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Biomedical subjects

M Chiba

Publications and source records attributed to M Chiba.

At least 199 records · Page 11Linked to original sources
PubMed1995

Potent and selective inactivation of human liver microsomal cytochrome P-450 isoforms by L-754,394, an investigational human immune deficiency virus protease inhibitor.

L-754,394, N-[2(R)-hydroxy-1(S)-indanyl]-5-[2(S)-(1,1-dimethylethylaminocarbonyl )-4- [(furo[2,3-b]pyridin-5-yl)methyl]piperazin-1-yl]-4(S)-hydroxy-2(R) - phenylmethylpentanamide, is a potent and specific inhibitor of the human immune deficiency virus (HIV) protease. The drug selectively inhibited human liver microsomal CYP 3A4-dependent testosterone 6 beta-hydroxylase and CYP 2D6-dependent bufuralol 1'-hydroxylase activities in a time- and concentration-dependent manner in the presence of an NADPH-generating system. L-754,394 was found to be a very potent inactivator of CYP 3A4. Thus, for testosterone 6 beta-hydroxylase, the inactivation kinetic constants, Kl and kinact, were 7.5 microM and 1.62 min-1, respectively, and the partition ratio (moles product formed per moles enzyme inactivated) was approximately 1.35. To a lesser extent, L-754,394 also was an inactivator of CYP 2D6, for which the corresponding values for Kl, kinact and partition ratio were 32 microM, 0.18 min-1 and 40, respectively. CYP 3A4 inactivation was reduced markedly by ketoconazole, a selective CYP 3A4 inhibitor. Similarly, CYP 2D6 inactivation also was prevented by quinidine, a specific competitive inhibitor of this isoform. However, exogenously added nucleophiles (GSH, semicarbazide and N-acetylcysteine) failed to protect against P-450 inactivation. These results suggest that the inactivation process likely is mediated by a reactive metabolite of L-754,394 that alkylates, and thereby destroys, the enzyme. Furthermore, this electrophilic intermediate may not be released into the medium before the inactivation event.

Cytochrome P-450 CYP2D6↗
PubMed1994

Determination of tin in biological materials by atomic absorption spectrophotometry and neutron activation analysis.

Concentrations of Tin (Sn) were determined in botanical, dietary and biological reference materials (RMs), and in human livers from Japanese and American subjects using atomic absorption spectrophotometry (AAS) and neutron activation analysis (NAA), either in the instrumental mode (INAA) or in the radiochemical mode (RNAA). The mean Sn concentrations (+/- 1 S.D.) found in various RMs are: total diet (NIST SRM-1548) 3.57 +/- 0.52 and 3.61 +/- 0.52 microgram/g by AAS and INAA, respectively; non-fat milk powder (NIST SRM-1549) 2.5 +/- 1.4 ng/g and 1.9 +/- 0.3 ng/g; bovine liver (NBS SRM-1577) 18 +/- 2 and 20 +/- 0.3 ng/g; and citrus leaves (NIST SRM-1542) 0.25 +/- 0.02 and 0.243 +/- 0.006 microgram/g by AAS and RNAA, respectively. These comparisons demonstrate good agreement between the two methods. In apple leaves (NIST SRM-1515) and peach leaves (NIST SRM-1547), the measured concentrations by AAS were 77.1 +/- 20 and 85 +/- 15 ng/g; interferences by 160Tb did not permit an accurate assessment by INAA at this concentration. The Sn results obtained for the American human liver specimens by RNAA ranged from 0.135-0.712 microgram/g wet weight, and the Sn concentrations in Japanese human liver specimens determined by AAS ranged from 0.078-1.122 microgram/g wet weight in 23 individuals. The results from this study show that it is feasible to use INAA/RNAA and AAS in combination to establish recommended values in RMs.

Animals↗
PubMed1994

Serotype G6 human rotavirus sharing a conserved genetic constellation with natural reassortants between members of the bovine and AU-1 genogroups.

Serotype G6 human rotavirus PA151 was examined by RNA-RNA hybridization in comparison with another G6 strain PA169 and two naturally-occurring G3 reassortants PCP5 and MZ58. PA151 possessed three gene segments that formed hybrids with AU-1 and seven gene segments that formed hybrids with bovine rotavirus NCDV. PA151 also possessed eight, 10 and 10 gene segments that formed hybrids with genomic RNAs from PA169, PCP5, and MZ58, respectively. Thus, PA151 was an intergenogroup reassortant formed in nature between members of the bovine and AU-1 genogroups and it shared a genome constellation with PA169, PCP5, and MZ58. These results suggest that naturally-occurring intergenogroup reassortants possessing such a genome constellation were perpetuated in human populations.

