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Biomedical subjects

K Chiba

Publications and source records attributed to K Chiba.

At least 343 records · Page 19Linked to original sources
PubMed1988

Characterization of hepatic microsomal metabolism as an in vivo detoxication pathway of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective neurotoxin to the nigrostriatal dopaminergic neurons, has been shown to be metabolized by microsomal flavin-containing monooxygenase (FMO) to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide and by cytochrome (cyt.) P-450 to 4-phenyl-1,2,3,6-tetrahydropyridine in the liver. The present study was conducted to determine whether and to what extent each of these metabolic processes would function as the detoxication pathway(s) of MPTP. Administration of either MPTP metabolites, MPTP N-oxide or 4-phenyl-1,2,3,6-tetrahydropyridine, to mice resulted in no significant reductions in striatal dopamine and its metabolites. Pretreatment of mice with alternate substrate of FMO, N-methylmercaptoimidazole or thiobenzamide significantly (P less than .001 to .05) enhanced MPTP-induced reductions in striatal dopamine and its metabolites. In contrast, neither pretreatments with cyt. P-450 inhibitors, SKF-525A (2-diethylaminoethyl-2,2-diphenyl-valerate), quinidine and cimetidine nor with the inducers, phenobarbital and 3-methyl-cholanthrene altered the neurotoxic effects of MPTP. The rate of clearance (Vmax/Km) of N-oxygenation by hepatic microsomes from intact mice was 32 times greater than that of N-demethylation. Although phenobarbital treatment increased Vmax/Km of N-demethylation by 100%, it was still 10 times lower than that of N-oxygenation. Thus, the different responsivenesses of MPTP-treated mice to alternate substrates of FMO and cyt. P-450 modulators appear to come from the difference in the rate of metabolism between N-oxygenation and N-demethylation of MPTP.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Effects of air and irrigating solutions on the corneal endothelium.

It is well established that the corneal endothelium reflects the trauma it experiences by changing its morphological appearance. We have studied the effect of mild trauma to the rabbit endothelium by replacing the aqueous humor with air. After either 2 or 4 h, the air was removed and then replaced with either physiological saline or balanced salt solution (BSS). Specular microscopy was then performed for 1 week to observe endothelial changes. Various transient morphological changes observed during this period included many nonhexagonal cells, enlarged cells, and clusters of small cells. The changes produced were more dramatic for the saline replacement group than the BSS replacement group, indicating that the recovery process of the endothelium following this mild trauma depends on the material used to replace the air. The air appears to sensitize the endothelium to subsequent insult. This model can perhaps be used to evaluate the relative safety of the various solutions that are used in the anterior chamber during ocular surgery.

Air↗
PubMed1987

Refractory hypertension in childhood--efficacy of captopril therapy.

Because of the advance of techniques and age-matched apparatus for blood pressure measurement, and because of the availability of age-related normal values in childhood, the knowledge of the number of children having elevated blood pressures has recently improved. In a group of healthy children, the first important task is to determine how many incidences of "essential hypertension" there are among them, which may appear in childhood and persist into adulthood. This should urge us to undertake periodical examinations of healthy children. On the other hand, the treatment of "secondary hypertension" has similarly been improved. Since 1979 in particular, captopril, an orally active angiotensin I-converting enzyme inhibitor, has successfully been administered to treat children with malignant hypertension and who respond poorly to conventional antihypertensive therapies. We report 3 cases that received captopril for refractory hypertension: a 2-year-old boy with renal and renovascular anomalies, a 7-year-old boy with moyamoya disease after surgical operation, and a 17-year-old youth with Cushingoid syndrome due to chronic administration of steroids against mixed connective tissue disease. After the introduction of captopril, good pressure control was obtained in all 3 cases, although reasonable effects of measurement values of the renin-angiotensin-aldosterone system (decrease in angiotensin I & II, increase in I/II ratio, etc.) were found only in the first case.

Adolescent↗
PubMed1987

Different conformation changes induced by calcium and terbium of the porcine intestinal calcium-binding protein.

