tbuckley/cabot-search huggingface dataset:
Anchoring Fusion Thrombomodulin to the Endothelial Lumen Protects against Injury-induced Lung Thrombosis and Inflammation
Authors: Bi-Sen Ding, Nankang Hong, Melpo Christofidou-Solomidou, Claudia Gottstein, Steven M. Albelda, Douglas B. Cines, Aron B. Fisher, Vladimir R. Muzykantov
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Endothelial thrombomodulin (TM) regulates thrombosis and inflammation. Diverse forms of pulmonary and vascular injury are accompanied by down-regulation of TM, which aggravates tissue injury. We postulated that anchoring TM to the endothelial surface would restore its protective functions.To design an effective and safe strategy to treat pulmonary thrombotic and inflammatory injury.We synthesized a fusion protein, designated scFv/TM, by linking the extracellular domain of mouse TM to a single-chain variable fragment of an antibody to platelet endothelial cell adhesion molecule-1 (PECAM-1). The targeting and protective functions of scFv/TM were tested in mouse models of lung ischemia-reperfusion and acute lung injury (ALI) caused by intratracheal endotoxin and hyperoxia, both of which caused approximately 50% reduction in the endogenous expression of TM.Biochemical assays showed that scFv/TM accelerated protein C activation by thrombin and bound mouse PECAM-1 and cytokine high mobility group-B1. After intravenous injection, scFv/TM preferentially accumulated in the mouse pulmonary vasculature. In a lung model of ischemia-reperfusion injury, scFv/TM attenuated elevation of early growth response-1, inhibited pulmonary deposition of fibrin and leukocyte infiltration, and preserved blood oxygenation more effectively than soluble TM. In an ALI model, scFv/TM, but not soluble TM, suppressed activation of nuclear factor-kappaB, inflammation and edema in the lung and reduced mortality without causing hemorrhage.Targeting TM to the endothelium using an scFv anchor enhances its antithrombotic and antiinflammatory effectiveness in models of ALI.
Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells
Authors: V. Planat-Bénard, C. Menard, M. André, M. Puceat, A. Perez, J.-M. Garcia-Verdugo, L. Pénicaud, L. Casteilla
Journal: Circulation Research (2003)

Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. As adipose tissues were recently demonstrated to contain pluripotent stem cells, the emergence of cardiomyocyte phenotype from adipose-derived cells was investigated. We demonstrated that rare beating cells with cardiomyocyte features could be identified after culture of adipose stroma cells without addition of 5-azacytidine. The cardiomyocyte phenotype was first identified by morphological observation, confirmed with expression of specific cardiac markers, immunocytochemistry staining, and ultrastructural analysis, revealing the presence of ventricle- and atrial-like cells. Electrophysiological studies performed on early culture revealed a pacemaker activity of the cells. Finally, functional studies showed that adrenergic agonist stimulated the beating rate whereas cholinergic agonist decreased it. Taken together, this study demonstrated that functional cardiomyocyte-like cells could be directly obtained from adipose tissue. According to the large amount of this tissue in adult mammal, it could represent a useful source of cardiomyocyte progenitors.
Reduced expression of the renal calcium-sensing receptor in rats with experimental chronic renal insufficiency.
Authors: R S Mathias, H T Nguyen, M Y Zhang, A A Portale
Journal: Journal of the American Society of Nephrology (1998)

