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Y Taguchi

Publications and source records attributed to Y Taguchi.

At least 109 records · Page 6Linked to original sources
PubMed1997

Anti-cancer drugs and glutathione stimulate vanadate-induced trapping of nucleotide in multidrug resistance-associated protein (MRP).

Multidrug resistance-associated protein (MRP), a member of the ABC superfamily transporters, functions as an ATP-dependent efflux pump that extrudes cytotoxic drugs from the cells. Although glutathione has been considered to play an important role in the function of MRP, there is no convincing evidence that glutathione directly interacts with MRP. Here we demonstrate that vanadate-induced trapping of 8-azido-ATP in MRP was stimulated in the presence of glutathione, oxidized glutathione and the anti-cancer drugs VP-16 and vincristine. MRP in membrane from a human MRP cDNA transformant was specifically photolabeled with 8-azido-[alpha-32P]ATP by the vanadate-trapping technique. Vanadate and Mg2+ were required for trapping of nucleotides, and vanadate trapping of nucleotides was inhibited by excess ADP as well as ATP. These results suggest that a stable inhibitory complex MRP x MgADP x Vi, an analog of the MRP x MgADP x Pi transition state complex, is formed in the presence of vanadate. Glutathione as well as anti-cancer drugs would directly interact with MRP, and stimulate the formation of the transition state of the ATPase reaction of MRP.

ATP-Binding Cassette Transporters↗
PubMed1997

Nitric oxide production by superficial and deep articular chondrocytes.

OBJECTIVE: Chondrocytes have been shown to produce large amounts of nitric oxide (NO) when appropriately stimulated with proinflammatory cytokines or bacterial lipopolysaccharide (LPS). In view of recent observations underscoring profound phenotypic differences between superficial and deep articular chondrocytes, these studies investigated NO production, inducible NO synthase (iNOS) activity, and messenger RNA (mRNA) expression of superficial and deep cartilage explants and cells. METHODS: Superficial and deep bovine and human articular cartilage explants and isolated bovine chondrocytes were cultured in the presence of stimulating cytokines or LPS. NO was measured by the Griess reagent. Inducible NOS activity was quantitated by conversion of L-14 C-arginine to L-14C-citrulline. Inducible NOS mRNA expression was quantitated by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. RESULTS: Superficial bovine cartilage explants stimulated with interleukin-1 alpha, LPS, or tumor necrosis factor alpha for 24 and 48 hours produced significantly more NO than did deep explants with all stimulants and at both times. Similar results were obtained with stimulated isolated superficial and deep cells. NO synthase activity, measured by the conversion of L-14C-arginine to L-14C-citrulline, paralleled NO production. Comparable results were obtained using explants from a normal human donor. Semiquantitation of iNOS mRNA by RT-PCR showed significantly larger amounts of PCR products in superficial cells and superficial explants. These results were confirmed by in situ hybridization of explants and isolated cells. CONCLUSION: Increased NO production at the cartilage surface-synovial fluid interface may play an important role in the modulation of cartilage damage in inflammatory arthritis.

Animals↗
PubMed1997

How does P-glycoprotein recognize its substrates?

We review how P-glycoprotein recognizes a wide variety of compounds and how it carries its substrates across membranes. Amino acid substitutions that affect the substrate specificity of P-glycoprotein have been found scattered throughout the molecule. In particular, some amino acid residues in the putative transmembrane domain (TM) 1 together with TM5-6 and TM11-12 may help to govern substrate specificity. The features that substrates for P-glycoprotein share are also discussed. The amphipathy of a substrate may decide whether the substrate can be intercalated into the lipid bilayer of the membrane. In addition, only certain molecular volumes and tertiary structures may make it possible for the substrate to fit into the substrate-binding site(s) of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Specific changes of urinary excretion of cross-linked N-telopeptides of type I collagen in pre- and postmenopausal women: correlation with other markers of bone turnover.

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22-77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45-55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0. 243-0.858, P < 0.05-0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2-10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years.

Adult↗
PubMed1997

Efficacy of interferons in treating children with chronic hepatitis C.

