Biomedical subjects

K Taniguchi

Publications and source records attributed to K Taniguchi.

At least 37 records · Page 2Linked to original sources

PubMed2003

Renal lesions in spontaneous insulin-dependent diabetes mellitus in the nonobese diabetic mouse: acute phase of diabetes.

The nonobese diabetic mouse is a model of spontaneous insulin-dependent diabetes mellitus. The present study made longitudinal observations of renal lesions in the acute-progressive phase of diabetic mice 0, 10, 20, 30, and 40 days after onset of diabetes without insulin therapy. Plasma creatinine and blood urea nitrogen concentrations gradually increased after onset of diabetes. Kidney weight increased and plateaued at day 20. Under electron microscopy the glomeruli demonstrated only mild changes on day 40. In the proximal tubules proliferating cell nuclear antigen-positive nuclei and nuclear divisions were increased on days 10 and 20. On day 40 of diabetes, increased periodic acid-Schiff-positive granules, confirmed as lysosomal dense bodies, increased neuronal nitric oxide synthase (nNOS) positive reaction, and decreased periodic acid-Schiff staining in the brush border were observed in the proximal straight tubules. In the juxtaglomerular apparatus stratified macula densa were decreased with time in diabetes compared with the findings on day 0, and this macula densa positively reacted with nNOS. No changes in renin levels were observed. In addition, apoptotic cells were not detected. In conclusion, this research represents the first thorough characterization of acute changes in nonobese diabetic mouse kidneys. The results demonstrated renal hypertrophy and slight glomerular injury in early stages and structural alteration of the proximal straight tubules at later stages during the acute phase of diabetes. Furthermore, increased nNOS may represent one of the pathogenic factors of diabetic nephropathy.

Animals↗

PubMed2002

Therapy of rat tracheal carcinoma IC-12 in SCID mice: vascular targeting with [213Bi]-MAb TES-23.

In previous work, we have demonstrated that vascular targeting of [213Bi], an alpha-emitter, to lung blood vessels could efficiently destroy tumour colonies growing in the lung. In order to expand this approach to treatment of tumours growing in other sites, we employed the monoclonal antibody (MAb) TES-23, which reacts with CD44H, preferentially expressed on new blood vessels in tumours. Biodistribution studies of N-succinimidyl [125I] 3-iodobenzoate (SIB)-radiolabelled MAb TES-23 in ICR-severe combined immunodeficient (SCID) mice bearing subcutaneous (s.c.) and intramuscular (i.m.) IC-12 tumours, demonstrated efficient tumour uptake. At 24 h, accumulation in small tumours was 45%ID/g for s.c. tumours, and 58%ID/g for i.m. tumours and in large tumours it was 25%ID/g for s.c. tumours and 17%ID/g for i.m. tumours. Micro-autoradiography data confirmed that radiolabel accumulated in or near tumour blood vessels. Normal tissues had very low levels of radioactivity. Treatment of mice bearing small IC-12 tumours with [213Bi] MAb TES-23 retarded tumour growth relative to animals treated with cold MAb TES-23. Biodistribution and therapy experiments were also performed in BALB/c mice bearing both s.c. and i.m. syngeneic, lung carcinoma (line 498) tumours. [I(125)] SIB MAb TES-23 accumulated efficiently in both s.c. and i.m. tumours (14%ID/g and 15%ID/g, respectively, at 4 h); however, no therapeutic effect of [213Bi] MAb TES-23 treatment could be demonstrated in this model system. The data demonstrate that the timing of vascularisation of the tumours and the delivery kinetics of MAb relative to the half-life of the therapeutic radionuclide are critical for effective therapy.

Animals↗

PubMed2002

Analysis of HLA in children with gelatin allergy.

Systemic immediate reactions including anaphylaxis to gelatin in vaccines have been reported. However, the number of such reports is very small compared with the number of children exposed to gelatin. The present study was designed to investigate whether susceptibility or resistance to gelatin allergy is associated with human leukocyte antigen (HLA) class II gene. Blood samples were obtained from 49 patients with gelatin allergy and specific IgE to gelatin. DNA-based HLA class II typing was performed to determine the DRB1, DQB1 and DPB1 alleles. Genotype frequencies were compared with those found in 240 unrelated controls. The frequency of DQB1*0303 (55.1%) was significantly higher in the patients than in the control subjects (32.1%). The frequency of DPB1*0402 was also significantly higher in the patients (32.7%) than in the control subjects (15.4%). On the other hand, the frequency of subjects carrying DRB1*15 (DRB1*1501 and DRB1*1502) was significantly lower among the patients group (18.4%) than among the controls (40.8%). We found that DQB1*0303 and DPB1*0402 were positively associated with the IgE response for gelatin, while DRB1*15 was negatively associated with it.

