Butylated hydroxyanisole inhibits tumor necrosis factor-induced cytotoxicity and arachidonic acid release

The mechanisms by which the antioxidant butylated hydroxyanisole (BHA) inhibits recombinant tumor necrosis factor alpha (rTNF-alpha)-induced cytotoxicity have been studied in WEHI 164 clone 13 (WEHI) and L929 fibrosarcoma cells. When BHA was added simultaneously with rTNF-alpha, it completely inhibited rTNF-alpha cytotoxicity in the WEHI and L929 cells. BHA also inhibited the toxicity when added 2 h after rTNF-alpha in WEHI cells, suggesting that BHA inhibits some late intracellular event(s) in rTNF-alpha cytotoxicity. Pretreating WEHI cells with BHA for 4 h did not decrease the binding of rTNF-alpha to its receptors as measured using flow cytometry. BHA inhibited rTNF-alpha toxicity in the presence of actinomycin D and cycloheximide, indicating that neither mRNA nor protein synthesis is necessary for the BHA effect. The antioxidant butylated hydroxytoluene (BHT) and indomethacin did not inhibit the rTNF-alpha-induced cytotoxicity nor the rTNF-alpha-induced release of [3H]arachidonic acid. By comparison, BHA completely inhibited the rTNF-alpha-induced release of arachidonic acid, suggesting that BHA somehow inhibits rTNF-alpha-induced activation of phospholipase(s). In WEHI cells, rTNF-alpha increased the level of protein-associated thiobarbituric acid reactive substances (TBARS) dose-dependently. BHA, but not BHT, blocked rTNF-alpha-induced cytotoxicity and rTNF-alpha-induced accumulation of protein-associated TBARS, suggesting that rTNF-alpha cytotoxicity is correlated with protein-associated TBARS. In conclusion, the results suggest that BHA blocks some post receptor event in rTNF-alpha-induced cytotoxicity, and that activation of phospholipase(s) coupled with the enzymatic formation of specific oxidized lipids could be a pivotal event in rTNF-alpha-induced cytotoxicity.     

Unilateral multilayered musculocutaneous V-Y advancement flap for the treatment of pressure sore

We have devised a modified technique using the gluteus maximus musculocutaneous flap as multilayered sliding V-Y advancement to cover pressure sores on the sacral area. Nine patients with relatively large (average 7 x 7 cm) sacral grade IV pressure sores underwent unilateral multilayered V-Y advancement flap. All patients were followed for a minimum of 8 weeks. The mean postoperative follow-up was 32.3 months, with a range of 24 to 39 months. Using this technique, the success of surgery, i.e., the percentage of sores that healed, was 100 percent in our patients. The advantages of this technique include sufficient advancement of the flap, coverage of large ulcer defects using only a unilateral musculocutaneous flap, and preservation of the contralateral gluteus maximus muscle for future use.     

Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-beta receptor

Hepatitis C virus (HCV) core protein is a multifunctional protein. We examined whether it can interact with cellular proteins, thus contributing to viral pathogenesis. Using the HCV core protein as a bait to screen a human liver cDNA library in a yeast two-hybrid screening system, we have isolated several positive clones encoding cellular proteins that interact with the HCV core protein. Interestingly, more than half of these clones encode the cytoplasmic domain of lymphotoxin-beta receptor (LT betaR), which is a member of the tumor necrosis factor receptor family. Their binding was confirmed by in vitro glutathione S-transferase fusion protein binding assay and protein-protein blotting assay to be direct and specific. The binding sites were mapped within a 58-amino-acid region of the cytoplasmic tail of LT betaR. The binding site in the HCV core protein was localized within amino acid residues 36 to 91 from the N terminus, corresponding to the hydrophilic region of the protein. In mammalian cells, the core protein was found to be associated with the membrane-bound LT betaR. Since the LT betaR is involved in germinal center formation and developmental regulation of peripheral lymphoid organs, lymph node development, and apoptotic signaling, the binding of HCV core protein to LT betaR suggests the possibility that this viral protein has an immunomodulating function and may explain the mechanism of viral persistence and pathogenesis of HCV.     

The level of serum thymic activity in patients with rheumatoid arthritis and systemic lupus erythematosus

Thymic serum activity (TSA) has been studied in 52 healthy subjects, 48 rheumatoid arthritis patients and 17 sufferers with systemic lupus erythematosus aged from 18 to 70. TSA was compared in patients under and over 40 years. In those under 40 TSA appeared significantly inhibited, while in older subjects it did not differ from age-matched control. No correlations were reported between TSA levels and clinical characteristics. Changes in TSA levels may be related both to low content of thymic hormones and formation of inactive complexes from thymic mediators with inhibitors.     

A new point mutation (3426, A to G) in mitochondrial NADH dehydrogenase gene in Korean diabetic patients which mimics 3243 mutation by restriction fragment length polymorphism pattern

Periodontitis is a chronic destructive inflammatory disease associated with periodontopathic bacteria. In addition, autoantigens such as collagen and heat shock proteins (hsp) have been suggested to play a role. Established periodontal lesions are characterized by dense infiltrations of immune cells such as cytokine-producing CD4+ and CD8+ T cells. CD4+ T cells specific for Prevotella intermedia can be isolated from lesional gingiva, suggesting an active role for CD4+ T cells in the response to this bacterium. We therefore investigated the characteristics of a panel of 13 P. intermedia-specific CD4+ T cells generated from the peripheral blood of a patient with chronic adult periodontitis. All 13 P. intermedia-specific CD4+ T cells recognized the antigens in the context of HLA-DR. The T cell clones were mainly classified as Th0, producing comparable amounts of interferon-gamma (IFN-gamma) and IL-4, and Th2, producing high amounts of IL-4 and almost no IFN-gamma. None of the P. intermedia-specific T cell clones recognized antigens of the periodontopathic bacteria Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis and of the autoantigens collagen and hsp. The reactivity profile of the T cell clones to size-fractionated cell envelope antigens of P. intermedia indicated that P. intermedia-specific CD4+ T cell clones recognize probably five different antigen specificities in the context of the MHC class II molecules, DR7 or DR15. These results suggest that a broad panel of cell-associated protein antigens play a role in the induction of P. intermedia-specific CD4+ T cell response.     

Influence of hyaluronic acid or phorbol 12-myristate 13-acetate on the migration capacity of a murine lymphoma cell line (Eb) and its metastatic variant (ESb)

Men's and women's affective reactions to their first sexual intercourse experience were examined. Eighty-seven college men and 122 college women completed questionnaires about first coital experience. Women were significantly more likely to report that their first sexual experience left them feeling less pleasure, satisfaction, and excitement than men, and more sadness, guilt, nervousness, tension, embarrassment, and fear. Factor analyses were used to group emotions into coherent factors for each sex. Four factors emerged for men: pleasure, romance, anxiety, and guilt. Three factors emerged for women: pleasure/romance, anxiety and guilt.