PubMed Health⌕ Search

Biomedical subjects

Y Kido

Publications and source records attributed to Y Kido.

At least 91 records · Page 5Linked to original sources

Nutrient-induced thermogenesis (NIT) following amino acid infusion.

Nutrient-induced thermogenesis (NIT) induced by parenteral infusion of amino acid (AA) mixtures of different composition and of the same AA mixtures given via different routes (parenteral or intraportal infusion) were investigated in rats using a small animal indirect calorimeter. When 8 different AA solutions of differing composition but with the same total concentration were infused parenterally, both standard NIT (each AA is assumed to generate 3.28 kcal/g) and specific NIT (heat energy of each AA is calculated assuming that it is oxidized to carbon dioxide and water, and metabolised to urea and sulphuric acid) values of the leucine (Leu)-rich and the glycine (Gly)-rich solutions were significantly greater than those of the control solution. Removal of Leu or Gly from the respective AA solutions reversed the increase of both NIT values down to control levels. When the parenteral and portal infusion routes were used in one rat, both NIT values for parenteral infusion of the Leu-rich solution were again significantly greater than those of the control. Likewise, both NIT values for intrportal infusion of the Leu-rich solution were also significantly greater than those of the control. However, no difference in NIT values was found between parenteral and portal infusion of either solution. The result of this study indicated that Leu and Gly may be thermogenic AAs, and the thermogenic effect of Leu is not dependent upon the route of infusion.

Journal Article↗

Epidermal growth factor-induced mitogen signals in cultured intestinal epithelial cells.

Epidermal growth factor (EGF) stimulated proliferation of an intestinal cell line (IEC-6 cells), derived from rat jejunal crypts. EGF-induced tyrosine phosphorylation was analyzed by immunoblotting with a monoclonal antibody specific for phosphotyrosine. EGF initiated rapid tyrosine phosphorylation of proteins with molecular masses of 185, 170, 55, and 42 kilodalton (kDa). In addition, EGF caused the rapid elevation of intracellular free Ca2+ concentration. Thus, EGF-stimulated proliferation and its mitogen signals were clearly observed in IEC-6 cells, suggesting that EGF may play an important role in the maintenance and repair of the intestinal mucosa in vivo.

Animals↗

Role of intracellular proteases in differentiation of L6 myoblast cells.

The activities of cathepsins B, L, and H increased by 3.0, 2.3, and 1.9 fold in differentiation of L6 myoblasts. Separating from the intrinsic inhibitor, both mu- and m-calpain activities also increased by 4.9 and 1.7 fold during differentiation. Calpeptin (10(-5)M), cell penetrating calpain inhibitor, blocked fusion of myoblast by 55% and increment of creatine phosphokinase (CPK) activity by 20.3% with inhibiting the activities of cathepsin L and mu-calpain. E-64(10(-4)M) did not block fusion of myoblasts but increment of CPK activity by 25.0% with inhibiting the activities of cathepsin L and B. Calpain may be involved in the process of myoblast fusion.

Animals↗

Modulation of cytotoxicity and cellular pharmacology of 1,2-diaminocyclohexane platinum (IV) complexes mediated by axial and equatorial ligands.

