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Biomedical subjects

K Kato

Publications and source records attributed to K Kato.

At least 325 records · Page 18Linked to original sources

Analysis of the addition products of alpha-tocopherol with phosphatidylcholine-peroxyl radicals by high-performance liquid chromatography with chemiluminescent detection.

A chemiluminescence-based high-performance liquid chromatographic method was developed for the analysis of the addition products of alpha-tocopherol with phosphatidylcholine-peroxyl radicals (TOO-PC). The TOO-PC eluted from a reversed-phase column was reacted with a chemiluminescent reagent consisting of a Cypridina luciferin analog and a lipid-soluble iron chelate in acidic methanol at 50 degrees C, and the generated chemiluminescence was monitored. The detection limit for TOO-PC by this method was about 1 pmol. This method was applied to the detection of TOO-PC in the peroxidized membranes prepared from rabbit erythrocyte ghosts. When the erythrocyte ghosts were peroxidized by the addition of a water-soluble free radical initiator, a peak corresponding to TOO-PC was detected on the chromatogram with chemiluminescent detection. The amount of TOO-PC in the erythrocyte membranes increased with the depletion of endogenous alpha-tocopherol. The results indicate that this method proved useful for the detection of the TOO-PC formed by the peroxyl-radical scavenging reactions of alpha-tocopherol in biological systems.

Animals↗

Fluoride and magnesium concentrations in human dental calculus obtained from Japanese and Chinese patients.

Calculus deposited on a total of 68 permanent teeth from patients 30-60 years old from Nagoya in Japan and Beijing in China was investigated. An abrasive microsampling method was used to examine the fluoride (F) and magnesium (Mg) distribution, using a fluoride ion-specific electrode and atomic absorption spectrophotometry, respectively. F concentrations decreased from the surface towards the interior of the calculus. Mg concentrations, however, gradually rose towards the innermost surface adjacent to the tooth. In all parts of the depth profiles, the average concentrations of both magnesium and fluoride were higher in the Japanese than in the Chinese calculus. Towards the inner surface of the calculus, F and Mg concentrations were also much higher in the Japanese than in the Chinese group. A greater intake of sea foods and greater use of fluoride dentifrices are possible reasons for the higher F and Mg concentrations in the Japanese individuals.

Adult↗

Changes in the expression of cardiac Na+-K+ ATPase subunits in the UM-X7.1 cardiomyopathic hamster.

Previous studies have shown that cardiac Na+ -K+ ATPase activity in the UM-X7.1 hamster strain is decreased at an early stage of genetic cardiomyopathy and remains depressed; however, the mechanism for this decrease is unknown. The objective of the present study was to assess whether changes in the expression of cardiac Na+-K+ ATPase subunits in control and UM-X7.1 cardiomyopathic hamsters are associated with alterations in the enzyme activity. Accordingly, we examined sarcolemmal Na+-K+ ATPase activity as well as protein content and mRNA levels for the alpha1, alpha2, alpha3 and beta1-subunit of the Na+-K+ ATPase in 250-day-old UM-X7.1 and age-matched, control Syrian hamsters; this age corresponds to the severe stage of heart failure in the UM-X7.1 hamster. Na+-K+ ATPase activity in UM-X7.1 hearts was decreased compared to controls (9.0 +/- 0.8 versus 5.6 +/- 0.8 micromol Pi/mg protein/hr). Western blot analysis revealed that the protein content of Na+-K+ ATPase alpha1- and beta1-subunits were increased to 164 +/- 27% and 146 +/- 22% in UM-X7.1 hearts respectively, whereas that of the alpha2- and alpha3-subunits were decreased to 82 +/- 5% and 69 +/- 11% of control values. The results of Northern blot analysis for mRNA levels were consistent with the protein levels; mRNA levels for the alpha1- and beta1-subunits in UM-X7.1 hearts were elevated to 165 +/- 14% and 151 +/- 10%, but the alpha2-subunit was decreased to 60 +/- 8% of the control value. We were unable to detect mRNA for the alpha3-subunit in either UM-X7. 1 or control hearts. These data suggest that the marked depression of Na+-K+ ATPase activity in UM-X7.1 cardiomyopathic hearts may be due to changes in the expression of subunits for this enzyme.

