tbuckley/cabot-search huggingface dataset:
Myeloma-Associated Paraprotein Directed against the HIV-1 p24 Antigen in an HIV-1-Seropositive Patient
Authors: Robert J. Konrad, Larry J. Kricka, David Goodman, June Goldman, Leslie Silberstein
Journal: New England Journal of Medicine (1993)

The spectrum of hematologic and immunologic abnormalities in human immunodeficiency virus type 1 (HIV-1) infection is broad1,2. Although the incidence of B-cell-associated neoplasms is increased, relatively few cases of multiple myeloma have been described3,4. There are, however, reports of patients in whom serum paraproteins present as single or oligoclonal bands5–11. These paraproteins have previously been thought of as part of the exuberant polyclonal response to HIV-110,11. In this report, we describe an HIV-1-positive patient with myeloma whose IgG-κ paraprotein specifically recognized the HIV-1 p24 gag antigen. It is possible that an HIV-1 . . .
P130A novel angiotensin Type I receptor antagonist, Fimasartan, prevents doxorubicin-induced Cardiotoxicity in rats without altering anticancer effect
Authors: E-S Jeon, Sa Jang, SH Yoon, BK Lim
Journal: Cardiovascular Research (2014)

Aims: Cardiac toxicity is the most important complications associated with doxorubicin (DOX)-based chemotherapy. Angiotensin receptor blockers (ARB) have been reported to have organ-protective effects in heart failure and may be also effective in DOX-induced cardiomyopathy (DOX-CMP). We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, Fimasartan (Fima), in DOX-CMP.
18F-FDG Uptake Changes in Liver and Mediastinum During Chemotherapy in Patients With Diffuse Large B-cell Lymphoma
Authors: Luca Ceriani, Sergio Suriano, Teresa Ruberto, Emanuele Zucca, Luca Giovanella
Journal: Clinical Nuclear Medicine (2012)

The main objective of this study was to assess the intrasubject and intersubjects variability of 18F-FDG uptake in liver (LIV) and mediastinum (MBP) among patients with diffuse large B-cell lymphoma (DLBCL), treated with different chemotherapy regimens.Fifty patients with DLBCL who underwent 18F-FDG PET/CT scan at baseline, after a few cycles of therapy (interim PET) and on completion of therapy (final PET), were enrolled retrospectively. SUVmean and SUVmax values for LIV and MBP, their differences (LIV - MBP SUVmean and LIV - MBP SUVmax), and their changes were calculated, respectively.Liver uptake significantly increased in the interim in comparison with baseline and final PET, respectively, whereas MBP activity remained stable during chemotherapy. The intersubject variability of 18F-FDG uptake in LIV and MBP ranged from 20.2% to 25.4%.The variability of the LIV uptake during chemotherapy should be taken into account when this parameter is used to score the interim PET scan and to make decisions in defining response-adapted therapeutic strategies. Vice versa, the stability of MBP activity during therapy provides a more reliable benchmark for the response assessment.Finally, the intersubjects variability of both parameters should be considered when the visual evaluation of the interim PET is performed by point score models.
Abstract 5430: Docosahexaenoic acid attenuates glycolytic metabolism and the Warburg phenotype by targeting hypoxia inducible factor 1 alpha in breast cancer.
Authors: Michael Mouradian, Keith D. Kikawa, Ronald S. Pardini
Journal: Cancer Research (2013)

