tbuckley/cabot-search huggingface dataset:
Site and Sequelae of Myocardial Infarction
Authors: Bernadine H. Bulkley
Journal: New England Journal of Medicine (1981)

New and improved noninvasive techniques have provided better understanding of the factors that determine the outcome of acute myocardial infarction. In a study described in this issue of the Journal, Asinger et al. used two-dimensional echocardiography to demonstrate that left ventricular thrombi were identifiable in one third of 35 patients with anterior-wall transmural infarction but in none of 35 with inferior-wall infarcts.1 Nearly half the patients with severe anteroapical involvement had left ventricular thrombi. Thus, through the unique ability to correlate the appearance of thrombi over time with regional changes in wall function, echocardiographically detectable left ventricular thrombi were . . .
Case 36-1978
Authors: Marshall M. Kaplan, James J. Galdabini
Journal: New England Journal of Medicine (1978)

Presentation of CaseA 53-year-old woman was admitted to the hospital because of biliary colic.There was a history of intermittent jaundice since childhood. At 29 years of age the conjugated bilirubin was 3 mg, the total bilirubin 5.7 mg, the cholesterol 172 mg, and the protein 7.9 g (the albumin 5.3 g, and the globulin 2.6 g) per 100 ml. The alkaline phosphatase was 3.4 Bodansky U, and the cephalin flocculation test + +. Oral and intravenous cholecystographic examinations revealed no opacification of the gallbladder. A laparotomy was performed. The liver was enlarged and very dark green. The gallbladder . . .
The Effect of the Prediabetic State on the Survival of the Fetus and the Birth Weight of the Newborn Infant
Authors: Herbert C. Miller
Journal: New England Journal of Medicine (1945)

ONE of the outstanding characteristics of infants born to diabetic mothers is a high fetal and neonatal mortality rate. In addition there occur in some infants born to diabetic mothers striking somatic and visceral changes, among which are an increased birth weight, cardiomegaly, hyperplasia of the islands of Langerhans, excessive extramedullary erythropoiesis, hyperplasia of the adrenal glands and an increase in the eosinophil elements of the anterior pituitary body.1 Similar observations have been made on infants born to mothers who were not diabetic at the time of delivery but in later months or years developed signs and symptoms of diabetes. . . .
Reduction of Suppressor T Lymphocytes in the Tropical Splenomegaly Syndrome
Authors: Stephen L. Hoffman, Willy F. Piessens, Sutanti Ratiwayanto, P. R. Hussein, Liliana Kurniawan, Patricia W. Piessens, James R. Campbell, Harijani A. Marwoto
Journal: New England Journal of Medicine (1984)

To study the pathogenesis of tropical splenomegaly syndrome, we compared immunologic findings in patients from Flores, Indonesia, with those obtained in local residents without splenomegaly and in controls. Villagers with tropical splenomegaly syndrome had markedly elevated levels of total IgM, higher titers of IgM antibodies to Plasmodium vivax, and reduced levels of circulating T lymphocytes. The latter were caused by a decrease in the total number of T cells with the suppressor/cytotoxic phenotype (T8+). Levels of B lymphocytes were similar in all groups. All immunologic abnormalities reverted toward normal in patients treated weekly for 9 to 26 months with chloroquine phosphate. These findings suggest that overproduction of immunoglobulins in patients with tropical splenomegaly syndrome is caused by an imbalance in the normal ratio of helper: suppressor T cells that regulate B-lymphocyte function, and that this imbalance is due to a decrease in suppressor T lymphocytes.
IMPS-26HARNESSING THE MYELOID CHECKPOINT CD47-SIRPa AXIS AGAINST ADULT AND PEDIATRIC MALIGNANT BRAIN TUMORS: A NOVEL IMMUNOTHERAPEUTIC MODALITY
Authors: Sharareh Gholamin, Siddhartha Mitra, Rogelio Esparza, Jie Liu, Abdullah Feroze, Yoon Jae Cho, Michael Zhang, Hannes Vogel, Michael Edwards, Irving Weissman, Samuel Cheshier
Journal: Neuro-Oncology (2015)

