Association between transforming growth factor-ß1 -509 C>T variants and hepatocellular carcinoma susceptibility: a meta-analysis.

The transcriptional activity of transforming growth factor-ß (TGF-ß) is increased in subjects with hepatocellular carcinoma (HCC). Recent studies have indicated that the -509C genotype in hepatitis B virus (HBV)-infected subjects and the -509T genotype in hepatitis C virus (HCV)-infected subjects can increase the transcriptional activity of the TGF-ß1 gene. We conducted a meta-analysis to clarify whether these two hepatitis viruses affect the association between TGF-ß1 C-509T variants and HCC susceptibility. Using data derived from 8 case-control studies available in the PubMed database (5 with Asian and 3 with Caucasian populations), including 1,427 cases and 3,735 controls [1,610 patients with chronic liver disease and 2,125 healthy controls], we calculated pooled odds ratios with corresponding 95% confidence intervals. We used dominant (TT + CT vs. CC), recessive (TT vs. CC + CT), and co-dominant (TT vs. CC and CT vs. CC) genetic models. An overall analysis showed no association between the TGF-ß1 C-509T variants and HCC susceptibility for all models. In contrast, a subgroup analysis, based on the infecting hepatitis viruses, provided the following results. Among the cases and controls with chronic liver disease, the TGF-ß1 C-509T variants were significantly associated with decreased HCC susceptibility for two models with HBV-infected subjects, whereas the variants were significantly associated with increased HCC susceptibility for one model with HCV-infected subjects. Among the cases and healthy controls, there was a significant association between the TGF-ß1 C-509T variants and increased HCC susceptibility for two models involving HCV-infected subjects. Among the cases and the entire control group, the same results were obtained for all genetic models with HCV-infected subjects. Although further data accumulation is required, our results suggest that these two hepatitis viruses affect the association between TGF-ß1 C-509T variants and HCC susceptibility in opposite manners.

Impact of lithium-ion ordering on surface electronic states of Li(x)CoO2.

Li(x)CoO(2) exhibits intriguing electronic properties due to a strong electron correlation and complex interplay between Co and Li ions. However, fundamental understanding of the nanoscale distribution of Li ions and its effect on the electronic properties remains unclear. We use scanning tunneling microscopy and density functional theory to elucidate the degree of Li(x)CoO(2) surface electronic state modification that can be achieved by Li ordering. The surface Li ions are highly mobile and preferentially form a (1 × 1) hexagonal lattice, whereas the surface CoO(2) layer shows metallic and insulating phases, indicating the coexistence of ordered and disordered Li ions in the subsurface layer. These results provide evidence of novel electronic properties produced by spatially inhomogeneous Li-ordering patterns.

Site-selective XAFS spectroscopy tuned to surface active sites of Cu/ZnO and Cr/SiO2 catalysts.

XAFS (X-ray absorption fine structure) spectra were measured by using the fluorescence spectrometer for the emitted X-ray from sample. The chemical shifts between Cu0 and Cu1 and between CrIII and CrVI were evaluated. Tuning the fluorescence spectrometer to each energy, the Cu0 and CuI site-selective XANES for Cu/ZnO catalyst were measured. The first one was similar to the XANES of Cu metal and the second one was the 5 : 5 average of XANES for CuI sites + Cu metal. The population ratio of copper site of the Cu/ZnO catalyst was found to be Cu metal: Cu2O : CuI atomically dispersed on surface = 70(+/-23) : 22(+/-14) : 8(+/-5). Site-selective XANES for CrIII site of Cr/SiO2 catalyst was also studied.

Closed-loop control using a stretch sensor for restoration of standing with functional electrical stimulation in complete paraplegia.

