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Biomedical subjects

S Shirakawa

Publications and source records attributed to S Shirakawa.

At least 73 records · Page 4Linked to original sources

Augmentation of interferon production after cell-differentiation of U937 cells by TPA.

Persistent infections with mumps virus were established in several human lymphoid cells of T-cell origin (Molt-4, TALL-1, and CCRF-CEM) and human monocyte cells (U937 and THP-1). 2',5'-Oligoadenylate synthetase (2-5AS) activity was demonstrated to be only slightly induced by interferon (IFN) or TPA (12-O-tetradecanoyl-phorbol-13-acetate) treatment in these cells. Treatment of the persistently infected cells with IFN or TPA did not stimulate an increase in the amount of synthetase mRNA. Induction of cell differentiation and augmentation of IFN production by TPA were demonstrated in U937 cells persistently infected with mumps virus (U937-MP). Similar results for IFN production were obtained from differentiated U937 cells. It is suggested that cell differentiation of U937 cells might be associated with the development of IFN inducibility.

2',5'-Oligoadenylate Synthetase↗

Investigation of IFN type-I receptor and IFN regulatory factor expression relating to induction of 2', 5'-oligoadenylate synthetase in cells persistently infected with the mumps virus.

Poor induction of interferon-induced 2', 5'-oligoadenylate synthetase (2-5AS) activity has been demonstrated in cells persistently infected with the mumps virus or human T-lymphotropic virus type-I (HTLV-I). The suppression of 2-5AS induction is the result of the repression of 2-5AS gene expression at the transcription level. In a general way, after the binding of interferon-alpha (IFN-alpha) to cell surface-specific receptors, expression of 2-5AS gene is thought to be regulated by some transacting factors, IFN-regulatory factors (IRF-1 and IRF-2) and the IFN-stimulated gene factor (ISGF-3, a complex consisting of STAT-1 alpha, STAT-2 and p48). To clarify the cause of the suppression mechanism(s), fluctuation in the number of IFN receptors and the levels of mRNAs in both IRF-1 and IRF-2 were examined in cells persistently infected with the mumps virus (FLMT and KBMT). There were few differences in the number of IFN receptors and the level of IRF-2 mRNA between persistently infected cells and uninfected control cells. After the treatment of cells with IFN, a slight reduction of IRF-1 mRNA was found in persistently infected cells as compared with that of the uninfected control cells.

2',5'-Oligoadenylate Synthetase↗

Seasonal variation of mood and behaviour in a healthy middle-aged population in Japan.

A population survey of seasonality in six representative cities in Japan was conducted using the Japanese version of the Seasonal Pattern Assessment Questionnaire (SPAQ). The questionnaires were given to 951 parents (male: female ratio 1:1 age range 34-59 years) of high-school students. Significant regional differences in seasonal variations of mood, length of sleep, and weight were observed; the proportion of individuals reporting high seasonality in the two northern cities was significantly higher than that in the other areas. These results provide evidence for a northern predominance in the prevalence of seasonal affective disorder in Japan.

Adult↗

PRAD1/Cyclin D1 gene overexpression in mantle cell lymphoma.

The t(11;14) (q13;q32) translocation and its molecular counterpart Bcl-1 rearrangement are consistent features of mantle cell lymphoma (MCL). This translocation activates the PRAD1/cyclin D1 gene that is considered to be the Bcl-1 oncogene. PRAD1/cyclin D1 gene overexpression is closely associated with MCL. The PRAD1/cyclin D1 protein is localized to the nucleus, and the strong correlation between PRAD1/cyclin D1 and MCL is also found in the protein level. This finding indicates that PRAD1/cyclin D1 expression is a highly specific and sensitive molecular marker for MCL. This gene may function as an oncogene in the malignant transformation of cells.

Cyclin D1↗

Prolonged interval from body temperature nadir to sleep offset in patients with delayed sleep phase syndrome.

In order to clarify the relationship between sleep-wake and core body temperature rhythms in the delayed sleep phase syndrome (DSPS), we conducted simultaneous monitoring of these rhythms in seven patients with DSPS and nine healthy control subjects for 6-10 days during their conventional sleep-wake schedules. The sleep onset and offset times were determined visually from sleep logs, and the temperature data were fitted to 24-hour cosinor curves by the least squares method. The sleep onset and offset times and temperature nadir were delayed significantly in patients with DSPS compared with the control subjects (p = 0.01, 0.003 and 0.02, respectively). We also found that sleep length and the temperature nadir to sleep offset interval were significantly longer in the DSPS than the control group (p = 0.03 and 0.02, respectively). The latter finding suggests that the inability of the patients with DSPS to normally phase-advance their circadian rhythm may be a consequence of masking of the advance portion of their phase-response curve by the last hours of their prolonged sleep episodes.

