Genetic analysis of Brugada syndrome in Western Japan: two novel mutations.

BACKGROUND: Brugada syndrome is a form of idiopathic ventricular fibrillation characterized by right bundle-branch block pattern and ST elevation in the right precordial leads of the ECG. The SCN5A gene encodes the alpha-subunit of the human heart sodium channel, which plays a critical role in cardiac excitability, and mutations of SCN5A could underlie Brugada syndrome. METHODS AND RESULTS: To detect mutations of SCN5A, DNA samples from 12 Japanese patients with Brugada syndrome were analyzed using direct sequencing. Two patients had novel mutations, G292S and S835L, but no other mutations of SCN5A were detected in the remaining patients. The first mutation, G292S, was identified adjacent to the pore-lining region between the DIS5 and DIS6 transmembrane segments of SCN5A, and the second mutation, S835L, was in the intracellular loop connecting the DIIS4 to DIIS5. Both mutations were not detected in 100 unrelated control subjects. CONCLUSION: Two novel SCN5A mutations have been found in Japanese patients with Brugada syndrome.     

Extracranial-intracranial bypass for internal carotid/middle cerebral atherosclerotic steno-occlusive diseases in conjunction with carotid endarterectomy for contralateral cervical carotid stenosis: clinical results and cognitive performance

Clinical results as well as cognitive performances after extracranial to intracranial (EC-IC) bypass in conjunction with contralateral carotid endarterectomy (CEA) are poorly understood. Data from 14 patients who underwent unilateral EC-IC bypass for atherosclerotic internal carotid artery (ICA)/middle cerebral artery (MCA) steno-occlusive disease in conjunction with CEA for contralateral cervical carotid stenosis were retrospectively reviewed. Postoperative results were evaluated by MRI imagings. Nine patients also underwent neuropsychological examinations (NPEs), including assessment by the Wechsler Adult Intelligence Scale-Third Edition and the Wechsler Memory Scale-Revised (WMS-R) before and about 6 months after bilateral surgeries. Postoperative MRI follow-up (median, 8 months; interquartile range, 7–8 months) confirmed successful bypass in all patients, with no additional ischemic lesions on T2WI when compared with preoperative imaging. Further, MRA showed patent bypass and contralateral smooth patency at CEA portion in all patients. In the group rate analysis, all five postoperative NPE scores (Verbal IQ, Performance IQ, WMS-memory, WMS-attention, and Average scores of all those four scores) were improved relative to preoperative NPE scores. Performance IQ and Average score improvements were statistically significant. Clinical results after EC-IC bypass in conjunction with contralateral CEA were feasible. Based on the group rate analysis, we conclude that successful unilateral EC-IC bypass and contralateral carotid endarterectomy does not adversely affect postoperative cognitive function.     

Design, synthesis, and discovery of a novel CCR1 antagonist

The CC chemokines may play an important role in the pathogenesis of chronic inflammatory diseases including rheumatoid arthritis, and their effects are thought to be mediated through CCR1 receptors. Several nonpeptide CCR1 receptor antagonists that showed high affinity for human CCR1 receptors have been identified; however, their effectiveness in animal models of inflammatory diseases has been scarcely demonstrated, probably due to species selectivity of the antagonists. To elucidate the pathophysiological role of CCR1 receptors in murine models of disease, we looked for a potent antagonist for both murine and human CCR1 receptors. Screening of our chemical collection for inhibition of (125)I-MIP-1alpha binding to human CCR1 receptors transfected in CHO cells led to the identification of xanthene-9-carboxamide 1a as the lead compound. Derivatization of 1a by quaternarizing the piperidine nitrogen with various alkyl groups and by installing substituents into the xanthene moiety dramatically improved the inhibitory activity against both human and murine CCR1 receptors. As a result, 2q-1 showing IC(50) values of 0.9 and 5.8 nM for human and murine CCR1 receptors, respectively, was discovered. This compound is the first murine CCR1 receptor antagonist and may be a useful tool for clarifying the role of CCR1 receptors in murine models of disease.     

Relationship between body mass index and infertility in healthy male Japanese workers: a pilot study

Our aim was to evaluate the relationship between men’s body mass index (BMI) and infertility and to examine the effects of factors related to metabolic syndrome such as hypertension, dyslipidaemia, and impaired glucose tolerance. Our sample comprised 74 healthy Japanese workers at a company who were married between 2003 and 2005. The outcome variable was whether a baby was born during the study period (median follow‐up period, 20 months; range, 8–42 months). Data for BMI and other factors were obtained from the results of an annual health checkup in the year of each employee’s marriage. Forty‐seven men (64%) did not father a baby. Having a baby was significantly associated with a low BMI (21.4 versus 23.2 kg m^?2; P = 0.006). A Cox proportional hazard regression model was performed to assess the association of BMI with fathering a baby. Adjusting for age, systolic and diastolic blood pressure, low density lipoprotein cholesterol, triglycerides, and haemoglobin A_1C, higher BMI was significantly associated with not fathering a baby (hazard ratio, 0.80; 95% confidence interval, 0.67–0.95; P = 0012). High BMI in men was independently associated with an increased risk of not siring a child.     

