Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 1,099 records · Page 61Linked to original sources

PubMed1990

[Clinical evaluation of sodium alginate on oral mucositis associated with radiotherapy].

We evaluated the effect of sodium alginate on 39 patients with oral mucositis associated with radiotherapy. Sodium alginate was administered during radiotherapy to 17 patients with head and neck cancer. Compared with 22 patients without administration, sodium alginate reduced the pain and the erosion of oral mucosa significantly. Consequently the interval of radiotherapy was shortened. It is, therefore, expected that the effect of radiotherapy improves by the administration of sodium alginate.

Adult↗

PubMed1990

Abnormal responses of myeloid progenitor cells to recombinant human colony-stimulating factors in congenital neutropenia.

The effects of recombinant human interleukin-3 (IL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) on the growth of myeloid progenitor cells (CFU-C) in semisolid agar culture were studied in two patients with Kostmann-type congenital neutropenia. CFU-C growth in bone marrow cells from patients was significantly reduced in response to various concentrations of either IL-3 or G-CSF alone, compared with that from normal subjects. There was no inhibitory effect of bone marrow cells from patients on normal CFU-C formation supported by IL-3 or G-CSF. However, the simultaneous stimulation with IL-3 and G-CSF induced the increase of CFU-C formation in patients with congenital neutropenia. Furthermore, CFU-C growth in both patients was supported when bone marrow cells were preincubated with IL-3 in liquid culture followed by the stimulation with G-CSF in semisolid agar culture. In contrast, that was not supported by the preincubation with G-CSF and the subsequent stimulation with IL-3. This evidence suggests that the hematopoietic progenitor cells in patients with congenital neutropenia have the potential for developing CFU-C in the combined stimulation with IL-3 and G-CSF, and that this growth may be dependent on the priming of IL-3 followed by the stimulation with G-CSF. The level of mature neutrophils in peripheral blood was not fully restored to normal levels by the daily administration of G-CSF in doses of 100 to 200 micrograms/m2 of body surface area for 20 to 25 days in both patients. These observations raise the possibility that the combination of IL-3 and G-CSF might have a potential role for the increase of neutrophil counts in patients with congenital neutropenia.

Agranulocytosis↗

PubMed1990

Lysosomal acid phosphatase is transported via endosomes to lysosomes.

Involvement of endosomes in transport of newly synthesized acid phosphatase to lysosomes was investigated using the Golgi fraction (GF1 + 2), enriched in endosomes. The Golgi fraction (GF1 + 2) was prepared from the livers of rats given [35S]methionine and asialofetuin conjugated-horseradish peroxidase (HRP). Newly synthesized acid phosphatase in the endosomes containing internalized asialofetuin-HRP was measured as a loss of the detectable labeled enzyme after 3,3'-diaminobenzidine (DAB) and H2O2 reaction, due to formation of insoluble polymers which reduce protein antigenicity. With this procedure, acid phosphatase was all but undetectable in the Golgi fraction. Thus, newly synthesized acid phosphatase is apparently transported to lysosomes by endosomes.

Acid Phosphatase↗

PubMed1990

A case-control study of prostatic cancer in Kyoto, Japan: sexual risk factors.

A case-control study on prostatic cancer was conducted in Kyoto, Japan, from 1981-1984, including 100 patients with prostatic cancer (PC) and age, hospital, and date-of-admission matched controls of benign prostatic hyperplasia (BPH) patients and general hospital patients. Analysis of several sexual factors obtained through a self-administered questionnaire revealed the following observations: 1) cancer patients had fewer sex partners before marriage (relative risk, RR = 0.35; 95% confidence interval: 0.13-0.93) than the hospital controls; 2) they had more vigorous sexual activities in the third (RR = 2.89; 1.01-8.28) and fourth decades of life (RR = 2.26: 1.03-4.95) than hospital controls, but no significantly different sexual activities from controls in other decades; 3) they had less frequent orgasms (RR = 2.55; 1.11-5.83) than BPH controls or (RR = 4.96: 1.78-13.9) hospital controls, and sexual intercourse appeared to be less satisfactory (RR = 2.08: 1.05-4.13) than that of hospital controls; and 4) they had less frequent episodes of sexually transmitted diseases (RR = 0.36: 0.16-0.83) than BPH controls. Marital status, fertility, ejaculation, masturbation, nocturnal emission, contraceptive use, and wife's episodes of sexually transmitted disease were not linked to prostatic cancer risk.