INTRODUCTION: Adult and pediatric brain tumors are among the most fatal cancers known with limited treatment options. One of the key tumor features facilitating its growth and progression is evading the immune system. Recent data suggests that the interaction between the cell surface antigen CD47 and its binding partner SIRPα is a mechanism by which non-solid and solid tumors can evade the innate immune system. Here, we show that disrupting the interaction of this anti-phagocytic surface protein, CD47 with its interacting partner on macrophages (SIRPa) induces the macrophages to 'eat and kill' brain cancer cells through modulating the innate immune system. METHODS: CD47 expression was evaluated on surgical patient and post-mortem samples from different brain tumor: Adult and pediatric Glioblastoma, Oligodendroglioma, DIPG, Medulloblastoma, Ependymoma, ATRT, PNET tissue samples were analyzed for CD47 expression. Using a novel humanized anti-CD47 monocloncal antibody we tested whether blocking CD47- SIRPα interaction induces phagocytosis. Orthotopic patient derived xenograft models were treated them with the humanized anti-CD47 mAb. Additionally, we tested the effect of huCD47-Ab antibody on normal neural cells. The ability of blocking the CD47-SIRPa axis to enhance the therapeutic response of available clinical monoclonal antibodies was also tested. RESULTS: CD47 expression was upregulated in all tumor types and was present in >90% of the cells in high-grade tumors. Blocking the CD47- SIRPα interaction increased phagocytosis by macrophages in tumor but not on normal neural cells. Systemic treatment with anti-CD47 antibody significantly reduced tumor burden and enhanced survival. NHP studies show that the huCD47 antibody can be administered safely at potentially therapeutic serum levels. CONCLUSION: Anti-CD47 therapy is a viable and effective treatment modality for human high-grade brain tumors. Currently a Phase I study is ongoing to evaluate its safety in patients with non-CNS tumors to be followed by safety in patients with CNS malignancies
Side effects of sunitinib malate (SM) treatment for patients (pts) with metastatic renal cell carcinoma (mRCC)
Authors: G. G. Cartenì, M. Montano, E. Perrotta, M. Otero, T. Guida, G. Ragone, G. Aurilio, L. Maiorino, C. Stavolo, N. Panza
Journal: Journal of Clinical Oncology (2007)

15617 Background: SM is a tyrosine kinase inhibitor recently approved for treatment of mRCC. Side effects of treatment have been investigated in 51 pts with mRCC and 35 out 51 enrolled pts resulted evaluable for response. Methods: Pts were clinically evaluated before therapy and each month during SM treatment; haematological and biochemical parameters were measured after each cycle. Thyroid function was also evaluated measuring thyroid-stimulating-hormone (TSH), serum free thyroxine (FT 4 ) and triiodothyronine (FT 3 ), before the start and after 6 months of treatment. Results: Toxicity was evaluated according to NCI-CTC. Neutropenia grade 3 was observed in 7 pts (13,7%), grade 2 in 13 (25%); anemia grade 3 was found in 3 pts (5,8%) and grade 2 in 6 (11,7%); thrombocytopenia grade 3 was found in 6 pts (11,7%), grade 2 in 5 (9,8%). Mucositis resulted a frequent side effect. In fact, 4 (7,8%) pts showed a grade 3 toxicity, 16 (31,3%) grade 2 and 10 (19,8%) grade 1 Among 29 out 35 (82,8%) pts who responded to therapy, 3 had mucositis grade 3, 15 grade 2, 9 grade 1. Conversely, among 6 out 35 (17,1%) pts who had progressive disease during treatment, mucositis was observed in only 2 pts. 24 pts out 35 who received 6 months SM treatment were reevalueted for thyroid function. No patient had thyroid dysfunction before treatment. Conversely, 8 pts showed severe ipothyroidism (TSH, FT3 and FT4 out of the normal range) and 6 others intermediate ipothyroidism (only TSH increased over 20 μU/ml) after at least 6 cycles of therapy. Conclusions: SM therapy represents a new interesting approach to the treatment of mRCC, but shows noteworthy side effects. Regular monitoring of thyroid function with administration of levothyroxin substitutive treatment at the appearance of the thyroid disfunction is required. A direct correlation between grade 2–3 mucositis and clinical response to treatment could be postulated on the basis of our data, although a statistical analysis on a greater cohort of subjects is required to confirm this observation. No significant financial relationships to disclose.
The Ribonucleic Complex HuR-MALAT1 Represses CD133 Expression and Suppresses Epithelial–Mesenchymal Transition in Breast Cancer
Authors: Elisa Latorre, Stephana Carelli, Ivan Raimondi, Vito D'Agostino, Ilaria Castiglioni, Chiara Zucal, Giacomina Moro, Andrea Luciani, Giorgio Ghilardi, Eleonora Monti, Alberto Inga, Anna Maria Di Giulio, Alfredo Gorio, Alessandro Provenzani
Journal: Cancer Research (2016)

