Increase in gap junctional intercellular communication by high molecular weight hyaluronic acid associated with fibroblast growth factor 2 and keratinocyte growth factor production in normal human dermal fibroblasts

The effects of different molecular weights of hyaluronic acid (HA), a major component of extracellular matrix, on gap junctional intercellular communication (GJIC) in normal human dermal fibroblasts (NHDF cells) were investigated. NHDF cells were cultured for 4 days with different molecular weights of HA and then the extent of GJIC was assessed by the scrape-loading dye transfer method, using Lucifer yellow. The area of dye transfer was greater in the dishes coated with HA than in those to which HA was added. Thus, NHDF cells cultured on surfaces coated with high molecular weight (HMW) HA (MW, 800 kDa) showed greatly enhanced GJIC. Furthermore, another aim of this study was to evaluate the effects of different molecular weights of HA on the production of FGF-2 and KGF, because both are important cytokines produced by NHDF cells. When FGF-2 and KGF cultured levels of cell extracts and media were determined by ELISA, both levels were significantly enhanced when cells were grown on plates coated with HMW HA. This finding indicated that the function of gap junction channels in NHDF cells grown on plates coated with HMW HA may promote the biosynthesis of growth factors such as FGF-2 and KGF.     

Negative conversion of antimitochondrial antibody in primary biliary cirrhosis: a case of autoimmune cholangitis

Autoimmune cholangitis is a clinical constellation of chronic cholestasis, histological changes of chronic nonsuppurative cholangitis and the presence of autoantibodies other than antimitochondrial antibody (AMA). It is uncertain whether this entity is definitely different from AMA positive primary biliary cirrhosis (PBC), though it shows some differences. We report a case of autoimmune cholangitis in a 59-year-old woman, who had been previously diagnosed as AMA-positive PBC associated with rheumatoid arthritis, has been converted to an AMA-negative and anticentromere antibody-positive PBC during follow-up. The response to ursodeoxycholic acid treatment is poor except within the first few months, but prednisolone was dropping the biochemical laboratory data.     

Formation of quinone methide in the self-cure of quinoid phenol formaldehyde resin

The study of the reaction of some methylenebisphenols with chloranil in ethanol and also of a phenol formaldehyde condensate prepared by acid catalysis, reveals that quinone methide is formed in the self-cure of quinoid phenol formaldehyde resin. The quinone methide reacts with ethanol to give an adduct. The structure of the alcohol adduct is identified by NMR and IR data and by means of pyrolysis.     

Association of MICA polymorphism with HLA-B51 and disease severity in Korean patients with Behcet's disease

The HLA-B51 allele is known to be associated with Behcet's disease (BD) in many ethnic group. However, it has not yet been clarified whether the HLA-B51 gene itself is the pathogenic gene related to BD or whether it is some other gene in linkage disequlibrium with HLA-B51. Recently, the Triplet repeat (GCT/AGC) polymorphism in transmembrane region of the MHC class I chain-related A (MICA) gene was identified. To investigate the association of MICA with BD, we studied the MICA polymorphism in 108 Korean BD patients and 204 healthy controls in relation to the presence of HLA-B51 and clinical manifestations. The triplet repeat polymorphism was determined by polymerase chain reaction (PCR)-denaturing polyacrylamide gel electrophoresis (PAGE). The phenotype frequency of the MICA*A6 allele (relative risk, RR=2.15, p=0.002) and HLA-B51(RR=1.87, p=0.022) were significantly increased in the Korean patients with BD. A strong linkage disequilibrium was observed between the MICA*A6 and HLA-B51 in both the patients with BD and control subjects. Stratification analysis showed that MICA*A6 homozygosity was strongly associated with BD in the HLA-B51-negative population, and HLA-B51 was also associated with MICA*A6-negative population. In conclusion, MICA*A6 rather than HLA-B51 was strongly associated with Korean patients with BD, and the MICA*A6 allele is a useful susceptibility marker of BD, especially in the HLA-B5-negative     

Expression of transforming growth factor-beta1 and transforming growth factor-beta receptors in hepatocellular carcinoma and dysplastic nodules.

