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Biomedical subjects

K Hirai

Publications and source records attributed to K Hirai.

At least 73 records · Page 4Linked to original sources
PubMed2001

Regulation of mouse mast cell surface Fc epsilon RI expression by dexamethasone.

It is now clear that the mast cell's functional response to IgE-dependent stimulation can be influenced significantly by the level of expression of the high-affinity IgE receptor (Fc epsilon RI) on the cell's surface. Thus, modulation of Fc epsilon RI surface expression represents a potentially important mechanism for regulating mast cell activity in allergic reactions. In this study, we examined whether a glucocorticoid, dexamethasone (DEX), can influence levels of mast cell Fc epsilon RI expression either in the presence or absence of IgE, an up-regulator of the mast cell surface Fc epsilon RI level. In the absence of IgE, DEX decreased the surface Fc epsilon RI levels in mouse peritoneal mast cells, mouse bone marrow-derived cultured mast cells and a mouse mast cell line, Cl.MC/C57.1. Moreover, DEX also partially suppressed the ability of IgE to enhance surface expression of Fc epsilon RI in these cells. Three different glucocorticoids, DEX, methylprednisolone and hydrocortisone, suppressed Fc epsilon RI expression in mast cells, whereas sex steroids, i.e. estradiol, progesterone and testosterone, did not, indicating that the Fc epsilon RI-suppressing effect is glucocorticoid specific. On the other hand, DEX did not affect levels of Fc epsilon RI alpha, beta or gamma mRNA, suggesting that its ability to decrease surface Fc epsilon RI reflects a post-transcriptional mechanism. Finally, DEX-treated mast cells showed a reduced degranulation response to antigenic stimulation through down-regulation of surface Fc epsilon RI expression in addition to DEX-induced changes in downstream signals. These results show that mast cell surface Fc epsilon RI expression is suppressed by glucocorticoids in both the presence and absence of IgE, and suggest that reduction of mast cell surface Fc epsilon RI levels may be one of the favorable anti-allergic actions of glucocorticoids.

Animals↗
PubMed2001

Randomized phase I study of standard-fractionated or accelerated-hyperfractionated radiotherapy with concurrent cisplatin and vindesine for unresectable non-small cell lung cancer: a report of Japan Clinical Oncology Group Study (JCOG 9601).

BACKGROUND: We attempted dose escalation of standard-fractionated and accelerated-hyperfractionated radiotherapy combined with concurrent cisplatin and vindesine to improve local control and survival in unresectable non-small cell lung cancer. METHODS: Twenty-one patients were enrolled between June 1996 and August 1997. There were 19 males and two females and their median age was 65 years (range 45-74 years). Performance status was 0 in 10 cases and 1 in 11 cases. Disease stage was IIIA in three cases and IIIB in 18 cases. The cases were randomized to a standard-fractionated arm (n = 10) or an accelerated-hyperfractionated radiotherapy arm (n = 11) with two or three cycles of concomitant cisplatin 80 mg/m(2) on day 1 and vindesine 3 mg/m(2) on days 1 and 8 every 4 weeks in both arms. Dose escalation from 60 Gy/30 fractions/6 weeks to 70 Gy/35 fractions/7 weeks was planned in the standard-fractionated radiotherapy group and from 54 Gy/36 fractions/3.6 weeks to 60 Gy/40 fractions/4 weeks and then 66 Gy/44 fractions/4.4 weeks in the accelerated-hyperfractionated radiotherapy group. RESULTS: Grade 3 or 4 hematological toxicities were observed as follows: in the standard-fractionated/accelerated-hyperfractionated radiotherapy group, leukocytopenia 9/10, anemia 2/3 and thrombocytopenia 0/2. Grade 3 non-hematological toxicity consisted of esophagitis 0/3, increased serum total bilirubin 2/0 and hypoxia 0/1. Two patients died of radiation pneumonitis in the standard-fractionated radiotherapy group. Dose-limiting toxicity was observed in four of the 10 and seven of the 11 patients at initial dose level of standard-fractionated radiotherapy, 60 Gy/30 fractions/6 weeks, and of accelerated-hyperfractionated radiotherapy, 54 Gy/36 fractions/3.6 weeks, respectively. Thus, we failed to escalate the dose of radiotherapy in both arms. The overall response rate in the standard-fractionated group and the accelerated-hyperfractionated radiotherapy group was 70 and 73% and the 1-year survival rate was 70 and 64%, respectively. CONCLUSIONS: We concluded that these schedules of radiotherapy with concurrent cisplatin and vindesine were unacceptable for use in patients with unresectable non-small cell lung cancer. Further modifications of the schedule for radiotherapy and evaluation of combination with new chemotherapy are warranted.

