RNAi screening of human glycogene orthologs in the nematode Caenorhabditis elegans and the construction of the C. elegans glycogene database.

In this study, we selected 181 nematode glycogenes that are orthologous to human glycogenes and examined their RNAi phenotypes. The results are deposited in the Caenorhabditis elegans Glycogene Database (CGGDB) at AIST, Tsukuba, Japan. The most prominent RNAi phenotypes observed are disruptions of cell cycle progression in germline mitosis/meiosis and in early embryonic cell mitosis. Along with the previously reported roles of chondroitin proteoglycans, glycosphingolipids and GPI-anchored proteins in cell cycle progression, we show for the first time that the inhibition of the functions of N-glycan synthesis genes (cytoplasmic alg genes) resulted in abnormal germline formation, ER stress and small body size phenotypes. The results provide additional information on the roles of glycoconjugates in the cell cycle progression mechanisms of germline and embryonic cells.

Additive antihypertensive and antihypertrophic effects of long-acting Ca blockers in uncontrolled hypertensive patients with angiotensin-receptor blocker based treatment.

The aim of the present study was to examine the antihypertensive and antihypertrophic effects of combined treatment with a long-acting calcium antagonist on top of an angiotensin II receptor blocker (ARB) in uncontrolled hypertensive patients. Patients with essential hypertension and a blood pressure > 140/90 mmHg on ARB monotherapy (losartan 50 mg/day or candesartan 8 mg/day) were randomly assigned to a nifedipine controlled release (CR) group (n = 15) or amlodipine group (n = 11). A significant additional antihypertensive effect was noted from 1 month with nifedipine and 2 months with amlodipine. The average daily dose was 25 mg for nifedipine and 5 mg for amlodipine. The cardiothoracic ratio was significantly reduced in both groups after 3 months. Left ventricular wall thickness and left ventricular mass index also decreased. Metabolic parameters, hepatic function, and renal function did not change significantly. Additional treatment with a long-acting calcium antagonist achieved further blood pressure reduction as well as an antihypertrophic effect in the uncontrolled patients with prior ARB monotherapy.

Prognostic factors for the long-term survival in patients with vasospastic angina--analysis of effects of patients' characteristics and therapeutic drugs.

OBJECTIVES: A retrospective study was conducted to elucidate contributing factors on the outcome of patients with vasospastic angina. SUBJECTS AND METHODS: Two hundred ninety-two patients with angina in whom coronary vasospasm was documented were followed up (mean 4.3+/-3.6 years) to determine the relationship between the occurrence of cardiovascular events with available clinical factors including therapeutic drugs. Cardiovascular events were defined as fatal and non-fatal cardiovascular disorder events. RESULTS: Several clinical variables including age, elevated creatinine level, low high-density lipoprotein (HDL) cholesterol level, presence of severe coronary artery stenosis, low left ventricular ejection fraction, low cardiac index (CI), large left ventricular mass, and use of beta-blockers proved to be significant risk factors for cardiovascular events. Further analysis by a stepwise regression analysis revealed that, older age (hazard ratio (HR)=1.42), low HDL cholesterol level (HR=0.877), presence of severe coronary artery stenosis (HR=49.32), and decreased CI (HR=14.18) proved to be independent prognostic factors. Ca antagonists were prescribed to 261 patients (89.4%). Among four Ca antagonists, there were significant differences in the frequency of cardiovascular events (2.6% with benidipine, 4.2% with nifedipine, 6.0% with diltiazem, 23.1% with amlodipine; amlodipine vs. benidipine, P<0.05) although the background characteristics of the four different patient groups were non-equivalent. CONCLUSION: These results indicate that the morbidity of patients with vasospastic angina increased with older age, lower CI or HDL cholesterol, and presence of severe coronary artery stenosis, and that treatment with benidipine appeared to reduce cardiovascular events in patients with vasospastic angina.

Increased carotid artery plaque score is an independent predictor of the presence and severity of coronary artery disease.

OBJECTIVES: Carotid ultrasonography is noninvasive and effective for the assessment of atherosclerotic lesions. The relationship between carotid ultrasound findings and presence and severity of coronary artery disease (CAD) was examined in Japanese patients. METHODS AND RESULTS: Subjects were 116 patients who underwent carotid ultrasonography and coronary angiography. In carotid ultrasonography, mean-intima-media thickness (IMT), common carotid artery max IMT, bifurcation max IMT, plaque number, and plaque score (PS). The coronary angiographic data was obtained in the same period as carotid ultrasonography was performed. Patients were divided into two groups based on the presence or absence of coronary artery stenosis (CAS and non-CAS) and CAS group was further categorized into three groups, 1 vessel disease (1VD), 2VD, and 3VD. Physical findings, biochemical data, and carotid ultrasonogram data between the groups were compared. Items showing a significant difference between CAS and non-CAS were age, gender (male), incidence of diabetes and dyslipidemia, fasting blood sugar (FBS), triglyceride, HDL-cholesterol (HDL-C), high-sensitivity C-reactive protein, and all carotid ultrasound findings. All of the above parameters also showed a significant difference between four different severity groups. Stepwise logistic regression analysis was performed to determine which factors predict the presence and/or severity of CAS. High PS showed the strongest predictive value for both and followed by low HDL-C and high FBS. The cut-off value of PS obtained by receiver operating characteristic curve for predicting the presence of CAS was 1.9. CONCLUSIONS: Assessment of PS by carotid ultrasonography together with other risk factor assessment was clinically relevant to predict the presence and severity of CAS.

Left main coronary trunk connecting into right atrium with an aneurysmal coronary artery fistula.

Congenital coronary artery fistula (CAF) is an infrequent vascular anomaly that establishes a direct link between an epicardial coronary artery and a cardiac chamber, major vessels, or other vascular structures. In this case there was an aneurysmal-CAF between a left main trunk and the right atrium, which was initially diagnosed as a Kawasaki disease by transthoracic echocardiography and subsequently confirmed by coronary angiography and multi-slice CT angiography. A multi-slice CT angiography might well become the modality of choice for the characterization of these rare congenital anomalies.

Atrial septal defect in apical hypertrophic cardiomyopathy associated with coronary spasm.

Apical hypertrophic cardiomyopathy (HCM) is a well-known myocardial disease, but the additional coexistence of an atrial septal defect (ASD) and coronary spasm is quite rare. We report here on a 62-year-old man suffering from congestive heart failure due to apical HCM complicated by coronary spasm and secundum-type ASD. The transthoracic, transesophageal echocardiography and cardiac catheterization were useful for diagnosing and evaluating of the patient's status. A calcium channel blocker was given to prevent coronary spasm, and a surgical patch closure operation was successfully performed. Afterwards, his symptoms were alleviated.

Successful catheter ablation of ventricular tachycardia originating from the idiopathic saccular apical left ventricular aneurysm.

Left ventricular (LV) aneurysm has been recognized to frequently become a substrate of ventricular tachyarrhythmias. We report a case of a 66-year-old woman with symptomatic sustained monomorphic ventricular tachycardia (SMVT) originating from saccular apical LV aneurysm without definite underlying diseases. We performed catheter ablation using electroanatomical and conventional bipolar potential mapping. During SMVT, we found an area of fragmented potential -40 ms preceding the earliest wide QRS complex in the area of the apical LV aneurysm. Radiofrequency applications were delivered to this area. Since then, SMVT was no longer inducible by programmed electrical stimulation. The patient has remained free of VT recurrences during a subsequent 12-month follow-up period.