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Biomedical subjects

K Chiba

Publications and source records attributed to K Chiba.

At least 361 records · Page 20Linked to original sources
PubMed1987

[Metastatic renal tumor originating from esophageal carcinoma: a case report].

A 61-year-old male, who had undergone operation of esophageal carcinoma 11 months earlier, was admitted for left flank pain and high fever. Intravenous pyelography showed a space occupying lesion in the upper half of the left kidney. Computed tomographic scan showed an irregular low density area in the upper half of the left kidney. Angiograms revealed a hypovascular mass with encasement vessels in the same site. Left nephrectomy and paraaortic lymph node biopsy was performed. Pathological examination revealed a metastatic squamous carcinoma from the esophageal carcinoma. Chemotherapy was conducted, but he died 2 months later. Autopsy revealed recurrence in the retroperitoneum, and no metastasis in the right kidney. The literature on secondary renal tumor is reviewed.

Carcinoma, Squamous Cell↗
PubMed1987

Pharmacological properties of the novel non-steroidal antiinflammatory agent N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2 -one.

The antiinflammatory activity of the novel pyrrolidin-2-one derivative N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-o ne (E-5110) was investigated and compared with those of indomethacin and piroxicam in various antiinflammatory, analgesic and antipyretic animal models. The acute antiinflammatory activity of E-5110 on the carrageenin paw edema was similar to that of indomethacin, and half that of piroxicam. The chronic inflammatory responses in established adjuvant- and type II collagen-induced arthritis, which are widely used models of rheumatoid arthritis, were suppressed as effectively by E-5110 as by indomethacin and piroxicam. E-5110 decreased the pleural exudate volume and inhibited leucocyte infiltration in a reversed passive Arthus reaction more potently than indomethacin, suggesting that mediators other than prostaglandin E2 may play an important role in this inflammatory process. The analgesic potency of E-5110 against inflammatory pain was similar to that of indomethacin or piroxicam, but the antipyretic activity of E-5110 was more potent than that of the reference drugs. The ulcerogenic effect of E-5110 on rat gastric mucosa was less than those of indomethacin and piroxicam. In conclusion, E-5110 is a very potent antiinflammatory compound acting against various types of inflammation, and has a favorable therapeutic index.

Animals↗
PubMed1986

Interactions of the 1-methyl-4-phenyl-2,3-dihydropyridinium species with synthetic dopamine-melanin.

This paper describes interactions between the 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+) metabolite of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with synthetic dopamine-melanin, a polymeric pigment which is similar to the neuromelanin found in the nigrostriatal cell bodies of humans and primates. Although MPTP and its 1-methyl-4-phenylpyridinium (MPP+) metabolite bind to the synthetic pigment at physiological pH, both compounds are recovered quantitatively upon treatment with acid. Unlike MPTP and MPP+, MPDP+ proved to be unstable in the presence of synthetic dopamine-melanin which promoted its conversion to the fully oxidized pyridinium product MPP+. The possible biological significance of this interaction is discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Hepatic microsomal cholesterol epoxide hydrolase: selective inhibition by detergents and separation from xenobiotic epoxide hydrolase.

Cholesterol epoxide hydrolase (CEHase) activities of mouse liver microsomes were completely inhibited by Emulgen 108 and Lubrol PX and approximately half by cholate, Triton WR-1339, and Tween 80 when preincubated with 0.1% of these detergents, while their xenobiotic epoxide hydrolase (XEHase) activities were markedly enhanced under the same preincubation conditions. The CEHase and XEHase activities were separately eluted from a gel column applied with mouse liver microsomes which were solubilized in a phosphate buffer containing cholate, glycerol, urea, dithiothreitol, and EDTA.

Animals↗
PubMed1986

Simultaneous quantitative measurement of fourteen adrenal steroids by capillary column gas chromatography-mass spectrometry, and its clinical application.

Until now, there has been little work covering all of the main native adrenal-cortical steroids in blood. We therefore established a method for the simultaneous quantitative measurement of 14 native adrenal-cortical steroids, which involves capillary column gas chromatography-mass spectrometry (GC--MS). Serum steroids were purified from serum with the Extrelut mini-column and then converted into stable derivatives for GC-MS by a combination of boronic cyclization and trimethylsilyl and methyloxime derivatization. The sensitivities (with a signal-to-noise ratio greater than or equal to 7) of our GC-MS method ranged from 0.1 to 1.0 ng/ml of serum, and the coefficients of variation of intra- and inter-assays were less than 19% for each steroid. Our newly devised method involving a capillary column GC-MS system has been proven to be a simple and suitable method for a diagnosis requiring simultaneous detection of many native adrenal steroids in clinical practice. The analysis time is only 4 h.

