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Biomedical subjects

H Ninomiya

Publications and source records attributed to H Ninomiya.

At least 127 records · Page 7Linked to original sources
PubMed1998

Glomerular vascular changes in KK-Ay mice with early diabetes: scanning electron microscopy of vascular resin casts.

Vascular changes, the angioarchitecture of renal glomerular fine vessels in early diabetic KK-Ay mice of 4 months of age were examined by scanning electron microscopy of corrosion casts. Histologically, enlargement of glomeruli and dilation of glomerular capillaries were found. In resin cast specimens, glomeruli with diabetes were larger than normal, and an increase in diameter of the glomerular vessels was found in diabetic mice. No capillary proliferation, distortion of glomerular vessels and destruction of glomerular capillary loops were found in diabetic mice. The increased vascular diameter may explain the increase in blood flow in the glomeruli, affecting kidney function in early diabetes.

Animals↗
PubMed1998

Histological changes in the endometrial arterioles during postpartum offthe Chinese hamster (Cricetulus griceus).

The morphology of the uterine wall in the postpartum Chinese hamster (Cricetulus griceus) was studied with particular reference to the changes in the arterioles in the mesometrial endometrium. At day 0 postpartum, the endometrial arterioles were characterized by the appearance of trophoblastic giant cells plugging ruptured arterioles. On days 1 to 3 postpartum, the giant cells were replaced by epitheloid cells. On days 4 to 5 postpartum, the epitheloid cell mass was invaded by fibroblasts to occlude the arterial lumens. On days 6 to 7 postpartum, endometrial regeneration was completed. The giant cell might play a role in hemostasis immediately after parturition.

Animals↗
PubMed1998

Multiple diffuse fibrosarcoma of bone associated with extramedullary hematopoiesis.

We report a case of multiple diffuse fibrosarcoma of bone. The patient, a 38-year-old man, was referred to our hospital with knee pain, anemia and thrombocytopenia. No solid mass was seen on radiographic examination of the kneejoint, but magnetic resonance imaging showed hypointensity of the distal femur. Femoral biopsy revealed proliferation of long spindle-shaped fibrosarcoma cells, while a bone marrow biopsy of iliac bone (which appeared normal on radiographic examinations) showed replacement of hematopoietic cells by fibroblast-like spindle cells. A diagnosis of multiple diffuse fibrosarcoma of bone was therefore made. Autopsy revealed tumor invasion into multiple bones and several visceral organs and extramedullary hematopoiesis in the liver, spleen and lymph nodes. As this patient had leukoerythroblastic anemia with poikilocytosis, splenomegaly exhibiting extramedullary hematopoiesis, and apparent fibrotic change in his bone marrow, we suggest that this extremely rare disease should be considered in the differential diagnosis of myelofibrosis.

Adult↗
PubMed1998

[A case of advanced gastric cancer with virchow's metastasis responding remarkably to combination chemotherapy of low-dose CDDP and 5-FU].

The patient was a 72-year-old female who had Stage IVb advanced gastric cancer with Virchow's and paraaortic lymph node metastases. She was considered nonresectable and placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU. After 1 course of administration, Virchow's metastasis disappeared, and the tumor was remarkably reduced in size. However, this chemotherapy was interrupted by toxicity of grade 3 appetite loss, nausea and vomiting, so that total gastrectomy and splenectomy were performed, which were non-curative operation because of paraaortic lymph node metastases. Histopathological examination of the section of the primary tumor revealed that cancer cells had almost disappeared, and only a few atypical cells remained in the granulation tissue. Eleven months after the surgery, there has been no progression of Virchow's and paraaortic lymph node metastases. Combination chemotherapy of low-dose CDDP and 5-FU appears useful as an inductive approach to advanced gastric cancer.

Adenocarcinoma↗
PubMed1998

Paracrine endothelin signaling in the control of basal cell proliferation in guinea pig tracheal epithelium.

