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At least 199 records · Page 11Linked to original sources
PubMed2004

A perspective on the current state of death education.

The author offers some views on the current state of death education with focus on the sparing attention given the death education of health professionals and of grief counselors. There is need for improved integration of the knowledge accumulated in the study of death, dying, and bereavement into the basic curricula of the parent disciplines and professional schools. Facilitation of personal engagement with the issue of mortality is an important component of the educative process. Various assessment problems are outlined and some suggestions for improvements are offered. The death education needs of various groups, including school age children and older adults, are noted. The article contains a list of references, many not cited in the text, recommended for an extensive review of developments in death education.

Adult↗
PubMedDate not supplied

New instruments for dry eye diagnosis.

Several non-invasive techniques for dry eye diagnosis have been developed in the past decade. These include quantitative assessment of tear volume, tear film stability, tear dynamics, and integrity of ocular surface epithelium. A combination of meniscometry and interferometry is useful for proving focal dry eye, by confirming whether or not tears at the meniscus have an effect on the ocular surface. Interferometer is also useful to evaluate tear dynamics on soft contact lenses. Fluorophotometry is useful for assessing the severity of dry eye from the view point of corneal epithelial barrier function and measuring the tear turnover rate. Both video-meibography and meibometry are useful for screening meibomian gland dysfunction. The advances in these techniques accumulate knowledge regarding pathophysiology of dry eye and allow precise diagnosis of dry eye. More targeted treatment will become feasible based on the clearer pathophysiology.

Corneal Topography↗
PubMed2002

Polyadenylate polymerase (PAP) and 3' end pre-mRNA processing: function, assays, and association with disease.

Polyadenylate polymerase (PAP) is one of the enzymes involved in the formation of the polyadenylate tail of the 3' end of mRNA. Poly (A) tail formation is a significant component of 3' processing, a link in the chain of events, including transcription, splicing, and cleavage/polyadenylation of pre-mRNA. Transcription, capping, splicing, polyadenylation, and transport take place as coupled processes that can regulate one another. The poly(A) tail is found in almost all eukaryotic mRNA and is important in enhancing translation initiation and determining mRNA stability. Control of poly(A) tail synthesis could possibly be a key regulatory step in gene expression. PAP-specific activity values are measured by a highly sensitive assays and immunocytochemical methods. High levels of PAP activity are associated with rapidly proliferating cells, it also prevents apoptosis. Changes of PAP activity may cause a decrease in the rate of polyadenylation in the brain during epileptic seizures. Testis-specific PAP may play an important role in spermiogenesis. PAP was found to be an unfavorable prognostic factor in leukemia and breast cancer. Furthermore, measurements of PAP activity may contribute to the definition of the biological profile of tumor cells. It is crucial to know the specific target causing the elevation of serum PAP, for it to be used as a marker for disease. This review summarizes the recently accumulated knowledge on PAP including its function, assays, and association with various human diseases, and proposes future avenues for research.

Breast Neoplasms↗
PubMed1996

Generalized ridge analysis with application to population pharmacokinetics/dynamics.

Given a set of measurements on a patient in clinical studies or on a drug response in bioassays and immunoassays, the data series for the individual can be incomplete, noisy, and haphazard. Hence, meaningful analysis on such limited data is at best difficult given the typical assumptions on the nonlinear structure of systematic and random components involving both individual and population effects. This paper describes a simple direct semiparametric procedure to incorporate population-wide information from as many individuals as required to support analysis of data on any specific individual. This notion is motivated by the pattern-processing capabilities of experts as they evaluate data on an individual based on their reservoir of accumulated knowledge of the given application on many individuals.

Biological Assay↗
PubMed2004

Assessing internal tobacco industry knowledge of the neurobiology of tobacco dependence.

The recent availability of internal tobacco industry documents provides a significant resource for evaluating industry understanding of the pharmacological, psychosocial, and behavioral mechanisms underlying tobacco dependence. In this study, we catalog the range of efforts undertaken by tobacco manufacturers seeking knowledge of these mechanisms. Some areas of industry research, such as cellular and molecular studies of nicotine and its effects, are widely available in the open literature. Of greater interest are internal research projects that have demonstrated direct influence on product development. These include studies of smoker psychology and behavior, evoked-response studies of tobacco-delivered nicotine, the effects of sensory perception, dose-related effects, and the development of nicotine analogs and synergists. Our findings suggest extensive industry knowledge of mechanisms that determine smoker perception and behavior, and application of this knowledge in product development, including control of sensory response, uptake of nicotine, and product effects. Independent research recently has begun to consider the contributions of tobacco product ingredients and design factors to the determination of risk, severity, and prevalence of addiction. However, the application of these findings to cessation and treatment efforts is still quite limited. We conclude that clinical research would greatly benefit from further examination of the decades of knowledge accumulated by tobacco manufacturers.

