Biomedical subjects

M Wolfson

Publications and source records attributed to M Wolfson.

At least 19 recordsLinked to original sources

PubMed2003

Labour market income inequality and mortality in North American metropolitan areas.

OBJECTIVE: To investigate relations between labour market income inequality and mortality in North American metropolitan areas. METHODS: An ecological cross sectional study of relations between income inequality and working age (25-64 years) mortality in 53 Canadian (1991) and 282 US (1990) metropolitan areas using four measures of income inequality. Two labour market income concepts were used: labour market income for households with non-trivial attachment to the labour market and labour market income for all households, including those with zero and negative incomes. Relations were assessed with weighted and unweighted bivariate and multiple regression analyses. RESULTS: US metropolitan areas were more unequal than their Canadian counterparts, across inequality measures and income concepts. The association between labour market income inequality and working age mortality was robust in the US to both the inequality measure and income concept, but the association was inconsistent in Canada. Three of four inequality measures were significantly related to mortality in Canada when households with zero and negative incomes were included. In North American models, increases in earnings inequality were associated with hypothetical increases in working age mortality rates of between 23 and 33 deaths per 100 000, even after adjustment for median metropolitan incomes. CONCLUSIONS: This analysis of labour market inequality provides more evidence regarding the robust nature of the relation between income inequality and mortality in the US. It also provides a more refined understanding of the nature of the relation in Canada, pointing to the role of unemployment in generating Canadian metropolitan level health inequalities.

Adult↗

PubMed2002

Taxol-induced apoptosis in human SKOV3 ovarian and MCF7 breast carcinoma cells is caspase-3 and caspase-9 independent.

Taxol is used in chemotherapy regimens against breast and ovarian cancer. Treatment of tumor model cell lines with taxol induces apoptosis, but exact mechanism is not sufficiently understood. Our results demonstrate that in response to taxol, various cell types differentially utilize distinct apoptotic pathways. Using MCF7 breast carcinoma cells transfected with caspase-3 gene, we showed that taxol-induced apoptosis occurred in the absence of caspase-3 and caspase-9 activation. Similar results were obtained with ovarian SKOV3 carcinoma cells, expressing high level of endogenous caspase-3. In contrast, staurosporine-induced apoptosis in these cells was accompanied by proteolytic cleavage of pro-caspase-3 and induction of caspase-3 enzymatic activity. The effect of taxol appears to be cell type-specific, since taxol-induced apoptosis in leukemia U937 cells involved caspase-3 activation step. We conclude that a unique caspase-3 and caspase-9 independent pathway is elicited by taxol to induce apoptosis in human ovarian and breast cancinoma cells.

Apoptosis↗

PubMed2002

[Heat shock proteins and malignancies of the female genital tract].

Heat shock proteins (Hsp) are cytoplasmic proteins that act as molecular chaperones for protein molecules in various intra-cellular processes. They play an important role in protein-protein interactions, including folding and conformation, and prevention of inappropriate protein aggregation. They are called "heat shock proteins" since they were first discovered in cells exposed to high temperatures. However, their synthesis is also accentuated under other stress conditions, such as exposure of the cell to inflammation, infection, ischemia, toxins, cytotoxic drugs and malignant transformation. Hsp have been classified into families according to their molecular weight. In ovarian carcinoma, over-expression of Hsp27 was associated with increased resistance to chemotherapy and a worse prognosis. In endometrial carcinoma, over-expression of Hsp70 was associated with poorly differentiated tumors and a worse prognosis, whereas over-expression of Hsp27 and Hsp90 were associated with well-differentiated tumors and better prognosis. The association between increasing expression of Hsp90 and better differentiation and prognosis seems to reflect high levels of sex steroid receptors in well-differentiated endometrial carcinomas. In cervical carcinoma, the presence of Hsp70 was associated with a worse outcome. Since Hsp are highly antigenic, their property to bind with tumor proteins and proteins produced by viruses may be used for the development of vaccines against cancers and viral diseases. It is speculated that examination of the lower genital tract secretions for IgA antibodies against Hsp will contribute to early detection of malignancies. Since Hsp may affect the growth of the tumor and its response to chemotherapy, it is speculated that using drugs that inhibit Hsp in combination with conventional chemotherapy may contribute to the improvement of the treatment results.

Cancer Vaccines↗

PubMed2001

Activation of HTLV-I long terminal repeat by stress-inducing agents and protection of HTLV-I-infected T-cells from apoptosis by the viral tax protein.

