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Y Minoshima

Publications and source records attributed to Y Minoshima.

5 recordsLinked to original sources

STAT5 induces macrophage differentiation of M1 leukemia cells through activation of IL-6 production mediated by NF-kappaB p65.

We recently demonstrated that STAT5 can induce a variety of biological functions in mouse IL-3-dependent Ba/F3 cells; STAT5-induced expression of pim-1, p21(WAF/Cip1), and suppressor of cytokine signaling-1/STAT-induced STAT inhibitor-1/Janus kinase binding protein is responsible for induction of proliferation, differentiation, and apoptosis, respectively. In the present study, using a constitutively active STAT5A (STAT5A1*6), we show that STAT5 induces macrophage differentiation of mouse leukemic M1 cells through a distinct mechanism, autocrine production of IL-6. The supernatant of STAT5A1*6-transduced cells contained sufficient concentrations of IL-6 to induce macrophage differentiation of parental M1 cells, and STAT3 was phosphorylated on their tyrosine residues in these cells. Treatment of the cells with anti-IL-6 blocking Abs profoundly inhibited the differentiation. We also found that the STAT5A1*6 transactivated the IL-6 promoter, which was mediated by the enhanced binding of NF-kappaB p65 (RelA) to the promoter region of IL-6. These findings indicate that STAT5A cooperates with Rel/NF-kappaB to induce production of IL-6, thereby inducing macrophage differentiation of M1 cells in an autocrine manner. In summary, we have shown a novel mechanism by which STAT5 induces its pleiotropic functions. Cytokines

Animals↗

Molecular cloning, expression analysis, promoter characterization, and chromosomal localization of the bovine PREF1 gene.

Pre-adipocyte factor-1 (pref-1), originally identified in mouse 3T3-L1 pre-adipocytes, is known to play a key role in inhibiting the adipose conversion. As a first step to study the involvement of the PREF1 gene in intramuscular adipose tissue development in cattle, which has an economic importance for beef cattle, we have isolated the bovine PREF1 cDNA and genomic clones and characterized expression in abdominal adipose and promoter region of the bovine PREF1 gene. We have detected two bovine PREF1 splice-isoforms, PREF1C2 and PREF1A, in abdominal fat tissue. The RT-PCR experiment revealed that the two isoforms are identified in neonatal, but no in adult abdominal fat tissue, suggesting age-dependent suppression of the bovine PREF1 gene expression in the form of PREF1C2 and PREF1A in abdominal fat tissue. By mapping the regulatory region of this gene, we have shown that at least two regions within 1121 bp upstream of putative transcription start site are sufficient to confer promoter activity, when accompanied by a short region including the transcription start site. The chromosomal location of the PREF1 gene was determined by fluorescence in situ hybridization (FISH). The PREF1 gene locates on bovine chromosome 21q24.

3T3 Cells↗

Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation.

To identify the key molecules that regulate differentiation of hematopoietic cells, we carried out retrovirus-mediated functional screening for cDNAs whose expression suppresses IL-6-induced differentiation of mouse myeloid leukemic M1 cells. From this screening, we obtained a full length cDNA encoding a mouse homologue of human MgcRacGAP. Overexpression of the anti-sense MgcRacGAP profoundly inhibited IL-6-induced macrophage-differentiation of M1 cells. On the other hand, overexpression of the full-length form of MgcRacGAP alone enhanced macrophage differentiation of M1 cells in response to IL-6, and induced macrophage differentiation of HL-60 leukemic cells. To determine how this protein regulates differentiation and proliferation, an antibody against MgcRacGAP was prepared. Immunohistochemical studies revealed that MgcRacGAP mainly localizes in the nucleus in interphase, accumulates on the mitotic spindle in metaphase, and is condensed in the midbody during cytokinesis. Overexpression of an N-terminal domain deletion mutant, which lacks the ability to localize to the midbody through association with tubulins, or a GAP-inactive mutant resulted in the formation of multinucleated cells in HeLa cells as well as in hemopoietic cells. Interestingly, MgcRacGAP in the midbody was phosphorylated probably on serine and threonine residues. These results indicate that MgcRacGAP regulates cytokinesis and cellular differentiation as a regulator of Rho family of GTPase and suggest that this process is controlled by some serine/threonine kinases.

Animals↗

Magnetic resonance images reveal a high incidence of asymptomatic pineal cysts in young women.

MACROSCOPIC BENIGN PINEAL cysts, according to previous reports, may preferentially occur in the young population at the fourth decade; symptomatic pineal cysts have been found mainly in females. To confirm the relationship of age and sex to the incidence of pineal cysts, we reviewed 8623 consecutive magnetic resonance images in 6023 patients. Tiny and obscure cysts in the pineal gland were ignored; only the pineal cysts > 5 mm were examined. The cysts were encountered in 79 (1.3%) of 6023 patients evaluated. The cysts predominantly occurred in females; we found 29 cysts in 3008 males and 50 cysts in 3015 females (P < 0.05). Young adults had higher incidence of these cysts, with a peak incidence occurring between the ages of 21 and 30 years, then the incidence gradually decreased with age. We found no significant age distribution in males. However, among all groups, young women between the ages of 21 and 30 years had the highest frequency (5.82%). The incidence of pineal cysts among women between the ages of 21 and 30 years was significantly higher than in any other group (P < 0.001; 21-30 versus 51-60, 61-70, and 71-80). In females, when the incidence below the age of 41 was compared with that above or equal to 41, the z score was 4.98 (P < 0.001). The cystic expansion of the pineal gland in females appeared to begin at adolescence, and presumably the pineal gland decreases in size with aging. In this article, we will also speculate about the relationship of these changes to the secretory activity of the pineal glands.

Adolescent↗

[Development of a light curing denture base resin].

We developed the light cured direct relining material and used it clinically. In this study, a partial change in its components was made to improve both its strength and manipulability with the aim of using it as a denture base material. The physical properties of the new material, bonding to resin teeth, fit, as well as procedure were discussed. As for physical properties, the bending strength of the new material was increased by improving its organic filler, it becoming comparable to that of heat curing resin. The water absorption of the new material was the lowest of compared materials. The bonding strength of this material to resin teeth was increased by treatment with a light cured bonding agent and the fit of the new material to a test model was comparable to that of heat curing resin. Thus, the new material seems to be quite clinically effective as a denture base resin.

Composite Resins↗