tbuckley/cabot-search huggingface dataset:
Molecular Basis for Hematopoietic/Mesenchymal Interaction during Initiation of Peyer's Patch Organogenesis
Authors: Kenya Honda, Hiroyasu Nakano, Hisahiro Yoshida, Satomi Nishikawa, Paul Rennert, Koichi Ikuta, Masakatsu Tamechika, Kazuhito Yamaguchi, Tetsuo Fukumoto, Tsutomu Chiba, Shin-Ichi Nishikawa
Journal: The Journal of Experimental Medicine (2001)

Mice deficient in lymphotoxin β receptor (LTβR) or interleukin 7 receptor α (IL-7Rα) lack Peyer's patches (PPs). Deficiency in CXC chemokine receptor 5 (CXCR5) also severely affects the development of PPs. A molecular network involving these three signaling pathways has been implicated in PP organogenesis, but it remains unclear how they are connected during this process. We have shown that PP organogenesis is initiated at sites containing IL-7Rα+ lymphoid cells and vascular cell adhesion molecule (VCAM)-1/intercellular adhesion molecule (ICAM)-1 expressing nonlymphoid elements. Here we characterize these lymphoid and nonlymphoid components in terms of chemokine signals. The lymphoid population expresses CXCR5 and has a strong chemotactic response to B lymphocyte chemoattractant (BLC). Importantly, chemokines produced by VCAM-1+ICAM-1+ nonlymphoid cells mediate the recruitment of lymphoid cells. Furthermore, we show that these VCAM-1+ICAM-1+ cells are mesenchymal cells that are activated by lymphoid cells through the LTβR to express adhesion molecules and chemokines. Thus, promotion of PP development relies on mutual interaction between mesenchymal and lymphoid cells.
Increased serum C reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee
Authors: M Sharif
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> Raised serum C reactive protein (CRP) and hyaluronate (HA) concentrations predict the progression of knee osteoarthritis (OA) in the long term but the consistency of these relations with time is unknown. The purpose of this work was therefore to determine if raised CRP and HA at entry and three years before entry (−3 years) predict radiological progression of knee OA in a group of patients between entry and five years. <h3>METHODS</h3> Knee radiographs from 90 patients with knee OA at entry and five years follow up were assessed for progression of disease over five years. The concentrations of serum CRP and HA were measured at entry (n=90) and also in 40 serum samples available from −3 years. Odds ratios (OR) for predicting progression were calculated by logistic regression. <h3>RESULTS</h3> Serum CRP at entry was not predictive of progression between entry and five years (OR 1.12, 95% CI 0.81, 1.55) but serum CRP at −3 years was predictive of progression (OR 1.90, 95% CI 1.01, 3.28). Serum HA concentration at entry predicted progression between entry and five years (OR 2.32, 95% CI 1.16, 4.66). <h3>CONCLUSION</h3> These results are consistent with previous reports relating to HA, and suggest that raised serum CRP reflects events that precede a period of later radiographic progression in knee OA. However, because of the large overlap between groups, the serum CRP or HA concentration are not good predictors of individual patient progression and have a poor sensitivity and specificity.
Data Resources in the Department of Veterans Affairs
Authors: Charles Maynard, Michael K. Chapko
Journal: Diabetes Care (2004)

To provide an overview of databases that are maintained by the Department of Veterans Affairs (VA) and are of relevance to investigators involved in epidemiologic, clinical, and health services research.We reviewed both national and local VA databases and identified their strengths and limitations. We also referenced specific studies that have assessed the validity and reliability of VA databases.There are numerous national databases housed at the Austin Automation Center in Austin, Texas. These include the Patient Treatment File (hospital abstracts), the Outpatient Care File, the Beneficiary Identification Record Locator System death file for assessing vital status, and the Decision Support System, which provides integrated clinical and financial information for managerial decision making. The major limitation of these databases is that clinical detail below the level of ICD-9-CM diagnosis and procedure codes is not uniformly available nationally. These databases offer an excellent opportunity to monitor the health of veterans over time because they track all inpatient and outpatient utilization in the VA. However, at the local or medical center level, the Veterans Health Information and Systems and Technology Architecture contains extensive clinical information, but has fewer patients, varies in format across medical centers, and poses difficulties with data extraction for statistical analysis.Both local and national VA databases are valuable resources for investigators who have interests in a wide array of research topics, including diabetes. The potential for investigating important scientific questions with VA databases becomes greater as communications and database management technologies improve.
Effect of a Second-Generation Venous Catheter Impregnated with Chlorhexidine and Silver Sulfadiazine on Central Catheter–Related Infections
Authors: Mark E. Rupp
Journal: Annals of Internal Medicine (2005)

