Relationship between tribological performance of liquid crystals and their molecular structure

The tribological behaviour of nematic and smectic liquid crystals was observed using a two-roller friction tester under the conditions of 735 N load and 220 rpm rotational speed. Each liquid crystal has two typical structures: a flexible structure (alkyl chain) and a rigid structure (cyanophenyl group). Structural features of the liquid crystals were (1) alkyl cyanobiphenyl (CB), (2) alkoxyl cyanobiphenyl (ECB) and (3) alkyl cyanophenyl cyclohexane (CPC). The frictional coefficient of the test samples was lower and the estimated film thickness was larger than those of synthetic oils. The friction coefficient was not affected by the carbon number of the alkyl chain, but was closely dependent on the molecular structure of the rigid part of the liquid crystal module. The frictional coefficient of CB which has a biphenyl group was 0.035, but CPC had a higher friction coefficient of 0.045. The molecular orientation of the rigid group was observed under shearing conditions. It is concluded that the flat structure of the biphenyl group plays an important role on the tribological behaviour.     

The relationship between deterioration and reversal of optic disc cupping in monkeys with chronic experimental high-pressure glaucoma

PURPOSE: To investigate the correlation between the deterioration in optic disc cupping during the chronic elevation of intraocular pressure (IOP) and the reversal of cupping during a subsequent reduction in IOP in experimental glaucoma. METHODS: We examined changes in the vertical and horizontal cup to disc ratios, the rim area to disc area ratio, and the cup volume to disc area ratio in 11 monkey eyes with laser-induced glaucoma using computerized stereo-image analysis. Correlations between changes in disc parameters during a spontaneous IOP reduction and changes in disc parameters during a period of chronic IOP elevation from baseline before laser exposure (baseline) to before the IOP reduction (pre-IOP reduction) and during the period from baseline to after the reduction in IOP (post-IOP reduction) were determined by linear regression analysis. RESULTS: All disc parameters improved significantly during IOP reduction and deteriorated significantly during the periods from baseline to the pre-IOP reduction and from baseline to the post-IOP reduction. The degree of reversal in disc parameters was correlated with the deterioration from baseline to the pre-IOP reduction and from baseline to the post-IOP reduction in the vertical cup to disc ratio (r = 0.68, P = 0.0218 and r = 0.97, P < 0.0001, respectively), the horizontal cup to disc ratio (r = 0.57, P = 0.0649 and r = 0.98, P < 0.0001, respectively), the rim area to disc area ratio (r = 0.68, P = 0.0227 and r = 0.98, P < 0.0001, respectively), and the cup volume to disc area ratio (r = 0.67, P = 0.0256 and r = 0.88, P = 0.0004, respectively). CONCLUSION: The degree of deterioration in cupping from baseline before the induction of glaucoma may be an important determinant of the degree of cupping reversal during subsequent reductions in IOP in primate glaucoma.     

In vivo characterization of T-794, a novel reversible inhibitor of monoamine oxidase-A, as an antidepressant with a wide safety margin

T-794 is a new reversible inhibitor of MAO type A. In order to predict its clinical utility as an antidepressant, we examined its pharmacological profile (i.e., MAO inhibitory activity, antidepressant-like activity and safety) in vivo in rodents. The p.o. administration of T-794 potentiated L-5-hydroxytryptophan-induced symptoms with ED50 = 1.01 mg/kg (mice) or 1.15 mg/kg (rats), and L-dopa-induced behavior with ED50 = 5.90 mg/kg (mice), whereas it did not alter the effect of beta-phenylethylamine even at 100 mg/kg (mice). In the L-5-hydroxytryptophan test in rats, the activity of T-794 (at twice the dose of ED50) disappeared by 8 h; the duration of action was similar to that of moclobemide. These results confirm the previous biochemical results that MAO-A inhibition by T-794 is highly selective and of short duration. T-794 was effective in three animal models of depression: reserpine reversal (mice, rats), behavioral despair test (mice) and learned helplessness (rats). In these tests, it had potency similar to or greater than moclobemide, tranylcypromine or imipramine. The p.o. administration of T-794 (30 mg/kg) did not affect the pressor effect of tyramine in anesthetized rats, whereas moclobemide (30 mg/kg) and tranylcypromine (6 mg/kg) potentiated the effect. Acute toxicity of T-794 proved to be very low (maximal tolerated dose > 2 g/kg p.o.) in contrast to brofaromine (maximal tolerated dose = 150 mg/kg p.o.). Unlike tricyclic antidepressants, T-794 did not prevent the oxotremorine-induced tremor even at 100 mg/kg p.o.; in this it demonstrated a lack of the anticholinergic activity. These results suggest that T-794 is an effective and particularly safe antidepressant and that it may make an important contribution in the treatment of depressive disorders.     