Animals↗
PubMed1994

Expression of HLA-DR antigens on colonic epithelium around lymph follicles. An anomalous expression in Crohn's disease.

The relationship between the lymph follicle and expression of HLA-DR antigens on the colonic epithelium was investigated. Colonic specimens containing lymph follicles were examined immunohistochemically for HLA-DR expression. Thirty-six biopsy specimens (29 from macroscopically uninvolved areas and seven from aphthoid lesions) were obtained from 10 patients with Crohn's disease, and another 43 specimens were obtained from 33 patients with various intestinal diseases (non-Crohn's disease). HLA-DR antigens were expressed on the epithelium around the lymph follicle in both groups. However, the rate of expression (31/36) in Crohn's disease was significantly higher than that (5/43) in non-Crohn's diseases (P < 0.001). In addition, the extent and intensity of expression were broader and stronger in Crohn's disease than in non-Crohn's disease. This study is the first demonstration of anomalous HLA-DR expression on the epithelium around the lymph follicle in Crohn's disease.

Adult↗
PubMed1994

A case of toxic megacolon in ulcerative colitis associated with cytomegalovirus infection.

Cytomegalovirus (CMV) infection, which has been shown to complicate the course of ulcerative colitis (UC), has been implicated as a possible etiologic factor in the exacerbation of UC, especially in toxic megacolon. However, CMV infection in patients with UC accompanied by toxic megacolon has rarely been reported. Here we report a case of CMV infection of the colon accompanied by toxic megacolon occurring in UC. A 38-year-old woman had been treated with intravenous hydrocortisone, rectal steroid, and central venous alimentation for 6 weeks under the diagnosis of UC. She was transferred to Akita University Hospital because of increasing bloody diarrhea and abdominal pain. Toxic megacolon was identified by examinations on admission, and she underwent a total colectomy. Examination of the surgical specimen showed severe inflammation of the colon. Microscopically, cytomegalic inclusions were observed in and around the endothelial cells in the inflamed submucosal layer. It can be assumed that CMV infection was a secondary, opportunistic invader superimposed on UC, and that it played an important role in altering the clinical course of the patient.

Adult↗
PubMed1994

Comparative study of methods for determining lanthanide elements in biological materials by using NAA, HPLC postcolumn reaction, and ICP-MS.

Mice were injected intravenously with one of the following elements: Y, La, Ce, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, or Yb, at a dose of 25 mg/kg body wt. After 20 h, the various organs were taken out, and the element concentrations were determined by NAA, HPLC postcolumn reaction, or ICP-MS. The results by these three methods were within the acceptable range. About 85% of the amount administered of each element was found in liver, lung, and spleen.

Animals↗
PubMed1994

Attenuated endothelium-dependent peripheral vasodilation and clinical characteristics in patients with chronic heart failure.

Impairment of endothelium-dependent vasodilation has recently been reported in the peripheral vascular bed in patients with chronic heart failure. However, the clinical implications of this type of vascular dysfunction have yet to be elucidated. We have determined the degree of impairment of endothelium-dependent vasodilation as evaluated by acetylcholine-induced changes in forearm blood flow and compared this to various clinical parameters in 23 patients with chronic heart failure. Cumulative changes in forearm blood flow induced by acetylcholine (3.0 and 4.5 micrograms/min/dl tissue volume) were significantly lower in patients with chronic heart failure than in normal controls (10.1 +/- 8.0 ml/min/100 ml vs 20.4 +/- 11.7 ml/min/100 ml tissue volume; p < 0.01). In patients with heart failure, no significant relation was found between acetylcholine-induced changes in forearm blood flow and age, sex, duration of symptoms, duration of hospital stay, or resting hemodynamic parameters, although a significant positive correlation was observed with peak oxygen uptake (r = 0.53, p < 0.05) and ventilatory threshold (r = 0.42, p < 0.05). These observations suggest that the impairment of endothelium-dependent peripheral vasodilation may be one of the factors contributing to exercise intolerance in patients with chronic heart failure, probably resulting from its limiting effect on nutritive skeletal muscle blood flow during exercise.

Acetylcholine↗
PubMed1994

Transport, binding, and metabolism of sulfate conjugates in the liver.