Abstract Dietary factors have been estimated to account for approximately 30-40 percent of cancer incidence and research has shown that high fat diets rich in n-3 polyunsaturated fatty acids (PUFAs) are associated with lower cancer occurrences, including breast cancer. The glycolytic switch, known as the Warburg Effect, is observed in many malignant models, which results in a unique metabolic shift in energy metabolism where tumor cells increase anaerobic glycolysis even in the presence of normal oxygen levels. In our laboratory, we have shown that the n-3 PUFA, docosahexaenoic acid (DHA; C22:6), significantly decreases total cellular ATP and the transcriptional activity and protein levels of hypoxia-inducible factor 1 alpha (HIF-1α), a major contributor to the Warburg phenotype. In this project, we set out to determine if DHA is responsible for attenuating the Warburg Effect through a HIF-1α-dependent mechanism. Alterations in glucose uptake and usage upon supplementation with DHA were examined in vitro in the breast cancer BT-474, MDA-MB-231, and non-transformed MCF-10A cell lines. Total glucose transporter 1 (GLUT 1) protein levels were determined in each cell line. No change was seen upon DHA supplementation in the MDA-MB-231 cell line, which may be due to overexpression of GLUT 1. However, GLUT 1 protein levels were significantly down in response to DHA treatment in the BT-474 cell line. We also observed significant decreases in glucose consumption through glycolysis and lactate production in the BT-474 and MDA-MB-231 cell lines upon DHA supplementation. However, no change was seen in the non-transformed cell line MCF-10A, suggesting that DHA is having anti-glucose-metabolism effects specifically on cancer cells, but not on non-transformed cells. Moreover, HIF-1α small interfering RNA (siRNA) experiments showed a similar trend in GLUT 1 expression and glycolytic capacity in the BT-474 and MDA-MB-231 cell lines, suggesting that DHA is exerting some of its anti-cancer effects through HIF-1α. Based on these findings, changes in glucose transporter expression and glucose usage likely contribute to the impaired growth and survival of malignant cell lines supplemented with DHA. Currently, therapies are being developed to target the Warburg Effect in the treatment of cancer and DHA could likely enhance such therapies. Citation Format: Michael Mouradian, Keith D. Kikawa, Ronald S. Pardini. Docosahexaenoic acid attenuates glycolytic metabolism and the Warburg phenotype by targeting hypoxia inducible factor 1 alpha in breast cancer. [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 5430. doi:10.1158/1538-7445.AM2013-5430
Abstract 1258: High-density protein lysate arrays: an essential tool in assessing antibody specificity for clinical applications
Authors: Dror I. Baruch, Donghui Ma, Youmin Shu, Zairen Sun, Wei-Wu He
Journal: Cancer Research (2012)

Abstract Antibodies for clinical applications require rigorous scrutiny qualifying them for diagnostics or therapeutic use. However, this is a lengthily and complicated process that provides only limited conformation. Protein microarrays are new tools that can determine the specificity and reactivity of Abs and help identifying their target in less than a day. We created a high-density protein array comprised from more than 10,000 over-expressed protein lysates made in human HEK293T cells. We tested more than 15 available antibodies to two cancer targets; the excision repair cross-complementation group 1 (ERCC1) and the receptor tyrosine kinase ERBB2 (Her2/neo). Our results demonstrated the ability of the lysate array in determining the specificity of antibodies with a single fast and easy assay. ERCC1 is a predictor of resistance to platinum based drugs and for poor prognosis in cancer. The commonly used anti ERCC1 antibody, mAb 8F1, is known to give non-specific cytoplasmic staining and to cross-react with an unknown protein of similar size. We tested 10 commercially available Abs to ERCC1 and identified four mono-specific ones (TrueMAb OriGene). Most of these specific Abs gave higher reactivity than clone 8F1. With this test we also identified a cytoplasmic protein of appropriate molecular weight that is cross-reacting with mAb 8F1. The above results were corroborated by WB analysis and IHC assays supporting the validity of this type of assays. We extended our tests to include anti ERBB2 Abs as this important biomarker is indicative for the use and response to the drug Herceptin. Our tests included mono and poly clonal antibodies and clone 4B5, a rabbit mAb currently used for IHC diagnostic. We found clone 4B5 to be reactive with two additional proteins besides ERBB2, one of them is ERBB4. We also tested a rabbit polyclonal anti ERBB2 serum and found it to be reactive with additional proteins unrelated to those recognized by mAb 4B5. Three out of the four mouse mAbs tested (TrueMAb OriGene) were determined to be specific. We submit that the over-expression protein lysate arrays can establish the reactivity and specificity of Abs and identify unknown targets. The speed and convenience of these assays make them an important tool in developing Abs for clinical use. 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 1258. doi:1538-7445.AM2012-1258
Knockout of Heregulin (HRG) Expression Reverts Paclitaxel-Resistance and Promotes Mesenchymal Epithelial Transition (MET) of Triple Negative Breast Cancer Cells.
Authors: J. Li, I. Espinoza, R. Lupu
Journal: Cancer Research (2009)

