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Biomedical subjects

K Chiba

Publications and source records attributed to K Chiba.

At least 181 records · Page 10Linked to original sources
PubMed1996

Simultaneous measurement of proguanil and its metabolites in human plasma and urine by reversed-phase high-performance liquid chromatography, and its preliminary application in relation to genetically determined S-mephenytoin 4'-hydroxylation status.

A simple high-performance liquid chromatographic (HPLC) assay method was developed for the measurement of proguanil (PG) and its major metabolites, cycloguanil (CG) and 4-chlorophenyl-biguanide (CPB), in human plasma and urine. The assay allowed the simultaneous determination of all analytes in 1 ml of plasma or 0.1 ml of urine. The detection limits of PG, CG, and CPB, defined as the signal-to-noise ratio of 3, were 1 and 5 ng/ml for plasma and urine samples, respectively. Recoveries of the analytes and the internal standard (pyrimethamine) were > 62% from plasma and > 77% from urine. Intra-assay and interassay coefficients of variation for all analytes in plasma and urine were < 10% except for the values of CG and CPB, which ranged from 10% to 15% at one or two concentrations among 4-5 concentrations studied. The clinical applicability of the method was assessed by the preliminary pharmacokinetic study of PG, CG, and CPB in six healthy volunteers with the individually known phenotypes (extensive and poor metabolizers) of S-mephenytoin 4'-hydroxylation, suggesting that individuals with a poor metabolizer phenotype of S-mephenytoin have a much lower capacity to bioactivate PG to CG compared with the extensive metabolizers.

Adult↗
PubMed1996

[A case of congenital ejaculatory duct obstruction].

We report a case of congenital ejaculatory duct obstruction treated successfully by transurethral incision. A 33-year-old man was referred for evaluation of primary infertility. His semen analysis showed volumes of 1.7 ml at average and azoospermia. Clinical examinations revealed right undescended testicle, absence of the left kidney and axial rotation of right kidney. Left vasogram showed dilated but intact seminal vesicle with no contrast material visible in the bladder. Following removal of right undescended testicle, transurethral incision of the left side of the prostatic urethral floor near the vermontanum was performed. Transurethral vesiculogram showed dilated but not cystic ejaculatory duct. Eight months postoperatively semen analysis showed a volume of 3.5 ml, a concentration of 61.3 x 10(6)/ml and motility rate of 51.8%. However, semen analysis 18 months postoperatively showed azoospermia again. After re-transurethral incision, his sperm concentration increased to 15.2 x 10(6)/ml. However, his wife didn't become pregnant yet.

Adult↗
PubMed1996

[Intravesical oxybutynin hydrochloride in the treatment of urge incontinence in the elderly].

PURPOSE: This study was carried out to determine the effectiveness of intravesical oxybutynin hydrochloride on urinary urge incontinence in elderly people. METHODS: The subjects consisted of 13 patients with an average age of 75 years who demonstrated uninhibited detrusor contraction on cystometrogram. The trial protocol consisted of a pretreatment cystometrogram followed by the intravesical administration of 10 ml solution containing 5 mg oxybutynin hydrochloride (pH 5.85). The urodynamic studies were repeated one hour later. RESULTS: The mean bladder capacity before and after one hour of intravesical oxybutynin hydrochloride was 161 +/- 62 ml and 196 +/- 71 ml (mean +/- 1 S.D., n.s.). The rate of improvement was 15.4% (2 cases) in all 13 patients. Four patients out of 13 patients continued intravesical administration of the solution twice daily. Urinary incontinence disappeared in two patients and incontinence was markedly decreased in one. In the remaining patient, urinary incontinence did not change because of increased residual urine. Three patients have continued this therapy over one years and no side effects were observed. In these patients, residual urine volume did not increase. CONCLUSION: It is suggested that intravesical oxybutynin hydrochloride is an effective option of therapy for intractable urge incontinence in elderly people, however, the immediate posttreatment cystometrogram was not predictive of the response to intravesical therapy on overactive bladder in the elderly.

