Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer

BACKGROUND: High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. METHODS: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate-specific antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39-89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4-68). RESULTS: The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001). Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent predictor of relapse. CONCLUSION: High-intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.     

The αβ T Cell Receptor Clustering Upon Superantigen/MHC Recognition

Antigen recognition by T cells is the key event for the antigen specific immune responses to be triggered. This recognition is initiated by the binding of the T cell receptor (TCR) to antigen peptide/major histocompatibility complex (MHC) on the surface of the antigen presenting cells. TCR on most of the T cells is a heterodimer composed of α and β chains which are associated with CD3 γδε as well as ζ chains, the signal transmission molecules. The dynamics of this TCR complex upon antigen/MHC recognition, however, has not been well understood. In this paper the authors analyse the configuration of TCR complex on T cells from a TCR β chain gene transgenic mouse (TGM) strain. Unlike many other TGM strains reported, a considerable proportion of T cells from this TGM expresses both transgene-encoded (Vβ3) and endogenous TCR β chains on their surface. By immunoprecipitation and immunoblotting analysis of T cells stimulated with a superantigen, staphylococcal enterotoxin B (SEB), the authors found that Vβ3 was coprecipitated with Vβ8, demonstrating the clustering of TCR αβ upon superantigen/MHC recognition.     

Genetic susceptibility to type 2 diabetic nephropathy in human and animal models

SUMMARY:   Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in Japan, Western Europe, and the United States. Mega studies such as Diabetes Control and Complication Trial (DCCT), Epidemiology of Diabetes Interventions and Complications (EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) clarified that poor glycemic and blood pressure control are undoubtedly involved in the development of nephropathy. However, these factors are not sufficient to predict which diabetic patients will develop renal disease, because not all patients with poor glycemic and blood pressure control develop renal disease. Since ethnic variations and familial clustering of diabetic nephropathy have been observed, genetic factors might contribute to susceptibility to this disease. Several methods such as (genome wide) association studies, sib-pair analysis, and quantitative trait loci (QTLs) analysis are available to examine polygenic diseases. However, no mutations that could explain the majority of nephropathy cases have been identified so far. The development of most diabetic nephropathy might be explained by the polygenic effect (i.e. many minor gene-gene interactions might be very important in the development of nephropathy). Identification of candidate genes of nephropathy enables targeting of therapy in patients at risk and development of novel therapeutic agents.     

YF476 is a new potent and selective gastrin/cholecystokinin-B receptor antagonist in vitro and in vivo

Background : We newly synthesized YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl)-1H-1,4-benzodiazepin-3-yl]-3-(3-methylamino-phenyl)urea) as a gastrin/cholecystokinin-B (CCK-B) receptor antagonist. We investigated the pharmacological profile of YF476 in vitro and in vivo .
Methods : We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, and the effect of YF476 on secretagogue-induced gastric acid secretion in rats and Heidenhain pouch dogs.
Results : YF476 replaced the specific binding of [¹²⁵I]CCK-8 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, with K _i values of 0.068, 0.62 and 0.19 n M , respectively. The affinity of YF476 for rat brain gastrin/CCK-B receptor was 4100-fold higher than that for rat pancreatic CCK-A receptor. In anaesthetized rats, intravenous YF476 inhibited pentagastrin-induced acid secretion with an ED ₅₀ value of 0.0086 μmol/kg, but did not affect histamine- and bethanechol-induced acid secretion at a dose of 10 μmol/kg. In Heidenhain pouch dogs, intravenous and oral YF476 inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner with ED ₅₀ values of 0.018 and 0.020 μmol/kg, respectively, but did not affect histamine-induced acid secretion.
Conclusion : These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK-B receptor antagonist, and that the gastrin/CCK-B receptor is not involved in histamine- or bethanechol-induced gastric acid secretion in dogs or rats.     

Effects of participatory workplace improvement program on stress-related biomarkers and self-reported stress among university hospital nurses: a preliminary study

Although participatory workplace improvement programs are known to provide favorable effects on high stress occupations like nursing, no studies have confirmed its effect using biomarkers. The aim of this study was to determine whether a participatory workplace improvement program would decrease stress-related symptoms as evaluated by biomarkers and self-reported stress among hospital nurses. Three actions to alleviate job stress, which were determined through focus group interviews and voting, were undertaken for two months. A total of 31 female Japanese nurses underwent measurement of inflammatory markers, autonomic nervous activity (ANA), and perceived job stress (PJS) at three-time points; before the program (T1), within a week after the completion of the program (T2), and three months after the program (T3). A series of inflammatory markers (Interferon-γ, Interleukin (IL)-6, and IL-12/23p40) decreased significantly at T2, and IL-12/23p40 and IL-15 significantly decreased at T3 compared to T1, while ANA and PJS remained unchanged. Our participatory program exerted beneficial effects in reducing inflammatory responses, but not for ANA and PJS. Further investigations with a better study design, i.e., a randomized controlled trial, and a larger sample size are warranted to determine what exerted beneficial effects on inflammatory markers and why other outcomes remained unchanged.     

Update on Stent Implantation in Acute Myocardial Infarction

Primary stent implantation in acute myocardial infarction (AMI) is defined as the intentional (not rescue) implantation of intracoronary stent(s) to the culprit lesion of AMI during emergency catheterization. All available data showed that this strategy has favorable short- and long-term clinical effects compared to primary balloon angioplasty.