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Biomedical subjects

Y Kitagawa

Publications and source records attributed to Y Kitagawa.

At least 325 records · Page 18Linked to original sources

Growth stimulating activity on 3T3 fibroblasts of the molecular weight 6,500-peptide purified from rat pancreatic juice.

Growth stimulating activity of the molecular weight 6,500-peptide purified from rat pancreatic juice was measured on 3T3 fibroblasts. This peptide was reported to be a cholecystokinin-releasing peptide and to stimulate pancreatic enzyme secretion in the rat small intestine in response to food intake. Incorporation of [3H]thymidine and [35S]methionine into 3T3 was significantly stimulated and the cell number was also increased after 24-48 hr incubation with 10-100 ng/ml of the peptide. The increase in [3H]thymidine incorporation was dose-related and started 12 hr after the incubation, a peak being reached 24 hr after the incubation. These results show that this peptide exhibits growth stimulating activity to the mammalian cells, and suggest that the peptide might have a physiological effect in vivo.

Animals↗

Presence of 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx) in dialysate from patients with uremia.

MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline), a carcinogenic heterocyclic amine, was found to be present in dialysis fluid of 8 patients with uremia, but not in fresh dialysis fluid before dialysis treatment. Concentrations of MeIQx in dialysates ranged from 14 to 32 pM. The mean absolute contents of MeIQx in dialysates (6 to 40 liters) was 334 p mole. These results indicate that the carcinogenic heterocyclic amine is present in the plasma of all patients with uremia.

Adult↗

3-Methylcholanthrene-induced ethoxyresorufin O-deethylase activity in alveolar type II cells of rabbit lung.

Lungs of 3-methylcholanthrene-treated rabbits and those of untreated rabbits were digested with protease, and the cells were separated into an alveolar type II cell-rich fraction and a Clara cell-rich fraction by the use of counter-flow centrifugal elutriation. Drug oxidation activities of the cell homogenate of each fraction were examined. Marked elevation of ethoxyresorufin O-deethylase activity was found mainly in the cell homogenate of the alveolar type II cell-rich fraction after 3-methylcholanthrene treatment. The activity increased 6-fold with the drug treatment. Coumarin hydroxylase activity was found mainly in the cell homogenates of the Clara cell-rich fraction of the 3-methylcholanthrene-treated and untreated rabbits. The activity increased 3.5-fold with the drug treatment.

Animals↗

Kinetics of the hydrolysis of monodispersed dihexanoyllecithin catalyzed by the phospholipase A2 from Agkistrodon halys blomhoffii venom.

The hydrolysis of 1,2-dihexanoyl-sn-glycero-3-phosphorylcholine (diC6PC), catalyzed by the phospholipase A2 from the venom of Agkistrodon halys blomhoffii, was studied at 25 degrees C and the ionic strength of 0.1 in the presence of 3-33.3 mM Ca2+, which can saturate the Ca2+-binding site of the enzyme. The initial velocity data, obtained at various concentrations of the substrate below the critical micelle concentration (cmc), were analyzed according to the Michaelis-Menten equation. The pH-dependence curve of the Km value exhibited only one transition below pH 8. The analytical results indicated that the pK value of 6.30 of an ionizable group changed to 6.54 on the binding of the monodispersed substrate. This ionizable group was assigned as the alpha-amino group on the basis of its pK value, which had been determined from the pH dependence of the binding constant of monodispersed n-dodecylphosphorylcholine (n-C12PC) (Ikeda and Samejima (1981) J. Biochem. 90, 799-804, and Haruki et al. (1986) J. Biochem. 99, 99-109). The pH-dependence curve of the kcat value exhibited two transitions, below pH 6.5 and above pH 9.5. The analytical results indicated the participation of two ionizable groups with pK values of 5.55 and 10.50. Deprotonation of the former and protonation of the latter group were found to be essential for the catalysis. The former ionizable group was assigned as His 48 in the active site on the basis of its pK value, which had been determined from the pH dependence of the binding constant of Ca2+ (Ikeda et al. (1981) J. Biochem. 90, 1125-1130).(ABSTRACT TRUNCATED AT 250 WORDS)

Catalysis↗

Amino acid sequence of copper,zinc-superoxide dismutase from spinach leaves.

The complete amino acid sequence of Cu,Zn-superoxide dismutase (SOD) from spinach leaves has been determined on the basis of peptides obtained by cyanogen bromide (BrCN) cleavage and by enzymic hydrolyses with Achromobacter lyticus lysylendopeptidase, Staphylococcus aureus V8 protease, trypsin, and thermolysin. The spinach SOD consists of a total of 154 amino acid residues with alanine as the amino(N)-terminus and valine as the carboxy(C-)terminus. The present sequence, which has been established for the enzyme from a plant, is also highly homologous to those of the enzymes from other species. Especially, the residues essential for metal binding and enzyme activity have been extensively conserved among all of the Cu,Zn-SODs hitherto analyzed.

Acetylation↗

Acute effects of phenytoin on brainstem auditory evoked potentials: clinical and experimental study.

In a patient with phenytoin (PHE) intoxication, the brainstem auditory evoked potentials (BAEPs) were lost except for wave I and wave V. The patient recovered. In rats given PHE, we found changes in amplitude, morphology, and latency of BAEP. Within 5 minutes, all waves disappeared except for wave I, and soon thereafter all waves were lost, with PHE plasma concentration between 45.8 and 52.1 micrograms/ml or above. Ninety minutes after infusion, waves gradually reappeared. Loss of BAEP cannot be used as a criterion for brain death unless PHE intoxication is ruled out.

