tbuckley/cabot-search huggingface dataset:
Prolonged B-cell depletion following rituximab therapy in systemic lupus erythematosus: a report of two cases
Authors: T Y-T Lu, T Jonsdottir, R F van Vollenhoven, D A Isenberg
Journal: Annals of the Rheumatic Diseases (2008)

Rituximab, a chimeric monoclonal antibody against the B-lymphocyte marker CD 20, has been previously used in open studies in the treatment of patients with systemic lupus erythematosus (SLE), with some success.1 2 Its therapeutic effect is attributed to the profound depletion of native and autoimmune B cells. The initial period of depletion has been reported to last for about 6 months, followed by a repopulation of peripheral B cells 9–12 months after treatment in most cases. We report two cases of prolonged B-cell depletion of 7 and 5 years’ duration, respectively, after a single course of rituximab treatment in two patients with SLE.

A 42-year-old woman with anti-SSA and anti-RNP positive SLE was initially referred to the Centre for Rheumatology Research, University College of London in 1995 for management of persistent fatigue, polyarthritis, Raynaud’s phenomenon and pleurisy. Despite treatment with various immunosuppressive agents, her disease remained clinically and serologically active (table 1). In September 2000 the patient underwent treatment with a single course of rituximab …
US doctors are judged more on bedside manner than effectiveness of care, survey finds
Authors: M. McCarthy
Journal: BMJ (2014)

When assessing a doctor, people tend to focus more on personality and the quality of their relationship with the doctor than on the effectiveness of the care provided, a new US survey has found.1

The survey was conducted by the Associated Press and the NORC Center for Public Affairs Research at the University of Chicago and funded by the Robert Wood Johnson Foundation. It sought to find out what people considered important when choosing a doctor and what resources they used to make their decision. A total of 1002 adults aged over 18 participated in the survey, and the overall margin of error was plus or minus four …
Alopecia universalis treated with bone morphogenetic protein?
Authors: K.S. Leslie, S.N. Shah, C. Darrah, A. Cooper, A. Valentin-Opran, A.D. Patel, S.T. Donell
Journal: British Journal of Dermatology (2005)

Sir, A 21‐year‐old man presented to the Dermatology Department at Norfolk & Norwich University Hospital in March 2004 with alopecia universalis (AU). He had first noticed patches of scalp hair loss 2 years previously. This had been rapidly progressive and within 6 months he had AU. His past medical history included asthma and childhood eczema, his maternal grandmother and one cousin both having had alopecia areata. Full blood count, urea and electrolytes, and liver function tests were normal and antinuclear factor was negative. One month later, he sustained a closed fracture of his left tibia while playing football. The fracture was fixed with a locked, reamed Russell–Taylor intramedullary tibial nail. Six days later, the patient consented to participate in a phase 1 trial using recombinant human bone morphogenetic protein‐2 (rhBMP‐2) with a new calcium phosphate matrix carrier (Wyeth Genetic/Research Institute, Cambridge, MA, U.S.A.). The closed tibial fracture was injected with rhBMP‐2 in a calcium phosphate matrix and he was subsequently discharged from hospital. Six weeks later, the patient noticed hair regrowth initially on his scalp. This became more extensive with hair returning to eyebrows, axillae, arms and pubic area. Hair regrowth was maintained for 6 months following the treatment with rhBMP‐2. Subsequently, he relapsed with the AU returning. His tibial fracture has healed without other complications.
Abstract LB-503: Pharmacological inhibition of microglia leads to increased survival in a murine model of glioblastoma multiforme in conjunction with ionizing radiation
Authors: Ian S. Miller, Sebastien Didier, David W. Murray, Magimairajan Issaivanan, Salvatore J. Coniglio, Jeffrey E. Segall, Yousef Al-Abed, Marc Symons
Journal: Cancer Research (2012)

