Down-regulation of CD5 expression on activated CD8+ T cells in familial hemophagocytic lymphohistiocytosis with perforin gene mutations

Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled activation of T cells and macrophages with overproduction of cytokines. Familial HLH type 2 (FHL2) is the most common form of primary HLH and is caused by mutations in PRF1. We have recently described a significant increase in the subpopulation of CD8+ T cells with clonal expansion and CD5 down-regulation in Epstein-Barr virus associated-HLH, which represented a valuable tool for its diagnosis. However, this unusual phenotype of CD8+ T cells has not been investigated fully in patients with FHL2. We performed immunophenotypic analysis of peripheral blood and measured serum pro-inflammatory cytokines in five patients with FHL2. All patients showed significantly increased subpopulations of activated CD8+ T cells with down-regulation of CD5, which were negligible among normal controls. Analysis of T-cell receptor Vβ repertoire suggested the reactive and oligoclonal expansion of these cells. The proportion of the subset declined after successful treatment concomitant with reduction in the serum levels of cytokines in all patients except one who continued to have a high proportion of the subset and died. These findings suggest that down-regulation of CD5 on activated CD8+ T cells may serve as a useful marker of dysregulated T cell activation and proliferation in FHL2. © 2013 American Society for Histocompatibility and Immunogenetics

睡眠時無呼吸症候群患者の睡眠に関連した生活習慣の調査

SAS患者は日中の眠気や倦怠感などの疾患に起因する症状を紛らわすために睡眠にとって悪い習慣を取ってしまっている可能性が指摘されている。しかしSAS患者の生活実態は明らかになっていない。そこで本研究はSAS患者の生活習慣の実態を明らかにし、Apnea Hypopnea Index (AHI)、Epworth Sleepiness Scale (ESS)、Pittsburgh Sleep Quality Index (PSQI)、Body Mass Index(BMI)との関連を検討することを目的として行った。方法は質問紙およびAHIのデータをカルテより転載し、分析を行った。対象者は睡眠時無呼吸症候群と診断され治療前の方、56名を対象として行い、回収率は86%であった。AHI、ESS、PSQI、BMIと喫煙、飲酒、カフェインの摂取、睡眠時間などとの関連をみたところ、飲酒とBMIとの間に有意な関連がみられた。また喫煙とPSQIに有意な関連がみられ、睡眠の質が低いと評価している人ほど喫煙本数が多かった。睡眠時間とESSおよび希望睡眠時間と睡眠時間の差とESSの間に相関がみられ、SASによる睡眠障害だけでなく、睡眠時間の不足も問題である可能性があると考えられた。ベッドパートナーの有無が睡眠を阻害する因子になりうる可能性が示唆された。今回の対象者では治療開始前であったが、SASの治療の第一選択であるCPAP療法には家族のサポートも重要である。そのため今後ベッドパートナーの有無がCPAP療法にどのような影響を及ぼすのかについても検討していくことが重要であると考える。It has been pointed out that Sleep Apnea Syndrome (SAS) patients may have adopted life-styles which are poor for their sleep in order to alleviate symptoms that originate in disorders such as sleepiness and fatigue during the day. However, there is no clear evidence of what kind of maladaptive life-styles have been adopted by SAS patients. This research was therefore conducted with the aim of revealing the life-styles of SAS patients, and exploring the relationships between those life-styles and their correlation with the Apnea Hypopnea Index (AHI) data, the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and the Body Mass Index (BMI). It was conducted on 56 pre-treated patients diagnosed with SAS via analysis of questionnaires and AHI data from their medical records. The response-rate was 86%. An analysis of the relationships between the data derived from AHI, ESS, PSQI, and BMI to smoking, alcohol consumption, caffeine intake and sleeping hours showed a significant relationship between alcohol consumption and BMI data. Furthermore, a significant relationship was evident between smoking and PSQI data, with those who evaluated their sleep quality as poor smoking the most. A correlation could also be seen between sleeping time and the ESS data, and the difference between desired hours of sleep and actual sleeping time and the ESS data, indicating that not only sleep disturbance was caused by SAS, but also the lack of sleep time could be a problem. In addition, it was also suggested that the existence of a bed partner could be one factor disturbing sleep. While the subjects of this research had not yet been treated, family support is important to CPAP treatment. For this reason, it will also be essential to study the effect of a bed partner on CPAP treatment in the future

Roles of Renal Proximal Tubule Transport in Acid/Base Balance and Blood Pressure Regulation

Sodium-coupled bicarbonate absorption from renal proximal tubules (PTs) plays a pivotal role in the maintenance of systemic acid/base balance. Indeed, mutations in the Na+-HCO3- cotransporter NBCe1, which mediates a majority of bicarbonate exit from PTs, cause severe proximal renal tubular acidosis associated with ocular and other extrarenal abnormalities. Sodium transport in PTs also plays an important role in the regulation of blood pressure. For example, PT transport stimulation by insulin may be involved in the pathogenesis of hypertension associated with insulin resistance. Type 1 angiotensin (Ang) II receptors in PT are critical for blood pressure homeostasis. Paradoxically, the effects of Ang II on PT transport are known to be biphasic. Unlike in other species, however, Ang II is recently shown to dose-dependently stimulate human PT transport via nitric oxide/cGMP/ERK pathway, which may represent a novel therapeutic target in human hypertension. In this paper, we will review the physiological and pathophysiological roles of PT transport

慢性腎不全患者に合併したBellini管腫瘍の1例

We report a hemodialysis patient with an atypical renal neoplasm. The tumor cells were arranged in a two-cell pattern similar to that in the usual excretory duct systems. The histochemical staining pattern with some lectins and monoclonal antibody corresponded to the distal nephrons of normal kidney tissue. These findings enabled us to diagnose this patient as having so-called Bellini's duct tumor