tbuckley/cabot-search huggingface dataset:
Indirect immunofluorescence microscopy of lichen planus
Authors: R. G. OLSEN, D. P. DUPLESSIS, E. JOY SCHULZ, C. CAMISA
Journal: British Journal of Dermatology (1984)

Indirect immunofluorescence microscopy using serum and lesional skin revealed a lichen planus specific antigen (LPSA) in 80% of patients with lichen planus. This antigen is found only in the stratum granulosum and stratum spinosum. It was demonstrated in skin lesions in Caucasians and Negroes in South Africa and the U. S. A. but was not found in the skin of normal people or patients with other dermatoses. Indirect immunofluorescence should prove useful in distinguishing atypical forms of lichen planus from other dermatoses.
Arterial Thromboembolic Events in Patients with Metastatic Carcinoma Treated with Chemotherapy and Bevacizumab
Authors: F. A. Scappaticci, J. R. Skillings, S. N. Holden, H.-P. Gerber, K. Miller, F. Kabbinavar, E. Bergsland, J. Ngai, E. Holmgren, J. Wang, H. Hurwitz
Journal: JNCI Journal of the National Cancer Institute (2007)

Although combination treatment with bevacizumab (humanized monoclonal antibody against vascular endothelial growth factor) and chemotherapy improves survival of patients with various metastatic carcinomas, an increased risk of arterial thromboembolic events has been observed in some trials. We characterized this risk by performing post hoc analyses of randomized controlled trials that evaluated combination treatment with bevacizumab and chemotherapy versus chemotherapy alone. Low-dose aspirin was permitted in these trials, and its safety was also analyzed. Data were pooled from five randomized controlled trials that included a total of 1745 patients with metastatic colorectal, breast, or non–small-cell lung carcinoma. The risk of an arterial or venous thromboembolic event was assessed by simple incidence rates, rates per 100 person-years, and/or hazard ratios (HRs). The association between patient characteristics and risk of an arterial thromboembolic event was investigated primarily by Cox proportional hazards regression. The relationship between low-dose aspirin and bleeding was explored by incidence rates and rates per 100 person-years. Combined treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with increased risk for an arterial thromboembolic event (HR = 2.0, 95% confidence interval [CI] = 1.05 to 3.75; P = .031) but not for a venous thromboembolic event (HR = 0.89, 95% CI = 0.66 to 1.20; P = .44). The absolute rate of developing an arterial thromboembolism was 5.5 events per 100 person-years for those receiving combination therapy and 3.1 events per 100 person-years for those receiving chemotherapy alone (ratio = 1.8, 95% CI = 0.94 to 3.33; P = .076). Development of an arterial thromboembolic event was associated with a prior arterial thromboembolic event ( P <.001) or age of 65 years or older ( P = .01). Baseline or on-study aspirin use was associated with modest increases in grade 3 and 4 bleeding events in both treatment groups, from 3.6% to 4.7% for bevacizumab-treated patients and from 1.7% to 2.2% for control subjects. Combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with an increased risk of arterial thromboembolism but not venous thromboembolism.
Effect of mild emphysema on left heart function
Authors: B. Mallia-Milanes
Journal: Thorax (2010)

Severe chronic obstructive pulmonary disease is sometimes associated with cor pulmonale, impaired left ventricular filling and reduced left ventricular stroke volume and cardiac output with preserved left ventricular ejection fraction. However, whether similar changes occur in less severe cases of emphysema and airflow obstruction is unknown.

In this study the authors hypothesised that mild emphysema and airflow obstruction were associated with a decrease in …
Tirofiban and Sirolimus-Eluting Stent vs Abciximab and Bare-Metal Stent for Acute Myocardial Infarction
Authors: Marco Valgimigli, Gianfranco Percoco, Patrizia Malagutti, Gianluca Campo, Fabrizio Ferrari, Dario Barbieri, Giordano Cicchitelli, Eugène P. McFadden, Fabia Merlini, Lucia Ansani, Gabriele Guardigli, Alessandro Bettini, Giovanni Parrinello, Eric Boersma, Roberto Ferrari, for the STRATEGY Investigators
Journal: JAMA (2005)