Immunofluorescent analyses revealed distinct cellular/subcellular localization of endothelin (ET) receptors and ET-1 in the epithelial cell layer of guinea pig trachea. ETA was expressed predominantly in the basal cells. ETB was expressed predominantly in the ciliated columnar cells and was polarized at the apical side of the cell body within the cells. Anti-ET-1-immunoreactive cytoplasmic granules were contained in the secretory cells that were scattered throughout the epithelial layer. Cell proliferation assays with immersion cultures of differentially plated cells (basal cell-enriched, non-basal cell-enriched and mixed cell cultures) indicated the presence of paracrine ET-1 signaling pathways that transmit both positive and negative effects on the basal cell proliferation. Direct activation of ETA expressed on the basal cells caused enhancement of their growth, whereas that of ETB expressed on the ciliated columnar cells caused suppression of the basal cell growth. The latter effect was transmitted by nitric oxide whose production was stimulated by ETB activation. Furthermore, blockade of either ETA or ETB compromised the epithelial cell layer formation under the air-interphase culture, which indicates the dependence of tracheal epithelial remodeling on a balance between the positive and negative effects of ET-1 on the basal cell growth.

Animals↗
PubMed1998

[A study of sialylated carbohydrate antigen in patients with benign bronchopulmonary disease].

We studied the levels of carbohydrate antigen (CA 19-9, SLX, CA 50, Span-1, and Dupan-2) in serum, bronchoalveolar lavage fluid, and tissue from patients with benign bronchopulmonary disease. Patients had bronchiectasis, healed pulmonary tuberculosis, pulmonary fibrosis, or other diseases. Bronchoalveolar lavage fluid levels and immunohistochemical findings for lung tissue samples, in the absence of digestive and other diseases, suggested that elevated serum sialylated Lewis(A) (CA 19-9, CA 50, and Span-1) and Lewis(X) (SLX) antigen in patients with benign broncho-pulmonary disease are due to marked production of sialylated carbohydrate antigen in respiratory bronchioles. Common features of patients with benign bronchopulmonary disease include elevated serum carbohydrate antigen levels and bronchiectasis.

Aged↗
PubMed1998

Aorto-atrial fistula associated with recurrent aortic dissection after ascending aorta replacement.

A 70-year-old woman with a bicuspid aortic valve had undergone ascending aorta replacement for acute DeBakey type I dissection. Computed tomography and aortography 2 months after the operation revealed a thrombosed false lumen in the ascending aorta proximal to the prosthetic graft. However, recurrence of dissection was found at the aortic root proximal to the graft 4 years after the initial operation. Significant aortic stenosis was also noted. Despite intensive medical treatment, she had refractory and progressive heart failure. At the second surgery, an aorto-right atrial fistula, which probably was responsible for the severe heart failure was revealed. Closure of the aorto-right atrial fistula, and aortic root replacement were performed using Piehler's method, with a composite graft. The etiology and management of this rare case are discussed.

Aged↗
PubMed1997

Palmitoylation of human endothelinB. Its critical role in G protein coupling and a differential requirement for the cytoplasmic tail by G protein subtypes.

By site-directed mutagenesis, three cysteine residues (amino acids 402, 403, and 405) in the carboxyl terminus of human endothelinB (ETB) were identified as potential palmitoylation sites. Substitutions of all of the three cysteine residues with serine gave an unpalmitoylated mutant, C2S/C3S/C5S. When expressed in Chinese hamster ovary cells, C2S/C3S/C5S was localized on the cell surface, retained high affinities to ET-1 and ET-3, and was rapidly internalized when bound to the ligand. However, unlike the wild-type ETB, C2S/C3S/C5S transmitted neither an inhibitory effect on adenylate cyclase nor a stimulatory effect on phospholipase C, indicating a critical role of palmitoylation in the coupling with G proteins, regardless of the G protein subtypes. Truncation of the carboxyl terminus including Cys403/Cys405 gave a deletion mutant Delta403 that was palmitoylated on Cys402 and lacked the carboxyl terminus downstream to the palmitoylation site. Delta403 did transmit a stimulatory effect on phospholipase C via a pertussis toxin-insensitive G protein but it failed to transmit an inhibitory effect on adenylate cyclase. These results indicated a differential requirement for the carboxyl terminus downstream to the palmitoylation site in the coupling with G protein subtypes, i.e. it is required for the coupling with Gi but not for that with Gq.

