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Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 37 records · Page 2Linked to original sources
PubMed2004

Isolation and characterization of a new major intestinal CYP3A form, CYP3A62, in the rat.

Based on information of the nucleotide sequence obtained from rat genome clones, a new CYP3A (CYP3A62) cDNA was isolated from the cDNA library of a rat liver. The CYP3A62 cDNA was 1746 base pairs (bp) in length, which included 1491 bp of an open reading frame and 93 bp and 209 bp of the respective 5'- and 3'-noncoding regions. Amino acid sequence deduced from CYP3A62 cDNA shared the highest similarity with rat CYP3A9 (79.9%) among human and rat CYP3A forms previously reported. CYP3A62 mRNA and protein were consistently detected in small intestines as well as livers. CYP3A62 was a major form in small intestines of both sexes but was a female-predominant form in livers of adult rats. CYP3A62 in both tissues of male and female rats were clearly enhanced by the treatment with dexamethasone. These expression profiles resembled those of CYP3A9. Despite clear detection of CYP3A62, no detectable levels of CYP3A1 and CYP3A2 proteins, as well as those of mRNAs, were found in the intestinal tract. Therefore, CYP3A62 may play major roles together with CYP3A9 and CYP3A18 in endogenous or exogenous detoxification at the absorption site.

Animals↗
PubMed2004

The usefulness of 2-nitroimidazole-sodium borocaptate-10B conjugates as 10B-carriers in boron neutron capture therapy.

We evaluated the usefulness of five new (10)B-compounds (TX-2016, TX-2017, TX-2018, TX-2041, and TX-2042) as (10)B-carriers in boron neutron capture therapy (BNCT). They are 2-nitroimidazole-sodium borocaptate-(10)B (BSH) conjugates, that is, hybrid compounds that have both hypoxic tumor cell sensitizing unit under gamma-ray irradiation, 2-nitroimidazoles, and thermal neutron-sensitizing unit, BSH. (10)B distribution analyses in tumors and blood indicated that TX-2041 has the most favorable characteristics for localizing a sufficient amount of (10)B into tumors and keeping the (10)B concentration high during neutron beam irradiation. In addition, TX-2041 showed a significantly higher radio-sensitization effect with reactor thermal neutron beams than BSH on both total (=proliferating (P) + quiescent (Q)) and hypoxia-rich Q cell populations in solid tumors. Further, TX-2041 clearly demonstrated a radio-sensitization effect with gamma-rays on both cell populations, which could never be achieved by BSH. (10)B-carriers with a hypoxic tumor cell-sensitizing effect on tumors with gamma-rays as well as the potential to selectively localize and keep (10)B in tumors, such as TX-2041, are promising for use in actual BNCT.

Animals↗
PubMed2004

Comparison of the healing process in plated and non-plated fractures of the mandible in rats.

We compared the healing process of plated and non-plated fractures. The mandibles of 72 male Wistar rats were fractured and more either plated or not plated (n = 36 in each group). The healing process of the two conditions was studied histologically and immunohistochemically using a specific antibody to bone morphogenetic protein-2 (BMP-2). The results showed that the healing process in the plated group was delayed by one week compared with the non-plated group. Trauma to the surrounding soft tissues affected the healing process. BMP-2 was expressed at all stages in both groups. We conclude that the healing process is disturbed by the fixing of a plate; that periosteum is one of the main sources of osteogenic cells; and that BMP-2 is an important regulator of morphogenesis.

Animals↗
PubMed2004

Prediction of differences in in vivo oral clearance of N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl] ethylamine monohydrochloride (NE-100) between extensive and poor metabolizers from in vitro metabolic data in human liver microsomes lacking CYP2D6 activity and recombinant CYPs.

1. It has previously been reported that N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) was predominantly metabolized by cytochrome P450 (CYP) 2D6 in human liver microsomes (HLM). In the present study, the contribution of CYP forms involved in the formation of the major metabolites of NE-100 in human liver lacking CYP2D6 activity (PM-HLM) has been predicted by use of in vitro kinetic data on recombinant CYPs microsomes (rCYPs). 2. In PM-HLM, NE-100 is predicted to be metabolized to N-despropyl-NE-100 (NE-098), p-hydroxy-NE-100 (NE-152) and m-hydroxyl-NE-100 (NE-163), but not to O-demethy-NE-100 (NE-125), which is a major metabolite in pooled human liver microsomes (EM-HLM). The relative activity factor approach assumed that NE-098 formation is predominantly catalysed by CYP3A4 and CYP2C9 and the NE-152+163mix (a mixture of two hydroxylated metabolites, NE-152 and NE-163) formation is only catalysed by CYP3A4. 3. The predicted contribution rates of CYP3A4 and CYP2C9 for NE-098 formation were 58.1 and 34.6%, respectively, in PM-HLM. These predicted results were strongly supported by kinetic and inhibition studies using PM-HLM. The intrinsic clearance of NE-100 predicted from rCYPs (the predicted CLint-HLM-total) corresponded to those observed from EM- and PM-HLM (the observed CLint-HLM). 4. The in vivo oral clearance (CLoral) of NE-100 in extensive metabolizers and poor metabolizers of CYP2D6 was predicted to be 50times higher in extensive metabolizers than poor metabolizers using in vitro-in vivo scaling method based on the dispersion model. These data suggest that polymorphism of CYP2D6 might greatly affect NE-100 metabolism in vivo.

