tbuckley/cabot-search huggingface dataset:
Identification of Copy Number Abnormalities and Inactivating Mutations in Two Negative Regulators of Nuclear Factor-κB Signaling Pathways in Waldenström's Macroglobulinemia
Authors: Esteban Braggio, Jonathan J. Keats, Xavier Leleu, Scott Van Wier, Victor H. Jimenez-Zepeda, Riccardo Valdez, Roelandt F.J. Schop, Tammy Price-Troska, Kimberly Henderson, Antonio Sacco, Feda Azab, Philip Greipp, Morie Gertz, Suzanne Hayman, S. Vincent Rajkumar, John Carpten, Marta Chesi, Michael Barrett, A. Keith Stewart, Ahmet Dogan, P. Leif Bergsagel, Irene M. Ghobrial, Rafael Fonseca
Journal: Cancer Research (2009)

Waldenström's macroglobulinemia (WM) is a distinct clinicobiological entity defined as a B-cell neoplasm characterized by a lymphoplasmacytic infiltrate in bone marrow (BM) and IgM paraprotein production. Cytogenetic analyses were historically limited by difficulty in obtaining tumor metaphases, and the genetic basis of the disease remains poorly defined. Here, we performed a comprehensive analysis in 42 WM patients by using a high-resolution, array-based comparative genomic hybridization approach to unravel the genetic mechanisms associated with WM pathogenesis. Overall, 83% of cases have chromosomal abnormalities, with a median of three abnormalities per patient. Gain of 6p was the second most common abnormality (17%), and its presence was always concomitant with 6q loss. A minimal deleted region, including MIRN15A and MIRN16-1, was delineated on 13q14 in 10% of patients. Of interest, we reported biallelic deletions and/or inactivating mutations with uniparental disomy in tumor necrosis factor (TNF) receptor-associated factor 3 and TNFalpha-induced protein 3, two negative regulators of the nuclear factor-kappaB (NF-kappaB) signaling pathway. Furthermore, we confirmed the association between TRAF3 inactivation and increased transcriptional activity of NF-kappaB target genes. Mutational activation of the NF-kappaB pathway, which is normally activated by ligand receptor interactions within the BM microenvironment, highlights its biological importance, and suggests a therapeutic role for inhibitors of NF-kappaB pathway activation in the treatment of WM.
Immunotherapy of cancer in 2012
Authors: John M. Kirkwood, Lisa H. Butterfield, Ahmad A. Tarhini, Hassane Zarour, Pawel Kalinski, Soldano Ferrone
Journal: CA A Cancer Journal for Clinicians (2012)

The immunotherapy of cancer has made significant strides in the past few years due to improved understanding of the underlying principles of tumor biology and immunology. These principles have been critical in the development of immunotherapy in the laboratory and in the implementation of immunotherapy in the clinic. This improved understanding of immunotherapy, enhanced by increased insights into the mechanism of tumor immune response and its evasion by tumors, now permits manipulation of this interaction and elucidates the therapeutic role of immunity in cancer. Also important, this improved understanding of immunotherapy and the mechanisms underlying immunity in cancer has fueled an expanding array of new therapeutic agents for a variety of cancers. Pegylated interferon-α2b as an adjuvant therapy and ipilimumab as therapy for advanced disease, both of which were approved by the United States Food and Drug Administration for melanoma in March 2011, are 2 prime examples of how an increased understanding of the principles of tumor biology and immunology have been translated successfully from the laboratory to the clinical setting. Principles that guide the development and application of immunotherapy include antibodies, cytokines, vaccines, and cellular therapies. The identification and further elucidation of the role of immunotherapy in different tumor types, and the development of strategies for combining immunotherapy with cytotoxic and molecularly targeted agents for future multimodal therapy for cancer will enable even greater progress and ultimately lead to improved outcomes for patients receiving cancer immunotherapy.
Horizon: Does the MMR Jab Cause Autism?
Authors: Domhnall MacAuley
Journal: BMJ (2005)

