Prospective study of high grade anal squamous intraepithelial neoplasia in a cohort of homosexual men: influence of HIV infection, immunosuppression and human papillomavirus infection

OBJECTIVE: To determine the risk of developing high grade anal squamous intraepithelial neoplasia (HG-AIN) in relation to HIV infection and immunosuppression, after controlling for the effects of human papillomavirus (HPV) infection. DESIGN: Prospective cohort study of 158 HIV-seropositive and 147 HIV-seronegative homosexual men presenting to a community-based clinic with initially negative anal cytologic and colposcopic findings. METHODS: Subjects completed self-administered questionnaires, underwent cytologic screening, and standardized unaided and colposcopic examination of the proximal anal canal for presence of abnormalities suggestive of AIN. Anal specimens were screened for HPV DNA. RESULTS: HG-AIN developed in eight (5.4%) and 24 (15.2%) HIV-seronegative and -seropositive men, respectively. Risk of HG-AIN among HIV-seronegative men was associated with detection of anal HPV types 16 or 18 by Southern transfer hybridization (STH), detection of HPV 16 or 18 at the lower levels by polymerase chain reaction but not by STH, and with number of positive HPV tests; HG-AIN risk among HIV-seropositive men was associated with detection of HPV 16 or 18 only by STH, detection of HPV types other than 16 or 18, CD4 count < or = 500 x 10(6)/l, and number of positive HPV tests. HIV-induced immunosuppression remained an independent predictor of HG-AIN after adjusting for type and level of detection of HPV; HIV infection predicted HG-AIN risk after adjustment for number of positive HPV tests. CONCLUSIONS: The association of HG-AIN with HIV, independent of HPV type, level of HPV detection and number of positive HPV tests, suggests that this increased risk cannot be entirely explained by an effect of HIV on HPV detection. Future studies focusing on factors more specific to the local microenvironment in the anal canal should help clarify these issues.     

Liquid-liquid extraction and separation of total rare earth (RE) metals from polymetallic manganese nodule leaching solution

The study on the solvent extraction for quantitative and selective separation of total rare earth metals from the polymetallic nodule leach liquor was investigated. The typical leach liquor bearing 0. 094 g/L total rare earth, 0. 23 g/L Mn, 0.697 g/L Cu, 0.2 g/L Fe, 0.01 g/L Co and 0.735 g/L Ni was subjected to the removal iron content by precipitation method using Ca(OH)2 at pH 3.95, prior to solvent extraction of rare earth metals. Three different organo-phosphoric acid reagents(D2EHPA, PC88 A, Cyanex 272) were used to ascertain their performances and selectivity towards the loading of rare earth metals in presence of other base metals. Based on the results of eq. pH effect, the performances of above three extractants followed the order as: D2EHPA>PC88A>Cyanex 272. To ensure the absence of extraction of base metals(Cu, Co, Ni), the eq. pH of the solution was optimized at the level of 2.21, though higher rare earth metal extraction efficiency was observed at higher eq. pH with either of the extractants. The complete process flow diagram for substantial recovery of total rare earth was developed using D2 EHPA. Extraction isotherm plot was constructed at A:O=12:1, 3-stages and pHe=2.21, using 0.8 mol/L D2 EHPA and the predicted condition of this study was further confirmed by 6-Cycles Counter Current Simulation(CCS) study. The stripping of total rare earth from loaded organic phase(LO) was conducted using HCl solution. Mc-Cabe Thiele diagram study carried out at A:O=1:5 using 4 mol/L HCl showed that three theoretical stages were needed for quantitative stripping of total rare earth. The subsequent stripped solution resulted thus led to contain total rare earth of 5.6 g/L indicating a very high enrichment of total metals by solvent extraction(SX) process.     

Role of an inhibitory pyrimidine element and polypyrimidine tract binding protein in repression of a regulated alpha-tropomyosin exon

The lipogenic enzyme fatty acid synthase (FAS) is elevated in various human primary cancers and certain human cancer cell lines. FAS overexpression in human neoplasia has clinical relevance because of its association with tumor aggression and potential chemotherapeutic intervention. Here, we surveyed FAS in cell lines established from normal murine mammary epithelium (NMuMG) and from mammary tumors induced by either rodent polyoma (Py) virus or murine mammary tumor virus (MMTV). Western blotting revealed greater content of FAS in Py-transformed A1-1 and T1 than NMuMG or MMTV-transformed Mm5MT, RIIIMT and MMT060562. These data suggest that signaling events mediated by Py transformation may increase cellular amounts of FAS. Although FAS content was elevated to similar levels in A1-1 and T1, specific activities were significantly different as enzyme activity in T1 was 3-fold higher than A1-1. Likewise, FAS activity in NMuMG was about 0.5-fold higher than the MMTV-transformed lines, even though enzyme content was similar. Immunoprecipitation studies employing anti-phosphoamino acid antibodies followed by immunoblot analysis with anti-FAS antisera (and vice versa) were used to characterize the constitutive phosphorylation state of the enzyme. Phosphoserine and phosphothreonine residues were detected in the more active FAS from T1 and NMuMG, but not in the less active FAS from Mm5MT or A1-1. Discovery of phosphorylated FAS suggests that the enzyme may have more immediate control over lipogenesis than previously thought. High-dose (10-4 M) dexamethasone induced FAS content and activity in NMuMG and MMTV-transformed lines but not Py-transformed cells. Lower concentrations (10-8, 10-6 M) of dexamethasone also activated FAS but without concomitant elevation of its protein content, which was consistent with a phosphorylated form of FAS. Finally, cell lines were treated with the FAS inhibitor cerulenin: almost all breast cancer lines were growth inhibited at significantly lower amounts of drug than normal cell lineages, suggesting that FAS plays a greater role in viability of tumor cells than normal cells. Pretreatment with palmitate (a primary end-product of FAS) prior to cerulenin rescued A1-1 cells only slightly from growth inhibition, whereas pretreatment with oleate (a monounsaturated fatty acid synthesized from palmitate) synergized cerulenin's cytotoxic effects.