Intestinal tuberculosis of the terminal ileum causing obstructive ileus and tuberculous peritonitis and presenting numerous peritoneal small red nodules: a case report

A 38-year-old woman suffering from lower abdominal pain was referred to our hospital. Abdominal computed tomography showed marked thickening of the terminal ileum to the cecum, localized collection of ascites, and multiple mesenteric lymphadenopathy. A barium contrast small bowel series showed solitary severe stenosis of the terminal ileum with marked swelling of the ileocecal valve, where colonoscopy could not pass through, suggesting that ileal stenosis was caused by intestinal tuberculosis. She also showed strongly positive tuberculin skin test. Laparoscopy-assisted ileocecal resection was performed for confirmation of diagnosis and removal of the stenotic intestinal lesion. Laparoscopically, numerous small red nodules scattered on the stenotic ileal serosa, peritoneum, and mesenterium. Histopathological examination revealed ileal tuberculosis causing ulcerative stricture, and mesenteric tuberculous lymphadenitis. The small red nodules were formed of hemorrhagic tuberculous nodules.     

Induction by Lactobacillus casei of increase in macrophage colony-forming cells and serum colony-stimulating activity in mice

The content of macrophage colony-forming cells (M-CFC) and the serum colony-stimulating activity (CSA) were investigated in mice after intravenous administration of Lactobacillus casei YIT9018 (LC9018). In normal BALB/c mice, 500 micrograms of LC9018 increased both femoral and splenic M-CFC; the highest levels were found a few days and a week, respectively, after the administration. LC9018 also induced an increase in splenic M-CFC in C3H/HeJ mice as well as in C3H/HeN mice, unlike lipopolysaccharide (LPS), which was ineffective in C3H/HeJ mice. In Meth A-bearing BALB/c mice, LC9018 (250 micrograms X 5) suppressed the growth of tumor cells and increased femoral and splenic M-CFC to much greater extents than Lactobacillus plantarum YIT0102 (250 micrograms X 5) did. LC9018 induced a rise of serum granulocyte-macrophage CSA in the same way as LPS. Sera taken 6 hr after LPS administration, when transferred to normal mice, induced increases in femoral and splenic M-CFC. However, sera taken 6 hr after LC9018 administration increased neither femoral nor splenic M-CFC. These results indicate that LC9018 modulates myelopoiesis at least at the stage of the proliferation of M-CFC in a different way from LPS, and this ability may be related to its antitumor activity.     

Hemodynamic difference accounted for the orientation of a Bj?rk-Shiley mitral prosthesis: a color Doppler echocardiographic study]

To determine whether the orientation of the major orifice of a mitral tilting disc prosthesis affects hemodynamics, intracavitary blood flow patterns were studied in 45 patients with well-functioning Bj?rk-Shiley mitral prosthesis using color Doppler flow imaging. The major orifice was oriented towards the septum in 23 patients (12 men, 11 women, age 58 +/- 11 years; group S), and towards the posterior wall in 22 patients (8 men, 14 women, age 55 +/- 9 years; group P). 1) The left ventricular end-diastolic dimensions (S: 4.8 +/- 0.9 cm, P: 5.2 +/- 1.0 cm), end-systolic dimensions (S: 3.6 +/- 0.9 cm, P: 3.8 +/- 1.2 cm), and left atrial dimensions (S: 5.0 +/- 1.0 cm, P: 4.7 +/- 0.9 cm) did not differ significantly between the 2 groups. 2) The peak mitral flow velocities (S: 1.43 +/- 0.38 m/sec, P: 1.43 +/- 0.27 m/sec), pressure gradients (S: 8.5 +/- 4.0 mmHg, P: 8.4 +/- 3.1 mmHg), and pressure half-times (S: 94.0 +/- 19.0 msec, P: 86.5 +/- 21.7 msec) did not differ significantly between the 2 groups. 3) Although mitral regurgitation was detected in 8 patients (35%) in the S group and in 2 patients (9%) in the P group, hemodynamically significant regurgitation was detected in only 4 patients in the S group (3 mild, one moderate). 4) The patients in the S group had reversed intracavitary blood flow; mitral flow was first directed towards the left ventricular outflow tract during diastole, while the outflow pattern was displaced into the left ventricular inflow tract.(ABSTRACT TRUNCATED AT 250 WORDS)     

Crystallization of excipients in tablets

Whisker-like crystals appeared on the surface of tablets that contained lactose or mannitol, a hygroscopic material such as docusate sodium, magnesium chloride, or potassium acetate, and other ingredients stored in an atmosphere of high relative humidity. The crystals were observed under a scanning electron microscope and were measured using differential scanning calorimetry and TLC. The crystals contained lactose or mannitol.