Do valsartan and losartan have the same effects in the treatment of coronary artery disease?

BACKGROUND: Many angiotensin II type 1 receptor blockers (ARBs) are available for clinical use, but because they do not all have the same effects, the present study investigated whether all benefits conferred by ARBs are class effects. METHODS AND RESULTS: Study 1 was a case-control study of patients with coronary artery disease, which showed that a non-depressor dose of valsartan significantly decreased the rate of target lesion revascularization at 6 months after stenting compared with the control group without ARB treatment. In Study 2, 44 patients with acute myocardial infarction who randomly received an initial lower dose of either valsartan or losartan after stenting were evaluated. The late loss and decrease in %diameter stenosis in the valsartan group were significantly lower than those in the losartan group as assessed by quantitative coronary angiography after 6 months. In addition, the valsartan group showed a significantly lower expression of intracellular adhesion molecule-1 and L-selectin. CONCLUSION: A non-depressor dose of ARB may have beneficial effects on coronary restenosis that are associated with the regulation of adhesion molecules, and these effects might not be a class effect of ARBs.     

Genetic polymorphisms in the tumour necrosis factor locus in childhood acute lymphoblastic leukaemia

Genetic polymorphisms in the tumour necrosis factor (TNF) locus influence the outcome of non-Hodgkin's lymphoma (NHL). We investigated whether these polymorphisms might contribute to the clinical course of childhood acute lymphoblastic leukaemia (ALL). Genomic DNA from 214 childhood ALL patients was analysed. Patients with a high-risk haplotype were older than patients with low-risk haplotype (P = 0.024). No statistically significant associations were found between TNF haplotype and sex, WBC counts, central nervous system involvement, immunophenotype, response to chemotherapy, and event-free survival. These data suggest that genetic polymorphisms in the TNF locus have a limited effect on the outcome of childhood ALL.     

MPO-ANCA-positive slowly progressive glomerulonephritis with focal tuft necrosis and crescents

A 37-year-old woman had been found to have proteinuria in October 1996. About 8 months later, the first renal biopsy was performed, revealing focal segmental necrotizing and crescentic glomerulonephritis. At that time, serum creatinine was 1.0 mg/dl and urinary protein 3+. In October 1999, laboratory tests revealed positivity for MPO-ANCA and a serum creatinine level of 1.42 mg/dl, anemia and proteinuria of 2+. A second renal biopsy showed almost the same histological findings. Accordingly, a diagnosis of MPO-ANCA positive glomerulonephritis was made. This patient was thought to be a rare case of MPO-ANCA-positive slowly progressive glomerulonephritis presenting focal segmental tuft necrosis and crescents.     

A 25-year-old patient with low cardiac risk factors having a combination of variant angina and severe coronary arterial lesions--a case report

A 25-year-old man with low cardiac risks underwent coronary arteriography because of chest pain at rest. His only risk factors for coronary artery disease was smoking. Both right and left coronary arteries were ectatic and the left anterior descending artery was obstructed. In the acetylcholine provocation test, the left circumflex coronary artery showed severe constriction. Thus, this patient was diagnosed as having a combination of variant angina and occlusive coronary artery disease.     

Correlation between haemoglobin level and type of erythropoiesis-stimulating agent at initiation of haemodialysis

International Journal of Clinical Pharmacy - Background Renal anaemia worsens because of the uraemic status immediately before the initiation of haemodialysis. The haemoglobin level in patients...     

Emetic Potentials of Newly Identified Staphylococcal Enterotoxin-Like Toxins

Staphylococcal enterotoxins (SEs) are a common causative agent of food poisoning. Recently, many new SE-like (SEl) toxins have been reported, although the role of SEls in food poisoning remains unclear. In this study, the emetic potentials of SElK, SElL, SElM, SElN, SElO, SElP, and SElQ were assessed using a monkey-feeding assay. All the SEls that were tested induced emetic reactions in monkeys at a dose of 100 μg/kg, although the numbers of affected monkeys were significantly smaller than the numbers that were affected after consuming SEA or SEB. This result suggests that these new SEs may play some role in staphylococcal food poisoning.     

