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M Okuma

Publications and source records attributed to M Okuma.

At least 55 records · Page 3Linked to original sources
PubMed1997

Leukotriene B4-activated human endothelial cells promote transendothelial neutrophil migration.

We explored the effect of leukotriene B4 (LTB4) on endothelial cells in LTB4-induced transendothelial migration (TEM) of neutrophils as an in vitro model of neutrophil extravasation. Chemotactic response of human neutrophils to LTB4 was significantly lower than that in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP), whereas the extent of TEM in response to LTB4 was significantly higher than that to fMLP. The study on random migration induced by LTB4 and fMLP also showed similar results, which indicated that LTB4 might affect the human umbilical cord vein endothelial cell (HUVEC) barrier. Neutrophil TEM was induced by pretreatment of HUVEC monolayer with LTB4 but not with fMLP. Treatment of endothelial cells by ONO-4057, a LTB4 receptor antagonist, abolished the effect of LTB4 almost completely whereas neutrophils treated with ONO-4057 could transmigrate through HUVEC treated with LTB4. These findings indicated that LTB4 could induce neutrophil TEM by acting on HUVEC.

Cell Movement↗
PubMed1997

Clinical trial of prophylactic endoscopic variceal ligation for esophageal varices.

Endoscopic variceal ligation is an effective therapy for variceal bleeding, and use of the method has recently been increasing. We evaluated the clinical usefulness of prophylactic endoscopic variceal ligation. Twenty-two patients with enlarged, tortuous varices and "red color signs" were selected. These patients were treated with ligation therapy alone and the varices were eradicated, i.e., reduced to small, straight varices without red color signs. Ligation therapy was withdrawn if the general condition of the patient worsened or if the varices could not be removed by suction. Follow-up endoscopy was performed every 4 months, and another ligation was performed if there were recurrent varices or variceal bleeding. The total reduction rate was 86.4%, and eradication required two sessions of therapy and 30 days of hospitalization on average. Complications included esophageal injury in 1 patient and treatment-induced bleeding in 1 patient; both complications were easily controlled. No variceal bleeding occurred after the eradication. There was no mortality due to gastrointestinal bleeding during the median follow-up period of 346 days. Prophylactic endoscopic variceal ligation made it possible to prevent fatal variceal bleeding with a minimum risk of complications, suggesting that this could be an alternative method for the prevention of first-time variceal bleeding.

Adult↗
PubMed1997

Mode of disease progression in primary myelodysplastic syndromes: a Japanese co-operative study. The Refractory Anemia Study Group of The Ministry of Health and Welfare, Japan.

Chronological changes in hematological findings were analyzed in 225 patients with myelodysplastic syndromes (MDS). They were diagnosed between 1990 and 1992. Their hematological findings, i.e. hemoglobin levels, leukocyte and platelet counts, proportions of peripheral blood (PB) blasts and monocytes, and proportion of blasts in bone marrow (BM), were recorded for up to 42 months after diagnosis, when available. BM was examined regularly in only a few patients. Therefore, it was impractical to use the French-American-British Cooperative Group criteria for subtype classification during the disease course. Thus, we used the percentage of PB blasts as the only indicator of stage evolution. We classified the disease into four stages: stage 1, less than 1% PB blasts; stage 2, 1-5% PB blasts; stage 3, 5-30% PB blasts; and stage 4, 30% or more PB blasts. There were 171 patients initially in stage 1, 37 initially in stage 2, and 17 initially in stage 3. Less than half (45%) of the patients initially in stage 1 progressed to stage 2, while 91% of the patients initially in stage 2 and all of the patients initially in stage 3 showed stage evolution. Eight variables, i.e. BM blasts 5% or more, male sex, karyotypic abnormalities, micromegakaryocytes, mononuclear large megakaryocytes, platelet counts 50 x 10(9)/l or higher, abnormal nucleus of granulocytes, and abnormal granules of granulocytes, were found to be significant risk factors for evolution from stage 1 to 2. Evolution from stage 1 to a higher stage within 15 months of diagnosis was associated with impending poor prognosis in most patients. However, of the 67 patients initially in stage 1 who died, 30 did not show stage evolution. Evolution from stage 2 to a higher stage and from stage 3 to stage 4 was also associated with impending poor prognosis. Higher levels of cytopenia were not associated with poorer prognosis in the stage 1 patients. In conclusion, our grading system proved to be useful in evaluating the chronological changes in MDS patients.

