Melastatin expression and prognosis in cutaneous malignant melanoma.

PURPOSE: Melastatin (MLSN-1), a novel melanocyte-specific gene recently identified using a genomic approach, is expressed in murine and human melanoma cells at levels inversely proportional to metastatic rates in vivo. We studied the relationship between expression of melastatin mRNA in the primary cutaneous tumor and prognosis in patients with localized malignant melanoma. PATIENTS AND METHODS: Melastatin mRNA was evaluated by in situ hybridization in primary cutaneous melanoma from 150 patients with localized disease (American Joint Committee on Cancer [AJCC] stage I and II). Multivariate Cox proportional hazards regression analysis was performed to assess the prognostic utility of melastatin mRNA expression while adjusting for other prognostic indicators. RESULTS: Uniform melastatin mRNA expression in the primary tumor was correlated with prolonged disease-free survival (P < .0001). Multivariate analysis revealed that melastatin status, mitotic rate, and tumor thickness influence disease-free survival independently. The 8-year disease-free survival rate in AJCC stage I patients whose tumors diffusely expressed melastatin mRNA was 100%, whereas in stage I patients with melastatin loss, the disease-free survival rate was 77% +/- 15% (median +/- SE). In patients with stage II disease whose tumors diffusely expressed melastatin mRNA, the 8-year disease-free survival rate was 90% +/- 7%, whereas in patients with melastatin loss, the disease-free survival rate was 51% +/- 8%. CONCLUSION: Downregulation of melastatin mRNA in the primary cutaneous tumor is a prognostic marker for metastasis in patients with localized malignant melanoma and is independent of tumor thickness and other variables. Used in combination, melastatin status and tumor thickness allow for the identification of subgroups of patients at high and low risk of developing metastatic disease.

Let the pyramid guide your food choices: capturing the total diet concept.

This paper discusses how the guideline "Eat a variety of foods" became "Let the Pyramid guide your food choices," presents background information on the food guidance system upon which the Food Guide Pyramid is based and reviews methods that have been used to assess aspects of the total diet, i.e., the variety, moderation and proportionality, promoted by this guidance. The methods include measures of dietary variety, patterns based on Pyramid food group intakes and scoring methods comprised of multiple dietary components. Highlights of results from these methods include the following. Although approximately one third of the U.S. population eat at least some food from all Pyramid food groups, only approximately 1-3% eat the recommended number of servings from all food groups on a given day. Fruits are the most commonly omitted food group. Vegetables and meat are the groups most commonly met by adults, and dairy the most commonly met by youth. Intakes of specific types of vegetables (i.e., dark green, deep yellow) and of grains (i.e., whole grains) are well below that recommended; intakes of total fat and added sugars exceed current recommendations. Scoring methods show those diets of the majority of the population require improvement, and that diets improve with increases in education and income. This paper also discusses the limitations and strengths of these approaches, and concludes with suggestions to improve current food guidance and methods to assess the total diet.

Patterns of melastatin mRNA expression in melanocytic tumors.

