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Disease States (disease + states)
Kinds of Disease States Selected AbstractsVisualizing feedback-enhanced contrast in magnetic resonance imagingCONCEPTS IN MAGNETIC RESONANCE, Issue 6 2007Susie Y. Huang Abstract A new approach to magnetic resonance imaging (MRI) contrast enhancement has recently been developed that exploits nonlinear feedback interactions to amplify contrast arising from small variations in the underlying MRI parameters. A unified framework for understanding feedback-enhanced contrast is presented here based on the concepts of instability and positive feedback. The specific mechanisms governing contrast enhancement under the feedback interactions of radiation damping, the distant dipolar field, and their joint effect are elucidated through numerical simulations illustrating the involved spin dynamics. Experimental demonstrations of feedback-enhanced contrast are shown on samples of in vitro human brain tissue, and applications to improving lesion detection in disease states such as epilepsy and cancer are discussed. © 2007 Wiley Periodicals, Inc. Concepts Magn Reson Part A 30A: 378,393, 2007. [source] Human monocyte CD163 expression inversely correlates with soluble CD163 plasma levelsCYTOMETRY, Issue 1 2005Bruce H. Davis Abstract Background CD163 is a monocyte/macrophage-restricted receptor involved in the clearance of hemoglobin,haptoglobin complexes and regulation of inflammatory processes. CD163 is shed from the cell surface and exists as a soluble form in plasma (sCD163). Monocyte CD163 and sCD163 are potential diagnostic tools in variety of disease states. Methods We determined the relation between plasma sCD163 levels by enzyme-linked immunosorbent assay, membrane expressions of CD163, CD64, and CD14 on blood monocytes by flow cytometry, and monocyte counts in 129 random blood samples. Results A strong inverse correlation was found between membrane CD163 expression and sCD163 levels (r = ,0.65, P < 0.001). Monocyte CD163 expression and SCD163 levels did not correlate with the monocyte absolute count. Conclusions The inverse relation between monocyte surface CD163 expression and sCD163 levels in human blood suggests that plasma sCD163 is derived from circulating monocytes, in addition to an unknown component from tissue macrophages. The lack of correlation with the absolute monocyte number suggests that such a balance is driven by the functional state of monocytes, rather than simply by numerical changes in circulating cells. We propose that further clinical evaluations of CD163 as a diagnostic parameter should include simultaneous measurements of soluble and cell-bound forms of this antigen. © 2004 Wiley-Liss, Inc. [source] Full Scope of Effect of Facial Lipoatrophy: A Framework of Disease UnderstandingDERMATOLOGIC SURGERY, Issue 8 2006BENJAMIN ASCHER MD BACKGROUND Facial lipoatrophy has been observed to occur in a variety of patient populations, with inherited or acquired disease, or even in aging patients as a natural progression of tissue change over time. There is currently no framework from which physicians of all medical specialties can communally discuss the manifestations, diagnoses, and management of facial lipoatrophy. OBJECTIVE The aim of this assembly was to derive a definition of facial lipoatrophy capable of being applied to all patient populations and develop an accompanying grading system. RESULTS The final consensus of the Facial Lipoatrophy Panel encompasses both aging and disease states: "Loss of facial fat due to aging, trauma or disease, manifested by flattening or indentation of normally convex contours." The proposed grading scale includes five gradations (Grades 1,5; 5 being the most severe), and the face is assessed according to three criteria: contour, bony prominence, and visibility of musculature. CONCLUSION Categorizing the presentation of facial lipoatrophy is subjective and qualitative, and will need to be validated with objective measures. Furthermore, during the assembly, several topics were exposed that warrant further research, including the physiology of volume loss, age and lipoatrophy, and human immunodeficiency virus and lipoatrophy. [source] The application of transcranial magnetic stimulation in psychiatry and neurosciences researchACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2002P. B. Fitzgerald Objective:,Over recent years transcranial magnetic stimulation (TMS) has become widely applied in the study of neuropsychiatric disorders. The aim of this article is to review the application of TMS as an investigative tool and as a potential therapeutic modality in psychiatric disorders. Method:,A comprehensive literature review. Results:,When applied as an investigative tool, TMS provides innovative ways to directly study the excitability of the cortex, cortical regional connectivity, the plasticity of brain responses and cognitive functioning in illness and disease states. A number of studies suggest the potential of treatment with TMS in disease states, especially in patients with depression, although difficulties exist with the interpretation of the published literature. Conclusion:,TMS has a considerable role in neuropsychiatric research. It appears to have considerable potential as a therapeutic tool in depression, and perhaps a role in several other disorders, although widespread application requires larger