Anti-annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody

We investigated anti-annexin V antibody (aANX) in patients with systemic lupus erythe-matosus (SLE), and correlated to positivity with lupus anticoagulant (LA)/anticardiolipin antibody (aCL). aANX was positive in 12/47 SLE patients (26%), including 7 with β₂-glycoprotein 1 (GPl)-dependent aANX. The positivity of aANX was higher in patients with aCL (19%) and LA/aCL (50%) than in those without LA/aCL (10%). From these results, it is concluded that aANX is an autoantibody closely related to LA/aCL, and can be a possible new risk marker for thrombosis. © 1994 Wiley-Liss, Inc.     

Impact of gender-based career obstacles on the working status of women physicians in Japan

Research has shown that women physicians work fewer hours and are more likely to become inactive professionally and to switch to part-time labor, compared with their male counterparts. The published literature suggests that a gender disparity still exists in medicine which may decrease work motivation among women physicians. The authors investigated whether the experience and the perception of gender-based career obstacles among women physicians in Japan are associated with their working status (i.e., full-time vs. part-time). The present cross-sectional study is based on surveys of alumnae from 13 private medical schools in Japan conducted between June 2009 and May 2011. Of those who agreed to participate in this study, 1684 completed a self-administered questionnaire (overall response rate 83%). Experience of gender-based obstacles was considered affirmative if a woman physician had been overlooked for opportunities of professional advancement based on gender. Perception of gender-based obstacles referred to the self-reported degree of difficulty of promotion and opportunities for a position in higher education. Approximately 20% of the study participants responded that they experienced gender-based obstacles while 24% answered that they were not sure. The scores for perception of gender-based career obstacles were statistically higher among part-time workers compared with full-time workers (mean difference = 1.20, 95% CI: 0.39–2.00). Adjusting for age, marital status, the presence of children, workplace, board certification, holding a PhD degree, overall satisfaction of being a physician, and household income, stepwise logistic regression models revealed that physicians with the strongest perception of gender-based career obstacles were more likely to work part-time rather than full-time (OR, 0.59; 95% CI: 0.40–0.88). Although the experience of gender-based obstacles was not associated with working status among women physicians, the results demonstrated that a strong perception of gender-based obstacles was associated with part-time practice rather than full-time practice.     

Clinical significance of the venous occlusion test on systemic lupus erythematosus patients with a focus on changes in blood levels of tissue plasminogen activator, von Willebrand factor antigen, and thrombomodulin.

We investigated the clinical significance of the venous occlusion (VO) test on patients with systemic lupus erythematosus (SLE) with or without circulating lupus anticoagulant (LA) concerning whether changes in the blood coagulation and fibrinolysis system in vivo subsequent to VO reflect mechanical stimulation of the endothelium or presence/development of endothelial damage. The tissue plasminogen activator antigen (tPA:Ag) before VO was much lower in the LA-positive patients than in the LA-negative ones (p < 0.01) and the von Willebrand factor antigen (VWF:Ag) pre-VO was significantly higher in the patient group, regardless of LA status, than in the control group (p < 0.01). But the mean increment in tPA:Ag and VWF:Ag post-VO, when expressed as the percentage of the baseline level, showed no appreciable difference between LA-positive and -negative groups. Thrombomodulin (TM) basically, on the other hand, was higher in the patients of either LA status than in the controls (p < 0.01) with a significant post-VO increase in the SLE group, which was more marked in the LA-positive patients, against no substantial change in the controls (p < 0.01). It is known that tPA and VWF:Ag are released simply as a result of endothelial stimulation and that the release of TM is preceded by endothelial damage. Based on the present results, we may well conclude that (1) the endothelium is functionally intact in SLE patients, (2) an injury of the endothelium, possibly as a consequence of vasculitis, preexists in LA-positive patients, and thus to measure the TM response to VO would offer a helpful tool in diagnosing the preexisting endothelial damage in these clinical settings.     

A dose-escalation and pharmacokinetic study of subcutaneously administered recombinant human interleukin 12 and its biological effects in Japanese patients with advanced malignancies.

A pilot dose-escalation study of recombinant human interleukin 12 (rhIL-12) was conducted in Japanese patients with advanced malignancies. Cohorts of three patients received escalating doses of rhIL-12 that increased from 50 to 300 ng/kg/day s.c. three times a week for 2 weeks followed by 1-week rest. The same dosage and schedule was repeated for two additional courses. Sixteen previously treated patients were registered, and 15 were evaluated. Common toxicities were fever and leukopenia; the abnormality of laboratory tests included elevations in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, C-reactive protein, and beta2-microglobin. Dose-limiting toxicity was the grade 3 elevation of aminotransferases, and was observed in two of six patients at the 300-ng/kg dose level after the first course in one patient and after the third course in the other. Leukopenia was observed at all of the dose levels; two of six patients at 300 ng/kg experienced grade 3 leukopenia. Thus, 300 ng/kg was determined to be the maximum acceptable dose. Peak plasma levels of rhIL-12 decreased in the second courses, but the areas under the curve were almost the same in the first and second courses. Biological effects included increases of plasma levels of IFN-gamma, tumor necrosis factor-alpha, IL-6, IL-10, and neopterin. In two patients with renal cell carcinoma, complete response and partial response of metastatic tumors were observed with 50 and 300 ng/kg; the responses lasted for 5 and 3.5 months, respectively. Although immunological response to rhIL-12 varies depending on administration route and schedule and on patients' physiological conditions, the recommended dose for Phase II studies is 300 ng/kg s.c. three times a week for 2 weeks followed by 1-week rest.     

Measurement of β2-glycoprotein i (apolipoprotein h)-independent anticardiolipin antibody in human immunodeficiency virus-1-positive and-negative hemophiliacs

The authors studied whether or not anticardiolipin antibody (aCL), which is frequently detected in hemophiliacs with human immunodeficiency virus-1 (HIV-1) infection, is dependent on β₂-glycoprotein I (GPI), a cofactor of cardiolipin (CL). GPI-independent aCL was positive in 27 of 36 hemophiliacs with HIV-1 antibody (75%) and in 23 of 29 patients without HIV-1 antibody (79%). However, only six HIV-1-positive and four HIV-1-negative patients were positive for GPI-dependent aCL. Thus the aCL in these hemophiliacs was GPI independent and therefore different from the aCL found in autoimmune diseases, such as systemic lupus erythematosus.