tbuckley/cabot-search huggingface dataset:
Global Analysis Reveals the Complexity of the Human Glomerular Extracellular Matrix
Authors: Rachel Lennon, Adam Byron, Jonathan D. Humphries, Michael J. Randles, Alex Carisey, Stephanie Murphy, David Knight, Paul E. Brenchley, Roy Zent, Martin J. Humphries
Journal: Journal of the American Society of Nephrology (2014)

The glomerulus contains unique cellular and extracellular matrix (ECM) components, which are required for intact barrier function. Studies of the cellular components have helped to build understanding of glomerular disease; however, the full composition and regulation of glomerular ECM remains poorly understood. We used mass spectrometry-based proteomics of enriched ECM extracts for a global analysis of human glomerular ECM in vivo and identified a tissue-specific proteome of 144 structural and regulatory ECM proteins. This catalog includes all previously identified glomerular components plus many new and abundant components. Relative protein quantification showed a dominance of collagen IV, collagen I, and laminin isoforms in the glomerular ECM together with abundant collagen VI and TINAGL1. Protein network analysis enabled the creation of a glomerular ECM interactome, which revealed a core of highly connected structural components. More than one half of the glomerular ECM proteome was validated using colocalization studies and data from the Human Protein Atlas. This study yields the greatest number of ECM proteins relative to previous investigations of whole glomerular extracts, highlighting the importance of sample enrichment. It also shows that the composition of glomerular ECM is far more complex than previously appreciated and suggests that many more ECM components may contribute to glomerular development and disease processes. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000456.
The Complete Mitochondrial Genome Sequence of the Spider Habronattus oregonensis Reveals Rearranged and Extremely Truncated tRNAs
Journal: Molecular Biology and Evolution (2004)

We sequenced the entire mitochondrial genome of the jumping spider Habronattus oregonensis of the arachnid order Araneae (Arthropoda: Chelicerata). A number of unusual features distinguish this genome from other chelicerate and arthropod mitochondrial genomes. Most of the transfer RNA gene sequences are greatly reduced in size and cannot be folded into typical cloverleaf-shaped secondary structures. At least nine of the tRNA sequences lack the potential to form TYC arm stem pairings, and instead are inferred to have TV-replacement loops. Furthermore, sequences that could encode the 3' aminoacyl acceptor stems in at least 10 tRNAs appear to be lacking, because fully paired acceptor stems are not possible and because the downstream sequences instead encode adjacent genes. Hence, these appear to be among the smallest known tRNA genes. We postulate that an RNA editing mechanism must exist to restore the 3' aminoacyl acceptor stems in order to allow the tRNAs to function. At least seven tRNAs are rearranged with respect to the chelicerate Limulus polyphemus, although the arrangement of the protein-coding genes is identical. Most mitochondrial protein-coding genes of H. oregonensis have ATN as initiation codons, as commonly found in arthropod mtDNAs, but cytochrome oxidase subunit 2 and 3 genes apparently use UUG as an initiation codon. Finally, many of the gene sequences overlap one another and are truncated. This 14,381 bp genome, the first mitochondrial genome of a spider yet sequenced, is one of the smallest arthropod mitochondrial genomes known. We suggest that posttranscriptional RNA editing can likely maintain function of the tRNAs while permitting the accumulation of mutations that would otherwise be deleterious. Such mechanisms may have allowed for the minimization of the spider mitochondrial genome.
Disseminated intravascular coagulation in catastrophic antiphospholipid syndrome: clinical and haematological characteristics of 23 patients
Authors: R A Asherson
Journal: Annals of the Rheumatic Diseases (2005)

