Helicobacter pylori and cancer among adults in Uganda

Data from Africa on infection with Helicobacter pylori (H. pylori) are sparse. Therefore, as part of an epidemiological study of cancer in Uganda, we investigated the prevalence and determinants of antibodies against H. pylori among 854 people with different cancer types and benign tumours. Patients were recruited from hospitals in Kampala, Uganda, interviewed about various demographic and lifestyle factors and tested for antibodies against H. pylori. In all patients combined, excluding those with stomach cancer (which has been associated with H. pylori infection), the prevalence of antibodies was 87% (723/833) overall, but declined with increasing age (p = 0.02) and was lower among people who were HIV seropositive compared to seronegative (p <0.001). Otherwise, there were few consistent epidemiological associations. Among those with stomach cancer, 18/21 (86%) had anti-H. pylori antibodies (odds ratio 0.8, 95% confidence intervals 0.2–2.9, p = 0.7; estimated using all other patients as controls, with adjustment for age, sex and HIV serostatus). No other cancer site or type was significantly associated with anti-H. pylori antibodies. The prevalence of H. pylori reported here is broadly in accord with results from other developing countries, although the determinants of infection and its' role in the aetiology of gastric cancer in Uganda remain unclear

Cancer survival in Kampala, Uganda

Epidemiological data on the occurrence of cancer in sub-Saharan Africa are sparse, and population-based cancer survival data are even more difficult to obtain due to various logistic difficulties. The population-based Cancer Registry of Kampala, Uganda, has followed up the vital status of all registered cancer patients with one of the 14 most common forms of cancer, who were diagnosed and registered between 1993 and 1997 in the study area. We report 5-year absolute and relative survival estimates of the Ugandan patients and compare them with those of black American patients diagnosed in the same years and included in the SEER Program of the United States. In general, the prognosis of cancer patients in Uganda was very poor. Differences in survival between the two patient populations were particularly dramatic for those cancer types for which early diagnosis and effective treatment is possible. For example, 5-year relative survival was as low as 8.3% for colorectal cancer and 17.7% for cervical cancer in Uganda, compared with 54.2 and 63.9%, respectively, for black American patients. The collection of good-quality follow-up data was possible in the African environment. The very poor prognosis of Ugandan patients is most likely explained by the lack of access to early diagnosis and treatment options in the country. On the policy level, the results underscore the importance of the consistent application of the national cancer control programme guidelines as outlined by the World Health Organization

Breast cancer risk among first-generation migrants in the Netherlands

We investigated breast cancer incidence in migrants in the Netherlands in 1988-1998. The standardised incidence ratio for breast cancer in Northwest-Netherlands was statistically significantly reduced for women born in Surinam (0.56), Turkey (0.29) and Morocco (0.22). The proportion of women with advanced stages (III and IV) did not differ significantly between migrants and women born in the Netherlands

The epidemiology of conjunctival squamous cell carcinoma in Uganda

As part of a larger investigation of cancer in Uganda, we conducted a case–control study of conjunctival squamous cell carcinoma in adults presenting at hospitals in Kampala. Participants were interviewed about social and lifestyle factors and had blood tested for antibodies to HIV, KSHV and HPV-16, -18 and -45. The odds of each factor among 60 people with conjunctival cancer was compared to that among 1214 controls with other cancer sites or types, using odds ratios, estimated with unconditional logistic regression. Conjunctival cancer was associated with HIV infection (OR 10.1, 95% confidence intervals [CI] 5.2–19.4; P<0.001), and was less common in those with a higher personal income (OR 0.4, 95% CI 0.3–1.2; P<0.001). The risk of conjunctival cancer increased with increasing time spent in cultivation and therefore in direct sunlight (χ2 trend=3.9, P=0.05), but decreased with decreasing age at leaving home (χ2 trend=3.9, P=0.05), perhaps reflecting less exposure to sunlight consequent to working in towns, although both results were of borderline statistical significance. To reduce confounding, sexual and reproductive variables were examined among HIV seropositive individuals only. Cases were more likely than controls to report that they had given or received gifts for sex (OR 3.5, 95% CI 1.2–10.4; P=0.03), but this may have been a chance finding as no other sexual or reproductive variable was associated with conjunctival cancer, including the number of self-reported lifetime sexual partners (P=0.4). The seroprevalence of antibodies against HPV-18 and -45 was too low to make reliable conclusions. The presence of anti-HPV-16 antibodies was not significantly associated with squamous cell carcinoma of the conjunctiva (OR 1.5, 95% CI 0.5–4.3; P=0.5) and nor were anti-KSHV antibodies (OR 0.9, 95% CI 0.4–2.1; P=0.8). The 10-fold increased risk of conjunctival cancer in HIV infected individuals is similar to results from other studies. The role of other oncogenic viral infections is unclear

