The mitotic checkpoint protein hBUB3 and the mRNA export factor hRAE1 interact with GLE2p-binding sequence (GLEBS)-containing proteins.

The mRNA export factor RAE1 (also called GLE2) and the mitotic checkpoint protein BUB3 share extensive sequence homology in yeast as well as higher eukaryotes, although the biological relevance of their similarity is unclear. Previous work in HeLa cells has shown that human (h)RAE1 binds the nuclear pore complex protein hNUP98 via a short NUP98 motif called GLEBS (for GLE2p-binding sequence). Here we report that the two known binding partners of hBUB3, the mitotic checkpoint proteins hBUB1 and hBUBR1, both carry a region with remarkable similarity to the GLEBS motif of hNUP98. We show that the GLEBS-like motifs of mouse (m)BUB1 and mBUBR1 are sufficient for mBUB3 binding. mBUB3 lacks affinity for the hNUP98 GLEBS, demonstrating its binding specificity for GLEBS motifs of mitotic checkpoint proteins. Interestingly, mRAE1 does not exclusively bind to the GLEBS motif of hNUP98 and can cross-interact with the mBUB1 GLEBS. We show that full-length RAE1 and BUB1 proteins interact in mammalian cells and accumulate both at the kinetochores of prometaphase chromosomes. Our findings demonstrate that GLEBS motifs reside in mammalian nucleoporins and mitotic checkpoint proteins and apparently serve as specific binding sites for either BUB3, RAE1, or both.

Salubrious effect of vitamin C and vitamin E on tamoxifen-treated women in breast cancer with reference to plasma lipid and lipoprotein levels.

Tamoxifen, a non-steroidal antiestrogen, has been used in the hormonal treatment for breast cancer. The hepatic estrogenic effect of tamoxifen causes severe triglyceridemia. The combined effect of tamoxifen, vitamin C and vitamin E on plasma lipid and lipoprotein is important, since, vitamin C and vitamin E encumbered the lipid abnormalities instigated by tamoxifen. Therefore supplementation of vitamin C (Celin 500 mg) and vitamin E (Evion 400 mg) for 90 days along with tamoxifen (10 mg twice a day) to postmenopausal breast cancer patients was ventured. In tamoxifen-treated patients, total cholesterol (TC), free cholesterol (FC), phospholipids (PL), free fatty acids (FFA), low density lipoprotein cholesterol (LDL) levels were decreased and the triglycerides (TG), ester cholesterol (EC), high density lipoprotein cholesterol (HDL) and very low density lipoprotein cholesterol (VLDL) levels were increased. Combination therapy reduce all the cholesterol level and VLDL, LDL. TG levels were significantly decreased and HDL, EC levels were significantly increased. These results suggested that tamoxifen treatment is the most effective during co-administration of vitamin C and vitamin E in that they reduce the tamoxifen-induced hypertriglyceridemia.

The salubrious effects of ascorbic acid on cyclophosphamide instigated lipid abnormalities in fibrosarcoma bearing rats.

The combined effect of cyclophosphamide and ascorbic acid on plasma lipids and lipoprotein profiles are important since, ascorbic acid encumbered the lipid abnormalities initiated by cyclophosphamide during cancer chemotherapy. Hence, the study was launched to appraise the salutary role of ascorbic acid in cyclophosphamide administered fibrosarcoma bearing rats. Fibrosarcoma cell line induced rats were treated with cyclophosphamide (10 mg/kg body weight) and ascorbic acid (200 mg/kg body weight) individually and in combination for 28 days. The concentration of plasma lipids and lipoprotein profiles were determined in control and experimental animals. The untreated, as well as cyclophosphamide administered fibrosarcoma bearing rats, divulged significantly increased levels of plasma total cholesterol, triglycerides, phospholipids, VLDL- and LDL-cholesterol, as compared with their respective control animals. In contrast, ester and HDL-cholesterol levels exhibited a marked decrease in these animals. Similar observations were also noticed in liver lipid values, as well. However, these lipid abnormalities were corrected by the co-administration of ascorbic acid. These results suggested, that some clinical entanglement of cyclophosphamide was refrained by co-administration of ascorbic acid in tumor stress condition.

Anthraquinones as a new class of antiviral agents against human immunodeficiency virus.

Various anthraquinones substituted with hydroxyl, amino, halogen, carboxylic acid, substituted aromatic group, and sulfonate were tested to determine their activity against human immunodeficiency virus type 1 (HIV-1) in primary human lymphocytes. Among the compounds tested, polyphenolic and/or polysulfonate substituted anthraquinones were found to possess the most potent antiviral activity. Hypericin, an anthraquinone dimer previously shown to have activity against nonhuman retroviruses also exhibited anti-HIV-1 activity in lymphocytes. the active anthraquinones inhibited HIV-1 reverse transcriptase. However, this enzyme inhibition was selective only for 1,2,5,8-tetrahydroanthraquinone and hypericin. Hypericin interacts nonspecifically with protein suggesting that this effect may dictate its inhibitory activity against the viral reverse transcriptase.

A Soil-free System for Assaying Nematicidal Activity of Chemicals.

A biological assay system for studying the nematicidal activity of chemicals has been devised using a model consisting of cucumber (Cucumis sativus L. cv. Long Marketer) seedlings growing in the diSPo(R) growth-pouch apparatus. Meloidogyne incognita was used as the test organism. The response was quantified in terms of the numbers of galls produced. Statistical procedures were applied to estimate the ED(50) values of currently available nematicides. This system permits accurate quantification of galling and requires much less space and effort than the currently used methods.