Characterization of the ubiquinone reduction site of mitochondrial complex I using bulky synthetic ubiquinones

A wide variety of alkyl derivatives of Q2 (6-geranyl-2, 3-dimethoxy-5-methyl-1,4-benzoquinone) and DB (6-n-decyl-2, 3-dimethoxy-5-methyl-1,4-benzoquinone), in which methoxy groups of the 2- and/or 3-positions of the quinone ring were replaced by other bulky alkoxy groups from ethoxy to butoxy, were prepared by novel synthetic procedures. Electron-accepting activities of the bulky quinones were investigated with bovine heart mitochondrial complex I and its counterpart of Paracoccus denitrificans(NDH-1) to elucidate structural and functional features of the quinone reduction site of the enzymes. The bulky quinone analogues served as sufficient electron acceptors from the physiological quinone reduction site of bovine complex I. Considering the very poor activities of even the ethoxy derivatives as substrates for other respiratory enzymes such as mitochondrial complexes II and III [He, D. Y., Gu, L. Q., Yu, L., and Yu, C. A. (1994) Biochemistry 33, 880-884], this result indicated that the quinone reduction site of bovine complex I is spacious enough to accommodate bulky exogenous substrates. In contrast to bovine complex I, bulky quinone analogues served as poor electron acceptors with Paracoccus NDH-1. These observations indicated that bovine complex I recognizes the substrate structure with poor specificity. The substituent effects in the 2- and 3-positions of the quinone ring on the electron-transfer activity with bovine complex I differed significantly between Q2 and DB series despite having the same total number of carbon atoms in the side chain. The inhibitory effect involving Q2 due to its geranyl side chain was markedly diminished by structural modifications of the quinone ring moiety. These findings indicate that the side chain plays a specific role in the redox reaction and that the quinone ring and side-chain moieties contribute interdependently to binding interaction. Moreover, structural dependency of the proton-pumping activity of the quinone analogues was comparable to that of the electron-transfer activity with bovine complex I, indicating that the mechanism of redox-driven proton-pumping does not differ depending upon the substrate structure.     

Familial occurrence of congenital bile duct cysts

Congenital bile duct cysts are now a well-documented anomaly of the biliary tree, and have become more common in Japan. Familial occurrence of congenital bile duct cysts, however, is extremely rare, with only six reported cases in the literature. We report a familial pattern of congenital bile duct cysts in a mother and her daughter. A 33-year-old female was admitted for evaluation of right upper quadrant abdominal pain and fever 6 days after an uneventful delivery of her second child. A computed tomography (CT) and ultrasound scan (US) revealed an obstructed biliary tract. Percutaneous transhepatic biliary drainage was then performed, and a cholangiogram revealed a Scholtz type B choledochocele without an anomalous connection of the pancreaticobiliary ducts. Endoscopic US demonstrated that the choledochocele was associated with a stone in the cyst. A pylorus-preserving pancreatoduodenal resection was performed, and a histological study revealed that the choledochocele was lined by biliary mucosa without evidence of malignancy. The newborn infant had an abdominal tumour. An US and CT revealed a congenital bile duct cyst. An operation was performed and the intraoperative cholangiogram showed an Alonso-Lej type I congenital bile duct cyst with an anomalous connection of the pancreaticobiliary ducts. Whether congenital bile duct cysts are hereditary remains to be elucidated.     

Transcriptional analysis of Marek''s disease virus (MDV) genes in MDV-transformed lymphoblastoid cell lines without MDV-activated cells

Prevention of the occurrence of diabetes-specific vascular complications is the final aim of clinical islet transplantation. Pancreatic islets isolated from adult pigs may be a suitable tissue source to transplant a large number of type 1 diabetic patients. Acute cellular rejection may be finally overcome by clinically applicable protocols for tolerance induction. However, primary nonfunction of the graft, as regularly observed in the porcine islet-to-rat xenotransplantation model, may be an additional problem. In this paper, species-specific inflammatory and immunological mechanisms are discussed which prevent early porcine islet graft function in rats but not in mice.     