trials and establishment of sustained response. [source] Fine-needle aspiration diagnosis of Hodgkin lymphoma using current WHO classification,Re-evaluation of cases from 1999,2004 with new proposalsDIAGNOSTIC CYTOPATHOLOGY, Issue 6 2006Jue-Rong Zhang M.D., Ph.D. Abstract With the advent of modern therapy, the differences in prognoses and treatment regimens among different subtypes of Hodgkin lymphoma (HL) have largely vanished. Stage and the presence of systemic symptoms are much more important than histologic subtypes as predictive factors. The current (2001) WHO classification markedly de-emphasizes spatial relationships as critical to the diagnosis of lymphoma and emphasizes cell morphology, immunophenotype, genetic features, and clinical information to define the disease states. This classification, thus, greatly enhances the capability of fine-needle aspiration (FNA) to accurately diagnose HL. We searched all the FNA cases in our institute in years 1999 through 2004 and found 42 cases, for which 13 were primarily diagnosed (31.0%), 2 were recurrent (4.8%), 5 were highly suspicious (11.9%), and 22 were suspicious (52.3%) for HL. On follow-up tissue biopsy, all the primarily diagnosed, recurrent, and highly suspicious cases were confirmed to be HL (100% agreement). For the 22 suspicious cases, 13 were HL (59.1%), 5 were other lymphomas (22.8%), 1 was lymphoma unclassifiable (4.5%), and 3 were reactive processes (13.6%). The effect of immunostains on the diagnosis of HL was examined, and its importance was emphasized. Analysis of demographic data and the distribution of HL subtypes demonstrate that the study sample is representative of the general HL patient population. On the basis of these results, we propose: (1) If the FNA diagnosis of HL is confirmed both by morphology and immunostains, no further tissue confirmation, subclassification and grading is necessary, and appropriate treatment regimens should follow. (2) The nodular lymphocyte predominant HL and classical HL can be differentiated by adequate immunostaining. (3) If a definitive diagnosis cannot be achieved by FNA, a second FNA or a tissue biopsy should be recommended. Diagn. Cytopathol. 2006;34:397,402. © 2006 Wiley-Liss, Inc. [source] Echocardiographic Evaluation of Ventricular Function in MiceECHOCARDIOGRAPHY, Issue 1 2007Jeffrey N. Rottman M.D. Ventricular dysfunction remains a hallmark of most cardiac disease. The mouse has become an essential model system for cardiovascular biology, and echocardiography an established tool in the study of normal and genetically altered mice. This review describes the measurement of ventricular function, most often left ventricular function, by echocardiographic methods in mice. Technical limitations related to the small size and rapid heart rate in the mouse initially argued for the performance of echocardiography under anesthesia. More recently, higher frame rates and smaller probes operating at higher frequencies have facilitated imaging of conscious mice in some, but not all, experimental protocols and conditions. Ventricular function may be qualitatively and quantitatively evaluated under both conditions. Particular detail is provided for measurement under conscious conditions, and measurement under conscious and sedated or anesthestized conditions are contrasted. Normal values for echocardiographic indices for the common C57BL/6 strain are provided. Diastolic dysfunction is a critical pathophysiologic component of many disease states, and progress in the echocardiographic evaluation of diastolic function is discussed. Finally, echocardiography exists among several competing imaging technologies, and these alternatives are compared. [source] The mitochondrial proteome: A dynamic functional program in tissues and disease states,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2010Robert S. Balaban Abstract The nuclear DNA transcriptional programming of the mitochondria proteome varies dramatically between tissues depending on its functional requirements. This programming generally regulates all of the proteins associated with a metabolic or biosynthetic pathway associated with a given function, essentially regulating the maximum rate of the pathway while keeping the enzymes at the same molar ratio. This may permit the same regulatory mechanisms to function at low- and high-flux capacity situations. This alteration in total protein content results in rather dramatic changes in the mitochondria proteome between tissues. A tissues mitochondria proteome also changes with disease state, in Type 1 diabetes the liver mitochondrial proteome shifts to support ATP production, urea synthesis, and fatty acid oxidation. Acute flux regulation is modulated by numerous posttranslational events that also are highly variable between tissues. The most studied posttranslational modification is protein phosphorylation, which is found all of the complexes of oxidative phosphorylation and most of the major metabolic pathways. The functional significance of these modifications is currently a major area of research along with the kinase and phosphatase regulatory network. This near ubiquitous presence of protein phosphorylations, and other posttranslational events, in the matrix suggest that not all posttranslational events have functional significance. Screening methods are being introduced to detect the active or dynamic posttranslational