Aged↗
PubMed2001

Oxidative damage is the earliest event in Alzheimer disease.

Recently, we demonstrated a significant increase of an oxidized nucleoside derived from RNA, 8-hydroxyguanosine (8OHG), and an oxidized amino acid, nitrotyrosine in vulnerable neurons of patients with Alzheimer disease (AD). To determine whether oxidative damage is an early- or end-stage event in the process of neurodegeneration in AD, we investigated the relationship between neuronal 8OHG and nitrotyrosine and histological and clinical variables, i.e. amyloid-beta (A beta) plaques and neurofibrillary tangles (NFT), as well as duration of dementia and apolipoprotein E (ApoE) genotype. Our findings show that oxidative damage is quantitatively greatest early in the disease and reduces with disease progression. Surprisingly, we found that increases in A beta deposition are associated with decreased oxidative damage. These relationships are more significant in ApoE epsilon4 carriers. Moreover, neurons with NFT show a 40%-56% decrease in relative 8OHG levels compared with neurons free of NFT. Our observations indicate that increased oxidative damage is an early event in AD that decreases with disease progression and lesion formation. These findings suggest that AD is associated with compensatory changes that reduce damage from reactive oxygen.

Aged↗
PubMed2001

Apoptosis of muscle cells causes weight loss prior to impairment of DNA synthesis in tumor-bearing rabbits.

The mechanism of weight loss induced by the growth of malignant tumors is still unknown. We investigated it by focusing on apoptosis of skeletal muscle. VX2-tumor was implanted into rabbits and the apoptotic index (AI) of skeletal muscle was measured by in situ end-labeling assay. Plasma of the tumor-bearing rabbits was perfused repeatedly through non-coated charcoal resin. The AI reached 54.6% early after tumor implantation, when weight loss amounted to an 18% decrease in lean body mass (LBM) without change in muscle DNA synthesis or urinary 3-methylhistidine / creatinine ratio (3-MH / Cr). When the decrease of LBM reached 30%, DNA synthesis was decreased by 48% and 3-MH / Cr was increased by 104%, whereas AI was only 4.7%. The plasma perfusion did not prevent apoptosis in muscle, but improved LBM, DNA synthesis, and 3-MH / Cr. There may be two mechanisms of muscle depletion during the tumor growth: apoptosis in the early stage and metabolic abnormalities in muscle in the late stage.

Animals↗
PubMed2001

Expression of apoptosis regulatory proteins in the skeletal muscle of tumor-bearing rabbits.

We reported finding that apoptosis occurred in skeletal muscle in the early stage after implantation. In the present study, we investigated expression of the apoptosis-related proteins Bax and Bcl-2 to determine the mechanism of the apoptosis. In the early stage of tumor bearing, 20 days after implantation, lean body mass (LBM) was reduced by 5.06 +/- 1.10% in the tumor-bearing group, compared with an increase of 4.96 +/- 1.26% in the control group. The apoptotic index (AI) of the skeletal muscle in the tumor-bearing group increased to 40.5 +/- 3.20% but was 0% in the control group, and Bax expression was strongly positive in 5 of the 10 rabbits in the tumor-bearing group, and significantly stronger than in the control group (P = 0.0002). In the late stage of tumor bearing, 40 days after implantation, the AI had declined to 0.93 +/- 0.96% in the tumor-bearing group, but was still 0% in the control group. Bax expression was rarely detected in either the tumor-bearing group or the control group, and there was no significant difference between the two groups (P = 0.706). No significant changes in Bcl-2 were observed in either group. The above results showed that apoptosis via Bax played a role in muscle wasting associated with progression of the malignant tumor. However, the apoptosis and expression of Bax were seen only in the early stage, within 20 days after implantation, not in the late stage. This suggested that the muscle wasting in the early stage might be caused by a different mechanism from that in the late stage.

