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Biomedical subjects

H Kita

Publications and source records attributed to H Kita.

At least 19 recordsLinked to original sources

Childhood asthma and human leukocyte antigen type.

Little is known about the relationship between human leukocyte antigen (HLA) class II genes and family history of asthma or atopy in relation to the incidence of childhood asthma. The objective of the study was to determine whether specific HLA class II genes (e.g., DRB1*03) are associated with asthma and whether such association explains the influences of family history of asthma or atopy on asthma incidence. A stratified random sample of 340 children who had HLA data available from the Rochester Family Measles Study cohort (n= 876) and a convenience sample of healthy children aged 5-12 years were the participants. We conducted comprehensive medical record reviews to determine asthma status of these children. The associations between the presence of specific HLA alleles and development of asthma and the role of family history of asthma or atopy in the association were evaluated by fitting Cox models. The cumulative incidence of asthma by 12 years of age among children who carry HLA DRB1*03 was 33%, compared to 24.2% among those who did not carry this allele. Adjusting for family history of asthma or atopy, gender, low birth weight, season of birth, HLA DRB1*04, and HLA DQB1*0302, the hazards ratio for HLA DRB1*03 carriers was 1.8 (95% confidence interval: 1.1-2.9, P= 0.020). We concluded that the HLA DRB1*03 allele is associated with asthma. However, the HLA class II gene does not explain the influences of family history of asthma or atopy on development of asthma. The mechanism underlying the association between asthma and HLA genes needs to be elucidated.

Adolescent↗

Double-balloon endoscopy for the diagnosis and treatment of small intestinal disease.

Evaluation of the small bowel has long been hampered because of its long and multiple complex loop configurations. Yamamoto et al have developed a new method of inserting an endoscope, known as the double-balloon method of enteroscopy, the Fujinon double-balloon endoscopy system being specialised for this application. Two types of endoscope are currently available for this technique. The EN-450 P5 is a thin endoscope for regular use, whereas the EN-450 T5 is a therapeutic double-balloon endoscope with a larger accessory channel of 2.8mm in diameter. Double-balloon endoscopy enables visualisation of the entire small bowel and also allows for interventional therapy in the small intestine. This method can be used either from an oral or an anal insertion. Observation of an affected area with controlled movement of the endoscope enables interventions, including biopsies, haemostasis, balloon dilatation, stent placement, polypectomy and endoscopic mucosal resection, to be performed. In our large study series, it was demonstrated that double-balloon endoscopy permitted exploration of the small intestine with the high success rate of total enteroscopy. The procedure is safe and useful, and it provides high diagnostic yields and therapeutic capabilities.

Clinical Trials as Topic↗

Immunomodulation using the recombinant monoclonal human B7-DC cross-linking antibody rHIgM12.

A patient with Waldenstrom's macroglobulinaemia expresses a high titre IgM antibody in serum that binds both mouse and human dendritic cells (DC) in a B7-DC (PD-L2)-dependent manner. We have reported previously that purified antibody from patient serum activates immature and mature DC in vitro, enhancing the ability of these professional antigen-presenting cells to activate naive T cells, take up antigen, resist a cytokine-depleted environment and secrete immunomodulatory cytokines, such as interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha. Systemic treatment of experimental animals with this antibody induces potent anti-melanoma immunity and modulates protectively the recall response against antigen challenge through the airway in an experimental model of inflammatory airway disease. Here we describe a monoclonal IgM antibody derived from this serum immunoglobulin that recapitulates each of these earlier observations, providing direct evidence that M protein from the Waldenstrom's patient mediates these potent immunomodulatory effects. Furthermore, cell lines expressing this recombinant form of the human antibody provide the basis for developing this reagent for clinical application.

Amino Acid Sequence↗

A critical role for vesicle-associated membrane protein-7 in exocytosis from human eosinophils and neutrophils.

