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PubMed1982

The effect of dexamethasone on the initiation of beta-globin gene transcription in differentiating Friend cells.

Plasmid subclones of the 5' and 3' regions of the beta major-globin gene have been used as probes to assay the level and character of the transcripts of this gene in differentiating Friend erythroleukemia cells treated with dexamethasone. Using an S1 nuclease protection protocol, it is shown that dexamethasone reduces the amount of precursor-specific sequences in differentiating Friend cells within 30 min without significantly affecting the nuclear turnover of these molecules. The sites of initiation and termination of transcription remained the same during the shutdown of transcription by the hormone. In contrast to the situation in Friend cells, dexamethasone failed to inhibit globin gene transcription in three normal erythroid tissues. The manner in which the Friend virus complex might render the globin genes sensitive to glucocorticoids is discussed.

Animals↗
PubMed1983

Effects of in vivo Friend leukemia virus infection on levels of serum thymic factors and on selected T-cell functions in mice.

The levels of serum thymic factor(s) (STF), of Thy-1.2 positivity of splenocytes [as measured by their azathioprine (AZ) sensitivity], and of Thy-1.2-positive "spontaneous" spleen rosette-forming cells (SSRFCs), as well as the presence of infectious virus in the thymus, were assessed as a function of time after virus inoculation in susceptible DBA/2, partially resistant BALB/c, and fully resistant C57BL/6 mice given the polycythemia- or anemia-inducing strain of Friend leukemia virus (FLV-P and FLV-A, respectively). As early as Days 2 to 3, the levels of STF and of AZ sensitivity of splenocytes were profoundly decreased in DBA/2 mice, and, to a lesser extent, in BALB/c mice given FLV-P; however, SSRFCs/spleen were increased in both mouse strains. Conclusive evidence of infectious FLV-P was obtained in the thymuses of DBA/2 mice soon after infection. In mice of the same strains infected with FLV-A, STF levels were similarly decreased, but AZ sensitivity of splenocytes was unaffected, and SSRFCs were decreased. Evidence of early FLV-A infection in the thymus of DBA/2 mice was likewise obtained. In C57BL/6 mice given FLV-A, STF levels, AZ sensitivity of splenocytes, and SSRFC showed changes similar to, but of lower magnitude than, those in BALB/c mice. On the other hand, in C57BL/6 mice given FLV-P, the decrease in STF and AZ sensitivity was almost as pronounced as in susceptible DBA/2 mice in the face of complete absence of infectious virus or viral markers in the thymuses. The observed changes are ascribed to virus infection in view of the following: (a) good temporal correlation between these changes and virus infection; (b) absence of any change in mice given heat-inactivated viruses or spleen homogenate of normal DBA/2 mouse spleen; (c) overall good correlation between mouse genotype and genetic (Fv-1 and Fv-2) restrictions of virus infection on one hand and the magnitude of the observed changes on the other. In particular, the decrease in STF and SSRFC levels is ascribed to the replication-competent (Friend-murine leukemia virus) component of Friend leukemia virus complex, whereas the decrease in AZ sensitivity of splenocytes and the increase of SSRFCs are ascribed to the defective spleen focus-forming virus component of the complex. All changes described so far were transient, since they were not detectable beyond 42 days after virus inoculation in overtly leukemic animals. The observed derangements of thymus-derived immune functions may play an important cofactor role during the onset of leukemia in mice genetically permissive to Friend leukemia virus replication and transformation, but they do not seem relevant to the maintenance of leukemia.

Animals↗
PubMed1981

Isolation of transplantable erythroleukemia cells from mice infected with helper-independent Friend murine leukemia virus.