Disease Progression↗
PubMed1997

Ca2+/Mg(2+)-dependent endonuclease in marrow CD34 positive and erythroid cells in myelodysplasia.

Endonucleases capable of producing internucleosomal DNA cleavage are one of the key enzymes in apoptosis. We examined endonuclease activities contained in nuclei of CD34+ and erythroid cells in the bone marrow (BM) from 12 patients with the myelodysplastic syndromes. The levels of Mg(2+)-dependent and acidic endonucleases showed little changes as compared with those from normal BM. By contrast, the level of Ca2+/Mg(2+)-dependent endonuclease was appreciably higher in MDS erythroid cells than normal counterparts, although the activity varied markedly in CD34+ and erythroid cells. Our results suggested that Ca2+/Mg(2+)-dependent endonuclease is related to ineffective erythropoiesis in MDS.

Adult↗
PubMed1997

Clinical application of hepatic venous hemodynamics by Doppler ultrasonography in chronic liver disease.

The phase differences of the hepatic vein (HV) Doppler waveform might be influenced by fibrosis and steatosis of the liver when using HV Doppler and pressure curve analysis. Because HV catheterization is invasive, we have advocated the noninvasive comparative index (QXs ratio) of the HV Doppler waveform phases recorded simultaneously with electrocardiography and phgonocardiography. Forty-three controls and 169 patients with a variety of liver diseases were enrolled in this study. The mean QXs ratio was 0.75 in the controls, 0.6 in the chronic hepatitis patients, 0.45 in the cirrhosis patients, and 0.90 in the fatty liver patients. There were significant differences between all pairs of these groups (p < 0.001). The QXs ratio may be used to assess the degree of hepatic fibrosis or steatosis.

Adult↗
PubMed1997

Phase shift of the hepatic vein flow velocity waveform in chronic liver disease: experimental and clinical studies.

We examined animal models and studied patients with chronic liver disease to evaluate phase shift of the flow-velocity waveform of the hepatic vein (HV). We decided the Doppler-Pressure (DP) ratio using electrocardiography, the HV Doppler waveform and HV pressure curves, and we calculated the DP ratios. In animal models, the mean DP ratio was 1.04 in controls, 0.68 in cirrhosis, and 1.22 in fatty liver. There were significant differences among these groups (p < 0.005). In the clinical study, the mean DP ratio was 1.03 in controls, 0.95 in chronic hepatitis and 0.79 in cirrhosis. The DP ratio in the Cirrhosis Group was significantly different from that in the Control Group (p < 0.001) and that in the Chronic Hepatitis Group (p < 0.05). We conclude that the DP ratio is decreased in certain hepatic disease states.

Adult↗
PubMed1997

Age-related changes of platelet arachidonic acid metabolism in normal subjects.

Platelet activation and thrombosis play a crucial role in cardiovascular diseases. It has been suggested that enhanced platelet function in vivo are present in the elderly and that they are associated with the development of these diseases [1-3]. In the present study, we addressed the question of whether platelet arachidonate metabolism was altered with aging.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1997

Demonstration of functionally distinct human polymorphonuclear leukocyte fractions by simultaneous measurement of phagocytosis and oxygen radical generation.

