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Biomedical subjects

K Kawai

Publications and source records attributed to K Kawai.

At least 19 recordsLinked to original sources

Mechanism of the rejection of major histocompatibility complex class I-disparate murine skin grafts: rejection can be mediated by CD4+ cells activated by allo-class I + II antigen in CD8+ cell-depleted hosts.

In the preceding article, we analyzed the immunohistochemical rejection mechanism of major histocompatibility complex (MHC) class I (H-2K)-disparate murine skin grafts, and showed that only CD8+ cells infiltrated at the site of the epithelial tissue of MHC class I-disparate graft. We also showed that perfect survival of MHC class I-disparate grafts were attained in thymectomized recipients treated with anti-Lyt-2 monoclonal antibody. In this report, we showed that these long-surviving allo-class I grafts were rejected in the absence of CD8+ cells by stimulation with allo-MHC class I + II-disparate graft as the second stimulation. Furthermore, it was immunohistochemically revealed that under that condition, a large number of CD4+ cells infiltrated into the epithelial tissue of these long-surviving class I grafts, which were going to be rejected 2-5 d after the transplantation of a second graft with MHC class I + II difference. This result directly shows that CD4+ cells are able to became effectors for the rejection of allo-MHC class I (H-2K) skin graft.

Animals

Additive effects of antitumor drugs and lymphokine-activated killer cell cytotoxic activity in tumor cell killing determined by lactate-dehydrogenase-release assay.

The effect of pretreatment with antitumor drugs on lymphokine-activated killer (LAK) cell cytotoxic activity, determined by lactate-dehydrogenase(LDH)-release assay, was investigated. LAK cells were induced by incubating peripheral blood lymphocytes of healthy donors in medium containing interleukin-2 (IL-2) and monoclonal anti-CD3 antibody for 6-7 days. A human lung squamous carcinoma cell line, SQ-5, was used as an adherent target. After 24 h exposure of the target cells to cisplatin, doxorubicin, or mitomycin C, the drugs were washed off and LAK cells were added at an E/T ratio of 5. During further incubation for 48 h, LDH release from cisplatin- or doxorubicin-pretreated target cells was markedly higher than that from non-pretreated target cells. The combination of cisplatin and LAK cells has an additive cytotoxic effect and that of mitomycin C and LAK cells does not; there may also be an additive effect late in the toxicity mechanism between doxorubicin and LAK cells.

Antineoplastic Agents

An artificial amino acid radiopharmaceutical for single photon emission computed tomographic study of pancreatic amino acid transports 123I-3-iodo-alpha-methyl-L-tyrosine.

123I-3-iodo-alpha-methyl-L-tyrosine (123I-L-AMT) was selected and its characteristics on pancreas accumulation, metabolic selectivity and metabolic stability of 125I-L-AMT were studied. The studies on rat tissue slice as well as mouse biodistribution proved very high accumulation of 125I-labeled L-AMT in the pancreas, which was remarkably inhibited by the active transport inhibitor, ouabain. 125I-L-AMT does not enter into protein synthesis and general amino acid catabolism. Moreover, 125I-L-AMT was very stable against enzymatic deiodination. Thus, the above studies indicated that the 123I-labeled L-AMT was an "artificial amino acid" radiopharmaceutical to be used for the selective measurement of the membrane amino acid transport rate in the pancreas.

Amino Acids

Blood pressure changes following extracorporeal shock wave lithotripsy for urolithiasis.

Hypertension after extracorporeal shock wave lithotripsy (ESWL) has been a controversial subject. Changes in blood pressure were studied in 262 patients (mean age 47.8 years) 18.6 months after ESWL. According to World Health Organization criteria the number of patients who showed a decrease exceeded those who showed an increase in blood pressure. The patients who have been on antihypertensive therapy showed a significantly greater decrease in blood pressure than those without medication. Of 192 normotensive patients diastolic pressure increased 1.2 mm. Hg and 2 (1.0%) had hypertension 18.4 months after ESWL. Annualized increase in diastolic pressure and new onset of hypertension were calculated to be 0.78 mm. Hg and 0.65%, respectively. Significant elevation of diastolic pressure was noted in the patients who received a larger number of shock waves. Blood pressure should be carefully followed after ESWL especially in patients who have been treated by a greater number of shock waves.