The Friend virus complex contains a helper-independent retrovirus, F-MuLV, and a replication-defective retrovirus, SFFV. Murine erythroleukemia cell lines (MEL) have been isolated previously from the leukemic tissues of mice infected with such stocks of Friend virus complex. Since our laboratory has shown that either F-MuLV or SFFV can induce a lethal erythroproliferative disease, it has been unclear which of the properties of conventional MEL cells were causally related to the infection of these cells by F-MuLV and which properties were related to the infection of these cells by SFFV. In this article, we have focused on the helper-independent component of the Friend virus complex, F-MuLV clone 57, which has recently been purified by molecular cloning. We report a method for the reproducible isolation of a new type of murine erythroleukemia cell that can be isolate from mice infected with F-MuLV clone 57. We have designated these cells as 57 TP-1, indicating their origin from mice infected with F-MuLV clone 57 and their characteristics as transplantable erythroleukemia cells. Upon subcutaneous, intraperitoneal, or intravenous inoculation of these cells, 57 TP-1 cells grow in the hematopoietic organs of the recipient mice. No subcutaneous or intraperitoneal nodules occur. Both F-MuLV and a Friend MCF virus can be detected in these cells, but no evidence to SFFV can be found.

Animals↗
PubMed1982

Friend viral pathogenesis in C57BL/6 reversible DBA/2 allophenic mice.

Infection of mice with Friend erythroleukemia virus initially causes massive proliferation of erythroid precursors accompanied by splenomegaly and reticulocytosis. Strains of mice differ among themselves in susceptibility to Friend virus and one of the major genes affecting the early response to viral infection is Fv-2. Allophenic mice compounded from a resistant strain C57BL/6 (Fv-2rr) and a susceptible one DBA/2 (Fv-2ss) were infected with the polycythemic strain of Friend virus to determine whether susceptibility/resistance was limited to cells of the respective genotypes or if there was an influence across the genotypic barriers. The manifestations of viral pathogenesis monitored were splenomegaly, reticulocytosis and leukocytosis. In addition, the proportion of red cells of the two genotypes in each animal was monitored before and after viral infection by analyses for strain specific electrophoretic variants of hemoglobin and glucose phosphate isomerase. The group of allophenic mice with 25% or more susceptible-strain red blood cells all developed symptoms of virus-induced disease and also revealed dramatic increases in the number of red cells of the susceptible-strain genotype. Thus, no evidence for protection of susceptible-strain cells by ones of the resistant strain could be observed and the disease developed primarily in susceptible strain cells. On the other hand infected animals with 15% or less DBA/2 red cells were severely retarded in the development of Friend disease. Under these circumstances susceptible strain target cells might fail to undergo viral induced replication as a result of direct protection by resistant strain cells. Alternatively, other more complex mechanisms might be involved such as protective anti-viral immune reactions.

Animals↗
PubMed1978

Incapacity of hematopoietic stem cell-deprived mice to produce tumor colonies induced by Friend virus-infected cells.

The role of host hematopoietic stem cells in the formation of tumor colonies in the spleen of (C57BL/6 X DBA/2) F1 mice after grafts of spleen cells from Friend virus (FVP)-infected donors has been investigated. Hematopoietic stem cell compartments of recipient mice were destroyed by Myleran treatment or gamma-ray irradiation. A single injection of Myleran reduced the pluripotent hematopoietic stem cells (CFU) and the erythropoietin responsive cells (ERC) in polycythemic mice to around 1% of that of controls. Repeated injections of erythropoietin (EPO) restored the erythropoietic precursor cell (ERC) population. Pretreatment of polycythemic hosts with Myleran totally suppressed the tumor colony forming ability of grafted Friend virus-infected spleen cells, whereas it had no effect on tumor colonies produced by inoculation of true tumoral Friend cells. After EPO injections in such Myleran-treated recipients, with a consequent appreciable ERC repopulation, splenic colonies again occurred. Similar results were obtained in hosts whose ERC populations were damaged by irradiation. These data strongly suggest that splenic colonies result from the proliferation of the host cells transformed by virus released by Friend virus-infected cells and not from the proliferation of donor tumor cells.

Animals↗
PubMed1995

Phosphoinositide signaling in nuclei of Friend cells: tiazofurin down-regulates phospholipase C beta 1.

