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Biomedical subjects

Y Itoh

Publications and source records attributed to Y Itoh.

At least 145 records · Page 8Linked to original sources
PubMed2000

Role of metabotropic glutamate receptor subclasses in modulation of adenylyl cyclase activity by a nootropic NS-105.

The involvement of metabotropic glutamate (mGlu) receptors in the modulatory actions of a novel cognition enhancer, (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105), on adenylyl cyclase activity in rat cerebrocortical membranes and primary neuronal cultures was investigated using selective antagonists and antisense oligodeoxynucleotides for mGlu receptor subclasses. In rat cerebrocortical membranes, the inhibitory action of NS-105 (0.1 microM) on forskolin-stimulated cAMP formation was blocked by a group II mGlu receptor antagonist, (+/-)-alpha-ethylglutamic acid, and by a group III antagonist, (+)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP-4), but not by a group I antagonist, (+/-)-1-aminoindan-1,5-dicarboxylic acid (AIDA), whereas the facilitation of cAMP formation by NS-105 (1 microM) in pertussis toxin-pretreated membranes was abolished by AIDA but not by (+/-)-alpha-ethylglutamic acid or MAP-4. In primary cultured neurons of mouse cerebral cortex, the inhibitory action of NS-105 on adenylyl cyclase activity disappeared after treatment with antisense oligodeoxynucleotides for group II (mGlu(2) and mGlu(3) receptors) and group III (mGlu(4) and mGlu(7) receptors) but not group I (mGlu(5) receptor) mGlu receptor subclasses. These findings suggest that the inhibitory action of NS-105 on adenylyl cyclase activity is mediated through group II and group III mGlu receptor subclasses while the facilitatory action is dependent on the group I mGlu receptor subclass.

Adenylyl Cyclases↗
PubMed2000

Liver-infiltrating T lymphocytes are attracted selectively by IFN-inducible protein-10.

We have demonstrated that interferon-inducible protein-10 (IP-10) is produced in hepatocytes surrounded by infiltrative mononuclear cells in chronic hepatitis. To clarify the role of IP-10 in hepatitis, we examined the chemoattractive activity of IP-10 on liver-infiltrating lymphocytes in experimental animal models of hepatitis. IP-10 was specifically induced in the livers of mice treated intravenously (i.v.) with Con A, while monocyte chemotactic protein-1 (MCP-1) showed a much lower level of induction and neither RANTES nor macrophage inflammatory protein-1alpha (MIP-1alpha) was detected. The liver-infiltrating lymphocytes in Con A-induced hepatitis were attracted only by IP-10, and not by other chemokines such as RANTES, MCP-1 and MIP-1alpha. The chemoattractive effect of IP-10 was dose-dependent and was neutralized by monoclonal antibodies to IP-10. The specific effect of IP-10 on liver-infiltrating lymphocytes was also seen on those obtained from rat livers with fulminant hepatitis induced by sequential treatment with killed Propionibacterium acnes (P. acnes) and LPS. Peripheral blood lymphocytes were slightly attracted by IP-10 as well as RANTES and MIP-1alpha, while hepatic resident lymphocytes were not. On the other hand, thioglycolate-elicited peritoneal macrophages did not respond to IP-10, although they did show a response to RANTES, MCP-1 and MIP-1alpha. These results indicated that IP-10 is a specific chemoattractant for T lymphocytes in the inflammatory liver tissues and may play a specific role in the development of hepatitis.

Animals↗
PubMed2000

TNF-alpha is a potent inducer for IFN-inducible protein-10 in hepatocytes and unaffected by GM-CSF in vivo, in contrast to IL-1beta and IFN-gamma.