UNLABELLED: Twenty-two children with chronic hepatitis serologically positive for hepatitis C virus (HCV) were treated with interferon-alpha (IFN-alpha). Liver biopsy showed chronic active hepatitis in 13 and chronic persistent hepatitis in 9 patients. A sustained clearance of HCV was observed in 8/22 children 12 months after the administration of IFN-alpha for 26 weeks, associated with normalization of HCV core antibody. Of these eight patients six had HCV genotype III and two HCV genotype II or IV. Hepatitis relapsed in seven other patients after completion of IFN-alpha with an increase in HCV core antibody titre, five with HCV genotype II, and two with HCV genotype III or IV. A second course of IFN-alpha suppressed the reactivation of HCV in all seven patients. Three of seven responders who relapsed after the first course remained negative for HCV RNA 12 months after their second course of IFN-alpha. However, the remaining four patients with HCV genotype II again relapsed after completing their second course of IFN-alpha. Seven children with the HCV genotype II resistant to IFN, including 8 weeks of IFN-beta administration, and showed no significant reduction in HCV core antibody titre. CONCLUSION: The genotype of HCV (III) and a reduction in the core antibody titre appear to be useful parameters for predicting the response to IFN-alpha therapy.

Adolescent↗
PubMed1997

Growth inhibition of Helicobacter pylori by a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone).

The anti-proliferative effect of methylglyoxal bis(cyclopentylamidino-hydrazone) (MGBCP), a multi-enzyme inhibitor of polyamine biosynthesis, on the growth of Helicobacter pylori was investigated. MGBCP inhibited the cell growth of H. pylori in a dose-dependent manner. The inhibition was partially reversed by the addition of spermidine. Synthesis of macromolecules, DNA, RNA and protein, was inhibited in the spermidine-depleted H. pylori cells. These findings suggest that MGBCP exhibits an anti-proliferative effect on H. pylori by suppression of macromolecule synthesis.

Anti-Bacterial Agents↗
PubMed1997

[Determination of cutoff value of serum anti-Legionella antibody titer--microplate agglutination test (MPAT)].

In order to promote the serological diagnosis of legionellosis in the clinical laboratory, the cutoff values of serum anti-Legionella antibody titers for microplate agglutination (MPAT) test were determined. Antibody levels were tested for 178 serum specimens including 98 healthy persons, 22 ordinally workers having either metabolic or renal failure, definitely diagnosed patients of 17 mycoplasmal and 9 chlamydial pneumonia, 32 patients of other bacterial pneumonia. Heat killed unstained cell suspension of each strain of Legionella pneumophila serogroup (SG) 1a, 1b, SGs 2 to 6, L. bozemanii, L. dumoffii, L. gormanii, and L. micdadei were used as antigens. Strains of L. pneumophila SG 1b were mainly isolated from environmental specimens. However, in some Legionella pneumonia cases, etiologic agents were determined as L. pneumophila SG 1 b. Thus the representative strain of SG 1b was used as an antigen for the determination of the patient's antibody titer. Quantitative agglutination was performed by using a 96-well U-bottom microplate for each antigen. Test sera were diluted from 1:16 to 1:256. Results were read after 20 h at 25 degrees C. Cutoff values for 11 antigens were determined, at this moment, as 4-fold or greater increase in level to > or = 1:128 in paired sera, and > or = 1:256 in single serum. However, final diagnosis should be given by over-all coordination of serological results and clinical symptoms together with other laboratory findings. Two culture-positive Legionella pneumonia cases due to either SG3 or 6 in which significant rise of serum antibody titers against organisms of corresponding SG estimated by MPAT method were discussed.

Agglutination Tests↗
PubMed1997

Mechanism of the acceleration of CO2 production from pyruvate in liver mitochondria by HCO3-.

To investigate the mechanism by which HCO3- accelerates pyruvate metabolism in guinea pig liver mitochondria, we measured continuously, at pH 7.4 and 37 degrees C, 13C16O2 production from [1-13C]pyruvate by mass spectrometry and NADH concentration by fluorescence and analyzed total malate, citrate, and beta-hydroxybutyrate produced by standard biochemical methods. When [1-13C]pyruvate is added to the mitochondrial suspension, 13C16O2 concentration rises steeply in the first seconds and then slows to a steady lower rate. Carbonic anhydrase (CA) eliminates this initial phase, which shows that decarboxylation of pyruvate produces CO2, not HCO3-, and it does this more rapidly than it can equilibrate without CA. HCO3- (25 mM) increased 13C16O2 production, O2 consumption and total malate and citrate production and decreased NADH concentration and total beta-hydroxybutyrate production. After obtaining the total amount of 13C16O2, malate, citrate, and beta-hydroxybutyrate produced, we calculated that the addition of 25 mM HCO3- to the suspension medium increased the amount of pyruvate decarboxylated by pyruvate dehydrogenase (PDH) 16% and increased the amount carboxylated by pyruvate carboxylase 300%. This supports our initial proposal that HCO3- accelerates the pyruvate carboxylation, which in turn consumes ATP directly and NADH and acetyl CoA secondarily, all of which increase PDH activity. However, we found no acceleration of pyruvate decarboxylation by 0.5 and 1 microM free Ca2+ concentration, unless the mitochondria were uncoupled and ATP was added.

