Search PubMed⌕ Search

Biomedical subjects

T Okamura

Publications and source records attributed to T Okamura.

At least 127 records · Page 7Linked to original sources

Distribution of H type 1-4 chains of the ABO(H) system in different cell types of human respiratory epithelium.

We used three anti-H monoclonal antibodies (MAbs) specific for H Type 1, H Type 2, and H Type 3/4 antigens to investigate the distribution of H Type 1-H Type 4 chains of the ABO(H) histo-blood group in the human respiratory system. Strong staining of H Type 1 chain and weak staining of H Type 2 chain were observed in mucous cells of submucosal glands of bronchial epithelium, which were dependent on the secretor status. No H Type 3/4 chains were detected in mucous cells. Serous cells of submucosal glands of respiratory system showed no staining by three anti-H antibodies. H Type 1 and H Type 3/4 antigens were detected heterogeneously in apical surfaces of bronchial epithelium from secretors but not from nonsecretors. In contrast, basal cells of bronchial epithelium expressed H Type 2 irrespective of the secretor status, probably regulated by the H gene. Some alveolar Type II cells contained only H Types 3/4, which were dependent on the secretor status, whereas alveolar Type I cells had no H antigens. Our results indicated that different cell types in respiratory epithelium expressed different types of carbohydrate chains of histo-blood group antigens under the control of the H or the Se gene.

ABO Blood-Group System↗

Angiodestruction and tissue necrosis of skin-involving CD56+ NK/T-cell lymphoma are influenced by expression of cell adhesion molecules and cytotoxic granule and apoptosis-related proteins.

We compared the expression of cell adhesion molecules (CAMs), cytotoxic granule proteins, and apoptosis-related proteins by immunohistology and in situ terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end labeling (TUNEL) of 10 cases of cutaneous CD56+ NK/T cell lymphoma with and 6 cases without angiodestruction. Lymphoma cells in cases with angiodestruction frequently expressed CAMs CD2, CD11a, and CD49d and their ligands CD58, CD54, and CD106 and were positive for CD122 and cytotoxic granule proteins TIA1, perforin, and granzyme B. Lymphoma cells in cases without angiodestruction mostly were negative for CD2, CD58, CD54, CD106, and TIA1 and weakly positive for perforin and granzyme B. In the TUNEL method, mean apoptotic indices (AI) for cases with angiodestruction showed a higher percentage than those without angiodestruction. CD95L, CD95, apoptosis-induced cysteine protease CPP32, apoptosis-promoting protein Bax, and proliferating marker (MIB1) frequently were positive in the lymphoma cells of cases with angiodestruction, but there was no expression of apoptosis-inhibitor protein Bcl2. In most cases without angiodestruction, lymphoma cells were positive for CD95L and Bax and negative for CD95, CPP32, and MIB1. CAMs and the 3 cytotoxic granule proteins and an apoptosis pathway might be important factors in the paracrine and autocrine mechanisms of tissue necrosis in cutaneous CD56+ NK/T cell lymphoma.

Aged↗

Validity and reliability of the Japanese version of the selected anger expression scale and age, sex, occupation and regional differences in anger expression among Japanese.

To examine the reliability and construct validity of the Japanese version of the Anger Expression Scale among four Japanese communities, and to examine distributions of anger expression scores according to sex, age, occupation, and community, we performed a cross-sectional study among 1,802 men and 3,229 women aged 20-70 in four geographic populations in 1995-97. We handed a self-administered questionnaire, which was selected from the Spielberger Anger Expression Scale, to the participants in the risk factor surveys and measured anger-in and anger-out as the anger expression scale. These scales had high internal consistency (Cronbach's alpha coefficient was 0.97-0.98 for anger-out and 0.77-0.86 for anger-in) and were of almost the same structure as the original. The Pearson correlation coefficients for the anger expression scale examined in 1995 and 1996 were 0.69 for anger-out and 0.57 for anger-in (both p < 0.001). The mean scores of both anger-out and anger-in were inversely associated with age. The mean anger-out score was higher for men than for women (p < 0.001), whereas the mean anger-in score did not vary significantly between the sexes. Furthermore, the mean scores of anger-out and anger-in varied among populations and occupational groups. The present study suggests that the Japanese version of the selected Anger Expression Scale is an acceptable scale for evaluating anger expression among Japanese.

Adult↗

Effect of thrombopoietin on acute myelogenous leukemia blasts.

