Human breast cancer cell metastasis to long bone and soft organs of nude mice : a quantitative assay

Bone is a common metastatic site in human breast cancer (HBC). Since bone metastasis occurs very rarely from current spontaneous or experimental metastasis models of HBC cells in nude mice, an arterial seeding model involving the direct injection of the cells into the left ventricle has been developed to better understand the mechanisms involved in this process. We present here a sensitive polymerase chain reaction (PCR) method to detect and quantitate bone and soft organ metastasis in nude mice which have been intracardially inoculated with Lac Z transduced HBC cells. Amplification of genomically incorporated Lac Z sequences in MDA-MB-231-BAG HBC cells enables us to specifically detect these cells in mouse organs and bones. We have also created a competitive template to use as an internal standard in the PCR reactions, allowing us to better quantitate levels of HBC metastasis. The results of this PCR detection method correlate well with cell culture detection from alternate long bones from the same mice, and are more sensitive than gross Lac Z staining with X-gal or routine histology. Comparable qualitative results were obtained with PCR and culture in a titration experiment in which mice were inoculated with increasing numbers of cells, but PCR is more quantifiable, less time consuming, and less expensive. This assay can be employed to study the molecular and cellular aspects of bone metastasis, and could easily be used in conjunction with RT-PCR-based analyses of gene products which may be involved with HBC metastasis.

Oral testosterone self-administration in male hamsters

The addiction potential of anabolic steroids remains largely unexplored. Here, we demonstrate voluntary oral testosterone intake in hamsters. Using a 2-bottle choice test, males preferred an aqueous solution of 200 microg/ml testosterone over vehicle. However, the taste of testosterone is not highly preferred. Addition of testosterone at 400 microg/ml increased fluid consumption from the nonpreferred bottle in a 2-bottle choice test, but cholesterol at the same concentration reduced drinking, suggesting that testosterone reward is not common to all sterols. With food-induced drinking, testosterone maintained fluid intake when food was withdrawn. These data demonstrate that oral self-administration of testosterone is reinforcing in hamsters, suggesting the potential for dependence in human users.

Cells Tissues Organs : preface

This volume stems from the 1st International Conference on Epithelial-Mesenchymal Transitions (EMT), which was convened by the editors on October 5–8, 2003 in the beautiful setting of Port Douglas, Queensland, Australia. EMT, the name given to the transformation of cells arranged in a coherent layer – epithelial cells – to more individualistic and potential motile cells – mesenchymal cells – was recognized decades ago by Prof. Elisabeth (Betty) Hay (Harvard Medical School, Boston, Mass., USA) as a primary mechanism in embryogenesis for remodelling tissues. More recently EMT has been seen as crucial to the spread and invasion of carcinoma, and more recently still, EMT-like changes have been detected in various pathologies marked by fi brosis. Despite the basic and clinical importance of EMT, this extremely rapidly growing fi eld had never previously had a conference devoted to it, and indeed the disciplines of developmental biology, cancer and pathology rarely interact although they have much to share. The chapters assembled for this volume encompass these three major themes of the meeting, development, pathology and cancer, and further highlight the commonality in terms of mechanisms and outcomes among them...

Correlates of physical activity in male and female youth

This study examined associations between psychosocial factors and physical activity in a group of youth (n = 520). Students completed the Previous Day Physical Activity Recall and a survey of potential determinants of physical activity. Regression analyses of intentions to be physically active revealed that enjoyment and self-efficacy predicted intentions for both males and females. Attitudes predicted moderate to vigorous activity (MVPA), and enjoyment and self-efficacy predicted vigorous activity (VPA) for males. Self-efficacy predicted both MVPA and VPA for females. The findings suggest that intervention programs targeted at youth should include developmentally appropriate activities that are fun and promote physical activity self-efficacy.

