The study of diethylstilbestrol toxic effect in the mouse sertoli cell line by comparison of miRNA and mRNA expression

It is important to acknowledge the harmful effects of environmental chemicals in human’s lives. The toxic effects of Diethylstilbestrol (DES), one of the endocrine-disrupting chemicals (EDCs), have been documented in many studies. As expected, DES affect male gendal hormone as well as female’s; therefore, epigenetic study should be considered. In this study, microarray technology was used to study harmful effects on the level of genomics, and here, two types of microarray chips- the Agilent mouse genome 4 × 44 K array for gene expression profiling and the Agilent mouse miRNA v13 for miRNA expression profiling-was used to study the relation between gene and miRNA expression profiles. As a result, we identified 4 miRNAs (miR 203, 350, 421, and 466i) that were similarly expressed at 3 hrs and 24 hrs of DES treat times. Twenty one genes matched between predicted target for 4 miRNAs and 118 genes expressed similarly. These genes have functions related to cell differentiation and cell cycle. Therefore, DES affects cellular function and induces toxicity in TM4 cells. In future studies, it is necessary to find more related functions and mechanisms of DES in the system.     

Heterogeneity of IgE response to TDI-HSA conjugates by ELISA in toluene diisocyanate (TDI) -induced occupational asthma (OA) patients.

Toluene diisocyanate (TDI), a low molecular weight reactive chemical, is known to be a main cause of occupational asthma (OA) in Korea. Although it is thought that inhaled TDI may act as a hapten, the precise mechanisms of TDI-induced OA are unknown. In this study, TDI-human serum albumin (HSA) conjugates (5, 10, 20 and 30 min) were prepared in the range of 1.5 to 5.0 TDI mole/HSA mole. Specific binding of serum IgE to TDI-HSA (30 min) was observed using IgE ELISA as well as ELISA inhibition assay. Around 40% of TDI-induced OA patients were positive for serum specific IgE by ELISA. Degrees of serum IgE binding were different depending on which TDI-HSA conjugate was used as an antigen. Moreover, binding patterns were different depending on the individuals. Interestingly, higher binding of IgE to TDI-HSA (5 min) than to TDI-HSA (30 min) which was more highly substituted was observed in some patients. Probably new antigenic epitopes on carrier proteins were targets of the specific IgE. The results of this study indicated that IgE responses to TDI-HSA conjugates were heterogeneous in TDI-induced OA patients and self-proteins modified by reactive chemicals can become a major target antigen of IgE in certain cases.     

Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis.

OBJECTIVES: Although some studies have reported that the arginine isoform on codon 72 of p53 increases the susceptibility to invasive cervical cancer, such data remain controversial. The objective of this study was to quantitatively summarize the evidence for such a relationship. METHODS: Our data sources consisted of a MEDLINE search of the literature published before December 2002, bibliography review, and expert consultation. Thirty-seven studies met the inclusion criteria. Information on sample size, study design, Hardy-Weinberg equilibrium, and method of genotype determination was abstracted by two reviewers using a standardized protocol. The overall odds ratio (OR) of the p53 gene on invasive cervical cancer was estimated using the Mantel-Haenzel method. RESULTS: The overall OR (95% confidence interval) for cervical cancer among those with the homozygous mutant (Arg/Arg) was 1.2 (1.1-1.3, P=0.001) compared with those with the heterozygous mutant (Arg/Pro). By a cellular type of cervical cancer, the overall OR among those with Arg/Arg was statistically significant in adenocarcinomas (1.7, 1.1-2.6, P=0.024), but not in squamous cell carcinomas (1.1, 0.9-1.2, P=0.960), compared with Pro/Pro. Compared with Arg/Pro, the OR among those with Arg/Arg was statistically significant in HPV types 16 (1,5, 1.2-2.0, P=0.002). CONCLUSIONS: Overall, the p53 gene was associated with increased risk for invasive cervical cancer. However, the risk varied by country, cellular, and HPV type.     

Enhanced tyrosine phosphorylation of striatal NMDA receptor subunits: effect of dopaminergic denervation and l-DOPA administration

Sensitization of striatal N-methyl- -aspartate receptors (NMDAR) has been linked to events leading to the motor response changes associated with the administration of dopaminomimetics to parkinsonian animals and patients. To determine whether tyrosine phosphorylation of NMDAR subunits contributes to the apparent long-term enhancement in synaptic efficacy of these receptors, we examined the effect of unilateral nigrostriatal dopamine system ablation with 6-hydroxydopamine followed by twice-daily treatment with -DOPA on the phosphorylation state of rat striatal NR2A and NR2B subunits. Three weeks of intermittent -DOPA administration produced a shortening in the duration of the rotational response to dopaminergic challenge and other changes mimicking those occurring in patients with Parkinson's disease. Concurrently, tyrosine phosphorylation of NR2A and especially of NR2B subunits increased ipsilateral to the lesion (20±5% and 46±7% of intact striatum, respectively; p<0.01) without attendant changes in subunit protein levels. Selective blockade of NR2B subunits with ACEA 10-1244, but not of NR2A subunits with MDL 100,453, reversed the -DOPA-induced response alterations. The intrastriatal injection of a tyrosine kinase inhibitor, genistein, at a dose (2.0 μg) that normalized the response shortening, attenuated the NR2A and NR2B phosphorylation increase by about 12% and 24%, respectively (p<0.01). Taken together, these results suggest that augmented tyrosine phosphorylation of NR2B subunits, alone or in combination with the smaller rise in NR2A subunit phosphorylation, contributes to the apparent enhancement in striatal NMDAR sensitivity and thus to the plastic alterations in dopaminergic responses in -DOPA-treated parkinsonian rats.     

Genetic determinants of statin intolerance

Background  

Statin-related skeletal muscle disorders range from benign myalgias – such as non-specific muscle aches or joint pains without elevated serum creatinine kinase (CK) concentration – to true myositis with >10-fold elevation of serum CK, to rhabdomyolysis and myoglobinuria. The genetic basis of statin-related muscle disorders is largely unknown. Because mutations in the COQ2 gene are associated with severe inherited myopathy, we hypothesized that common, mild genetic variation in COQ2 would be associated with inter-individual variation in statin intolerance. We studied 133 subjects who developed myopathy on statin monotherapy and 158 matched controls who tolerated statins without incident or complaint.     

Bilateral versus unilateral sudden sensorineural hearing loss.

OBJECTIVES: To analyze the clinical characteristics and treatment results between bilateral (bi-) and unilateral (uni-) sudden sensorineural hearing loss (SSNHL). STUDY DESIGN AND SETTING: A retrospective study. METHODS: Three hundred twenty-four patients with SSNHL were classified into two groups; simultaneous bi-SSNHL (n = 16) and uni-SSNHL (n = 308). We compared clinical characteristics, medical history, hearing level, and treatment results between the 2 groups. RESULTS: The incidence of bi-SSNHL was 4.9 percent of overall patients with SSNHL. Bi-SSNHL occurs more commonly in patients of older age, with preexisting diabetes mellitus, and lipid panel abnormalities compared with uni-SSNHL. Ten patients (62.5%) in the bi-SSNHL group showed hearing recovery in 1 or both ears compared with 56.5 percent of patients with uni-SSNHL. Only 12 (37.5%) of all 32 ears recovered in bi-SSNHL, which was significantly lower than in uni-SSNHL. CONCLUSION: Bi-SSNHL has a very low incidence and lower recovery rate than uni-SSNHL. Recognition of similarities and differences between bilateral and unilateral SSNHL can help in counseling and managing the patients.