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H Kita

Publications and source records attributed to H Kita.

At least 73 records · Page 4Linked to original sources
PubMed1999

Effects of dopamine agonists and antagonists on optical responses evoked in rat frontal cortex slices after stimulation of the subcortical white matter.

Effects of dopamine agonists and antagonists on the optical response of frontal cortical slices to stimulation of the subcortical white matter were examined using a voltage-sensitive dye and a high-speed image sensor. In the slices treated with bicuculline, stimulation of the white matter evoked optical responses propagating to the overlaying cortex. Bath application of the D1 agonist, chloro-APB (1 microM), consistently decreased the intensity of the early part of the response but increased the duration of the response occurring at the superficial layers of the cortex. Application of the D1 antagonist, SCH 23390 (1 microM), resulted in a small increase in both the intensity and the duration of the response. Bath application of the D2 agonist, quinpirole (1-10 microM), reduced the response occurring after 10 ms from stimulation. The effects of chloro-APB and quinpirole were additive. Application of the D2 antagonist, eticlopride, did not cause a significant change in the response but effectively blocked the quinpirole effects. This study suggests that although both D1 and D2 agonists reduced the peak optical response evoked in the slices of the frontal cortex, the two agonists exerted different temporal and spatial effects.

2-Amino-5-phosphonovalerate↗
PubMed1999

Expression of N-methyl-D-aspartate receptor-dependent long-term potentiation in the neostriatal neurons in an in vitro slice after ethanol withdrawal of the rat.

To examine changes in corticostriatal synaptic transmission in rats with ethanol withdrawal syndrome, intracellular and extracellular responses to subcortical white matter stimulation were recorded in neostriatal slice preparations. The resting membrane potential, input resistance and depolarizing postsynaptic potentials to single cortical white matter stimulation were similar in the neostriatum of naive and ethanol withdrawal rats. Repetitive stimulation of the white matter induced more pronounced N-methyl-D-aspartate receptor-mediated postsynaptic potentials in ethanol withdrawal than naive rat neostriatum. In intracellular recording, tetanic stimulation (50 Hz, 20 s) induced more pronounced post-tetanic potentiation of depolarizing postsynaptic potentials in the neostriatum of ethanol withdrawal than naive rats. However, in extracellular recording, tetanic stimulation induced smaller post-tetanic depression of population spikes in the neostriatum of ethanol withdrawal than naive rats. Tetanic stimulation of the subcortical white matter induced long-term potentiation of postsynaptic potentials and population spikes in the ethanol withdrawal rat neostriatum, while long-term depression was evoked in the naive rat neostriatum. The induction of long-term potentiation was blocked by D-2-amino-5-phosphonovaleric acid or 7-chlorokynurenic acid, N-methyl-D-aspartate receptor antagonists, but not by (RS)-methyl-4-carboxyphenyl-glycine, a metabotropic glutamate receptor antagonist. Dopamine also significantly depressed the induction of long-term potentiation in ethanol withdrawal rat neostriatum and this depressant effect was antagonized by the D2 antagonist L-sulpiride but not by the D1 antagonist SCH23390. These results indicate that the N-methyl-D-aspartate component of the corticostriatal glutamatergic responses, which might be necessary for induction of long-term potentiation, was enhanced in ethanol withdrawal rats. The depression of long-term potentiation induction by activation of D2 receptor suggests that corticostriatal N-methyl-D-aspartate response or intracellular mechanisms involving in the induction of the long-term potentiation can be suppressed by D2 activation and that the D2 effects are inhibited in the neostriatum of ethanol withdrawal rats.

Animals↗
PubMed1999

Chronic treatment with an ACE inhibitor, temocapril, lowers the threshold for the infarct size-limiting effect of ischemic preconditioning.

