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Refractoriness of host haemocytes to parasite immunosuppressive factors as a putative resistance mechanism in the Biomphalaria glabrata-Echinostoma caproni system.

In contrast to the growing knowledge accumulated on plant resistance to pathogens, mechanisms of parasite resistance largely remain to be elucidated in animal species. In the present study we investigated mechanisms underlying resistance/susceptibility in the snail-trematode system Biomphalaria glabrata-Echinostoma caproni. In particular, we compared the effect of the parasite excretory-secretory (E-S) products on the defence functions of haemocytes from 2 susceptible and 2 resistant snail strains. In vitro experiments showed that E. caproni E-S products inhibit adhesion and phagocytosis of haemocytes from susceptible snails. A partial biochemical characterization also suggested that the interfering factor(s) is (are) heat-labile glycosylated polypeptides of molecular mass between 10 and 30 kDa. Interestingly, haemocytes from resistant snails remained unaffected by the parasite E-S products, suggesting that a constitutive difference results in their refractoriness to the parasite's immunosuppressive factor(s).

Animals↗

The evolution of ecological tolerance in prokaryotes.

The ecological ranges of Archaeobacteria and Eubacteria are constrained by a requirement for liquid water and the physico-chemical stability limits of biomolecules, but within this broad envelope, prokaryotes have evolved adaptations that permit them to tolerate a remarkable spectrum of habitats. Laboratory experiments indicate that prokaryotes can adapt rapidly to novel environmental conditions, yet geological studies suggest early diversification and long-term stasis within the prokaryotic kingdoms. These apparently contradictory perspectives can be reconciled by understanding that, in general, rates and patterns of prokaryotic evolution reflect the developmental history of the Earth's surface environments. Our understanding of modern microbial ecology provides a lens through which our accumulating knowledge of physiology, molecular phylogeny and the Earth's history can be integrated and focussed on the phenomenon of prokaryotic evolution.

Adaptation, Biological↗

Delusion formation and insight in the context of affective disturbance.

OBJECTIVE: Delusions and lack of insight have traditionally been viewed as the defining characteristics of insanity and in modern psychiatry continue to be central to the diagnosis of psychosis. Little is known about the mechanisms of delusion formation and much of the research into delusions and lack of insight has been focussed on schizophrenia, in spite of the fact that these symptoms are also prominent in other disorders e.g., affective psychosis. The objective of this paper is to review the literature on existing theories of delusions and insight with reference to the effects of affective disturbance on memory processes. METHOD: Narrative review supplemented by literature searches using Medline, PsycINFO and EMBASE databases for the period 1980 to present using terms "delusion", and "insight" and "affect". RESULTS: The role of affect on memory in normal psychology and delusions in psychopathology is being increasingly recognised. We sketch out a theory which gives weight to locating the formation and maintenance of mood congruent and mood incongruent delusional beliefs (and insight into such beliefs) within a model of normal memory processes. CONCLUSION: We conclude that delusional beliefs may represent false or biased memories of internal or external events modified and strengthened of by affective states. We propose that insight rests on an ability to identify these memories as internally generated or biased. In view of the growing body of knowledge accumulating from the study of memory, emotion and their neuropsychological correlates we would suggest using this as an evidence base for the further neuropsychiatric investigation of delusional beliefs.

Delusions↗

Molecular signals for development of neuronal circuitry in the retina.

In this review article, we summarize recently accumulated knowledge regarding the molecular mechanisms, which control retinal development. Retinal neurons are born in two waves of cytogenesis. In the first wave, neurons of cone circuitry are generated, whereas in the second wave, rod circuitry is added. Neurons generated in these two waves of cytogenesis differ in many respects, including the molecular cues used for migrational guidance. The neurons generated in the second phase of proliferation are arranged in radial columns associated with Müller cells, whereas those of the first phase are often found outside the radial columns. Certain early born cone photoreceptors may form templates for the arrangement of additional mosaics of other cell types. These mosaic arrangements of cell bodies are subsequently refined by lateral displacement of cells and apoptosis. Müller cells may play an important role in directing migration of second phase neurons within groups of radial columns and also in guiding the projections of these neurons so that specific connections are formed. The Müller cell's ability to exert these influences perhaps resides in a variety of cell adhesion molecules such as L1/NgCAM, F11, and 5A11, which are expressed on the surface of Müller cells and retinal neurons. CAMs also promote neurite outgrowth through second messenger pathways.