Administration, Oral↗
PubMed2004

Serum granulysin is a marker for Th1 type immunity in pre-eclampsia.

Recent studies suggest that pre-eclampsia is associated with a Th1 predominant state and may be considered a failure of tolerance. Granulysin is a cytotoxic granule protein of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Recently, we developed an enzyme-linked immunosorbent assay (ELISA) system for detecting serum granulysin, and reported that serum granulysin is a useful marker to evaluate the cell-mediated immunity. In this study, we show that the serum levels of granulysin were significantly elevated in pre-eclamptic patients compared with those in normal pregnancy subjects. In addition, the serum granulysin levels in pre-eclamptic patients were well associated with mean blood pressure, percentage of peripheral blood Th1 cells and Th1/Th2 ratios. The present results suggest that the serum granulysin levels would be a useful and novel serum marker to evaluate the Th1/Th2 balance, especially Th1 type immunity in pre-eclampsia.

Adult↗
PubMed2004

Increase in Ksp37-positive peripheral blood lymphocytes in mild extrinsic asthma.

Killer-specific secretory protein of 37 kDa (Ksp37), identified as a Th1/Tc1 specific secretory protein is expressed preferentially in cytotoxic T lymphocytes (CTL) and natural killer (NK) cells and might be involved in essential processes of CTL-mediated immunity. Although extrinsic asthma is linked currently to a Th2-dominated pathogenesis, there is increasing evidence for Th1/Tc1-mediated processes in the aetiopathology of asthma. CTL from patients with asthma have been shown to express cytokines and effector molecules which were different from healthy controls. We hypothesized that Ksp37 could indicate the involvement of CTL in the pathogenesis of extrinsic asthma. We therefore investigated Ksp37 expression in PBMC from patients with mild extrinsic asthma (n = 7) and healthy controls (n = 7). Flow cytometric analysis was used to quantify Ksp37+ cells and to investigate cellular Ksp37 expression as relative mean fluorescence intensities (MFI). We found a significantly (P = 0.016) higher percentage of Ksp37+ cells within the total lymphocyte population obtained from patients with mild extrinsic asthma compared with healthy controls. Subdifferentiation revealed a significant difference limited exclusively to the CD8+ subset (P = 0.010). In addition, Ksp37 secretion from cultured peripheral blood mononuclear cells (PBMC) and MFI of Ksp37+ lymphocytes were increased in patients with asthma compared with healthy controls. We conclude that mild extrinsic asthma appears to be associated with an increased expression of the Tc1 related protein Ksp37. The functional role of Ksp37 in the pathogenesis of asthma remains to be elucidated.

Adult↗
PubMed2003

Observation of arterial and venous thrombus formation by scanning and transmission electron microscopy.

BACKGROUND: In order to examine the process of thrombosis formation in artery and vein, the reactions of the arterial and venous endothelial surfaces were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in the photothrombosis model. MATERIALS AND METHODS: Thirty-nine rats were divided into the following 4 groups: 1) Sham group (n = 5) without illumination, 2) group A (n = 10) irradiated for 1 min, 3) group B (n = 10) irradiated for 5 min, 4) group C (n = 14) irradiated for 10 min at the level of the left common carotid artery and internal jugular vein. RESULTS: SEM provided no evidence of damage or adhesion of blood platelets to the endothelium of either the artery or vein in shams or group A animals. In group B, evidence of damage to endothelial cell membrane (e.g., plasmalemmal pits, crater-like structures associated with tears between endothelial cells, and decreased number of microvilli) was obtained in the arterial wall but not in the vein. In group C, there was extensive or widespread adhesion of blood platelets and other cells, tears between arterial endothelial cells, and a decrease in the number of microvilli in the artery but not in the vein (p < 0.05). CONCLUSIONS: Cell membrane injuries, tears between the endothelial cells, and endothelial detachment occur before adhesion of blood platelets and thrombus formation in the blood vessel occlusion model by photochemical reaction. These changes occur significantly earlier in the artery than in the vein.