Chronic renal insufficiency is associated with elevated serum parathyroid hormone (PTH) levels (2 degrees HPT), deficiency of 1,25-dihydroxyvitamin D (1,25(OH)2D), and hypocalciuria. In chronic renal insufficiency, the 2 degrees HPT may result from reduced expression of the parathyroid gland extracellular Ca(2+)-sensing receptor (CaSR). Since the CaSR was cloned from rat and human kidney, this study examined in rats whether expression of the renal CaSR is altered in experimental chronic renal insufficiency. Four weeks after chronic renal insufficiency was induced by 5/6 nephrectomy (Nx) in Sprague Dawley rats, the serum creatinine concentration was 0.96+/-0.06 mg/dl compared with 0.35+/-0.02 mg/dl in sham-operated animals (P < 0.05). The serum total Ca2+ and phosphorus concentrations were not different. In the Nx group, the serum concentration of amino-PTH was higher (65+/-8 pg/ml), and the concentration of 1,25(OH)2D was significantly lower (47+/-5 pg/ml) compared with 45+/-5 pg/ml and 61+/-4 pg/ml (P = 0.05) in the sham group, respectively. In a subset of rats studied, the Nx group was hypocalciuric (1.4+/-0.5 mg/kg per d) compared with the sham group (3.7+/-0.5 mg/kg per d) (P < 0.05). In the Nx rats, CaSR mRNA expression and CaSR protein levels were found to be reduced by 35 and 38%, respectively, than those observed in controls. These results suggest that reduced renal CaSR expression in chronic renal insufficiency may play a role in disordered mineral ion homeostasis, including hypocalciuria.
Plasma Protein Profiling for Diagnosis of Pancreatic Cancer Reveals the Presence of Host Response Proteins
Authors: John M. Koomen, Lichen Nancy Shih, Kevin R. Coombes, Donghui Li, Lian-chun Xiao, Isaiah J. Fidler, James L. Abbruzzese, Ryuji Kobayashi
Journal: Clinical Cancer Research (2005)

Plasma protein profiling using separations coupled to matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) has great potential in translational research; it can be used for biomarker discovery and contribute to disease diagnosis and therapy. Previously reported biomarker searches have been done solely by MS protein profiling followed by bioinformatics analysis of the data. To add to current methods, we tested an alternative strategy for plasma protein profiling using pancreatic cancer as the model. First, offline solid-phase extraction is done with 96-well plates to fractionate and partially purify the proteins. Then, multiple profiling and identification experiments can be conducted on the same protein fractions because only 5% of the fractions are used for MALDI MS profiling. After MALDI MS analysis, the mass spectra are normalized and subjected to a peak detection algorithm. Over three sets of mass spectra acquired using different instrument variables, approximately 400 unique ion signals were detected. Classification schemes employing as many as eight individual peaks were developed using a training set with 123 members (82 cancer patients) and a blinded validation set with 125 members (57 cancer patients). The sensitivity of the study was 88%, but the specificity was significantly lower, 75%. The reason for the low specificity becomes apparent upon protein identification of the ion signals used for the classification. The identifications reveal only common serum proteins and components of the acute phase response, including serum amyloid A, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and inter-alpha-trypsin inhibitor.
Targeted delivery of non-viral vectors to cartilage in vivo using a chondrocyte-homing peptide identified by phage display
Authors: Yanbin Pi, Xin Zhang, Junjun Shi, Jinxian Zhu, Wenqing Chen, Chenguang Zhang, Weiwei Gao, Chunyan Zhou, Yingfang Ao
Journal: Biomaterials (2011)
Remitting seronegative symmetrical synovitis with pitting oedema: disease or syndrome?
Authors: T Schaeverbeke, E Fatout, S Marce, J P Vernhes, O Halle, J F Antoine, L Lequen, B Bannwarth, J Dehais
Journal: Annals of the Rheumatic Diseases (1995)

To evaluate the outcome of patients with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE).In a retrospective chart review study, we identified all the patients presenting with polyarthritis and pitting oedema in the past 20 years. We tried to recall the 24 patients with characteristics of RS3PE according to McCarty et al. Two patients had died and four could not be traced. Five could not be seen after the initial period of follow up; relevant data were obtained from their practitioner. For the remaining 13 patients, clinical, radiological, and biological evaluation was performed in our department, with the last assessment in 1993.The follow up period was from one to 18 years (mean 4.6 (SD 4.5) years). Eleven patients developed one or several recurrences of articular manifestations consisting of mild oligoarthritis (n = 8), definite spondyloarthropathy (n = 2), and rheumatoid arthritis (n = 1). The delay of the first recurrence was 18 months to 12 years after the first attack. Thirteen patients had no recurrence, but three of them developed remarkable features: rheumatoid factor, antinuclear antibodies (1/2000), Sjögren's syndrome. HLA B typing was performed in nine patients and revealed B7 (n = 2), B27 (n = 2) and B22 (n = 2). Isolated HLA B27 typing was performed in two other patients and was positive in one.The long term outcome of RS3PE can lead to different rheumatic diseases. RS3PE appears to be a syndrome related to the elderly onset of the rheumatic diseases, including spondyloarthropathy and rheumatoid arthritis, rather than a specific entity.
Decentration of Flexible Loop Posterior Chamber Intraocular Lenses in a Series of 222 Postmortem Eyes
Authors: Steven O. Hansen, Manfred R. Tetz, Kerry D. Solomon, Mark D. Borup, Robert N. Brems, David J.C. O'morchoe, Omar Bouhaddou, David J. Apple
Journal: Ophthalmology (1988)
Solid persistent facial oedema (Morbihan's disease) following rosacea, successfully treated with isotretinoin and ketotifen
Authors: C. Mazzatenta, G. Giorgino, P. Rubegni, G.de Aloe, M. Fimiani
Journal: British Journal of Dermatology (1997)