Case-Control Studies↗

PubMed1990

Prediction of the resistance of human tumors to adriamycin by chemosensitivity tests and DNA analysis of the multidrug resistance gene.

In order to predict natural resistance to Adriamycin (ADM), the amplification of multidrug resistance gene 1 (MDR1) was investigated in 50 human cancer specimens using Southern blot analysis. Genomic DNA was extracted from both human solid tumors and adjacent normal tissues for the analysis. MDR1 gene amplification was not observed in any of the patients tested, including 5 patients in whom ADM was not clinically effective. On the other hand, chemosensitivity tests performed on the tumor cells of these 5 patients indicated resistance to ADM. Our results therefore indicate that MDR1 gene amplification is rarely seen among clinical samples and that conventional chemosensitivity tests might be more useful for the prediction of ADM resistance in cancer patients than the analysis of MDR1 gene amplification.

Blotting, Southern↗

PubMed1990

Relation of Na+, K(+)-ATPase to delayed motor nerve conduction velocity: effect of aldose reductase inhibitor, ADN-138, on Na+, K(+)-ATPase activity.

The role of sorbitol, myo-inositol, and Na+, K(+)-adenosine triphosphatase (ATPase) activity on motor nerve conduction velocity (MNCV) in streptozotocin (STZ)-diabetic rats was studied. Reduction of MNCV and Na+, K(+)-ATPase in caudal nerves appeared after 3 weeks of diabetes, and at this time treatment with aldose reductase inhibitor (ARI), ADN-138 and 1% myo-inositol supplement was begun. One percent myo-inositol supplement for 3 weeks resulted in a significant increase in myo-inositol levels in diabetic nerves, but left MNCV and sorbitol levels unchanged. In contrast, treatment with ADN-138 for 3 weeks reduced sorbitol levels in diabetic nerves and resulted in significant increases in MNCV and Na+, K(+)-ATPase in the nerves. Since ADN-138 did not restore myo-inositol levels, the increase in Na+, K(+)-ATPase levels by ADN-138 treatment was independent of myo-inositol levels. Also, nerve Na+ levels in ADN-138-treated rats were reduced and the ratio of K+ to Na+ was raised, while 1% myo-inositol supplement did not affect them. These results suggest that treatment with ADN-138 elevates MNCV through a series of processes: ARI----reduction of sorbitol level----increase in Na+, K(+)-ATPase activity----correction of K+, Na+ imbalance----increase in MNCV.

Aldehyde Reductase↗

PubMed1990

Reversible changes of skeletal muscular capillaries after application of a tourniquet.

Morphological studies of skeletal muscular capillaries after a 60-min tourniquet application were performed in the rat extensor hallucis proprius muscle. On the basis of the period of reflow, the rats were divided into three groups (15-min group, 24-hr group, and 7-day group). FITC-albumin was injected intravenously to detect open capillaries. The percentage of interstitial space of the muscle was high in the 24-hr group, but had recovered in the 7-day group. Capillary density, calculated under a fluorescence microscope, was low in both the 15-min and 24-hr groups, but in the 7-day group, it had recovered. Intramuscular pressure was high in the 15-min group, whereas it was almost normal in the 7-day group. Electron microscopic studies showed stenosis or collapse of the capillaries in the 15-min group, whereas it was almost normal in the 7-day group. We consider that the changes in the microcirculatory system in the rat extensor hallucis proprius muscle after a 60-min tourniquet application are reversible.

Animals↗

PubMed1990

Suppression of plasminogen activator inhibitor 1 release by fibrin from human umbilical vein endothelial cells.

