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Biomedical subjects

Akira Takahashi

Publications and source records attributed to Akira Takahashi.

At least 19 recordsLinked to original sources
PubMed2007

Case of metastatic melanoma in an epitrochlear lymph node arising in a pregnant woman.

We describe a rare case of metastatic melanoma in an epitrochlear lymph node in a 29-year-old female patient. The patient had been aware of a brown macule on her right posterior forearm at puberty. Because the lesion had enlarged rapidly, she was referred to our hospital. Histological examination revealed a malignant melanoma. She underwent wide local excision with 3-cm margins and split thickness skin graft closure, but we were not able to perform sentinel node biopsy. She also received three cycles of systemic chemotherapy with dacarbazine, nimustine, vincristine and interferon-beta. However, an epitrochlear node (interval node) metastasis occurred during pregnancy (seventh week) 2 years after the operation. We emphasize that it is important for clinicians to pay attention to the possibility of epitrochlear node metastasis in patients with malignant melanoma in the upper extremity and that it is necessary to perform sentinel node biopsy to identify uncommon lymph node metastasis.

Adult↗
PubMed2006

Adult pancreatic islets require differential pax6 gene dosage.

Pax6, a paired homeodomain transcription factor, plays crucial roles in morphogenesis of eye, central nervous system, and pancreatic islets. Recently, heterozygosity for pax6 mutation has been reported in some individuals with glucose intolerance and aniridia. To investigate the role of pax6 for pancreatic islet function, we examined the pancreatic phenotype of small eye rat strain (rSey(2)) with a point mutation in the pax6 locus resulting in truncated PAX6 proteins. Analyses of the insulin secretory profile of heterozygous rSey(2)/+ revealed that insulin secretion is significantly increased in response to membrane-depolarizing stimuli such as arginine, tolbutamide, and KCl. The processes of insulin granule exocytosis were suggested to be enhanced in rSey(2)/+. On the other hand, pancreatic insulin and glucagon content and islet architecture in rSey(2)/+ showed no significant differences compared to wild-type. These findings indicate differential requirements for pax6 gene dosage in displaying function and maintaining architecture of adult pancreatic islets.

Aging↗
PubMed2006

Intrahepatic mRNA levels of type I interferon receptor and interferon-stimulated genes in genotype 1b chronic hepatitis C. Association between IFNAR1 mRNA level and sustained response to interferon therapy.

OBJECTIVE: The aim of this study was to determine the association between pretreatment intrahepatic mRNA levels of interferon receptor and interferon-stimulated genes and response to interferon therapy for genotype 1b chronic hepatitis C. METHODS: Forty-four patients with genotype 1b chronic hepatitis C who underwent liver biopsy and then received interferon therapy participated in this study. Pretreatment intrahepatic mRNA levels of interferon receptor genes (IFNAR1, IFNAR2b, and IFNAR2c) and interferon-stimulated genes (OAS1 and PKR) were quantified by competitive polymerase chain reaction. RESULTS: In the genes examined, only IFNAR1 mRNA level was significantly higher in patients with sustained virological and biochemical response to interferon therapy versus those with nonsustained response (p < 0.01). Moreover, mRNA expression ratios of IFNAR1 to IFNAR2 were also significantly higher in patients with sustained virological and biochemical response to IFN therapy (p < 0.01 and p < 0.05, respectively). On the other hand, mRNA levels of IFNAR2b, IFNAR2c, and PKR were significantly higher in patients with histologically active or advanced liver rather than patients with mild or less advanced liver. CONCLUSIONS: High intrahepatic mRNA levels of IFNAR1 and mRNA ratio of IFNAR1 to IFNAR2 before treatment may be associated with a favorable response to interferon therapy.

2',5'-Oligoadenylate Synthetase↗
PubMed2006

Escherichia coli isolates associated with uncomplicated and complicated cystitis and asymptomatic bacteriuria possess similar phylogenies, virulence genes, and O-serogroup profiles.

The genetic and serological characteristics of Escherichia coli isolates from patients with uncomplicated cystitis (UC), complicated cystitis (CC), and complicated asymptomatic bacteriuria (CASB) were determined. Phylogenetic group B2 was predominant in all categories. The prevalences of 14 out of 18 virulence factor genes were similar among the three categories, while pap, iha, ompT, and PAI were more frequently seen in isolates associated with UC than CC or CASB.

Bacteriuria↗
PubMed2006

NO-1886, a lipoprotein lipase activator, attenuates vascular smooth muscle contraction in rat aorta.