Abstract Glioblastoma multiforme (GBM) is the most malignant and lethal form of astrocytoma. GBM patients have a median survival time of approximately one year and therefore it is essential to identify novel targets and effective therapies. There is mounting evidence that microglia (specialized brain-resident macrophages) play a significant role in the development and progression of GBM tumors. We have established a microglia-glioma cell co-culture system consisting of normal microglia from C57Bl/6J mice and syngeneic GL261 glioma cells. We have demonstrated that microglia strongly stimulate the invasive behavior of GL261 cells in this system. Our preliminary data also indicate that the microglia significantly stimulate GL261 cell proliferation and resistance to ionizing radiation (IR) in these conditions. In a search for small molecule inhibitors that block the stimulatory effects of microglia on glioma cells, we have examined CNI-1493, a drug that is known to selectively interfere with macrophage function. We found that CNI-1493 potently inhibits microglia-stimulated GL261 invasion. We also examined the effect of intracranially administered CNI-1493 on orthotopic GL261 tumors in the presence or absence of fractionated whole brain irradiation (10 Gy total). We found that although CNI-1493 only has a marginal benefit in the absence of IR, it strongly stimulates animal survival in combination with IR: whereas IR treatment increases survival by 10 days, IR in combination with CNI-1493 treatment extends survival beyond 40 days. In conclusion, our observations support the notion that pharmacological targeting of microglia may be beneficial as adjuvant therapy in conjunction with ionizing radiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-503. doi:1538-7445.AM2012-LB-503
MEDICINE IN THE WAR: A RETROSPECTIVE SKETCH
Authors: W. Herringham
Journal: BMJ (1919)

WVHEN one looks back upon the nearly five years of war certain recollections stand out, certain ex- periences of disease and its treatment seem more important than others.CEREBRO-SPINAL FEVER.In the first winter, early in January, we saw our first cases of cerebro-spinal fever; few out there had ever seen it in the epidemic form.The British out- breaks had been few and slight, and had occurred at a distance from London.It was a new thing to find strong young men affected, and as we saw more cases the horror of the disease, its unaccountability, our powerlessness to cure it, our inability even to predict its course from da,y to day, affected us stronigly.Sisters were usually changed every fortnight; the disease preyed on their spirits if they nursed it longer.It was thought that the Canadians brought it with them.Their first troops landed just before Christ- mas, 1914.But that is doubtful.Cases arose singly from all down the whole of the front.We hardly ever saw two from the same unit, nior could any contact withi a previous case be slhown.The cases were most distressing to witness.They suffered greatly from pain, were usually unconscious or stupid most of their time, were fed with difficulty, and kept clean withi more difficulty still, while erpes and
Abstract LB-340: Mechanism of bevacizumab internalization and fate by brain endothelial cells .
Authors: Gaelle M. Muller-Greven, Cathleen Carlin, Candece L. Gladson
Journal: Cancer Research (2013)

Abstract Antiangiogenic immunotherapy shows great promise for treatment of malignancies, including cancer. Bevacizumab is a humanized monoclonal antibody that inactivates vascular endothelial growth factor-A (VEGF-A), thereby inhibiting angiogenesis. It has received FDA approval for patients with recurrent glioblastoma (GBM); however, more than 30% of patients are non-responsive. The internalization and fate of bevacizumab in endothelial cells (ECs) may play a critical role in the response to therapy, i.e., bevacizumab may be degraded, recycled to the vessel lumen, or transcytosed to the sub-basal EC where tumor cell VEGF-A is found. We examined the internalization of bevacizumab by normal brain ECs in different conditions and found that internalization increased in a time-dependent manner (30 min - 24 hrs). Epidermal growth factor (EGF) stimulated internalization, suggesting bevacizumab enters the cells by an endocytic pathway that is induced by growth factors, such as macropinocytosis. Also, internalized bevacizumab was compartmentalized into vesicles that in part co-localized with the EGF receptor. Treatment with Amiloride (inhibitor of macropinocytosis) decreased the number of bevacizumab-containing vesicles per cell, suggesting macropinocytosis may be one mechanism of internalization. Treatment with Bafilomycin A1 (inhibitor of lysosomal acidification) caused accumulation of bevacizumab, suggesting one fate is lysosomal degradation. Ongoing experiments will determine the endocytic compartment(s) containing bevacizumab, its trafficking, and whether it is transcytosed across normal brain and tumor-associated ECs. Understanding the mechanism of internalization and trafficking of bevacizumab in brain ECs will positively impact the design and modification of monoclonal antibody therapy for GBM patients and for other cancers. Citation Format: Gaelle M. Muller-Greven, Cathleen Carlin, Candece L. Gladson. Mechanism of bevacizumab internalization and fate by brain endothelial cells . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-340. doi:10.1158/1538-7445.AM2013-LB-340
CLINICAL BENEFITS OF GLYCOPROTEIN IIB/IIA INHIBITORS IN PATIENTS WITH ACUTE ST-ELEVATION MYOCARDIAL INFARCTION PRETREATED WITH CLOPIDOGREL BEFORE PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Doo Sun Sim, Youngkeun Ahn, Myung Ho Jeong, Young Jo Kim, Sung Chull Chae, Taek Jong Hong, In Whan Seong, Jei Keon Chae, Chong Jin Kim, Myeong Chan Cho, Ki Bae Seung, Seung Jung Park
Journal: Journal of the American College of Cardiology (2010)
FDA approves test for prostatic cancer
Authors: F B Charatan
Journal: BMJ (1994)

