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Biomedical subjects

Y Kanazawa

Publications and source records attributed to Y Kanazawa.

At least 145 records · Page 8Linked to original sources
PubMed1987

Initial phase II clinical studies on midaglizole (DG-5128). A new hypoglycemic agent.

Midaglizole (DG-5128), 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate, is a new type of oral antidiabetic agent that has an alpha 2-adrenoceptor-antagonizing effect. As previously reported, midaglizole reduces plasma glucose, mainly by stimulation of insulin secretion, and inhibits epinephrine-induced platelet aggregation in normal human subjects. In this study, the clinical safety and efficacy of short-term administration of midaglizole were evaluated in 47 patients with non-insulin-dependent diabetes mellitus (NIDDM). After an observation period on diet or sulfonylurea treatment (1 patient was on insulin), patients received 150-250 mg 3 times a day of midaglizole for 2-4 wk, (some patients continued treatment for greater than 4 wk). In 20 of the patients first treated with diet and then switched to midaglizole treatment, fasting plasma glucose (FPG) decreased significantly from 187 +/- 10 mg/dl (mean +/- SE) to 147 +/- 13 mg/dl (P less than .05) and 120 +/- 6 mg/dl (P less than .01) 2 and 4 wk, respectively, after administration of midaglizole. Glycosylated hemoglobin (HbA1) also decreased from 12.0 +/- 0.7 to 11.3 +/- 1.1 and 10.7 +/- 0.6% after 2 and 4 wk, respectively. In 23 of the patients whose treatment was changed from sulfonylureas to midaglizole, FPG, and HbA1 levels were maintained at the same values obtained before administration of midaglizole. In patients treated with midaglizole for greater than 12 wk, FPG and HbA1 were kept at the lowered levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Metabolic pathway of 2-deoxy-2-fluoro-D-glucose studied by F-19 NMR.

The behavior of 2-deoxy-2-fluoro-D-glucose (FDG) in mouse has been studied by F-19 NMR method for long period. The F-19 NMR signals of FDG or its metabolites were observed in tissues without serious broadening. FDG was found to be accumulated in organs in the form of FDG or FDG-6-phosphate and 2-deoxy-2-fluoro-D-mannose (FDM) or FDM-6-phosphate, and the latter dominated the former in the heart sampled at 24 hr or later. The fluorine compounds were excreted in urine in both forms. The clearance was rapid from brain, liver, and blood, but was slow from heart.

Animals↗
PubMed1986

Familial disorder with increased number of insulin receptors: a new category of insulin receptor abnormality.

We found a family in which 6 of 13 family members had extremely high insulin binding to their erythrocytes. The specific binding values of these patients were 3- to 4-fold higher (22.8-28.6% of added [125I]insulin) than normal (mean +/- SD, 7.1 +/- 0.8%; r = 44). Scatchard analysis revealed that in each patient increased insulin binding was due to increased binding capacity, with little change in affinity. In all patients, reticulocyte counts were within the normal range. From the pedigree analysis, the pattern of inheritance was considered to be autosomal dominant. The propositus was more extensively studied. His mononuclear leukocytes and Triton X-100-solubilized preparations of erythrocyte ghosts also had high (approximately 3-fold) insulin-binding capacity compared to that of normal subjects. In contrast, the number of ouabain-binding sites and kinetics of sugar transport were normal. From these findings, we propose a new type of inherited abnormality of the insulin receptor.

Adult↗
PubMed1986

Neurofibromatosis presenting with aqueductal stenosis due to a tumor of the aqueduct: case report.

A 17-year-old boy with neurofibromatosis presented with delayed puberty and epileptic seizures of recent onset. A computed tomographic scan revealed aqueductal stenosis due to a tumor of the aqueduct. This tumor was found at autopsy to be a pilocytic astrocytoma. Aqueductal stenosis in neurofibromatosis is uncommon and has been considered to be a result of periaqueductal gliosis. This seems to be the first report of neurofibromatosis associated with a tumor of the aqueduct.

Adolescent↗
PubMed1986

Quantitative estimation of islet cell surface antibodies in sera of patients with diabetes mellitus, using BK virus-induced insulinoma, rat islet or fish islet cells and 125I-antihuman IgG antibody.