The chemical compound [4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]-phosphonic acid diethyl ester (NO-1886) is a lipoprotein lipase activator having beneficial effects on both diabetes control and the cardiovascular system. Preventing accumulation of lipids in the cell wall, in addition to improving insulin actions on vasculature, may indirectly contribute to the reducing effect of NO-1886 on vascular resistance. However, the direct effect of NO-1886 on vascular resistance, i.e., whether NO-1886 directly modulates the function of vascular endothelium and/or smooth muscle cells has not been investigated. In this study we therefore investigated the direct effect of NO-1886 on vascular contractility using rat aortic rings and cultured smooth muscle cell-line A10. The results show that administration of NO-1886 attenuated aortic contraction induced by phenylephrine and/or a high K(+) environment, in both the presence and absence of aortic endothelium. 1-(5-Chloronaphthalene-1-sulfonyl)homopiperazine hydrochloride (ML-9), a myosin light chain kinase (MLCK) inhibitor, blocked this inhibitory effect of NO-1886, whereas inhibitors of other signaling molecules such as calmodulin, protein kinase C and Rho-kinase had no effect. The vasorelaxant effect of NO-1886 was blocked in the absence of extracellular Ca(2+), or in the presence of the Ca(2+) channel inhibitor, verapamil. NO-1886 attenuated smooth muscle contraction induced by the cumulative addition of CaCl(2). In A10 cells, NO-1886 inhibited the membrane depolarization-induced initial peak of [Ca(2+)](i) in the presence of extracellular Ca(2+). This inhibition did not occur in the absence of extracellular Ca(2+). Taken together these results demonstrate that NO-1886 attenuates smooth muscle contraction and causes vasorelaxation by an extracellular Ca(2+)- and MLCK-dependent mechanism.

Adrenergic alpha-Agonists↗
PubMed2006

Haemolysin produced by Vibrio mimicus activates two Cl- secretory pathways in cultured intestinal-like Caco-2 cells.

Haemolysin (VMH) is a virulent factor produced by Vibrio mimicus, a human pathogen that causes diarrhoea. As intestinal epithelial cells are the primary targets of haemolysin, we investigated its effects on ion transport in human colonic epithelial Caco-2 cells. VMH increased the cellular short circuit current (Isc), used to estimated ion fluxes, and 125I efflux of the cells. The VMH-induced increases in Isc and 125I efflux were suppressed by depleting Ca2+ from the medium or by pretreating the cells with BAPTA-AM or by Rp-adenosin 3',5'-cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS). The Cl- channel inhibitors 4,4'-disothiocyanatostibene-2,2'-disulfonic acid (DIDS), glybenclamide, and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) suppressed the VMH-induced increases in Isc and 125I efflux. Moreover, VMH increased the intracellular concentrations of Ca2+ and cAMP. Thus, VMH stimulates Caco-2 cells to secrete Cl- by activating both Ca2+ -dependent and cAMP-dependent Cl- secretion mechanisms. VMH forms ion-permeable pores in the lipid bilayer that are non-selectively permeable to small ions. However, the ion permeability of these pores was not inhibited by glybenclamide and DIDS, and VMH did not change the cell membrane potential. These observations indicate that the pores formed on the cell membrane by VMH are unlikely to be involved in VMH-induced Cl- secretion. Notably, VMH stimulated fluid accumulation in the iliac loop test that was fully suppressed by a combination of DIDS and glybenclamide. Thus, Ca2+-dependent and cAMP-dependent Cl- secretion may be important therapeutic targets with regard to the diarrhoea that is induced by Vibrio mimicus.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2006

Molecular cloning of a murine glycerol-3-phosphate acyltransferase-like protein 1 (xGPAT1).

A novel murine glycerol-3-phosphate acyltransferase-like protein 1 (named xGPAT1) has been cloned. The mouse xGPAT1 gene is located on mouse Chromosome 2, spans >19 kb, and consists of at least 23 exons. The protein is 32% identical and 72% similar to mouse mitochondrial GPAT (mtGPAT) on the amino acid level. Sequencing analysis confirmed that xGPAT1 has a 2403-bp open reading frame (ORF) that encodes an 801-amino acid protein with an estimated molecular mass of 89.1 kDa. A hydropathy plot of the deduced xGPAT1 protein showed a high degree of similarity with that of the mtGPAT protein. Using 5'-rapid amplification of cDNA ends, two alternate, untranslated exon 1 (1a and b) isoforms were obtained, generating variants xGPAT1-v1 and xGPAT1-v2. xGPAT1-v1 is expressed in mouse heart, liver, spleen, kidney and murine inner medullary collecting duct 3 (mIMCD3) cells, while xGPAT1-v2 is expressed in mouse liver, spleen, kidney, white and brown adipose tissues and 3T3-L1 pre- and post-adipocytes. xGPAT1 was distributed in the membrane fraction and showed GPAT activity when epitope-tagged xGPAT1 was expressed in Chinese hamster ovary (CHO)-K1 cells.

