Underlying ambiguities in genetic privacy legislation.

Advances in genetic testing and research are creating increasing concern regarding genetic privacy. Current and proposed federal and state legislation has failed to provide adequate protection due to confusion over the meaning of privacy, inconsistency in the definition of genetic information, and lack of clarity with regard to the role of insurers in a market driven healthcare environment. Drawing on examples of current and proposed legislation, this paper explores these ambiguities with a view toward future health policy alternatives.

Decision-making through dialogue: reconfiguring autonomy in genetic counseling.

Nondirective genetic counseling developed as a means of promoting informed and independent decision-making. To the extent that it minimizes risks of coercion, this counseling approach effectively respects client autonomy. However, it also permits clients to make partially informed, poorly reasoned or ethically questionable choices, and denies counselors a means of demonstrating accountability for the use of their services. These practical and ethical tensions result from an excessive focus on noncoercion while neglecting the contribution of adequate information and deliberative competence to autonomous decision-making. A counseling approach that emphasizes the role of deliberation may more reliably produce thoroughly reasoned decisions. In such an approach, characterized by dialogue, counselors are responsible for ensuring that decisions are fully informed and carefully deliberated. Counseling remains nonprescriptive, but in the course of discussion counselors may introduce unsolicited information and/or challenge what they believe are questionable choices. By this means clients can be better assured that the decisions they make are fully considered, while counselors demonstrate a limited degree of professional accountability.

Menhaden, coconut, and corn oils and mammary tumor incidence in BALB/c virgin female mice treated with DMBA.

Omega-3 fatty (n-3) acids are believed to inhibit the rate of occurrence and the growth of mammary tumors in rats treated with 7,12-dimethylbenz[a]anthracene (DMBA). Linoleic acid, on the other hand, has been shown to promote mammary tumorigenesis. This study was undertaken to see whether replacing 18% of the corn oil (high in linoleic acid) in a 20% fat diet with menhaden oil (high in n-3 fatty acids, low in linoleic acid) or coconut oil (low in n-3 fatty acids, low in linoleic acid), while keeping constant the cholesterol, antioxidant, and total fat content, would affect tumor incidence in virgin female BALB/c mice dosed with DMBA. Dietary treatment had no effect on body weight, feed intake, or survival to 44 weeks of age (36 wks after the first of 6 DMBA doses). Mammary tumor incidence was the same in the menhaden oil and coconut oil diet groups but was significantly higher in the 20% corn oil diet group. The protective effect of menhaden oil and coconut oil may be due, at least in part, to the decreased linoleic acid content of these diets relative to the corn oil diet. We conclude that n-3 fatty acids per se do not seem to inhibit tumor formation.

The effect of diet, exercise and 7,12-dimethylbenz(a)anthracene on food intake, body composition and carcass energy levels in virgin female BALB/c mice.

This study investigated the effect of diet, exercise and , 7,12-dimethylbenz(a)anthracene (DMBA), a mammary-tumor carcinogen, on food intake, energy consumption, body weight and body composition in virgin female BALB/c mice. Interactions were examined among three diet conditions (standard AIN-76A, restricted AIN-76A and high fat AIN-76A diet), two exercise conditions (with and without treadmill exercise) and two treatment conditions (carcinogen or corn oil sham). Mice were randomized to one of 12 groups at 6 wk of age; beginning at 8 wk of age, all mice received either 7,12-dimethylbenz(a)anthracene (1 mg/0.2 mL corn oil) or 0.2 mL of corn oil via gastric tube once each week for six consecutive weeks. Exercise in a rotating-drum treadmill was initiated at 10 wk of age and was increased to a final rate of 6 m/min for 60 min, 5 d/wk. Mice were killed at 24 wk of age, confirmed to be tumor-free and analyzed for protein and fat content, from which body energy was calculated. Energy consumption was highest in the standard diet-fed groups followed by the high fat diet-fed groups and the restricted diet-fed groups. The groups fed the standard diet and restricted diet had similar body weight and carcass energy. Exercise or DMBA treatment generally reduced food consumption, energy intake, body weight and carcass energy. In summary, diet, exercise and DMBA all had pronounced effects on energy consumption, which in turn affected body composition. These treatments may influence expression of breast cancer via their effects on body composition.

Reduced energy intake and moderate exercise reduce mammary tumor incidence in virgin female BALB/c mice treated with 7,12-dimethylbenz(a)anthracene.

This study evaluated the concurrent effects of diet (standard AIN-76A, restricted AIN-76A and high-fat diet) and moderate rotating-drum treadmill exercise on the incidence of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in virgin female BALB/cMed mice free of murine mammary tumor virus. Exercise significantly reduced food consumption in the groups fed the standard diet and high fat diet. Although food consumption varied widely, final body weight was similar in all groups. Exercise had no effect on mammary tumor incidence in the standard diet-fed groups (without exercise, 47%; with exercise, 45%); however, exercise reduced mammary tumor incidence in the other groups as follows: restricted diet/no exercise, 28%; restricted diet/with exercise, 13%; high fat diet/no exercise, 31%; high fat diet/with exercise, 19%. Restricting food intake reduced mammary tumor incidence, but had no effect on body weight. Although energy intake was related to mammary tumor incidence, neither body weight nor dietary fat predicted tumor incidence.

The effect of four chemical forms of selenium on mammary tumor incidence in BALB/c female mice treated with 7-12-dimethylbenz[a]anthracene.

