SgIGSF is a novel biliary-epithelial cell adhesion molecule mediating duct/ductule development

Spermatogenic immunoglobulin superfamily (SgIGSF) is an intercellular adhesion molecule of the nectin-like family. While screening its tissue distribution, we found that it was expressed in fetal liver but not adult liver. In the present study, we examined which cells in developing and regenerating liver express SgIGSF via immunohistochemistry and Western blot analysis. In developing mouse liver, SgIGSF expression was transiently upregulated at perinatal ages and was restricted to the lateral membrane of biliary epithelial cells (BECs). In regenerating rat livers from the 2-acetylaminofluorene/partial hepatectomy model, SgIGSF was detected exclusively in oval cells that aligned in ductal and trabecular patterns by the second week posthepatectomy. In human livers, fetal and newborn bile ducts and cirrhotic bile ductules were clearly positive for SgIGSF, whereas disease-free adult bile ducts were negative. To investigate the role of SgIGSF in bile duct/ductule formation, we used an in vitro model in which rat hepatocyte aggregates embedded in collagen gels containing insulin and epidermal growth factor extend epithelial sheets and processes in the first week and form ductules within a month. The process and ductular cells were continuously positive for SgIGSF and cytokeratin 19, a BEC marker. When the aggregate culture was started in the presence of a function-blocking anti-SgIGSF antibody, the number of epithelial processes per aggregate was reduced by 80%. CONCLUSION: We propose that SgIGSF is a novel and functional BEC adhesion molecule that is expressed for a limited time during active bile duct/ductule formation.     

Current epidemiological situation of tuberculosis in the workplace: considering the risk of tuberculosis among nurses

OBJECTIVE: To observe the trends and methods of tuberculosis (TB) detection in different occupations; to estimate the incidence of TB among nurses, and calculate the relative risk by comparing with the aged-matched general population; and to estimate the incidence of TB and relative risk also for teachers and doctors. MATERIALS AND METHODS: The background of TB patients was analyzed using the annual reports of TB registry for the period between 1987 and 2004. The population obtained from the national census, which was conducted every five years, was used for the calculation of TB incidence by specific occupation. The annual population between the two census years was obtained by interpolation. The TB registry assigns the same occupation code for nurses, public nurses and nursery teachers, and similarly assigns a common code for teachers and medical doctors. Therefore, TB incidence of nurses was calculated by subtracting the estimated number in nursery teachers. The number of nursery teachers contracting TB was obtained assuming that their TB incidence was the same as that for the 20-59 year-old population of the same sex. On the other hand, TB incidence for teachers and doctors was calculated together, because of the difficulties in separating the two occupations. RESULTS: Among nurses with TB, the proportion of cases detected by periodic mass screening in the workplace increased gradually from 21.4% in 1987 to 40.4% in 2004. Conversely, the proportion of cases detected by symptomatic vist to medical institutions declined from 69.4% in 1987 to 43.9% in 2004. In general population, the proportion of cases detected by contact tracing is low. Among nurses, however, cases detected by contact tracing had increased since around 1995 ; the proportion was 1-2% before 1995, increased to 7.0% in 1999 and leveled off at around 6-9%. TB incidence of female nurses declined slightly from 54.1 per 100,000 population in 1987 to 46.3 in 2004 (14.4%), and that of male nurses also declined from 127.0 in 1987 to 82.5 in 2004 (35.0%). However, the relative risk of female nurses increased from 2.1 (95%CI: 1.9-2.3) in 1987 to 4.3 (95% CI: 3.9-4.8) in 2004, and that of male nurses also increased from 2.4 (95%CI: 1.6-3.4) in 1987 to 3.8 (95%CI: 2.8-5.2) in 2004. The relative risk had increased gradually from the middle of 1990s in both sexes. TB incidence of female teachers and doctors decreased from 14.8 per 100,000 population in 1987 to 10.0 in 2004 (32.4%), and that of male teachers and doctors decreased from 39.3 in 1987 to 18.8 in 2004 (52.2%). While the relative risk was below 1 in both sexes, the relative risk in females increased from 0.6 (95%CI: 0.5-0.7) in 1987 to 0.8 (95% Cl: 0.7-1.1) in 2004, and that in males also increased from 0.7 (95%CI: 0.7-0.8) in 1987 to 0.9 (95%CI: 0.8-1.0) in 2004. CONCLUSION: Based on the relative risk data, approximately 80% of nurses with TB might have been infected by nosocomial infection and developed the disease. Since about half of them were detected in an early stage by mass screening in the workplace or contact tracing, TB control measures for nurses may be considered effective. However, the relative risk of TB among nurses had continued to increase without any trend of decline. The infection control at the hospitals may be inadequate, and should be reinforced by evaluating the methods or contents of control measures conducted so far.     

Clinical analysis of HLA-DR-negative non-M3 AML

The type of leukemia was defined as HLA-DR(-) non-M3-AML, when HLA antigens were detected by flow cytometry at an incidence of < 20% of the blast population excluding M3-AML. Out of 109 patients with de novo acute myeloid leukemia, 8 patients had HLA-DR(-) non-AML-M3. According to the French-American-British criteria, 7 patients could be subdivided into 3 patients with M1, 4 patients with M2 and 1 patient with M4. The morphological features of bone marrow aspiration demonstrated no dysplasia and peroxidase stain positivity was noted in over 86% of the blast cells in all patients, the blast cells with fine granularity in 7 patients. The cytogenetic analysis revealed a normal karyotype. There was no expression marker of the blast antigens except CD13, CD14, CD33, CD34 and CD56. All of 7 patients who underwent induction therapy attained complete remission. Overall survival and disease-free survival showed no significant differences between the HLA-DR(-) non- M3-AML group and the HLA-DR(+) AML group.     

Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitis

BACKGROUND: The clinical efficacy of corticosteroids in the treatment of ulcerative colitis (UC) is well-established. However, prolonged usage of these drugs can result in serious complications. Rebamipide {2-(4-chlorobenzoylamino)-3[2-(1H)-quinolinon-4-yl] propionic acid}, a cytoprotective agent, has been reported to have anti-inflammatory activity and to repair mucosal injury in animal colitis models. The aim of the present study was to assess the clinical efficacy and safety of a novel Rebamipide enema therapy in UC patients. METHODS: Twenty patients with the active distal type of UC in whom corticosteroid treatment had been unsuccessful were treated with rectal administration of Rebamipide twice a day for 3 weeks, during which corticosteroid dosage was kept constant. The efficacy of treatment was assessed from clinical symptoms and endoscopic findings. The anti-inflammatory effect of Rebamipide was also examined by monitoring changes in the intensity of histological inflammation and levels of cytokine activity in the rectal mucosa. RESULTS: At 3 weeks after the initiation of Rebamipide enema therapy, 11 patients (55%) achieved clinical remission. Sixteen (80%) were colonoscopically judged to be responders, with decreased levels of interleukin (IL)-1beta but not of IL-8, and an increased ratio of IL-1 receptor antagonist/IL-1beta in organ cultures of mucosal tissues. The change in the number of infiltrating neutrophils was not significantly correlated with the clinical response to this therapy. No side-effects were noted in any patients. CONCLUSION: Rebamipide enema therapy proved to be safe and useful in corticosteroid-refractory patients with the active distal type of UC.     

Vpr in plasma of HIV type 1-positive patients is correlated with the HIV type 1 RNA titers

Vpr, an accessory gene product of HIV-1, has been reported in the plasma of HIV-1-positive patients, and exogenous Vpr induces the reactivation of viral production from latently infected cells and the apoptosis of T cells in vitro. These observations imply that Vpr is important in AIDS development, but the clinical relevance of the findings cannot be evaluated fully because the actual plasma Vpr concentration in HIV-1-positive patients is unknown. Here we generated two monoclonal antibodies against different portions of Vpr and successfully identified Vpr as a 14-kDa protein in HIV-1-positive patients. Semiquantitative analysis using a recombinant Vpr revealed that the concentration of Vpr in patient plasma was approximately 0.7 nM (10 ng/ml). Cross-sectional analysis of 52 HIV-1-positive patients revealed that the presence of Vpr detected in 20 patients was positively correlated with HIV-1 RNA copy number (p > 0.03), but not with the number of CD4(+) T cells. This is the first report demonstrating the actual amount of Vpr in HIV-1-positive patients, and the possible linkage of Vpr and viral titers indicates that it is important to continue to carry out the sequential analysis of Vpr, especially in clinical courses of HIV-1-positive patients. The threshold of viral titers, where Vpr appears in the patients' plasma, if present, contributes to better understanding the role of Vpr in AIDS pathogenesis.     

Paravertebral extramedulary hematopoiesis arising with osteopetrosis tarda

Extramedullary hematopoiesis predominantly occurs in the liver, spleen, and lymph nodes with hemolytic anemia. Occurrence with osteopetrosis tarda in the paravertebral region is very rare. We discuss the examination of the third known case of paravertebral extramedullary hematopoiesis arising with osteopetrosis tarda.     

Early tumor regression following severe lung injury after allogeneic stem cell transplantation in a patient with renal cell carcinoma

We describe a 65-year-old man who had repeated lung injuries after reduced-intensity allogeneic stem cell transplantation (RIST) for renal cell carcinoma. Severe pneumonitis developed twice at the time of neutrophil recovery and acute graft-versus-host disease. Both episodes were successfully treated with steroid pulse therapy. Metastases regressed after the first episode and were stable during these lung disorders, but he died of tumor progression 6 months after RIST. This case suggests that certain local inflammatory reactions may be associated with an anti-tumor effect.     

Gender differences in the clinical effects of fluvoxamine and milnacipran in Japanese major depressive patients

Gender differences in the treatment response to fluvoxamine (selective serotonin re-uptake inhibitor) and milnacipran (serotonin/norepinephrine re-uptake inhibitor) were investigated in Japanese major depressive patients. A total of 125 Japanese patients was included in the present study. Sixty-six patients received fluvoxamine treatment. The daily dose was 50 mg/day for the first week and increased to 100 mg after 1 week, up to 200 mg after another week. Fifty-nine patients were given milnacipran. The daily dose was 50 mg/day for the first week, and up to 100 mg/day thereafter. Patients were divided into three groups: younger women (<44 years of age), older women (> or =44 years of age) and men. Depressive symptoms were evaluated using the Montgomery and Asberg Depression Rating Scale (MADRS) before treatment and at 1, 2, 4 and 6 weeks after the beginning of the study. In comparison with other groups, younger women treated with fluvoxamine demonstrated a significant difference in the time course of MADRS score change. However, these gender/age-related differences of antidepressant response were not observed in the patients treated with milnacipran. The results suggest that fluvoxamine is more effective in younger female patients than older female patients and male patients, while milnacipran is generally effective irrespective of gender or age.