It has been shown that the expression of c-mp1, which is a specific receptor for thrombopoietin (TPO), is restricted to the surface of megakaryocytes, platelets, human CD34+ progenitor cells and human erythroid/megakaryocytic leukemic cell lines. Recently, however, it has been reported that some acute myelogenous leukemia (AML) blasts expressed c-mp1 on their cell surface and proliferated in response to TPO. We therefore investigated the effect of thrombopoietin on the growth of leukemic blasts from patients with CD7-positive acute myelogenous leukemia (AML), which is a distinct biological and clinical subtype of AML. Significant growth responses of leukemic blasts to TPO were seen in 10/10 CD7+ and 7/20 CD7- AML cases using 3H-thymidine incorporation, while synergistic stimulatory effects of TPO with stem cell factor (SCF), interleukin-3 (IL-3), granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor were observed in both groups. In a leukemic blast colony assay, significant growth response to TPO was observed in 5/6 CD7+ and 4/17 CD7- AML cases examined. Furthermore, the expression of c-mp1 seemed to be higher in CD7+ AML cases than in CD7- cases, suggesting a relationship between the expression of c-mp1 and the proliferative response to TPO. These findings imply that CD7+ leukemic blasts express functional TPO receptors and proliferate in response to TPO. Thus CD7 expression on AML blasts may indicate the involvement of leukemic progenitors at an early stage of multipotent hemopoietic stem cells. In this review, we discuss the effect of TPO on AML blasts, especially in CD7+ AML cases.

Animals↗

Efficient introduction of macromolecules and oligonucleotides into brain capillary endothelial cells using HVJ-liposomes.

In this study, we examined the feasibility of introducing macromolecules into cultured mouse brain capillary endothelial cells (MBEC4 cells) by utilizing the hemagglutating virus of Japan (HVJ)-liposomes with fusogenic activity. We used fluorescein isothiocyanate dextran (FITC-Dextran) and FITC-labeled oligodeoxynucleotide (FITC-ODN) as models of a macromolecule and an ODN, respectively. Intracellular fluorescence appeared rapidly after the exposure of MBEC4 cells to FITC-Dextran-containing HVJ-liposomes, and remained detectable for at least 3 days. Only a control level of intracellular fluorescence was seen after treatment with FITC-Dextran alone, FITC-Dextran with empty HVJ-liposomes or FITC-Dextran-containing liposomes without fusogenic activity. In the early phase after administration (0-30 min), the introduction of FITC-Dextran into MBEC4 cells by the HVJ-liposome method resulted in a rapid and time-dependent increase of intracellular fluorescence intensity. Moreover, FITC-ODN was also introduced into MBEC4 cells by the HVJ-liposome method, although FITC-ODN alone was not introduced. These results indicate that the HVJ-liposome method is useful for the efficient introduction of macromolecules, including ODN, into brain capillary endothelial cells.

Animals↗

Microvascular decompression for cochlear symptoms.

OBJECT: The object of this study was to evaluate the efficacy of a new neurovascular decompression technique in relieving symptoms of cochlear nerve dysfunction. METHODS: Nineteen patients with slowly progressive hearing loss, low-frequency fluctuating hearing loss, and high-pitched tinnitus due to neurovascular compression (NVC) of the eighth cranial nerve in a triangular space between the seventh and eighth cranial nerves (the VII-VIII triangle) of the cerebellopontine angle (CPA) were treated using a new technique for microvascular decompression that was developed by anatomical study in 24 cadaver specimens of the CPA. In 12 of 19 patients the anterior inferior cerebellar artery (AICA) was observed to cause compression in the VII-VIII triangle and this vessel was easily mobilized medially for placement of a silicone sponge or Teflon cushion between the compressing artery and nerve. Postoperatively, hearing loss of 20 dB or more that was present in 11 of the 19 patients with NVC improved by more than 5 dB in seven (64%), including the patient with the most severe hearing loss. Of 18 patients presenting with tinnitus preoperatively, eight (44%) had no tinnitus and an additional nine (for a total of 94%) had good improvement in tinnitus after surgery and at long-term follow up. CONCLUSIONS: The microvascular decompression technique described is highly successful in treating symptoms due to direct or indirect compression of the cochlear nerve, with minimal risk of complications. Recordings of auditory brainstem responses confirmed the clinical diagnosis of NVC of the eighth cranial nerve and correlated with clinical results after microvascular decompression of the cochlear nerve.

Adult↗

NADPH/quinone oxidoreductase is a priority target of glioblastoma chemotherapy.

