Molecular genetics of human cervical cancer: role of papillomavirus and the apoptotic cascade

Cervical cancer is rated the second most common malignant tumour globally, and is aetiologically linked to human papillomavirus (HPV) infection. Here the cellular pathology under consideration of stem/progenitor cell carcinogenesis is reviewed. Of the three causative molecular mechanisms of cervical cancer, two are associated with HPV: firstly, the effect of the viral oncogenes, E6 and E7; and secondly, integration of the viral DNA into chromosomal regions of tumour phenotype. The third process involved is the repetitive loss of heterozygosity in some chromosomal regions. HPV can be classified into high- and low-risk types; the high-risk types encode two oncoproteins, E6 and E7, which interact with tumour suppressor proteins. The association results in the inactivation of tumour suppressor proteins and the abrogation of apoptosis. Apoptosis is referred to as programmed cell death, whereby a cell deliberately commits suicide, and thus regulates cell numbers during development and maintenance of cellular homeostasis. This review attempts to elucidate the role of apoptotic genes, and considers external factors that interact with HPV in the development and progression of cervical cancer. Therefore, an in-depth understanding of the apoptotic genes that control molecular mechanisms in cervical cancer are of critical importance. Useful targets for therapeutic strategies would be those that alter apoptotic pathways in a manner where the escape of HPV from surveillance by the host immune system is prevented. Such an approach directed at the apoptotic genes maybe useful in the treatment of cervical cancer.     

Production of exopolysaccharide by Pseudomonas sp. ATCC 31461 (Pseudomonas elodea ) using whey as fermentation substrate

An improved strain of Pseudomonas sp. ATCC 31461 (Pseudomonas elodea), capable of producing broth viscosities of 11 000 and 4700 mPa s (cP) when grown in enriched whey permeate and enriched sweet whey broths respectively, was isolated. The isolation was by serial transfers of the parent on lactose-rich and sweet whey broths. Maximum viscosities and biopolymer production were observed in 25% (v/v) whey concentration. In whey concentrations of 50% (v/v) or greater, residual glucose was detected in the broth and biopolymer production was low. This strain is capable of totally utilising the lactose in up to 50% (v/v) whey in 64 h. Enzyme activities suggest that the transport of lactose in P. elodea is by the permease system as opposed to the phosphotransferase system. The location of β-galactosidase is mainly intracellular. The improved strain is able to utilise lactose better than the parent and produce 1.6 times more intracellular β-galactosidase activity compared to the parent. Received: 3 May 1996 / Received revision: 8 August 1996 / Accepted: 10 August 1996     

Women with Pregnancies Had Lower Adherence to 1% Tenofovir Vaginal Gel as HIV Preexposure Prophylaxis in CAPRISA 004, a Phase IIB Randomized-Controlled Trial

Background

Antiretroviral prophylaxis may be a critical strategy to reduce periconception HIV transmission. Maximizing the benefit of periconception pharmacologic HIV risk-reduction requires an understanding of the links between pregnancy and adherence to this prevention strategy.

Methods

We assessed study gel adherence among women with pregnancies compared to women without pregnancies enrolled in the CAPRISA 004 phase IIB trial of 1% vaginal tenofovir gel. Pregnancy was assessed with monthly urine tests. Adherence was measured monthly and defined as proportion of sex acts covered by two returned, used applicators based on pre- and post-coital dosing. High adherence was defined as a median adherence score of >80%, that is, more than 80% of sex acts were covered by two applications of study gel. A multivariate generalized estimating equations (GEE) model with a binomial distribution was used to assess covariates associated with high adherence (>80%) over time. Median adherence before and after pregnancy was compared using Wilcoxon signed rank test.

Results

Among 868 women, 53 had at least 1 pregnancy (4.06 per 100 woman years, 95% CI: 3.04, 5.31). Women with pregnancies had lower median adherence compared to women without pregnancies (50% [IQR: 45–83] vs. 60% [IQR: 50–100], p = 0.02). Women with pregnancies also had a 48% lower odds of high adherence compared to women without pregnancies when adjusting for confounders (aOR 0.52, 95%CI: 0.41–0.66, p<0.0001). Among women with pregnancies, adherence before and after pregnancy was not different (50% [IQR: 46–83] vs. 55% [IQR: 20–100], p = 0.68).