Animals↗
PubMed2003

Platelet-derived growth factor and bone morphogenetic protein in the healing of mandibular fractures in rats.

We studied the effects of platelet-derived growth factor-B (PDGF-B) and bone morphogenetic protein-2 (BMP-2) during the healing of mandibular closed fractures in rats by immunohistochemical methods. Unilateral closed fractures were created in the mandibles of thirty 12-week-old rats. BMP-2 was expressed during all stages of healing, but PDGF-B was expressed mainly in the early and middle stages, and not in the later stage of the healing process. We conclude that PDGF-B was associated with the proliferation and migration of primitive mesenchymal cells. BMP-2 was related to the differentiation of mesenchymal cells into osteoblasts and chondroblasts. PDGF-B and BMP-2 both have distinct regulatory effects on the healing of fractures.

Animals↗
PubMed2003

Muscle endurance and power spectrum of the triceps brachii in wheelchair marathon racers with paraplegia.

OBJECTIVE: To investigate differences in triceps brachii endurance and electrical activity between elite marathon and recreational wheelchair athletes with paraplegia. DESIGN AND METHODS: Nine male elite wheelchair athletes between 20 and 46 years of age (average 29.0 +/- 8.2 years) with complete (ASIA-A) T4-L1 paraplegia were compared to a group of six male height- and weight-matched recreational wheelchair athletes with similar ages and injuries. Right triceps brachii maximum voluntary contraction (MVC), as well as the duration of the ability to maintain a 50% MVC were determined for all subjects. Median frequency (MF) and mean power frequency (MPF) were evaluated with fast Fourier transform spectrum analysis. MF and MPF rates of change were calculated and compared with the Student's t-test. SETTING: : Department of Rehabilitation Medicine, University of Occupational and Environmental Health, Japan. RESULTS: Right triceps brachii MVCs of the marathoners (42.4 +/- 8.8 N m (range 33-55 N m)) and recreational athletes (41.6 +/- 9.3 N m (range 32-56 N m)) did not differ significantly (P = 0.63). Endurance, however, did. All of the athletes, but none of the control subjects, were able to maintain a 50% MVC contraction of the right triceps brachii for 2 min (the average contraction duration in the latter group was 75.5+/-16.2 s). MF and MPF of the triceps brachii decreased linearly in both groups, but the slopes in the marathoners (-8.9 +/- 4.6 (-3.8 to -16.4) and -9.7 +/- 4.6 (-4.0 to -17.2)%/min, respectively) were statistically less steep than those in the recreational athletes (-22.3 +/- 8.2 (-9.6 to -31.4) and -21.2 +/- 6.4 (-11.4 to -28.6)%/min, respectively). CONCLUSION: Elite marathoners and active wheelchair users have similar triceps brachii strength. The marathoner's triceps brachii, however, display a significantly improved endurance and a slower decline of MF and MPF with time than do those of their recreational athlete control group.

Adult↗
PubMed2003

In vitro inhibition of human small intestinal and liver microsomal astemizole O-demethylation: different contribution of CYP2J2 in the small intestine and liver.

1. The effects of chemical agents on the metabolism of the antihistamine drug astemizole were investigated to evaluate drug-drug interactions. 2. Chemical inhibitors of astemizole O-demethylation were screened using the small intestinal and liver microsomes from rabbit as an animal model for the first-pass metabolism of humans. In the rabbit small intestine, astemizole O-demethylation was clearly inhibited by ebastine, arachidonic acid, alpha-naphthoflavone, ketoconazole, tranylcypromine, troglitazone and terfenadine. 3. In humans, these inhibitors also reduced microsomal astemizole O-demethylation in both the small intestine and liver. However, the inhibition rate of almost all these chemicals were clearly greater in the small intestine than in the liver. Thus, a different contribution of cytochrome p450 in each tissue is suggested. 4. All the chemicals inhibited astemizole O-demethylation in recombinant CYP2J2 microsomes. The results suggest that CYP2J2 is involved in astemizole O-demethylation in both the human small intestine and liver; however, the contribution in the liver is lower than in the small intestine. The effects of the CYP2J2 inhibitors during first-pass metabolism may be more important in the small intestine than in the liver. Since all the inhibition profiles of astemizole O-demethylation were different in the liver and small intestine, involvement of another p450 in astemizole O-demethylation in human liver may be speculated. 5. In the rabbit microsomal systems, the same metabolites found in humans were qualitatively detected and the inhibition profiles of the chemical agents in the microsomes resembled that of humans.