Disseminated intravascular coagulation (DIC) is an acquired syndrome characterised by formation of microthrombi and fibrin deposition in the microvasculature. The catastrophic antiphospholipid syndrome (APS) is characterised by multiorgan thrombosis, mainly involving small vessels. A broad spectrum of disorders may develop DIC features; however, the catastrophic APS has not previously been recognised as a cause of DIC.To analyse the clinical and laboratory characteristics of catastrophic APS patients with DIC features.The web site based international registry of patients with catastrophic APS (CAPS registry) (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM) was analysed and the cases with DIC features selected.In 173 patients with catastrophic APS, 23 (13%) were found with DIC features. The clinical and immunological characteristics were similar in catastrophic APS patients with and without DIC features; a significant difference was found only in the prevalence of thrombocytopenia (100% in patients with DIC features v 59% in those without DIC features).DIC features are not rare in catastrophic APS, supporting the need for systematic screening of antiphospholipid antibodies in all patients with DIC features without precipitating factors. The presence of DIC features in the context of an APS makes it imperative to rule out the catastrophic variant of this syndrome.
DURATION OF DUAL ANTIPLATELET THERAPY AFTER DRUG-ELUTING STENT TREATMENT BY GEOGRAPHIC REGION
Authors: Laura Mauri, Jorge Belardi, Sigmund Silber, Petr Widimsky, Martin Leon, Patrick Serruys, Stephan Windecker, Ian Meredith, Franz-Joseph Neumann, Alan Yeung, Shigeru Saito
Journal: Journal of the American College of Cardiology (2012)
Studies on Bacterial Hypersensitivity in Man
Authors: J. v. Mayenburg, B. Heymer, H. Düngemann, K. H. Schleifer, P. H. Seidl, A. Neibz, S. Borelli
Journal: Allergy (1982)

The nature and extent of bacterially induced allergies are difficult to define. Since peptidoglycan, the main component of the cell wall of almost all bacteria, has been available in a highly purified, chemically and immunologically well-defined form, investigation of the allergological significance of this cell component is feasible. Intracutaneous tests were carried out on 181 test subjects with five different peptidoglycan (PG) preparations from Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus Pyogenes. The results of the investigation were compared with the result of determination of serum PG antibodies and serum IgE concentrations. It was shown that test subjects with dual and later reactions to three different staphylococcal PGs displayed significantly higher PG antibody titers than test subjects with negative reactions. Such a relationship could not be found with the cutaneous reactions to streptococcal PG. The total serum IgE values were very much higher in test subjects with immediate reactions to staphylococcal PG than in test subjects with a negative reaction. Typical Arthus reaction or late granulomatous reactions were not observed. Humoral antibodies are involved at least in part in the elicitation of dual and late reactions. Thus, there are interesting parallels to allergy to fungal spores and organic dusts.
Optical Methods for Monitoring Neuron Activity
Authors: L. B. Cohen, B. M. Salzberg, A. Grinvald
Journal: Annual Review of Neuroscience (1978)

A method for monitoring neuron activity that does not require electrodes might be useful in situations where the use of electrodes is difficult because of neuron size, geometry, or number. A neuron will interact with electromagnetic or ultrasonic radiation in many different ways. If any one of these interactions changes during neuron activity, then its measurement could be used as a noninvasive method for monitoring that activity. The use of an optical method was suggested by the discovery of changes in light scattering, birefringence, and fluorescence that accompany the action potential (Co­ hen, Keynes & Hille 1968, Tasaki et al 1968). However, because the signal-to-noise ratios of these signals were too small to be used to monitor activity in individual neurons, a search for larger signals was initiated (Davila, Cohen & Waggoner 1 972, Cohen, 1973). At present, the largest signals are changes in absorption of light by axons stained with the merocyanine dyes (Ross et al 1977, Salzberg et al 1977), whose structures are shown in Figure 1. These absorption signals are about 100 times larger than the largest signal available in 1 971. The first part of this article presents evidence that the absorption changes of these dyes somehow result from the changes in membrane potential rather than from the ionic currents or the increases in membrane permeability that occur during an action potential. This is followed by a review of our efforts to find larger signals. The use of a dye may lead to pharmacologic effects or to photodynamic damage, and both possible problems are discussed briefly. Because the light from many different parts of a preparation can be measured simultaneously, it should, in principle, be possible to monitor activity in many neurons at once. It is this application that has inspired our interest in optical
GENE EXPRESSION OF MATRIX-DEGRADING ENZYMES IN PATELLAR TENDINOPATHY
Authors: T Samiric, C J Handley, J Cook, J Parkinson
Journal: British Journal of Sports Medicine (2013)

