Expression profiles of genes associated with viral entry in HCV-infected human liver.

Recent studies have demonstrated that several cellular factors are involved in entry of hepatitis C virus (HCV) into host cells. Detailed gene expression profiles of these factors in HCV-infected livers have not been reported for humans. Transcriptional levels of LDL receptor (LDLR), CD81, scavenger receptor class B type I (SR-BI), claudin-1, and occludin genes in liver samples from patients with chronic hepatitis C were investigated. Serum levels of LDL-cholesterol (LDL-C) and HCV core antigen were also evaluated, and expression of claudin-1 and occludin were immunohistochemically analyzed. Compared with normal liver, transcription of LDLR and claudin-1 genes was significantly suppressed (P < 0.0001) and occludin transcription was significantly up-regulated in HCV-infected livers (P < 0.0001). Significant positive correlations were found for LDLR versus occludin, LDLR versus claudin-1, occludin versus claudin-1, and CD81 versus SR-BI in HCV-infected (P = 0.0012, P < 0.0001, P = 0.0004, and P < 0.0001, respectively) and normal livers (P < 0.0001, P = 0.0051, P < 0.0001, and P < 0.0001, respectively). Positive correlation was observed between serum levels of HCV core antigen and LDL-C (P = 0.0147), with their levels negatively correlated to LDLR (P = 0.0270 and P = 0.0021, respectively). Immunohistochemically, hepatocellular expression of claudin-1 and occludin was increased in HCV-infected livers. Different levels of expression were demonstrated at the mRNA and protein levels for occludin and claudin-1 in HCV-infected and normal livers. Correlation of elements associated with viral entry was comparable in HCV-infected and normal livers.

Therapeutic effect of bezafibrate against biliary damage: a study of phospholipid secretion via the PPARalpha-MDR3 pathway.

OBJECTIVE: Bezafibrate (BF) has been used to treat biliary damage, particularly in patients with primary biliary cirrhosis (PBC), and its clinical efficacy has been demonstrated. The mechanism of action is thought to involve activation of the PPARalpha-MDR3-phospholipid (PL) secretion pathway. We tried to confirm this hypothesis in patients with hepatobiliary disease. METHODS: The levels of serum gamma-glutamyl transpeptidase and alkaline phosphatase, and those of bile components were examined before and after BF administration in patients with obstructive jaundice undergoing percutaneous transhepatic biliary drainage (PTBD). Hepatic expression of PPARalpha and MDR3 was quantified by real-time PCR in patients with PBC or non-alcoholic fatty liver disease (NAFLD). RESULTS: In patients with obstructive jaundice, BF decreased the serum levels of biliary enzymes and increased the bile concentration of PL. In patients with PBC or NAFLD, the expression levels of MDR3 were already up-regulated before starting the BF treatment. Although BF treatment did not further up-regulate MDR3 expression in NAFLD patients, PPARalpha expression was significantly increased. CONCLUSIONS: BF enhanced the secretion of PL into bile in cholestatic patients undergoing PTBD. However, in patients with PBC or NAFLD, diseases that represent cholesterol overload, MDR3 was already expressed at a high level to compensate for bile acids overproduction, and its expression was hardly affected by BF. In patients with chronic liver diseases such as PBC, BF may induce clinical effects via mechanisms independent of PL secretion.

[Left ventricular pacemaker-lead implantation through left thoracotomy for cardiac resynchronization therapy].

We performed direct implantation of a left ventricular pacemaker-lead through left thoracotomy for cardiac resynchronization therapy (CRT). We exposed the left ventricular free wall using a pericardium lifting method without hemodynamic deterioration or arrhythmia. Intraoperative ultrasonic cardiography is useful for determining a suitable implantation site for CRT.

Receptor-mediated effects of clonidine on need-induced 3% NaCl and water intake.