BACKGROUND: Granulocyte exocytosis is proposed to be critically dependent on the interaction of soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNAREs) located on granules/vesicles (v-SNAREs) and plasma membrane (t-SNAREs). Previous studies indicated that the v-SNARE, vesicle-associated membrane protein (VAMP)-2, as well as t-SNAREs (SNAP-23, syntaxin-4 and -6) are implicated in exocytosis from human granulocytes. Vesicle-associated membrane proteins-7 and -8 have been implicated in endosome/lysosome trafficking, however, their role in granulocyte exocytosis remains obscure. OBJECTIVE: We sought to investigate the expression and functional role of SNARE isoforms in the secretion of different granule-derived mediators in human eosinophils and neutrophils. METHODS: The expression of SNAREs was determined by subcellular fractionation and flow cytometry. SNARE-specific antibodies were examined for their ability to impair mediator release from permeabilized eosinophils and neutrophils. RESULTS: Vesicle-associated membrane proteins-7 and -8 were localized to granule and membrane-enriched fractions in eosinophils and neutrophils, whereas syntaxin-6 was not detectable. In permeabilized cells, anti-VAMP-7, but not anti-VAMP-8, antibody impaired the secretion of all mediators examined (in eosinophils, eosinophil peroxidase and eosinophil-derived neurotoxin; in neutrophils, myeloperoxidase, lactoferrin and matrix metalloprotease-9) in a dose-dependent manner. In contrast, anti-VAMP-2 modestly and selectively impaired secretion from small granules and vesicles. Syntaxin-4, but not syntaxin-6, was found to interact with SNAP-23 and was partially involved in mediator secretion from multiple compartments. CONCLUSION: Our observations indicate for the first time a critical role for VAMP-7 in both eosinophil and neutrophil mediator release.

Blotting, Western↗

Esophageal candidiasis as a side effect of inhaled fluticasone propionate dry powder: recovery by switching over to hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP).

BACKGROUND: Esophageal candidiasis is one of the local side effects of inhaled corticosteroid treatment, and it is difficult to prevent this condition. Our previous report indicated that the prevalence of esophageal candidiasis among patients treated with inhaled fluticasone propionate dry powder (FP-dp) reached up to 37% in Japanese patients. Although a reduction in the daily dose of inhaled FP-dp can eliminate this infection, it may lead to asthma not being well-controlled in these patients. OBJECTIVE: The aim of this study was to estimate whether switching to an equal daily dose of inhaled hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP), the oropharyngeal deposition of which is very low, can eliminate the infection without deterioration of asthma. METHODS: A total of 10 stable asthmatic patients with esophageal candidiasis, induced by inhaled FP-dp treatment (400 or 800 microg/ day), were enrolled in this study. A second upper GI endoscopy was performed, more than 1 month but less than 3 months after switching to an equal dose of inhaled HFA-BDP with a tube spacer device, Duopacer. The patients' medications were not changed during the study. RESULTS: Esophageal candidiasis was eliminated in 9 of the 10 patients. The degree of candidiasis reduced in another patient. The forced expiratory volume in 1 sec (FEV1.0) did not worsen during the study. CONCLUSION: Switching from FP-dp to HFA-BDP with Duopacer is useful in preventing esophageal candidiasis.

Administration, Inhalation↗

Helicobacter pylori eradication induces marked increase in H+/K+-adenosine triphosphatase expression without altering parietal cell number in human gastric mucosa.