Sulfate conjugates are a heterogeneous class of polar, anionic metabolites that result from the conjugation of endogenous and exogenous compounds. Sulfate conjugates exhibit a high degree of binding to albumin, the extent of which usually exceeds those of their parent compounds. Preponderant direct and indirect evidence suggests that sulfation activity is slightly higher in the periportal than in the perivenous (centrilobular) region of the liver, but recent immunohistochemical studies imply that specific isoforms of the sulfotransferases may also be preferentially localized in the perivenous region. Entry of sulfate conjugates into the liver cell is poor unless discrete carriers are present. Although known transport carriers exist for the sulfated bile acids, the specificity of the carriers for drug sulfate conjugates is presently unknown. The removal of sulfates is usually by way of biliary excretion while, on occasion, sulfates can be desulfated and participate in futile cycling with their parent compounds. The binding, transport, and hepatic elimination of various drug sulfate conjugates are examined. Non-recirculating studies carried out in the perfused rat liver with the multiple indicator dilution technique under varying input sulfate conjugate concentrations have provided essential information on the effects of vascular (red blood cells and plasma protein) binding on transport and removal of the conjugates. These studies clearly demonstrate the need to study protein binding, transmembrane transfer characteristics across the liver basolateral (sinusoidal) and canalicular membranes, and enzyme zonation in a distributed-in-space fashion in order to properly define the handling of sulfate conjugates in the liver.

Animals↗
PubMed1994

Effect of addition of dried healthy or diseased parsnip root tissue to a modified AIN-76A diet on cell proliferation and histopathology in the liver, oesophagus and forestomach of male Swiss Webster mice.

Umbelliferous crop plants, including the parsnip (Pastinaca sativa L.), elaborate enhanced levels of furocoumarins, including psoralens, when subjected to biotic or abiotic stress. These furocoumarins are recognized to lead to phototoxicity. In this study, the effect of these agents, which are present in diseased parsnip root tissue, on the liver and two tissues on the route of entry to the body (the oesophagus and forestomach) were investigated. Young male Swiss Webster mice were fed for approximately 30 days with modified AIN-76A diets containing 32.5% dried healthy, 32.5% apparently healthy or 32.5% fungicide-treated parsnip root tissue, and 8, 16 or 32.5% dried diseased (Phoma complanata-infected) parsnip root tissue. As controls, three modified AIN-76A diets differing in their edible starch-to-sucrose ratios (C1-C3) were administered for an equal time. Dried healthy parsnip root tissue, compared with controls, did not significantly affect any of the indices of cellular proliferation or histopathological parameters that were assessed. Histopathological examination of the oesophagus and forestomach demonstrated no significant changes as a result of feeding any of the diets containing parsnip tissue. In the liver, the highest level (but neither of the two lower levels) of dried diseased parsnip root tissue led to swelling of the cytoplasm in cells surrounding the central vein of hepatic lobules, with consequent compression of the peripheral cells. Using [3H]thymidine radioautography, a dose-related increase in cell labelling with the level of diseased parsnip root tissue was demonstrated in the liver. Compared with control diet C2 only, the extent of [3H]thymidine labelling in the liver was increased in mice receiving apparently healthy parsnip tissue; a slight, not statistically significant, increase was also noted with fungicide-treated parsnip tissue. Increased [3H]thymidine labelling with the feeding of diseased parsnip tissue was also found in the greater curvature of the forestomach and the region of the oesophageal-forestomach junction, but not at the glandular junction of the forestomach nor in the mid-oesophagus.

Animal Feed↗
PubMed1994

Application to cows and horses of Spotchem, a dry-chemistry blood analyzer for use in veterinary clinics.

The usefulness of a dry-chemistry blood analyzer, Spotchem SP-4410 (SP-4410) in a veterinary clinic for analysis of bovine and equine blood chemistry was studied. We quantitated total protein (TP), albumin (Alb), total bilirubin (T-Bil), blood urea nitrogen (BUN), total cholesterol (T-Cho), glucose (Glu), calcium (Ca), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), creatinine phosphokinase (CPK), and alkaline phosphatase (ALP) in bovine sera. Each sample was assayed with both the SP-4410 and an automated blood analyzer which served as a wet-chemistry reference system, and the data were analyzed with regression analysis. The correlation coefficient for AST was 0.997 being the highest for all the parameters, and all the correlation coefficients were 0.93 or higher. The coefficients of variation were lower than 5.0 except in the case of bovine T-Bil where it was 5,756. The ranges of normal reference values measured by SP-4410 were the same as those reported by other investigators in most cases, but those for GGT and CPK were slightly higher. The strongest interference was observed with hemoglobin. It seems that dry-chemical-analysis of blood serum using the SP-4410 is useful for analysis of bovine and equine blood.

Animals↗
PubMed1994

1,25-Dihydroxyvitamin D3 transcriptionally activates the beta 3-integrin subunit gene in avian osteoclast precursors.