In this study we analyzed by immunohistochemistry the expression of TGF-beta1 protein and TGF-beta receptors I and II in 4 low-grade dysplastic nodules, 2 high-grade dysplastic nodules, 6 early, 22 small, and 62 advanced hepatocellular carcinomas. The expression of TGF-beta1 protein by hepatocytes was decreased in advanced hepatocellular carcinoma compared with small or early hepatocellular carcinoma(P < .05). Frequent and intense staining of TGF-beta1 protein was noted in the sinusoidal endothelium of advanced hepatocellular carcinomas despite of its decreased staining in hepatocellular carcinoma cells. Reduced expression of TGF-beta receptors I and II compared with surrounding nontumorous tissue were noted from the early hepatocellular carcinoma stage suggesting that down-regulation of TGF-beta receptors is correlated with progression from premalignant to malignant phenotype. Reduced expression of both TGF-beta1 and TGF-beta receptor II in neoplastic hepatocytes were also significantly correlated with increased tumor size and increased proliferative activity(P < .05). These findings suggest that during hepatocarcinogenesis, the inhibitory effects of TGF-beta1 protein on hepatocellular carcinoma cells is outweighed by its effects on stromal elements, which, overall, contributes indirectly to a tumor growth stimulatory environment. Also, the growth-inhibitory effects of TGF-beta1 may have been further negated by reduced TGF-beta receptors on hepatocellular carcinoma cells.     

AMPK as a metabolic switch in rat muscle,liver and adipose tissue after exercise

An increasing body of evidence has revealed that activation of adenosine monophosphate (AMP)‐activated protein kinase (AMPK)‐activated protein kinase increases fatty acid oxidation by lowering the concentration of malonyl coenzyme A (CoA), an inhibitor of carnitine palmitoyl transferase 1. Studies carried out primarily in skeletal muscle suggest that AMPK modulates the concentration of malonyl CoA by concurrently phosphorylating and inhibiting acetyl CoA carboxylase (ACC), the rate limiting enzyme in malonyl CoA synthesis, and phosphorylating and activating malonyl CoA decarboxylase (MCD), an enzyme involved in its degradation. We have recently observed that AMPK and MCD activities are increased and ACC activity diminished in skeletal muscle, liver and, surprisingly, in adipose tissue 30 min following exercise (treadmill run) in normal rats. In liver and adipose tissue these changes were associated with a decrease in the activity of glycerol‐3‐phosphate acyltransferase (GPAT), which catalyses the first committed reaction in glycerolipid synthesis and, which like ACC, is phosphorylated and inhibited by AMPK. Similar changes in ACC, MCD and GPAT were observed following the administration of 5‐aminoimidazole 4‐carboxamide‐riboside (AICAR), further indicating that the exercise‐induced alterations in these enzymes were AMPK‐mediated. Conclusions: (1) AMPK plays a major role in regulating lipid metabolism in multiple tissues following exercise. (2) The net effect of its activation is to increase fatty acid oxidation and diminish glycerolipid synthesis. (3) The relevance of these findings to the regulation of muscle glycogen repletion in the post‐exercise state and to the demonstrated ability of AMPK activation to decrease adiposity and increase insulin sensitivity in rodents remains to be determined.     

Effect of Alkyl Groups of Latent Cationic Catalysts on Cure and Dynamic Mechanical Behaviors of Epoxy Resins

Summary: The latent thermal cationic initiators, benzyl‐2,5‐dimethylpyrazinium hexafluoroantimonate (BDPH) and benzyl‐2‐ethylpyrazinium hexafluoroantimonate (BEPH), were synthesized to investigate the effect of substituted alkyl groups on cure and dynamic mechanical behaviors of difunctional epoxy system. The cure temperature and activation energy of the diglycidyl ether of bisphenol A (DGEBA)/BDPH were higher than those of the DGEBA/BEPH, resulting from the steric hindrance of the substituted groups. The cross‐linking density of the DGEBA/BDPH was higher than that of the DGEBA/BEPH, whereas the T_g's of both specimens are similar. This may be explained by the free volume and the intermolecular hydrogen bonding induced by the hydrogen of the substituted methyl groups. Consequently, the position and number of the substituted groups of the latent thermal initiator were very important in the control of the latent thermal and dynamic mechanical behaviors of the epoxy resin.

Dynamic DSC curves of DGEBA cured by each initiator.