Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature

Development of metastasis is a leading cause of cancer-induced death. Acquisition of an invasive tumor cell phenotype suggests loss of cell adhesion and basement membrane breakdown during a process termed epithelial-to-mesenchymal transition (EMT). Recently, cancer stem cells (CSC) were discovered to mediate solid tumor initiation and progression. Prostate CSCs are a subpopulation of CD44⁺ cells within the tumor that give rise to differentiated tumor cells and also self-renew. Using both primary and established prostate cancer cell lines, we tested the assumption that CSCs are more invasive. The ability of unsorted cells and CD44-positve and -negative subpopulations to undergo Matrigel invasion and EMT was evaluated, and the gene expression profiles of these cells were analyzed by microarray and a subset confirmed using QRT-PCR. Our data reveal that a subpopulation of CD44⁺ CSC-like cells invade Matrigel through an EMT, while in contrast, CD44⁻ cells are non-invasive. Furthermore, the genomic profile of the invasive cells closely resembles that of CD44⁺CD24⁻ prostate CSCs and shows evidence for increased Hedgehog signaling. Finally, invasive cells from DU145 and primary prostate cancer cells are more tumorigenic in NOD/SCID mice compared with non-invasive cells. Our data strongly suggest that basement membrane invasion, an early and necessary step in metastasis development, is mediated by these potential cancer stem cells. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Minimally invasive techniques for the treatment of intervertebral disk herniation

Hemilaminectomy with diskectomy, the original surgical option to address intervertebral disk herniation, was superseded by open microdiskectomy, a less invasive technique recognized as the surgical benchmark with which minimally invasive spine surgery techniques have been compared as they have been developed. These minimally invasive surgical techniques for patients with herniated nucleus pulposus and radiculopathy include laser disk decompression, arthroscopic microdiskectomy, laparoscopic techniques, foraminal endoscopy, and microendoscopic diskectomy. Each has its own complications and requires a long learning curve to develop familiarity with the technique. Patient selection, and especially disk morphology, are the most important factors in choice of technique. The optimal candidate has a previously untreated single-level herniation with limited migration or sequestration of free fragments.     

Hemisphere-scale differences in conifer evolutionary dynamics

Fundamental differences in the distribution of oceans and landmasses in the Northern and Southern Hemispheres potentially impact patterns of biological diversity in the two areas. The evolutionary history of conifers provides an opportunity to explore these dynamics, because the majority of extant conifer species belong to lineages that have been broadly confined to the Northern or Southern Hemisphere during the Cenozoic. Incorporating genetic information with a critical review of fossil evidence, we developed an age-calibrated phylogeny sampling ∼80% of living conifer species. Most extant conifer species diverged recently during the Neogene within clades that generally were established during the later Mesozoic, but lineages that diversified mainly in the Southern Hemisphere show a significantly older distribution of divergence ages than their counterparts in the Northern Hemisphere. Our tree topology and divergence times also are best fit by diversification models in which Northern Hemisphere conifer lineages have higher rates of species turnover than Southern Hemisphere lineages. The abundance of recent divergences in northern clades may reflect complex patterns of migration and range shifts during climatic cycles over the later Neogene leading to elevated rates of speciation and extinction, whereas the scattered persistence of mild, wetter habitats in the Southern Hemisphere may have favored the survival of older lineages.     

Effectiveness of Respondent-Driven Sampling to Recruit High Risk Heterosexual Men Who Have Multiple Female Sexual Partners: Differences in HIV Prevalence and Sexual Risk Behaviours Measured at Two Time Points

Regular HIV bio-behavioural surveillance surveys (BBSS) among high risk heterosexual (HRH) men who have multiple female sexual partners is needed to monitor HIV prevalence and risk behaviour trends, and to improve the provision and assessment of HIV prevention strategies for this population. In 2006 and 2008 we used respondent-driven sampling to recruit HRH men and examine differences in HIV prevalence and risk behaviours between the two time points. In both surveys, the target population had little difficulty in recruiting others from their social networks that were able to sustain the chain-referral process. Key variables reached equilibrium within one to six recruitment waves and homophily indices showed neither tendencies to in-group nor out-group preferences. Between 2006 and 2008 there were significant differences in condom use with main sexual partners; numbers of sexual partners; and alcohol consumption. Further BBSS among this population are needed before more reliable trends can be inferred.     