Child↗

PubMed2002

Clenbuterol induces expression of multiple myosin heavy chain isoforms in rat soleus fibres.

Clenbuterol, a beta2-agonist, administration results in hypertrophy of fast fibres and an increase in the fast myosin heavy chain (MHC) composition of both fast and slow muscles. The present study was designed to determine the phenotypic response at the single fibre level. Clenbuterol was added to the drinking water (30 mg L(-1)) of adult male Wistar rats for 4 weeks. Single fibres from the soleus muscle of control (10 rats; 555 fibres) and clenbuterol-treated (10 rats; 577 fibres) were dissected and their MHC isoform composition was determined using sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis. Body, heart, and soleus weights were 9, 24, and 27% higher in clenbuterol-treated than control rats. The mean cross-sectional areas of fast and slow/fast hybrid fibres were approximately 64 and approximately 74% larger in the clenbuterol-treated than control rats, whereas the size of the slow fibres were similar in the two groups. Fibres from control soleus showed three MHC patterns: pure type I (84%), pure type IIa (4%), and type I + IIa (12%) MHC. Some fibres from clenbuterol-treated soleus showed a de novo expression of type IIx MHC resulting in the following fibre type proportions: pure type I (62%), pure type IIa (2%), type I + IIa (26%), type I + IIa + IIx (6%), and type IIa + IIx (1%). In those fibres containing multiple MHCs, there was a shift towards the faster MHC isoforms after clenbuterol treatment. These data indicate that clenbuterol results in muscle fibre hypertrophy, stimulates a de novo expression of type IIx MHC and increases the percentage of fibres containing multiple MHC isoforms in the rat soleus muscle. These phenotypic changes at the single fibre level are consistent with a clenbuterol-related shift in the functional properties of the soleus towards those observed in a faster muscle.

Animals↗

PubMed2002

Detection of a human rotavirus with G12 and P[9] specificity in Thailand.

G12 rotavirus has not been detected anywhere in the world since the first detection of a human strain, L26 (G12, P1B[4]), in the Philippines in 1990. In this study, we isolated a human rotavirus (strain T152) with a VP7 of G12 specificity from the stool of an 11-month-old diarrheic patient in Thailand. The strain T152 exhibited a long RNA pattern and subgroup I specificity. In the comparison of the nucleotide and amino acid sequences of the VP7 gene of strain T152 with those of rotaviruses with different G type specificities, strain T152 showed the highest identity, 90.9 and 93.9%, respectively, to G12 prototype strain L26. In contrast, the VP4 gene of strain T152 showed the highest identity with P[9] specificity of human strains K8 and AU-1 and feline strains Cat2 and FRV-1, with homologies of 89.3 to 90.6% at the nucleotide level and 93.9 to 95.6% at the amino acid level. Thus, strain T152 was found to be a natural reassortant strain with G12 and P[9] specificities.

Amino Acid Sequence↗

PubMed2001

Discovery of a N'-hydroxyphenylformamidine derivative HET0016 as a potent and selective 20-HETE synthase inhibitor.

N-(4-Butyl-2-methylphenyl)-N'-hydroxyformamidine (HET0016) was evaluated as the first potent and selective inhibitor of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) synthase. The IC(50) value of HET0016 for the production of 20-HETE from arachidonic acid (AA) by human renal microsomes was 8.9+/-2.7 nM, with over 200 times the selectivity of xenobiotic-metabolizing cytochrome P450 enzymes. An examination of the structure-activity relationship revealed that the unsubstituted hydroxyformamidine moiety and the substituent at the para-position of the N-hydroxyformamidine moiety are necessary for the potent activity of HET0016.

Amidines↗

PubMed2001

mRNA sequence of the Xenopus laevis paxillin gene and its expression.

Paxillin is a cytoskeletal protein found in structures of focal adhesions where cells adhere to the extracellular matrix. We isolated paxillin cDNA from the Xenopus laevis ovary. The cDNA sequence encodes a protein of 539 amino acids with four LIM and five LD motifs. 80% of the amino acids of frog paxillin are shared by human and chicken paxillins. Northern analysis showed that the frog gene is expressed in the spleen, kidney, testis and ovary. Immunocytochemistry showed that paxillin protein is accumulated in the nucleus as well as in the periphery of the cytoplasm of the A6 cell. This intriguing result shows that paxillin, which has been characterized as a cytoskeletal protein, is capable of translocating to the nucleus.

