HRAD1 and MRAD1 encode mammalian homologues of the fission yeast rad1(+) cell cycle checkpoint control gene

Eukaryotic cells arrest at the G2checkpoint in the presence of DNA damage or incompletely replicated DNA. This cell cycle checkpoint prevents the development and propagation of genomic instability. In the fission yeast, this process requires the action of a number of genes, including rad1(+) . We report here the identification of human and mouse cDNAs that exhibit extensive sequence homology to rad1(+) . The human gene, called HRAD1 , encodes a 282 amino acid protein that is 27% identical and 53% similar to yeast Rad1p. The human homologue maintains its sequence similarity over the full length of the protein, including the three proposed 3'-->5' exonuclease domains, and the leucine rich repeat region. The mouse gene, called MRAD1 , encodes a 280 amino acid protein that is 90% identical and 96% similar to HRAD1 at the amino acid level. Expression of HRAD1 in yeast rad1 mutants partially restores radiation resistance and G2checkpoint proficiency to these mutants. Evolutionaryconservation of structure between HRAD1 , MRAD1 , rad1(+), Saccharomyces cerevisiae RAD17 and the Ustilago maydis REC1 checkpoint genes suggests that the function of the encoded proteins is conserved as well. The ability of HRAD1 to partially complement yeast rad1 mutants suggests that this gene is required for G2checkpoint control in human cells.     

Antiprogestins mediate differential effects on glucocorticoid receptor remodeling of chromatin structure

We examined the mechanism(s) by which the progesterone receptor (PR) is able to inhibit glucocorticoid receptor (GR) activation from the mouse mammary tumor virus (MMTV) promoter in vivo. Using specific hormone antagonists, we demonstrate that the PR complexed with an type II antiprogestin blocks glucocorticoid-induced activation of the MMTV promoter. However, when complexed with a type I antiprogestin the PR is unable to block glucocorticoid-induced activation. PR repression of GR activity results from the inhibition of the ability of the GR to remodel chromatin such that the antiprogestin-occupied/PR prevents the glucocorticoid induced assembly of a preinitiation complex at MMTV promoter. These experiments suggest that the specific chromatin organization of the MMTV promoter provides a mechanism for regulating cross-talk between the GR and PR in vivo.     

Risk factors for HIV infection in a rural cohort in Zimbabwe: a pilot study

OBJECTIVE: To identify demographic, sexual behavioural and cultural risk factors for human immunodeficiency virus (HIV) infection in a rural community in Zimbabwe. DESIGN: Prospective study. SETTING: Rural area in Zimbabwe. SUBJECTS: 207 subjects (81 males, 126 females) mean age 31.6 years (SD 15.3), range 12 to 76 years living in the area. MAIN OUTCOME MEASURES: HIV seropositivity and seroconversion, exposure or no exposure to risk factor. RESULTS: Prevalence of HIV was 7.7% and was associated with being divorced or widowed [Odds ratio (OR) 4.26, 95% confidence interval (CI) 1.17 to 14.97] and past history of sexually transmitted diseases (STDs) [(OR 3.54, 95% CI 1.31 to 9.89)]. Seroconversion rate was 3.6% per year and was associated with history of STD [Relative Risk (RR) 13.22, 95% CI 1.15 to 156.1)] during the follow up period. Individuals over 20 years of age, those reporting one or more sexual partners, those reporting irregular use of condoms and those scarified were at greater risk than their counterparts. Individuals who reported being circumcised were at slightly lesser risk than those who did not report circumcision. CONCLUSION: STDs were major determinants of HIV transmission in the study area. In addition being divorced or widowed was a risk factor for HIV infection. Scarification, tattooing and circumcision require further investigations.     

Future of petrochemical raw materials in oleochemical markets

The petrochemical industry (PCI) has undergone profound changes during the last decade and is continuing to adjust to changing world economic conditions. One of the most important of these is the price of crude oil. Although an equilibrated pricing structure remains to be demonstrated, anticipated adequacy of supply and versatile, innovative methods of converting crude and natural gas to high valued products assures it a vital and healthy future. The product areas in which the PCI and the oleochemical industry (OCI) overlap are actually quite small in terms of the total capacity. In those limited areas of overlap, we expect the role of the PCI during the next several years to continue to be cone of a complementary nature. By providing security of supply at competitive prices, it will create confidence and reliability which will benefit both the petrochemical and oleochemical industries. And most significantly, the resources of the petrochemical industry will also allow it to respond to new market conditions, particularly those of accelerated volume needs and specific performance, with the flexibility and creativity which have been its hallmarks.     

Induction of apoptotic nuclei by interferon-gamma and by predesquamin in cultured keratinocytes

Predesquamin is a glycoprotein found in the transition layer and the lower stratum corneum of human epidermis. Interferon-gamma (IFN-gamma) induces the synthesis of predesquamin by keratinocytes in culture. We now show ultrastructurally that exogenous addition of either predesquamin or IFN-gamma to cultured keratinocytes induces apoptotic nuclei with condensed chromatin. Degradation of cellular DNA is also evident as a ladder pattern in an agarose gel. After incubation with both predesquamin and IFN-gamma (but not either alone), the mobility of plasmid DNA in a gel shows retardation specific for guanine residues. This binding to the DNA may impart to it a conformational change that facilitates access by endogenous cellular nucleases. In epidermal cells cultured with IFN-gamma supplementation, we also show by RT-PCR that there is an upregulation of the genes c-myc, p53, gadd45, dsRNA-activated protein kinase, and 2'-5'-oligo(A)-dependent RNase, which have all been implicated in apoptosis in other cell types. These results are pertinent to the mechanism of occurrence of apoptosis in the epidermis in vivo, where predesquamin and IFN-gamma are endogenous. Programmed cell death is an inherent step in the terminal differentiation and desquamation of the epidermis.     

Calbistrins, novel antifungal agents produced by Penicillium restrictum. I. Production, taxonomy of the producing organism and biological activity

Over a 14-year period, from 1971 to 1985, there were 15 patients referred to the Princess Margaret Hospital in Toronto for postoperative radiotherapy to the cervical lymph nodes following radical neck surgery for metastatic cancer. An intensive investigation failed to yield a primary site in any patient. All of the patients had extensive neck disease with significant indications for postoperative radiotherapy (massive neck nodes, invasion of extra nodal structures or fixation to unresectable adjacent structures). Of this highly selected group of patients with advanced neck disease: 4/15 (27%) died within one year of uncontrolled local disease, a further 2/15 (13%) died within four years of metastatic/recurrent disease, 6/15 (33%) died of intercurrent disease and 3/15 (20%) were alive with at least four years follow-up. Although all patients presented with advanced disease, survival and significant palliation was possible in this select group of patients.