Clonidine combined with adrenergic antagonists were injected in the medial septal area in order to characterize the type of receptors involved with its inhibitory effect on 3% NaCl and water intake of sodium-depleted (furosemide + 24 h of removal of ambient sodium) and 30-h water-deprived rats, respectively. The inhibitory effect of clonidine (20 nmol) on need-induced water intake was reduced 50% by an 80-nmol dose of either idazoxan, yohimbine or prazosin. The inhibitory effect of clonidine (30 nmol) on need-induced 3% NaCl intake was completely antagonized by idazoxan (80, 160 nmol), not altered by yohimbine (40-160 nmol), and partially potentiated (40 nmol) or inhibited (160 nmol) by prazosin. Propranolol did not alter the effects of clonidine on either water (80 nmol) or 3% NaCl (40-160 nmol) intake. The results suggest that the inhibitory effects of clonidine on 3% NaCl and water intake are mediated by different types of alpha2-adrenergic receptors.

Antagonism of the renin-angiotensin system and water deprivation-induced NaCl intake in rats.

Adult male rats (n = 5-7 per group) were water deprived for 24 h with only food available. Then they had access to water for 2 h. At the end of the 2 h, 1.5% NaCl was offered to the animals and the intake was measured for another 2 h. The rats drank an average of 9.8 +/- 3.0 ml/120 min of 1.5% NaCl; water intake during this time was negligible (not more than 1.0 ml/120 min). Captopril injected i.p. at the doses of 12 and 24 mg/ kg induced 60-90% inhibition of the intake. Losartan or PD123319 injected i.c.v. induced 50-80% inhibition of the intake. Losartan (80 nmol) inhibited the intake at a lower dose than PD123319 (160 nmol). Neither losartan nor PD123319 inhibited 10% sucrose intake. The inhibition of 1.5% NaCl intake was not related to alterations in arterial pressure. The results show that the antagonism of the renin-angiotensin system inhibits the 1.5% NaCl intake induced by water deprivation. The inhibition induced by the angiotensin II antagonists suggest that this peptide is important for the control of salt intake induced by water deprivation.

Central alpha-adrenergic agonists and need-induced 3% NaCl and water intake.

In the present study, noradrenaline (NOR, alpha-non-specific adrenergic agonist), clonidine (CLO, alpha 2), phenylephrine (PHE, alpha 1) or isoproterenol (ISO, beta-agonist) was injected in the medial septal area (MSA) of water-deprived, sodium-deplete or food-deprived rats. NOR (80, 160 nmol) inhibited the intake of 3% NaCl, water deprivation-induced and meal-associated water intake. Food deprivation-induced food intake and 10% sucrose intake were not altered by NOR. CLO (10, 20, 30, 40 nmol) inhibited (80-100% inhibition compared to control during 60 min) the intake of 3% NaCl, water deprivation-induced and meal-associated water intake. CLO had a weaker inhibition on food and 10% sucrose intake (30-50% less than the control during 60 and 15 min, respectively). PHE (160 nmol) inhibited 3% NaCl intake and 10% sucrose intake (30% less than the control for 15-30 min). ISO (160 nmol) did not alter water or 3% NaCl intake. NOR induced an increase, CLO and ISO induced a decrease, and PHE no alteration in mean arterial pressure. NOR did not alter water or 3% NaCl intake when injected unilaterally into the caudate nucleus. The results suggest that NOR injected in the MSA acts on alpha 2-adrenergic receptors inducing a specific inhibition of 3% NaCl and water intake.

Sedation and need-free salt intake in rats treated with clonidine.

The effect of intraperitoneal injection of clonidine (9-72 microg/kg) on need-free 1.5% NaCl intake and on performance (defined as percent of a complete trial) in the rotarod test, was studied in normovolemic adult male rats. Clonidine (18 and 36 microg/kg) inhibited the 1.5% NaCl intake in a 2-h test at doses that did not alter the performance in the rotarod test. The dose of 36 microg/kg did not inhibit 10% sucrose intake. Only the highest dose (72 microg/kg) of clonidine inhibited the 1.5% NaCl intake and the performance in the rotarod test, and produced signs of sedation. Sedation was determined either by change in posture (immobility or lack of postural tonus) of the animals during the ingestive test or by their performance in the rotarod test. The results suggest that sedation is not a determinant effect on the inhibition of 1.5% NaCl intake induced by clonidine.

Antagonism of clonidine injected intracerebroventricularly in different models of salt intake.