Introduction A predominant feature of tendinopathy is a change in the appearance and organisation of the extracellular matrix including greater amounts of the large aggregating proteoglycans, aggrecan and versican. We have shown that in patellar tendinopathy these large proteoglycans are also rapidly degraded so that mainly fragments remain in the tissue.1 This catabolism of large proteoglycans is likely to be mediated by a number of matrix-degrading proteinases such as the matrix metalloproteinases (MMPs) and the aggrecanases (ADAMTSs). The aim of this work was to investigate whether in patellar tendinopathy there is a change in the gene expression of the matrix proteinases involved in proteoglycan catabolism including the MMPs and ADAMTSs, as well as their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs). Methods Total mRNA isolated from ∼100mg tissue samples of normal (n=9) and pathologic (n=12) tendon was assayed by relative quantitative RT-PCR for MMP (-1, -2, -3, -9, and -13), ADAMTS (-1, -4, -5), and TIMP (-1, -2, -3, and -4), and normalised to GAPDH. Results Expression of mRNA for MMP-9 and TIMP-1 was significantly up-regulated in pathologic tendons (p=0.019 and p=0.013, respectively). A trend toward a down-regulation of expression of MMP-3 was observed in pathologic tendons (p=0.06). There were no significant changes in ADAMTS-1, -4, or -5 gene expressions. Discussion These results suggest that the elevated expression of MMP-9 and TIMP-1 genes is likely to reflect the changes in collagen metabolism in pathologic tendons. However, these results also suggest that the proteolysis of proteoglycans in the pathologic tendons is not likely to be affected at the gene expression level of proteinases and their inhibitors. These observations are consistent with others, who showed no difference in the expression of ADAMTS-1, -4, and -5 genes between human Achilles tendons with chronic pain and normal tendons.2 3 Therefore, it is likely that proteoglycan catabolism is elevated by the activation of ADAMTSs and possibly MMPs and not by increased gene expression. This activation may be driven by growth factors and cytokines such as IL-1α, TGF-β and TNF-α, which are shown to be increased in overuse tendinopathy. However, the details of the mechanisms of these regulatory processes warrant further investigation.
Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias
Authors: M. Okamoto, T. Hoshino, Y. Kitasato, Y. Sakazaki, T. Kawayama, K. Fujimoto, K. Ohshima, H. Shiraishi, M. Uchida, J. Ono, S. Ohta, S. Kato, K. Izuhara, H. Aizawa
Journal: European Respiratory Journal (2010)

Idiopathic interstitial pneumonias (IIPs) are histopathologically classified into several types, including usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and cryptogenic organising pneumonia (COP). We investigated whether periostin, a matrix protein, could be used as a biomarker to assess histopathological types of IIPs. We performed immunohistochemical analyses in each histopathological type of IIP, examined serum levels of periostin in IIP patients and analysed the relationship between serum levels of periostin and the pulmonary functions in patients with idiopathic pulmonary fibrosis (IPF). Periostin was strongly expressed in lungs of UIP and fibrotic NSIP patients, whereas expression of periostin was weak in the lungs of cellular NSIP and COP patients, as well as in normal lungs. Serum levels of periostin in IPF were significantly higher than those of healthy subjects and COP patients. Furthermore, periostin levels in IPF patients were inversely correlated with their pulmonary functions. Thus, we have found that periostin is a novel component of fibrosis in IIP. Periostin may be a potential biomarker to distinguish IIP with fibrosis.
Initial Events in Establishing Vaginal Entry and Infection by Human Immunodeficiency Virus Type-1
Authors: Florian Hladik, Polachai Sakchalathorn, Lamar Ballweber, Gretchen Lentz, Michael Fialkow, David Eschenbach, M. Juliana McElrath
Journal: Immunity (2007)

Understanding the initial events in the establishment of vaginal human immunodeficiency virus type-1 (HIV-1) entry and infection has been hampered by the lack of appropriate experimental models. Here, we show in an ex vivo human organ culture system that upon contact in situ, HIV-1 rapidly penetrated both intraepithelial vaginal Langerhans and CD4(+) T cells. HIV-1 entered CD4(+) T cells almost exclusively by CD4 and CCR5 receptor-mediated direct fusion, without requiring passage from Langerhans cells, and overt productive infection ensued. By contrast, HIV-1 entered CD1a(+) Langerhans cells primarily by endocytosis, by means of multiple receptors, and virions persisted intact within the cytoplasm for several days. Our findings shed light on the very earliest steps of mucosal HIV infection in vivo and may guide the design of effective strategies to block local transmission and prevent HIV-1 spread.
The Effect of Endoscopic Therapy in Patients Receiving Omeprazole for Bleeding Ulcers with Nonbleeding Visible Vessels or Adherent Clots
Authors: Joseph J.Y. Sung, Francis K.L. Chan, James Y.W. Lau, Man-Yee Yung, Wai-Keung Leung, Justin C.Y. Wu, Enders K.W. Ng, S.C Sydney Chung
Journal: Annals of Internal Medicine (2003)

