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Extravillous trophoblast apoptosis--a workshop report.

During normal pregnancy, extravillous trophoblast cells invade maternal uterine tissues. The interstitial trophoblast penetrates decidual tissues reaching the inner third of the myometrium. A subset of the interstitial trophoblast, the intramural/endovascular trophoblast transforms uterine spiral arteries into large-bore conduits to enable the adequate supply of nutrients and oxygen to the placenta and thus the fetus. Control of invasion is still a mystery and therefore, in this workshop report already existing concepts as well as new models are discussed. Maternal cells such as macrophages and endothelial cells have a clear impact on trophoblast invasion and apoptosis. However, the trophoblast cells need to be susceptible to undergo apoptosis. Thus, an intrinsic program within the trophoblast needs to be activated before induction from the outside can be successful. Quantification of apoptosis further clarified that apoptosis of interstitial trophoblast is not the ultimate means to lead to pathologically shallow invasion. On the other hand, apoptosis of intramural/endovascular trophoblast seems to be highly relevant for a correct transformation of spiral arteries.

Animals↗

Placental diagnostic criteria and clinical correlation--a workshop report.

Placental pathology is a valuable link explaining how underlying pregnancy risk factors result in adverse pregnancy outcome. This potentially useful information is currently underutilized due to a general lack of rigor in placental diagnosis. This lack of rigor is in large part due to a failure to appreciate the importance of the information provided and hence to demand accurate and clinically responsive reporting. This workshop reviewed the results of a recent initiative by the Perinatal Section of the Society for Pediatric Pathology to systematize and validate diagnostic schema for the description of lesions related to three important pathologic processes: amniotic fluid infection, maternal vascular underperfusion, and fetal vascular obstruction. This was followed by presentation of three studies correlating these pathologic processes with the following clinical outcomes: complications of prematurity, fetal growth restriction, and neurodisability following term delivery.

Female↗

Advanced techniques in placental biology -- workshop report.

Major advances in placental biology have been realized as new technologies have been developed and existing methods have been refined in many areas of biological research. Classical anatomy and whole-organ physiology tools once used to analyze placental structure and function have been supplanted by more sophisticated techniques adapted from molecular biology, proteomics, and computational biology and bioinformatics. In addition, significant refinements in morphological study of the placenta and its constituent cell types have improved our ability to assess form and function in highly integrated manner. To offer an overview of modern technologies used by investigators to study the placenta, this workshop: Advanced techniques in placental biology, assembled experts who discussed fundamental principles and real time examples of four separate methodologies. Y. Sadovsky presented the principles of microRNA function as an endogenous mechanism of gene regulation. J. Robinson demonstrated the utility of correlative microscopy in which light-level and transmission electron microscopy are combined to provide cellular and subcellular views of placental cells. A. Croy provided a lecture on the use of microdissection techniques which are invaluable for isolating very small subsets of cell types for molecular analysis. Finally, G. Rice presented an overview methods on profiling of complex protein mixtures within tissue and/or fluid samples that, when refined, will offer databases that will underpin a systems approach to modern trophoblast biology.

Animals↗

Implantation, embryo-maternal interactions, immunology and modulation of the uterine environment -- a workshop report.

The Workshop discussed five topics which were considered to be topical. 1) A comparison was made between rodents and primates regarding how uNK cells are distributed at the implantation site in these species. 2) The possibility that the functions of uNK cells may be different in mice and humans are discussed. 3) Trophoblast MHC expression in the Rhesus monkey (haemochorial) and the sheep (epitheliochorial) was compared in order the gauge the importance of these molecules in these two fundamentally different types of placentation. 4) New data were presented on the intriguing molecule, HLA-G, whose function is still unclear. 5) A discussion was initiated to debate the role of the innate and the adaptive immune systems in human implantation.

Animals↗

Workshop on trichothecenes with a focus on DON: summary report.

A number of mycotoxins of the class of trichothecenes are produced by a variety of Fusarium fungi commonly found on cereals. Unfavourable weather conditions may lead to a high level of Fusarium infections in crops such as wheat and correspondingly high trichothecene contents. The ILSI Europe Natural Toxin Task Force therefore organised a workshop on trichothecenes with a special focus on deoxynivalenol (DON). A number of experts reviewed the current knowledge on trichothecenes with respect to occurrence, including aspects of mould growth, toxin formation, storage and effects of processing; prevention; analytical methodologies, including sampling; surveillance and exposure assessments; and toxicology and risk assessment. A number of recommendations were given under the headings: prevention, sampling and analytical methods, exposure assessment, and toxicology. Gaps in knowledge were also identified.

