Analysis of the core region of HCV genome isolated from patients with chronic hepatitis C during intervals of normal ALT concentration

We determined the core region nucleotide and amino acid sequences in specimens from two patients with chronic hepatitis C during intervals of normal and elevated alanine aminotransferase (ALT) concentrations. When the ALT concentrations remained normal, the serum HCR-RNA concentration exceeded that before therapy and most of the clones that could be sequenced had a deletion or an amber mutation. The clones isolated from a HLA B44-positive patient had a mutation at amino acid 91. These results suggest that expression of the wild-type HCV core region genome may be associated with liver cell damage.     

Response of the left anterior descending coronary artery to acetylcholine in patients with chest pain and angiographically normal coronary arteries

Because atherosclerotic plaque burden affects the likelihood of plaque rupture, it is important to determine the presence and extent of atherosclerotic plaque. We hypothesized that endothelial dysfunction becomes more prominent with development of atherosclerotic plaque; therefore, we examined the relation between coronary endothelial dysfunction and the presence of atherosclerotic plaque. In 36 patients with normal coronary arteries, acetylcholine (ACh; 3 and 30 μg/min) and nitroglycerin were infused into the left coronary ostium, and the diameter of the left anterior descending (LAD) coronary artery was quantitatively measured in response to each drug. The plaque burden was measured in the same segment using intravascular ultrasonography. The plaque burden was 31.2 ± 2.1% and correlated inversely with changes in coronary diameter induced by 3 μg/min of ACh (r = −0.754, p <0.0001), 30 μg/min of ACh (r = −0.552, P = 0.0005), and nitroglycerin (r = −0.531, P = 0.0009). Multivariate regression analysis showed that the change in coronary diameter induced by 3 μg/min of ACh was associated with plaque burden, independent of the effects of nitroglycerin-induced dilation. Receiver-operating characteristics analysis demonstrated that a cut-off value for the change in coronary diameter induced by 3 μg/min of ACh for predicting a plaque burden of>30% was 0%, with a sensitivity of 0.82 and a specificity of 0.95. These findings suggest that coronary endothelial dysfunction is correlated with atherosclerotic plaque burden, indicating that atherosclerotic plaque may be detected based on coronary endothelial function as assessed by low-dose ACh infusion.     

Two patients with acute hepatitis B with suspected sexual transmission of hepatitis G virus

Two patients with acute hepatitis B with suggested sexual transmission of hepatitis G virus (HGV) are reported. A total of 18 patients with community acquired acute hepatitis B were analyzed in this study. Two of the 18 patients (patients 1 and 2) were positive for serum HGV RNA at the initial consultation. Both patients had had sexual contact with prostitutes several weeks before the onset of acute hepatitis, and hepatitis B virus (HBV) was suggested to be infected through the sexual contacts. These patients showed no other history of exposure to possible transmission routes for blood-borne hepatitis viruses. Patient 1 was diagnosed as with acute HGV infection because the antibody to HGV envelope-2 protein seroconverted to positive during the course of acute hepatitis. HGV RNA was negative in a serum sample collected from patient 2 before the onset of acute hepatitis, also suggesting acute HGV infection. These results indicate that in patients 1 and 2 HGV was infected along with HBV through sexual contact. The clinical manifestations of acute hepatitis in the two patients with HGV co-infection did not differ from those in the 16 patients with HBV infection alone. (Received Aug. 6, 1997; accepted Oct. 30, 1997)     

Echocardiographic prediction of left ventricular dysfunction after mitral valve repair for mitral regurgitation as an indicator to decide the optimal timing of repair

OBJECTIVES: This study sought to determine whether echocardiography before mitral valve repair (MVR) for mitral regurgitation (MR) was predictive of postoperative left ventricular (LV) dysfunction and useful for deciding the optimal timing of repair. BACKGROUND: Some reports have shown that the preoperative echocardiographic data of left ventricular ejection fraction (LVEF) and left ventricular end-systolic diameter (LVDs) were good predictors of postoperative LV dysfunction. However, few reports were based on long-term follow-up data of large numbers of patients who underwent MVR in the last decade. METHODS: A total of 274 patients with moderate or severe MR underwent MVR between October 1, 1991, and September 30, 2000. Among them, 171 patients who had both an operation for isolated MR due to degenerative pathology and a postoperative echocardiogram were studied. Postoperative echocardiograms were performed 3.9 +/- 2.4 years after the operation.The LVEF decreased from 66 +/- 10% before surgery to 63 +/- 11% after surgery (p < 0.0001). On univariate analysis, preoperative LVEF and LVDs correlated with postoperative LVEF (r = 0.41 and r = -0.39, respectively). Overall, postoperative LV dysfunction (defined as LVEF <50%) was not frequent (12%). However, the incidence of postoperative LV dysfunction was high in patients with preoperative LVEF <55% (38%) or LVDs > or =40 mm (23%). CONCLUSIONS: In patients with MR, the echocardiographic data of LVEF and LVDs were good predictors of postoperative LV dysfunction. When a decrease in LVEF or an increase in LVDs is detected, MVR should be considered to preserve postoperative LV function.     

The HNF-1α-SNARE connection

Maturity-onset diabetes of the young (MODY) is a monogenic form of type 2 diabetes mellitus that is characterized by impairment of glucose-stimulated insulin secretion from pancreatic β-cells. We previously reported that heterozygous mutations of the hepatocyte nuclear factor (HNF)-1α gene cause a form of MODY (MODY3). We have subsequently found that collectrin, a recently cloned kidney-specific gene of unknown function, is a novel target of HNF-1α in pancreatic β-cells. In addition, we have demonstrated that collectrin forms a complex with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex by direct interaction with snapin, a protein that is thought to be involved in neurotransmission by binding to synaptosomal-associated protein, 25 KD (SNAP25). Collectrin favours the formation of SNARE complexes and controls insulin exocytosis.     

