Search

In the last twenty years, powerful new molecular techniques were introduced that made it possible to advance knowledge in human biology using a reductionist approach. Now, the need for scientists to deal with complexity should drive a movement toward an integrationist approach to science. We propose that nutritional science is one of the best reservoirs for this approach. The American Society for Nutritional Sciences can play an important role by developing and delivering a cogent message that convinces the scientific establishment that nutrition fills this valuable niche. The society must develop a comprehensive strategy to develop our image as the reservoir for life sciences integration. Our efforts can start with our national meeting and publications, with the research initiatives for which we advocate, with our graduate training programs and with the public relations image we project for ourselves. Defining the image and future directions of nutrition as the discipline that can integrate scientific knowledge from the cell and molecule to the whole body and beyond to populations can be the most important task that our society undertakes. If we do not effectively meet this challenge, a golden opportunity will pass to others and nutritional scientists will be left to follow them. J. Nutr. 131: 1319-1321, 2001. KEY WORDS: * nutrition * American Society for Nutritional Sciences * long range planning * scientific integration

The National Cancer Institute has sponsored an investigational new drug application, in collaboration with Protein Technologies International, to conduct single-dose, phase 1 pharmacokinetic and safety studies of well-characterized isoflavone mixtures in men and women. Before the initiation of the trial, a sensitive analytical method was developed and validated to measure free and conjugated genistein and daidzein in plasma and urine. The proprietary mixtures were administered on the basis of genistein. Five groups of three subjects were administered the mixtures at 1, 2, 4, 8 and 16 mg/kg body weight. Blood and urine samples were collected and analyzed to determine pharmacokinetic parameters. Safety was monitored by clinical signs, clinical chemistry values, hematology and follow-up. Results from the study in men will be presented. Pharmacologic plasma levels of free genistein up to ~100 ng/mL and of conjugated genistein up to ~7500 ng/mL were achieved. The repeat-dose portion of the phase 1 studies is now being initiated.

The concept of the nutritional phenotype is proposed as a defined and integrated set of genetic, proteomic, metabolomic, functional, and behavioral factors that, when measured, form the basis for assessment of human nutritional status. The nutritional phenotype integrates the effects of diet on disease/wellness and is the quantitative indication of the paths by which genes and environment exert their effects on health. Advances in technology and in fundamental biological knowledge make it possible to define and measure the nutritional phenotype accurately in a cross section of individuals with various states of health and disease. This growing base of data and knowledge could serve as a resource for all scientific disciplines involved in human health. Nutritional sciences should be a prime mover in making key decisions that include: what environmental inputs (in addition to diet) are needed; what genes/proteins/metabolites should be measured; what end-point phenotypes should be included; and what informatics tools are available to ask nutritionally relevant questions. Nutrition should be the major discipline establishing how the elements of the nutritional phenotype vary as a function of diet. Nutritional sciences should also be instrumental in linking the elements that are responsive to diet with the functional outcomes in organisms that derive from them. As the first step in this initiative, a prioritized list of genomic, proteomic, and metabolomic as well as functional and behavioral measures that defines a practically useful subset of the nutritional phenotype for use in clinical and epidemiological investigations must be developed. From this list, analytic platforms must then be identified that are capable of delivering highly quantitative data on these endpoints. This conceptualization of a nutritional phenotype provides a concrete form and substance to the recognized future of nutritional sciences as a field addressing diet, integrated metabolism, and health. [ABSTRACT FROM AUTHOR]

It is rapidly becoming possible to measure hundreds or thousands of metabolites in small samples of biological fluids or tissues. This makes it possible to assess the metabolic component of nutritional phenotypes and will allow individualized dietary recommendations. ASNS has to take action to ensure that appropriate technologies are developed and that metabolic databases are constructed with the right inputs and organization. The relations between diet and metabolomic profiles and between those profiles and health and disease must be established. ASNS also should consider the social implications of these advances and plan for their appropriate utilization. [ABSTRACT FROM AUTHOR]