sites to focus attention on sites that might provide insight into regulatory mechanisms. Environ. Mol. Mutagen., 2010. Published 2010 Wiley-Liss, Inc. [source] A compendium of human mitochondrial gene expression machinery with links to diseaseENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2010Timothy E. Shutt Abstract Mammalian mitochondrial DNA encodes 37 essential genes required for ATP production via oxidative phosphorylation, instability or misregulation of which is associated with human diseases and aging. Other than the mtDNA-encoded RNA species (13 mRNAs, 12S and 16S rRNAs, and 22 tRNAs), the remaining factors needed for mitochondrial gene expression (i.e., transcription, RNA processing/modification, and translation), including a dedicated set of mitochondrial ribosomal proteins, are products of nuclear genes that are imported into the mitochondrial matrix. Herein, we inventory the human mitochondrial gene expression machinery, and, while doing so, we highlight specific associations of these regulatory factors with human disease. Major new breakthroughs have been made recently in this burgeoning area that set the stage for exciting future studies on the key outstanding issue of how mitochondrial gene expression is regulated differentially in vivo. This should promote a greater understanding of why mtDNA mutations and dysfunction cause the complex and tissue-specific pathology characteristic of mitochondrial disease states and how mitochondrial dysfunction contributes to more common human pathology and aging. Environ. Mol. Mutagen., 2010. © 2010 Wiley-Liss, Inc. [source] Angiopoietin/tie-2 as mediators of angiogenesis: a role in congestive heart failure?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2004A. Y. Chong Abstract Angiogenic factors, in particular vascular endothelial growth factor (VEGF) and the angiopoietins, Ang-1 and -2, have recently generated significant interest, especially in oncology. The process of angiogenesis is also thought to occur in response to ischaemic conditions, which lie at the core of cardiovascular disease states such as coronary artery disease and congestive heart failure. However, current data do not conclusively show evidence of angiogenesis per se in these conditions, despite (for example) the presence of high levels of VEGF and Ang-2. High levels of these angiogenic factors in heart disease also have not translated into clinically significant new vessel formation, as in accelerated cancer growth or proliferative retinopathy. Indeed, we would hypothesize that these angiogenic markers , especially the angiopoietins , do not necessarily translate into new vessel formation in congestive heart failure (CHF), but may well reflect disturbances of endothelial integrity in CHF. [source] Novel therapeutic targets in multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2000Faith E. Davies The aim of this review is to focus on a number of key areas where recent advances in the biology of the disease have not only yielded an understanding of the disease pathogenesis but have also suggested novel treatment approaches. Factors mediating myeloma cell growth, survival and the complex interaction of myeloma cells with the bone marrowmicroenvironment have provided a framework for the rational design of therapeutic agents. The development of such biologically based treatments which target both the tumour cell and the microenvironment, in order to achieve more complete and selective eradication of myeloma cells and the maintenance of minimal residual disease states, may ultimately lead to improved disease-free survivial and potentially a cure. [source] Selective 5-HT1B receptor inhibition of glutamatergic and GABAergic synaptic activity in the rat dorsal and median rapheEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006Julia C. Lemos Abstract The dorsal (DR) and median (MR) raphe nuclei contain 5-hydroxytryptamine (5-HT) cell bodies that give rise to the majority of the ascending 5-HT projections to the forebrain. The DR and MR have differential roles in mediating stress, anxiety and depression. Glutamate and GABA activity sculpt putative 5-HT neuronal firing and 5-HT release in a seemingly differential manner in the MR and DR, yet isolated glutamate and GABA activity within the DR and MR has not been systematically characterized. Visualized whole-cell voltage-clamp techniques were used to record excitatory and inhibitory postsynaptic currents (EPSC and IPSC) in 5-HT-containing neurons. There was a regional variation in action potential-dependent (spontaneous) and basal [miniature (m)] glutamate and GABAergic activity. mEPSC activity was greater than mIPSC activity in the DR, whereas in the MR the mIPSC activity was greater. These differences in EPSC and IPSC frequency indicate that glutamatergic and GABAergic input have distinct cytoarchitectures in the DR and MR. 5-HT1B receptor activation decreased mEPSC frequency in the DR and the MR, but selectively inhibited mIPSC activity only in the MR. This finding, in concert with its previously described function as an autoreceptor, suggests that 5-HT1B receptors influence the ascending 5-HT system through multiple mechanisms. The disparity in organization and integration of glutamatergic and GABAergic input to DR and MR neurons and their regulation by 5-HT1B receptors may contribute to the distinction in MR and DR regulation of forebrain regions