Sex-Dimorphic Association of Plasma Fatty Acids with Cardiovascular Fitness in Young and Middle-Aged General Adults: Subsamples from NHANES 2003⁻2004.

To explore the potential association of plasma fatty acids (FAs) and cardiovascular fitness level (CVFL), data of 449 subjects from 2003⁻2004 National Health and Nutrition Examination Survey (NHANES) were analyzed. Among these 249 men and 200 women, aged 20⁻50 years (33.4 ± 8.4 year, mean ± Standard Deviation), 79 low, 166 moderate and 204 high CVFL were categorized by age- and gender- specific percentile, respectively. Twenty-four fatty acids were quantified from fasting plasma. Higher levels of 2 very long-chain saturated FAs (VLSFAs): Arachidic acid (AR1, C20:0) and Docosanoic acid (DA1, C22:0) as well as 2 n-6 polyunsaturated FAs (PUFAs): Arachidonic acid (AA, C20:4n-6) and Docosatetraenoic acid (DTA, C22:4n-6) were observed in the subjects with low CVFL. Notably this association exists only in men. Estimated maximal oxygen consumption (VO2max), the marker for cardiorespiratory fitness, was used for further regression analysis. After the adjustment of potential confounding factors (age, smoking, hypertension status, body mass index (BMI), insulin resistance status, and C-reactive protein (CRP), AA was the only FA correlated with low VO2max in women; while in men AR1, DA1, AA, and DTA remain negatively associated with VO2max. This preliminary analysis suggests a sex-dimorphic relationship between these plasma VLSFAs and n-6 PUFAs with CVFL and merits further investigation.

Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity.

Adiponectin gene polymorphisms have recently been reported to be associated with obesity, insulin sensitivity, and the risk of type 2 diabetes. We examined a T94G polymorphism of the adiponectin gene in 245 ostensibly normal nondiabetic subjects. The G allele frequency was lower among subjects with higher BMI (> or =27) than in those with lower BMI. BMI was inversely correlated with the dose of G allele. Multivariate linear regression analyses showed that the adiponectin genotypes were significantly related to BMI after adjusting for age and gender. The dose of the G allele was associated with a reduction of approximately 1.12 kg/m(2) in BMI. We further found that the relative mRNA levels of G allele were consistently higher than those of T allele in the omental adipose tissue from 21 heterozygous subjects. Finally, we observed that the expression levels of adiponectin affected insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In conclusion, the allele-specific differential expression of this common polymorphism could be responsible for its biological effects observed in this and the other studies.

Sex-related differences between adiponectin and insulin resistance in schoolchildren.

OBJECTIVE: To study the effect of body composition and adiponectin on insulin resistance and beta-cell function in schoolchildren during puberty. RESEARCH DESIGN AND METHODS: Plasma adiponectin level and its relationships with insulin sensitivity and beta-cell function were analyzed in 500 randomly recruited nondiabetic Taiwanese schoolchildren (245 boys and 255 girls) aged 6-18 years in a national survey program for diabetes in 1999. Insulin resistance and beta-cell function were evaluated by homeostasis model assessment (HOMA). Plasma adiponectin concentrations were determined with radioimmunoassay. RESULTS: Plasma glucose levels remained stable, whereas insulin resistance increased with a compensatory rise in beta-cell function during this period. A transient drop of adiponectin level with a trough at 10-12 years was found in boys but not in girls. This pubertal drop of adiponectin levels in boys coincides with the sharp rise in testosterone concentration. A negative correlation between testosterone levels and adiponectin concentration was also noted in boys (r = -0.142, P = 0.032). Plasma adiponectin levels correlated inversely with relative body weight, fasting insulin concentrations, and insulin resistance index by HOMA in boys aged 15-18 years and in girls aged 11-14 years. No association was observed between adiponectin levels and beta-cell function by HOMA. CONCLUSIONS: There is a transient drop in the level of adiponectin during male puberty, correlated with the increase in testosterone level in boys. Plasma adiponectin levels were inversely correlated with obesity and insulin resistance in boys and girls during the pubertal period.

Multinucleated giant cells in fine needle aspirates. Can they help differentiate papillary thyroid cancer from benign nodular goiter?