BBC 2, 29 May at 9 pm ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> O h no. Surely the MMR (measles, mumps, rubella) vaccine story has been hammered to death. Why is the BBC now picking through the remains of yesterday's news? At our baby clinic on Tuesday afternoons we still have concerned mums and dads, but most are happy to go along with our advice. Like most doctors, I have trotted out my own unsystematic interpretation of guidance from experts, government departments, and advice leaflets. But, I should confess, there was still a tiny voice in the back of my mind wondering if there might still be a grain of truth in the story about a suggested link between autism and MMR. Depending on the day, I watch programmes about MMR with a varying balance of natural cynicism and scientific acceptance. The BBC is usually fair and well researched, so I … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Follow-up: 15 Years After Captivity in SE Asia; 50 Years After World War II Flight Training
Authors: Timothy F. Kirn
Journal: JAMA (1989)

ON FEBRUARY 14, 1973, the first 20 American prisoners of war (POWs) arrived from Vietnam at Clark Air Base in the Philippines (<i>JAMA</i>. 1973;224:972-974). Since then, those men and their almost 650 fellow prisoners have afforded the Navy a unique opportunity to study the long-term effects of extended captivity. More than 15 years later, their bodies still bear scars from combat injuries and, in some cases, from being tortured by their captors. But, the study suggests, the POWs have readjusted to American life, even prospered, and their overall health is good. Theirs had been one of the more grueling experiences of the conflict in Southeast Asia. Most were Air Force, Navy, or Marine pilots who managed to eject themselves from crippled jet aircraft, although some were Army helicopter crew members or ground troops and one was a seaman who fell overboard. Some had spent as long as 7 wretched years
Which Clinical Variables Predict an Abnormal Double-Contrast Barium Enema Result?
Authors: Thomas M. Zarchy, Daniel Ershoff
Journal: Annals of Internal Medicine (1991)

Objective: To determine the relations among patient history, symptoms, objective indicators, and abnormal double-contrast barium enema results in outpatients. Patients and Setting: Seven hundred and ninety-four patients receiving care in a large multispecialty medical group. Design: Physicians completed a form before ordering a double-contrast barium enema, listing information about patient history, symptoms, and objective findings, including the results of a complete blood count, stool hemoccult, and sigmoidoscopy. Measurements and Main Results: Outcome measures were colon cancer and any abnormal finding. The results of 18.6% of the barium enemas were abnormal. The most frequent positive findings were of polyps (8.8%) and colon cancer (2.9%). Over 50% of the barium enemas were ordered solely on the basis of symptoms, yet there was no statistical correlation between symptoms and colon cancer or any positive finding. Using logistic regression, four variables were shown to be significant predictors of colon cancer (P < 0.05): abnormal sigmoidoscopy, iron deficiency anemia, positive stool hemoccult results, and relevant history. The respective odds ratios of these variables were 3.76 (95% CI, 2.89 to 4.90); 2.86 (CI, 2.13 to 3.74); 1.87 (CI, 1.46 to 2.39); and 1.91 (CI, 1.44 to 2.52), respectively. In a patient without any of these indicators, the predicted probability of having colon cancer was only 0.7%. In a patient with at least two objective indicators, the probability of having colon cancer was greater than 15%. Conclusions: Symptoms without objective indicators or pertinent risk factors do not correlate with an abnormal double-contrast barium enema result. Objective indicators are useful predictors of an abnormal barium enema result, particularly when looking for colon cancer.
Abstract 4963: <i>In vivo</i> and <i>in vitro</i> effect of a nutrient mixture on murine 4T1 breast cancer
Authors: M. Waheed Roomi, John Cha, Nusrath Roomi, Aleksandra Niedzwiecki, Matthias Rath
Journal: Cancer Research (2014)