Brain↗
PubMed2001

Neuroendocrine pathogenesis in adenocarcinoma of the prostate.

BACKGROUND: In the prostate, the importance of sex hormones for its normal development and function is well known. However, it has been proposed that various neuroendocrine (NE) hormones and growth factors may be involved in the pathogenesis of prostatic carcinoma (CaP). Neuroendocrine differentiation appears to be associated with tumour progression and the androgen-independent state, for which there is currently no successful therapy. Therefore, we need to improve our understanding of NE cells, their regulatory products and influence on the prostate gland. Finally, new therapeutic protocols need to be developed. METHODS: Information is presented on prostatic NE cells and neuroendocrine differentiation (NED) in prostatic carcinoma. Neuroendocrine secretory products and interactions with epithelial prostate cells are investigated in order to understand their significance for the pathogenesis of the prostate gland, prognosis and therapy. RESULTS: Recent research suggests that NE-secreted products. such as serotonin, somatostatin and bombesin, may influence growth, invasiveness, metastatic processes and angiogenesis in CaP. During recent years. new experimental models for NED have been developed to provide evidence that NE products may promote proliferation and confer antiapoptotic capabilities on non-neuroendocrine cells in close proximity to NE cells. Cancerous epithelial cells may become more responsive to NE factors by upregulation of receptors for neuropeptides, or may induce NE cells to upregulate the secretion and synthesis of NE factors. In the androgen independent state, neuropeptides and their intracellular signals may activate the androgen receptor. Furthermore, androgen ablation may lead to downregulation of neural endopeptidase 24.11 (a zinc-dependent metalloproteinase) and PSA, which would lead to increased levels of NE products becoming available. These studies confirm that NE cells and NED may have a significant impact on prostate cancer, especially in the androgen independent state. CONCLUSIONS: Recent developments in molecular biology and pathophysiology of prostate cancer have increased our understanding of the NE regulatory mechanisms. Hopefully, this will lead to the development of entirely new therapeutic modalities. For example, somatostatin agonists may suppress angiogenesis and proliferation, and simultaneously promote apoptosis in prostate cancer cells. Somatostatin may thus have an important role in tumour biology, and in the future there may be a potential role for somatostatin analogues in the treatment of prostate cancer, but also for serotonin and bombesin receptor antagonists. However, a review of the accumulated knowledge in this field suggests that we still need to improve our understanding of NE cells and their regulatory products and influence on the prostate gland. and that clinical trials are needed, to test drugs based on neuroendocrine hormones and their agonists/antagonists.

Adenocarcinoma↗
PubMed2005

Listeria monocytogenes as a probe of immune function.

For almost half a century, the mouse model of Listeria monocytogenes infection has been used to analyse both innate and adaptive components of immunity and to discover key immune genes. Vast accumulated knowledge about the disease in mice provides a unique framework for identifying and characterising immune molecules using a variety of experimental approaches. To illustrate the range of questions that can be addressed using modern genetics and genomics tools, the authors provide an overview of the analysis of components of immune signalling networks using the mouse model of L. monocytogenes infection.

Animals↗
PubMed1983

Serial observations on the pathophysiology of acute stroke. The transition from ischaemia to infarction as reflected in regional oxygen extraction.

Regional cerebral blood flow, fractional oxygen extraction and oxygen metabolism have been measured in 34 patients after acute nonhaemorrhagic cerebral hemispheric infarction. Nine cases showed elevated oxygen extraction in the region of the early infarct, and these were the patients studied earliest after the onset of stroke. The results of serial studies to follow the evolution of the pathophysiology of acute stroke in these 9 patients are presented. The elevated oxygen extraction within the early infarct showed a significant reduction over the week following the onset of stroke. The reason for this fall in the fractional use of available oxygen varied in individual cases, and at the extremes was associated with a marked reduction in oxygen metabolism with a further small fall in residual blood flow, or a return of flow without recovery of oxygen metabolism. The significance of oxygen extraction in terms of potential viability of the tissue is discussed. The finding of a lower oxygen extraction in subcortical grey and white matter compared to cortex within the first hours or days of a major stroke is considered indicative of an earlier change from ischaemia to infarction in the deep tissues, probably related to the anatomy of the microvasculature. The interpretation of the results in the light of knowledge accumulated from studies of ischaemia in animals is presented, and problems imposed on data analysis by current limitations in positron emission tomography are discussed.