Previous investigations have demonstrated the presence of conventional lipid kinases and phospholipase C (PLC) activities in nuclei of Friend erythroleukemia cells. Moreover, when Friend erythroleukemia cells are treated for 96 h with the antitumor drug tiazofurin, the induction of erythroid differentiation is accompanied by changes in amounts of both phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate due to the inhibition of an uncharacterized nuclear PLC activity. Here, we show that the nuclear PLC beta 1 isoform is down-regulated by tiazofurin (5 microM) treatment of Friend erythroleukemia cells as shown by both Western blot and Northern blot analyses for PLC beta 1 message. This indicates that PLC beta 1 down-regulation is tightly linked with erythroid differentiation of Friend erythroleukemia cells and that the autonomous nuclear signaling via inositol lipid cycle can be controlled by the antitumor drug tiazofurin.

Animals↗
PubMed1994

Inhibition of Friend cells proliferation by spi-1 antisense oligodeoxynucleotides.

The spi-1 proto-oncogene encodes the transcription factor PU.1 which is normally expressed in all hematopoietic cell lineages except in T cell lines. During the murine acute erythroleukemia induced by the Friend retrovirus, SFFV, spi-1 deregulation by insertional mutagenesis results in the overexpression of Spi-1/PU.1 in the malignant proerythroblastic cell. To assess the Spi-1 role in the proliferation and the differentiation arrest of the Friend tumor cells we inhibited spi-1 gene expression in two Friend cell lines by using antisense oligodeoxyribonucleotides. Proliferation and cloning efficiency of both cell lines were significantly inhibited by spi1 antisense. This antiproliferative effect was not related to an apparent maturation of erythroleukemic cells demonstrating that repression of spi-1 expression is not sufficient per se to restore the ability of the proerythroblastic cells to spontaneously differentiate in mature erythroblasts. These data suggest that the spi-1 gene would be involved in the Friend leukemic process by promoting the proerythroblast to proliferate.

Base Sequence↗
PubMed1997

Folate deficiency delays the onset but increases the incidence of leukemia in Friend virus-infected mice.

Clinical studies have indicated that folate deficiency may enhance the development of various malignancies. In animal studies that examined the effect of folate deficiency on malignancies, conflicting results have been reported. In some studies, folate deficiency increased the development and growth of malignant tumors; in others, it decreased the development and growth of malignancies. We examined the effect of transient folate deficiency on the development of leukemia in mice infected with the anemia-inducing strain of Friend leukemia virus. Friend virus disease can be considered as a model for human acute leukemias that are preceded by a preleukemic period. These include leukemias that develop in patients who received previous chemotherapy and/or radiation therapy, as well as patients with chronic granulocytic leukemia or myelodysplasia. Folate deficiency around the time of Friend virus-infection delayed the onset but increased the incidence of leukemia. The rates of rearrangement of the Spi-1 (PU.1 ) oncogene by provirus integration and alteration of the p53 tumor-suppressor gene were the same in leukemia cell lines derived from folate-deficient mice as they were in cell lines from control mice. These results indicate that folate deficiency did not exert its enhancement of leukemogenesis through changes in either Spi-1 or p53, even though these two genes have been found to be the most frequently altered ones in Friend virus-induced leukemias. Our results suggest that folate deficiency may enhance the development of acute leukemia in patients who are at high risk for this disease.

Animals↗
PubMed1978

Induction of erythroid differentiation in Friend leukemia cells by bromodeoxyuridine.

