The stem cell marker prominin-1/CD133 interacts with vascular endothelial growth factor and potentiates its action

Prominin-1, a pentaspan transmembrane protein, is a unique cell surface marker commonly used to identify stem cells, including endothelial progenitor cells and cancer stem cells. However, recent studies have shown that prominin-1 expression is not restricted to stem cells but also occurs in modified forms in many mature adult human cells. Although prominin-1 has been studied extensively as a stem cell marker, its physiological function of the protein has not been elucidated. We investigated prominin-1 function in two cell lines, primary human endothelial cells and B16-F10 melanoma cells, both of which express high levels of prominin-1. We found that prominin-1 directly interacts with the angiogenic and tumor survival factor vascular endothelial growth factor (VEGF) in both the primary endothelial cells and the melanoma cells. Knocking down prominin-1 in the endothelial cells disrupted capillary formation in vitro and decreased angiogenesis in vivo. Similarly, tumors derived from prominin-1 knockdown melanoma cells had a reduced growth rate in vivo. Further, melanoma cells with knocked down prominin-1 had diminished ability to interact with VEGF, which was associated with decreased bcl-2 protein levels and increased apoptosis. In vitro studies with soluble prominin-1 showed that it stabilized dimer formation of VEGF₁₆₄, but not VEGF₁₂₁. Taken together, our findings support the notion that prominin-1 plays an active role in cell growth through its ability to interact and potentiate the anti-apoptotic and pro-angiogenic activities of VEGF. Additionally, prominin-1 promotes tumor growth by supporting angiogenesis and inhibiting tumor cell apoptosis.     

A double-blind, placebo-controlled trial of reserpine for the treatment of cocaine dependence

BACKGROUND: Cocaine's increase of dopamine is strongly associated with its reinforcing properties and, thus, agents that reduce dopamine have received much attention as candidate cocaine-dependence treatments. The potential efficacy of reserpine, a dopamine depletor, for treating cocaine dependence is suggested by both pre-clinical research and a small clinical trial. METHOD: One hundred and nineteen participants who met DSM-IV criteria for cocaine dependence were enrolled into this 12-week, double-blind, placebo-controlled outpatient trial. Participants received either reserpine (0.5 mg/day) or matching placebo. All participants received 1h of manualized individual cognitive behavioral therapy on a weekly basis. Outcome measures included cocaine use as determined by self-report confirmed with urine benzoylecgonine results, cocaine craving, addiction severity index scores, and clinical global impression scores. Safety measures included adverse events, EKGs, vital signs, laboratory tests, and the Hamilton Depression Inventory. RESULTS: Seventy-nine participants (i.e., 66%) completed the 12-week trial. The safety results suggest that reserpine was safe and well tolerated by the participants. The efficacy measures indicated no significant differences between reserpine and placebo. CONCLUSION: These results do not support the efficacy of reserpine as a cocaine-dependence treatment.     

Survival of neural precursor cells in growth factor-poor environment: implications for transplantation in chronic disease

A key issue for therapeutic neural stem cell transplantation in chronic diseases is the long-term survival of transplanted cells in the brain. The normal adult central nervous system does not support the survival of transplanted cells. Presumably, the limited availability of trophic factors maintains the survival of resident cells but is insufficient for supporting the survival of transplanted cells. Specifically, in multiple sclerosis, a chronic relapsing disease, it would be necessary to maintain long-term survival of transplanted cells through phases of relapses and remissions. It may be beneficial to transplant cells as early as possible, in a form that will keep their survival independent of tissue support and ready for immediate mobilization upon tissue demand during disease relapse. In the present study, we examined whether, in the form of neurospheres, multipotential neural precursor cells (NPCs) survive in a growth factor-poor environment while maintaining their potential to respond to environmental cues. We found that after removal of growth factors from the culture medium of neurospheres in vitro, NPC proliferation decreased significantly, but most cells survived for a prolonged time and maintained their stem cell characteristics. After re-exposure to growth factors, neurosphere cells resumed proliferation and could differentiate along neural lineages. Furthermore, neurospheres, but not single NPCs, that were transplanted into the brain ventricles of intact animals survived within the ventricles for at least a month and responded to induction of experimental autoimmune encephalomyelitis and brain inflammation by extensive migration into the brain white matter and differentiated into glial lineage cells.     

Israeli men in nursing: social and personal motives

AIM: This paper intends to explore what leads Israeli men to choose nursing as their profession. BACKGROUND: In the early years of nursing education in Israel, like in other western societies, men were excluded from the profession. Shortage in nursing personnel and urgent needs led to recruitment of men into the profession for a short period of time. Only since the early 1990s the nursing profession is experiencing a gradual but steady influx of men. Yet, nursing is generally perceived as women's work, and men have to cope with the stereotypes attributed to them as a prominent minority in a profession primarily occupied by women. Currently, no study had examined who are the Israeli men who are willing to enter the profession and why. METHODS: A 52-item questionnaire was distributed among all registered female and male nurses in three general and three psychiatric hospitals during 1997-98. The questionnaire covered sociodemographic characteristics, exposure to the profession and reasons for choosing the profession. The response rate of 74% included 123 male and 137 female registered nurses. CONCLUSIONS: Early exposure to the profession and the fact that the majority of male nurses belong to ethnic minorities and recent immigrants to the Israeli society were the most prominent factors in the selection of the nursing profession by these men. Surprisingly, economic considerations did not constitute a compelling motive in this population.     