Amino Acid Sequence↗
PubMed1997

Bromodeoxyuridine-induced expression of endothelin A in A375 human melanoma cells.

Expression of endothelin (ET) receptor subtypes was examined in an experimental model of A375 human melanoma cell differentiation using the pyrimidine analog bromodeoxyuridine (BUdR). BUdR (10 microM)-treated cells had an increased surface area and an increased dendricity, were contact-inhibited and lacked tumorigenecity in athymic nude mice. The untreated A375 cells exclusively expressed ETB and BUdR-induced phenotypical changes were accompanied by induction of ETA expression as evidenced by northern blotting, [125I]ET-1 binding assay and [Ca2+]i measurement. Thus, BUdR-induced differentiation of A375 melanoma cells may provide a model system to study the receptor subtype switch in melanocyte development.

Animals↗
PubMed1997

Cloning and characterization of a brain-specific cationic amino acid transporter.

rCAT3 (rat cationic amino acid transporter 3), a cDNA that encodes a novel member of the murine CAT family was isolated. The protein encoded by rCAT3 contained 619 amino acids, 53-58% of which were identical with those of the murine CAT family proteins previously described (mouse CAT1, CAT2a, CAT2b, and rat CAT1). Transient expression of rCAT3 and L-[14C]arginine incorporation experiments in COS7 cells verified a high affinity system y+ transporter activity of rCAT3. First, rCAT3-mediated L-[14C]arginine incorporation was time-dependent and saturable with half-saturation constant (Km) values of 103 +/- 12 microM (mean +/- S.E., n = 3). Second, the incorporation was specific for cationic amino acids as evidenced from the inhibition by L-arginine, L-lysine, and L-ornithine. Third, neither sodium nor chloride ions in the extracellular medium were required for the activity. Fourth, the incorporation was inhibited by high potassium-induced membrane depolarization. On Northern blot using RNAs from various rat tissues, the expression of rCAT3 mRNA was restricted to the brain. These results indicated a role of rCAT3 in the system y+ transporter activity in the nervous tissue.

Amino Acid Sequence↗
PubMed1997

Activated eosinophils stimulate endothelin-1 release from airway epithelial cells by direct adherence via adhesion molecules.

Endothelin-1 (ET-1), synthesized in airway epithelial cells, has a potent constrictive action on airway smooth muscle. In this study, we investigated the effect of eosinophils on ET-1 release from guinea pig cultured tracheal epithelial cells. Eosinophils with or without the activation were directly co-cultured with tracheal epithelial cells. Eosinophils activated by GM/CSF or IL-5 potentiated ET-1 release, but non-activated ones did not. Treatment of activated eosinophils with antibodies against macrophage-1 (Mac-1) and/or very late antigen-4 (VLA-4) suppressed the potentiated ET-1 release. However, inhibition of lipid mediators derived from activated eosinophils could not suppress the potentiated ET-1 release. Moreover, separated co-culture of activated eosinophils with tracheal epithelial cells using Millicell-CM had no effect on ET-1 release. These observations suggest that adherence of activated eosinophils to epithelial cells via adhesion molecules such as Mac-1 and VLA-4 was essential for potentiation of ET-1 release. Since presence of eosinophils in the epithelial layer has been commonly demonstrated in bronchial biopsies and autopsy specimens from patients with asthma, epithelial cells would be activated by adherence of eosinophils via adhesion molecules and potentiate ET-1 release in vivo.