This study examined whether chronic inhibition of the angiotensin-converting enzyme (ACE) lowers the threshold of preconditioning (PC) and potentiates cardio-protection of subthreshold PC. Rabbits were orally administered either 0.5 mg/kg/day temocapril or placebo for 14 days and were randomly subjected to subthreshold PC (i.e., PC with 2 minutes ischemia/5 minutes reperfusion) or no PC before a 30-minute coronary artery occlusion and a 3-hour reperfusion. The size of the infarct was determined by tetrazolium staining and was expressed as the percent of the area at risk (%IS/AR). At the end of the experiment, the lungs were sampled for a tissue ACE activity assay. There was no significant difference in %IS/AR among the rabbits given placebo alone, placebo plus 2 minutes PC, and temocapril alone (%IS/AR = 59.5 +/- 5.8%, 43.6 +/- 3.7%, and 56.7 +/- 7.1%, respectively). However, %IS/AR was significantly reduced in the group that received temocapril and 2 minutes PC before infarction (%IS/AR = 35.4 +/- 4.8%, P < 0.05 vs. placebo control and temocapril control). The lung tissue ACE activity did not differ in the placebo-treated rabbits with and without PC (12.6 +/- 2.8 vs. 13.7 +/- 2.0 nmol/g protein/min) but was suppressed in temocapril-treated rabbits despite 2 minutes PC (0.9 +/- 0.1 vs. 1.5 +/- 0.2 nmol/g protein/min, both P < 0.05 vs. placebo-treated groups). The present results suggest that chronic inhibition of ACE is beneficial for potentiating the anti-infarct effect of subthreshold PC.

Administration, Oral↗
PubMed1999

Cytokine and chemokine induction using cell wall component and toxin derived from gram-positive bacteria in the rat middle ear.

Lipoteichoic acid (LTA) is one of the components present within the cell wall layer of most gram-positive bacteria. It plays an important role in the initiation and progression of bacterial infection. In this study, we performed a rat middle ear and nasal perfusion with LTA purified from two different gram-positive bacterial species. Using ELISA and RT-PCR, the production and mRNA expression of rat chemokine, GRO/CINC-1, proinflammatory cytokine, TNF-alpha, in rat middle ear lavage and mucosa were investigated. GRO/CINC-1 in middle ear lavage was produced by stimulation of LTA in a time-dependent fashion; however, TNF-alpha production into the lavage was not detectable using ELISA assay. The mRNA expressions of GRO/CINC-1 and TNF-alpha in the middle ear mucosa were both induced after LTA and exotoxin exposures. The expression of IL-10 mRNA was also induced after 6 h of LTA and exotoxin exposures. The profile of the production of GRO/CINC-1 and TNF-alpha in rat nasal lavage was similar to that in the middle ear; however, the mRNA expressions of GRO/CINC-1, TNF-alpha and IL-10 in the nasal mucosa were different from those in the middle ear mucosa. These results suggest that the cell wall component and exotoxin of gram-positive bacteria can induce several cytokines in vivo and play an important role in the initiation of the inflammatory cascade in the middle ear.

Animals↗
PubMed1999

Expression profiling by iAFLP: A PCR-based method for genome-wide gene expression profiling.

The availability of comprehensive sets of genes has prompted the researchers to carry out systematic collection of gene expression data. RT-PCR has the highest specificity and sensitivity for transcript detection among all available methods. Low throughput, especially when quantitative data are desired, has precluded RT-PCR from genome-wide application. Here we report a PCR-based expression profiling method, introduced amplified fragment length polymorphism (iAFLP), that has the same specificity and sensitivity as RT-PCR and a throughput level comparable to that of DNA-microarray hybridization. In this method, restricted ends of total cDNAs from six sources were ligated with adaptors having various length of short insertions to a common sequence (polymorphic adaptors). Amplification of a pool of these differentially adapted cDNAs with a gene-specific primer and an adaptor primer allows us to quantitate the abundance of any transcript in six mRNA sources. Using three different primer colors this technique allows quantitation of expression of 864 genes across six different sources per day with a single autosequencer, which is comparable to the throughput of microarray analysis in terms of number of genes x number of sources.

Animals↗
PubMed1999

In vivo and in vitro toxicodynamic analyses of new quinolone-and nonsteroidal anti-inflammatory drug-induced effects on the central nervous system.

