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H Z Lin

Publications and source records attributed to H Z Lin.

25 records · Page 2Linked to original sources

Tumor necrosis factor alpha promotes nuclear localization of cytokine-inducible CCAAT/enhancer binding protein isoforms in hepatocytes.

Hepatocytes were cultured in the presence of recombinant tumor necrosis factor (TNF) alpha or mutated TNF alpha peptides that specifically activate either p55 or p75 TNF receptors to determine if TNF alpha can activate cytokine-inducible CCAAT/enhancer binding protein (C/EBP) isoforms by post-transcriptional mechanisms that are initiated by TNF receptors. Within 5-10 min after treatment with any of these agents, nuclear concentrations of C/EBP beta and C/EBP delta double and remain 2-4-fold greater than control cultures for 30 min (p < 0.01). Consistent with these results, gel mobility shift assays demonstrate 3-fold increased nuclear C/EBP beta- and C/EBP delta-DNA binding activity in TNF alpha-treated cells, and immunocytochemistry confirms rapid redistribution of these C/EBP isoforms into the nucleus. In contrast, mRNA and whole cell protein concentrations of C/EBP beta and delta are not altered by TNF alpha exposure, and nuclear concentrations of another C/EBP isoform, C/EBP alpha, are decreased by 80%. This novel evidence that TNF alpha initiates post-transcriptional activation of cytokine-inducible C/EBP isoforms identifies a mechanism that enables hepatocytes to respond immediately to inflammatory stress.

Amino Acid Sequence↗

Alcohol and cytokine-inducible transcription factors.

Cytokines, such as TNF alpha, modulate the behavior of many cells by regulating the expression of a wide array of genes. When a cytokine binds to its receptor on the cell surface, the receptor becomes activated and activates signal transduction cascades. These cascades typically involve a series of phosphorylation reactions that lead to sequential activation of various kinases. The targets of these kinases include DNA binding proteins that regulate the transcription of target genes. The activity of DNA binding proteins, such as c-Jun and NF-kappa B, titrates the transcriptional activity of cytokine-regulated genes. Both acute and chronic alcohol consumption of ethanol increase hepatic expression of TNF alpha. After acute ethanol consumption, this is associated with increased induction of several TNF-dependent regenerative events, including the activation of c-Jun and increased binding activity of NF-kappa B. However, chronic consumption of ethanol appears to impede TNF alpha signaling in the liver because it attenuates the increases in c-JUN activity and NF-kappa B binding, which normally follow partial hepatectomy. These results suggest that one mechanism by which ethanol influences liver cell behavior is by influencing local expression of TNF alpha and changing the activity of TNF-regulated transcription factors.

Alcohol Drinking↗

Tumor necrosis factor-alpha modulates CCAAT/enhancer binding proteins-DNA binding activities and promotes hepatocyte-specific gene expression during liver regeneration.

Injury-related cytokines, such as tumor necrosis factor-alpha (TNF), may preserve liver-specific gene expression during the subsequent regenerative response by modulating the activity of transcription factors, including CCAAT/enhancer binding proteins (C/EBPs), which regulate differentiated gene expression in hepatocytes. To test this theory, rats were treated with neutralizing antibody to TNF or nonimmune immunoglobulin before partial hepatectomy (PH) and regenerative changes in the messenger RNAs (mRNAs), proteins, and DNA-binding activities of C/EBP isoforms and the expression of a C/EBP-regulated gene, phosphoenol pyruvate carboxykinase (PEPCK), were compared. Before PH, the expressions of C/EBP-alpha, C/EBP-beta, and C/EBP-gamma were similar in the two treatment groups. Dimers containing C/EBP-alpha and C/EBP-beta accounted for virtually all of the C/EBP DNA binding activity and mRNA for PEPCK, the rate limiting hepatocyte enzyme for gluconeogenesis, was barely detected. After PH, in control rats, mRNA and nuclear protein concentrations of C/EBP-beta and C/EBP-gamma increased approximately fivefold by 3 hours after PH. This was accompanied by increased DNA binding activity of these C/EBP isoforms and decreased DNA binding activity of C/EBP-alpha. mRNA levels of PEPCK, a gene that is strongly transactivated by non-alpha C/EBP isoforms, increased fivefold. Pretreatment with anti-TNF antibodies prevented regenerative induction of C/EBP beta and gamma expression and DNA-binding activity. The nature of dimers binding to C/EBP cis-acting elements remained similar to that observed in liver before PH and increases in PEPCK mRNA were blunted. These results support the theory that TNF helps maintain liver-specific gene expression during liver regeneration by altering transcription factor complexes that regulate differentiated gene expression in hepatocytes.

