Genetic analysis of 22 candidate genes for hypertension in the Japanese population

OBJECTIVE: We performed association studies between 118 single-nucleotide polymorphisms (SNPs) of 22 candidate genes (or gene family) and hypertension in a Japanese population. DESIGN AND PARTICIPANTS: The study population consisted of 1880 subjects representing the general population in Japan, recruited from the Suita study. The candidate genes were selected based on their functions, including insulin resistance (APM1, CD36, HSD11B1), oxidative stress (CYBA, GPX1, GSTMs), steroid hormone (ESR1, ESR2, HSD11B2), renal functions (PTGS2, KLK1, NPHS1, NPHS2, SGK, SLC12A1, PTGES), and others related to cardiovascular physiology (GJA4, NOS1, NTRK3, P2RX4, SPP1, ALDH2). RESULTS: Multiple logistic analyses, with age and body mass index as covariates, indicated that 13 SNPs (eight genes), six SNPs (four genes) and 11 SNPs (four genes) were associated with hypertension (P < 0.05) in the total, male, and female populations, respectively. PTGS2 seems to be a promising candidate gene for hypertension in men. GSTM3 and SLC12A1 seem to be promising candidate genes for hypertension in women. Especially, a polymorphism in SLC12A1 was significantly associated with hypertension in women even after correction by the Bonferroni method (corrected P = 0.0236). Multiple logistic analyses, with age and body mass index as covariates, indicated that the prevalence of hypertension in females was significantly higher in subjects with the CC genotype than in those with the TT + TC genotypes (P < 0.0001, odds ratio = 1.967, 95% confidence interval = 1.430-2.712). CONCLUSION: Although the present results should be replicated in other study populations for confirmation, the present results suggest that SLC12A1 may contribute to hypertension in Japanese women.     

Endoscopic and chromoendoscopic atlas featuring dysplastic lesions in surveillance colonoscopy for patients with long-standing ulcerative colitis

Clinical and epidemiological studies have revealed that the incidence of colorectal cancer associated with ulcerative colitis increases with long-term chronic inflammation. Careful endoscopic observation and histological studies to check for dysplasia in the colon are important in detecting neoplasia. Current surveillance protocols mainly involve frequent step biopsies to yield a reasonable rate of dysplasia detection. However, recent studies using chromoendoscopy or magnifying endoscopy have proposed that neoplastic changes may be detected efficiently. Therefore, it is very important to understand the typical endoscopic findings found in neoplastic changes in patients proven to have long-standing ulcerative colitis. In this review, we demonstrate the typical endoscopic findings by conventional endoscopy and chromoendoscopy.     

Nitric oxide induces caspase-dependent apoptosis and necrosis in neonatal rat cardiomyocytes

Excessive nitric oxide (NO) production has been implicated in the pathophysiology of cardiomyocyte (CMC) apoptosis and necrosis induced by ischemia/reperfusion, inflammation and NO-donating chemicals. Although caspases are known to be involved in apoptosis, the present study examined whether caspases also play a role in NO-induced CMC necrosis. Neonatal rat CMCs were labeled with Annexin-V and propidium iodide, and apoptosis and necrosis were analyzed by confocal images and fluorescence activated cell sorter analysis. CMC apoptosis and necrosis were also evaluated by determining DNA fragmentation in the cell and the supernatant fractions. Treatment of CMCs with the NO donor, diethylenetriamine NO (DETA/NO) or S-nitroso-N-acetyl-penicillamine (SNAP) at concentrations of 10 and 100 microM for 24h induced predominantly apoptosis over necrosis, but a higher concentration (1mM) of DETA/NO or SNAP provoked both apoptosis and necrosis. The lower doses of DETA/NO-induced apoptosis was associated with a gradual increase in caspase-3 activity over 24h without appreciable activation of poly ADP-ribose polymerase (PARP), while the higher dose of DETA/NO induced a marked increase in caspase-3 activity and CMC apoptosis until 2h after the treatment, and increased necrotic CMCs thereafter associated with robust activation of PARP. The caspase inhibitor Z-DEVD-FMK but not the poly ADP-ribose polymerase (PARP) inhibitor 3-aminobenzamide (3-AB) abolished caspase-3 activation and CMC apoptosis induced by 100 microM DETA/NO. However, both Z-DEVD-FMK and 3-AB abolished PARP activation and CMC necrosis induced by 1mM DETA/NO. The amount of nicotinamide adenine dinucleotide (NAD) and adenine nucleotides in CMCs was not significantly affected by treatment with 10 and 100 microM DETA/NO, but was significantly reduced by treatment with 1mM DETA/NO without a decline of adenylate energy charge. The depletion of NAD and adenine nucleotides was abrogated by Z-DEVD-FMK and 3-AB. These results suggest that caspase activation play a crucial role in CMC apoptosis induced by lower concentrations of NO as well as in CMC necrosis induced by a higher concentration of and a longer exposure to NO. NO-induced CMC necrosis is likely mediated by PARP activation which occurs as a consequence of caspase activation.     

