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Biomedical subjects

M Okamoto

Publications and source records attributed to M Okamoto.

At least 487 records · Page 27Linked to original sources

[Treatment results for unselected patients with acute myelogenous leukemia. During a 10-year period, August 1984 to July 1994].

In order to analyse the clinical characteristics and outcome in acute myelogenous leukemia, 129 consecutive adult patients admitted to our hospital over a 10-year period, from August 1984 to July 1994, were studied. Their median age was 51 years, 17 (13.2%) of them had antecedent myelodysplastic syndrome (MDS) and 9 (7.0%) had secondary leukemia. Seventy-eight patients (60.5%) were considered eligible for cure-oriented intensive chemotherapy. Forty-four patients were ineligible of one or more of the following; age over 70, antecedent MDS or secondary leukemia. Additional 7 patients were excluded due to concurrent severe diseases. The median survival of the 129 patients was 441 days with an actuarial 5-year survival of 28.6 +/- 4.4%, and the disease-free survival (DFS) decreased with the increasing age of the patient. In 78 patients who were eligible for intensive chemotherapy, complete remission was achieved in 84.6% and overall DFS was 41.1 +/- 5.9% at 5 years, and their survival was longer than that of ineligible patients. It was suggested that considerable selection of patients, for example, due to old age, already existed before visiting our hospital. Analysis of clinical data of unselected patients might enable the development of a rational approach to the management of elderly patients.

Adolescent↗

Rapid progression of flat warts in a patient with malignant lymphoma after PBSCT.

A 51-year-old man with non-Hodgkin's lymphoma in his third remission received autologous PBSCT. He had had a couple of flat warts on his right hand since admission, which showed no progression during conventional dose chemotherapy. On day 15 of PBSCT, however, the warts began to develop and spread to his forehead, face, neck and arms over several days. The diagnosis of flat warts was made and human papilloma virus type 3 was detected by PCR analysis. Severe immunosuppression associated with PBSCT may have caused this rapid and disseminated growth of flat warts.

Hematopoietic Stem Cell Transplantation↗

[Adult T-cell leukemia lymphoma primarily involving the epipharynx].

A 53-year-old woman was admitted to our hospital in April 1995, because of nasal obstruction, bloody rhinorrhea and hearing disturbance. She had no lymphadenopathy or skin eruptions. Laboratory examinations revealed a WBC count of 2.7 x 10(9)/L without abnormal cells, positive serum anti-HTLV-I antibody, normal lactate dehydrogenase and normal calcium level. MRI showed an epipharyngeal mass. No involvement was detected by CT scanning of the chest and abdomen, 67Ga scintigraphy and bone marrow biopsy. The pathological diagnosis of the biopsied specimen from the epipharyngeal mass was T-cell diffuse lymphoma, pleomorphic type. Monoclonal integration of HTLV-I proviral DNA was detected in lymphoma cells, which confirmed a diagnosis of extranodal adult T-cell leukemia lymphoma primarily involving the epipharynx. She was treated with CAMBO-VIP regimen followed by adjuvant involved-field radiotherapy and she continues to be in complete remission as of April 1996.

Female↗

[Follow-up study of obese pupils and their life styles in the lower grades of primary schools].

Physical examinations and a questionnaire survey of life style were carried out on all pupils (105 boys and 110 girls) at the first grade of primary school in Saigo town, Fuse village, Goka village, and Tsuma village of Shimane prefecture in 1992. In 1994, physical examinations and a questionnaire survey were again performed along with a newly-added blood examination on the same cohort. Parents of the pupils answered the questionnaire. The pupils who were included in both the first (in 1992) and the second (in 1994) examinations and surveys (89 boys and 101 girls, but 71 boys and 77 girls for blood examination) were subjects in this study to analyse the relationship between obesity and life style. The results showed (a) the proportional rates of obese boys and girls increased during the two years; (b) the obesity index of boys and girls in the third grades correlated with the obesity index of their mothers; (c) obese boys ate snacks frequently, had a higher speed in eating, and disliked physical exercise; and (d) the obesity index of boys and girls correlated with serum total cholesterol. These findings indicate that obesity occurs as early as the lower grades of primary schools and that it continues for at least two years.