Phagocytosis and oxygen radical generation by human polymorphonuclear leukocytes (PMNLs) were studied by a two-color flow cytometric analysis, where the red fluorescent product(s) of hydroethidine was used as an indicator of intracellular generation of oxygen radicals and opsonized zymosan (OZ) as an indicator of phagocytosis. Unstimulated cells formed a single population of cells without any significant fluorescence. PMNLs stimulated by OZ exhibited a high red fluorescence. Most PMNLs phagocytosed OZ and generated oxygen radicals when stimulated by zymosan particles opsonized with human AB serum at concentrations of more than 10%, whereas three distinct subpopulations (designated as R1, R2 and R3) appeared when stimulated by zymosan particles opsonized with 3% serum; R1 cells enhanced neither green nor red fluorescence, R2 cells enhanced green fluorescence but not red fluorescence, and R3 cells enhanced both green and red fluorescence. The R2 cells completely disappeared by the addition of Trypan blue. Most of the R3 cells disappeared by the addition of cytochalasin B. These findings on the three fractions were confirmed by the observation under fluorescence microscopy of cells in each fraction obtained by sorting. In conclusion, PMNLs could be separated into three functionally distinct subpopulations when stimulated by zymosan particles opsonized with a suboptimal concentration of serum.

Cell Differentiation↗
PubMed1997

Central administration of PACAP stimulates gastric secretion mediated through the vagal pathway in anesthetized rats.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide that was originally isolated from ovine hypothalamic tissue. The peptide has two amidated forms, PACAP38 and PACAP27. In this study, we examined the effects of centrally administered PACAP38 and PACAP27 on gastric secretion in anesthetized rats. Centrally administered PACAP stimulated gastric acid and pepsin secretion in a dose-dependent manner. PACAP38 was 1.5-2 times more potent than PACAP27 on gastric secretion. By contrast, intravenously administered PACAP38 had no effect on basal or pentagastrin-stimulated gastric secretion. PACAP6-38, a PACAP antagonist, by itself at high doses also stimulated gastric and pepsin secretion, but at lower doses had no effect. Centrally administered PACAP6-38 at a dose that had no effect on gastric secretion, atropine pretreatment, or vagotomy pretreatment, suppressed the stimulatory effect of PACAP38. It is concluded that centrally administered PACAP may have a regulatory effect on gastric secretion through PACAP receptors and the vagal pathway.

Anesthesia↗
PubMed1997

Endoscopic resection of rectal carcinoid tumors using aspiration lumpectomy.

BACKGROUND AND STUDY AIMS: Although carcinoid tumors have malignant potential, complete resection can be curative if the lesion is located within the submucosal layer. In this study, we evaluated the effectiveness of endoscopic aspiration lumpectomy for the treatment of small rectal carcinoid tumors. PATIENTS AND METHODS: Eight patients with rectal carcinoid tumors less than 10 mm in diameter and located within the submucosa were treated by aspiration lumpectomy. It was confirmed that none of the patients had any metastatic lesions before treatment. The procedure was carried out using an endoscope with a cylinder attached to the tip and a Teflon tube along its outer axis. The lesion was aspirated into the cylinder, grasped by a snare passed through the tube, and then resected. RESULTS: All lesions were excised completely, without any complications. The resected specimens were circular, with the lesions located in the center of the surrounding mucosa. The diameter of the specimens (mean +/- SD) was 18.3 +/- 6.2 mm. All tumors were histologically typical, and the lateral and bottom margins of the specimens were free of tumor cells. No recurrences or distant metastases were found in any of the patients during the mean observation period of 13.3 months. CONCLUSIONS: We conclude that aspiration lumpectomy is a useful and safe technique for the treatment of small rectal carcinoid tumors contained within the submucosa.

Carcinoid Tumor↗
PubMed1997

[Clinical efficacy of lomefloxacin for associated infection in patients with hematological diseases].

We have studied the clinical effect of lomefloxacin (LFLX) for the documented infections in the patients with hematological disorders, and also analyzed the prophylactic usefulness of LFLX for the prevention of succeeding infection after the chemotherapy. Fifty five patients were entered in the trial, and 51 patients were eligible. Among 51 eligible patients, 40 patients were suffered from accompanied infections, and 11 patients were registered for the prophylaxis of the infection. In the group of documented infection, the ratio of out-patients was 62.5%, and 63.0% in prophylactic usage. In the treatment of the documented infection, LFLX was effective in 20 patients; the efficacy rate was 50.0%. In the prophylactic administration, LFLX was effective in 9 patients, yielded the efficacy rate of 81.8%. LFLX was effective for all 5 patients with urinary tract infection, in 10 out of 18 patients with respiratory tract infection (efficacy rate; 55.6%), in 5 out of 12 patients with fever from undetermined origin (41.7%), showed no effect for cholecystitis, colitis, and phlegmon. Bacteriological examinations revealed that all of the bacteria detected as pathogens were eradicated. The efficacy rate in the group of the malignant disorders such as leukemia/ lymphoma was smaller than that of non-tumorigenic diseases as aplastic anemia. As myelodysplastic syndrome (MDS), four infection-bearing patients and five patients with prophylactic usage were analyzed. The efficacy rate of LFLX was 50.0 and 80.0%, respectively, and the overall efficacy rate was 66.7%. All MDS patients without prophylactic administration failed to have infections. Thus, LFLX was thought to be useful in the prevention of succeeding infections after the chemotherapy. No clinical and laboratory adverse reactions were reported.