Amino Acid Sequence↗
PubMed2006

Gatifloxacin acutely stimulates insulin secretion and chronically suppresses insulin biosynthesis.

Gatifloxacin can cause both hypoglycemia and hyperglycemia in both diabetic and non-diabetic patients. Gatifloxacin recently has been reported to stimulate insulin secretion by inhibition of ATP-sensitive K(+) (K(ATP)) channels in pancreatic beta-cells. Gatifloxacin-induced hypoglycemia is associated with concomitant use of sulfonylureas, and usually occurs immediately after administration of the drug. We find that gatifloxacin acutely stimulates insulin secretion from mouse pancreatic islets and that glibenclamide has additive effects on gatifloxacin-induced insulin secretion. On the other hand, gatifloxacin-induced hyperglycemia often takes several days to develop. We also demonstrate that chronic gatifloxacin treatment decreases islet insulin content by inhibiting insulin biosynthesis, which process may be associated with gatifloxacin-induced hyperglycemia. Moreover, discontinuation of gatifloxacin results in improved insulin secretory response. These data clarify the differing mechanisms of gatifloxacin-induced hyper- and hypoglycemia, and suggest that blood glucose levels should be carefully monitored during gatifloxacin administration, especially in elderly patients with renal insufficiency, unrecognized diabetes, or other metabolic disorders. Because the risk of potentially life-threatening dysglycemia is increased during gatifloxacin therapy, these findings have important implications for clinical practice.

Animals↗
PubMed2006

Role of SGT1 in resistance protein accumulation in plant immunity.

A highly conserved eukaryotic protein SGT1 binds specifically to the molecular chaperone, HSP90. In plants, SGT1 positively regulates disease resistance conferred by many Resistance (R) proteins and developmental responses to the phytohormone, auxin. We show that silencing of SGT1 in Nicotiana benthamiana causes a reduction in steady-state levels of the R protein, Rx. These data support a role of SGT1 in R protein accumulation, possibly at the level of complex assembly. In Arabidopsis, two SGT1 proteins, AtSGT1a and AtSGT1b, are functionally redundant early in development. AtSGT1a and AtSGT1b are induced in leaves upon infection and either protein can function in resistance once a certain level is attained, depending on the R protein tested. In unchallenged tissues, steady-state AtSGT1b levels are at least four times greater than AtSGT1a. While the respective tetratricopeptide repeat (TPR) domains of SGT1a and SGT1b control protein accumulation, they are dispensable for intrinsic functions of SGT1 in resistance and auxin responses.

Arabidopsis↗
PubMed2006

Monoamine oxidase A activity and norepinephrine level in hippocampus determine hyperwheel running in SPORTS rats.

An understanding of neurological mechanisms for wheel running by rodents, especially with high exercise activity, would be applicable to a strategy for promotion of exercise motivation in humans. One of several brain regions that are candidates for the regulation of physical exercise is the hippocampus. Here we examined the running activity of Spontaneously-Running-Tokushima-Shikoku (SPORTS) rat, a new animal model for high levels of wheel-running activity, and its relation with the hippocampal norepinephrine (NE) system including the levels of NE, adrenergic receptors, and degradation enzymes for monoamines. In the hippocampus of SPORTS rats, the level of NE in extracellular fluid was augmented, whereas the level in the homogenate of the whole tissue was decreased even for sedentary conditions. Elevated extracellular NE caused downregulation of alpha(2)-adrenergic receptors in the hippocampus of SPORTS rats. Local administration of alpha(2)-adrenergic receptor antagonist yohimbine, but not of alpha(2)-agonist clonidine, into the hippocampus suppressed high running activity in SPORTS rats. The protein expression and the activity levels of monoamine oxidase A (MAOA), a critical enzyme for the degradation of NE, were decreased in the hippocampus of SPORTS rats to increase extracellular NE level. Thus, inhibition of oxidase activity in normal Wistar rats markedly increased wheel-running activity. These results indicate that decreased MAOA activity, elevation of extracellular NE, and alpha(2)-adrenergic receptors in the hippocampus determine the neural basis of the psychological regulation of exercise behavior in SPORTS rats.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2006

Insulin resistance and low sympathetic nerve activity in the Tsumura Suzuki obese diabetic mouse: a new model of spontaneous type 2 diabetes mellitus and obesity.