Background: Central venous catheter–related infections are a significant medical problem. Improved preventive measures are needed. Objective: To ascertain 1) effectiveness of a second-generation antiseptic-coated catheter in the prevention of microbial colonization and infection; 2) safety and tolerability of this device; 3) microbiology of infected catheters; and 4) propensity for the development of antiseptic resistance. Design: Multicenter, randomized, double-blind, controlled trial. Setting: 9 university-affiliated medical centers. Patients: 780 patients in intensive care units who required central venous catheterization. Intervention: Patients received either a standard catheter or a catheter coated with chlorhexidine and silver sulfadiazine. Measurements: The authors assessed catheter colonization and catheter-related infection, characterized microbes by molecular typing, and determined their susceptibility to antiseptics. Patient tolerance of the catheter was monitored. Results: Patients with the 2 types of catheters had similar demographic features, clinical interventions, laboratory values, and risk factors for infection. Antiseptic catheters were less likely to be colonized at the time of removal compared with control catheters (13.3 vs. 24.1 colonized catheters per 1000 catheter-days; P < 0.01). The center-stratified Cox regression hazard ratio for colonization controlling for sampling design and potentially confounding variables was 0.45 (95% CI, 0.25 to 0.78). The rate of definitive catheter-related bloodstream infection was 1.24 per 1000 catheter-days (CI, 0.26 to 3.62 per 1000 catheter-days) for the control group versus 0.42 per 1000 catheter-days (CI, 0.01 to 2.34 per 1000 catheter-days) for the antiseptic catheter group (P = 0.6). Coagulase-negative staphylococci and other gram-positive organisms were the most frequent microbes to colonize catheters. Noninfectious adverse events were similar in both groups. Antiseptic susceptibility was similar for microbes recovered from either group. Limitations: The antiseptic catheter was not compared with an antibiotic-coated catheter, and no conclusion can be made regarding its effect on bloodstream infection. Conclusions: The second-generation chlorhexidine–silver sulfadiazine catheter is well tolerated. Antiseptic coating appears to reduce microbial colonization of the catheter compared with an uncoated catheter.
Hyaluronan Enhances Contraction of Collagen by Smooth Muscle Cells and Adventitial Fibroblasts
Authors: Jeffrey A. Travis, Michael G. Hughes, James M. Wong, William D. Wagner, Randolph L. Geary
Journal: Circulation Research (2001)

