Isolation and expression of the retinoid X receptor from last instar nymphs and adult females of the soft tick Ornithodoros moubata (Acari: Argasidae)

Retinoid X receptors (RXR) exist broadly from invertebrates to vertebrates, and play essential roles in physiological processes of these organisms. In arthropods, RXRs form a complex with the ecdysteroid receptor (EcR) and ecdysteroids to mediate the regulation of ecdysis and reproduction. Compared to EcR, RXR and its homologue ultraspiracle (USP) are much less well understood. Therefore, we identified RXR of the soft tick Ornithodoros moubata (OmRXR) and used real-time PCR to examine the expression of OmRXR. This is the first report of RXR from a soft tick. OmRXR showed higher homology to hard tick, crustacean and vertebrate RXRs than insect RXRs and USPs. OmRXR expression was observed during molting in the last instar nymphs coinciding with EcR expression and increases in ecdysteroid titers. Tick vitellogenesis normally occurs soon after engorgement and OmRXR expression coinciding with EcR expression and ecdysteroid titers in engorged females occurred before vitellogenin (Vg) synthesis and egg maturation. The ecdysteroid/EcR/RXR complex appears to be important in the regulation of molting and vitellogenesis of soft ticks.     

Overexpression of p53 protein and histologic grades of dysplasia in colorectal adenomas

PURPOSE: To clarify the relation between tumor-suppressor gene p53 expression and histologic grades of dysplasia in colorectal adenomas, we performed immunohistochemical analysis in a series of 59 colorectal polyps and 40 advanced carcinomas. METHODS: Adenomatous polyps were stained by hematoxylin and eosin and classified into mild, moderate, and severe dysplasia (intramucosal carcinoma), according to the World Health Organization's classification. RESULTS: p53 was positive in 7.1 percent (2/28) of mild, 29.4 percent (5/17) of moderate, and 62.5 percent (5/8) of severe dysplasia. In submucosal and advanced carcinomas, positivity rates were 75 percent (3/4) and 47.5 percent (19/40), respectively. Different staining patterns were found, according to grades of dysplasia. In the adenomas with mild or moderate dysplasia, a few focal crypts showed localized p53-positive staining. Adenomas with severe dysplasia had two different staining types. One was a focal staining type as shown in mild or moderate dysplasia; the other was a diffuse staining type, in which glands with mild or moderate dysplasia, surrounding severe dysplasia area, were also stained. Submucosal and advanced carcinomas showed a strong positive staining in cancer cells only. CONCLUSIONS: Overexpression of p53 protein in adenomas with mild or moderate dysplasia and existence of two types of expression in adenomas with severe dysplasia were observed. These facts suggested the possible existence of different pathways in the adenoma to carcinoma progression.     

Selective expansion of donor‐derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome

IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA‐matched sibling donor. We could achieve engraftment and regimen‐related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor‐derived Tregs and disappearance of anti‐villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor‐derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs.     

Changing site distribution of colorectal cancer in Japan

PURPOSE: In North America and other high-risk areas, there has been a proximal shift in the subsite distribution of colorectal cancer. We wanted to determine whether any similar change has occurred in Japan, and where the incidence of this disease has increased sharply. METHODS: Data from the Reports of the Japanese Society for Cancer of the Colon and Rectum were used to analyze the time trend of colorectal cancer in Japan between 1974 and 1994 according to the patients age at diagnosis and sex, and the site of the tumor within the colon or rectum. RESULTS: The percentage of patients over the age of 70, especially females, increased. The increase in the percentage of right-sided colon cancer in colorectal cancer cases was accompanied by a continuous decline in the percentage of rectal cancer in both sexes at all ages. In general, the percentage of right-sided colon cancer in colon cancer cases was stable in men, but increased in women. The rate among patients older than 70 years increased in men, but predominated and remained stable in women. No proximal shift in colon cancer was found in either sex under the age of 69. CONCLUSION: These findings indicated that a proximal shift in the subsite distribution of colorectal cancer has occurred in Japan. This rightward shift of colorectal cancer is due to the decreasing proportion of rectal cancer. Furthermore, the increasing proportion of older patients, especially females, may be another major determinant of the changing colon cancer subsite distribution.     

Crosstalk between Iron and Arteriosclerosis

Iron is an important element for life; however, intracellular labile iron overload can lead to the generation of reactive oxygen species and cellular damage. Although iron is mainly utilized for heme synthesis and is incorporated into hemoglobin, body iron status is often implicated in the pathogenesis of cardiovascular diseases. In a cell, iron is used for basic processes such as cell growth, maintenance, and repair. Thus, iron is considered to be involved in the pathogenesis of arteriosclerosis. In fact, clinical and experimental studies have shown an association between iron and arteriosclerosis. These data suggest the crosstalk between iron and arteriosclerosis. However, iron metabolism in arteriosclerosis is often complicated, and the systemic and cellular mechanisms of iron homeostasis in arteriosclerosis remain completely unsolved. Thus, in this review, we aimed to examine the role of iron in arteriosclerosis.     

Administration of angiotensin-converting enzyme inhibitors is associated with slow progression of mild aortic stenosis in Japanese patients

It is almost unknown which demographic factors or medications affect the progression of aortic stenosis (AS) in Japanese patients with mild AS. We identified a total of 194 patients with native tricuspid valvular AS, defined as a continuous-wave Doppler determined peak aortic valve jet velocity of ≥ 2.0 m/s, in whom echo Doppler studies were repeated at an interim of at least 6 months. Annualized change in peak jet velocity was calculated, and effects of age, sex, diabetes mellitus, blood pressure, serum low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels, and use of statins and antihypertensive agents on the progression of AS were retrospectively evaluated. Peak aortic valve jet velocity was 2.36 ± 0.79 m/s (mean ± SD) and annualized increase in peak aortic valve jet velocity was 0.17 ± 0.32 m/s/year for all the studied patients. The increase in peak aortic valve jet velocity was lower in patients taking angiotensin-converting enzyme inhibitors (ACE-Is) than in those not taking ACE-Is (0.04 ± 0.22 vs. 0.20 ± 0.32 m/s/year, P < 0.05). Such protective associations were not observed for other first-line antihypertensive agents and statins. Multiple linear regression analysis revealed that ACE-I treatment, decrease in left ventricular ejection fraction, and higher peak aortic valve jet velocity at the first echocardiogram were associated with slower progression of AS. Administration of ACE-Is was associated with the slow progression of mild AS in Japanese patients. Prospective study to assess this hypothesis is needed.     

AN AuTOPSY CASE OF IMPETIGO HERPETIFORMIS HEBRA

A 24 years old male case who died of suicide in a peak of Impetigo herpetiformis was reported. Initially he developed skin eruptions at the age of 6 years. During the last twenty-three months, skin eruptions relapsed sixteen times. Intensive therapy of adreno-cortical hormone, sex hormone and antibiotics were given. Pathological findings of endocrine and genital organs were considered to be caused by the intensive hormone therapy, No etiological finding was found in internal organs pathologically. Staphylococci aureus and epidermis were found only once in blood, twice in the pustules. However, secondary infection could not be ruled out. This case indicated that I.h. was a disease of only skin.