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Biomedical subjects

M Wolfson

Publications and source records attributed to M Wolfson.

At least 73 records · Page 4Linked to original sources

The Health Utility Index: measuring health differences in Ontario by socioeconomic status.

The positive relationship between socioeconomic status (SES) and longevity has long been established. Comparable evidence exists for SES and morbidity, but observations of this relationship tend to be limited to specific health indicators. In this article, a comprehensive quantitative measure of health status, the Health Utility Index (HUI), is applied to an analysis of the relationship between SES and the health status of people aged 25 and over in Ontario. The HUI, based on a set of questions included in the 1990 Ontario Health Survey (OHS), provides a summary index of the health of each respondent. The OHS data show that lower levels of education, income, and occupation are associated with lower HUI values. Health status differences across SES groups are greater in late middle-age than at younger or older ages, a pattern consistent with the findings of other studies. The development of summary indicators like the HUI is part of a larger effort to construct measures for monitoring the health of Canadians.

Adult↗

Recombinant human erythropoietin utilization in Department of Veterans Affairs dialysis units.

This study was carried out to determine the use of recombinant human erythropoietin (rHuEPO) in the Veterans Affairs dialysis program and any strategies being carried out to enhance its effectiveness. The data were collected from a survey that was conducted using a questionnaire sent to all Veterans Affairs dialysis programs. The survey included all patients treated with hemodialysis or peritoneal dialysis for at least 3 months and who were receiving rHuEPO for at least 3 months. Patients diagnosis, age, length of time of dialysis, mode of dialysis, length of rHuEPO treatment, route of administration, assessment of iron stores, use of iron supplementation, and use of androgens were assessed by this questionnaire and analyzed for their effect on dose required to achieve a target hematocrit. Subcutaneous administration resulted in a significantly lower dose requirement compared with the dose required when rHuEPO was administered intravenously. Concomitant use of androgens resulted in a lower dose requirement for rHuEPO when it was given intravenously, but not when rHuEPO was given subcutaneously. The dose required to maintain the hematocrit at the designated level appeared to increase with time of treatment.

Adult↗

Reversal of the measles virus-mediated increase of phosphorylating activity in persistently infected mouse neuroblastoma cells by anti-measles virus antibodies.

To investigate the effect of persistent measles virus infection on signal transduction in cells of neuronal origin, the mouse neuroblastoma cell line NS20Y/MS, which is persistently infected with measles virus, was used. The results demonstrate an approximate 50% increase in total phosphorylation and a similar increase in protein kinase C (PKC) activity. Western blot analysis with anti-total PKC or anti-PKC-alpha antibodies revealed a significant increase in the level of an 80K immunoreactive PKC in NS20Y/MS cells. Following incubation of NS20Y/MS cells with polyclonal anti-measles virus antibodies, which down-regulate the level of measles virus proteins, total and PKC-mediated phosphorylation returned to the basal level of uninfected cells. This effect was reversible and removal of the antibodies resulted in restoration of the high level of total and PKC-mediated phosphorylation. The release of infectious measles virus was strongly inhibited by incubation of NS20Y/MS cells with the PKC inhibitor, 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7). These results demonstrate that measles virus induces elevation in cellular phosphorylation which is essential for measles virus production.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

The ability of young people to purchase alcohol without age identification in northeastern Minnesota, USA.

The purpose of this study was to determine the rate at which young people can purchase alcohol without age identification in off-premises businesses, and the factors which influence the rate of purchase. All retail outlets licensed to sell distilled spirits and/or full strength beer and wine in 28 northern Minnesota communities were visited on different occasions by three 21-year-old female buyers who appeared to be aged 19 or younger. These youthful buyers were able to purchase beer without age identification in 47% of the 336 purchase attempts. Almost four-fifths of the businesses sold beer to these buyers at least once in three attempts. These results provide clear evidence that many commercial off-sale businesses in the US supply alcohol to youthful buyers, and that practices vary significantly by community and by business. These results support the need for greater attention to availability as a factor in teenage drinking patterns.

Age Factors↗

Stimulation of virus production and induction of self-syncytium formation in human T-cell leukemia virus type I- and type II-infected T cells by 12-O-tetradecanoylphorbol-13-acetate.

