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Biomedical subjects

T Okamura

Publications and source records attributed to T Okamura.

At least 433 records · Page 24Linked to original sources

Responsiveness to dopamine of isolated epicardial coronary arteries from humans, monkeys, and dogs.

Dopamine is widely used for the treatment of cardiogenic and hypovolemic shock. This study was undertaken to compare the response to dopamine in epicardial conduit coronary arteries of humans, Japanese monkeys, and dogs, and to determine the mechanism of vasoconstriction and vasodilation. In helical strips of coronary arteries from humans and monkeys partially contracted with prostaglandin F2 alpha, dopamine produced a concentration-related contraction; the human artery contraction was greater. The contractions were reversed to a relaxation by treatment with phentolamine. Relaxation of monkey arteries treated with the alpha adrenoceptor antagonist was not influenced by metoprolol, a beta 1 antagonist, or endothelium denudation, but was reversed to contraction by SCH23390, a dopamine1 receptor antagonist. On the other hand, dog coronary arteries responded to dopamine with a relaxation that was abolished by metoprolol, but not influenced by SCH23390 or butoxamine, a beta 2 antagonist. We conclude that dopamine in clinical doses elicits significant contractions, mediated possibly by alpha adrenoceptors, in human and monkey coronary arteries; thus, care has to be taken when the amine is used in patients with variant angina pectoris. Relaxation of monkey coronary arteries appears to be associated with activation of dopamine1 receptors, whereas those of the dog arteries are mediated mainly by beta 1 receptors.

Aged↗

A patient with congenital plasminogen deficiency manifesting primary pulmonary hypertension.

A 25-year-old Japanese man was diagnosed as having primary pulmonary hypertension, on the basis of the findings of cardiac catheterization and ventilation-perfusion scintiscans. The plasma level of plasminogen in this patient was found to be reduced to 43% by a functional assay and 61 mg/l by an antigenic assay. Based on the family study, the patient was considered to have a heterozygous congenital plasminogen deficiency. Accordingly, it is suggested that the defective fibrinolysis in this patient may have played an important role in the development of primary pulmonary hypertension through microthrombosis.

Adult↗

Bone marrow findings in malignant histiocytosis and/or malignant lymphoma with concurrent hemophagocytic syndrome.

We examined bone marrow specimens from 19 patients with malignant histiocytosis (MH) and/or malignant lymphoma (ML) with concurrent hemophagocytic syndrome (HS) who suffered from high fever, hepatosplenomegaly, liver dysfunction, profound cytopenia, and erythrophagocytosis. There was little lymph-node enlargement or no tumor formation. The neoplastic cells in 3 patients exhibited histiocytes/macrophages phenotype with positive reactions for fluoride-sensitive nonspecific esterase, lysozyme and CD68 (KP1). Twelve other patients showed a T-cell (CD3) phenotype, in which 5 patients expressed CD30 (BerH2) as well. B-cell characteristics with CD20 (L26), CIg. nu lambda and gamma kappa were manifest in 2 patients, but indeterminate markers were found in the 2 remaining patients. Eighteen patients showed an infiltration of large neoplastic cells mainly with noncohesive interstitial growth pattern, ranging from 1.7% to 74.2% of the nucleated cells in the bone marrow. A large number of histiocytes/macrophages and dendritic cells was diffusely observed in 15 patients. Severely decreased hematopoiesis in all three series of hematopoietic cells was found in 16 patients. Bone marrow infiltration by the neoplastic cells and numerous reactive cells with erythrophagocytosis appears to be an important factor of profound cytopenia in patients of MH and/or ML with HS. The infiltrating pattern of the neoplastic and reactive cells in the bone marrow of MH and/or ML with HS was different from that of other types of peripheral T-cell ML, B-cell ML in high grade malignancy, and Hodgkin's disease. Cell characteristics and lineage of the neoplastic cells in MH and/or ML with HS are also discussed in this study.

Adolescent↗

[Immunoblastic lymphadenopathy (IBL)-like T cell lymphoma associated with granulocytopenia and autoimmune hemolytic anemia].

A 65 year-old woman was admitted in May 1990, because of fever, generalized lymphadenopathy and eruption. Laboratory examination showed granulocytopenia, polyclonal hypergammaglobulinemia, positive Coombs' test, positive cold antibody and positive anti-E erythrocyte antibody. 7 days after admission autoimmune hemolytic anemia developed. The appearance of the anti neutrophil leukocyte antibody was suspected because of the absence of the segmented neutrophils in marrow specimen. Histological findings of the biopsied lymph node and the marker study of the tumor cell disclosed IBL-like T cell lymphoma. The patient was treated with G-CSF and VEPA chemotherapy. Granulocytes increased and she showed marked symptomatic improvement with complete remission. Our case showed various clinical pictures with hemolytic anemia and granulocytopenia, which could be based on the autoimmune mechanisms.