Adult↗

[Toxicity assessments of chemical substances using primary culture of rat hepatocytes].

A primary hepatocyte culture was used as a model system to assess the toxicity of various chemical substances. Chemical substances tested in this experiment included 14 kinds of organic solvents, arsenic acid and N-nitrosodiumethylamine, most of which are known as hepatotoxic materials. Enzyme (GPT and LDH) leakage and albumin secreted from the hepatocytes to culture medium were measured to evaluate the cell damage after exposure to the chemical substances at various concentrations for 3 d. Cell counts and protein contents before and after exposure to the chemical substances were also measured during the course of these experiments. The extent of LDH leakage from hepatocytes was parallel to that of GPT leakage after exposure to the chemicals. Albumin secreted from the hepatocytes in the culture medium evidently decreased at concentrations of the chemicals which increased the enzyme leakage. Viable cell counts were significantly decreased by chemicals that increased the enzyme leakage, although the cell protein contents were not significantly affected. The minimum concentration of the chemicals at which enzyme leakage from hepatocytes was significantly increased was defined as the lowest toxic concentration (TCL0). Judging from TCL0 values, the degree of toxicity in these chemicals seems to be almost identical to the degree of in vivo hepatotoxicity reported previously. We, furthermore, observed that there is a positive correlation (r = 0.780, p less than 0.01) between PT50 calculated by the LD50 value reported previously and -Log magnitude of TCL0.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

Elevated serum CA19-9 levels in poorly controlled diabetic patients.

Serum CA19-9 levels were measured in 60 diabetic patients and 40 healthy volunteers. Serum CA19-9 concentration was correlated with hemoglobin A1 (HbA1) (r = 0.4368 P less than 0.005) and fasting plasma glucose levels (r = 0.3410 P less than 0.01). None of the 40 healthy subjects showed elevated CA19-9 concentrations over 37 units/ml as the upper normal value. The percentage of positive serum CA19-9 levels in poorly controlled patients (fasting plasma glucose greater than 200 mg/dl or HbA1 greater than 13%) and moderately to well controlled patients was 50% and 10%, respectively. No correlation was found between the level of CA19-9 and those total cholesterol, and triglycerides, or the duration of diabetes. In patients who had diabetic retinopathy or persistent proteinuria, the CA19-9 concentration was significantly elevated when compared with those without these complications. It has been shown that patients with adenocarcinoma of the gastrointestinal tract have high plasma CA19-9 levels and those who have benign disease have normal CA19-9 levels. Even though diabetes mellitus is not a malignant disease, serum CA19-9 levels were increased in diabetic patients. These results indicate that HbA1 and fasting plasma glucose should be examined in patients with high CA19-9 levels.

Adult↗

Defect of the first-phase insulin secretion to glucose stimulation in the perfused pancreas of the nonobese diabetic (NOD) mouse.

To investigate the development of impaired insulin secretion in type I diabetes mellitus, the pancreata of ICR and NOD mice (10-50 wk of age) were perfused. According to insulin responses to 30 mM glucose and to 19 mM arginine, we classified the NOD mice into four groups: those having normal insulin secretion to glucose and to arginine similar to that of control ICR mice (group 1); those with a defect in the first-phase insulin secretion to glucose stimulation but with almost normal insulin secretion to arginine, total insulin release to glucose being significantly smaller than that of group 1 (group 2); those having only a small insulin response to either stimulus, but a fasting plasma glucose level still within the normal range (group 3); and those being overtly diabetic, showing no insulin response to either stimulus (group 4). The severity of insulitis and insulin concentration of the pancreas in each group of NOD mice was well correlated with the insulin release from the perfused pancreas. These results indicate that the initial sign of B-cell damage in NOD mice is a defect of the first phase of glucose-induced insulin secretion, which is followed by a total loss of ability to respond to glucose or arginine stimulation.

Animals↗

[Transference of antibiotics into prostatic tissues: sampling method by transurethral resection for the measurement of the concentration of antibiotics in prostatic tissue].

The transeference of two antibiotics, i.e. cefmetazole (CMZ) and fosfomycin (FOM), into prostatic tissues was examined. Prostatic tissue samples were obtained from patients with benign prostatic hyperplasia while undergoing open prostatectomy or transurethral resection of the prostate (TUR-P). 2 g of CMZ or 4 g of FOM was intravenously administered within about 10 minutes starting 1 hour before the removal or resection of the prostate, and blood samples were collected at the end of the administration and during surgery. In TUR-P, resected prostatic tissues were washed with the TUR perfusate and the antibiotic in the tissue was presumed to be released into the perfusate. The following preliminary experiments were, therefore, carried out. The removed prostate was divided into three segments, i.e. urethral region, central region and capsular region, and the CMZ or FOM level in each tissue was measured. The remaining tissues were cut into small pieces for immersion in the TUR perfusate for 10-90 minutes. The tissue fragments were removed every 10 minutes to measure the tissue concentration of CMZ or FOM. The concentration of CMZ or FOM in the prostatic tissues did not vary among the three regions, however it markedly decreased with increase in the period of immersion. This suggested that the concentration of these agents into the prostatic tissues was represented by the concentration in the tissues near the urethra obtained immediately after the start of TUR-P.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