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Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 1,189 records · Page 66Linked to original sources
PubMed1988

Effects of alpha-difluoromethylornithine on initiation and promotion of urinary bladder carcinogenesis in a heterotopically transplanted rat urinary bladder.

We previously demonstrated that repeated intravesical instillation of DFMO, an irreversible inhibitor of ornithine decarboxylase, inhibits (or retards) urinary bladder carcinogenesis in rats. The present investigation was conducted to determine if high intraluminal concentration of DFMO alters initiation by MNU and to determine if DFMO inhibition is due to arrest of tumor progression or simply retardation of the tumor development. Results showed that the inhibitory effects demonstrated by DFMO treatment during the early phase of study disappeared as the observation period was extended. Failure to suppress tumor development might be due to failure to control intracellular polyamine levels below the critical level and this failure in turn might be due to the rapid fall of intravesical DFMO concentration following instillation.

Animals↗
PubMed1988

The prevention of experimental cholesterol gallstones by ileectomy in mice.

After a lithogenic diet containing 0.5 per cent cholesterol and 0.25 per cent sodium cholate was fed to a group of normal Crj-ICR male mice for 10 days, cholesterol gallstones developed. No formation of gallstones occurred, however, in a group of mice from which 20 cms of terminal ileum had been removed prior to the feeding of the lithogenic diet. The biliary concentrations of cholesterol, phospholipids and bile acids were markedly lower in the ileectomized mice, with the decrease in cholesterol concentration being most significant. On the other hand, fecal excretion of sterols and bile acids increased in the ileectomized mice. The pool size of bile acids increased after the feeding of the lithogenic diet, but ileectomy decreased the pool size in mice fed the ordinary or lithogenic diets. The biliary concentration of cholic acid increased after the feeding of the lithogenic diet, but decreased with ileectomy. The biliary concentration and fecal excretion of deoxycholic acid markedly increased, while those of beta-muricholic acid and its secondary bile acids, omega-muricholic acid and hyodeoxycholic acid, decreased. The increase in plasma and liver cholesterol levels after the feeding of the lithogenic diet was prevented by ileectomy. These data suggest that ileectomy prevents the formation of cholesterol gallstones after the feeding of a lithogenic diet due to a decrease in cholic acid absorption.

Animals↗
PubMed1988

Existence of endogenous substrate proteins for Ca2+/calmodulin-dependent and Ca2+/phospholipid-dependent protein kinases in rat adrenal glomerulosa cells.

In rat adrenal glomerulosa cells, endogenous substrate proteins for Ca2+/calmodulin (CaM)-dependent protein kinase (glomerulosa CaM kinase) and Ca2+/phospholipid-dependent protein kinase (protein kinase C) were investigated. In a 105,000 g-supernatant fraction (cytosol), the Mr 100,000 protein was phosphorylated in the presence of calcium (calculated free Ca2+ concentration, 460 microM) alone or calcium and CaM, and the phosphorylation of this protein was completely inhibited by the CaM antagonists pimozide (500 microM) and melittin (5 microM) in the presence of calcium alone, respectively. These results indicate that the Mr 100,000 protein is a major substrate for glomerulosa CaM kinase, and considerable amounts of endogenous CaM might be present in the cytosol. In the presence of phospholipids (the micelles of 8 micrograms of phosphatidyl serine and 1 microgram of diacylglycerol), at least twelve proteins of Mr 127,000, 80,000, 70,000, 36,000, 35,000, 33,000, 32,000, 30,000, 27,000, 22,000, 19,000 and 17,000 were phosphorylated, and the phosphorylation of these proteins was enhanced by the addition of calcium, indicating that these proteins are substrates for protein kinase C. No endogenous protein phosphorylation was found in a 105,000 g-particulate fraction. Thus, these findings demonstrate that adrenal glomerulosa cells have specific substrate proteins for glomerulosa CaM kinase and protein kinase C, respectively.

Adrenal Glands↗
PubMed1988

S phase fraction of human bladder tumor measured in situ with bromodeoxyuridine labeling.

A total of 18 patients with transitional cell bladder cancer was given a 0.5-hour intravenous infusion of bromodeoxyuridine at the time of endoscopic biopsy or transurethral resection to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method with anti-bromodeoxyuridine monoclonal antibody as the first antibody. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. All grade 1 tumors had an S phase fraction of lower than 10 per cent. The average S phase fractions for noninvasive (11 cases) and invasive (7) tumors were 9.8 and 20.0 per cent, respectively. Two distant metastatic bladder tumors showed an average S phase fraction of 25.3 and 30.0 per cent. Thus, transitional cell bladder cancers with an S phase fraction of greater than 10 per cent appears to grow faster and be more invasive more often than those with an S phase fraction of less than 10 per cent. The higher S phase fraction may indicate greater biological malignancy. Our preliminary results suggest that measurement of the bromodeoxyuridine labeling index in bladder tumors may be a new objective and quantitative assay of biological potential of individual tumors.

