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H Ninomiya

Publications and source records attributed to H Ninomiya.

At least 163 records · Page 9Linked to original sources
PubMed1996

The effects of calcitonin gene-related peptide on tracheal smooth muscle of guinea-pigs in vitro.

1. The effect of calcitonin gene-related peptide (CGRP) on airway smooth muscle is controversial. The aim of this study was to determine whether the action of CGRP on tracheal strips of guinea-pigs is modulated by epithelium and whether this peptide-induced action involves other mediators including nitric oxide (NO) and endothelin (ET)-1. 2. CGRP produced a weak dose-dependent increase in guinea-pig tracheal tension in vitro (-logEC50 = 8.5 +/- 0.1, maximum contraction = 8.3 +/- 1.2% of 50 mM KCl-induced contraction, n = 6). In epithelium-depleted preparations, CGRP (10(-7) M)-induced contraction was significantly potentiated from 9.0 +/- 1.9% to 41.1 +/- 6.0% (n = 6). 3. L-NG-nitro-arginine methyl ester (L-NAME, 10(-4) M), which inhibits NO synthesis, enhanced the contractile response to CGRP from 9.0 +/- 1.9% to 31.2 +/- 1.1% (n = 6). Indomethacin (10(-5) M) also enhanced the response to CGRP, although the effect was weak (13.4 +/- 3.2%, n = 6). 4. Anti-ET-1 serum changed the CGRP-induced contraction into a relaxation. After incubation of the trachea with ET-1 (10(-7) M) to attenuate ET-1-induced responses, the CGRP-induced contraction also changed into a relaxation. BQ-123 (an ETA receptor antagonist) and BQ-788 (an ETB receptor antagonist) caused the same conversion of the CGRP response, from contraction to relaxation, although the relaxing effect elicited by BQ-788 was more potent than that by BQ-123. Maximum inhibitory responses were -31.0 +/- 3.3% and -13.0 +/- 2.3% of 50 mM KCl-induced contraction, respectively (n = 6). 5. In primary culture, guinea-pig tracheal epithelial cells released ET-1, and CGRP (10(-5) M) significantly increased the release of ET-1. 6. These data suggest that the action of CGRP is modulated by airway epithelium and this mechanism involves the release of NO and ET-1. Especially, the majority of contractile action elicited by CGRP consists of an action of ET-1 via the predominant ETB receptor.

Animals↗
PubMed1996

Chronic neutrophilic leukemia associated with monoclonal gammopathy of undetermined significance.

A 30-year-old man with chronic neutrophilic leukemia (CNL) in association with monoclonal gammopathy is presented. Physical examination on admission revealed moderate hepatosplenomegaly. Initial blood count showed neutrophilic leukocytosis (42.2 x 10(9)/1 with 90% mature neutrophils). Leukocyte alkaline phosphatase (LAP) score was elevated. Bone marrow aspiration showed myeloid hyperplasia without dysplastic features. Karyotypic and molecular analyses of bone marrow cells showed the absence of Philadelphia (Ph1) chromosome and bcr gene rearrangement. Because there was no underlying infection or neoplasm, he was diagnosed as having CNL associated with IgG kappa-type monoclonal gammopathy (IgG, 1,269 mg/dl). In addition to its association with monoclonal gammopathy of undetermined significance (MGUS), the present case was also characterized by spontaneous remission of CNL during the 12-year follow-up, accompanied by a gradual increase in serum IgG levels up to 3,000 mg/dl. As far as we know, there have been 19 cases of CNL associated with monoclonal gammopathy in the literature. The median survival of these cases was 5 years. Although there have been only 6 cases of CNL associated with MGUS, survival of these cases was particularly favorable. Taken together with the observation that leukocytosis and hepatosplenomegaly in the present case subsided without specific treatment, we speculate that myeloid proliferation in the present case may have been a leukemoid reaction to underlying monoclonal gammopathy.

Adult↗
PubMed1996

Morphometric study on the fetal thyroid gland in the nude mouse (BALB/cAnNCrj-nu/nu).