Tsumura Suzuki obese diabetic (TSOD) mouse is a new model of type 2 diabetes mellitus and obesity. The TSOD mice had hypoadiponectinemia. To assess the glucose utilization and insulin sensitivity, we examined the effect of insulin (1U/kg) on peripheral tissue glucose uptake in vivo in the TSOD and Tsumura Suzuki nonobese mouse using 2-deoxy-d-[(3)H]glucose. The rates constant of glucose uptake in basal condition without insulin were similar in the peripheral tissues in both strains. Insulin-stimulated glucose uptake by skeletal muscles and adipose tissues in vivo was diminished in the TSOD mice. In addition, we assessed norepinephrine turnover in brown adipose tissue and adrenal epinephrine (E) content and E turnover because disturbances in the sympathetic activities relate to many features in obese and diabetic syndrome. In these mice, the rate of norepinephrine turnover was decreased, and adrenal E content was at most one half of the Tsumura Suzuki nonobese mice and E turnover had extremely low rates. The TSOD mice showed hypercorticosteronemia. These results suggest that TSOD mice have insulin resistance and both low sympathetic nervous activities and low adrenomedullary activity, and have high adrenocortical activity, which are significant features of the TSOD mouse.

Adiponectin↗
PubMed2006

Aeromonas sobria hemolysin causes diarrhea by increasing secretion of HCO3-.

Aeromonas sobria hemolysin (ASH) is one of the major virulence factors produced by A. sobria, a causative agent of diarrhea in humans. We investigated the effects of ASH on anion transport in human colonic epithelial cells. ASH increased short circuit currents across the intestinal epithelia, which were suppressed by anion channel antagonists, such as carbonic anhydrase inhibitors, and by the removal of external HCO3-. Iliac fluid accumulation was also inhibited by carbonic anhydrase inhibitors. The results suggest that ASH activates HCO3- secretion, whose level correlates with the severity of diarrhea.

Aeromonas↗
PubMed2006

[Inactivation of Cryptosporidium parvum oocysts in copper tubing].

We studied whether the infectivity of Cryptosporidium parvum oocysts for suckling mice could be inactivated by copper tubing or by other types of tubing used to construct water distribution systems, including stainless steel, rigid polyvinyl chloride (PVC), PVC-lined steel, polyethylene (PE), cross-linked PE, and polybutene (PB), using glass tubing as the control. Oocysts were incubated in each tubings for 24 hours. The extent of inactivation of infectious oocysts by copper tubing was -1.303 log, which significantly inactivated of infectivity. In contrast, other types of tubing had no significant effect on some oocyst infectivity, although PB did show a maximum inactivation of -0.313 log. 25% of oocysts showed degeneration morphologically after passing through copper tubing, while 0.3% to 1.8% showed degeneration after passing through other tubing. Significant inactivation of infectious oocysts was not caused by water in which copper tubing had been let stand for 24 hours, although it had a cupric ion (Cu2+) concentration of 2.4 mg/L. The direct contact of oocysts with copper surface resulted in a decrease in the recovery percentage of oocysts and generation of hydrogen peroxide (0.5 mg/L) after 24 h of incubation. The percentage of degenerating oocysts was 29%. Such cryptosporidicidal effects of the copper surface on oocysts were completely inhibited by overlaying the surface with a Millipore filter before adding oocysts and incubating oocysts in the presence of catalase, an antioxidant enzyme. These findings suggest that copper tubing inactivates infectious C. parvum oocysts cytotoxically which may be due to oxygen radicals generated by the interaction between Cu2+ and hydrogen peroxide on the tubing surface.

Animals↗
PubMed2006

Congestive myelopathy due to cervical perimedullary arteriovenous fistula evaluated by apparent diffusion coefficient values - case report.

A 22-year-old woman presented with a cervical perimedullary arteriovenous fistula (AVF) manifesting as right upper and lower extremity weakness. T2-weighted magnetic resonance (MR) imaging showed intramedullary hyperintensity believed to be caused by venous congestion. Preoperative diffusion-weighted MR imaging showed increased apparent diffusion coefficient (ADC) value. Spinal angiography demonstrated an AVF fed mainly by the right C-5 radicular artery. Complete obliteration of AVF was achieved by endovascular embolization and microsurgical shunt occlusion. The ADC value was normalized and her neurological deficits improved after endovascular surgery, whereas T2-weighted MR imaging still demonstrated the lesion. The high preoperative ADC value probably indicated reversible vasogenic edema and immediate normalization of the ADC value suggests a good clinical outcome.