Administration, Intravesical↗
PubMed1996

Determination of absolute configuration and biological activity of new immunosuppressants, mycestericins D, E, F and G.

Mycestericins D, E, F and G were isolated from the culture broth of Mycelia sterilia ATCC 20349 as potent immunosuppressants. Mycestericins F and G were identical with dihydromycestericins D and E, respectively. Their absolute configurations were determined by use of the modified MOSHER'S method and by comparison of the CD spectra of their benzoate derivatives with those of synthetic analogs. Mycestericins D, E, F and G suppressed the proliferation of lymphocytes in the mouse allogeneic mixed lymphocyte reaction.

Animals↗
PubMed1996

[Renal cell carcinoma accompanied with ossification: a case report].

Renal cell carcinoma accompanied with ossification reported in Japan is very rare. We report a case of renal cell carcinoma with ossification pathologically in a 61-year-old woman. She suddenly presented with hypercalcemia that caused acute renal failure, 6 months after the operation and died shortly thereafter. We discuss the relationship between the tumor and the hypercalcemia.

Acute Kidney Injury↗
PubMed1996

Identification of human cytochrome P450 isoforms involved in the stereoselective metabolism of mianserin enantiomers.

To identify cytochrome P450 (CYP) isoform(s) involved in the major metabolic pathways of mianserin (MS) enantiomers in humans, we examined the metabolites formed from S-(+)- and R-(-)-MS using human liver microsomes and eight recombinant human CYP isoforms (i.e., CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4). The mean V(max)/K(m) values of the 8-hydroxylation and N-oxidation were greater for S-(+)- than for R-(-)-MS, whereas that of the N-demethylation gave the opposite observation. When relationships were evaluated in microsomes from 10 human livers between the metabolism of substrates toward the respective CYP isoforms and stereoselective metabolism of MS at a low (5 microM) and at a high (200 microM) MS concentration, significant correlations existed in: 2-hydroxylation of desipramine vs. 8-hydroxylation of S-(+)-MS (r = 0.94, P < .01), O-deethylation of phenacetin vs. N-demethylation of S-(+)-MS (r = 0.85, P < .01) and R-(-)-MS (r = 0.69, P < .05) or N-oxidation of S-(+)-MS (r = 0.94, P < .01) at the low concentration; and 6 beta-hydroxylation of testosterone vs. three metabolic reactions of both MS enantiomers at the high concentration (r = 0.68-0.93, P < .05-.01). Quinidine inhibited the 8-hydroxylation of both enantiomers by < 40% of the respective control values. Furafylline and alpha-naphthoflavone showed a potent inhibitory effect on the N-demethylation and N-oxidation of S-(+)-MS (by up to < 50% of the respective control activities). In addition, troleandomycin inhibited the N-demethylation and N-oxidation of R-(-)-MS by < 50% of the respective control activities. Among the recombinant human CYP isoforms, CYP2D6, 2B6, 3A4 and 1A2 catalyzed the 8-hydroxylation, and CYP1A2 and 3A4 were involved exclusively in the N-oxidation, whereas CYP2B6, 2C19, 1A2, 3A4 and 2D6 showed a catalytic activity for the N-demethylation, for either or both of MS enantiomers. Taken together, the 8-hydroxylation for both MS enantiomers is mediated mainly via CYP2D6, whereas the N-demethylation for both the enantiomers and N-oxidation for S-(+)-MS are catalyzed mainly via CYP1A2. The two in vitro experiments suggested that CYP3A is involved to a certain extent in each of the stereoselective MS metabolic pathways.

Cytochrome P-450 Enzyme System↗
PubMed1996

[Rapidly deteriorating adult hydronephrosis due to an aberrant vessel: a case report].

Hydronephrosis due to ureteropelvic junction (UPJ) obstruction generally progresses gradually. We experienced a case of hydronephrosis due to UPJ obstruction deteriorating rapidly in an adult woman. In spite of percutaneous nephrostomy, 99mTc-DTPA renogram showed a non-functional pattern. A nephrectomy was done. Peri-operatively, the aberrant lower pole vessel was found to be obstructing the UPJ. The hydronephrosis deteriorated rapidly because the extrarenal pelvis dilated in the shape of box, became suspended from the aberrant vessel. Therefore, we believe that the box pelvis is one of the most important factors deteriorating hydronephrosis.