Using a radioligand assay with 125I-antihuman IgG antibody as well as an 125I-protein A binding assay, we quantitatively evaluated islet cell surface antibodies (ICSA) in the sera of diabetic patients already proven to contain antibodies by the immunofluorescence method (IF). It was possible to use not only rat islet but also BK virus-induced hamster insulinoma cells and yellow tail fish (Serolia quinqueradiata) islet cells as target cells in these radioassays. 7 out of 8 diabetic subjects, positive for ICSA by IF, showed levels of binding of 125I-antihuman IgG antibody greater than 2SD above the mean for normal controls. Additionally 3 diabetic subjects negative for ICSA by IF showed levels of binding of 125I-antihuman IgG antibody less than 2SD above the mean for normal controls, and 2 subjects negative for ICSA by IF had levels slightly higher than 2SD above the mean for normal controls. The quantitative ICSA radioligand assay reported here is both sensitive and specific in the detection of the IgG of ICSA. It is also more convenient to use than other methods, and may use any of several different kinds of target cells, each of which may be easily and reproducibly obtained. These radioimmunological methods for the detection of ICSA appear to be ideal for screening large numbers of patients for ICSA.

Adenoma, Islet Cell↗
PubMed1986

[A study on the disc sensitivity for ceftizoxime].

Susceptibilities of 175 strains of 27 bacterial species to ceftizoxime (CZX) were determined by the 2-fold agar dilution method in parallel with the diameter of inhibition zones by the single-disc method under the experimental conditions established by Kanazawa. The experiments demonstrated a significant correlation between MIC by the dilution method and diameter of inhibition zone in each of the conventional assay of over-night (about 16 hours) incubation, the delayed assay (about 24 hours incubation), and the rapid assay (about 3 approximately 4 or 5 approximately 6 hours incubation), thus confirming the applicability of the single-disc assay for CZX. Analysis of the data obtained by using CZX disc containing 30 micrograms revealed the primary regression equation to be: D (diameter, mm) = 27.3-9.7 log MIC (micrograms/ml) in conventional assay, D = 32.5-12.3 log MIC (micrograms/ml) in delayed assay, D = 22.8-7.5 log MIC (micrograms/ml) in 5 approximately 6 hours rapid assay, and D = 17.9-5.1 log MIC (micrograms/ml) in 3 approximately 4 hours rapid assay, respectively. The range of variations in MICs estimated from the diameter of inhibition zone by the disc test was then calculated in comparison with that in MIC determined by the 2-fold agar dilution test, as a reference for the experimental errors which may be involved in the estimation of MIC of CZX by the single-disc assay.

Bacteria↗
PubMed1986

[A study of the disc sensitivity test for cephapirin].

Susceptibility of 203 strains of 34 bacterial species or subspecies to cephapirin (CEPR) was determined by the 2-fold agar dilution method in parallel with the determination of inhibition zone diameter in the single-disc method. These experiments demonstrated a significant correlation between the MIC by the dilution method and the diameter of inhibition zone determined by the conventional assay using an over-night (about 16 hours) incubation, the delayed assay (about 24 hours incubation), or the rapid assay (after 3-4 or 5-6 hours incubation), hence applicability of the single-disc assay for CEPR was confirmed. An analysis of the data obtained using CEPR discs (each containing 30 micrograms) revealed that primary regression equations were as follows: D (diameter, mm) = 25.8-9.7 log MIC (microgram/ml) in the conventional assay; D = 31.2-12.3 log MIC in the delayed assay; D = 21.7-7.1 log MIC in the 5-6-hour rapid assay and D = 17.9-5.0 log MIC in the 3-4-hour rapid assay, and especially for beta-lactamase producing Staphylococci, they were: D = 24.9-9.2 log MIC in the conventional assay, D = 20.4-7.4 log MIC in the 5-6-hour rapid assay and D = 17.5-5.8 log MIC in the 3-4-hour rapid assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Agar↗
PubMed1986

[Biliary excretion and clinical evaluation of cefoperazone in the biliary tract infections].

Biliary excretion Cefoperazone (CPZ) in a dose of 1 g was intravenously injected to each of 13 cases with obstructive jaundice. Entire bile was collected through percutaneous transhepatic cholangiodrainage (PTCD) catheter in every 1 hour for 6 hours. The mean concentration of CPZ in serum was 112.1 +/- 17.8 micrograms/ml (mean +/- S.E.) at 1 hour and 55.1 +/- 19.2 micrograms/ml at 6 hours after injection. The mean recovery of CPZ in bile within 6 hours was 1.13 +/- 0.60%. Average CPZ concentrations in bile were 64.0 +/- 45.8 micrograms/ml in the 1 hour fraction, 142.7 +/- 78.4 micrograms/ml in the 2 hours fraction and 72.2 +/- 34.0 micrograms/ml in the 6 hours fraction. Biliary excretion of CPZ was low in cases where the serum concentration of total bilirubin was high, but maximum CPZ level in bile in patients with higher serum bilirubin concentrations than 30 mg/dl was still more than 3 micrograms/ml. Clinical evaluation. CPZ was administered to 43 patients with biliary tract infections. The efficacy ratio was 88.4% (excellent and good cases) in all cases, and especially high in cases with cholecystolithiasis. But no difference in efficacy ratio was observed among cases with cholecystolithiasis, choledocholithiasis without gallstone and cases subjected to PTCD. In 10 patients examined by ultrasonography, 8 cases showed reduced diameters of gallbladder. No adverse effect of CPZ was noted in any cases. These results suggest that a fairly large portion of CPZ was excreted through bile and that CPZ is a very useful drug for the treatment of biliary tract infections.