BACKGROUND AND AIMS: Gastric acid secretion is downregulated by Helicobacter pylori infection and upregulated after its eradication, but the mechanisms are still unclear. We examined the effects of H pylori eradication on the number of parietal cells and on expression of molecules functioning in acid secretion in the human gastric mucosa. METHODS: We enrolled 111 consecutive men with chronic gastritis induced by H pylori. Biopsy specimens were endoscopically obtained before and 12 weeks after successful eradication of H pylori and parietal cell numbers were counted. mRNA expression levels of H+/K+-adenosine triphosphatase (H+/K+-ATPase), anion exchanger 2, M3 muscarinic receptor, intrinsic factor, and interleukin 1beta were determined with a real time reverse transcriptase-polymerase chain reaction method. The severity of gastric atrophy was evaluated using the serum pepsinogen I/II ratio. RESULTS: No significant difference was observed in parietal cell numbers before and after H pylori eradication. Median mRNA expression levels of H+/K+-ATPase in the gastric mucosa increased 250-fold after H pylori eradication accompanied by attenuation of interleukin 1beta. A large increase in H+/K+-ATPase expression was observed even in patients with severe atrophic gastritis. In contrast, fold increases in mRNA expression levels, including intrinsic factor, anion exchanger 2, and M3 muscarinic receptor, after eradication therapy, were limited to 1.4, 2.3, and 2.5 times, respectively. CONCLUSIONS: In the absence of alteration of parietal cell number, gastric H+/K+-ATPase mRNA expression was markedly restored after successful H pylori eradication, suggesting a central role for the restoration of H+/K+-ATPase expression in gastric acid secretion recovery after H pylori eradication.

Chronic Disease↗

Histamine-2 receptor expression in gastric mucosa before and after Helicobacter pylori cure.

BACKGROUND: Helicobacter pylori infection prevents the occurrence of the tolerance phenomenon of Histamine-2 (H2) receptor antagonists. Gastro-esophageal reflux disease develops in some cases with the restoration of acid secretion after H. pylori eradication therapy. AIM: To clarify the mechanisms of H2 receptor restoration after the eradication of H. pylori on parietal cells. METHODS: We enrolled 80 consecutive asymptomatic male patients with H. pylori infection, having chronic gastritis with or without the presence of peptic ulcers. Biopsy specimens from the greater curvatures at the mid-corpus of the stomach were obtained endoscopically from all subjects before and 12 weeks after the eradication of H. pylori. Degrees of gastric atrophy were evaluated by serum pepsinogen levels. The amounts of mRNA expression of H2 receptor were evaluated in each subject's gastric mucosa by real time reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: H2 receptor mRNA expression levels significantly correlated with serum pepsinogens I and II ratios. The expression level of H2 receptor mRNA was lower in subjects with hypergastrinemia. The median expression level of H2 receptor after H. pylori eradication was threefold greater than prior to treatment. In addition, its restoration became more pronounced in subjects with severe gastric atrophy. However, a comparatively low restoration of H2 receptor mRNA was found in subjects with hypergastrinemia. CONCLUSIONS: H2 receptor mRNA levels decrease with the progression of gastric atrophy induced by H. pylori infection, and are restored after H. pylori eradication. Such expression levels of H2 receptor may explain a part of the tolerance phenomenon to H2 receptor antagonists.

Anti-Bacterial Agents↗

Comparison of hemostatic effects by route of H2 receptor antagonist administration following endoscopic mucosal resection in patients with neoplastic gastric lesions.

BACKGROUND: To date, there has not been an in-depth investigation to identify differences in the effects of bleeding prevention among different routes of administration of H2 receptor antagonists to treat gastric ulcers following endoscopic mucosal resection (EMR). AIM: To prospectively compare the frequency of bleeding following EMR between patients treated with intravenous (IV) famotidine and those with oral famotidine. METHODS: Fifty-three patients with neoplastic gastric lesions (33 carcinoma and 20 adenoma) treated by EMR were included. Subjects underwent EMR with circumferential mucosal incision assisted by submucosal injection of sodium hyaluronate (EMRSH), followed by IV or oral (PO) administration of famotidine at a dosage of 40 mg/day for 2 days. Patients with odd ID numbers were assigned to IV therapy (30 cases) while even numbers were given PO therapy (23 cases). Frequencies and endoscopic findings of bleeding during the first 2 days after EMR were examined. RESULTS: Frequency of bleeding within 2 days after EMR was 3 and 4% in IV and PO patients, respectively, showing no significant difference. No significant difference was seen in the endoscopic findings of bleeding and therapy, either, with respective IV and PO findings at 23 and 26%. CONCLUSIONS: No significant difference was observed in frequency of bleeding within 2 days after gastric EMR between IV and oral administrations of famotidine.

