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Biomedical subjects

A Sumiyoshi

Publications and source records attributed to A Sumiyoshi.

At least 55 records · Page 3Linked to original sources

Ultrastructural study of TPA-induced cell motility: human well-differentiated rectal adenocarcinoma cells move as coherent sheets via localized modulation of cell-cell adhesion.

We previously found that 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced invasion of Matrigel was associated with augmentation of cell motility but not with metalloproteinase activity in a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1. In a two-dimensional cell motility assay, TPA induced active L-10 cell locomotion with characteristic morphology; the cells moved outwards from the cell islands mainly as a localized coherent sheet of cells. The leading cells showed locomotor morphologies with fan-shaped leading lamellae while the following cells had cell contacts on all sides and appeared to lack leading lamellae. In the present ultrastructural study, the following cells frequently showed tapering cytoplasmic protrusions and leading lamella-like processes underlapping a preceding cell, indicating that the locomotion mechanism is almost the same for both the leading and following cells. For this type of locomotion as a coherent sheet we propose that localized modulation of cell-cell adhesion was induced such that wide intercellular gaps occurred at the lower portion of the cells to allow the cells to extend the tapering cytoplasmic processes and leading lamellae while close cell-cell contacts remained at the upper portion of the cells. These TPA-induced changes took place predominantly in the cells at the periphery of the cell islands, while the cells in the middle of the cell islands maintained close cell-cell contacts including complex interdigitation all around the cells, suggesting the modulation of TPA action by cell-cell interaction. Additionally, consistent with the evidence for junctional complexes between the cells moving outwards, the Lucifer-yellow dye transfer studies showed some, limited cell-cell coupling, suggesting the presence of at least some gap junctional intercellular communication in the moving cell sheets.

Actin Cytoskeleton↗

Effects of suramin on metastatic ability, proliferation, and production of urokinase-type plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12C-PM6.

Effects of suramin, a polysulfonated naphthylurea compound, on metastatic ability, proliferation, and production of plasminogen activators and plasminogen activator inhibitors were studied using the highly metastatic human renal cell carcinoma cell line, SN12C-PM6. After renal subscapular implantation of tumor cells in nude mice, suramin significantly inhibited metastasis of tumor cells to the lungs and liver. In vitro growth of tumour cells was inhibited by suramin in a dose-dependent manner, at relatively low doses (ID50 = 105 micrograms/ml). Plasminogen activator inhibitor type 2 (PAI-2) production by tumor cells was enhanced by suramin (100 micrograms/ml), whereas urokinase-type plasminogen activator (uPA) production was suppressed. Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin. Therefore suramin may be beneficial for the treatment of patients with an early stage of renal cancer with potential risk of metastasis.

Animals↗

Aneurysm of the transverse cervical artery occurring in association with a cavernous hemangioma as a complication of Klippel-Trénaunay syndrome: report of a case.

We report herein the case of a 14-year-old girl with Klippel-Trénaunay syndrome who developed an aneurysm of the transverse cervical artery. Because it was continuing to increase in size, with an associated risk of rupture, an aneurysmectomy was performed. Pathological examination of the resected specimen revealed a cavernous hemangioma located near the aneurysm. To our knowledge no other case of an aneurysm occurring in association with a cavernous hemangioma as a complication of Klippel-Trénaunay syndrome has ever been reported.

Adolescent↗

Immunohistochemical identification of adrenomedullin in human, rat, and porcine tissue.

The histological localization was investigated of adrenomedullin (AM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma. The immunohistological distribution was examined of AM in human, rat, and porcine tissues using a polyclonal antibody to a fragment comprising C-terminal amino acids 40-52 of human adrenomedullin [AM(40-52)NH2]. Almost all of the human pheochromocytoma and normal adrenal medullary cells of all three species were immunostained and found to be intensely positive for AM. Furthermore, AM-immunoreactive cells were present in the pancreatic islets, gastrointestinal neuroendocrine system, anterior pituitary, and choroid plexus with some degree of interspecies heterogeneity. These findings indicate that AM-immunoreactive cells are widely distributed in the endocrine and neuroendocrine system, suggesting that AM plays some important role in the control of systemic and local circulation and also of humoral secretion.