Adrenal Cortex Hormones↗
PubMed1986

Cholinergic system of brain tissue in rats poisoned with the organophosphate, 0,0-dimethyl 0-(2,2-dichlorovinyl) phosphate.

The cholinergic system of the brain was investigated in rats acutely poisoned with the organophosphate, 0,0-dimethyl 0-(2,2-dichlorovinyl) phosphate (DDVP), (6 mg/kg, sc, with saline as a control). The amounts of three fractions of acetylcholine (ACh)--free (extraterminal), labile-bound (intraterminal/cytoplasmic), and stable-bound (intraterminal/vesicular)--increased in the rats over a period of 5 to 60 min after injection of DDVP, showing peaks which were 2.45, 1.82, and 1.4 times as high as the respective control amounts. No difference was seen in the amount of any fraction of ACh between treated and control rats killed 3 and 24 hr after injection. Acetylcholinesterase (AChE) activity decreased to between 12 and 43% of the control over a period of 5 to 180 min and recovered almost completely within 24 hr after injection. No appreciable changes were seen in either spontaneous or potassium-induced ACh release in brain tissue slices obtained from rats treated with DDVP. ACh synthesis in slices was suppressed significantly 20 min, but not 24 hr, after injection of DDVP. In the brain crude synaptosomal preparation, high-affinity choline uptake, which is generally thought to be a rate-limiting step for ACh synthesis, was suppressed 20 min after DDVP. No appreciable changes were seen in high-affinity choline uptake at 24 hr low-affinity choline uptake, and choline acetyltransferase activity after injection of DDVP. These results suggest that ACh synthesis and high-affinity choline uptake may be in a suppressed state when ACh concentration, especially intraterminal ACh, is increased and AChE activity is decreased in the brain cholinergic system of rats poisoned with DDVP. The increase in the intraterminal ACh may be due to an inhibition of AChE activity at this site and/or a re-uptake of ACh in the synaptic cleft, not to an inhibition of ACh release or an increase in ACh synthesis.

Acetylcholine↗
PubMed1986

Antipyrine clearance and metabolism in patients with psoriasis.

The kinetic parameters of antipyrine obtained from saliva samples and the appearance of major antipyrine metabolites (4-hydroxyantipyrine, norantipyrine and 3-hydroxymethylantipyrine) in urine samples were measured in 10 patients with psoriasis (six nonsmokers and four smokers) and in 20 healthy subjects (11 nonsmokers and nine smokers). The volume of distribution and total clearance of antipyrine were not significantly different between psoriatric patients and control subjects subdivided according to smoking habit. However, antipyrine half-life was significantly (P less than 0.05) shorter in nonsmoking psoriatrics than in nonsmoking controls. There were no significant differences in mean values for the amounts (% dose) and partial clearances for production of major antipyrine metabolites between non-smoking patients and non-smoking controls, between smoking patients and smoking controls, and between patients overall and controls overall. The total clearance of antipyrine and the partial clearances of antipyrine to its three main metabolites were significantly (P less than 0.05 to 0.01) greater in smoking controls than in nonsmoking controls, and the total clearance of antipyrine and the partial clearance to 4-hydroxyantipyrine were significantly (P less than or equal to 0.05) greater in smoking patients than in nonsmoking patients. These findings provide no evidence that psoriasis is associated with an alteration in hepatic microsomal monooxygenase activity, at least insofar as the formation of major antipyrine metabolites is concerned.

Aged↗
PubMed1986

[Evaluation of thallium-201 myocardial emission computed tomography based on a comparison with postmortem findings].

The correlative study of myocardial perfusion assessed by 201Tl myocardial ECT with the pathological finding of the heart was performed in 10 autopsied cases with mean age of 77 years old (range: 60-90 y). In 6 cases with myocardial infarction (MI) 7 perfusion defects were observed, that was, 3 in anteroseptal wall, 1 in anterolateral wall and 3 in posterior wall on the images of SPECT. Seven MIs were also found in postmortem examination. Six MIs were observed at autopsy corresponding to perfusion defect on SPECT images. In one myocardial perfusion defect at inferoposterior portion on SPECT, a non-transmural MI was found at anteroseptum. In one case with valvular disease a false positive result was obtained at posterior wall where neither myocardial necrosis nor fibrosis was observed at autopsy. This case had aortic stenosis due to bicuspid aortic valve by autopsy. The ventricle was divided into 16 segments in each of 4 short axial images to evaluate extent of MI. SPECT for extent of MI showed sensitivity of 81.9%, specificity of 96.0% and diagnostic accuracy of 92.5%. False negative segment was apt to be observed at the surrounding of non-transmural MI or basal half of left ventricle (LV) with transmural MI, while false positive segment was at posterior portion of basal half of LV. It was concluded that myocardial ECT was useful for evaluation of the site and extent of MI.

