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Biomedical subjects

H Ninomiya

Publications and source records attributed to H Ninomiya.

At least 91 records · Page 5Linked to original sources

Complement-induced procoagulant alteration of red blood cell membranes with microvesicle formation in paroxysmal nocturnal haemoglobinuria (PNH): implication for thrombogenesis in PNH.

Complement-induced procoagulant alteration of red blood cell (RBC) membranes in paroxysmal nocturnal haemoglobinuria (PNH) was examined. Microvesicles, deficient in acetylcholinesterase, were generated and released from PNH RBC upon complement activation. The microvesicles generated from complement-activated PNH RBC accelerated factor Xa-dependent plasma coagulation more than those generated from RBC by the treatment with ionophore A23187. When assessed by factor Xa-catalysed prothrombin activation, complement activation enhanced procoagulant properties of both normal and PNH RBC similarly, although PNH RBC were lysed but normal RBC were not. This enhancement of factor Xa-dependent prothrombinase activity of complement-activated RBC was inhibited by the treatment of the RBC with annexin V, a protein with binding affinity for anionic phospholipids especially for phosphatidylserine (PS). Neither the enhanced procoagulant properties of RBC nor apparent RBC population with annexin V-binding affinity were demonstrated before complement activation in any of the four PNH patients studied. PS-externalized PNH RBC and microvesicles may contribute to the removal of PNH RBC from the circulation. We conclude that although PNH RBC do not constantly exhibit enhanced procoagulant properties in vivo, complement activation induces a procoagulant alteration of RBC membranes with microvesicle formation, potentially contributing to the thrombogenesis in PNH.

Annexin A5↗

Endoderm differentiation and inductive effect of activin-treated ectoderm in Xenopus.

When presumptive ectoderm is treated with high concentrations of activin A, it mainly differentiates into axial mesoderm (notochord, muscle) in Xenopus and into yolk-rich endodermal cells in newt (Cynops pyrrhogaster). Xenopus ectoderm consists of multiple layers, different from the single layer of Cynops ectoderm. This multilayer structure of Xenopus ectoderm may prevent complete treatment of activin A and subsequent whole differentiation into endoderm. In the present study, therefore, Xenopus ectoderm was separated into an outer layer and an inner layer, which were individually treated with a high concentration of activin A (100 ng/mL). Then the differentiation and inductive activity of these ectodermal cells were examined in explantation and transplantation experiments. In isolation culture, ectoderm treated with activin A formed endoderm. Ectodermal and mesodermal tissues were seldom found in these explants. The activin-treated ectoderm induced axial mesoderm and neural tissues, and differentiated into endoderm when it was sandwiched between two sheets of ectoderm or was transplanted into the ventral marginal zone of other blastulae. These findings suggest that Xenopus ectoderm treated with a high concentration of activin A forms endoderm and mimics the properties of the organizer as in Cynops.

Activins↗

Non-Hodgkin's lymphoma followed by plasmacytoma, both arising in A thyroid gland with Hashimoto's disease.

We describe here a rare case of malignant lymphoma followed by plasmacytoma in Hashimoto's thyroiditis. The patient developed malignant lymphoma (small, non-cleaved cell, and non Burkitt's type by Working Formulation classification), and remained in remission for 2 years after receiving combination chemotherapy, and then developed plasmacytoma in the same lesion. Rearrangement bands for IgH from both specimens showed different bands, indicating that both were of monoclonal type but of a different clonal origin. Considering the clinical course in this case, thyroidectomy may be indicated for lymphoproliferative diseases in Hashimoto's thyroiditis treated with chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Collagen fiber arrangement in canine hepatic venules.

Cell-maceration/scanning electron microscopy, serial sections and scanning electron microscopy of vascular resin casts were employed to demonstrate the arrangement of collagen fibers in the terminal hepatic venules, involving the central, intercalated and collecting veins in dog liver. In cell-maceration specimens, each collagen fiber was observed to run in various directions, forming a sheath with a compact meshwork of collagen fibers. The collagenous meshwork in the hepatic venules was looser than those of the terminal portal venules and hepatic arterioles. Some collagen fibers formed bundles with an elongated spiral arrangement encircling the wall of the terminal hepatic venules. In resin casts, these venules were observed as a twisted configuration caused by spiral collagen bundles. A helical modification of such connective tissue bundles might provide a mechanically stable vascular structure and permit reversible changes in linear and circumferential vascular dimensions at the terminal tributaries of veins. Round or oval pores with diameters of approximately 9 microns were also observed in the sheath of collagen fibers. These pores, together with the relatively loose collagenous meshwork in the hepatic venules, might play a role in lymphocyte migration from these venules into the surrounding tissue and provide high permeability to the venule walls. No such helical configuration and pores were observed in either the portal venules or the hepatic arterioles.