The effect of fibrin stimulation on the fibrinolytic potential in cultured human umbilical vein endothelial cells (HUVEC) was investigated in the normal state and aged state. The amount of antigen of the two fibrinolytic factors, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1), was determined using ELISA and the ABC method, respectively. When a fibrin clot was overlayered on the normal HUVEC, the secretion of t-PA or PAI-1 from the HUVEC was greatly changed. That is, PAI antigen was decreased 3-fold and t-PA antigen increased slightly in the conditioned medium. On the other hand, when the aged HUVEC were stimulated by a fibrin clot, PAI antigen was increased 3-fold and t-PA antigen did not change in the conditioned medium. When the level of fibrinolytic activity in the conditioned medium was expressed as the molar ratio of PAI and t-PA (PAI/t-PA), the value in the fibrin-stimulated normal HUVEC was markedly reduced (a 3.5-fold decrease) when compared with that of the non-stimulated normal HUVEC, reflecting a profibrinolytic state. On the other hand, the value in the fibrin-stimulated aged HUVEC was markedly increased (a 5-fold increase) when compared with that of the non-stimulated aged HUVEC, reflecting an antifibrinolytic state. Actinomycin D- or cycloheximide-treated HUVEC showed no response to the fibrin stimulation. We conclude that the level of HUVEC-mediated fibrinolytic activity was regulated mainly by the production and secretion of PAI from the HUVEC to protect against the generation of thrombi. In the aged HUVEC, the regulatory mechanism acts in an opposite manner and a thrombotic process may be induced.

Cell Survival↗

PubMed1990

Purification and characterization of a plasma factor which cleaves single-chain form of t-PA and u-PA.

Low molecular weight heparin (LMW-heparin) enhanced the amidolytic activity of plasma when the chromogenic substrate, H-D-Ile-Pro-Arg-pNA (S-2288), was used. The amidolytic activity increased in a time-dependent manner as the LMW-heparin concentration increased and reached its peak at around 15 mu/ml. Factor XII-deficient plasma increased the S-2288 amidolytic activity by LMW-heparin. In order to clarify the mechanism of the heparin-induced enhancement of the amidolytic activity, a plasma factor was purified. The plasma factor was obtained from human normal plasma by ammonium sulfate fractionation, followed by successive column chromatography with heparin-Sepharose, zinc chelate-Sepharose, aprotinin-Sepharose and protein A-Sepharose. The plasma factor so purified revealed a major band (88% of total protein) at 80 kD with several minor bands on analysis by SDS-PAGE. The plasma factor exhibited an intrinsic amidolytic activity, which was enhanced by heparin. The plasma factor further enhanced the amidolytic activity of sct-PA and scu-PA, the enhancement of which was of much greater degree than that for LMW-heparin. However, when the two-chain form of t-PA or u-PA was reacted with the plasma factor and LMW-heparin, no enhancement of the amidolytic activity of these enzymes was observed. The plasma factor cleaved a peptide bond of sct-PA and scu-PA and induced a structural change from a single-chain to a two-chain form. The amidolytic activity of the plasma factor was not inhibited by anti-t-PA IgG, anti-u-PA IgG, anti-plasminogen IgG, anti-factor XII IgG or anti-plasma prekallikrein IgG. These findings suggest an important role for the plasma factor in the activation of sct-PA and scu-PA in heparin-dependent fibrinolysis.

Amides↗

PubMed1990

Inhibition by antimanic drugs of hyperactivity induced by methamphetamine-chlordiazepoxide mixture in mice.

The effects of lithium chloride and other antimanic drugs on locomotor hyperactivity induced by a mixture of methamphetamine (MAMP) and chlordiazepoxide (CDZP) were examined in mice, using an Animex activity meter. CDZP (12.5 mg/kg) given SC in combination with MAMP (1 mg/kg) caused a marked increase in locomotor activity, as compared with that in mice treated with MAMP alone. However, when CDZP (12.5 mg/kg) was administered together with 0.5 or 2.0 mg/kg of MAMP, no significant enhancement was observed. Lithium (2 and 3 mEq/kg, IP) and carbamazepine (4 and 8 mg/kg, IP) inhibited the hyperactivity induced by the MAMP (1 mg/kg)-CDZP (12.5 mg/kg) mixture to the level of activity in animals treated with MAMP (1 mg/kg) alone. Lithium and carbamazepine alone at these doses caused no significant inhibition of locomotor activity in saline- or MAMP-treated mice. Haloperidol (0.1 mg/kg, IP) and chlorpromazine (0.5 mg/kg, IP) decreased the MAMP-CDZP mixture-induced hyperactivity without significantly inhibiting locomotor activity in the saline- or MAMP-treated group. However, haloperidol (0.2 mg/kg) and chlorpromazine (1 mg/kg) alone significantly inhibited locomotor activity in all of the saline-, MAMP- and MAMP-CDZP mixture-treated groups. These results indicate that antimanic drugs selectively inhibit the hyperactivity induced by the MAMP-CDZP mixture, but that neuroleptics are less selective in inhibiting the hyperactivity.