CFTR expression is regulated during both the cycle of the seminiferous epithelium and the oestrous cycle of rodents

Severely reduced fertility is a common finding in cystic fibrosis (CF). We used in situ hybridization to examine the cell-specific expression of CFTR in the reproductive organs of rodents. In males CFTR mRNA is found in the round spermatids (spermatogenic stages V-X) and in the principal cells that line the initial segment of the epididymis. In both the testis and the epididymis, CFTR expression is developmentally regulated suggesting that the defect in the genital tract of male CF patients is of developmental origin. CFTR expression in the luminal and glandular epithelium of the uterus is regulated during the oestrous cycle and is maximal at pro-oestrus. Our results provide a biological rationale for the reduced fertility of CF patients, and suggest a possible cause for the comparatively poorer prognosis for women with CF.

Influence of cytochrome P-450 inhibitors on the inhalative uptake of methyl chloride and methylene chloride in male B6C3F1 mice

Dichloromethane (DCM) is thought to be metabolized in vivo by two independent pathways: a glutathione (GSH) dependent pathway that yields CO2 and a cytochrome P-450 mediated one that yields both CO and CO2 (Gargas et al 1986). With a physiologically based pharmacokinetic (PB-PK) model, Andersen et al (1987) calculate the quantitative parameters for both metabolic pathways. Using the kinetic parameters thus obtained and the results of two carcinogenicity studies with rodents (Serota et al 1986; NTP 1985), the authors then estimate the tumour risk for humans.

Species differences in the glutathione transferase GSTT1-1 activity towards the model substrates methyl chloride and dichloromethane in liver and kidney

Glutathione transferase (GST) GSTT1-1 is involved in the biotransformation of several chemicals widely used in industry, such as butadiene and dichloro methane DCM. The polymorphic hGSTT1-1 may well play a role in the development of kidney tumours after high and long-term occupational exposure against trichloroethylene. Although several studies have investigated the association of this polymorphism with malignant diseases little is known about its enzyme activity in potential extrahepatic target tissues. The known theta-specific substrates methyl chloride (MC) dichloromethane and 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) were used to assay GSTT1-1 activity in liver and kidney of rats, mice, hamsters and humans differentiating the three phenotypes (non-conjugators, low conjugators, high conjugators) seen in humans. In addition GSTT1-1 activity towards MC and DCM was determined in human erythrocytes. No GSTT1-1 activity was found in any tissue of non-conjugators (NC). In all organs high conjugators (HC) showed twofold higher activity towards MC and DCM than low conjugators (LC). The activity in human samples towards EPNP was too close to the detection limit to differentiate between the three conjugator phenotypes. GSTT1-1 activity towards MC was two to seven-times higher in liver cytosol than in kidney cytosol. The relation for MC between species was identical in both organs: mouse > HC > rat > LC > hamster > NC. In rats, mice and hamsters GSTT1-1 activity in liver cytosol towards DCM was also two to seven-times higher than in the kidney cytosol. In humans this activity was twice as high in kidney cytosol than in liver cytosol. The relation between species was mouse > rat > HC > LC > hamster > NC for liver, but mouse > HC > LC/rat > hamster/NC for kidney cytosol. The importance to heed the specific environment at potential target sites in risk assessment is emphasized by these results.

Sexual selection in true fruit flies (Diptera: Tephritidae) : transcriptome and experimental evidences for phytochemicals increasing male competitive ability

In male tephritid fruit flies of the genus Bactrocera, feeding on secondary plant compounds (sensu lato male lures = methyl eugenol, raspberry ketone and zingerone) increases male mating success. Ingested male lures alter the male pheromonal blend, normally making it more attractive to females and this is considered the primary mechanism for the enhanced mating success. However, the male lures raspberry ketone and zingerone are known, across a diverse range of other organisms, to be involved in increasing energy metabolism. If this also occurs in Bactrocera, then this may represent an additional benefit to males as courtship is metabolically expensive and lure feeding may increase a fly's short-term energy. We tested this hypothesis by performing comparative RNA-seq analysis between zingerone-fed and unfed males of Bactrocera tryoni. We also carried out behavioural assays with zingerone- and cuelure-fed males to test whether they became more active. RNA-seq analysis revealed, in zingerone-fed flies, up-regulation of 3183 genes with homologues transcripts to those known to regulate intermale aggression, pheromone synthesis, mating and accessory gland proteins, along with significant enrichment of several energy metabolic pathways and gene ontology terms. Behavioural assays show significant increases in locomotor activity, weight reduction and successful mating after mounting; all direct/indirect measures of increased activity. These results suggest that feeding on lures leads to complex physiological changes, which result in more competitive males. These results do not negate the pheromone effect, but do strongly suggest that the phytochemical-induced sexual selection is governed by both female preference and male competitive mechanisms.