Aged↗

[Acquired inhibitors (autoantibodies) to coagulation factors in non-hemophilic patients].

We reported two cases with severe bleeding tendency. Coagulation tests revealed the development of high titer inhibitors to coagulation factor VIII. As results of immunological analyses, the inhibitor from case 1 was found to be IgG type autoantibody having both kappa and lambda light chains. The subclasses were IgG1 and IgG4. The inhibitor from case 1 recognized the COOH-terminal light chain (72kDa thrombin fragment) on the factor VIII molecule as an epitope. On the other hand, the inhibitor from case 2 recognized both epitopes of heavy chain (44kDa thrombin fragment) and light chain (72kDa thrombin fragment). The characteristics of the inhibitors demonstrated no difference between autoantibody and alloantibody from hemophilics as mentioned by Fulcher. These fragments (A2 and C2 domain) may be important on the function of factor VIII. On further progress of epitope analysis of inhibitors, it may be useful to know the structure-function relationship of factor VIII, and applicable to treat the inhibitor patients with some way such as extracorporeal adsorption using a peptide affinity column or peptide-induced neutralization.

Aged↗

An immunohistochemical study of helix pomatia agglutinin binding on carcinomas of the esophagus.

In many factors affecting the biologic behavior of malignant cells, alterations in the carbohydrate composition of cell membrane glycoproteins and glycolipids are considered to underlie the changes in cell adhesion that accompany malignant transformation and the development of invasive and metastatic properties. We investigated the alterations of the cell surface glycoproteins structure of carcinoma of the esophagus cells by HPA staining. The rate of patients with positive HPA staining increases with progression of depth of carcinoma invasion and venous invasion, and the survival in patients with positive HPA was poorer than in those with negative HPA. HPA-positive cells of carcinoma of the esophagus represent high malignant potentials. The HPA staining method is available to predict the prognosis of patients with carcinoma of the esophagus.

Acetylgalactosamine↗

Nitric oxide-mediated retinal arteriolar and arterial dilatation induced by substance P.

PURPOSE: The present study was undertaken to compare vasodilatations caused by substance P in retinal arterioles in vivo and in the extraocular retinal central arteries in vitro, and to analyze the mechanisms of its action. METHODS: In the in vivo study, changes of the retinal arteriolar diameter were continuously measured using a retinal fundus camera. In the in vitro study, changes in the isometric tension were recorded in helical strips of extraocular retinal arteries with and without the endothelium, exposed to aerated bathing media. RESULTS: In anesthetized dogs, infusions of substance P into the carotid artery produced a dose-dependent dilatation of the intraocular retinal arteriole; the maximal response was obtained about 15 seconds later. The vasodilator response was significantly attenuated by treatment with NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor, and the inhibition was reversed by L-arginine. On the other hand, vasodilatations caused by nitroglycerin were not influenced by L-NA and L-arginine. In the isolated retinal artery just before entering into the eyeball, the addition of substance P produced a concentration-dependent relaxation only when the endothelium of the strips was intact. Removal of the endothelium abolished the response. The peptide-induced relaxation was abolished by L-NA, whereas relaxations caused by NO and nitroglycerin were unaffected. The inhibitory effect of L-NA was reversed by L-arginine but not by D-arginine. Treatment with methylene blue or oxyhemoglobin abolished the relaxation induced by substance P, NO, and nitroglycerin. CONCLUSIONS: Substance P-induced retinal arteriolar dilatation in vivo appears to be mediated by NO synthesized from L-arginine possibly in the endothelium. The endothelium-dependency would be supported by the findings obtained from isolated retinal arteries.

Animals↗

A study on cerebral nicotine receptor distribution, blood flow, oxygen consumption, and other metabolic activities--a study on the effects of smoking on carotid and cerebral artery blood flow.

We investigated middle cerebral artery flow velocity (MCA-FV) by a noninvasive method to determine whether or not smoking causes an increase in cerebral blood flow (CBF). Furthermore we determined sequentially the changes in CBF caused by smoking in order to evaluate changes in responses at different times in daily activities and the effect from meals. The subjects were 25 healthy individuals ranging in age from 20 to 36 yr. MCA-FV was measured by a transcranial Doppler system. They smoked a filtered cigarette for 5 min at 1 P.M., 3 P.M., 6 P.M., 8 P.M., 10 P.M., 8 A.M., and 11 A.M. Results (1) Smoking caused increases in both common carotid artery flow volume and MCA-FV, and the percentage increase of these parameters showed a good correlation (r = 0.809). (2) MCA-FV increased significantly during the first (by 6.6%) and second halves (by 5.4%) of the smoking period. (3) The change in MCA-FV after meals was slight. (4) Smoking tended to increase MCA-FV during each smoking session but the changes were not significant. The pulsatility index reduced significantly during almost every smoking session. These results lead to the conclusion that smoking reduces vascular resistance in cerebral arteries and increases CBF.