Animals↗

The criminogenic, clinical, and social problems of forensic and civil psychiatric patients.

Forensic psychiatric patients consume an increasing proportion of mental health resources in Canada and the United States. To inform mental health policy and practice, we compared the criminogenic, clinical, and social problems of forensic patients to those of civilly committed psychiatric patients in two Canadian studies. We predicted that forensic patients would score higher on criminogenic problems and lower on clinical and social problems than civil patients in two studies: one comparing 83 forensic and 189 civil inpatients on a clinician-completed form, the Resident Assessment Instrument--Mental Health, at an urban mental health center, and the second comparing 423 forensic and 178 civil patients assessed at different times using the Patient Problem Survey. The two studies were quite similar in their findings, despite differences in their samples, measures, and data collection methods. In both studies, forensic patients were similar to or lower than civil psychiatric patients in all criminogenic, clinical, and social problems. We conclude that forensic mental health services would benefit greatly by drawing from knowledge accumulated in the general psychiatric literature. This finding also supports the idea that many forensic patients can be appropriately diverted to nonforensic mental health services.

Adult↗

A developmental-ecological perspective on antisocial behavior in children and adolescents: toward a unified risk and intervention framework.

A developmental-ecological perspective is offered as a framework for prediction and prevention of antisocial behavior in children and adolescents. The primary assumptions of the approach and the advantages of such an approach for relating prediction, prevention, and implementation are high-lighted. It is suggested that such an approach facilitates integration of the recent advances in prevention theory and methods, the accumulating knowledge about the causes and effective interventions for antisocial behavior, and the need for careful consideration of context. Six key advances in the field are listed, and important steps are suggested.

Adolescent↗

The application of bone morphogenetic proteins to dental tissue engineering.

Progress in understanding the role of bone morphogenetic proteins (BMPs) in craniofacial and tooth development, the demonstration of stem cells in dental pulp and accumulating knowledge on biomaterial scaffolds have set the stage for tissue engineering and regenerative therapy of the craniofacial complex. Furthermore, the recent approval by the US Food and Drug Administration (FDA; Rockville, MD, USA) of recombinant human BMPs for accelerating bone fusion in slow-healing fractures indicates that this protein family may prove useful in designing regenerative treatments in dental applications. In the near term, these advances are likely to be applied to endodontics and periodontal surgery; ultimately, they may facilitate approaches to regenerating whole teeth for use in tooth replacement.

Bone Morphogenetic Proteins↗

ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus.

Accumulated knowledge in the molecular processes of tumour development combined with the availability of genetically modified viruses resemble the basis for new promising cancer therapeutics. The main advantages of employing replication-competent viruses are achievement of tumour selective killing and amplification of their oncolytic potential within the tumour mass. In this review, we describe the development of ONYX-015, one of the first and most advanced replication-competent viruses for cancer therapy. We discuss the molecular biology of this therapeutic approach and the interesting results obtained with this virus in clinical trials.

Adenoviridae↗

Cellular factors influencing Semliki Forest Virus vector biology.

Viral vectors are currently the best tools for gene delivery in a therapeutic setting, especially for in vivo use. Alphaviruses, a family of positive singlestranded RNA viruses, have been engineered to allow the formation of a highly efficient replicon. Using these replicons, it is possible to generate recombinant particles. Parental viruses and recombinant vectors share certain pathways while interacting with their target cells. In this review, we describe the consecutive events leading to transduction, and transgene expression, in view of the cellular factors that affect each individual step. Classical virology will benefit from the knowledge accumulated studying vectors, and such work will shed light on crosstalk between intruding viruses and their hosts. Ultimately, these data should help the design of vectors adapted to specific target cells.

Cells↗

Candidate tumour suppressor genes at 11q23-q24 in breast cancer: evidence of alterations in PIG8, a gene involved in p53-induced apoptosis.