Animals↗

PubMed1990

Collateral drug sensitivity induced in CPT-11 (a novel derivative of camptothecin)-resistant cell lines.

Collateral drug sensitivity was induced in CPT-11-resistant cell lines (CPT-K and T). Ten of the 19 kinds of antineoplastic agents (especially, 5 of 6 kinds of DNA topoisomerase II inhibiting agents) were effective in inducing collateral drug sensitivity. Alteration of DNA topoisomerase I seemed to be unrelated to acquisition of multidrug resistance.

Antineoplastic Agents, Phytogenic↗

PubMed1990

Isolation and characterization of VP-16 resistant human leukemia cell line.

VP-16 resistant cells, designated VP-16K6-1 (K6-1) were isolated from human acute lymphoblastic leukemia cell line RPMI 8402. IC50 value against VP-16 were 11-fold higher than their sensitive parental cell line. The membrane permeability of the drug was not responsible for resistance in K6-1 cells. K6-1 cells showed resistance in drug-induced DNA strand breaks (single strand breaks) determined by the alkaline sucrose gradient sedimentation method. Dot-blot analysis of RNA extracted from 2 cell lines showed that the mRNA levels of DNA topoisomerase II in K6-1 cells decreased slightly compared with that of parent cells. However, Topo II activities were similar in wild-type and K6-1 cells. In addition, K6-1 cells exhibited cross-resistance only to VM-26. These data suggest that a reduced intracellular Topo II level may contribute to drug resistance as an important factor in K6-1 cells.

DNA Replication↗

PubMed1990

Reduced DNA topoisomerase II in VP-16 resistant mouse breast cancer cell line.

VP-16 resistant cells, FvprB350 (50B-3), were isolated from mouse breast cancer cell line FM3A. 50B-3 cells showed 84-fold higher resistance than their parent cells. Reduced drug uptake was not found in resistant cells. Quantitative analysis of drug-stimulated DNA cleavage activity using 3'32P end-labeled pBR322 restriction fragments showed that VP-16 stimulated DNA-topoisomerase II cleavable complex forming activity in crude nuclear extract from 50B-3 cells was approximately one-fifth as compared with that of FM3A wild-type cells. Dot-blot analysis of RNA extracted from the two cell lines showed that mRNA levels of topoisomerase II in 50B-3 cells drastically decreased and catalytic activity was also 1/2-1/3 as compared with that of parent cells. 50B-3 cells showed cross resistance to VM-26, m-AMSA, adriamycin. These findings suggest that reduced topoisomerase II activity (cellular levels) and cleavable complex forming activity may be significant factors in the marked drug resistance.

Animals↗

PubMed1990

Usefulness and limitations of methotrexate, vinblastine, doxorubicin and cisplatin for the treatment of advanced urothelial cancer.

Methotrexate, vinblastine, doxorubicin and cisplatin were used to treat 66 patients with advanced urothelial cancer. Of these 66 patients 58 could be evaluated for response. A total of 84 sites was evaluated in these patients. Response rates were 73% in the bladder, 67% in the renal pelvis, 50% in the ureter, 60% in the lung, 68% in the lymph nodes, 14% in the liver and 25% in the bone. Ten patients (17%) had a complete response and 23 (40%) had a partial response, with an over-all response rate of 57% (the 95% confidence limits are 44 to 69%). The mean durations of response were 10.1 months for complete response patients and 6.2 months for partial response patients. The most prominent toxicity was severe myelosuppression that resulted in 2 septic deaths. While this chemotherapy regimen provided an excellent over-all response rate, the matters of concern were the short duration of response and low effectiveness in the liver and bone.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Interaction of arginine vasopressin and angiotensin II on Ca2+ in vascular smooth muscle cells.