We investigated the correlation between an in vivo isobologram based on the concentrations of new quinolones (NQs) in brain tissue and the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) for the occurrence of convulsions in mice and an in vitro isobologram based on the concentrations of both drugs for changes in the gamma-aminobutyric acid (GABA)-induced current response in Xenopus oocytes injected with mRNA from mouse brains in the presence of NQs and/or NSAIDs. After the administration of enoxacin (ENX) in the presence or absence of felbinac (FLB), ketoprofen (KTP), or flurbiprofen (FRP), a synergistic effect was observed in the isobologram based on the threshold concentration in brain tissue between mice with convulsions and those without convulsions. The three NSAIDs did not affect the pharmacokinetic behavior of ENX in the brain. However, the ENX-induced inhibition of the GABA response in the GABAA receptor expressed in Xenopus oocytes was enhanced in the presence of the three NSAIDs. The inhibition ratio profiles of the GABA responses for both drugs were analyzed with a newly developed toxicodynamic model. The inhibitory profiles for ENX in the presence of NSAIDs followed the order KTP (1.2 microM) > FRP (0. 3 microM) > FLB (0.2 microM). These were 50- to 280-fold smaller than those observed in the absence of NSAIDs. The inhibition ratio (0.01 to 0.02) of the GABAA receptor in the presence of both drugs was well-fitted to the isobologram based on threshold concentrations of both drugs in brain tissue between mice with convulsions and those without convulsions, despite the presence of NSAIDs. In mice with convulsions, the inhibitory profiles of the threshold concentrations of both drugs in brain tissue of mice with convulsions and those without convulsions can be predicted quantitatively by using in vitro GABA response data and toxicodynamic model.

Animals↗
PubMed1999

Effect of interleukin-3, interleukin 5 and hyaluronic acid on cultured eosinophils derived from human umbilical cord blood mononuclear cells.

BACKGROUND: Several studies have shown that cultured eosinophils can be generated from human umbilical cord blood mononuclear cells (UCMC) in the presence of interleukin (IL)-3 and IL-5 in vitro. Other reports have indicated that cellular adhesion to hyaluronic acid (HA) enhances the proliferation of cultured eosinophils derived from CD34+ cells purified from UCMC. The aim of this study was to obtain large numbers of mature eosinophils from UCMC using IL-3, IL-5 and HA, and to investigate their functions. METHODS: We examined several combinations of IL-3 and IL-5 and their effect on eosinophil development from UCMC in HA-coated on non-coated flasks. We also examined whether cultured eosinophils degranulated eosinophil-derived neurotoxin (EDN) induced by secretory immunoglobulin A conjugated to sepharose beads (sIgA-beads) and responded to eotaxin. RESULTS: Culture with HA-coated flasks for 35 days (in the presence of IL-3 and IL-5, with IL-3 omitted after day 14 of culture) caused a 11.2-fold augmentation in the proliferation of UCMC. On day 35 of the culture, 98% of cultured cells were eosinophils judging from May-Grünwald and Giemsa staining and transmission electron micrographs. The EDN content of the cultured eosinophils on day 35 was 156 ng/105 cells. Cultured eosinophils degranulated EDN induced by sIgA-beads and responded to eotaxin by chemotaxis and intracellular Ca2+ mobilization. CONCLUSION: We found a useful culture system to obtain large numbers of eosinophils derived from UCMC, which may facilitate the investigation of eosinophil function, since there was no significant difference in response to sIgA-beads and eotaxin between cultured and peripheral eosinophils.

Cell Degranulation↗
PubMed1999

Intracellular signaling pathways in human eosinophil activation: role of a beta2 integrin, alphaMbeta2.

Cellular adhesion is crucial roles for eosinophil effector functions such as degranulation. Here, we focused on the role of a beta2 integrin, alphaMbeta2, in intracellular signaling pathways of human eosinophil activation. We found that the ligation of alphaMbeta2 triggers the activation of an intracellular signaling cascade, including protein tyrosine phosphorylation and phosphoinositide turnover, and subsequent cellular degranulation in human eosinophils. These signaling events may play important roles in adhesion-dependent cellular functions of eosinophils.

Cell Adhesion↗
PubMed1999

The efficacy of a custom-fabricated nasal mask on gas exchange during nasal intermittent positive pressure ventilation.