The melanocyte-specific gene Melastatin (MLSN1) shows an inverse correlation of mRNA expression with metastatic potential in human and murine cell lines in vitro. Melastatin mRNA expression in primary cutaneous melanoma also has been found to correlate with disease-free survival. The histologic patterns of Melastatin mRNA expression in nevi, primary melanoma, and melanoma metastases have not been described previously. Using in situ hybridization with (35)S-labeled probes, we examined Melastatin mRNA expression in 64 cases of normal skin, benign melanocytic nevi, primary cutaneous melanomas, and melanoma metastases. Ubiquitous melanocytic expression of Melastatin mRNA was observed in all benign melanocytic proliferations (14 of 14), although some nevi showed a gradient of reduced Melastatin expression with increased dermal depth (3 of 14). Uniform expression of Melastatin mRNA was observed in 49% of primary cutaneous melanomas (18 of 37 cases, including 1 case of in situ melanoma). Melastatin mRNA loss by a portion of the melanoma was identified in 53% of the invasive melanoma samples (19 of 36) and 100% of the melanoma metastases (11 of 11). Primary melanomas without mRNA loss ranged in thickness from 0.17 to 2.75 mm (median, 0.5 mm; mean, 0.73 mm), whereas tumors that showed Melastatin mRNA down-regulation ranged in thickness from 0.28 to 5.75 mm (median, 1.7 mm; mean, 2.13 mm). A focal aggregate or nodule of melanoma cells without detectable signal was the most commonly observed pattern of Melastatin loss (13 of 19 cases), whereas complete loss of Melastatin mRNA expression by all of the dermal melanoma cells was observed in only 4 of the 19 cases. Two invasive melanomas displayed a scattered, nonfocal pattern of Melastatin mRNA loss. Of the 11 melanoma metastases examined, 64% displayed focal Melastatin mRNA loss, and 36% had complete loss of Melastatin mRNA expression. We observed several patterns of Melastatin mRNA expression in primary melanoma that may be distinguished from expression in benign melanocytic nevi. Melastatin mRNA expression appears to correlate with melanocytic tumor progression, melanoma tumor thickness, and the potential for melanoma metastasis. HUM PATHOL 31:1346:1356.

Synthesis and Anti-Candida Activity of Cobalt(II) Complexes of Benzene-1,2-Dioxyacetic Acid (bdoaH(2)). X-Ray Crystal Structures of [Co(bdoa)(H(2)O)(3)] 3.5H(2)O and {[CO(phen)(3)](bdoa)}(2)24H(2)O (phen = 1,10-Phenanthroline).

Co(CH(3)CO(2))(2)4H(2)O reacts with benzene-1,2-dioxyacetic acid (bdoaH(2)) to give the Co(2+) complexes [Co(bdoa)(H(2)O)(3)]H(2)O (1a) and [Co(bdoa)(H(2)O)(3)] 3.5H(2)O (1b). Subsequent reaction of 1a with 1,10- phenanthroline produces [CO(phen)(3)] bdoa10H(2)O (2a) and {[CO(phen)(3)](bdoa)}(2)24H(2)O (2b). Molecular structures of 1b and 2b were determined crystallographically. In 1b the bdoa(2-)- ligates the metal by two carboxylate oxygens and two ethereal oxygens, whereas in 2b the bdoa(2-) is uncoordinated. The Mn(2+) and Cu(2+) complexes [Mn(bdoa)(phen)(2)]H(2)O (3) and [Cu(pdoa)(imid)(2)] (4) were also synthesised, 1a-4 and other metal complexes of bdoa H(2) (metal = Mn(2+), Co(2+) ,Cu(2+), Cu(+) ) were screened for their ability to inhibit the growth ofhe yeast Candida albicans. Complexes incorporating the 1,10-phenanthroline ligand were the most active.

Role of mu heavy chain in B cell development. I. Blocked B cell maturation but complete allelic exclusion in the absence of Ig alpha/beta.

There is good evidence for a signaling role played by Ig heavy chain in the developmental transition through the pre-B cell stage. We have previously described signal-capable or signal-incapable mutants of mu heavy chain in which a signaling defect is caused by failure to associate with the Ig alpha/beta heterodimer. To further characterize the role of Ig heavy chain-mediated signaling in vivo, as well as in B cell development and allelic exclusion, we have created transgenic mice in which the B cells express these signal-capable and signal-incapable mutant mu chains. Failure of mu to signal via Ig alpha/beta results in a block in B cell development in mice expressing the signal-incapable mu. A small number of B cells in these animals do escape the developmental block and are expressed in the spleen and the periphery as B220+ transgenic IgM+ cells. These cells respond to LPS by proliferating but show no response to T-independent-specific Ag. In contrast, B cells expressing the signal-capable B cell receptor show a strong signaling response to Ag-specific stimulus. There is no Ig alpha seen in association with signal-deficient IgM. Thus, the B cell receptor complex is not assembled, and no signal can be delivered. Despite the block in developmental signaling, allelic exclusion is complete. There is no detectable coexpression of transgenic IgM and endogenous murine IgM, nor is there rearrangement of the endogenous heavy chain genes. This suggests that differing signaling mechanisms are responsible for the developmental transition and allelic exclusion and thus allows for separate examination of these signaling mechanisms.

