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Biomedical subjects

H Chiba

Publications and source records attributed to H Chiba.

At least 127 records · Page 7Linked to original sources
PubMed1996

Native lipoproteins inhibit platelet activation induced by oxidized lipoproteins.

Copper-catalyzed oxidation of low-density lipoproteins (LDL) (0.8 g protein/l LDL, 20 mumol/l CuSo4, 37 degrees C) resulted in the formation of thiobarbituric reactive substances that was substantially completed at 24 hrs whereas their formation from high-density lipoproteins (HDL) plateaued at only 25% of that amount after 8 hrs. The oxidized lipoproteins induced aggregation and increases in [Ca2+]i in washed platelets, but not in platelet-rich plasma, and these activating effects were not inhibited by aspirin or EGTA but were inhibited by both of the native lipoproteins. These results show that oxidized HDL, like oxidized LDL, have platelet activating ability and suggest that the native lipoproteins may play a crucial role in preventing the oxidized lipoprotein-mediated platelet activation.

Aspirin↗
PubMed1996

The proportion of free to total prostate specific antigen: a method of detecting prostate carcinoma.

BACKGROUND: Prostate specific antigen (PSA) is the most useful marker for prostate carcinoma (CaP). However, the sensitivity and specificity for PSA are not sufficient for the diagnosis of organ-confined prostate carcinoma. Recent studies have revealed that anti-PSA antibody identifies both PSA complexed to alpha-1-antichymotrypsin and free PSA, whereas anti-gamma-seminoprotein antibody recognizes free PSA exclusively. To enhance the ability of PSA to detect CaP in patients with total PSA levels of 10 ng/mL or lower, we developed the ratio of gamma-seminoprotein and PSA (free/total PSA index). METHODS: We measured free/total PSA indices for 285 patients who had serum PSA levels of 10 ng/mL or lower and who were diagnosed pathologically. RESULTS: Of the 285 patients, 228 had no prostate carcinoma (NC) and 57 had CaP. The mean total PSA level for CaP (5.137 +/- 2.483 ng/mL; mean +/- standard deviation) was significantly greater (P < 0.0001) than that for NC (3.251 +/- 2.129). The mean free/total PSA index for CaP (0.774 +/- 0.468 was significantly lower (P < 0.0001) than that for NC (1.563 +/- 0.938). The sensitivity for the free/total PSA index was similar to that for total PSA (78.9% vs. 75.4%). However, the specificity, positive predictive value, and overall accuracy for the free/total PSA index (75.9%, 45%, and 76.5%, respectively) increased by 15-20% compared with those for total PSA (56.6%, 30.3%, and 60.4%, respectively). CONCLUSIONS: The free/total PSA index improved the specificity of PSA without impairing the sensitivity in detecting CaP among patients with serum PSA levels of 10 ng/mL or lower.

Humans↗
PubMed1996

Three cases of hereditary nonspherocytic hemolytic anemia associated with red blood cell glutathione deficiency.

Three unrelated Japanese patients with chronic nonspherocytic hemolytic anemia wer found to have marked deficiency of red blood cell (RBC) reduced glutathoine (GSH) (4.4%, 13.1%, and 6.9% of normal, respectively). A panel of RBC enzyme assays showed that one patient had decreased glutathione synthetase activity and the other two were moderately deficient in gamma-glutamylcystine synthetase. Some family members of each patient showed mild deficiency of the respective enzymes. RBCs of these patients also showed a decreased level of glutathione-S-transferase as in previously described GSH-deficient cases. Hemolytic anemia was their only manifestation, and neither 5-oxoprolinemia nor 5-oxoprolinuria, which are usually associated with to generalized type of glutathione synthetase deficiency, was noted in our patients.

Adolescent↗
PubMed1996

Effect of omeprazole in the treatment of refractory acid-related diseases in childhood: endoscopic healing and twenty-four-hour intragastric acidity.

