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Biomedical subjects

K Iwata

Publications and source records attributed to K Iwata.

At least 415 records · Page 23Linked to original sources
PubMed1982

[Early fundus changes caused by repeated small crises in the Posner-Schlossman syndrome: a model for glaucoma simplex].

In Posner-Schlossman syndrome a repeated crisis of intraocular pressure (IOP) elevation to 25-45 mmHg continues for 3-10 days. During the relapses glaucomatous damage often occurs. The IOP and its variation during the crisis are similar to those in glaucoma simplex. Therefore, the syndrome can be considered as a natural model for investigations into glaucoma simplex. By analyzing five cases of Posner-Schlossman syndrome in which the glaucomatous lesions ranged from the earliest to advanced stages, the development and progression of glaucomatous damage of the optic nerve at varying chronically elevated IOP levels became evident. The earliest evident fundus change is a nerve fiber layer defect (NFLD) in the Bjerrum tangent, and not the enlargement of the physiologic excavation. The latter does not develop before stage IV. The slit-like NFLD shows a decrease in sensitivity of 0.2-0.4 log ND unit, which is thus easily overlooked. As the disease progresses the NFLD becomes more pronounced, its width increases and it becomes wedge-shaped. Due to a considerable loss of nerve fibers at the wedge-shaped defect, a small notch which develops in the direction of NFLD is not observed until stage IV. Goldmann perimetry demonstrated a certain abnormality at stages IV-V; in addition to the wedge-shaped NFLD, diffuse thinning of the NFLD begins around the optic disk and develops into a large, concentric excavation. For identification of the most delicate NFLDs, stereo fundus photography in color with 8-fold magnification, on 6 x 6 film is recommended.

Female↗
PubMed1982

Affinity labeling of a transforming growth factor receptor that does not interact with epidermal growth factor.

Membrane components that interact with epidermal growth factor (EGF) and transforming growth factors (TGFs) have been identified by covalent crosslinking to their respective 125I-labeled ligands. Under appropriate conditions, disuccinimidyl suberate or hydroxysuccinimidyl p-azidobenzoate cross-link receptor-bound 125I-labeled EGF to a 140- to 170-kilodalton (kDal) receptor species in membranes from both A431 human carcinoma cells and normal rat kidney cells. 125I-Labeled sarcoma growth factor (SGF), a TGF from virally transformed mouse 3T3 cells, also can be affinity-crosslinked to the 140- to 170-kDal EGF receptor species in membranes from A431 and rat kidney cells. The labeling of this receptor is inhibited when either excess unlabeled EGF or SGF is present during incubation of membranes with either 125I-labeled EGF or 125I-labeled SGF. In contrast, a second receptor species of 60 kDal is affinity-labeled with 125I-labeled SGF but not with 125I-labeled EGF in membranes from both A431 and rat kidney cells. SGF and a TGF from virally transformed rat embryo cells inhibit the labeling of the 60-kDal species when present in excess during incubation of membranes with 125I-labeled SGF, whereas EGF is completely ineffective in inhibiting the labeling of this receptor. The data suggest that a specific 60-kDal receptor that displays high affinity for TGFs but not for EGF may mediate induction of the transformed phenotype. In addition, SGF and other TGFs interact with the 140- to 170-kDal EGF receptor that appears to mediate normal cell growth effects.

Affinity Labels↗
PubMed1982

Enzyme immunoassay for clenbuterol, an beta 2-adrenergic stimulant.

A sensitive double antibody and heterologous enzyme immunoassay for the quantitation of clenbuterol is established. Specific antiserum to this agent was raised in rabbits by immunization with diazotized clenbuterol and human serum albumin conjugate. For competitive reactions, antibody was incubated with a mixture of diazotized clenbuterol analog (NA 1141) labelled with beta-D-galactosidase and unlabelled standard or sample clenbuterol. The antibody-bound enzyme hapten was separated from free hapten by anti-rabbit IgG immobilized to a polystyrene ball. Activity of the enzyme on the solid phase was fluorometrically determined. The assay system made it possible to ascertain values as low as 0.5 pg /tube of clenbuterol. By use of this assay method, the time course of plasma levels of clenbuterol was examined after a single oral administration (20 micrograms) to 3 healthy volunteers. It was shown that the maximum level was achieved after 2-3 hr with approximately 10 ng clenbuterol/dl of plasma.

Adult↗
PubMed1982

Effect of proteinase inhibitors having anti-inflammatory activity on gelatinase, elastase and cathepsin G isolated from rat polymorphonuclear leukocytes.

Gelatinase, elastase and cathepsin G isolated from the granule extract of rat polymorphonuclear leukocytes (PMNs) had similar properties to the enzymes of human PMNs already reported. Effect of proteinase inhibitors on these neutral proteinases isolated from rat PMNs was studied. Epsilon-Amino-n-caproic acid n-hexyl ester, a proteinase inhibitor having anti-inflammatory activity, inhibited cathepsin G, whereas elastase was activated by the inhibitor. On the other hand, leupeptin, L-1-tosylamide-2-phenylethyl chloromethyl ketone and N-alpha-p-tosyl-L-lysine chloromethyl ketone, which had been reported as anti-inflammatory inhibitors, had no inhibitory effect on these neutral proteinases. These results suggest that proteinase inhibitors reported as anti-inflammatory agents exert their anti-inflammatory actions not by direct inhibition of the neutral proteinases released from PMNs, but by other effects such as suppression of the infiltration of PMNs into inflammatory locus.

