Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Biologic pathways”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed2005

Identification of temporal pattern of mandibular condylar growth: a molecular and biochemical experiment.

OBJECTIVES: Based on the phenomenon that expression of type X collagen and capillary endothelium correlates with endochondral ossification, the prime aim of this study was to establish the temporal pattern of condylar growth in Sprague-Dawley rats by biochemically identifying the expression of these two factors. DESIGN: Sprague-Dawley rats were divided into five groups representing five different stages during somatic pubertal growth. In situ hybridization and immunoperoxidase were performed to examine expression of type X collagen in hypertrophic zone and capillary endothelium in erosive zone of condylar cartilage. Computer-assisted imaging analyses were conducted to allow for a quantitative assessment of the expression of these two factors, from which the temporal pattern of condylar growth was inferred. RESULTS: (1) Synthesis of type X collagen and emergence of capillary endothelium were critical factors during the transition of condylar cartilage from chondrogenesis into osteogenesis, a biological pathway that leads to endochondral bone formation, the mode through which the condyle grows. (2) Quantitative analyses revealed the temporal pattern of the expression of these two factors, indicating that the thrust of natural growth of the condyle in the rats occurred in concomitance with somatic pubertal growth, featured by an acceleration starting from day 38, a maximum growth rate on day 56, followed by a decrease afterwards. CONCLUSION: It is suggested that the biochemical examination of growth markers, such as type X collagen, might be a new approach to accurately depict temporal pattern of condylar growth which is too delicate to be reflected by gross measurement not only in Sprague-Dawley rats but potentially also in other species.

Animals↗
PubMed2004

Efficient extraction of mapping rules of atoms from enzymatic reaction data.

Many computational problems and methods have been proposed for analysis of biological pathways. Among them, this paper focuses on extraction of mapping rules of atoms from enzymatic reaction data, which is useful for drug design, simulation of tracer experiments, and consistency checking of pathway databases. Most of existing methods for this problem are based on maximal common subgraph algorithms. In this paper, we propose a novel approach based on graph partition and graph isomorphism. We show that this problem is NP-hard in general, but can be solved in polynomial time for wide classes of enzymatic reactions. We also present an O(n(1.5)) time algorithm for a special but fundamental class of reactions, where n is the maximum size of compounds appearing in a reaction. We develop practical polynomial-time algorithms in which the Morgan algorithm is used for computing the normal form of a graph, where it is known that the Morgan algorithm works correctly for most chemical structures. Computational experiments are performed for these practical algorithms using the chemical reaction data stored in the KEGG/LIGAND database. The results of computational experiments suggest that practical algorithms are useful in many cases.

Algorithms↗
PubMed1995

Heat-shock proteins Hsp104 and Hsp70 reactivate mRNA splicing after heat inactivation.

BACKGROUND: The heat-shock protein Hsp104 plays a crucial role in the survival of cells exposed to high temperatures and other severe stresses, but its specific functions and the biological pathways on which it operates have been unclear. Indeed, very little is known about the specific cellular processes in which any of the heat-shock proteins acts to affect thermotolerance. One essential process that is particularly sensitive to heat in many organisms is the splicing of intervening sequences from mRNA precursors. RESULTS: We have examined the role of Hsp104 in the repair of splicing after disruption by heat shock. When splicing in the budding yeast Saccharomyces cerevisiae was disrupted by a brief heat shock, it recovered much more rapidly in wild-type strains than in strains containing hsp104 mutations. Constitutive expression of Hsp104 promoted the recovery of heat-damaged splicing in the absence of other protein synthesis, but did not protect splicing from the initial disruption, suggesting that Hsp104 functions to repair splicing after heat damage rather than to prevent the initial damage. A modest reduction in the recovery of splicing after heat shock in an hsp70 mutant suggested that Hsp70 may also function in the repair of splicing. The roles of Hsp104 and Hsp70 were confirmed by the ability of the purified proteins to restore splicing in extracts that had been heat-inactivated in vitro. Together, these two proteins were able to restore splicing to a greater degree than could be accomplished by an optimal concentration of either protein alone. CONCLUSIONS: Our findings provide the first demonstration of the roles of heat-shock proteins in a biological process that is known to be particularly sensitive to heat in vivo. The results support previous genetic arguments that the Hsp104 and Hsp70 proteins have different, but related, functions in protecting cells from the toxic effects of high temperatures. Because Hsp104 and Hsp70 are able to function in vitro, after the heat-damaged substrate or substrates have been generated, neither protein is required to bind to its target(s) during heating in order to effect repair.