Adult↗
PubMed1988

Bone resorption induced by transplanted bladder tumor (MBT-2) in mice.

The high incidence of metastatic bone resorption in urological cancer makes it necessary for clinicians to look for a valid experimental model to investigate basic interaction between cancer cells and bone in order to improve the treatment. A new model of bone resorption has been defined, namely the subcutaneous injection of tumor cell suspensions of invasive transitional cell carcinoma of the bladder (MBT-2) into mice after the periosteum of the calvaria has been disrupted. The tumor induced osteolysis associated with osteoclast proliferation with reactive bone formation. Moreover, we were able to show hypercalcemia accompanied with local bone resorption in this model.

Animals↗
PubMed1988

Synthesis and in vitro activity of various derivatives of a novel thromboxane receptor antagonist, (+/-)-(5Z)-7-[3-endo-[(phenylsulfonyl)amino]bicyclo[2.2.1] hept-2-exo-yl]heptenoic acid.

Several sulfonyl derivatives (13a-t) of (+/-)-(5Z)-7-(3-endo-aminobicyclo[2.2.1]hept-2-exo-yl)heptenoic acid (VI) were synthesized via its methyl ester 10. Sulfonylation of 10 with 11a-t followed by saponification yielded 13a-t. Inhibitory concentrations (IC50) of the corresponding sodium salts 14a-t for platelet aggregation were measured with rat washed platelets (WP) and rabbit platelet-rich plasma (PRP). IC50 values of some derivatives for contraction of the rat aorta were also measured. The IC50 values for rat WP increased from 2.9 to 26 nM in the order of 14a, 14c, 14d, and 14b for derivatives with an arylsulfonyl residue, depending on the number of of intervening methylene groups. Methyl derivative 14e exhibited a higher IC50 value than n-hexyl derivative 14f. Substitution with a p-methyl, p-fluoro-, or p-chloro group in 14a retained or slightly reduced its IC50 value, while a p-n-pentyl or p-oxycarbonyl group augmented it significantly. The representative 14a suppressed (15S)-15-hydroxy-11,9-(epoxymethano)prosta-5(Z),13(E)-dienoic acid (U-46619) induced aggregation of human WP with an IC50 value of 7.7 nM, which corresponds well to the IC50 value of 3 nM obtained for each displacement by 14a of [3H]-U-46619 or (5Z,15 xi)-9 alpha, 11 alpha-(dimethylmethano)-15-hydroxy-16-(3-[125I]iodo- 4-hydroxyphenyl)-17,18,19,20-tetranor-13-aza-11a-carbathrombo-5-en oic acid [( 125I]-PTA-OH) bound to human WP. Synthesis of thromboxane A2 (TxA2) in human WP stimulated by thrombin was not inhibited by 14a at a concentration up to 10 microM. From these observations, the corresponding acid 13a (S-145) was concluded to be a potent TxA2 receptor antagonist.

Animals↗
PubMed1988

4-vinyl and 2,4-divinyl deuteration effects on the low frequency resonance Raman bands of myoglobin: correlation with the structure of vinyl group.

Resonance Raman spectra of myoglobin (Mb) reconstituted with 4-vinyl and 2,4-divinyl deuterated protoheme IX were studied in several oxidation, spin, and ligation states (deoxyMb, MbO2, MbCO, metMbH2O, and metMbCN-) with special attention to the low frequency vibrations. Frequency shifts observed on deuteration enabled us to assign some Raman bands to vibrations specifically involving the 2- or 4-vinyl group. The most significant deuteration effect was found for a band around 410 cm-1 in the ferrous state, which loses intensity on 4-vinyl deuteration and is ascribed to a porphyrin in-plane vibration strongly coupled with the skeletal bend of the vinyl group at position 4. Such strong coupling implies that the vinyl group lies in the same plane as the pyrrole II ring, as in the crystalline state. Thus, frequency shifts on vinyl deuteration may be useful as a probe of the orientation of the vinyl group. Resonance Raman spectra of Mb coordinated with various sizes of isocyanides are interpreted in terms of vinyl orientational changes induced by ligation.

Deuterium↗
PubMed1988

Total parathyroidectomy with forearm autograft for secondary hyperparathyroidism in chronic renal failure.