Breast Cancer in Hong Kong, Southern China: The First Population-Based Analysis of Epidemiological Characteristics, Stage-Specific, Cancer-Specific, and Disease-Free Survival in Breast Cancer Patients: 1997–2001

Background: Cancer registries have been set up worldwide to provide information for cancer health planning. There are known variations in breast cancer incidence and mortality worldwide. However, breast cancer incidence, pathological characteristics, and survival data is still underreported in Asian countries. This is the first comprehensive population-based breast cancer study performed using population database of the Hong Kong Cancer Registry. Methods: A retrospective review of medical records of 8,961 subjects who were diagnosed with breast cancer between January 1, 1997 to December 31, 2001 and followed up to December 31, 2007. Descriptive statistics were employed to analyze the epidemiological and clinical data. Estimates of overall, disease-free, and cancer-specific survival at 5 years were estimated by the Kaplan-Meier method and stage-specific relative survival rates were calculated. Results: A total of 7,630 breast cancer patients' medical records and dataset were available during this period, and 7,449 subjects were eligible for the final analysis. Median follow-up was 84 months. A total of 47.4% were diagnosed with breast cancer at age 49 years and younger;22.2%, 46.9%, 10.8%, and 4.1% presented at stages I, II, III, and IV, respectively. A total of 53.5% had ER-positive cancer, and 20.3% had HER2-positive cancers;13.4% had triplenegative cancers. The relative, cancer-specific, and diseasefree survival rates at 5 years were 84%, 85.2%, and 81.2%, respectively. Discussion. We performed the first comprehensive population-based breast cancer epidemiology study in Southern China using the Hong Kong Cancer Registry database. This provides a baseline study cohort for comparative studies with other Asian countries and Chinese who have migrated to the West. © The Author(s) 2011. This article is published with open access at Springerlink.com.published_or_final_versionSpringer Open Choice, 21 Feb 201

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg

The Vinculin-ΔIn20/21 Mouse: Characteristics of a Constitutive, Actin-Binding Deficient Splice Variant of Vinculin

BACKGROUND: The cytoskeletal adaptor protein vinculin plays a fundamental role in cell contact regulation and affects central aspects of cell motility, which are essential to both embryonal development and tissue homeostasis. Functional regulation of this evolutionarily conserved and ubiquitously expressed protein is dominated by a high-affinity, autoinhibitory head-to-tail interaction that spatially restricts ligand interactions to cell adhesion sites and, furthermore, limits the residency time of vinculin at these sites. To date, no mutants of the vinculin protein have been characterized in animal models. METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigate vinculin-DeltaEx20, a splice variant of the protein lacking the 68 amino acids encoded by exon 20 of the vinculin gene VCL. Vinculin-DeltaEx20 was found to be expressed alongside with wild type protein in a knock-in mouse model with a deletion of introns 20 and 21 (VCL-DeltaIn20/21 allele) and shows defective head-to-tail interaction. Homozygous VCL-DeltaIn20/21 embryos die around embryonal day E12.5 showing cranial neural tube defects and exencephaly. In mouse embryonic fibroblasts and upon ectopic expression, vinculin-DeltaEx20 reveals characteristics of constitutive head binding activity. Interestingly, the impact of vinculin-DeltaEx20 on cell contact induction and stabilization, a hallmark of the vinculin head domain, is only moderate, thus allowing invasion and motility of cells in three-dimensional collagen matrices. Lacking both F-actin interaction sites of the tail, the vinculin-DeltaEx20 variant unveils vinculin's dynamic binding to cell adhesions independent of a cytoskeletal association, and thus differs from head-to-tail binding deficient mutants such as vinculin-T12, in which activated F-actin binding locks the protein variant to cell contact sites. CONCLUSIONS/SIGNIFICANCE: Vinculin-DeltaEx20 is an active variant supporting adhesion site stabilization without an enhanced mechanical coupling. Its presence in a transgenic animal reveals the potential of splice variants in the vinculin gene to alter vinculin function in vivo. Correct control of vinculin is necessary for embryonic development