Arteries↗
PubMed1996

In vivo and in vitro characterization of CYP2E1 activity in Japanese and Caucasians.

Chlorzoxazone's disposition after oral administration was determined in 20 young healthy Caucasian men and a similar group of Japanese men. The drug's plasma concentrations were significantly higher and its rate of elimination slower in Japanese compared to Caucasian men. Accordingly, chlorzoxazone's oral clearance was smaller (40%) in Japanese men and a similar difference (30%) was still apparent after normalizing for body weight (3.74 +/- 1.23 versus 5.05 +/- 1.41 ml.min-1.kg-1, P < .05). This slower elimination was associated with a reduced (fractional) clearance by 6-hydroxylation (2.34 +/- 1.04 ml.min-1.kg-1 versus 3.23 +/- 1.10, P < .05). Because such metabolism is mediated by cytochrome P4502E1 (CYP2E1), these findings suggest a lower level of the enzyme's catalytic activity in Japanese men. This was confirmed by in vitro studies with microsomes prepared from livers of individuals representative of the two racial groups. CYP2E1 levels were lower (61% P < .002) and CYP2E1-mediated chlorzoxazone 6-hydroxylase (22%, P < .001) and aniline 4-hydroylase (35%, P < .0001) activities were reduced in Japanese preparations compared to those from Caucasians. No relationships were found between measures of CYP2E1 activity, both in vivo and in vitro, and genomic polymorphisms in the CYP2E1 gene identified by Rsal/Pstl and Dral restriction fragment length polymorphisms. Collectively, these data show an interracial difference in CYP2E1 activity. Because this enzyme is importantly involved in the activation of environmental procarcinogens, such a difference may account, in part, for the lower rate of some cancers, e.g., lung cancer, in Japanese compared to Caucasians men.

Adolescent↗
PubMed1996

Treatment protocol for fractures of the odontoid process.

Treatment results in 104 patients with odontoid fractures were reviewed. There were 2 type I, 62 type II, 32 type III fractures and eight epiphysiolyses in children <7 years old. Thirty-seven patients were managed nonoperatively using plaster casts, cervical braces, or halo devices. Sixty-seven patients were treated surgically including anterior screw fixation (ASF), posterior fusion (PF), and transoral anterior fusion (TAF). Plaster casts and cervical braces were effective for type I fractures and epiphysiolyses only. Halo devices provided successful results in stable type III fractures. ASF is the treatment of choice for most type II and unstable III fractures including some old cases. PF also provided successful union, although impaired cervical motion remained. It should be reserved for irreducible fractures, established nonunions, and as a salvage procedure. TAF should be limited to exceptional cases requiring anterior spinal cord decompression.

Adolescent↗
PubMed1996

[Stimulation of corneal endothelial cell proliferation by interleukins, complete mitogens and corneal parenchymal cell-derived factors].

The effects of various cytokines and mitogens on proliferation of rabbit corneal endothelial cells were examined in a serum-free culture. Complete mitogens such as epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and hepatocyte growth factor (HGF) stimulated proliferation of corneal endothelial cells 1.5 to 2 times the control. The effect was dose-dependent up to 10 ng/ml and flattened out at higher concentrations. Interleukins (IL-x) such as IL-1 alpha, IL-1 beta, IL-2, IL-3 or IL-4 by themselves had little or no stimulatory effect on cell proliferation. The combination of IL-1 beta and EGF, or IL-1 beta and TGF-alpha, however, showed a 5- to 6-fold stimulation over the control. IL-1 beta, thus, can be regarded as a co-mitogen that can amplify the stimulatory effect of complete mitogens (EGF and TGF-alpha). The number of corneal endothelial cells increased to 200% when corneal endothelial cells were co-cultured with corneal parenchymal cells. Addition of conditioned medium obtained from the culture of corneal parenchymal cells also increased the number of corneal endothelial cells more than 2-fold. These results suggest that factors which stimulate cell proliferation of corneal endothelial cells are secreted by corneal parenchymal cells.