Fungal Proteins↗
PubMed2005

Persistent organic pollutants and metals in the freshwater biota of the Canadian Subarctic and Arctic: an overview.

Over 1999-2002, an extensive series of contaminant studies was conducted on freshwater biota of Canada's Arctic and Subarctic regions. The majority of inorganic contaminant studies focused on mercury and fish. While mercury concentrations were low in benthic feeding fish such as whitefish, predatory fish such as lake trout, pike, and walleye frequently had mercury levels which exceeded 0.2 mug/g, the consumption guideline for frequent consumers of fish, and 0.5 microg/g, the guideline for the commercial use of fish. Numerous consumption advisories were issued for lakes along the Mackenzie River. Relatively high mercury levels appear to be due to a combination of relatively old fish populations (because of light fishing pressures) and tend to be more prevalent in smaller lakes where warmer summer water temperatures and watershed influences result in greater mercury and methyl mercury inputs. Mercury levels were substantially lower in char than in lake trout, possibly due to a combination of a less fish-rich diet, a colder environment, and smaller MeHg watershed inputs. Less research has been conducted on other metals but some, such as rubidium, show pronounced variations in concentration that may be related to geological influences. Temporal trend monitoring has revealed little evidence of declining mercury levels in fish that can be attributed to declining atmospheric inputs. Because mercury follows complex pathways in the environment, other factors may operate to counteract reductions in atmospheric mercury sources, e.g., climatic variability, changes in the commercial fishery, and interactions between fish species. Most organochlorine (OC) investigations were based on long term trend monitoring and focused on char (Cornwallis Island), burbot (Great Slave Lake, Yukon lakes, Slave River at Fort Smith, Mackenzie River at Fort Good Hope) and lake trout (Yukon lakes, Great Slave Lake). There was strong evidence of declining OC concentrations in char, particularly SigmaHCH and Sigmachlordane, which may reflect a response to declining atmospheric inputs. Endosulfan concentrations increased, as in the atmosphere. There also was evidence of declining OC concentrations in burbot in the Slave and Mackenzie rivers but not in Great Slave Lake and Yukon lakes. OC concentrations decreased in lake trout in Yukon lakes in the 2000s, most probably because of changes in the fish themselves (i.e., reduced lipid content, condition factor) and possibly climatic variability. Similarly, OCs declined in Great Slave Lake trout. New research on PDBEs and perfluorinated compounds determined that these contaminants are widespread in freshwater fish and concentrations may be increasing. Global warming is a major issue of concern for Arctic and Subarctic waters and may have adverse impacts on contaminant levels in fish and other biota. There is a need for contaminant studies in the north to be broadened to investigate climatic effects. In addition, monitoring studies should be broadened to consider factors affecting other aspects of fish biology. Foremost among these is integrating contaminant monitoring studies on lakes such as Lake Laberge and Great Slave Lake with stock assessment studies. Ecosystem based studies should be conducted on Great Slave Lake and Lake Laberge to more effectively understand contaminant trends and should consider inputs (atmospheric, river inflow, resupension), losses (sedimentation, volatilization), and biological pathways.

Animals↗
PubMed2005

Positron emission tomography for radiation treatment planning.