Animals↗

Obstructive uropathy and hydronephrosis in male KK-Ay mice: a report of cases.

Uropathy associated with hydronephrosis was observed frequently in our male KK-Ay mouse colony during a long-term study of diabetes. The lesion occurred in 24 of the 31 KK-Ay male mice and accounted for the greatest number of spontaneous deaths among them. It was observed after 4 months of age and involved about hard plugs of altered seminal material resembling the seminal vesicle secretion. The plugs became impacted in the urethral bulb and the bladder. The penile anatomy, with its flexure, pressure on the urethra from the bulbocavernosus muscle, and the characteristic ability of the seminal fluid to easily coagulate to form the vaginal plug may have contributed to the lesion. Correlation between development of the uropathy and diabetes has not been established.

Animals↗

Underdevelopment of fetal thyroid follicular cells in athymic nude mouse (BALB/cAnNCrj-nu/nu) observed by electron microscopic morphometry.

Fetal thyroid follicular cells of congenitally athymic nude mouse (BALB/cAnNCrj-nu/nu) were studied with an electron microscope. The area of the entire cell, nucleus and mitochondrion were measured and compared in athymic and euthymic fetal nude mice (BALB/cAnNCrj-nu/+) at 18 days of gestation. The mean area of cytoplasm was significantly smaller in homozygous athymic nude mice than in heterozygous euthymic ones. The mean area of the mitochondrion was also smaller in homozygous athymic nude mice, but the difference was not statistically significant. There was no significant difference between the two groups in the area of the nucleus. These findings suggest that the thyroid gland of athymic nude mice is still underdeveloped at the end of gestation as compared to that of their euthymic littermates.

Animals↗

Pseudoaneurysm of the subclavian artery due to Xanthomonas pneumonia in a patient with acute myeloid leukemia: its rupture treated by transcatheter coil embolization.

A 52-year-old male with acute myeloid leukemia developed pseudoaneurysm of the subclavian artery. Pneumonia due to Xanthomonas maltophilia, which was multi-drug resistant, progressed to a lung abscess even under administration of antibiotics. This lung infection contiguous to the left carotid and subclavian arteries was suggested to have caused the pseudoaneurysm of the subclavian artery. The rupture of the aneurysm by penetration to the trachea amounted to about 1,000 ml of bleeding; fortunately the bleeding ceased spontaneously. Nonetheless, an emergency transcatheter coil embolization prevented re-bleeding. Endovascular treatment should be considered especially for aneurysms which develop in patients with underlying diseases.

Aneurysm, False↗

Improvement of control cable system of trans-humeral body-powered prostheses.

For the purpose of improving the efficiency of a body-powered prosthesis, a control cable system was developed which uses a pulley and a cable housing which includes a highly slippery plastic liner. Improvements were also made to the harness. In this paper, the mechanism of these systems is firstly described and then, the results of a clinical evaluation test of a practical model is presented along with an efficiency evaluation by a testing instrument. For the design of each system, the material and size suitable for the conditions of cosmetic and general versatility were considered. The clinical test was performed on 12 subjects to prove the effectiveness of the system. This test procedure was repeated. These tests proved the effectiveness of the systems.

Humans↗

High-dose chemotherapy with peripheral blood stem cell rescue in blastoid natural killer cell lymphoma.

A 25-year-old man was referred because of skin rash, lymphadenopathy and anemia. Laboratory examinations revealed severe anemia (Hb, 4.8 g/dl) and elevated levels of GOT, GPT, LDH and soluble interleukin-2 receptor. Work-up studies disclosed the involvement of lymphoma cells in lymph nodes, skin, bilateral kidneys and bone marrow. Lymph node biopsy revealed diffuse proliferation of medium- to large-sized lymphoblastic cells. Bone marrow aspiration showed massive infiltration of large blastic cells with no cytoplasmic granules. The lymphoma cells in bone marrow and lymph node showed surface CD3-, cytoplasmic CD3epsilon+, CD4+, CD8-, CD56+, CD57-, CD16- and CD43 (MT-1)+ phenotype. Analyses of T cell receptor beta and gamma genes showed germ line configurations. EBER-1 was not detectable in the lymphoma cells. He was diagnosed as having blastoid natural killer (NK) cell lymphoma. In spite of several courses of combination chemotherapy, the lymphoma was progressive. He was then treated with high-dose chemotherapy and peripheral blood stem cell rescue, achieving remission which has now lasted for more than 12 months. We consider that blastoid NK cell lymphoma is an extremely aggressive subtype of CD56-positive lymphomas, and high-dose chemotherapy with peripheral blood stem cell rescue should be included for the choice of the treatment.