Isomers (R,R-, S,S-, and cis-) of 1,2-diaminocyclohexane (DACH) platinum(IV) complexes with selected axial and equatorial ligands were synthesized and evaluated for in vitro antitumor activity, cellular uptake, and total DNA-Pt adducts. L1210 cells, sensitive to cis-diamminedichloroplatinum(II) (CDDP) and tetraplatin (L1210/0), 160-fold resistant to CDDP [L1210/diamminedichloroplatinum (DDP)], or 70-fold resistant to tetraplatin (L1210/DACH), were used in conjunction with compounds having the general structure DACH-Pt(IV)-X2Y2, where X and Y are axial and equatorial ligands and X2Y2 are specifically Cl2Cl2,Ac2Cl2, (TFA)2Cl2, (OH)2Cl2, and Cl2CBDCA (Cl, chloro; Ac, acetato; TFA, trifluoroacetato; OH, hydroxo; CBDCA, 1,1-cyclobutanedicarboxylato). Comparison of cytotoxicities between isomers of Cl2Cl2,Ac2Cl2, or Cl2CBDCA indicated that R,R-isomers were the most effective against all three cell lines. The relatively lower activity of the S,S- and cis-isomers was cell line dependent: against L1210/DACH, both isomers of Cl2Cl2 were only 2- to 3-fold less effective, and this contrasted with 7- and 26-fold lower cytotoxicities, respectively, against L1210/DDP. Cross-resistance factors in the L1210/DDP and L1210/DACH lines depended on both isomeric form and the nature of axial or equatorial ligand. The L1210/DDP cells were 6- to 9-fold cross-resistant to the R,R-isomer, 8- to 15-fold to S,S-isomer, and 13- to 38-fold to cis-isomer. The L1210/DACH line was only 4- to 7-fold cross-resistant to the three isomers of Ac2Cl2 but cross-resistance to the isomers was 47- to 79-fold for Cl2Cl2 and 22- to 56-fold for Cl2CBDCA complexes. Compared with CDDP, accumulation (2 h at 100 microM drug concentration) of Ac2Cl2 in the three L1210 cell lines was 26-50%, while uptake of Cl2Cl2 and (TFA)2Cl2 was 100-170% and 320-570%, respectively. The greatest DNA binding was seen with Cl2Cl2 in all cell lines, followed by (TFA)2Cl2, CDDP, and Ac2Cl2. DNA binding correlated directly with potency (1/concentration producing 50% inhibition) in the L1210/0 model (r = 0.973, P < 0.016) but not in the L1210/DDP and L1210/DACH models. Accumulation and DNA-binding studies indicated that binding efficiency to DNA was: Cl2Cl2 > Ac2Cl2 > CDDP > (TFA)2Cl2. In a nonreducing environment, the Pt(IV) complexes (20 microM) did not react with salmon sperm DNA. Reduced glutathione (100 microM), as a reducing agent, rendered full binding capacity to Cl2Cl2; binding was 25-30% of the expected maximum for (TFA)2Cl2, while Ac2Cl2 remained inert.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Preparation, characterization, and antitumor activity of new ethylenediamine platinum(IV) complexes containing mixed carboxylate ligands.

A series of ethylenediamine platinum(IV) complexes of the type PtIV(en)XA2 and PtIV(en)X'2A2, where X = 1,1-cyclobutanedicarboxylato or malonato, X' = chloro, cyclobutanecarboxylato, cyclopentanecarboxylato, or cyclohexanecarboxylato, and A = acetato or trifluoroacetato were synthesized and characterized by elemental analysis, infrared, and NMR (13C and 195Pt) spectroscopic techniques. These compounds had good to excellent antitumor activity against murine leukemia L1210 cells. Complexes with axial trifluoroacetate groups were superior to those with acetate ligands. Those possessing both axial trifluoroacetate groups and monodentate bis-carboxylate ligands in the equatorial positions were the most active in the series investigated.

Animals↗

Distinct P-glycoprotein expression in two subclones simultaneously selected from a human colon carcinoma cell line by cis-diamminedichloroplatinum (II).

