tbuckley/cabot-search huggingface dataset:
IgA pemphigus associated with diffuse large B-cell lymphoma showing unique reactivity with desmocollins: unusual clinical and histopathological features
Authors: A. Asahina, H. Koga, Y. Suzuki, T. Hashimoto
Journal: British Journal of Dermatology (2012)

Journal Article IgA pemphigus associated with diffuse large B‐cell lymphoma showing unique reactivity with desmocollins: unusual clinical and histopathological features Get access A. Asahina, A. Asahina Department of Dermatology, National Hospital Organisation, Sagamihara National Hospital, 18‐1 Sakuradai, Minami‐ku, Sagamihara, Kanagawa 252‐0392, Japan Search for other works by this author on: Oxford Academic Google Scholar H. Koga, H. Koga Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Suzuki, Y. Suzuki Department of Haematology, Kitasato University School of Medicine, Sagamihara, Japan E‐mail: asahina‐tky@umin.ac.jp Search for other works by this author on: Oxford Academic Google Scholar T. Hashimoto T. Hashimoto Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 1, 1 January 2013, Pages 224–226, https://doi.org/10.1111/j.1365-2133.2012.11127.x Published: 01 January 2013
iRHOM2 is a critical pathogenic mediator of inflammatory arthritis
Authors: Priya Darshinee A. Issuree, Thorsten Maretzky, David R. McIlwain, Sébastien Monette, Xiaoping Qing, Philipp A. Lang, Steven L. Swendeman, Kyung-Hyun Park-Min, Nikolaus Binder, George D. Kalliolias, Anna Yarilina, Keisuke Horiuchi, Lionel B. Ivashkiv, Tak W. Mak, Jane E. Salmon, Carl P. Blobel
Journal: Journal of Clinical Investigation (2013)

iRHOM2, encoded by the gene Rhbdf2, regulates the maturation of the TNF-α convertase (TACE), which controls shedding of TNF-α and its biological activity in vivo. TACE is a potential target to treat TNF-α-dependent diseases, such as rheumatoid arthritis, but there are concerns about potential side effects, because TACE also protects the skin and intestinal barrier by activating EGFR signaling. Here we report that inactivation of Rhbdf2 allows tissue-specific regulation of TACE by selectively preventing its maturation in immune cells, without affecting its homeostatic functions in other tissues. The related iRHOM1, which is widely expressed, except in hematopoietic cells, supported TACE maturation and shedding of the EGFR ligand TGF-α in Rhbdf2-deficient cells. Remarkably, mice lacking Rhbdf2 were protected from K/BxN inflammatory arthritis to the same extent as mice lacking TACE in myeloid cells or Tnfa-deficient mice. In probing the underlying mechanism, we found that two main drivers of K/BxN arthritis, complement C5a and immune complexes, stimulated iRHOM2/TACE-dependent shedding of TNF-α in mouse and human cells. These data demonstrate that iRHOM2 and myeloid-expressed TACE play a critical role in inflammatory arthritis and indicate that iRHOM2 is a potential therapeutic target for selective inactivation of TACE in myeloid cells.
Identification of a human synaptotagmin-1 mutation that perturbs synaptic vesicle cycling
Authors: Kate Baker, Sarah L. Gordon, Detelina Grozeva, Margriet van Kogelenberg, Nicola Y. Roberts, Michael Pike, Edward Blair, Matthew E. Hurles, W. Kling Chong, Torsten Baldeweg, Manju A. Kurian, Stewart G. Boyd, Michael A. Cousin, F. Lucy Raymond
Journal: Journal of Clinical Investigation (2015)