ContextBare-metal stenting with abciximab pretreatment is currently considered a reasonable reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus-eluting stents significantly reduce the need for target-vessel revascularization (TVR) vs bare-metal stents but substantially increase procedural costs. At current European list prices, the use of tirofiban instead of abciximab would absorb the difference in cost between stenting with sirolimus-eluting vs bare-metal stents.ObjectiveTo evaluate the clinical and angiographic impact of single high-dose bolus tirofiban plus sirolimus-eluting stenting vs abciximab plus bare-metal stenting in patients with STEMI.Design, Setting, and PatientsProspective, single-blind, randomized controlled study (Single High Dose Bolus Tirofiban and Sirolimus Eluting Stent vs Abciximab and Bare Metal Stent in Myocardial Infarction [STRATEGY]) of 175 patients (median age, 63 [interquartile range, 55-72] years) presenting to a single referral center in Italy with STEMI or presumed new left bundle-branch block and randomized between March 6, 2003, and April 23, 2004.InterventionSingle high-dose bolus tirofiban regimen plus sirolimus-eluting stenting (n = 87) vs standard-dose abciximab plus bare-metal stenting (n = 88).Main Outcome MeasuresThe primary end point was a composite of death, nonfatal myocardial infarction, stroke, or binary restenosis at 8 months. Secondary outcomes included freedom, at day 30 and month 8, from major cardiac or cerebrovascular adverse events (composite of death, reinfarction, stroke, and repeat TVR).ResultsCumulatively, 14 of 74 patients (19%; 95% confidence interval [CI], 10%-28%) in the tirofiban plus sirolimus-eluting stent group and 37 of 74 patients (50%; 95% CI, 44%-56%) in the abciximab plus bare-metal stent group reached the primary end point (hazard ratio, 0.33; 95% CI, 0.18-0.60; P<.001 [P<.001 by Fischer exact test]). The cumulative incidence of death, reinfarction, stroke, or TVR was significantly lower in the tirofiban plus sirolimus-eluting stent group (18%) vs the abciximab plus bare-metal stent group (32%) (hazard ratio, 0.53; 95% CI, 0.28-0.92; P = .04), predominantly reflecting a reduction in the need for TVR. Binary restenosis was present in 6 of 67 (9%; 95% CI, 2%-16%) and 24 of 66 (36%; 95% CI, 26%-46%) patients in the tirofiban plus sirolimus-eluting stent and abciximab plus bare-metal stent groups, respectively (P = .002).ConclusionTirofiban-supported sirolimus-eluting stenting of infarcted arteries holds promise for improving outcomes while limiting health care expenditure in patients with myocardial infarction undergoing primary intervention.
Early Gains Versus Late Pains: Management Options in Stage I Testicular Cancer
Authors: Jörg Beyer
Journal: Journal of Clinical Oncology (2015)

TO THE EDITOR: In an editorial in Journal of Clinical Oncology, Vaughn describes a patient with clinical stage I testicular seminoma with an increased risk of occult metastatic disease. Post orchiectomy, this patient experiences a relapse after 1 year of active surveillance. Vaughn writes that he feels quite comfortable performing active surveillance in all subgroups of clinical stage I cancers. As a patient, I would feel highly uncomfortable with the prospect of receiving three cycles of toxic bleomycin, etoposide, and cisplatin (BEP) with its associated shortand long-term adverse effects, and would consider every effort to avoid such treatment. A single cycle of adjuvant carboplatin with few short-term and no known long-term adverse effects could have avoided the risk of nausea, hair loss, polyneuropathy, tinnitus, and cardiovascular toxicity associated with three to four cycles of BEP. The early gains of active surveillance come at the high price of late pains in the form of relevant adverse effects in those unfortunate patients in whom salvage treatment is needed. When the overall survival is close to 100%, as in clinical stage I testicular cancer, reduction of early and late toxicities should be the main focus of treatment strategies.
Myocardial Contractile Function and Heart Rate in Mice With Myocyte-Specific Overexpression of Endothelial Nitric Oxide Synthase
Authors: Friedrich Brunner, Penelope Andrew, Gerald Wölkart, Rudolf Zechner, Bernd Mayer
Journal: Circulation (2001)