and their differential function in the aetiology and pharmacological treatment of psychiatric disease states. [source] The role of corticotropin-releasing hormone in immune-mediated cutaneous inflammatory diseaseEXPERIMENTAL DERMATOLOGY, Issue 3 2006Marina O' Kane Abstract:, Corticotropin-releasing hormone (CRH) coordinates the systemic stress response via hypothalamic-pituitary-adrenal (HPA) axis activation with subsequent modulation of the inflammatory response. Stress is known to affect expression of immune-mediated inflammatory diseases, many of which are associated with HPA axis abnormalities. HPA axis components including CRH and its receptors (CRH-R) exist in the skin and exhibit differential expression according to cell type, physiological fluctuations and disease states. This confirms a local functioning cutaneous HPA-like system. Peripheral CRH may exhibit proinflammatory effects. Animal studies confirm that peripheral CRH is required for induction of the inflammatory response in vivo. CRH and CRH-R are upregulated in inflammatory arthritis synovium and psoriatic skin. CRH may influence mast cell activation, direct modulation of immune cells, angiogenesis and induction of the novel orphan nuclear receptor NURR1. This transcription factor is part of the steroid/thyroid superfamily of related nuclear receptors that includes receptors for steroids, retinoids and vitamin D; ligands of these receptors are effective in treating psoriasis. The roles of CRH and NURR1 in psoriasis and inflammatory skin diseases, especially those associated with stress, remain to be elucidated. This stress may be psychological or physical. CRH, produced locally or delivered by peripheral nerves, may mediate interactions between a cutaneous HPA axis-like system and the central HPA axis , the ,brain-skin axis'. [source] Role of protease-activated receptor-2 during cutaneous inflam-mation and the immune responseEXPERIMENTAL DERMATOLOGY, Issue 9 2004M. Steinhoff Protease-activated receptors (PARs) constitute a new subfamily of G-protein-coupled receptors with seven transmembrane domains which are activated by various serine proteases such as thrombin, cathepsin G, trypsin or tryptase, and bacterial proteases or mite antigens, for example. PAR2 is a receptor for mast cell tryptase or house dust mite allergens, which is released during inflammation and allergic reactions. In the skin, PAR2 is diversely expressed by keratinocytes, endothelial cells, and occasionally sensory nerves of human skin in various disease states. Moreover, immunocompetent cells such as T cells and neutrophils express functional PAR2, thereby contributing to inflammation and host defense. Own data revealed that PAR2 contributes to neurogenic inflammation by releasing neuropeptides from sensory nerves resulting in oedema, plasma extravasation and infiltration of neutrophils. Thus, mast cells may communicate with sensory nerves in inflammatory tissues by activating PAR2 via tryptase. Moreover, PAR2 agonists upregulate the expression of certain cell-adhesion molecules and cytokines such as interleukin-6 and interleukin-8 on dermal microvascular endothelial cells or regulate neutrophil migration, indicating that PAR2 plays an important role in leucocyte/endothelial interactions. These effects may be partly mediated by NF-,B, an important transcription factor during inflammation and immune response. PAR2 stimulation results in the activation of NF-,B on microvascular endothelial cells and keratinocytes, thereby regulating ICAM-1 expression. We also demonstrate evidence for a diverse expression of PAR2 in various skin diseases and highlight the recent knowledge about the important role of PAR2 during inflammation and the immune response. Together, PAR2 -modulating agents may be new tools for the treatment of inflammatory and allergic diseases in the skin. [source] Potential clinical relevance of the ,little brain' on the mammalian heartEXPERIMENTAL PHYSIOLOGY, Issue 2 2008J. A. Armour It is hypothetized that the heart possesses a nervous system intrinsic to it that represents the final relay station for the co-ordination of regional cardiac indices. This ,little brain' on the heart is comprised of spatially distributed sensory (afferent), interconnecting (local circuit) and motor (adrenergic and cholinergic efferent) neurones that communicate with others in intrathoracic extracardiac ganglia, all under the tonic influence of central neuronal command and circulating catecholamines. Neurones residing from the level of the heart to the insular cortex form temporally dependent reflexes that control overlapping, spatially determined cardiac indices. The emergent properties that most of its components display depend primarily on sensory transduction of the cardiovascular milieu. It is further hypothesized that the stochastic nature of such neuronal interactions represents a stabilizing feature that matches cardiac output to normal corporal blood flow demands. Thus, with regard to cardiac disease states, one must consider not only cardiac myocyte dysfunction but also the fact that components within this neuroaxis may interact abnormally to alter myocyte function. This review emphasizes the stochastic behaviour displayed by most peripheral cardiac neurones, which appears to be a consequence of their predominant cardiac chemosensory inputs, as well as their complex functional interconnectivity. Despite