OBJECTIVE: To determine the clinical efficacy of once-daily treatment with omeprazole in refractory acid-related diseases in children. METHODS: Endoscopic healing and 24-hour intragastric pH values were assessed in 13 patients with refractory reflux esophagitis (n = 5), refractory and/or giant duodenal ulcer (n = 6), or giant gastric ulcer (n = 2). The mean dose of omeprazole was 0.6 mg/kg per day (range, 0.3 to 0.7 mg/kg per day). Pharmacokinetic studies of omeprazole were performed in seven patients. RESULTS: The cumulative healing rates at 2, 4, 6, and 8 weeks of treatment were 46%, 85%, 92%, and 92%, respectively. Esophagitis in one patient did not heal despite increases in doses of up to 1.6 mg/kg per day (40 mg/day). The mean intragastric pH of omeprazole-treated patients was 5.2 (range, 3.0 to 6.6) and mean hydrogenion activity was 1.78 mmol/L (range, 0.01 to 10.42 mmol/L). There was wide interindividual variation in the reduction of gastric acid production. Mean intragastric H+ activity in omeprazole-treated patients was significantly lower than that of control subjects (p < 0.005) and that of patients treated with histamine type 2(H2)-receptor antagonists (p < 0.05). Mean intragastric H+ activity was not significantly correlated to the area under the concentration-time curve of omeprazole. No severe adverse effects were reported during treatment or at follow-up. CONCLUSIONS: Omeprazole has a potent antisecretory effect and is a suitable alternative for short-term treatment of refractory acid-related diseases; a relatively low dose (0.6 mg/kg per day) appears to be optimal in most patients. Unhealed esophagitis at 8 weeks of treatment was considered to be refractory to omeprazole.

Anti-Ulcer Agents↗
PubMed1996

Phase-Dependent effects of transforming growth factor beta 1 on osteoblastic markers of human osteoblastic cell line sV-HFO during mineralization.

A human osteoblastic cell line (SV-HFO) established in our laboratory expresses osteoblastic markers, including mineralization in vitro, in response to differentiation-inducing agents such as dexamethasone. In this study, we examined the effects of transforming growth factor beta 1 (TGF-beta 1) on the mineralization of SV-HFO cells and show that TGF-beta 1 inhibited the mineralization of the cells via down regulation of tetranectin and alkaline phosphatase without influencing other osteoblastic markers. To examine precisely the effects of TGF-beta 1 on the process of mineralization, we tentatively divided the whole process of mineralization into four phases: induced ALP activity (days 0-5), maximal ALP activity (days 5-10), early mineralization (days 10-15), and progressive mineralization (days 15-20). These inhibitory effects of TGF-beta 1 on the expression of tetranectin and alkaline phosphatase, like that on mineralization, were observed only when TGF-beta 1 was applied in the early phase of the process of mineralization. On the other hand, the other osteoblastic markers were not influenced by treatment with TGF-beta 1. These results suggest that TGF-beta 1 may inhibit mineralization of osteoblasts by the downregulation of tetranectin and alkaline phosphatase expression in the early phase. Thus, TGF-beta 1 has phase-dependent effects on a human osteoblastic cell line during the process of mineralization.

Alkaline Phosphatase↗
PubMed1996

Augmentation of epirubicin cytotoxicity by cycloheximide.

The effect of cycloheximide (CH) on the cytotoxic activity of the anthracycline antibiotic epirubicin (EPI) was examined in cell cultures of murine leukemia doxorubicin (DOX)-sensitive P388 and -resistant P388 cells. The addition of CH (0.002 mu g/ml) to the growth medium markedly enhanced the EPI-induced cytotoxic effect in sensitive cells as well as that observed in resistant cells. CH, however, did not affect the intracellular content of EPI. The inhibition of DNA synthesis in leukemia cells was remarkable with the combination of EPI and CH compared with each drug alone. These results suggest that the combination of EPI and CH appears to be useful in killing mouse leukemia cells.

Animals↗
PubMed1996

[Physiology and pathology of the lipid transport in the brain].

Apolipoprotein E is the major lipid carrier protein in the brain. This protein is contained in HDL1-like particles in human and rat cerebrospinal fluid. Cerebrospinal fluid apolipoprotein metabolism is resistant to the alteration in plasma lipoprotein metabolism and to age-related changes. In a patient with multiple sclerosis, immunoreactive apolipoprotein E was seen in astrocytes and macrophages in the brain section with a pathological change, indicating that apolipoprotein E has a significant role in the lipid redistribution process after demyelination. The epsilon4 allele is more frequent in Japanese patients with Alzheimer's disease than in control, as well as Caucasians, suggesting the significant contribution of the epsilon4 allele to the pathogenesis of the disease.

Adult↗
PubMed1996

Reversal of multidrug resistance by tacrolimus hydrate.