Abstract The growth factor Heregulin (HRG) is expressed in about 30% of breast cancer tumors, and induces tumorigenicity and metastasis of breast cancer cells. We have demonstrated previously that HRG overexpression renders breast cancer cells resistance to the microtubule-interfering agent Taxol, a drug of choice for the treatment of metastatic breast cancer. The mechanism by which HRG induces Taxol resistance is largely unknown. It is also known that triple negative breast cancer tumors do express high levels of HRG and unfortunately they do not respond to HRG. Our studies were aimed at targeting HRG with the goal of achieving a therapeutic target as well as restoring the response to Taxol, while preventing the formation of metastasis. Thus, we knocked-down HRG expression in three different breast cancer cell lines: MDA-MB-23, HS578T and BT549. Our data demonstrates that HRG expression is an absolute requirement for the anchorage-independent growth for triple negative breast cancer cells, since none of the breast cancer cells MDA-MB-231, HS578T and BT549 stable expressing the silencing (shRNA) for HRG, were capable of forming colony in soft agar. Furthermore, these cells, not only no longer were not anchorage-independent were no longer resistant to Taxol, to the contrary the shRNA/HRG cells were exquisitely sensitive to Taxol, to induce growth inhibition and apoptosis. More importantly, we observed that the disorganized structured observed in 3D matrigel culture observed for triple negative cells, was completely abolished once HRG was knockdown and a very organized structure. These characteristics resembled an EMT (epithelial-mesenchymal epithelial transition (MET). This should be deemed a potential target in developing therapies for triple negative breast carcinomas. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1142.
Accuracy of the Hyperband EUS in Superficial Neoplasia in Barrett''s Esophagus
Authors: K Wang, G Prasad, L Lutzke, S Papenfuss, L Borkenhagen
Journal: Endoscopy (2006)

Rationale: Routine radial EUS has been felt to be inadequate to stage mucosal and submucosal neoplasia in Barrett's Esophagus (BE). The newly developed hyperband (Olympus GF-UM 160) echoendoscope uses composite piezo-electric material provides broadband scanning with four different frequencies, resulting in high-resolution ultrasound images. The yield and accuracy of this instrument has not been reported previously in superficial neoplasia in Barrett's esophagus. Aim: To assess the accuracy of the GF-UM 160 echoendoscope in the staging of neoplastic lesions arising in BE using endoscopic resection (EMR) specimens as the gold standard. Methods: A prospectively collected cohort of 33 consecutive patients with HGD/Carcinoma and BE seen at the Mayo Barrett's Unit was studied. All patients underwent a standard protocol assessment with EGD, 4 quadrant biopsies every centimeter. Visible lesions were resected using either the Olympus EMR kit (88%) or the Wilson-Cook Duette Multi-Band mucosectomy system (12%). Staging was performed prior to resection in all patients using the Olympus GF-UM 160 instrument by a single experienced endosonographer. Results: 25 (76%) were males. The mean age was 68 years (SEM 1.7). The pre-procedure diagnosis was HGD in 24 patients (73%) and cancer in the remainder (27%). The median BE segment length was 2.5cm (IQR 1–6). 73% of patients had a visible nodule/mucosal irregularity on EGD. Staging with EUS revealed no abnormality (uT0) in 88%, uT1 disease in 9% (mucosal disease in 1 patient and submucosal in 2 patients), and uT2 disease in 3%. No patients had metastatic lymph nodes. 58% of patients underwent 1 EMR and the remainder had 2–6 EMRs. EMR pathology revealed carcinoma in 5 patients (submucosal in 4; mucosal in 1). 43% of the resected lesions contained only HGD. 3 patients with submucosally invasive cancer underwent esophagectomy; one with mucosal cancer was treated with EMR alone. The patient with T2 cancer elected to pursue comfort care only. Discussion: The sensitivity of Hyperband EUS in detecting cancers was 80% with a specificity of 100%. EUS hyperband staging of cancers in terms of mucosal/submucosal extent correlated well with staging on histopathology. Hyperband EUS accurately predicted EMR resectability of lesions in all patients.
Biliary Sludge as a Cause of Acute Pancreatitis
Authors: S P Lee, J F Nicholls, H Z Park
Journal: New England Journal of Medicine (1992)

In about 20 to 40 percent of cases of acute pancreatitis, no cause can be found, and these are labeled idiopathic. In this study, we sought to determine the frequency with which patients with acute idiopathic pancreatitis have biliary sludge, a suspension of cholesterol monohydrate crystals or calcium bilirubinate granules that is found predominantly in the gallbladder.
OP29 * PRIMARY BRAIN LYMPHOMA: THE REALITY FOR PATIENTS
Authors: J. Lemberger, A. Hindley
Journal: Neuro-Oncology (2014)