Treatment of Friend leukemia cells with BrdU, the thymidine analog which interferes with DMSO induced differentiation in these cells as well as the expression of differentiated character in many other cell systems, is capable of inducing erythroid differentiation. Globin mRNA, as assayed by hybridization to globin cDNA, increases 2.5- to 30-fold after appropriate treatment with BrdU. This effect was observed with several different subclones of three independent Friend tumor cell lines. After BrdU treatment, globin mRNA content may reach up to 10-20% of the levels in DMSO induced cultures. The induction of erythroid differentiation is also apparent when accumulated heme content or the appearance of benzidine positive cells is monitored. One Friend cell line (745) we examined was not induced by BrdU although it incorporated an amount of BrdU into its DNA comparable to that incorporated by the other cell lines. In addition, BrdU did interfere with DMSO induction in this cell line. These results suggest that two different mechanisms may be operative in regulating erythroid differentiation in Friend leukemia cells. While BrdU interferes with the mechanism activated by DMSO treatment, this analog could independently activate an alternative mechanism.

Benzidines↗
PubMed1979

Perturbation of growth and differentiation of Friend murine erythroleukemia cells by 5-bromodeoxyuridine incorporation in early S phase.

Cultured Friend murine erythroleukemia cells (Friend cells) are induced to undergo erythroid differentiation when grown in the presence of dimethylsulfoxide (DMSO) and other compounds. The effects of unifilar substitution of bromouracil (BU) for thymidine in the DNA (BU-DNA) of Friend cells were examined. Cells were grown in the presence of 5-bromodeoxy-uridine (BrdU) for one generation, then centrifuged and resuspended in medium containing DMSO without BrdU. These cells exhibited a delay in the appearance of heme-producing, benzidine-reative (B+) cells and a decreased rate of cell proliferation in comparison to the control not containing BU-DNA. A transient inhibition of entry into S phase was observed when control cells or cells containing BU-DNA were grown in the presence of DMSO) for 10 to 20 hours. This transient inhibition was increased in the BrdU culture. Thus BU-substitution in Friend cells alters other cellular functions in addition to erythroid differentiation. The rate of increase in the percent of cells committed to differentiate (those forming B+ colonies in plasma clots) was similar in the BrdU and control cultures until 40 to 50 hours. After this time, a delay in the appearance of committed cells was observed in the BrdU culture. The effect of BrdU on the appearance of B+ cells was more pronounced and occurred earlier than its effect on the rate of commitment. Therefore, the delay in the appearance of B+ cells in the BrdU culture was due primarily to perturbation of post-commitment events such as the accumulation of hemoglobin. We also examined the effect on growth and differentiation after BrdU was incorporated during different intervals of S phase in cells synchronized by centrifugal elutriation or by double thymidine block and hydroxyurea treatment. The delay in the appearance of B+ cells and inhibition of cell proliferation were only observed when BrdU was incorporated in the first half of S phase. BrdU (10 muM) had no effect on growth or differentiation when present during late S or G1 and G2. These results, using two very different methods to achieve cell synchrony, indicate that the effects of BrdU on growth and differentiation described above are due to its incorporation into DNA sequences replicating during early S.

Animals↗
PubMed1984

Friends can be good medicine: an excursion into mental health promotion.

This paper describes Friends Can Be Good Medicine, a multi-media, mental health promotion campaign conducted in 1982 throughout California. The creative design, pilot-test, implementation and results are reviewed. Conceptually, Friends was derived from evidence linking supportive personal relationships with increased physical and mental health. Three major campaign elements were: broadcast media, an array of educational materials, and community activities. Evaluation findings revealed that Friends was most effective when campaign elements reinforced one another. Resulting changes in knowledge, attitudes, and intentions among those reached by Friends were maintained after one year. It is contended that, for better or worse, mass media is part of the health care system.

Attitude↗
PubMed1988

Friendly visiting as a means of informing homebound senior citizens of health-related community services.