Omega-3 fatty acid content of the US food supply.

In this study, levels and sources of omega-3 fatty acids (FA) available for consumption in the US food supply, dating from 1935, are estimated. omega-3 FA assessed are eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linolenic acid (LNA). Estimates are based on annual per capita food use data and data on the omega-3 FA content of foods. Although fish use increased, the EPA level was slightly lower in 1985 than in 1935-1939, reflecting a marked decline in use of certain fatty fish. The level of DHA increased, due to greater use of poultry. The level of LNA increased because of greater use of soybean oil. These estimates are currently the only source of data on omega-3 FA in the American diet.

Food sources of energy, macronutrients, cholesterol, and fiber in diets of women.

Data from the 1985 Continuing Survey of Food Intakes by individuals were used to calculate the contributions of individual foods to women's intakes of energy, protein, carbohydrate, fat, saturated fatty acids, cholesterol, and fiber. We separated nearly all food mixtures into their constituent ingredients, grouped the ingredients together with similar foods, and examined the contributions of those foods. Yeast breads that were neither whole grain nor higher fiber contributed about 7% of the energy to the diets, which made them the leading source of energy of the foods we examined. The leading sources of protein were animal products: poultry contributed approximately 12%, beef contributed about 19%, cheese contributed about 8%, and pork contributed about 6%. The various fats and oils were the greatest contributors to fat, and cheese was the chief source of saturated fatty acids. Eggs were the major source of cholesterol; they provided around 36% of the total. Two of the top three sources of carbohydrate--regular soft drinks and sugar--are composed entirely of simple sugars. Potatoes provided around 11% of the fiber, which made them the leading source of fiber. This article shows that the relative ranking of foods and the contribution of each food depend on the way food codes are combined. Therefore, citing one food as the major source of a particular food component without including documentation of how foods are combined can be misleading.

Contributions of food groups to intakes of energy, nutrients, cholesterol, and fiber in women's diets: effect of method of classifying food mixtures.

This study examined the effect of using two different methods for categorizing food mixtures when calculating the contribution of various food groups to energy, macronutrient, cholesterol, and fiber intakes. Using method 1, each food mixture was classified as a single item and assigned to a food group according to its main ingredient. Using method 2, most of the food mixtures were separated into their constituent ingredients, and each ingredient was assigned to its appropriate food group. Data were from 1,032 women who provided at least 4 days of dietary data in the U.S. Department of Agriculture's 1985 Continuing Survey of Food Intakes by Individuals. We found that the importance of each food group's contribution to individual dietary components varied depending on the method used to categorize the food mixtures. When food mixtures were separated into their constituent ingredients before assigning foods to food groups, the contributions of meat, fish, poultry, and grain products declined for each of the seven dietary components studied. At the same time, the contributions of milk products, fats, and oils increased for most of the seven components. The results highlight the importance of foods eaten as part of food mixtures to the intake of energy, macronutrients, cholesterol, and fiber.

Use of focus groups to explore consumers' preferences for content and graphic design of nutrition publications.

The purpose of this research was to determine consumers' preferences for the content and design of nutrition print materials through the use of focus group interviews. Thirty-seven non-pregnant, non-nursing female consumers 20 to 50 years of age attended one of six focus group interviews. Existing nutrition print materials were used to stimulate discussion on content and graphic design features of the materials. Content features discussed included glossaries, quizzes, diet evaluation checklists, diet monitoring forms, and "factual" vs. "how to " information. Graphic design features discussed included color, format, size, organization, and general appearance. Participants were asked to discuss the personal impressions and practical considerations that formed the basis of their opinions regarding each feature and to elaborate on how the existing materials might be improved to meet their particular needs. Features that drew the most positive reactions were bright food colors, organizational cues, clear information and explanations, features that help personalize the issue being addressed, and "how to" information.