Fetal thyroid glands of athymic nude mice (BALB/cAnNCrj-nu/nu) were examined morphometrically on day 18 of gestation. Compared to euthymic litter mate controls (BALB/ cAnNCrj-nu/+), both the cell height and diameter of thyroid follicles were significantly smaller; fewer well-developed follicles were found in the peripheral region of the thyroid; the body weight and total volume of the thyroid gland were also smaller in nude mice. These results suggest underdevelopment of the fetal thyroid gland of the athymic nude mouse.

Animals↗
PubMed1996

Hemolytic anemia associated with myotonic muscular dystrophy.

Hemolytic anemia developed in a male who had been diagnosed as having myotonic muscular dystrophy (MMD). His red cell life-span examined by 51Cr-labeling method was shortened (T 1/2 = 6.5 days). Specific abnormalities of red cells were not found other than increased osmotic resistance, increased intracellular sodium, and decreased intracellular potassium of red cells. A clinical review of 18 other patients with MMD did not reveal any signs of hemolysis. It may be suggested that the underlying red cell membrane defects due to MMD contributed to this rare association with hemolysis.

Anemia, Hemolytic↗
PubMed1996

[Invasive thymoma associated with pure red cell aplasia and lung cancer].

A 71-year-old man was admitted to our hospital with vertigo and general fatigue. Examination of his blood and bone marrow showed pure red cell aplasia. His chest X-ray film revealed an anterior mediastinal mass and a nodular shadow in the right lower lobe. Extended thymothymectomy and right lower lobectomy were done. The mediastinal mass appeared to be an invasive thymoma and the nodular shadow in the right lower lobe proved to be from an adenocarcinoma. The patient was treated with radiation and steroids. Thymoma, pure red cell aplasia, and lung cancer had not recurred and he was alive and well as of 2 years after surgery.

Adenocarcinoma, Papillary↗
PubMed1996

Endothelin-1-induced mitogenic responses of Chinese hamster ovary cells expressing human endothelinA: the role of a wortmannin-sensitive signaling pathway.

In the current study, endothelin-1 (ET-1) worked as a mitogen on Chinese hamster ovary cells stably expressing human endothelinA; when applied to serum-deprived cells, ET-1 caused dose-dependent increase in [3H]thymidine incorporation and cell proliferation. No synergism was observed between the effect of ET-1 and that of insulin-like growth factor-1/basic fibroblast growth factor. Both the inhibition of intracellular Ca2+ response by phospholipase C inhibitor U73122 and the down-regulation of protein kinase C (PKC) by pretreatment with phorbol 12-myristate-13-acetate (PMA) partially blocked the ET-1-induced mitogenic responses. Wortmannin, a phosphatidylinositol-3-kinase inhibitor, caused dose-dependent inhibition of the ET-1-induced mitogenic responses in both PMA-treated and -untreated cells. Wortmannin also inhibited ET-1-induced increase in phosphatidylinositol trisphosphate formation and activation of mitogen-activated protein kinase (MAPK), whereas it failed to inhibit PMA-induced activation of MAPK. In accordance with its effect on MAPK activation, wortmannin inhibited ET-1-induced activation of Raf-B, whereas it failed to inhibit the effect of PMA. These results suggested the role of a Ca2+/PKC-independent, wortmannin-sensitive signaling pathway that linked ETA and MAPK cascade in the mitogenic signaling activated by ETA.

Amino Acid Sequence↗
PubMed1996

Involvement of endothelins in immediate and late asthmatic responses of guinea pigs.