our limited understanding of the whole, current data indicate that the emergent properties displayed by most neurones comprising the cardiac neuroaxis will have to be taken into consideration when contemplating the targeting of its individual components if predictable, long-term therapeutic benefits are to accrue. [source] Mapping of the 45M1 epitope to the C-terminal cysteine-rich part of the human MUC5AC mucinFEBS JOURNAL, Issue 3 2008Martin E. Lidell Mucins are large glycoproteins protecting mucosal surfaces throughout the body. Their expressions are tissue-specific, but in disease states such as cystic fibrosis, inflammation and cancer, this specificity can be disturbed. MUC5AC is normally expressed in the mucous cells of the epithelia lining the stomach and the trachea, where it constitutes a major component of the gastric and respiratory mucus. A number of mAbs have been raised against the gastric M1 antigen, an early marker for colonic carcinogenesis. Several of these mAbs recognize epitopes present on MUC5AC, suggesting that MUC5AC is the antigen. However, some of the mAbs raised against the gastric M1 antigen are widely used as antibodies against MUC5AC, despite the fact that their specificity for MUC5AC has not been clearly shown. In this study, we have tested the reactivity of the latter antibodies against a recombinantly expressed C-terminal cysteine-rich part of human MUC5AC. We demonstrate for the first time that the widely used mAb 45M1, as well as 2-12M1 and 166M1, are true antibodies against MUC5AC, with epitopes located in the C-terminal cysteine-rich part of the mucin. [source] R120G ,B-crystallin promotes the unfolding of reduced ,-lactalbumin and is inherently unstableFEBS JOURNAL, Issue 3 2005Teresa M. Treweek ,-Crystallin is the principal lens protein which, in addition to its structural role, also acts as a molecular chaperone, to prevent aggregation and precipitation of other lens proteins. One of its two subunits, ,B-crystallin, is also expressed in many nonlenticular tissues, and a natural missense mutation, R120G, has been associated with cataract and desmin-related myopathy, a disorder of skeletal muscles [Vicart P, Caron A, Guicheney P, Li Z, Prevost MC, Faure A, Chateau D, Chapon F, Tome F, Dupret JM, Paulin D & Fardeau M (1998) Nat Genet20, 92,95]. In the present study, real-time 1H-NMR spectroscopy showed that the ability of R120G ,B-crystallin to stabilize the partially folded, molten globule state of ,-lactalbumin was significantly reduced in comparison with wild-type ,B-crystallin. The mutant showed enhanced interaction with, and promoted unfolding of, reduced ,-lactalbumin, but showed limited chaperone activity for other target proteins. Using NMR spectroscopy, gel electrophoresis, and MS, we observed that, unlike the wild-type protein, R120G ,B-crystallin is intrinsically unstable in solution, with unfolding of the protein over time leading to aggregation and progressive truncation from the C-terminus. Light scattering, MS, and size-exclusion chromatography data indicated that R120G ,B-crystallin exists as a larger oligomer than wild-type ,B-crystallin, and its size increases with time. It is likely that removal of the positive charge from R120 of ,B-crystallin causes partial unfolding, increased exposure of hydrophobic regions, and enhances its susceptibility to proteolysis, thus reducing its solubility and promoting its aggregation and complexation with other proteins. These characteristics may explain the involvement of R120G ,B-crystallin with human disease states. [source] Anti-disialosyl antibodies mediate selective neuronal or Schwann cell injury at mouse neuromuscular junctionsGLIA, Issue 3 2005Susan K. Halstead Abstract The human paralytic neuropathy, Miller Fisher syndrome (MFS) is associated with autoantibodies specific for disialosyl epitopes on gangliosides GQ1b, GT1a, and GD3. Since these gangliosides are enriched in synaptic membranes, anti-ganglioside antibodies may target neuromuscular junctions (NMJs), thereby contributing to disease symptoms. We have shown previously that at murine NMJs, anti-disialosyl antibodies induce an ,-latrotoxin-like effect, electrophysiologically characterized by transient massive increase of spontaneous neurotransmitter release followed by block of evoked release, resulting in paralysis of the muscle preparation. Morphologically, motor nerve terminal damage, as well as perisynaptic Schwann cell (pSC) death is observed. The relative contributions of neuronal and pSC injury to the paralytic effect and subsequent repair are unknown. In this study, we have examined the ability of subsets of anti-disialosyl antibodies to discriminate between the neuronal and glial elements of the NMJ and thereby induce either neuronal injury or pSC death. Most antibodies reactive with GD3 induced pSC death, whereas antibody reactivity with GT1a correlated with the extent of nerve terminal injury. Motor nerve terminal injury resulted in massive uncontrolled exocytosis with paralysis. However, pSC ablation induced no acute (within 1 h) electrophysiological or morphological changes to the underlying nerve terminal. These data suggest that at mammalian NMJs, acute pSC injury or ablation has no major deleterious influence on synapse function. Our studies provide evidence for highly selective targeting of mammalian NMJ membranes, based on ganglioside composition, that