Adult↗
PubMed2003

From Alzheimer to Huntington: why is a structural understanding so difficult?

An increasing family of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, prion encephalopathies and cystic fibrosis is associated with aggregation of misfolded polypeptide chains which are toxic to the cell. Knowledge of the three-dimensional structure of the proteins implicated is essential for understanding why and how endogenous proteins may adopt a non-native fold. Yet, structural work has been hampered by the difficulty of handling proteins insoluble or prone to aggregation, and at the same time that is why it is interesting to study these molecules. In this review, we compare the structural knowledge accumulated for two paradigmatic misfolding disorders, Alzheimer's disease (AD) and the family of poly-glutamine diseases (poly-Q) and discuss some of the hypotheses suggested for explaining aggregate formation. While a common mechanism between these pathologies remains to be proven, a direct comparison may help in designing new strategies for approaching their study.

Alzheimer Disease↗
PubMed2001

In vitro control of floral transition in tomato (Lycopersicon esculentum Mill.), the model for autonomously flowering plants, using the late flowering uniflora mutant.

In vitro control of floral transition in tomato (Lycopersicon esculentum Mill.), the model plant for autonomously flowering species has been investigated using the late flowering mutant uniflora (uf). Apices collected from truly vegetative plants were cultivated on solid media supplemented with different combinations of growth regulators and chemicals. Several chemical factors implicated in the promotion of floral transition of the uf mutant have been identified: sucrose, cytokinins and nitrogenous nutrients have all to be supplied at optimal concentrations. In contrast, gibberellic acid was found to be inhibitory. These results are discussed in relation to knowledge accumulated on the nature of the flowering signals circulating, at floral transition, in other plants, especially in photoperiodic species. This study suggests that tomato could constitute an adequate model to investigate the genetic and physiological control of floral transition and contribute in unravelling pathways which are constitutively regulating this important step of plant life cycle.

Adenine↗
PubMed2006

Characterization of tomato (Solanum lycopersicum L.) mutants affected in their flowering time and in the morphogenesis of their reproductive structure.

The impact of the season on flowering time and the organization and morphogenesis of the reproductive structures are described in three tomato mutants: compound inflorescence (s), single flower truss (sft), and jointless (j), respectively, compared with their wild-type cultivars Ailsa Craig (AC), Platense (Pl), and Heinz (Hz). In all environmental conditions, the sft mutant flowered significantly later than its corresponding Pl cultivar while flowering time in j was only marginally, but consistently, delayed compared with Hz. The SFT gene and, to a lesser extent, the J gene thus appear to be constitutive flowering promoters. Flowering in s was delayed in winter but not in summer compared with the AC cultivar, suggesting the existence of an environmentally regulated pathway for the control of floral transition. The reproductive structure of tomato is a raceme-like inflorescence and genes regulating its morphogenesis may thus be divided into inflorescence and floral meristem identity genes as in Arabidopsis. The s mutant developed highly branched inflorescences bearing up to 200 flowers due to the conversion of floral meristems into inflorescence meristems. The S gene appears to be a floral meristem identity gene. Both sft and j mutants formed reproductive structures containing flowers and leaves and reverting to a vegetative sympodial growth. The SFT gene appears to regulate the identity of the inflorescence meristem of tomato and is also involved, along with the J gene, in the maintenance of this identity, preventing reversion to a vegetative identity. These results are discussed in relation to knowledge accumulated in Arabidopsis and to domestication processes.

DNA, Complementary↗
PubMed2000

Understanding suicide attempts by adolescent Hispanic females.

This article presents integrative model to aid clinicians in understanding suicide attempts by adolescent Hispanic females. On the basis of knowledge accumulated through clinical and research experience, the model describes a convergence of sociocultural, familial, developmental, and psychological factors that include considerations of family and parental functioning; adolescent female development; and the relationships of fathers, mothers, and daughters.

Adolescent↗
PubMed2003

Bacterial infections: small intestine and colon.

Bacterial infections of the small intestine and colon represent a major health problem for developing and developed nations. Recent technological progress has helped research groups to obtain important information on bacterial structure, identify evolutionary relationship between bacterial species, and learn details of the mechanisms involved in the interplay between host and microbes that culminate in disease expression. It is hoped that accumulated knowledge from in vitro experiments and animal models will translate into clinical benefit by means of developing new therapeutic strategies and effective vaccines.

Journal Article↗
PubMed2004

Inhibitors in hemophilia A: mechanisms of inhibition, management and perspectives.