Age Factors↗

Difference between proximal and distal right coronary flow velocity pattern in humans.

The purpose of this study is to clarify the difference between proximal and distal right coronary artery flow velocity pattern in humans. Each portion of the coronary artery in thirteen patients with chest pain syndrome was measured by means of Doppler guide wire. The systolic/diastolic peak velocity ratio and velocity integral ratio at the proximal portion of the right coronary artery were significantly higher than those at distal portion of the right coronary artery (0.97 +/- 0.27, 0.61 +/- 0.20, 0.66 +/- 0.19, 0.44 +/- 0.13, respectively). In the right ventricular branch, coronary flow velocity pattern showed systolic dominancy. Systolic/diastolic peak velocity ratio and integral ratio showed 1.69 +/- 0.62 and 1.00 +/- 0.62 in the right ventricular branch, respectively. It is speculated that the less marked diastolic predominant pattern in the proximal right coronary artery flow velocity may be due to the fact that the proximal right coronary artery supplies both the right and left ventricle but that the distal right coronary artery supplies only the left ventricular inferior wall.

Aged↗

[Effect of macrophage colony-stimulating factor on complement receptors and complement regulatory proteins on human peripheral white blood cells].

The effect of M-CSF and C5a on the expression of complement-related membrane proteins on the peripheral white blood cells was investigated. M-CSF or C5a was added into the suspension of the peripheral white blood cells. The expression of the complement receptors, CD35 (CR1) and CD11b/18 (CR3), and inhibitory membrane proteins, DAF and MCP, was measured by flow cytometry. M-CSF increased CR3 on polymorphonuclear cells (PMNs) and CR1, CR3, MCP and DAF on monocytes. C5a increased CR1, CR3 and DAF on PMNs, but did not affect the expression of those on monocytes. It is concluded that M-CSF possessed the activity of increase expression of both complement regulatory proteins and complement receptors of monocytes and C5a selectively affected the expression of those on PMNs.

Adult↗

Tobacco MAP kinase: a possible mediator in wound signal transduction pathways.

A complementary DNA encoding a mitogen-activated protein (MAP) kinase homolog has been isolated from tobacco plants. Transcripts of the corresponding gene were not observed in healthy tobacco leaves but began to accumulate 1 minute after mechanical wounding. In tobacco plants transformed with the cloned complementary DNA, trans inactivation of the endogenous homologous gene occurred, and both production of wound-induced jasmonic acid and accumulation of wound-inducible gene transcripts were inhibited. In contrast, the levels of salicylic acid and transcripts for pathogen-inducible, acidic pathogenesis-related proteins were increased upon wounding. These results indicate that this MAP kinase is part of the initial response of higher plants to mechanical wounding.

Amino Acid Sequence↗

Moloney murine leukemia virus infection accelerates lymphomagenesis in E mu-bcl-2 transgenic mice.

E mu-bcl-2 transgenic mice bearing the bcl-2 proto-oncogene linked to the immunoglobulin enhancer (E mu) sporadically develop B or T cell lymphomas after a long latent period. To identify genes that play important roles in development of lymphoid malignancies, proviral insertional mutagenesis with Moloney murine leukemia virus (MMuLV) was carried out in two lines of transgenic mice expressing the bcl-2 gene primarily in B or T cells. MMuLV infection of non-transgenic mice induced primarily mature T cell lymphomas. By contrast, infection of newborn E mu-blc-2 mice with the virus accelerated lymphomagenesis, and nearly all of the mice eventually succumbed to clonal pre-B, B, or mainly immature T cell lymphoma, indicating the active contribution of the bcl-2 gene in lymphomagenesis. Southern blot analysis of tumor DNA from MMuLV-infected transgenic mice revealed a proviral insertion at the c-myc gene in 26% (9/35) of tumors, at the pim-1 gene in 6% (2/35) and at the pim-2 (recently renamed tic-1) gene in 23% (8/35). Some tumors carried two activated oncogenes. No insertion was detected at the bmi-1 gene. These data suggest the usefulness of this transgenic system for analysis of lymphomagenesis involving the activated bcl-2 gene.