To explore the pathophysiological roles of endothelin isopeptides and receptor subtypes in asthmatic responses, a guinea pig model for asthma was used to test the effects of antiendothelin (ET) serum and selective ET receptor antagonists for antigen-induced specific airway conductance changes as measured by whole-body plethysmography. In this model, all of the animals so far tested demonstrated both the immediate and late asthmatic responses. Although preimmune serum had no apparent effects, anti-ET antiserum suppressed the maximal reduction of specific airway conductance in both the immediate and late asthmatic responses, which suggested that ET(s) are involved in the pathophysiology of both the immediate and late asthmatic responses. The ETB selective antagonists, BQ788 and RES701-1, blocked the immediate asthmatic response but not the late asthmatic response, whereas the ETA antagonists, BQ123 and (Shionogi) 97-139, suppressed only the late asthmatic response without influencing the immediate asthmatic response. In vitro constrictive responses of isolated tracheas and bronchi to ET1 were inhibited mainly by BQ123 and BQ788, respectively, which suggested that distribution of ETA and ETB receptors for bronchoconstriction are topographically distinct along airways. Furthermore, thromboxane A2 and platelet activating factor (PAF) antagonists were effective in suppressing the late asthmatic response but not the immediate asthmatic response. Taken together, our present observations suggest that ET(s) influences pulmonary functions by constricting airway smooth muscle via ETB receptors during the immediate asthmatic response and by modulating pulmonary inflammation via ETA receptors during the late asthmatic response, respectively.

Analysis of Variance↗
PubMed1996

[Superior septal approach for mitral valve surgery].

The superior septal approach (SSA) for mitral valve surgery is a useful approach, but it may bring about demage to sinus node function or an atrial electrical vulnerable condition because the sinus node artery is divided and a large portion of both atria is incised. From April 1992 to December 1994, we used this approach in 17 patients. There was no hospital death and none had perioperative complications associated with the approach. All nine patients in sinus rhythm preoperatively returned to sinus rhythm before discharge from the hospital and remained so at late follow-up. Five of 9 patients with sinus rhythm had electrophysiological examination preoperatively and all 9 patients had the examination postoperatively. Atrial vulnerability was not deteriorated after the operation in all cases. Under pharmacologic autonomic blockade, sinoatrial conduction time (SACT), sinus node recovery time (SNRT) after overdrive atrial pacing, and corrected SNRT were 73 +/- 35 msec, 1142 +/- 168 msec, and 365 +/- 122 msec, respectively. All these values were with in normal range and these were no significant differences between before and after the operation. All patients with sinus rhythm had 3 minutes of Bruce stage 1 exercise 9 months after the operation. The heart rate response to the exercise was as good as in healthy control people. In conclusion, as far as the midterm postoperative period, the effect of SSA on sinus node function and atrial vulnerability was acceptable.

Adult↗
PubMed1996

[Significance of hot shot in patients with unstable angina undergoing emergency coronary artery bypass graft surgery].

We investigated the efficacy of terminal warm blood cardioplegia (hot shot) in patients with cardioplegic techniques. From January 1991 through April 1993, 68 patients recieved hypothermic cardioplegia induced by cold modified St. Thomas' Hospital solution containing 10mg/L of diltiazem hydrochloride followed by intermittent infusion of the cold crystalloid solution or cold blood cardioplegia without hot shot. From May 1993 through December 1994, 65 patients recieved hot shot before removal of aortic cross-clamp following the hypothermic cardioplegia. The earlier group consisted of 51 patients with stable angina undergoing elective CABG and 17 patients with unstable angina undergoing emergency of urgent CABG. The later group consisted of 44 patients with stable angina and 21 patients with unstable angina. The unstable angina undergoing coronary artery bypass graft surgery (CABG) using antegrade incidence of perioperative myocardial infarction was significantly higher in patients with unstable angina without hot shot (35%) compared to those with stable angina with and without hot shot (2% and 4%, respectively) and those with unstable angina with hot shot (5%). The level of maximum creatine kinase-MB (IU/L) was significantly greater in patients with unstable angina without hot shot (134 +/- 26) compared to those with stable angina with and without hot shot (57 +/- 7 and 65 +/- 4, respectively) and those with unstable angina with hot shot (57 +/- 8). The doses of dopamine and dobutamine (mg/kg) administered during 48 hours after CABG was not different between patients with stable angina with and without hot shot (13.9 +/- 0.9 vs 13.9 +/- 0.9), but tended to be lower in patients with unstable angina with hot shot (13.7 +/- 1.3) compared to those without hot shot (18.6 +/- 2.1). Left ventricular stroke work index (g.m/m2/b) immediately after CABG was comparable between patients with stable angina with and without hot shot (40 +/- 2.0 vs 36 +/- 1.5), but significantly greater in patients with unstable angina with hot shot (39 +/- 2.3) compared to those without hot shot (29 +/- 2.2). These results suggest that hot shot may provide a significant benefit in myocardial preservation during CABG especially in patients with unstable angina.

