Relapsed childhood acute myeloid leukemia patient with inversion of chromosome 16 harboring a low FLT3 internal tandem duplication allelic burden and KIT mutations

Inversion of chromosome 16 [inv(16)] has a good prognosis in acute myeloid leukemia (AML), but additional genetic aberrations influence the outcome. We herein describe the case of a 15‐year‐old Japanese boy with inv(16) harboring a low‐allelic burden internal tandem duplication of FLT3 (FLT3‐ITD) and KIT mutations. Conventional chemotherapy eradicated a clone with a low‐allelic burden FLT3‐ITD mutation, although another clone with a KIT mutation occurred 17 months later. Further investigation is necessary to identify AML with inv(16) conferring poor prognosis, to facilitate appropriate treatment with additional drugs, such as dasatinib or gemtuzumab ozogamicin.     

Effects of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic treatment: analysis of molecular alterations by a randomised controlled trial

Background:

Whether Helicobacter pylori eradication actually suppresses the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) remains controversial. The aims of this study were to clarify (1) the molecular markers related to carcinogenesis in intestinal metaplasia (IM) by a cross-sectional study, and (2) the changes of those markers by an open-label, randomised controlled trial (RCT) of H. pylori treatment.

Methods:

First, we evaluated microsatellite instability (MSI), the methylation status at hMLH1, CDKN2A and APC genes, and immunoreactivity using the monoclonal antibody (mAb) Das-1 in IM in the background mucosa of 131 patients who underwent ER for gastric neoplasia and 22 chronic gastritis cases (control). Next, we performed an RCT to evaluate the changes of MSI between the H. pylori-eradicated (n=19) and non-eradicated patients (n=17) at 1 year among the H. pylori-positive patients.

Results:

Microsatellite instability and mAb Das-1 reactivity showed significantly higher incidences in both the H. pylori-positive and -negative patients compared with the control group, thus suggesting that MSI and mAb Das-1 reactivity are associated with gastric neoplasia (OR=5.06 for MSI; OR=2.51 for mAb Das-1 reactivity). The RCT showed that H. pylori eradication did not provide significant reversals of any molecular alterations including MSI (the primary end point) and other methylation statuses and mAb Das-1 reactivity (secondary end points).

Conclusions:

H. pylori eradication did not produce significant changes in the molecular alterations related to carcinogenesis, suggesting that H. pylori treatment may not prevent the development of MGC in background mucosa with IM.     

Aldosterone breakthrough caused by chronic blockage of angiotensin II type 1 receptors in human adrenocortical cells: possible involvement of bone morphogenetic protein-6 actions

Circulating aldosterone concentrations occasionally increase after initial suppression with angiotensin II (Ang II) converting enzyme inhibitors or Ang II type 1 receptor blockers (ARBs), a phenomenon referred to as aldosterone breakthrough. However, the underlying mechanism causing the aldosterone breakthrough remains unknown. Here we investigated whether aldosterone breakthrough occurs in human adrenocortical H295R cells in vitro. We recently reported that bone morphogenetic protein (BMP)-6, which is expressed in adrenocortical cells, enhances Ang II- but not potassium-induced aldosterone production in human adrenocortical cells. Accordingly, we examined the roles of BMP-6 in aldosterone breakthrough induced by long-term treatment with ARB. Ang II stimulated aldosterone production by adrenocortical cells. This Ang II stimulation was blocked by an ARB, candesartan. Interestingly, the candesartan effects on Ang II-induced aldosterone synthesis and CYP11B2 expression were attenuated in a course of candesartan treatment for 15 d. The impairment of candesartan effects on Ang II-induced aldosterone production was also observed in Ang II- or candesartan-pretreated cells. Levels of Ang II type 1 receptor mRNA were not changed by chronic candesartan treatment. However, BMP-6 enhancement of Ang II-induced ERK1/2 signaling was resistant to candesartan. The BMP-6-induced Smad1, -5, and -8 phosphorylation, and BRE-Luc activity was augmented in the presence of Ang II and candesartan in the chronic phase. Chronic Ang II exposure decreased cellular expression levels of BMP-6 and its receptors activin receptor-like kinase-2 and activin type II receptor mRNAs. Cotreatment with candesartan reversed the inhibitory effects of Ang II on the expression levels of these mRNAs. The breakthrough phenomenon was attenuated by neutralization of endogenous BMP-6 and activin receptor-like kinase-2. Collectively, these data suggest that changes in BMP-6 availability and response may be involved in the occurrence of cellular escape from aldosterone suppression under chronic treatment with ARB.     

Association between future events of brain infarction and soluble levels of intercellular adhesion molecule-1 and C-reactive protein in patients with type 2 diabetes mellitus

We investigated the influence of the reciprocal association between serum levels of high-sensitivity C-reactive protein (hs-CRP) and intercellular adhesion molecule-1 (sICAM-1) on the risk of brain infarction in type 2 diabetic patients. One hundred seventy nine middle-aged and elderly diabetic patients without histories of cardiovascular events were followed up for an average of 8 years. Fourteen patients developed symptomatic brain infarction (BI) during follow-up. These patients had significantly higher blood pressure, longer duration of diabetes, silent brain infarction, microvascular complications such as macroalbuminuria, and higher creatinine, sICAM-1 and hs-CRP levels at baseline as compared with those without BI. A high risk of stroke was observed in patients with high levels of sICAM-1 (>260microg/L) and hs-CRP (>0.83mg/L) at baseline, respectively, and patients with high levels of both were more likely to develop BI. In addition, sICAM-1 levels were significantly correlated with systolic blood pressure and glycemic control index, whereas hs-CRP levels were correlated with fasting insulin levels, HDL-cholesterol, triglycerides, and uric acid. Consequently, sICAM-1 and hs-CRP levels were, respectively, reflected in different cardiovascular risk factors. This study suggests that both measurements of hs-CRP and sICAM-1 levels are useful as a predictor of future stroke in diabetic subjects.     