Clonidine, an alpha 2-adrenergic agonist, injected into the brain inhibits salt intake of animals treated by the diuretic model of sodium depletion. In th present study, we address the question of whether central injection of clonidine also inhibits salt intake in animals deprived of water or in the need-free state. Saline or clonidine (30 nmol) was injected into the anterior third ventricle of 24-h sodium-depleted (furosemide + removal of ambient sodium), of 24-h water-deprived and of normovolemic (need-free state) adult male rats. Clonidine injected intracerebroventricularly (i.c.v.) inhibited the 1.5% NaCl intake for 1209 min by 50 to 90% in every model tested. Therefore, different models of salt intake are inhibited by i.c.v. injection of clonidine. Idazoxan, an alpha 2-adrenergic antagonist, injected i.c.v. at a dose of 160 nmol, inhibited the effect of clonidine only in the furosemide + removal of ambient sodium model of salt intake. This indicates that the antagonism of this effect by idazoxan is dependent on the body fluid/sodium status of the animal.

An evaluation of crystal structure of mannan I by X-ray powder diffraction and molecular mechanics studies.

The present study reports the re-examination of the crystal structure of mannan I by the X-ray powder diffraction study combined with the miniature crystal model simulation. A primary objective of this study was to investigate an adequate chain staggering position along the fiber axis. Among the several crystal structure models proposed for mannan I, that derived from the electron diffraction study of the single crystals was adopted as a starting model. The X-ray crystallographic residuals were calculated for the single crystal structure at different chain staggering positions, while the ab projection was kept invariant. In a similar fashion, the miniature crystal models consisting of seven mannotetraoses were constructed, each having different chain staggering values and the three-dimensional structures of all the models were subsequently optimized by using the MM3(92) program without introducing any constraint. Both the X-ray residual and lattice energy plots with respect to the chain staggering position showed the common minima around the -0.25 x c chain staggering. The minimum models were subjected to a search for preferred orientations of O2 and O6 hydroxyl groups. It was found that the hydroxyl groups present inside the minicrystal tended to rotate into particular orientations during the structure optimizations to form the O5-H-O2 and O3-H-O6 intermolecular hydrogen bonds between the adjacent oligomers in an alternative direction.

[Intraaortic balloon pumping in patients undergoing coronary artery bypass grafting].

UNLABELLED: Beneficial effect of preoperative intraaortic balloon pumping (IABP) treatment in high-risk patients who had open heart surgery have been demonstrated. The purpose of this study is to determine the impact of preoperative IABP use on survival in high-risk patients undergoing coronary artery bypass grafting (CABG). METHODS: Two hundred seventy-seven consecutive patients having CABG at our institution were reviewed. Patients having an IABP were identified retrospectively and grouped into one of 3 groups as follows. Group A (n = 14): preoperative IABP for high-risk urgent or elective cases. Group B (n = 26): preoperative IABP for emergency cases. Group C (n = 6): unplanned intraoperative or postoperative IABP. RESULTS: Forty-six patients had an IABP (16.6% of total). Parsonnet score in group B was significantly higher (p < 0.05). Length of operation for group C was significantly longer (p < 0.05). Overall hospital mortality in the total group of 277 cases was 4.2%. Hospital mortality was 7.1% in group A, 7.7% in group B, and 50% in group C. Hospital mortality in group C was significantly higher (p < 0.01). CONCLUSIONS: The beneficial effect of preoperative treatment with IABP in high-risk patients undergoing CABG was confirmed. This approach resulted in a significantly lower hospital mortality.

[Preoperative autologous blood donation in patients undergoing open heart surgery].

We examined the possibility to avoid the homologous blood transfusion in patients undergoing open heart surgery by predonation of 200 ml or 400 ml on the day before operation. Between March 1999 and December 2001, 117 patients underwent scheduled open heart surgery. In these patients, preoperatively collected autologous blood on the day before operation amounted 200 ml or 400 ml. We divided these patients into 3 groups according to the necessity of homologous blood, no transfusion (group A, n = 77), intraoperative transfusion (group B 1, n-29) and postoperative transfusion (group B 2, n = 11). In 65.8% of patients the homologous blood transfusion could be avoided. Preoperative, intraoperative and postoperative factors were compared in the 3 groups. Especially, old age, female, body weight and preoperative hemoglobin value were significantly different between 3 groups. Postoperative Svo2 and postoperative hemoglobin value were significantly different between 3 groups. The purpose of this study was to evaluate that the predonation of 200 ml or 400 ml on the day before operation may be to avoid the homologous blood transfusion and that preoperative, intraoperative and postoperative factors in regard to homologous blood transfusion.

