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Meeting report--National Institute on Aging Workshop on the Comparative Biology of Aging.

This Perspective is a summary of the Comparative Biology of Aging Workshop that was held in February 2002 by the National Institute on Aging in Bethesda, MD. Participants discussed ways to exploit similarities and differences in aging among diverse species to learn more about critical factors that affect aging and regulate life expectancy in animals. The aim of the workshop was to stimulate new approaches to understanding the molecular bases for differences in aging rates and life expectancy among species.

Aging↗

A workshop on medical ethics at the College of Medicine, Lagos University.

As part of an effort to improve the teaching of medical ethics in the College of Medicine, Lagos University two-day workshops were organised. Participants included people from various walks of life, for example politicians, lawyers, doctors, and patients. The workshops were quite successful, and have led to more extensive teaching of medical ethics in the college.

Bioethical Issues↗

Recommended minimum data to be collected in research studies on Alzheimer's disease. The MRC (UK) Alzheimer's Disease Workshop Steering Committee.

In order to be able to compare the results of research work carried out in different centres on Alzheimer's disease and dementia, it is necessary for there to be standardised assessment methods. The Medical Research Council organised a workshop in order to see whether workers in Britain in the field of dementia research could agree on such standardised assessment methods. The workshop agreed guidelines for the minimum data which should be collected, in clinical and pathological studies, on patients with presumed Alzheimer's disease and dementia. These recommendations are compared with other approaches based on research diagnostic criteria.

Aged↗

Evaluating comprehensive tobacco control interventions: challenges and recommendations for future action. Report of a workshop convened by the Institute for Global Tobacco Control, Johns Hopkins Bloomberg School of Public Health.

This report summarises a workshop on evaluation of tobacco control interventions convened in Santa Fe, New Mexico in June 2001 by the Institute for Global Tobacco Control at the Johns Hopkins Bloomberg School of Public Health. The evaluation of such interventions is filled with complexities which intensify as the scope of tobacco control programmes increase. Evaluators are charged with the task of determining the effect of interventions in terms of magnitude of change, the relative contribution of programme components, and the relative impact for different populations. The report explores the theoretical foundations of tobacco control evaluation and provides a conceptual framework for capturing elements necessary for evaluating interventions. It then provides two case studies of challenges encountered when evaluating large scale tobacco control initiatives. The report summarises the discussions and recommendations of the workshop's three working groups. Participants were certain and unanimous that the current state of evaluation research must be improved to evaluate accurately the dynamic nature of comprehensive tobacco control programmes. Hierarchical or multilevel modelling approaches were seen as promising for further research. Coordinated evaluation will provide a better understanding of local, state, and national tobacco control efforts.

Guidelines as Topic↗

Summary of final report: Space Life Sciences Planning Workshop (SLSPW). June 5-7, 2000 Mont Tremblant, Quebec.

A Space Life Sciences Planning Workshop was sponsored by the Canadian Space Agency to identify key questions in the major research areas supported by the Life Sciences Program, to identify Canadian strengths and capabilities as they relate to these research areas, and to make recommendations for the future directions of the Life Sciences Program. The conclusions reached by the workshop participants have been presented to the Canadian Space Agency. This report is a summary of those conclusions.

Biological Science Disciplines↗

Workshop on late effects of irradiation to the head and neck in infancy and childhood.

A summary statement for the Workshop on Late Effects of Irradiation to the Head and Neck in Infancy and Childhood is presented. The Workshop, conducted by the National Cancer Institute with the cooperation of several other organizations, was convened to determine the present status of knowledge about thyroid disease related to irradiation of the head and neck and to develop guidelines with respect to detection, diagnosis, treatment, and followup. It was decided that surgical exploration should be considered for all palpable thyroid nodules, particularly those that are firm and clearly demarcated and appear as a "cold" area on the scan. Persons at risk because of prior irradiation to the head or neck should have regular reexaminations every one to two years.

Child↗

Proceedings of a National Cancer Institute workshop: MR spectroscopy and tumor cell biology.