HTLV-I is etiologically implicated with tropical spastic paraparesis/HTLV-I associated myelopathy, adult T-cell leukemia and certain other diseases. However, after infection the virus enters into a dormant state, whereas the characteristics of the HTLV-I related diseases indicate that their genesis requires activation of the dormant virus by a Tax-independent mechanism. In the present study we demonstrate that a variety of stress-inducing agents (TPA, cisplatin, etoposide, taxol, and 3-methylcholanthrene) are capable of Tax-independent activation of HTLV-I LTR and that this activation is detected mainly in cells that are undergoing through the apoptotic process. Furthermore, it is demonstrated that both apoptosis induction and HTLV-I LTR activation are inhibited by Bcl-2 and by PKC, indicating that these two processes are mechanistically cross-linked. In addition, using an HTLV-I producing human T-cell line which permanently express the negatively transdominant tax mutant, Delta58tax, under the Tet-Off control system, we prove that the virally encoded Tax protein protects the host cells from apoptosis. Together, these data suggest that activation of the dormant virus in the carriers' infected T-cells by certain stress-inducing conditions and protecting these cells from the consequent apoptotic death by the viral Tax protein emerging after this activation, might be the basis for switching the virus from latency to a pathogenic phase.

Antineoplastic Agents↗

PubMed2001

The role of ERK 1/2 and p38 MAP-kinase pathways in taxol-induced apoptosis in human ovarian carcinoma cells.

Taxol is an anticancer agent of natural origin with significant activity against a number of human cancers including ovarian and breast carcinomas. Its cytotoxic activity has been attributed to its ability to stabilize microtubules and to promote microtubule assembly. Recently it has become clearer that Taxol has additional activities including effects in cell signaling and gene expression. We have shown previously that Taxol activates ERK 1/2 MAP-kinases and results in the formation of GRB2/SHC complexes in murine macrophage-like RAW 267.4 cells. Here we demonstrate that Taxol activates ERK 1/2 and p38 MAP-kinases in human ovarian carcinoma cells with distinct kinetics. Activation of ERK1/2 has been observed at low concentrations of Taxol (1-100 nM) within 0.5-6 h, whereas longer exposure(24 h) to nanomolar concentrations of Taxol resulted in an abrogation of the ERK1/2 phosphorylation/activation. Higher concentrations (1-10 microM) resulted in a sharp inhibition of ERK1/2 activity. p38 kinase was activated by high concentrations (1-10 microM) of Taxol within 2 h and remained active for more than 24 h. The kinetic studies showed that these effects of Taxol coincided with an inhibition of proliferation, and the onset of apoptosis. The appearance of the fragmented chromatin visualized by DAPI staining, and DNA fragments seen on an agarose gel, coincided with the decrease in ERK1/2 activation and concomitant increase of the level of active p38 MAPK. The inhibitor PD98059 abrogated ERK 1/2 activation and increased the cytotoxic effect of Taxol. An inhibitor of p38 kinase, SB203580, protected the cells partially from Taxol and, unexpectedly, activated ERK 1/2 kinases. We conclude that the alternative use of ERK1/2 and p38 MAP-kinase pathways may be necessary for the transition from proliferation state to Taxol-induced apoptosisin human ovarian carcinoma cells.

Apoptosis↗

PubMed2001

On measuring inequalities in health.

In a recent series of papers, Murray et al. have put forward a number of important ideas regarding the measurement of inequalities in health. In this paper we agree with some of these ideas but draw attention to one key aspect of their approach--measuring inequalities on the basis of small area data--which is flawed. A numerical example is presented to illustrate the problem. An alternative approach drawing on longitudinal data is outlined, which preserves and enhances the most desirable aspects of their proposal. These include the use of a life course perspective, and the consideration of non-fatal health outcomes as well as the more usual information on mortality patterns.

Analysis of Variance↗

PubMed2000

Nordidemnin potently inhibits inositol uptake in cultured astrocytes and dose-dependently augments lithium's proconvulsant effect in vivo.

It has been suggested that inositol uptake across the cell membrane is of importance for maintenance of the inositol pool involved in lithium's therapeutic effect in bipolar disease and in the lithium-pilocarpine seizure test in freely moving rats (measuring the latency of a normally subconvulsive concentration of pilocarpine to seizure induction in the additional presence of lithium). We have tested this hypothesis by: 1) demonstrating an extremely high potency of nordidemnin as an inhibitor of myo-inositol uptake in primary cultures of mouse astrocytes; and 2) determining the dose-response correlation of a nordidemnin-induced decrease in the latency before appearance of seizures in the lithium-pilocarpine test after intracerebroventricular injection of minute samples (10 microl) of virtually isotonic saline solution.

Animals↗

PubMed2000

Chronic treatment of human astrocytoma cells with lithium, carbamazepine or valproic acid decreases inositol uptake at high inositol concentrations but increases it at low inositol concentrations.