We have recently shown that IFN-inducible protein 10 (IP-10), a member of the CXC chemokine family, is induced in hepatocytes surrounded by infiltrative mononuclear cells in human livers with chronic hepatitis. Hence, we examined the kinds of stimuli that can induce IP-10 expression in hepatocytes in vivo. While the liver expressed three chemokine genes (IP-10, JE/MCP-1, KC/GRO) in a tissue-specific fashion following systemic treatment with pro-inflammatory cytokines, IP-10 mRNA expression showed the most marked liver-specificity. Pretreatment with GM-CSF selectively inhibited IL-1beta, but not TNF-alpha-induced IP-10 mRNA expression. In situ hybridization analysis in the liver and Northern hybridization analysis in isolated liver cell fractions from rodents treated with pro-inflammatory cytokines revealed cellular sources of chemokine expression. IP-10 mRNA expression in hepatocytes was induced by i.v. administration of TNF-alpha, and to a much lesser extent in response to IL-1beta and IFN-gamma, whereas Kupffer cells and endothelial cells expressed IP-10 mRNA equivalently in response to these three stimuli. On the other hand, JE/MCP-1 mRNA expression was detected only in non-parenchymal cells in response to TNF-alpha and IL-1beta, but not in response to IFN-gamma. KC/GRO mRNA expression was also induced mainly in sinusoidal cells by treatment with TNF-alpha or IL-1beta, although it was detected to a lesser extent in hepatocytes. Our results demonstrated that chemokine induction is stimulus-, tissue- and cell type-specific and that IP-10 (but not MCP-1) is inducible in hepatocytes by TNF-alpha most potently, even in the presence of GM-CSF, suggesting the specific role of TNF-alpha-induced IP-10 on intralobular mononuclear infiltration in chronic hepatitis.

Animals↗
PubMed2000

Readministration of tamoxifen after adjuvant therapy for recurrent breast cancer.

BACKGROUND: Previous series concerning tamoxifen (TAM) rechallenge did not obtain satisfactory results. Using stricter criteria, we now assess the usefulness of readministration of TAM as an initial therapy for patients with recurrent breast cancer. METHOD: The eligibility criteria were postmenopausal, estrogen receptor (ER) positive or unknown, at least 12 months of adjuvant TAM, a 6-month or longer drug-free period and no previous therapy after recurrence. A total of 10 patients were enrolled. TAM was administered in daily doses of 20 or 30 mg. RESULTS: The mean age of the patients at the time of recurrence was 64.8 years. The receptor status was positive in 8 patients and unknown in 2. The median disease-free interval (DFI) after mastectomy was 71.7 months. A complete response was observed in one patient, a partial response in 6, stable disease in 2, and progression in one. The response rate was thus 70%, with an additional two patients showing no progression over 6 months. Although only one patient with a DFI of less than 48 months showed a positive response, all patients with a DFI longer than 48 months showed a clinical response. The duration of response was less than 12 months in 3 patients and longer in 4. CONCLUSION: The post-adjuvant readministration of tamoxifen is a useful first choice therapy for postmenopausal recurrent breast cancer patients with positive ER and longer DFI.

Aged↗
PubMed2000

Japanese patients with sporadic Hirschsprung: mutation analysis of the receptor tyrosine kinase proto-oncogene, endothelin-B receptor, endothelin-3, glial cell line-derived neurotrophic factor and neurturin genes: a comparison with similar studies.

UNLABELLED: We report on mutation analysis of five genes involved in the receptor tyrosine kinase (RET) or the endothelin-signalling pathways in 28 sporadic Japanese patients with Hirschsprung disease. Analysis of DNA obtained from peripheral blood cells revealed six mutations in the RET proto-oncogene, four of which were disease-causing mutations in exon 9 (D584G), the splice donor site of intron 10 (+2T to A), exon 11 (A654T), and exon 12 (T706A). A heterozygous A to G transition was found in 47 bases upstream from the 5' end of exon 2 in two HD patients but was also seen in one control subject (2/28; 1/24). A silent 2307T to G transversion was observed in exon 13. Two disease-causing mutations were detected in the endothelin receptor (EDNRB) gene, in the non-coding region of exon 1 (-26 G to A) and in exon 4 (A301T); the latter mutation was a novel one. One silent mutation was observed in exon 4 (codon 277). One heterozygous T to C mutation was found in the glial cell line-derived neurotrophic factor gene in 25 bases upstream of the coding region in exon 1. No nucleotide changes were detected in either the endothelin-3 or neurturin genes. Disease-causing mutation rates in the RET proto-oncogene and the EDNRB gene were estimated at 14.3% (4/28) and 10.7% (3/28), respectively. In addition to mutations in the RET and EDNRB genes, embryonic environmental factors and/or other genetic factors appear to be involved in the development of Hirschsprung disease. Further systematic studies of genetic variation in a large series of patients and controls are necessary for elucidating the pathogenesis of this disorder. CONCLUSION: This study provides further gene alterations as disease-causing mutations in Japanese cases of sporadic Hirschsprung disease. However, the low mutation rate of the susceptibility genes may indicate that Hirschsprung disease arises from a combination of genetic and environmental factors.