Adrenomedullin↗

Pulmonary tumor thrombotic microangiopathy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is characterized by widespread fibrocellular intimal proliferation of the small pulmonary arteries and arterioles in patients with metastatic carcinoma. Microscopic pulmonary tumor emboli have frequently occurred in patients with malignant tumors; however, few cases of PTTM have been reported. A rare case of a patient with gastric adenocarcinoma who presented with acute dyspnea and lethal respiratory failure is described. Histologically, diffuse fibromuscular intimal thickening causing luminal stenosis and obstruction but containing rather few cancer cells was observed in the small pulmonary arteries and arterioles. These findings were consistent with PTTM. Although PTTM is a rare phenomenon, PTTM should be considered in the differential diagnosis of acute dyspnea or pulmonary hypertension in patients with carcinoma.

Adenocarcinoma↗

[Acute necrotizing gastritis associated with adult T-cell leukemia in the course of chemotherapy].

A 63-year-old man with smoldering adult T-cell leukemia (ATL) which became acute was admitted. During chemotherapy, he experienced epigastric pain and fever due to neutropenia. The combination therapy of antimicrobials and rhG-CSF was ineffective and he died. Autopsy revealed systemic invasion of ATL cells. The stomach findings resembled those of phlegmonous gastritis, a rare form of bacterial gastritis, along with diffuse, mucosal necrosis with hemorrhage. The pathogenesis of necrotizing gastritis remains to be elucidated. The patient had also received histamine H2 antagonist for gastric ulceration, which might have influenced the gastric bacterial flora.

Aged↗

Functional relation between nitric oxide and noradrenaline for the modulation of vascular tone in rat mesenteric vasculature.

As previously reported, N omega-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide (NO) synthesis, decreased transmural field stimulation (TFS)-induced noradrenaline overflow from the isolated perfused rat mesenteric vasculature attached to the intestine. The decrease was attenuated by L-arginine. This suggests that NO may increase noradrenaline release (Yamamoto et al. 1993). The present experiments with this preparation were done in order to monitor changes in vascular perfusion pressure caused by TFS or by noradrenaline infusion in parallel with those in the noradrenaline outflow caused by TFS in the presence of atropine (0.1 mumol/l) (to block acetylcholine-induced release of endothelial NO) and of indomethacin (3 mumol/l) (to inhibit L-NNA-induced production of vasoconstrictor prostanoids). (1) TFS (2-10 Hz) caused a frequency-dependent increase in noradrenaline overflow and perfusion pressure. (2) L-NNA (10 and 30 mumol/l) caused a concentration-dependent inhibition of TFS-induced noradrenaline overflow, whereas the TFS-induced pressure increase was augmented by L-NNA in a concentration-dependent manner. At any given concentration of L-NNA, the potentiation of vasoconstriction by L-NNA became greater in magnitude as the frequency of the TFS was raised. (3) Infusion of noradrenaline (0.38-6 nmol) caused a dose-dependent increase in perfusion pressure up to a value comparable with that caused by TFS. The pressure increase in response to noradrenaline infusion was also enhanced by L-NNA, relatively, to a greater extent than the enhancement, by L-NNA, of the pressure response to TFS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibitory effects of prostacyclin analogue, TFC-132, on aortic neointimal thickening in vivo and smooth muscle cell proliferation in vitro.

Effects of a new prostacyclin analogue, TFC-132, on neointimal thickening following intimal mechanical injury and on the proliferation of cultured aortic smooth muscle cells (SMCs) were studied. The intimal injury was induced by indwelling of polyethylene tubing for 24 h in the rabbit aorta. Rabbits were killed 10 days after drawing out the tubing. TFC-132 (0.6 mg/kg or 1.2 mg/kg) was given orally at 8-h intervals through the experiment. The serum concentrations of the analogue rose significantly 1 and 2 h after administration. The mean intimal thickening in the TFC-132 treated groups was significantly thinner than in the control one. Human aortic SMCs were cultured and 3H-thymidine incorporation into DNA (DNA synthesis) was measured at the varying concentrations of TFC-132. The analogue inhibited DNA synthesis of cultured SMCs at 10(-6) and 10(-5) M. These data indicate that a new prostacyclin analogue, TFC-132, has an inhibitory effect on the neointimal thickening after intimal injury and on the aortic SMC proliferation.