Animals↗
PubMed2001

Activation of TRAF5 and TRAF6 signal cascades negatively regulates the latent replication origin of Epstein-Barr virus through p38 mitogen-activated protein kinase.

Latent Epstein-Barr virus (EBV) is maintained by the virus replication origin oriP that initiates DNA replication with the viral oriP-binding factor EBNA1. However, it is not known whether oriP's replicator activity is regulated by virus proteins or extracellular signals. By using a transient replication assay, we found that a low level of expression of viral signal transduction activator latent membrane protein 1 (LMP1) suppressed oriP activity. The binding site of the tumor necrosis factor receptor-associated factor (TRAF) of LMP1 was essential for this suppressive effect. Activation of the TRAF signal cascade by overexpression of TRAF5 and/or TRAF6 also suppressed oriP activity. Conversely, blocking of TRAF signaling with dominant negative mutants of TRAF5 and TRAF6, as well as inhibition of a downstream signal mediator p38 MAPK, released the LMP1-induced oriP suppression. Furthermore, activation of TRAF6 signal cascade by lipopolysaccharides (LPS) resulted in loss of EBV from Burkitt's lymphoma cell line Akata, and inhibition of p38 MAPK abolished the suppressive effect of LPS. These results suggested that the level of oriP activity is regulated by LMP1 and extracellular signals through TRAF5- and TRAF6-mediated signal cascades.

Binding Sites↗
PubMed2001

Identification of major phosphorylation sites of Epstein-Barr virus nuclear antigen leader protein (EBNA-LP): ability of EBNA-LP to induce latent membrane protein 1 cooperatively with EBNA-2 is regulated by phosphorylation.

Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is a phosphoprotein suggested to play important roles in EBV-induced immortalization of B cells. One of the potential functions of EBNA-LP is a cooperative induction with EBNA-2 of viral and cellular gene expression, including that of the genes for viral latent membrane protein 1 (LMP-1) and cellular cyclin D2. We report here that the phosphorylation of EBNA-LP by cellular kinase(s) is critical to its ability to cooperate with EBNA-2 in up-regulating the expression of LMP-1 in a B-lymphoma cell line. Our conclusion is based on the following observations. (i) Mass-spectrometric analysis of purified EBNA-LP and mutational analyses of EBNA-LP revealed that the serine residue at position 35 in the W2 repeat domain is the major phosphorylation site of EBNA-LP in vivo. (ii) Substitutions of this site in each W2 repeat domain with alanine markedly reduced the ability of the protein to induce LMP-1 expression in combination with EBNA-2 in Akata cells. (iii) Replacement at the major phosphorylation sites with glutamic acids restored the wild-type phenotype. It is well established that this substitution mimics constitutive phosphorylation. These results indicated that the coactivator function of EBNA-LP is regulated by phosphorylation.

Alanine↗
PubMed2001

Calcium preconditioning inhibits mitochondrial permeability transition and apoptosis.

We tested the hypothesis whether calcium preconditioning (CPC) reduces reoxygenation injury by inhibiting mitochondrial permeability transition (MPT). Cultured myocytes were preconditioned by a brief exposure to 1.5 mM calcium (CPC) and subjected to 3 h of anoxia followed by 2 h of reoxygenation (A-R). Myocytes were also treated with 0.2 microM/l cyclosporin A (CsA), an inhibitor of MPT, before A-R. A significant increase of viable cells and reduced lactate dehydrogenase release was observed both in CPC- and CsA-treated myocytes compared with the A-R group. Cytochrome c release was predominantly observed in the cytoplasm of myocytes in the A-R group in contrast with CPC- or CsA-treated groups, where it was restricted only to mitochondria. Similarly, the cell death by apoptosis was also markedly attenuated in these groups. Electron-dense Ca(2+) deposits in mitochondria were also less frequent. Atractyloside (20 microM/l), an adenine nucleotide translocase inhibitor, caused changes similar to those in the A-R group, suggesting a role of MPT in A-R injury. Protection by inhibition of MPT by CsA and CPC suggests that MPT plays an important role in reoxygenation/reperfusion injury. The data further suggest that preconditioning inhibits MPT by inhibiting Ca(2+) accumulation by mitochondria.