Synaptotagmin-1 (SYT1) is a calcium-binding synaptic vesicle protein that is required for both exocytosis and endocytosis. Here, we describe a human condition associated with a rare variant in SYT1. The individual harboring this variant presented with an early onset dyskinetic movement disorder, severe motor delay, and profound cognitive impairment. Structural MRI was normal, but EEG showed extensive neurophysiological disturbances that included the unusual features of low-frequency oscillatory bursts and enhanced paired-pulse depression of visual evoked potentials. Trio analysis of whole-exome sequence identified a de novo SYT1 missense variant (I368T). Expression of rat SYT1 containing the equivalent human variant in WT mouse primary hippocampal cultures revealed that the mutant form of SYT1 correctly localizes to nerve terminals and is expressed at levels that are approximately equal to levels of endogenous WT protein. The presence of the mutant SYT1 slowed synaptic vesicle fusion kinetics, a finding that agrees with the previously demonstrated role for I368 in calcium-dependent membrane penetration. Expression of the I368T variant also altered the kinetics of synaptic vesicle endocytosis. Together, the clinical features, electrophysiological phenotype, and in vitro neuronal phenotype associated with this dominant negative SYT1 mutation highlight presynaptic mechanisms that mediate human motor control and cognitive development.
OCULAR PEMPHIGUS WITH GENERALISED BULLOUS ERUPTION.
Authors: R. E. CHURCH, I. B. SNEDDON
Journal: British Journal of Dermatology (1956)

Journal Article OCULAR PEMPHIGUS WITH GENERALISED BULLOUS ERUPTION. Get access R. E. CHURCH, M.A., M.D., M.R.C.P.(Ed), R. E. CHURCH, M.A., M.D., M.R.C.P.(Ed) Senior Registrar Search for other works by this author on: Oxford Academic Google Scholar I. B. SNEDDON, M.B., Ch.B., M.R.C.P. I. B. SNEDDON, M.B., Ch.B., M.R.C.P. Consultant Dermatologist, United Sheffield Hospitals, Royal Infirmary Unit, Sheffield Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 68, Issue 4, 1 April 1956, Pages 128–131, https://doi.org/10.1111/j.1365-2133.1956.tb12797.x Published: 01 April 1956
Nebulised salbutamol administered during sputum induction improves bronchoprotection in patients with asthma
Authors: Muriel Delvaux, Monique Henket, L. Lau, P. Kange, Pierre Bartsch, R. Djukanovic, Renaud Louis
Journal: Thorax (2004)

<b>Background:</b> Inhalation of hypertonic or even isotonic saline during sputum induction may cause bronchospasm in susceptible patients with asthma, despite premedication with 400 µg inhaled salbutamol delivered by pressurised metered dose inhaler (pMDI). The bronchoprotection afforded by additional inhaled salbutamol administered through the ultrasonic nebuliser during sputum induction was investigated. <b>Methods:</b> Twenty patients with moderate to severe asthma underwent sputum induction by inhaling saline 4.5% (or 0.9% if post-bronchodilation forced expiratory volume in 1 second (FEV<sub>1</sub>) &lt;65% predicted) for 10 minutes according to two protocols given 1 week apart in random order. At visit A the patients received 400 µg salbutamol administered through a pMDI + spacer 20 minutes before induction while at visit B the premedication was supplemented by 1500 µg nebulised salbutamol inhaled throughout the induction procedure. Both the investigator and the patients were blind to the nebulised solution used. FEV<sub>1</sub> was recorded during sputum induction at 1, 3, 5, and 10 minutes. Sputum cell counts and histamine, tryptase and albumin levels in the supernatants were determined. <b>Results:</b> The mean (SE) maximal reduction in FEV<sub>1</sub> over the 10 minute period of sputum induction was 11.7 (2.8)% at visit A, which was significantly greater than at visit B (2.6 (1.2)%; mean difference 9% (95% CI 2.7 to 15.4), p&lt;0.01). Total and differential sputum cell counts as well as albumin, tryptase, and histamine levels did not differ between the two visits. <b>Conclusion:</b> The addition of inhaled salbutamol through an ultrasonic nebuliser markedly improves bronchoprotection against saline induced bronchoconstriction in patients with moderate to severe asthma undergoing sputum induction without affecting cell counts and inflammatory markers.
EXPERIMENTAL INTRADERMAL PNEUMOCOCCUS INFECTION IN RABBITS
Authors: K. Goodner
Journal: The Journal of Experimental Medicine (1928)