can be exploited for examining axonal,glial interactions both in disease states and in normal NMJ homeostasis. © 2005 Wiley-Liss, Inc. [source] The kidney disease wasting: Inflammation, oxidative stress, and diet-gene interactionHEMODIALYSIS INTERNATIONAL, Issue 4 2006Kamyar KALANTAR-ZADEH Abstract The 350,000 maintenance hemodialysis (MHD) patients in the United States have an unacceptably high mortality rate of >20%/year. Almost half of all deaths are assumed to be cardiovascular. Markers of kidney disease wasting (KDW) such as hypoalbuminemia, anorexia, body weight and fat loss, rather than traditional cardiovascular risk factors, appear to be the strongest predictors of early death in these patients. The KDW is closely related to oxidative stress (SOX). Such SOX markers as serum myeloperoxidase are associated with pro-inflammatory cytokines and poor survival in MHD patients. Identifying the conditions that modulate the KDW/SOX-axis may be the key to improving outcomes in MHD patients. Dysfunctional lipoproteins such as a higher ratio of the high-density lipoprotein inflammatory index (HII) may engender or aggravate the KDW, whereas functionally intact or larger lipoprotein pools, as in hypercholesterolemia and obesity, may mitigate the KDW in MHD patients. Hence, a reverse epidemiology or "bad-gone-good" phenomenon may be observed. Diet and gene and their complex interaction may lead to higher proportions of pro-inflammatory or oxidative lipoproteins such as HII, resulting in the aggravation of the SOX and inflammatory processes, endothelial dysfunction, and subsequent atherosclerotic cardiovascular disease and death in MHD patients. Understanding the factors that modulate the KDW/SOX complex and their associations with genetic polymorphism, nutrition, and outcomes in MHD patients may lead to developing more effective strategies to improve outcomes in this and the 20 to 30 million Americans with chronic disease states such as individuals with chronic heart failure, advanced age, malignancies, AIDS, or cachexia. [source] Clinical implications of telomerase detectionHISTOPATHOLOGY, Issue 6 2001P Matthews Clinical implications of telomerase detection In 1994 a sensitive method for the detection of telomerase was described. This assay, which was based on the polymerase chain reaction, suggested that telomerase activity was associated with immortal and cancer cells. Since then more than a thousand studies have documented the expression and activity of the enzyme in diseased tissues, primarily tumours. This review gives an overview of the biological significance of telomerase expression and methods for detecting its activity. This is followed by an organ system-based discussion of expression in normal tissues and disease states. We finish with speculation as to the future role of telomerase detection in diagnostic histopathology. [source] Glycolipid targets of CD1-mediated T-cell responsesIMMUNOLOGY, Issue 3 2001D. Branch Moody Summary Members of the CD1 family of antigen-presenting molecules bind and present a variety of mammalian and microbial glycolipids for specific recognition by T cells. CD1 proteins accomplish their antigen-presenting function by binding the alkyl chains of the antigens within a deep, hydrophobic groove on the membrane distal surface of CD1, making the hydrophilic elements of the antigen available for contact with the variable regions of antigen-specific T-cell receptors. Most models of CD1-restricted T cells function in infectious, neoplastic, or autoimmune diseases and are based on the premise that CD1-restricted T-cell responses are initiated by alterations in cellular glycolipid content. Although a growing number of self, altered self and foreign glycolipid antigens have been identified, the cellular mechanisms that could lead to the generation of antigenic glycolipids within cells, or control the presentation of particular classes of altered self or microbial glycolipids in disease states have only recently come under investigation. Here we review the structures of known glycolipid antigens for T cells and discuss how the chemical nature of these antigens, which is quite different from that of peptides, influences their recognition by T cells. [source] The six-minute walk test: a useful metric for the cardiopulmonary patientINTERNAL MEDICINE JOURNAL, Issue 8 2009T. Rasekaba Abstract Measurement of exercise capacity is an integral element in assessment of patients with cardiopulmonary disease. The 6-min walk test (6MWT) provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions. A distance less than 350 m is associated with increased mortality in chronic obstructive pulmonary disease, chronic heart failure and pulmonary arterial hypertension. Desaturation during a 6MWT is an important prognostic indicator for patients with interstitial lung disease. The 6MWT is sensitive to commonly used therapies in chronic obstructive pulmonary disease such as pulmonary rehabilitation, oxygen, long-term use of inhaled corticosteroids and lung volume reduction surgery. However, it appears less reliable to detect changes in clinical status associated with medical therapies for heart failure. A change in walking distance of more than 50 m is clinically significant in most disease states. When interpreting the results of a 6MWT, consideration should be given to choice of predictive values and the methods by which the test