Treatment of human T-cell leukemia virus type I (HTLV-I)- and HTLV-II-infected T-cell lines with 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated virus release. However, this stimulation was mainly detected at 42 to 48 h of treatment, whereas later virus release declined rapidly. During the first 48 h, TPA had no effect on cell growth, but later, the number of viable cells was profoundly lower in the TPA-treated than in the untreated cultures. This shift in virus release and cell number resulted from self-fusion of a large proportion of the virus-producing cells, which seemed to consequently enter into a dying process. This fusion, which resulted in syncytium formation, was strongly inhibited by anti-HTLV-I env monoclonal antibodies. Furthermore, no self-fusion was detected in three different uninfected T-cell lines similarly treated with TPA. On the other hand, stimulation of virus production by 3-methylcholanthrene (3-MC) treatment failed to induce self-fusion in the infected cells. Moreover, no syncytium was detected when these 3-MC-treated infected cells were cocultured with any of the TPA-treated uninfected cells. The effects of TPA on virus production and syncytium formation were both abolished by three different protein kinase C inhibitors. Taken together, these data suggest that the self-fusion observed in these experiments required both enhanced virus production and protein kinase C-phosphorylated viral or/and virally induced cellular component(s).

Cell Line↗

Lung management with perfluorocarbon liquid ventilation improves pulmonary function and gas exchange during extracorporeal membrane oxygenation (ECMO).

We investigated whether pulmonary function and gas exchange would improve with liquid perfluorocarbon ventilation (LV) during ECMO for severe respiratory failure. Lung injury was induced in 11 young sheep 15.1 +/- 3.7 kg in weight utilizing right atrial injection of 0.07 cc/kg oleic acid followed by saline pulmonary lavage. When (A-a)DO2 > or = 600 mmHg and PaO2 < or = 50 mmHg with FiO2 = 1.0, ECMO was instituted. Animals were then ventilated with either standard ECMO "lung rest" gas ventilator settings (ECMO, n = 5) or with "total" liquid ventilation at standard ventilator device settings (LIQ-ECMO, n = 6) utilizing perflubron (perfluooctyl bromide, Liquivent; Alliance Pharmaceutical Corp.). After 3 hours on ECMO, pulmonary physiologic shunt decreased (ECMO = 88 +/- 11% vs LIQ-ECMO = 31 +/- 1%; p < .001) and pulmonary compliance increased (ECMO = 0.50 +/- 0.06 cc/cmH2O/kg vs. LIQ-ECMO = 1.04 +/- 0.19 cc/cmH2O/kg; p < .001). The ECMO flow rate required to maintain the PaO2 in the 50-80 mmHg range was decreased significantly (ECMO = 116 +/- 14 ml/kg/min vs. LIQ-ECMO = 14 +/- 5 ml/kg/min; p < .001). In this model requiring extracorporeal support for severe respiratory failure, lung management with liquid ventilation improves pulmonary function and gas exchange.

Animals↗

Enforcement of the legal minimum drinking age in the United States.

We studied patterns and levels of enforcement of the legal drinking age in the United States. Major findings include: (1) rates of enforcement of the legal drinking age are very low; (2) actions against outlets or adults providing alcohol to youth are particularly rare; (3) two of every thousand occasions of illegal drinking by youth under 21 are estimated to result in an arrest; (4) five of every 100,000 youth drinking occasions are estimated to result in an Alcohol Beverage Control agency action against an alcohol outlet; (5) penalties appear too lenient to deter providers of alcohol; and (6) levels of enforcement of the drinking age vary significantly across states. Recommendations for public policy and enforcement actions include: (1) increased enforcement effort be directed at those who provide alcohol to underage youth; (2) significant increases in the numbers of Alcohol Beverage Control enforcement personnel are needed; (3) one or more officers in each local enforcement agency should be designated as the alcohol control officer; (4) regular sting operations in retail alcohol outlets are needed; (5) all police-attended alcohol-involved incidents should include a record of the source of the alcohol; and (6) effective long-term efforts will require attention to the broader environment that encourages youth drinking.

Adolescent↗

Synergistic effect of interferon-gamma and phorbol myristate acetate on superoxide production by human monocytes.

This study demonstrates a synergistic effect of IFN gamma and PMA on superoxide generation by human monocytes. A strict correlation was observed between the induction of superoxide production and PK-C activation by PMA alone. No such correlation was evident for IFN gamma. However, exposure of the cells to IFN gamma for 10 to 15 hr prior to PMA treatment enhanced both superoxide production and PK-C activation. Using protein kinase inhibitors, we noticed that while PMA exerted its effect by activating PK-C, IFN gamma operated via activation of calcium/calmodulin-dependent or some other calcium-dependent protein kinases. These kinases appeared to be involved in the effect of IFN gamma on superoxide production, as well as in its potentiation of PMA activity.