Animals↗
PubMed1997

Possible overlapping potentials of the auditory P50 in humans: factor analysis of middle latency auditory evoked potentials.

The auditory P50 in humans may consist of overlapping potentials. To test this hypothesis, we manipulated the conditions of stimulus discrimination and motor response difficulty and evaluated the data by factor analysis. Twenty right-handed males (mean age 27 years) performed the following 4 tasks: (1) a counting task, (2) an easy Go, No-Go task, (3) a difficult Go, No-Go task, and (4) a choice reaction task. Middle latency auditory evoked potentials were obtained with 100 times summation triggered by the onset of the auditory stimulus. Four factors were extracted by factor analysis for a 0-100 ms time period. Factor 1, the maximum factor loading at 91 ms, corresponded to N1, and factor 4, the maximum factor loading at 23 ms, appeared to correspond to P30. The latency of the maximum factor loading in factor 2 was adjacent to that in factor 3, the latency of factor 2 being 12 ms earlier than that of factor 3. Factor 2 and factor 3 latencies were approximately 55 ms which corresponded to the P50. Factor 3 started rising at the point that factor 2 reached the maximum factor loading, and the factor score demonstrated a significant group difference only when analyzed by motor response criteria. These results suggest that the P50 in humans consists of overlapping potentials and that a part of the potential might relate to a motor response process.

Adult↗
PubMed1997

Multiple schwannomas in the radial nerve.

We present a case of multiple schwannomas in the radial nerve. The occurrence of multiple schwannomas in a single major nerve is very rare. Magnetic resonance imaging was useful in detecting the tumours. As schwannomas may be multiple without clinical symptoms, we recommend MR imaging of the entire limb when schwannomas occur in a major nerve in the upper extremity.

Adult↗
PubMed1997

Excess soluble urokinase-type plasminogen activator receptor in the plasma of patients with paroxysmal nocturnal hemoglobinuria inhibits cell-associated fibrinolytic activity.

The plasma levels of soluble urokinase-type plasminogen activator receptor (uPAR; CD87) measured by enzyme-linked immunosorbent assay were higher in patients with paroxysmal nocturnal hemoglobinuria (PNH) (5.8 +/- 4.7 ng/ml, mean +/- S.D., n = 9) than in normal donors (2.0 +/- 0.8 ng/ml, mean +/- S.D., n = 15). The high level of soluble uPAR in PNH plasma competed with the membrane uPAR expressed by normal blood neutrophils for binding to urokinase-type plasminogen activator (uPA). We also found that uPA complexed with soluble uPAR was partly resistant to inactivation by plasminogen activator inhibitors in the plasma, although uPA was inactivated similarly by plasma containing high and low levels of uPAR. PNH-affected blood cells are deficient in urokinase-type PAR, a glycosyl-phosphatidylinositol (GPI)-anchored protein. The deficiency of uPAR on PNH-affected leukocytes and the increased soluble uPAR in the PNH plasma may synergistically contribute to the development of thrombosis in PNH by inhibiting the cell-associated fibrinolytic activity.

Adult↗
PubMed1997

Elevated serum levels of eosinophil major basic protein in patients with myeloproliferative disorders without eosinophilia.

The 12- to 14-kDa eosinophil major basic protein (MBP) is primarily translated as 25-kDa pro-MBP. HL-60, a promyelocytic leukemia cell line, produces pro-MBP but not MBP, suggesting production of pro-MBP by immature granulocytes. We measured the serum levels of total MBP, using an ELISA that detects both pro-MBP and MBP, in 25 patients with leukemia (six acute myelogenous leukemia (AML), seven acute lymphoblastic leukemia (ALL), eight chronic myelogenous leukemia (CML), four chronic lymphocytic leukemia (CLL)) and five recipients of allogeneic bone marrow transplants (BMT). None of these patients except one AML (M4Eo) showed eosinophilia. Serum levels of total MBP were elevated in all the patients with CML and AML, but not in any of those with ALL or CLL. In all four recipients of BMT who obtained engraftments, serum levels of total MBP started to increase 12-14 days after BMT and reached the highest levels (4-10 times the basal levels) at days 19-32. In a recipient of BMT who did not obtain an engraftment, serum levels of total MBP were not increased. These findings suggested that pro-MBP could be used as a marker for proliferation of immature granulocytes with normal or malignant nature.