One hundred twenty-eight patients with chronic renal failure and secondary hyperparathyroidism underwent total parathyroidectomy with forearm autograft. Postoperative clinical improvement was remarkable. In all cases, the grafted tissue functioned well, and reimplantation of the cryopreserved parathyroid tissues was unnecessary. Intact 1-84 parathyroid hormone was more sensitive than C-terminal parathyroid hormone in parathyroid hormone level (PTH) gradient assays of grafted and nongrafted forearm. The study of hypocalcemia was also helpful in obtaining more distinct PTH gradients. Five of 119 patients had supernumerary parathyroid glands (4.2%), which preoperative noninvasive image diagnosis of parathyroid glands was helpful in detecting.

Adult↗
PubMed1988

Preventive effect of 3-aminobenzamide on the reduction of NAD levels in rat liver following administration of diethylnitrosamine.

Nicotinamide adenine dinucleotide is utilized as the substrate of a chromatin-bound enzyme, poly(ADP-ribose) polymerase. The effects of diethylnitrosamine and/or 3-aminobenzamide, a potent inhibitor of poly(ADP-ribose) polymerase, on the cellular NAD levels in rat liver were investigated. 3-Aminobenzamide (600 mg/kg) administered intraperitoneally was not detectable in the liver within 12 hr after administration; the inhibitor had a calculated half life of 90 min. Diethylnitrosamine reduced the NAD levels in rat liver in a dose-dependent way. The NAD content reached a minimum level at 8 hr, returning to 78% of the control value after 48 hr. The reduction of the NAD levels caused by diethylnitrosamine was completely prevented when 3-aminobenzamide was administered either simultaneously with diethylnitrosamine or 4 hr after diethylnitrosamine treatment. Furthermore, an immunohistochemical study showed that nuclear poly(ADP-ribose) decreased 1 hr after the administration of 3-aminobenzamide. These results suggest that inhibition of poly(ADP-ribosyl)ation is involved in the initiation of liver carcinogenesis by diethylnitrosamine and 3-aminobenzamide.

Animals↗
PubMed1988

Vitamin K-reversible hypoprothrombinemia in rats. I. Sex differences in the development of hypoprothrombinemia and the effects of beta-lactam antibiotics.

Male and female rats were fed an ordinary diet which contained about 500 ng vitamin K/g or a vitamin K-deficient diet containing less than 5 ng vitamin K/g. Hypoprothrombinemic changes such as prolongation of the prothrombin time (PT) and activated partial thromboplastin time (APTT) were detected in male rats within 4-6 days after feeding of the vitamin K deficient diet. Blood clotting factor VII and descarboxy prothrombin (PIVKA) levels changed rapidly, with maximum alteration at 2-4 days. Similar changes in factor VII and PIVKA levels were observed in female rats, but they appeared only after feeding of the K deficient diet for a long period. PT and APTT in female rats showed slight or no alteration even after 10 day feeding of the K-deficient diet. These results indicate that male rats are more susceptible to vitamin K deficiency than female rats. Administration of latamoxef led to a dose-dependent development of hypoprothrombinemia in vitamin K-deficient female rats. The hypoprothrombinemia in vitamin K-deficient female rats was caused by beta-lactam antibiotics with N-methyltetrazolethiol, thiadiazolethiol and methyl-thiadiazolethiol as the 3'-position substituent of the cephem nucleus.

Animals↗
PubMed1988

Effects of 1-S replaced and/or decarboxylated latamoxef on rabbit platelet aggregation in vitro.

Latamoxef, 1-S replaced and/or decarboxylated derivatives of latamoxef were examined for their effects on ADP-, collagen- and platelet activating factor (PAF)-induced rabbit platelet aggregation in vitro. The results were compared with those of cefotaxime, cefmetazole, carbenicillin and aspirin. Latamoxef produced a dose-dependent inhibition of platelet aggregation at concentrations over about 4 mM, and the potency was almost similar to that produced by the other beta-lactam antibiotics, although the inhibiting effect of ADP-induced aggregation was more potent for latamoxef, whereas that on collagen-induced aggregation was stronger for cefmetazole and carbenicillin. The inhibitory effect of beta-lactam antibiotics on collagen-induced aggregation was, however, much weaker than that of aspirin. With respect to drug potency, replacement of the oxygen atom in the oxacephem ring with a sulfur atom caused no significant change in ADP-induced aggregation or slightly stronger inhibition of collagen- and PAF-induced aggregations. The decarboxylated derivatives of latamoxef and the 1-S replaced analogue of latamoxef showed slightly weaker inhibition of ADP-induced aggregation, but much stronger inhibition of collagen- and PAF-induced aggregation than the parent compounds. These data suggest that 1) the oxygen atom in the oxacephem ring is not responsible for the inhibitory effect of latamoxef on platelet aggregation and 2) the carboxyl group in the amide side chain had no significant role in this inhibition.

Animals↗