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Biomedical subjects

M Wolfson

Publications and source records attributed to M Wolfson.

At least 37 records · Page 2Linked to original sources

Adolescent alcohol use and the community health agenda: a study of leaders' perceptions in 28 small towns.

The study assessed leaders' perceptions of adolescent alcohol use as a public health issue in 28 small communities in northern Minnesota, as part of formative evaluation for a community-based intervention to reduce adolescent alcohol access and consumption. One hundred and eighteen leaders from five key community sectors were interviewed about their perceptions of social, health and alcohol-related problems in their communities. Analyses indicated that school representatives and police chiefs perceived adolescent alcohol use and related problems to be serious; newspaper editors mentioned other social problems more often; and mayors and business representatives did not perceive adolescent alcohol problems to be as serious. In relation to efforts to affect local policy, the study suggested government and business sectors in these communities may need to be educated about the problem to build its importance on the community agenda of health issues. Thus community leaders in some sectors may comprise a key target audience for intervention.

Adolescent↗

Perceived abuse and neglect as risk factors for suicidal behavior in adolescent inpatients.

The aim of this study was to assess relative risk of histories of different types of abuse (sexual, physical, and emotional) and neglect (physical and emotional) for suicidal behavior (attempts, ideation, and self-mutilation) in psychiatrically hospitalized adolescents. Seventy-one adolescent inpatients (34 boys, 37 girls) completed self-report measures of abuse and neglect, current suicidal ideation, and lifetime suicide and self-mutilation attempts. The prevalence of sexual and physical abuse was 37.5% and 43.7%, respectively, with 31.3% and 61% of youngsters reporting emotional and physical neglect. Fifty-one percent of youngsters had made suicide attempts, and 39% had self-mutilated. Suicide attempters were significantly more likely to be female, Latino, to report sexual, physical, and emotional abuse, and to endorse emotional neglect. In multivariate analyses, female gender, sexual abuse, and emotional neglect remained significant predictors of self-mutilation and suicidal ideation. Female gender and sexual abuse remained significant predictors of suicide attempts. These findings suggest that emotional neglect is an important and deleterious component of maltreatment experiences and may be a more powerful predictor of suicidal behavior in hospitalized adolescents than physical abuse, emotional abuse, and physical neglect.

Adolescent↗

Management of protein and energy intake in dialysis patients.

Malnutrition is not uncommon in patients with end-stage renal disease treated with maintenance dialysis. The presence of several abnormal parameters of nutritional status are reported to be predictive of poorer outcomes in these patients, compared to dialysis patients without evidence of malnutrition. This article describes methods that may be used to recognize the presence of malnutrition in end-stage renal disease patients and the management of protein and energy intake. Whether the correction of malnutrition will improve outcomes, such as morbidity and mortality, is unknown.

Dietary Proteins↗

Chronic treatment with lithium and pretreatment with excess inositol reduce inositol pool size in astrocytes by different mechanisms.

Chronic treatment with a lithium salt is the classical treatment for manic-depressive disorder. It is hypothesized that the therapeutic action of lithium is caused by its inhibition of inositol phosphatases which leads to a relative deficiency of inositol and, therefore, an impairment of inositol recycling and production of precursor for the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). However, peculiarly enough, treatment with high doses of inositol also has an antidepressant effect. In the present work, we have studied the acute and chronic effects of lithium and of excess inositol, in separation or together, on accumulation of 50 microM [3H]inositol (a physiologically relevant concentration) into primary cultures of mouse astrocytes. Two parameters were investigated: (1) rate of unidirectional uptake across the cell membrane (measured during short-term exposure to the radioisotope), and (2) magnitude of the intracellular pool of inositol, equilibrating with extracellular inositol (measured during long-term exposure to the radioisotope). Inositol uptake was highly concentrative and occurred with a Km of approximately 500 microM and a Vmax of 1.5 nmol/min/mg protein. The uptake rate was not affected by either acute or chronic treatment with LiCl (or both), but it was substantially reduced ('down-regulated') after pretreatment with a high concentration of inositol. The inositol pool size was decreased to a similar extent as the uptake rate by previous exposure to excess inositol. In spite of the fact that inositol uptake rate was unaffected by lithium, the magnitude of the inositol pool was significantly decreased by chronic treatment with a pharmacologically relevant concentration of LiCl (1 mM), but not by treatment with lower concentrations. This decrease is likely to reflect a reduction in either inositol synthesis or replenishment of inositol from IP3, due to the inhibition of inositol phosphatases by the lithium ion. In agreement with the different mechanisms by which lithium and pretreatment with excess inositol appear to reduce the pool size of inositol, the effects of pretreatment with excess inositol and of LiCl were additive. It is noteworthy that both effects could be observed in astrocytes, suggesting that there might be a significant astrocytic target during clinical treatment.