Abstract Breast cancer patients often have detectable or occult metastases at diagnosis and most patients will develop metastatic lesions during the course of the disease. We investigated the effect of a nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract on murine breast cancer 4T1, a unique metastatic breast cancer model that has the capacity to metastasize efficiently to sites affected in human breast cancer. After one week of isolation, 5-6 week old female Balb/C mice were inoculated with 5x105 4T1 cells into the mammary pad and randomly divided into two groups; group A was fed a regular diet and group B a regular diet supplemented with 0.5% NM. After four weeks, the mice were sacrificed and their tumors, lungs, livers, kidneys, hearts and spleens were excised and processed for histology. Dimensions (length and width) of tumors were measured using a digital caliper, and the tumor burden was calculated using the following formula: 0.5 x length x width. We also tested the effect of NM in vitro on 4T1 cells, measuring cell proliferation by MTT assay, MMP secretion by zymography, invasion through Matrigel , migration by scratch test and morphology by H&amp;E staining. NM inhibited tumor weight and burden of 4T1 tumors by 50% (p =0.02) and 53.4% (p&amp;lt;0.0001), respectively. Lung metastasis was profoundly inhibited by NM supplementation: mean number of colonies was reduced by 87% (p&amp;lt;0.0001) and mean weight of lungs by 60% (p=0.0001) compared to control mice. Metastasis to liver, spleen, kidney and heart was significantly reduced with NM supplementation. In vitro, NM exhibited 50% toxicity over the control at 250 and 500 µg/ml concentrations. Zymography demonstrated MMP-2 and MMP-9 secretion which was inhibited by NM in a dose dependent fashion, with virtual total inhibition of both at 1000 µg/ml. Migration by scratch test and Invasion through Matrigel were inhibited in a dose dependent manner with total block of invasion at 250 µg/ml and of migration at 1000 µg/ml. These results suggest that NM has therapeutic potential in treatment of breast cancer. Citation Format: M. Waheed Roomi, John Cha, Nusrath Roomi, Aleksandra Niedzwiecki, Matthias Rath. In vivo and in vitro effect of a nutrient mixture on murine 4T1 breast cancer. [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 4963. doi:10.1158/1538-7445.AM2014-4963
Differential Effects of Anti–β <sub>2</sub> -Glycoprotein I Antibodies on Endothelial Cells and on the Manifestations of Experimental Antiphospholipid Syndrome
Authors: Jacob George, Miri Blank, Yair Levy, Pierluigi Meroni, Maya Damianovich, Angela Tincani, Yehuda Shoenfeld
Journal: Circulation (1998)

The antiphospholipid syndrome (APS) entails a prothrombotic state associated with the presence of anticardiolipin antibodies (aCL). aCL were shown to promote endothelial cell and platelet activation and to induce an APS-like syndrome in mice when administered intravenously. Recent data suggest that aCL target the plasma cofactor beta2-glycoprotein I (beta2GPI) rather than negatively charged phospholipids. However, it has not been determined whether different epitope-specific anti-beta2GPI antibodies obtained from one patient possess pathogenic properties.Three beta2GPI-binding IgM monoclonal antibodies (mAbs) (ILA-1, ILA-3, and ILA-4) were cloned from a patient with APS. The three antibodies were shown to bind beta2GPI immobilized on irradiated plates, yet only ILA-1 bound beta2GPI coated onto nonirradiated plates. Furthermore, when using the anti-beta2GPI enzyme-linked immunosorbent assay, ILA-1 was the only mAb inhibited by fluid phase beta2GPI. ILA-1 and ILA-3, but not ILA-4, induced adherence of U937 cells to endothelial cells in vitro (reflecting activation of endothelial cells). mAbs ILA-1 and ILA-3 as opposed to ILA-4 induced significant expression of adhesion molecules when preincubated with human umbilical vein endothelial cells. Passive administration of ILA-1 and ILA-3 to pregnant BALB/c mice induced clinical findings consistent with APS (increased fetal resorptions, reduced platelet counts, and prolonged activated partial thromboplastin time), whereas both ILA-4 and the control human IgM did not produce similar effects.The results of the study demonstrate the differential effects of various populations of anti-beta2GPI antibodies on endothelial cell activation and on experimental APS.
The Decision to Study Medicine
Authors: Irwin A. Brody
Journal: New England Journal of Medicine (1955)