Acute Disease↗
PubMed1997

The involvement of a novel mechanism distinct from the thrombin receptor in the vasocontraction induced by trypsin.

1. The vasocontracting effect of a serine protease trypsin and its mechanisms were investigated by monitoring the isometric tension in endothelium-denuded rings of rabbit thoracic aortae and its effects on intracellular free Ca2+ concentrations ([Ca2+]i) in dispersed rabbit vascular smooth muscle cells with a Ca2+ indicator fura-2. The actions of trypsin were compared with those of thrombin. 2. Both thrombin and trypsin reversibly contracted aortic rings without endothelium in a concentration-dependent manner. The vasocontraction induced by trypsin was well correlated with the protease activity of trypsin actually added to the tissue baths containing the aortic rings and was completely blocked by soybean trypsin inhibitor and phenylmethylsulphonyl fluoride (PMSF), a serine protease inhibitor. 3. The trypsin-induced contractions of the aortic rings were not the result of irreversible damage to vascular smooth muscle cells, since the contractile responses induced by noradrenaline or 30 mM KCl were unaffected by pretreatment with trypsin. 4. The contractions induced by either thrombin or trypsin were reduced to about 30% of control responses after removal of extracellular Ca2+, indicating that most of the contraction is dependent on extracellular Ca2+. By contrast, the contractions induced by either of the proteases were reduced by an antagonist of L-type voltage-operated Ca2+ channels, nifedipine, to about 70% of control responses, indicating that both nifedipine-sensitive and -resistant Ca2+ channels are involved in these contractions. 5. In the aortic rings precontracted by a maximally effective concentration of thrombin, the second application of thrombin virtually failed to induce contractions but trypsin could still induce contractions amounting to 10% of control values by it's protease activity. 6. After the first application of a maximal concentration of thrombin, the second application of thrombin could not induce an increase in [Ca2+]i, but an application of trypsin could still induce an increase in [Ca2+]i in dispersed rabbit vascular smooth muscle cells. 7. These data suggest that in addition to activation of a thrombin receptor, trypsin can contract rabbit aortae by a proteinase-activated receptor 2 or a novel mechanism.

Animals↗
PubMed1997

The Na+,K+-ATPase alpha subunit requires gastrulation in the Xenopus embryo.

Na+,K+-ATPase participates in reabsorption of ions and water and produces an electrochemical gradient between the intra- and extracellular spaces across the cell membrane. It also plays an important role in many developmental phenomena such as a blastocoele formation and neural formation. To elucidate the expression pattern of Na+,K+-ATPase in the Xenopus embryo, the spatial expression patterns of the Na+,K+-ATPase alpha subunit were studied in a normal embryo by whole-mount in situ hybridization. These transcripts were localized around the dorsal blastopore at the gastrula stage, in the neural tube at the neurula stage, and then in the pronephros and cloaca at the tail-bud stage. To study the function of Na+,K+-ATPase in embryogenesis after mid-blastula transition, the expression of the Na+,K+-ATPase alpha subunit was inhibited by the injection of specific antisense RNA. Embryos injected with Na+,K+-ATPase antisense RNA showed inhibition of gastrulation. When antisense RNA was injected into the dorsal blastomeres, head differentiation was markedly inhibited. These results suggest that this transcript plays an important role during gastrulation and head differentiation.

Activins↗