Prevalence of venous thromboembolism at a teaching hospital in Okinawa, Japan

Limited data suggest that Asian Americans may have a lower risk of venous thromboembolism (VTE) than Caucasians. However, the actual prevalence of VTE among Asians remains controversial, and has not been described in Japan. We studied all 131,060 patients hospitalized at a single medical centre in Japan (January 1987 - December 1999). Patients with VTE were identified through discharge diagnoses. Hospital records were reviewed for information on patient demographics, risk factors, and diagnostic modalities. VTE occurred in 0.11% of admissions (n=141, 95%CI 0.09-0.13%). Mean age (+/-SD) was 64+/-17 years, 70% were women, 91% had deep vein thrombosis, and 29% pulmonary embolism. Among hospitalized patients 50-69 years old, VTE was significantly more common among women than men (0.31% vs. 0.08%; OR 3.88; 95%CI 1.45-6.31). We found a low prevalence of VTE in Japan compared to that reported in the US. Future studies are needed to clarify the reasons for our findings.     

Classic Rett syndrome in a boy with R133C mutation of MECP2

About 80% of female patients with Rett syndrome (RTT) display a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, but most males with MECP2 mutation experience severe fatal encephalopathy or non-specific X-linked mental retardation (XLMR). The existence of male RTT has been extensively discussed. We report herein a boy with classic RTT in a family with a missense mutation in MECP2. The mother exhibited slight mental retardation and was a carrier for R133C. The patient could stand with support at 12-months-old, and stereotypic hand movements appeared at 3-years-old. He became bed-ridden by 8-years-old. The R133C mutation was present in MECP2 without somatic mosaicism. A sister with R133C displayed classic RTT. The R133C mutation has been detected in female patients with classic and preserved speech variant RTT, but not in males with non-specific XLMR. These results suggest that clinical phenotypes caused by DNA mutation in MECP2 are determined by position of the mutation in the gene, and R133 represents a critical amino acid residue in the induction of RTT symptoms in humans.     

Dendritic cell-based immunotherapy for malignant gliomas

Despite dramatic advances in surgical techniques, imaging and adjuvant radiotherapy or chemotherapy, the prognosis for patients with malignant glial tumors remains dismal. Based on the current knowledge regarding immune responses in the healthy CNS and glioma-bearing hosts, this review discusses dendritic cell-based immunotherapeutic approaches for malignant gliomas and the relevance of recent clinical trials and their outcomes. It is now recognized that the CNS is not an immunologically tolerated site and clearance of arising glioma cells is a routine physiologic function of the normal, noncompromised immune system. To escape from immune surveillance, however, clinically apparent gliomas develop complex mechanisms that suppress tumoricidal immune responses. Although the use of dendritic cells for the treatment of glioma patients may be the most appropriate approach, an effective treatment paradigm for these tumors may eventually require the use of several types of treatment. Additionally, given the heterogeneity of this disease process and an immune-refractory tumor cell population, the series use of rational multiple modalities that target disparate tumor characteristics may be the most effective therapeutic strategy to treat malignant gliomas.     

Human immunodeficiency virus type 1 transport across the in vitro mouse brain endothelial cell monolayer

Human immunodeficiency virus type 1 (HIV-1) is associated with a neuroinflammatory dementia. Cognitive impairment remains a common complication of late-stage HIV-1 infection. Previous studies have shown that entry of HIV-1 into the central nervous system (CNS) occurs soon after infection. For these reasons, it is important to understand how HIV-1 crosses the BBB. We used primary mouse brain microvessel endothelial cell (MBEC) monolayer models to study interactions between brain endothelial cells and radioactively labeled HIV-1 CL4 (131I-HIV-1), which had been rendered noninfectious with aldithiol, and compared to radioactively labeled bovine serum albumin (131I-BSA or 125I-BSA) and detected HIV-1 on MBEC monolayer with electron microscopic analysis. The permeability of the monolayers to HIV-1 was measured by determining the percent material transported (PMT). Luminal to abluminal PMT of 131I-HIV-1 was 4.65 times greater than that of the much smaller 131I-BSA, showing that the MBEC monolayer is more permeable to HIV-1 than to BSA. Electron microscopy showed that HIV-1 was transported through a trans-cellular pathway from luminal side to basolateral space with some virus associated with the nucleus. Unlabeled HIV-1 did not affect the transport of 131I-HIV-1 or break down the MBEC monolayer. Wheatgerm agglutinin (WGA) increased 131I-HIV-1 penetration across the MBEC monolayer, consistent with absorptive endocytosis as the mechanism for HIV-1 penetration. The enhanced transport of HIV-1 was unidirectional, as the abluminal to luminal PMT of 131I-HIV-1 was not different from that of BSA nor enhanced by WGA. Characterization of the radioactivity transported from the luminal to abluminal chamber on Sepharose 4B-200 columns showed the transported radioactivity represented intact virus. MBEC monolayers preloaded from the luminal surface with 131I-HIV-1 showed most of the virus was retained by the endothelial cells, while the remainder was effluxed mainly to the luminal surface. MBEC monolayers preloaded from the abluminal surface with 131I-HIV-1 retained little virus and most of the virus was effluxed mainly to the abluminal surface. In conclusion, cell-free, intact 131I-HIV-1 crossed brain endothelial cell monolayers unidirectionally in the luminal to abluminal direction through an adsorptive endocytotic pathway. HIV-1 taken up from luminal side by monolayers of brain endothelial cells was mainly released to the luminal side. HIV-1 efflux mechanisms are different from influx mechanisms.     

Associations between disease risk and eight polymorphisms adopted for genotype announcements at Nagoya University Hospital

Genetic polymorphisms have the potential to predict disease susceptibility. This may be especially useful among individuals with a high-risk lifestyle, so that the genotyping could be adopted for disease prevention through modifications toward a lower-risk lifestyle. We started a program of free genotype announcements in a polymorphism study among health checkup examinees at the Nagoya University Hospital on June 9, 2003. Since such announcements remain controversial for fear of unexpected harmful effects and counseling system, the accumulated evidence on the association between disease risk and genotypes announcements in our study was reviewed in this article. The genotypes used were those of alcohol dehydrogenase 2 (ADH2) Arg47His, aldelhyde dehydlrogenase 2 (ALDH2) Glu487Lys, NAD(P)H: quinone oxidoreductase (NQO1) C609T, glutathlione S transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), interleukin-1B (IL-1B) C-31T, and tumor necrosis factor A (TNF-A) T-1031C, angiotensin converting enzyme (ACE) Ins/Del. Since showed a potential for widespread use in health checkups, the information on the above polymorphisms seems worth documenting. Although there have been no complaints from the participants to date, careful treatments are requested.