Social support, self-efficacy and psychological stress responses among outpatients with diabetes in Yogyakarta, Indonesia

We attempted to study whether social support promotes self-efficacy and reduces stress responses of patients with diabetes in Yogyakarta, Indonesia. Diabetic outpatients at Dr. Sardjito Hospital voluntarily participated in a questionnaire survey. Data from 125 patients were subjected to analysis. The questionnaires included the scales and subscales of social support, self-efficacy, psychological stress response, and demographic measure. Data were analyzed by Spearman's rank correlation test to examine the relationships between parameters, Mann-Whitney U-test and Kruskal-Wallis test to compare the scales by characteristics, and structural equation modeling to explore the best-fit model. This study was performed in September 2003. It was found that augmentation of emotional support to patients significantly increased the 'active coping for the disease' and 'controllability of health', and that 'helplessness' was reduced significantly. Behavioral support affected only 'controllably of health'. Self-efficacy reduced stress response of the patients. It was also found that subjects who received support from their children significantly scored higher in perceived availability of social support than those without support from their children. To know their behavioral support better as well as emotional support may be one area to focus on in improving the health status of people with diabetes in Yogyakarta.     

Continuous irrigation with suction started at early days after pancreatic surgery prevents severe complications

The management of pancreatic leakage is important after pancreatic resection because such leakagge can be associated with additional complications. In this paper, we present a new therapy "irrigation with suction" after pancreatic surgery. The addition of suction permits the start of irrigation early after surgery and prevents severe post-operative complications. Between January 1995 and June 2003, 29 consecutive patients underwent surgical treatment of the pancreas for a variety of indications. Among them, 18 patients were treated with continuous irrigation with suction prophylactically. In these 29 patients, we did not encounter any additional complications such as intraabdominal hemorrhage or abscess formation. A representative case report demonstrates the application of this treatment. The irrigation with suction therapy was started on the first post-operative day after the pylorus-preserving pancreatoduodenectomy with left lobectomy of the liver. CT with irrigation of contrast reagent showed that the reagent did not spread to the uninvolved abdominal area, and the patient did not develop hemorrhage or abscess. It seems that continuous irrigation with suction therapy was effective in preventing additional serious complications after pancreatic resection.     

Rapid detection of Vibrio vulnificus using a loop-mediated isothermal amplification method

Vibrio vulnificus is found in marine waters near the coast around the world. Infection with this gram-negative rod, via ingestion of raw seafood or via a skin wound following contact with contaminated estuarine or marine water, can cause necrotizing fasciitis and sepsis. Most of patients with Vibrio vulnificus infection have underlying liver dysfunction or diabetes mellitus. Due to the high mortality and short latent periods, control of this infection depends on early identification of the bacterial species and prompt initiation of intensive care. Accordingly, the development of a technique that can identify this microbe quickly and accurately is of great importance. Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method to detect specific genes with rapidity and high sensitivity. In this study, we developed LAMP for the detection of Vibrio vulnificus. Using 28 Vibrio vulnificus strains and 53 other bacterial strains, we confirmed the high specificity of this method. Moreover, our LAMP method also showed high sensitivity, with a minimum detection level of one colony-forming unit per test. Furthermore, we developed simplified and conventional pretreatments for the method using experimental animal models. All of these attempts have lod to our non being able to detect Vibrio vulnificus within 1 hour.     

Effect of tacrolimus on the cauda epididymis in rats: analysis of epididymal biochemical markers or antioxidant defense enzymes

The effect of tacrolimus on epididymal biochemical markers was investigated following single daily subcutaneous doses of 1, 2 and 3 mg kg(-1) day(-1) for 2 weeks to male adult rats. The tacrolimus 2 and 3 mg kg(-1) day(-1) groups showed a significant and dose-dependent decrease in sperm count in the cauda epididymis. Among tissue levels of L-carnitine, alpha-glucosidase and acid phosphatase, only L-carnitine level in the cauda epididymis was significantly reduced in the tacrolimus 3 mg kg(-1)day(-1) group. However, no significant difference was seen in the plasma L-carnitine. It was suggested that lowering of L-carnitine in the cauda epididymis was attributable to the adverse effect on epididymal function to transport and/or concentrate L-carnitine. Since L-carnitine has been reported to have antioxidant potential, antioxidant defense enzymes in the cauda epididymis such as superoxide dismutase (SOD), catalase, glutathione peroxidase and glutathione reductase were evaluated. The results showed no significant differences in activities, confirming that the treatment with tacrolimus did not affect the activities of these antioxidant enzymes. In conclusion, this study indicates that tacrolimus induces a decrease in L-carnitine level in the cauda epididymis, which is probably caused by impairment of epididymal function to transport and/or concentrate L-carnitine from bloodstream, and a decrease in sperm count.