Health-related community services designed for the senior population include delivered and congregate meals, visiting health-aides and nurses, adult day care and telephone and postal checks. Friendly visiting programs may prove helpful in informing homebound senior citizens of these health-related community services. The purpose of this study was to investigate the effectiveness of friendly visiting as a means of informing homebound senior citizens of health-related community services. Visited homebound seniors were contrasted with homebound controls. Visiting occurred in two forms. One group received visitors from an ongoing friendly visiting program (VISITING AS IS) in their community and a second group received visitors who were specifically trained to convey community referral information (REACH). A control group received no visiting of any kind. All three groups were administered pre- and post-interviews asking their knowledge of eight community services. At the end of the twelve week program, the post-interview means of the two homebound visited groups did differ significantly from the mean of the unvisited controls when contrasts were made using pre-interview scores as the covariate, F(2,78) = 8.19 (p less than .05). The homebound senior citizens visited by the REACH visitors increased their knowledge of services significantly more than the homebound seniors contacted by VISITING AS IS visitors F(1,52) = 7.20 (p less than .01). While the simple act of being visited did lead to increased knowledge at the .05 level, trained visitors were able to convey such information to a greater degree (p less than .01). Awareness of community services can be effectively transmitted by friendly visitors and improved when a program is implemented to train the visitors to meet his goal.

Aged↗
PubMed2004

Differential contribution of parents and friends to smoking trajectories during adolescence.

The purpose of this study was to assess the relative contribution of friends' and parents' smoking on the age of smoking initiation. A sample of 812 preadolescents, who were part of an accelerated longitudinal design, participated in the study over a 4-year period. Three smoking trajectory groups were first established: an age 11-12 starters group (5.7% of the sample), an age 12-13 starters group (11.1% of the sample), and an age 13-14 starters group (7.9% of the sample). A fourth trajectory group included the children who had not started smoking by age 15 years and who represented the majority of the participants (75.4%). After controlling for parental education, gender, and participants' behavioral and academic maladjustment, a series of logistic regressions revealed that parents' smoking assessed during the same year predicted membership in the age 11-12 starters trajectory group. Both parents' and friends' smoking predicted membership in the age 12-13 starters group. Finally, only friends' smoking predicted membership in the age 13-14 starters group. The results are discussed in light of the controversy about the contribution of parents' and friends' smoking behavior to smoking initiation in adolescents.

Adolescent↗
PubMed2006

Preadolescents' report of exposure to violence: association with friends' and own substance use.

PURPOSE: To evaluate whether children's Exposure to Violence (EV) is associated with their own or their friends' use of alcohol, tobacco, and other drugs (ATOD). METHODS: The Violence Exposure Scale for Children-Revised (VEX-R) and the Substance Exposure Assessment (SXA) were given to 104 children participating in a longitudinal study of in-utero cocaine exposure (IUCE) at age 8.5, 9.5, and 11 years. Survival analyses evaluated the association of the quartile of VEX total score (higher scores indicating more violence exposure) at age 8.5 years, with time to first report of their own and their friends' use of ATOD from age 8.5-11 years. RESULTS: The sample consisted of 90% African-American/Caribbean children (mean age 8.5 years, SD 3 years), 53% males, and 49% with IUCE. The percentage of children who reported having substance-using friends was 12% at 8.5 years, 25% by 9.5 years, and 45% by 11 years. In multivariate survival analyses controlling for caregiver type, IUCE category, and child gender, children in the upper quartile of VEX-R total score at age 8.5 years were at significantly greater risk of having reported friends' use of ATOD by age 11 compared to those in the first through third quartiles (hazard ratio = 2.2; 95% CI = 1.14, 4.23; p = .02). Quartiles of the VEX score, however, were not significantly associated with children's acknowledgment of their own use (p = .85). CONCLUSIONS: Our findings suggest an association between EV in childhood and report of peer ATOD use at school age. Campaigns to prevent ATOD use should address the impact of childhood exposure to violence.

Child↗
PubMed2003

Transplant Friends: an interactive education program for patients awaiting kidney transplantation.