was carried out. [source] Valuation of health states in the US study to establish disability weights: lessons from the literatureINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 1 2010Jürgen Rehm Abstract The metric of disability-adjusted life years (DALYs) has become the global standard of measuring burden of disease. DALYs are comprised of years of life lost due to premature mortality and years of healthy life lost due to living with disability. In order to calculate the second part of the DALY equation, disease specific disability weights have to be established, i.e. measures for the decline of health associated with these disease states, which vary between zero for perfect health and one for death. Although these disability weights are key for estimating DALYs, there have not been many comprehensive studies with empirical determinations of them. This article describes a systematic review on the state of the art with respect to empirically determining disability weights. Based on this review, a multi-method approach is outlined, which has also been implemented in a US study to measure burden of disease. This approach involves the use of psychometric methodology as well as economic trade-off methods for determining the value of health states. It is conceptualized as a disaggregated approach, where the disability weight of any health state can be calculated if the attributes of this health state are known. The US study received the collaboration of experts from more than 20 institutes of the National Institutes of Health and of the Centers for Disease Control and Prevention. First results will be available by the end of this year. Copyright © 2010 John Wiley & Sons, Ltd. [source] Quantification of dental caries by osteologists and odontologists,a validity and reliability study,INTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 5 2010C. Liebe-Harkort Abstract As in modern populations, dental caries in early populations is linked to diet and general health. In order to record not only advanced disease states with frank cavitation of teeth but also early lesions, indicating the presence of the disease in a population, it is important that the archaeologist can correctly detect and classify lesions of varying severity. The present study compares and contrasts quantification of dental caries by osteologists and odontologists. Four osteologists and four odontologists undertook visual and radiographic inspection of 61 teeth from three different sources: medieval, 19th century and modern. Separate sets of criteria were applied to disclose observer confidence in detecting a lesion and in estimating lesion extent. For validation of visual assessments, the teeth were sectioned. Radiographic assessments were validated by a specialist in dental radiography. The results disclosed that the odontologists in general showed greater sensitivity than the osteologists, correctly identifying carious lesions, but the osteologists had higher specificity, correctly identifying healthy teeth. Thus, the osteologists tend to overlook carious lesions (under-diagnosis), while the odontologists tend to incorrectly record lesions in healthy teeth (over-diagnosis). For both osteologists and odontologists, correct assessment was poorer for radiographs than for visual inspection. Copyright © 2009 John Wiley & Sons, Ltd. [source] Signaling mechanisms in skeletal muscle: Acute responses and chronic adaptations to exerciseIUBMB LIFE, Issue 3 2008Katja S.C. Röckl Abstract Physical activity elicits physiological responses in skeletal muscle that result in a number of health benefits, in particular in disease states, such as type 2 diabetes. An acute bout of exercise/muscle contraction improves glucose homeostasis by increasing skeletal muscle glucose uptake, while chronic exercise training induces alterations in the expression of metabolic genes, such as those involved in muscle fiber type, mitochondrial biogenesis, or glucose transporter 4 (GLUT4) protein levels. A primary goal of exercise research is to elucidate the mechanisms that regulate these important metabolic and transcriptional events in skeletal muscle. In this review, we briefly summarize the current literature describing the molecular signals underlying skeletal muscle responses to acute and chronic exercise. The search for possible exercise/contraction-stimulated signaling proteins involved in glucose transport, muscle fiber type, and mitochondrial biogenesis is ongoing. Further research is needed because full elucidation of exercise-mediated signaling pathways would represent a significant step toward the development of new pharmacological targets for the treatment of metabolic diseases such as type 2 diabetes. © 2008 IUBMB IUBMB Life, 60(3): 145,153, 2008 [source] A Drosophila Model of Mitochondrial DNA Replication: Proteins, Genes and RegulationIUBMB LIFE, Issue 8 2005Rafael Garesse Abstract Mitochondrial biogenesis is a critical process in animal development, cellular homeostasis and aging. Mitochondrial DNA replication is an essential part of this process, and both nuclear and mitochondrial DNA mutations are found to result in mitochondrial dysfunction that leads to developmental defects and delays, aging and disease. Drosophila provides an amenable model system to study mitochondrial biogenesis in normal and disease states. This review provides an overview of current approaches to study