tbuckley/cabot-search huggingface dataset:
A New Class of Anti-HIV Therapy and New Challenges
Authors: Raphael Dolin
Journal: New England Journal of Medicine (2008)

The development of new drugs against human immunodeficiency virus type 1 (HIV-1) has resulted in combination therapy that can inhibit various steps of viral replication. Maraviroc is an example of a new class of such drugs that have a novel mechanism of action against HIV-1.1 Maraviroc binds to the human chemokine receptor 5 (CCR5), which also serves as a coreceptor for a major phenotype of HIV-1, R5 tropic virus, and thereby interferes with an essential early step in viral replication. Maraviroc has shown activity both in vitro and in vivo against R5 HIV-1 strains. In two large-scale trials reported in . . .
The Radiation Syndrome
Authors: Elizabeth E. Painter, Austin M. Brues
Journal: New England Journal of Medicine (1949)

IN EARLIER studies of radiation effects in mammals, dosages of 1000 r and above have generally been employed locally or over large areas of the body. Actually, when irradiation is given as a single total-body dosage, the quantity necessary to kill 50 per cent of the animals in thirty days or less is relatively small: 175 to 250 r for the guinea pig, 325 r for the dog, 350 r for the goat, 530 r for mice, 600 r for rats, and 800 r for rabbits.1 , 2 Where the LD50 for man lies is questionable, but it is probably somewhere . . .
Abstract 1539: Tumor-educated macrophages promote proliferation of human pancreatic cancer cells <i>in vitro</i> and <i>in vivo</i>.
Authors: Yukihiko Hiroshima, Masashi Momiyama, Mohamed Hassanein, Ali Maawy, Rhiana Menen, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
Journal: Cancer Research (2013)

Abstract Macrophages promote tumor growth by stimulating tumor-associated angiogenesis, cancer-cell invasion, migration, and intravasation, as well as suppression of antitumor immune responses. We previously defined the macrophages which were harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as “tumor-educated macrophages (EMϕ)” and demonstrated EMϕ promoted tumor growth and metastasis in orthotopic mouse models. The aim of this study is to elucidate the mechanism of tumor promotion by EMϕ. Transgenic nude mice ubiquitously-expressing GFP were injected subcutaneously with the human pancreatic cancer cell line XPA1 stably expressing RFP in the cytoplasm and GFP in the nucleus. GFP-expressing macrophages from the GFP mice with the dual-color pancreatic tumor were harvested and defined as EMϕ. Macrophages were also harvested from transgenic GFP mice without tumors and identified as “naïve macrophages (NMϕ)”. EMϕ and NMϕ were compared for their ability to enhance cancer-cell proliferation. Using a skin-flap-window imaging model, the mitotic index of the cancer cells significantly increased after injection of EMϕ compared to NMϕ (p = 0.001). Next, we cultured cancer cells in 3-D on Gelfoam® and found that the cancer cells cultured with EMϕ proliferated to a greater extent compared to those cultured with NMϕ (p = 0.014). We also found that the cancer cells cultured in the conditioned medium harvested from EMϕ had enhanced proliferated compared to cancer cells cultured in the conditioned medium from NMϕ (p = 0.016). These results suggest that EMϕ secrete factors which increase cancer cell growth and can serve as a novel therapeutic target for pancreatic cancer. Citation Format: Yukihiko Hiroshima, Masashi Momiyama, Mohamed Hassanein, Ali Maawy, Rhiana Menen, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman. Tumor-educated macrophages promote proliferation of human pancreatic cancer cells in vitro and in vivo. [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 1539. doi:10.1158/1538-7445.AM2013-1539
Targeted therapies in pulmonary arterial hypertension
Authors: David Montani, Marie-Camille Chaumais, Christophe Guignabert, Sven Günther, Barbara Girerd, Xavier Jaïs, Vincent Algalarrondo, Laura C. Price, Laurent Savale, Olivier Sitbon, Gérald Simonneau, Marc Humbert
Journal: Pharmacology & Therapeutics (2013)
Impaired Monocyte Cyclic AMP Responses and Monocyte Cytotoxicity in Atopic Dermatitis
Authors: Troels Herlin, Knud Kragballe
Journal: Allergy (1980)