BACKGROUND: Organ transplantation is the preferred treatment for end-stage renal disease. Renal transplant recipients are surviving longer with a better quality of life. Although many hospitals have transplant education programs in place, transplant patients indicate that there is a need for additional information. Transplant Friends is a program designed to meet these needs. PATIENTS AND METHODS: At the University of Alberta, 128 patients attended the Transplant Friends program between September 2002 and February 2003. Each patient completed an evaluation form consisting of 15 questions designed to evaluate patient's satisfaction regarding session content, ease of scheduling, and the sessions facilitators. Responses were recorded using 5-point Likert scales. RESULTS: All 128 participants completed the questionnaires. The predominantly male (59.1%) and Caucasian (91.6%) population had a median age of 49.1 years. Of the 128 patients, 110 patients (86%) felt that the content of the program met or exceeded their expectations; 120 patients (94%) felt the program facilitators met or exceeded their expectations; and 113 patients (88%) evaluated the scheduling favorably. CONCLUSION: Patients require complete information prior to renal transplantation to make an informed decision about whether to proceed with transplant as well as to enhance the overall transplant experience. Patients evaluated the Transplant Friends program as successfully meeting these needs through a comprehensive interactive teaching program. We recommend that institutions performing renal transplants incorporate an educational program such as Transplant Friends during the workup process of this unique patient population.

Alberta↗
PubMed2000

Body image and body change methods in adolescent boys. Role of parents, friends and the media.

OBJECTIVE: This study examines sociocultural influences affecting both body image and body change methods in adolescent boys. METHODS: Twenty boys in grade 7 (aged 12-13) and twenty boys in grade 9 (aged 14-15) were individually interviewed. The influence of parents, siblings, friends and the media on both body image and body change methods was evaluated. RESULTS: For approximately a third of the boys, parents, siblings, friends and the media were perceived to have at least some influence over boys' feelings about their bodies and body change methods. In particular, feedback from mothers and female friends were viewed as having a positive impact on boys' body image whereas feed-back from fathers and male friends was viewed as more important in influencing body change methods. The media was also viewed as contributing to boys' body satisfaction but it was seen to encourage greater exercise to alter body size and shape. CONCLUSION: The differences and similarities between the sociocultural messages received by males and females are discussed. The implication of these findings in fostering better health among adolescent males are explored.

Adolescent↗
PubMed2003

"Because you know there's an end to it": caring for a relative or friend with advanced breast cancer.

OBJECTIVE: The aim of this paper is to delineate the particular nature of the end-of-life care experience from the perspective of family members and friends. Ideas drawn from feminist analyses of caring and the sociology of death and dying are used to illuminate study respondents' accounts. METHODS: Qualitative study with people who cared for a family member or friend who died of breast cancer. Two interviews were conducted with each of 12 study participants, and one carer responded by letter to a series of questions drawn from the interview guide. Accounts were analyzed with reference to grounded theory methods. RESULTS: The analysis presented here suggests that anticipating the death of an ill relative or friend generates imperatives to care, imperatives that are both "felt" and linked to wider social structures and processes. The value assigned to closeness with the ill person can be seen to reflect cultural injunctions toward a "good death," and to shape informal carers' perceptions of their labor. Also discussed in this paper are the complex negotiations undertaken by relatives and friends, for the life and death of someone with advanced cancer. SIGNIFICANCE OF RESULTS: This paper offers insight into the social processes of caregiving, revealing how care may be shaped in particular ways by an awareness of approaching death.

Adult↗
PubMed1997

Close friend and group influence on adolescent cigarette smoking and alcohol use.

The relative influence of adolescents closest friends and their friendship group on their cigarette smoking and alcohol use was investigated in a short-term, longitudinal study of 1,028 students in the 6th, 8th, and 10th grades in 2 school systems. The amount of influence over the school year was modest in magnitude and came from the closest friend for initiation of cigarette and alcohol use. Only the friendship group use predicted transition into current cigarette use, whereas only the close friend use predicted transition into current alcohol use. Both group and close friends independently contributed to the prediction of adolescents' drinking to intoxication. No difference in the amount of influence, was found between stable and unstable close friendships or friendship groups; neither grade nor gender of the adolescents related to the amount of influence.

Adolescent↗