The US Food and Drug Administration (FDA) last month approved a blood test for prostate specific antigen as an early test for prostatic cancer in men over 50 when combined with digital rectal examination. The test was first approved by the FDA in 1986 to monitor progress in patients already diagnosed as having prostatic cancer. The current approval expands the use to include helping to diagnose the disease.

“This test - used with other procedures - can help detect those men at risk of prostatic cancer early on, when more treatment options are available,” said FDA commissioner Dr David Kessler, “but for the test …
Torsades de pointes upon fluconazole administration in a patient with acute myeloblastic leukemia
Authors: Hiro Tatetsu, Norio Asou, Miki Nakamura, Nobuyoshi Hanaoka, Fumihiko Matsuno, Kentaro Horikawa, Hiroaki Mitsuya
Journal: American Journal of Hematology (2006)

Abstract Prolonged QT syndrome often causes torsades de pointes (Tdp), a potentially lethal arrhythmia. A 55‐year‐old woman with M4Eo who was receiving consolidation chemotherapy had an episode of prolonged QT and Tdp following fluconazole (FCZ) administration. Intravenous supplementation of magnesium sulfate and multiple attempts at electrocardioversion led to recovery from the arrhythmia. FCZ appears to contribute to the development of QT prolongation, in particular with low concentrations of serum potassium or magnesium. Although mechanisms of Tdp development in patients with QT prolongation remain to be determined, it is possible that FCZ administration leads to manifestation of Tdp. Special cautions should be exercised upon the emergence of QT prolongation following FCZ administration. Am. J. Hematol. 81:366–369, 2006. © 2006 Wiley‐Liss, Inc.
Letter: Treatment of clonorchiasis.
Authors: W H Jopling
Journal: BMJ (1975)

discontinuation of the therapy and the pat- ient with intractable diarrhoea relapsed while on therapy and died.No response was observed in the patient with acute myeloblastic leukaemia after two months of continuous therapy.No adverse or side effects were noted.On the basis of this limited experience we believe that loperamide is a valuable adjunct to the management of life-threatening diarr- hoea of varying aetiology and that further studies are warranted in larger series of pat- ients.-Weare, etc.,
Treatment of tennis elbow: the evidence
Authors: Simon Mellor
Journal: BMJ (2003)

Tennis elbow is an overuse syndrome most prevalent in the fourth decade. Predominant symptoms of lateral elbow pain on gripping or resisted wrist dorsiflexion result in many consultations in primary care and days lost from work. Most patients will recover within a year.1 This should be remembered when considering the results of this Clinical Evidence extract, which is based on a Cochrane review of the subject.

The review identified randomised controlled trials (RCTs) of numerous treatment modalities for lateral elbow pain. The risks of blindly accepting “evidence based medicine” are known,2 and there are some limitations within …
Biopersistence of the mineral matter of coal mine dusts in silicotic human lungs: is there a preferential release of iron?
Authors: J L Tourmann, R Kaufmann
Journal: Environmental Health Perspectives (1994)