1. The intradermal inoculation of rabbits with Type I pneumococci gives rise to a local lesion and a definite sequence of other events that offer many analogies to pneumococcus lobar pneumonia, and for this reason the condition is being employed for a resurvey of the subject of pneumococcic infection. 2. This symptom-complex has been described in detail particularly as to the development of the local lesion, the temperature reaction, the bacteriemia, the white count, the persistence of organisms in the lesion, and the development of protective substances. 3. A certain number of animals recover from this condition after a definite course and by a process spoken of as crisis. The events correlated with this crisis have been described. 4. If sufficient antipneumococcic serum is given intravenously at 24 hours, prompt recovery can be brought about. The essential points of this recovery have been established. 5. Within 5 days after a single vaccination with dead pneumococci the normal rabbit develops an immunity to infection. If the rabbit is vaccinated and then infected within the period necessary for the development of this immunity the course of the consequent disease is shortened in proportion to the interval between vaccination and infection.
In vivo anti-cancer efficacy of magnetite nanocrystal - based system using locoregional hyperthermia combined with 5-fluorouracil chemotherapy
Authors: Tsung-Ju Li, Chih-Chia Huang, Pin-Wei Ruan, Kuei-Yi Chuang, Kuang-Jing Huang, Dar-Bin Shieh, Chen-Sheng Yeh
Journal: Biomaterials (2013)
The airway inflammatory response in allergic asthma and its relationship to clinical disease
Authors: Peter H. Howarth
Journal: Allergy (1995)

Endobronchial biopsy and lavage studies have revealed the presence of mast cell, eosinophil, T‐lymphocyte and epithelial cell activation in asthma, along with the structural changes of tissue eosinophil infiltration, loss of superficial columnar ciliated epithelial cells and enhanced collagen deposition in the laminar reticularis. As these cellular and structural changes underlie the clinical features of asthma, i.e., symptom expression, variable airflow obstruction and bronchial hyperresponsiveness, an understanding of their induction and regulation is essential to the understanding of the asthmatic process. The acute airway response to allergen has been studied by the technique of local endobronchial allergen challenge with direct airway sampling in asthma. These studies identify allergen‐mast cell interaction as the initial airway event, with mediator release inducing bronchoconstriction and enhancing vascular permeability. As preformed cytokines are present in mast cells, cytokine release from this cell population is likely to initiate the process of endothelial cell activation, with upregulation of cell adhesion molecules, and tissue cell recruitment. Subsequent cytokine elaboration from airway macrophages and T‐lymphocytes will perpetuate this response while in chronic clinical disease T‐lymphocytes, mast cells, matrix tissue, epithelial cells and eosinophils themselves are all likely to contribute to the cytokine pool within the airways and thus to the regulation of inflammatory cell migration and activation.
Plasma-Cell Myeloma
Authors: Frank W. Putnam
Journal: New England Journal of Medicine (1959)

THE biochemical alterations in various hematologic diseases have proved of great interest because of their frequent high degree of specificity and their ease of detection, diagnostic value and metabolic significance. Recent examples include the relation of specific protein factors to coagulation disorders and the discovery of the abnormal hemoglobins. Multiple myeloma represents the earliest known example in which a specific protein was related to a particular disease, but despite the long history of Bence-Jones protein, much remains to be clarified about the alterations in protein metabolism in myeloma. Part of the uncertainty arises from the increasing awareness that there is . . .
A Strong Effect of AT Mutational Bias on Amino Acid Usage in Buchnera is Mitigated at High-Expression Genes
Authors: Carmen Palacios, Jennifer J. Wernegreen
Journal: Molecular Biology and Evolution (2002)

The advent of full genome sequences provides exceptionally rich data sets to explore molecular and evolutionary mechanisms that shape divergence among and within genomes. In this study, we use multivariate analysis to determine the processes driving genome-wide patterns of amino usage in the obligate endosymbiont Buchnera and its close free-living relative Escherichia coli. In the AT-rich Buchnera genome, the primary source of variation in amino acid usage differentiates high- and low-expression genes. Amino acids of high-expression Buchnera genes are generally less aromatic and use relatively GC-rich codons, suggesting that selection against aromatic amino acids and against amino acids with AT-rich codons is stronger in high-expression genes. Selection to maintain hydrophobic amino acids in integral membrane proteins is a primary factor driving protein evolution in E. coli but is a secondary factor in Buchnera. In E. coli, gene expression is a secondary force driving amino acid usage, and a correlation with tRNA abundance suggests that translational selection contributes to this effect. Although this and previous studies demonstrate that AT mutational bias and genetic drift influence amino acid usage in Buchnera, this genome-wide analysis argues that selection is sufficient to affect the amino acid content of proteins with different expression and hydropathy levels.
127. Modulation of Adenoviral Vector Transduction by Hyaluronan and CD44 In Vivo
Authors: Joshua N. Mallam, Saumya Chaudhuri, Patricia Chevez-Barrios, Lalita Wadhwa, Mary Y. Hurwitz, Richard L. Hurwitz
Journal: Molecular Therapy (2006)