Adult↗

Effect of granulocyte-colony stimulating factor on empiric therapy with flomoxef sodium and tobramycin in febrile neutropenic patients with hematological malignancies. Kan-etsu Hematological Disease and Infection Study Group.

The clinical effects of concomitant use of granulocyte-colony stimulating factor (G-CSF) on empiric antibiotic therapy in febrile neutropenic patients were evaluated in a randomized fashion. Two hundred and fourteen neutropenic febrile episodes (neutrophil counts < 1.0 x 10(9)/l) were treated with flomoxef sodium and tobramycin with or without G-CSF. The resolution of fever at day 4 (excellent response) or at day 7 (good response) was deemed effective. Among 157 evaluable episodes, the observed excellent responses were 31 (38.8%) and the good responses were 20 (25.0%) in the G-CSF group; those in the control group were 26 (33.8%) and 25 (32.5%), respectively. The overall efficacy rate was 63.8% (51/80) in the G-CSF group and 66.2% (51/77) in the control group (not significant). The initial neutrophil count was 0.186 +/- 0.249 x 10(9)/l in the G-CSF group and 0.235 +/- 0.290 x 10(9)/l in the control group, and rose to 2.889 +/- 4.198 x 10(9)/l and 0.522 +/- 0.844 x 10(9)/l, respectively, at day 7. These results indicate that G-CSF does not affect the rate of response to empiric antibiotic therapy in febrile neutropenic patients, although a significant effect of G-CSF was observed on neutrophil recovery.

Adolescent↗

Structural basis of the function of endothelin receptor.

Endothelin receptor is a good model for analysis of the function of heptahelical G-protein coupled receptor. In ligand binding to the heptahelical receptor, the receptor has two functions, i.e. 'message' and 'address' functions. Each function has been assigned to different domain of the receptor. A different part of the ligand structure also corresponds to each domain of the receptor. Classically, classification of receptor has been done according to the difference of address domain, i.e. affinity difference of the receptor. However, present results predict that the classification of receptor is also possible according to the message domain. After stimulation of ET receptor by a ligand, the receptor transmits a signal to G-protein. Several kinds of G-proteins can possibly be activated. Different structural domains of the receptor are assigned to the coupling of the different Galpha-protein. Activated G-protein transmits the message to effector. Each Galpha-protein acts on different target molecules, resulting in different responses. However, the activation of each Galpha-protein presumably depends on its intracellular level. Even if the same receptor is activated with the same ligand, resulting final response is different from cell to cell. Therefore, classification of receptor according to the function of the receptor is difficult.

Animals↗

[T-cell prolymphocytic leukemia with CD4+8+25+ phenotype in a patient presenting with venous thrombosis in the lower leg].

A 58-year-old man was referred to our hospital because of painful swelling in the left lower leg and leukocytosis in January 1999. Moderate hepatosplenomegaly but no lymph node swelling was observed. Marked leukocytosis (leukocytes 44.9 x 10(4)/microliter with 95% morphologically prolymphocytes) and thrombocytopenia were detected. The surface phenotype of the leukemia cells was CD1-2+3+5+7+4+8+25+. Magnetic resonance imaging revealed dilated veins in the left lower leg. An abnormal 47XY, +22 karyotype was detected in 1/20 cells. Tests for HTLV-I antibody were negative. A diagnosis of T-cell prolymphocytic leukemia (T-PLL) was made on the basis of data including cytochemical and electron microscopic findings. Although 2 courses of chemotherapy comprising vincristine, cyclophosphamide, and prednisolone improved the venous thrombosis in the leg, the leukemia cells were refractory to chemotherapy. To prevent the recurrence of venous thrombosis due to leukostasis, the patient underwent repeated leukapheresis. The leukocyte count was maintained at around 20.0 x 10(4)/microliter after total 7 courses of leukapheresis, one course of which comprised 7l of extracorporeal circulation. In addition to the rare presentation of venous thrombosis, the CD4+8+25+ phenotype observed in this case is rare in patients with T-PLL.

CD4-CD8 Ratio↗

Role of nonselective cation channels as Ca2+ entry pathway in endothelin-1-induced contraction and their suppression by nitric oxide.