Animals↗
PubMed2003

Decrease of T-helper 2 and T-cytotoxic 2 cells at implantation sites occurs in unexplained recurrent spontaneous abortion with normal chromosomal content.

BACKGROUND: In normal pregnancy, predominant type 2 cytokines help maintain pregnancy, and a T-helper (Th)1 type response is associated with unexplained recurrent spontaneous abortion (RSA). However, Th2 and T-cytotoxic (Tc)2 cells have not been localized at the implantation site in RSA. METHODS: Twenty-one cases with RSA were classified into RSA with normal chromosomal content (RSA-N, n = 10) and RSA with abnormal chromosomal content (RSA-A, n = 11). As a control, we selected 15 gestational age-matched cases of induced abortion with no history of spontaneous abortion. We immunostained paraffin-embedded decidual sections for a specific Th2 and Tc2 cell marker termed 'chemo-attractant receptor-homologous molecule expressed on Th2 cells (CRTH2)' and T-cell markers CD3 and CD8. The numbers and percentages of Th2 (CRTH2(+)CD8(-)CD3(+)) and Tc2 (CRTH2(+)CD8(+)) cells were compared between the decidua basalis and decidua parietalis. RESULTS: Th2 and Tc2 cells accumulated in the decidua basalis in normal pregnancy. Accumulation of Tc2 cells and both Th2 and Tc2 cells decreased in the decidua basalis in RSA-A and RSA-N respectively. The number and percentage of Th2, and Tc2 cells in the decidua parietalis were similar in normal pregnancy, RSA-A and RSA-N. CONCLUSION: Decreased Th2 and Tc2 cells at the implantation site may contribute to RSA-N.

Abortion, Habitual↗
PubMed2002

Effect of acid suppression therapy on development of gastric erosions after cure of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori eradication markedly improves histological inflammation and decreases peptic ulcer recurrence, but little is known about the subsequent development of gastric mucosal injury. AIM: To investigate whether acid suppression treatment after eradication influences the development of gastric erosions. METHODS: Eighty-one patients (gastritis or peptic ulcer) after successful H. pylori eradication were divided into two groups: 40 received an H2-blocker for 6 months (H2-blocker-positive) and 41 received no treatment (H2-blocker-negative). Endoscopy was performed before, and at 3 and 6 months after completion of eradication. RESULTS: Cumulative prevalence of gastric erosions in the H2-blocker-positive group was significantly lower than in the H2-blocker-negative group, 25% vs. 42%, respectively. In the H2-blocker-negative group but not the H2-blocker-positive group, the cumulative prevalence of gastric erosions after eradication was higher in patients with less severe corpus atrophy or more severe corpus gastritis. CONCLUSIONS: Development of gastric erosions after H. pylori eradication may be controlled by acid suppression treatment. Less severe atrophy or more severe gastritis in oxyntic glands before eradication may be involved in the development of gastric erosions. These results support the idea that recovery of acid secretion may be one of factors for development of gastric mucosal erosions after successful eradication.

Biopsy↗
PubMed2002

Comparison of attractiveness in Japan and China of three synthetic pheromone blends based on geographic variations in the rice leaffolder, Cnaphalocrocis medinalis(Lepidoptera: Pyralidae).

Field bioassays using three different synthetic sex pheromone blends (Indian, Philippine and Japanese) based on geographic variations of Cnaphalocrocis medinalis Guenée were carried out at 11 sites in Japan and in Hangzhou, China. In all of the tests, only the Japanese pheromone blend attracted a significant number of male moths, while the Indian and Philippine pheromone blends showed no marked activity. The findings in Japan showed no evidence that moths of Philippine or Indian origin were able to migrate to Japan. The results from China also showed that most populations of C. medinalisin the Hangzhou region responded to the Japanese blend. This is consistent with the current hypothesis that most populations of C. medinalisin Japan are migrants from areas to the south of the Yangzhe Valley, including the region surrounding Hangzhou, China. Furthermore, populations in the Hangzhou region can not hibernate, but are considered migrants from the southernmost parts of China and southeast Asian countries such as Vietnam where they breed continuously. Consequently, at least some populations in these areas may respond to the Japanese pheromone blend.

Animals↗
PubMed2002

Influence of alcohol consumption on the association between serum lipids and colorectal adenomas.