Aged↗
PubMed1996

[Inhaled nitric oxide for postoperative pulmonary hypertensive crisis in a patient with complete atrioventricular canal associated with Down's syndrome: a case report].

Two-year-old boy with Down's syndrome was treated with inhaled nitric oxide for pulmonary hypertensive crisis after correction of complete atrioventricular canal and persistent ductus arteriosus. The acute rise in pulmonary pressure and hemodynamic instability occurred on 3rd, 4th and 6th post operative days and pulmonary vasodilation with prostaglandin E1 and amrinone had failed. Twenty ppm of inhaled nitric oxide effectively reduced the pulmonary pressure and the patient was subsequently weaned from ventilation. Inhaled nitric oxide exerted a pulmonary vasodilation without decreasing systemic pressure in this patient with postoperative pulmonary hypertensive crisis.

Acute Disease↗
PubMed1996

[Surgical treatment for recrudescent Stanford type A early closing dissection].

Two cases of recrudescent Stanford type A dissection were reported. They had non-opacified false channel on their initial CT and aortography. The first case was 65-year-old woman having a stable blood pressure and no chest pain after admission. However, recrudescent opacified false lumen was found at the mid-ascending aorta about three weeks later. She received ascending aortic replacement on 26th day after onset. The second case was 66-year-old woman having a unstable blood pressure and having periodic chest pain and back pain after admission. CT and angiography performed on the 41th day after onset revealed recrudescent descending aortic dissection and ulcer like projection at mid-ascending aorta. The ulcer like projection increased in size gradually. Ascending aorta replacement was performed on 110th day after onset. Two cases had a good post operative days. Some cases of Stanford type A early closing aortic dissection had recrudescent dissection later, even if they had a stable course after onset. Thus, careful follow up for long term is essential in these cases

Aged↗
PubMed1996

[Successful treatment of combined interferon-alpha and hydroxycarbamide for chronic myelogenous leukemia following therapy for malignant lymphoma].

A 57-year-old woman was diagnosed as having non-Hodgkin lymphoma (follicular mixed cell, B-cell type, Stage III) in February 1988. Since then, she had been treated with radiation and chemotherapy contained with alkylating agents and etoposide for 6 years. In April 1994, peripheral blood study disclosed leukocytosis with basophilia and thrombocytosis. Bone marrow was hypercellular. The karyotype of bone marrow cells was 46, XX, t(9:22) (q34:q11). Rearrangement of bcr was detected in bone marrow, but not in lymph node cells. On the basis of these findings, she was diagnosed as having the chronic phase of chronic myelogenous leukemia (CML) following the therapy for malignant lymphoma and treated with interferon-alpha (IFN-alpha) and hydroxycarbamide. Following this therapy, the lymphoadenopathy promptly disappeared and chromosome analysis showed disappearance of Ph chromosome positive cells. Although CML is rare in secondary leukemia, the present case seemed therapy-related CML and the treatment with IFN-alpha and hydroxycarbamide was effective for both CML and malignant lymphoma.

Antineoplastic Agents, Alkylating↗
PubMed1996

Serum thrombopoietin (TPO) levels in patients with amegakaryocytic thrombocytopenia are much higher than those with immune thrombocytopenic purpura.