Adult↗
PubMed2005

Human airway trypsin-like protease stimulates human bronchial fibroblast proliferation in a protease-activated receptor-2-dependent pathway.

Human airway trypsin-like protease (HAT) was isolated from airway secretions and localized to bronchial epithelial cells by immunohistochemistry. In the present study, we examined whether HAT could stimulate DNA synthesis and proliferation of primary human bronchial fibroblasts (HBF). HAT significantly stimulated the proliferation of HBF by 20-55%, a level similar to that of the mitogenic activity of lung mast cell tryptase (MCT). HAT also stimulated the incorporation of [3H]thymidine in HBF, and this HAT-induced DNA synthesis was abolished by leupeptin. Protease-activated receptor-2 (PAR-2) mRNA was expressed and localized to the cell surface in HBF. PAR-2 activating peptide (AP) also enhanced DNA synthesis, and both HAT and PAR-2 AP induced receptor internalization, similar to the response to trypsin. Pretreatment of HBF with anti-PAR-2 antibody significantly suppressed both HAT and PAR-2 AP-induced DNA synthesis. In addition, HAT and PAR-2 AP induced intracellular Ca2+ mobilization in HBF. The HAT-induced increase in Ca2+ was desensitized by pretreatment with trypsin or PAR-2 AP. U0126, a specific MAPK inhibitor, completely inhibited HAT-induced DNA synthesis as well as HAT-induced phosphorylation of MAPK. The effect of HAT and MCT together was additive, whereas the effect of HAT and insulin together on HBF DNA synthesis was synergistic. These results indicate that HAT stimulates fibroblast proliferation in bronchial airways through a PAR-2-dependent MEK-MAPK mediated pathway and that HAT is linked to airway processes involving fibroblasts.

Aged↗
PubMed2005

Expression of progesterone receptor B is associated with G0/G1 arrest of the cell cycle and growth inhibition in NIH3T3 cells.

Previously, we found a significant reduction of progesterone receptor B (PR-B) expression levels in the Ras-mediated NIH3T3 cell transformation, and re-expression of exogenous PR-B eliminated the tumorigenic potential. We hypothesized that this reduction is of biological significance in cell transformation. In the present study, we determined the correlation between PR-B expression and cell cycle progression. In synchronized NIH3T3 cells, we found an increase in PR-B protein and p27 CDK inhibitor levels in the G0/G1 phase and a reduction due to redistribution in the S and G2/M phases. The MEK inhibitor or cAMP stimulation arrested NIH3T3 cells in the G0/G1 phase of the cell cycle. The expression of PR-B and p27 CDK inhibitors was up-regulated by treatment with both the MEK inhibitor and cAMP. Treatment of synchronized cells with a PKA inhibitor in the presence of 1% calf serum resulted in a significant reduction in both PR-B and p27 levels. The decrease in the PR-B levels caused by anti-sense oligomers or siRNA corresponded to the reduction in p27 levels. PR-B overexpression by adenovirus infection induced p27 and suppressed cell growth. Finally, we showed that PR-B modulation involved in the regulation of NIH3T3 cell proliferation was independent of nuclear estrogen receptor (ER) activity but dependent on non-genomic ER activity.

Adenoviridae↗
PubMed2005

14-3-3 and calmodulin control subcellular distribution of Kir/Gem and its regulation of cell shape and calcium channel activity.

Individual members of the RGK family of Ras-related GTPases, which comprise Rad, Gem/Kir, Rem and Rem2, have been implicated in important functions such as the regulation of voltage-gated calcium channel activity and remodeling of cell shape. The GTPase Kir/Gem inhibits the activity of calcium channels by interacting with the beta-subunit and also regulates cytoskeleton dynamics by inhibiting the Rho-Rho kinase pathway. In addition, Kir/Gem interacts with 14-3-3 and calmodulin, but the significance of this interaction on Kir/Gem function is poorly understood. Here, we present a comprehensive analysis of the binding of 14-3-3 and calmodulin to Kir/Gem. We show that 14-3-3, in conjunction with calmodulin, regulates the subcellular distribution of Kir/Gem between the cytoplasm and the nucleus. In addition, 14-3-3 and calmodulin binding modulate Kir/Gem-mediated cell shape remodeling and downregulation of calcium channel activity. Competition experiments show that binding of 14-3-3, calmodulin and calcium channel beta-subunits to Kir/Gem is mutually exclusive, providing a rationale for the observed regulatory effects of 14-3-3 and calmodulin on Kir/Gem localization and function.

14-3-3 Proteins↗