Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Glossopharyngeal neurinoma causing symptomatic hemorrhage: case report

A 86-year-old man was admitted to our hospital because of swallowing disturbance and deterioration of consciousness. He had been aware of hearing disturbance on the right side for twelve months. Computed tomography (CT) scan demonstrated an inhomogeneous hyperdense mass lesion, 3.2 X 2.3 cm in size, at the right cerebello-pontine angle, and ventricular enlargement with intraventricular hemorrhage. Skull tomogram revealed destructive enlargement of the right jugular foramen. The angiogram showed avascular mass with elevation of anterior inferior cerebellar artery, and downward shift of posterior inferior cerebellar artery. Operative and histological findings were compatible with glossopharyngeal neurinoma of Antoni type A dominance. This tumor had numerous abnormal vessels probably causing massive hemorrhage. Only fifteen cases of intracranial neurinoma with symptomatic hemorrhage have been reported in the world literature. This case is reported as the sixteenth one and the first glossopharyngeal neurinoma among them. Possible etiology of such hemorrhage is discussed.     

An elderly case of idiopathic retroperitoneal fibrosis]

An elderly case of idiopathic retroperitoneal fibrosis (IRPF) with bilateral ureteral obstruction was reported. A 74-year-old man was admitted with complaints of general fatigue and loss of appetite. An elastic hard mass with a smooth surface was palpated in the left upper quadrant of the abdomen. Abnormal ESR and CRP were noticed. Abdominal ultrasonography showed both a homoechoic mass which surrounded the aorta in the retroperitoneal space and bilateral hydronephrosis. Computed tomography revealed a retroperitoneal mass involving bilateral ureters. Magnetic resonance imaging demonstrated a mass with a sharp image and signal intensity. Furthermore the morphological relationship between the mass and the ureters and major vessels clearly indicated the characteristics of benign retroperitoneal fibrosis. Based upon the above findings, a diagnosis of IRPF was made. After confirming the histological diagnosis by biopsy, treatment consisting of bilateral ureterolysis, intra-abdominal transposition of ureters and oral administration of prednisolone was performed, resulting in a normalization of laboratory findings. Analysis of 86 previously cases of IRPF reported up to 1990 in Japan, revealed the peak age to be in the 7th decade with predominance in males (males: females = 57:29).     

Acute type a aortic dissection complicated with acute inferior myocardial infarction following aortic valve replacement

Acute aortic dissection complicated with acute myocardial infarction (AMI) is the most fatal situation. We experienced the successful treatment for acute type A aortic dissection complicated with inferior AMI following aortic valve replacement (AVR). A 60-year-old man had had AVR for aortic regurgitation. Sixteen months after the AVR, he had a sudden onset of severe chest pain with complete atrioventricular block. Immediately, temporary pacing and cardiac catheterization were conducted, showing the occlusion of the right coronary artery due to acute type A aortic dissection. On his way to our hospital, direct current shock was conducted 3 times for ventricular fibrillation. We replaced the ascending aorta combined with coronary artery bypass grafting and the postoperative course was uneventful. The key to treat acute aortic dissection complicated with AMI is early accurate diagnosis, prompt temporary pacing for bradycardia, defibrillation for lethal arrhythmia and insertion of a perfusion catheter if possible. These preoperative hemodynamic stabilization gives us the chance to save these patients.     

Feeding behavior and ambulatory activity in rats with D-galactosamine-induced hepatic failure.

This study was undertaken to investigate changes in feeding behavior and ambulatory activity, in rats with D-galactosamine (D-GAL)-induced hepatic failure. D-GAL was administered (1000 mg/kg) IP at 1800, just before the dark phase. The first significant decrease of ambulatory activity in rats with hepatic failure was observed between 0000 and 0300 h. A significant increase in drinking behavior was observed between 1800 and 2100 h, and a significant decrease was observed between 2100 and 0300 h. A significant decrease in food intake occurred between 1800 and 2400 h. Thereafter, there was no difference in food intake. In conclusion, we demonstrated significant changes in ambulatory activity, drinking behavior and food intake produced by D-GAL. A wide variation in systems, including monoamine turnover, and amino acid disturbance could be expected in these animals, and such changes might also have contributed to the results observed.     