Number of days of food intake records required to estimate individual and group nutrient intakes with defined confidence.

The number of days of food intake data needed to estimate the intake of 29 male (n = 13) and female (n = 16) adult subjects, individually and as a group, was determined for food energy and 18 nutrients. The food intake records were collected in a year-long study conducted by the U.S. Department of Agriculture's Beltsville Human Nutrition Research Center. Each individual's average intake of nutrients and standard deviation over the year were assumed to reflect his or her "usual" intake and day-to-day variability. Confidence intervals (P less than 0.05) for each individual's usual intake were constructed, and from these the number of days of dietary records needed for estimated individual and group intake to be within 10% of usual intake was calculated. The results indicated that the number of days of food intake records needed to predict the usual nutrient intake of an individual varied substantially among individuals for the same nutrient and within individuals for different nutrients; e.g., food energy required the fewest days (averaging 31) and vitamin A the most (averaging 433). This was considerably higher than the number of days needed to estimate mean nutrient intake for this group, which ranged from 3 for food energy to 41 for vitamin A. Fewer days would be needed for larger groups.

Food group system of analysis with special attention to type and amount of fat--methodology.

A system for reporting dietary data in terms of food groups is described. The scheme was developed jointly by the National Heart, Lung, and Blood Institute (NHLBI) and the U.S. Department of Agriculture to identify food use patterns in various population groups. The system comprises 14 major groups and 75 minor groups based on major nutrient composition with special attention to fats. One-day dietary recalls from 5,640 participants in the Lipid Research Clinics (LRC) Prevalence Study were analyzed to determine the frequency of food group usage by males and females in age groups 6 to 9, 10 to 19, 20 to 59, and 60 and older. Food group use is reported as percent of the population reporting use as obtained by the dietary recall as well as the average number of times each food group was mentioned by the users. LRC food selection patterns are compared with the Dietary Guidelines. Findings in this report indicate that, for the LRC population, some of the foods emphasized in the guidelines are not eaten with a high degree of frequency.

Food choices among white adolescents: the Lipid Research Clinics Prevalence Study.

Food groups have been widely used in nutrition education but relatively few studies have employed food groups to interpret dietary intake. The 24-h dietary recalls of 534 male and 476 female adolescents, aged 10-19 yr, were analyzed using a food grouping scheme. Foods were grouped with emphasis placed on fats and carbohydrates. Frequency of use and contribution of food groups to the macronutrients were determined. When nutrient intake was analyzed as a percentage of total calories, both males and females were found to have similar profiles. More than 60% of each macronutrient was contributed by combinations of three major food groups. The meat/fish/poultry, milk/cheese/yogurt, and bread/cereal products food groups contributed 81.2% of the protein; milk/cheese/yogurt, bread/cereal products and sweets accounted for 63.0% of the carbohydrate intake; and 74.3% of the dietary fat consumption was attributable to the meat/fish/poultry, milk/cheese/yogurt, and fats food groups. There were no notable differences in the food groups used by males and females. However, differences between the sexes emerged when nutrient intakes as a percentage of calories were stratified and food group usage was investigated. Food groups associated with macronutrients that are believed to affect health status have been identified.

Characterizing food usage by demographic variables.

On the basis of an analysis of three-day food records, food comsumption by major segments of the U.S. population was examined for 65 food groups and subgroups. This study indicates that demographic factors, particularly age, race, and region, can affect both the percentage of persons using certain foods and the mean frequency of their use. Both the similarities and the differences on these parameters are of interest when food usage is examined by demographic variables.

Medium for the selective enumeration of lactic acid bacteria from foods.

A nitrite actidione polymyxin agar was developed for the enumeration of lactic acid bacteria. It was effective in recovering organisms from pure cultures and from foods.