Epithelial-to-mesenchymal transition (EMT) is a core process underlying cell movement during embryonic development and morphogenesis. Cancer cells hijack this developmental program to execute a multi-step cascade, leading to tumorigenesis and metastasis. CD133 (PROM1), a marker of cancer stem cells, has been shown to facilitate EMT in various cancers, but the regulatory networks controlling CD133 gene expression and function in cancer remain incompletely delineated. In this study, we show that a ribonucleoprotein complex including the long noncoding RNA MALAT1 and the RNA-binding protein HuR (ELAVL1) binds the CD133 promoter region to regulate its expression. In luminal nonmetastatic MCF-7 breast cancer cells, HuR silencing was sufficient to upregulate N-cadherin (CDH2) and CD133 along with a migratory and mesenchymal-like phenotype. Furthermore, we found that in the basal-like metastatic cell line MDA-MB-231 and primary triple-negative breast cancer tumor cells, the repressor complex was absent from the CD133-regulatory region, but was present in the MCF-7 and primary ER+ tumor cells. The absence of the complex from basal-like cells was attributed to diminished expression of MALAT1, which, when overexpressed, dampened CD133 levels. In conclusion, our findings suggest that the failure of a repressive complex to form or stabilize in breast cancer promotes CD133 upregulation and an EMT-like program, providing new mechanistic insights underlying the control of prometastatic processes. Cancer Res; 76(9); 2626-36. ©2016 AACR.
A Randomized Trial of Acyclovir for 7 Days or 21 Days with and without Prednisolone for Treatment of Acute Herpes Zoster
Authors: Martin J. Wood, Robert W. Johnson, Michael W. McKendrick, Julie Taylor, Bibhat K. Mandal, Jane Crooks
Journal: New England Journal of Medicine (1994)