Volume reduction surgery for advanced hepatocellular carcinoma

Purpose The aim of this study was to evaluate the prognostic impact of reductive surgery on the survival of patients with advanced hepatocellular carcinoma (HCC).Methods Eligible patients had a main tumor greater than 10 cm in diameter with multiple intrahepatic metastases (>5 nodules), and good liver function (Child-Pugh class A), but no tumor thrombus in the main portal vein. The main tumor was surgically removed but the metastases were not removed and were treated with repeated transcatheter hepatic arterial chemo-embolization (TAE).Results From Jun 1997 to May 2003, 13 patients (median age 61 years, range: 48–74) were prospectively enrolled. The median diameter of the main tumor was 14 cm (range 11.5–18.0). No major surgical complications were observed and the median hospital stay was 12 days (range 7–20). The first TAE was performed 1 month after hepatectomy in all patients and was repeated for median of 5 (range: 1 to 16) times. Complete remission was observed in two patients. One patient had recurrence afterwards but another patient survived 41 months without recurrence. Three patients survived more than 3 years. The overall 1-, 3-, and 4-year survival rates of the 13 patients were 67.7%, 40.6%, and 40.6%, respectively.Conclusions Volume reduction surgery followed by TAE might prolong the survival of patients with a large HCC and intrahepatic metastases, especially those with a main tumor on the right side.Source of support: this study was supported by grants-in-aid for cancer research from the Ministry of Health, Labour and Welfare of Japan.     

Successful laparoscopic distal pancreatectomy for a large solid pseudopapillary neoplasm: A case report

A 30‐year‐old Japanese woman presented at our hospital with a pancreatic tumor. Contrast‐enhanced CT revealed a tumor with a 12‐cm diameter in the pancreatic body and tail. In the preoperative setting, endoscopic ultrasound‐guided fine‐needle aspiration permitted a histopathological diagnosis of solid pseudopapillary neoplasm. Twhe patient underwent laparoscopic distal pancreatectomy with splenectomy. Our procedure involved three steps. Firstly, the splenic artery was occluded to block inflow of blood to the tumor. Then, we transected the neck of the pancreas using radical antegrade modular pancreatosplenectomy. Finally, hand‐assisted laparoscopic surgery allowed us to secure the operating field and easily handle the large tumor. This enabled us to accomplish laparoscopic distal pancreatectomy, and en‐bloc resection was completed. The patient was discharged without major complications. Laparoscopic distal pancreatectomy for huge solid pancreatic tumors can be completed safely.     

A case of thrombus of the descending aorta successfully diagnosed on preoperative endoscopic ultrasonography

A 45-year-old woman presented with left lower abdominal pain. A plain CT scan showed a slightly high-density, cord-like structure extending from the level of the diaphragm of the descending aorta to the superior mesenteric artery. Transgastric endoscopic ultrasonography (EUS) revealed a floating mass, smoothly attaching to the aortic intima and depicted as a hyperechoic region containing a mixture of hyperechoic and hypoechoic areas. EUS elastography revealed that the body of the mass consisted of medium soft tissue, with hard tissue at its base. On histopathological examination after surgery, the mass was found to consist mainly of fibrin, with no atypical cells. EUS examination should be used for the differential diagnosis between thrombi and tumors in the aorta.     

TAFI polymorphisms at amino acids 147 and 325 are not risk factors for cerebral infarction

Thrombin-activatable fibrinolysis inhibitor (TAFI) was reported as an anaphylatoxin-inactivating enzyme generated by proteolytic cleavage of its zymogen, and is the same enzyme as that first designated by our group as procarboxypeptidase R (proCPR). Its level in plasma appears to influence vascular disease. In addition, TAFI activity is strongly influenced by genetic polymorphism, especially at amino acids 147 and 325. We investigated whether these TAFI polymorphisms would act as a risk factor for cerebral infarction (CI) by examining 253 samples in which the diagnosis was cliniconeuropathologically confirmed. We found little that was statistically significant in terms of these polymorphisms among patients with no vascular problems or in a population-based control group. In the present study of an elderly Japanese group, our samples revealed a lower percentage of the Ile allele at Thr/Ile-325 compared with western counterparts. Although patients with severe infarcts had a lower percentage of the Ile allele (10%) at amino acid position 325 compared with the slightly and moderately affected patients and the population-based control group (15-18%), no statistical significance was found. None of our results showed any statistical correlation between TAFI polymorphisms and CI.