Adult↗

Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells.

BACKGROUND: Lethal midline granuloma is now considered to be a malignant lymphoma derived from peripheral T cells or from natural killer cells. The therapeutic outcome of nasal T-cell lymphoma (NL) treated by conventional chemotherapy for non-Hodgkin's lymphoma is poor, although some patients have a good response to radiotherapy. To clarify the mechanisms of drug resistance, the expression of P-glycoprotein (P-gp)/MDR1, which is the product of the multidrug resistance (MDR) 1 gene, and MDR3 mRNA in NL cells, were examined. METHODS: Ten Japanese patients with NL were studied. Nine of these patients were examined before therapy. P-glycoprotein expression and phenotypes of lymphoma cells were examined by immunohistochemical staining using UIC2 as an anti-P-gp monoclonal antibody. In one case, the Rhodamine-123 efflux test was performed. MDR1 and MDR3 mRNA were detected by reverse transcription polymerase chain reaction. RESULTS: Nine of the 10 patients were P-gp positive. In one of nine, functional P-gp expression was observed. MDR1 mRNA was detected in all seven examined patients with P-gp positive NLs, whereas MDR3 mRNA was negative. Retrospectively, patients who received chemotherapy alone had poorer outcome than those treated by combination chemotherapy after irradiation. CONCLUSION: The poor prognosis for patients with NL treated with chemotherapy may be explained by P-gp expression of the NL cells.

ATP Binding Cassette Transporter, Subfamily B↗

Accelerated cell-cycling of hematopoietic progenitor cells by growth factors.

Recent advances in molecular biology have led to the identification of hematopoietic growth factors that support and influence the proliferation of hematopoietic progenitor cells in vitro and in vivo. Although these factors have been extensively studied, little is known of their role in the regulation of cell-cycling of hematopoietic progenitors, especially in the early stage of hematopoiesis. In the present study, we examined the effects of early acting growth factors on proliferative kinetics of hematopoietic progenitors by monitoring the number of cells in individual developing colonies, using an in vitro clonal assay. Interleukin-11 (IL-11) or steel factor (SF), alone or in combination, shortened the time for the size of IL-3-dependent colonies to double. Consecutive replating experiments provided evidence for direct action of growth factors on the growth rate of hematopoietic progenitor cells. Shortening of the time for the total cell number in the colonies to double was due to a reduction in time for each single cell within the respective colonies to become two daughter cells, and there was no alteration in the incidence of cells with a proliferative capacity. Cell-cycle analysis demonstrated that IL-11 has the potential to induce a shortened time for cell-cycle of hematopoietic progenitor cells without affecting distribution of each fraction of the cell-cycle, whereas SF has the potential to reduce cell-cycle time mainly by decreasing the time required for hematopoietic progenitor cells to go through the G1 phase. These results suggest that growth factors may modulate cell-cycling of hematopoietic progenitor cells.

Animals↗

Expression of interleukin-5 receptors on acute myeloid leukaemia cells: association with immunophenotype and karyotype.

Eosinophilia sometimes occurs in acute myeloid leukaemia (AML) and several laboratories have reported that cells with the t(8;21) or structural abnormalities of chromosome 16 can proliferate and differentiate to eosinophils in the presence of IL-5 in vitro. However, cases without these chromosomal abnormalities can also have eosinophilia. We investigated the association between the expression of IL-5 receptor (IL-5R) gene, karyotype and phenotype in 35 patients with AML. All cases expressed the IL-3R but the IL-5R gene was expressed predominantly in leukaemic cells with either t(8;21) or CD4-positive immunophenotype and was associated with the presence of eosinophilia.

Acute Disease↗

Potent and specific inhibition of human immunodeficiency virus type 1 replication by 4-(2,6-dichlorophenyl)-1,2,5-thiadiazol-3-Y1 N,N-dialkylcarbamate derivatives.