Tacrolimus hydrate, a potent immunosuppressant produced by Streptomyces tsukubaensis, was examined for its effect on epirubicin activity in multidrug-resistant P388 leukemia (P388/R) cells overexpressing P-glycoprotein and the parent (P388/S) cells. In the absence of modulator, the 50% inhibitory concentration for epirubicin after 48-h incubation, determined using a microculture tetrazolium assay, was 0.8 microgram/ml in P388/R cells and 0.009 microgram/ml in P388/S cells. P388/R cells demonstrated a 90-fold reduction in sensitivity to epirubicin. Tacrolimus hydrate (1 and 10 microM) markedly enhanced epirubicin cytotoxicity by 4.2- and 26.7-fold for P388/R cells. A significant increase in LDH release from cells by tacrolimus hydrate was also observed in P388/R cells treated with epirubicin. Tacrolimus hydrate had a marked effect on epirubicin-induced G2/M blockade in the resistant cells. Both tacrolimus hydrate and cyclosporin A dramatically increased the accumulation of epirubicin by the resistant cells, while these compounds had no effect on epirubicin accumulation in the parent cells. Thus, tacrolimus hydrate is able to down-modulate P-glycoprotein-associated resistance through inhibition of P-glycoprotein function, suggesting that the drug may be a candidate for killing drug-resistant tumor cells.

Animals↗
PubMed1995

Transforming growth factor-beta 1 downregulates dexamethasone-induced tetranectin gene expression during the in vitro mineralization of the human osteoblastic cell line SV-HFO.

In the present study, we examined the regulation of tetranectin gene expression using a human osteoblastic cell line, SV-HFO, that undergoes mineralization upon treatment with dexamethasone. We found that the expression of tetranectin and alkaline phosphatase mRNA was induced by dexamethasone treatment as evidenced by Northern blotting. When transforming growth factor-beta 1 (TGF-beta 1) was added together with dexamethasone to the SV-HFO cell cultures, the mineralization process was markedly suppressed and the expression of tetra nectin and alkaline phosphatase was downregulated in a dose-dependent manner. These results demonstrate that the expression of tetranectin in these osteoblastic cells is regulated by dexamethasone and TGF-beta 1 and that tetranectin expression is tightly linked to the process of mineralization.

Biomarkers, Tumor↗
PubMed1995

The 3'-terminal exon of the family of steroid and phenol sulfotransferase genes is spliced at the N-terminal glycine of the universally conserved GXXGXXK motif that forms the sulfonate donor binding site.

The guinea pig estrogen sulfotransferase gene has been cloned and compared to three other cloned steroid and phenol sulfotransferase genes (human estrogen sulfotransferase, human phenol sulfotransferase, and guinea pig 3 alpha-hydroxysteroid sulfotransferase). The four sulfotransferase genes demonstrate a common outstanding feature: the splice sites for their 3'-terminal exons are identically located. That is, the 3'-terminal exon splice sites involve a glycine that constitutes the N-terminal glycine of an invariably conserved GXXGXXK motif present in all steroid and phenol sulfotransferases for which primary structures are known. This consistency strongly suggests that all steroid and phenol sulfotransferase genes will be similarly spliced. The GXXGXXK motif forms the active binding site for the universal sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate. Amino acid sequence alignment of 19 cloned steroid and phenol sulfotransferases starting with the GXXGXXK motif indicates that the 3'-terminal exon for each steroid and phenol sulfotransferase gene encodes a similarly sized C-terminal fragment of the protein. Interestingly, on further analysis of the alignment, three distinct amino acid sequence patterns emerge. The presence of the conserved functional GXXGXXK motif suggests that the protein domains encoded by steroid and phenol sulfotransferase 3'-terminal exons have evolved from a common ancestor. Furthermore, it is hypothesized that during the course of evolution, the 3'-terminal exon further diverged into at least three sulfotransferase subdivisions: a phenol or aryl group, an estrogen or phenolic steroid group, and a neutral steroid group.

Amino Acid Sequence↗
PubMed1995

Conditional site-specific recombination in mammalian cells using a ligand-dependent chimeric Cre recombinase.