PURPOSE: To evaluate the impact of positron emission tomography (PET) on target volume delineation for radiation treatment planning. MATERIAL AND METHODS: The data of the literature concerning the use of PET in target volume delineation are summarized. The following points are discussed for each tumor entity: biological background for the PET investigation, sensitivity and specificity of PET (with different tracers) in comparison to computed tomography (CT) and magnetic resonance imaging (MRI) and impact of PET on target volume definition. New PET tracers, which could visualize biological pathways, such as hypoxia, proliferation, angiogenesis, apoptosis and gene expression patterns, will also be discussed. RESULTS: The results of clinical studies on the integration of PET in target volume definition for lung, head-and-neck, genitourinary and brain tumors were analyzed. Fluorodeoxyglucose-(FDG-)PET has a significant impact on GTV (gross tumor volume) and PTV (planning target volume) delineation in lung cancer and can detect lymph node involvement and differentiate malignant tissue from atelectasis. In head-and-neck cancer, the value of FDG-PET for radiation treatment planning is still under investigation. For example, FDG-PET could be superior to CT and MRI in the detection of lymph node metastases and unknown primary cancer and in the differentiation of viable tumor tissue after treatment. Therefore, it might play an important role in GTV definition and sparing of normal tissue. Choline PET and acetate PET are promising tracers in the diagnosis of prostate cancer, but their validity in local tumor demarcation, lymph node diagnosis and detection of recurrence has to be defined in future clinical trials. FDG-PET seems to be particularly valuable in lymph node status definition in cervical cancer. In high-grade gliomas and meningiomas, methionine PET helps to define the GTV and differentiate tumor from normal tissue. For other entities like gastrointestinal cancer, lymphomas, sarcomas, etc., the data of the literature are yet insufficient. The imaging of hypoxia, cell proliferation, angiogenesis, apoptosis and gene expression leads to the identification of different areas of a biologically heterogeneous tumor mass that can individually be targeted using intensity modulated radiotherapy (IMRT). In addition, a biological dose distribution can be generated, the socalled dose painting. However, systematic experimental and clinical trials are necessary to validate this hypothesis. CONCLUSION: Regarding treatment planning in radiotherapy, PET offers advantages in terms of tumor delineation and the description of biological processes. To define the real impact of this investigation in radiation treatment planning, subsequent experimental, clinical and cost-benefit analyses are required.

Brain Neoplasms↗
PubMed2005

Pooling samples within microarray studies: a comparative analysis of rat liver transcription response to prototypical toxicants.

Combining or pooling individual samples when carrying out transcript profiling using microarrays is a fairly common means to reduce both the cost and complexity of data analysis. However, pooling does not allow for statistical comparison of changes between samples and can result in a loss of information. Because a rigorous comparison of the identified expression changes from the two approaches has not been reported, we compared the results for hepatic transcript profiles from pooled vs. individual samples. Hepatic transcript profiles from a single-dose time-course rat study in response to the prototypical toxicants clofibrate, diethylhexylphthalate, and valproic acid were evaluated. Approximately 50% more transcript expression changes were observed in the individual (statistical) analysis compared with the pooled analysis. While the majority of these changes were less than twofold in magnitude ( approximately 80%), a substantial number were greater than twofold (approximately 20%). Transcript changes unique to the individual analysis were confirmed by quantitative RT-PCR, while all the changes unique to the pooled analysis did not confirm. The individual analysis identified more hits per biological pathway than the pooled approach. Many of the transcripts identified by the individual analysis were novel findings and may contribute to a better understanding of molecular mechanisms of these compounds. Furthermore, having individual animal data provided the opportunity to correlate changes in transcript expression to phenotypes (i.e., histology) observed in toxicology studies. The two approaches were similar when clustering methods were used despite the large difference in the absolute number of transcripts changed. In summary, pooling reduced resource requirements substantially, but the individual approach enabled statistical analysis that identified more gene expression changes to evaluate mechanisms of toxicity. An individual animal approach becomes more valuable when the overall expression response is subtle and/or when associating expression data to variable phenotypic responses.

Animals↗
PubMed2004

Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta.

