Novel associations between blood DNA methylation and body mass index in middle-aged and older adults.

BACKGROUND/OBJECTIVES: There is increasing evidence of a relationship between blood DNA methylation and body mass index (BMI). We aimed to assess associations of BMI with individual methylation measures (CpGs) through a cross-sectional genome-wide DNA methylation association study and a longitudinal analysis of repeated measurements over time. SUBJECTS/METHODS: Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined in baseline peripheral blood samples from 5361 adults recruited to the Melbourne Collaborative Cohort Study (MCCS) and selected for nested case-control studies, 2586 because they were subsequently diagnosed with cancer (cases) and 2775 as controls. For a subset of 1088 controls, these measures were repeated using blood samples collected at wave 2 follow-up, a median of 11 years later; weight was measured at both time points. Associations between BMI and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. These were applied to cases and controls separately, with results combined through fixed-effects meta-analysis. RESULTS: Cross-sectional analysis identified 310 CpGs associated with BMI with P<1.0 × 10-7, 225 of which had not been reported previously. Of these 225 novel associations, 172 were replicated (P<0.05) using the Atherosclerosis Risk in Communities (ARIC) study. We also replicated using MCCS data (P<0.05) 335 of 392 associations previously reported with P<1.0 × 10-7, including 60 that had not been replicated before. Associations between change in BMI and change in methylation were observed for 34 of the 310 strongest signals in our cross-sectional analysis, including 7 that had not been replicated using the ARIC study. CONCLUSIONS: Together, these findings suggest that BMI is associated with blood DNA methylation at a large number of CpGs across the genome, several of which are located in or near genes involved in ATP-binding cassette transportation, tumour necrosis factor signalling, insulin resistance and lipid metabolism.

Overexpression of PI3K-p110α in the progression of uterine cervical neoplasia and its correlation with pAkt and DJ-1.

OBJECTIVE: To investigate the expression of PI3K-p110α, pAkt, PTEN, the signaling molecules from PI3K/Akt signaling pathway, DJ-1, an oncoprotein and HSP90a, a molecular chaperone, and their correlation in uterine cervical neoplasia, in order to elucidate their role in cervical carcinogenesis. MATERIALS AND METHODS: Using immunohistochemistry, the authors analyzed the expression of PI3K-p110α, pAkt, PTEN, DJ-1 and HSP90α, and their correlation in ten normal tissues, cervical intraepithelial neoplasia (CIN) including 30 CIN1 and 31 CIN3, and 33 cases of invasive squamous cell carcinoma (SCC). RESULTS: The expression of all proteins significantly increased in CIN3 compared to CIN1, and only the expression of PI3K-p110α significantly increased in invasive SCC compared to CIN3. There was a significant positive correlation between the expression of PI3K-p110α and DJ-1, as well as PI3K-p110α and pAkt in CIN3 and invasive SCC. CONCLUSION: Overexpression of PI3K-p110α is associated with progression of uterine cervical neoplasia, and the expression of pAkt and DJ-1 is positively correlated with PI3K-p110α expression in this process.

Combined microcystic adnexal carcinoma and squamous cell carcinoma arising in the ovarian cystic teratoma--a brief case report.

Malignant transformation of mature cystic teratoma of the ovary can develop with an incidence of 1-2%. Squamous cell carcinoma is the most common malignant tumor arising in benign cystic teratoma. The authors have recently experienced a case of combined microcystic adnexal carcinoma and squamous cell carcinoma arising in a benign cystic teratoma of the ovary in a 72-year-old Korean woman. The right ovarian cystic mass had been ruptured and firmly adhered with salpinx and omental fat tissue on operation. Thickened cystic wall with yellowish white solid infiltrative lesion was noted grossly, and two different malignant tumors of microcystic adnexal carcinoma exhibiting both eccrine and hair follicular differentiation and squamous cell carcinoma were observed microscopically. PAS and CEA positivities suggested eccrine differentiation in areas of microcystic adnexal carcinoma.

Fibrillary glomerulonephritis in a 9-year-old girl.

A 9-year-old girl presented with mild proteinuria and microscopic hematuria. Renal biopsy disclosed highly organized fibrillary deposits in glomerular mesangial areas by ultrastructural examination. The microfibrils were 10-15 nm in diameter, up to 1,200 nm in length and in parallel array. They did not have a microtubular appearance. The diameter of the microfibrils was larger than that of amyloid fibrils. Congo red and crystal violet stains were negative. There was no clinical or serologic evidence of paraproteinemia, cryoglobulinemia, light chain disease or systemic lupus erythematosus. To date, most of the reported cases of fibrillary glomerulonephritis have occurred in adults; this disorder is extremely rare in children. We believe that this glomerulopathy can occur in the pediatric age group and should be considered in renal biopsy diagnoses.

Human syngamosis: the first case in Korea.

Parasites of the genus Mammomonogamus affect the respiratory tract of domestic mammals but have only rarely been reported in humans. In this case report the diagnosis of human syngamosis is described following bronchoscopic examination of a patient whose initial symptoms were simply of community acquired pneumonia. The patient had a persistent and productive cough with intermittent fever during 10 days of observation. After bronchoscopic extraction of the parasites and treatment with albendazole he recovered fully. This is one of the first recognised cases of human syngamosis in Korea.

Giant-cell interstitial pneumonia in a gas station worker.

Giant-cell interstitial Pneumonia (GIP) is a very uncommon respiratory disease. The majority of cases of GIP are caused by exposure to cobalt, tungsten and other hard metals. In this report, we describe GIP in a patient who worked in gas station and dealt in propane gas vessels. He presented with clinical features of chronic interstitial lung disease and underwent an open lung biopsy that showed DIP-like reaction with large numbers of intra-alveolar macrophages and numerous large, multinucleated histiocytes which were admixed with the macrophages. Analysis of lung tissue for hard metals was done. Cobalt was the main component of detected hard metals. Corticosteroid therapy was started and he recovered fully.