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.     

A case of intraductal papillary mucinous neoplasm with internal pancreatic fistula causing left ureteral obstruction]

A 75-year-old man had been admitted to another hospital because of left abdominal pain, and was given a diagnosis of left hydronephrosis and acute pancreatitis. After a JJ stent insertion and medication, he was transferred to our hospital for further examinations. US and EUS revealed a chronic pancreatitis-like pattern and multicystic lesion in the pancreas head and body. At that time enhanced CT findings showed an extrapancreatic low density area to be inflammatory change, extending from the pancreas body to the left crus of the diaphragm and posteriorly the spreading from the left crus of the diaphragm via the left urinary duct into the left iliopsoas muscle, in which MRI revealed partial high intensity. ERCP and MRCP showed focal irregular narrowing of the pancreatic duct of unknown cause, and we decided that an internal pancreatic fistula due to pancreatitis had induced left ureteral obstruction, caused by a protein plug or alcohol. Follow-up 6 months later showed that extrapancreatic spreading of the low density area had markedly regressed without any change in the ureteral obstruction.     

Association of sixty-one non-synonymous polymorphisms in forty-one hypertension candidate genes with blood pressure variation and hypertension.

We previously selected a group of hypertension candidate genes by a key word search using the OMIM database of NCBI and validated 525 coding single nucleotide polymorphisms (SNPs) in 179 hypertension candidate genes by DNA sequencing in a Japanese population. In the present study, we examined the association between 61 non-synonymous SNPs and blood pressure variations and hypertension. We used DNA samples taken from 1,880 subjects in the Suita study, a population-based study using randomly selected subjects. Analyses of covariance adjusting for age, body mass index, hyperlipidemia, diabetes, smoking, drinking, and antihypertensive medication revealed that 17 polymorphisms in 16 genes (APOB, CAST, CLCNKB, CTNS, GHR, GYS1, HF1, IKBKAP, KCNJ11, LIPC, LPL, P2RY2, PON2, SLC4A1, TRH, VWF) were significantly associated with blood pressure variations. Multivariate logistic regression analysis with adjustment for the same factors revealed that 11 polymorphisms in 11 genes (CAST, CTLA4, F5, GC, GHR, LIPC, PLA2G7, SLC4A1, SLCI8A1, TRH, VWF) showed significant associations with hypertension. Five polymorphisms in five genes, CAST(calpastatin), LIPC (hepatic lipase), SLC4A1 (band 3 anion transporter), TRH (thyrotropin-releasing hormone), and VWF (von Willebrand factor), were significantly associated with both blood pressure variation and hypertension. Thus, our study suggests that these five genes were susceptibility genes for essential hypertension in this Japanese population.     

A novel method to estimate the contribution of the vapor activity of essential oils in agar diffusion assay.

By the combined use of agar diffusion, agar vapor and agar vapor-inhibitory assays, contribution of the vapor activity of essential oils was quantitatively estimated. The test organisms were Trichophyton mentagrophytes and Aspergillus fumigatus. Agar vapor assay was used to confirm the vapor activity of the oils. The parameter delta defined as a contribution index of the vapor activity was calculated by (1 - b-c/a-c) x 100, where a is inhibitory diameter in the diffusion assay, b is inhibitory diameter in the vapor-inhibitory assay and c is diameter of the sealed ring in the vapor-inhibitory assay (21 mm). Many of the essential oils examined showed a delta value near 100, thus providing the major contribution of the vapor activity to the inhibitory diameter. Essential oils containing aldehyde as major constituent showed low delta value, indicating the major inhibition was due to agar diffusion. Major essential oil components behaved similarly; the delta value was increased in the following order: aldehyde < phenol < alcohol < ester, oxide, hydrocarbon, indicating the enhanced contribution of the vapor activity in that order.     

Prognostic value of blood glucose in patients with cardiogenic shock.

BACKGROUND: Although an elevated blood glucose has prognostic value in cardiovascular disease, few data are available regarding its prognostic value for patients across the spectrum of cardiogenic shock. METHOD AND RESULTS: A total of 81 patients with cardiogenic shock whose blood glucose and adrenaline were measured on arrival at the emergency room (ER) were enrolled in this prospective study. The primary endpoint was death from any cause in hospital. The rate of death was 12.3% (10/81), and the glucose level was lower among patients who were discharged alive than among those who died (8.7+/-3.7 mmol/L vs 13.8+/-6.7 mmol/L, p<0.001). The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of glucose level (p<0.05). The blood glucose level of 9.2 mmol/L had the highest combined sensitivity and specificity for the identification of death. In the multiple logistic-regression analysis for the primary outcome, the adjusted odd ratio for a glucose level of 9.2 mmol/L or more was 5.8 (95% confidence interval, 1.0-32.8, p=0.047). There was a significant positive correlation between the glucose and adrenaline levels (R=0.726, p<0.0001). CONCLUSION: The measurement of blood glucose level on ER arrival provides predictive information for use in risk stratification across the spectrum of cardiac emergencies complicated by cardiogenic shock.     