Adult

Global cerebral ischemia associated with cardiac arrest in the rat: I. Dynamics of early neuronal changes.

Light microscopic neuronal changes were studied in rats subjected to 10 min of global ischemia produced by compression of the major cardiac vessels. Observations of cresyl violet-stained sections revealed early changes involving predominantly GABAergic neurons in various locations. In rats killed 15 min after recirculation, the changes were characterized by the appearance of a clear peripheral zone with condensation of the remaining neuronal cytoplasm. After 1 h, these zones appeared to be compartmentalized into individual pearl-like vacuoles, especially prominent in the nucleus reticularis thalami. After 3 h, the cytoplasmic vacuoles disappeared and the neuronal changes, particularly in the cerebral cortex, striatum, hippocampus, and pars reticulata of the substantia nigra, consisted mainly of hyperchromasia or loss of Nissl substance. After 2 days, the cerebral cortex and thalamus contained occasional neurons with conspicuously large nucleoli. After 7 days, the hippocampus revealed an approximately 50% loss of CA1 pyramidal neurons, associated with intense microglial reactivity in the stratum radiatum, whereas the neuronal destruction was more complete in the nucleus reticularis thalami. Our observations suggest a possibility that early changes in GABAergic neurons may provide a period of neuronal disinhibition and thus contribute to an excitatory ischemic damage in regions connected by GABAergic circuitry.

Animals

Comparison of the insulinotropic activity of glucagon-superfamily peptides in rat pancreas perfusion.

Previous studies have demonstrated that glucagon-superfamily peptides stimulate insulin release from the pancreatic islets in a glucose dependent manner. In this study we have carried out a structure-activity study of their insulinotropic activity using a rat pancreas perfusion with 5.5 mM glucose concentration. The following peptides were examined: glucagon-like peptide-1(7-36)amide (tGLP-1), glucagon, gastric inhibitory peptide (GIP), peptide having an amino-terminal histidine and carboxy-terminal isoleucine amide (PHI), vasoactive intestinal polypeptide (VIP), growth hormone releasing factor(1-29)amide (GRF), GRF(1-27)amide and synthetic hybrid-peptides of PHI-GRF, PHI(1-11)-GRF(12-27) and PHI(1-20)-GRF(21-27). Their potencies were evaluated as: tGLP-1 = GIP > glucagon > PHI = VIP > PHI(1-20)-GRF(21-27) > PHI(1-11)-GRF(12-27) >> GRF(1-29) = GRF(1-27). It is clear that 0.1 nM tGLP-1 stimulated insulin release, whereas 1 microM GRF(1-29) did not. These results indicate that 1) in addition to N-terminal amino acid (histidine or tyrosine), position 4 (glycine), position 9 (aspartic acid) and position 11 (serine) in the amino acid sequence are important for their insulinotropic activity, 2) not only the N-terminal portion but also the C-terminal portion of these peptides contribute to their insulinotropic activity.

Amino Acid Sequence

A clinical decision analysis to assess the value of laparoscopic cholecystectomy in the treatment of gallstone disease.

Laparoscopic cholecystectomy has been introduced for gallstone therapy and its use appears currently to be spreading very rapidly. A clinical decision analysis was performed to assess this new technique by quantitative comparison with other therapeutic modalities. A decision tree-based state transition model implemented to simulate a five-year period of follow-up was constructed. Non-surgical treatments were superior to surgical treatments in enhancing both life expectancy and quality-adjusted life expectancy on the basis of the optimal indications; one radiolucent stone < 2 cm for extracorporeal shock-wave lithotripsy and multiple floating stones for oral dissolution therapy respectively, especially in the elderly. Laparoscopic cholecystectomy was superior to open cholecystectomy in enhancing the quality of life for all eligible patients. Sensitivity analysis revealed that a higher incidence of the bile duct injury resulting from laparoscopic cholecystectomy would result in a poorer quality-adjusted life expectancy. The results of the analysis suggest the following. Nonsurgical treatments are acceptable alternatives to surgery on the basis of their optimal indications. Laparoscopic cholecystectomy has an advantage over open cholecystectomy in enhancing the patient's utility, and appears to be an attractive therapeutic modality. A proper training program is necessary to ensure the quality of this procedure in order to maintain its advantage.