Two drug-resistant sublines, CP2.0 and RT, were simultaneously selected by cis-diamminedichloroplatinum (CDDP) from the human colon carcinoma cell line LoVo by the conventional method of continuous drug exposure. The 2 sublines differed in morphology, growth kinetics and pattern of gene expression. Genetic signature analysis indicated that the lines were independent subclones but that both arose from LoVo. These sublines were maintained in a growth medium containing 2.0 micrograms/ml CDDP. However, CP2.0 cells were 3 times more resistant to CDDP than were RT cells. Although both were cross-resistant to mustargen and 5-fluorouracil, only CP2.0 was resistant to Adriamycin and vincristine. Western-blot analysis, immunocytochemical staining and in vitro phosphorylation experiments indicated that the level of P-glycoprotein was significantly elevated in CP2.0 but not in RT. Despite the differences between these sublines, they possess similar CDDP-resistance mechanisms, including decreased intracellular CDDP accumulation, elevated levels of glutathione and metallothionein-like proteins, increased glutathione transferase-pi mRNA, and enhanced susceptibility to CDDP cytotoxicity after treatment with DL-buthionine-[S,R]-sulfoximine. Nevertheless, our results suggest that, in certain tumor types, P-glycoprotein-mediated multi-drug resistance and CDDP-resistance phenotypes can coexist in cells with primary resistance to CDDP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Comparison of postoperative results following terminal esophagoproximal gastrectomy and esophageal transection for esophageal varices.

The results of 44 terminal esophagoproximal gastrectomies (TEPG) and 53 esophageal transections (ET) for esophageal varices, performed during the period between January, 1975 and March, 1989, were retrospectively compared. The results examined prognosis, recurrence of esophageal varices and late postoperative complications. The 5-year survival rates for patients who underwent selective or prophylactic surgery were 85.9% following TEPG and 81.6% following ET. However, the 10-year survival rate for the former group was significantly lower than that for the latter group at 59.3% versus 70.0% (P < 0.05) because of the number of deaths due to hemorrhage and liver failure caused by anastomotic ulcers. The respective 5-year recurrence rates of varices for the TEPG and ET groups were 18.4% and 26.4%, respectively, while the 10-year recurrence rate for the former group was again significantly lower than that for the latter group at 27.1% versus 53.7% (P < 0.01). As for postoperative late complications, reflux esophagitis and/or anastomotic ulcers were found twice as frequently after TEPG as after ET. Thus, although TEPG was more effective for preventing variceal recurrence it left the potential for an anastomotic ulcer to develop, which was the dominant cause of death more than 5 years after surgery.

Adult↗

Effect of indomethacin on postoperative protein metabolism after gastrectomy under total parenteral nutrition.

A randomized trial was undertaken to evaluate the effects of postoperative indomethacin (IDM) administration on protein metabolism in 20 patients who underwent an uncomplicated distal gastrectomy and were placed on post-operative total parenteral nutrition (TPN). Ten patients (the IDM group) received 50 mg of IDM every 8 h after operation up to postoperative day (POD) 4 while the other ten patients (the control group) received neither IDM nor any other non-steroidal anti-inflammatory drug, postoperatively. Though the requirement for postoperative plasma transfusion was significantly greater in the IDM group, the albumin level on POD 1 was significantly lower in this group than in the control group. The postoperative changes of C-reactive protein, retinol binding protein, and pre-albumin between the two groups showed no difference. Moreover, the urinary 3-methylhistidine excretion, N-balance, and plasma aminogram on POD 4 also demonstrated no difference. We thus concluded that post-operative IDM administration after elective surgery has no additional anti-catabolic effect on the presence of TPN.

Blood Proteins↗

Effect of islet hormones on secretin-stimulated exocrine secretion in isolated perfused rat pancreas.

To clarify the effect of islet hormones on pancreatic ductular cell function, we measured the exocrine secretion elicited by 10 pM secretin in the presence or absence of islet hormones using an isolated perfused rat pancreas model. Insulin significantly increased secretin-stimulated pancreatic juice secretion, but not protein secretion. The potentiating effect of insulin on pancreatic juice secretion was concentration-dependent, and the maximal effect was observed with 1 microM insulin. Ouabain, a specific Na+,K(+)-ATPase inhibitor, caused concentration-dependent inhibition of the potentiating effect of insulin without affecting secretin action. Glucagon (100 nM) significantly inhibited secretin-stimulated pancreatic juice secretion and also tended to inhibit protein secretion. A somatostatin analog, SMS 201-995 (10 nM) significantly inhibited both the pancreatic juice and protein secretion stimulated by secretin. The inhibitory effect of SMS 201-995 was concentration-dependent and was maximal at 1-10 nM. These results demonstrate that insulin potentiates the secretory response to secretin, at least partly by increasing Na+,K(+)-ATPase activity, whereas glucagon and somatostatin inhibit this response. Thus, pancreatic islet hormones regulate the secretory function of pancreatic ductular and centroacinar cells.