Adenocarcinoma↗

Effects of (R)- and (S)-isomers of beta-adrenergic agonists on eosinophil response to interleukin-5.

BACKGROUND: Racemic beta2-adrenergic receptor agonists (beta2-agonists) are used frequently to treat patients with asthma. Potential differences in the biological activities and clinical efficacies among racemic beta2-agonists and their isomers are controversial, and research into these possible differences is limited. OBJECTIVE: We hypothesized that the (S)- and the (R)-isomers of beta2-agonists have opposing effects on the activation of inflammatory cells. METHODS: Isolated human eosinophils were pretreated with 1:1 racemic (R,S)-, (R)- or (S)-albuterol, isobutyl methylxanthine (IBMX), and stimulated with IL-5. The kinetics of superoxide production were examined by reduction of cytochrome c, and the effects of pharmacological agents on superoxide production were monitored for 180 min. RESULTS: (R,S)-albuterol inhibited IL-5-induced superoxide production. This inhibition was enhanced by a cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor, IBMX, and was reversed by the selective beta2-adrenergic receptor antagonist, ICI 118, 551, verifying the involvement of both cAMP and the beta2-adrenergic receptor. In addition, (R)-albuterol alone, similarly to (R,S)-albuterol, significantly inhibited IL-5-induced superoxide production up to 60 min (P<0.05, n=4), but the inhibition was lost with longer incubation. In contrast, (S)-albuterol with IBMX did not inhibit IL-5-induced superoxide production before 60 min, but it significantly enhanced IL-5-mediated superoxide production after 60 min (P<0.05, n=4). When both were present as racemic (R,S)-albuterol, the inhibitory effect of (R)-albuterol was not affected by (S)-albuterol. CONCLUSION: When incubated with IL-5-activated eosinophils, (R)-albuterol shows anti-inflammatory effects and (S)-albuterol shows pro-inflammatory effects in the presence of IBMX. The kinetics of these effects are different, and when used simultaneously, (R)-albuterol predominates. When marked usage of the (S)-isomer is anticipated, racemic (R,S)-albuterol should be used clinically with caution.

1-Methyl-3-isobutylxanthine↗

Down-regulation of metabotropic glutamate receptor 1alpha in globus pallidus and substantia nigra of parkinsonian monkeys.

Enhanced glutamatergic neurotransmission via the subthalamopallidal or subthalamonigral projection seems crucial for developing parkinsonian motor signs. In the present study, the possible changes in the expression of metabotropic glutamate receptors (mGluRs) were examined in the basal ganglia of a primate model for Parkinson's disease. When the patterns of immunohistochemical localization of mGluRs in monkeys administered systemically with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were analysed in comparison with normal controls, we found that expression of mGluR1alpha, but not of other subtypes, was significantly reduced in the internal and external segments of the globus pallidus and the substantia nigra pars reticulata. To elucidate the functional role of mGluR1 in the control of pallidal neuron activity, extracellular unit recordings combined with intrapallidal microinjections of mGluR1-related agents were then performed in normal and parkinsonian monkeys. In normal awake conditions, the spontaneous firing rates of neurons in the pallidal complex were increased by DHPG, a selective agonist of group I mGluRs, whereas they were decreased by AIDA, a selective antagonist of group I mGluRs, or LY367385, a selective antagonist of mGluR1. These electrophysiological data strongly indicate that the excitatory mechanism of pallidal neurons by glutamate is mediated at least partly through mGluR1. The effects of the mGluR1-related agents on neuronal firing in the internal pallidal segment became rather obscure after MPTP treatment. Our results suggest that the specific down-regulation of pallidal and nigral mGluR1alpha in the parkinsonian state may exert a compensatory action to reverse the overactivity of the subthalamic nucleus-derived glutamatergic input that is generated in the disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Pericryptal fibroblast sheath in intestinal metaplasia and gastric carcinoma.