The fluorescence of 1-anilino-8-naphthalenesulfonate (ANS) is progressively enhanced with increasing concentration of it, showing a proportionate blue shift of the emission maximum, by the interaction with the porcine intestinal Ca2+-binding protein (CaBP) in the absence of Ca2+. The apo-CaBP has a single binding site for ANS as determined by the fluorescence change, the apparent dissociation constant (Kd) estimated at 49.1 microM. Addition of Ca2+ or Tb3+ to the ANS-apo-CaBP system is capable of enhancing its fluorescence up to about 2- or 5-fold, respectively, causing further blue shift of the emission maximum. These metal ions do not affect the capacity of ANS binding, but Ca2+ slightly increases the Kd value. Increase of the fluorescence of the ANS-CaBP complex by increasing binding of Ca2+ to it was monophasic, while that with Tb3+ was biphasic, both saturated at the same molar ratio, 2, of added cations to the complex. Biphasic change of response has also been observed in UV absorption of the CaBP with increasing concentration of Tb3+. With a half-saturating concentration of Tb3+, Ca2+ can induce a much higher enhancement of the ANS fluorescence than excess Ca2+ alone. All these results indicate that the CaBP molecule contains a single ANS binding site and the conformation and/or microenvironment surrounding bound ANS of the protein is altered reversibly with binding of Ca2+ or Tb3+ to it and that there are differences between Ca2+- and Tb3+-induced conformation changes around the ANS-binding site and the tyrosine residue of it.

Anilino Naphthalenesulfonates↗
PubMed1987

Pharmacological properties of N-methoxy-3-(3,5-ditert-butyl-4-hydroxybenzylidene)-2-pyrrolidone (E-5110), a novel nonsteroidal antiinflammatory agent.

The antiinflammatory activity of a novel pyrrolidone derivative E-5110 was investigated using anti-inflammatory, analgesic and antipyretic animal models in comparison to indomethacin (IND) and piroxicam (PIR). The acute antiinflammatory activity of E-5110 on carrageenin paw edema was similar to IND, and half of PIR. E-5110 inhibited the pleural exudate volume and leucocyte infiltration in a reversed passive Arthus reaction more potent than IND. The chronic inflammatory responses in the established adjuvant- and type II collagen-induced arthritis were suppressed by E-5110 similar to IND and PIR. The analgesic potency of E-5110 was similar to IND and PIR, but the antipyretic activity of E-5110 was more potent than that of IND, and slightly more potent than that of PIR. The ulcerogenic effect of E-5110 on rat gastric mucosa was less than that of the reference drugs.

Animals↗
PubMed1987

Morphometric analysis of corneal endothelium following radial keratotomy.

We performed morphometric analysis of the central corneal endothelium on 24 eyes of 19 patients who had had anterior radial keratotomy. The endothelium was analyzed for a variety of parameters, including cell area, perimeter, side lengths, cell shape, and number of sides. Mean, standard deviation, and coefficient of variation were calculated for each parameter. The mean cell density decreased from 2,835 to 2,677 cells/mm2, mean cell perimeter increased from 71.4 micron to 74.3 micron, and mean side length increased from 11.8 micron to 12.3 micron following surgery. The changes in these three parameters were statistically significant (P less than 0.05). The coefficient of variation of cell area (polymegathism) changed from 0.319 to 0.307, the hexagonality changed from 62.5% to 59.6%, and the cell shape changed from 0.872 to 0.867. The changes in these parameters were not statistically different before and after surgery. The group of patients that had no reported microperforations showed only a small decrease of cell density (1.6%), while the group of patients that had microperforations showed a large decrease of cell density (14.3%). The cell perimeter and side lengths showed a similar pattern. The group of corneas with the optical zone diameter less than 3.5 mm showed a decrease in mean cell density from 2,994 to 2,725 cells/mm2, and the cell shape changed from 0.874 to 0.866 following surgery. The changes in these parameters were statistically significant (P less than 0.05) before and after surgery. Among all factors associated with radial keratotomy, microperforation and a small diameter of central optical zone appear to be the two greatest risk factors.

Adult↗
PubMed1987

Disposition kinetics and dynamics of nicainoprol, a new antiarrhythmic agent, in humans.

Kinetics and resting and exercise-induced hemodynamic and ECG effects of nicainoprol, a new antiarrhythmic structurally resembling propafenone or propranolol, were investigated in eight healthy male subjects receiving a 1-hour infusion (100 mg) and oral dose (200 mg) in a randomized-crossover fashion. Nicainoprol in plasma and urine was determined by a specific HPLC assay. Plasma concentration-time data were fitted to a triexponential equation. Mean postinfusion kinetic data were: alpha-phase half-life = 3.1 minutes, beta-phase half-life = 106.6 minutes, and gamma-phase half-life = 12.4 hours; volume of central compartment = 0.114 L/kg; steady-state volume of distribution = 0.67 L/kg; total clearance = 3.6 ml/min/kg; and renal clearance = 0.56 ml/min/kg. Absolute bioavailability was approximately 70% and peak plasma drug concentration occurred 2.3 hours after oral administration. Interindividual variability in AUC was 1.6- and 2.4-fold after intravenous and oral administration, respectively. Cumulative fraction excreted unchanged in urine was approximately 15% and 9% of the dose after intravenous and oral administration, respectively. Resting heart rates were increased, whereas exercise-induced heart rates were unchanged after both doses. QRS durations were widened after both doses. PR and QTc intervals were prolonged during intravenous study. The results suggest that nicainoprol is an enzyme-limited or poorly extracted drug suitable for both intravenous and oral administration and devoid of beta-blocking action in humans, at least with doses tested in this study. Its ECG properties appear to be similar to those of class I antiarrhythmics.