Adolescent↗
PubMed1997

Qualitative platelet 12-lipoxygenase abnormality in a patient with essential thrombocythemia.

Quantitative platelet 12-lipoxygenase (12-LOX) deficiency has been reported in some patients with myeloproliferative disorders (MPD). We report here for the first time a novel qualitative abnormality of the 12-LOX enzyme of platelets from a patient with essential thrombocythemia. The anti-12-LOX immunoprecipitates from the patient's platelet homogenates showed a deficiency of 12-LOX activity, but contained normal amount of 12-LOX protein. There was no difference in subcellular localization of the enzyme between the patient's platelets and normal ones. This 12-LOX protein lacking its enzyme activity showed slightly larger electrophoretic mobility than normal one, suggesting a molecular abnormality of the enzyme. However, we could not detect any genetic mutation causing such abnormalities in all exons of 12-LOX gene by sequencing the patient's PCR-amplified DNA. Thus, our results indicate that the deficient activity of this abnormal 12-LOX protein is probably due to a posttranslational modification, and the possibility that platelets of some MPD patients have qualitative abnormality of the 12-LOX enzyme besides quantitative ones.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1997

Long distance polymerase chain reaction for detection of chromosome translocations in B-cell lymphoma/leukemia.

To establish a rapid and sensitive method to detect neoplastic cells carrying a specific chromosomal translocation in B-cell lymphoma/leukemia, we have developed a novel strategy based on long distance polymerase chain reaction (LD-PCR) amplification. Genomic DNA were extracted from tumor cells carrying a t(14;19)(q32;q13), a t(8;14)(q24;q32), a t(3;22)(q27;q11), a t(2;3)(p12;q27), and a t(3;14)(q27;q32). Oligonucleotide primer pairs were designed to be complementary to exons or flanking sequences of the BCL3, c-MYC and BCL6 oncogenes, and to constant region genes of the IG genes. LD-PCR with a newly available Taq polymerase for longer product synthesis successfully amplified fragments representing BCL3/C alpha junctional sequences for t(14;19); c-MYC/C mu, c-MYC/C gamma and c-MYC/C alpha for t(8;14); BCL6/C lambda for t(3;22); BCL6/C kappa for t(2;3); 5'-BCL6/C mu and 5'-BCL6/C gamma for t(3;14), respectively. The sizes of the amplified fragments were varied from 1.8 kb to 12 kb, which were specific to each material. Present study provides a useful tool for diagnosis and subsequent management of B-cell lymphoma/leukemia characterized with specific chromosomal translocation.

B-Cell Lymphoma 3 Protein↗
PubMed1997

Rearrangement of the BCL6 gene in B-cell lymphoid neoplasms.

We report here a large series of B-cell neoplasms with regard to rearrangement of the BCL6 gene on chromosome band 3q27. Southern blot analysis using probes from the major translocation cluster (MTC) region of the BCL6 revealed rearrangement in 32 of a total of 222 patients with various subtypes of B-cell neoplasm. In non-Hodgkin's lymphoma (NHL), rearrangements of the BCL6 gene were not closely associated with a specific histopathologic subtype but distributed in subcategories in the Working Formulation. A comparative study between NHL associated either with BCL2 or BCL6 rearrangement showed that advanced disease and bone marrow involvement were more frequent in BCL2(+) NHL. In contrast, extranodal involvement was more frequently observed in the BCL6(+) NHL. The survival curve of BCL6(+) NHL was characterized by a rapid decline followed by a plateau. Of the total of 32 BCL6(+) patients, 6 carried both BCL2 and BCL6 rearrangements, and showed clinicopathological properties of follicular lymphoma. This study suggests that BCL6 rearrangement is primarily associated with large cell lymphoma, and that BCL2(-)BCL6(+) NHL could potentially be curable with modern combination chemotherapy.