In the arterial circulation, regions of disturbed flow (DF), which are characterized by flow separation and transient vortices, are susceptible to atherogenesis, whereas regions of undisturbed laminar flow (UF) appear protected. Coordinated regulation of gene expression by endothelial cells (EC) may result in differing regional phenotypes that either favor or inhibit atherogenesis. Linearly amplified RNA from freshly isolated EC of DF (inner aortic arch) and UF (descending thoracic aorta) regions of normal adult pigs was used to profile differential gene expression reflecting the steady state in vivo. By using human cDNA arrays, approximately 2,000 putatively differentially expressed genes were identified through false-discovery-rate statistical methods. A sampling of these genes was validated by quantitative real-time PCR and/or immunostaining en face. Biological pathway analysis revealed that in DF there was up-regulation of several broad-acting inflammatory cytokines and receptors, in addition to elements of the NF-kappaB system, which is consistent with a proinflammatory phenotype. However, the NF-kappaB complex was predominantly cytoplasmic (inactive) in both regions, and no significant differences were observed in the expression of key adhesion molecules for inflammatory cells associated with early atherogenesis. Furthermore, there was no histological evidence of inflammation. Protective profiles were observed in DF regions, notably an enhanced antioxidative gene expression. This study provides a public database of regional EC gene expression in a normal animal, implicates hemodynamics as a contributory mechanism to athero-susceptibility, and reveals the coexistence of pro- and antiatherosclerotic transcript profiles in susceptible regions. The introduction of additional risk factors may shift this balance to favor lesion development.

Animals↗
PubMed1993

Serum aluminum transport and aluminum uptake in chronic renal failure: role of iron and aluminum metabolism.

Several factors have been blamed for increasing gastrointestinal absorption of aluminum. The likely role of iron metabolism was suggested some years ago. As iron and aluminum share many chemical properties, it is reasonable to think they also share biological pathways. The aim of this study was: (a) to evaluate serum aluminum transport and its relationship with iron-binding capacity, and (b) to investigate aluminum hydroxide absorption as a function of iron and aluminum. We investigated 127 patients with chronic renal failure undergoing hemodialysis in a study divided into two phases: phase 1, a basal study to investigate serum iron and aluminum status, and phase 2 in which an aluminum absorption test was performed. In phase 1, we found that the lower basal serum iron and iron transferrin saturation the greater serum aluminum (p < 0.001). In phase 2, we found a negative relationship between serum aluminum increments after the test and basal levels of serum aluminum and iron (r = -0.70; p < 0.001). These results suggest that the amount of either aluminum or iron carried by transferrin may influence the transferrin capacity to bind the other element and also may modulate, together with other factors, the gastrointestinal absorption of iron and aluminum.

Aluminum↗
PubMed2026

A Computational Workflow for Prioritizing Microbial Metabolite-Associated Host Genes in Constipation-Predominant Irritable Bowel Syndrome.

No standardized computational pipeline exists for systematically prioritizing microbial metabolite-associated host genes and protein-ligand complexes from publicly available chemical, genomic, and structural databases. This article describes an eight-stage workflow that accepts a user-defined set of gut microbiota-derived metabolites and produces a ranked shortlist of candidate metabolite-associated host genes, enriched biological pathways, and structurally prioritized protein-ligand complexes for experimental follow-up. The pipeline integrates (i) chemoinformatic metabolite profiling; (ii) multi-database candidate target prediction using protein-chemical interaction and ligand-based target-prediction tool and a molecular docking program; (iii) differential gene expression analysis of publicly available transcriptomic data; (iv) target-differentially expressed gene overlap; (v) protein-protein interaction network construction and pathway enrichment; (vi) molecular docking with a molecular docking program; (vii) 200 ns molecular dynamics simulation using a molecular dynamics engine with a protein force field used for molecular dynamics simulations; and (viii) MM-PBSA binding free-energy estimation. As a worked example, nine gut microbiota-derived or microbiota-modified metabolites representing short-chain fatty acids, bile acids, tryptophan-derived metabolites, and urolithin A were processed using the public IBS-C rectal mucosal transcriptomic dataset GSE36701. The workflow ranked 17 unique predicted metabolite-associated genes that were differentially expressed in this dataset. Docking, molecular dynamics simulation, and MM-PBSA analyses structurally prioritized five metabolite-protein complexes: lithocholic acid-VDR, lithocholic acid-NR1H4/FXR, ursodeoxycholic acid-NR1H4/FXR, tryptamine-HTR2A (simulated in an explicit 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer), and urolithin A-CASP3. The protocol is designed to be adaptable to other metabolite sets, disease transcriptomic datasets, and target classes; all outputs are hypothesis-generating computational predictions that require independent transcriptomic replication, protein-level validation, and functional ligand-response assays before causal or therapeutic conclusions can be drawn.

