scalpel biopsy. After Feulgen restaining of the specimens on glass slides, nuclear DNA-contents were measured using a TV image analysis system. RESULTS: A small reddish lesion of the tongue was diagnosed as malignant through EC and DNA-image-cytometry, whereas the synchronous histology from the same area showed only mild dysplasia. A subsequent scalpel biopsy 32 months after the first examination showed an in situ carcinoma. CONCLUSIONS: Non-invasive brush biopsies are of great importance for the very early identification of mucosal areas with a high risk for malignant transformation through cytological and DNA-cytometric examination.     

轻度认知损伤患者记忆功能的随访研究

目的探讨轻度认知损伤（MCI）患者记忆功能的变化特点及其与预后的关系。方法采用临床记忆量表、词语流畅性测验、词语即刻和延迟回忆测验对14名MCI患者和18名正常老年人进行3年随访研究。结果与正常老年人相比，在第2年随访时MCI患者词语延迟回忆成绩明显下降（P〈0．05），有1名进展为阿尔茨海默病（AD）；在第3年随访时MCI患者无意义图形回忆、词语即刻回忆、词语延迟回忆成绩明显下降（P〈0．05），有2名进展为AD。结论MCI患者较正常老年人的记忆功能衰退速度更快，而且早期以言语性情节记忆减退为主。MCI患者进展为痴呆的危险性更大。