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Biomedical subjects

H Ninomiya

Publications and source records attributed to H Ninomiya.

At least 181 records · Page 10Linked to original sources
PubMed1995

Structural basis of G protein specificity of human endothelin receptors. A study with endothelinA/B chimeras.

The endothelin (ET) family of peptides acts via two subtypes of guanine nucleotide-binding regulatory protein (G protein)-coupled receptors termed ETA and ETB. ET-1 stimulated cAMP formation in Chinese hamster ovary (CHO) cells stably expressing human wild-type ETA (CHO/hETA cells) while it inhibited cAMP formation in CHO cells expressing human wild-type ETB (CHO/hETB cells), and pharmacological evidence indicated that the opposite effects were due to the selective coupling of each receptor subtype with G alpha s/G alpha i. To find out a receptor domain(s) that determined the selective coupling, a series of chimeric receptors between hETA and hETB was expressed on CHO cells, and the effect of ET-1 on cAMP formation in each cell line was tested. hETA with the replacement of second and/or third intracellular loop (ICLII and/or -III) to the corresponding region(s) of hETB failed to transmit the stimulatory effect of ET-1. hETB with the replacement of ICLIII to the corresponding region of hETA failed to transmit the inhibitory effect of ET-1. A chimeric receptor with ICLII of hETB and with ICLIII of hETA failed to transmit both effects. In cells expressing chimeric receptors with ICLII of hETA and with ICLIII of hETB, ET-1 inhibited cAMP formation while it stimulated cAMP formation when cells were pretreated with pertussis toxin. These results indicated the roles of ICLII and -III of hETR as a major determinant of the selective coupling of hETA and hETB with G alpha s/G alpha i, respectively. We also demonstrated that each receptor subtype expressed on the same cell could work independently, i.e. for hETA to activate G alpha s and for hETB to activate G alpha i, resulting in dose-dependent dual effects of ET-1 on cAMP formation.

Animals↗
PubMed1995

Serum concentrations of IL-5, GM-CSF, and IL-3 and the production by lymphocytes in various eosinophilia.

The concentrations of interleukin-5 (IL-5), granulocyte-macrophage colony-stimulating factor GM-CSF, and interleukin-3 (IL-3) in serum and in IL-2-stimulated lymphocyte culture medium (L-IL2-CM) prepared from patients with reactive eosinophilia were measured by enzyme-linked immunosorbent assay (ELISA). Serum IL-5 levels were increased in 16 out of 42 cases. GM-CSF and IL-3 were below the detectable levels in all sera examined. The concentrations of IL-5 and GM-CSF in L-IL2-CM were increased in 10 out of 29 patients. IL-3 was below the detectable levels in all L-IL2-CM.

Angioedema↗
PubMed1995

Major basic protein binding to thrombomodulin potentially contributes to the thrombosis in patients with eosinophilia.

The contribution of an eosinophil granule protein, major basic protein (MBP), to the pathogenesis of thrombosis seen in patients with eosinophilia was investigated. The sera from eosinophilic patients containing elevated levels of MBP inhibited thrombomodulin (TM) function as a cofactor for the thrombin-catalysed activation of protein C more significantly than those from normal individuals (means 48.5% v 17.4%, respectively). It was suggested that the binding of mature MBP in the sera to TM was electrostatic, because mature MBP (pI 10.9) bound to TM, whereas pro-MBP (pI 6.2) did not. The inhibition of TM cofactor activity by eosinophil granule proteins was mainly attributed to the mature MBP, because MBP-depleted eosinophil granule proteins did not inhibit TM cofactor activity significantly. This inhibition seemed to be due to the specific thrombin-binding to TM being blocked. We concluded that eosinophil granule proteins, particularly MBP, potentially contribute to the hypercoagulation seen in some conditions of eosinophilia, at least because of the inhibition of TM function as a cofactor of the anticoagulation system.

Blood Proteins↗
PubMed1995

Clinical significance of elevated soluble interleukin-6 receptor levels in the sera of patients with plasma cell dyscrasias.