Animals↗

The content of urokinase-type plasminogen activator and tumor recurrence in superficial bladder cancer.

The contents of urokinase-type plasminogen activator were estimated in superficial bladder cancer from 42 patients undergoing transurethral resection for the first time. Tumor recurred in 11 of 16 patients (68.8%) with high urokinase-type plasminogen activator content (8 ng. urokinase-type plasminogen activator per mg. protein and more) and in 12 of 26 (46.2%) with low urokinase-type plasminogen activator content. In the high content group 8 patients (50%) had disease progression compared to 2 (7.7%) in the low content group (p < 0.01). The progression rates in the high urokinase-type plasminogen activator group with stage pTa disease or tumors more than 1 cm. large were significantly higher than those in the low urokinase-type plasminogen activator group (p < 0.05). The recurrence and progression rates in the high content group with stage pT1, grades 2 and 3, single and multiple tumors, and tumors less than 1 cm. large were higher than those in the low content group. The progression-free survival rate in the high content group was significantly lower than that in the low content group (p < 0.005). In conclusion, urokinase-type plasminogen activator content may be a useful marker to predict recurrence and progression of superficial bladder cancer.

Aged↗

Suramin inhibits intimal thickening following intimal injury in the rabbit aorta in vivo.

OBJECTIVE: Proliferation of vascular smooth muscle cells is a major event in atherogenesis. Several growth factors have been well documented to control this proliferation. Inhibition by suramin of the binding of some growth factors to their receptors has recently been reported. The aim of this study was to examine the effects of this agent on neointimal thickening following intimal mechanical injury, as well as on platelet function. METHODS: Intimal thickening was induced by indwelling of polyethylene tubing for 24 h in the rabbit aorta. Rabbits were killed 10 d after drawing out the tubing. Throughout the experiment, suramin (15 mg.kg-1) was injected intravenously every 24 h. Morphological and morphometrical studies were performed in the suramin treated group (n = 6) and in a control group (n = 6). Platelet-rich plasma was prepared from animals before and 3 h after injection of suramin. Platelet aggregation and ATP release induced by collagen were examined. Platelet adhesion on the de-endothelialised area of the rabbit aorta was also examined in the two groups. RESULTS: The mean intimal thickening in the suramin treated group was significantly less than in the control group. Smooth muscle cell replication and cell density in the thickened intima of the suramin treated group were less than in control. Suramin did not affect collagen induced platelet aggregation, ATP release, or platelet adhesion. CONCLUSIONS: Suramin has an inhibitory effect on the neointimal thickening and intimal smooth muscle cell proliferation after intimal injury in the rabbit aorta, but has no effect on platelet function.

Animals↗

Magnetic resonance imaging of bone marrow changes after irradiation.

RATIONALE AND OBJECTIVES: Signal changes of irradiated bone marrow are thought to represent fatty change. However, more recent studies have indicated that other factors may contribute to these signal changes. We performed animal studies to investigate magnetic resonance (MR) signal change factors in correlation with histologic findings. MATERIALS AND METHODS: Forty-two male Wistar rats were given single doses (3, 8, and 20 Gy) of irradiation. Magnetic resonance imaging (1.5 T) was performed using spin-echo technique. RESULTS: In the acute phase (days 1-3), the T1 time was prolonged, probably secondary to decreased cellularity and edema. After this phase, the irradiated marrow showed marked T1 and T2 shortening that correlated with hemorrhage. In the chronic phase (after day 10), fatty replacement, fibrosis, and regeneration were observed. T2 times were stable in spite of regeneration because of the susceptibility effect of hemosiderin. CONCLUSION: The MR signal changes of irradiated marrow reflect not only fatty replacement, but hemorrhage as well.

Animals↗

Ki-1 (CD30)-positive large cell lymphoma presented with leukemia: a case report.

A 77 year-old woman with Ki-1 positive large cell lymphoma who presented with leukemic phase of the disease is reported. She noticed general fatigue and fever in 1992 and was found to have anemia and abnormal lymphoid cells in the peripheral blood. The bone marrow was diffusely involved by these cells, differentials of which included acute megakaryocytic leukemia, malignant histiocytosis, and anaplastic large cell lymphoma. Immunophenotypic analysis showed that they were positive for CD3, HLA-DR, CD25 and CD30, but negative for CD4, CD8, CD19, FVIII and GpIIb/IIIa indicating Ki-1 positive lymphoma with T-cell lineage. It may involve bone marrow, but leukemic phase of the disease is rarely seen. Therefore, it should be added to the differential diagnosis when large anaplastic or pleomorphic cells are seen in the bone marrow and/or peripheral blood.