Acyclovir given for 7 to 10 days is of proved benefit in acute herpes zoster, but studies of its effectiveness in preventing postherpetic neuralgia have had conflicting results. The role of corticosteroids in the treatment of herpes zoster is also controversial.We conducted a double-blind, controlled trial in patients with acute herpes zoster to determine whether either 21 days of acyclovir therapy or the addition of prednisolone offered any improvement over 7 days of acyclovir therapy. Patients with a rash of less than 72 hours' duration were assigned to receive acyclovir (800 mg orally, five times daily) for 7 days with either prednisolone or placebo, or acyclovir for 21 days with either prednisolone or placebo. Prednisolone therapy was initiated at a dose of 40 mg per day and tapered over a three-week period. Patients were assessed frequently through day 28 and then monthly through month 6 to assess postherpetic neuralgia.Of 400 patients recruited, 349 completed the study. No significant differences were detected between the four groups in the progression of the rash (P > 0.1). With steroid therapy, a significantly higher proportion of the rash area had healed on days 7 and 14 (P = 0.02). Pain reduction was greater during the acute phase of disease in patients treated with steroids or 21 days of acyclovir (P < 0.01 and P = 0.02, respectively, on day 7; P < 0.01 for steroid therapy on day 14). However, on follow-up there were no significant differences between any of the groups in the time to a first or a complete cessation of pain. The steroid recipients reported more adverse events.In acute herpes zoster, treatment with acyclovir for 21 days or the addition of prednisolone to acyclovir therapy confers only slight benefits over standard 7-day treatment with acyclovir. Neither additional treatment reduces the frequency of postherpetic neuralgia.
M9 Lung Health of OPiate Users (LHOp): A pilot study to assess the respiratory health of opiate misusers attending a community substance misuse clinic
Authors: A Pitt, C Mitchell, B Colwell, I Appelqvist, F Ashby, C Lloyd, S Gilbody, R Lawson
Journal: Thorax (2015)

<h3>Introduction</h3> MDTs promote harm reduction in the care of opiate misusers (OMUs) through the prescription of opiate substitute medication and by encouraging smoking rather than injecting (to reduce the risk of blood-bourne virus transmission and venous thromboembolism). The average life expectancy for a male OMU is 41 years and whilst evidence suggests that the current cohort of older OMUs are dying prematurely from non-drug related deaths, all-cause mortality studies rarely report the prevalence of chronic health problems. A recent case-controlled study reported a higher prevalence of asthma and COPD in OMUs after adjusting for tobacco consumption and other factors. The study objective was to investigate the prevalence and illness burden of respiratory problems (asthma, COPD, symptomatic but undiagnosed lung disease) in patients with a history of current and/or past opiate misuse. <h3>Methods</h3> Opportunistic clinic-based participant recruitment. Resting spirometry and researcher administered socio-demographic, inhaled drug use and validated respiratory patient reported outcome questionnaires: 1) prior diagnosis of asthma (ACT; mini-ARQoL) or COPD (CCQ); 2) respiratory health screening if no prior diagnosis (LFQ). <h3>Results</h3> There were 36 participants (26 male; 10 female; aged 24–53). Only 8 had a diagnosis (all asthmatics); 35/36 smoked tobacco; 34/36 smoked heroin; 33/36 smoked cocaine; and 31/36 smoked cannabis. All asthmatics had poor control (&lt;13) on the ACT (median score 8) and frequent beta-agonist use (none used inhaled corticosteroids). Of the others, 22/28 scored ≤18 on LFQ suggesting high symptom burden and three of these had obstructive resting spirometry increasing the possibility of COPD. <h3>Conclusions</h3> Chronic respiratory health in drug users is an under-researched area with few screening or high quality intervention studies evident. We identified a significant respiratory symptom burden within this OMU cohort. Most smoked tobacco, heroin, cocaine and cannabis. Asthmatics reported poor control and were potentially at risk of severe exacerbations, hospital admission and early progression to COPD. Four further LHOp studies are planned: a pharmacy based intervention to improve asthma control/uptake of preventive interventions (smoking cessation; vaccinations); a case control study of GP asthma medication prescribing; prospective prognostic respiratory health cohort studies; and a qualitative study of asthmatic OMUs’ perspectives on respiratory health and inhaler use.
L-Phenylalanine Mustard (L-PAM) in the Management of Primary Breast Cancer
Authors: Bernard Fisher, Paul Carbone, Steven G. Economou, Robert Frelick, Andrew Glass, Harvey Lerner, Carol Redmond, Marvin Zelen, Pierre Band, Donna L. Katrych, Norman Wolmark, Edwin R. Fisher
Journal: New England Journal of Medicine (1975)