FROM the time that he prepares his application for medical school to the time that he sits down to write his memoirs the physician frequently finds himself confronted with the question of why he chose to become a doctor. Often his answer is considered to indicate the chances of his future success in medicine or the degree of his present devotion to the profession. Experts in vocational guidance have designated certain attitudes and aptitudes as prerequisite for the prospective physician, and the general public entertains its own notions of what prompts a young man to study medicine; but it may . . .
Post-decompression shock due to extravasation of plasma.
Authors: E. E. Barnard, J. M. Hanson, M. A. Rowton-Lee, A. G. Morgan, A. Polak, D. R. Tidy
Journal: BMJ (1966)

MBOR LThe two patients presented here had grossly enlarged bilharzial spleens.Both showed an initial high uptake of 5'Cr radioactivity over the spleen and both had evidence of hypervolaemia.In both patients, therefore, pooling of red cells had occurred in the spleen, with a markedly increased plasma volume.In the first patient, however, there was in addition to hypervolaemia evidence of intrasplenic red-cell destruction (hypersplenism)-51Cr red-cell half-life shortened to 14.5 days, a rising accumulation of radioactivity over the spleen, and an increase in spleen: liver ratio.The studies of Holzbach et al. (1964) support the concept that increased spleen size in itself can result in hyperfunction.This does not appear to occur in the enlarged bilbarzial spleen, since both in our past work (Farid et al., 1964) and in the two patients presented here intrasplenic red-cell destruction was not related to the size of the spleen.We suggest that, rather than the size of the spleen, a deranged spleen circulation with slowing of passage of blood in the fibrotic and congested bilharzial spleen determines the occurrence of intrasplenic red-cell destruction.Prankerd (1963) stressed the importance of hypervolaemia as a cause of refractory dilution anaemia in patients with enlarged spleens in leukaemias, Gaucher's disease, and thalassaemia.We suggest that this phenomenon of hypervolaemia plays an important part in the production of the chronic anaemia of bilharzial splenomegaly regardless of the occurrence of red-cell destruction by the spleen.Splenectony in Case 1 resulted in an immediate haemato- logical improvement; this was probably due to removal of the site of red-cell destruction, as well as to a reduction in the plasma volume (hence the immediate improvement without relapse).In our opinion splenectomy would also have bene- fited the second patient, simply by reducing the hypervolaemia and thus raising the haemoglobin.He refused operation.
Diagnosis of Nasopharyngeal Carcinoma by DNA Amplification of Tissue Obtained by Fine-Needle Aspiration
Authors: Raphael Feinmesser, Isao Miyazaki, Roy Cheung, Jeremy L. Freeman, Arnold M. Noyek, Hans-Michael Dosch
Journal: New England Journal of Medicine (1992)