the proteins involved in mitochondrial DNA replication, the genes that encode them and their regulation. It also presents a survey of cell and animal models under development to mimic the pathophysiology of human mitochondrial disorders. IUBMB Life, 57: 555-561, 2005 [source] Genetic and epigenetic mechanisms in the early development of the vascular systemJOURNAL OF ANATOMY, Issue 2 2006Domenico Ribatti Abstract The cardiovascular system plays a critical role in vertebrate development and homeostasis. Vascular development is a highly organized sequence of events that requires the correct spatial and temporal expression of specific sets of genes leading to the development of a primary vascular network. There have been intensive efforts to determine the molecular mechanisms regulating vascular growth and development, and much of the rationale for this has stemmed from the increasing clinical importance and therapeutic potential of modulating vascular formation during various disease states. [source] Effects of choice and relative frequency elicitation on overconfidence: further tests of an exemplar-retrieval modelJOURNAL OF BEHAVIORAL DECISION MAKING, Issue 2 2003Winston R. Sieck Abstract An experiment is reported in which participants rendered judgments regarding the disease states of hypothetical patients. Participants either reported likelihoods that patients had the target disease (no choice), or classified patients into disease categories and then reported likelihoods that their classifications were correct (choice included). Also, participants' likelihood judgments were made in response to either a probability probe question, or a relative frequency probe. Two distinct exemplar-memory models were compared on their ability to predict overconfidence under these procedures. Both propose that people learn and judge by storing and retrieving examples. The exemplar retrieval model (ERM) proposes that amount of retrieval drives choice inclusion and likelihood probe effects. The alternative model assumes that response error mediates choice inclusion effects. Choice inclusion and the relative frequency probe reduced overconfidence, but the combined effects were subadditive. Only the ERM predicted this pattern, and it further provided good quantitative fits to these results. Copyright © 2003 John Wiley & Sons, Ltd. [source] FT-IR spectroscopy in diagnosis of diabetes in rat animal modelJOURNAL OF BIOPHOTONICS, Issue 8-9 2010Feride Severcan Abstract In recent years, Fourier Transform Infrared (FT-IR) spectroscopy has had an increasingly important role in the field of pathology and diagnosis of disease states. In the current study, FT-IR spectroscopy together with cluster analysis were used as a diagnostic tool in the discrimination of diabetic samples from control ones in rat kidney plasma membrane apical sides (brush-border membranes), liver microsomal membranes and Extensor digitorum longus (EDL) and Soleus (SOL) skeletal muscle tissues. A variety of alterations in the spectral parameters, such as frequency and signal intensity/area was observed in diabetic tissues and membranes compared to the control samples. Based on these spectral variations, using cluster analysis successful differentiation between diabetic and control groups was obtained in different spectral regions. The results of this current study further revealed the power and sensitivity of FT-IR spectroscopy in precise and automated diagnosis of diabetes. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Role of TIEG1 in biological processes and disease statesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2007Malayannan Subramaniam Abstract A novel TGF, Inducible Early Gene-1 (TIEG1) was discovered in human osteoblast (OB) cells by our laboratory. Over the past decade, a handful of laboratories have revealed a multitude of organismic, cellular, and molecular functions of this gene. TIEG1 is now classified as a member of the 3 zinc finger family of Krüppel-like transcription factors (KLF10). Other closely related factors [TIEG2 (KLF11) and TIEG3/TIEG2b] have been reported and are briefly compared. As described in this review, TIEG1 is shown to play a role in regulating estrogen and TGF, actions, the latter through the Smad signaling pathway. In both cases, TIEG1 acts as an inducer or repressor of gene transcription to enhance the TGF,/Smad pathway, as well at other signaling pathways, to regulate cell proliferation, differentiation, and apoptosis. This review outlines TIEG1's molecular functions and roles in skeletal disease (osteopenia/osteoporosis), heart disease (hypertrophic cardiomyopathy), and cancer (breast and prostate). J. Cell. Biochem. 102: 539,548, 2007. © 2007 Wiley-Liss, Inc. [source] Oxidative stress: the role of cytochromes P450 in oxygen activationJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 10 2002David F, V Lewis Abstract Oxidative stress is associated with a number of degenerative disease states, such as cancer and AIDS. Fundamental to oxidative stress is the generation of superoxide, peroxide and other reactive oxygen species (ROS). This review focuses on the importance of cytochrome P450 (CYP) enzymes in the activation of oxygen and ROS generation, together with a discussion of defence mechanisms which can offer protection against oxidative stress. © 2002 Society of Chemical Industry. [source] | ||||||||||||||||||||||||||||||||||||||||