Irritable Bowel Syndrome↗
PubMed2003

Recognition of double-stranded RNA by proteins and small molecules.

Molecular recognition of double-stranded RNA (dsRNA) is a key event for numerous biological pathways including the trafficking, editing, and maturation of cellular RNA, the interferon antiviral response, and RNA interference. Over the past several years, our laboratory has studied proteins and small molecules that bind dsRNA with the goal of understanding and controlling the binding selectivity. In this review, we discuss members of the dsRBM class of proteins that bind dsRNA. The dsRBM is an approximately 70 amino acid sequence motif found in a variety of dsRNA-binding proteins. Recent results have led to a new appreciation of the ability of these proteins to bind selectivity to certain sites on dsRNA. This property is discussed in light of the RNA selectivity observed in the function of two proteins that contain dsRBMs, the RNA-dependent protein kinase (PKR) and an adenosine deaminase that acts on dsRNA (ADAR2). In addition, we introduce peptide-acridine conjugates (PACs), small molecules designed to control dsRBM-RNA interactions. These intercalating molecules bear variable peptide appendages at opposite edges of an acridine heterocycle. This design imparts the potential to exploit differences in groove characteristics and/or base-pair dynamics at binding sites to achieve selective binding.

Acridines↗
PubMed2005

A theoretical framework for strain-related trabecular bone maintenance and adaptation.

It is assumed that density and morphology of trabecular bone is partially controlled by mechanical forces. How these effects are expressed in the local metabolic functions of osteoclast resorption and osteoblast formation is not known. In order to investigate possible mechano-biological pathways for these mechanisms we have proposed a mathematical theory (Nature 405 (2000) 704). This theory is based on hypothetical osteocyte stimulation of osteoblast bone formation, as an effect of elevated strain in the bone matrix, and a role for microcracks and disuse in promoting osteoclast resorption. Applied in a 2-D Finite Element Analysis model, the theory explained the formation of trabecular patterns. In this article we present a 3-D FEA model based on the same theory and investigated its potential morphological predictability of metabolic reactions to mechanical loads. The computations simulated the development of trabecular morphological details during growth, relative to measurements in growing pigs, reasonably realistic. They confirmed that the proposed mechanisms also inherently lead to optimal stress transfer. Alternative loading directions produced new trabecular orientations. Reduction of load reduced trabecular thickness, connectivity and mass in the simulation, as is seen in disuse osteoporosis. Simulating the effects of estrogen deficiency through increased osteoclast resorption frequencies produced osteoporotic morphologies as well, as seen in post-menopausal osteoporosis. We conclude that the theory provides a suitable computational framework to investigate hypothetical relationships between bone loading and metabolic expressions.

Adaptation, Physiological↗
PubMed2006

Microsphere-based protease assays and screening application for lethal factor and factor Xa.

BACKGROUND: Proteases regulate many biological pathways in humans and are components of several bacterial toxins. Protease studies and development of protease inhibitors do not follow a single established methodology and are mostly protease specific. METHODS: We have created recombinant fusion proteins consisting of a biotinylated attachment sequence linked to a GFP via a protease cleavage site to develop a multiplexable microsphere-based protease assay system. Using the proteases lethal factor and factor Xa, we performed kinetic experiments to determine optimal conditions for inhibitor screens and detect known inhibitors using the HyperCyt flow cytometry system. RESULTS: We have demonstrated specific cleavage of lethal factor and factor Xa substrates, optimized screening conditions for these substrates, shown specific inhibition of the proteases, and demonstrated high throughput detection of these inhibitors. CONCLUSIONS: The assay developed here is adaptable to any site-specific protease, compatible with high throughput flow cytometry systems, and multiplexable. Coupled with flow cytometry, which provides continuous time resolution and intrinsic resolution of free vs. bound fluorophores, this assay will be useful for high throughput screening of protease inhibitors in general and could simplify assays designed to determine protease mechanism.