Purified monocytes from 21 patients with mild and severe atopic dermatitis (AD) were compared with 22 healthy controls with respect to antibody‐dependent cell‐mediated cytotoxicity (ADCC) and cyclic adenosine 3′,5′‐monophosphate (cAMP) responses to stimulatory agents. ADCC was depressed in both severe and mild atopic dermatitis. The patients showed decreased cAMP responses to isoproterenol and histamine, the decrement being more distinct in severe atopic dermatitis. Formation of cAMP was diminished with PGE, only in patients with severe AD. ADCC is inhibited by the agents that increase cAMP. In the severe dermatitis group reduced inhibition induced by isoproterenol, histamine, but not PGE 1 , was obtained. It is suggested that a general suppression of membrane activation may explain the reduced cAMP responses to various stimulatory agents and the impaired monocyte cytotoxicity.
Bim-mediated deletion of antigen-specific CD8+ T cells in patients unable to control HBV infection
Authors: A. Ross Lopes, Paul Kellam, Abhishek Das, Claire Dunn, Antonia Kwan, Joanna Turner, Dimitra Peppa, Richard J. Gilson, Adam Gehring, Antonio Bertoletti, Mala K. Maini
Journal: Journal of Clinical Investigation (2008)

HBV-specific CD8(+) T cells are critical for a successful immune response to HBV infection. They are markedly diminished in number in patients who fail to control the virus, but the mechanisms resulting in their depletion remain ill defined. Here, we dissected the defective HBV-specific CD8(+) T cell response associated with chronic HBV infection by gene expression profiling. We found that HBV-specific CD8(+) T cells from patients with different clinical outcomes could be distinguished by their patterns of gene expression. Microarray analysis revealed that overlapping clusters of functionally related apoptotic genes were upregulated in HBV-specific CD8(+) T cells from patients with chronic compared with resolved infection. Further analysis confirmed that levels of the proapoptotic protein Bcl2-interacting mediator (Bim) were upregulated in HBV-specific CD8(+) T cells from patients with chronic HBV infection. Blocking Bim-mediated apoptosis enhanced recovery of HBV-specific CD8(+) T cells both in culture and directly ex vivo. Consistent with evidence that Bim mediates apoptosis of CD8(+) T cells expressing low levels of CD127 (IL-7R), the few surviving HBV-specific CD8(+) T cells were CD127(hi )and had elevated levels of the antiapoptotic protein Mcl1, suggesting they were amenable to IL-7-mediated rescue from apoptosis. We therefore postulate that Bim-mediated attrition of HBV-specific CD8(+) T cells contributes to the inability of these cell populations to persist and control viral replication.
Priming of circulating human eosinophils following late response to allergen challenge
Authors: L Koenderman
Journal: European Respiratory Journal (1997)

The eosinophil is recognized as an important effector cell in asthma. To investigate the role of eosinophils in the aetiology of asthma, we have examined whether peripheral blood eosinophils are primed following whole-lung allergen challenge. Nineteen mild asthmatics, who each demonstrated a late asthmatic response (LAR), were studied. The priming of eosinophils following allergen challenge was assessed by measuring: 1) platelet-activating factor (PAF) and complement factor 5a (C5a) stimulated H2O2 release upon fibrinogen-coated tissue culture plates (n = 8); and 2) ex-vivo cell survival (n = 11). Subjects were venepunctured before and 24 h after allergen challenge and eosinophils were prepared by immunomagnetic separation. Basal H2O2 release was increased from eosinophils following allergen challenge. The response to PAF stimulation was significantly increased in terms of cell sensitivity (negative log of concentration producing half the maximal effect (pD2)) and responsiveness (maximum effect Emax). With C5a, although there was no change in sensitivity there was a significant increase in the maximal response. Ex-vivo eosinophil survival (at 3 days and cell half-life) was significantly prolonged following allergen challenge. In conclusion, we have demonstrated the priming of circulating eosinophils following allergen challenge.
Key Facts in Pulmonary Disease
Authors: Harry B. Greenberg
Journal: JAMA (1985)