The present study was carried out to clarify the role of nonselective cation channels as a Ca2+ entry pathway in the contraction and the increase in [Ca2+]i induced by endothelin- in endothelium-denuded rat thoracic aorta rings, and their suppression by nitric oxide (NO). In Ca2+-free medium, the endothelin-1-induced contraction was suppressed to about 20% of control values, although the increase in [Ca2+]i became negligible. The contraction and the increase in [Ca2+]i monitored by fura 2 fluorescence were unaffected by a blocker of L-type voltage-operated Ca2+ channels nifedipine. A blocker of nonselective cation channels 1-[beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl]-1H-imida zole . HCl(SK&F 96365) suppressed the endothelin-1-induced contraction and increase in [Ca2+]i to the level similar to that after removal of extracellular Ca2+. SK&F 96365 had no further effect on the endothelin-1-induced contraction in the absence of extracellular Ca2+. The endothelin-1-induced contraction and increase in [Ca2+]i were abolished by a donor of NO sodium nitroprusside. The effects of another NO donor 3-morpholinosydnonimine (SIN-1) were also tested and yielded essentially similar results to those for sodium nitroprusside on the endothelin-1-induced contraction. Furthermore, the inhibitory effects of sodium nitroprusside could be blocked with a guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) at 30 microM. These findings suggest that Ca2+ entry through nonselective cation channels but not voltage-operated Ca2+ channels plays a critical role in the endothelin-1-induced increase in [Ca2+]i and the resulting contraction and that inhibition by NO of the endothelin-1-induced contraction is mainly the result of blockade of Ca2+ entry through these channels.

Animals↗

Endothelin-induced apoptosis of A375 human melanoma cells.

Endothelin-1 (ET-1) inhibited serum-dependent growth of asynchronized A375 human melanoma cells, and the growth inhibitory effect was markedly enhanced when ET-1 was applied to the cells synchronized at G1/S boundary by double thymidine blocks. Flow cytometric analysis revealed that ET-1 did not inhibit the cell cycle progression after the release of the block but caused a significant increase of the hypodiploid cell population that is characteristic of apoptotic cell death. ET-1-induced apoptosis was confirmed by the appearance of chromatin condensation on nuclear staining and DNA fragmentation on gel electrophoresis. The increase in the hypodiploid cell peak was manifest within 16 h of exposure to 5 nM ET-1. Within the same time range, ET-1 caused actin reorganization and drastic morphological changes of the surviving cells from epithelioid to an elongated bipolar shape. These phenotypical changes were preceded by ET-1-induced increase and nuclear accumulation of the tumor suppressor protein p53. All of these effects of ET-1 were mediated by ETB via a pertussis toxin-sensitive G protein. Flow cytometric analysis with fluorescent dye-labeled ET-1 revealed up-regulation of ETB expressed by the cells in G1/early S phases, and overexpression of the receptor protein by cDNA microinjection conferred the responsiveness (both apoptosis and morphological changes) to ET-1 irrespective of the position of the cell in the cell cycle. These results indicated the presence of ETB-mediated signaling pathways to apoptotic cell machinery and cytoskeletal organization. Furthermore, the densities of ETB expressed by individual A375 melanoma cells appeared to be regulated by a cell cycle-dependent mechanism, and the receptor density can be a limiting factor to control the apoptotic and cytoskeletal responses of the cells to ET-1. Although the molecular mechanisms remain to be elucidated, these findings added a new dimension to the diverse biological activities of ETs and also indicated a novel mechanism to control the responsiveness of the cell to the peptides.

Cell Division↗

Neuromagnetic fields preceding unilateral movements in dextrals and sinistrals.

Movement-related magnetic fields were recorded with a whole-head magnetoencephalographic system in three dextrals and three sinistrals during right or left index finger extension. The motor field (MF) demonstrated an asymmetrical isofield map pattern with larger field reversal over the contralateral hemisphere for dominant hand movement and an almost symmetrical pattern for non-dominant hand movement in each subject. The equivalent current dipole moment of the MF for the contralateral hemisphere was significantly larger than the ipsilateral hemisphere for dominant hand movement, and almost equal for both hemispheres for non-dominant hand movement. These results were congruent for both dextrals and sinistrals, suggesting a more important role of the hemisphere contralateral to the dominant hand in unilateral voluntary movement, regardless of handedness.

Brain↗

Stochastic determination of the chromosomal region responsible for expression of human glial fibrillary acidic protein in astrocytic tumors.

Previous investigators have localized the human glial fibrillary acidic protein (GFAP) gene in the segment 17q21 in chromosome 17. In the present study, we statistically assessed the association between the allelic status in thirty-three microsatellite loci and the immunohistochemical expression of GFAP in twenty human astrocytic tumors. The results demonstrated that the loss of heterozygosity in only one locus (D17S795 located in 17q21.2) was significantly associated with the impaired expression of GFAP (P = 0.0280, Pc = 0.0384 by Fisher's exact test). The adjacent loci located in 17q21.1 and 17q21.3 were not relevant to GFAP expression. Those data suggest that the critical region responsible for GFAP expression (coding sequence and regulatory elements) is located close to the locus D17S795 in the segment 17q21.2.

Astrocytoma↗