Animals↗

Rapid syncytium formation between human T-cell leukaemia virus type-I (HTLV-I)-infected T-cells and human nervous system cells: a possible implication for tropical spastic paraparesis/HTLV-I associated myelopathy.

Tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM), is characterized by infiltration of human T cell leukaemia virus type-I (HTLV-I)-infected T-cells, anti-HTLV-I cytotoxic T cells and macrophages into the patients' cerebrospinal fluid and by intrathecally formed anti-HTLV-I antibodies. This implies that the disease involves a breakdown of the blood-brain barrier. Since astrocytes play a central role in establishing this barrier, the authors investigated the hypothesis that the HTLV-I infected T cells disrupt this barrier by damaging the astrocytes. The present study revealed the HTLV-I-producing T cells conferred a severe cytopathic effect upon monolayers of astrocytoma cell line in co-cultures. Following co-cultivation, HTLV-I DNA and proteins appeared in the monolayer cells, but after reaching a peak their level gradually declined. This appearance of the viral components was proved to result from a fusion of the astrocytic cells with the virus-producing T cells, whereas their subsequent decline reflected the destruction of the resulting syncytia. This fusion could be specifically blocked by anti HTLV-I Env antibodies, indicating that it was mediated by the viral Env proteins expressed on the surface of the virus-producing cells. Similar fusion was observed between the HTLV-I-producing cells and certain other human nervous system cell lines. If such fusion of HTLV-I-infected T cells occurs also with astrocytes and other nervous system cells in TSP/HAM patients, it may account, at least partially, for the blood-brain barrier breakdown and some of the neural lesions in this syndrome.

3T3 Cells↗

Effectiveness of nutrition interventions in the pre-ESRD and the ESRD population.

Malnutrition is present in approximately 40% of patients treated with maintenance dialysis, and several serum proteins that are associated with malnutrition are also associated with decreased survival in this patient population. This article will review interventions to treat malnutrition in patients with chronic renal failure, as well as those treated with maintenance hemodialysis and peritoneal dialysis. Effectiveness of the interventions, as well as the design of trials to evaluate these interventions, are discussed.

Humans↗

Youth access to tobacco: policies and politics.

The late 1980s marked the beginning of a sea change in research and intervention on tobacco use by young people, when the first studies were published demonstrating the ease with which adolescents could purchase cigarettes. Since then concern with the commercial availability of tobacco products to youth has grown, becoming deeply entrenched in both research and policy efforts. This paper reviews the history of restrictions on youth access to tobacco, the evidence that commercial sources of tobacco are available and important to adolescents, and the rationale for various components of policies to restrict access. We also review the recent expansion of policies addressing youth access to tobacco at all levels of government, the tobacco industry response to this expansion, and issues that have arisen as this expansion has developed.

Adolescent↗

Leucine turnover in patients with nephrotic syndrome: evidence suggesting body protein conservation.

Whole-body leucine flux was measured in eight patients with nephrotic syndrome and in five healthy subjects by primed-constant infusion of L-[1-13C leucine]. Plasma enrichment of 13C leucine and 13C alpha-keto-isocaproate (13C KIC) was measured by gas chromatography/mass spectrometry, and expired 13CO2 was measured by isotope ration mass spectrometry. Leucine kinetics, calculated from the primary pool enrichment [13C leucine], showed no difference between the nephrotic patients and the control subjects. Kinetics derived from the reciprocal pool [1-13C KIC] enrichment, however, showed that leucine turnover rates were reduced in the nephrotic patients. The values (mumol/kg per h, means +/- SD) comparing the patients and the control subjects are as follows: rate of leucine release from protein degradation, 99 +/- 6 and 117 +/- 12 (P = 0.007); leucine oxidation rate, 15 +/- 7 and 22 +/- 3 (P = 0.04); rate of leucine incorporation into body protein [S], 84 +/- 10 and 95 +/- 6 (P = 0.04); protein turnover rate, 3.99 +/- 0.49 and 4.72 +/- 0.25 g/kg per d (P = 0.007). Nitrogen balance, measured only in the nephrotic patients, showed a mean positive balance of 0.5 g/d. In the nephrotic and control subjects, protein intake levels were 0.84 +/- 0.16 and 1.17 +/- 0.18 g/kg per d (P = 0.002), respectively, and energy intake levels were 33.3 +/- 8.5 and 33.9 +/- 2.4 kcal/kg per d, respectively. Linear correlations between leucine turnover rates and protein intake were highly significant. This study found that nephrotic patients given a modestly protein-restricted diet were able to maintain positive nitrogen balance. Moreover, leucine flux measurements showed downregulation of protein degradation and amino acid oxidation, reflecting appropriate adaptation to a lower protein intake.

Adult↗

Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine).