Commercially available nasal masks have a large mask volume and give rise to considerable air leaks around the mask during nasal intermittent positive pressure ventilation (NIPPV) which may reduce alveolar ventilation (VA per breath). The effects of a custom-fabricated nasal mask (F-mask) versus a commercially available mask (C-mask) on arterial blood gas measurements, dead space including both physiological and apparatus dead space (VD), air leak and VA per breath were compared in patients with restrictive thoracic disease during short-term NIPPV sessions while using a volume cycled ventilator with equivalent settings for both masks. The mask volume of the C-mask was significantly larger than that of the F-mask (p<0.003). The arterial carbon dioxide tension (Pa,CO2) during NIPPV with either the F-mask (5.56+/-1.35 kPa) (mean+/-SD) or the C-mask (6.87+/-0.96 kPa) was significantly lower than during spontaneous breathing (7.75+/-0.81 kPa; p<0.003), but the Pa,CO2 decreased more during NIPPV with the F-mask than with the C-mask (p<0.003). The VD was significantly smaller (p<0.03), the air leak was significantly less (p<0.03), and the VA per breath was significantly larger (p<0.03) during NIPPV with the F-mask than with the C-mask. In conclusion, nasal intermittent positive pressure ventilation with the F-mask was more effective than nasal intermittent positive pressure ventilation with the commercially available mask due to its smaller dead space and less air leak. Further studies are needed to extend these results to all the commercially available-masks.

Blood Gas Analysis↗
PubMed1999

[An autopsy case of MPO-ANCA-positive microscopic polyangiitis with manifestations of pulmonary hemorrhage and diffuse alveolar damage].

A 68-year-old woman was admitted to our hospital because of fever of unknown origin and pain in the lower extremities. Six weeks after onset, diffuse infiltrative shadows were observed on chest X-ray films, and marked hypoxemia and progressive renal dysfunction suddenly developed. Corticosteroid therapy (2 courses of pulse therapy, each consisting of methylprednisolone at 500 mg/day for 3 days) was not effective, and the patient died 9 weeks after onset because of respiratory failure. Serologic tests were positive for MPO-ANCA. Histopathologic findings at autopsy disclosed arteriolar fibrinoid necrosis in tissues of the liver, spleen, lungs, and kidneys, thus yielding a diagnosis of microscopic polyangiitis. Lung specimens also demonstrated massive alveolar hemorrhaging in the mid-lung fields and diffuse alveolar damage (DAD) in all lobes. Pulmonary hemorrhage coexistent with DAD worsens the prognosis for microscopic polyangiitis in patients positive for MPO-ANCA.

Aged↗
PubMed1998

A Case of Dermatofibrosarcoma Protuberans in the Skin over the Breast of a Young Woman.

A 19-year-old woman with dermatofibrosarcoma protuberans (DFSP) of the breastis described. She presented with a tumor of the left breast with redness and swelling. She had noticed a small tumor five years previously, but it had begun togrow rapidly three months previously. Mammography, ultrasonography and aspiration biopsy cytology demonstrated an apparently benign tumor of the breast preoperatively. Wide excision was performed to confirm the diagnosis. Histologically, the tumor was composed of a uniform population of fibroblasts in a distinct storiform pattern. DFSP was diagnosed in the skin over the breast. This lesion ordinarily originates from the dermis in the trunk and proximal extremities. It is important to diagnose a soft tissue lesion accurately when it occurs in the breast.

Journal Article↗
PubMed1998

Interaction with secretory component stimulates effector functions of human eosinophils but not of neutrophils.

Eosinophils and their products are important in the pathophysiology of allergic inflammation in mucosal tissues. Secretory component bound to IgA mediates transepithelial transport of IgA and confers increased stability on the resultant secretory IgA; however, the effect of secretory component on the biologic activity of IgA is unknown. Here, we report that secretory IgA and secretory component preferentially activate human eosinophils. When eosinophils were stimulated with immobilized secretory IgA, degranulation and superoxide production were two- to threefold greater than when stimulated with serum IgA. In contrast, neutrophils responded similarly to secretory IgA and serum IgA. Flow cytometric analysis showed that eosinophils bound to purified secretory component. The binding of 125I-labeled secretory component was inhibited by unlabeled secretory component or secretory IgA but not by serum IgA. Superoxide production by eosinophils stimulated with cytokines or IgG was enhanced synergistically by immobilized secretory component; secretory component showed no effect on neutrophil activation. Finally, anti-CD18 mAb abolished eosinophil superoxide production stimulated with secretory IgA or secretory component but not with serum IgA, suggesting a crucial role for beta2 integrins in eosinophil interactions with secretory IgA or secretory component. Thus, secretory component plays important roles in activating eosinophil functions but not neutrophil functions. This preferential interaction between secretory component and eosinophils may provide a novel mechanism to regulate mucosal tissue inflammation.