How quality of center-based child care relates to early cognitive and language development was examined longitudinally from 6 to 36 months of age in a sample of 89 African American children. Both structural and process measures of quality of child care were collected through observation of the infant classroom. Results indicated that higher quality child care was related to higher measures of cognitive development (Bayley Scales of Infant Development), language development (Sequenced Inventory of Communication Development), and communication skills (Communication and Symbolic Behavior Scales) across time, even after adjusting for selected child and family characteristics. In addition, classrooms that met professional recommendations regarding child:adult ratios tended to have children with better language skills. Classrooms that met recommendations regarding teacher education tended to have girls with better cognitive and receptive language skills. These findings, in conjunction with the growing child-care literature, provide further evidence that researchers and policymakers should strive to improve the quality of child care to enhance early development of such vulnerable children. [ABSTRACT FROM AUTHOR]

A potent immunosuppressor factor, known as SER (suppressive E-receptor factor) has been identified in the body fluids of cancer patients. SER has been proven to be immunochemically analogous to the fetal form of haptoglobin. In this paper, we examine the role of SER immune suppressor in the immune surveillance mechanism of the host, using an affinity-purified SER. As shown in this study, SER, at µg/ml concentrations, inhibits the T-cell proliferation induced with either monoclonal or polyclonal T-cell activators in vitro in human, and also inhibits the primary antibody response to T-dependent antigens in vivo in mice. Likewise, SER also inhibits the immunoglobulin synthesis of human B lymphocytes induced by a B-cell mitogen, pokeweed mitogen, in the presence of a tumour promoter, phorbol myristate acetate (PMA). In contrast to the T-dependent antibody response in vivo in mice or T-dependent mitogen response in vitro in human, SER does not interfere with the T-independent antibody responses to DNP-Ficoll or TNP-LPS in mice. SER also interferes with the natural killer cell function of human peripheral blood mononuclear cells. Although SER inhibits the phagocytic functions of human peripheral neutrophils, it requires at least 10-20 times the concentration of SER present in normal human plasma. Since this concentration of SER is attainable in the sera of solid tumour-bearing patients, highly elevated levels of SER could predispose the patients to microbial infections as well. This study demonstrates that purified SER manifests multi-faceted down-regulatory effects on the defence mechanism of hosts, thereby it could compromise the patients' cell-mediated immunity in vivo. [ABSTRACT FROM AUTHOR]

The mechanisms which drive initiated cells to progress to form carcinomas are poorly understood. CWSV-1 rat hepatocytes, in which p53 protein is inactivated by SV40 large T antigen, respond by inducing p53-independent apoptosis when acutely switched to medium containing low choline (16% apoptotic at 48 h in 5 microM choline) as compared with controls (1% apoptotic at 48 h in 70 microM choline). The rate of apoptosis was inversely correlated with cellular phosphatidylcholine content. Choline deficiency (CD)-induced apoptosis is probably mediated by TGFbeta1 and reactive oxygen species, since immunoneutralization of TGFbeta1 in the medium or treatment with N-acetylcysteine (an antioxidant) or addition of neocuproine (a transition metal chelator) prevented CD-induced apoptosis. CWSV-1 hepatocytes could be gradually adapted to survive in 5 microM choline. CD-adapted cells had increased membrane phosphatidylcholine concentrations (compared with acute CD cells). Adapted cells acquired relative resistance to CD-induced apoptosis (7% of adapted cells compared with 19% of non-adapted cells were apoptotic at 48 h in 5 microM choline). They also became relatively resistant to another p53-independent form of apoptosis (TGFbeta1-induced). CD-adapted hepatocytes developed increased capability for anchorage-independent growth and formed tumors when transplanted into nude mice; passage-matched control hepatocytes did not possess these properties. Cell transformation was dependent on exposure to the selective pressure of CD apoptosis, as we observed that when CD apoptosis was inhibited with an antioxidant during adaptation, cells did not become anchorage independent. Acquisition by p53-deficient cells of resistance to p53-independent inducers of apoptosis (CD, TGFbeta1 and reactive oxygen species) may leave cells without another important apoptotic defensive barrier and may be responsible for the progression of initiated cells to frank carcinomas. [ABSTRACT FROM PUBLISHER]