Abundant expression of the membrane-anchored protease-regulator RECK in the anterior pituitary gland and its implication in the growth hormone/insulin-like growth factor 1 axis in mice

The tumor suppressor gene Reversion-inducing cysteine-rich protein with Kazal motifs (Reck) encodes a membrane-anchored protease regulator expressed in multiple tissues in mouse embryos and is essential for embryonic development. In postnatal mice, however, physiological roles for the RECK protein remain unclear. We found in this study that Reck is abundantly expressed in growth hormone (GH)-producing cells (somatotrophs) in the anterior pituitary gland (AP). We also found that two types of viable Reck mutant mice, one with reduced RECK expression (Hypo mice) and the other with induced Reck deficiency from 10 days after birth (iKO mice treated with tamoxifen), exhibit common phenotypes including decreases in body size and plasma levels of insulin-like growth factor-1 (IGF1). To gain insights into the function of RECK in the AP, we characterized several somatotroph-associated molecules in the AP of these mice. Immunoreactivity of GH was greatly reduced in tamoxifen-treated iKO mice; in these mice, two membrane receptors involved in the stimulation of GH secretion [growth hormone secretagogue receptor (GHSR) and growth hormone releasing hormone receptor (GHRHR)] were decreased, however, their mRNAs were increased. Decrease in GHSR immunoreactivity and concomitant increase in its mRNA were also found in the other mutant line, Hypo. Furthermore, reduced immunoreactivity of growth hormone receptor (GHR) and concomitant increase in its mRNA was also found in the liver of Hypo mice. These results raise the possibility that RECK supports proper functioning of the GH/IGF1 axis in mice, thereby affecting their growth and metabolism

Efficacy of N-acetylcysteine and aminophylline in preventing contrast-induced nephropathy

SummaryBackgroundContrast-induced nephropathy (CIN) is one of the important complications of coronary angiography (CAG) and percutaneous coronary intervention (PCI), especially in patients with chronic kidney disease (CKD). Prophylactic administration of N-acetylcysteine (NAC) and aminophylline has been reported to be effective in some trials, but the results still remain controversial. We investigated the efficacy of NAC or aminophylline in preventing CIN.Methods and resultsForty-five consecutive patients undergoing CAG and/or PCI were randomly assigned to receive hydration and NAC (704mg orally twice daily; NAC group, n=15), hydration and aminophylline (250mg intraveneously 30min before CAG and/or PCI; aminophylline group, n=15), or hydration alone (control group, n=15). We compared serum creatinine (SCr), creatinine clearance (Ccr), blood beta-2 microglobulin, and urinary beta-2 microglobulin levels at baseline and 48h after CAG and/or PCI. In the NAC group, SCr decreased from 1.00±0.36 to 0.67±0.16mg/dl (p<0.01), and Ccr significantly increased from 62.4±15.6 to 80.4±8.39ml/min (p<0.01). In the aminophylline group, SCr and Ccr were unchanged. In the control group, SCr significantly increased from 0.94±0.21 to 1.28±0.21mg/dl (p<0.01), and Ccr significantly decreased from 63.7±16.1 to 46.1±10.6ml/min (p<0.01) after CAG and/or PCI. In the NAC group, mean blood beta-2 microglobulin significantly decreased from 2.38±0.58 to 1.71±0.38mg/dl (p<0.01), and in the aminophylline group, mean urinary beta-2 microglobulin concentration significantly decreased from 337±31.0 to 239±34μg/ml (p<0.01).ConclusionsThese results suggest that both prophylactic NAC and aminophylline administration are effective in preventing CIN, but not with hydration alone. It appears that the two compounds work in different ways against CIN

New challenges for text mining: mapping between text and manually curated pathways