One of the most consistently deleted chromosomal regions in solid tumours is 11q23-q25, which consequently has been postulated to harbour one or more tumour suppressor loci. Despite large efforts to identify the responsible genes, the goal remains elusive, but as knowledge accumulates new candidates are emerging. The present study was undertaken in an attempt to assess the possible implication of four genes residing at 11q23-q24, in a population of early onset breast cancer (n=41). The coding sequence of PIG8, CHK1, LOH11CR2A and PPP2R1B were screened for mutations using the protein truncation test or single-strand conformational polymorphism, in combination with direct DNA sequencing. Varying proportions of alterations were detected, ranging from 6% in PPP2R1B to 39% in PIG8. Many of these changes were deletions, in some cases corresponding to complete exons, thus likely to represent splice variants, while others were presumed to arise from aberrant splicing, since they occurred at sites with resemblance to exon/intron borders. Considering only bona fide mutations, the highest alteration frequency (17%) was again found in PIG8. Most of these alterations were likely to have an adverse impact on the translated protein as they either altered the reading frame or affected phylogenetically conserved residues. Our data represent the first evidence of alterations in the PIG8 gene in human malignancies, a finding that substantiates its role as a potential tumour suppressor gene as suggested by its involvement in p53-induced apoptosis.

Adult↗

The 8;21 translocation in leukemogenesis.

A common chromosomal translocation in acute myeloid leukemia (AML) involves the AML1 (acute myeloid leukemia 1, also called RUNX1, core binding factor protein (CBF alpha), and PEBP2 alpha B) gene on chromosome 21 and the ETO (eight-twenty one, also called MTG8) gene on chromosome 8. This translocation generates an AML1-ETO fusion protein. t(8;21) is associated with 12% of de novo AML cases and up to 40% in the AML subtype M2 of the French-American-British classification. Furthermore, it is also reported in a small portion of M0, M1, and M4 AML samples. Despite numerous studies on the function of AML1-ETO, the precise mechanism by which the fusion protein is involved in leukemia development is still not fully understood. In this review, we will discuss structural aspects of the fusion protein and the accumulated knowledge from in vitro analyses on AML1-ETO functions, and outline putative mechanisms of its leukemogenic potential.

Cell Differentiation↗

Short-range interactions between non-ionic surfactant layers.

Short-range interactions between surfactant and lipid layers are of great importance in technical applications in complex fluids such as foams, dispersions and emulsions, as well as in the formulation and performance of dispersants, detergents and flocculants. It is also of utmost importance in biological systems where interactions between biomembranes influence a range of processes. The field of short-range interactions has been thoroughly investigated during the past 30 years, following the emergence of a number of techniques to measure interaction forces. Thus, our understanding has increased considerably and it is timely to summarize relevant knowledge accumulated in this area. In this review we focus on the nature of short-range interactions between non-ionic and zwitterionic surfactant and lipid layers exposing their polar groups to the surrounding medium. We discuss the complex interplay of short-range (van der Waals, hydration, steric and other) forces based on recent theoretical and experimental results.

Emulsions↗

The future of vaccination as a treatment strategy in dermatological diseases.

Vaccination approaches are increasingly explored as means for both prevention and therapy of skin diseases. These development are boosted by the rapidly accumulating knowledge of the molecular and cellular bases of these disease and the antigens involved, on the one hand, and of the components and mechanisms of cellular and humoral immune responses, on the other. In a number of cases these newly developed vaccination strategies are already tested in clinical trials. Although most of them are still in very early stages of the development, it is foreseeable that vaccination will emerge as an important option for prevention and treatment of infectious skin diseases as well as of cancer, allergies and maybe, auto-immune disorders.

Antigens↗

Patient adherence to treatment: three decades of research. A comprehensive review.

Low compliance to prescribed medical interventions is an ever present and complex problem, especially for patients with a chronic illness. With increasing numbers of medications shown to do more good than harm when taken as prescibed, low compliance is a major problem in health care. Relevant studies were retrieved through comprehensive searches of different database systems to enable a thorough assessment of the major issues in compliance to prescribed medical interventions. The term compliance is the main term used in this review because the majority of papers reviewed used this term. Three decades have passed since the first workshop on compliance research. It is timely to pause and to reflect on the accumulated knowledge. The enormous amount of quantitative research undertaken is of variable methodological quality, with no gold standard for the measurement of compliance and it is often not clear which type of non-compliance is being studied. Many authors do not even feel the need to define adherence. Often absent in the research on compliance is the patient, although the concordance model points at the importance of the patient's agreement and harmony in the doctor-patient relationship. The backbone of the concordance model is the patient as a decision maker and a cornerstone is professional empathy. Recently, some qualitative research has identified important issues such as the quality of the doctor-patient relationship and patient health beliefs in this context. Because non-compliance remains a major health problem, more high quality studies are needed to assess these aspects and systematic reviews/meta-analyses are required to study the effects of compliance in enhancing the effects of interventions.

Attitude to Health↗

The interactive language of the hypothalamus for the gonadotropin releasing hormone (GNRH) system.