Animals↗

Enteric vaccines for pediatric use. Workshop summary.

Diarrheal diseases remain a major cause of death in children under 5 in less developed countries (LDCs). Vaccine development and implementation offers the best near-term approach to alleviating this problem. For this reason, a workshop to examine the possibilities for making enteric vaccines available to meet the specific needs of children in LDCs was convened in Virginia on April 24-26, 2004. Discussants considered research and development needs, regulatory and business issues, and previous experiences with enteric vaccine development and implementation. No insurmountable roadblocks to progress in this area were noted, and the possibility currently exists that properly supported efforts will enable the realization of enteric vaccines for pediatric use.

Bacterial Vaccines↗

School-based research and initiatives: fruit and vegetable environment, policy, and pricing workshop.

BACKGROUND: Foods sold outside the school meals program are widely available and comprise an increasing share of the foods students purchase and consume at school. Federal policies provide little regulation of foods sold outside the school meals program. State and district policies are also limited, and few specifically address fruit and vegetable availability. METHODS: School-based interventions to promote consumption of fruit and vegetables among students in school settings have primarily consisted of multicomponent interventions that sometimes included an environmental intervention component. RESULTS: Results of these interventions have been positive, especially in their effects on fruit intake. The results of shorter term environmental interventions that used lower prices or increased availability as strategies to increase fruit and vegetable intake have been positive. Several new approaches currently being piloted in schools include school gardening programs, salad bars using fresh produce from local Farmer's Markets, and in-school, free fruit and vegetable distribution programs. CONCLUSIONS: Better information is needed on the economics of competitive foods and the role that financial profitability plays in decisions about food availability and sales in the school setting. Although no model programs were identified at the workshop, several promising strategies were identified to promote fruit and vegetable intake among students in school settings.

Feeding Behavior↗

Proteases, extracellular matrix, and cancer: a workshop of the path B study section.

The role of the extracellular matrix (ECM) in the tumor microenvironment is not limited to being a barrier against tumor invasion. The ECM is a reservoir of cell binding proteins and growth factors that affect tumor cell behavior. It is also substantially modified by proteases produced by tumor cells or stroma cells. As a result of the activity of these proteases, cell-cell and cell-ECM interactions are altered, new biologically active ECM molecules are generated, and the bioavailability and activity of many growth factors, growth factor receptors, and cytokines are modified. ECM-degrading proteases also play a critical role in angiogenesis, where they can act as positive as well as negative regulators of endothelial cell proliferation and vascular morphogenesis. This review article summarizes some of the most relevant findings made over the recent years that were discussed at a workshop organized by the Path B Study Section of the National Institutes of Health in October 2002.

Animals↗

Combined immunodeficiency disease associated with adenosine deaminase deficiency. Report on a workshop held in Albany, New York, October 1, 1973.

Fifty-five children with CID and known ADA status were studies at a workshop held in Albany, New York. Erythrocyte ADA determinations were performed in 22 of the 55 patients, 13 of whom were ADA negative. The ADA defect appears to be transmitted as an autosomal recessive trait. Some patients with CID and ADA deficiency have characteristic radiologic abnormalities of the skeleton, which are not found in other illnesses. The thymus glands of all patients with CID and ADA deficiency who could be examined have evidence of thymic involution manifested by presence of Hassall's corpuscles and differentiated germinal epithelium; this is in contrast to "classic" thymus findings in CID with normal ADA. Adenosine deaminase probably plays an important, although as yet undefined, role in lymphocyte development and/or function. The deficiency of ADA in CID is the first enzyme defect observed in a deficiency disease of specific immunity.

Adenosine↗

Workshop: the use of muscarinic toxins in the study of muscarinic receptors.

One of the most interesting recent developments in the pharmacology of muscarinic receptors has been the finding of small proteins in the venoms of mamba snakes that bind with high affinity and selectivity to different subtypes of muscarinic receptors. In the workshop on muscarinic toxins, the practicalities of isolating, characterising and using these toxins as tools in the study of muscarinic receptors were discussed.