Aging↗

Enhancement of transformation in vitro of a nontumorigenic rat urothelial cell line by interleukin 6.

Chronic inflammation of the urinary tract is a significant risk factor for the development of bladder cancer. We have shown that acute and chronic inflammation induced by intravesical instillations of killed Escherichia coli strikingly enhances N-methyl-N-nitrosourea (MNU)-initiated rat bladder carcinogenesis. To test the hypothesis that cytokines released during inflammation may be involved in the enhancement of bladder carcinogenesis, we conducted an in vitro experiment. Using soft agar growth as an index of transformation, we examined the effect of inflammation-associated cytokines on the enhancement of MNU-initiated transformation of MYP3 cells, an anchorage-dependent nontumorigenic rat bladder epithelial cell line. In the first experiment, after 1-h exposure to MNU (50 micrograms/ml), cells (5 x 10(4)) were grown in soft agar in the presence of interleukin (IL)-1 alpha, IL-6, IL-8, or tumor necrosis factor-alpha (10 to 100 ng/ml). Colonies consisting of more than 20 cells were counted 4 weeks later. Among the cytokines tested, IL-6 (100 ng/ml) significantly increased colony counts over those for the untreated controls (P < 0.001). In the second experiment, the cells treated with MNU similarly as in the first experiment were cultured with or without IL-6 (100 ng/ml) for 1 week before the cells (5 x 10(4)) were grown in soft agar in the presence or absence of IL-6. IL-6 pretreatment increased colony counts irrespective of subsequent IL-6 treatment (P < 0.05). Moreover, IL-6-stimulated anchorage-dependent growth of MNU transformants far exceeded that of the parental MYP3. However, among the transformants, there was no parallel relationship in response to IL-6 between anchorage-dependent and -independent growth. Our results suggest that IL-6 may provide a selective growth advantage to MNU-initiated bladder epithelial cells in vitro and that it may be a factor accounting for the marked enhancement of inflammation-associated rat bladder carcinogenesis.

Animals↗

Group II phospholipase A2 activates mitogen-activated protein kinase in cultured rat mesangial cells.

Group II phospholipase A2 (PLA2) is a mediator of inflammation in various disease including glomerulonephritis. We recently found that urinary excretion of PLA2 was increased in patients with mesangial proliferative glomerulonephritis and that interleukin-1 (IL-1) enhanced platelet derived growth factor-stimulated mesangial cell proliferation through the action of group II PLA2 secreted in response to IL-1 stimuli. Here we report signal transducing mechanism through group II PLA2 in mesangial cells. Group II PLA2 (1-15 U/ml) rapidly activated mitogen-activated protein (MAP) kinase. IL-1 beta activated MAP kinase in two phases and the slow activation in the late phase, proceeding in parallel with increased group II PLA2 secretion elicited by IL-1 treatment, was inhibited by the specific antibody raised against group II PLA2. This suggests that the late phase activation of IL-1-induced MAP kinase was mediated, at least in part, by secreted group II PLA2.

Animals↗

N-alkylated nitrogen-in-the-ring sugars: conformational basis of inhibition of glycosidases and HIV-1 replication.