Adult↗

Lectin immunohistochemical evaluation of human bladder carcinomas. A comparison of Carnoy's and formalin fixation.

A lectin immunohistochemical analysis of 51 human bladder carcinomas, including 44 cases of transitional cell carcinoma (TCC) (G1, 15 cases; G2, 17 cases; G3, 12 cases) and 7 cases of squamous cell carcinoma (SCC), was performed. Tissues were obtained by cold punch biopsies, fixed in Carnoy's or 10% formalin solution, stained for binding of 10 different lectins, and evaluated under the light microscope. The lectins used were concanavalin agglutinin (Con A), soybean agglutinin (SBA), Lotus tetragonolobus agglutinin (LTA), Dolichos biflorusa agglutinin (DBA), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA1), Ulex europaeus agglutinin I, II (UEA-I, II), wheat germ agglutinin (WGA), and Pisum sativum agglutinin (PEA). TCC prepared with Carnoy's fixation tended to show moderately positive Con A, UEA-I, and WGA reactions for G1, and strongly positive reactions for G2 and G3 lesions. UEA-II was mainly negative in G1, but tended to increase to become moderate in G3. DBA tended to show a moderately positive reaction in G1 and G2, but was mainly negative in G3. With formalin fixation, only RCA1 demonstrated grade specific variation, tendency to react moderately in the G1 and G2 cases, and strongly in G3. There were no further differences among the histopathological grades of TCC for other lectins. Thus, Carnoy's fixation appears superior for distinguishing between grades of lesions. SCC tended to react more strongly than TCC with all the various lectins except PEA, independent of fixation.

Adult↗

[Radiation-induced cerebrovasculopathy: a case report and review of the literature].

We reported a case of a patient who suffered from a cerebrovasculopathy after irradiation therapy for astrocytoma located at the left temporal lobe. An eleven year-old boy who presented himself with headache and vomiting as his chief complaints received partial removal of a tumor. Histological diagnosis of the tumor was astrocytoma (grade II). His preoperative cerebral angiograms showed mass sign solely, without stenosis or occlusion of the cerebral vessel. Postoperatively, he was treated with irradiation therapy involving the whole brain with a total of 30 Gy, and gamma knife therapy. Six months after irradiation, he started suffering from frequent cerebral ischemic attacks, but there was no regrowth of the tumor visible on CT scans. Cerebral angiograms were made again, and revealed multifocal stenoses in the bilateral internal carotid arteries, middle cerebral arteries, and the anterior cerebral artery. His symptoms did not improve after conservative treatment with steroids, calcium antagonist, or low molecular weight dextran. Although he received a superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses bilaterally, multiple cerebral infarctions appeared. Although irradiation therapy is acceptable in patients with brain tumor, a cerebrovasculopathy after irradiation should be considered as one of the most important complications, and the risk incurred by irradiation therapy should lead to more careful consideration and caution when treating intracranial brain tumors, especially in children. From our experience, the usefulness of bypass surgery for radiation-induced cerebrovasculopathy is still controversial.

Astrocytoma↗

[ATP radionuclide ventriculography; its usefulness for the evaluation of ischemic heart disease].

To evaluate the usefulness for the detection of ischemic heart disease (IHD), ATP first pass radionuclide ventriculography (RVG) was performed in 10 patients. Coronary angiography was performed in all patients. Among these patients, 2 had single vessel disease, 2 had double vessel disease, 3 had triple vessel disease, and 3 had normal coronary arteries. RVG was performed at rest, then, ATP was infused at the rate of 0.16 mg/kg/min and ATP-RVG was done 4 minutes later. The left ventricular ejection fraction (LVEF) was calculated, and the regional wall motion (RWM) was graded as normal, hypokinesis, akinesis, and dyskinesis. In the patients with coronary artery disease, RWM decreased in 5 of 7 patients and LVEF decreased in 6 of 7 patients by ATP. However, RWM and LVEF did not decrease in the patients with normal coronary arteries. These results suggested that ATP-RVG might provide useful information for the evaluation of IHD.