Osteoclasts are polykaryons and the principal, if not exclusive, resorptive cell of bone. They are members of the monocyte/macrophage family whose precursors differentiate under the influence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Bone resorption is dependent on osteoclast-bone attachment, and we have shown that the integrin alpha v beta 3 is critical to the resorptive process. Thus, we asked whether 1,25-(OH)2D3 enhances the expression of alpha v beta 3 on the surface of osteoclast precursors and if the steroid modulates expression of the beta 3-integrin subunit. We found that 1,25-(OH)2D3 promotes the plasma membrane appearance of alpha v beta 3 on avian bone marrow-derived osteoclast precursors and does so at physiological concentrations (10(-11) M) of the steroid. The effect is time dependent, appearing within 1 day of treatment. A full-length avian cDNA was cloned to explore the molecular mechanisms of beta 3 expression. The deduced amino acid sequence of the cDNA is 81% identical and 89% similar to that of human beta 3. Northern analysis demonstrates that beta 3 mRNA levels in vitamin D-treated osteoclast precursors mirror protein expression. Nuclear run-on experiments document the transcriptional nature of the event.

Amino Acid Sequence↗
PubMed1994

[The effect of doxorubicin on the unimpeded eruption rates of rat mandibular incisors].

We examined the effects of daily injections of doxorubicin, an anti-tumor drug, on unimpeded eruption rates, pulp cells, odontoblasts, periodontal ligament and dentine formation in the rat mandibular incisor. The experimental animals were intraperitoneally injected with 5 mg of doxorubicin/kg body weight/day for a period of 7 days. The eruption rates decreased gradually; and on the seventh day, the mean eruption rate had decreased to 14% of the control value. In addition, we noticed marked destruction of pulp cells and periodontal cells at the basal region of the incisor. The amount of dentine formation was measured using the tetracycline labeling method, but significant decreases in dentine formation were not observed. These results suggest that destruction of the basal tissues is related to inhibition of incisor eruption rates, but that tooth eruption is not related to dentine formation.

Animals↗
PubMed1994

[Analysis of trace elements in biological materials by microwave induced plasma-mass spectrometry].

Analytical conditions have been established for determination of trace elements in biological materials by microwave induced plasma-mass spectrometry (MIP-MS). Possible elemental contaminants were checked in the water and reagents used, and during the wet-ashing process. Among 72 elements tested, contamination by Na, Mg, K, Ca, Fe, Ba, and Pb were observed. This contamination was estimated to occur mainly during the process of preparing samples due to the water, reagents and surroundings. Contamination by Ca, Mg, Zn and Pb from tubes for storage was also observed. Adequate conditions for multielement analyses in plasma and bone samples were evaluated. Both plasma and bone samples were digested by the wet-ashing technique before applying MIP-MS. The recovery rates of elements added were decreased depending on the contents of plasma or bone samples in the measuring solutions. The interfering effects of matrix modification due to organs were improved by correction with an internal standard. Recovery rates of elements added, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Rb, Sr, Mo, Cd, Sn, Ba, Pb and fourteen lanthanide elements (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) were within 100 +/- 5% in analytical samples containing 1% volume of human plasma when Ga or Tl was used as the internal standard. Recoveries of Sn and Zn in the bone samples containing 0.1% bone as the original bone material, however, were 100 +/- 10% even after correction by the internal standard, suggesting the necessity of combined use of standard addition methods. The concentrations of V, Cr, Mn, Fe, Cu, Zn, Rb, Sr, Mg, and Ca in plasma from two healthy women were determined by MIP-MS. The data were consistent with the values reported elsewhere, and agreed very closely with those obtained by atomic absorption spectrometry. The accuracy of the values obtained by this method was confirmed using standard reference materials. These results indicate that MIP-MS is a useful method for multielement determination of biological materials.

Animals↗
PubMed1994

Induction of HLA-DR antigen expression on human colonic epithelium by tumor necrosis factor-alpha and interferon-gamma.

BACKGROUND: We investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on HLA-DR expression on human normal colonic epithelium, using an organ culture technique. METHODS: Biopsy specimens from normal colonic mucosa were cultured for 24 h with various concentrations of TNF-alpha and/or IFN-gamma. Epithelial HLA-DR antigens were identified by an indirect immunoperoxidase staining method. RESULTS: No expression of epithelial HLA-DR antigens was observed in specimens cultured with medium alone. Concentrations of 10(3) U/ml or higher of TNF-alpha and 10(2) U/ml or higher of IFN-gamma induced expression of HLA-DR antigens in a dose-dependent manner. Expression of HLA-DR was increased in specimens cultured with both TNF-alpha and IFN-gamma compared with those cultured with either cytokine alone. CONCLUSIONS: Our findings suggest that both TNF-alpha and IFN-gamma play important roles in regulating the expression of HLA-DR on colonic epithelium in patients with inflammatory bowel disease.

Aged↗