Antigens, Bacterial↗
PubMed2006

Assessing protein similarity with Gene Ontology and its use in subnuclear localization prediction.

BACKGROUND: The accomplishment of the various genome sequencing projects resulted in accumulation of massive amount of gene sequence information. This calls for a large-scale computational method for predicting protein localization from sequence. The protein localization can provide valuable information about its molecular function, as well as the biological pathway in which it participates. The prediction of localization of a protein at subnuclear level is a challenging task. In our previous work we proposed an SVM-based system using protein sequence information for this prediction task. In this work, we assess protein similarity with Gene Ontology (GO) and then improve the performance of the system by adding a module of nearest neighbor classifier using a similarity measure derived from the GO annotation terms for protein sequences. RESULTS: The performance of the new system proposed here was compared with our previous system using a set of proteins resided within 6 localizations collected from the Nuclear Protein Database (NPD). The overall MCC (accuracy) is elevated from 0.284 (50.0%) to 0.519 (66.5%) for single-localization proteins in leave-one-out cross-validation; and from 0.420 (65.2%) to 0.541 (65.2%) for an independent set of multi-localization proteins. The new system is available at http://array.bioengr.uic.edu/subnuclear.htm. CONCLUSION: The prediction of protein subnuclear localizations can be largely influenced by various definitions of similarity for a pair of proteins based on different similarity measures of GO terms. Using the sum of similarity scores over the matched GO term pairs for two proteins as the similarity definition produced the best predictive outcome. Substantial improvement in predicting protein subnuclear localizations has been achieved by combining Gene Ontology with sequence information.

Algorithms↗
PubMed2005

An SVM-based system for predicting protein subnuclear localizations.

BACKGROUND: The large gap between the number of protein sequences in databases and the number of functionally characterized proteins calls for the development of a fast computational tool for the prediction of subnuclear and subcellular localizations generally applicable to protein sequences. The information on localization may reveal the molecular function of novel proteins, in addition to providing insight on the biological pathways in which they function. The bulk of past work has been focused on protein subcellular localizations. Furthermore, no specific tool has been dedicated to prediction at the subnuclear level, despite its high importance. In order to design a suitable predictive system, the extraction of subtle sequence signals that can discriminate among proteins with different subnuclear localizations is the key. RESULTS: New kernel functions used in a support vector machine (SVM) learning model are introduced for the measurement of sequence similarity. The k-peptide vectors are first mapped by a matrix of high-scored pairs of k-peptides which are measured by BLOSUM62 scores. The kernels, measuring the similarity for sequences, are then defined on the mapped vectors. By combining these new encoding methods, a multi-class classification system for the prediction of protein subnuclear localizations is established for the first time. The performance of the system is evaluated with a set of proteins collected in the Nuclear Protein Database (NPD). The overall accuracy of prediction for 6 localizations is about 50% (vs. random prediction 16.7%) for single localization proteins in the leave-one-out cross-validation; and 65% for an independent set of multi-localization proteins. This integrated system can be accessed at http://array.bioengr.uic.edu/subnuclear.htm. CONCLUSION: The integrated system benefits from the combination of predictions from several SVMs based on selected encoding methods. Finally, the predictive power of the system is expected to improve as more proteins with known subnuclear localizations become available.

Algorithms↗
PubMed1992

How much physical activity is good for health?

