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Biomedical subjects

Y Kido

Publications and source records attributed to Y Kido.

At least 109 records · Page 6Linked to original sources

The effect of fructose on fructose 2,6-bisphosphate level and fructose 6-phosphate, 2-kinase activity in the perfused rat liver.

In order to investigate the effect of fructose on the metabolic rates of liver glycolysis, changes in fructose 2,6-bisphosphate content and fructose 6-phosphate, 2-kinase (F6P2kinase) activity were examined using perfused rat liver. When the starved liver was perfused with 0.5 mM fructose, the fructose 2,6-bisphosphate level was 6.66 nmol/g liver, or the maximum. However, with further increases in the fructose concentration, increments in the fructose 2,6-bisphosphate level gradually decreased. F6P2kinase was inactive in the starved rat liver. By perfusion with the medium containing fructose or even without fructose, however, the enzyme was activated. The suppression of the increase in the fructose 2,6-bisphosphate level by perfusion at higher fructose concentrations was at least partly due to the inhibition of F6P2kinase by F1P.

Adenosine Triphosphate↗

[Plasma cholecystokinin levels in rats with pancreatic insufficiency induced by intra ductal injection of oleic acid].

Plasma cholecystokinin (CCK) levels in rats with pancreatic insufficiency induced by a single injection of 50 microliters oleic acid into the pancreatic duct were determined by a sensitive and specific bioassay using the isolated rat pancreatic acini. Treatment with oleic acid significantly decreased pancreatic wet weight within 7 days, which lasted until the end of observation (56 days). Histologic examination revealed the destruction of acinar cells and the epithelium of intra- and interlobular ducts. Plasma CCK bioactivity was significantly increased from the pre-treatment values of 0.8 +/- 0.1pM to 5.1 +/- 1.4pM at 24h after oleic acid treatment. After this peak, plasma CCK levels gradually decreased. Even after 56 days, however, plasma CCK levels in oleic acid-treated rats were significantly high compared with those in control rats. In the present study, plasma CCK levels in rats with chronic pancreatitis did not correlate with the progress of pancreatic insufficiency.

Animals↗

[Effect of cholecystokinin and secretin on insulin binding to rat pancreatic acini and pancreatic cancer cell line AR42J cells].

In order to clarify the interaction of hormones which exert various effects on the exocrine pancreas, we investigated the effect of cholecystokinin (CCK) and secretin on subsequent insulin binding to pancreatic acini and cultured AR42J cells derived from azaserine-induced acinar cell carcinoma of the pancreas. CCK at concentrations of 100pM-10nM inhibited subsequent 125I-insulin binding to pancreatic acini. 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited 125I-insulin binding whereas A23187 had little effect, suggesting that the inhibitory effect of CCK is mediated by protein kinase C. On the other hand, 100pM-10nM secretin had no effect on subsequent 125I-insulin binding to pancreatic acini, although higher concentrations of forskolin and 8 bromoadenosine 3', 5'-cyclic monophosphate inhibited 125I-insulin binding. In addition, secretin exerted no potentiating effect on the inhibitory effect of CCK on 125I-insulin binding to pancreatic acini. Based on these results, we further investigated the effect of CCK and TPA on subsequent 125I-insulin binding to AR42J cells. In this carcinoma cell line, inhibitory effect of CCK and TPA on insulin binding was completely abolished. The present results suggest, therefore, that hormonal interaction may play an important role in the regulation of exocrine pancreatic function including acinar cell growth.

Animals↗

Schedule-dependent inhibition of thymidylate synthase by 5-fluorouracil in gastric cancer.

