Spontaneously hypertensive rats develop pronounced hepatic steatosis induced by choline-deficient diet: Evidence for hypertension as a potential enhancer in non-alcoholic steatohepatitis

Aim: Patients with non‐alcoholic steatohepatitis (NASH) frequently have many co‐morbidities including essential hypertension, which is reported to increase vascular production of reactive oxygen species (ROS) and alter the hepatic anti‐oxidant defense system. Since ROS play a role in the pathogenesis of NASH, it is hypothesized that hypertension modulates the hepatic oxidative status and influences the development of NASH. The aim of this study was to investigate the potential effects of hypertension on the progression of NASH. Methods: Spontaneously hypertensive rats (SHR) and Wistar‐Kyoto (WKY) rats as normotensive controls were fed choline‐deficient (CD) diet for 5 weeks. Histological changes, messenger RNA (mRNA) expression and thiobarbituric acid reactive substances (TBARS) levels in the liver were assessed in each group. Results: Choline‐deficient diet led to pronounced hepatic steatosis in SHR with an 8‐fold increase of the hepatic triglyceride content, while there was no significant increase in WKY. These changes in SHR were associated with significant reduction in the expression of mRNA for peroxisome proliferator activated receptor α, acyl‐CoA oxidase, microsomal triglyceride transfer protein, and apolipoprotein B100. Consistent with the significant reduction of hepatic superoxide dismutase activity and marked downregulation of the gene expression of hepatic antioxidant enzymes, the hepatic TBARS level and the plasma level of alanine aminotransferase were only increased in SHR on CD diet. Conclusions: Spontaneously hypertensive rats receiving CD diet showed severe hepatic steatosis associated with reduction of hepatic anti‐oxidant capacity, leading to increased hepatic oxidative stress and tissue damage. Accordingly, hypertension might have a potential effect on the progression of NASH.     

Spectroscopic diagnosis of chronic fatigue syndrome by multivariate analysis of visible and near-infrared spectra

We have recently evaluated the possibility of visible and near-infrared (Vis-NIR) spectroscopy for diagnosis of chronic fatigue syndrome(CFS). Vis-NIR spectra in the 600-1,100 nm region for sera from CFS patients and healthy donors were subjected to principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA) to develop multivariate models to discriminate between CFS patients and healthy donors. The PCA and SIMCA model predicted successful prediction of the masked samples. Furthermore, taking advantage of Vis-NIR spectroscopy to enable noninvasive analysis, our preliminary results have shown that SIMCA model from Vis-NIR spectra of thumb has achieved 70-80% correct determinations. In this review, we will introduce the potential of the Vis-NIR spectroscopy for CFS diagnosis.     

Sequence dependence of hydrogen exchange kinetics in DNA duplexes at the individual base pair level in solution.

The kinetics for hydrogen exchange at individual base pairs in self-complementary deoxydodecanucleotide duplexes have been estimated from NMR saturation recovery measurements on the resolved imino protons as a function of temperature. The imino protons of dA . dT base pairs in the center of the fully alternating d(C-G-C-G-T-A-T-A-C-G-C-G) duplex exchange a factor of 2- to 3-fold faster than the corresponding protons at the same positions in the partially alternating d(C-G-C-G-A-A-T-T-C-G-C-G) duplex. These exchange parameters are a direct measure of the rate constants for transient opening of individual dA . dT base pairs in the dodecanucleotide duplexes and demonstrate faster opening kinetics for the "TATA" box region compared to the related "AATT" segment.     

Three human alcohol dehydrogenase subunits: cDNA structure and molecular and evolutionary divergence.

Class I human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) consists of several homo- and heterodimers of alpha, beta, and gamma subunits that are governed by the ADH1, ADH2, and ADH3 loci. We previously cloned a full length of cDNA for the beta subunit, and the complete sequence of 374 amino acid residues was established. cDNAs for the alpha and gamma subunits were cloned and characterized. A human liver cDNA library, constructed in phage lambda gt11, was screened by using a synthetic oligonucleotide probe that was matched to the gamma but not to the beta sequence. Clone pUCADH gamma 21 and clone pUCADH alpha 15L differed from beta cDNA with respect to restriction sites and hybridization with the nucleotide probe. Clone pUCADH gamma 21 contained an insertion of 1.5 kilobase pairs (kbp) and encodes 374 amino acid residues compatible with the reported amino acid sequence of the gamma subunit. Clone pUCADH alpha 15L contained an insertion of 2.4 kbp and included nucleotide sequences that encode 374 amino acid residues for another subunit, the alpha subunit. In addition, this clone contained the sequences that encode the COOH-terminal part of the beta subunit at its extended 5' region. The amino acid sequences and coding regions of the cDNAs of the three subunits are very similar (approximately 93-95% identity). A high degree of resemblance is observed also in their 3' noncoding regions. However, distinctive differences exist in the vicinity of the Zn-binding cysteine residue at position 46--i.e., Cys-Gly-Thr in the alpha, Cys-Arg-Thr in the wild-type beta 1, Cys-His-Thr in the Oriental-type beta 2, and Cys-Arg-Ser in the gamma, reflecting the differences in their kinetic properties. Based on the cDNA sequences and the deduced amino acid sequences of the three subunits, their structural and evolutionary relationships are discussed.     