We investigated the clinical significance of the serum soluble interleukin-6 receptor (sIL-6R) in 42 patients with plasma cell dyscrasias (27 with multiple myeloma (MM), 13 with monoclonal gammopathy of undetermined significance (MGUS), and two with plasma cell leukaemia (PCL)). Serum levels of sIL-6R in normal individuals were 77 +/- 21 ng/ml (mean +/- SD, n = 18); those in patients with MGUS and with MM were elevated (102 +/- 33 ng/ml, mean +/- SD, P < 0.05 and 126 +/- 60 ng/ml, mean +/- SD, P < 0.01, respectively). Significant correlations were not found between the serum levels of sIL-6R and known prognostic factors (C-reactive protein, haemoglobin levels, calcium, creatinine, beta 2-microglobulin, amounts of M-protein, or percentages of plasma cells in bone marrow). Elevated serum sIL-6R did not affect the survival of the patients with MM. Serial measurements of sIL-6R together with the clinical course of patients with plasma cell neoplasias revealed a good correlation between the sIL-6R level and disease activity. We conclude that sIL-6R can be used as a clinical factor correlated with the disease activity, at least in some patients with plasma cell neoplasias.

Antigens, CD↗
PubMed1995

Megakaryopoiesis in patients with cyclic thrombocytopenia.

Megakaryopoiesis was examined in 10 patients (eight females and two males) with cyclic thrombocytopenia (CT) to investigate the underlying pathogenesis. Numbers of CFU-Meg and megakaryocytes and the mean cytoplasmic area (mean area) of megakaryocytes at the peak, nadir, ascent mid phase, and descent mid phase of the platelet cycle were determined. The patients were classified as female cases group I (cases 1-4; previously diagnosed as ITP and CT occurred during remission), female cases group II (cases 5-8; persistent CT from initial diagnosis), and male CT (cases 9 and 10). In three of the four female cases in group I, numbers of CFU-Meg and megakaryocytes were normal or increased persistently during the platelet cycle, whereas the mean area fluctuated in synchrony with the platelet cycle, suggesting failure of cyclic production rather than platelet destruction. In the female cases in group II and one female case in group I, numbers of CFU-Meg and megakaryocytes were also normal or increased at four phases of the cycle, but the mean area did not fluctuate, remaining large during the cycle, suggesting cyclic destruction or platelet clearance. In contrast, in the male patients values for numbers of CFU-Meg, megakaryocytes and mean cytoplasmic area fluctuated during the platelet cycle, indicating that cyclic changes in megakaryopoiesis generated the platelet cycle. These findings indicate that the measurement of cytoplasmic area is useful for distinguishing cyclic platelet production from cyclic destruction or clearance in CT.

Adult↗
PubMed1995

Long-lasting activation of cation current by low concentration of endothelin-1 in mouse fibroblasts and smooth muscle cells of rabbit aorta.

