Normally occurring environmental and behavioral influences on gene activity: from central dogma to probabilistic epigenesis

The central dogma of molecular biology holds that "information" flows from the genes to the structure of the proteins that the genes bring about through the formula DNA-->RNA-->Protein. In this view, a set of master genes activates the DNA necessary to produce the appropriate proteins that the organism needs during development. In contrast to this view, probabilistic epigenesis holds that necessarily there are signals from the internal and external environment that activate DNA to produce the appropriate proteins. To support this view, a substantial body of evidence is reviewed showing that external environmental influences on gene activation are normally occurring events in a large variety of organisms, including humans. This demonstrates how genes and environments work together to produce functional organisms, thus extending the author's model of probabilistic epigenesis.     

ENRICHMENT OF TORTILLAS WITH SOY PROTEINS BY LIME COOKING OF WHOLE RAW CORN-SOYBEAN MIXTURES

A simple and inexpensive method for enriching tortillas with soy proteins was studied. The method consisted of application of the traditional process for making corn tortillas to whole raw corn-soybean mixtures: lime cooking of a mixture, allowing the cooked mixture to stand overnight in the cooking liquor, washing the mixture with tap water, grinding the cooked mixture into a dough, and making tortillas from the dough. This method of enrichment was found to give tortillas with significantly higher protein content and protein quality than normal un-enriched tortillas. PER and NPU values of tortillas containing 8% and 16% soya were found to be comparable to those obtained with tortillas enriched with soy flour or with amino acids lysine and tryptophane. The presence of soybeans in tortillas so enriched was found to be not significantly detectable by a trained panel, at least up to a soya level of 16%. Toxic factors present in raw soybeans were not detected in enriched tortillas by the urease method, having been apparently inactivated by the tortilla-making process. Enrichment by this method is cheaper than enrichment with soy flour or with amino acids. The method permits uniform introduction of soya proteins within the tortillas, and changes neither food recipes nor eating habits.     

Phase I studies with Baker's Antifol (BAF) (NSC 139105)

Phase I studies were conducted in 58 adult cancer patients with Baker's Antifol (BAF), a new active-site directed inhibitor of dihydrofolate reductase. Dose escalation ranged from 10 to 250 mg/m2/day X 5 days and courses of treatment were repeated every 2-3 weeks. Biologic effects were observed mostly at doses greater than 100 mg/m2/day X 5 days. The patients developed myelosuppression during 19% of the trials. Other types of toxicity were dermatitis in 12 to 30% and stomatitis in 7 to 38% of the trials. Toxicity was directly related to the impairment of the patient's liver function. Two partial responses (in a patient with adenocarcinoma of the lung and a patient with transitional cell carcinoma of the bladder) occurred. BAF is an active new chemotherapeutic agent which deserves further clinical trials in patients with various malignancies.     

The metabolism of IgE. Studies in normal individuals and in a patient with IgE myeloma

IgE metabolic turnover studies with purified radioiodinated IgE were performed in normal individuals and in a patient with IgE myeloma. The validity of the turnover studies was established in several ways, including comparisons of radioiodinated IgE turnover with the turnover of endogenously labeled 14C-IgE and with the turnover of infused unlabeled IgE in a patient with hypogammaglobulinemia. The geometric mean serum IgE concentration in 73 normal adults was 96 ng/ml with a 68% confidence interval of 24 to 386 ng/ml. Metabolic turnover studies in 10 control individuals disclosed a geometric mean total circulating IgE of 4.1 mug/kg, a mean percentage of the total exchangeable IgE in the intravascular space of 41%, a mean half-time of survival of IgE of 2.7 days, a mean fractional catabolic rate of 94% of intravascular pool per day, and a geometric mean synthetic rate of 3.8 mug/kg/day. IgE has the lowest synthetic rate and highest fractional catabolic rate of the five major classes of immunoglobulin molecules. In contrast to these normal values, a patient with IgE myeloma had a serum IgE comcentration of 42 mg/ml, a total circulating IgE of 1.7 g/kg, and a synthetic rate of 270 mg/kg/day. Furthermore, although the synthetic rate was vastly increased, the survival time was prolonged and the fractional catabolic rate was decreased to 5.1 days and 16 to 22% of the intravascular pool per day, respectively. These data are compatible with the concept that IgE is catabolized in part by a mechanism common to all immunoglobulin classes and in part by a unique mechanism not available to other immunoglobulins. At very high IgE serum concentrations, such as those encountered in patients with IgE myeloma, the unique mechanism would be saturated and only the catabolic pathways available to all immunoglobulins would be available to IgE.     

