Comparative Analysis of Apoptosis and Inflammation Genes of Mice and Humans

Apoptosis (programmed cell death) plays important roles in many facets of normal mammalian physiology. Host-pathogen interactions have provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses through NFκB induction. Proteins involved in apoptosis and NFκB induction commonly contain evolutionarily conserved domains that can serve as signatures for identification by bioinformatics methods. Using a combination of public (NCBI) and private (RIKEN) databases, we compared the repertoire of apoptosis and NFκB-inducing genes in humans and mice from cDNA/EST/genomic data, focusing on the following domain families: (1) Caspase proteases; (2) Caspase recruitment domains (CARD); (3) Death Domains (DD); (4) Death Effector Domains (DED); (5) BIR domains of Inhibitor of Apoptosis Proteins (IAPs); (6) Bcl-2 homology (BH) domains of Bcl-2 family proteins; (7) Tumor Necrosis Factor (TNF)-family ligands; (8) TNF receptors (TNFR); (9) TIR domains; (10) PAAD (PYRIN; PYD, DAPIN); (11) nucleotide-binding NACHT domains; (12) TRAFs; (13) Hsp70-binding BAG domains; (14) endonuclease-associated CIDE domains; and (15) miscellaneous additional proteins. After excluding redundancy due to alternative splice forms, sequencing errors, and other considerations, we identified cDNAs derived from a total of 227 human genes among these domain families. Orthologous murine genes were found for 219 (96%); in addition, several unique murine genes were found, which appear not to have human orthologs. This mismatch may be due to the still fragmentary information about the mouse genome or genuine differences between mouse and human repertoires of apoptotic genes. With this caveat, we discuss similarities and differences in human and murine genes from these domain families.     

Stimulation and resection of Vidian nerve in patients with chronic hypertrophic non-allergic rhinitis: effect on histamine content in nasal mucosa

Parasympathetic innervation of nasal mucosa plays an important role in the pathogenesis of chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.). The present study investigated the effect of Vidian nerve stimulation and resection on the histamine contents and on the morphological pattern in mucosal samples of patients with C.H.N.A.R. Vidian nerve stimulation determines a significant decrease in histamine content in the samples examined; microscopical observations showed significant variations in the glandular, stromal and vascular components.The changes indicate an enhanced secretory activity, intensive vasodilatation and active degranulation of mast cells, which were significantly decreased in number in the samples obtained after 90 sec of stimulation.The neurectomy of the Vidian nerve resolves quite completely the clinical symptomatology and in parallel decreases the mucosal histamine contents, which are increased in patients with C.H.N.A.R. before the operation in comparison with the normal controls.     

Donor Choriocarcinoma Transmission From Solid Organ Transplantation: A Case Report

Transplantation of any organ has some inherent risk of disease transmission, such as infection and malignancy. The present study aims to describe 2 cases of choriocarcinoma transmission after kidney and liver transplantation originating from the same patient. The donor was a 17-year-old woman who died of cerebral hemorrhage. Both organ recipients died of metastatic choriocarcinoma few months after the transplantation, within days after starting chemotherapy. Retrospective hCG (human chorionic gonadotropin hormone) analysis in donor's blood stored at the time of donation had a result of 9324 mIU/mL. Despite its rarity, clinicians should be aware of the risk of transplant-related choriocarcinoma from female donors in childbearing age. In some cases, hCG dosage should be performed before donation.     

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

Hormones in male-patients with advanced esophageal-carcinoma

Hormones are believed to play a dominant role as promoters in the growth and development of hormone-dependent cancers. Much less is known about the circulating hormones in male patients with oesophageal cancer. This lack of attention led us to evaluate the role of peptide and steroid hormones (by RIA) in male patients with oesophageal cancer (n=49). Blood samples of patients were collected pretherapeutically and data was compared with age matched controls (n=25). In this retrospective study, significantly high levels of FSH (P<0.02), LH (P<0.001) and prolactin (P<0.001) were observed with concomitant low levels of estradiol (P<0.001), DHEA-S (P<0.02) and testosterone (P<0.001) in patients when compared with respective controls. The patients when grouped according to anatomical site and histological type of the tumor, intergroup variation was not observed in these hormones. From our, study, it seems that hormonal imbalance or altered ratio of peptide and steroid hormones might be playing a significant role in the development and/or progression of oesophageal carcinoma in men.     

Mutagenic activity in waste from an aluminum products factory in Salmonella/microsome assay

The mutagenic activity of waste material originating from an aluminum products factory was determined by the Salmonella/microsome assay, using the bacterial strains TA100, TA98 and YG1024. The material was obtained by sweeping the factory floor at the end of the work shift. Organic compounds were extracted by ultrasound for 30 min in dichloromethane or 70% ethanol. After evaporation of solvent, these extracts were dissolved in dimethylsulfoxide, and tested for the mutagenic activity at varying concentrations. All the extracts from the factory had mutagenic activity, especially in the YG1024 strain, suggesting the presence of aromatic amines, later confirmed by chemical analysis. The TA98 strain also showed mutagenic activity, though it did not exhibit the highest mutagenicity index observed with the YG1024 strain. In TA100, mutagenic activity was not observed. This study should serve as an alert to management and those who are occupationally exposed, and as a warning that this type of waste should not be discarded in the environment without any control.