A closed-loop control system for standing with functional electrical stimulation (FES) using percutaneous intramuscular electrodes in complete paraplegia is described. The system consisted of ultrafine percutaneous intramuscular electrodes, a 32-channel stimulator and a stretch sensor with active current control to detect knee buckling. The closed-loop control system was applied in a T8 completely paraplegic patient. Compared to the stretch sensor with a wide use flexible goniometer for direct current control during standing, the stretch sensor was superior to the flexible goniometer in both ease of use and response. The average time delay from the start of knee buckling until the sensor turned on was 0.56+/-0.19 seconds (Mean+/-S.D.) in the goniometer and 0.21+/-0.06 seconds in the stretch sensor. The average time delay from the start of knee buckling until the recovery from knee buckling was 1.01+/-0.05 seconds in the goniometer and 0.78+/-0.06 seconds in the stretch sensor. The continuous standing ability of the patient increased from 12 minutes with open-loop stimulation to 30 minutes with the closed-loop control. No complications such as falling occurred during clinical use. This system prevented falling due to knee buckling during standing and prolonged upright activities in complete paraplegics.

Focal nodular hyperplasia coexistent with hemangioma and multiple cysts of the liver.

We report here a case of hepatic focal nodular hyperplasia (FNH) associated with hepatic hemangioma and multiple hepatic cysts in a 71-year-old man. He was admitted to our hospital because of body weight loss. Ultrasonography detected multiple cysts. and two tumors in the liver one, 3.5 cm and one, 1.6 cm. Color Doppler ultrasonography showed arterial signals within the large tumor. On dynamic computed tomography, the large tumor was a hypodense lesion which was enhanced during the arterial phase and almost isodense during the delayed phase: the small tumor was also a hypodense lesion, and was enhanced during both the arterial and delayed phases. On magnetic resonance imaging using superparamagnetic iron oxides, the large tumor had decreased signal intensity on the T2-weighted image. On hepatic arteriography, the feeding artery of the large tumor showed a spoke-wheel appearance and that of the small tumor showed a cotton-wool appearance. Ultrasonographically guided fine-needle aspiration biopsy of the large tumor revealed hepatocellular hyperplasia. Finally, we diagnosed the two hepatic tumors as FNH and hemangioma. There was no intracranial lesion. The cause of the patient's emaciation was psychogenic anorexia. To our knowledge, this is the first case report that describes the simultaneous occurrence of these three kinds of hepatic lesions. The pathogenesis of FNH still remains unclear, but this association suggests that FNH may arise because of a vascular anomaly.

A Three-Center Orbital Interaction in the Diels-Alder Reactions Catalyzed by Lewis Acids.

Ab initio calculations were performed on title reactions between butadiene and acrolein with BCl(3), AlCl(3), GaCl(3), InCl(3), ZnCl(2), SnCl(2), and SnCl(4). A dimethyl ether molecule is explicitly considered in various reaction systems to examine solvent effects. First, the reaction path of an AlCl(3)-promoting reaction was examined thoroughly. This reaction has two channels. The first one involves a weak reactant-like complex (precursor) and a normal [4 + 2] addition. The second does three elementary processes, one-center addition, ring closing, and Claisen shift. The first channel is more favorable by 12.1 kcal/mol (B3LYP/6-311+G(2d,p) SCRF//B3LYP/6-31G SCRF) than the second one. Then the first channels with other Lewis acids were traced with and without an ether molecule. The ether molecule has an appreciable effect not on geometries but on activation energies. BCl(3) is desolvated and has extraordinarily strong catalytic ability. Even with the strongest catalyst, not a [2 + 4] but a normal [4 + 2] cycloaddition takes place. Except for BCl(3), SnCl(4) is the strongest Lewis acid with the ether molecule. The frontier orbital, LUMO, of acrolein is distorted in the course of the reaction so that the formation of two C-C covalent bonds is possible. The precursor formation and the one-center addition were discussed also by the frontier orbital theory.

Plasma levels of type II phospholipase A2 and nitrite/nitrate in patients with burns.

Type II phospholipase A2 (type II PLA2), nitrite/nitrate (NOx), tumor necrosis factor-alpha (TNF-alpha) and endotoxin were studied in burn patients. Type II PLA2 values and NOx values were both significantly higher in the group that died, the group with shock as a complication and the group with multiple organ dysfunction syndrome (MODS) as a complication, than in the group that survived, the group without shock as a complication and the group without MODS as a complication, respectively. The results suggested that type II PLA2 and nitric oxide (NO) may play a major role in the pathology of burn patients. Significant correlations were found between TNF-alpha and type II PLA2 values and between type II PLA2 and NOx values, suggesting the possibility of involvement in each other's production.