BACKGROUND: There have been no reports that low serum cholesterol levels increase the risk of colorectal adenoma, although many studies have shown that they do increase the risk of colorectal cancer. Alcohol intake, which is associated with a risk of colorectal adenomas, and serum cholesterol levels are closely related. The purpose of this study was to evaluate the influence of alcohol consumption on the association between serum cholesterol levels and colorectal adenoma. METHODS: The subjects were 1,349 male patients who underwent both barium enema examination and total colonoscopy. They answered a questionnaire regarding their alcohol consumption history, and their blood samples were analysed. The subjects were divided into three groups: those with no tumour (with neither adenoma nor adenocarcinoma), those with adenoma and those with adenocarcinoma. Among the groups, the serum total cholesterol and triglyceride levels were compared in all the patients, in the patients who did not drink daily and in the patients who did. RESULTS: In all the patients, the serum cholesterol and triglyceride levels did not differ between the patients with and those without adenoma. In the daily drinkers, the serum cholesterol and triglyceride levels were significantly lower in patients with adenoma than in those without. CONCLUSIONS: Significantly lower levels of serum cholesterol and triglycerides were found in daily drinkers with adenoma than in those without.

Adenocarcinoma↗
PubMed2001

Coronary smooth muscle differentiation from proepicardial cells requires rhoA-mediated actin reorganization and p160 rho-kinase activity.

We recently reported that the first detectable expression of SMC-specific proteins during coronary smooth muscle cell (CoSMC) differentiation from isolated proepicardial cells was restricted to cells undergoing epithelial-to-mesenchymal transformation (EMT). The objectives of this study were to examine more closely the relation between actin cytoskeletal rearrangements and serum response factor (SRF)-dependent transcription, and to specifically test whether rhoA-GTPase signaling is required for CoSMC differentiation. We report here that PDGF-BB stimulates EMT and promotes SRF-dependent expression of SMC marker genes calponin, SM22alpha, and SMgamma(actin) (SMgammaA) in proepicardial cells. C3 exoenzyme or rhoGDI, inhibitors of rhoA signaling, blocked PDGF-BB-induced EMT, prevented actin reorganization into stress fibers, and inhibited CoSMC differentiation. Incubation with the selective p160 rho-kinase (p160RhoK) inhibitor Y27632 (RKI) blocked EMT, prevented the appearance of calponin and SMgammaA-positive cells, and abolished expression and nuclear localization of SRF. To test the role of RhoK signaling for CoSMC differentiation in vivo, quail proepicardial organs (PEOs) were pretreated with RKI or vehicle and then grafted into age-matched host chick embryos to produce a chimeric epicardium. The ability of grafted cells to participate in coronary vessel formation was monitored by staining with antibodies for quail cell nuclear antigen and SMC marker proteins. Proepicardial cells pretreated with RKI failed to form CoSMCs in vivo. Time course studies traced this deficiency to a failure of epicardial-derived mesenchymal cells to migrate into or survive within the myocardium. In summary, these data point to important roles for rhoA-RhoK signaling in molecular pathways controlling cytoskeletal reorganization, SRF-dependent transcription, and cell survival that are required to produce CoSMCs from proepicardial cells.

Actins↗
PubMed2001

Identification of ST2A1 as a rat brain neurosteroid sulfotransferase mRNA.

A hydroxysteroid sulfotransferase (ST2A1) was identified as a form mediating neurosteroid sulfation in rat brain. The sole expression among known rat ST2A forms was indicated by brain RT-PCR. All nucleotide sequences of seven ST2A cDNA clones isolated from brain matched completely with that of hepatic ST2A1. The recombinant ST2A1 protein mediated neurosteroid sulfation. These data strongly suggest a functional role of ST2A1 as a neurosteroid sulfotransferase in rat brain.

Animals↗
PubMed2001

Expression of hepatocyte growth factor activator and hepatocyte growth factor activator inhibitor type 1 in human hepatocellular carcinoma.

Hepatocyte growth factor activator inhibitor type 1 (HAI-1), a Kunitz-type serine protease inhibitor for hepatocyte growth factor activator (HGFA), is responsible for proteolytic activation of hepatocyte growth factor. We examined the expression of HGFA and HAI-1 in liver tissues of chronic liver diseases including hepatocellular carcinoma (HCC). HGFA expression was detected not only in the liver tissues of chronic hepatitis and cirrhosis and in the nontumorous liver tissues surrounding HCC, but also in HCC tissues. On the other hand, none of the liver tissues of hepatitis and cirrhosis and none of the nontumorous tissues surrounding HCC were stained with anti-HAI-1. However, 35% of HCC tissues were stained with anti-HAI-1, and HAI-1 positivity increased as the histological grade decreased and as serum alpha-fetoprotein increased. Transduction of antisense HAI-1 inhibited the growth of human hepatoma cells. These results suggest the possibility that HAI-1 plays an important role in the progression of HCC.

Base Sequence↗