Methodological considerations in the analysis of fecal glucocorticoid metabolites in tufted capuchins (Cebus apella)

Analysis of fecal glucocorticoid (GC) metabolites has recently become the standard method to monitor adrenocortical activity in primates noninvasively. However, given variation in the production, metabolism, and excretion of GCs across species and even between sexes, there are no standard methods that are universally applicable. In particular, it is important to validate assays intended to measure GC production, test extraction and storage procedures, and consider the time course of GC metabolite excretion relative to the production and circulation of the native hormones. This study examines these four methodological aspects of fecal GC metabolite analysis in tufted capuchins (Cebus apella). Specifically, we conducted an adrenocorticotrophic hormone (ACTH) challenge on one male and one female capuchin to test the validity of four GC enzyme immunoassays (EIAs) and document the time course characterizing GC me- tabolite excretion in this species. In addition, we compare a common field-friendly technique for extracting fecal GC metabolites to an established laboratory extraction methodology and test for effects of storing “field extracts” for up to 1 yr. Results suggest that a corticosterone EIA is most sensitive to changes in GC production, provides reliable measures when extracted according to the field method, and measures GC metabolites which remain highly stable after even 12 mo of storage. Further, the time course of GC metabolite excretion is shorter than that described yet for any primate taxa. These results provide guidelines for studies of GCs in tufted capuchins, and underscore the importance of validating methods for fecal hormone analysis for each species of interest

The Effect of Oxidant and the Non-Oxidant Alteration of Cellular Thiol Concentration on the Formation of Protein Mixed-Disulfides in HEK 293 Cells

Cellular molecules possess various mechanisms in responding to oxidant stress. In terms of protein responses, protein S-glutathionylation is a unique post-translational modification of protein reactive cysteines forming disulfides with glutathione molecules. This modification has been proposed to play roles in antioxidant, regulatory and signaling in cells under oxidant stress. Recently, the increased level of protein S-glutathionylation has been linked with the development of diseases. In this report, specific S-glutathionylated proteins were demonstrated in human embryonic kidney 293 cells treated with two different oxidative reagents: diamide and hydrogen peroxide. Diamide is a chemical oxidizing agent whereas hydrogen peroxide is a physiological oxidant. Under the experimental conditions, these two oxidants decreased glutathione concentration without toxicity. S-glutathionylated proteins were detected by immunoblotting and glutathione concentrations were determined by high performance liquid chromatography. We further show the effect of alteration of the cellular thiol pool on the amount of protein S-glutathionylation in oxidant-treated cells. Cellular thiol concentrations were altered either by a specific way using buthionine sulfoximine, a specific inhibitor of glutathione biosynthesis or by a non-specific way, incubating cells in cystine-methionine deficient media. Cells only treated with either buthionine sulfoximine or cystine-methionine deficient media did not induce protein S-glutathionylation, even though both conditions decreased 65% of cellular glutathione. Moreover, the amount of protein S-glutathionylation under both conditions in the presence of oxidants was not altered when compared to the amount observed in regular media with oxidants present. Protein S-glutathionylation is a dynamic reaction which depends on the rate of adding and removing glutathione. Phenylarsine oxide, which specifically forms a covalent adduct with vicinal thiols, was used to determine the possible role of vicinal thiols in the amount of glutathionylation. Our data shows phenylarsine oxide did not change glutathione concentrations, but it did enhance the amount of glutathionylation in oxidant-treated cells