Suppression of cell growth by ectopic expression of N-cadherin

We found that ectopic expression of N-cadherin in 3Y1 caused tight association of cells and, thereby, substantially suppressed cell growth. N-cadherin expression inhibited neither tyrosine phosphorylation of cellular proteins, GTP uptake onto Ras, nor activation of MAP kinase, suggesting that it does not directly interfere the Ras-MAP kinase pathway. However, co-expression of N-cadherin with dominant negative Ras, S17N Ras, showed synergestic growth inhibitory effect, suggesting that N-cadherin signaling antagonizes the Ras-MAP kinase signaling. In addition, we found that N-cadherin yielded cell-cycle arrest at G0/G1 phase. These results strongly suggest that N-cadherin cell adhesion machinery works as a negative controller of cell cycle in 3Y1 and this growth suppressive function of cadherin is distinct from the epithelial morphogenetic function.     

Small polypoid lesions of the gallbladder: differential diagnosis and surgical indications by helical computed tomography

We report the case of a 16-year-old girl who experienced sudden cardiac arrest from ventricular fibrillation, complicating an arrhythmogenic right ventricular dysplasia, a rare heart muscle disorder, occurring typically in young adults, characterized by a fibrofatty replacement of the right ventricular myocardium. Symptomatic ventricular arrhythmias are frequent, and sudden death has been reported. In our case, diagnosis of arrhythmogenic dysplasia was based on the association of one major criterion and two minor criteria as suggested by the relevant task force. In contrast with most other reports, the chest ECG did not display the typical features. An automatic transvenous pectoral cardioverter-defibrillator was implanted. The authors emphasise that juvenile forms are more exposed to ventricular fibrillation and sudden cardiac death, and consequently require the early detection of the disease. Family cases have been described and the occurrence in one individual must lead to investigations in the relatives.     

Role of TAK1 and TAB1 in BMP signaling in early Xenopus development

Transforming growth factor-beta (TGF-beta) superfamily members elicit signals through stimulation of serine/threonine kinase receptors. Recent studies of this signaling pathway have identified two types of novel mediating molecules, the Smads and TGF-beta activated kinase 1 (TAK1). Smads were shown to mimic the effects of bone morphogenetic protein (BMP), activin and TGF-beta. TAK1 and TAB1 were identified as a MAPKKK and its activator, respectively, which might be involved in the up-regulation of TGF-beta superfamily-induced gene expression, but their biological role is poorly understood. Here, we have examined the role of TAK1 and TAB1 in the dorsoventral patterning of early Xenopus embryos. Ectopic expression of Xenopus TAK1 (xTAK1) in early embryos induced cell death. Interestingly, however, concomitant overexpression of bcl-2 with the activated form of xTAK1 or both xTAK1 and xTAB1 in dorsal blastomeres not only rescued the cells but also caused the ventralization of the embryos. In addition, a kinase-negative form of xTAK1 (xTAK1KN) which is known to inhibit endogenous signaling could partially rescue phenotypes generated by the expression of a constitutively active BMP-2/4 type IA receptor (BMPR-IA). Moreover, xTAK1KN could block the expression of ventral mesoderm marker genes induced by Smad1 or 5. These results thus suggest that xTAK1 and xTAB1 function in the BMP signal transduction pathway in Xenopus embryos in a cooperative manner.     

Measurement of Flow Stress in Supercooled Austenite for High Hardenability Steel

In this article, the isothermal flow stress in supercooled austenite was measured for a high hardenability steel. Supercooled austenite forms at the nonequilibrium phase and changes into other phases within a short time. It was confirmed that conventional tensile tests, which require maintaining a constant temperature before stretching, cannot accurately measure the flow stress in supercooled austenite. Therefore, a new tensile test named “the continuous cooling tensile test” was developed. In this test, stretching is conducted during continuous cooling. In the continuous cooling tensile test, the flow stress between 673 K and 973 K (400 °C and 700 °C) was measured. Microscopic observations of the continuous cooling test results verified that the microstructures were supercooled austenite.