CD18 Antigens↗
PubMed1998

Sulfonylureas inhibit cytokine-induced eosinophil survival and activation.

Eosinophils play a key role in the pathogenesis of asthma and other allergic inflammatory diseases. We have previously shown that treatment of eosinophils with lidocaine preferentially inhibits IL-5-induced survival. This inhibition cannot be overcome by increasing concentrations of IL-5 and is not due to the blocking of Na+ channels by lidocaine. Here we report that one class of K+ channel blockers, the sulfonylureas, inhibits eosinophil survival in a manner similar to lidocaine. The sulfonylurea glyburide inhibits eosinophil survival even at high concentrations of IL-5. In contrast, increasing concentrations of IL-3 or granulocyte-macrophage CSF overcome glyburide inhibition. Glyburide also blocks cytokine-induced eosinophil superoxide production. Similar results were seen with the sulfonylureas tolbutamide and glipizide. Interestingly, the effects of glyburide are not antagonized by the ATP-sensitive K+ channel openers cromakalim, pinacidil, or diazoxide. Although Scatchard analysis of [3H]glyburide binding to eosinophil membranes indicated that the high affinity sulfonylurea receptor (SUR1) is not present on eosinophils, human eosinophils do express mRNA homologous to the sulfonylurea receptor family, in keeping with the presence of a sulfonylurea receptor. Finally, coculture of eosinophils with combinations of glyburide, lidocaine, and dexamethasone resulted in synergistic inhibition of cytokine-mediated eosinophil survival and superoxide production. These results have intriguing clinical implications for the treatment of eosinophil-associated diseases.

ATP-Binding Cassette Transporters↗
PubMed1998

Lidocaine and its analogues inhibit IL-5-mediated survival and activation of human eosinophils.

Eosinophils and cytokines active on eosinophils, especially IL-5, are believed to be critically involved in chronic allergic diseases. IL-5 activates eosinophils and enhances their survival in vitro by delaying apoptosis. In this study, we found that lidocaine and six analogues blunt responses of eosinophils to IL-5. Lidocaine and its derivatives inhibit IL-5-mediated eosinophil survival in a concentration-dependent manner (IC50 = 110 microM for 30 pg/ml IL-5). At suboptimal lidocaine concentrations, the eosinophil survival response to IL-5 shifts and more IL-5 is required to maintain survival. The inhibitory effect requires at least 24-h exposure of eosinophils to lidocaine, and the protein kinase C activator, PMA, completely reverses the inhibition. A multiparameter flow-cytometric analysis shows that lidocaine hastens the apoptosis of eosinophils normally delayed by IL-5. Lidocaine does not affect IL-5R expression or IL-5-induced protein tyrosine phosphorylation. Lidocaine also inhibits eosinophil survival mediated by IL-3 or granulocyte-macrophage CSF, although less potently than that mediated by IL-5. Furthermore, lidocaine inhibits eosinophil superoxide production stimulated by IL-5, granulocyte-macrophage CSF, or IL-3, but not that stimulated by platelet-activating factor, immobilized IgG, or PMA. Lidocaine and its derivatives show novel immunomodulatory properties and are able to blunt eosinophil responses to cytokines in addition to their local anesthetic or antiarrhythmic properties. Thus, lidocaine and its derivatives may represent a new class of therapeutic agents to treat patients with allergic diseases.

Apoptosis↗
PubMed1998

Localization of eosinophil-derived neurotoxin and eosinophil cationic protein in neutrophilic leukocytes.

Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are generally regarded as eosinophil-specific proteins. We tested whether EDN and ECP are present in mature neutrophils. By indirect immunofluorescence, both eosinophils and neutrophils stained with antibodies to EDN and ECP. Lysates of purified (<0.1% eosinophil contamination) neutrophils contained EDN, 112+/-4 ng/10(6) cells, and ECP, 163+/-2 ng/10(6) cells, whereas eosinophil major basic protein (MBP) was not detectable. Electron microscopic examination of immunogold-labeled buffy coat cells stained with EDN antibody showed that EDN is localized to neutrophil granules. Finally, EDN mRNA was detected in lysates of highly purified neutrophils (0.001% eosinophil contamination) by the reverse transcription-polymerase chain reaction. We conclude that proteins that are either identical to or immunologically cross-reactive with EDN and ECP are present in neutrophils and that EDN is synthesized and localized to neutrophil granules. Thus, caution must be exercised in interpreting the presence of EDN and ECP as specific markers of eosinophil-associated inflammation in human disease.