OBJECTIVE: To determine whether multinucleated giant cells (MGCs) in fine needle aspirates can help differentiate papillary thyroid carcinoma (PTC) from benign nodular goiter (BNG). STUDY DESIGN: Specimens from 100 cases of PTC and 100 cases of BNG with surgical and pathologic proof were randomly retrieved. The morphologic characteristics and frequency distribution of the maximal size and number of MGC nuclei were analyzed. A retrospective review of medical records was also undertaken. RESULTS: MGCs were twice as frequent (40%) in PTC than in BNG (26%) (odds ratio = 1.90). Most MGCs in BNG tended to be smaller and ovoid, with foamy cytoplasm, and had fewer nuclei. No MGC in BNG was > 116 microns in diameter or had > 27 nuclei. In contrast, MGCs in PTC were more diverse in size, shape, cytoplasm and number of nuclei. No significant association was found between the presence or nature of MGCs and disease extent in PTC. CONCLUSION: The presence of large MGCs with dense cytoplasm in a thyroid nodule without clinical evidence of thyroiditis should prompt careful exclusion of associated PTC.

Submassive liver necrosis in a hepatitis B carrier with Cushing's syndrome.

Reactivation of hepatitis B virus (HBV) replication in hepatitis B surface antigen (HBsAg)-positive patients is associated with immunosuppressive therapy. However, the interactions between endogenous glucocorticoid in Cushing's syndrome and HBV-related hepatitis remain unclear. Here, we describe the management of a 32-year-old male HBV carrier with Cushing's syndrome caused by an adrenal cortical adenoma, who developed severe hepatitis B. Repeated episodes of septicemia resulting from hypercortisolemia-related immunosuppression further compromised his hepatic condition. Adrenalectomy could not be performed due to coagulopathy. Lamivudine was not available at that time in Taiwan, and this patient died of hepatic failure and sepsis. At autopsy, his liver showed submassive necrosis with small regenerative nodules. The hepatocytes were positive for HBsAg (membrane and cytoplasmic) and hepatitis B core antigen (nuclear and cytoplasmic). Screening for HBsAg is of crucial significance for immunocompromised individuals. Once positive HBsAg is detected in immunosuppressed patients, liver function and viral status should be closely monitored to enable earlier diagnosis and prompt treatment with the newer nucleoside analogues that actively fight HBV.

Lysosome-related genes are regulated in the orbital fat of patients with graves' ophthalmopathy.

PURPOSE: The molecular mechanism involved in the hypertrophy of the orbital fat in patients with Graves' ophthalmopathy or thyroid eye disease (TED) remains unclear. Comparison of genome-wide expression profiles may help in the search for the gene sets involved in TED. METHODS: Twenty-five orbital adipose tissue specimens were obtained, from which the RNA was isolated. Four of the tissue specimens (from four individuals, two with TED and two control subjects) were subjected to cDNA microarray analysis. The data were analyzed by the gene set enrichment analysis (GSEA) to survey the biological pathways involved in the pathogenesis of TED. Messenger RNA levels of some top-ranked genes in GSEA-selected pathways are validated by quantitative PCR (QPCR). RESULTS: The expression of specific gene sets related to lytic vacuoles, lysosomes, and vacuoles were different between the specimens obtained from patients with TED and control subjects (P < 0.001). These three gene sets overlapped. For QPCR, four top-ranked genes were selected from these overlapping gene sets and another one that related to visual failure, using 21 independent samples of patients with TED (n = 15) and control subjects (n = 6). The results showed that ceroid-lipofuscinosis, neuronal 2, late infantile (CLN2; P = 0.044) and ceroid-lipofuscinosis, neuronal 3, juvenile (CLN3, which related to visual failure; P = 0.012) were significantly downregulated in the orbital fat of patients with TED. The expression of the beta subunit of hexosaminidase A (HEXB) was reduced as well, but the change did not reach statistical significance (P = 0.058). CONCLUSIONS: Lysosome-related genes, such as CLN2, CLN3, and HEXB, may be involved in the pathogenesis of adipose tissue hypertrophy in TED.