Effects of personal controls on cortisol secretion during stress processes

This study investigated effects of personal control on psychobiological stress responses. Salivary cortisol was used as an index of hypothalamic pituitary-adrenocortical axis response. Healthy males (N = 20) were exposed five times serially to a psychosocial stressor: mental arithmetic under time pressure. "Chance control", "other powerful controls" and "internality" were reported personality-dependent aspects of personal controls; "personal control as coping" under the psychosocial stress situation was also assessed with a questionnaire after the session ended. Cortisol response showed significant increase (F (16,304) = 6.69, p < 0.01). From the view point of personality, the high "chance control" score group showed higher levels of cortisol compared to the low score group before stressful tasks. On the other hand, the high "personal control as coping" score group showed higher levels of cortisol compared to the low score group after the stressful tasks. We inferred that the high "personal control as coping" score group conducted stressful tasks with high concentration and effort. The effects of such personal controls as personality and as ways of coping were demonstrated in this experiment through cortisol secretion in different stress-process phases.     

Excimer laser coronary atherectomy prior to paclitaxel-coated balloon angioplasty for de novo coronary artery lesions

This study aimed to evaluate the efficacy and safety of excimer laser coronary atherectomy (ELCA) prior to paclitaxel-coated balloon angioplasty for de novo coronary artery lesions. This retrospective observational study analyzed 118 eligible patients with de novo coronary artery disease whose only percutaneous coronary intervention was a drug-coated balloon angioplasty (i.e., no subsequent stent placement). Data related to our primary outcomes of interest—incidence of major adverse cardiovascular and cerebral events (MACCE), and incidence of procedural complications (bailout stenting and minor complications)—were collected and retrospectively analyzed. ELCA was used significantly more often in the cases of main branch and ostial lesions (i.e., of the circumflex, right coronary, or left anterior descending arteries, or high lateral branch), normally associated with poor treatment outcomes (55.6% vs. 14.3%, p < 0.0005). However, the two groups were not different in terms of cumulative incidence as estimated by the Kaplan–Meier method (log-rank test, p = 0.603) and a causal relationship between ELCA and MACCE was not identified (OR, 2.223; 95% CI, 0.614–8.047; p = 0.223). This study confirms the safety of ELCA prior to paclitaxel DCB angioplasty to treat de novo coronary artery lesions. While difficult-to-treat lesions were significantly more prevalent in the group treated by ELCA, the study revealed similar efficiency as conventional pre-dilation methods. Our findings provide grounds for a prospective randomized trial with consistent lesion and procedural characteristics to evaluate the potential benefits of combining paclitaxel DCB angioplasty following ELCA for de novo coronary artery lesions.

     

Redifferentiation as a basis for remodeling of carcinogen-induced hepatocyte nodules to normal appearing liver

A system is described for the detailed study of the remodeling of hepatic nodules that appear regularly during liver carcinogenesis with chemicals. With the use of the resistant hepatocyte model and by focusing on the caudate lobe, it has been possible to label with [3H]thymidine all the hepatocytes in hepatocyte nodules without any significant degree of labeling of the surrounding hepatocytes. Through such a model, the persistence of the label, in relation to the organization and appearance of the hepatocytes in the nodules, has been followed for 26 weeks. Nodules do not "disappear" to any significant degree by regression or by replacement with hepatocytes from the surrounding liver. Rather, nodule hepatocytes undergo differentiation to an adult liver phenotype. Thus, differentiation ("redifferentiation") of a carcinogen-induced altered hepatocyte population is seen regularly during carcinogenesis despite the irreversible nature of some of the changes induced by a chemical carcinogen during initiation.     

Dietary orotic acid enhances the incidence of {gamma}-glutamyltransferase positive foci in rat liver induced by chemical carcinogens

Feeding male Fischer F-344 rats for 5 weeks a diet containing1% orotic acid, a precursor for pyrimidine nucleotide biosynthesis,resulted in an increased incidence of -glutamyltrans-ferase(EC 2.3.2.2 [EC] ) positive foci induced by chemical carcinogens including1,2-dimethylhydrazine, diethylnitrosamine, benzo[a]pyrene, andaflatoxin B₁. This unique effect of orotic acid can be accentuatedby supplying a liver cell proliferative stimulus. The enzymealtered hepatocytes have a higher labelling index (4.4%) comparedwith that of the hepatocytes in the surrounding liver (0.26%).The effect of orotic acid on the increased incidence of focicannot be attributed to either the induction of liver cell proliferationor the imposition of a preferential inhibitory effect on theproliferation of normal hepatocytes while permitting the carcinogen-modifiedhepatocytes to respond to an endogenous or exogenous liver cellproliferative stimulus and grow to form foci. Orotic acid alsodid not behave like some of the promoters of liver carcinogenesissuch as phenobarbital and polychlorinated biphenyls in thatit did not induce either the phase I or phase II componentsof hepatic drug metabolizing enzyme systems. Some of the possiblemechanisms by which orotic acid enhances the incidence of -glutamyltransferasepositive foci by carcinogens are discussed.