Biopsy↗
PubMed1998

Sulochrin inhibits eosinophil activation and chemotaxis.

OBJECTIVE: Because eosinophils likely play important roles in the pathophysiology of allergic diseases, specific inhibitors of eosinophils may be desirable to treat such diseases. To evaluate the capacity of a novel compound, sulochrin, as an inhibitor of eosinophilic inflammation, we examined the effects of this compound on various effector functions of eosinophils. MATERIALS AND METHODS: We examined the effects of sulochrin on degranulation of human eosinophils stimulated with platelet-activating factor (PAF) or Sepharose 4B beads coated with secretory IgA (sIgA) or IgG. The effects of sulochrin on other effector functions of human eosinophils, including superoxide anion (O2-) production, leukotriene (LT) C4 release, and interleukin (IL)-8 production induced by sIgA-beads were also studied. Finally, using PAF and LTB4 as chemoattractants, we evaluated the potency of sulochrin to inhibit eosinophil migration in vitro and in vivo. RESULTS: Sulochrin inhibited EDN release by eosinophils stimulated with sIgA-beads. IgG-beads and PAF in a concentration-dependent manner; IC50 values were 0.75 microM, 0.30 microM and 0.03 microM. Eosinophil O2- production, LTC4 release, and IL-8 production were also inhibited by sulochrin. Furthermore, PAF-induced chemotaxis of human eosinophils and LTB4-induced chemotaxis of guinea pig eosinophils were abolished by 1 microM of sulochrin. Finally, sulochrin potently inhibited LTB4-induced infiltration of eosinophils into the skin of guinea-pig in vivo. CONCLUSIONS: These results suggest that sulochrin is a potent inhibitor of various effector functions of eosinophils. Sulochrin and its derivatives may be useful in the development of therapeutic approaches for patients with allergic diseases.

Animals↗
PubMed1998

Eosinophilia and gastrointestinal symptoms after ingestion of shiitake mushrooms.

BACKGROUND: Shiitake mushrooms are a dietary staple in Asia and are increasingly popular worldwide. A cholesterol-lowering study with shiitake showed that 17 of 49 participants withdrew because of rash or abdominal discomfort, and two had marked eosinophilia. One of these latter participants was subsequently challenged for 14 days with shiitake powder and again had eosinophilia. OBJECTIVE: We investigated whether ingestion of shiitake mushroom powder induces eosinophilia or symptoms. METHODS: We studied 10 normal persons. Each participant ingested 4 gm shiitake powder (open label) daily for 10 weeks (trial 1), and the protocol was repeated in these same subjects after 3 to 6 months (trial 2). Blood counts and serum samples were obtained biweekly (trial 1) or weekly along with stool specimens (trial 2). Eosinophil major basic protein and IL-5, IgE, and IgG antishiitake antibodies were measured in sera. Eosinophil-derived neurotoxin was measured in stool extracts. We defined responders as subjects having peak eosinophil counts four or more times their average baseline counts. RESULTS: Each trial had four responders, and trial 2 had one new and three repeat responders. Eosinophilia ranged from 400 to 3900/mm3. Responders had increased blood eosinophils, serum major basic protein, stool eosinophil-derived neurotoxin, and factors that enhanced eosinophil viability. Antishiitake IgE was not detected, and antishiitake IgG increased in two responders. Gastrointestinal symptoms coincided with eosinophilia in two subjects. Symptoms and eosinophilia resolved after discontinuing shiitake ingestion. CONCLUSIONS: Daily ingestion of shiitake mushroom powder in five of 10 healthy persons provoked blood eosinophilia, increased eosinophil granule proteins in serum and stool, and increased gastrointestinal symptoms. Shiitake ingestion suggests a model to study the eosinophil's role in the blood and gastrointestinal tract. Finally, our report raises concerns of possible adverse systemic reactions to this increasingly popular food.

Adult↗