Administration, Oral↗
PubMed1987

Evidence for polymorphic oxidation of sparteine in Japanese subjects.

The metabolism of sparteine which exhibits a genetic polymorphism in Caucasians was studied in 84 unrelated Japanese subjects. In contrast to a recent study where debrisoquine was used as a probe and no poor metabolizers could be observed in Japanese involving 100 subjects, two subjects had a urinary metabolic ratio of sparteine greater than 20 and thus were poor metabolizers of sparteine. The incidence of poor metabolizer phenotype of sparteine oxidation of 2% seems to be lower in Japanese as compared with various Caucasian populations where 5 to 10% are poor metabolizers of sparteine. However, this is not conclusive, because the 95% confidence interval of the observed frequency, 0.6 to 8%, covers the range reported in the literature for Caucasians.

Adult↗
PubMed1987

A clinicopathologic correlation study of thallium-201 myocardial scintigraphy in diagnosis of myocardial infarction.

In a series of 1,000 consecutive autopsy cases, we evaluated the clinical utility of thallium-201 (Tl-201) myocardial scintigraphy and electrocardiography (ECG) in 101 patients who had been studied while alive. Fifty-five cases had myocardial infarctions (MI) at autopsy. The Tl-201 scintigram and ECG in diagnosis of MI showed sensitivities of 68% and 60%, specificities of 87% and 83%, and diagnostic accuracies of 76% and 70%, respectively. The sensitivity of the Tl-201 scintigram was 70% in anterior MI, 80% in postero-inferior MI, 25% in lateral and subendocardial infarction. The sensitivity was 88% for large massive MI, but was low in scattered (50%) or middle-sized MI (17%). The diagnostic limit of the resolution of Tl-201 scintigrams was 4.5 cm in long diameter. All 8 cases with MI of less than 4 cm could not be diagnosed with the technique. There were 48 cases of large MI (more than 5 cm), but 8 cases could not be diagnosed by scintigraphy because of non-transmural or scattered MI. A comparison of the Tl-201 scintigram and ECG showed that 27 cases out of 60 cases were diagnosed by both methods, 14 only by the Tl-201 scintigram, 9 only by ECG and 10 by neither method.

Aged↗
PubMed1987

[Clinical evaluation of gallium-67 scintigraphy in comparison with autopsy findings in the elderly, with particular reference to histological findings and classification of pulmonary cancer].

A correlative study of autopsy findings and retrospective review of gallium scintigrams were performed in 106 elderly patients. Of the cases studied, 57% demonstrated positive gallium study in the present series. Histological correlation was undertaken in cases of lung cancer. Among them, squamous cell carcinoma showed the highest incidence of positive results (83%), whereas adenocarcinoma was the lowest (35%). There is no apparent correlation between subtypes of histological classification of adenocarcinoma and abnormal accumulation of gallium. However, abnormal accumulation of the nuclide seems to be rather related with interstitial reactions, namely fibrotic changes, lymphocyte infiltration and vascularization.

Adenocarcinoma↗
PubMed1987

[Carcinoma of the urachus with variable pathological findings: report of a case and review of literature].

A 71-year-old man was admitted with the chief complaint of gross hematuria. Cystoscopic examination showed a broadbased papillary tumor at the apex of the bladder. There was edema of the mucous membrane around the tumor. CT-scan demonstrated a mass extending from the bladder dome superiorly. Partial resection of the bladder was done. Pathological examination revealed grade 3 transitional cell carcinoma, with scattered adenocarcinoma and squamous cell carcinoma foci. Chemotherapy with bleomycin (BLM) and cis-dichlorodiamine platinum (CDDP) was done postoperatively. Ten months after the operation, he was readmitted because of recurrence in retroperitoneal lymph nodes. Chemotherapy with BLM and CDDP was done, but he died of pulmonary complications. Autopsy revealed retroperitoneal lymph node metastasis of transitional cell carcinoma. There was no metastasis to any other organ. We briefly discuss 275 cases of the carcinoma of the urachus collected from the Japanese literature.

Adenocarcinoma↗