Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity.

Troglitazone is a thiazolidinedione insulin sensitizer drug that is metabolized mainly to a sulfate conjugate (M-1) in humans. It was reported to cause hepatotoxicity, although the cause has not been fully clarified. The objective of this study was to identify whether organic anion transporting polypeptide (OATP) transporters expressed at the basolateral membrane of human hepatocytes participate in troglitazone-associated hepatotoxicity.

Expression of a testis-specific form of TBP-related factor 2 (TRF2) mRNA during mouse spermatogenesis.

The gene encoding TATA-binding protein-related factor 2 (TRF2/TLF/TLP/TRP), essential for the progress of spermiogenesis, is abundantly expressed in mammalian testis. A sequence database search revealed that mouse TRF2 is encoded by two mRNAs containing the same protein-coding region and different 5'-untranslated regions. Northern blot analysis using DNA probes specific for the 5'-untranslated regions demonstrated that these two mRNAs are distinguished from each other by the expression patterns: ubiquitous and testis-specific expression.

CRE-mediated gene transcription in the peri-infarct area after focal cerebral ischemia in mice.

Cyclic AMP response element binding protein (CREB) is a transcription factor expressed constitutively primarily in neurons and is activated by phosphorylation at Ser(133) residue. CREB mediates expression of several neuroprotective proteins, including B-cell CLL/lymphoma 2 (BCL-2) and brain-derived neurotrophic factor (BDNF). Although phosphorylation of CREB after ischemia has been investigated extensively, CRE-mediated gene transcription after ischemia is not as well studied.

Preparation characteristics of water-in-oil-in-water multiple emulsions using microchannel emulsification.

Microchannel (MC) emulsification is a novel technique for preparing monodispersed emulsions. This study demonstrates preparing water-in-oil-in-water (W/O/W) emulsions using MC emulsification. The W/O/W emulsions were prepared by a two-step emulsification process employing MC emulsification as the second step.

Amelioration of hippocampal neuronal damage after transient forebrain ischemia in cyclooxygenase-2-deficient mice.

Several studies have suggested that cyclooxygenase-2 (COX-2) plays a role in ischemic neuronal death. Genetic disruption of COX-2 has been shown to reduce susceptibility to focal ischemic injury and N-methyl-d-aspartate-mediated neurotoxicity. The purpose of this study was to examine the effects of COX-2 deficiency on neuronal vulnerability after transient forebrain ischemia.

Myosin light chain isoforms modify force-generating ability of cardiac myosin by changing the kinetics of actin-myosin interaction.

Objective: To investigate the functional role of myosin light chain (MLC) isoforms in cardiac muscles, we examined the motor function of two different myosins the structure of which differed only in the MLC.

Methods: We purified myosin from atria (A-myosin) and ventricles (V-myosin) of young rats, which contained atrial-type and ventricular-type MLCs, respectively, but having identical alpha-heavy chain isoform. Actin filament velocity (Vel) was determined in the in vitro motility assay.

Effect of interfacial tension on the dynamic behavior of droplet formation during microchannel emulsification.

Microchannel (MC) emulsification is a novel technique for producing monodisperse emulsions. In this study, we investigated the effect of interfacial tension on the dynamic behavior of droplet formation with various surfactant concentrations. Interfacial tension did not affect the resultant droplet diameter in lower flow velocity ranges, but it did affect the time-scale parameters.

Early head penetration into cemented Hylamer Ogee socket.

The authors reviewed 18 consecutive cemented total hip arthroplasties with the Hylamer Ogee socket. The average follow-up period was 47 months. All Hylamer Ogee sockets were sterilized by gamma irradiation in air, and the average period from production to surgery was 12 months.

Preparation of gelatin microbeads with a narrow size distribution using microchannel emulsification.

The purpose of this study was to prepare monodisperse gelatin microcapsules containing an active agent using microchannel (MC) emulsification, a novel technique for preparing water-in-oil (W/O) and oil-in-water (O/W) emulsions. As the first step in applying MC emulsification to the preparation of monodisperse gelatin microcapsules, simple gelatin microbeads were prepared using this technique. A W/O emulsion with a narrow size distribution containing gelatin in the aqueous phase was created as follows.