Toxic potency of quartz-containing dusts, including coal mine dusts, is usually inhibited by protective clay mineral layers on the surface of quartz particles. This investigation of 11 dusts recovered from lungs of coal miners with different silicosis grade shows that such layers persist during long-term contact with human lung tissues. On the other hand, the results suggest that an apparently preferential release of iron occurred in lungs with massive fibrosis. These preliminary results support the hypothesis of an iron-related harmfulness of coal mine dusts.
Recurrent Erysipelas and Epidermophytosis Pedis
Authors: Leonard D. Grayson
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Concerning the Question and Answer on "Recurrent Erysipelas" (<i>JAMA</i><b>188</b>:333 [April 20] 1964), the consultant omitted one factor. In many cases of recurrent erysipelas or cellulitis of the legs, one should look for foci of epidermophytosis pedis. Many times the fissuring and maceration of interdigital spaces by fungus organisms open a portal for bacterial organisms to enter and set up a cellulitis. I think every patient with recurrent cellulitis of the legs should be investigated as to potential athlete's foot and the latter should be vigorously treated to prevent further secondary infection.
Abstract 3197: Differential senescent and apoptotic responses to HDM2 antagonism in p53 wild-type human solid cancer cells
Authors: Suxing Liu, Yinghui Lin, Asra Mirza, Cynthia Seidel-Dugan, Yaolin Wang, Daniel J. Hicklin, W. Robert Bishop
Journal: Cancer Research (2010)

Abstract The p53 protein is a primary regulator of the cellular response to DNA damage and is a critical tumor suppressor. Restoration of p53 function in soft tissue sarcomas and hepatocellular carcinomas in mice was reported to cause tumor regressions associated with cellular senescence. These findings led us to investigate the ability of HDM2 antagonism to induce cellular senescence as well as apoptosis in a broad panel of wild-type p53 cell lines derived from human solid tumors. Here we report that the small molecule HDM2 antagonist Nutlin-3a activates p53 and induces cellular senescence in 10 out of 12 human tumor cell lines tested. Only two of these tumor cell lines also demonstrated an apoptotic response to Nutlin-3a. The kinetics of senescence induction by Nutlin-3a was slower than that of the apoptotic response, suggesting that apoptosis may be the first-line response, while senescence may be triggered as a back-up program when the apoptotic response fails to execute. A distinct expression profile of p53 target genes associated with apoptosis, cell cycle and senescence was observed and corresponded with the distinct phenotypic responses in this panel of cell lines. Depletion of p53 protein expression using shRNA blocked cellular senescence induced by HDM2 antagonism demonstrating the critical role for p53 in this process. The pronounced effects of Nutlin-3a on senescence in multiple wild-type p53 tumor cell lines underscores the unique anti-tumor mechanisms of HDM2 antagonism. This approach may provide a novel therapeutic strategy for future cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3197.
Safety of cetirizine in infants 6 to 11 months of age: A randomized, double-blind, placebo-controlled study
Authors: F.Estelle R. Simons, Peter Silas, Jay M. Portnoy, Joseph Catuogno, Douglass Chapman, Abayomi O. Olufade, None PharmD
Journal: Journal of Allergy and Clinical Immunology (2003)
Renal insufficiency associated with excessive lead exposure.
Authors: B C Campbell, A D Beattie, M R Moore, A Goldberg, A G Reid
Journal: BMJ (1977)

Water lead concentrations were measured in 970 households throughout Scotland. Blood lead concentrations were measured in 283 people living in houses with water lead levels of over 0-48 mumol/l (100 mug/l). A highly significant correlation was found between lead concentrations in water and blood. Raised blood lead concentrations were associated with renal insufficiency, reflected in raised serum urea concentrations, and with hyperuricaemia, although there was no evidence of clinical disease in any of the affected people. This is further evidence that excessive lead in domestic water supplies has a harmful effect on the community's health.
Functional Lymphangiectasia of the Duodenal Mucosa
Authors: J. Femppel, G. Lux, B. Kaduk, W. Roesch
Journal: Endoscopy (1978)

Tiny millet-like prominent villi with dilated lymphatics may be part of a food-induced functional lymphangiectasia. Peroral olive oil load causes diffuse transient lymphangiectasia, the gross aspect, histological findings and electron-microscopy of which is described in detail.
Cardiac ischemia causes inhibition of the Na/K ATPase by a labile cytosolic compound whose production is linked to oxidant stress
Authors: W Fuller
Journal: Cardiovascular Research (2003)