Leafing through the 598 pages ofKey Facts in Pulmonary Diseasewill almost certainly jog a physician's memory, particularly if the physician has a pulmonary problem in mind. I believe a physician's first impressions are correct more often than not. If so, this process of rumination and reflection may or may not benefit the patient. However, it will assuredly make the physician's life more interesting.  Written almost entirely in outline form, Sharma and Balchum's thick paperback has 20 contributors. They use a variety of graphs, tables, charts, equations, roentgenograms, microphotographs, and pictures of lung scans to illustrate the book's 37 chapters. As usual, they begin with howto-do-it outlines of physical examination and history-taking. From there, they take up one pulmonary disease after another and end with succinct chapters on antibiotics, bronchodilator drugs, mechanical ventilation, and oxygen therapy.  In his chapter on the more common pneumonias, Dr Brown sketches first the
Hemolytic anemia and severe rhabdomyolysis caused by compound heterozygous mutations of the gene for erythrocyte/muscle isozyme of aldolase, ALDOA(Arg303X/Cys338Tyr)
Authors: David C. Yao, Dean R. Tolan, Michael F. Murray, David J. Harris, Basil T. Darras, Alon Geva, Ellis J. Neufeld
Journal: Blood (2003)
Abstract P1-07-04: A novel bioactive approach to inhibit leptin-induced epithelial-mesenchymal transition in breast cancer
Authors: D Sharma, D Avtanski, A Nagalingam, P Kuppusamy, N Saxena
Journal: Cancer Research (2013)

Abstract Introduction: Molecular effects of obesity, a well-established risk factor for breast cancer progression, are mediated by adipocytokine leptin. Recent studies from our lab reveal that leptin induces epithelial-mesenchymal transition (EMT) and tumorsphere formation via concomitant activation of Akt/GSK3b and MTA1/Wnt1 signaling axes leading to β catenin activation. Given the important role of leptin in breast cancer growth and metastasis, novel strategies to antagonize biological effects of leptin are much desired. We showed previously that honokiol, a bioactive polyphenol from Magnolia grandiflora, inhibits breast carcinogenesis. The present study provides first evidence for the efficacy of honokiol against oncogenic effects of leptin including EMT. Methods: Efficacy of honokiol to inhibit oncogenic effects of leptin was evaluated by using clonogenicity, anchorage–independent growth, matrigel-invasion and spheroid-migration assays. RT-PCR, western blot and immunofluorescence analyses were used to examine the molecular changes associated with EMT as well as underlying molecular pathways. Functional importance of MTA1/Wnt1/ β catenin axis was examined by using overexpression, phospho-deficient constructs and specific inhibitors. Finally, mouse xenografts, immuniohistochemical, RT-PCR and western blot analysis of tumors was used. Results: Honokiol treatment circumvents leptin-induced EMT-associated phenotypic changes. A biochemical hallmark of EMT is loss of expression of epithelial markers with a concurrent increase in mesenchymal marker expression. Honokiol elicits increased expression of E-cadherin, occludin and keratin-18 (epithelial markers) and decreased expression of vimentin, fibronectin and N-cadherin (mesenchymal markers) in leptin-treated cells providing molecular evidence for reversal of EMT. Honokiol also inhibits expression and nuclear translocation of transcriptional effectors of EMT; Snail, Slug, Zeb1 and Zeb2. Analysis of underlying molecular mechanisms reveals that Honokiol effectively inhibits leptin-induced MTA1/Wnt1/ β catenin axis. Furthermore, using nontoxic doses of honokiol, we show that honokiol treatment effectively inhibits leptin-induced breast tumorigenesis in vivo. Analysis of breast tumors show that honokiol treatment reverses leptin-associated signaling (MTA1/Wnt1/ β catenin axis) along with decreased expression of mesenchymal markers and increased expression of epithelial markers. Conclusions: In this study, we demonstrate for the first time that HNK is able to abolish leptin-induced EMT and provide in vitro and in vivo evidence for the integral role of a previously unrecognized crosstalk between honokiol and MTA1/Wnt1/ β catenin axis. Thus, HNK may be used as a non-toxic and non-endocrine rational therapeutic strategy for breast carcinoma in obese patients with high leptin levels. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-07-04.
World-Wide Needs in Medical Education and Their Fulfilment
Authors: Edward Grzegorzewski
Journal: JAMA (1962)

WHEREAS MEDICAL SCIENCE is essentially universal, medical practice is strongly influenced by the various local circumstances. Medical education being based on both the science and the practice, contains and should contain the universal and the local elements in a well-balanced proportion in order to meet the objectives. <h3>The Needs</h3> The needs in medical education may be assessed in a number of ways. The most direct way is to relate these needs to the "production" of medical graduates capable of coping with the work facing them. This, however, should not obscure other functions of medical education, for instance to give opportunities for further learning and provide a basis for the continuous progress of medical knowledge, for which international contacts act as stimuli, even at the most advanced levels. Furthermore, medical education plays a fundamental role in attaining the highest possible standards of medical practice in the community and country in its
Efficacy of Fluorine-18-Deoxyglucose Positron Emission Tomography in Detecting Tumor Recurrence After Local Ablative Therapy for Liver Metastases: A Prospective Study
Authors: B.S. Langenhoff, W.J.G. Oyen, G.J. Jager, S.P. Strijk, Th. Wobbes, F.H.M. Corstens, T.J.M. Ruers
Journal: Journal of Clinical Oncology (2002)