Cells, Cultured↗

Diet as culprit or therapy. Stone disease, chronic renal failure, and nephrotic syndrome.

A number of renal disorders are amenable to dietary manipulation. This article reviews nutritional strategies for the management of renal stone disease, chronic renal failure, and nephrotic syndrome. The first portion discusses dietary factors that promote urolithiasis and dietary recommendations utilized in the medical management of stone disease. The second segment discusses the pathophysiology of the progression of renal disease and nutritional interventions to delay progression. Finally, the third portion examines losses of protein, vitamins, and minerals in the nephrotic syndrome and makes recommendations for replacement.

Diet↗

Career earnings and death: a longitudinal analysis of older Canadian men.

There is widespread interest in disparities in health status across income groups and other classifications of socioeconomic status. In Canada, as in many other countries, there is considerable evidence showing such disparities. This study reports an analysis of male mortality at ages 65 to 74 in relation to socioeconomic characteristics, specifically employment and self-employment earnings histories during the 10 to 20 years prior to age 65, marital status, disability, and age at retirement. The analysis is based on administrative data from the Canada Pension Plan covering more than 500,000 individuals. Significant mortality gradients are found throughout the earnings spectrum. These gradients are also clearly evident in a multivariate context. The results illustrate the major potential of administrative data for research. Substantively, the results cast doubt on the primacy of causal explanations such as "reverse causality" and "health selection" and raise important questions regarding pension and health policy.

Aged↗

Background, conceptualization and design of a community-wide research program on adolescent alcohol use: Project Northland.

Project Northland is a community-wide research program funded by the National Institute on Alcoholism and Alcohol Abuse, for a 5-year period (1990-95). The aim of the study is to prevent or delay onset of alcohol use among young adolescents, as well as to reduce use among those who are already drinkers. Twenty communities were recruited in northeastern Minnesota, an area referred to as the Northland, Arrowhead or Iron Range region, and then were randomly assigned to either Education or Delayed Program conditions. The 10 Education school districts have agreed to participate in 3 years of intervention programs in schools, with parents and in the community-at-large. One group of young adolescents, the Class of 1998 (sixth grade students in the 1991-92 school year), form the study cohort. Surveys (1991-94) of the Class of 1998, their parents, community leaders and alcohol merchants are the primary components of the program's evaluation. Many conceptual and methodological questions emerged during the development of the research protocols for Project Northland over the past 2 years. These questions are the impetus for this article. Specifically, the focus on young adolescents and alcohol use was selected, as contrasted with older adolescents or with multiple problem behaviors. The project was designed using a community-wide model that addresses both supply and demand issues, rather than limited to a school-based model. Intervention strategies and evaluation methods were chosen that could address community-level as well as individual-level behavior change, which required the development and application of new technologies. The rationale for these decisions may be useful to others considering community-wide health promotion efforts.

Adolescent↗

The evolution, operation and future of Minnesota SAFPLAN: a coalition for family planning.

Health coalitions are a key means by which health educators can pursue policy objectives. However, little research to date has focused on the formation, operation and maintenance of health coalitions. This paper examines the development and operation of Minnesota SAFPLAN (Statewide Association for Family Planning), a coalition of organizations and individuals that came together in 1990 to address the problem of inadequate state-subsidized family planning funds. Data were collected through 31 structured interviews with coalition member representatives and lobbyists, review of documentary data, and participant observation in coalition activities and meetings. The paper focuses on SAFPLAN's recruitment of members and division of labor. Recruitment of member organizations of SAFPLAN relied heavily on existing interpersonal and interorganizational networks. While this allowed rapid mobilization of a coalition that was an effective force in the state legislature, it left important gaps in SAFPLAN's membership and lingering questions about whom the coalition was designed to represent. A division of labor that reflected variation in members' commitment, skill, knowledge and discretionary time was developed. The SAFPLAN model merits careful consideration by health educators and others interested in affecting public policy through health coalitions.

Family Planning Services↗

The population health impact of arthritis. POHEM Workshop Group.

The workshop was convened to develop quantitative estimates of the incidence of progressional musculoskeletal diseases in order to estimate the population health impact of arthritis. Estimates were developed for (a) the prevalence of arthritis, (b) a weighting strategy to adjust for the quality of life for the range of health states associated with arthritis, and (c) transition probabilities to represent the likelihood of disease onset and progression through the range of possible health states. A simulation "game" was designed to follow the progression of a cohort of 200 healthy persons or persons with arthritis, creating the basis for the estimation of transition probabilities and thus generating simulated longitudinal data that allow calculation of the quantitative estimate of the burden of illness from musculoskeletal diseases within the Canadian population.

