Cytokine-related genes play critical roles in extrafollicular growth of follicular lymphoma cells

Follicular lymphoma (FL) is a germinal center-derived B-cell lymphoma that is known to proliferate in the intrafollicular region. However, lymphoma cells can be identified in the extrafollicular regions, which are related to disease dissemination. We purified the intrafollicular and extrafollicular regions of FL cells by laser microdissection and conducted microarray analysis in order to characterize the gene expression profiles of FL cells from both regions. BCL2 and genes of germinal B-cell markers clearly separated intrafollicular and extrafollicular regions of reactive follicular hyperplasia, suggesting the adequacy of the current analysis. In FL cases, cytokine-related genes were significantly enriched in extrafollicular regions compared with those in the intrafollicular regions. In intrafollicular regions of FL, cell-cycle–related genes were enriched. We found that the FL cells in the extrafollicular region more strongly expressed IL3RA and CXCL12 than those of intrafollicular regions. The cytokines might be also derived from stroma cells in the extrafollicular regions, which may initiate activation and migration of the tumor cells to this region. Our results suggest that FL cell interaction with surrounding stroma cells plays an important role in the pathophysiology of FL and that such interactions should be a good target for therapy.     

Galanin-Like Peptide (GALP) Facilitates Thermogenesis via Synthesis of Prostaglandin E2 by Astrocytes in the Periventricular Zone of the Third Ventricle

Administration of galanin-like peptide (GALP) leads to a decrease in both total food intake and body weight 24 h after injection, compared to controls. Moreover, GALP induces an increase in core body temperature. To elucidate the mechanism by which GALP exerts its effect on energy homeostasis, urethane-anesthetized rats were intracerebroventricularly injected with GALP or saline, after which oxygen consumption, heart rate, and body temperature were monitored for 4 h. In some cases, animals were also pretreated with the cyclooxygenase (COX) inhibitor, diclofenac, via intracerebroventricular (i.c.v.) or intravenous (i.v.) injection. c-Fos expression in the brain was also examined after injection of GALP, and the levels of COX and prostaglandin E₂ synthetase (PGES) mRNA in primary cultured astrocytes treated with GALP were analyzed by using qPCR. The i.c.v. injection of GALP caused biphasic thermogenesis, an effect which could be blocked by pretreatment with centrally (i.c.v.), but not peripherally (i.v.) administered diclofenac. c-Fos immunoreactivity was observed in astrocytes in the periventricular zone of the third ventricle. GALP treatment also increased COX-2 and cytosolic PGES, but not COX-1, microsomal PGES-1, or microsomal PGES-2 mRNA levels in cultured astrocytes. We, therefore, suggest that GALP elicits thermogenesis via a prostaglandin E₂-mediated pathway in astrocytes of the central nervous system.     

Difference in Left Ventricular Mass Index Between Hypertensive Patients With and Without Renal Artery Stenosis by Propensity Score Analysis

This study aimed to define the difference in cardiac hypertrophy between hypertensive patients with and without renal artery stenosis (RAS). When cardiac ultrasonographic examination was performed in 971 consecutive hypertensive outpatients, renal peak systolic velocity (PSV) was examined. Compared with patients without RAS, those with RAS (PSV ≥180 cm/s, 4.1%) were significantly older and included a higher proportion of male patients and had a higher left ventricular mass index (LVMI). A stratified analysis in the selected 120 patients showed that the LVMI was significantly higher in patients with RAS than in those without RAS for each confounding factor such as age and blood pressure. RAS was independently associated with a higher LVMI on propensity score analysis and multivariate analysis. Thus, the difference in LVMI between hypertensive patients with and without RAS was confirmed, irrespective of age and blood pressure, by stratified propensity score analysis and multivariate regression analysis.     

Perception of hunger and satiety induced by 2-deoxy-D-glucose in anorexia nervosa and bulimia nervosa

The effect of intracellular glucopenia induced by 2-deoxy-D-glucose (2-DG) on changes in hunger ratings, blood glucose, plasms cortisol, and prolactin levels were examined in six female patients with primary anorexia nervosa, three patients with bulimia nervosa, and six age-and sex-matched volunteers. In the normal subjects, hunger ratings obtained by the linear visual analog technique increased significantly at 60 minutes after 2-DG infusion and remained elevated. In Patients with anorexia nervosa, however, hunger ratins paradoxically decreased significantly at 90 minutes. In normal subjects, the ingestion of a 20-minute lunch relieved hunger, but neither the anorexic patients nor bulimic patients felt satiety even after food intake. These results suggest that the perception of hunger induced by 2-DG in anorexia nervosa and that of satiety in anorexia nervosa and bulimia nervosa are disturbed.     

Urinary sorbitol measurement and the effect of an aldose reductase inhibitor on its concentration in the diabetic state

The amounts of sorbitol (SOR) excreted in 24-h urine were determined on two groups, i.e., diabetic and nondiabetic patients, using an improved method in which ion exchange resin column processing was applied, and these levels were compared with SOR levels in whole blood. Urinary SOR concentration was also determined in diabetic and normal rats in the same manner and its relationship to aldose reductase (AR) activity in whole blood was investigated. Changes in SOR levels in urine and whole blood were compared in diabetic rats after administration of an AR inhibitor (ARI). Whole blood SOR levels and urinary SOR excretion were significantly higher in diabetic patients than in nondiabetic patients. The same results were obtained in the animal models. In diabetic rats, the urinary SOR excretion was about five times higher than that in control rats, and the AR activity in whole blood was also significantly higher. The increase in urinary SOR excretion and whole blood SOR levels, as well as AR activity, in blood in the diabetic state was inhibited by ARI administration. The influence of the diabetic state and the efficacy of the ARI were more marked in urinary SOR excretion than in whole blood SOR levels. These data indicate that determinations of urinary SOR excretion and AR activity are easily measurable and of benefit to assessing the diabetic condition.     

体外培养骨髓基质细胞在珊瑚羟磷灰石上生长的表面形态观察

目的 观察体外培养的骨髓基质细胞与珊瑚羟基磷灰石复合后的生长特性,论证珊瑚羟磷灰石作为骨组织工程学载体材料的可行性.方法 分离纯化的狗骨髓基质细胞与珊瑚羟基磷灰石复合体体外培养,分别在相差显微镜下、扫描电镜下观察细胞的表面形态结构.结果 骨髓基质细胞在珊瑚羟基磷灰石上贴附生长良好,功能正常.结论 骨髓基质细胞在珊瑚羟基磷灰石上生长增殖良好,珊瑚羟磷灰石是骨组织工程载体材料的可靠选择.