Animals↗

Workshop on taste and smell in the elderly: an overview.

The purpose of the workshop entitled Taste and Smell in the Elderly: Behavioral and Nutritional Consequences was 1) to review the current state of knowledge in the area of taste and smell, with emphasis on age-related changes, 2) to identify existing gaps in our knowledge, and 3) to develop future research strategies. There was general agreement that the majority of scientific studies have found impairments in taste and smell acuity in the elderly. These losses may result from normal aging, certain disease states especially Alzheimer's disease, medications, surgical interventions, and environmental exposure. However, there are gaps in our knowledge of the basic mechanisms by which aging and environmental factors may impair the chemical senses in the elderly. Further research is also required in a variety of areas including chemosensory test procedures, food intake, and nutrition to understand fully the impact of chemosensory dysfunction on older individuals.

Aged↗

Microarray workshop on aging.

The advent of microarrays in studying gene expression in aging has created tremendous excitement due to its potential for uncovering molecular mechanisms of aging and age-related disease. However, the appropriate implementation of this technology in the science of aging requires serious attention to methodological detail and statistical rigor. This report highlights discussions from the microarray workshop on aging held at the First Conference on Functional Genomics of Aging in Seville, Spain. The topics discussed by the participants included technical issues relating to the printing of arrays, RNA isolation, cDNA labeling and hybridization, optimal design of microarray experiments, and statistical analysis of these data. Microarray analysis of complex tissues through the use of laser capture microdissection was also discussed.

Aging↗

Workshop: options for therapy in ovarian cancer.

Current and future options for sequential therapy for first and subsequent relapses in ovarian cancer were discussed in three workshops centered around a number of case studies. The participants included investigator oncologists from the USA, Europe, and Asia. For a platinum-resistant patient, topotecan or pegylated liposomal doxorubicin was considered the treatment of choice at first relapse. Since optimal tolerability with topotecan is achieved in less heavily pretreated patients, it may be best to use it earlier rather than later in the treatment schedule. For subsequent relapse within 6 months, most clinicians would use liposomal-encapsulated doxorubicin if the prior treatment had been topotecan and vice versa. Alternative agents may be considered with the aim of achieving symptom palliation rather than prolongation of survival. For late relapse after optimal debulking and treatment with carboplatin/paclitaxel, retreatment with carboplatin/paclitaxel (possibly after further surgery) was considered the best approach in platinum-sensitive patients. For first relapse after 10 months in a suboptimally debulked patient, retreatment with carboplatin/paclitaxel was also considered a viable option. Alternatively, single-agent therapy with paclitaxel, pegylated liposomal doxorubicin, or topotecan may be appropriate to prolong the platinum-free interval. For second relapse, oral etoposide was felt to be useful. Treatment for subsequent relapses included gemcitabine, docetaxel, and agents above not previously utilized. Topotecan tolerability and convenience may be improved by employing a lower dose, shorter schedule, 21-day continuous infusion or weekly dosing in relapsed/refractory disease. The progression-free interval may be extended by continuing topotecan until disease progression in patients with stable disease or by topotecan consolidation therapy in treatment responders.

Aged↗

Challenges in preventing relapse in major depression. Report of a National Institute of Mental Health Workshop on state of the science of relapse prevention in major depression.

On 21 and 22 May 2001, the National Institute of Mental Health convened a workshop to explore imminent scientific opportunities and encourage new research on preventing relapse in major depression, as a part of a larger effort to find treatments capable of producing durable long-term recovery from major depression. Participants considered definitional and developmental perspectives on depression relapse, the prophylactic potential of current treatments and their cost effectiveness and the neurobiological and psychological risk factors for episode return. It was recommended that the definition of the relapse construct be expanded to capture salient features of incomplete recovery or partial response to treatment that are associated with significant functional impairment. This information is often overlooked by the categorical criteria currently in use. With respect to interventions, there was support for sequencing pharmacological remission with psychological prophylaxis. Provision of focal, short-term treatments that embed relapse prevention skills augment the routes to effective prevention available to patients, beyond that afforded by continuation pharmacotherapy. The challenge will be to identify those subgroups of patients for whom each treatment algorithm is indicated. Finally, the link between basic science findings of biological and psychological markers of relapse vulnerability and treatment design needs to be strengthened. This could be accomplished by assessing patients in clinical prevention trials for the presence of, and changes in, relapse vulnerability markers, thereby providing direct, outcome-based data to gauge the protective value of different treatments that modify these markers.