Adult↗
PubMed1985

Spin trapping of a free radical intermediate formed during microsomal metabolism of hydrazine.

A radical formed during oxidative metabolism of hydrazine in rat liver microsomes was spin-trapped with alpha-phenyl-t-butylnitrone. The trapped species was identified as hydrazine radical by comparison of its ESR parameters and mass spectrum with those of the adduct formed during CuCl2 catalyzed oxidation of hydrazine. The requirement for oxygen and NADPH in the microsomal oxidation and the occurrence of a typical binding spectrum by difference spectroscopy suggest the involvement of the participation of the cytochrome P-450 enzyme system in the formation of hydrazine radical which must be a precursor of diimide during microsomal oxidation of hydrazine.

Animals↗
PubMed1985

Restriction fragment length polymorphism of the insulin gene region in Japanese diabetic and non-diabetic subjects.

A polymorphic locus flanking the 5' end of the insulin gene was studied in 154 unrelated Japanese diabetic and nondiabetic subjects. A predominance of the small allele was found with the following frequency: of 64 nondiabetic subjects, only 3 of 128 alleles were of the large class (2%); none of 78 alleles were of the large class in 39 Type 1 (insulin-dependent) diabetic subjects, and 4 of 102 alleles (4%) were of the large class in 51 Type 2 (non-insulin-dependent) diabetic subjects. The very low frequency of large allele may relate to the lower prevalence of atherosclerosis in Japanese. However, this possibility requires further examination.

Alleles↗
PubMed1985

Serum free C-peptide response to oral glucose loading as a parameter for the monitoring of pancreatic B-cell function in diabetic patients.

As a parameter for evaluating pancreatic B-cell function, the accuracy of measuring serum free C-peptide immunoreactivity (CPR) was compared with that of measuring plasma immunoreactive insulin (IRI) and urine CPR in diabetic patients during a 100 g oral glucose tolerance test. In 25 non-obese patients receiving oral hypoglycemic agent or diet treatment alone, a positive correlation between the sum of serum free CPR (sigma serum free CPR) and the sum of plasma IRI (sigma plasma IRI) was noted (r = 0.68, P less than 0.001). However, the sum of blood glucose values was found to be negatively correlated to sigma free CPR (r = -0.56, P less than 0.0025), but not to sigma plasma IRI (r = -0.25, NS). In 23 patients receiving diet, oral hypoglycemic agent or insulin treatment, a positive correlation between sigma serum free CPR and urine CPR was noted (r = 0.75, P less than 0.001). However, no significant correlation was found when only insulin-treated patients were investigated (r = 0.37, NS, n = 17). In addition, patients with insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus were better differentiated by measuring sigma serum free CPR than urine CPR. Thus, we concluded that the measurement of serum free CPR during OGTT provides an extremely valuable method for monitoring pancreatic B-cell function in diabetic patients, whether they are receiving insulin treatment or not.

Adolescent↗
PubMed1985

Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia.

Familial hyperproinsulinemia is characterized by the accumulation of proinsulin-like material (PLM) in the plasma of affected patients. This disorder is inherited in an autosomal dominant fashion. The accumulation of PLM is thought to be due to the impaired conversion of proinsulin to insulin. Although PLM has been suggested to have an amino acid substitution, it has been impossible to locate and identify a substituted amino acid, due to the difficulty in isolating sufficient amounts of PLM from plasma samples. Therefore, we analyzed leukocyte DNA from one member of a proinsulinemic family, and we found a point mutation that changed guanine to adenine in the insulin gene. This transition implies that a substitution of histidine for arginine has occurred at amino acid position 65. Furthermore, it indicates that arginine at 65 is essential for the conversion of proinsulin to insulin. Our results suggest a novel mechanism by which disease can be incurred: a heritable disorder can result from a posttranslational processing abnormality caused by a point mutation.

Amino Acid Sequence↗