Prognostic significance of the MDM2/HMGA2 ratio and histological tumor grade in dedifferentiated liposarcoma

Dedifferentiated liposarcoma (DDLPS) is a relatively common soft tissue sarcoma that results from the progression of well‐differentiated liposarcoma (WDLPS). This study aimed to investigate the progression process and to clarify the pathological and genetic factors related to poor prognosis in DDLPS. In 32 DDLPS cases and five WDLPS cases, genetic factors were analyzed by custom comparative genomic hybridization (CGH) array, which was designed to densely cover gene regions known to be frequently amplified in WD/DDLPS. The analyses comparing primary and metastatic lesions and those comparing histologically different areas in the same tumor revealed intra‐tumoral genetic heterogeneity and progression. According to a prognostic analysis comparing the good‐prognosis and the poor‐prognosis groups, we selected MDM2 and HMGA2 as candidate genes associated with poor and good prognosis, respectively. The ratios of the amplification or gain levels of MDM2 and HMGA2 expressed in log ratios (log[MDM2/HMGA2] = log[MDM2]‐log[HMGA2]) were significantly associated with prognosis. An amplification or gain level of MDM2 that was more than twice that of HMGA2 (MDM2/HMGA2 > 2, log[MDM2/HMGA2] > 1) was strongly related to poor OS (P < .001) and poor distant metastasis‐free survival (DMFS) (P < .001). In the pathological analysis of 44 cases of DDLPS, histological tumor grade, cellular atypia, and MDM2 immunoreactivity were related to overall survival (OS), while HMGA2 immunoreactivity tended to be associated with OS. Cellular atypia was also associated with DMFS. In conclusion, histological grade and MDM2 expression were determined to be prognostically important, and the MDM2/HMGA2 amplification or gain ratio was found to have significant prognostic value by the custom CGH array analysis.     

Streamlined human antibody generation and optimization by exploiting designed immunoglobulin loci in a B cell line

Monoclonal antibodies (mAbs) are widely utilized as therapeutic drugs for various diseases, such as cancer, autoimmune diseases, and infectious diseases. Using the avian-derived B cell line DT40, we previously developed an antibody display technology, namely, the ADLib system, which rapidly generates antigen-specific mAbs. Here, we report the development of a human version of the ADLib system and showcase the streamlined generation and optimization of functional human mAbs. Tailored libraries were first constructed by replacing endogenous immunoglobulin genes with designed human counterparts. From these libraries, clones producing full-length human IgGs against distinct antigens can be isolated, as exemplified by the selection of antagonistic mAbs. Taking advantage of avian biology, effective affinity maturation was achieved in a straightforward manner by seamless diversification of the parental clones into secondary libraries followed by single-cell sorting, quickly affording mAbs with improved affinities and functionalities. Collectively, we demonstrate that the human ADLib system could serve as an integrative platform with unique diversity for rapid de novo generation and optimization of therapeutic or diagnostic antibody leads. Furthermore, our results suggest that libraries can be constructed by introducing exogenous genes into DT40 cells, indicating that the ADLib system has the potential to be applied for the rapid and effective directed evolution and optimization of proteins in various fields beyond biomedicine.     

Ultrasonographic evaluation of gastrointestinal graft‐versus‐host disease after hematopoietic stem cell transplantation

Gastrointestinal graft‐versus‐host disease (GI‐GVHD) is a major and life‐threatening complication of hematopoietic stem cell transplantation (HSCT). This study evaluated the efficacy of ultrasonography (US) for assessing and monitoring GI‐GVHD. GI tract was evaluated by US in 81 patients. US findings were positive in 43 patients, including 11 false positive, and negative in 38 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of US for the diagnosis of GI‐GVHD were 100%, 78%, 74%, 100%, and 86%, respectively. Diffuse wall thickening of the ileum was the most frequent finding in patients with GI‐GVHD. Severity of GI‐GVHD was correlated with the thickness of internal low echoic layer of the wall, the echogenicity of mesenteric fat tissue, and the intensity of Doppler signaling. We classified US findings of GI‐GVHD into four US grades. There was a significant correlation between clinical stage of GI‐GVHD and the US grade. These ultrasonographic abnormalities were improved with clinical improvement of GI‐GVHD upon treatment. Thus, US is an effective and efficient non‐invasive means of identifying the extent and severity of GI‐GVHD and monitoring response to treatment.     

Functional fitness may be related to life satisfaction in older Japanese adults.

The relationship between functional fitness status and life satisfaction was assessed in older Japanese people from the perspective of quality of life (QOL). A total of 123 older men and women (M = 74.3 years, SD = 5.4) participated in the study. The questionnaire contained 21 questions covering eight structural factors pertaining to the feelings of life satisfaction in older people. The functional fitness test consisted of nine items representing the following five areas of fitness: muscular strength, agility, coordination, balance, and flexibility. The analysis revealed no overall correlation between the total fitness and the total life satisfaction scores, but some of the life satisfaction factors were significantly related to some functional fitness items (P < .01). The results suggest it is important for older people to maintain their functional fitness in order to manage a high quality of life.