INTRODUCTION: Brain lymphoma is known to be more common in immuno-compromised patients. There have been no phase III trials comparing treatment. The literature implies that chemotherapy is the treatment of choice, but in practice many patients do not receive this, or any treatment. We aimed to determine the outlook for such patients treated at Royal Preston Hospital. METHOD: A retrospective review of casenotes of patients treated by one clinician (AH) over a 13 year period obtained from neuropathology and radiotherapy databases. Kaplan-Myer survival curves were generated using SPSS software. RESULTS: 40 Patients were studied. The following symptoms were recorded at presentation;- confusion in 40%, headache in 28%, falls in 22%, weakness in 18%, visual problems in 12%, memory loss in 10%, incontinence in 10%, dysphasia in 8%, impotence in 2%. 35% had multifocal disease, 5% had vitreous involvement and 7% did not undergo biopsy. 38% of patients received radiotherapy alone. 32% received primary chemotherapy, median survivals were 11.5 and 18 months respectively. Untreated patients (30%) had a median survival of 1.5 months. Patients who received radiotherapy alone had a mean age of 69 and a mean WHO score of 1.9;- those who received chemotherapy had a mean age of 53 years and a mean WHO score of 0.9. 31% of patients died during chemotherapy. 54% of patients who had radiotherapy exhibited symptoms of neurotoxicity. 61% of these patients were over 60 years old. CONCLUSION: Primary brain lymphoma is rapidly fatal if untreated. Chemotherapy +/- radiotherapy produces the best survival, but often leads to toxicity which may be fatal. Radiotherapy alone produces long survival but at the cost of neurotoxicity.
Predictive and mechanistic factors of tyrosine kinase inhibitor (TKI)-induced macrocytosis.
Authors: P. Hamberg, R. Dulfer, A. Oosten, M. M. von Lindern, I. A. Boere, L. van Doorn, E. V. Meerten, S. Sleijfer, J. Verweij, W. H. Kruit
Journal: Journal of Clinical Oncology (2010)

3052 Background: Macrocytosis (MCV >100fL) is a known toxicity of some TKIs, but its exact incidence, course and pathogenesis are unknown. Methods: In a longitudinal study patients (pts) with baseline MCV ≤ 100 fL, treated with sunitinib (Su), sorafenib (So) or imatinib (I) for at least 3 months were assessed for possible predictive factors and followed for a maximum of 1 year after start of therapy. Effects of Su, So, and I on erythroid cell morphology were tested in erythroblast in vitro cultures to elucidate its pathogenesis. Results: In 173 pts Su and I induced macrocytosis in 50% and 25% of the pts. Additionally, MCV increased > 10fL, while remaining ≤100fL, in 20% and 31% of pts. Su and I yielded a significant MCV increase of 12 and 10 fL, respectively (both p<0.00005). So did not affect MCV at all. Macrocytosis, if occurring, was observed at 4 months (median), and reached plateau thereafter. Macrocytosis was preceded by an elevation of red cell distribution width (RDW) during the first 4 months (median 18% at 4 months, normal 12-16%), thereafter RDW normalized. In 46% of pts with normal baseline hemoglobin, hemoglobin remained normal despite developing macrocytosis. No consistent change in reticulocyte count was observed. Serial vitamin B12 testing, in 38 pts with macrocytosis, revealed only one pt with a deficiency. Upon substitution, MCV of this pt decreased but remained >100fL. Folic acid deficiency was not observed. Age, gender, liver and renal function, leucocytes, thrombocytes were not predictive for the occurrence of macrocytosis.In vitro, in erythroblast cultures, all TKIs acted directly on erythroid development yielding macrocytosis. I promoted differentiation, whereas Su and So delayed differentiation. Conclusions: Su and I induce macrocytosis preceded by an increased RDW, in a large proportion of pts, while So lacks this effect. RDW-normalization once MCV plateaus, points towards equal enlargement of the entire erythrocyte population. Although the various TKIs had opposite effects on in vitro erythroid maturation, it is likely that the mechanism of macrocytosis is a direct effect of TKIs on the erythroid progenitor resulting in erythrocyte enlargement. No significant financial relationships to disclose.
Management of Hepatocerebral Intoxication
Authors: Robert T. Manning, Mahlon Delp
Journal: New England Journal of Medicine (1958)