Adenoviral vectors have the ability to deliver transgenes to a broad spectrum of dividing and non-dividing cells. Ocular vitreous enhances transgene expression when cells are transduced with either adenovirus serotype 5 vectors (AdV5) or chimeric adenovirus serotype 5 vectors containing a shorter/shaft knob structure derived from adenovirus serotype 35 vectors (AdV5F35). Hyaluronan, a large polysaccharide found in extracellular matrix and intracellular and pericellular locations including vitreous, is at least partially responsible for this enhancement. Adenoviral transduction in Jurkat cells, a cell line that does not bind hyaluronan, is not enhanced by hyaluronan; however, when the cells are engineered to express the hyaluronan receptor CD44, enhancement of transgene expression in the presence of hyaluronan occurs. The enhancement of transgene expression in the presence of hyaluronan is independent of fiber/receptor interactions and occurs without increasing the number of viral particles bound to the cell. KM114, an antibody that blocks hyaluronan binding to murine CD44, prevents AdV5 transduction of murine epithelial (EpH4) cells in vitro. Pretreatment of murine conjunctiva with KM114 antibody but not an isotype-matched control antibody prevents AdV5 transduction of murine conjunctiva in vivo. Hyaluronan interaction with its receptor may provide a target for modulating adenoviral transduction or infection.
The Effect of Rosuvastatin on Platelet-Leukocyte Interactions in the Setting of Acute Coronary Syndrome
Authors: Travis R. Sexton, Eric L. Wallace, Tracy E. Macaulay, Richard J. Charnigo, Virgilio Evangelista, Charles L. Campbell, Alison L. Bailey, Susan S. Smyth
Journal: Journal of the American College of Cardiology (2015)
Lichen planus and dyslipidaemia: a case-control study
Authors: J. Dreiher, J. Shapiro, A.D. Cohen
Journal: British Journal of Dermatology (2009)

Previous reports have demonstrated an association between psoriasis and dyslipidaemia.As lichen planus (LP) is also a chronic inflammatory disorder, we investigated the association between LP and dyslipidaemia in Israel.A case-control study was performed utilizing the database of Clalit Health Services, a large healthcare provider organization in Israel. Patients aged 20-79 years who were diagnosed as having LP were compared with a sample of enrollees without LP regarding the prevalence of dyslipidaemia. Data on other health-related lifestyle factors and comorbidities were collected.The study included 1477 patients with LP and 2856 controls without LP. The prevalence of dyslipidaemia was significantly higher in patients with LP (42.5% vs. 37.8%, P = 0.003; odds ratio, OR 1.21, 95% confidence interval, [CI]: 1.06-1.38). A multivariate logistic regression model demonstrated that LP was significantly associated with dyslipidaemia even after controlling for confounders, including age, sex, smoking, hypothyroidism, diabetes, hypertension, socioeconomic status and obesity (multivariate OR 1.34, 95% CI: 1.14-1.57, P < 0.001).In the present study, LP was found to be associated with dyslipidaemia.
Unethical Trials of Interventions to Reduce Perinatal Transmission of the Human Immunodeficiency Virus in Developing Countries
Authors: P Lurie, S M Wolfe
Journal: New England Journal of Medicine (1997)