The enormous diversity in neurochemical signals employed within the network of afferents to GnRH neurons is well-documented. An examination of novel and accumulating knowledge on the operation of these messengers indicates the presence of an interactive language governing GnRH secretion. The basic operational structures identified to date to affirm this interactive form of communication summarized in this review are the following: (i) the demonstration of interconnections within various components of the afferent network; (ii) coexistence and possible co-release of excitatory and inhibitory neurotransmitters/neuromodulators; (iii) co-action of various messengers at synaptic targets, and (4) modulation by gonadal steroids of the synthesis and release of signals and their receptors, and induction of synaptic plasticity for the timely relay of signals for GnRH secretion. Unraveling the molecular sequelae that promote this interactive communication to elicit periodic GnRH secretion is now a new challenge.

Afferent Pathways↗

Challenges and benefits of assessment, diagnosis, and taxonomy for clinical practice and research.

OBJECTIVE: To outline nosological (top-down) and empirically based (bottom-up) approaches to assessment and taxonomy of psychopathology. METHOD: The two approaches were compared and contrasted to highlight similarities and differences between them. RESULTS AND CONCLUSIONS: To advance services and research, we need to make optimal use of assessment data (i) to identify the distinguishing features of each case, and (ii) to link individual patterns of functioning with taxonomic constructs that can help us apply previously accumulated knowledge to new cases. The time may be ripe for integrating nosological and empirically based approaches. One way to integrate these approaches is to construct empirically based and DSM-oriented scales from the same item pools and to generate age- and gender-specific standard scores and cut-off points from the same normative samples. Integration of the approaches was illustrated with profiles of empirically based and DSM-oriented scales scored from the same item pools and quantified in relation to the same normative samples. To facilitate use by clinicians and researchers under diverse conditions, data are readily obtained on forms completed independently by parents, teachers and others. The data can be quickly scored by hand or computer. To take account of situational and informant variations, the computer software systematically compares data from multiple informants on empirically based and DSM-oriented scales.

Adolescent↗

Von Willebrand factor and von Willebrand disease.

von Willebrand disease (vWD) is caused by quantitative and/or qualitative defects of the von Willebrand factor (vWF), a multimeric high molecular weight glycoprotein. Typically, it affects the primary hemostatic system, which results in a mucocutaneous bleeding tendency simulating a platelet function defect. The vWF promotes its function in two ways: (i) by initiating platelet adhesion to the injured vessel wall under conditions of high shear forces, and (ii) by its carrier function for factor VIII in plasma. Accumulating knowledge of the different clinical phenotypes and the pathophysiological basis of the disease translated into a classification that differentiated between quantitative and qualitative defects by means of quantitative and functional parameters, and by analyzing the electrophoretic pattern of vWF multimers. The advent of molecular techniques provided the opportunity for conducting genotype-phenotype studies which have recently helped, not only to elucidate or confirm important functions of vWF and its steps in post-translational processing, but also many disease causing defects. Acquired von Willebrand syndrome (avWS) has gained more attention during the recent years. An international registry was published and recommendation by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis in 2000. It concluded that avWS, although not a frequent disease, is nevertheless probably underdiagnosed. This should be addressed in future prospective studies. The aim of treatment is the correction of the impaired hemostatic system of the patient, ideally including the defects of both primary and secondary hemostasis. Desmopressin is the treatment of choice in about 70% of patients, mostly with type 1, while the others merit treatment with concentrates containing vWF.

Clinical Laboratory Techniques↗

Tea and health: the underlying mechanisms.

Detailed multidisciplinary research on the effect of tea and the associated tea polyphenols has led to major advances on the underlying mechanisms. In most studies, green and black tea have similar effects, four of which are reviewed in this paper. 1) Tea polyphenols are powerful antioxidants that may play a role in lowering the oxidation of LDL-cholesterol, with a consequent decreased risk of heart disease, and also diminish the formation of oxidized metabolites of DNA, with an associated lower risk of specific types of cancer. 2) Tea and tea polyphenols selectively induce Phase I and Phase II metabolic enzymes that increase the formation and excretion of detoxified metabolites of carcinogens. 3) Tea lowers the rate of cell replication and thus the growth and development of neoplasms. 4) Tea modifies the intestinal microflora, reducing undesirable bacteria and increasing beneficial bacteria. The accumulated knowledge suggests that regular tea intake by humans might provide an approach to decrease the incidence of and mortality from major chronic diseases.

Animals↗