Abstract —Remodeling contributes to restenosis when cells shrink the artery wall at sites of injury. This may be analogous to wound healing, where tissue remodeling achieves wound contraction. Hyaluronan (HA) is prominent in wound matrix and inhibits fetal scarring. HA is also produced in the artery wall after angioplasty, where it may inhibit constrictive remodeling. This hypothesis was tested in vitro using a model of matrix contraction. Primate aortic smooth muscle cells and adventitial fibroblasts were seeded into collagen I gels containing increasing amounts of HA (0% to 50%, wt/wt). Both cell types reduced the diameter of collagen alone ≈65% at 18 hours. HA significantly increased gel contraction (diameter in mm: 0% HA, 7.7±0.9; 2%, 7.1±0.7; 10%, 6.7±0.5; 50%, 5.6±0.9; P &lt;0.05 for ≥10%), cell spreading and telopodia, and pericellular accumulation of collagen fibrils. These effects were mediated in part by cellular HA binding, because an antibody against CD44 receptors blocked pericellular collagen accumulation and enhanced gel contraction without altering cell shape. The role of CD44 was specific, because inhibiting receptor for hyaluronic acid–mediated motility (RHAMM) had no effect. Blocking β 1 -integrins completely inhibited contraction of collagen, but gels containing HA required CD44 and β 1 -integrin blockade for complete inhibition. Enhanced collagen reorganization and contraction were not attributable to increased collagenase activity, because the metalloproteinase inhibitor batimastat had no effect. In summary, HA enhanced collagen reorganization by the cell types most likely to mediate constrictive remodeling after angioplasty. These effects were CD44-dependent, thus providing a potential target for therapies to prevent constrictive remodeling and restenosis.
Presence of Activated Mobile Fibroblasts in Bronchoalveolar Lavage from Patients with Mild Asthma
Authors: Kristoffer Larsen, Ellen Tufvesson, Johan Malmström, Matthias Mörgelin, Marie Wildt, Annika Andersson, Anna Lindström, Anders Malmström, Claes-Göran Löfdahl, György Marko-Varga, Leif Bjermer, Gunilla Westergren-Thorsson
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Activated fibroblasts are suggested to be involved in the deposition of extracellular matrix in the formation of peribronchial fibrosis in asthma. We report the novel finding of activated elongated fibroblasts accompanied by elevated numbers of eosinophils in bronchoalveolar lavage fluid from 5 out of 12 patients with mild asthma (= 42%), whereas no fibroblasts were observed in the control subjects without asthma (n = 17). The elongated fibroblasts migrated twice as far when compared with fibroblasts from corresponding bronchial biopsies from the same patients, accompanied by an induced expression of RhoA and Rac1, indicating that the increased expression of these proteins are linked to increased migratory capabilities. Moreover, the elongated fibroblasts had an elevated production of the proteoglycans biglycan, versican, perlecan, and decorin, which correlated to an active cytoplasm in these cells. Differential expression patterns between the two fibroblast groups in motility-regulating proteins, such as cofilin, nuclear chloride ion channel protein, and heat-shock protein 20, were identified by two-dimensional electrophoresis and mass spectrometry. These findings indicate the presence of activated and mobile fibroblasts accompanied by an induced inflammatory response outside the airway epithelium in patients with mild asthma, results that may play a role in formation of airway fibrosis.
Detecting Patches of Protein Sites of Influenza A Viruses under Positive Selection
Authors: C. Tusche, L. Steinbruck, A. C. McHardy
Journal: Molecular Biology and Evolution (2012)

Influenza A viruses are single-stranded RNA viruses capable of evolving rapidly to adapt to environmental conditions. Examples include the establishment of a virus in a novel host or an adaptation to increasing immunity within the host population due to prior infection or vaccination against a circulating strain. Knowledge of the viral protein regions under positive selection is therefore crucial for surveillance. We have developed a method for detecting positively selected patches of sites on the surface of viral proteins, which we assume to be relevant for adaptive evolution. We measure positive selection based on dN/dS ratios of genetic changes inferred by considering the phylogenetic structure of the data and suggest a graph-cut algorithm to identify such regions. Our algorithm searches for dense and spatially distinct clusters of sites under positive selection on the protein surface. For the hemagglutinin protein of human influenza A viruses of the subtypes H3N2 and H1N1, our predicted sites significantly overlap with known antigenic and receptor-binding sites. From the structure and sequence data of the 2009 swine-origin influenza A/H1N1 hemagglutinin and PB2 protein, we identified regions that provide evidence of evolution under positive selection since introduction of the virus into the human population. The changes in PB2 overlap with sites reported to be associated with mammalian adaptation of the influenza A virus. Application of our technique to the protein structures of viruses of yet unknown adaptive behavior could identify further candidate regions that are important for host-virus interaction.
Preclinical assessment of CNS drug action using eye movements in mice
Authors: Hugh Cahill, Amir Rattner, Jeremy Nathans
Journal: Journal of Clinical Investigation (2011)

The drug development process for CNS indications is hampered by a paucity of preclinical tests that accurately predict drug efficacy in humans. Here, we show that a wide variety of CNS-active drugs induce characteristic alterations in visual stimulus-induced and/or spontaneous eye movements in mice. Active compounds included sedatives and antipsychotic, antidepressant, and antiseizure drugs as well as drugs of abuse, such as cocaine, morphine, and phencyclidine. The use of quantitative eye-movement analysis was demonstrated by comparing it with the commonly used rotarod test of motor coordination and by using eye movements to monitor pharmacokinetics, blood-brain barrier penetration, drug-receptor interactions, heavy metal toxicity, pharmacologic treatment in a model of schizophrenia, and degenerative CNS disease. We conclude that eye-movement analysis could complement existing animal tests to improve preclinical drug development.
Gianotti Disease in a Child and Acute Hepatitis B in Mother
Authors: Venusto H. San Joaquin
Journal: JAMA (1981)