<p>Abstract</p> <p>Background</p> <p>Associating literature with pathways poses new challenges to the Text Mining (TM) community. There are three main challenges to this task: (1) the identification of the mapping position of a specific entity or reaction in a given pathway, (2) the recognition of the causal relationships among multiple reactions, and (3) the formulation and implementation of required inferences based on biological domain knowledge.</p> <p>Results</p> <p>To address these challenges, we constructed new resources to link the text with a model pathway; they are: the GENIA pathway corpus with event annotation and NF-kB pathway. Through their detailed analysis, we address the untapped resource, ‘bio-inference,’ as well as the differences between text and pathway representation. Here, we show the precise comparisons of their representations and the nine classes of ‘bio-inference’ schemes observed in the pathway corpus.</p> <p>Conclusions</p> <p>We believe that the creation of such rich resources and their detailed analysis is the significant first step for accelerating the research of the automatic construction of pathway from text.</p

Effect of semen characteristics on pregnancy rate following intrauterine insemination

Objective : To assess the effects of semen characteristics on the success of intrauterine insemination (IUI). Design : A retrospective study. Settings : The Department of Obstetrics and Gynecology, Tokushima University Hospital, Japan. Patients : Between 2004 and 2008, 1,177 IUI cycles in 283 couples were studied. Intervention : IUI cycles were preceded with ovarian stimulation. Main Outcome Measure : Clinical pregnancy. Result : A total of 82 clinical pregnancies were obtained (7.0% pregnancy rate per cycle, 28.9% per case). Their subsequent outcomes of pregnancies were 18 miscarriages (21.9%), 2 ectopic pregnancies (2.4%) and 60 live births (73.2%). Of the 82 clinical pregnancies, 2 were twin pregnancies (2.4%). There was no triple or higher order multiple pregnancies. At the end of the sixth cycle, 73 clinical pregnancies had been achieved (89.0%). After diagnostic laparoscopy, the pregnancy rate per cycle for patients 35 years age was 18%, which is significantly higher than that of patients 35 years of age. Pregnancies occurred up to the fifth cycle after laparoscopy. The pregnancy rate (PR) per cycle was significantly higher in cases of sperm movement rates more than 30% (PR9.3%) and total motile sperm counts more than 10 106/ml (PR 8.2%). A study comparing the washed and unwashed cases did not reveal any differences. Conclusion : In male sub-fertility cases of sperm parameters as motility rates 30% and motile sperm concentration 10 106/ml, IUI could be a useful option for infertility treatment J. Med. Invest. 5

Pancreatic RECK inactivation promotes cancer formation, epithelial-mesenchymal transition, and metastasis

膵癌悪性化の分子機構解明 --RECK発現の低下が膵癌の浸潤・転移を引き起こす--. 京都大学プレスリリース. 2023-09-19.RECK is downregulated in various human cancers; however, how RECK inactivation affects carcinogenesis remains unclear. We addressed this issue in a pancreatic ductal adenocarcinoma (PDAC) mouse model and found that pancreatic Reck deletion dramatically augmented the spontaneous development of PDAC with a mesenchymal phenotype, which was accompanied by increased liver metastases and decreased survival. Lineage tracing revealed that pancreatic Reck deletion induced epithelial-mesenchymal transition (EMT) in PDAC cells, giving rise to inflammatory cancer-associated fibroblast–like cells in mice. Splenic transplantation of Reck-null PDAC cells resulted in numerous liver metastases with a mesenchymal phenotype, whereas reexpression of RECK markedly reduced metastases and changed the PDAC tumor phenotype into an epithelial one. Consistently, low RECK expression correlated with low E-cadherin expression, poor differentiation, metastasis, and poor prognosis in human PDAC. RECK reexpression in the PDAC cells was found to downregulate MMP2 and MMP3, with a concomitant increase in E-cadherin and decrease in EMT-promoting transcription factors. An MMP inhibitor recapitulated the effects of RECK on the expression of E-cadherin and EMT-promoting transcription factors and invasive activity. These results establish the authenticity of RECK as a pancreatic tumor suppressor, provide insights into its underlying mechanisms, and support the idea that RECK could be an important therapeutic effector against human PDAC

Association of Transcription Factor Gene LMX1B with Autism

Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217) showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (p = 0.008). Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p = 0.049). Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report