Animals↗

Small molecular weight heat shock-related protein, HSP20, exhibits an anti-platelet activity by inhibiting receptor-mediated calcium influx.

We have shown that Hsp20, one of small molecular weight heat shock protein, which is present at a high concentration both in vascular smooth muscle cells and in circulating blood in patient with vascular disease, strongly inhibits platelet aggregation in vitro and ex vivo. To clarify the mechanism, we investigated the effect of Hsp20 on free calcium concentration in human platelet cytoplasm using fura 2. Hsp20 inhibited thrombin-induced calcium influx without affecting calcium release from intracellular calcium stores. The degree of inhibition is well-correlated with that of suppression of thrombin-induced platelet aggregation by this substance. Hsp20 also inhibited the elevation of cytoplasmic free calcium level triggered by collagen, but not that by A-23187. In contrast, Hsp28, another type of small molecular weight Hsp, failed to affect the cytoplasmic free calcium level. These findings suggest that Hsp20 inhibits the receptor-mediated calcium influx of platelets without affecting calcium release from intracellular calcium stores, leading to its anti-platelet activity.

Biological Transport↗

Improvement by the insulin-sensitizing agent, troglitazone, of abnormal fibrinolysis in type 2 diabetes mellitus.

This study evaluated abnormal fibrinolysis in diabetic patients in terms of the pathophysiological significance and reversibility by oral hypoglycemic agents. Forty-seven patients with type 2 diabetes mellitus were randomly treated for 4 weeks with glibenclamide (n = 23) or troglitazone (n = 24). Before and after treatment, glycemic control, steady-state plasma glucose and insulin (SSPG and SSPI, respectively), and markers of fibrinolysis (tissue plasminogen activator [tPA] and plasminogen activator inhibitor-1 [PAI-1]) were analyzed in each patient. Pretreatment plasma PAI-1 in diabetic patients, but not tPA, was well correlated with the severity of retinopathy assessed by the fluorescence technique. Four weeks of treatment with troglitazone significantly decreased hemoglobin A1c (HbA1c), SSPG, and PAI-1 without an alteration of tPA. The troglitazone-induced decrease in plasma PAI-1 (50.3 v28.8 micromol/L; P < .05) was correlated with HbA1c (8.80% v7.21%, r = .539, P < .01) and SSPG (16.2 v 8.97 mmol/L, r = .562, P < .01) but not with SSPI. In contrast, treatment with glibenclamide for 4 weeks also reduced the HbA1c titer to almost the same extent as troglitazone (1.38% v 1.59%), but did not change the plasma PAI-1 or SSPG titer. These results suggest that an abnormal fibrinolytic state, especially overproduction of PAI-1, may be a pathogenic factor in the development of diabetic complications such as retinopathy, which may be improved by correction of the insulin resistance with troglitazone.

Aged↗

Congenital primitive epithelial tumor of the liver showing focal rhabdoid features, placental involvement, and clinical features mimicking multifocal hemangioma or stage 4S neuroblastoma.

We describe an unusual case of congenital primitive epithelial tumor of the liver with focal rhabdoid features. The present case is unique and informative in the following aspects: (1) a first case of congenital epithelial tumor of the liver with no hepatocytic differentiation but focal rhabdoid features, (2) clinical similarities to multicentric hemangioma or stage 4S neuroblastoma, (3) diagnosis obtained from histological examination of the placenta immediately after birth.

Adult↗

Effects of dopamine, NMDA, opiate, and serotonin-related agents on acute methamphetamine-induced self-injurious behavior in mice.