We assayed serum thrombopoietin (TPO) levels in amegakaryocytic thrombocytopenia (AMT) and immune thrombocytopenic purpura (ITP) patients by using a newly established enzyme-linked immunosorbent assay (ELISA). TPO levels in AMT patients were quite high (mean +/- SD = 13.7 +/- 11.2 fmoles/ml, n = 4), whereas those in ITP patients were only slightly higher (1.25 +/- 0.39, n = 12) than those of the healthy donors (0.55 +/- 0.2, n = 20). Furthermore, in ITP patients no correlation was observed between platelet counts and serum TPO levels (correlation coefficient = 0.14). We further assayed serum TPO levels sequentially during steroid treatment in patients with AMT and ITP. In one AMT patient serum TPO levels started to decrease in accordance with the increase of megakaryocyte counts, which preceded the increase in platelet counts. However, in ITP patients serum TPO levels did not change significantly throughout the course of the treatment despite the recovery of platelet counts. Based on these findings, we conclude that serum TPO levels may be regulated at least in part by megakaryocyte counts.

Adult↗
PubMed1996

[Management of postoperative pulmonary hypertensive crisis in children--indication and usefulness of inhaled nitric oxide therapy as a pulmonary vasodilator].

Among 176 pediatric patients who underwent open heart surgery from 1990 to 1996, 7 developed severe pulmonary hypertensive crisis (PHC) postoperatively. All patients were treated with conventional medical therapy consisting of hyperventilation and deep sedation. Prostaglandin E1 and/or amrinone were administered initially as a pulmonary vasodilator, and in 3 of the 7 patients this resulted in immediate improvement in hemodynamics. These patients subsequently weaned off ventilatory support and they were discharged from the hospital. In 4 other patients, pulmonary vasodilator therapy with prostaglandin E1 and amrinone had failed and they were treated with inhaled nitric oxide (NO). In all patients, inhalation of NO resulted in immediate decrease in pulmonary pressure without significant change in systemic arterial pressure. Two patients successfully weaned from the ventilator, whereas in 2 patients decrease in pulmonary pressure was transient. They developed airway bleeding and died as a result of respiratory insufficiency. Although inhaled NO effectively reduced pulmonary pressure in patients with PHC, this effect was not maintained over 12 hours in patients associated with bronchopulmonary dysplasia. In patients at risk for severe PHC, rapid treatment with NO inhalation after initial event as well as the prevention of lung injury caused by mechanical ventilation were found to be important in the postoperative management.

Administration, Inhalation↗
PubMed1995

Capacitative Ca2+ entry in human platelets is resistant to nitric oxide.

Both sodium nitroprusside (SNP) and a phospholipase C inhibitor U73122, when applied to human platelets after the stimulation with thrombin (0.2 U/ml), caused dose-dependent inhibition of Ca2+ influx. The inhibition, however, was not complete for either substance and the U73122-resistant Ca2+ influx was also resistant to SNP. Two lines of evidence suggested that the SNP/U73122-resistant Ca2+ influx was due to the capacitative Ca2+ entry. First, U73122-resistant fraction of Ca2+ influx induced by thapsigargin was also resistant to SNP. Second, both U73122 and SNP failed to inhibit the Ca2+ influx induced by an acid extract from thrombin-stimulated platelets that contained the Ca2+ influx factor activity. We suggest that the capacitative Ca2+ entry in human platelets, once triggered by inositol trisphosphate-induced store-depletion, is not affected by nitric oxide.

Aspirin↗
PubMed1995

The induction of cell differentiation and polarity of tracheal epithelium cultured on the amniotic membrane.

We have developed a culture system of guinea pig tracheal epithelial cells using the epithelium-denuded human amnion as a source of basement membrane. Culture medium fluid over the epithelial cells was replaced by air after 7-day immersion culture and thereafter maintained for 2 weeks. Electron microscopical observations revealed that the height of epithelial cells and the ratio of ciliated epithelial cells looked like that of normal guinea pigs epithelium growth in 2 weeks after the air interface, but that no goblet cells could be found. In order to study cell polarity, we measured endothelin-1 levels in the media of apical and basal sides of the epithelial cell monolayer by means of the enzyme-linked immunosorbent assay. The endothelin-1 content of the submucosal side was over 30 times higher than that of the apical side. These findings suggest that ET-1 would be mainly released from airway epithelial cells toward the submucosal side.

Amnion↗