Comprehensive immune complexome analysis detects disease-specific immune complex antigens in seminal plasma and follicular fluids derived from infertile men and women

Background: Autoimmune reactions and subsequent inflammation may underlie spermatogenic dysfunction and endometriosis-related infertility.The aim of this study is to identify disease-specific antigens in immune complexes (ICs) in seminal plasma (SP) and in follicular fluid (FF).Methods: Immune complexome analysis, in which nano-liquid chromatography-tandem mass spectrometry is employed to comprehensively identify antigens incorporated into ICs in biological fluids, was performed for specimens collected from infertile couples undergoing assisted reproduction.Forty-two male patients consisting of subjects with oligozoospermia (n=6), asthenozoospermia (n=8), and normal semen analysis (n=28). Fifty-eight female patients consisting of subjects with ovarian endometriosis (n=10) and control women without disease (n=48).Results: Four disease-specific antigens were identified in subjects with oligozoospermia, while five disease-specific antigens were detected in subjects with asthenozoospermia, some of which are involved in sprematogenesis. Eight antigens were detected only in subjects with endometriosis.Conclusion: Functional characteristics of disease-specific antigens were found to correspond to the pathogenesis of male and female infertility. The formation of ICs may contribute to spermatogenic dysfunction and endometriosis-related infertility via loss of function of the related proteins. Immune complexome analysis is expected to be a valuable tool for the investigation of novel diagnostic methods and treatment strategies for infertility

失業問題・雇用政策とサードセクター

1 Carta nàutica

Superoxide anion production by neutrophils in myelodysplastic syndromes (preleukemia).

Superoxide anion (O2-) production by neutrophils from 14 untreated patients with acute nonlymphocytic leukemia (ANLL) was significantly less than that of healthy controls (4.93 +/- 1.99 vx 6.20 +/- 1.53 nmol/min/10(6) neutrophils, p less than 0.05). In 10 patients with myelodysplastic syndrome (MDS), however, it was not significantly different from the control level although 6 of the 10 patients had low levels, when individual patients were compared with the lower limit of the control range. An inverse correlation between the O2- production of neutrophils and the percentage of leukemic cells in the marrow existed in ANLL (r = -0.55, p less than 0.01), but not in MDS. Three of 4 MDS patients who died of pneumonia prior to leukemic conversion showed a low level of O2- production. The impaired O2- production by neutrophils from some MDS patients, probably due to the faulty differentiation from leukemic clones, may be one of the causes of enhanced susceptibility to infection.</p

A case of esophageal cancer with mesojejunal lymph node metastasis after total gastrectomy

A 56-year-old man was diagnosed with esophageal cancer by upper gastrointestinal endoscopy for examination of dysphagia. The patient had undergone total gastrectomy and jejunal interposition 4 years previously for a gastric cancer at the pT1N0M0 stage according to the UICC-TNM classification. Enhanced CT findings revealed a 3-cm-diameter mass located near the superior mesenteric artery. We conducted subtotal esophagectomy associated with partial jejunectomy including mesojejunectomy. The mass was histologically diagnosed to be mesojejunal lymph node metastasis from esophageal cancer. Mesojejunal lymph node metastasis from esophageal cancer developing after total gastrectomy has been reported in only three cases including ours. The present lymph node metastases may have occurred via the newly developed lymphatic drainage route through the esophagojejunostomy, and this metastatic lymph node can be considered the regional lymph node. Therefore, resection of the interposed jejunal limb with mesojejunectomy may be rational in surgery on esophageal cancer developing after total gastrectomy

Rearrangement of the breakpoint cluster region in Philadelphia chromosome positive acute leukemia.

The rearrangement of breakpoint cluster region (ber) was examined in leukemic cells obtained from 3 patients initially diagnosed as having Ph+ acute leukemia, 2 with acute lymphocytic leukemia (ALL) and one with acute mixed leukemia. DNA was digested with Bgl II and BamH I. The ber rearrangement was present in the case of acute mixed leukemia (Case 1), but was absent in the 2 cases of ALL (Cases 2 and 3). These results suggest that Case 1 represented a type of blast crisis of chronic myelocytic leukemia which was unusual in the sense of the occurrence of a myeloid-lymphoid conversion and lack of an apparent chronic phase. Cases 2 and 3 appeared to be de novo Ph+ ALL.</p

ATM mediates pRBfunction to control DNMT1 protein stability and DNA methylation

The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression owing to its ability to physically bind to many chromatin modifiers. However, the biological and clinical significance of this activity was not well elucidated. To address this, we performed genetic and epigenetic analyses in an Rb-deficient mouse thyroid C cell tumor model. Here we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability and hence controls the DNA methylation status in the promoters of at least the Ink4a, Shc2, FoxO6, and Noggin genes. Furthermore, we demonstrate that inactivation of pRB promotes Tip60 (acetyltransferase)-dependent ATM activation; allows activated ATM to physically bind to DNMT1, forming a complex with Tip60 and UHRF1 (E3 ligase); and consequently accelerates DNMT1 ubiquitination driven by Tip60-dependent acetylation. Our results indicate that inactivation of the pRB pathway in coordination with aberration in the DNA damage response deregulates DNMT1 stability, leading to an abnormal DNA methylation pattern and malignant progression