Research studies over the past several decades confirm the health benefits of regular physical activity, a concept with foundations in antiquity. The effects of activity on certain individual health conditions, the precise dose of activity that is required for specific benefits, the role (if any) of intensity of effort, and the elucidation of biological pathways whereby activity contributes to health are topics for further research. Although details remain to be clarified, it is now clear that regular physical activity reduces the risk of morbidity and mortality from several chronic diseases and increases physical fitness, which leads to improved function. Table 3 outlines the relationship of activity to several diseases, a judgment on the strength of the evidence, and a rough determination of the amount of research extant. Results from clinical exercise studies and epidemiological investigations can be integrated into a consistent and coherent theory of healthful physical activity. However, some differences between these two research streams need to be reconciled. Exercise physiologists have generally recommended relatively intensive activity and a formal approach to exercise prescription. The epidemiological studies suggest a linear dose-response relationship, at least up to a point, between physical activity and health and functional effects. These data support public health recommendations directed toward the most sedentary and unfit stratum of the population and emphasize doing at least moderate physical activity. If this group of adults would accumulate 30 minutes of walking per day (or the equivalent energy expenditure in other activities), they would receive clinically significant health benefits. An important point is that it does not matter what type of physical activity is performed: Sports, planned exercise, household or yard work, or occupational tasks are all beneficial. The key factor is total energy expenditure; if that is constant, improvements in fitness and health will be comparable. There are probably 40 million adults in the US whose sedentary habits place them at considerably increased risk of morbidity and mortality from several diseases. These same individuals also are more likely to have functional limitations, especially as they move into the later years of life. The sizable independent relative risk for impaired health in sedentary persons, and the large number at risk, leads to a substantial public health burden. This problem deserves continued and increased attention by physicians and other health professionals, scientists, and the public health establishment.

Biological Evolution↗
PubMed2003

Depression and pain comorbidity: a literature review.

Because depression and painful symptoms commonly occur together, we conducted a literature review to determine the prevalence of both conditions and the effects of comorbidity on diagnosis, clinical outcomes, and treatment. The prevalences of pain in depressed cohorts and depression in pain cohorts are higher than when these conditions are individually examined. The presence of pain negatively affects the recognition and treatment of depression. When pain is moderate to severe, impairs function, and/or is refractory to treatment, it is associated with more depressive symptoms and worse depression outcomes (eg, lower quality of life, decreased work function, and increased health care utilization). Similarly, depression in patients with pain is associated with more pain complaints and greater impairment. Depression and pain share biological pathways and neurotransmitters, which has implications for the treatment of both concurrently. A model that incorporates assessment and treatment of depression and pain simultaneously is necessary for improved outcomes.

Antidepressive Agents↗
PubMed2000

Evaluating patients with arthritis of recent onset: studies in pathogenesis and prognosis.

Inflammatory synovitis of recent onset poses a diagnostic and prognostic challenge to primary care physicians and rheumatologists. A lack of understanding of the underlying etiologic and pathogenic processes limits the ability to distinguish forms of arthritis that follow a benign, self-limiting course from forms that proceed to an aggressive, erosive disease requiring intensive immunosuppressive therapy. It is estimated that between 30% and 40% of patients presenting with early synovitis have disease that remains unclassified. Using data from a cohort of patients with early synovitis and reviewing current literature, we discuss investigational approaches toward a new classification of patients with early synovitis. Although a lack of understanding of this heterogeneous clinical syndrome has led clinicians to take a largely empirical approach to treatment thus far, the evolving awareness of disease predisposition at a genetic level and the expanding ability to specifically manipulate biological pathways may ultimately change the approach to this clinical problem. JAMA. 2000;284:2368-2373.

Adult↗
PubMed1998

Possible mechanisms mediating an association between physical activity and breast cancer.

The epidemiologic, methodologic, and biologic evidence that physical activity may be related inversely to breast cancer risk was the focus of a recent workshop. This article presents the workshop summary on biologic mechanisms that may mediate this association between physical activity and breast cancer. There is some evidence that physical activity may reduce breast cancer risk, although the exact biologic pathways have not been determined. Among the potential mechanisms discussed at the workshop were reductions in endogenous steroid exposure, alterations in menstrual cycle patterns, delay of age at menarche, increased energy expenditure and reduction in body weight, changes in insulin-like and other growth factors, and enhancement of natural immune mechanisms. Although physical activity may prove to be a modifiable risk factor for breast cancer, further mechanistically oriented research is necessary to both verify whether this is the case and to clarify the details of this association so that public health recommendations can be developed.

Breast Neoplasms↗