Animals↗
PubMed2001

Clinical evaluation of the Q-tip test in normal pregnant women.

The crisis frequency of stress incontinence (SI) is known to be high among pregnant women. This preliminary study was performed to determine whether the diagnostic standard of the Q-tip test used in the diagnosis of SI in nonpregnant women is applicable to pregnant women. The Q-tip tests were performed regularly during pregnancy and after parturition on primipara (n = 71) and multipara (n = 55) who were not in SI crisis at any time during the pregnancy. The values measured in multipara were significantly higher than in primipara (p = 0.0001), and the tendency to be higher was more prominent at 2-5 months and 10 months of pregnancy. These findings show that different normal values of the Q-tip test are necessary for primipara and multipara.

Adult↗
PubMed2001

Cirsoid aneurysm after hysterectomy.

Cirsoid aneurysm, an uncommon abnormal either congenital or acquired arteriovenous communication, is described. As massive life-threatening bleeding can be a consequence, diagnosis is very important. Earlier, angiography was the only imaging method available for visualizing vascular lesions and recent developments in imaging techniques have made diagnostic imaging of cirsoid aneurysms possible using ultrasonography, color flow mapping, magnetic resonance imaging and magnetic resonance angiography. In this report, a patient with intrapelvic cirsoid aneurysm posthysterectomy who died 8 h after she had been kicked in the abdomen is described and the results obtained by various imaging techniques are discussed.

Abdominal Injuries↗
PubMed2001

Regulation of surface FcepsilonRI expression on human eosinophils by IL-4 and IgE.

BACKGROUND: Recent studies have demonstrated that eosinophils from allergic patients express low levels of FcepsilonRI on their surface, but the regulatory mechanisms of eosinophil surface FcepsilonRI expression are not fully understood. We investigated whether IL-4 and IgE, which are reported to regulate surface FcepsilonRI expression on human mast cells, are able to affect surface FcepsilonRI expression in normal human eosinophils. METHODS: Eosinophils purified from peripheral blood were cultured with IL-5 and with or without IL-4 and/or IgE, and surface FcepsilonRI expression was analyzed by flow cytometry using an anti-FcepsilonRI mAb, CRA-1. RESULTS: Apparent FcepsilonRI expression (approximately 1% of mast cell FcepsilonRI levels) was observed in eosinophils cultured with both IL-4 and IgE. A combination of IL-4 (>or=1 ng/ml) and IgE (>or= 0.5 microg/ml) was necessary for the maximal induction of surface FcepsilonRI expression. In the presence of IL-4 and IgE, eosinophils cultured for 2 days demonstrated low but statistically significant levels of surface FcepsilonRI, which reached a plateau after 7 days of culture. However, cross-linkage of surface FcepsilonRI molecules by CRA-1 or anti-IgE did not induce any eosinophil activation. CONCLUSIONS: IL-4 and IgE can affect the levels of surface FcepsilonRI on normal human eosinophils. FcepsilonRI expression on eosinophils may be regulated by a mechanism similar to that in mast cells.

Cells, Cultured↗
PubMed2001

Regulation of chemokine receptor expression in eosinophils.

Signals via chemokine receptors play an important role in the accumulation of eosinophils at allergic inflammatory sites. Eosinophils constitutively express CC chemokine receptor 3 (CCR3) and, to a lesser extent, CCR1. CCR3 is mainly responsible for migration of resting eosinophils, and its specific ligand, eotaxin, represents the most potent chemoattractant for eosinophils. Some reports also suggest the expression of CXC chemokine receptor 1 (CXCR1) and/or CXCR2 in eosinophils. In addition, we recently reported the functional expression of CXCR4. The ligand of CXCR4, stromal cell-derived factor-1 (SDF-1), was able to induce a strong migratory response comparable to that by eotaxin. In contrast to the CCR3/eotaxin system which is mainly regulated at the level of ligand production, the CXCR4/SDF-1 system is regulated at the level of receptor expression. CXCR4 expression was completely attenuated by IL-4 and IL-5 and upregulated by IFN-gamma and dexamethasone, while CCR3 expression was only marginally affected. The balance between the biological effects of these chemokine systems may affect the distribution and migration of eosinophils.