BACKGROUND: An optimal treatment schedule of 5-fluorouracil (5-FU) remains to be clarified. METHODS: A randomized study was conducted to investigate schedule-dependent thymidylate synthase (TS) inhibition by 5-FU in 16 patients with gastric cancer who underwent surgical resection. Surgical specimens of tumor, normal gastric mucosa, and regional lymph nodes were obtained 12 hours after administration of 5-FU either as a continuous infusion (1000 mg/m2 for 48 hours) or as a bolus injection (500 mg/m2 x 2 in 48 hours). RESULTS: The total TS activity (567.8 +/- 294 fmol/mg protein) and the rate of TS inhibition (74.7 +/- 23.1%) in cancer tissues were significantly higher in the continuous-infusion group than in the bolus-injection group (228.5 +/- 104.6 fmol/mg protein and 48.8 +/- 12%, respectively). Likewise, the total TS activity (807.4 +/- 440.3 fmol/mg protein) and the rates of TS inhibition in lymph nodes (72.3 +/- 17.1%) and in normal gastric mucosa (85.1 +/- 12.2%) were significantly higher in the continuous-infusion group than those in the bolus-injection group (232.4 +/- 142.3 fmol/mg protein and 53.6 +/- 17.0% in lymph nodes and 46.5 +/- 14.3% in normal gastric mucosa, respectively). There was a significant correlation between the total TS activity and TS inhibition. CONCLUSIONS: Continuous infusion of 5-FU provides a superior antimetabolic effect in the treatment of gastric cancer, which may lead to a superior antitumor effect.

Aged↗

Concurrent adrenal pheochromocytoma and papillary adenocarcinoma of the thyroid in a 20-year-old man.

A 20-year-old man was admitted to Kyushu University Hospital with complaints of severe headache and episodic hypertension (200/100 mmHg). Ultrasonograms and computed tomographs revealed tumors in the left adrenal region and in the right lower lobe of the thyroid gland. Total thyroidectomy and left adrenalectomy were performed. The excised thyroid tumor and adrenal tumor were pathologically diagnosed as papillary adenocarcinoma and pheochromocytoma, respectively. A chromosome analysis revealed no karyotypic abnormality. Whereas the world literature records such occurrences in women, this is the first report of a simultaneous occurrence of pheochromocytoma and papillary adenocarcinoma of the thyroid in a young man.

Adenocarcinoma, Papillary↗

Synthesis, characterization, and antitumor activity of new chloroethylamine platinum complexes.

A series of cis-bis-(2-chloroethylamine)platinum(II) and platinum(IV) complexes were synthesized and characterized by elemental analysis, IR, and 1H and 195Pt NMR spectroscopic techniques. Complexes were tested in vitro against murine L1210 leukemia and human ovarian A2780 cell lines and in vivo against the L1210 leukemia model. Some of these complexes showed excellent antitumor activity in both systems. However, all were inactive against cisplatin-resistant A2780/CP cells.

Animals↗

Schedule dependent inhibition of thymidylate synthase and tumor growth by 5-fluorouracil in Yoshida sarcoma bearing rats.

Schedule dependent inhibition of thymidylate synthase (TS) and tumor growth by 5-fluorouracil (FUra) was examined in Yoshida sarcoma (YS) bearing Donryu rats. After implantation of YS cells (1 x 10(4), FUra (20 mg/kg/day) was continuously (group C) or daily bolus injection (group B) administered for 6 days. On day 7, tumor weight was 1.57 +/- 0.58 g in group C and 0.45 +/- 0.10 g in group B (P less than 0.01), free TS was 2.23 +/- 83 fmol/mg protein in group B and 96 +/- 55 fmol/mg protein in group C (P less than 0.05), and inhibition rate of TS was 88.3 +/- 5.3% in group C and 94.7 +/- 3.0% in group B (P less than 0.05). A significant correlationship was found between free TS and tumor weight (P less than 0.05). As the next step, continuous infusion (group C) or daily bolus injection (group B) for 6 days was started on day 5 after implantation of YS cells. The relative increase of tumor on day 9 was 256 +/- 111% in group C and 112 +/- 22.1% in group B (P less than 0.05). On day 11, total TS of the resected tumor was 650 +/- 153 fmol/mg protein in group C and 391 +/- 124 fmol/mg protein in group B (P less than 0.05), and inhibition rate of TS was 78.8 +/- 12.4% in group C and 84.4 +/- 8.6% in group B. Daily bolus injection of FUra causes a superior antitumor and antimetabolic effect. The schedule dependent cytotoxicity of FUra should be taken into account when a chemotherapeutic protocol is designed.

Animals↗

Establishment of a multi-dose study of chondroitin sulfate iron colloid for evaluation of the reticuloendothelial system function.