The major source of nitric oxide (NO) in the heart is the constitutive form of NO synthases (eNOS, NOS III) that is expressed in vascular endothelium and cardiac myocytes. NO mediates endothelium-dependent vasodilation and may modulate cardiac function. We examined the role of NO in hearts from transgenic (TG) mice overexpressing eNOS exclusively in cardiac myocytes.Three independent TG lines with varying levels of NOS activity were selected, and the hearts were isolated and retrogradely perfused at constant flow. We found that NO is positively inotropic in spontaneously beating hearts from wild-type (WT) mice, whereas hearts overexpressing eNOS had reduced basal contractility that was partially reversed by NOS blockade. Heart rate was not altered. Acetylcholine (10 to 1000 nmol/L) increased contractility in unstimulated hearts and decreased contractility after beta-adrenergic stimulation with norepinephrine, and these responses were identical in WT and TG hearts. Finally, resting systolic intracellular calcium (Ca(2+)(i)) tended to be lower in TG than in WT hearts, and the beat-to-beat responsiveness to Ca(2+)(i) was reduced in hearts with eNOS overexpression.High levels of endogenous myocyte-derived NO blunt myofilament Ca(2+) sensitivity. The similar effects of acetylcholine on contractility and heart rate, as well as the identical basal intrinsic heart rate in WT and TG hearts, provide a solid argument against NO as an important modulator of neurohormonal control of myocardial function.
Memory B Cells Are Biased Towards Terminal Differentiation: A Strategy That May Prevent Repertoire Freezing
Authors: Christophe Arpin, Jacques Banchereau, Yong-Jun Liu
Journal: The Journal of Experimental Medicine (1997)

Isolation of large numbers of surface IgD+CD38- naive and surface IgD-CD38- memory B cells allowed us to study the intrinsic differences between these two populations. Upon in vitro culture with IL-2 and IL-10, human CD40-activated memory B cells undergo terminal differentiation into plasma cells more readily than do naive B cells, as they give rise to five- to eightfold more plasma cells and three- to fourfold more secreted immunoglobulins. By contrast, naive B cells give rise to a larger number of nondifferentiated B blasts. Saturating concentrations of CD40 ligand, which fully inhibit naive B cell differentiation, only partially affect that of memory B cells. The propensity of memory B cells to undergo terminal plasma cell differentiation may explain the extensive extra follicular plasma cell reaction and the limited germinal center reaction observed in vivo after secondary immunizations, which contrast with primary responses in carrier-primed animals. This unique feature of memory B cells may confer two important capacities to the immune system: (a) the rapid generation of a large number of effector cells to efficiently eliminate the pathogens; and (b) the prevention of the overexpansion and chronic accumulation of one particular memory B cell clone that would freeze the available peripheral repertoire.
Quantitative videobronchoscopy: a new technique to assess airway caliber.
Authors: L Forkert, H Watanabe, K Sutherland, S Vincent, J T Fisher
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Quantitative assessment of airway caliber is generally confined to indirect physiologic methods or to radiographic techniques. Fiberoptic bronchoscopy provides a direct view of airways, permitting quantification of airway caliber by image analysis. We investigated the characteristics of a bronchoscopic imaging system, determined its limitations in quantification and the corrections necessary for accurate assessment of image dimension, validated the methodology with airway models, and applied the technique to airways in vivo. The system comprised a bronchoscope, videocamera, videocassette recorder (VCR), computer with a frame grabber, and image-analysis program. Image quantification was affected by two sources of distortion: (1) Distance distortion: a loss of image resolution with increasing distance between the object and bronchoscope, requiring determination of the operational distance range. (2) Radial distortion: a progressive reduction in image size from the center to the periphery of the bronchoscopic field of view (FOV), requiring correction of airway dimension according to airway size and location in FOV. Validation of the methodology with different sized airway models indicated an underestimation of measured diameters, which normalized with distortion correction. We provide an example of quantitative videobronchoscopy with measurements of in vivo airway narrowing due to vagal stimulation in the anesthetized dog. Measurements of airway narrowing made with videobronchoscopy were also compared with those made with high-resolution computer-assisted tomography (HRCT) which suggested that the two technologies provide unique but complementary perspectives on airway dimensions. We conclude that videobronchoscopy and image analysis provide a novel and accurate method for the quantification of airway caliber.
HTLV-I associated Sjogren's syndrome is aetiologically distinct from anti-centromere antibodies positive Sjogren's syndrome
Authors: A. Hida, Y. Kawabe, A. Kawakami, K. Migita, M. Tominaga, H. Nakamura, K. Eguchi
Journal: Annals of the Rheumatic Diseases (1999)