In nasopharyngeal carcinoma the primary lesion is often difficult to find. Metastatic lesions occur frequently but are difficult to distinguish from other head and neck tumors. The viral genome of the Epstein-Barr virus (EBV) can be identified in the cells of this carcinoma.We used the polymerase chain reaction (PCR) to test for the presence of EBV genomes in 15 samples of metastatic squamous-cell carcinoma of the neck obtained by fine-needle aspiration and in 26 samples obtained by biopsy of lymph nodes. For controls we used disease-free lymph nodes from 10 patients with various head and neck tumors, tonsillar tissue from 46 subjects, blood from 59 EBV-seropositive blood donors, and mononuclear cells from 8 patients with fatal lymphoproliferative lesions.Of the 41 malignant lesions examined, only the nine nasopharyngeal carcinomas (one primary lesion and eight metastases) contained EBV genomes. None of the 20 nodes with other types of cancer, the 10 disease-free nodes, or any of the 105 normal control samples contained detectable EBV. In two patients with suspected metastases from occult primary tumors, the presence of EBV was predictive of nasopharyngeal carcinoma; in both cases overt nasopharyngeal carcinoma developed within one year.In patients with suspected nasopharyngeal carcinoma, fine-needle aspiration can provide tissue for diagnosis by DNA amplification of EBV genomes. The presence of EBV in metastases from an occult primary tumor is predictive of the development of overt nasopharyngeal carcinoma.
Fish-Oil Supplementation and Rheumatoid Arthritis
Authors: Zimmerman Kf, Schlesinger Pa, Bloss Tj, Stillman Mt
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 August 1987Fish-Oil Supplementation and Rheumatoid ArthritisKURT F. ZIMMERMAN, M.D., PETER A. SCHLESINGER, M.D., THOMAS J. BLOSS, M.D., M. THOMAS STILLMAN, M.D.KURT F. ZIMMERMAN, M.D.Search for more papers by this author, PETER A. SCHLESINGER, M.D.Search for more papers by this author, THOMAS J. BLOSS, M.D.Search for more papers by this author, M. THOMAS STILLMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-107-2-263_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Kremer and associates (1), in reporting the results of their placebo-controlled crossover trial of fish oil in active rheumatoid arthritis, note that "the washout period after receipt of fish oil supplements was not long enough to prevent some carryover of benefits in patients crossing over to placebo." In their discussion they claim that this carryover "would result in an underestimation of the true differences between study groups during weeks 18 to 32, an effect that would serve to mask the possible effects of fish oil during this period." We feel the carryover effect may in fact lead...Reference1. KREMERJUBIZMICHALEK JWA. Fish-oil fatty acid supplementation in active rheumatoid arthritis: a double-blinded, controlled, crossover study. Ann Intern Med. 1987;106:497-503. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByRheumatoid Arthritis and Fish OilADRIAN A. KYRIAKOPOULOS, M.D. 1 August 1987Volume 107, Issue 2Page: 263-263KeywordsOilsRheumatoid arthritis Issue Published: 1 August 1987 PDF DownloadLoading ...
RECORD OF WOMEN IN MEDICINE
Authors: SAMUEL E. LEARD
Journal: Annals of Internal Medicine (1967)

Letters and Comments1 July 1967RECORD OF WOMEN IN MEDICINESAMUEL E. LEARD, M.D., F.A.C.P.SAMUEL E. LEARD, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-67-1-221 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: In the May 1967 ANNALS, the article by Drs. Rosenlund and Oski on "Women in Medicine" and the editorial note "Women In and Out of Medicine" were read with interest. Since Boston University School of Medicine was founded in 1873 when it merged with the New England Female Medical College founded in 1848, a 1965 survey of this school's alumni might be of interest.Seven hundred thirty-eight of 1,712 alumni from the classes of 1930 through 1960 were board-certified. One hundred forty-five alumni had attained professorial rank in 54 medical schools of the United States.Of the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1967Volume 67, Issue 1Page: 221-222KeywordsAlumni Issue Published: 1 July 1967 PDF downloadLoading ...
Breath hydrogen analysis in patients with ileoanal pouch anastomosis.
Authors: E Bruun, J N Meyer, J J Rumessen, E Gudmand-Hoyer
Journal: Gut (1995)

The possible influence on functional outcomes of hydrogen production in the ileoanal pouch after restorative proctocolectomy was investigated by means of lactulose H2 breath tests. Eight of 15 patients had significant increases in breath hydrogen after 10 g lactulose. One patient declined to participate in further investigations, the remaining seven responders had no evidence of small bowel bacterial overgrowth after glucose H2 breath tests. The ability to produce hydrogen by anaerobic fermentation of lactulose in the pouch was unrelated to the age of the patients or of the pouch. Seven of eight responders had successive breath tests after ingestion of lactulose 20 g and wheat starch 100 g. Five of seven had significant increases after lactulose but none after wheat starch. The overall function of the pouch continence, spontaneity of defecation, and 24 hour stool frequency was significantly better in responders than in non-responders. The absence of H2 production of 100 g wheat starch may indicate either increased absorption or defective fermentation.