The conformations of nitrogen-in-the-ring sugars and their N-alkyl derivatives were studied from 1H NMR analyses, mainly using 3J(H,H) coupling constants and quantitative NOE experiments. No significant difference was seen in the ring conformation of 1-deoxynojirimycin (1), N-methyl-1-deoxynojirimycin (2), and N-butyl-1-deoxynojirimycin (3). However, it was shown that the C6 OH group in 1 is predominantly equatorial to the piperidine ring, while that in 2 or 3 is predominantly axial, and its N-alkyl group is oriented equatorially. In the furanose analogues 1,4-dideoxy-1,4-imino-D-arabinitol (4) and its N-methyl (5) and N-butyl (6) derivatives, the five-membered ring conformation differed significantly by the presence or absence of the N-substituted group and the length of the N-alkyl chain. Compound 3 reduced its inhibitory effect on almost all glycosidases, resulting in an extremely specific inhibitor for processing alpha-glucosidase I since N-alkylation of 1 is known to enhance both the potency and specificity of this enzyme in vitro and in vivo. This preferred (C6 OH axial) conformation in 2 and 3 appears to be responsible for their strong alpha-glucosidase I activity. Compound 4 is a good inhibitor of intestinal alpha-glucohydrolases, alpha-glucosidase II, and Golgi alpha-mannosidases I and II, but its N-alkyl derivatives 5 and 6 markedly decreased inhibitory potential for all enzymes tested. In the case of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP, 7), which is a potent beta-galactosidase inhibitor, its N-methyl (8) and N-butyl (9) derivatives completely lost potency toward beta-galactosidase as well. N-Alkylation of compounds 4 and 7, known well as potent yeast alpha-glucosidase inhibitors, resulted in a serious loss of inhibitory activity toward yeast alpha-glucohydrolases. Activity of these nine analogues against HIV-1 replication was determined, based on the inhibition of virus-induced cytopathogenicity in MT-4 and MOLT-4 cells. Compounds 2 and 3, which are better inhibitors of alpha-glucosidase I than 1, proved active with EC50 values of 69 and 49 micrograms/mL in MT-4 cells and 100 and 37 micrograms/mL in MOLT-4 cells, respectively, while none of the furanose analogues exhibited any inhibitory effects on HIV-1. The change in potency and specificity of bioactivity by N-alkylation of nitrogen-in-the-ring sugars appears to be correlated with their conformational change.

Alkylation↗

Frog cytochrome P-450 (11 beta,aldo), a single enzyme involved in the final steps of glucocorticoid and mineralocorticoid biosynthesis.

A cDNA for cytochrome P-450(11 beta,aldo) was cloned from a library of bullfrog interrenal tissue (tissue corresponding to the mammalian adrenal gland). The 1919-bp cDNA encoded a protein of 517 amino acids. Its amino acid sequence was highly similar to the sequences of bovine P-450(11 beta) and rat P-450(11 beta,aldo) when P-450(11 beta) family enzymes reported to date were examined. The enzyme expressed in COS7 cells had the 11 beta-hydroxylation, 18-hydroxylation activities and aldosterone synthetic activity. Northern-blot and immunoblot analyses suggested that a single P-450(11 beta) enzyme was expressed in bullfrog interrenal tissue. These results suggest that a single enzyme catalyzes the final steps of glucocorticoid and mineralocorticoid biosynthesis in bullfrog interrenal tissue as in bovine adrenal gland. A phylogenetic tree of CYP11B genes suggests that the frog enzyme diverged at an earlier evolutionary time from other vertebrate enzymes. Immunohistochemical and in situ hybridization studies indicated that steroidogenic cells existed in the outer region of interrenal tissue more densely than in the inner region, whereas some medullary cells made clusters like islets. Most of the cells were diffusely distributed in the tissue.

Amino Acid Sequence↗

Sensitive detection and structural characterization of trimethyl(p-aminophenyl)-ammonium-derivatized oligosaccharides by electrospray ionization-mass spectrometry and tandem mass spectrometry.

Mass spectrometric methodologies which use electrospray ionization (ESI) for oligosaccharide structural determination and which are linked to classical procedures, such as reductive amination, have been established. Several derivatives of a model oligosaccharide were prepared and their ionization efficiencies in electrospray ionization (ESI) and fast-atom bombardment (FAB) mass spectrometry were investigated. The trimethyl-(p-aminophenyl)ammonium (TMAPA) derivatives showed extremely high sensitivity in positive-ion ESI-MS and gave Y- and Z-series sequence ions by ESI tandem mass spectromety (MS/MS). This study suggests that TMAPA-derivatized oligosaccharides used in ESI-MS and ESI-MS/MS would be effective for structural characterization of oligosaccharides that are available only in limited quantities.

Aminopyridines↗