Journal Article Solid persistent facial oedema (Morbihan's disease) following rosacea, successfully treated with isotretinoin and ketotifen Get access C. Mazzatenta, C. Mazzatenta Department of Dermatology, of Siena University, Viale Bracci, 1‐53100 Siena, Italy E‐mail: mazzatenta@unisi.it Search for other works by this author on: Oxford Academic Google Scholar G. Giorgino, G. Giorgino Department of Dermatology, of Siena University, Viale Bracci, 1‐53100 Siena, Italy E‐mail: mazzatenta@unisi.it Search for other works by this author on: Oxford Academic Google Scholar P. Rubegni, P. Rubegni Department of Dermatology, of Siena University, Viale Bracci, 1‐53100 Siena, Italy E‐mail: mazzatenta@unisi.it Search for other works by this author on: Oxford Academic Google Scholar G.de Aloe, G.de Aloe Department of Dermatology, of Siena University, Viale Bracci, 1‐53100 Siena, Italy E‐mail: mazzatenta@unisi.it Search for other works by this author on: Oxford Academic Google Scholar M. Fimiani M. Fimiani Department of Dermatology, of Siena University, Viale Bracci, 1‐53100 Siena, Italy E‐mail: mazzatenta@unisi.it Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 6, 1 December 1997, Pages 1020–1021, https://doi.org/10.1111/j.1365-2133.1997.tb01577.x Published: 01 December 1997
Familial Variation in Episode Frequency in Bipolar Affective Disorder
Authors: Maria E. Fisfalen, Thomas G. Schulze, J. Raymond DePaulo, Leslie J. DeGroot, Judith A. Badner, Francis J. McMahon
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Bipolar affective disorder is a familial illness characterized by recurrent episodes of mania and depression, but little is known about the familial nature of episode recurrence or its associated clinical features. The authors analyzed the recurrence frequency of affective episodes (episode frequency), along with associated clinical and demographic variables, in families with at least three members with a major affective disorder. METHOD: Members of 86 families ascertained through probands with bipolar affective disorder who had two or more first-degree relatives with a major affective disorder were interviewed by psychiatrists and assigned an all-sources diagnosis. Data for 407 subjects with a major affective disorder were analyzed. Episode frequency was estimated as the number of episodes of major depression, mania, and hypomania per year of illness. RESULTS: Episode frequency was smoothly distributed over the range of 0.02–20.2 episodes/year. Episode frequency was significantly correlated among relatives (r=0.56, p<0.004). Earlier age at onset, bipolar II disorder, hallucinations or delusions, alcoholism, and suicidal behavior were all more prevalent in the highest than in the lowest quartiles of episode frequency. Female gender and recurrent major depression were more prevalent in the lowest quartile. Panic disorder, substance abuse, and thyroid disease were all unrelated to episode frequency. Subjects with DSM-IV rapid cycling did not differ from other affected subjects for most of the variables tested. CONCLUSIONS: Episode frequency is a highly familial trait in bipolar affective disorder, associated with several indicators of severity, and may be useful in defining clinical subtypes of bipolar affective disorder with greater genetic liability. DSM-IV rapid cycling was not supported by these data as the best predictor of familiality or severity.
Polymorphisms of Death Pathway Genes FAS and FASL in Esophageal Squamous-Cell Carcinoma
Authors: T. Sun, X. Miao, X. Zhang, W. Tan, P. Xiong, D. Lin
Journal: JNCI Journal of the National Cancer Institute (2004)