The non-osmotic release of arginine vasopressin (AVP) is associated with the concomitant activation of the renin-angiotensin and sympathetic nervous systems. In vivo studies suggest that a positive interaction may occur between AVP and angiotensin II (Ang II), and other Ca2+ mobilizing hormones. In the present study, the cellular mechanisms of this interaction between AVP and Ang II in vascular smooth muscle cell (VSMC) were examined. These results support the existence of a positive interaction between AVP and Ang II on Ca2+ mobilization in VSMC. In fact, the challenge of VSMC with combined AVP and Ang II, in a range from 5 x 10(-11) to 10(-8) M, enhanced cytosolic free Ca2+ ([Ca2+]i) and 45Ca2+ efflux in a more than additive manner. This potentiation, which was not dependent of the presence of extracellular calcium, correlated with an increased VSMC shape change. Moreover, the combination of subthreshold doses of AVP and Ang II (5 x 10(-11) M), which do not release Ca2+ alone, evoked a Ca2+ mobilizing response. A subthreshold dose of Ang II also shifted to the left the concentration-response curve of the AVP-mediated 45Ca2+ efflux. Since there were no changes in receptor binding of either hormone by the other hormone and the interaction of the two hormones on the production of inositol phosphatides was additive, the AVP and AII positive interaction on Ca2+ mobilization on VSMC may occur at the level of the intracellular Ca2(+)-releasing mechanism itself. Such an interaction can occur at hormone concentrations below the Ca2+ release threshold and may explain an increased functional response to the combination of pressor hormones compared to that of each hormone alone.

Angiotensin II↗

PubMed1990

Advantages in combination chemotherapy using cisplatin and its analogues for human testicular tumor xenografts.

The antitumor effects and toxicities of combination chemotherapies using cisplatin (CDDP) and its analogues were compared with those of single drug therapies. Congenitally athymic nude BALB/c (nu/nu) mice were used to estimate antitumor activities of these compounds against human testicular tumor (Ht-14) xenografts and hetero-BALB/c (nu/+) mice were used to evaluate the toxic effects of the drugs. Combination therapy with half dosages of CDDP and carboplatin (JM8) (CDDP: 2, JM8: 20 mg/kg/day for 5 days), or of CDDP and (glycolato-O,O')-diammineplatinum (II) (254S) (CDDP: 2,254S: 4 mg/kg/day for 5 days), resulted in significant tumor regression. The combination of CDDP and JM8 had the highest therapeutic efficacy while the CDDP and 254S combination had a lower antitumor potency. In addition, the toxicities of the combination therapies were lower than what was produced by the highest dosage of CDDP (4 mg/kg/day for 5 days). These results demonstrated that the antitumor activities of these combination chemotherapies were equal or superior to the activity of CDDP or an analogue alone, and that the toxicities produced by these combinations were more manageable than those produced by single drug therapies.

Animals↗

PubMed1990

Electroencephalographic changes during and after water intoxication.

A case of water intoxication with remarkable hyponatremia was investigated with a special reference to EEG changes during and after the episode. The patient recovered his EEG as his consciousness disturbance had improved through an intravenous infusion of high osmolality saline, correlating with the serum sodium level. Further, the clinical importance of recording EEG for water intoxication was stressed.

Adult↗

PubMed1990

Regulation of histamine turnover via muscarinic and nicotinic receptors in the brain.

To clarify the regulation of central histaminergic (HAergic) activity by cholinergic receptors, the effects of drugs that stimulate the cholinergic system on brain histamine (HA) turnover were examined, in vivo, in mice and rats. The HA turnover was estimated from the accumulation of tele-methylhistamine (t-MH) during the 90-min period after administration of pargyline (65 mg/kg, i.p.). In the whole brain of mice, oxotremorine, at doses higher than 0.05 mg/kg, s.c., significantly inhibited the HA turnover, this effect being completely antagonized by atropine but not by methylatropine. A large dose of nicotine (10 mg/kg, s.c.) also significantly inhibited the HA turnover. This inhibitory effect was antagonized by mecamylamine but not by atropine or hexamethonium. A cholinesterase inhibitor, physostigmine, at doses higher than 0.1 mg/kg, s.c., significantly inhibited the HA turnover. This effect was antagonized by atropine but not at all by mecamylamine. None of these cholinergic antagonists used affected the steady-state t-MH level or HA turnover by themselves. In the rat brain, physostigmine (0.1 and 0.3 mg/kg, s.c.) also decreased the HA turnover. This inhibitory effect of physostigmine was especially marked in the striatum and cerebral cortex where muscarinic receptors are present in high density. Oxotremorine (0.2 mg/kg, s.c.) and nicotine (1 mg/kg, s.c.) also decreased the HA turnover in the rat brain. However, these effects showed no marked regional differences. These results suggest that the stimulation of central muscarinic receptors potently inhibits the HAergic activity in the brain and that strong stimulation of central nicotinic receptors can also induce a similar effect.

Animals↗