Adult

Epidemiological study of peptic ulcer disease among Japanese and Koreans in Japan.

Peptic ulcer among Japanese and Koreans in Japan has rarely been studied. In this 10-year study of hospital-based endoscopy, we focused on the epidemiology of peptic ulcer among these ethnic groups in Japan. Between 1980 and 1990, 81.2% of all patients examined via endoscopy at Saikyo Hospital in Kyoto completed a life-style questionnaire: 1,264 Japanese (70.5%), 503 Koreans (28.1%), and 25 persons of unknown ethnicity (1.4%). Characteristics of ulcer disease were almost identical for Koreans and Japanese. Like other world-wide patterns, the male to female ratio was 2.3:1. Unlike results from Western countries, however, the overall gastric ulcer rate was 1.5 times higher than for duodenal ulcer. This higher rate was due to the relatively high rate of gastric ulcer in the older age groups; among persons less than 40 years of age, duodenal ulcer was diagnosed more often than gastric ulcer. The mean age at diagnosis of duodenal ulcer (40.7 years) was significantly lower (p less than 0.005) than that for gastric ulcer (53.7 years). Multivariate-adjusted odds ratios were calculated using a multiple logistic regression model. Cigarette smoking significantly increased the risk for both gastric ulcer (odds ratio = 3.10, 95% confidence interval [CI] 2.1-4.6) and duodenal ulcer (odds ratio = 1.9, 95% CI 1.2-2.9). Age greater than or equal to 40 years (odds ratio = 2.3, 95% CI 1.6-3.3) and consumption of salty foods (odds ratio = 1.5, 95% CI 1.0-2.1) also significantly increased the risk for gastric ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Modifying effects of fungal and herb metabolites on azoxymethane-induced intestinal carcinogenesis in rats.

Modifying effects of a fungal product, flavoglaucin, and four plant-derived chemicals, shikonin, gingerol, oleanolic acid and paeoniflorin, on intestinal carcinogenesis were examined in a rat model using azoxymethane (AOM). A total of 280 male F344 rats, 6 weeks old, were divided into 12 groups. Group 1 (30 rats) was given two subcutaneous injections of 15 mg/kg of AOM at the start of the experiment. Groups 2 (30 rats), 3 (20 rats), 4 (20 rats), 5 (30 rats) and 6 (30 rats) received a test chemical (flavoglaucin, shikonin, gingerol, oleanolic acid or paeoniflorin, respectively) in the diet at a concentration of 0.02% for 3 weeks, during which time AOM was applied, and then kept on basal diet until the end of experiment (one year). Groups 7-11 (each 20 rats) were given a test chemical corresponding to Groups 2-6, respectively. Group 12 (20 rats) served as a control. The incidence and average number of intestinal tumors in Group 2 (47%, 0.57 +/- 0.68) were significantly less than in Group 1 (74%, 1.07 +/- 0.87) (P < 0.05, respectively). Multiplicity of intestinal neoplasms of Group 3 (0.55 +/- 0.60) or 4 (0.47 +/- 0.51) was also significantly smaller than that of Group 1 (P < 0.05 and P < 0.01, respectively). These results suggest that flavoglaucin, shikonin and gingerol might be promising chemopreventive agents for intestinal neoplasia.

Animals

Heat treatment of Japanese lacquerware renders it hypoallergenic.

Japanese lacquer is made from the sap of the Japanese lacquer tree (Toxicodendron vernicifluum), a member of the Anacardiacae plant family. Objects painted with this material are described collectively as lacquerware. Both fresh lacquer and lacquerware may evoke allergic contact reactions ascribable to the urushiols contained therein. In this study, we have examined the effects of heating on the ability of lacquerware to elicit an allergic contact reaction. Lacquer films prepared with and without heat treatment were tested on urushiol-sensitive subjects. Patch test reactions were strongest to untreated film and decreased with increasing level of heat treatment. Assays for free urushiol in the lacquer films demonstrated that free urushiol content decreased with increasing heat treatment and that urushiols with saturated and monounsaturated alk(en)yl chains predominated.