Understanding the new context of the male sex work industry

The article reviews past and recent research on male sex work to offer a context to understand violence in the industry. It provides a critical review of research to show, first, the assumptions made about male sex workers and violence and, second, how such discourses have shaped thinking on the topic. The article presents a case study and original findings from two studies conducted by the authors in Australia and Argentina on violence in the male sex industry. Finally, the article reviews examples of legislative reforms to show how the sex industry is being regulated.

A prostitute's progress : male prostitution in scientific discourse

This paper examines discourses of male prostitution through an analysis of scientific texts. A contrast is drawn between nineteenth-century understandings of male prostitution and twentieth-century accounts of male prostitution. In contrast to female prostitution, male prostitution was not regarded as a significant social problem throughout the nineteenth century, despite its close association with gender deviation and social disorder. Changing conceptions of sexuality, linked with the emergence of the ‘adolescent’, drew scientific attention to male prostitution during the 1940s and 1950s. Research suggested that male prostitution was a problem associated with the development of sexual identity. Through the application of scientific techniques, which tagged and differentiated male prostitute populations, a language developed about male prostitution that allowed for normative assessments and judgements to be made concerning particular classes of male prostitute. The paper highlights how a broad distinction emerged between public prostitutes, regarded as heterosexual/masculine, and private prostitutes, regarded as homosexual/effeminate. This distinction altered the way in which male prostitution was understood and governed, allowing for male prostitution to be constituted as a public health concern.

New pleasures and old dangers: reinventing male sex work

Understandings of male sex workers (MSWs) shift with technological, conceptual, and social changes. Research has historically constructed MSWs as psychologically unstable, desperate, or destitute victims and their clients as socially deviant perverts. These perceptions, however, are no longer supported by contemporary research and changing societal perceptions of the sex industry, challenging how we understand and describe “escorts.” The changing understandings of sexuality and the increasing power of the Internet are both important forces behind recent changes in the structure and organization of MSWs. The growth in the visibility and reach of escorts has created opportunities to form an occupational account of MSWs that better accounts for the dynamic and diverse nature of the MSW experience in the early 21st century. Recent changes in the structure and organization of male sex work have provided visibility to the increasingly diverse geographical distribution of MSW, the commodification of race and racialized desire, new populations of heterosexual men and women as clients, and the successful dissemination of safer sexual messages to MSWs through online channels. This article provides a broad overview of the literature on MSWs, concentrating its focus on studies that have emerged over the past 20 years and identifying areas for future research.

Recruiting, Sampling and Data Collection with Difficult Populations: Clients of Male Sex Workers.

Although there are many potential new insights to be gained through advancing research on the clients of male sex workers, significant social, ethical and methodological challenges to accessing this population exist. This research project case explores our attempts to recruit a population that does not typically form a cohesive or coherent 'community' and often avoids self-identifying to mitigate the stigma attached to buying sex. We used an arms-length recruitment campaign that focussed on directing potential participants to our study website, which could in turn lead them to participate in an anonymous telephone interview. Barriers to reaching male sex-work clients, however, demanded the evolution of our recruitment strategy. New technologies are part of the solution to accessing a hard-to-reach population, but they only work if researchers engage responsively. We also show how we conducted an in-depth interview with a client and discuss the value of using secondary data.