To investigate whether Sjögren's syndrome (SS) with anti-HTLV-I antibodies is aetiopathologically distinguishable from SS without these antibodies, the study compared prevalence of autoantibodies in serum samples of SS patients with or without anti-HTLV-I antibodies.The test group included 135 patients with primary SS and 97 patients with secondary SS. Serum samples of the patients were examined for the presence of anti-nuclear antibodies (ANA), anti-SS-A/Ro antibodies, anti-SS-B/La antibodies, anti-centromere antibodies (ACA), and anti-HTLV-I antibodies.Anti-HTLV-I antibodies were detected in 25.0% of primary SS patients and in 29.2% of secondary SS patients. There were no significant differences in the mean age, sex, values of asparate aminotransferase, alanine aminotransferase, alkaline phosphatase, serum complements and IgG between HTLV-I seropositive and seronegative SS patients. The rheumatoid factor, ANA, anti-SS-A/Ro, and anti-SS-B/La antibodies in serum samples of SS patients were detected in 60.0%, 84.0%, 51.9%, and 12.0%, respectively. There was no significant difference in the prevalence of these antibodies between HTLV-I seropositive and seronegative SS patients. Using the indirect immunofluorescence test, 14.2% showed a discrete speckled staining pattern. All serum samples contained significant amounts of ACA determined by enzyme linked immunosorbent assay. These antibodies were detected in only 4% of HTLV-I seropositive SS patients but were present in 19.9% of HTLV-I seronegative SS patients. Furthermore, the prevalences of anti-SS-A/Ro and anti-SS-B/La antibodies in serum samples of ACA positive patients were significantly lower than those in ACA negative SS patients.These results suggest that SS patients with anti-SS-A/Ro or anti-SS-B/La antibodies, or both, might be aetiopathologically distinct from SS patients with ACA. HTLV-I might be involved in the pathogenesis of SS in a subset of patients with anti-SS-A/Ro or anti-SS-B/La antibodies, or both, but not SS patients with ACA.
Commentary: "Histiocytosis X"
Authors: D. V Parums
Journal: Thorax (1998)

Langerhans' cell histiocytosis may cause irreversible respiratory failure due to progressive destruction of lung parenchyma and widespread cystic change.Transplantation oVers a therapeutic option.A case is described of recurrence of Langerhans' cell histiocytosis which was associated with deterioration in lung function four years following bilateral lung transplantation.Patients transplanted for Langerhans' cell histiocytosis should be followed up with this complication in mind.
Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation
Authors: Qiang Pan-Hammarström, Aleksi Lähdesmäki, Yaofeng Zhao, Likun Du, Zhihui Zhao, Sicheng Wen, Victor L. Ruiz-Perez, Deborah K. Dunn-Walters, Judith A. Goodship, Lennart Hammarström
Journal: The Journal of Experimental Medicine (2006)

Class switch recombination (CSR) and somatic hypermutation (SHM) are mechanistically related processes initiated by activation-induced cytidine deaminase. Here, we have studied the role of ataxia telangiectasia and Rad3-related protein (ATR) in CSR by analyzing the recombinational junctions, resulting from in vivo switching, in cells from patients with mutations in the ATR gene. The proportion of cells that have switched to immunoglobulin (Ig)A and IgG in the peripheral blood seems to be normal in ATR-deficient (ATRD) patients and the recombined S regions show a normal "blunt end-joining," but impaired end joining with partially complementary (1-3 bp) DNA ends. There was also an increased usage of microhomology at the mu-alpha switch junctions, but only up to 9 bp, suggesting that the end-joining pathway requiring longer microhomologies (> or =10 bp) may be ATR dependent. The SHM pattern in the Ig variable heavy chain genes is altered, with fewer mutations occurring at A and more mutations at T residues and thus a loss of strand bias in targeting A/T pairs within certain hotspots. These data suggest that the role of ATR is partially overlapping with that of ataxia telangiectasia-mutated protein, but that the former is also endowed with unique functional properties in the repair processes during CSR and SHM.
Initiation of Autoimmune Diabetes by Developmentally Regulated Presentation of Islet Cell Antigens in the Pancreatic Lymph Nodes
Authors: Petter Höglund, Justine Mintern, Caroline Waltzinger, William Heath, Christophe Benoist, Diane Mathis
Journal: The Journal of Experimental Medicine (1999)

Little is known about the events triggering lymphocyte invasion of the pancreatic islets in prelude to autoimmune diabetes. For example, where islet-reactive T cells first encounter antigen has not been identified. We addressed this issue using BDC2.5 T cell receptor transgenic mice, which express a receptor recognizing a natural islet beta cell antigen. In BDC2.5 animals, activated T cells were found only in the islets and the lymph nodes draining them, and there was a close temporal correlation between lymph node T cell activation and islet infiltration. When naive BDC2.5 T cells were transferred into nontransgenic recipients, proliferating cells were observed only in pancreatic lymph nodes, and this occurred significantly before insulitis was detectable. Surprisingly, proliferation was not seen in 10-day-old recipients. This age-dependent dichotomy was reproduced in a second transfer system based on an unrelated antigen artificially expressed on beta cells. We conclude that beta cell antigens are transported specifically to pancreatic lymph nodes, where they trigger reactive T cells to invade the islets. Systemic or extrapancreatic T cell priming, indicative of activation via molecular mimicry or superantigens, was not seen. Compromised presentation of beta cell antigens in the pancreatic lymph nodes of juvenile animals may be the root of a first “checkpoint” in diabetes progression.
Obesity genomics: assessing the transferability of susceptibility loci across diverse populations
Authors: Yingchang Lu, Ruth JF Loos
Journal: Genome Medicine (2013)

