Identification of differentially expressed molecules in adult T-cell leukemia cells proliferating in vivo

HTLV-I is the causative agent of adult T-cell leukemia (ATL). However, the precise mechanism underlying the neoplastic cell growth of ATL remains unclear. In this study, we established a leukemic cell line, termed SYK-11L(+), from tumor cells (S-YU) in an in vivo cell proliferation model of ATL using severe combined immunodeficiency (SCID) mice. Unexpectedly, SYK-11L(+) was found to have no tumorigenicity in SCID mice. Flow cytometric analysis showed that S-YU expressed cell adhesion molecules including CD44, ICAM-1 and OX40, whereas SYK-11L(+) had lost the expression of these molecules. The administration of anti-OX40 monoclonal antibody inhibited the engraftment of S-YU cells into SCID mice, suggesting that OX40 is a potential target for immunotherapy. Significant differences in responsiveness to IL-2 and IL-15 were observed between the two cell types. To better understand the molecular basis of tumorigenicity, cDNA microarray analysis was performed using tumorigenic S-YU and non-tumorigenic SYK-11L(+) cells. We obtained several candidate genes differentially overexpressed in S-YU compared with SYK-11L(+). Interestingly, one such gene, regulator of G protein signaling 1 (RGS1), was shown to be overexpressed in most ATL patients. Further characterization of the differentially expressed molecules, such as OX40 and RGS1, would provide useful information not only to elucidate the mechanism of ATL cell growth in vivo, but also to develop novel molecularly targeted therapies.     

Effects of histamine on functional maturation of dendritic cells

There is increasing evidence that histamine affects dendritic cell (DC) activation, maturation, and preference for Th1/Th2 differentiation. In this paper we report that histamine affects interleukin (IL)-12 and IL-6 production in an immature DC (iDC) line derived from murine spleen. Histamine treatment of iDC significantly increased the IL-12 p40 mRNA and protein levels compared to histamine untreated iDC. In the presence of tumor necrosis factor (TNF)-alpha histamine also increased IL-12 p40 and IL-6 production. However, histamine significantly decreased IL-12 p40 production by lipopolysaccharide (LPS)-stimulated DC in a concentration dependent manner. When expressions of histamine H1 (H1R) and H2 (H2R) receptors in DC were analyzed by RT-PCR, both receptors were down-regulated after LPS or TNF-alpha stimulation compared to unstimulated iDC. Histamine treatment significantly increased the expression of H2R mRNA in iDC and H1R mRNA in LPS-activated DC. However, histamine treatment decreased the expression of both histamine receptors in TNF-alpha-stimulated DC. Similar results were obtained by flow cytometry with FITC-conjugated histamine. These results demonstrate that histamine can regulate the expression of its own receptors and activate iDC, which may influence subsequent functional states of mature DC in a maturation signal-dependent manner. Consequently, histamine may contribute to an immune response outcome.     

Reading span as an individual difference and cognitive problem solving performance

This study investigated the performance on a computer game called Mastermind, playing of which consumes a large amount of working memory resource. First, 143 college students took a Japanese version of reading span test (RST). They then played Mastermine under two conditions: with or without display of past game records. There were 105 participants who relied under both conditions on a tactical strategy that caused high memory load, and their performance data were analyzed. Results indicated that low-span readers (87 students) were more constrained than high- and medium-span readers (18 students) under the condition without display, and performance of the low was affected by the content of display. It was argued that working memory resource that RST measured was involved in the process of cognitive problem solving.     

Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension

Adipocyte-derived leucine aminopeptidase (ALAP) inactivates angiotensin II and/or generates bradykinin in the kidney, suggesting a possible role for ALAP in the regulation of blood pressure. We considered the hypothesis that genomic variants of the ALAP gene are associated with hypertension or individual variations in blood pressure. We screened for mutations in the ALAP gene in 48 unrelated Japanese individuals and identified 33 polymorphisms including 15 novel polymorphisms. We then performed a two-stage analysis. In the first stage, the eight missense polymorphisms were evaluated for associations with blood pressure in 96 apparently healthy individuals. In the second stage, only the most promising polymorphisms were evaluated for association with essential hypertension in 143 hypertensive and 348 normotensive subjects. Among the eight missense polymorphisms, the Ile276Met and Lys528Arg polymorphisms showed significant association with blood pressure. Subsequent analysis confirmed association between the Lys528Arg polymorphism and essential hypertension. The estimated odds ratio for essential hypertension was 2.3 for presence of the Arg allele at codon 528, in comparison with presence of the Lys/Lys genotype (P = 0.004). These findings support involvement of ALAP in the regulation of blood pressure.     

Evaluation of psychological factors in orthodontic patients with TMD as applied to the "TMJ Scale"

Physical and psychological evaluation have been required for TMD patients whose problems are multi dimensional. The questionnaire named the "TMJ Scale" was created to differentiate subjective TMD symptoms of patients. The purpose of this study was to clarify the reliability of the TMJ Scale for Japanese orthodontic patients with TMD and to differentiate the symptoms. Fifty orthodontic patients (average age 21y4m) with a chief complaint of TMD symptoms were compared with thirty patients (average age 21y1m) without TMD symptoms. The results were as follows: female patients in the symptom group in particular showed a higher degree of stress due to the chronic pain and abnormalities than those in the non-symptom group. Significant differences were observed in Pain Report, Joint Dysfunction and Global Scale at the 0.1% significant level, in Non-TM Disorder, Psychological Factor and Chronicity at the 1% level, and in Palpation Pain and Perceived Malocclusion at the 5% level in females. Few psychological problems were observed in male patients in the symptom group. Significant differences were observed in Range of Motion limitation at the 5% level in males. The differences in the psychological factors between male and female patients were clarified by using the TMJ Scale. These findings suggested that it was useful to differentiate the multiple symptoms, especially the psychological factors, by using the TMJ Scale for orthodontic patients with TMD.     

The effects of interferon-gamma and transforming growth factor-beta on adherence and survival of group B Streptococcus type III strains in ECV304 cells

Group B streptococci (GBS) are an important cause of neonatal sepsis, pneumonia and meningitis. In some newborns, GBS sepsis may have a severe course, including septic shock with high mortality rate, whereas other newborns are colonized with GBS on their surfaces without any clinical signs of bacterial infections. Interferon (IFN)-gamma is produced in neonatal GBS sepsis, and transforming growth factor (TGF)-beta is also found in the uterus. The involvement of IFN-gamma and TGF-beta in the earliest phase of infection might be a determinant of susceptibility and/or progression of infection in vivo. The aim of this study was to assess the effect of IFN-gamma and TGF-beta on adherence and intracellular viability in ECV304 cells of GBS serotype III isolated from cerebrospinal fluid (CSF) and vagina (strains 90356 and 80340, respectively). Interaction of GBS-ECV304 cells showed that the CSF isolate exhibited a more efficient adherence mechanism than the vagina isolate (P<0.001). Intracellular viability was observed for the CSF 90356 isolate within 2 h incubation. Results suggest the expression of additional bacterial virulence factors that favor some GBS type III strains to cause invasive disease. Detection of genotypic virulence marker (162-kb) in the CSF 90356 isolate by PFGE emphasizes the high risk of invasive infection by some GBS-III strains. Treatment of ECV304 cells with IFN-gamma and/or TGF-beta increased adherence of both GBS strains (P<0.001). Intracellular survival of the CSF 90356 isolate was observed after 24 h incubation following treatment of ECV304 cells with IFN-gamma and TGF-beta. Our data suggest that both IFN-gamma and TGF-beta may favor virulence of GBS strains. Variation of IFN-gamma and TGF-beta producing capacity of host cells of different individuals may influence development of invasive disease by GBS-III.