4-(2,6-Dichlorophenyl)-1,2,5-thiadiazol-3-yl N,N-dialkylcarbamate (TDA) derivatives were found to be highly potent and specific inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in a variety of cell cultures. The most potent congener of TDA derivatives, RD4-2024, inhibited HIV-1 replication by 50% at concentrations of 12.5 and 4.8 nM in MT-4 cells and peripheral blood mononuclear cells, respectively. These concentrations were more than 2,000- and 30,000-fold lower than its 50% cytotoxic concentrations, respectively. Although the TDA derivatives were active against 3'-azido-3'-deoxythymidine-resistant HIV-1, no antiviral activities were observed against HIV-2 and nonnucleoside reverse transcriptase inhibitor-resistant mutants of HIV-1. The TDA derivatives inhibited recombinant HIV-1 reverse transcriptase activity, depending on the template-primer used for the assay. However, they did not interact with HIV-2 reverse transcriptase. Thus, the TDA derivatives belong to the family of nonnucleoside reverse transcriptase inhibitors. Because of their potent anti-HIV-1 activities in vitro and their low levels of toxicity in mice, the TDA derivatives deserve further evaluation as candidate drugs for the treatment of patients with AIDS.

Antiviral Agents↗

Motion correction in exercise first-pass radionuclide ventriculography without an external point source.

UNLABELLED: Exercise first-pass radionuclide ventriculography provides valuable diagnostic and prognostic information in patients with coronary artery disease. In this procedure, motion correction of the images is commonly performed using a second external point source attached to the chest wall during exercise (dual-isotope method). Recently, a motion correction algorithm without an external point source (single-isotope method) was developed and the results compared with those of the dual-isotope method. METHODS: To examine the accuracy of the motion correction method, a phantom study was performed using a moving cardiac phantom with a motion speed of up to 169 cycle/min and motion amplitude up to 6 cm. Count fluctuation in the phantom region by motion was calculated as a coefficient of variation (CV). In the clinical study, time-activity curves of the left ventricular phase were created for quantitative assessment of variation as CV values of the ejection fraction in the central five cardiac cycles after correction by the two methods during exercise radionuclide ventriculography in 17 patients. RESULTS: In the moving phantom, both the single- and dual-isotope methods reduced the CV values less than 10%. In the clinical study, the single-isotope method provided less CV value of ejection fraction (9.8% +/- 5.6%) than the dual-isotope method (24.8% +/- 10.5%) (p < 0.01), indicating less individual variation of ejection fraction values. CONCLUSION: These data indicate that object motion can be accurately corrected in the moving phantom by both single- and dual-isotope methods. In clinical studies, the single-isotope method is more accurate.

Algorithms↗

Frequent expression of shared idiotypes in mantle cell lymphoma and extranodal small lymphocytic/non-mantle cell diffuse small cleaved lymphoma.

A panel of 14 anti-shared idiotype (Sid) monoclonal antibodies selected according to their high cross-reactivity to various lymphomas was immunohistologically tested for reactivity with seven reactive lymphoid tissue specimens and 227 B cell lymphoma specimens obtained from Japanese patients. In the reactive lymphoid tissues, the anti-Sld antibodies each reacted with a subpopulation of cells in the mantle zone and interfollicular areas; they rarely reacted with cells in the germinal center. In the B cell lymphomas, 13 anti-Sld antibodies reacted with a total of 78 of 186 (42%) specimens bearing immunoglobulin; none of the antibodies reacted with 41 specimens not bearing immunoglobulin. In mantle cell lymphomas (15/19, 79%) and extranodal small lymphocytic/non-mantle cell diffuse small cleaved lymphomas (11/15, 73%), the reactivity of the antibodies was high compared with that in the other lymphomas (52/152, 34%; P = 0.0002 and 0.004, respectively), including follicular lymphomas (11/42, 27%; P = 0.002 and 0.002, respectively). Since idiotypes are associated with the hypervariable regions and antigen-binding sites of immunoglobulin, these findings may reflect the differences in the regions/sites in each of these diseases.

Antibodies, Monoclonal↗

Protein phosphatase inhibitors, okadaic acid and calyculin A, induce alkaline phosphatase activity in osteoblastic cells derived from newborn mouse calvaria.

To determine whether protein phosphatases can affect bone regulation, we examined the effects of okadaic acid (OA) and calyculin A (CA), specific inhibitors of protein phosphatases type 1 and type 2A, on alkaline phosphatase activity of mouse osteoblastic cells. Clone MC3T3-E1 cells were cultured with varying concentrations of OA and CA. OA and CA stimulated alkaline phosphatase (ALP) activity in the cells in dose-dependent fashion with a maximal effect at concentrations of 5 nM and 2 nM, respectively. The properties of OA-induced and native ALP in the cells were the same and they were liver-bone-kidney type. These results show that protein phosphatase inhibitors stimulate bone formation in vitro and that phosphorylation and dephosphorylation of specific proteins in the cells may be involved in bone regulation in vivo as well.