Prolonged l-phenylalanine mustard (L-PAM) administration as an adjuvant to mastectomy in the management of patients with primary breast cancer and pathologically positive axillary nodes was evaluated by a prospective, randomized, clinical trial. Treatment failures occurred in 22 per cent of 108 patients receiving placebo and 9.7 per cent of 103 women given L-PAM (p = 0.01). A statistically significant difference (p = 0.02) existed in favor of L-PAM relative to disease-free interval. In premenopausal women, the difference with respect to disease-free interval of treated and control groups was highly significant (p = 0.008). A treatment failure occurred in 30 per cent of premenopausal patients receiving placebo and 3 per cent of those treated with L-PAM (p = 0.008). Whereas a similar trend was observed in postmenopausal patients, the difference is not statistically significant. Thus, L-PAM has been demonstrated to be effective in the treatment of women with primary breast cancer, particularly those who are premenopausal. Results were achieved with minimal undesirable side effects.
Hypertrophied Adenoids Causing Pulmonary Hypertension and Severe Congestive Heart Failure
Authors: Arthur M. Levy, Burton S. Tabakin, John S. Hanson, Richard M. Narkewicz
Journal: New England Journal of Medicine (1967)

ALTHOUGH upper-airway obstruction of varying degrees is a common phenomenon in children, very few cases of cor pulmonale in association with hypertrophied adenoids or tonsils have been reported.1 2 3 In many of these cases the exact hemodynamic changes have not been documented since relief of the respiratory airway obstruction was instituted before diagnostic studies. Thus, the severity of the pulmonary vascular obstruction could only be surmised from the improvement in the clinical course after surgery. The case reported below does document the severe pulmonary hypertension existing before any therapy, the almost instantaneous reversal of this hypertension with temporary relief of obstruction . . .
Treatment of Resistant Malignant Lymphoma with Cyclophosphamide, Total Body Irradiation, and Transplantation of Cryopreserved Autologous Marrow
Authors: Gordon L. Phillips, Roger H. Herzig, Hillard M. Lazarus, Joseph W. Fay, Steven N. Wolff, William B. Mill, Hsiu-san Lin, Patrick R. M. Thomas, Glenn P. Glasgow, Don C. Shina, Geoffrey P. Herzig
Journal: New England Journal of Medicine (1984)

Original Article from The New England Journal of Medicine — Treatment of Resistant Malignant Lymphoma with Cyclophosphamide, Total Body Irradiation, and Transplantation of Cryopreserved Autologous Marrow
Circulating Immune Complexes and the Prognosis of Acute Myeloid Leukemia
Authors: Nicole A. Carpentier, Denis M. Fiere, Daniel Schuh, Ghislaine T. Lange, Paul-Henri Lambert
Journal: New England Journal of Medicine (1982)

We studied the relation between the clinical course and the presence of circulating immune complexes at diagnosis and/or during complete remission in 186 patients with acute myeloid leukemia. Patients with immune complexes at diagnosis had significantly fewer complete remissions (32 vs. 94 per cent), remissions of shorter duration (median, 4.3 vs. 15.0 months), and shorter survival times (median, 1.8 vs. 22.3 months) than patients without such complexes (all comparisons, P<0.01). All patients with immune complexes during the first two months of remission remained in remission for less than six months, whereas only 11 per cent of patients without complexes within this period had such early relapse. Of 23 patients who relapsed after long remissions, 18 (78 per cent) had immune complexes that preceded hematologic evidence of relapse by three weeks to six months (median, 3.7 months). These findings suggest that circulating immune complexes may reflect an important aspect of the pathophysiology of acute myeloid leukemia, and that measurement of these complexes can provide useful prognostic information at diagnosis and during remission. (N Engl J Med. 1982; 307:1174–80.)
Graft-versus-Host Disease Associated with Transfusion of Blood from Unrelated HLA-Homozygous Donors
Authors: Ramesh A. Shivdasani, Frank G. Haluska, Nancy L. Dock, Jeffrey S. Dover, Elise J. Kineke, Kenneth C. Anderson
Journal: New England Journal of Medicine (1993)