1. Recombinant human ETA receptors were expressed in a mouse fibroblast cell line (Ltk- cell) and functional coupling of the receptors with Ca2+ permeable channels at low concentrations of endothelin-1 (ET-1) was investigated using whole-cell recordings and monitoring the changes in intracellular free Ca2+ concentrations ([Ca2+]i) with a Ca2+ indicator, fluo-3. A similar type of coupling was investigated in freshly dispersed vascular smooth muscle cells (VSMCs) of rabbit thoracic aorta by use of whole-cell recordings. 2. In Ltk- cells expressing recombinant human ETA receptors, concentrations of ET-1 (10(-8) M, 10(-9) M) evoked an initial transient peak and a subsequent sustained elevation in [Ca2+]i whereas a lower concentration of ET-1 (10(-10) M) evoked only a sustained elevation of [Ca2+]i. After removal of extracellular Ca2+, ET-1 evoked only an initial peak without a sustained elevation of [Ca2+]i. The sustained elevation induced by 10(-10) M ET-1 was blocked by 300 microM mefenamic acid (a cation channel blocker) but not by 10 microM nifedipine (a blocker of voltage-operated Ca2+ channel). 3. In whole-cell recordings with Ltk- cells, a brief (3-5 min) application of ET-1 (10(-10) M) induced a sustained inward current at a holding potential of -60 mV. The current-voltage relationship revealed that the reversal potential of the ET-1-induced current was close to 0 mV (1.9 mV) and was not altered by reducing the concentration of Cl- in the bath solution, indicating that the current is carried by cations. The current was reversibly blocked by 300 microM mefenamic acid, and it persisted after all cations in the bath solution had been replaced by Ca2+ (5 or 30 mM) and nonpermeant cation N-methyl-D glucamine,indicating that the ET-1-activated channel is permeable to Ca2+. Activation of the current was independent of membrane potential and the current was induced even after addition of a high concentration (10 mM) of a Ca2+ chelator, EGTA, to the pipette solution.4. In whole-cell recordings from rabbit aortic VSMCs, ET-l (101-10 M) induced a sustained inward current at a holding potential of -60 mV. The reversal potential was - 12 mV and was not altered when the concentration of Cl- in the pipette solution was decreased, indicating that the current is carried by cations. Again activation of the current was independent of membrane potential and was observed even after addition of a high concentration (10 mM) of a Ca2+ chelator, EGTA to the pipette solution. The current was reversibly blocked by 300 microM mefenamic acid and was permeable to Ca2+,showing marked similarities to ET-1-induced cationic current in Ltk- cells.5. These results indicate that in Ltk- cells transfected with cDNA for recombinant ETA receptors andVSMCs, ETA receptors can functionally couple with a nonselective cation channel permeable to Ca2+.Thus the present data suggest that the cation channel plays an essential role in the sustained elevation of[Ca2+]i at low concentrations of ET-l by causing Ca2+ entry through the channel.

Aniline Compounds↗
PubMed1995

Effects of anti-platelet glycoprotein Ib and/or IIb/IIIa autoantibodies on the size of megakaryocytes in patients with immune thrombocytopenia.

To determine whether anti-platelet autoantibodies react with megakaryocytes, as well as with platelets, in immune thrombocytopenia (ITP), 38 ITP patients were studied. They were classified into four groups; anti-platelet glycoprotein Ib-positive (group A, n = 5), anti-platelet glycoprotein II/b/IIIa-positive (group B, n = 2), positive to both antibodies (group C, n = 3), and negative to both antibodies (group D, n = 28). The number and size of megakaryocytes in each group were compared. The number of megakaryocytes in groups A, B, C, and D was 12.8 +/- 8.9, 75.2, 29.1, and 17.0 +/- 21.7/mm2, respectively. The mean cytoplasmic area of megakaryocytes in groups A, B, C, and D was 1001 +/- 26.3, 1621, 1109, and 1311 +/- 235.6/micrograms2, respectively. This finding indicated that, in the presence of anti-platelet glycoprotein Ib, megakaryocytes were not increased in number and were small in size, whereas, in the presence of anti-platelet glycoprotein IIb/IIIa, megakaryocytes were increased in number and in cytoplasmic area. Our study suggested that anti-platelet glycoprotein Ib may impair platelet production by megakaryocytes in ITP.

Antibody Specificity↗
PubMed1995

Simultaneous measurements of megakaryocyte-associated IgG (MAIgG) and platelet-associated IgG (PAIgG) in chronic idiopathic thrombocytopenic purpura.

We have simultaneously measured platelet-associated IgG (PAIgG) and megakaryocyte-associated IgG (MAIgG) in 30 untreated patients with chronic idiopathic thrombocytopenic purpura (CITP). Megakaryocytes were purified from bone marrow by 35% Percoll gradient centrifugation, followed by negative immunopanning using magnetic immunobeads. The normal range of MAIgG in 30 healthy donors was 15.5 +/- 10.0 ng/10(5) megakaryocytes, whereas MAIgG in the 30 CITP patients was 140 +/- 59.3 ng/10(5) megakaryocytes, although the values were widely distributed. From the PAIgG and MAIgG data, CITP patients were classified into three types; type I (PAIgG < 200 ng/10(7) platelets and MAIgG < 150 ng/10(5) megakaryocytes), type II (PAIgG > 200 ng and MAIgG > 150 ng), and type III (PAIgG < 200 ng and MAIgG > 150 ng). Patients with types I and III had good clinical courses, but, in contrast, patients with type II responded poorly to steroid therapy followed by splenectomy or became refractory to treatment. In splenectomized patients, MAIgG of responder was promptly decreased to normal range and, in contrast, that of non-responder was persistently elevated. These results indicate that anti-platelet autoantibodies are able to bind with megakaryocytes in the bone marrow as well as with platelets in the peripheral blood, and the results also suggest that megakaryopoiesis in CITP is heterogeneous. Simultaneous measurement of PAIgG and MAIgG may predict the clinical outcome of CIPT.