In December 1991, the National Cancer Institute held a workshop to evaluate the role of magnetic resonance (MR) spectroscopy in human cancer biology. The clinical and basic cancer research issues requiring use of MR spectroscopy, the advantages and limitations of MR spectroscopy, and future directions in MR spectroscopy of cancer were discussed. Consensus-building panels were formed on the following four topics: cell membrane biochemistry, tumor therapeutic response or drug resistance, appropriate model systems, and potential clinical applications of MR spectroscopy. The workshop members concluded that large prospective clinical studies as well as in vivo animal and human studies to define prognostic variables should be performed, with correlation between MR spectroscopic results and biochemical and physiologic features. Studies of phospholipid metabolism, the pharmacokinetics of anticancer agents, and effects of new cancer treatments on the tumor vasculature and normal tissues are needed.

Humans↗

NHLBI workshop report: endothelial cell phenotypes in heart, lung, and blood diseases.

Endothelium critically regulates systemic and pulmonary vascular function, playing a central role in hemostasis, inflammation, vasoregulation, angiogenesis, and vascular growth. Indeed, the endothelium integrates signals originating in the circulation with those in the vessel wall to coordinate vascular function. This highly metabolic role differs significantly from the historic view of endothelium, in which it was considered to be merely an inert barrier. New lines of evidence may further change our understanding of endothelium, in regard to both its origin and function. Embryological studies suggest that the endothelium arises from different sites, including angiogenesis of endothelium from macrovascular segments and vasculogenesis of endothelium from microcirculatory segments. These findings suggest an inherent phenotypic distinction between endothelial populations based on their developmental origin. Similarly, diverse environmental cues influence endothelial cell phenotype, critical to not only normal function but also the function of a diseased vessel. Consequently, an improved understanding of site-specific endothelial cell function is essential, particularly with consideration to environmental stimuli present both in the healthy vessel and in development of vasculopathic disease states. The need to examine endothelial cell phenotypes in the context of vascular function served as the basis for a recent workshop sponsored by the National Heart, Lung, and Blood Institute (NHLBI). This report is a synopsis of pertinent topics that were discussed, and future goals and research opportunities identified by the participants of the workshop are presented.

Animals↗

Surgical workshop on liver surgery using isolated perfused livers in moulded casts of the upper abdomen.

The basic training in liver surgery on isolated perfused livers used at the workshop in the First Surgical Course of the Alps--Adriatic Hepatobiliary School is presented. The methods for the excision, preservation, perfusion and preparation of the liver are described, as is the manner of manufacturing the upper abdomen moulded casts, into which an isolated perfused liver is placed for training. The methods proved to be sufficiently successful, enabling participants to perform basic liver surgery like an intraoperative ultrasound investigation, as well as liver dissection techniques, liver suturing, segmental resection and even hepatectomy. Some technical improvements are proposed for future surgical workshops, such as washing out the blood from the liver, and a triple perfusion.

Abdomen↗

Expanding the use of magnetic resonance in the assessment of tumor response to therapy: workshop report.

Although dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and magnetic resonance spectroscopy (MRS) have great potential to provide routine assessment of cancer treatment response, their widespread application has been hampered by a lack of standards for use. Thus, the National Cancer Institute convened a workshop to assess developments and applications of these methods, develop standards for methodology, and engage relevant partners (drug and device industries, researchers, clinicians, and government) to encourage sharing of data and methodologies. Consensus recommendations were reached for DCE-MRI methodologies and the focus for initial multicenter trials of MRS. In this meeting report, we outline the presentations, the topics discussed, the ongoing challenges identified, and the recommendations made by workshop participants for the use of DCE-MRI and 1H MRS in the clinical assessment of antitumor therapies.

Humans↗

Mouse Models of Human Cancers Consortium Workshop on Nervous System Tumors.