[Left ventricular-right atrial communication detected by pregnancy; report of a operative case].

A 24-year-old pregnant female was admitted to our hospital because of congestive heart failure. When she was 3 month old, she underwent closure of patent ductus arteriosus. Echocardiography, cardiac catheterization and selective angiocardiography showed a left ventricular-right atrial shunt. At the operation, we found a left ventricular right-atrial communication (group I) and repaired the defect directly. The patient was discharged and returned to her social life.

[Results of surgical treatment for thymic epithelial tumors with special reference to the WHO classification].

We examined the clinical significance of World Health Organization (WHO) classification based on a surgical experience with 71 patients. There were 6, 21, 6, 10, 14, and 14 patients with type A, AB, B1, B2, B3 and C tumors. In these patients, average stage by Masaoka's classification was significantly associated with the WHO classification. Invasive tumors of stage III and IV were seen more frequently in patients with type B2, B3 and C tumors than in those with type A, AB and B1. The incidence of tumors invading the lung, the pericardia or the pleura was higher in type B2, B3 and C than in type A, AB or B1. Furthermore, tumor recurrences and tumor-related deaths were seen only in patients with type B2, B3 or C. This study suggested that type B2, B3 and C tumors had more malignant nature in terms of invasiveness, recurrence and prognosis following operation, and that WHO classification may be a useful guideline for planning treatment of thymic epithelial tumors.

Mesoporous Magnetic Materials Based on Rare Earth Oxides.

A novel family of mesoporous oxides of rare earth metals (Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) were synthesized with specific surface areas of 253-348 m(2) g(-1) and pore diameters of 2.5-3.0 nm (see Scheme). The mesoporous solids and their surfactant mesophase precursors are paramagnetic and exhibit a magnetic anomaly due to the mesostructured atomic arrangement.

NGF stimulates differentiation of osteoblastic MC3T3-E1 cells.

The activities of NGF on induction of IL-6, ALP and collagen were studied in cultured osteoblastic cells, MC3T3-E1. Treatment of the cells with NGF induced IL-6 production in a dose dependent manner and enhanced ALP activity and collagen biosynthesis without affecting cell proliferation. Cyclo-oxygenase was activated in NGF-treated cells and prostaglandinE2 was detected as a major metabolite from arachidonic acid. Since prostaglandinE2 is an enhancer of ALP activity and collagen biosynthesis in MC3T3-E1 and was found to induce IL-6 production in this study, it is possible that NGF works on MC3T3-E1 cells through the mediation by endogenous prostaglandinE2.

Suppressive effect of norzoanthamine hydrochloride on experimental osteoporosis in ovariectomized mice.

Norzoanthamine is an alkaloid isolated from a colonial zoanthid. We examined the effects of norzoanthamine hydrochloride on bone weight, strength and morphology in ovariectomized mice, a postmenopausal osteoporosis model. Norzoanthamine hydrochloride significantly suppressed the decrease in femoral weight and bone biomechanical parameters caused by ovariectomy without an increase in uterine weight. This means that norzoanthamine hydrochloride does not have an estrogen-like effect on reproductive organs. Morphological observations of longitudinally ground sections of the humeri showed that norzoanthamine hydrochloride administration (2 mg/kg/d, p.o.) completely suppressed the loss of trabecular bone. Furthermore, norzoanthamine hydrochloride thickened the cortical bone. Based on these results, norzoanthamine hydrochloride may act as both a suppressor of bone resorption and an enhancer of bone formation in vivo.

4-Phenylthiazole derivatives inhibit IL-6 secretion in osteoblastic cells and suppress bone weight loss in ovariectomized mice.

A series of 4-phenylthiazole derivatives were synthesized and tested their inhibitory effect on the interleukin-6 secretion stimulated by PTH in osteoblastic cells. SCRC2941-18, 2-amino-4-(4-chlorophenyl)-5-methylthiazole, was found to be the most potent inhibitor in the derivatives. Furthermore, SCRC2941-18 significantly suppressed the bone weight loss in the ovariectomized mice, an osteoporosis model.