3-Hydroxybutyric Acid↗
PubMed1997

Osteopontin expression by osteoclast and osteoblast progenitors in the murine bone marrow: demonstration of its requirement for osteoclastogenesis and its increase after ovariectomy.

Osteoclast development requires cell-to-cell contact between hematopoietic osteoclast progenitors and bone marrow stromal/osteoblastic support cells. Based on this, we hypothesized that osteopontin, an adhesion protein produced by osteoclasts and osteoblasts, plays a role in osteoclastogenesis. Using in situ hybridization, we demonstrate that cells expressing the osteopontin messenger RNA (mRNA) appear after 3 days of culturing murine bone marrow cells. The number of these cells increases thereafter, reaching a peak on day 5. In the same cultures, cells expressing alkaline phosphatase (AP) or tartrate resistant acid phosphatase (TRAP), phenotypic markers for osteoblastic and osteoclast-like cells, respectively, appeared subsequent to the appearance of the osteopontin-positive cells. By means of a combination of in situ hybridization and histostaining, it was shown that the osteopontin mRNA was localized in 30-50% of the AP-positive or the TRAP-positive, as well as in nonspecific esterase (NSE)-positive, cells. The number of cells expressing both the osteopontin mRNA and either one of the three phenotypic markers was significantly increased in bone marrow cultures from estrogen-deficient mice, as compared with controls. Conversely, the number of all three populations of double positive cells was decreased in cultures treated with a specific antimouse rabbit osteopontin antibody or an RGD peptide. These findings indicate that osteopontin is expressed during the early stages of the differentiation of osteoclast and osteoblast progenitors in the bone marrow and that its cell adhesion properties are required for osteoclastogenesis.

Animals↗
PubMed1997

Pulmonary involvement in polymyositis and dermatomyositis: sequential evaluation with CT.

OBJECTIVE: The characteristic findings of pulmonary involvement in polymyositis (PM) or dermatomyositis (DM) and the change in findings before and after treatment were evaluated with sequential high-resolution CT studies. MATERIALS AND METHODS: CT images of pulmonary involvement in 19 patients with PM or DM were reviewed. During a period of 2-61 months, 17 of these patients underwent sequential CT before and after treatment with corticosteroids, immunosuppressants, or both. RESULTS: Findings of the initial CT studies included pleural irregularities and prominent interlobular septa (n = 19), ground-glass attenuation (n = 19), patchy consolidation (n = 19), parenchymal bands (n = 15), irregular peribronchovascular thickening (n = 15), and subpleural lines (n = 7). Honeycombing was not detected on any CT images. These findings were more remarkable in the lower portion and the subpleural area of the lungs. In 16 of the 17 patients who underwent sequential CT conditions such as patchy consolidation, parenchymal bands, and irregular peribronchovascular thickening improved, becoming pleural irregularities and prominent interlobular septa, ground-glass attenuation, and subpleural lines on follow-up CT scans. CONCLUSION: Consolidation with patchy and subpleural distribution, parenchymal bands, and irregular peribronchovascular thickening were characteristic and reversible CT findings in patients with PM or DM.

Adult↗
PubMed1997

Helicobacter pylori inhibits the secretory activity of gastric parietal cells in patients with chronic gastritis. An ultrastructural study.

BACKGROUND: Previous in vitro studies suggested that Helicobacter pylori may inhibit the acid secretion of gastric parietal cells. The aim of this study was to investigate ultrastructurally the influence of H. pylori infection on the gastric parietal cell function in vivo. METHODS: This study comprised 28 patients with chronic gastritis. Biopsy specimens were taken from the gastric body in all cases and examined by electron microscopy. Gastric parietal cells were counted in each ultrathin section and classified into secretory and non-secretory types. The pH of the gastric juice was also measured in all patients. RESULTS: The number of parietal cells in the secretory phase was significantly lower in H. pylori-infected (n = 16) patients than in those (n = 12) without H. pylori infection. The intragastric pH was significantly higher in patients with H. pylori-associated gastritis than in those without H. pylori infection. Parietal cells in secretory phase tended to decrease in proportion to the activity of the gastric mucosal inflammation. CONCLUSIONS: The results of this investigation suggests that H. pylori-associated gastritis is related to a decreased secretory activity of the gastric parietal cells.