Factor VIII (FVIII) replacement therapy remains the mainstay in hemophilia A care. The major complication of replacement therapy is formation of antibodies, which inhibit FVIII activity, thus dramatically reducing treatment efficiency. The present review summarizes the accumulated knowledge on epitopes of FVIII inhibitors and mechanisms of their inhibitory effects. FVIII inhibitors most frequently target the A2, C2 and A3 domains of FVIII and interfere with important interactions of FVIII at various stages of its functional pathway; a class of FVIII inhibitors inactivates FVIII by proteolysis. We discuss therapeutic approaches currently used for treatment of hemophilia A patients with inhibitors and analyze the factors that influence the outcome. The choice between options should depend on the level of inhibitors and consideration of efficacy, safety, and availability of particular regimens. Advances of basic science open avenues for alternative targeted, specific and long-lasting treatments, such as the use of peptide decoys for blocking FVIII inhibitors, bypassing them with human/porcine FVIII hybrids, neutralizing FVIII-reactive CD4 T cells with anti-clonotypic antibodies, or inducing immune tolerance to FVIII with the use of universal CD4 epitopes or by genetic approaches.

Animals↗
PubMed2004

An update on the cytokine network in rheumatoid arthritis.

PURPOSE OF REVIEW: To update the knowledge accumulated on the contribution of cytokines to rheumatoid arthritis and related animal models. Publications from the end of 2002 and 2003 period were analyzed for a selection. RECENT FINDINGS: A better understanding of the clinical results with tumor necrosis factor-alpha inhibitors has come from studies in treated patients. The expected effect of infliximab on the apoptosis of cells expressing tumor necrosis factor-alpha was not observed in synovium biopsy specimens. The mode of action of tumor necrosis factor-alpha on bone destruction has been clarified in gene-defective mice. Tumor necrosis factor-alpha acts through osteoclasts--an effect that is inhibited with osteoprotegerin. New interleukin-1 inhibitors with a potential for increased efficacy, such as interleukin-1trap, have been manufactured and are now being tested in rheumatoid arthritis. The list of cytokines of interest for therapeutic intervention has been growing rapidly. The results with animal models have provided clues to control arthritis with natural interleukin-18 inhibitors, such as interleukin-18 BP. Additional results have been accumulated that indicate the contribution of T cell subsets in inflammation and destruction through the production of interleukin-17. Synergistic interactions with other cytokines are critical in the interleukin-17 tuning effects. Macrophage inhibitory factor was described many years ago. Its comeback is based on properties of synoviocyte activation and proliferation. SUMMARY: Such findings are critical for a better understanding of response heterogeneity in patients treated with the cytokine inhibitors now on the market. New therapeutic approaches are been planned from these results.

Animals↗
PubMed2000

The more things change, the more they stay the same.

For decades, the hospital environment has been described as turbulent and hostile. At the same time, the transfer of business practices into hospitals has been advocated, accompanied by the largely untested assumption that these practices are crucial to performance and even survival. As this pattern became entrenched, the accumulated knowledge gained within the industry of managing in a hostile and turbulent environment has been overlooked. We argue that it is time to question the pattern.

Commerce↗
PubMed1998

Lowering the burden of suffering from child psychiatric disorder: trade-offs among clinical, targeted, and universal interventions.

OBJECTIVE: To examine the trade-offs among clinical, targeted, and universal interventions aimed at lowering the burden of suffering from child psychiatric disorders. METHOD: Data from clinical and research studies were organized to show the advantages and disadvantages of the three strategies. RESULTS: Important trade-offs exist among these three approaches. The strategy to reduce the burden of suffering from child psychiatric disorder should consist of a number of concurrent steps. First, effective universal programs should be in place. Targeted programs should follow for those not helped sufficiently by the universal programs. Finally, for those unaffected by the targeted programs, clinical services should be available. CONCLUSION: An optimal mix of universal, targeted, and clinical programs is needed. The nature of the combination will change as knowledge accumulates, and there will always be trade-offs among these three. Acad.

Child↗
PubMed1998

Evolution of neuroablative surgery for involuntary movement disorders: an historical review.

Surgical therapy of involuntary movement disorders has evolved during the past century from gross destructive ablations of the central nervous system to refined, accurate, discrete lesioning of sites deep within the brain. The understanding of neuroanatomic and physiological systems improved tremendously through experimentation in animals and empirical observations of surgery in humans. A continuum of accumulated knowledge has been achieved through ablation or lesioning of virtually all aspects of the central and peripheral nervous system predicated on previous successes or failures. This compilation of surgical history of involuntary movement disorders has provided present neurosurgeons with the foundations on which they base their therapeutic measures and will direct future endeavors within this field.

Basal Ganglia↗