Aged↗
PubMed1986

[Estimation of 99mTc-dimercaptosuccinic acid renal uptake using single photon emission computed tomography].

Renal function was assessed by measurement of 99mTc-dimercaptosuccinic acid (DMSA) uptake by the kidney based on the transsectional tomographic image obtained by single photon emission computed tomography (SPECT). The renal uptake was expressed as percentage of the total radioactivity detected in the kidney, the volume of which was measured by convolution method, against the amount dosed. Absorption was corrected by GE-STAR method using cut off level of 42%. In order to determine normal range, measurement was made for 40 kidneys of each of 10 male and female volunteers confirmed of having normal kidneys both morphologically and functionally. The average volume of the kidney was 220.4 ml for the right and 239.3 ml for the left for males, and 205.9 ml and 236.5 ml, respectively for females. The renal uptake of radioactivity (at 2 h after injection), was 26.8% for the right and 27.6% for the left for males, with corresponding figures for females being 26.4% and 27.9%, respectively. Distribution range of renal volume and renal uptake was obtained by bivariate analysis with 90% and 95% probability. From these results, our method of renal function determination based on renal uptake of 99mTc-DMSA obtained from renal transactional tomogram by SPECT is considered to be accurate and potentially useful for clinical purpose.

Adult↗
PubMed1985

Active uptake of MPP+, a metabolite of MPTP, by brain synaptosomes.

Mouse brain synaptosomal preparations were used to study uptake of N-methyl-4-phenylpyridine (MPP+), a metabolite of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). The uptake of [3H]-MPP+ by striatal synaptosomes was approximately 25 X greater than that of [3H]-MPTP, with a KM of 0.48 microM and a Vmax of 5.3 nmoles/g tissue/min. Uptake was Na+ dependent and inhibited by ouabain, cocaine and dopamine (Ki 0.12 microM). Synaptosomes prepared from the corpus striatum accumulated [3H]-MPP+ at a rate 5-10 times higher than preparations from other brain regions. This selective uptake of MPP+ may contribute to the specificity of the toxic effects of MPTP on nigrostriatal dopaminergic neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Potential bioactivation pathways for the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

The metabolism of the selective nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been studied in rat brain mitochondrial incubation mixtures. The 1-methyl-4-phenylpyridinium species MPP+ has been characterized by chemical ionization mass spectral and 1H NMR analysis. Evidence also was obtained for the formation of an intermediate product which, with the aid of deuterium incorporation studies, was tentatively identified as the alpha-carbon oxidation product, the 1-methyl-4-phenyl-2,3-dihydropyridinium species MPDP+. Comparison of the diode array UV spectrum of this metabolite with that of the synthetic perchlorate salt of MPDP+ confirmed this assignment. The oxidation of MPTP to MPDP+ but not of MPDP+ to MPP+ is completely inhibited by 10(-7) M pargyline. MPDP+, on the other hand, is unstable and rapidly undergoes disproportionation to MPTP and MPP+. Based on these results, we speculate that the neurotoxicity of MPTP is mediated by its intraneuronal oxidation to MPDP+, a reaction which appears to be catalyzed by MAO. The interactions of MPDP+ and/or MPP+ with dopamine, a readily oxidizable compound present in high concentration in the nigrostriatum, to form neurotoxic species may account for the selective toxic properties of the parent drug.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Comparison of steady-state pharmacokinetics of valproic acid in children between monotherapy and multiple antiepileptic drug treatment.

Steady-state pharmacokinetics of valproic acid (VPA) with or without other antiepileptic drug (AED) treatment were studied in 37 children. Children (N = 16) receiving multiple AED therapy had a higher clearance (23.5 vs 13.0 ml/hr/kg, P less than 0.001), larger volume of distribution (0.30 vs 0.22 L/kg, P less than 0.01), and shorter half-life (9.4 vs 12.3 hours, P less than 0.01) than did those (n = 21) receiving VPA only. Inverse correlations of age with clearance (R = -0.559, P less than 0.01) and apparent volume of distribution of VPA (r = -0.490, P less than 0.05) were observed in children receiving monotherapy. In determining the dose and dosing interval of VPA, consider a possible alteration in the pharmacokinetics relating to age and other concurrent AED therapy.

Adolescent↗