Biopsy↗
PubMed1997

Gastric juice levels of lactoferrin and Helicobacter pylori infection.

BACKGROUND: Recently, in vitro studies suggested that lactoferrin (Lf) might play an important role in the physiopathology of Helicobacter pylori-associated gastritis. However, whether Lf is present in the gastric juice and its relationship with H. pylori infection have not as yet been reported. In the present investigation the presence of Lf in gastric juice and its correlation with H. pylori infection were assessed. METHODS: This study comprised 30 H. pylori-positive and 14-negative patients with chronic gastritis. Gastric juice levels of Lf were measured with enzyme-linked immunoassays. Gastric juice concentration of Lf was also investigated in accordance with the histologic findings of biopsy specimens in the gastric body and antrum. RESULTS: Lf concentration in gastric juice was significantly higher in H. pylori-positive than in -negative patients (P = 0.033). The pH values are known to influence the levels of Lf. However, intragastric Lf levels were also significantly increased in H. pylori-positive patients as compared with H. pylori-negative patients after correcting the Lf levels for pH values (P = 0.029) or after adjusting the pH values of the gastric juice with NaHCO3 solution in both groups of patients (P = 0.0007). In addition, the gastric juice levels of Lf correlated significantly with the gastric mucosal concentrations of Lf in the gastric body (P < 0.005, r = 0.568) and the antrum (P < 0.05, r = 0.401). CONCLUSIONS: This study showed for the first time that Lf is present in gastric juice and that it correlates with H. pylori infection. Lf may constitute a good marker for H. pylori-associated gastritis. Although correlation does not prove causation, this study suggests that Lf might play an important role in the physiopathology of H. pylori-associated gastritis.

Biomarkers↗
PubMed1997

Relation of lactoferrin levels in gastric mucosa with Helicobacter pylori infection and with the degree of gastric inflammation.

OBJECTIVES: Lactoferrin (Lf) is an iron-binding glycoprotein present in milk, lacrimae, saliva, and gastroduodenal secretions. In vitro studies disclosed contradicting results regarding the relation of Lf with Helicobacter pylori (HP) infection. This study aimed to investigate the relationship between the gastric mucosal concentration of Lf and HP infection of the stomach. The relationship of the gastric mucosal level of Lf with the gastric mucosal concentration of interleukin-8 (IL-8) and with the intragastric ammonia levels was also assessed. In addition, the gastric mucosal Lf levels before and after irradication of HP infection were also evaluated. METHODS: This study was composed of 27 HP-positive and 12 HP-negative patients with chronic gastritis. Gastric mucosal biopsy specimens were obtained from all subjects by endoscopy, and the degree of histological inflammatory changes were assessed according to the Sydney system. The gastric mucosal levels of Lf and IL-8 were measured by immunoassays. Assessment of the effect of therapy on the gastric mucosal level of Lf was performed in 10 patients with HP-associated duodenal ulcer. RESULTS: Lf, IL-8, and ammonia levels were significantly higher in patients with HP-positive gastritis compared with those with HP-negative gastritis in both the antrum and the gastric body. Histologically, the degree of inflammatory changes correlated significantly with the Lf levels in the gastric mucosa. Furthermore, the degree of HP colonization was more significant in biopsy samples from the antrum than in those from the corpus of the stomach. The gastric mucosal levels of Lf and IL-8 correlated significantly in the antrum and the gastric body. The ammonia intragastric level significantly correlated with the mucosal Lf level in the antrum and in the gastric body. Therapy significantly decreased the Lf levels in the gastric mucosa of the antrum (p < 0.005) and the gastric body (p < 0.005). CONCLUSION: The results of the present investigation showed, for the first time in vivo, that Lf concentration is increased in the biopsy specimens of patients with HP-related gastritis, and that the levels of Lf correlate significantly with the degree of inflammation of the gastric mucosa. The gastric mucosal level of Lf may constitute an excellent marker of HP infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

[Abducens palsy].

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Abducens Nerve↗