Identification of stathmin 1 expression induced by Epstein-Barr virus in human B lymphocytes.

INTRODUCTION: The Epstein-Barr virus transforms resting B cells into proliferating lymphoblastoid cells, the origin of cell lines. METHOD AND RESULTS: Our cDNA microarray analyses led to the identification of 232 up-regulated and 112 down-regulated genes with more than a 3-fold difference in lymphoblastoid cell lines compared to resting B cells. The functional classification of these genes exhibited the distinct expression signature for cell proliferation, cell cycle and an immune response. Among them, we verified the differential expression of several oncogenes such as stathmin 1 (STMN1), RAB27A, RAB9A, BACH1 and BACH2 using quantitative real-time reverse transcriptase-polymerase chain reactions or Western blot analysis. Expression of STMN1 (which is involved in regulation of the microtubule filament system, cell growth and S-phase of cell cycle) was increased in lymphoblastoid cell line as well as in 7-day post-Epstein-Barr virus infection B cells, compared to resting B cells. CONCLUSION: Thus, this study suggests that Epstein-Barr virus infection induces STMN1 expression, which play a role in cell cycle progression and proliferation in the human B lymphocyte.

Fatty acids, inhibitors for the DNA binding of c-Myc/Max dimer, suppress proliferation and induce apoptosis of differentiated HL-60 human leukemia cell.

c-Myc is instrumental in the progression of Burkitt's lymphoma including HL-60 human leukemia cells. We tested fatty acids for their inhibitory effect on the DNA binding of c-Myc/Max dimeric proteins of human origin, prepared as recombinant proteins encompassing DNA binding (basic) and dimerization (HLHZip) domain, and found that those suppress proliferation and induce apoptosis of DMSO-differentiated HL-60 cells. The analyzed IC50 values of myristic acid, stearic acid, gamma-linolenic acid, linoleic acid, linolenic acid and arachidonic acid by EMSA were 97(+/-3), 2.2(+/-1.2), 55(+/-5), 32(+/-2), 62(+/-12), 22(+/-2)microM for DNA binding of recombinant c-Myc/Max, respectively. According to the results shown by XTT assay, their influence on proliferation was quite different from the rank order of IC50. Whereas the degree of influence of the unsaturated fatty acids on the proliferation of DMSO-differentiated HL-60 cells was similar, the influence of saturated fatty acids, stearic acid in particular, was very weak at same concentrations. In addition, we confirmed that these fatty acids have no influence on the expression of c-Myc in DMSO-differentiated HL-60 cells. Our experiments demonstrated that the inhibitors for the DNA binding of c-Myc/Max contribute to the downregulation of Myc-dependent proliferation and to the inducement of apoptosis, and serve as an exploration of potent new inhibitors.

Polymorphism of the angiotensin-converting enzyme gene in patients with cerebral infarction in Koreans.

The relationship between cerebrovascular disease and an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is still being debated. The frequency of the DD genotype of the ACE gene was significantly higher in subjects with than those without cerebral infarction in Japan. The aim of the present study was to assess the relationship between ACE gene polymorphism and the development of cerebral infarction in a population from Korea. We examined its possible role as a risk factor in patients with cerebral infarction. The association between ACE gene polymorphism and cerebral infarction was examined in 106 patients with cerebral infarction and 498 controls without cerebral infarction. Frequencies of the genotypes and alleles of the ACE gene were investigated. The ACE genotype was analyzed by the polymerase chain reaction (PCR). The frequency of D allele was 37.7% in patients and 39.1% in controls (chi2 = 0.128, p = 0.720). The frequencies of the genotypes of the ACE gene were II: 39.6%, ID: 45.3%, and DD: 15.1% in patients, and II: 37.1%, ID: 47.6%, and DD: 15.3% in controls (chi2 = 0.127, p = 0.721). There was no significant difference in the frequency of the DD genotype of the ACE gene, and we did not find any association between ACE polymorphism and cerebral infarction. These results indicate that ACE polymorphism is not a risk factor for the development of cerebral infarction in a Korean population.

Human chorionic gonadotropin induces nitric oxide synthesis by murine microglia.

This study investigated the effects of human chorionic gonadotropin (hCG) on the synthesis of nitric oxide (NO) in murine neonatal microglial cells. When hCG was used in combination with interferon-gamma (IFN-gamma), there was a marked cooperative induction of NO synthesis in a dose-dependent manner. This increase in NO synthesis was reflected as an increased amount of iNOS protein. The increase of NO synthesis by IFN-gamma-plus-hCG was associated with the increase of tumor necrosis factor-alpha (TNF-alpha) secretion and hCG-induced NO production was decreased by the treatment with anti-murine TNF-alpha neutralizing antibody. This study provides evidence that hCG activates expression of iNOS protein in murine microglial cells accompanied by NO accumulation via pathway dependent on L-arginine in the culture medium, and further offers that TNF-alpha acts on the NO synthesis from IFN-gamma-primed murine microglial cells.

Prenatal detection of de novo inversion of chromosome 9 with duplicated heterochromatic region and postnatal follow-up.

We report the first de novo case of a heterochromatic duplication on the long arm of the chromosome 9, which then was pericentrically inverted at p11q13. This condition was detected prenatally and carry to term. We then performed the follow up for over 1 year. So far, there seems to be no phenotypical abnormalities.