Background: The optimal treatment of ulcers with nonbleeding visible vessels and adherent clots is unclear. Objective: To compare intravenous omeprazole infusion plus endoscopic therapy with intravenous omeprazole infusion alone for prevention of recurrent bleeding from ulcers with nonbleeding visible vessels or adherent clots. Design: Single-blind randomized study with blinded evaluation of study end points. Setting: An endoscopy center in a university hospital in Hong Kong. Patients: 156 persons with upper gastrointestinal bleeding and ulcers showing nonbleeding visible vessels or adherent clots. Intervention: Combination of endoscopic therapy and omeprazole infusion versus sham endoscopic therapy and omeprazole infusion. Measurements: Recurrent ulcer bleeding before discharge and within 30 days. Results: 78 patients were recruited in each group. Ulcer bleeding recurred before discharge in seven patients who received intravenous omeprazole alone (9%) and no patients who received combined therapy (difference, 9 percentage points [95% CI, 1.7 to 17.6 percentage points]; P = 0.01). The probability of recurrent bleeding within 30 days was 11.6% (9 patients) in the omeprazole-alone group and 1.1% (1 patient) in the combined therapy group (difference, 10.5 percentage points [CI, 1.7 to 19.8 percentage points]; P = 0.009). Patients in the combined therapy group required less transfusion (difference in median units of blood transfused, 1 unit [CI, 0 to 2 units]; P = 0.02). One patient in the combined therapy group had surgery for ulcer perforation. Four patients receiving omeprazole alone (5.1%) and two patients receiving combined therapy (2.6%) died within 30 days. Conclusion: The combination of endoscopic therapy and omeprazole infusion is superior to omeprazole infusion alone for preventing recurrent bleeding from ulcers with nonbleeding visible vessels and adherent clots.
Receptor Tyrosine Kinase Axl Modulates the Osteogenic Differentiation of Pericytes
Authors: Georgina Collett, Alan Wood, M. Yvonne Alexander, Brian C. Varnum, Raymond P. Boot-Handford, Vasken Ohanian, Jacqueline Ohanian, Yih-Woei Fridell, Ann E. Canfield
Journal: Circulation Research (2003)

Vascular pericytes undergo osteogenic differentiation in vivo and in vitro and may, therefore, be involved in diseases involving ectopic calcification and osteogenesis. The purpose of this study was to identify factors that inhibit the entry of pericytes into this differentiation pathway. RNA was prepared from pericytes at confluence and after their osteogenic differentiation (mineralized nodules). Subtractive hybridization was conducted on polyA PCR-amplified RNA to isolate genes expressed by confluent pericytes that were downregulated in the mineralized nodules. The subtraction product was used to screen a pericyte cDNA library and one of the positive genes identified was Axl, the receptor tyrosine kinase. Northern and Western blotting confirmed that Axl was expressed by confluent cells and was downregulated in mineralized nodules. Western blot analysis demonstrated that confluent pericytes also secrete the Axl ligand, Gas6. Immunoprecipitation of confluent cell lysates with an anti-phosphotyrosine antibody followed by Western blotting using an anti-Axl antibody, demonstrated that Axl was active in confluent pericytes and that its activity could not be further enhanced by incubating the cells with recombinant Gas6. The addition of recombinant Axl-extracellular domain (ECD) to pericyte cultures inhibited the phosphorylation of Axl by endogenous Gas6 and enhanced the rate of nodule mineralization. These effects were inhibited by coincubation of pericytes with Axl-ECD and recombinant Gas6. Together these results demonstrate that activation of Axl inhibits the osteogenic differentiation of vascular pericytes.
Spiral computed tomography and operative staging of gastric carcinoma: a comparison with histopathological staging
Authors: J Davies, A G Chalmers, H M Sue-Ling, J May, G V Miller, I G Martin, D Johnston
Journal: Gut (1997)

