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Biomedical subjects

M Winick

Publications and source records attributed to M Winick.

At least 19 recordsLinked to original sources

Nutrition training in graduate medical (residency) education: a survey of selected training programs.

Because limited information exists about nutrition training of residents, we studied the teaching practices of nationally recognized nutrition programs. Two hundred thirty-eight nutrition educators and 787 residency-program directors identified 160 institutions with strong nutrition training. The 23 highest-ranked programs were surveyed and 7 were visited. The results showed that 1) clinically active physician-nutritionist role models are the key elements in teaching residents clinical nutrition; 2) multidisciplinary nutrition support teams are valuable learning resources unless they function primarily as technical support services; 3) nutrition elective rotations, although highly effective, are taken by a minority of residents; 4) the nutrition curriculum should include practical learning materials and conferences; and 5) a research environment is important to attract qualified physician-nutritionist role models. A major deficit is teaching nutritionally based approaches to disease prevention in the ambulatory setting. Finally, a shortage of nutrition-oriented physician role models is probably the major constraint in teaching nutrition to residents.

Curriculum

Calories and cancer.

The author presents the hypothesis that no single nutrient or class of food by itself significantly affects risk for most cancers. Rather, it is the dietary pattern or the mix of nutrients and foods that affects cancer risk. And the overall caloric intake or perhaps the caloric balance is central to whether a particular dietary pattern will affect cancer risk. Supporting evidence for this hypothesis, as well as implications if correct, is also presented.

Animals

The effect of early caloric restriction on colonic cellular growth in rats.

Although the inhibitory effect of caloric restriction on tumorigenesis is substantial and well known, the pertinent mechanisms remain to be determined. We recently suggested that the risk of cancer may be directly related to the total number of dividing cells within an affected organ. This study evaluates the effects of early caloric restriction on the cellular growth of the colon. The experiment began one day postpartum and ended six weeks later with the killing of all animals. It consisted of two consecutive periods: a) three weeks of suckling and b) three weeks postweaning. Animals whose food was restricted only during the suckling period showed normal colons when killed at six weeks. Caloric restriction (40%) for three weeks postweaning resulted in colons of lower weight with fewer cells (less total DNA) and reduced total DNA synthesis [( 3H]thymidine uptake, dpm/colon) when compared with animals fed ad libitum postweaning. Conversely, only rats fed ad libitum from birth through the first three weeks after weaning demonstrated an increase (21%) in the rate of DNA synthesis (dpm/mg DNA) compared with other animals. In addition, the colonic crypts showed no differences in the number of cells or the number of dividing cells, as determined by autoradiography. By contrast, the total number of crypts (and/or the number of mucosal cells between crypts) are reduced, and hence the total number of colonic mucosal cells dividing at any given time are similarly decreased. The reduced number of dividing cells in the colons of these animals (i.e., those restricted postweaning) could explain previous data suggesting that they are resistant to the induction of colon cancer.

Animals

The effect of elevated selenium intake on colonic cellular growth in rats.

Both selenium and calorie restriction are anticarcinogenic in many tumor models, but the mechanisms of action are unknown. This study compared the effects of elevated selenium (Se) intake and calorie restriction on colonic cellular growth. Female weanling rats were divided into four groups: control, 40% calorie restricted, and 4 or 6 mg Se/l H2O as selenate. Control rats and rats given Se consumed the control diet ad libitum. Rats in the 40% calorie-restricted group were pair fed 40% less than the total intake of control rats with a diet designed to provide equal nutrients except calories from carbohydrate. After three weeks, rats were injected with [3H]thymidine (1 muCi/g body wt) and killed one hour later. Se at 4 and 6 mg/l H2O and 40% calorie restriction significantly decreased food intake, weight gain, colon weight, and total colon DNA compared with controls. Total number of cells per crypt was not affected by any treatment, whereas total DNA synthesis was significantly decreased, suggesting that the total number of colonic crypts are reduced by calorie restriction and Se treatment. The rate of cell division was decreased only in rats given 6 mg Se/l H2O. These results indicate that elevated Se intake and caloric restriction decrease colonic mucosal growth by decreasing growth in general, but only very high intakes of Se affect colonic cell turnover.