We have developed a strategy to generate mutant genes in mammalian cells in a conditional manner by employing a fusion protein, Cre-ER, consisting of the loxP site-specific Cre recombinase linked to the ligand-binding domain of the human estrogen receptor. We have established homozygous retinoid X receptor alpha-negative (RXR alpha-/-) F9 embryonal carcinoma cells constitutively expressing Cre-ER and have shown that estradiol or the estrogen agonist/antagonist 4-hydroxytamoxifen efficiently induced the recombinase activity, whereas no activity was detected in the absence of ligand or in the presence of the antiestrogen ICI 164,384. Furthermore, using a targeting vector containing a selection marker flanked by loxP sites, we have inactivated one retinoic acid receptor alpha allele in such a line, demonstrating that the presence of the recombinase does not inhibit homologous recombination. Combining this conditional site-specific recombination system with tissue-specific expression of Cre-ER may allow modification of the mammalian genome in vivo in a spatiotemporally regulated manner.

DNA Nucleotidyltransferases↗
PubMed1995

Evaluation of G-to-A substitution in the apolipoprotein A-I gene promoter as a determinant of high-density lipoprotein cholesterol level in subjects with and without cholesteryl ester transfer protein deficiency.

The effect of a polymorphism, guanine (G) to adenine (A) substitution in the promoter of apolipoprotein A-I gene at a position 78 bp upstream of the transcription initiation site, on the serum high-density lipoprotein (HDL)-cholesterol level was studied in 168 Japanese subjects with HDL-cholesterol levels ranging from 26 to 171 mg/dl. Considering the significant effect of cholesteryl ester transfer protein (CETP) on the HDL-cholesterol level and the common occurrence of its deficiency, we performed statistical analyses separately for two groups: one without CETP deficiency (n = 126) and the other with CETP deficiency (n = 42). In the group without CETP deficiency, in which the numbers of G/G, G/A, and A/A genotypes were 92 (73.0%), 28 (22.2%), and 6 (4.8%), respectively, the frequency of the A allele in the subjects with HDL-cholesterol levels of > or = 70 mg/dl did not differ from subjects with HDL-cholesterol levels of < or = 69 mg/dl, irrespective of gender: 0.154 and 0.145 in males, and 0.182 and 0.174 in females, respectively, for the > or = 70 mg/dl and < or = 69 mg/dl groups. Additionally, the HDL-cholesterol levels for the subjects with the G/G genotype did not differ from those for the subjects with the A allele: 64 +/- 22, 58 +/- 14, 77 +/- 14 and 62 +/- 16 mg/dl, respectively, for the G/G, G/A, A/A, and G/A + A/A in males, and 72 +/- 18, 74 +/- 24, 63 +/- 4, and 73 +/- 23 mg/dl in females. For the group with CETP deficiency, in which the numbers of G/G and G/A + A/A genotypes were 25 (59.5%) and 17 (40.5%), the HDL-cholesterol levels also did not differ: 98 +/- 24 mg/dl and 99 +/- 30 mg/dl, respectively, for the G/G and G/A + A/A genotypes. Thus, there is no evidence that the polymorphism has any effect on serum HDL-cholesterol levels regardless of CETP status. We conclude that the G-to-A substitution in the promoter of apolipoprotein A-I gene does not significantly alter serum HDL-cholesterol level.

Adult↗
PubMed1995

Glucocorticoids induce mineralization coupled with bone protein expression without influence on growth of a human osteoblastic cell line.

Mineralization was induced by glucocorticoid treatment in a human osteoblastic cell line derived from normal bone in vitro, designated SV-HFO, immortalized with simian virus 40 (CHIBA, H. et al. (1993). Jpn. J. Cancer Res., 84: 290-297). Mineralization was revealed by electron microscopy, von Kossa staining and electron spectroscopic analysis, which indicated that the Ca/P ratio was approximately 1.70, corresponding to the value of hydroxyapatite. The effect was dose- (10(-8)-10(-6) M) and time-dependent (days 7-28), was greatest at day 28, and was preceded by expression of alkaline phosphatase (ALP) and osteopontin (OPN). The ALP activity induced was highest at day 7, whereas OPN reached its highest level at day 28. When the induction of ALP activity was inhibited by 10(-4) M levamisole, mineralization of SV-HFO cells by glucocorticoid treatment was markedly reduced, suggesting that elevated ALP activity in the early phase is important in the mineralization of human osteoblastic cells. Glucocorticoid treatment did not alter cell proliferation. These results indicated that glucocorticoids play crucial roles in the formation of mineralized matrix in human osteoblasts by inducing differentiation of SV-HFO cells without modulating their proliferative activity.

Alkaline Phosphatase↗