A Case of Glucagonoma with Liver Metastasis: Complete Response to Dacarbazine

Abstract: We report a case of glucagonoma syndrome with liver metastasis, who responded completely to dacarbazine chemotherapy. A 77-year-old woman complained of itching skin eruptions (diagnosed as necrolytic migratory erythema) and weight loss. She was found to have glucose intolerance, anemia, hypoproteinemia and hyperglucagonemia. Abdominal CT and celiac arteriography showed a hypervascular tumor in the pancreatic tail and a metastatic tumor in the left hepatic lobe. Immunohistochemical examination of the metastatic liver tumor obtained by laparoscopic biopsy revealed the tumor cells to be positive for glucagon. The patient was treated with 20 courses of 300 mg/day intravenous dacarbazine for 5 consecutive days followed by a 4 week drug-free interval. No major side effects were noted. Treatment resulted in disappearance of the skin lesions and correction of anemia, glucose intolerance, hypoproteinemia and hyperglucagonemia. Follow-up abdominal CT showed complete resolution of both the primary pancreatic tumor and the metastatic liver tumor. We suggest that dacarbazine be considered as the treatment of choice for metastatic glucagonoma.     

Studies on the polymerization of bifunctional monomers. XVII. Cyclopolymerization of malealdehyde and the structure of the polymer

Polymerizations of malealdehyde were carried out with alkalimetal alkoxides, AlEt₃, pyridine, AlEt₃? TiCl₄ and BF₃OEt₂ as catalysts. All the polymers obtained with other catalysts than AlEt₃ and AlEt₃? TiCl₄ were composed only of the cyclized unit (dialkoxydihydrofuran ring) (> 95%) and the 1.2-addition structure (< 5%). IR spectra of the polymers obtained with AlEt₃ and AlEt₃? TiCl₄ catalysts were suggestive of the presence of five-membered lactone rings which may occur as a result of termination by hydride transfer. The steric structure (cis vs. trans) of the dialkoxydihydrofuran ring in polymer was inferred from the comparison of the IR spectra of the polymer with those of the isomeric dialkoxydihydrofurans in the 800 cm^?1 region. Anionic catalysts gave higher contents of the cis configuration, while coordinated anionic catalysts gave comparable amounts of the cis and trans structures.     

HLA class I distribution in Japanese patients with schizophrenia

Several Caucasian studies and one Japanese study have observed associations between human leukocyte antigen (HLA) class I specificities, including A24 (9) and A26 (10) and schizophrenia. Most of those studies were conducted in 1970s and early 1980s, when the typing technique of HLA was not adequately reliable. Also, an operational diagnostic system was not employed in many of the studies. The present study investigated frequencies of HLA-A specificities in schizophrenia patients (ICD-10 and DSM-III-R, n=98) and sex-matched healthy controls (n=392) from population in the southwestern part of Japan. HLA-B and -C specificities were studied in addition. Frequencies of subjects possessing A24 and A26 were not different between the patients and controls (54% and 24% in the patients and 62% and 24% in the controls, respectively). No significant difference was found in frequencies of other class I (A, B, and C) specificities between the patients and the controls. Thus, the present study provided no evidence for an association between the HLA class I specificities, including A24, A26, and others, and schizophrenia in the Japanese population.     

Sinus Histiocytosis With Massive Lymphadenopathy A Histogenic Analysis of Histiocytes Found in the Fourth Japanese Case

The present paper deals with immunohistochemical and ultrastructural study of the lymph nodes of sinus histiocytosis with massive lymphadenopathy (Rosai and Dorfman, SHML) of a 12-year-old Japanese boy. This is the fourth case in Japan. Osseous manifestation was also found in the bilateral ulnae. With hallmarks of S-100 protein and interdigitating cytoplasmic extensions, the phagocytizing histiocytes proliferating in the sinuses were considered to be derived mostly from interdigitating cells in the paracortex or T cell dependent area, which have heretofore been regarded as nonphagocytizing. Furthermore, it is most interesting that lymphoid cells bearing thymic cortical cell-antigen (OKT 6) were increasingly recognized in the patient's peripheral blood. These results suggested that SHML is a specialized reactive histiocytosis analogous to histiocytosis X and histiocytic medullary reticulosis.