Effects of liposteroid on the hemophagocytic syndrome in systemic lupus erythematosus

Hemophagocytic syndrome (HPS) is a life-threatening disorder characterized by pancytopenia and activation of macrophages. Recently, corticosteroid incorporated in lipid microspheres (liposteroid) has been reported to be taken up by macrophages and to suppress their functions. Here we present a case of systemic lupus erythematosus complicated by HPS that was successfully treated with liposteroid in addition to an oral corticosteroid and intravenous high-dose cyclophosphamide therapy. The serum levels of tumor necrosis factor-alpha and ferritin that have been reported to be associated with activity of macrophages remarkably reduced after liposteroid administration. This case suggests that liposteroid is useful for the treatment of HPS.     

Guidelines for the antiviral therapy of hepatitis C virus carriers with normal serum aminotransferase based on platelet counts.

Aim: We aimed to identify the candidates for antiviral therapy, among patients who are hepatitis C virus (HCV) carriers with normal serum aminotransferase (ALT), focused on the inhibition of hepatocellular carcinoma (HCC). Methods: Four hundred and sixty-four HCV carriers with normal serum ALT and 129 HCV carriers with persistently normal ALT (PNALT) and platelet (PLT) counts >/=150 000/muL who received liver biopsies were enrolled. HCV carriers with normal serum ALT were divided into four groups according to their ALT levels (/=150 000/muL or <150 000/muL). Results: In 129 HCV carriers with PNALT, the rate of progression of fibrosis stage was 0.05/year and no HCC was detected during the follow up for 10 years. Approximately 20% of patients with ALT /=150 000/muLwere at stage F2-3; however, approximately 50% of patients with ALT /=31 U/L when we focus on the inhibition of the development of HCC.     

Increased expression of cytokines and adhesion molecules in rat chronic esophagitis

BACKGROUND/AIMS: Cytokines and adhesion molecules regulate many inflammatory processes in several gastrointestinal diseases. The dynamics of cytokines and adhesion molecules in reflux esophagitis are unknown in detail. We examined the expression and dynamics of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-2, GRO/cytokine-induced neutrophil chemoattractant-2alpha (CINC-2alpha), intercellular adhesion molecule-1 (ICAM-1), leukocyte function-associated antigen 1 (LFA-1; CD11a/CD18), and Mac-1 (CD11b/CD18) in rat chronic reflux esophagitis. METHODS: Chronic acid reflux esophagitis was induced in Wistar rats by ligating the transitional region between the forestomach and the glandular portion and wrapping the duodenum near the pylorus with a small piece of an 18-Fr Nélaton catheter. Rats were killed 3 or 21 days after operation. The levels of mRNA expression of cytokines and ICAM-1 were determined by real-time quantitative RT-PCR. Localization of adhesion molecules and cytokines was investigated by immunohistochemical staining, and numbers of LFA-1- or Mac-1-positive cells were quantified. RESULTS: IL-1beta, TNF-alpha, MCP-1, MIP-1alpha, MIP-2, CINC-2alpha, and ICAM-1 mRNA expression was significantly increased in esophageal lesions compared with normal esophagus. There were few these cytokines- or adhesion molecule-positive cells in normal esophagus. In regions of esophagitis, numerous inflammatory leukocytes in lamina propria and the submucosal layer exhibited positive reactions for these cytokines and endothelial cells were intensely stained for ICAM-1. Numbers of LFA-1- and Mac-1-positive cells were significantly increased in rat chronic esophagitis. Treatment with rabeprazole almost completely inhibited development of chronic acid reflux esophagitis and significantly decreased expression of cytokines and ICAM-1 mRNA in esophageal tissue compared with control. CONCLUSION: Cytokines and adhesion molecules play important roles in the pathogenesis of chronic reflux esophagitis in this rat model.     

Paradoxical effects of pirenzepine on parasympathetic activity in chronic heart failure and control

We studied the effect of intravenous pirenzepine (3 mg) in normal subjects (n=15, 43+/-16 years old) and in patients with chronic heart failure (n=15, 61+/-12 years old) to assess the effect of low-dose pirenzepine on vagal activity. R-R intervals and the standard deviations, low-frequency power (LF: ln ms2, 0.04-0.15 Hz), high-frequency power (HF: ln ms2, 0.15-0.40 Hz) and the ratio of low- to high-frequency power (LF/HF ratio) were measured 10 min before and after pirenzepine using a Holter analysis system. Pirenzepine was found to cause a significant increase in the R-R interval from 903+/-112 to 956+/-129 ms in the control group (P<0.0001) and from 927+/-141 to 958+/-168 ms in patients with chronic heart failure (P<0.01). Pirenzepine also increased HF significantly from 4.29+/-0.32 to 5.16+/-0.38 ln ms2 in the control group (P<0.0001) and from 4.04+/-0.16 to 4.48+/-0.24 ln ms2 in the chronic heart failure group (P<0.05). Pirenzepine did not significantly alter the LF/HF ratio in either group. We emphasize that pirenzepine appears to have a vagoinimetic effect in patients with chronic heart failure and that it may be useful for augmenting vagal control of the heart in some patients with chronic heart failure.