Amino Acid Sequence↗

PubMed2001

Amino-terminal fragment of urokinase-type plasminogen activator inhibits HIV-1 replication.

CD8+ T lymphocytes have been shown to produce unidentified soluble factors active in suppressing HIV-1 replication. In this study, we purified an HIV-1 suppressing activity from the culture supernatant of an immortalized CD8+ T cell clone, derived from an HIV-1 infected long-term nonprogressor, and identified this activity as the amino-terminal fragment (ATF) of urokinase-type plasminogen activator (uPA). ATF is catalytically inactive, but suppresses the release of viral particles from the HIV-1 infected cell lines via binding to its receptor CD87. In contrast, cell proliferation and the secretion of an HIV-1 LTR driven reporter gene product were not affected by ATF. These findings suggest that ATF may inhibit the assembly and budding of HIV-1, which provides a novel therapeutic strategy for AIDS.

CD4-Positive T-Lymphocytes↗

PubMed2001

Weak vasoconstrictor activity of melatonin in human umbilical artery: relation to nitric oxide-scavenging action.

We evaluated the nitric oxide (NO)-scavenging property of melatonin, demonstrated in a recent in vitro study, on vascular reactivity in the human umbilical artery. Helical sections of human umbilical artery were prepared following elective Cesarean deliveries near term. Changes in maximal tension induced by prostaglandin F(2 alpha)(5 x 10(-5) M) were measured in artery sections with an intact endothelium. Melatonin at concentrations higher than 10(-6) M increased prostaglandin F(2 alpha)-induced vascular tension. The vasospastic effect of melatonin was much less than that of L-N(G)-monomethylarginine (L-NMA, 2 x 10(-4) M), an inhibitor of NO synthesis (2.8+/-1.4%, 9.1+/-1.7%, 16.5+/-2.5%, and 29.6+/-5.9% of the L-NMA effect at melatonin concentrations of 10(-8), 10(-7), 10(-6), and 10(-5) M, respectively). Removal of the endothelium significantly reduced the vasoconstrictive effect of melatonin. Treatment with L-NMA (2 x 10(-4) M) prior to addition of prostaglandin F(2 alpha) also significantly reduced the vasoconstrictive effect of melatonin (10(-5) M). Treatments with melatonin (10(-5) M) did not affect calcium ionophore A 23187-induced relaxation or 5-hydroxytryptamine-induced constriction. The findings indicate that melatonin may potentiate vascular tension in human umbilical artery by scavenging endogenous endothelial NO, but not by inhibiting NO synthesis. However, the NO-scavenging vasoconstrictive effect of melatonin may be negligible at physiologic concentrations and very weak at pharmacologic concentrations below 10(-7) M.

Dinoprost↗

PubMed2001

Li K-edge spectra of lithium halides.

We measured the Li K-edge spectra of lithium halides by means of total electron yield method (TEY), using the soft x-ray Beam Line 2 (BL2) of the compact synchrotron radiation facility at Ritsmeikan University in Japan. In lithium halides, the spectra have a sharp peak at about 60eV and a broad peak at the higher energy side. Various peak structures that appear in the absorption spectra are assigned to the corresponding Li-1s to valence band free orbitals transitions, which have been calculated by the Discrete Variational (DV)-Xalpha molecular orbital calculation method.

Journal Article↗

PubMed2001

Rat glioma cell death induced by cationic liposome-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment.

BACKGROUND AND OBJECTIVES: We studied antitumor effects and cell death induced by cationic liposome-mediated gene transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene followed by ganciclovir treatment in cultured rat T9 glioma cells and in experimental gliomas produced from this cell line. METHODS: To transfer genes we used small unilamellar cationic liposomes containing N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride. Video-enhanced contrast differential interference contrast microscopy was used for morphologic observations of cultured cells. RESULTS: When we treated the cells or implanted gliomas with the liposomes and ganciclovir, a strong effect was seen against tumor cells, and survival of tumor-implanted rats was increased. Morphologically, cell death observed after HSV-tk gene/liposome and ganciclovir treatment in the cultured glioma cells included both apoptosis and necrosis. CONCLUSIONS: Introduction of the HSV-tk gene in a DNA-liposome complex followed by ganciclovir treatment induced both apoptosis and necrosis, which together resulted in a potent antitumor effect.