Nervous system tumors are clinically challenging neoplasms that form within the central and peripheral nervous system. Although there have been many clinical trials using novel agents for the treatment of primary brain tumors, there have been few advances that positively affect overall patient survival. Over the past several years, there has been significant progress in the development of accurate small-animal spontaneous brain tumor models, small-animal neuroimaging, and tools for the bioinformatic analysis of complex molecular data sets, all of which have contributed to an improved understanding of the pathogenesis of human brain tumors. Whereas these models will continue to be of great value in basic science investigations, they can also be used to identify and validate potential therapies for brain tumors and to evaluate these drugs in preclinical trials. The National Cancer Institute recently convened a workshop to review the current state of small-animal brain tumor modeling and to make recommendations about the use of these models to improve the clinical outcome for patients with brain tumors. In this meeting report, we outline the current state of small-animal models for brain tumors, the potential applications of these models, and the recommendations made by the workshop participants for the use of mouse models in the preclinical evaluation of potential brain tumor therapies.

Animals↗

The ISOBM TD-7 Workshop on hCG and related molecules. Towards user-oriented standardization of pregnancy and tumor diagnosis: assignment of epitopes to the three-dimensional structure of diagnostically and commercially relevant monoclonal antibodies directed against human chorionic gonadotropin and derivatives.

The ISOBM TD-7 hCG Workshop was established to characterize the molecular epitope structure and specificities of a panel of diagnostically relevant monoclonal antibodies (MAbs) directed against human chorionic gonadotropin (hCG) and its derivatives, and to consider how this information could be used to improve comparability of immunoassay results for these analytes. In this multicenter study, 27 MAbs have been characterized in detail as to their main and fine specificities by direct binding-, competitive- and sandwich-RIA, -ELISA, BIAcore and Western blotting. Antigens used in the study included the upcoming first WHO reference reagents for immunoassay, i.e. nick-free hCG (hCG), nicked hCG (hCGn), hCG alpha-subunit (hCGalpha), hCG beta-subunit (hCGbeta), nicked hCG beta-subunit (hCGbetan), hCG beta-core fragment (hCGbetacf), synthetic peptides of hCGbeta C-terminal peptide (hCGbetaCTP), and homologous hormones, luteinizing hormone (LH) and subunits (LHbeta) from various species. Correct classification of blinded internal controls demonstrated the reliability of the MAb referencing approach. Three-dimensional molecular epitope assignment was possible in many instances by comparing immunoreactivity of the ISOBM MAbs (n = 27) to a large panel of MAbs (n = 18) previously well characterized in the Innsbruck (P.B.) and Paris (J.M.B.) laboratories. All three major antibody specificities (alpha, n = 1; beta, n = 21; alphabeta, n = 5) were represented in the TD-7 MAb panel. HCGbeta MAbs could further be subdivided into (i) those recognizing hCGbeta only (epitopes: beta(6), n = 1; beta(7), n = 2; beta(14), n = 1) and (ii) those recognizing hCGbeta + hCG (beta1, beta2, beta4, beta5, n = 10; beta8 and beta9, n = 9). Members of the latter group were specific either for hCG + hCGbeta + hCGbetacf (beta1, n = 3) or hCG + hCGbeta + hCGbetaCTP (beta8, n = 6; beta9, n = 1) or in addition to hCG + hCGbeta + hCGbetacf recognized hLH/hLHbeta to a minor (beta2, n = 3; beta4, n = 3) or similar degree (beta5, n = 1). Epitopes were (i) located on the first and third loops protruding from the cystine knot of hCGbeta (beta2-beta6, aa hCGbeta20-25 and 68-77), (ii) presumably centered around the knot itself (beta1), or (iii) on hCGbetaCTP (epitope beta8 = hCGbeta141-144, beta9 = hCGbeta113-116). The ISOBM panel of MAbs represents all major epitope specificities suitable for the design of specific sandwich immunoassays. High analyte variability in serum and urine during the course of pregnancy and tumor development favors certain epitope combinations. For routine diagnostic purposes, assays recognizing a broad spectrum of hCG/hCGbeta variants such as hCG + hCGn + hCGbeta + hCGbetan + hCGbetacf + -CTPhCG + -CTPhCGbeta may be useful. Low cross-reactivity against related glycoprotein hormones (e.g. hLH) and their derivatives is mandatory. These criteria are best met by combinations of MAbs directed against epitopes located around the cystine knot (beta1) and against those encompassing the top of loops 1 and 3 on hCGbeta (beta2, beta4). The first WHO reference reagents for immunoassay of hCG and hCG-related molecules being prepared by the IFCC should facilitate characterization of what assays for 'hCG' are measuring. The next step towards improving between-laboratory comparability of measurements of hCG/hCG derivatives in pregnancy and oncology is provided by results of this TD-7 Workshop.