Glutathione is a major cellular antioxidant that protects protein thiols and inhibits cellular damage due to oxygen free radicals. It has been reported previously that patients undergoing dialysis have low levels of blood glutathione, which may lead to increased susceptibility to oxidant stress. L-2-oxothiazolidine-4-carboxylic acid (OTZ) is a cysteine prodrug that raises cellular glutathione levels by increasing delivery of cysteine, the rate-limiting substrate for glutathione synthesis. This study investigates the effect of OTZ on blood glutathione in a blinded, placebo-controlled study of patients with chronic renal failure treated by peritoneal dialysis. Twenty patients were randomly selected to receive OTZ (0.5 g three times a day orally with meals) or placebo for 14 d. Patients visited the clinic for predose blood collection and safety evaluation at baseline (days 3, 7, and 14 and again at 14 d from the last dose [follow-up]). Glutathione concentrations were determined in whole blood by HPLC. OTZ resulted in a significant rise in whole-blood glutathione at days 7 (594 +/- 129 mumol/L) and 14 (620 +/- 108 mumol/L) compared with baseline (544 +/- 139 mumol/L) (P < 0.01 and P < 0.05, respectively). Glutathione was also significantly increased at days 7 and 14 when normalized by hematocrit (Hct) or hemoglobin to correct for anemic status (e.g., 20.7 +/- 5.7 mumol/L per % Hct [day 7] and 20.9 +/- 4.0 mumol/L per % Hct [day 14] versus 18.0 +/- 4.2 mumol/L per % Hct [baseline]; P < 0.05). Glutathione levels did not change in the placebo group at any patient visit, and levels in the OTZ-treated group returned to baseline at follow-up. There were no serious adverse events attributable to OTZ, and the drug appeared to be well tolerated by patients with renal failure treated by continuous ambulatory peritoneal dialysis. Our results show that OTZ increases blood glutathione levels, which may improve antioxidant status in dialysis patients.

Administration, Oral↗

The effects of community policies to reduce youth access to tobacco.

OBJECTIVES: This study tested the hypothesis that adoption and implementation of local policies regarding youth access to tobacco can affect adolescent smoking. METHODS: A randomized community trial was conducted in 14 Minnesota communities. Seven intervention communities participated in a 32-month community-organizing effort to mobilize citizens and activate the community. The goal was to change ordinances, merchant policies and practices, and enforcement practices to reduce youth access to tobacco. Outcome measures were derived from surveys of students before and after the intervention and from tobacco purchase attempts in all retail outlets in the communities. Data analyses used mixed-model regression to account for the clustering within communities and to adjust for covariates. RESULTS: Each intervention community passed a comprehensive youth access ordinance. Intervention communities showed less pronounced increases in adolescent daily smoking relative to control communities. Tobacco purchase success declined somewhat more in intervention than control communities during the study period, but this difference was not statistically significant. CONCLUSIONS: This study provides compelling evidence that policies designed to reduce youth access to tobacco can have a significant effect on adolescent smoking rates.

Adolescent↗

The effects of measles virus persistent infection on AP-1 transcription factor binding in neuroblastoma cells.

Measles virus (MV) persistence in brain cells has broad effects on different cellular functions. We have previously shown that NS20Y clone, originally derived from C1300 neuroblastoma cells, persistently infected with MV (NS20Y/MS), displays constitutively elevated levels of c-fos and PKC mRNAs, implying MV-mediated effects on transcriptional regulation. Nonetheless, the mode by which virus affects the transcriptional machinery still remains obscure. In order to define this phenomenon, we studied the binding properties of major transcription factors (AP-1 and NFkappaB) in NS20Y/MS cells. Using electrophoretic mobility shift approach (EMSA) with the appropriate oligonucleotide probes, we have found that the persistent MV infection does not affect NFkappaB binding, while the AP-1 binding was significantly decreased. Similar inhibition was not observed in NS20Y cells acutely infected with MV. Anti-measles antibody-mediated restriction of viral gene expression restored AP-1 binding, thus suggesting that measles virus proteins may affect the components of the host transcriptional machinery.

Animals↗

Taxol induces tyrosine phosphorylation of Shc and its association with Grb2 in murine RAW 264.7 cells.

Taxol, a natural product with significant anti-tumor activity, stabilizes microtubules and arrests cells in the G2/M phase of the cell cycle. It has been reported that taxol has additional effects in cells, including an increase in tyrosine phosphorylation of proteins and activation of MAP kinase. We investigated a possible effect of taxol on tyrosine phosphorylation of Shc and on formation of the Shc/Grb-2 complex in the murine macrophage-like cell line RAW 264.7. Shc, an SH2 domain containing adaptor protein, was immunoprecipitated from lysates of taxol-treated cells with anti-phosphotyrosine antibody and its identity determined by Western blotting with anti-Shc antibody. Non-denatured Shc containing protein complexes were immunoprecipitated with anti-Shc antibody, and analysis with an anti-Grb2 antibody revealed the presence of the 24-kDa Grb2 protein. Taxol also activated Raf-1 kinase and ERK1/ERK2 MAP kinases in these cells. These results demonstrate that taxol affects tyrosine phosphorylation of Shc and this may result in the activation of the Raf-1/MAPK cascade.