GIANOTTI disease (GD) is considered a clinical expression of hepatitis B virus (HBV) infection in infants and children.<sup>1</sup>The principal features of the disease include an erythematous papular exanthem distributed mainly on the face and extremities, an anicteric hepatitis, and HBV surface antigenemia.<sup>2,3</sup>The pathogenesis of these distinctive clinical manifestations is unclear but appears to be an age-dependent response to HBV infection. During an epidemic in Matsuyama, Japan, parents who contracted HBV infection from children with GD had development of acute hepatitis with jaundice; most did not have the characteristic rash present in the index patients.<sup>1</sup> In spite of the worldwide distribution of GD,<sup>4</sup>we are aware of only four reported cases among children in the United States.<sup>5-7</sup>Furthermore, two of these cases had negative test results for hepatitis B surface antigen (HBsAg)<sup>6</sup>; one other patient was not tested for it.<sup>7</sup>We describe
Rheumatoid and other diseases of the cervical interspinous bursae, and changes in the spinous processes.
Authors: E G Bywaters
Journal: Annals of the Rheumatic Diseases (1982)

Bursal spaces between the cervical interspinous processes were found at necropsy in 14 out of 27 "normal9 adult necks, especially when the spines were close together. In this random series they were the seat of crystallopathic disease in 2 instances out of 14 cases. In spines from 9 cases of adult-onset rheumatoid arthritis, rheumatoid bursitis was seen in 2 and banal bursitis in 2. In juvenile-onset chronic arthritis inflammatory bursal changes of rheumatoid nature were found in 2 out of 5 cases, and are compared with the "normal9. A third case showed crystallopathic destruction. In one instance of adult RA very severe changes were seen, with destruction of the spinous processes, and this was associated with hypermobile segments dependent on discal destruction starting in the oncovertebral joints. An association is described between discal lesions, spinous erosion, enthesopathy, and interspinous bursitis.
Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma?
Authors: R. Sabatier, J.C. Eymard, J. Walz, J.L. Deville, H. Narbonne, J.M. Boher, N. Salem, M. Marcy, S. Brunelle, P. Viens, F. Bladou, G. Gravis
Journal: Annals of Oncology (2011)
Intramedullary Extension Of Osteogenic Sarcoma
Authors: H. Gunter Seydel
Journal: JAMA (1973)

To the Editor.—  Intramedullary extension of osteogenic sarcoma has been described.1-4Only the last paper contains incidence data, indicating that in the Mayo Clinic at the time of analysis, 20 of 50 patients showed extension of osteogenic sarcoma along the medullary cavity at time of amputation. In 13 of 42 patients with optimal preoperative roentgenograms, there were no radiographic changes that might have made the surgeon suspect such finding prior to surgery. As our search of the literature did not reveal additional detailed data regarding this finding, the following case report appears of interest.  Report of a Case.—  In a 20-year-old white woman with pain and swelling in the lower part of the left femur of approximately two months' duration, radiography revealed a 4.8 × 2.7 cm lesion in the posterolateral aspect of the left femur immediately above the epiphyseal line (Fig 1). A soft tissue mass was palpable
Lung Function Decline, Chronic Bronchitis, and Occupational Exposures in Young Adults
Authors: Jordi Sunyer, Jan Paul Zock, Hans Kromhout, Raquel Garcia-Esteban, Katja Radon, Deborah Jarvis, Kjell Toren, Nino Künzli, Dan Norbäck, Angelo d'Errico, Isabel Urrutia, Félix Payo, Mario Olivieri, Simona Villani, Marc Van Sprundel, Josep M. Antó, Manolis Kogevinas
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Occupational exposures to vapors, gas, dust, or fumes have been shown to be a risk factor of airway obstruction in cross-sectional studies in the general population.Our aim was to study the relationships between specific occupations and occupational exposures during a 9-yr follow-up period and changes in lung function and symptoms of chronic bronchitis.Subjects from the general population aged 20 to 45 yr were randomly selected in 1991-1993 within the European Community Respiratory Health Survey. Follow-up took place from 1998 to 2002 among 4,079 males and 4,461 females in 27 study centers. A total of 3,202 men and 3,279 women twice completed lung function measurements. Job history during follow-up was linked to a job exposure matrix and consequently translated into cumulative exposure estimates.Individuals exposed to dusts, gases, and fumes during the period of follow-up did not have a steeper decline of FEV1 than did individuals with consistently white-collar occupations without occupational exposures (relative change among men and women, + 1.4 and -3.1 ml/yr, respectively; p > 0.2), nor an increase of prevalence or incidence of airway obstruction defined as an FEV1/FVC ratio of less than 0.7. The incidence of chronic phlegm increased in men exposed to mineral dust (relative risk, 1.94 [1.29-2.91]) and gases and fumes (relative risk, 1.53 [0.99-2.36]), which was not modified by smoking.Occupational exposures to dusts, gases, and fumes occurring during the 1990s are associated with incidence of chronic bronchitis, although these did not impair lung function in a population of relatively young age.
Corin Variant Associated With Hypertension and Cardiac Hypertrophy Exhibits Impaired Zymogen Activation and Natriuretic Peptide Processing Activity
Authors: Wei Wang, Xudong Liao, Koichi Fukuda, Sabine Knappe, Faye Wu, Daniel L. Dries, Jun Qin, Qingyu Wu
Journal: Circulation Research (2008)