Inositol uptake was measured at concentrations of 25, 40 and 50 microM in human astrocytoma cell cultures treated for 1-3 weeks with pharmacologically relevant concentrations of LiCl, valproic acid or carbamazepine as well as in control cultures that had not been treated with any drug. After at least 2 weeks of treatment, each of these 3 conventional anti-bipolar drugs increased the uptake significantly at 25 microM inositol, had no effect at 40 microM, and decreased it at 50 microM inositol. Reduction of the drug concentrations by 50% abolished the stimulation of uptake at 25 microM inositol by lithium and valproic acid and reduced that by carbamazepine. These findings may contribute to an understanding of the mechanisms of action for anti-bipolar medication, and explain the controversy in the literature whether or not brain inositol is reduced after chronic administration of lithium.

Antimanic Agents↗

PubMed2000

A model of inositol compartmentation in astrocytes based upon efflux kinetics and slow inositol depletion after uptake inhibition.

Intracellular compartmentation of inositol was demonstrated in primary cultures of mouse astrocytes, incubated in isotonic medium, by determination of efflux kinetics after "loading" with [3H]inositol. Three kinetically different compartments were delineated. The largest and most slowly exchanging compartment had a halflife of approximately 9 hr. This slow release leads to retention of a sizeable amount of pre-accumulated inositol in the tissue 24 hr after the onset of uptake inhibition, as confirmed by the observation that the inositol uptake inhibitor fucose caused a larger inhibition of unidirectional inositol uptake than of inositol pool size, measured as accumulated [3H]inositol after 24 hr of combined exposure to the inhibitor and the labeled isotope. Based upon the present observations and literature data, it is suggested that the large, slowly exchanging compartment is largely membrane-associated and participating in signaling via the phosphatidylinositide second messenger system, whereas inositol functioning as an osmolyte is distributed in the cytosol and located in one or both of the compartments showing a faster release.

Animals↗

PubMed2000

Exposure to violence and victimization, depression, substance use, and the use of violence by young adolescents.

OBJECTIVE: To examine the relationships among exposure to violence; tobacco, alcohol, and other substance use; depression; church attendance; and the use of violence among very young adolescents. METHODS: An 86-item confidential questionnaire was administered to 722 sixth grade students (mean age = 11.9+/-0.8 years) attending 4 middle schools serving neighborhoods in and around public housing. RESULTS: Boys had a higher mean violence scale score than girls (P < or =.0001), and students living in public housing had higher violence scale scores than other students (P< or =.0001). Self-reported use of violence was significantly associated with exposure to violence (r =.45); age (r =.28); frequency of church attendance (r = -.14); depression (r =.28); the probability of being alive at age 25 (r = -.09); the frequency of use of cigarettes (r =.39), alcohol (r =.37), and multiple substances (r =.38); and interest in a gang (r =.37). When all of these variables were analyzed with multiple linear regression, multiple substance use, exposure to violence, interest in a gang, male gender, cigarette smoking, and depression level accounted for 49.7% of the variation in the use of violence scale. CONCLUSION: Recent multiple substance use and lifetime exposure to violence and victimization were the strongest correlates with the frequency that these youth reported using violence and carrying weapons.

Adolescent↗

PubMed2000

Communities mobilizing for change on alcohol: outcomes from a randomized community trial.

OBJECTIVE: Communities Mobilizing for Change on Alcohol (CMCA) was a randomized 15-community trial of a community organizing intervention designed to reduce the accessibility of alcoholic beverages to youths under the legal drinking age. METHOD: Data were collected at baseline before random assignment of communities to intervention or control condition, and again at follow-up after a 2.5-year intervention. Data collection included in-school surveys of twelfth graders, telephone surveys of 18- to 20-year-olds and alcohol merchants, and direct testing of the propensity of alcohol outlets to sell to young buyers. Analyses were based on mixed-model regression, used the community as the unit of assignment, took into account the nesting of individual respondents or alcohol outlets within each community, and controlled for relevant covariates. RESULTS: Results show that the CMCA intervention significantly and favorably affected both the behavior of 18- to 20-year-olds (effect size = 0.76, p<.01) and the practices of on-sale alcohol establishments (effect size = 1.18, p<.05), may have favorably affected the practices of off-sale alcohol establishments (effect size = 0.32, p = .08), but had little effect on younger adolescents. Alcohol merchants appear to have increased age-identification checking and reduced propensity to sell to minors. Eighteen- to 20-year-olds reduced their propensity to provide alcohol to other teens and were less likely to try to buy alcohol, drink in a bar or consume alcohol. CONCLUSIONS: Community organizing is a useful intervention approach for mobilizing communities for institutional and policy change to improve the health of the population.

Adolescent↗

PubMed2000

Maternal obesity and pregnancy outcome.