BACKGROUND AND AIMS: In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype which is closely related to gastric carcinoma. However, to date, it has not been elucidated whether the intestinal metaplasia is merely a change in the epithelium or whether the underlying mesenchyme also changes from gastric type to intestinal type. We have investigated the relationship between intestinal metaplasia and the pericryptal fibroblast sheath (PCFS) in the mesenchyme. In addition, we also examined PCFS in gastric carcinoma. METHODS: We determined the existence of PCFS in the intestinal metaplastic mucosa and carcinoma of both human and Cdx2 transgenic mouse stomach. PCFS was determined using the antibody against alpha-smooth muscle actin and electron microscopic observations. RESULTS: PCFS formed an almost complete layer around the small and large intestinal crypts while it did not exist around the normal gastric glands in both mice and humans. PCFS was seen around the glands of intestinal metaplastic mucosa in both Cdx2 transgenic mouse and human stomachs. However, PCFS was virtually absent in the intestinal-type gastric adenocarcinoma area. CONCLUSION: We successfully demonstrated that the epithelium as well as the mesenchyme changed from the gastric type to the intestinal type in intestinal metaplasia and that PCFS disappeared in intestinal-type gastric carcinoma.

Actins↗

[Successful treatment of bronchial mucoepidermoid carcinoma by bronchoplasty].

A 63-year-old man who was pointed out abnormal shadow on chest X-ray admitted to our hospital. Chest computed tomography (CT) showed a tumor originated from right upper bronchus and grew into right main bronchus. The tumor was diagnosed as mucoepidermoid carcinoma by bronchoscopic biopsy. Fluorodeoxyglucose positron emission tomography (FDG-PET) showed abnormal uptake localized at the tumor. The standardized uptake values of the tumor 60 minutes after injection were 2.86, and 120 minutes after injection, it increased to 3.97. Right upper lobectomy with bronchoplasty by deep wedge resection of right main bronchus at the orifice of right upper bronchus and lymphadenectomy was performed. Pathological diagnosis was high-grade mucoepidermoid carcinoma without lymph nodes metastasis which was compatible with FDG-PET. Postoperative course was uneventful.

Bronchi↗

Rat intralaminar thalamic nuclei projections to the globus pallidus: a biotinylated dextran amine anterograde tracing study.

The topographical organization and ultrastructural features of the intralaminar thalamic nuclei (ITN) projections to the globus pallidus (GP) were studied using the biotinylated dextran amine (BDA) anterograde tracing method in the rat. To assess the functional association of BDA injection sites in the ITN, the known topographical organization of the ITN-neostriatal (Str) projections and calcium binding protein (CaBP) immunostaining patterns of the Str and GP were used. BDA injection in the lateral part of the lateral parafascicular nucleus and the caudal part of the central lateral nucleus labeled fibers and boutons mainly in the dorsolateral sensorimotor territory of the Str and the middle territories of the GP. BDA injection in the medial part of the lateral parafascicular nucleus and the central lateral nucleus labeled mainly the middle association territory of the Str and the border and the caudomedial territories of the GP. BDA injection in the medial parafascicular nucleus and the central medial nucleus labeled mainly the medial limbic territory of the Str. The medial parafascicular nucleus projected to the medial-most region of the GP, while the central medial nucleus projection to the GP was very sparse. Electron microscopic observations indicated that BDA-labeled boutons form asymmetric synapses mainly on 0.5-2.0 microm diameter dendritic shafts in the GP. The boutons were small but had a relatively long active zone. The present observations together with the known topographical organization of striatopallidal projections indicated that the ITN-GP projections were topographically organized in parallel to the ITN-Str projections. Thus, each part of the ITN projecting to the sensorimotor, the association, and the limbic territories of the Str also projects to the corresponding functional territories of the GP.