In vivo fractional P(i) absorption and NaPi-II mRNA expression in rainbow trout are upregulated by dietary P restriction.

Mammalian type II sodium-phosphate cotransporter (NaPi-II) and inorganic phosphate uptake stimulator (PiUS) genes are upregulated by dietary phosphorus (P) restriction to increase intestinal and renal P transport, but little is known about NaPi-II and PiUS regulation in other vertebrates. We studied the 1). the tissue distribution and dietary regulation of NaPi-II, PiUS, and sodium-glucose cotransporter (SGLT1) mRNA and NaPi-II protein in juvenile rainbow trout (Oncorhynchus mykiss) and 2).

Unloaded shortening increases peak of Ca2+ transients but accelerates their decay in rat single cardiac myocytes.

It is of paramount importance to investigate the relation between the time-dependent change in intracellular Ca2+ concentration ([Ca2+]i) (Ca2+ transients) and the mechanical activity of isolated single myocytes to understand the regulatory mechanisms of heart function. However, because of technical difficulties in performing mechanical measurements with single myocytes, the simultaneous recording of Ca2+ transients and mechanical activity has mainly been performed with multicellular cardiac preparations that give conflicting results concerning Ca2+ transients during isometric twitches and during twitches with unloaded shortening. In the present study, we coupled intracellular Ca2+ measurement optics with a force measurement system using carbon fibers to examine the relation between Ca2+ transients and the mechanical activity of rat single ventricular myocytes over a wide range of load.

Implication of cyclooxygenase-2 on enhanced proliferation of neural progenitor cells in the adult mouse hippocampus after ischemia.

Global ischemia promotes neurogenesis in the dentate gyrus of the adult mouse hippocampus. Cyclooxygenase (COX)-2, the principal isoenzyme in the brain, modulates inflammation, glutamate-mediated cytotoxicity, and synaptic plasticity. We demonstrated that delayed treatment with different classes of COX inhibitor significantly blunted enhancement of dentate gyrus proliferation of neural progenitor cells after ischemia.

Peripheral MR angiography: separation of arteries from veins with flow-spoiled gradient pulses in electrocardiography-triggered three-dimensional half-Fourier fast spin-echo imaging.

The authors evaluated a nonenhanced magnetic resonance (MR) angiographic technique that allows separation of arteries from veins. In 15 healthy subjects, peripheral MR angiography was performed with readout flow-spoiled gradient pulses in electrocardiography-triggered three-dimensional half-Fourier fast spin-echo MR imaging. Appropriate flow-spoiled gradient pulses were measured and applied in the three-dimensional acquisition to differentiate arteries and veins in the peripheral vasculature.

Reversibility of proliferative lesions and induction of non-papillary tumors in rat urinary bladder treated with phenylethyl isothiocyanate.

Phenylethyl isothiocyanate (PEITC), generally thought to be a chemopreventive agent for various kinds of genotoxic carcinogens, has been found to induce rat urinary bladder carcinomas in our laboratory. To cast light on the underlying mechanisms, the reversibility of urothelial proliferative lesions and the frequencies of H-ras and p53 mutations in the induced rat urinary bladder tumors were investigated. F344 male rats were given diet containing 0.

[Regulatory role of mechanical stress response in cellular function: development of new drugs and tissue engineering].

The investigation of mechanotransduction in the cardiovascular system is essentially important for elucidating the cellular and molecular mechanisms involved in not only the maintenance of hemodynamic homeostasis but also etiology of cardiovascular diseases including arteriosclerosis. The present review summarizes the latest research performed by six academic groups, and presented at the 75th Annual Meeting of the Japanese Pharmacological Society. Technology of cellular biomechanics is also required for research and clinical application of a vascular hybrid tissue responding to pulsatile stress.

Time-modulated oscillatory structures in phase-separating reactive mixtures.

We investigate the effect of temporal modulation on the spatiotemporal patterns produced by phase separation in chemically reactive ternary mixtures. The temporal modulation is introduced by making one of the reaction rates periodic in time. Our main concern is the stability of traveling waves, which appear above a Hopf-type bifurcation at a finite wave number and are stable in the absence of external modulation.