Animals↗

Characterization of monoclonal antibodies directed against squamous cell carcinoma antigens: report of the TD-10 Workshop.

Thirteen monoclonal antibodies directed against squamous cell carcinoma antigens (SCCA1 and SCCA2) were obtained from five international collaborating laboratories participating in the ISOBM TD-10 Workshop. Native and recombinant forms of SCCA were used in a wide variety of approaches to determine the reactivity and specificity of these antibodies. Based on reactivity, the antibodies could be divided into three groups: the SCCA1-reactive group containing those that reacted only with recombinant SCCA1 (rSCCA1) and native SCCA1 (nSCCA1) antigens, the SCCA2-reactive group containing those that reacted only with recombinant SCCA2 (rSCCA2), and the pan-reactive group containing those antibodies that reacted with rSCCA1, nSCCA1, and rSCCA2. Binding to radioiodinated rSCCA1 showed that all reactive antibodies were of a high affinity (K(d) <2 x 10(-9) mol/l). Binding to labelled rSCCA2 demonstrated that five antibodies were of a high affinity (K(d) <2 x 10(-9) mol/l). Antibody reactivity on Western blots was tested with nonreduced and reduced native and recombinant SCCA1 and SCCA2. In general, these findings showed that reduction had little effect on binding to SCCA1, but often a strong effect on the binding to SCCA2. Binding of antibodies to rSCCA1 and rSCCA2 in complexes with cathepsin L and G, respectively, was used to assist in the localization of epitope regions in enzyme-complexed SCCA. Cross-inhibition experiments showed that SCCA1-reactive antibodies represent two different epitope groups, and this is supported by their ability to make SCCA1-specific assays by combining antibodies from the two epitope groups. The SCCA2-reactive group represents two related antibodies and one unique as seen in cross-inhibition, but they do not form successful assay combinations. Classification of the pan-reactive antibodies is more difficult, as some epitope groups differ when results from rSCCA1 are compared with rSCCA2 as the target. However, two antibodies are outstanding, SCC107 and SCC113, as they are high-affinity antibodies which react equally well with free and protease complexes of SCCA1 and SCCA2. The precise location of epitopes was further studied using sequential overlapping peptides and homology modelling. The findings from this workshop strongly indicate that the recombinant antigens (rSCCA1 and rSCCA2) are very similar in epitope structure to the native counterparts in saliva, and squamous epithelium from normal and cancer tissues. Therefore, it is reasonable to conclude that the specificities found are reliable and have application for antibody measurement of all forms of squamous cell carcinoma in serum except SCCA2 in complex with its protease.

Antibodies, Monoclonal↗

Cell transplantation as future therapy for cardiovascular disease?: A workshop of the National Heart, Lung, and Blood Institute.

Despite the development of improved therapies and the significant advances in the understanding of the basis of disease pathogenesis, millions of Americans continue to live with life-threatening cardiovascular diseases. Recent breakthroughs suggest exciting directions that are likely to produce more effective therapies for the treatment of cardiovascular disease. One such area, cell transplantation (grafting of healthy cells into the diseased heart), holds enormous potential as an approach to cardiovascular pathophysiology. Once thought to be a scientific long shot, cell transplantation is becoming recognized as a viable strategy to strengthen weak hearts and limit infarct growth. The technology could also be used for the long-term delivery of beneficial recombinant proteins to the heart, which is a strategy to complement molecular biology advances and provide an alternative strategy for gene therapy. On August 24, 1998, the National Heart, Lung, and Blood Institute convened a workshop to discuss the current status of this fast-moving line of research and to explore its promise for treating cardiovascular disease. The participants included basic and clinical researchers, with representatives from academic and commercial research settings. The workshop was designed to establish the state-of-the-art and to equate current research with practical clinical application. The group recommended short- and long-term goals to assist in realizing, in the most expedient manner, the potential utility of cell transplantation for the treatment of cardiovascular disease. A summary of the meeting discussions and recommendations for future areas of research is presented.