Animals↗
PubMed1982

Hyperthermic irrigation of urinary bladder tumor in rabbits.

Hyperthermic treatment for bladder tumor in the rabbit was investigated by the irrigation with hot saline through cystostomy after the transplantation of V2 carcinoma cells. When the bladder was irrigated with 42-44 degrees C saline, the inhibitory effect on transplanted tumor growth in the urinary bladder was significant in comparison with control groups. Antitumor effect on the survival and changes in body weight were also significant. Histological study showed the tumor cells were more susceptible to heat than normal mucosal layer. The results suggest that the hyperthermic irrigation of the urinary bladder was effective in preventing the tumor growth with minimum damage on the normal bladder mucosa. Moreover, this malignant bladder tumor of rabbit seems especially suitable for the purpose of studying the new method for transurethral hyperthermic treatment of the urinary bladder cancer.

Animals↗
PubMed1982

In vitro studies of aculeacin A, a new antifungal antibiotic.

Aculeacin A is a cyclopeptide-containing long-chain fatty acid, representing a new class of antibiotics. It has a relatively narrow antifungal spectrum in vitro and is highly active against some groups of yeasts. Of 31 strains of Candida ad Torulopsis tested, the majority were susceptible to aculeacin A at 0.31 micrograms per ml or less. On the other hand, the antibiotic was scarcely active or inactive against other yeasts, such as Cryptococcus neoformans, and all filamentous and dimorphic fungi tested. A distinct inoculum effect has been observed in vitro with a number of strains of C. albicans; minimum growth-inhibitory concentrations (MIC) have tended to increase with increased incubation time. MIC values were also increased in the presence of serum. Aculeacin A is fungicidal for growing cells of C. albicans. It was most lethal against sensitive yeasts at 0.08 to 0.31 micrograms per ml, and increases in the concentrations of the drug above this range reduced, rather than increased, its lethal effect.

Antifungal Agents↗
PubMed1982

Studies on the mechanism of antifungal action of aculeacin A.

Aculeacin A was lethal for proliferating cultures of C. albicans. However, there was a paradoxical relationship between the drug concentration and the fungicidal activity; the lethal effect was greatest at levels of 0.08 to 1.25 microgram/ml and increases in the drug concentration above this range reduced its lethal effect. A similar anomalous dose-response patterns were also observed for the inhibitory effect of the drug on several cellular and subcellular biochemical activities. Association of this lethal effect of the drug was the formation of visible cell aggregates and the development of extremely huge forms in treated cultures. Aculeacin A induced osmotically fragile cells and viability of treated cultures was markedly reversed under high osmolarity. Tracer experiments and chemical analysis revealed that synthesis of alkali insoluble glucan was inhibited by the drug to a greater extent than synthesis of mannan and any other species of macromolecules, with resultant formation of alkali-insoluble glucan-deficient cells. Aculeacin A inhibited synthesis of beta-glucan from UDP-glucose catalyzed by cell-free extracts from C. albicans and S. cerevisiae. These data are consistent with the view that one of the principal target of aculeacin A action is on the beta-1,3-glucan synthetase reaction.

Antifungal Agents↗
PubMed1982

Increased level of ribonucleotide reductase and associated resistance to aphidicolin in mouse FM3A cell mutants selected for simultaneous resistance to 9-beta-D-arabinofuranosyladenine and 1-beta-D-arabinofuranosylcytosine.

Mutants simultaneously resistant to 9-beta-D-arabinofuranosyladenine and 1-beta-D-arabinofuranosylcytosine were isolated by single-step selection from mutagenized mouse FM3A cells with a frequency of about 10(-5). Most of the mutants showed cross-resistance to aphidicolin and excess thymidine. In some of these mutants, the level of ribonucleotide reductase was 2 approximately 5 times that of the parent with concomitantly greater resistance to hydroxyurea than that of the parent, and their reductase showed normal sensitivity in vitro to the allosteric negative effector dATP. Consequently, the intracellular pools of dATP and dCTP were expanded in the mutants. These mutants thus differ from the aphidicolin-resistant mutants isolated previously, which have an altered reductase desensitized to dATP with a concomitant increase in the dATP pool. Therefore, either increase in the level of ribonucleotide reductase or its structural change leading to desensitization to dATP seems to confer resistance to the nucleoside analogs and to aphidicolin.

Animals↗
PubMed1981

Conditional thymidine auxotrophic mutants of mouse FM3A cells due to thermosensitive thymidylate synthase and their prototrophic revertants.