Aged↗

N omega-nitro-L-arginine, an inhibitor of nitric oxide synthesis, decreases noradrenaline outflow in rat isolated perfused mesenteric vasculature.

In the isolated perfused rat mesenteric vasculature with intestine attached N omega-nitro-L-arginine (L-NNA) (30 mumol/l), an inhibitor of nitric oxide (NO) synthesis from L-arginine, did not alter spontaneous noradrenaline outflow. Transmural field stimulation (2-10 Hz) caused a frequency-dependent increase in noradrenaline outflow. The evoked overflow was reduced by L-NNA. L-Arginine (0.3 mmol/l) attenuated the inhibition of noradrenaline overflow by L-NNA. These results suggest that NO increases the release of noradrenaline in rat mesenteric vasculature.

Animals↗

Expression of dipeptidyl aminopeptidase IV activity in human lung carcinoma.

Dipeptidyl aminopeptidase IV (DAP IV) staining was examined in various histological types of lung carcinomas to evaluate this enzyme activity. A total of 45 lung carcinomas were examined for their enzyme activity. Almost all (93.1%) cases of adenocarcinoma were positive for DAP IV activity, whereas all cases of squamous cell carcinoma, small cell carcinoma, large cell carcinoma and carcinoid were negative. DAP IV activity of microsomes in lung carcinomas was significantly higher in papillary adenocarcinomas than in squamous cell carcinomas. These data suggest that DAP IV may be a good marker to distinguish adenocarcinoma from other histological types of lung carcinoma.

Adenocarcinoma↗

Re-evaluation of a case of progressive multifocal leukoencephalopathy previously diagnosed as simian virus 40 (SV40) etiology.

A case of progressive multifocal leukoencephalopathy (PML) reported previously to be of simian virus (SV40) etiology was re-evaluated. The supernatant from a 10% homogenate of brain material was inoculated into African green monkey kidney cells and BSC-1 cells which are permissive for SV40. However no cytopathic effect (CPE) developed and no virus was isolated. The brain supernatant agglutinated human group O erythrocytes and contained 5120 units/mL. The Hirt supernatant from the brain contained three DNA bands corresponding to forms I, II and III of circular double-stranded viral DNA. Restriction endonuclease cleavage analysis revealed that this viral DNA was different from SV40 DNA, but similar to JC virus DNA. After cloning of this viral DNA into pBR322 at the BamHI site, DNA homology of this virus and of SV40 was investigated. Cloned DNA from the brain hybridized with all the HpaI/EcoRI fragments of the SV40 genome at the effective temperature of Tm -50 degrees C [corrected]. At Tm -28 degrees C, however, the cloned DNA hybridized with only HpaI/EcoRI fragment B of the SV40 genome. In contrast to this, JC virus DNA hybridized with all five EcoRI/BamHI/HindIII fragments of cloned DNA even at Tm -28 degrees C. Therefore, the causative agent of this PML case was not SV40 but JC virus.

Cell Line↗

[Histopathology of thrombotic thrombocytopenic purpura].

The most striking lesions of thrombotic thrombocytopenic purpura (TTP) are the subendothelial hyaline deposits and multiple occlusive thrombi. They are found in the small arteries, arterioles, and capillaries of many organs, especially the heart, brain, kidneys, and adrenal glands. Immunohistochemical examination demonstrates that the thrombi in TTP are strongly positive for von Willebrand factor (vWF) antigen, but only weakly for fibrinogen/fibrin. Electronmicroscopically, the thrombi in TTP were composed of tightly packed platelets, showing varying degrees of cytoplasmic alteration and degranulation with a small amount of interspersed fibrin and amorphous materials. Many etiological factors causing intravascular platelet aggregation have been postulated, including unusually large vWF multimers, platelet agglutinating proteins and immune abnormalities. All the lesions in TTP are strongly positive for vWF antigen. This result suggests that vWF multimers may play an important role in the pathogenesis of TTP.

Arteries↗