Asian People↗
PubMed2000

Ischemic hepatitis induced by mesenteric volvulus in a patient with chronic obstructive lung disease.

A 66-year-old man with chronic obstructive lung disease was admitted to our hospital, presenting with mesenteric volvulus and mild liver injury. A superior mesenteric angiogram revealed that the arteries supplying the small intestine were twisted in the arterial phase, while the portal vein was not visualized in the late phase. A celiac angiogram demonstrated that portal blood flow from the splenic venous return was maintained. The patient's symptoms had almost resolved the day after admission, and his serum transaminases level had gradually decreased to normal with conservative therapy. A superior mesenteric angiogram on the 13th hospital day showed a normal arteriogram and the portal vein demonstrated blood flow from the superior mesenteric vein. Liver biopsy revealed hemorrhagic necrosis around the central veins, which was compatible with ischemic hepatitis. Since the patient's O2 saturation level on admission was not low enough to have caused ischemic hepatitis by itself, we suspect that a sudden decrease in portal blood flow was the additional factor that allowed the threshold for the initiation of ischemic liver damage to be reached.

Aged↗
PubMed2000

Histological evaluation of allograft bone after acetabular revision arthroplasty: report of two cases.

We recently had the opportunity to take histological sections from two patients who underwent acetabular reconstruction in which allograft and ME Müller acetabular roof reinforcement rings were used. In one patient (case 1), histological sections of the chipped allograft were taken on two separate occasions from the same area, at 7 months, and at 3 years and 11 months after the bone graft. The histology of the chipped allograft showed necrosis at 7 months, but almost normal morphology of trabecular bone formation at 3 years and 11 months after the bone graft. In the other patient (case 2) histological sections of the block allograft and chipped allograft were taken at 1 year and 8 months after the bone graft. The block allograft showed only a small amount of admixture of newly formed bone with the necrotic bone, while the chipped allograft showed a large amount of newly formed bone, with only a small amount of necrotic bone remaining. Therefore, we principally use chipped allograft for acetabular reconstruction, in order to achieve early and complete graft incorporation. If a block allograft is used in a weight-bearing area, it should be protected from excessive load by using an acetabular reinforcement device.

Acetabulum↗
PubMed2000

Transgenic apple (Malus x domestica) shoot showing low browning potential.

Transgenic apple shoots were prepared from leaf disks by using Agrobacterium tumefaciens carrying the kanamycin (KM) resistance gene and antisense polyphenol oxidase (PPO) DNA. Four transgenic apple lines that grew on the medium containing 50 microgram/mL KM were obtained. They contained the KM resistance gene and grew stably on the medium for >3 years. Two transgenic shoot lines containing antisense PPO DNA in which PPO activity was repressed showed a lower browning potential than a control shoot.

Agrobacterium tumefaciens↗
PubMed2000

Association of Clara cell 10-kDa protein, spontaneous regression and sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder with a high rate of spontaneous regression. Clara cell 10-kDa protein (CC10), the predominant product of nonciliated bronchiolar epithelial cells, is a potent immunoregulatory and anti-inflammatory agent. CC10 levels were measured in sera and bronchoalveolar lavage (BAL) fluids from 31 sarcoidosis patients (nine progressive disease and 22 regressive disease) and their relevance to spontaneous regression investigated. The inhibitory effects of recombinant CC10 on interferon gamma (IFN-gamma) production were examined using lipopolysaccharide (LPS)-stimulated sarcoid BAL fluid cells, and the blocking effects of monoclonal antibody TY-5, directed against CC10, on CC10 function were also tested. Serum and BAL fluid CC10 levels in the regressive disease group were significantly higher than those in the progressive disease group (serum, p<0.05; BAL fluid, p<0.005) and healthy subjects (serum, p<0.0001; BAL fluid, p<0.005). CC10 inhibited, in part, IFN-gamma production from LPS-stimulated sarcoid BAL fluid cells (CC10 inhibition: 1,000 ng x mL(-1), 30%; 100 ng x mL(-1), 14%). TY-5 restored IFN-gamma production by blocking CC10 function. Sarcoidosis patients with regressive disease showed increased Clara cell 10-kDa protein levels in their sera and bronchoalveolar lavage fluids. Clara cell 10-kDa protein may be a regulator of the inflammatory process in sarcoidosis.

Adult↗
PubMed2000

Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame Herba, on rats fed a high-fat diet.