Epitope analysis of antibodies in Japanese to human cytomegalovirus phosphoprotein 150 with synthetic peptides.

Serological detection of antibodies specific to human cytomegalovirus (HCMV) is not reliable because the assay uses the whole HCMV protein fraction. Antigenic materials composed of well-characterized viral proteins are being tried for serodiagnosis in Europe. Epitopes of antibodies to HCMV phosphoprotein 150 (pp150) encoded by UL32 in Japanese individuals were investigated for comparison with the results in Europe.

Characterization of copy number mutants of plasmid pSC101.

We have characterized three copy number mutants of the plasmid pSC101. These mutations caused single amino acid substitutions at the 46th, 83rd and 115th codons in the rep gene and an increase in the copy number by 4- to 8-fold. Although the in vivo and in vitro repressor activities of these mutated Rep proteins were quite different from each other, the intracellular concentrations of the proteins were maintained at higher levels than the wild-type protein.

Regulation of spermatogenesis by testis-specific, cytoplasmic poly(A) polymerase TPAP.

Spermatogenesis is a highly specialized process of cellular differentiation to produce spermatozoa. This differentiation process accompanies morphological changes that are controlled by a number of genes expressed in a stage-specific manner during spermatogenesis. Here we show that in mice, the absence of a testis-specific, cytoplasmic polyadenylate [poly(A)] polymerase, TPAP, results in the arrest of spermiogenesis.

The total amount of DNA damage determines ultraviolet-radiation-induced cytotoxicity after uniformor localized irradiation of human cells.

We have recently developed a micropore ultraviolet irradiation technique. An isopore membrane filter with 3 microm diameter pores shields ultraviolet C radiation from cultured human fibroblasts, leading to partial irradiation within the cells with an average of about three exposed areas per nucleus. This study addressed the question of whether the spatial distribution of DNA damage within a cell nucleus is important in triggering ultraviolet-induced cytotoxicity.

Detection of human cytomegalovirus DNA in perilymph of patients with sensorineural hearing loss using real-time PCR.

Although cytomegalovirus (CMV) has been detected in the inner ear fluid of patients who succumbed to the complications of symptomatic congenital CMV infection, it has not been detected in the inner ear fluid of living patients. In this study, real-time polymerase chain reaction (PCR) was used to measure CMV DNA in clinical samples (including perilymph) collected from five patients with deafness. In case 1, diagnosed as a symptomatic congenital CMV infection, 3 copies/microl of CMV DNA were detected in perilymph, although no viral DNA was detected in peripheral blood mononuclear cells (PBMCs) or urine samples.

Differential Akt phosphorylation at Ser473 and Thr308 in cultured neurons after exposure to glutamate in rats.

Akt kinase is involved in growth factor-mediated neuronal protection. In the present study, we found in cultured neurons exposed to glutamate, that phosphorylation at Ser473 was transiently induced, but the level of phosphorylation at Thr308 and Akt activity were unchanged. Inhibition of phosphoinositide 3-kinase with LY294002 decreased phosphorylation and Akt activity, however, pretreatment with LY294002 did not affect glutamate toxicity.

Facile synthesis of N-alkyl-N'-arylimidazolium salts via addition of imidazoles to arynes.

[reaction: see text] A novel synthetic approach to N-alkyl-N'-arylimidazolium salts has been developed on the basis of addition of imidazoles to arynes. A variety of N-alkyl-N'-arylimidazolium salts can be synthesized straightforwardly in modest to good yields. Furthermore, utility of the resulting imidazolium salts has been demonstrated by the palladium-catalyzed Suzuki-Miyaura coupling of aryl chlorides.

Evaluating mental fatigue in patients with obstructive sleep apnea syndrome by the Maastricht Questionnaire.

Mental fatigue in patients with obstructive sleep apnea syndrome (OSAS) was investigated and compared with subjects without OSAS. The study series comprised 189 habitual snoring patients and 75 controls. To measure subjective mental fatigue and somnolence, subjects were asked to complete the Maastricht Questionnaire (MQ) and the Epworth Sleepiness Scale (ESS), respectively, and patients also underwent diagnostic polysomnography.