The study was conducted to determine the effect of four forms of selenium on inhibition of DMBA-induced mammary tumors. BALB/c virgin female mice were fed the AIN-76 diet containing 0.2 or 2.0 ppm Se as selenite, selenate, selenomethionine, or selenocystine prior to and for 6 months post DMBA-treatment. At necropsy, mammary glands were histologically treated for confirmation of adenocarcinomas and the livers were removed for analysis of glutathione-peroxidase (GSHPx) activity and selenium concentrations. Dietary levels or forms of selenium had no effect on body weights. Inorganic selenium fed at 2.0 ppm Se (selenite and selenate) decreased mammary tumor incidence, but organic selenium (selenomethionine and selenocystine) had no effect on mammary tumor incidence. Hepatic GSHPx activity was highest with the 2.0 ppm selenium as selenocystine diet, but hepatic selenium levels were highest with the 2.0 ppm selenium as selenite. This study showed that the dietary form of selenium affects inhibition of mammary tumorigenesis. Furthermore, the study suggested that the pathways for selenium incorporation into GSHPx and for tumor inhibition are different.

The predictability of thought disordered speech in schizophrenic patients.

Previous research has resulted in inconsistent findings regarding the predictability of schizophrenic speech samples. It was hypothesized that the predictability of schizophrenic speech varies as a function of clinically manifest thought disorder. In an experiment based on the Cloze procedure, raters were asked to predict ten passages of schizophrenic speech and eight passages of normal speech under conditions of fourth- and fifth-word deletion. Differences emerged between the samples only for the fifth-word deletion procedure. When the schizophrenic samples were grouped according to the presence of thought disorder, thought-disordered speech was significantly less predictable than normal and non-thought disordered schizophrenic speech. Furthermore, non-thought-disordered schizophrenic speech was no less predictable than normal speech. It is concluded that schizophrenia should be more carefully defined and that thought disorder should be routinely assessed in future investigations.

In vitro analysis of proliferating epithelial cell populations from the mouse mammary gland: fibroblast-free growth and serial passage.

Normal and neoplastic mouse mammary epithelial cells were cultured in nutrient medium containing D-valine substituted for L-valine. Fibroblast overgrowth was prevented and epithelial cell functions and morphology were retained in cultures maintained in D-valine medium up to 2 months. A nonenzymatic technique was devised to dissociate epithelial cell monolayers. The combined use of this dissociation buffer and D-valine nutrient medium made it possible to passage serially normal and neoplastic mammary epithelial cells. Normal cells were derived from mammary glands of animals stimulated with exogenous hormones for various periods. The period of in vivo hormonal stimulation influenced the ability of normal mammary epithelial cells to attach and proliferate in primary and serially passaged cultures. A greater proportion of cells derived from glands following 2 to 4 weeks of hormonal stimulation were recovered after replating and showed higher labeling indices during serial passage than cells from unstimulated or 5- to 7-week stimulated groups.

Biochemical studies on mitochondria isolated from Normal and Neoplastic Tissues of the Mouse Mammary Gland.

Mitochondria isolated from spontaneous and transplanted mammary adenocarcinomas of two strains of mice were compared, by various biochemical criteria, to mitochondria from mammary glands of midpregnant or hormonally stimulated, cancer-free mice. The specific activities of several mitochondrial enzymes including cytochrome oxidase, alpha-glycerophosphate oxidase, and succinate dehydrogenase were twofold to threefold lower, whereas the activity of monoamine oxidase was two fold higher in tumor mitochondria. Malate dehydrogenase, adenylate kinase, and NADH oxidase showed similar levels of activity in tumor and midpregnant mammary gland mitochondria. In addition, mitochondrial polypeptide composition was analyzed by electrophoresis on sodium dodecyl sulfate-urea polyacrylamide gels. Midpregnant mammary gland and mammary tumor mitochondria were similar in polypeptide composition; however, several differences were observed. A high-molecular-weight polypeptide, present in mid-pregnant mammary gland mitochondria was absent from tumor mitochondria. Also, tumor mitochondria contained an additional high-molecular-weight polypeptide not found in the midpregnant mammary gland. There were numerous differences in the relative proportions of many polypeptides common to both tumor and midpregnant mammary gland mitochondria.

Physicochemical characterization of Novikoff hepatoma mitochondrial DNA.

Mitochondrial DNA's (mtDNA) isolated from rat liver and the Novikoff hepatoma grown as both solid tumors and cells in monolayer culture were examined by a variety of physicochemical techniques. Buoyant densities in analytical CsCl equilibrium gradients and thermal denaturation profiles revealed no significant differences in base composition among the mtDNA's isolated from liver, tumor, and hepatoma cells. Sedimentation in neurtral and alkaline CsCl showed no differences in mtDNA size. However, tumor and hepatoma cell mtDNA's were slightly smaller and more heterogeneous in size than liver mtDNA when molecular contour lengths were measured in the electron microscope. Based on chemical determinations, neoplastic mitochondria contained four to five times more DNA per mitochondrion than liver. Also, electron microscopy showed the proportion of mtDNA in complex forms (catenated dimers and oligomers) to be much higher in tumor (18%) and hepatoma cells (15%) than liver (4%).

Biochemical properties of simian virus 40-transformed 3T3 cell mitochondria.

Mitrochondria isolated from simian virus 40-transformed 3T3 and nontransformed 3T3 cells were compared by various biochemical criteria. Transformed and nontransformed cell mitochondria had identical densities in linear sucrose and discontinuous bovine serum albumin gradients. The activities of several mitochondria-specific enzymes including cytochrome oxidase, adenylate kinase, nicotinamide adenine dinucleotide (NADH)-cytochrome c reductase, and NADH oxidase were similar in both cell types. However, the activity of the mitochondrial outer membrane enzyme, monoamine oxidase. In the virus-transformed cell mitochondria was reduced to 50% of that in nontransformed cell mitochondria.