The FAS receptor-ligand system is a key regulator of apoptotic cell death, and loss of FAS expression and gain of FAS ligand (FASL) expression play important roles in the development and progression of cancer. Single-nucleotide polymorphisms in the promoter region of the FAS (G or A at position -1377 [FAS -1377G/A] and A or G at position -670 [FAS -670A/G]) and FASL (T or C at position -844 [FASL -844T/C]) genes alter the transcriptional activity of these genes. We examined the association between these polymorphisms and risk of the development and metastasis of esophageal squamous-cell carcinoma.Genotypes of 588 case patients with esophageal squamous-cell carcinoma and 648 control subjects were determined by polymerase chain reaction-based restriction fragment length polymorphism. Associations with the risk of esophageal squamous-cell carcinoma were estimated by logistic regression. All statistical tests were two-sided.We observed a statistically significantly increased risk of esophageal squamous-cell carcinoma associated with the FAS -1377AA (odds ratio [OR] = 1.79, 95% confidence interval [CI] = 1.29 to 2.48; P<.001) or FAS -670GG (OR = 1.72, 95% CI = 1.26 to 2.34; P<.001) genotype, which are in strong linkage disequilibrium compared with the FAS -1377GA or GG or the FAS -670AG or AA genotype, respectively. An increased risk of esophageal squamous-cell carcinoma was also associated with the FASL -844CC genotype (OR = 2.06, 95% CI = 1.64 to 2.59; P<.001) compared with the FASL -844CT or TT genotype. Gene-gene interactions of FAS and FASL polymorphisms increased the risk of esophageal squamous-cell carcinoma in a multiplicative manner (OR for the presence of both FAS -1377AA and FASL -844CC genotypes = 4.55, 95% CI = 2.75 to 7.48; P =.001, test for homogeneity). Statistically significant interactions were found between these polymorphisms in FAS and FASL and tobacco smoking. None of the polymorphisms was associated with risk of differentiation or metastasis of esophageal squamous-cell carcinoma at diagnosis.Genetic polymorphisms in the death pathway genes FAS and FASL appear to be associated with an increased risk of developing esophageal squamous-cell carcinoma.
Phase II Clinical Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, As First-Line Therapy in Patients With Metastatic Breast Cancer Previously Treated With Anthracycline Chemotherapy
Authors: Henri Roché, Louise Yelle, Francesco Cognetti, Louis Mauriac, Craig Bunnell, Joseph Sparano, Pierre Kerbrat, Jean-Pierre Delord, Linda Vahdat, Ronald Peck, David Lebwohl, Rana Ezzeddine, Hervé Curé
Journal: Journal of Clinical Oncology (2007)

There is a need for new agents to treat metastatic breast cancer (MBC) in patients for whom anthracycline therapy has failed or is contraindicated. This study was conducted to assess the efficacy and safety of the novel antineoplastic, the epothilone B analog ixabepilone, in patients with MBC previously treated with an adjuvant anthracycline.Patients were age >or= 18 years and had received a prior anthracycline-based regimen as adjuvant treatment. Ixabepilone as first-line metastatic chemotherapy was administered as a 40 mg/m(2) intravenous infusion during 3 hours every 3 weeks. The primary efficacy end point was objective response rate (ORR). Secondary efficacy end points included duration of response, time to response, time to progression, and survival.All 65 patients were assessable for response. Their median age was 52 years (range, 33 to 80 years). ORR was 41.5% (95% CI, 29.4% to 54.4%), median duration of response was 8.2 months (95% CI, 5.7 to 10.2 months), and median time to response was 6 weeks (range, 5 to 17 weeks). Median survival was 22.0 months (95% CI, 15.6 to 27.0 months). Treatment-related adverse events were manageable and mostly grades 1/2: the most common of these (other than alopecia) was mild to moderate neuropathy, which was primarily sensory and mostly reversible in nature.Ixabepilone is efficacious and has a predictable and manageable safety profile in women with MBC previously treated with an adjuvant anthracycline.
Cardiac disease in myotonic dystrophy
Authors: M.F. Phillips, P.S. Harper
Journal: Cardiovascular Research (1997)