Animals↗
PubMed2001

Stilbenoids in lianas of Gnetum parvifolium.

Five new stilbene dimers were isolated from the lianas of Gnetum parvifolium in addition to known stilbenoids. The structures of the compounds were established on the basis of spectroscopic evidence, including long-range coupling and nuclear Overhauser effect experiments, in NMR spectrum. Among the isolates, 2b-hydroxyampelopsin F showed potent inhibitory activity in the Maillard reaction.

Acetylation↗
PubMed2001

[Awareness of the health and defecation tendencies among college students by location of domicile].

In order to compare the food habits and defecation tendencies by region, a questionnaire survey was conducted of 1722 college women (18-20 years of age) living in Sapporo (146), Sendai (183), Osaka (1214), and Kumamoto (179). (1) When questioned about food habits, less than 58.5% of the respondents in the four groups considered their food intake to be sufficient to maintain their health. In regard to knowledge about their food intake requirements, the positive response was the highest in Sendai (85.8%), followed by Kumamoto (58.2%) and Osaka (50.9%) with the lowest in Sapporo (41.1%) (p < 0.01, among the four groups). (2) The students in Sendai, Osaka, Kumamoto and Sapporo, 96.2%, 93.5%, 92.9% and 92.5%, respectively, considered that constipation could affect their health (p < 0.05, among four groups). The percentage of those with regular bowel movements every day, tended to decrease in the order of Osaka (22.2%), Sapporo (21.2%) and Sendai (20.8%), with the lowest in Kumamoto (12.3%). Bowel movements of less than three times a week were reported by 24.7% in Sapporo, 24.0% in Sendai, 23.2% in Osaka and 22.3% in Kumamoto (p < 0.01, among the four groups). (3) Of those who defecated every day, in terms of time of day, the percentage was high between waking and after breakfast, with the highest percentage in Kumamoto (72.8%) and the lowest in Sapporo (61.2%) (p < 0.05, among the four groups). For subjects that responded that they should have a bowel movement every day, the highest percentage was in Osaka (91.0%) and the lowest was in Sapporo (83.9%) (p < 0.05, among the four groups).

Adolescent↗
PubMed2001

Isolation of monoclonal antibodies that inhibit the binding of infectious bursal disease virus to LSCC-BK3 cells.

Three hybridoma cell lines producing monoclonal antibodies (MAbs) against LSCC-BK3 cells which are susceptible to infectious bursal disease virus (IBDV) infection were produced and characterized. The MAbs, designated T7, Q11 and Q13, inhibited the attachment of IBDV to LSCC-BK3 cells. Furthermore, these MAbs bound to LSCC-BK3 but not to nonpermissive cells in flow cytometry. MAb T7 detected a 110-kDa membrane protein of LSCC-BK3 cells, whereas Q11 and Q13 reacted with membrane proteins of molecular weights 58-, 85-, 90- and 110-kDa. These observations imply that the 110-kDa protein recognized by all the MAbs is associated with IBDV binding. The MAbs established in this study are useful for studying the interaction between IBDV and its target cell.

Animals↗
PubMed2001

Detection of cell membrane proteins that interact with virulent infectious bursal disease virus.

To detect the molecules that interact with infectious bursal disease virus (IBDV), the chicken B lymphoblastoid cell line, LSCC-BK3, which is permissive for virulent IBDV infection was investigated. The sodium dodecyl sulfate-solubilized plasma membrane fraction from the cells was subjected to a virus overlay protein binding assay. The IBDV specifically bound to proteins in LSCC-BK3 plasma membranes with molecular weights of 70, 82 and 110 kDa. This is the first report to demonstrate cellular molecules that interact with virulent IBDV.

Animals↗