Conclusions

Women with pregnancies were less likely to have high adherence to study gel compared to women without pregnancies. Understanding these differences may inform findings from HIV prevention trials and future implementation of antiretroviral prophylaxis for at-risk women who choose to conceive. The protocol for the parent trial is registered on ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT00441298","term_id":"NCT00441298"}}NCT00441298, http://www.clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00441298","term_id":"NCT00441298"}}NCT00441298.     

Impact of mucosal inflammation on cervical human immunodeficiency virus (HIV-1)-specific CD8 T-cell responses in the female genital tract during chronic HIV infection

The female genital tract is the major route of heterosexual human immunodeficiency virus (HIV) acquisition and transmission. Here, we investigated whether HIV-specific CD8 T-cell-mediated immune responses could be detected in the genital mucosa of chronically HIV-infected women and whether these were associated with either local mucosal HIV shedding or local immune factors. We found that CD8⁺ T-cell gamma interferon responses to Gag were detectable at the cervix of HIV-infected women but that the magnitude of genital responses did not correlate with those similarly detected in blood. This indicates that ex vivo HIV responses in one compartment may not be predictive of those in the other. We found that increased genital tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) levels correlated significantly with levels of Gag-specific CD8⁺ T cells at the cervix. Women who were detectably shedding virus in the genital tract had significantly increased cervical levels of TNF-α, IL-1β, IL-6, and IL-8 compared to women who were not detectably shedding virus. We were, however, unable to detect any association between the magnitude of cervical HIV-specific responses and mucosal HIV shedding. Our results support the hypothesis that proinflammatory cytokines in the female genital tract may promote HIV replication and shedding. In addition, we further show that inflammatory cytokines are associated with increased levels of HIV-specific CD8 effector cells at the genital mucosa but that these were not able to control genital HIV shedding.     

Plant induced fertile islands as possible indicators of desertification in a succulent desert ecosystem in northern Namaqualand,South Africa

Zones of nutrient enrichment beneath shrubs, the so called 'fertile islands', are the result of a range of interacting physical and biotic concentrating mechanisms. These concentrating mechanisms lead to specific spatial patterns of soil properties across a landscape and it has been suggested that disruption of the normal patterns into more aggregated 'fertile islands' might be a useful index of desertification in semi-arid regions. The objective of this paper was to determine whether 'fertile islands' are as characteristic a feature of succulent deserts as they are of shrub dominated deserts. Results indicate that, even in a community dominated by succulent species fertile islands develop under extremely arid conditions and that the degree of development is dependent on plant dynamics. Long-lived species showed greater concentration effects. However, the patterns of nutrient accretion in islands are very different to shrub invaded grasslands in North America. In particular nitrogen accretion dominated the 'fertile islands' in Namaqualand, and we suggest that these islands are more ephemeral than carbon and phosphorus dominated islands reported for other systems. These more dynamic islands are a consequence of rapid community dynamics since the Namaqualand region is characterised by many short-lived perennials which turnover generations very rapidly in response to environmental conditions. Using the development of 'fertile islands' to assess desertification as applied elsewhere might be inappropriate in Namaqualand because of the different patterns of community dynamics underlying the formation and characteristics of these islands.     

Short Communication: Optimization of bioprocess conditions for exopolysaccharide production by Klebsiella oxytoca

Optimization of bioprocess conditions increased exopolysaccharide production by a strain of Klebsiella oxytoca from 6g/l to 15g/l; this corresponded to an increase in medium viscosity from 36cP at 12s–1 to 20,000 cP at 0.6 s–1. A combination of equal proportions of tryptone nitrogen and urea nitrogen proved to be the best nitrogen source. Lactose was shown to be the preferred carbon source. At an optimum temperature of 25°C, a pH of 7 was found to be the best for exopolysaccharide production. The concentration of exopolysaccharide produced on whey, enriched whey, enriched whey permeate and lactose-rich medium was comparable.     

Influences of geochemical factors and substrate availability on Gram-positive and Gram-negative bacterial distribution and bio-processes in ageing municipal landfills

International Microbiology - Bacteria are primary agents of organic substrate metabolisation and elemental cycling in landfills. Two major bacterial groups, namely, Gram-positive (GP) and...