The prevalence of obesity has nearly doubled worldwide over the past three decades, but substantial differences exist between nations. Although these differences are partly due to the degree of westernization, genetic factors also contribute. To date, little is known about whether the same genes contribute to obesity-susceptibility in populations of different ancestry. We review the transferability of obesity-susceptibility loci (identified by genome-wide association studies) using both single nucleotide polymorphism (SNP) and locus-wide comparisons. SNPs in FTO and near MC4R, obesity-susceptibility loci first identified in Europeans, replicate widely across other ancestries. SNP-to-SNP comparisons suggest that more than half of the 36 body mass index-associated loci are shared across European and East Asian ancestry populations, whereas locus-wide analyses suggest that the transferability might be even more extensive. Furthermore, by taking advantage of differences in haplotype structure, populations of different ancestries can help to narrow down loci, thereby pinpointing causal genes for functional follow-up. Larger-scale genetic association studies in ancestrally diverse populations will be needed for in-depth and locus-wide analyses aimed at determining, with greater confidence, the transferability of loci and allowing fine-mapping. Understanding similarities and differences in genetic susceptibility across populations of diverse ancestries might eventually contribute to a more targeted prevention and customized treatment of obesity.
Oncologic Outcomes Following Three Different Approaches to the Distal Ureter and Bladder Cuff in Nephroureterectomy for Primary Upper Urinary Tract Urothelial Carcinoma
Authors: Wei-Ming Li, Jung-Tsung Shen, Ching-Chia Li, Hung-Lung Ke, Yu-Ching Wei, Wen-Jeng Wu, Yii-Her Chou, Chun-Hsiung Huang
Journal: European Urology (2010)
(15) Protein losing enteropathy due to SLE
Authors: M.L. Wood, R.E. Church
Journal: British Journal of Dermatology (1986)

Journal Article (15) Protein losing enteropathy due to SLE Get access M.L. Wood, Drs, M.L. Wood, Drs Search for other works by this author on: Oxford Academic Google Scholar R.E. Church R.E. Church Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s30, 1 July 1986, Pages 58–59, https://doi.org/10.1111/j.1365-2133.1986.tb07710.x Published: 01 July 1986
Critical Roles of DMP1 in Human Epidermal Growth Factor Receptor 2/neu-Arf-p53 Signaling and Breast Cancer Development
Authors: Pankaj Taneja, Dejan Maglic, Fumitake Kai, Takayuki Sugiyama, Robert D. Kendig, Donna P. Frazier, Mark C. Willingham, Kazushi Inoue
Journal: Cancer Research (2010)

Abstract Human epidermal growth factor receptor 2 (HER2) overexpression stimulates cell growth in p53-mutated cells while it inhibits cell proliferation in those with wild-type p53, but the molecular mechanism is unknown. The Dmp1 promoter was activated by HER2/neu through the phosphatidylinositol-3′-kinase-Akt-NF-κB pathway, which in turn stimulated Arf transcription. Binding of p65 and p52 subunits of NF-κB was shown to the Dmp1 promoter and that of Dmp1 to the Arf promoter on HER2/neu overexpression. Both Dmp1 and p53 were induced in premalignant lesions from mouse mammary tumor virus-neu mice, and mammary tumorigenesis was significantly accelerated in both Dmp1+/− and Dmp1−/− mice. Selective deletion of Dmp1 and/or overexpression of Tbx2/Pokemon was found in &amp;gt;50% of wild-type HER2/neu carcinomas, although the involvement of Arf, Mdm2, or p53 was rare. Tumors from Dmp1+/−, Dmp1−/−, and wild-type neu mice with hemizygous Dmp1 deletion showed significant downregulation of Arf and p21Cip1/WAF1, showing p53 inactivity and more aggressive phenotypes than tumors without Dmp1 deletion. Notably, endogenous hDMP1 mRNA decreased when HER2 was depleted in human breast cancer cells. Our study shows the pivotal roles of Dmp1 in HER2/neu-p53 signaling and breast carcinogenesis. Cancer Res; 70(22); 9084–94. ©2010 AACR.