Animals↗

PubMed2001

Sequence analysis of genes encoding structural and nonstructural proteins of a human group B rotavirus detected in Calcutta, India.

Nucleotide sequences of RNA segments encoding structural proteins(VP4, VP6, and VP7) and nonstructural proteins(NSP1 and NSP3) of a human group B rotavirus CAL-1, which was detected in Calcutta, India, were determined and their relatedness with cognate genes of other group B rotaviruses was analyzed. The CAL-1 genes showed generally high sequence identities (more than 90%) to those of human group B rotavirus, adult diarrheal rotavirus (ADRV) in China, while identities with bovine, murine, and ovine viruses were considerably lower (58-73%). Among RNA segments analyzed, sequence identity of the VP6 gene was relatively high compared with other gene segments. In the CAL-1 VP7 sequence, many characteristics were shared by ADRV, but not by other animal group B rotaviruses. In contrast, VP4 and NSP3 of CAL-1 were single amino acid and 23 amino acids longer than those of ADRV strain, respectively, due to differences of a few nucleotides. These findings suggested that human group B rotaviruses CAL-1 and ADRV might have originated from a common ancestral virus distinct from animal group B rotaviruses reported so far, while some notable sequence differences indicated the distinct nature of these viruses.

3' Untranslated Regions↗

PubMed2001

Postoperative evaluation of pylorus-preserving procedures compared with conventional distal gastrectomy for early gastric cancer.

We evaluated postoperative function in 98 patients who underwent surgery for early gastric cancer between 1995 and 1998 to compare the results of pylorus-preserving procedures to those of conventional distal gastrectomy with Billroth I (B-I). The pylorus-preserving procedures included endoscopic mucosal resection (EMR), performed in 12 patients; local resection (Local), performed in 14 patients; segmental resection (Seg), performed in 8 patients; and pylorus-preserving gastrectomy (PPG), performed in 19 patients. B-I was performed in 45 patients. The nutritional status and serum albumin (Alb) levels after PPG, the hemoglobin (Hb) levels after EMR, Local, and PPG, and the present/preoperative body weight ratios after EMR, Local, Seg, and PPG were superior to those after B-I. The time before oral intake was recommenced after EMR and Local, the volume of oral intake tolerated after EMR, Local, Seg, and PPG, and the postoperative hospital stay after EMR were all superior to those after B-I. Moreover, significantly fewer patients suffered reflux symptoms after EMR, Local, and PPG, abdominal fullness after EMR, and early dumping syndrome after EMR, Local, and PPG than after B-I. There was also less evidence of gastritis after EMR, Local, and PPG, and of bile reflux after EMR, Local, and PPG, than after B-I. These findings indicate that pylorus-preserving procedures may result in a better postoperative quality of life for selected patients with early gastric cancer.

Adult↗

PubMed2001

Analysis of anti-rotavirus activity of extract from Stevia rebaudiana.

Anti-human rotavirus (HRV) activity of hot water extracts from Stevia rebaudiana (SE) was examined. SE inhibited the replication of all four serotypes of HRV in vitro. This inhibitory effect of SE was not reduced on the prior exposure of SE to HCl for 30 min at pH 2. Binding assay with radiolabeled purified viruses indicated that the inhibitory mechanism of SE is the blockade of virus binding. The SE inhibited the binding of anti-VP7 monoclonal antibody to HRV-infected MA104 cells. The inhibitory components of SE were found to be heterogeneous anionic polysaccharides with different ion charges. The component analyses suggested that the purified fraction named as Stevian with the highest inhibitory activity consists of the anionic polysaccharide with molecular weight of 9800, and contains Ser and Ala as amino acids. Analyses of sugar residues suggest uronic acid(s) as sugar components. It did not contain amino and neutral sugars and sulfate residues. These findings suggest that SE may bind to 37 kD VP7 and interfere with the binding of VP7 to the cellular receptors by steric hindrance, which results in the blockade of the virus attachment to cells.

Animals↗

PubMed2001

Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1.

Muscle-eye-brain disease (MEB) is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, and lissencephaly. Mammalian O-mannosyl glycosylation is a rare type of protein modification that is observed in a limited number of glycoproteins of brain, nerve, and skeletal muscle. Here we isolated a human cDNA for protein O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGnT1), which participates in O-mannosyl glycan synthesis. We also identified six independent mutations of the POMGnT1 gene in six patients with MEB. Expression of most frequent mutation revealed a great loss of the enzymatic activity. These findings suggest that interference in O-mannosyl glycosylation is a new pathomechanism for muscular dystrophy as well as neuronal migration disorder.