We examined the biochemical processes responsible for acute methamphetamine (MAP)-induced self-injurious behavior (SIB) in mice. In initial experiments, a single dose of MAP (5, 10, or 15 mg/kg, IP) or an equivalent volume of saline was administered to male BALB/c mice. Acute MAP administration dose dependently increased the incidence of SIB (p < 0.05). In further experiments, we evaluated the effects of SCH23390, sulpiride, MK-801, naloxone or 5-hydroxy-L-tryptophan (5-HTP) on the incidence of acute MAP (15 mg/kg, IP)-induced SIB. Both SCH23390 (0.5 and 1.0 mg/kg, IP) and 5-HTP (100 and 200 mg/kg, IP) reduced the incidence of MAP-induced SIB (p < 0.05). MK-801 (0.125 and 0.25 mg/kg, IP) completely blocked the SIB induced by MAP (p < 0.001). In contrast, neither sulpiride (25, 50, and 100 mg/kg, IP) nor naloxone (1, 5, and 10 mg/kg, IP) affected the incidence of MAP-induced SIB. It is concluded that dopamine D(1), NMDA, and serotonin neurotransmission may be involved in critical biochemical processes responsible for acute MAP-induced SIB.

5-Hydroxytryptophan↗

Real-time quantitative reverse transcription-polymerase chain reaction for the detection of AML1-MTG8 fusion transcripts in t(8;21)-positive acute myelogenous leukemia.

Quantification of AML1-MTG8 fusion transcripts was performed by using real-time reverse transcription-polymerase chain reaction (RT-PCR) and the clinical value of this method was evaluated in t(8;21)-positive acute myelogenous leukemia (AML). A t(8;21)-positive cell line, Kasumi-1, was used for constructing standard curves and the corrected AML1-MTG8 mRNA expression level relative to the expression of the GAPDH housekeeping gene was calculated. Bone marrow samples from 14 patients with t(8;21)-positive AML were sequentially examined. The corrected AML1-MTG8 expression level at diagnosis varied in the range from 0.4 to 2.7 (median, 1.5) among the patients. When samples at 1, 3 and 6 months were examined after diagnosis, the corrected AML1-MTG8 expression level was found to decrease sequentially in all but one. AML1-MTG8 fusion transcripts were also detected in four of eight samples from patients in remission for more than 1 year. In conclusion, real-time RT-PCR can provide a rapid and accurate quantification of AML1-MTG8 fusion transcripts. This system could be useful to reveal the prognostic relevance of minimal residual disease in t(8;21)-positive AML.

Adolescent↗

End-tidal CO2 pressure decreases during exercise in cardiac patients: association with severity of heart failure and cardiac output reserve.

OBJECTIVES: We measured end-tidal CO2 pressure (PETCO2) during exercise and investigated the relationship between PETCO2 and exercise capacity, ventilatory parameters and cardiac output to determine the mechanism(s) of changes in this parameter. BACKGROUND: It is unclear whether PETCO2 is abnormal at rest and during exercise in cardiac patients. METHODS: Cardiac patients (n = 112) and normal individuals (n = 29) performed exercise tests with breath-by-breath gas analysis, and measurement of cardiac output and arterial blood gases. RESULTS: PETCO2 was lower in patients than in normal subjects at rest and decreased as the New York Heart Association class increased, whereas the partial pressure of arterial CO2 did not differ among groups. Although PETCO2 increased during exercise in patients, it remained lower than in normal subjects. PETCO2 in relation to cardiac output was similar in patients and normal subjects. PETCO2 at the respiratory compensation point was positively correlated with the O2 uptake (r = 0.583, p < 0.0001) and the cardiac index at peak exercise (r = 0.582, p < 0.0001), and was negatively correlated with the ratio of physiological dead space to the tidal volume. The sensitivity and specificity of PETCO2 to predict an inadequate cardiac output were 76.6% and 75%, respectively, when PETCO2 at respiratory compensation point and a cardiac index at peak exercise that were less than the respective control mean-2 SD values were considered to be abnormal. CONCLUSIONS: PETCO2 was below normal in cardiac patients at rest and during exercise. PETCO2 was correlated with exercise capacity and cardiac output during exercise, and the sensitivity and specificity of PETCO2 regarding decreased cardiac output were good. PETCO2 may be a new ventilatory abnormality marker that reflects impaired cardiac output response to exercise in cardiac patients diagnosed with heart failure.