Arthritis↗

Elevated activities of protein kinase C and tyrosine kinase correlate to leukemic cell aggressiveness.

We report a linkage between cell aggressiveness, protein kinase C (PKC) activity, tyrosine kinase (PTK) activity and serum requirement. We used 2 leukemic cell lines induced by Moloney murine leukemia virus (MLV). One line was highly aggressive (BS-24-1) and required low serum concentrations (3%) for optimal growth in comparison to the less aggressive line (RO2T) that needed 10% serum for optimal growth. The more malignant cells exhibited higher PKC and PTK activity. This activity was independent of serum concentration between 0.01-10%. In contrast, the weakly malignant cells need a high serum concentration (10%) for optimal PKC or PTK activity. Immunoblot analysis revealed a higher level of PKC protein in the BS-24-1 cells than in the RO2T cells. Serum induction of PKC activity did not change the amount of PKC protein in the cytosol or the membrane fractions, indicating post-translational mechanism regulation of PKC. We suggest that the aggressiveness of BS-24-1 resulted from its ability to become independent of growth regulation by serum factors, via autocrine stimulation of PKC and PTK.

Animals↗

Antibody-dependent transcriptional regulation of measles virus in persistently infected neural cells.

Application of neutralizing anti-hemagglutinin antibodies to mouse neuroblastoma cells (NS20Y/MS) persistently infected with measles virus (MV) leads to a significant reduction of viral structural proteins within 6 days. While the transcriptional gradient for MV-specific mRNAs remained unaffected upon antibody treatment, the total amount of MV-specific transcripts dropped by 80% after 24 h. The expression of genomic RNA was affected similarly, with slightly slower time kinetics. Both transcription and expression of the viral structural proteins could be completely reactivated when viral antibodies were removed from the tissue culture. The same findings could be obtained in rat glioma cells persistently infected with subacute sclerosing panencephalitis virus (C6/SSPE) but not in cells of nonneural origin. The data indicate that antibody-induced antigenic modulation affects the early stages of viral transcription within a few hours after the addition of antibodies and leads to an almost complete repression of viral gene expression in cells of neural origin.

Animals↗

Vitamin B-6 deficiency and renal function and structure in chronically uremic rats.

In preliminary studies, rats with chronic renal failure (CRF) demonstrated worsening renal function, as measured by urea clearance, when fed vitamin B-6-deficient diets. However, urea clearance is not a precise measure of glomerular filtration rate (GFR) and these studies did not indicate the mechanism for the reduced GFR. To measure renal function more precisely and to assess whether B-6 deficiency augments renal injury, we examined [14C]inulin clearance, urine oxalate excretion, and renal histopathology in rats with CRF pair fed to receive a pyridoxine-replete or -deficient diet for 3 or 6 wk. After 3 or 6 wk, pyridoxine-deficient rats had significantly lower [14C]inulin clearances and increased urine oxalate excretion. Histological evaluation indicated increased renal damage in kidneys from pyridoxine-deficient rats as compared with tissue from pyridoxine-replete rats. These findings suggest that in rats with CRF, vitamin B-6 deficiency reduces the GFR and increases renal scarring.

Animals↗

Regulatory effects of persistent measles virus infection on tumorigenicity and protooncogene expression in neuroblastoma cells.

MS is among the infectious agents known to persistently infect cells of the CNS. Clones NS20/Y and NS20/MS persistently infected with MS, both originating from the C1300 mouse neuroblastoma, were used. Multiple effects of the MS infection on the neuronal cell communication, expression of protooncogenes tumorigenicity and on the presence of immunoregulatory molecules were studied. Our results demonstrate that the level of the MHC class I and II antigens and beta-2 microglobulin was elevated in the MS infected cells. Furthermore, MS infection results in the significant increase of protein kinase C (PKC) activity concomitantly with the elevation of PKC-I specific m-RNA. The MS infection was found to affect also the expression of the protooncogenes known to associate with the PKC signaling system. Thus, the level of c-fos mRNA was elevated in the MS infected cells, while there were almost no changes in the c-myc gene expression. Ki-ras and Ha-ras appeared to be regulated differently by MS infection. The level of Ki-ras mRNA was unchanged, but the expression of the Ha-ras gene was markedly depressed, correlating well with the low tumorigenicity of the MS infected neuroblastoma cells in nude mice. Our results suggest that viral infection may be beneficial in certain cases of depressing oncogenic genes which may contribute to the development and maintenance of the malignant phenotype.

Animals↗