The assay system of chondroitin sulfate iron colloid (CSFe) was established to evaluate the reticuloendothelial system (RES) function in individual rabbits. In the multi-dose study of CSFe, CSFe was repeatedly administered to each individual rabbit with increasing doses (0.6, 1.2, 2.4, 6.0 mg/kg) at set intervals. Blood samples were serially collected after injection of CSFe and the concentration of CSFe in serum was directly measured as an iron concentration by modifying the previously described assay method [1] to minimize the sample volume. The clearance rate of CSFe at each injected dose was computed by the least-squares method and the double-reciprocal plotting of the doses against the phagocytic velocities by the Lineweaver-Burk method was obtained in each rabbit. The maximum phagocytic velocity (Vmax) and the CSFe concentration producing 1/2 Vmax (Kp) obtained in ten rabbits were 0.129 +/- 0.025 mg/kg per min and 0.417 +/- 0.121 mg/kg (mean +/- S.D.), respectively. The results obtained from this multi-dose study were comparable to our previous results obtained from the mean values of five groups given different doses [1]. The clearance rates of CSFe (0.6, 1.2, 6 mg/kg) decreased after the co-injection of 80 mg/kg of carbon colloid. The calculated Vmax and Kp in 29 rabbits were 0.125 mg/kg per min and 1.167 mg/kg. The Kp was apparently greater than that of the control (Vmax = 0.128 mg/kg per min, Kp = 0.421 mg/kg). Carbon colloid (80 mg/kg) was injected to six rabbits after the completion of the first multi-dose study of CSFe and then the second multi-dose study of CSFe was repeated after 24 h. No differences were found in Vmax and Kp between the two studies as were in the control group (10 rabbits) where saline was injected instead of carbon colloid. These results indicated that carbon colloid (80 mg/kg) gives a competitive and reversible inhibition on the RES. This multi-dose study of CSFe may be applicable for a bed-side analysis of the RES function in a patient.

Animals↗

Effects of protein intake on immune parameters in mice surviving streptococcal infection.

Groups of mice were fed for 2 weeks on isocaloric diets containing 5, 7, 20 and 40% (w/w) casein, respectively, then injected intraperitoneally with group B streptococci, and observed for their survival rates. The mice fed 7% or 20% casein had lower mortalities than those fed 5% or 40% casein. In order to explain the different survival rates, other groups of mice were fed on the experimental diets and examined for the number of leukocytes in the blood, of spleen cells and thymocytes, for IgG and IgM antibody titres to the streptococci, for haemolytic titres of sera, the amount of complement component 3 (C3), for chemiluminescence and opsonic activity of peritoneal exudate cells (PEC) and spleen cells (SP), production of superoxide anion from PEC and SP, and production of immunoglobulins from cultured SP. After 2 weeks on a 7 or 20% casein diet mice showed increased serum levels of IgM antibodies reactive with the whole bacterial cells on days 3-5 when they were immunised with a sublethal dose of group B streptococci. The mice fed on the 7% casein diet also showed a higher C3 titre than the other diet groups when assayed by enzyme immunoassay. Furthermore, opsonophagocytic activity was highest when PEC or SP taken from mice on the 20% case in diet were incubated with radiolabelled microorganisms in the presence of fresh serum taken from the 7% casein group. The production of superoxide anions from PEC and SP was lowest in the mice fed on 5% casein when activity was expressed as nano-mol per animal. It is suggested from these results that the greater activity of phagocytic cells in the presence of increased amounts of C3 and IgM explains the heightened resistance in the mice fed on a 7% casein diet, and that suppressed opsonophagocytic activity resulting from the decreased number of leukocytes in the blood and other phagocytic cells explains the lowest resistance in the 5% casein group. However, mice fed on a 40% casein diet showed all these immunological parameters untouched, and their lowered resistance could not be explained. Different factors seem to be operative in them.

Animals↗

Secretion of beta-2-microglobulin from human hepatoblastoma and hepatoma cells on stimulation with interleukin-6.

beta 2-microglobulin (beta 2-M) was secreted in a dose- and time-dependent manner after interleukin-6 (IL-6) treatment of human hepatoblastoma (HuH-6) and hepatoma cells (HuH-7). Pancreatic secretory trypsin inhibitor, which is one of the acute phase proteins secreted in these cells, was also secreted dose- and time-dependently in HuH-6 cells and dose-dependently in HuH-7 cells. It is conceivable that IL-6 induces the production of beta 2-M as an acute phase protein in the liver.

Carcinoma, Hepatocellular↗

5838-DNI, a deoxyribonuclease inhibitor produced by Streptomyces sp. strain no. A-5838.