Objective: Intracellular Na rises rapidly during cardiac ischemia and this has been attributed to the combination of increased influx of Na via sodium–proton exchange and decreased activity of the Na/K ATPase. The aim of these studies was to investigate the effects of ischemia on Na/K ATPase function in Langendorff-perfused rat hearts. Methods: Na/K ATPase activity was determined by measuring ouabain-sensitive phosphate generation from ATP by cardiac homogenates. Results: Global ischemia (15 and 30 min) caused a substantial reduction in Na/K ATPase function despite high substrate availability in the assay. When sarcolemmal membranes were purified away from the cytosol a profound activation of the Na/K ATPase was revealed following ischemia, indicating that the inhibition was due to the cytosolic accumulation of an inhibitor of Na/K ATPase. The half-life of the inhibitor in cardiac homogenates was 10±3 min at room temperature. Perfusion with the antioxidant MPG (1 mmol/l) reduced the accumulation of this inhibitor, however MPG was without effect on Na/K ATPase function when added directly to the Na/K ATPase activity assay. While the inhibitor reduced the activity of cardiac and brain forms of the Na/K ATPase in bioassay experiments, no effect was observed on the renal and skeletal muscle forms of the enzyme. Conclusions: An unstable cardiac and brain-specific inhibitor of the Na/K ATPase whose production is linked to oxidant stress, accumulates intracellularly during ischemia. Intracellular Na is a primary determinant of electro-mechanical recovery on reperfusion, so inhibition of the Na/K ATPase by this compound may be crucial in determining recovery from ischemia.
(11) Oesophageal strictures in cicatricial pemphigoid
Authors: J.N. Leonard, N. Stafford, I. Barrison, C.E.M. Griffiths, A.V. Powles, P. Wright, L. Fry
Journal: British Journal of Dermatology (1987)

Journal Article (11) Oesophageal strictures in cicatricial pemphigoid Get access J.N. Leonard, J.N. Leonard Department of Dermatology, Ear, Nose and Throat Search for other works by this author on: Oxford Academic Google Scholar N. Stafford, N. Stafford Department of Dermatology, Ear, Nose and Throat Search for other works by this author on: Oxford Academic Google Scholar I. Barrison, I. Barrison Department of Gastroenterology, St Mary's Hospital, London W2 Search for other works by this author on: Oxford Academic Google Scholar C.E.M. Griffiths, C.E.M. Griffiths Department of Dermatology, Ear, Nose and Throat Search for other works by this author on: Oxford Academic Google Scholar A.V. Powles, A.V. Powles Department of Dermatology, Ear, Nose and Throat Search for other works by this author on: Oxford Academic Google Scholar P. Wright, P. Wright The External Diseases Clinic, Moorfields Eye Hospital, London EC1 Search for other works by this author on: Oxford Academic Google Scholar L. Fry L. Fry Department of Dermatology, Ear, Nose and Throat Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue s32, 1 June 1987, Page 37, https://doi.org/10.1111/j.1365-2133.1987.tb12029.x Published: 01 June 1987
Abstract 1325: Profilin-1 overexpression downregulates phosphorylation of p27kip1 leading to its nuclear accumulation in breast cancer cells
Authors: Chang Jiang, William Veon, Partha Roy
Journal: Cancer Research (2014)

Abstract Profilin-1 is a ubiquitously expressed actin-binding protein that is downregulated in human breast cancer. Overexpression of profilin-1 in human breast cancer cells suppresses their tumorigenic potential. We had previously shown that profilin-1 overexpression elevates the expression level of p27kip1 leading to cell-cycle arrest in G1 phase. In the present work, we explore the underlying mechanism. Our studies showed that profilin-1-induced accumulation of p27kip1 in breast cancer cells occurs most dramatically in the nuclear compartment and this is due to impaired protein degradation. Consistent with these observations, we found that phosphorylation of p27kip1 at T187 (a prerequisite for p27kip1 degradation by SCF-Skp2 complex in the nucleus) and S10 (a post-translational event that promotes nuclear export of p27kip1) residues are both significantly inhibited by profilin-1 overexpression. Elevating profilin-1 level suppresses AKT activation, and hyper-activating AKT through overexpression of a constitutively active mutant relieves profilin-1-induced inhibition of T187 phosphorylation and elevation of p27kip1. These data demonstrate that profilin-1 can control the cellular level of p27kip1 in breast cancer cells through affecting its post-translational modification in an AKT-dependent pathway. These findings may provide mechanistic insights underlying the tumor-suppressive action of profilin-1. Citation Format: Chang Jiang, William Veon, Partha Roy. Profilin-1 overexpression downregulates phosphorylation of p27kip1 leading to its nuclear accumulation in breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1325. doi:10.1158/1538-7445.AM2014-1325