Adaptor Proteins, Signal Transducing↗

Age-specific education and income gradients in morbidity and mortality in a Canadian province.

While important age-related trends in the use of health care services over the past two decades in Canada have been well described, a comprehensive description of socioeconomic gradients in morbidity and mortality across age cohorts for a representative population has not been accomplished to date in Canada. The objective of this study was to describe age-specific socioeconomic differentials in mortality and morbidity for a representative sample of a single Canadian province. The study sample was formed from the linkage of individual respondent records in the 1986 census to vital statistics records and comprehensive records of health care utilization for a 5% sample of residents of the province of Manitoba. Using two measures of socioeconomic status derived from census responses, attained education and household income, individuals were stratified into age-specific quartile ranks. Based on diagnostic information contained on health care utilization records, the proportion of the sample in treatment during a 12-month observation period was calculated for 15 broadly defined categories of morbidity and tested for differences across socioeconomic quartiles. Mortality was inversely associated with both income and education quartile rank. In the analysis of morbidity, no association between socioeconomic status and treatment prevalence was observed in the majority, no association between socioeconomic status and treatment prevalence was observed in the majority of the 122 age- and disorder-specific strata tested. Of the observed associations, however, negative relationships were dominant, indicating a higher treatment prevalence among individuals of lower attained education or lower household income. Across the age course, negative relationships were most frequently present among young and middle aged adults, those aged 30-64, and were more consistently found for income than for education. The general findings of this study of a representative Canadian population support observations from other developed country settings that socioeconomic differences in relative rates of mortality and morbidity over the life course are greatest in the adult years.

Adolescent↗

Persistent measles virus infection of murine neuroblastoma cells differentially affects the expression of PKC individual isoenzymes.

Measles virus (MV) is among the infectious agents displaying a propensity for establishing persistent infections of the CNS. It is assumed that continuous presence of MV defective particles or viral genome in persistently infected cells may influence host cellular processes and perturb biochemical signal transduction pathways operating in linkage to various cell surface receptors. PKC expression in a MV persistently infected neuroblastoma cell line (NS20Y/MS) was investigated. The relative levels of PKC isoenzymes were determined by Western blot analysis. We found that protein levels of PKCalpha, epsilon and zeta, but not PKCdelta, were increased in NS20Y/MS cells. PKCbeta, gamma and eta were undetectable. Treatment of NS20Y/MS cells with anti-MV Abs, which downregulated MV protein synthesis, also reduced PKCalpha expression to the basal level observed in the uninfected NS20Y cells. Our results suggest that a persistent MV infection has specific effects on the expression of certain PKC isoenzymes. We postulate that the MV-associated neurologic changes may reflect virus induced changes in biochemical signaling pathways and that these effects are likely to be regulated by the host's anti-viral humoral immune response.

Animals↗

Creating tobacco control policy at the local level: implementation of a direct action organizing approach.

This article describes the community activation and policy change process in seven Minnesota communities involved in the Tobacco Policy Options for Prevention (TPOP) study. The study's intervention employed a direct action organizing model, which relies on mobilizing large numbers of people to alter decision making and leverage the power of elites. As part of the organizing process, TPOP organizers and teams made 1,319 personal contacts with community members, generated 309 media stories, and initiated 445 public events related to tobacco use. These actions resulted in the establishment of comprehensive tobacco ordinances in all seven communities. The authors discuss the goals, training, activities and political factors relevant to four phases of the TPOP intervention: information gathering and team recruitment, community awareness building and ordinance development, preparing for city council, and ordinance establishment and enforcement. Included are suggestions for practitioners interested in using policy change and community-based advocacy to resolve public health problems.

Adolescent↗

Adolescent smokers' provision of tobacco to other adolescents.

OBJECTIVES: This study examined adolescent smokers provision of tobacco to other adolescents. METHODS: Data from a survey of 8th-, 9th-, and 10th-grade students in Minnesota were analyzed by using mixed-model logistic regression. RESULTS: More than two thirds (68.8%) of adolescent smokers had provided tobacco to another adolescent in the previous 30 days. Mother's smoking, number of friends who smoke, owning tobacco merchandise, number of cigarettes smoked in the past week, source of last cigarette (commercial), and recent attempt to buy cigarettes were associated with providing. CONCLUSIONS: The social availability of tobacco to youth needs further examination.

Adolescent↗