Cardiovascular Diseases↗

Obesity. Workshop III. AHA Prevention Conference III. Behavior change and compliance: keys to improving cardiovascular health.

The workshop provided the opportunity to discuss issues and develop and integrate ideas. The following recommendations for public policies, education programs, and high-priority research initiatives were developed: Recommendations for Public Policies: Focus on prevention by requiring school programs to emphasize appropriate diet, physical activity, and general health guidance to promote cardiovascular health and prevent disease through federal funding. Provide better access to exercise (city planning, work-site interventions). Influence food availability and accessibility. Influence reimbursement policies for effective early intervention and prevention strategies for obesity. Reevaluate policies for use of drugs in the treatment of obesity. Recommendations for Education Programs: Sponsor scientific workshop to: Define the most appropriate weight standards for prevention and treatment. Identify who should lose weight and why, when, and how. Promote the fact that obesity is an important health risk factor, even at moderate levels, and that excess visceral fat is particularly hazardous. Target health care professionals, consumers, and the media for education about: Nature of obesity as a heterogeneous syndrome. Recommendations for diet, exercise, behavioral interventions, drugs, and surgery. Recognition of special needs of populations of different ethnicity, gender, age, etc. State-of-the-art treatment and treatment programs. High-Priority Research Initiatives: Build better bridges between basic research and treatment/prevention practices. Acknowledge that obesity is a heterogeneous syndrome that may best be characterized as different obesities. Research on defining subtypes. Implications for etiology and treatment. Better characterization of genotypes and phenotypes. Study the effects of weight loss, weight gain,and weight cycling on medical and psychosocial outcomes and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

DNA damage and repair in central nervous system injury: National Institute of Neurological Disorders and Stroke Workshop Summary.

BACKGROUND AND PURPOSE: DNA damage and repair are areas of research with important implications for stroke and cerebral trauma. DNA damage is present in central nervous system (CNS) injury, and defects in repair mechanisms are associated with neurodegenerative disease. METHODS: A workshop, DNA Damage and Repair in CNS Injury, was organized by the National Institute of Neurological Disorders and Stroke in Bethesda, Md, on September 11, 1995. The objective of this workshop was to promote inquiry and to foster application of research in DNA damage and repair after stroke and trauma. RESULTS: The participants discussed the connection between the fields of DNA damage and repair and stroke and trauma and identified gaps in knowledge to be filled to expand research of DNA damage and repair in CNS injury. Specific recommendations were made targeting research opportunities in the areas of DNA repair and damage in stroke and trauma. CONCLUSIONS: Research in the science of DNA injury and repair will likely provide new and important information on mechanisms of cell damage and provide opportunities for the development of novel and effective therapies to reduce CNS injury in stroke and trauma.

Animals↗

Pharmacogenetics and pharmacogenomics in drug development and regulatory decision making: report of the first FDA-PWG-PhRMA-DruSafe Workshop.

The use of pharmacogenetics and pharmacogenomics in the drug development process, and in the assessment of such data submitted to regulatory agencies by industry, has generated significant enthusiasm as well as important reservations within the scientific and medical communities. This situation has arisen because of the increasing number of exploratory and confirmatory investigations into variations in RNA expression patterns and DNA sequences being conducted in the preclinical and clinical phases of drug development, and the uncertainty surrounding the acceptance of these data by regulatory agencies. This report summarizes the outcome of a workshop cosponsored by the Food and Drug Administration (FDA), the Pharmacogenetics Working Group (PWG), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the PhRMA Preclinical Safety Committee (DruSafe). The specific aim of the workshop was to identify key issues associated with the application of pharmacogenetics and pharmacogenomics, including the feasibility of a regulatory "safe harbor" for exploratory genome-based data, and to provide a forum for industry-regulatory agency dialogue on these important issues.

Clinical Trials as Topic↗