A number of temperature-sensitive conditional thymidine auxotrophs were isolated from mutagenized mouse FM3A cells. Upon temperature shift from 33.5 degrees C to 39.5 degrees C, the mutant cells rapidly lost thymidylate synthase activity with concomitant decrease in intracellular dTTP and changes in other dNTP pools. Thymidylate synthase obtained from these mutants was inactivated in a manner following first order kinetics by heat treatment, which did not affect the parental enzyme. When bound covalently to 5-fluoro-2'-deoxyuridine 5'-[32P]monophosphate and 5,10-methylenetetrahydrofolate, the enzyme of one mutant migrated slower than the parental enzyme on nondenaturing polyacrylamide gel electrophoresis, whereas it did not do so on sodium dodecyl sulfate gel electrophoresis. Spontaneous prototrophic revertants were isolated from most of the mutant lines. In some revertants, the enzyme regained the heat resistance of the wild type completely or partially. In other revertants, the enzyme was overproduced, but its heat-sensitive nature was unaltered. The results demonstrate unequivocally that the conditional thymidine auxotrophy in the mutants was caused by thermosensitive thymidylate synthase due, at least in one particular line, to a missense mutation in its structural gene.

Animals↗
PubMed1981

Alteration of ribonucleotide reductase in aphidicolin-resistant mutants of mouse FM3A cells with associated resistance to arabinosyladenine and arabinosylcytosine.

Aphidicolin-resistant mutants of mouse FM3A cells were isolated and characterized. Most of the mutants were of a type showing associated resistance to arabinosyladenine, arabinosylcytosine, deoxyadenosine, and excess thymidine. This phenotype could also be observed in a variant line selected by resistance to a low level of arabinosylcytosine. In cell-cell hybrids, aphidicolin resistance as well as this cross-resistance behaved a codominant traits. The mutants had an increased dATP pool and decreased ability to incorporate labeled deoxycytidine into macromolecules. Genetic and biochemical evidence suggested that the mutation conferring the pleiotropic phenotype resulted from a change in ribonucleotide reductase activity such that the enzyme was desensitized to the allosteric negative effector dATP. This alteration of the enzyme could account for the marked change in deoxynucleotide pools and for the aphidicolin resistance of the mutants.

Adenosine Triphosphate↗
PubMed1981

Selection of mammalian thymidine auxotrophic cell mutants defective in thymidylate synthase by their reduced sensitivity to methotrexate.

Thymidine auxotrophic mutants were selectively isolated from mutagenized mouse FM3A cells by resistance to methotrexate in the presence of thymidine and 5-methyl-tetrahydrofolate with a frequency of 10(-5)-10(-6). In most of the thymidine auxotrophs the activity of thymidylate synthase was very low or undetectable, but dihydrofolate reductase activity was normal. Upon starvation of thymidine, the mutant cells immediately stopped growing and started to lyse within one day. In the presence of thymidine, the mutant cells grew quite normally. This phenotype behaved recessively in cell-cell hybrids, and the segregation profile of its marker indicated that the lesions in the mutants are not linked to the X chromosome. Prototrophic revertants could be isolated from these mutants, and they showed almost the normal level of thymidylate synthase activity. The selection method described here should be useful for isolating large numbers of thymidylate synthase-negative mutants from various mammalian cell lines.

Animals↗
PubMed1981

Evaluation of therapeutic arterial embolization in renal cell carcinoma using microencapsulated mitomycin C.

The therapeutic arterial embolization in the case of renal cell carcinoma using microencapsulated mitomycin C (MMC) was investigated by an angiographic evaluation in comparison with nonencapsulated MMC. The Gelfoam embolization supplemented with nonencapsulated MMC could not necessarily prevent the recanalization and collateral circulation, while the Gelfoam embolization supplemented with microencapsulated MMC completely or considerably eliminated the revascularization with a distinct advantage in this degree. Moreover, peripheral blood MMC level after the embolization using microencapsulated MMC was reduced to 39 per cent of that after nonencapsulated MMC infusion. The result was consistent with the previous experiments, indicating that the transcatheter infusion of microencapsulated MMC is the therapeutic arterial embolization of the tumor-supplying vessels together with regional anticancer chemotherapy. Further clinical application to various malignancies is in progress.

Aged↗
PubMed1981

Induction of active melanocytes in mouse skin by carcinogens: a new method for detection of skin carcinogens.

Application of potent skin carcinogens, such as 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, benzo[a]pyrene and 4-nitroquinoline-1-oxide, induced numerous dihydroxyphenylalanine (dopa)-positive cells in the interfollicular epidermis of C57BL/6 mice in a dose- and time-dependent fashion. Chrysene, a weak skin carcinogen, and croton oil, a tumor promoter, also induced 3--4 times more dopa-positive cells than acetone. Liver carcinogens, such as 3'-methyl-4-dimethylaminoazobenzene and N-2-acetylaminofluorene, and non-carcinogenic aromatic hydrocarbons, such as anthracene, fluoranthene, fluorene and pyrene, did not induce increase in these cells. These results indicate that increase in the number of dopa-positive cells after application of chemicals is well correlated with the abilities of these compounds to induce skin carcinogenesis and suppress sebaceous glands.

Animals↗