Amino Acid Sequence↗

PubMed2001

Melatonin counteracts potentiation by lysophosphatidylcholine of serotonin-induced vasoconstriction in human umbilical artery: relation to calcium influx.

We evaluated mechanisms underlying the antioxidant property of melatonin as related to vasospastic effects in the human umbilical artery from lysophosphatidylcholine (LPC), a component of oxidized lipoprotein. Helical sections of umbilical artery without endothelium were obtained at elective cesarean delivery between 37 and 39 wk of gestation. Changes in 5-hydroxytryptamine (5-HT)-induced vasoconstriction were measured. Arterial sections were treated with LPC (15 or 30 microM) alone or pretreated with a hydroxyl radical (.OH) scavenger, mannitol (20 mM), an H2O2 scavenger, catalase (1,200 U/mL), or melatonin (0.1 or 1.0 microM). The effect of LPC on the response of arterial sections to external calcium in the presence of KCl (20 mM) was determined. LPC potentiated 5-HT-induced vasoconstriction in a concentration-dependent manner; pretreatment with mannitol or catalase significantly reduced this vasospastic effect. LPC (30 microM) significantly augmented the contractile response to external calcium. Melatonin (1.0 microM) pretreatment significantly suppressed the contractile response to external calcium. The results suggest that LPC potentiates 5-HT-induced umbilical artery vasoconstriction, in part by increasing the calcium influx into smooth muscle cells via activation of voltage-dependent calcium channels. Given a previous finding, the vasospastic effect of LPC on the umbilical artery also appears to involve the suppression of endothelial nitric oxide production. Melatonin significantly suppresses the vasospastic effect of LPC, probably by scavenging .OH arising from LPC.

Antioxidants↗

PubMed2001

Melatonin protects against oxidative mitochondrial damage induced in rat placenta by ischemia and reperfusion.

We assessed the effects of melatonin, a powerful scavenger of oxygen free radicals, on ischemia/reperfusion-induced oxidative damage to mitochondria in the rat placenta. In Wistar rats at day 19 of pregnancy, feto-placental ischemia was induced by occluding both utero-ovarian arteries for 20 min. Reperfusion was achieved by releasing the occlusion and restoring circulation for 30 min. Melatonin solution or the vehicle alone was injected intraperitoneally at dose of 10 mg/kg 1 hr before occlusion. Sham-ischemic animals were treated with vehicle. Each group consisted of 10 pregnant rats. We measured placental mitochondrial respiratory control index (RCI; a marker of mitochondrial respiratory activity), the ratio of the added adenosine 5-diphosphate (ADP) concentration to consumption of oxygen during state 3 respiration (ADP/O), and the concentration of thiobarbituric acid reactive substances (TBARS) in each group. RCI and ADP/O were significantly decreased by ischemia/reperfusion, while TBARS were increased. Melatonin prevented these changes. These results indicate that exogenous melatonin protects against ischemia/reperfusion-induced oxidative damage to mitochondria in rat placenta. Melatonin could be useful in treating preeclampsia and possibly other clinical states involving excess free radical production, such as fetal growth restriction and fetal hypoxia.

Adenosine Diphosphate↗

PubMed2001

HET0016, a potent and selective inhibitor of 20-HETE synthesizing enzyme.

The present study examined the inhibitory effects of N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine (HET0016) on the renal metabolism of arachidonic acid by cytochrome P450 (CYP) enzymes. HET0016 exhibited a high degree of selectivity in inhibiting the formation of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) in rat renal microsomes. The IC(50) value averaged 35+/-4 nM, whereas the IC(50) value for inhibition of the formation of epoxyeicosatrienoic acids by HET0016 averaged 2800+/-300 nM. In human renal microsomes, HET0016 potently inhibited the formation of 20-HETE with an IC(50) value of 8.9+/-2.7 nM. Higher concentrations of HET0016 also inhibited the CYP2C9, CYP2D6 and CYP3A4-catalysed substrates oxidation with IC(50) values of 3300, 83,900 and 71,000 nM. The IC(50) value for HET0016 on cyclo-oxygenase activity was 2300 nM. These results indicate that HET0016 is a potent and selective inhibitor of CYP enzymes responsible for the formation of 20-HETE in man and rat.

Amidines↗