Ocular chrysiasis correlated with gold concentrations in the crystalline lens during chrysotherapy

The eyes of 11 patients with rheumatoid arthritis (RA) who received extended chrysotherapy (mean cumulative dose greater than 7 grams during a mean 6-year period) were examined biomicroscopically. Minute reddish-purple particles were seen in the cornea (corneal chrysiasis) in 5 and in the lens (lens chrysiasis) in 4 patients. Particulate deposits were absent in 11 other RA patients who had not received gold treatment. Seven crystalline lenses from 5 gold-treated patients were removed surgically because of incidental cataract formation and analyzed for gold content using neutron activation analysis. Although the mean lens gold concentration was higher in these patients than in non-gold-treated controls without RA (0.0073 microgram/grams versus 0.001 microgram/grams), the absolute gold level was markedly lower than that found in 25 diverse tissue analyzed previously. This finding is compatible with the absence of clinical gold-related lens disease or visual impairment.     

The effects of patterned calorie-restricted diets on mammary tumor incidence and plasma endothelin levels in DMBA-treated rats

Chronic caloric restriction has been shown to inhibit mammary tumor promotion in the 7,12-dimethyl-benz[a]anthracene (DMBA) rat mammary tumor model. The objectives of this study were to determine (i) the effects of chronic caloric cycling (yo-yo dieting) on mammary tumor promotion by high fat diets and (ii) the effect of three dietary regimens +/- superimposed mammary tumor burden on plasma endothelin-1,2 (ET) levels. Female Sprague-Dawley rats were treated with DMBA (5 mg/rat) and divided into three dietary groups: ad libitum (AL) (containing 15% corn oil); 40% calorie restricted (CR) (containing 20% corn oil so consumption of fat was equivalent between AL and CR); a calorie cycled (CC) group fed alternatively AL and CR diets each 48 h period. After 10 weeks, tumor incidences were: AL, 63%; CR, 27%; CC, 57% (AL versus CR, P < 0.05; CC versus CR, P < 0.05; AL versus CC, NSD). ET levels (pg/ml plasma) were: AL, 16.0 +/- 6.54; CR, 32.31 +/- 0.34; CC, 23.44 +/- 5.04 (AL versus CR, P < 0.01; CC versus CR, P < 0.01; AL versus CC, P < 0.05). Plasma ET levels were independent of tumor incidence and tumor burden, but plasma ET levels were significantly increased in rats with a prior history of calorie restriction. As expected, maintained caloric restriction reduced mammary tumor incidence but intermittent caloric restriction (caloric cycling or yo-yo dieting) was without similar benefit.     

Retroactive excitation: Posttraining social experience with siblings consolidates maternal imprinting in ducklings (Anas platyrhynchos).

Previous studies have revealed that if mallard ducklings are given social experience with broodmates after their initial exposure to a stuffed mallard (Anas platyrhynchos) hen, they later show a visual preference for the familiar mallard over an unfamiliar redhead (Aythya americana) model. Birds kept in isolation do not make this difficult discrimination. We examined when the social experience with siblings must occur in order to contribute to maternal imprinting. We allowed 24-hr-old domestic mallard ducklings to follow a stuffed mallard hen for 30 min (training). This experience resulted in a preference for the familiar mallard over the unfamiliar redhead hen in a simultaneous choice test 48 hrs after hatching only if the birds were allowed social experience with broodmates after the training trial (i.e., from 24 to 48 hrs). Thus the visual features of the mallard hen that are necessary in order to distinguish it from the redhead hen become consolidated only after more than 1 hr into the posttraining social rearing; we term this process retroactive excitation. These results provide evidence of a nonobvious experiential contribution that conspecifics make to the development of species-typical social behavior. They also suggest that some learning and memorial processes may operate rather differently in adults and immature animals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Improving the social status of mainstreamed retarded children.

37 mainstreamed educable mentally retarded (EMR) children in Grades 3, 4, and 5 were randomly assigned to a control group or to an experimental treatment given during regular class activities for the purpose of improving their social status among nonretarded classmates. On the average, Ss were 8–20 mo older than their normal classmates. Each experimental S worked in a small cooperative group with 4–6 nonretarded classmates on highly structured, manipulative tasks using multimedia materials. The treatment was provided in 2 cycles which lasted a total of 8 wks. Sociometric tests were given before and after treatment to pupils in classes with experimental and control EMR Ss. By 2–4 wks following completion of treatment, nonretarded Ss' social acceptance of their experimental peers improved significantly more than that of control Ss. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)