Animals↗

Tumor necrosis factor-alpha induces c-jun during the regenerative response to liver injury.

After liver injury, remaining hepatocytes proliferate to regenerate the liver. Although the precise mechanisms that initiate and localize regeneration are unknown, local induction of c-jun is a critical, early step in the response. Treatment of rats with antibodies to tumor necrosis factor-alpha (TNF-alpha), a mediator of liver injury, inhibits regenerative induction of jun nuclear kinase activity and nuclear c-jun expression and alters the DNA binding activity of the c-jun transcription factor, AP-1, in liver. Pretreatment with anti-TNF antibodies does not affect pulmonary or renal c-jun expression or AP-1 binding activity post-partial hepatectomy. In primary hepatocyte cultures, TNF-alpha directly promotes the proliferative actions of mitogens, supporting in vivo evidence that it sensitizes hepatocytes to mitogens. Thus local release of TNF may act in a paracrine fashion to initiate regeneration in the injured liver by promoting induction of critical growth-related genes, such as c-jun.

Animals↗

[Campylobacter pyloridis (Cp) infection of gastric mucosa in the high and low risk areas of gastric cancer in Liaoning province].

Gastric biopsies in 690 subjects from the high and low risk areas of gastric cancer were examined for identification of Cp in the gastric mucosa by Warthin-Starry, Gimenez and Gram's stains. The result showed that the positive rate was 60-62% in the high risk area whereas it was only 12.6% in the low risk area in Liaoning province. 81-85% of the positive subjects had active chronic gastritis including chronic superficial and atrophic gastritis. The result indicates a close correlation between the active chronic gastritis and Cp infection. Therefore, control of the Cp infection in the gastric mucosa is very important for lowering the incidence of chronic gastritis, a well known precursor of gastric cancer.

Adolescent↗

Retinal detachment following neodymium-YAG laser capsulotomy.

Five patients developed retinal detachments within one month of undergoing neodymium-YAG laser posterior capsulotomy. In four patients rhegmatogenous retinal detachments developed in association with typical aphakic breaks; in the fifth patient a previously stable extramacular traction detachment extended into the fovea. In all five patients scleral buckling or vitrectomy successfully reattached the retina and visual acuity improved. None of the findings associated with the detachments could be definitely attributed to the YAG laser. These included the lack of structural or positional changes in the vitreous as well as the absence of retinal damage. We were unable to learn the specific settings used for each laser but were told that the minimum energy levels needed to produce a capsulotomy were used.

Aged↗

Digital infrared fundus reflectance.

An infrared sensor was inserted at the film plane of a fundus camera. The signal was visualized on an oscilloscope. In this manner we measured infrared reflectance from the surface of the fundus. The purpose was to characterize choroidal malignant melanomas more reliably than is done with infrared color translation photography. Control lesions were choroidal nevi, metastatic tumors, and disciform macular degenerations. Correlations were made with radioactive phosphorus (32P) uptake, fluorescein angiography, and histopathologic findings. Several cases are presented, one in which this new method of infrared detection was the first diagnostic test to detect the spread of a choroidal melanoma. The simplicity of this technique and its increased accuracy justify the needed further refinements.

Adult↗