We attempted to determine a target of chemotherapy specific to glioblastoma cells to ensure a favorable response to anticancer drugs, through comparison in biologic nature related to drug resistance with other types of cancer cells. Using 13 human cancer cell lines including 3 glioblastoma lines, gene expression analysis and biochemical quantitative assay were performed for a total of 12 properties, which have been linked to drug action. Although most of genes related to drug resistance, such as MDR1, MRP, MGMT and GSTpi, were overexpressed in T98G, U-373MG, and U-251MG glioblastoma cells, Topo I (topoisomerase I) expression was relatively low and alpha- and beta-TUB (tubulin) expression was comparable to other types of 10 cell lines. The glioblastoma cell lines also showed an increased expression of NADPH/quinone oxidoreductase gene (NQO1), but the respective enzyme NQO activated MMC. Among the drugs targeting such properties, MMC was more active than Topo I inhibitors and docetaxel (TXT) due to the lack of other sensitivity (resistance) determinants. Differing from MMC, MGMT was shown to participate in the resistance of Topo I inhibitors (CPT-11, SN-38 and DX-8951f), while GSTpi and MDR1 were involved in docetaxel (TXT) resistance. MMC was also more active than ACNU and CDDP in the three glioblastoma cells. NQO may be a priority target of glioblastoma chemotherapy suitable for biochemical nature of the cells, and expression analysis of NQO1, alpha-TUB, beta-TUB, MGMT, MDR1 and GSTpi may help to seek a truly active drug against glioblastomas.

Antineoplastic Agents↗

Overexpression of manganese superoxide dismutase mRNA may correlate with aggressiveness in gastric and colorectal adenocarcinomas.

The expression or activity of manganese superoxide dismutase (Mn-SOD) is reduced in a variety of malignant tumors and Mn-SOD may act as a new type of tumor suppressor gene. On the other hand, increased expression of Mn-SOD can diminish the cytotoxic effects of several anticancer modalities, including tumor necrosis factor alpha, ionizing radiation, certain chemotherapeutic agents and hyperthermia. Although Mn-SOD expression and its role in various cancers are intensely studied, little is known about its function in gastrointestinal carcinomas. To examine the expression level and significance of Mn-SOD in gastrointestinal carcinomas, Mn-SOD mRNA expression was examined in 53 gastric carcinoma and 38 colorectal carcinoma by reverse transcription-polymerase chain reaction and was compared with those in the corresponding normal mucosal tissues. The tumor/normal (T/N) ratio was calculated and the data were clinicopathologically analyzed. The average T/N ratios of Mn-SOD mRNA expression in gastric and colorectal carcinomas were 2.19 and 3. 72, respectively. Clinicopathologic analyses revealed positive correlation between the Mn-SOD expression level and venous invasion in both gastric and colorectal carcinomas (p<0.05 and p<0.05, respectively). Furthermore, the colorectal carcinoma with lymph node metastasis showed significantly higher Mn-SOD expression than those without it (p<0.05). Our results suggest that Mn-SOD mRNA overexpression can occur in gastric and colorectal carcinomas and may be related to increased aggressiveness.

Adenocarcinoma↗

Delineation of the frequently deleted region on chromosome arm 13q in B-cell non-Hodgkin's lymphoma.

The loss of a specific chromosomal region provides a clue to the elucidation of the putative tumor suppressor gene implicated in the pathogenesis and progression of tumors. To delineate the specific region(s) involved in lymphomagenesis, we performed a survey of loss of heterozygosity for 11 polymorphic microsatellite loci scattered on variable chromosome arms. We examined 20 primary lymphoma samples, including both indolent and aggressive B-cell non-Hodgkin's lymphoma (B-NHL) and Hodgkin's disease (HD), and found a significant number of B-NHLs with loss of genetic material on chromosome arm 13q at the RB1 locus (50%; 4 of 8 informative cases for the RB1 locus). To specify the 13q deletion and to narrow the critical deleted region, we examined the same 20 lymphomas by intensive microsatellite mapping analysis using 12 microsatellite markers, mapping from 13q12.3 to 13q14. We confirmed the frequent 13q14 deletion to be in the vicinity of the RB1 locus (50% of the informative NHLs for at least 1 of 12 microsatellite loci; 5 of 10 aggressive NHLs and 2 of 4 indolent NHLs, but none of 6 HDs) and determined a subchromosomal region deleted in lymphoma on 13q14 defined by D13S164-D13S273, which is an overlapped region frequently lost in chronic lymphocytic leukemia. Taken together, our data indicate that the 13q alterations are present in a wide variety of NHLs including both indolent and aggressive B-NHLs, suggesting that loss of genetic material at chromosome band 13q14 may play an important role in the formation or development of a wide variety of mature lymphoid malignancies.