Animals↗
PubMed1996

Identification of human cytochrome P450 isoforms involved in the 3-hydroxylation of quinine by human live microsomes and nine recombinant human cytochromes P450.

Studies using human liver microsomes and nine recombinant human cytochrome P450 (CYP) isoforms (CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4) were performed to identify the CYP isoform(s) involved in the major metabolic pathway (3-hydroxylation) of quinine in humans. Eadie-Hofstee plots for the formation of 3-hydroxyquinine exhibited apparently monophasic behavior for all of the 10 different microsomal samples studies. There was interindividual variability in the kinetic parameters, as follows: 1.8-, 3.2- and 3.5-fold for K(m) Vmax and Vmax/K(m), respectively. The mean +/- S.D. values for K(m), Vmax and Vmax/K(m) were 106.1 +/- 19.3 microM, 1.33 +/- 0.48 nmol/mg protein/min and 12.8 +/- 5.1 microliters/mg protein/min, respectively. With 10 different human liver microsomes, the relationships between the 3-hydroxylation of quinine and the metabolic activities for substrates of the respective CYP isoforms were evaluated. The 3-hydroxylation of quinine showed an excellent correlation (r = 0.986, P < .001) with 6 beta-hydroxylation of testosterone, a marker substrate for CYP3A4. A significant correlation (r = 0.768, P < .01) between the quinine 3-hydroxylase and S-mephenytoin 4'-hydroxylase activities was also observed. However, no significant correlation existed between the 3-hydroxylation of quinine and the oxidative activities for substrates for CYP1A2 (phenacetin), 2C9 (diclofenac), 2D6 (desipramine) and 2E1 (chlorzoxazone). Ketoconazole and troleandomycin (inhibitors of CYP3A4) inhibited the 3-hydroxylation of quinine by human liver microsomes with respective mean IC50 values of 0.026 microM and 28.9 microM. Anti-CYP3A antibodies strongly inhibited quinine 3-hydroxylation, whereas weak inhibition was observed in the presence of S-mephenytoin or anti-CYP2C antibodies. Among the nine recombinant human CYP isoforms, CYP3A4 exhibited the highest catalytic activity with respect to the 3-hydroxylation of quinine, compared with the minor activity of CYP2C19 and little discernible or no effect of other CYP isoforms. Collectively, these data suggest that the 3-hydroxylation of quinine is mediated mainly by CYP3A4 and to a minor extent by CYP2C19. Other CYP isoforms used herein appear to be of negligible importance in this major pathway of quinine in humans.

Antibodies↗
PubMed1995

Development and preliminary application of high-performance liquid chromatographic assay of urinary metabolites of diazepam in humans.

A simple high-performance liquid chromatographic method for the measurement of diazepam (DZP) and its major metabolites, N-desmethyldiazepam (DMDZP), temazepam (TZP) and oxazepam (OZP) in urine was developed. Preliminary studies of DZP metabolism were also undertaken in four healthy volunteers after administration of a single oral dose (4 mg) of DZP. The assay allowed the simultaneous determination of all analytes in 1 ml of urine and the detection limit was 2 ng/ml with a signal-to-noise ratio of 3. None of 22 drugs and 17 metabolites, except for mianserin, maprotiline and imipramine N-oxide, interfered with the detection of DZP metabolites. Recoveries of the analytes and the internal standard (prazepam) were > 82%. Intra- and inter-assay coefficients of variation for all analytes were < 5.5 and 4.1%, respectively. The mean (+/- S.D.) cumulative urinary excretions of DMDZP, TZP and OZP over 96 h after a single oral administration of DZP were 3.9 +/- 0.4, 6.6 +/- 1.4 and 2.8 +/- 0.6% of the dose, respectively. The urinary excretion of DZP was under the detection limit.

Chromatography, High Pressure Liquid↗