Background —Much controversy exists as to the value of computed tomography (CT) in the preoperative staging of gastric cancer, because of its limited ability to identify correctly lymph node (LN) metastases, invasion of adjacent organs, or hepatic and peritoneal metastases. Spiral CT scanners have a number of potential advantages over conventional scanners, including the absence of respiratory misregistration, image reconstruction smaller than scan collimation permitting overlapping slices and optimisation of intravenous contrast enhancement. Aim —To compare the performance of spiral CT and operative assessment against formal (TNM) pathological staging. Patients and methods —A study of 105 consecutive patients who underwent both spiral CT and operative staging was performed. All CT scans were reviewed by a radiologist who commented on tumour location and size, evidence of adjacent organ invasion, lymph node metastases to both N1 and N2 nodes, and evidence of hepatic and peritoneal metastases. All patients underwent careful operative assessment at the time of surgery, along the lines suggested by Rohde and colleagues. Results —Spiral CT remained poor at identifying LN metastases to both N1 and N2 lymph nodes, with sensitivity ranging from 24 to 43%; specificity, however, was 100%. Operative staging was superior, with sensitivities between 84 and 94%, but specificity was much lower (63–74%). Spiral CT correctly detected 13 of 17 cases of invasion of either the colon or the mesocolon (sensitivity 76%) compared with 16 of 17 cases at operative staging (sensitivity 94%). Spiral CT correctly identified three of six cases with invasion of the pancreas (sensitivity 50%) compared with six of six cases on operative staging (sensitivity 100%). Spiral CT correctly identified 12 of 17 cases of peritoneal metastases (sensitivity 71%) and four of seven cases of hepatic metastases (sensitivity 57%). Conclusion —Whilst spiral CT remains poor at identifying lymph node metastases, it correctly identified most cases with invasion of either the colon or the mesocolon and half the cases of pancreatic invasion. It was of value in detecting peritoneal metastases and some cases with hepatic metastases. At present, at Leeds General Infirmary spiral CT is performed routinely on all patients with gastric cancer and a selective staging laparoscopy policy is adopted in those patients in whom the status of the peritoneal cavity and liver is in doubt.
Cardiorespiratory Fitness in Young Adulthood and the Development of Cardiovascular Disease Risk Factors
Authors: Mercedes R Carnethon, Samuel S Gidding, Rodrigo Nehgme, Stephen Sidney, David R Jacobs, Kiang Liu
Journal: JAMA (2003)

Low cardiorespiratory fitness is an established risk factor for cardiovascular and total mortality; however, mechanisms responsible for these associations are uncertain.To test whether low fitness, estimated by short duration on a maximal treadmill test, predicted the development of cardiovascular disease risk factors and whether improving fitness (increase in treadmill test duration between examinations) was associated with risk reduction.Population-based longitudinal cohort study of men and women 18 to 30 years of age in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants who completed the treadmill examination according to the Balke protocol at baseline were followed up from 1985-1986 to 2000-2001. A subset of participants (n = 2478) repeated the exercise test in 1992-1993.Incident type 2 diabetes, hypertension, the metabolic syndrome (defined according to National Cholesterol Education Program Adult Treatment Panel III), and hypercholesterolemia (low-density lipoprotein cholesterol > or =160 mg/dL [4.14 mmol/L]).During the 15-year study period, the rates of incident diabetes, hypertension, the metabolic syndrome, and hypercholesterolemia were 2.8, 13.0, 10.2, and 11.7 per 1000 person-years, respectively. After adjustment for age, race, sex, smoking, and family history of diabetes, hypertension, or premature myocardial infarction, participants with low fitness (<20th percentile) were 3- to 6-fold more likely to develop diabetes, hypertension, and the metabolic syndrome than participants with high fitness (> or =60th percentile), all P<.001. Adjusting for baseline body mass index diminished the strength of these associations to 2-fold (all P<.001). In contrast, the association between low fitness and hypercholesterolemia was modest (hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.1-1.7; P =.02) and attenuated to marginal significance after body mass index adjustment (P =.13). Improved fitness over 7 years was associated with a reduced risk of developing diabetes (HR, 0.4; 95% CI, 0.2-1.0; P =.04) and the metabolic syndrome (HR, 0.5; 95% CI, 0.3-0.7; P<.001), but the strength and significance of these associations was reduced after accounting for changes in weight.Poor fitness in young adults is associated with the development of cardiovascular disease risk factors. These associations involve obesity and may be modified by improving fitness.