BACKGROUND: Obesity, a common condition in developed countries, is recognized as a threat to health. OBJECTIVES: To describe the distribution of weight in pregnant women and evaluate the influence of obesity on pregnancy outcome in a high parity northern Israeli population. METHODS: The study included 887 women who gave birth in the Western Galilee Medical Center during the period August to November 1995. The patients were classified as underweight, normal weight, overweight, or obese according to body mass index. Maternal demographic, obstetric, and perinatal variables were compared. A control group of 167 normal weight women were matched with the obese group for maternal age, parity, and gestational age. RESULTS: Obese mothers had a higher incidence of gestational diabetes and pregnancy-induced hypertension compared to normal weight mothers (5.4% vs. 1.8%, and 7.2% vs. 0.6% respectively, P < 0.01), a higher rate of labor induction (20.4% vs. 10.2%, P < 0.01), and a higher cesarean section rate (19.6% vs. 10.8%, P < 0.05). There was also a significant difference in the prevalence of macrosomia in the offspring (16.8% vs. 8.4%, P < 0.05). CONCLUSION: Obese pregnant women are at high risk for complications during delivery and therefore need careful pre-conception and prenatal counseling, as well as perinatal management.

Adult↗

PubMed2000

Preliminary findings from the National Pre-ESRD Education Initiative.

Regardless of age or race, more patients preferred peritoneal dialysis (PD) than would be expected from the current ratio of patients treated with PD in the U.S. The percent of patients choosing PD seems to be largely influenced by the scope of information they receive prior to therapy initiation. In the absence of thorough treatment option education, a significant number of patients may be assigned a therapy when, in reality, they would have selected an alternative option. There is a need to further understand the correlation between a practice's PD utilization rate and the extent to which patients are given dialysis treatment options.

Adult↗

PubMed1999

Relation between income inequality and mortality: empirical demonstration.

OBJECTIVE: To assess the extent to which observed associations at population level between income inequality and mortality are statistical artefacts. DESIGN: Indirect "what if" simulation by using observed risks of mortality at individual level as a function of income to construct hypothetical state level mortality specific for age and sex as if the statistical artefact argument were 100% correct. SETTING: Data from the 1990 census for the 50 US states plus Washington, DC, were used for population distributions by age, sex, state, and income range; data disaggregated by age, sex, and state from the Centers for Disease Control and Prevention were used for mortality; and regressions from the national longitudinal mortality study were used for the individual level relation between income and risk of mortality. RESULTS: Hypothetical mortality, while correlated with inequality (as implied by the logic of the statistical artefact argument), showed a weaker association with states' levels of income inequality than the observed mortality. CONCLUSIONS: The observed associations in the United States at the state level between income inequality and mortality cannot be entirely or substantially explained as statistical artefacts of an underlying individual level relation between income and mortality. There remains an important association between income inequality and mortality at state level over and above anything that could be accounted for by any statistical artefact. This result reinforces the need to consider a broad range of factors, including the social milieu, as fundamental determinants of health.

Adult↗

PubMed1999

Intraperitoneal nutrition.

Provision of nutrients through the peritoneum is as old as peritoneal dialysis (PD) itself. Studies with a shelf-stable amino acid-based dialysis solution have shown that the amino acids absorbed during one exchange quantitatively exceed the daily losses of proteins and amino acids. The supplementary amino acids are well tolerated and can induce protein anabolism in many malnourished PD patients, as is evident from increased nitrogen balance, insulin-like growth factor-1, and increased concentrations of serum proteins. Such solutions offer a convenient means of providing nutritional supplementation to address the major nutritional needs of PD patients.

Humans↗

PubMed1999

Effectiveness of nutrition interventions in the management of malnourished patients treated with maintenance dialysis.

Malnutrition is not uncommon in patients with end-stage renal disease treated with maintenance dialysis. In addition, malnutrition is associated with increased morbidity and mortality in these patients. A number of interventions have been undertaken to increase nutrient intake or to provide growth factors to induce anabolism. These interventions have met with varying degrees of success. The most efficient and effective method of managing malnutrition in the dialysis patient is still unclear. More research is needed to determine the most appropriate method of management of malnutrition.

Humans↗

PubMed1999

Assessing ecologic proxies for household income: a comparison of household and neighbourhood level income measures in the study of population health status.

This paper examines the validity of using ecologic measures of socioeconomic status as proxies for individual-level measures in the study of population health. Based on a representative 5% sample of households in a Canadian province, the study integrated three sources of information: administrative records of individual health care utilization, records of deaths and 1986 census records which contained information on household income and average neighbourhood income. Thirteen measures of health status were developed from these sources of information. The hypothesis that risk estimates derived from ecologic income measures will be attenuated relative to estimates obtained from household income was not supported. These results provide evidence for the use of ecologic-level measures of income in studies which do not have access to individual-level income measures.

Adolescent↗

PubMed1999

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↗