Independent component analysis of resting state activity in pediatric obsessive‐compulsive disorder

Obsessive‐compulsive disorder (OCD) is an often severely disabling illness with onset generally in childhood or adolescence. Little is known, however, regarding the pattern of brain resting state activity in OCD early in the course of illness. We therefore examined differences in brain resting state activity in patients with pediatric OCD compared with healthy volunteers and their clinical correlates. Twenty‐three pediatric OCD patients and 23 healthy volunteers (age range 9–17), matched for sex, age, handedness, and IQ completed a resting state functional magnetic resonance imaging exam at 3T. Patients completed the Children's Yale Brown Obsessive Scale. Data were decomposed into 36 functional networks using spatial group independent component analysis (ICA) and logistic regression was used to identify the components that yielded maximum group separation. Using ICA we identified three components that maximally separated the groups: a middle frontal/dorsal anterior cingulate network, an anterior/posterior cingulate network, and a visual network yielding an overall group classification of 76.1% (sensitivity = 78.3% and specificity = 73.9%). Independent component expression scores were significantly higher in patients compared with healthy volunteers in the middle frontal/dorsal anterior cingulate and the anterior/posterior cingulate networks, but lower in patients within the visual network. Higher expression scores in the anterior/posterior cingulate network correlated with greater severity of compulsions among patients. These findings implicate resting state fMRI abnormalities within the cingulate cortex and related control regions in the pathogenesis and phenomenology of OCD early in the course of the disorder and prior to extensive pharmacologic intervention. Hum Brain Mapp 35:5306–5315, 2014. © 2014 Wiley Periodicals, Inc.     

Exposure of the mitral valve using flexible self-retaining retractors and an atrial hook

We hereby present our technique for using the self-retaining flexible arm retractor and its attachments for mitral valve exposure. The Aortic Valve Assistant, which was developed for aortic valve exposure, is also very useful for exposure of the inferior wall of the left atrium. Our modified atrial hook provides excellent exposure of the anterior mitral annulus. Extensive dissection and the combined use of the flexible arm and attachments allows us comfortable access for mitral valve operations.     

Mechanics of wrinkle formation: micromechanical analysis of skin deformation during wrinkle formation in ultraviolet‐irradiated mice

Background/purpose: The mechanical aspects of wrinkle formation were studied in the dorsal skin of hairless mice. Methods: Wrinkles were induced by irradiating with ultraviolet (UV) B for 10 weeks, while observing skin deformation during wrinkle formation. Changes in skin dimensions were also observed during the specimen excision process. Wrinkle depth and interval were measured before and after removal of the cutaneous muscle layer. Local deformation of wrinkled skin during uniaxial stretch was also measured. Changes in curvature of skin specimens upon muscle layer removal were then observed to determine the force balance in skin layers. Results: The skin showed spontaneous contraction in response to UV irradiation. Wrinkled skin showed a marked decrease in the wrinkle depth and a slight increase in wrinkle interval following muscle layer removal, a peculiar mechanical response that cannot be explained by homogeneous deformation of the skin. This response was due to compressive deformations of dermal tissue caused by the muscle layer and concentrated at valleys of the wrinkles. Curvature measurements indicated that the muscle layer compressed the dermal tissue predominantly in the craniocaudal direction. Morphological observations showed that the wrinkles coincided with rows of pores and sulci cutis, where the structural stiffness of the horny layer was relatively low. The horny layer showed significant thickening. Conclusion: Taken together, we propose the following hypothetical mechanisms of wrinkle formation during UV irradiation: spontaneous contraction of the dermis while maintaining or increasing the epidermal area induces buckling of the epidermis into the dermis at mechanically weak lines, namely, the rows of pores and sulci cutis, and buckling may be amplified by the axial compression of the dermis by the muscle layer.