OBJECTIVE: To investigate the inhibitory effects of CT-II, extract of Nomame Herba, on lipase activity in vitro and on obesity in rats fed a high-fat diet in vivo. DESIGN: The assay for the inhibitory effect of CT-II on lipase activity was performed by measuring released free fatty acids after the incubation of the medium with CT-II, porcine pancreatic lipase and triolein (experiment 1). In vivo experiments, lean rats or obese rats (570-718 g) were fed a high-fat diet containing 60% fat with or without CT-II for 8 weeks (experiment 2), for 14 days (experiment 3) or for 12 weeks (experiment 4), respectively. MEASUREMENT: The time course of body weight, food intake, organ weight (parametrial fat, liver, heart and kidney) and plasma parameters (triglyceride, total cholesterol, glucose, AST, ALT and insulin), fecal output of total fat and total cholesterol were measured. Hepatic histological examinations were also performed. RESULTS: CT-II inhibited the porcine lipase activity dose-dependently in vitro (experiment 1). Body and liver weight were reduced and hepatic histological examination showed an amelioration of fatty liver in CT II treated animals (experiment 2). CT-II significantly inhibited body weight gain and plasma triglyceride elevation in a dose-dependent manner, without affecting food intake in lean rats fed the high-fat diet. Elevated plasma AST and ALT were also decreased (experiment 3). When obese rats fed the high-fat diet were treated with CT-II for up to 6 months, body weight was initially reduced and thereafter weight gain was significantly suppressed. Total body fat was also significantly reduced and significant reduction of plasma AST and ALT was observed (experiment 4). CONCLUSIONS: These results demonstrated that the lipase inhibitor CT-II is effective in preventing and ameliorating obesity, fatty liver and hypertriglyceridemia in rats fed a high-fat diet.

Alanine Transaminase↗
PubMed2000

Induction of MTG8-specific cytotoxic T-cell lines: MTG8 is probably a tumour antigen that is recognized by cytotoxic T cells in AML1-MTG8-fused gene-positive acute myelogenous leukaemia.

Several reports have demonstrated the persistent detection of AML1-MTG8 fusion products, representing minimal residual disease (MRD), in patients with t(8;21) acute myelogenous leukaemia (AML) who are in long-term remission. It is probable that immune-mediated mechanisms that are able to suppress the expansion of MRD may result in the continuance of remission. It was previously shown that some t(8;21) AML patients had high anti-MTG8 antibody titres. MTG8 expression in normal adult tissues is limited to the brain or heart in which human leucocyte antigen (HLA) class I cell-surface antigens are either not or are only faintly detectable. We hypothesized that the overexpression of the MTG8 gene in t(8;21) AML cells could act as a possible tumour antigen, which might be able to induce the immune-mediated suppression of the expansion of MRD. We were able to induce HLA-A0201-restricted cytotoxic T-lymphocyte (CTL) lines against an MTG8 peptide (MTG8b amino acids 182-191) using monocyte-derived dendritic cells from a healthy donor. T-cell receptor (TCR)Valpha17, TCRVbeta14 and 15, and TCRJbeta2.1 and 2.3 are predominantly used in these CTL lines. Our data, which suggest that the MTG8 protein could be one of the tumour antigens recognized by CTLs, may be helpful in further investigations of TCR analysis in t(8;21) AML patients with HLA-A0201 who are in long-term remission.

Antigens, Neoplasm↗
PubMed2000

Divergent structure of the ComQXPA quorum-sensing components: molecular basis of strain-specific communication mechanism in Bacillus subtilis.

In Bacillus subtilis, the ComQXPA quorum-sensing system controls cell density-dependent phenotypes such as the production of degradative enzymes and antibiotics and the development of genetic competence. Bacillus subtilis (natto) NAF12, a mutant defective in poly-gamma-glutamate (gamma-PGA) production, was derived from B. subtilis (natto) NAF4 by Tn917-LTV1 insertional mutagenesis. Determination of the mutant DNA sequences flanking the Tn917-LTV1 insert revealed that the insertion had inactivated comP in this mutant, indicating that gamma-PGA synthesis in B. subtilis (natto) is under the control of the ComP-ComA signal transduction system. A comparison of the amino acid sequences revealed striking variation in the primary structures of ComQ (44% identity), ComX (26%) and the sensor domain of ComP (36%) between B. subtilis (natto) NAF4 and B. subtilis 168. In contrast, the amino acid and nucleotide sequences of the kinase domains of ComP and of the ComA response regulator share 95% and 100% identity respectively. The comP genes of NAF4 and 168 restored the impaired competence of B. subtilis BD1658 (comP:cat) and gamma-PGA production of B. subtilis (natto) NAF12 (comP:Tn917-LTV1) to only 15% of the level achieved by the respective parent comP genes. However, when introduced together with the cognate comQ and comX genes, the comP genes restored the relevant defect of the heterologous comP mutants nearly to wild-type levels. Analogous to the comCDE system of Streptococcus strains and the agrBCDE system of Staphylococcus aureus, the concerted variation in the comQXP genes appears to establish specific intercellular communication between B. subtilis strains sharing the same pheromone system.