It was published almost 3 years ago that zidovudine administered orally to HIV-infected pregnant women, intravenously during labor, and later administered to newborn infants reduces the incidence of HIV infection in infants by two-thirds. This regimen, known as the ACTG 076 regimen and capable of saving the life of one of every seven infants born to HIV-infected women, subsequently became the standard of care in the US. However, the high cost of zidovudine and the ACTG 076 regimen impedes their use in developing countries. A regimen as effective but less expensive than ACTG 076 is therefore highly desirable in countries worldwide, but especially in developing countries. The authors oppose the use of placebo-controlled trials as unethical in the search for alternative antiretroviral drug regimens to prevent the perinatal transmission of HIV. 15 trials in developing countries are identified in which some or all of the participants are not being provided with antiretroviral drugs. Those studies violate recent guidelines designed specifically to address ethical issues regarding studies in developing countries. An urgent need exists to develop and adhere to a universally recognized code of ethics for medical research upon human subjects.
Aortic Arch Reconstruction by Transluminally Placed Endovascular Branched Stent Graft
Authors: K. Inoue, H. Hosokawa, T. Iwase, M. Sato, Y. Yoshida, K. Ueno, A. Tsubokawa, T. Tanaka, S. Tamaki, T. Suzuki
Journal: Circulation (1999)

Recently, thoracic aortic stent grafting has emerged as an alternative therapeutic modality for patients with thoracic aortic aneurysms and aortic dissections. However, its application has been limited to descending thoracic aortic aneurysms distal to the aortic arch. We report our initial clinical experience of endovascular branched stent graft repair for aortic arch aneurysms.Endovascular grafting with Inoue branched stent grafts was attempted for 15 patients with thoracic aortic aneurysms and aortic dissections under local anesthesia (n=14) or general anesthesia (n=1). Single-branched stent grafts were used in 14 patients, and a triple-branched stent graft in one. The branched stent grafts were delivered through a 22F or a 24F sheath under fluoroscopic guidance and implanted across the aneurysmal aortic arch. In 2 patients, the single-branched stent graft did not pass through the 22F sheath used. Complete thrombosis of the aneurysm was ultimately achieved in 11 patients (73%). Of 4 persistent leaks, 1 minor leak spontaneously thrombosed and 1 major leak was successfully treated by additional straight stent graft placement. In 1 patient, the right external iliac artery ruptured during the withdrawal of the sheath and was successfully repaired by the implantation of a straight stent graft. One patient with severe stenosis of the aortic graft section was successfully managed by additional stent deployment. Peripheral microembolization to a toe occurred in 1 patient, and cerebral infarction occurred in 1 other patient. Two patients who had failed to receive endovascular stent grafts died during an average follow-up of 12.6 months, 1 of pneumonia and the other of rupture of a concomitant abdominal aortic aneurysm.This report demonstrates the technical feasibility of endovascular branched stent graft repair for aneurysms located at the aortic arch. Careful, longer follow-up and further extensive clinical trials are awaited toward establishing this technique as a recommendable alternative to surgical treatment of thoracic aortic aneurysms.
Aspirin Attenuates Cytomegalovirus Infectivity and Gene Expression Mediated by Cyclooxygenase-2 in Coronary Artery Smooth Muscle Cells
Authors: Edith Speir, Zu-Xi Yu, Victor J. Ferrans, Eng-Shang Huang, Stephen E. Epstein
Journal: Circulation Research (1998)

Human cytomegalovirus (CMV) infection of smooth muscle cells generates reactive oxygen species (ROS) and thereby activates nuclear factor kappaB (NFkappaB), which causes expression of viral and cellular genes involved in immune and inflammatory responses. These changes could account for the mounting evidence suggesting that CMV may contribute causally to restenosis and atherosclerosis. We found that CMV induces ROS, at least partly, through a cyclooxygenase-2 (COX-2)-dependent pathway. Moreover, the viral immediate-early (IE) gene products, IE72 and IE84, have the capacity to transactivate the COX-2 promoter. Aspirin and indomethacin, both cyclooxygenase inhibitors as well as direct ROS scavengers, reduce CMV-induced ROS, probably through both of these activities. Sodium salicylate also has antiviral effects as the result of its potent antioxidant properties. Furthermore, by reducing ROS, aspirin and sodium salicylate inhibit CMV-induced NFkappaB activation, the ability of IE72 to transactivate its promoter, CMV IE gene expression after infection of SMCs, and CMV replication in SMCs. This is the first time aspirin has been shown to have antiviral effects. Thus, it is possible that aspirin has previously unrecognized therapeutic effects in various clinical situations, such as in viral infections (when used as an antipyretic agent) and in atherosclerosis (when used as an antiplatelet agent).