Autoantibodies↗
PubMed1995

Specific binding of endothelin-1 to canine tracheal epithelial cells in culture.

We have studied the binding of endothelin-1 (ET-1) to cultured canine tracheal epithelial cells. A single specific binding site for 125I-labeled ET-1 was identified with an apparent dissociation constant (Kd) of 0.2 nM, maximal binding sites (Bmax) of 6.7 x 10(3) sites/cell, and half-maximal inhibition (IC50) of 0.3 nM during a 2-h incubation period. The binding of 125I-ET-1 to these cells was inhibited by the presence of unlabeled ET-1, ET-2, or BQ-123, whereas ET-3 and sarafotoxin S6c did not compete for this binding site. These binding characteristics are consistent with those of the ETA receptor. At 37 degrees C, specific binding continuously increased over 18 h, while at 4 degrees C, it reached a plateau by 2 h. The increase in binding at 37 degrees C was not associated with DNA synthesis but was dependent upon protein synthesis, suggesting that epithelial binding sites were produced continuously under these incubation conditions. Our results indicate that canine tracheal epithelial cells possess specific binding sites for ET-1 with characteristics similar to those of the ETA receptor subtype. Because these cells are demonstrated to both release and bind ET-1, the results further suggest that ET-1 is involved in paracrine and/or autocrine control mechanisms in the airway epithelium.

Animals↗
PubMed1995

A case of one eye with gelatinous drop-like corneal dystrophy and the other eye with band-shaped spheroidal corneal degeneration.

The first case of gelatinous drop-like corneal dystrophy in one eye and band-shaped spheroidal corneal degeneration in the other eye was reported. She was a member of Japanese family with gelatinous drop-like corneal dystrophy. A close association between gelatinous drop-like corneal dystrophy and band-shaped spheroidal corneal degeneration was suggested.

Adult↗
PubMed1995

Suppression of endothelin-1-induced mitogenic responses of human aortic smooth muscle cells by interleukin-1 beta.

When applied to quiescent human aortic smooth muscle cells (AOSMC), endothelin-1 (ET-1) caused significant increases in mitogen-activated protein kinase (MAPK) activity, [3H]thymidine incorporation, and cell proliferation, confirming an activity of ET-1 as a potent mitogen on AOSMC. As an in vitro model to evaluate the significance of the mitogenic activity of ET-1 on smooth muscle cells during atherogenesis, we studied possible modulations of the responsiveness of the cells by treatment with various cytokines (IL-1 beta, IL-8, TNF alpha, and TGF beta). Of the four cytokines tested, we found that the treatment of the cells with IL-1 beta dramatically reduced the responsiveness of the cells to ET-1; IL-1 beta treatment at the concentration of 0.2 ng/ml for 8 h completely abolished the activity of ET-1 to induce the mitogenic responses. IL-1 beta treatment caused no changes in the responses induced by EGF, basic fibroblast growth factor, or PDGF. Studies on ET-1-induced intracellular signaling events in IL-1 beta-treated cells revealed that the failure of ET-1 to induce mitogenic responses was due to an increase in cAMP formation secondary to ET-1-induced activation of prostanoid metabolism. These findings on AOSMC in vitro raise the possibility that, under some inflammatory conditions in vivo, ETs may work as a negative modulator of smooth muscle cell proliferation.

Amino Acid Sequence↗
PubMed1995

Intrahepatic portal-venous changes in dogs with dirofilariasis: scanning electron microscopy of resin casts of vasculature.

