The association of PBX1 polymorphisms with overweight/obesity and metabolic alterations in the Korean population

Pre-B-cell leukemia transcription factor 1 (PBX1), which is located on chromosome 1q23, was recently reported to be associated with type 2 diabetes mellitus. We examined whether single nucleotide polymorphisms (SNPs) of the PBX1 gene are associated with overweight/obesity in a Korean population. We genotyped 66 SNPs in the PBX1 gene and investigated their association with clinical phenotypes found in 214 overweight/obese subjects and 160 control subjects using the Affymetrix Targeted Genotyping chip array. Seven SNPs (g.+75186C>T, g.+78350C>A, g.+80646C>T, g.+138004C>T, g.+185219G>A, g.+191272A>C, and g.+265317T>A) were associated with the risk of obesity in three models (codominant, dominant, and recessive) (P=0.007-0.05). Haplotype 1 (CAC) and 3 (TAC) of block 3 and haplotype 2 (GGAAT) of block 10 were also strongly associated with the risk of obesity. In the control group, subjects that had homozygote for the major allele for both g.+185219G>A and g.+191272A>C showed lower high density lipoprotein-cholesterol (HDL-C) level compared to those possessing the minor allele, suggesting that the association between the homozygote for the major allele for both g.+185219G>A and g.+191272A>C and HDL-C is attributable to the increased risk of obesity. This study suggests that the PBX1 gene is a possible risk factor in overweight/obese patients

Ganoderma lucidum extract stimulates glucose uptake in L6 rat skeletal muscle cells

The effect of Ganoderma lucidum extract on glucose uptake was studied in L6 rat skeletal muscle cells. G. lucidum extract increased glucose uptake about 2-fold compared to control. The extract stimulated the activity of phosphatidylinositol (PI) 3-kinase which is a major regulatory molecule in the glucose uptake pathway. About 7-fold increased activity of a PI 3-kinase was observed after treatment with G. lucidum extract, whereas PI 3-kinase inhibitor, LY294002, blocked the G. lucidum extract-stimulated PI 3-kinase activity in L6 skeletal muscle cells. Protein kinase B, a downstream mediator of PI 3-kinase, was also activated by G. lucidum extract. We then assessed the activity of AMP-activated protein kinase (AMPK), another regulatory molecule in the glucose uptake pathway. G. lucidum extract increased the phosphorylation level of both AMPK α1 and α2. Activity of p38 MAPK, a downstream mediator of AMPK, was also increased by G. lucidum extract. Taken together, these results suggest that G. lucidum extract may stimulate glucose uptake, through both PI 3-kinase and AMPK in L6 skeletal muscle cells thereby contributing to glucose homeostasis

The Effect of Optic Disc Center Displacement on Retinal Nerve Fiber Layer Measurement Determined by Spectral Domain Optical Coherence Tomography.

To investigate the effect of optic disc center displacement on retinal nerve fiber layer (RNFL) measurement determined by spectral domain optical coherence tomography (SD-OCT).The optic disc center was manipulated at 1-pixel intervals in horizontal, vertical, and diagonal directions. According to the manipulated optic disc center location, the RNFL thickness data were resampled: (1) at a 3.46-mm diameter circle; and (2) between a 2.5-mm diameter circle and 5.4-mm square. Error was calculated between the original and resampled RNFL measurements. The tolerable error threshold of the optic disc center displacement was determined by considering test-retest variability of SD-OCT. The unreliable zone was defined as an area with 10% or more variability.The maximum tolerable error thresholds of optic disc center displacement on the RNFL thickness map were distributed from 0.042 to 0.09 mm in 8 directions. The threshold shape was vertically elongated. Clinically important unreliable zones were located: (1) at superior and inferior region in the vertical displacement; (2) at inferotemporal region in the horizontal displacement, and (3) at superotemporal or inferotemporal region in the diagonal displacement. The unreliable zone pattern and threshold limit varied according to the direction of optic disc displacement.Optic disc center displacement had a considerable impact on whole RNFL thickness measurements. Understanding the effect of optic disc center displacement could contribute to reliable RNFL measurements

Optic disc center displacement between optic disc photography and optical coherence tomography (OCT).