Alkaline Phosphatase↗

[Assessment of left ventricular wall thickening with gated 99mTc-MIBI SPECT--value of normal file].

The wall thickening was assessed by regional count increase from end-diastole (ED) to end-systole (ES) in gated 99mTc-MIBI SPECT. The wall thickening index was calculated as (ES count--ED count)/ED count x 100 (% thickening). Gated SPECT was performed three hours after injection of 600 MBq of 99mTc-MIBI in 20 normal subjects to create normal files (ED, ES perfusion maps and % thickening map). In normal ED and ES perfusion maps, distribution in anterior and lateral regions were higher than other regions, indicating heterogeneous perfusion. In addition, the % thickening in apex was higher than anterior and lateral and septal regions, suggesting heterogeneous % thickening in normal subjects. Furthermore, the % thickening was different between male and female. We conclude that quantitative analysis of regional thickening can be performed by gated 99mTc-MIBI SPECT with normal files.

Adult↗

Frequent expression of CD3 epsilon in CD3 (Leu 4)-negative nasal T-cell lymphomas.

Adult natural killer (NK) cells had not generally been thought to express CD3 proteins other than zeta; however they were recently demonstrated to express CD3 epsilon in an activated condition. This prompted us to investigate the tumor tissues from 17 patients with Leu4-negative peripheral T-cell lymphoma, including eight with nasal T-cell lymphoma (NTCL), for the expression of CD3 epsilon. The tissues were immunohistologically stained with rabbit anti-human CD3 epsilon antibody. The expression of CD3 epsilon was more frequent in the tissues of nasal lymphoma than in the non-nasal lymphoma tissues: specimens from six of eight of the NTCL patients expressed CD3 epsilon, while only one of nine of the non-NTCL patients did so. The NTCL patients presented clinically with lethal midline granuloma, had histologic findings of tumor necrosis and angioinvasion, and had a peculiar CD2+, Leu4-, CD3 epsilon+, CD5-, CD7+, CD45RO+, CD4-, CD8-, beta F1-, T-cell receptor (TRC) delta 1-, CD56+ phenotype. This peculiar phenotype seems to be closely associated with NTCL. No clonal rearrangement of the TCR genes was detected in three NTCL patients examined. The NK cell origin of NTCL has been suggested by previous investigators. The phenotypic correspondence of our nasal tumors to adult activated NK cells supports this possibility, together with their lack of clonal rearrangement of the TCR genes.

Adult↗

[Efficacy of early administration of G-CSF after intensive chemotherapy in acute leukemia: a randomized controlled trial. Tokai Infection Study Group on Hematological Disorders].

The effect of granulocyte colony-stimulating factor (G-CSF) on neutropenia and infection was studied in a randomized trial in patients receiving intensive chemotherapy for acute leukemia. Fifty seven patients with acute leukemia (35 cases of refractory acute myeloid leukemia, 19 cases of acute lymphoblastic leukemia and 3 cases of blast crisis of chronic myeloid leukemia) were given G-CSF under either of the following two conditions; 1) Group A: starting G-CSF (200 micrograms/m2iv) administration 24 hrs after chemotherapy. 2) Group B: the same dose of G-CSF administration after a febrile episode of 38 degrees C with neutropenia (less than 1,000/microliters). Five patients were excluded from the study. Group A (27 patients) showed a shorter febrile period (2.15 +/- 2.98 days) than the 25 patients of Group B (3.40 +/- 4.78 days), but the difference was not statistically significant. Compared to Group B, Group A showed significantly early recovery of neutrophil counts as well as early recovery from documented infections. There was no evidence that early administration of G-CSF accelerates the growth of leukemic cells nor causes early relapse of acute leukemia.

Acute Disease↗

Elevated plasma tissue factor antigen level in patients with disseminated intravascular coagulation.

The plasma tissue factor (TF) antigen level was measured in patients with disseminated intravascular coagulation (DIC). The plasma TF antigen was detected in normal volunteers, and it was significantly higher in DIC patients than in non-DIC patients. However, in some patients with DIC, the plasma TF antigen level was within the normal range. The plasma TF antigen level in patients with DIC significantly decreased after therapy, but it was not correlated with organ failure or outcome. The plasma TF antigen level in patients with DIC was not correlated with other hemostatic markers. The plasma TF antigen level tended to be higher in DIC patients with nonlymphoid leukemia than in those with lymphoid tumor. TF might be implicated in the occurrence and progression of DIC.

Antigens↗