Quantitative analysis of mutually competitive binding of human Raf-1 and yeast adenylyl cyclase to Ras proteins.

Ras proteins appear to have two distinct downstream effectors, adenylyl cyclase in Saccharomyces cerevisiae and a product of raf-1 protooncogene in higher organisms. We found that in vitro activation of adenylyl cyclase by yeast Ras2 and human H-Ras proteins is subject to competitive inhibition by its leucine-rich repeats domain and by the N-terminal regulatory domain of human Raf-1 protein. Kinetic analyses of the inhibition patterns enabled us to determine exact dissociation constants (Kd) of the two polypeptides for Ras2 and H-Ras. The leucine-rich repeats domain bound to the posttranslationally modified Ras2 with the Kd of approximately 13 nM, which was close to the value (7 nM) of the whole adenylyl cyclase. The Kd of Raf-1 for the modified H-Ras, 3.5 nM, was significantly lower than that for Ras2, 24 nM, whereas adenylyl cyclase bound preferentially to Ras2. Similar inhibition was also observed in vivo by suppression of RAS2Val-19-dependent heat shock sensitivity and of Ras-dependent cAMP response to glucose upon overexpression of Raf-1 in yeast. These results indicate that the leucine-rich repeats domain contains the Ras protein-binding site and that Raf-1 and adenylyl cyclase, sharing no structural homology with each other, bind to a similar, if not identical, region of Ras with comparable affinities.

Antibody mimicking the action of RAS proteins on yeast adenylyl cyclase: implication for RAS-effector interaction.

Polyclonal antisera were raised against various subregions of Saccharomyces cerevisiae adenylyl cyclase in order to examine the molecular mechanism of interaction between adenylyl cyclase and RAS proteins. One of the antisera was found to activate adenylyl cyclase to an extent comparable to that activated by saturating amounts of yeast RAS2 protein produced in Escherichia coli. The stimulatory effect of this antiserum was shown to be additive with RAS2 protein when both antisera and RAS2 protein were present at low concentrations. At saturating amounts of RAS2 protein, the antisera did not exhibit additional stimulatory effects, suggesting that the actions of RAS2 protein and the antisera are complementary with each other. The antigenic determinant for the antibody involved in the activation was mapped to a 14-amino-acid segment, 1452-NSVDNGADVANLSY-1465, located between the leucine-rich repeats and the catalytic domain of adenylyl cyclase. Certain missense mutations affecting this 14-amino acid segment significantly reduced the response of adenylyl cyclase to both activating antibody and RAS proteins. These results suggest that this segment of adenylyl cyclase is intimately involved in the mechanism by which RAS proteins activate this downstream effector.

Submandibular hemangioma as the initial manifestation of Kasabach-Merritt syndrome.

Kasabach-Merritt syndrome (thrombocytopenia, consumption coagulopathy and occasional hemolysis) is an infrequent but often fatal complication of rapidly growing hemangiomas in infants. We describe a 1-month-old infant with a huge hemangioma involving the left submandibular region associated with a severe consumptive coagulopathy, who was successfully treated with transfusion of blood products, prednisone and radiation therapy. It is stressed that pediatric otorhinolaryngologists should always be aware of the lethal status of this condition in infants.

[Two cases of hemorrhagic shock and encephalopathy syndrome].

A 10-month-old male infant (case 1) and another male infant aged 1 year and 11 months (case 2) were admitted to our department because of fever, watery diarrhea and convulsion. On admission, they were unconscious and showed rigidity of the limbs. Laboratory examination revealed a marked increase in GOT and GPT, a decrease in platelet and antithrombin III and an increase in FDP. Metabolic acidosis was found by blood gas analysis. Brain CT showed an extensive area of low density in case 1, and low density centering on the cerebral basal ganglia and brainstem in case 2. Rotavirus was detected in case 2 by fecal examination. The clinical pictures in these cases closely resembled those of hemorrhagic shock and encephalopathy (HSE) reported by Levin et al. in 1983. The etiology of this disease is currently unknown, and its prognosis is poor. The relationship between this disease and rotavirus should be examined in future studies.