Adult↗

Prospective study on alcohol intake and risk of subarachnoid hemorrhage among Japanese men and women.

BACKGROUND: Few prospective data are available to evaluate potential risk factors of subarachnoid hemorrhage among the Japanese, although several prospective studies conducted in the United States and in Europe have shown a positive relationship between alcohol intake and the risk of subarachnoid hemorrhage. METHODS: A 9.4 year follow-up study was conducted on 12,372 men and women age 40 to 69 years who had no history of stroke, in six communities in Japan. The incident cases of subarachnoid hemorrhage were confirmed with computed tomography findings and/or clinical findings. Alcohol intake and other cerebrovascular risk factors were measured at the baseline examination. A Cox proportional hazard analysis was used to estimate the relative risks and 95% confidence intervals of the incidence of subarachnoid hemorrhage. RESULTS: During the follow-up assessment, 71 cases of subarachnoid hemorrhages occurred. For men, heavy drinking appeared to be an independent risk factor for subarachnoid hemorrhage; multivariate-adjusted relative risk was 4.3 (95% confidence interval [CI]: 1.1-16.8; p = 0.04). Among women, no excess risk was found for heavy drinking, probably due to the small number of heavy drinkers (n = 15). The combination of heavy drinking with smoking or hypertension increased the risk of subarachnoid hemorrhage substantially for men; the multivariate-adjusted relative risk was 6.0 (95% CI: 1.8-20.1;p = 0.004) for heavy drinking smokers and 13.0 (95% CI: 3.9-43.9; p < 0.001) for heavy drinking hypertensives. CONCLUSIONS: A reduction in alcohol intake, smoking cessation, and control of hypertension are important in preventing subarachnoid hemorrhage among Japanese men.

Adult↗

Molecular analysis of a candidate metastasis-associated gene, MTA1: possible interaction with histone deacetylase 1.

We previously identified a novel rat candidate metastasis-associated gene, mta1, based on its differential expression in highly metastatic cells compared to nonmetastatic cells. Furthermore, we showed that overexpression of its human counterpart, MTA1, correlated with the invasiveness or lymph node metastasis of gastric, colorectal and esophageal carcinomas. The aim of this study was to analyze the domains of the MTA1 and investigate the function(s) of this protein. Structural analysis revealed that the MTA1 protein contained a GATA-like zinc-finger domain, a leucine zipper domain, a SANT domain similar to the DNA binding domain of myb-related proteins, a src homology 3-binding domain important in protein-protein interactions, two highly acidic regions characteristic of the acidic activation domains of many transcription factors, and nuclear localization signals. Immunofluorescence staining of COS-7 cells transfected with a myc-epitope-tagged MTA1 expression vector clearly showed nuclear localization of MTA1. Coimmunoprecipitation of myc-tagged MTA1 and FLAG-tagged histone deacetylase 1 (HDAC1), followed by western blot analysis using anti-myc and anti-FLAG monoclonal antibodies showed that MTA1 physically bound with HDAC1 in COS-7 cells. Together with the recent finding that the NURD (nucleosome remodeling and histone deacetylase activities) complex contains an MTA1-related gene product, named MTA2, MTA1 may be another component of this complex and be involved in the alteration of chromatin structure and transcription repression.

Animals↗

MLL gene rearrangement in t(9;11) acute myelogenous leukemia with minimal myeloid differentiation (FAB subtype M0).

A 25-year-old man was diagnosed with acute myelogenous leukemia (AML), French-American-British (FAB) subtype M0, based on cytochemical and flow cytometric findings. Cytogenetic analysis revealed the chromosome translocations t(9;11)(p22;q23), and MLL gene rearrangement was identified by Southern blotting. In adult AML, MLL gene rearrangement was initially reported in FAB M4 and M5 cases, and recently in M1 and M2 cases, but was rare in M0 or M3 cases. Because the sensitivity of detecting MLL gene rearrangement by cytogenetic analysis is extremely low compared with Southern blotting analysis, the MLL gene may be involved in substantial numbers of adult AML cases, regardless of FAB subtype.

Adult↗

Chronic graft-versus-host disease in children and adolescents after bone marrow transplantation from HLA-matched donors.