5838-DNI, an inhibitor of deoxyribonuclease (DNase) II from porcine spleen was produced by Streptomyces sp. strain No. A-5838. The structure of 5838-DNI was shown to be 1,4,4a,5,12,12a-hexahydro-4,4a,11,12a-tetrahydroxy-3,8-dimethoxy-9- methoxycarbonyl-10-methyl-1,5,12-trioxo naphthacene. Although similar in structure to tetracenomycin C, which is an antibiotic against Gram-positive bacteria, 5838-DNI has different antibacterial activity. 5838-DNI was distinguished from 5923-DNI, a previously reported DNase II inhibitor, in inhibitory activity against each enzyme. 5838-DNI showed dependency of inhibition on pH and temperature, and inhibited phosphodiesterase I in a competitive manner. These data suggest that 5838-DNI is the first reported example of an inhibitor of microbial origin which is able to inhibit DNase II and phosphodiesterase I.

Animals↗

[Inhibitory effect of somatostatin analog, SMS 201-995, on exocrine secretion from isolated rat pancreatic acini].

In vitro effect of somatostatin analog, SMS 201-995 (SMS), on pancreatic exocrine secretion was investigated using isolated rat pancreatic acini. SMS had no effect on basal, cholecystokinin octapeptide (CCK-8)- or secretin-stimulated amylase release. SMS inhibited pancreatic amylase release in response to simultaneous stimulation with secretin and CCK-8 in a dose-dependent manner. Significant inhibition was observed with 10 nM SMS and maximal inhibition with 0.1-1 microM SMS. Amylase release in response to the combination of 100 pM CCK-8, 1 nM secretin and 0.1-1 microM SMS was similar to that to 100 pM CCK-8 alone. Secretin significantly increased acinar cell cAMP content. SMS partially inhibited an increase in cAMP content induced by secretin. The present study has demonstrated, therefore, that SMS directly inhibits the potentiating effect of secretin on exocrine secretion in part by inhibiting an increase in secretin-induced cAMP accumulation in rat pancreatic acinar cells.

Amylases↗

Protein deficiency and excess lipid synergistically augmented lipid peroxidation in growing rats.

The influence of dietary protein and lipid on superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH) and tissue lipid peroxidation, as measured by thiobarbituric acid-reactive substances (TBARS), was investigated in post-weaning male Wistar rats, fed either a diet containing 5% or 20% corn oil with 5%, 10% or 20% soy protein isolate (SPI) for four weeks. TBARS concentrations in 5% corn oil group was highest in 5% SPI group for all organs, followed by 10 and 20% SPI groups in the liver and 10 and 20% SPI groups in other organs. High lipid diet significantly increased TBARS formation in the liver of 10% SPI group. The liver and kidney SOD and GPx activities were higher in 5% and 10% SPI groups than in 20% SPI group, suggesting an augmented formation of radical substrates for these enzymes in low protein groups. Organ GSH concentrations did not show a linear correlation with dietary protein level. These results suggest that protein deficiency along with high lipid intake accelerates the peroxidative damage of the tissues by increasing oxy-radical formations and/or decreasing the defense mechanism.

Animals↗

[A study on a postoperative change of beta-2-microglobulin in surgical patients].

Various renal tubular functions were monitored perioperatively in 42 surgical patients and the validity of beta-2-microglobulin (BMG) was evaluated. NAG index (urine NAG titer/urine creatinine), the absolute value of free water clearance and fractional excretion of sodium were worse at 3 to 5 hours after the beginning of operation, indicating the latent renal tubular damage took place during operation. On the other hand, fractional excretion of BMG (FE-BMG; BMG clearance/creatinine clearance) slowly elevated after operation and reached a peak on the 2nd postoperative day. The postoperative change of C-reactive protein (CRP), was similar with that of FE-BMG, showing a significant correlation (r = 0.716, p less than 0.001). The close relationship between CRP and FE BMG was confirmed in 26 patients with or without abnormal liver function who underwent abdominal operation. The peak value of FE BMG was significantly (p less than 0.01) lower in 5 patients with ICG 15' greater than 25% than in 21 patients with ICG 15' less than 20%. Similarly, the peak value of CRP tended to be lower in the former group. In conclusion, FE BMG can not be employed as an indicator of renal tubular function during postoperative period. It reacts as an acute phase reactant like CRP and is probably produced in the liver.

Acetylglucosaminidase↗