Graft-versus-host disease (GVHD) is a well-known complication of allogeneic bone marrow transplantation and is increasingly being recognized after solid-organ transplantation and transfusion1–3. Like GVHD occurring after bone marrow transplantation, transfusion-associated GVHD is characterized by fever, skin rash, diarrhea, and hepatitis. However, transfusion-associated GVHD typically occurs much sooner (median, 10 to 12 days after transfusion), is frequently associated with bone marrow aplasia, usually does not respond to immunosuppressive therapy, and is fatal in most cases4–10. Since gamma irradiation of cellular blood components before transfusion can prevent the development of transfusion-associated GVHD, it is critical to identify susceptible . . .
Mediator Production and Tumorigenesis of Murine Monocyte Lines2, 3, 4
Authors: Yasuhiro Yamamura, Julian W. Procter, Beth C. Fischer
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Mediator Production and Tumorigenesis of Murine Monocyte Lines, , Get access Yasuhiro Yamamura, Yasuhiro Yamamura Search for other works by this author on: Oxford Academic PubMed Google Scholar Julian W. Procter, Julian W. Procter Search for other works by this author on: Oxford Academic PubMed Google Scholar Beth C. Fischer Beth C. Fischer Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 66, Issue 6, June 1981, Pages 1067–1075, https://doi.org/10.1093/jnci/66.6.1067 Published: 01 June 1981 Article history Received: 23 February 1979 Revision received: 24 November 1980 Accepted: 10 December 1980 Published: 01 June 1981
Identification of differentially expressed genes regulated by Interleukin-1beta in normal human tracheobronchial epithelial cells using oligonucleotide microarray
Authors: Zhenlin Ju, Dong-Joo Cheon, Kyounga Cheon, Keith Newton, Ja Seok P. Koo
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4685 

Interleukin-1beta (IL-1beta) is a pleiotropic proinflammatory cytokine involved in lung inflammation. We have shown that IL-1beta induced mucus hypersecretion in cultured normal human tracheobronchial epithelial (NHTBE) cells. Recently, it also has been demonstrated that IL-1beta was involved in tumor invasiveness and angiogenesis. To determine the genes or pathways regulated by IL-1beta, we performed oligonucleotide microarray analysis using total RNA isolated from NHTBE cells after treatment with IL-1beta (2.5 ng/ml) for 8 hr. Microarray analysis using Affymetrix Genechip, U133A, revealed that 52 genes were upregulated and 2 genes were down regulated by more than three folds (lower bound of 90% confidence interval) in IL-1beta treated cells compared to the untreated cells. The substantially upregulated genes include chemokines, such as C-C-motif ligand 20 (CCL20), C-X-C-motif ligand (CXCL) 2, CXCL3, CXCL5, and CXCL6. Cyclooxygenase-2 and matrix metalloproteinase 12 were also significantly upregulated by IL-1beta. These genes were known to be involved in inflammation and metastasis. Besides, anti-apoptotic genes such as BCL2A1, TNF5, and NF-kappaB were found upregulated. Our results indicated that the effects of IL-1beta on inflammation and metastasis might be mediated mainly through upregulation of these chemokines and inhibit apoptosis in NHTBE cells via upregulation of BCL2A1, TNF5, and NF-kappaB. This work was supported in part by NIEHS and Eli Lilly Company.
Production of Antibody in Patients with Uremia
Authors: Irwin L. Stoloff, Robert Stout, Ralph M. Myerson, W. Paul Havens
Journal: New England Journal of Medicine (1958)

THE reasons for rejection of homotransplants of renal and other tissues are not defined exactly, although there is considerable evidence that lack of success with this procedure is related in part to the production of antibody to the graft by the recipient.1 , 2 Whether such a cytotoxic substance is freely circulating in the blood or whether rejection may be the result of the development of a delayed type of hypersensitivity state has been the subject of many investigations. The available evidence is controversial; however, there is much to suggest that intracellular antibody may have a prominent role in bringing about rejection . . .