Adenosine Triphosphate↗

Neurogenic and non-neurogenic relaxations caused by nicotine in isolated dog superficial temporal artery.

Nicotine produced a transient contraction followed by biphasic (rapid and slow) relaxations in dog superficial temporal arterial strips denuded of the endothelium. The responses to nicotine were abolished by treatment with hexamethonium. The nicotine-induced contraction was abolished by phentolamine and potentiated by NG-nitro-L-arginine (L-NA), a nitric oxide synthase inhibitor. The slowly developing relaxation was markedly suppressed by indomethacin and tranylcypromine, a prostaglandin I2 synthetase inhibitor, whereas the rapid relaxation was abolished by L-NA. The inhibitory effect of L-NA was reversed by L-, but not D-, arginine. NG-nitro-D-arginine had no effect. Transmural electrical stimulation elicited a transient relaxation in phentolamine-treated arteries. The relaxation was not influenced by indomethacin but was abolished by L-NA and tetrodotoxin. Nicotine increased intracellular cyclic AMP and cyclic GMP in the endothelium-denuded arteries. The increment of cyclic AMP was inhibited by indomethacin but not by L-NA, whereas that of cyclic GMP was not influenced by indomethacin but was abolished by L-NA. It may be concluded that nicotine stimulates the adrenergic and nitroxidergic nerves innervating the temporal arterial wall, resulting in a contraction and a rapidly developing relaxation, respectively; the latter is mediated by cyclic GMP. Potentiation by the nitric oxide synthase inhibitor of the contractile response to nicotine is expected to be a suppression of the relaxation mediated by the nerve-derived nitric oxide. Slow relaxations caused by nicotine appear to be associated with the elevation of cyclic AMP produced possibly by prostaglandin I2, which is released from subendothelial, non-neuronal tissues.

Adrenergic Fibers↗

Mechanisms of histamine-induced relaxation in external and internal ophthalmic arteries.

PURPOSE: Mechanisms that underlie the relaxant response to histamine were examined in dog external (a branch of external carotid artery) and internal (a branch of internal carotid artery) ophthalmic arteries (EOA and IOA). METHODS: Changes in isometric tensions were recorded in helical strips of the arteries with and without the endothelium. RESULTS: Histamine predominantly produced relaxations in EOA and IOA, partially contracted with prostaglandin (PG) F2 alpha. The relaxation of IOA almost was abolished by treatment with cimetidine (10(-5) mol/l), whereas the response of EOA was partially attenuated by treatment with cimetidine or chlorpheniramine (10(-6) mol/l) and was abolished with their combined treatment. Endothelium denudation depressed the relaxation in EOA but did not affect the response of IOA. The response to histamine of EOA was inhibited by treatment with indomethacin (10(-6) mol/l) or tranylcypromine (10(-4) mol/l), a PGI2 synthesis inhibitor, only when the endothelium was present, but additional treatment with chlorpheniramine did not further inhibit relaxation. On the other hand, IOA's response to histamine was not inhibited by indomethacin, despite the presence of endothelium. CONCLUSIONS: The histamine-induced relaxation in EOA may be associated with the release of vasodilator PGI2 through the activation of H1 receptors in the endothelium and with the direct action on H2 receptors in smooth muscle, whereas the relaxation in IOA is mediated exclusively by H2 receptors in smooth muscle.

Animals↗

[A case of primary pulmonary lymphoma associated with Sjögren syndrome and IgM monoclonal gammopathy confirmed by DNA rearrangement].

A 70-year-old man was admitted for evaluation of an abnormal shadow on his chest X-ray film, consisting of a mass containing an air bronchogram. He was also found to have a monoclonal gammopathy (IgM kappa type) and Sjögren syndrome. Open lung biopsy was performed with the suspicion of primary pulmonary lymphoma or pseudolymphoma. Southern blot analysis of the tissue revealed clonal rearrangements of immunoglobulin gene, supporting the diagnosis of B-cell lymphoma. Using conventional immunoperoxidase staining (PAP) method, the monoclonality in the tissue specimen is sometimes quite difficult to prove. Southern blot analysis, however, gives more accurate and reliable results. The analysis of immunoglobulin gene rearrangements is quite useful in determining the presence or absence of monoclonality in a specimen in cases of suspected lymphoproliferative disease such as primary pulmonary lymphoma and pseudolymphoma. We strongly recommend the use of Southern blot analysis in making the diagnosis of lymphoproliferative disease.

Aged↗

AE0047, a new dihydropyridine Ca2+ entry blocker, inhibits the responses to adrenergic nerve stimulation and substance P in dog mesenteric arteries.