Adult

Evaluation of skin irritancy of sodium lauryl sulphate: a comparative study between the replica method and visual evaluation.

For 20 years, using the replica method, we have evaluated the skin irritancy of about 10,000 commercial products which come into contact with the skin. In this method, test substances are usually applied on the flexor side of the upper arm for 24 h by semi-open patch test. Subsequently, skin replicas are taken and skin irritancy is evaluated microscopically. In the semi-open patch test, test substances are not completely occluded as in the closed patch test. Thus, this method is less invasive than the closed patch test method to the tested subjects. In this study, we investigated the sensitivity of microscopic scoring (MS) of the replica and visual scoring (VS) of the skin. Sodium lauryl sulphate (SLS) at 0.02%, 0.05%, and 0.2% was applied on 20 subjects' upper arms, using closed and semi-open methods. In both the closed patch test and the semi-open patch test, the value of MS correlated with the concentration of SLS, while VS did not show such a clear correlation. In addition, we compared 2 clinical tests for skin irritancy which are commonly performed in Japan: VS of 48 h closed patch test reaction on the subjects' upper backs and MS of 24 h semi-open patch test reaction on the subjects' upper arms (replica method). MS on the upper arms resulted in a constant score, regardless of the location of application, while VS on the upper back produced results which differed widely depending on the location. Thus, the replica method is a useful clinical test for skin irritancy, because it is sensitive, reproducible and non-invasive.

Adolescent

NAD(P)H-dependent chromium (VI) reductase of Pseudomonas ambigua G-1: a Cr(V) intermediate is formed during the reduction of Cr(VI) to Cr(III).

An NAD(P)H-dependent Cr(VI) reductase (molecular weight = 65,000) was purified from a Cr(VI)-resistant bacterium, Pseudomonas ambigua G-1. Stoichiometric analysis of the enzymatic reaction showed that the enzyme catalyzed the reduction of 1 mol of Cr(VI) to Cr(III) while consuming 3 mol of NADH as an electron donor. Chromium(VI) was reduced to Cr(V) by one equivalent NADH molecule in the absence of the enzyme. Electron spin resonance analysis showed that Cr(V) species (g = 1.979) was formed during the enzymatic reduction. The amount of Cr(V) species formed was about 10 times larger than that of the nonezymatic reduction. These findings show that the Cr(VI) reductase reduced Cr(VI) to Cr(III) with at least two reaction steps via Cr(V) as an intermediate.

Chromatography, Liquid

Inhibition of the activation of heat shock factor in vivo and in vitro by flavonoids.

Transcriptional activation of human heat shock protein (HSP) genes by heat shock or other stresses is regulated by the activation of a heat shock factor (HSF). Activated HSF posttranslationally acquires DNA-binding ability. We previously reported that quercetin and some other flavonoids inhibited the induction of HSPs in HeLa and COLO 320DM cells, derived from a human colon cancer, at the level of mRNA accumulation. In this study, we examined the effects of quercetin on the induction of HSP70 promoter-regulated chloramphenicol acetyltransferase (CAT) activity and on the binding of HSF to the heat shock element (HSE) by a gel mobility shift assay with extracts of COLO 320DM cells. Quercetin inhibited heat-induced CAT activity in COS-7 and COLO 320DM cells which were transfected with plasmids bearing the CAT gene under the control of the promoter region of the human HSP70 gene. Treatment with quercetin inhibited the binding of HSF to the HSE in whole-cell extracts activated in vivo by heat shock and in cytoplasmic extracts activated in vitro by elevated temperature or by urea. The binding of HSF activated in vitro by Nonidet P-40 was not suppressed by the addition of quercetin. The formation of the HSF-HSE complex was not inhibited when quercetin was added only during the binding reaction of HSF to the HSE after in vitro heat activation. Quercetin thus interacts with HSF and inhibits the induction of HSPs after heat shock through inhibition of HSF activation.

Animals