Algorithms↗

Pleomorphic expressions of unipolar depressive disease: summary of the 1996 CINP President's Workshop.

Data presented during the 1996 CINP President's Workshop supported the conclusion that unipolar major depressive disorder (MDD) is a pleomorphic mood disorder consisting of a cluster of depressive subtypes existing in a relatively homogeneous symptomatic clinical continuum, extending from subsyndromal depressive symptomatology (SSD) through minor depressive episode, dysthymic disorder, major depressive episode and double depression. This indicates that common unipolar depressive subtypes can be conceptualized as alternate forms or different symptomatic phases of the same parent illness. Although there appears to be great overlap across time in the symptomatological expressions of these clinical depressive subtypes, they may be derived from different etiological and genetic factors. The one exception may be major depressive episode with psychotic features, which exists on a severity continuum with other subtypes of unipolar MDD, but does not appear to be on a symptomatic continuum with dysthymic, subsyndromal or minor depressions. By contrast, SSD and minor depressive disorder represent clinically significant depressive subtypes, which are commonly observed during the course of illness of patients with unipolar major depressive illness. Compared to no depressive symptoms, SSD is associated with harmful dysfunction, as evidenced by significant increases in psychosocial impairment, signifying that SSD is an active, inter-episode disease state of unipolar major depressive disorder. Finally, SSD, possibly jointly with subthreshold anxiety symptoms, may also represent potent risk factors for rapid depressive episode relapse. In the aggregate, these findings and conclusions have broad and important implications for diagnostic and treatment strategies of unipolar MDD.

Affective Disorders, Psychotic↗

Cross-reactivity with bovine cells of monoclonal antibodies submitted to the 6th International Workshop on Human Leukocyte Differentiation Antigens.

Twelve subpanels of monoclonal antibodies (MAb) included within the 6th International Workshop on Human Leukocyte Differentiation Antigens (6th HLDA) were assayed for reactivity with bovine peripheral blood leukocytes. Sixty-nine of the 807 MAb (8.6%) stained bovine cells. These MAb represented 30 different human CD groups. Nine of the MAb to different human CD antigens (CD19, CD23, CD39, CD47, CD86, CD117, CD120b, CDw149, CD165) potentially recognized antigens on cattle cells that had not previously been identified. These were investigated further by two-colour immunofluorescence to compare the cellular expression of the antigen on cattle cells with that reported for the different CD antigens in humans. Four of the MAb that belonged to CD23, CD39, CD47, and CDw149 stained bovine cells in a manner that indicated an almost identical cellular distribution of the antigen to that reported in humans. This implied that these MAb reacted with the homologous cattle molecules. Further work would be necessary to confirm specificity of CD19, CD86, CD117, CD120b and CD165 MAb. Other cross-reacting MAb either recognized antigens already defined in cattle or antigens not yet clustered in humans. The study has identified valuable new reagents for studies of cattle and confirmed that most common cross-reactive MAb are to epitopes on integrins.

Animals↗

Summary of workshop findings for porcine myelomonocytic markers.

About 65 monoclonal antibodies (mAb) including 17 internal controls were analyzed for their ability to recognize and bind to various cells of the myelomonocytic lineage. Flow cytometry (FCM) utilizing both single and double staining, and immunoprecipitation (IP) assays were used in the analysis. About 38 of the mAb were reactive with myelomonocytic cells, resulting in nine clusters of interest. Although the exact identity of many of the molecules on the cells bound by the mAb remains undetermined, information obtained about the mAb analyzed in this workshop should be helpful in further identifying various populations of myelomonocytic cells and their stages of differentiation. Out of 12 mAbs with potential CD11 specificity, seven were assigned to three different swine specific alpha chains of the CD11/CD18 integrin heterodimer, the assignment of the remaining four was tentative. One antibody had a binding specificity consistent with SWC3 and one with SWC8. CD14 expression on pig cells was characterized with a panel of CD14-positive antibodies, two of these antibodies were assigned to swine CD14. Two antibodies were assigned to CD163. Further work is required to determine the antigens recognized by many of the other mAb.

Animals↗