Animals↗

In vitro inhibitory effect of somatostatin on secretin action in exocrine pancreas of rats.

BACKGROUND: Exocrine pancreatic function is influenced by pancreatic islet hormones. Although the existence of somatostatin receptors has been shown on pancreatic acinar cells, the in vitro effect of somatostatin on exocrine secretory function has not been established. METHODS: Using isolated rat pancreatic acini, the effect of somatostatin analog SMS 201-995 (SMS) and somatostatin 14 (S-14) on amylase release, cyclic adenosine monophosphate (cAMP) production, and hormone binding were determined. RESULTS: SMS inhibited the potentiating effect of secretin on amylase response to cholecystokinin octapeptide (CCK-8) in a concentration-dependent manner. The inhibitory effects of SMS and S-14 were similar on a molar basis and were observed when vasoactive intestinal polypeptide (VIP) but not 8bromoadenosine 3':5' cyclic monophosphate was used instead of secretin and when carbachol, bombesin, A23187, and 12-O-tetradecanoylphorbol 13-acetate were used instead of CCK-8. SMS inhibited secretin-induced cAMP production, and the dose-inhibition curve for cAMP was similar to that for amylase release. SMS had no influence on 125I-secretin and 125I-VIP binding. CONCLUSIONS: Somatostatin acts directly on acinar cells and inhibits secretin potentiation of secretory response in part by inhibiting secretin-induced cAMP production.

8-Bromo Cyclic Adenosine Monophosphate↗

Differential cytotoxicity, uptake and DNA binding of tetraplatin and analogous isomers in sensitive and resistant cancer cell lines.

Some platinum complexes contain 1,2-diaminocyclohexane (DACH) as a stable carrier ligand, which can exist as the R,R-, S,S- and cis-isomers. Tetraplatin, for instance, is a mixture of R,R- and S,S-DACH-Cl4-Pt(IV). We have examined each of the three individual isomers of DACH-Cl4-Pt(IV) with respect to cytotoxicity, uptake of platinum and total DNA-platinum in three murine leukemia L1210 (cisplatin-sensitive L1210/0, 50-fold cisplatin-resistant L1210/DDP and 36-fold tetraplatin-resistant L1210/DACH) and human ovarian carcinoma A2780 (cisplatin-sensitive) and A2780cp (8-fold cisplatin-resistant) cell lines. Against A2780, A2780cp and L1210/DDP cell lines, the R,R-isomer was the most potent followed by the S,S-isomer and then the cis-isomer. However, the three isomers demonstrated similar IC50 values against the L1210/0 and L1210/DACH cell lines. The cis-isomer demonstrated cross-resistance (9- to 20-fold) to cisplatin in L1210/DDP and A2780cp cell lines. On the other hand, R,R- and S,S-isomers demonstrated minimal (2- to 4-fold) cross-resistance against these tumor models. Intracellular platinum accumulation over a 2 h period at 40 microM drug concentration was significantly (p < 0.05) greater for the R,R-isomer than the cis-isomer in L1210/0 (122 versus 101 ng Pt/mg protein) and L1210/DDP (73 versus 50) cell lines, while no difference was observed in L1210/DACH cells (55 versus 56). In L1210/DDP cells, total DNA-bound platinum was significantly (p < 0.05) greater for the R,R-isomer compared with the cis-isomer (10.3 versus 7.5 ng Pt/mg DNA).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of platelet on protein degradation in rat skeletal muscle.