Anaerobic Threshold↗

Optical and atomic force microscopy of an explanted AcrySof intraocular lens with glistenings.

PURPOSE: To assess the surface morphology and cause of glistenings in an explanted AcrySof intraocular lens (IOL). SETTING: Shakai Hoken Kobe Central Hospital, Kobe, Japan. METHODS: A 63-year-old Japanese man had implantation of an AcrySof IOL in the capsular bag. One month postoperatively, he had a neodymium:YAG laser capsulotomy for posterior capsule opacification, which changed the IOL's position in the capsular bag. A few months later, the patient developed disabling night glare from intralenticular glistenings and progressive hyperopic refractive error. The IOL was explanted and then analyzed by optical microscopy and atomic force microscopy (AFM). Laboratory analysis of control AcrySof IOLs kept in a balanced salt solution at steady room and body temperature for 2 months was also performed to evaluate the cause of the glistenings observed clinically. RESULTS: Optical microscopy showed that the explanted AcrySof IOL had several microvacuoles; no abnormalities were observed in the control AcrySof IOLs before or after folding at the room and body temperatures. The AFM analysis showed a significant change in the surface morphology of the explanted IOL, including vacuolar formations in the posterior surface as well as numerous anterior surface irregularities. No microvacuoles or surface morphology alterations were observed in the control AcrySof IOLs by AFM analysis. CONCLUSIONS: The glistenings in the explanted AcrySof IOL were likely caused by temperature changes and not mechanical stress from folding.

Acrylic Resins↗

Unilateral upregulation of cyclooxygenase-2 following cerebral, cortical photothrombosis in the rat: suppression by MK-801 and co-distribution with enzymes involved in the oxidative stress cascade.

Cyclooxygenase-2 (COX-2) is an essential enzyme for prostaglandin synthesis from arachidonic acid, during which considerable amounts of superoxide are produced. During pathological conditions, superoxide and nitric oxide (NO) rapidly form peroxynitrite, a potent cytotoxin, causing symptoms referred to as oxidative stress response. Superoxide is controlled by enzymes such as manganese- or copper-zinc-dependent superoxide dismutase (Mn-SOD, CuZn-SOD), glutathione peroxidase (GPx) and antioxidants derived from heme oxygenase (HO) activity such as biliverdin and bilirubin. NO derives from 3 NO-synthases (NOS I-III) from which the calcium-dependent NOS-I and III are activated rapidly due to hyperexcitation. We studied the induction of COX-2 by immunohistochemistry at days 1, 2 and 5 following cortical photothrombosis in normal and MK-801 treated rats. The results showed a weak constitutive, neuronal expression of COX-2 in cortex and amygdala. Layers II+III contained considerably more COX-2 than infragranular layers. One and 2 days following injury COX-2 was highly upregulated in the supragranular layers of the whole injured hemisphere compared with sham-operated animals and compared to the contralateral unlesioned hemisphere, whereas at day 5 COX-2 levels had returned to baseline. MK-801 treatment caused a reduction in COX-2 upregulation at day one and by day 2 no significant differences between injured and contralateral hemisphere were measurable. COX-2 positive neurons were found in close association with NOS-I containing neurons and their fibers but were not colocalized. In addition, codistribution of COX-2 was found with HO-1, CuZn-SOD and GPx containing cells, whereas COX-2 was colocalized with HO-2 and/or MnSOD in cortical neurons.

Amygdala↗

Effects of sesquiterpenoids from "Oriental incenses" on acetic acid-induced writhing and D2 and 5-HT2A receptors in rat brain.