We analyzed 98 pediatric patients who underwent bone marrow transplantation (BMT) from serologically HLA-matched related donors (RD) or unrelated donors (UD) at our institute to clarify the actual status of chronic graft-versus-host disease (cGVHD). There were 36 evaluable cases of RD-BMT and 35 of UD-BMT. cGVHD was observed in 8 RD-BMT cases (22.2%) and in 23 UD-BMT cases (65.7%). In the RD-BMT cases, the limited and extensive types of cGVHD were observed in 4 cases each, whereas in the UD-BMT cases, the limited type was seen in 11 cases and the extensive type in 12. Prior acute GVHD was observed in 6 RD-BMT cases and in 18 UD-BMT cases. Two RD-BMT patients with extensive type cGVHD died of relapse and cytomegalovirus infection, and 4 UD-BMT patients died because of bronchiolitis obliterans, fungal infection, liver failure, and multiple organ failure, respectively. The incidence of cGVHD in these pediatric patients was as high as that in adult patients when UD-BMT was performed. Some UD-BMT patients required long-term immunosuppressive therapy after BMT. These findings suggest that cGVHD is a serious problem in pediatric UD-BMT. Therefore, intensive prophylaxis and treatment of GVHD must always be performed after UD-BMT.

Adolescent↗

[Prophylaxis with FK-506 for graft-versus-host disease after transplantation of bone marrow from unrelated donors].

Forty-eight patients who underwent bone marrow transplantation (BMT) from serologically HLA-matched unrelated donors received tacrolimus (FK506) alone or with methotrexate (MTX) and/or methylprednisolone (mPSL) to prevent graft-versus-host disease (GVHD). We analyzed retrospectively the efficacy of FK506 for GVHD prophylaxis, and its toxicity, by comparing three groups of patients: those given FK506 alone, those given FK506 + mPSL, and those given FK506 + MTX + mPSL. Grade III and IV acute GVHD occurred in five of 10 patients given FK506 alone and in 11 of 30 patients given FK506 + mPSL. In these groups, severe acute GVHD was commonly seen in the patients who discontinued FK506 administration early after BMT and in those who received bone marrow from genotypically HLA-mismatched donors. Early withdrawal of FK506 was due mainly to severe nephrotoxicity. The incidence of nephrotoxicity was very high in patients who received high-dose FK506 as well as melphalan-containing preconditioning (80% and 50%). None of eight patients who received FK506 + mPSL + MTX developed grade III-IV acute GVHD even though five of them received bone marrow from genotypically HLA-mismatched donors. In patients receiving bone marrow from unrelated donors, adjustment of the initial dose of FK506 seems essential in order to avoid severe nephrotoxicity, and combination of MTX and FK506 is useful for preventing severe acute GVHD.

Adolescent↗

[State of the treatment for gastrointestinal cancer].

We reviewed the results of chemotherapy for gastrointestinal cancer. In Western countries, FAMTX or ECF is recognized as the standard therapy for gastric cancer. In Japan, no standard chemotherapeutic regimen has been established yet, but FP or MTX/5-FU are often used as a first line chemotherapy. There have been only a few clinical trials of adjuvant chemotherapy for gastric cancer in which this regimen was identified as having a statistically significant effect. For colon cancer, 5-FU plus LV are now used as the standard therapy. Recently, however, it has been shown that 5-FU + LV combined with CPT-11 is more active than 5-FU + LV alone. The efficacy of oral anticancer agents such as UFT + LV, S-1, and capecitabin have also been shown to be equally or more active than i.v. administration of 5-FU and LV, so that the standard therapy for colon cancer will be changed in near future.

Antineoplastic Combined Chemotherapy Protocols↗

[Tacrolimus administration to a patient with cyclosporine-induced encephalopathy after allogeneic bone marrow transplantation].

A 25-year-old woman with severe aplastic anemia received allogeneic bone marrow transplantation from an HLA-identical sibling. Pretransplant conditioning comprised 3.6 Gy of total body irradiation and 200 mg/kg cyclophosphamide. Cyclosporine (CSP) and methotrexate were administered to prevent graft-versus-host disease (GVHD). The patient complained of severe headache soon after CSP administration on day-1. On day 3, convulsion developed and she lost consciousness for 15 min. CT and MRI demonstrated low density areas and high signals, respectively, in the frontal and parietooccipital lobes and splenium of the corpus callosum, suggesting brain edema probably induced by CSP. After immediate withdrawal of CSP, glycerol and prednisolone were instituted, and the patient's condition improved. Thereafter, she developed grade II acute GVHD. This was treated with tacrolimus, which produced no adverse effects including central nervous system (CNS) toxicity. This case illustrates that careful management of CNS disorders induced by CSP can be important in patients undergoing allogeneic bone marrow transplantation.

Adult↗