<p>The infrared image of deviation map displayed the optic disc margin (black line) and center (black cross) information as well as abnormally deviated area from normative database. It was overlaid and registered with optic disc photograph according to the retinal blood vessels. Clinically visible optic disc margin (green dots) was segmented in optic disc photograph and its center (green cross) was calculated by averaging the coordinates of margin. In this case, clinically visible optic disc center was nasally displaced 1 pixel from the center of OCT image.</p

Characteristics of healthy subjects.

<p>Characteristics of healthy subjects.</p

Adjustment of optic disc center displacement using Cirrus HD-OCT Research Browser.

<p>(A) The optic disc margin detection error (arrowheads) was highly suspect compared with the red-free photograph, and led to miscalculation of the optic disc center [0.09, 0 mm]. (B) Cirrus HD-OCT Research Browser provides an editing tool for adjusting the optic disc center and margin. After the optic disc center was adjusted to [0.18, -0.09 mm] by semi-automatic manipulation using the editing tool, the original shape of the optic disc margin was restored (arrowheads). Comparing two coordinates of the optic disc centers, superotemporal [-0.09, 0.09 mm] displacement (red asterisk) was observed. This corresponds to the boundary of the cautious threshold limit and should be interpreted with caution. (C) We can estimate or confirm the effect of optic disc center displacement using the displacement error-encoded map. In superotemporal displacement, the major clinical concern is the inferotemporal unreliable zone in which the greatest decrease is expected. Indeed, the red-coded area and its angular width increased 2.45 to 2.69 mm² (9.8%) and 23.7 to 26.5° (11.8%). Minor changes in the superotemporal (increased yellow-coded area) and inferonasal region (decreased yellow- and red-coded area) were also consistent with the displacement error-encoded map. OCT = optical coherence tomography</p

Interpretation of optic disc center displacement in Guided Progression Analysis (GPA).

<p>(A) At second baseline exam in GPA, the optic disc margin (yellow arrowhead) showed eccentric shape compared with other exams (black arrowheads). As a result, following RNFL thickness change maps showed RNFL progression at unusual region (inferonasal rectangles) and superotemporal region (asterisk). (B) Manual delineation (blue irregular arc) indicated that the direction of optic disc center displacement was estimated to be temporal (thin black arrows). (C) In temporal displacement, overestimated inferonasal region (rectangle) at baseline study might lead to false RNFL progression in GPA. In contrast, underestimated inferotemproal region (thick gray arrows) at baseline showed increasing RNFL thickness in follow-up exams (thick black arrows). Mild superotemporal underestimation (asterisk) at baseline might underestimate actual RNFL progression. (D) Using manual selection mode in GPA, we removed second exam from analysis. Abnormal RFNL progression at inferonasal region was proven to be the effect of optic disc center displacement. Superotemporal RNFL progression became larger and more obvious. RNFL = retinal nerve fiber layer</p

Optic disc center displacement and circumpapillary RNFL thickness error.

<p>Average RNFL thickness showed the smallest error for optic disc center displacement in 8 directions. The red marks on graphs represent the first significantly different optic disc center displacement between the original and resampled RNFL measurements on repeated measures ANOVA. The central green and yellow zone represents the maximum tolerable (5% or less variability) and cautious (10% or less variability) thresholds of optic disc center displacement. RNFL = retinal nerve fiber layer; ANOVA = analysis of variance</p

Interpretation of optic disc center displacement in case of floater.

<p>(A) Floater (arrowheads) interfered with the optic disc margin detection (black irregular circle) in the inferior region. Manual delineation (blue irregular arc) indicated that the direction of optic disc center displacement was estimated to be inferonasal (arrows). (B) At next follow-up exam (6 month interval), the floater (arrowhead) moved nasal side, and then optic disc margin was clearly detected. Although inferotemporal and superotemporal RNFL defects seemed to be progressed in the RNFL deviation map, there had been no evidence of such rapid progression in other structural and functional tests. Optic disc center displacement might affect the change of red and yellow-coded area. (C) In inferonasal displacement, there was greater chance of overestimation of RNFL thickness in inferotemporal region. Superotemporal region also was suspicious of mild overestimation. These were consistent with relatively small RNFL defects in first exam. RNFL = retinal nerve fiber layer</p