NBCn1 and NHE1 expression and activity in DeltaNErbB2 receptor-expressing MCF-7 breast cancer cells: contributions to pHi regulation and chemotherapy resistance.

Altered pH-regulatory ion transport is characteristic of many cancers; however, the mechanisms and consequences are poorly understood. Here, we investigate how a truncated, constitutively active ErbB2 receptor (DeltaNErbB2) common in breast cancer impacts on the Na(+)/H(+)-exchanger NHE1 and the Na(+),HCO(3)(-)-cotransporter NBCn1 in MCF-7 human breast cancer cells and address the roles of these transporters in chemotherapy resistance. Upon DeltaNErbB2 expression, mRNA and protein levels of NBCn1, yet not of NHE1, increased several-fold, and the localization of both transporters was altered paralleling extensive morphological changes. The rate of pH(i) recovery after acid loading increased by 50% upon DeltaNErbB2 expression. Knockdown and pharmacological inhibition confirmed the involvement of both NHE1 and NBCn1 in acid extrusion. NHE1 inhibition or knockdown sensitized DeltaNErbB2-expressing cells to cisplatin-induced programmed cell death (PCD) in a caspase-, cathepsin-, and reactive oxygen species-dependent manner. NHE1 inhibition augmented cisplatin-induced caspase activity and lysosomal membrane permeability followed by cysteine cathepsin release. In contrast, NBCn1 inhibition attenuated cathepsin release and had no net effect on viability. These findings warrant studies of NHE1 as a potential target in breast cancer and demonstrate that in spite of their similar transport functions, NHE1 and NBCn1 serve different functions in MCF-7 cells.

Shattered childhood: a key issue in suicidal behavior among drug addicts?

AIMS: To assess the relative importance of various adverse childhood experiences for the occurrence of later suicidal behavior in terms of experienced suicide attempts and suicidal ideation among drug addicts, and to assess possible gender differences in these associations. DESIGN: Cross-sectional survey. SETTING: Residential and outpatient treatment units for drug addicts in Norway. PARTICIPANTS: National sample of 800 drug addicts admitted to treatment in 1992-93. MEASUREMENTS: Self-reports of attempted suicide (life-time prevalence) and suicidal ideation (1 month prior to admission). Data collected from structured interviews with therapists. FINDINGS: A total of 38.0% of the drug addicts reported having attempted suicide once or several times; the proportion was higher among those who reported various adverse experiences during childhood (sexual or violent assaults, bullying, parents' alcohol abuse, parents' psychiatric problems, school adjustment problems and own psychiatric problems), and increased with number of areas of such adverse childhood experiences. Forty-two per cent of the clients reported suicidal ideation in the month prior to admission, displaying the same kind of associations with adverse childhood experiences, and also a significant association when controlling for previous suicide attempts. There were relatively small gender differences in self-reported suicidal behavior, the proportion being somewhat higher among women, but only among those with no or few adverse childhood experiences. CONCLUSIONS: Self-reported suicidal behavior and ideation among drug addicts is highly prevalent and more so with increasing number of areas of childhood adversities.

Reported adoption of dietary fat and fiber recommendations among consumers.

OBJECTIVE: To identify constraints in adopting dietary fat and fiber recommendations. DESIGN: A questionnaire was mailed to a sample of the general population, a convenience sample of persons with heart disease and cancer in 11 states, and registered dietitians in 5 states. The survey included questions on demographic and attitudinal factors that were correlated with specific practices to reduce fat intake and increase fiber intake. SETTING: From the general population sample of 6,206 eligible respondents (return rate of 51.5%), those selected were respondents who indicated that they would adopt a dietary recommendation if it were good for them (n = 2,682). Subsamples from the general population were matched to 362 registered dietitians and 147 persons with cancer or heart disease on selected demographic variables. Factors associated with adoption of specific behaviors were identified. STATISTICAL ANALYSIS PERFORMED: Statistical analysis included chi 2, factor analysis, and analysis of variance. RESULTS: The majority of persons who said they would adopt a fat-reducing behavior if it were good for their health reported practicing that behavior often or usually. More than 60% reported consuming whole grains; however, only 15% reported eating fruits and vegetables frequently. Among the general population sample, those more likely to practice a behavior had the following characteristics: female, college educated, older than 60 years, white, higher income, no children younger than 18 years, perceived health status as excellent, and absence of chronic disease. Registered dietitians and those with chronic disease were also more likely to follow dietary fat and fiber recommendations. APPLICATIONS: Nutrition education messages that lead to increased consumption of dietary fiber need to be developed. Nutrition educators should provide strategies for consumers for increasing use of fruits and vegetables in all meals. Good taste and convenience are critical components. The food industry may assist by providing a wider array of convenience entrees or side dishes that feature produce and whole grains.

Balancing on the edge of death: suicide attempts and life-threatening overdoses among drug addicts.

AIMS: Assessment of prevalence of non-fatal overdoses and suicide attempts and predictors of and co-variation between such behaviours among drug addicts. DESIGN: Cross-sectional survey. SETTING: Inpatient and outpatient treatment units in Norway. PARTICIPANTS: National sample of 2051 drug addicts admitted to treatment in Norway in 1992-93. MEASUREMENTS: Self-reports of suicide attempts and of life-threatening overdoses from structured interviews with therapists. FINDINGS: Almost half (45.5%) the clients reported having experienced one or more life-threatening overdoses. A third (32.7%) reported one or more suicide attempts. Suicide attempts were more often reported among those who had overdosed (odds ratio (OR) = 6.3), and the number of life-threatening overdoses and number of suicide attempts were positively and moderately associated (Pearson's r = 0.39). Drug addicts who had exhibited both life-threatening behaviours were characterized by polydrug use, poor social functioning and HIV risk-taking behaviour. Suicide attempters were also characterized by psychiatric problems. CONCLUSIONS: The substantial co-variation between suicide attempts and drug overdose suggests some common underlying causal factors. These seem to be related to heavy drug use and poor social integration.

A stage-of-change classification system based on actions and beliefs regarding dietary fat and fiber.

PURPOSE: The objectives of this study were to develop a stage-of-change classification system and to determine the degree to which various adult subgroups have adopted the behavioral changes necessary to achieve a low-fat and/or high-fiber diet as recommended by the Dietary Guidelines for Americans. DESIGN: The study used a mail survey randomly sent to 7110 adults. SETTING: The survey was conducted in 11 states and the District of Columbia. SUBJECTS: The random sample included males and females over age 18. Of the eligible respondents, 3198 (51.5%) were included in this analysis, with 2004 and 2066 unambiguously classified into stages of change for fat and fiber, respectively. MEASURES: Stage of change was defined by an algorithm based on self-reported intent and behaviors to limit fat and/or increase fiber. RESULTS: 45% of the respondents were classified as being in action/maintenance for fat and 38% for fiber. Women, older adults, individuals with advanced education, persons with diet-related chronic disease, people with higher levels of relevant nutrition knowledge and attitudes, and persons who indicated that health concerns were a primary influence on their diet were more likely to be in action/maintenance than other respondents. CONCLUSIONS: The algorithm in this study presents a model that more closely reflects the proportions of the adult population that have achieved low-fat diets and classifies a greater proportion in the preparation stage than classification systems in previous studies.