Six sesquiterpenoids, namely jinkoh-eremol, agarospirol, alpha- and beta-santalols, dehydrocostus lactone and costunolide, isolated from oriental incenses inhibited acetic acid-induced writhing in mice. The incidence of writhing produced by jinkoh-eremol, alpha-santalol and costunolide were revealed by administration of naloxone (mu-, kappa- and delta-antagonists). Inhibitory activities of alpha-santalol on opioid receptors were shown only by the delta antagonist, but not by the mu- and kappa-antagonists. The delta2-antagonist, but not the delta-antagonist, inhibited the activity of alpha santalol. The mechanism of inhibitory activity on the opioid receptor by alpha-santalol was different from that of morphine. Alpha-santalol was shown to be the most potent of the six as an antagonist of dopamine D2 and serotonine 5-HT2A receptor binding. The effect of alpha-santalol, was the same as that of chlorpromazine as an antipsychotic agent, although alpha-santalol was less potent than chlorpromazine.

Acetic Acid↗

Bone marrow transplantation for children with acute myelogenous leukaemia in the first complete remission.

Of 52 children aged 9 months to 16 years old with acute myelogenous leukaemia (AML) in first complete remission undergoing bone marrow transplantation at our institution, 31 received allogeneic transplants (allo-BMT) and 21 received autologous transplants (ABMT). Initial induction and consolidation chemotherapy were not uniform. BMT was performed at a median of 7 months (range: 2.5 to 22.5 months) from the diagnosis. Conditioning included chemotherapy (n=43: 4 x 4 mg/kg of busulfan and 3 x 60 to 70 mg/m(2) of melphalan) or total body irradiation (12 Gy) plus chemotherapy (n=9). Graft-versus-host disease (GVHD) prophylaxis in allo-BMT cases consisted of methotrexate +/- cyclosporin A. Unpurged marrow was used in ABMT cases. All patients showed sustained engraftment. Amongst allograft cases, acute or chronic GVHD developed in 7 patients each (23%). 8 patients (15%) died (5 with allo-BMT, 3 with ABMT), including transplant-related mortality in 3 of the allo-BMT patients. 7 patients had relapses (3 with allo-BMT, 4 with ABMT). As of June 1999, 43 patients are alive and well 13 to 160 months after BMT (median, 71), with 5-year disease-free survival rates after BMT of 84% for allo-BMT, 81% for ABMT and 83% altogether. Although the presented data are based on a retrospective evaluation, we consider BMT for childhood AML during first complete remission an effective treatment for eradicating leukaemia.

Bone Marrow Transplantation↗

Tyk2 plays a restricted role in IFN alpha signaling, although it is required for IL-12-mediated T cell function.

Janus kinases (Jaks) play an important role in signal transduction via cytokine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mice to study the requirement for tyk2 in vivo. Tyk2-deficient mice show no overt developmental abnormalities; however, they display a lack of responsiveness to a small amount of IFNalpha, although a high concentration of IFNalpha can fully transduce its signal even in the absence of tyk2. Furthermore, IL-12-induced T cell function is defective in these mice. In contrast, these mice respond normally to IL-6 and IL-10, both of which activate tyk2 in vitro. These observations demonstrate that tyk2 plays only a restricted role in mediating IFNalpha-dependent signaling while being required in mediating IL-12-dependent biological responses.

Animals↗

Experimental prostate carcinogenesis - rodent models.

A number of rodent models of prostate carcinoma development have been established to study mechanisms and modifying potential. All except for transgenic mouse models need long experimental periods for generation of a high yield of cancers. Spontaneous prostate tumor models, while not practical in terms of time and tumor incidences, allow the natural course of multistep neoplasia to be followed without a need for chemical exposure. Carcinogens, especially in combination with testosterone, can induce prostate carcinomas in rats, but none are prostate-specific, so that tumor development in other organs is a complicating factor. Induction of invasive prostate carcinomas in the rat frequently requires long-term administration of a pharmacological dose of testosterone with or without application of a chemical carcinogen. While there are several transgenic mouse models, each also has strong and weak points, and it is therefore necessary to select the best model for the purpose of any experimental study.

Aminobiphenyl Compounds↗