Intra hepatic portal-venous changes in dogs with dirofilariasis, in which characteristic cavernous transformation has been histologically observed, were studied by scanning electron microscopy (SEM) of resin casts of vasculature. Changes in the central and sublobular veins were the most significant. The venous channels were extremely dilated, thin-walled and showed cavernous structure. SEM observation showed multi-saccular formation with beads-like, helical and extremely dilated configuration. The conducting venules, i.e. terminal tributaries of the portal vein, showed a rapid taper just before the point of merging into sinusoids. Neither vascular proliferation nor collateral circulation around the portal channels could be detected in the present resin cast study.

Animals↗
PubMed1995

Vascular pattern of a metastatic liver tumor in a dog:--a scanning electron microscopic study of resin casts.

Metastasis of a malignant mixed tumor occurring in the abdominal wall was found in the liver of a 15-year-old dog male. The vascular system of the metastatic lesion was examined by scanning electron microscopy using the resin cast technique. The existence of arterio-portal shunts was confirmed. The shunts arose from branches of the hepatic artery in retrograde or vertical direction and merged into the capillary plexus replacing the branches of the portal vein, forming the so-called thread and streaks vessel in the field of hepatic angiography. Vessels with the thread and streaks appearance histologically represented tumor emboli growing in the lumen of a large branch of the portal vein. There were capillaries running inside along the portal vein and forming a longitudinal dense network in the vein. Branches of the hepatic artery feeding the metastatic lesion were well developed and formed a coarse arterial network in their course. Tributaries of the hepatic vein from the lesion were also well developed.

Animals↗
PubMed1995

CD34-positive blastoma in a patient with idiopathic myelofibrosis.

We report CD34-positive "blastoma" which developed in a patient with idiopathic myelofibrosis (IMF). A 48-year-old woman was diagnosed as having essential thrombocythemia, then the disease had transformed into IMF 41 months later. Finally, a subcutaneous tumor, composed of blastic cells positive for CD34 but negative for lineage-specific antigens, developed without any evidence of systemic leukemia transformation.

Antigens, CD34↗
PubMed1995

[von Recklinghausen's disease complicated by macroglobulinemia, malignant schwannoma and pheochromocytoma].

We reported a case of von Recklinghausen's disease complicated by macroglobulinemia, malignant Schwannoma and pheochromocytoma. A 43-year-old male patient who was diagnosed as von Recklinghausen's disease developed abdominal masses at 5 years after the adrenalectomy for pheochromocytoma. Computed tomography showed multiple heterogeneous tumors in abdominal cavity. Histological examination of resected tumor was compatible with malignant Schwannoma. At the same time, peripheral blood and bone marrow smears showed a large number of plasmacytoid lymphocytes. Immunoelectrophoresis revealed M-protein of IgM, kappa type. He was also diagnosed of coexistence with macroglobulinemia. The chemotherapeutic protocols used were not effective against both malignant Schwannoma and macroglobulinemia. The present case is a rare case of von Recklinghausen's disease associated with triple neoplasms.

Abdominal Neoplasms↗
PubMed1995

[Minimally differentiated hypoplastic leukemia].

Sixty-seven years-old female, who was an atomic bomb survivor in Hiroshima, was pointed out as having leukopenia and anemia in 1991. She was referred to Tsukuba University Hospital in June 1992. Her peripheral blood count showed pancytopenia- 2,600/microliters WBC, 10.5 g/dl hemoglobin, and 80,000/microliters platelets- at that time. BM biopsy revealed hypoplastic marrow and increased peroxidase-negative blasts (32.8%). Surface marker analysis of the blasts showed a feature of CD2+ CD33+ CD34+ CD13+ CD3-. Electronmicroscopically, myeloperoxidase was positive. She was diagnosed as having hypoplastic leukemia of which the blasts had a feature of AML-M0 by FAB-group. After 6 months' silent period, her pancytopenia became profound. We successfully reduced the blasts by BAM therapy. However, she died of bacterial pneumonia during the myelosuppressive state. This is a case of minimally differentiated hypoplastic AML.

Aged↗