Active vegetations can be differentiated from chronic vegetations by visual inspection of standardized two-dimensional echocardiograms

The ability to differentiate active from chronic valvular vegetations (VEGs) by digital image processing and by visual observation was evaluated in 18 patients with a clinical diagnosis of infective endocarditis (IE). Two-dimensional echocardiographic (2-DE) examinations were performed on all patients at diagnosis and after a mean period of 52 days. Two comparable images (active and chronic) from the same patient and in the same phase of the cardiac cycle were digitized, magnified, and displayed on a high resolution monitor. The mean pixel intensity (MPI) was 72+/-14 in the active stage and 143 +/-23 in the chronic stage (P<0.0001). The VEG size was 0.64+/- 0.15 cm(2) in the active stage and decreased to 0.46+/-0.17 cm(2) in the chronic stage (P<0.001). Two experienced echocardiographers, who were blinded to the age of the VEGs, identified each echocardiographic image as active or chronic based on visual observation of density of the VEGs. The VEGs were correctly identified as active or chronic in 17 out of the 18 patients. In summary, although digital image processing of 2-DE may be useful, the density of VEGs assessed by visual inspection will help differentiate between active and chronic VEGs of IE. The standardization procedure at the time of the initial study and use of identical gain settings in subsequent studies are key factors in making this distinction.     

Daily administration of the progesterone antagonist RU 486 prevents implantation in the cycling guinea pig.

Since progesterone is required to prepare the endometrium for implantation of an embryo, a progesterone antagonist may inhibit nidation and thus prevent pregnancy. We addressed this possibility in the guinea pig, the small laboratory animal whose reproductive physiology most resembles that of women. Daily administration of the antiprogestin RU 486 (0, 1, 2, or 3 mg/kg, subcutaneously) for 9 days after mating inhibited implantation in a dose-dependent fashion. When this compound was given daily throughout the estrous cycle, cyclic vaginal changes, ovulation, and mating were suppressed in up to 17%, 28%, and 55% of animals, respectively. Two of seven mated female animals receiving RU 486, 1 mg/kg/day, had implantation sites. Nidation was completely blocked at higher doses. Thus daily antiprogestin administration prevented pregnancy in sexually active, normally cycling guinea pigs. A similar strategy using a daily antinidatory dose of an antiprogestin may offer a novel approach to human fertility control.     

Cumulative incidence of rheumatic fever in an endemic region: a guide to the susceptibility of the population?

Aboriginal Australians in northern Australia are subject to endemic infection with group A streptococci, with correspondingly high rates of acute rheumatic fever and rheumatic heart disease. For 12 communities with good ascertainment, the estimated lifetime cumulative incidence of acute rheumatic fever was approximately 5.7%, whereas over the whole population, with less adequate ascertainment, the cumulative incidence was only 2.7%. The corresponding prevalences of established rheumatic heart disease were substantially less than the cumulative incidences of acute rheumatic fever, at least in part because of poor ascertainment. The cumulative incidence of acute rheumatic fever estimates the proportion of susceptible individuals in endemically exposed populations. Our figures of 2.7-5.7% susceptible are consistent with others in the literature. Such comparisons suggest that the major part of the variation in rheumatic fever incidence between populations is due to differences in streptococcal exposure and treatment, rather than to any difference in (genetic) susceptibility.     

Prenatal cytogenetic diagnosis of 1,400 consecutive amniocenteses.

We report on the incidence of chromosomal abnormalities in 1,400 amniocenteses. Thirty-one cases (2.21%) were found to have various types of chromosomal abnormality. The majority of abnormal cases (54.84%) were trisomies. All individuals with trisomic fetuses chose to terminate the pregnancy with the exception of one who gave birth to a Down's syndrome child. However, fetuses with apparently balanced translocations were phenotypically normal at birth.     

Indications for operation when peritonitis occurs in patients on chronic ambulatory peritoneal dialysis

Although peritonitis is a common complication in patients on CAPD, laparotomy is necessary in only a small proportion of instances. In order to determine the most reliable method to identify which patients require laparotomy, 78 episodes of peritonitis were studied over a 27 month period. History, physical examination and routine laboratory parameters were not useful. If multiple enteric organisms were cultured from a patient and abdominal pain persisted, the results of laparotomy always revealed significant abdominal pathologic findings. No patient required laparotomy if multiple enteric organisms were not recovered. These findings suggest that the only reliable parameter in the selection of patients for laparotomy is the presence of multiple enteric organisms in the dialysate. When abdominal pain persists in a patient with multiple enteric organisms, a laparotomy should be performed.