Amino Acid Sequence↗
PubMed2000

Reduction of intramembranous particles in the periacrosomal plasma membrane of boar spermatozoa during in vitro capacitation: a statistical study.

Membrane remodeling in the periacrosomal plasma membrane (PAPM) of boar spermatozoa during incubation in capacitation medium was examined by the freeze-fracture technique. In the preservation medium (PM) group, the major small (about 8 nm) intramembranous particles (IMP) and the minor large (> 10 nm) IMP were distributed evenly in the PAPM. The IMP-free area increased during capacitation. To correct the IMP-free area, arithmetically redistributed (ARD)-IMP density was used for statistical analysis. In the PM group, the mean density +/- SD of large IMP was 379 +/- 64 and 266 +/- 58/microm2, and that of small IMP was 1450 +/- 155 and 672 +/- 252/microm2 in protoplasmic (P) and external (E) faces, respectively. During capacitation, the significant (P < 0.01) reduction of large IMP density was encountered only in the E face of a few incubation groups, while that of the small IMP density occurred in the P face by 2 h. Consequently, reduction of the total IMP density of both faces was not significant in the large IMP, but it was significant (P < 0.01) in the small IMP. One-fifth of the total small IMP density reduced by 2 h. Filipin-sterol complexes (FSC) were numerous in the PAPM, and FSC-free areas also increased during capacitation. The mechanism of IMP-free area formation and the behavior of the small IMP in the PAPM during capacitation were discussed in relation to membrane stability.

Acrosome↗
PubMed2000

Negligible glucose-6-phosphatase activity in cultured astroglia.

2-Deoxy[14C]glucose-6-phosphate (2-[14C]DG-6-P) dephosphorylation and glucose-6-phosphatase (G-6-Pase) activity were examined in cultured rat astrocytes under conditions similar to those generally used in assays of glucose utilization. Astrocytes were loaded with 2-[14C]DG-6-P by preincubation for 15 min in medium containing 2 mM glucose and 50 microM 2-deoxy[14C]glucose (2-[14C]DG). The medium was then replaced with identical medium including 2 mM glucose but lacking 2-[14C]DG, and incubation was resumed for 5 min to diminish residual free 2-[14C]DG levels in the cells by either efflux or phosphorylation. The medium was again replaced with fresh 2-[14C]DG-free medium, and the incubation was continued for 5, 15, or 30 min. Intracellular and extracellular 14C contents were measured at each time point, and the distribution of 14C between 2-[14C]DG and 2-[14C]DG-6-P was characterized by paper chromatography. The results showed little if any hydrolysis of 2-[14C]DG-6-P or export of free 2-[14C]DG from cells to medium; there were slightly increasing losses of 2-[14C]DG and 2-[14C]DG-6-P into the medium with increasing incubation time, but they were in the same proportions found in the cells, suggesting they were derived from nonadherent or broken cells. Experiments carried out with medium lacking glucose during the assay for 2-deoxyglucose-6-phosphatase activity yielded similar results. Evidence for G-6-Pase activity was also sought by following the selective detritiation of glucose from the 2-C position when astrocytes were incubated with [2-3H]glucose and [U-14C]glucose in the medium. No change in the 3H/14C ratio was found in incubations for as long as 15 min. These results indicate negligible G-6-Pase activity in cultured astrocytes.

Animals↗
PubMed2000

A case of subcutaneous cysticercosis (Cysticercus cellulosae cutis).

Cysticercosis is an infection resulting from the larval form of the pork tapeworm, and domestic infection is rare in Japan. We report a case of Cysticercus cellulosae cutis in a Japanese woman who was thought to be infected in an endemic area and offer a brief review of the literature.

Animals↗