Hypertension and cognitive functioning among the elderly: an overview

This paper reviews the longitudinal studies in which the association between hypertension and cognitive functioning has been explored. The findings of these studies are far from being consistent: positive, adverse, or no relationships between cognitive performance and blood pressure have been reported. In some studies, cognitive functioning was related only to systolic blood pressure, whereas in others, it was related to diastolic blood pressure alone. Most probably, the inconsistency is due to the variability in research design, the measures employed, and data management. Some of the main methodological issues are the wide range in the age of the subjects and the variability in hypertension at baseline. Length of exposure to hypertension was rarely considered, and the search for the possible effects of the different antihypertensive treatments on cognitive ability is in its infancy. Many studies seek to identify cognitively impaired elderly and do not distinguish between the different types of dementia or the different cognitive domains. Thus, the possibility that hypertension affects specific cognitive functions has not been explored. The use of subdivisions of blood pressure values may have obscured nonlinear relationship. Nevertheless, the pattern that emerges is that midlife hypertension enhances cognitive impairment later in life, but at old age, mild hypertension may increase cognitive performance. Directions for future research to further elucidate the complex relationship between age, blood pressure, and cognition are discussed.     

Prevalence and risk factors for erectile dysfunction in men with diabetes,hypertension, or both diseases: a community survey among 1,412 Israeli men

BACKGROUND: Erectile dysfunction (ED) and cardiovascular disease share common risk factors and may be further aggravated by medical treatment for reducing them. HYPOTHESIS: The study was undertaken to assess the prevalence of ED in patients with diabetes (DM), hypertension (HTN), or both diseases, and to evaluate the effect of patient age, medical treatment, and disease duration and control on the prevalence of ED in this population. METHODS: A group of 150 primary practitioners who had patients with known DM and/or HTN conducted a survey, utilizing IIEF-15, a 15-item multidimensional, self-administered questionnaire used for the clinical assessment of ED. Results: In all, 1,412 patients were included: 37% had DM, 38% had HTN, and 25% had both diseases. Their mean age was 55, 58, and 60 years, and 62, 46, and 67% had some degree of ED, respectively. The prevalence of ED increased with age and disease duration in each age group and was higher in subjects with DM than in those with HTN, especially in those aged < 65 years. Poor glycemic control was associated with a higher prevalence rate of ED early in the course of the disease. There was no significant difference in the prevalence of ED according to type and number of antihypertensive drugs. CONCLUSIONS: Erectile dysfunction is common among patients at high risk for cardiovascular disease because of diabetes and/or HTN. Diabetic men are affected earlier than those with HTN. Given the high frequency of ED in young patients with these risk factors, physicians should encourage an open discussion on the subject during routine visits to promote early detection and treatment.     

Lysyl oxidase-related protein-1 promotes tumor fibrosis and tumor progression in vivo

The lysyl oxidase gene family members function as extracellular matrix modulating enzymes. We have found that another member of this family, lysyl oxidase related protein-1 (LOR-1), is highly expressed in metastatic breast cancer-derived cell lines but not in the nonmetastatic estrogen-dependent MCF-7 cells. Furthermore, LOR-1 expression in periductal tumor cells of breast carcinomas is significantly correlated with increased tumor malignancy. MCF-7 cells expressing recombinant LOR-1 formed estrogen-dependent tumors that developed much slower than tumors derived from empty vector-transfected MCF-7 cells. The cells of these LOR-1-expressing tumors were surrounded by a high concentration of dense collagen fibers, and the tumors contained many fibrotic foci. Induction of fibrosis in vivo by lysyl oxidase-like enzymes has never been observed before and suggests that LOR-1 may function as an autonomous inducer of fibrosis. The appearance of fibrotic foci in spontaneous breast cancer tumors is correlated with poor prognosis and metastasis, and we, therefore, examined the invasiveness of the LOR-1-expressing tumors. LOR-1-expressing MCF-7 cells invaded the pseudocapsules surrounding the tumors. In contrast, vector-transfected MCF-7 cells did not invade the pseudocapsules. This observation suggests that LOR-1 enhances the malignancy of the tumors. Furthermore, the LOR-1-expressing tumor cells invaded blood vessels, nerves, and muscles adjacent to the tumor, indicating that the LOR-1-expressing MCF-7 cells acquired metastatic properties. We conclude that LOR-1 promotes tumor fibrosis and tumor invasiveness simultaneously, which indicates that these two processes may be associated.