Corin is a cardiac serine protease that acts as the pro–atrial natriuretic peptide (ANP) convertase. Recently, 2 single-nucleotide polymorphisms (SNPs) (T555I and Q568P) in the human corin gene have been identified in genetic epidemiological studies. The minor I555/P568 allele, which is more common in African Americans, is associated with hypertension and cardiac hypertrophy. In this study, we examined the effect of T555I and Q568P amino acid substitutions on corin function. We found that corin frizzled-like domain 2, where T555I/Q568P substitutions occur, was required for efficient pro-ANP processing in functional assays. Mutant corin lacking this domain had 30±5% ( P &lt;0.01) activity compared to that of wild type. Similarly, corin variant T555I/Q568P had a reduced (38±7%, P &lt;0.01) pro-ANP processing activity compared to that of wild type. The variant also exhibited a low activity (44±15%, P &lt;0.05) in processing pro–brain natriuretic peptide (BNP). We next examined the biochemical basis for the loss of activity in T555I/Q568P variant and found that the zymogen activation of the corin variant was impaired significantly, as indicated by the absence of the activated protease domain fragment. This finding was confirmed in human embryonic kidney (HEK)293 cells and murine HL-1 cardiomyocytes. Thus, our results show that the corin gene SNPs associated with hypertension and cardiac hypertrophy impair corin zymogen activation and natriuretic peptide processing activity. Our data suggest that corin deficiency may be an important mechanism in hypertensive and heart diseases.
Use of monoclonal antibodies to detect disease associated HLA-DRB1 alleles and the shared epitope in rheumatoid arthritis
Authors: I. Wicks, G. McColl, A. D'Amico, L. Dougherty, B. Tait
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To use a panel of monoclonal antibodies (Mab) which recognise HLA class II alleles associated with rheumatoid arthritis for fluorescence activated cell sorter (FACS) analysis of peripheral blood mononuclear cells (PBMNC) from patients with early and established rheumatoid arthritis and to compare these results against DNA oligotyping of HLA class II molecules in the same patients. <h3>METHODS</h3> 27 patients (18 from an early arthritis clinic, nine with established rheumatoid arthritis) were studied using both techniques. PBMNC were stained with Mab which recognise the shared epitope, the HLA-DRB1*04 molecule and its *0401, *0404 subtypes in the presence of bound peptide. Mab stained cells were analysed by FACS. Genomic DNA was prepared from PBMNC and used for DNA oligotyping and sequencing by standard methods. <h3>RESULTS</h3> FACS analysis of Mab stained PBMNC gave identical results to those obtained by DNA oligotyping in 26/27 patients. The antibodies identified the shared epitope in 14/14 cases and the presence of an HLA-DRB1*04 molecule in 12/12 cases. HLA-DRB1*0404 was identified in 4/4 cases. HLA-DRB1*0401 was identified in 5/6 cases. One patient oligotyped as HLA-DRB1*0401, but consistently failed to react with the *0401 Mab. DNA sequencing of the second exon of the HLA-DRB1*0401 allele in this patient confirmed a normal HLA-DRB1*0401 genotype. <h3>CONCLUSIONS</h3> FACS analysis of PBMNC stained with Mab recognising the shared epitope and rheumatoid arthritis associated HLA susceptibility molecules provides a rapid, reliable, and more accessible alternative to DNA oligotyping. The apparent discordance between phenotypic and genetic analysis of HLA-DRB1*0401 in one patient, may reflect variability in HLA-DRB1*0401 gene expression or in class II peptide presentation.