Bone Marrow↗
PubMed1996

Application of long-distance polymerase chain reaction to detection of junctional sequences created by chromosomal translocation in mature B-cell neoplasms.

Junctional sequences created by chromosomal translocations in mature B-cell neoplasms, which involve immunoglobulin gene loci (IG) and putative proto-oncogenes on reciprocal partner chromosomes, are unique to neoplastic cells characterized by particular histological and immunological phenotypes. To establish a rapid and sensitive method to detect neoplastic cells carrying a specific chromosomal translocation, we have developed a novel strategy based on long-distance polymerase chain reaction (LD-PCR) amplification. Genomic DNA was extracted from tumor cells carrying t(14;19)(q32;q13), t(8;14)(q24;q32), t(3;22)(q27;q11), t(2;3)(p12;q27), or t(3;14)(q27;q32). Thirty-two to 35-mer oligonucleotide primer pairs were designed to be complementary to exons or flanking sequences of the BCL3, c-MYC and BCL6 oncogenes, and to IG constant region genes. LD-PCR with a newly available Taq polymerase for longer product synthesis successfully amplified fragments representing BCL3/C alpha junctional sequences for t(14;19); c-MYC/C mu, c-MYC/C gamma, and c-MYC/C alpha for t(8;14); BCL6/C lambda for t(3;22); BCL6/C kappa for t(2;3); 5'-BCL6/C mu, and 5'-BCL6/C gamma for t(3;14). In Burkitt's lymphoma/leukemia, all materials in which c-MYC rearrangements were detectable by conventional Southern blot hybridization showed positive LD-PCR amplification. The sizes of the amplified fragments varied from 1.8 kb to 12 kb, and these were specific to each material. Serial dilution of tumor cells or DNA in negative materials demonstrated a single band on agarose gel electrophoresis stained with ethidium bromide at a level of sensitivity of 10(-3), and hybridization with radioactive probe improved the level by one order of magnitude (1 cell in 10(4)), indicating that this LD-PCR approach is a sensitive technique capable of detecting minimal residual disease. Thus, the present study provided a useful tool for diagnosis and subsequent management of B-cell neoplasms characterized by specific chromosomal translocations.

Base Sequence↗
PubMed1996

Two thromboxane A2 receptor isoforms in human platelets. Opposite coupling to adenylyl cyclase with different sensitivity to Arg60 to Leu mutation.

Thromboxane A2 (TXA2) receptor is a key molecule in hemostasis as its abnormality leads to bleeding disorders. Two isoforms of the human TXA2 receptor have been cloned; one from placenta and the other from endothelium, here referred to as TXR alpha and TXR beta, respectively. These isoforms differ only in their carboxyl-terminal tails. We report that both isoforms are present in human platelets. The two isoforms expressed in cultured cells show similar ligand binding characteristics and phospholipase C (PLC) activation but oppositely regulate adenylyl cyclase activity; TXR alpha activates adenylyl cyclase, while TXR beta inhibits it. The Arg60 to Leu mutant of TXR alpha, which has been shown to impair PLC activation (Hirata, T., A. Kakizuka, F. Ushikubi, I. Fuse, M. Okuma, and S. Narumiya. 1994. J. Clin. Invest. 94: 1662-1667), also impairs adenylyl cyclase stimulation, whereas that of TXR beta retains its activity to inhibit adenylyl cyclase. These findings suggest that the pathway linked to adenylyl cyclase inhibition might be involved in some of the TXA2-induced platelet responses such as shape change and phospholipase A2 activation which remain unaffected in the patients with this mutation.

Adenylyl Cyclases↗