Cardiac disease is a well-known complication of myotonic dystrophy, understanding of which has been increased by recent advances in both molecular techniques and cardiological investigations. Conduction disturbances and tachyarrhythmias occur commonly in myotonic dystrophy. These have been shown to have a broad correlation in severity with both neuromuscular disease and the extent of the molecular defect in some, but not all, studies. Clinical evidence of generalised cardiomyopathy is unusual. The rate of progression differs widely between individuals; sudden death may be caused by ventricular arrhythmias or complete heart block, and this can be at an early stage of disease. A familial tendency towards cardiac complications has been shown in some studies. The histopathology is of fibrosis, primarily in the conducting system and sino-atrial node, myocyte hypertrophy and fatty infiltration. Electron microscopy shows prominent I-bands and myofibrillar degeneration. Myotonin protein kinase, the primary product of the myotonic dystrophy gene, may be located at the intercalated discs and have a different isoform in cardiac tissue. The role of other genes or the normal myotonic dystrophy allele in myotonic heart disease has yet to be determined. Suggestions for clinical management include a careful cardiac history and a 12-lead ECG at least every year, with a low threshold for use of 24 h Holter monitoring. Extra care should be taken before, during and after general anaesthetics, which carry a high frequency of cardiorespiratory complications. Finally, myotonic dystrophy should be considered in previously undiagnosed patients presenting to a cardiologist or general physician with suspected arrhythmia or conduction block.
Cell Membrane Fluid–Mosaic Structure and Cancer Metastasis
Authors: Garth L. Nicolson
Journal: Cancer Research (2015)

Cancer cells are surrounded by a fluid-mosaic membrane that provides a highly dynamic structural barrier with the microenvironment, communication filter and transport, receptor and enzyme platform. This structure forms because of the physical properties of its constituents, which can move laterally and selectively within the membrane plane and associate with similar or different constituents, forming specific, functional domains. Over the years, data have accumulated on the amounts, structures, and mobilities of membrane constituents after transformation and during progression and metastasis. More recent information has shown the importance of specialized membrane domains, such as lipid rafts, protein-lipid complexes, receptor complexes, invadopodia, and other cellular structures in the malignant process. In describing the macrostructure and dynamics of plasma membranes, membrane-associated cytoskeletal structures and extracellular matrix are also important, constraining the motion of membrane components and acting as traction points for cell motility. These associations may be altered in malignant cells, and probably also in surrounding normal cells, promoting invasion and metastatic colonization. In addition, components can be released from cells as secretory molecules, enzymes, receptors, large macromolecular complexes, membrane vesicles, and exosomes that can modify the microenvironment, provide specific cross-talk, and facilitate invasion, survival, and growth of malignant cells.
Clinical Lecture on a Case of Epilepsy and Vertigo, in which Blood-Letting was Employed with Advantage
Authors: C. H. Jones
Journal: BMJ (1868)

GENTLEMEN-" Medio tutissimus ibis" is a wise old saw, but one which it seems not easy to act upon.The pendulum of opinion com- monly deviates to one side or other of the true line.It appears to me, that at present there is some tendency to error of this kiind in the case of Epilepsy, which seems to be regarded by some too much as if it were invariably associated with deficient blood-supply to the brain.Very often this is the case; but that the encephalon is by no means un.frequently hypermmic in epileptic states, and that this hypernemia may even materially contribute to the production of the disorder, I think I shall be able to prove.Let me ask your attention to the following hiistory.W. F., aged 49, stableman, was seen on Aug. i5th, 1865.He was sent to me by my friend Dr. Palmer, from whom I received the follow- ing statement."Eleven years ago, he had a severe epileptic fit for the first time; he continued vertig.inous,weak, and unable to work for several days; his pulse feeble and small; his skin cool and moist.Leeches, cold to the head, free purging, and ioclide of potassium, failed to relieve him.He was then admitted into St.Mary's.On coming out, he told me that he was cupped and had various remedies, but all failed to do him good