The effects of activated platelet (Plt) on muscle degradation were investigated, employing the in vivo disseminated intravascular coagulation (DIC) model induced by thrombin injection and the in vitro tissue culture system of skeletal muscles in rats. Both the release of tyrosine and leucine into the culture medium during 2 h incubation from the muscles harvested 30 min after thrombin injection increased by about 50% compared with control muscles. The addition of thrombin-activated platelet supernatant (TAPS) significantly increased the release of leucine into the incubation medium of the soleus muscles dissected from normally fed rats by 31% in comparison with the respective controls. No significant effect was observed in terms of the release of tyrosine or leucine from the incubated muscles by aspirin treatment before obtaining TAPS, or by the addition of thrombin itself up to the concentration of 0.67 micron/ml which was contained in the incubation medium of TAPS. These data suggest that protein catabolism is accelerated in the muscle from the thrombin-treated rats exhibiting DIC. The supernatant of activated Plt might contain a factor which modulates protein metabolism. That factor is different from prostaglandins or thrombin. Thus, active consumption of Plt may contribute to an increase of muscle breakdown in various catabolic states.

Animals↗

Syntheses of 3-substituted 1-methyl-6-phenylpyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones (6-phenyl analogs of toxoflavin) and their 4-oxides, and evaluation of antimicrobial activity of toxoflavins and their analogs.

6-Phenyl analogs of toxoflavin (1-methyl-6-phenylpyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones ) (7a--f) and their 4-oxides (8a-f) were synthesized by nitrosative or nitrative cyclization of the aldehyde hydrazones (6a-f) of 6-(1-methylhydrazino)-3-phenyluracil (5). Both sets of compounds, 7a-f and 8a-f, gave the corresponding 1-demethyl derivatives (10a-f) upon treatment with nucleophiles such as dimethylformamide (DMF) and acetic acid under heating. The activities of toxoflavins (1a-e), toxoflavin 4-oxides (3a-e) and their 6-phenyl analogs (7a-f and 8a-f) against a variety of bacterial and fungal strains were examined. Most of the compounds showed strong inhibitory activities against gram-positive bacteria. Among the compounds, 1c, 1d, 1e, and 3c exhibited the strongest inhibitions of Micrococcus lutea (0.5 micrograms/ml minimal growth-inhibitory concentration) and Staphylococcus aureus 4R (1 microgram/ml), as well as Bacillus subtilis and Staphylococcus aureus (1-2 micrograms/ml). Most of the compounds had strong antifungal activity (2-100 micrograms/ml minimal growth-inhibitory concentration) against Candida albicans and Saccharomyces cerevisiae.

Anti-Bacterial Agents↗

[Synthesis and antiulcer effects of 5-hydroxy-4-[2-substituted-(E)-ethenyl]-2(5H)-furanone. (1)].

gamma-Hydroxybutenolides possessing conjugated substituents at the beta-position and their related compounds have been synthesized by the previously reported procedure with minor modifications and their antiulcer activities have been examined in the HCl-ethanol induced ulcer model often used for the evaluation of gastric mucosal protective factor enhancing effect. The compound A-1 5-hydroxy-4-[2-(2,6,6-trimethyl-1-cycohexenyl-1-yl)-(E)-ethenyl]-2 (5H)-furanone showed a pronounced effect at a low dosage of 5 mg/kg p.o. and some analogues compounds also exhibited potent inhibitory activity as compared with the reference drugs. The relationship between the structure of gamma-hydroxybutenolides and the antiulcer effect has been also examined and then the 5-hydroxyl group has been found to be essentially functional one to have antiulcer activity.

4-Butyrolactone↗

Pharmacokinetics of sulfadimethoxine in skin of broiler-chicken after single and multiple intravenous injections.