Animals

Are cell number and cell proliferation risk factors for cancer?

Relatively little is known about the mechanisms underlying carcinogenesis in humans. Caloric restriction strongly inhibits the development of neoplasia in rodents, and there is evidence of a positive relationship between cancer and body weight in humans. Caloric restriction early in life is also known to permanently diminish organ cellularity. A recent link between adult stature and cancer incidence similarly implicates a lasting effect for growth and possibly for early nutrition in carcinogenesis. It is postulated that cancer risk is proportional to the number of proliferating cells, which in turn depends on both the number of cells and the rate of cell division within the tissue. This hypothesis is consistent with several aspects of human carcinogenesis, including multistage models and the epithelial origin of most cancers.

Body Height

Effects of pre-weaning undernutrition on 21 day-old male rat skull form as described by the finite element method.

Conventional Roentgenographic Cephalometric Methods (RCM) have certain conceptual and geometric constraints that ensure that their descriptions of cephalic growth and comparisons of cephalic form are reference-frame-dependent; and it is impossible to determine which, if any, RCM reference frame provides a biologically more correct description or comparison. The use of the concepts of continuum mechanics and of the numerical techniques of the Finite Element Method (FEM) overcomes these constraints and provides reference-frame-independent (invariant) growth descriptions and form comparisons. In the FEM, the structure of the head is subdivided (discretized) into a number of smaller, finite, elements. The FEM then describes the growth behavior, or compares the form, of the entire continuum of points enclosed with each element independently; in RCM only the behaviors, or comparisons, of the landmark points are described. The FEM is described and its use illustrated by a comparison of the cephalic forms of 4 groups of weanling (21 d old) rats. The 1st (control) group is derived from normally nourished dams, while the other 3 groups are derived from dams who were malnourished throughout the weaning period in 3 group specific manners. The FEM permitted reference-frame-independent comparisons of the 4 different, and group specific, head forms. These differences were reflected in the forms of each of the finite elements. The differences in element forms between the 4 groups were shown to be related primarily to nutritionally produced alterations of either neurocranial or splanchocranial viscera. These differences were expressed in the alterations of the forms of the continua enclosed within the boundaries of the several finite elements, and secondarily in the form of the cranial skeleton.

Animals

The effects of maternal cigarette smoking on placental morphology, histomorphometry, and biochemistry.

We related cigarette smoking during pregnancy to the macroscopic and microscopic morphology, histomorphometry, and biochemistry of the placenta among participants in The Prenatal Project, a randomized, controlled trial of nutritional supplementation during pregnancy. The aim was to ascertain if the harmful effects of cigarette smoking on the fetus were reflected, and possibly mediated, by changes in the placenta, and whether such changes might be modified by the nutritional supplements, parallel to the nutritional reversal of birthweight depression among heavy smokers. Maternal smoking was associated with increased alkaline ribonuclease (RNase) levels, possibly resulting in disturbed protein synthesis. More smokers had placentas with villous hyperplasia on histologic examination. This was accompanied by biochemical evidence of significantly increased cellularity (increased DNA/gm of placental mass and decreased protein/DNA ratios) and (nonsignificant) trends to reduced syncytial villous cell size on histomorphometry. There were joint effects of cigarette smoking and use of either form of nutritional supplementation on the fibrin and stoma components of the villi, but such changes are not necessarily pathologic. The significant reduction in pathology of the stem villi among smokers was confined to those who were nutritionally supplemented, particularly heavy smokers. This change may thus have reflected the protective effects of supplementation on the birthweight of the offspring of these heavy smokers.

Cell Division

Behavioral and physiological effects of early handling and early malnutrition in rats.