AE0047, a new dihydropyridine-type Ca2+ entry blocker, significantly inhibited the contractions induced by transmural electrical stimulation and norepinephrine in dog mesenteric artery strips. The inhibition was greater in the case of the response to nerve stimulation. The 3H-overflow ratio evoked by electrical stimulation from strips previously soaked in [3H]norepinephrine was significantly reduced by AE0047 but not by nicardipine in a concentration sufficient to attenuate the response to norepinephrine. In aorta homogenate preparations, [3H]bunazosin binding was not replaced by AE0047 but by phentolamine. In strips treated with indomethacin, the endothelium-dependent relaxation caused by substance P and bradykinin was attenuated by treatment with AE0047 but not with nicardipine. The nitric oxide (NO)-induced relaxation was not influenced by AE0047. Cyclic GMP levels in the artery strips increased in response to substance P; the increase was markedly suppressed by AE0047 but not by nicardipine. In contrast to nicardipine, AE0047 appeared to inhibit the release of norepinephrine from adrenergic nerves and of NO from endothelial cells. The inhibition may be associated with the decreased transmembrane influx of Ca2+ in these tissues.

Adrenergic alpha-Agonists↗

Acrolein initiates rat urinary bladder carcinogenesis.

Acrolein, a reactive, alpha,beta-unsaturated aldehyde which is ubiquitous in the environment, forms DNA adducts, is mutagenic, and is teratogenic. However, studies have not indicated a carcinogenic effect in rodent bioassays. Since it is present in cigarette smoke and is the toxic metabolite of cyclophosphamide with respect to the urinary tract, we investigated the possibility that acrolein might have carcinogenic activity toward the rat urinary bladder. We also evaluated whether it possessed initiating and/or promoting activity. To evaluate initiating activity, acrolein was administered at a dose of 2 mg/kg i.p. twice a week for 6 weeks followed by uracil as 3% of the diet for 20 weeks and then control diet for 6 weeks. N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide (FANFT) as 0.2% of the diet followed by uracil was used as a positive control, and a negative control group was administered solvent control (water) i.p. during the 6-week initiation period followed by uracil. Acrolein followed by uracil produced an incidence of 18 of 30 rats (60%) with papilloma compared to 8 of 30 rats (27%) treated with solvent control followed by uracil. FANFT followed by uracil produced an incidence of 70% carcinomas and 30% papillomas, clearly indicating that it is a much more potent initiating agent than acrolein. Acrolein for 6 weeks followed by control diet produced no tumors. To evaluate promoting activity, groups of rats were fed FANFT for 6 weeks followed by acrolein. Acrolein administered during the initial 6 weeks and continued for the second phase of the experiment (to evaluate complete carcinogenic activity) resulted in severe toxicity. Administration of acrolein had to be terminated after 21 weeks of the experiment. The animals were maintained for 53 weeks of the experiment without further chemical treatment, and there was no evidence of papilloma or carcinoma development. This study clearly indicates that acrolein has initiating activity for the urinary bladder when administered by i.p. injection to the male F344 rat, but toxicity precluded evaluation of its promoting or complete carcinogenic activity.

Acrolein↗

Granulocyte colony-stimulating factor receptors on human acute leukemia: biphenotypic leukemic cells possess granulocyte colony-stimulating factor receptors.

Granulocyte colony-stimulating factor (G-CSF) receptors on the gated leukemic blast cells from newly diagnosed patients with acute leukemia or crisis of chronic myelogenous leukemia were investigated using flow cytometric detection. Surface marker analysis and cytochemical studies were conducted simultaneously to characterize the blast cells. Among 24 leukemia cases examined, G-CSF receptor-positive blast cells were detected in all 11 cases of acute myeloblastic leukemia even though the percentage range of positive cells was widely variable. On the other hand, they were not detected on the blast cells from patients with peroxidase-negative acute lymphoblastic leukemia with no myeloid surface antigens. However, G-CSF receptors were demonstrated in significant amounts on blast cells from 5 of 8 cases of peroxidase-negative acute leukemia expressing both myeloid and lymphoid surface antigens (biphenotypic leukemia). The percentage of blast cells positive for G-CSF receptors was significantly smaller in biphenotypic cases [33 +/- 14% (SD)] than in acute myeloblastic leukemia cases [65 +/- 22%] (P less than 0.01). The percentage expression of CD13 antigen by blast cells was significantly related to their percentage positivity for G-CSF receptors (rs = 0.50, P less than 0.05). These findings indicate that the distribution of flow cytometrically detectable G-CSF receptors on leukemic cells possessing myeloid characteristics may be related to the maturation process.

Antigens, CD↗