Pharmacokinetics of sulfadimethoxine (SDMX) in skin of broiler chicken after intravenous and in-drinking-water administrations were investigated to examine the reason for a longer residue of SDMX in the skin which was observed in the residue study after administration via drinking water at a concentration of 1,000 ppm. The decay curve of SDMX in the skin after single intravenous injection of 200 mg/kg, the highest dose, was fitted to the two compartment model with T1/2 of 4.4 hrs in the first elimination phase and 173 hrs in the second one. The extrapolated concentrations in the skin at 24 hrs after the injection were calculated to be 69.0 micrograms/g for the 1st phase and 0.11 micrograms/g for the 2nd phase. The decay curves in the skin after single injection of 30 and 100 mg/kg were fitted to the one compartment model with T1/2 of 3.2 and 5.7 hrs, respectively. Dividing a high dose into 3 to 5 doses and injecting sequentially with intervals of the previously measured T1/2, SDMX concentrations in the skin were about half of those in the plasma and ran parallel. The plasma concentration-time curves after single intravenous injection of SDMX more than 100 mg/kg showed nonlinear kinetics with concentrations over 100 micrograms/ml for 12-30 hrs after the injection. By administration of SDMX via drinking water, a sustained residue curve of SDMX in the skin at 1,000 ppm reported previously was not observed at 500 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The sensitivity of hyperthermo-chemo-radiotherapy for neoplastic cells in vitro on contact-sensitive plates.

On plastic dishes, the Chinese hamster cell line (V-79) easily formed colonies and enabled us to examine the effects of various treatments utilizing a colony formation assay while a different human cancer cell line (KSE-1) was found to have a low colony-forming ability which made it difficult to examine when using only a small number of cells. However, on the contact-sensitive plate (CSP), the KSE-1 line was able to form a sufficient amount of colonies in order to conduct examinations. Using CSPs, we were able to investigate the killing effects of various treatments on two malignant cells (V-79 and KSE-1). For the V-79 cells, hyperthermo-chemo-radiotherapy (HCR) was observed to be more effective than any other treatment. For KSE-1 cells, on the other hand, bleomycin had little killing effect, while both radiotherapy alone or hyperthermo-radiotherapy in doses of more than 4 Gy X-ray were found to be effective. These results indicated that it is necessary to examine the sensitivities of cells to different treatments in clinical cases in order to avoid non-effective treatments. In this report, we suggest that the use of CSPs allows for the effective examination of the effects of HCR while using only a small number of malignant cells, which have a low cloning efficiency on plastic surfaces.

3T3 Cells↗

[Inhibitory effect of somatostatin analogue, SMS 201-995, on secretin-stimulated exocrine secretion in isolated perfused rat pancreas].

In order to clarify the effect of somatostatin of the ductal secretion of the exocrine pancreas, we measured pancreatic juice and protein secretion stimulated with 10 pM secretin and/or 10 pM cholecystokinin (CCK) in the presence or absence of somatostatin analogue, SMS 201-995 (SMS) utilizing the isolated perfused pancreas of rats. SMS significantly inhibited both pancreatic juice flow and protein output elicited by 10 pM secretin without affecting basal secretion. The inhibitory effect of SMS was dose-dependent and maximal inhibition was observed with 1-10 nM. Half-inhibitory dose of SMS for juice secretion was 140 pM. Because CCK is thought to potentiate secretin action on the ductal system, we examined the effect of SMS on pancreatic secretory response to 10 pM secretin in combination with 10 pM CCK. In the experimental system we used, the amounts of pancreatic juice and protein secreted during a 30-min stimulation with secretin and CCK were additive. SMS inhibited both pancreatic juice and protein secretion to the level comparable with that obtained with either stimulus and SMS. SMS had no effect on CCK-stimulated pancreatic juice secretion but significantly inhibited protein output. The present study demonstrated, therefore, that SMS inhibits ductal secretion in response to physiological concentration of secretin.

Animals↗