This experiment employed a 2 x 2 design in which the nutritional and early stimulation conditions of rat pups were manipulated during the 1st 3 weeks of postnatal life. Animals were observed in various open field activities at 22, 23, 29, 36, and 50 days of age, and killed at 55 days of age for neurochemical analysis. Early handling decreased the behavioral differences due to malnutrition and resulted in fewer, but larger cells in rat forebrain for both well-nourished and malnourished groups.

Adrenal Glands

The effects of folic acid supplementation during pregnancy in the rat.

1. Twenty-four Sprague-Dawley female rats were randomly assigned to three groups (groups A, B, C). Group A was given a folic acid-free diet and groups B and C received 0.0018 g folic acid/kg diet. Rats in group C were also given a supplement of 1 mg folic acid/d by intraperitoneal injection. 2. After 14 d of feeding the rats were mated. The diets were continued throughout gestation. On day 21, of gestation the dams were killed and their livers and products of conception assayed for RNA, DNA, protein and tetrahydrofolate dehydrogenase (5,6,7,8-tetrahydrofolate dehydrogenase; EC 1.5.1.3) activity. 3. The foetuses, placentas and livers from supplemented rats (group C) were significantly larger than those from groups A and B and had a higher content of RNA, DNA and protein. Those tissues from group A dams were smaller than those from the other groups and had a correspondingly reduced nucleic acid and protein content. 4. The activity of tetrahydrofolate dehydrogenase, the first and rate-limiting enzyme in the metabolism of folate, was increased in the folate supplemented rats (group C) and reduced in the rats given a folic acid-free diet (group A). These changes in enzyme activity could explain the differences in nucleic acid biosynthesis and growth shown by the different groups.

Animals

Effect of malnutrition and rehabilitation on the metabolism of polyamines in rat liver.

In adult male rats the activity of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMD) and the concentration of putrescine and spermidine increased markedly 3 to 4 weeks after feeding the animals a 6% casein diet. Incorporation of [14C]orotic acid into nuclear RNA also increased during this period of time. In contrast, spermine concentration remained unchanged. During the fifth week of protein restriction enzyme activities, putrescine and spermidine concentrations and orotic acid incorporation returned to control levels. After the restricted rats were put on a control diet there was a rapid increase above control levels in ODC activity and a proportionally smaller increase in SAMD activity. Putrescine and spermidine concentration also increase above control levels. Both enzyme activities and polyamine concentrations were within normal levels 96 hours after refeeding. Spermine values were unmodified by refeeding. After a transient rise 12 hours after refeeding, incorporation of labeled orotic acid into RNA decreased significantly for the rest of the experiment.

Adenosylmethionine Decarboxylase

Studies on ribosomal RNA synthesis in vivo in rat liver during short-term protein malnutrition.

To better understand the increased incorporation of [14C] orotate into rRNA, as detailed study of liver rRNA synthesis was performed on young rats fed a 6% casein diet for 1 week. From 10 to 180 minutes after i.v. injection of [14C] orotate, nucleolar RNA specific activity of malnourished rats was 1.6 times higher than controls. Polyacrylamide gel electrophoresis revealed that 45S pre-rRNA from malnourished rats was synthesized more rapidly than controls. Specific activities of other nucleolar RNA species was increased but the time of appearance of labeled peaks did not change. The cellular cytoplasmic rRNA pool was reduced to 70% of controls, the time of appearance of labeled rRNA in the cytoplasm was the same, but cytoplasmic rRNA specific activity was 2.1 times greater than controls. Absorbance profiles and radioactivity patterns of nucleoplasmic RNA were similar in the two groups of rats. Nucleoplasmic radioactivity patterns were complex and heterodispersed, and the amount of radioactivity was greatest in RNA from malnourished rat liver. Our data indicate that short-term dietary protein restriction leads to cellular events which increase the synthesis of nuclear RNA. Nucleolar RNA is processed and transported to the cytoplasm in a manner similar to controls.

Animals