Animals↗

A case of inflammatory fibroid polyp causing small-bowel intussusception in which retrograde double-balloon enteroscopy was useful for the preoperative diagnosis.

We showed a newly developed method, retrograde double-balloon enteroscopy, to be useful for preoperative diagnosis in a case of inflammatory fibroid polyp accompanied by small-bowel intussusception. A 64-year-old woman was admitted to our hospital with small-bowel intussusception. Results of radiographic and ultrasonographic examination were suggestive of a small-bowel mass. Retrograde double-balloon enteroscopy was performed in an attempt to make a preoperative diagnosis. Endoscopic observation, in combination with histological findings derived from endoscopic biopsy, was suggestive of an inflammatory fibroid polyp. The patient then underwent laparotomy with minimal incision, which revealed a polypoid mass leading to a jejunojejunal intussusception, without bowel necrosis, and a partial small-bowel resection was performed. The pathological diagnosis was an inflammatory fibroid polyp.

Endoscopy, Gastrointestinal↗

Role of ionotropic glutamatergic and GABAergic inputs on the firing activity of neurons in the external pallidum in awake monkeys.

The neurons in the external segment of the pallidum (GPe) in awake animals maintain a high level of firing activity. The level and pattern of the activity change with the development of basal ganglia disorders including parkinsonism and hemiballism. The GPe projects to most of the nuclei in the basal ganglia. Thus exploring the mechanisms controlling the firing activity is essential for understanding basal ganglia function in normal and pathological conditions. To explore the role of ionotropic glutamatergic and GABAergic inputs to the GPe, unit recordings combined with local injections of receptor antagonists were performed in awake monkeys. Observations on the effects of local application of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate antagonist 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulfonamide, the N-methyl-D-aspartic acid (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, and the GABAA antagonist gabazine as well as the effects of muscimol blockade of the subthalamic nucleus on the spontaneous firing rate, firing patterns, and cortical stimulation induced responses in the GPe suggested the following: sustained glutamatergic and GABAergic inputs control the level of the spontaneous firing of GPe neurons; both AMPA/kainate and NMDA receptors are activated by glutamatergic inputs; some GPe neurons receive glutamatergic inputs originating from areas other than the subthalamic nucleus; no GPe neurons became silent after a combined application of glutamate and GABA antagonists, suggesting that GPe neurons have intrinsic properties or nonionotropic glutamatergic tonic inputs that sustain a fast oscillatory firing or a combination of a fast and a slow oscillatory firing in GPe neurons.

Animals↗

Activation of group III metabotropic glutamate receptors presynaptically reduces both GABAergic and glutamatergic transmission in the rat globus pallidus.

To investigate the role of group III metabotropic glutamate receptors (mGluRs) in the globus pallidus (GP), whole-cell recordings were performed using rat brain slice preparations. Application of the group III mGluRs specific agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) suppressed the amplitude of striatal stimulation-induced IPSCs and internal capsule stimulation-induced EPSCs in most of the GP neurons that were capable of generating repetitive firing without spike accommodation. The suppression of IPSCs and EPSCs was accompanied by an increase in the paired-pulse ratio. The L-AP4 effects were antagonized by (R,S)-alpha-cyclopropyl-4-phosphophenylglycine, a blocker for group II/III mGluRs. L-AP4 reduced the frequency of mIPSCs and mEPSCs without changing their amplitude distribution. L-AP4 failed to change iontophoretic glutamate induced responses. These results suggest that the subthalamo-pallidal glutamatergic input might homo- and hetero-synaptically control GABAergic and glutamatergic transmission in the GP.

Animals↗