THERAPY for patients with actual or impending hepatic coma has been unsatisfactory in the majority of cases, being hindered by a lack of knowledge regarding the fundamental alterations of metabolic processes that occur in this syndrome of combined liver failure and Central-nervous-system dysfunction. Recently, considerable evidence has accumulated that defective nitrogen metabolism is intimately involved in the genesis of hepatic coma1 2 3 4 5 6 7; such a defect is associated with the diminished removal of ammonia as urea by the liver.Progressive mental changes, deterioration in the state of consciousness, variable neurologic deficit, flapping tremor, fetor hepaticus, elevated blood ammonia and electroencephalographic abnormalities . . .
AB0919 Influence of enthesitis pain on ankylosing spondylitis disease activity score (ASDAS)
Authors: W. Hamdi, M.M. Ghannouchi, I. Zouch, M.M. Kchir
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing spondylitis disease activity score (ASDAS) is a new disease activity index that didn’t include enthesitis pain assessment. Correlation of ASDAS with enthesitis pain scores in patients hasn’t be investigated previously. <h3>Objectives</h3> To investigate correlation between the ASDAS and enthesitis pain assessed by the Maastricht ankylosing spondylitis enthesitis score (MASES) and visual analogical score (VAS). <h3>Methods</h3> A cross sectional study was conducted in our department of Rheumatology that includes 56 patients (45 male/10 female) with ankylosing spondylitis according to the modified New York criteria. Clinical data used for calculation of ASDAS, MASES and enthesitis pain VAS were collected. ASDAS formula B was used (calculated with erythrocyte sedimentation rate) [1]. <h3>Results</h3> Patients mean age were 38,35±11 years [16-73]. The mean ASDAS was 4,5±2,3 [0,5-10,2]. The mean MASES was 3,4±3,5 [0-13]. The mean VAS enthesitis pain was 5,6±2,9 [0 -10]. ASDAS was positively correlated to MASES (r: 0.315, p: 0,033) and to VAS enthesitis pain (r:0.273, p: 0,042) [fig1]. Figure 1: Distribution of ASDAS, enthesitis VAS and MASES in patients with ankylosing spondylitis. <h3>Conclusions</h3> ASDAS is positively correlated to MASES and enthesitis pain VAS despite the fact that he didn’t include enthesitis assessment in his score <h3>References</h3> C Lukas, R Landewe’, J Sieper, et al. Development of an ASAS-endorsed disease activity (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009;68:18–24. <h3>Disclosure of Interest</h3> None Declared
Case 8-2006
Authors: Daniel K. Podolsky, R. Gilberto Gonzalez, Robert P. Hasserjian
Journal: New England Journal of Medicine (2006)

A 71-year-old woman with Crohn's disease, who had been receiving treatment with mercaptopurine and infliximab, had fatigue, blurred vision, headache and mood changes, and an inguinal mass. She had a sudden onset of left-sided weakness; brain imaging disclosed a mass, and she was transferred to this hospital. Shortly after admission, she had a seizure and became unresponsive.
Brief encounters
Authors: Des Spence
Journal: BMJ (2007)

views & Reviews T his year, like previous years, has seen a spate of coverage in the British media of maulings by dogs.The most recent available data from the Royal Society for the Prevention of Accidents (www.rospa.co.uk) show that 70 000 people attended UK emergency departments in 2002 for injuries caused by dog bites.Many of these are attacks on children by the family pet and take place in the home (European Journal of Pediatrics 2003;162:254-8).Dog bites have become a public health concern and a child protection issue.As with many public health issues, however, individuals are reluctant to take responsibility and modify their behaviour.The medical profession is left to mop up the mess.Children are particularly vulnerable; one American study found that children under 5 were the age group most likely to have severe head and neck injuries (American Surgeon 1999;65:863-4).Undoubtedly, few people bitten by dogs die or are left with a profound disability.However, the number of people admitted to UK hospitals after being bitten by a dog is rising, despite a fall in dog ownership.Data collected by the Information Centre for Health and Social Care (www.hesonline.nhs.uk) show that 4133 patients were admitted to hospital in England in 2006 as a result of injuries from dog bites, almost double the number in 1996, and that 22% of these people were children under 9. Apart from the psychological and physical consequences (including infections) of dog bites, they result in unnecessary expense.It is clear that the 1991 Dangerous Dogs Act does not work.For a start, it does not cover the majority of bites that occur in the family home, and only 764 people were prosecuted under the act in 2005.Also, all dogs bite, not just the four breeds prohibited under the act (the pit bull terrier, Japanese tosa, Argentine dogo, and fila Brasileiro, including cross-breeds).Indeed, one study showed that the most common dog bites