The aims of this prospective study were to investigate the potential role of fluorine-18-deoxyglucose (FDG) positron emission tomography (PET) in determining the efficacy of the local tumor ablative process and to determine the added value of FDG-PET in the detection of tumor recurrence during follow-up.Twenty-three patients with unresectable colorectal liver metastases were followed up after local ablative therapy consisting of a standard protocol including FDG-PET scanning, computed tomography (CT) scanning, and carcinoembryonic antigen measurements. The mean follow-up period was 16 months (range, 10 to 21 months).Ninety-six lesions was treated, 56 by local ablative treatment. Within 3 weeks after local ablative treatment, 51 lesions became photopenic on FDG-PET, while five lesions (in five patients) showed persistent activity on FDG-PET. In four of five FDG-PET-positive lesions, a local recurrence developed during follow-up; one FDG-PET-positive lesion turned out to be an abscess. None of the FDG-PET-negative lesions developed a local recurrence during a mean follow-up period of 16 months. During follow-up, 11 patients showed recurrence in the liver outside of the treated area. In all cases, previously negative FDG-PET scans became positive. Extrahepatic recurrence was encountered in nine patients during follow-up; FDG-PET showed all nine cases of tumor recurrence. There was one false-positive FDG-PET caused by an intra-abdominal abscess. In all patients, the time point of detection of recurrence by FDG-PET was considerably earlier than the detection by CT.FDG-PET seems to have a significant impact in measuring treatment efficacy directly after local ablative therapy. Furthermore, FDG-PET has an added value in patient follow-up because it reveals recurrences earlier than conventional diagnostic modalities.
Treatment for hepatitis C in jailhouses in doable and successful: Preliminary data of national French study
Authors: A.J. Remy, A. Galinier, E. Gosset, E. Wagner-Kerdranvat, E. Leguhennec, E. Diaz, S. Bellon, C. Wartelle, N. Abdelli, P. Chossegros, E. Gamahut, K. Barange, E. Fix, C. Saccardy, P. Griguere, E. Leroy-Doucy, E. Gluszak, H. Picard
Journal: Journal of Hepatology (2003)
FDA warns Bayer about illegally marketing two over the counter products containing aspirin
Authors: Z. Kmietowicz
Journal: BMJ (2008)

The German drug giant Bayer has been sent warning letters by the US Food and Drug Administration for illegally marketing and “misbranding” two of its products.

Bayer Women’s Low Dose Aspirin with Calcium and Bayer Aspirin with Heart Advantage contain aspirin with either calcium or phytosterols in single tablets. They are sold over the counter and labelled as helping to reduce the risk of heart disease and “fight” osteoporosis, but neither product has been approved by the FDA for these uses in the United States. The only approval they have is for use as an analgesic.

Because both products are …
Altered Plasma Versus Vascular Biopterins in Human Atherosclerosis Reveal Relationships Between Endothelial Nitric Oxide Synthase Coupling, Endothelial Function, and Inflammation
Authors: Charalambos Antoniades, Cheerag Shirodaria, Mark Crabtree, Ruth Rinze, Nicholas Alp, Colin Cunnington, Jonathan Diesch, Dimitris Tousoulis, Christodoulos Stefanadis, Paul Leeson, Chandi Ratnatunga, Ravi Pillai, Keith M. Channon
Journal: Circulation (2007)

Background— Tetrahydrobiopterin (BH 4 ) is a key regulator of endothelial nitric oxide synthase (eNOS) activity and coupling. However, the extent to which vascular and/or systemic BH 4 levels are altered in human atherosclerosis and the importance of BH 4 bioavailability in determining endothelial function and oxidative stress remain unclear. We sought to define the relationships between plasma and vascular biopterin levels in patients with coronary artery disease and to determine how BH 4 levels affect endothelial function, eNOS coupling, and vascular superoxide production. Methods and Results— Samples of saphenous veins and internal mammary arteries were collected from 219 patients with coronary artery disease undergoing coronary artery bypass grafting. We determined plasma and vascular levels of biopterins, vasomotor responses to acetylcholine, and vascular superoxide production in the presence and absence of the eNOS inhibitor N G -nitro- l -arginine methyl ester. High vascular BH 4 was associated with greater vasorelaxations to acetylcholine ( P &lt;0.05), whereas high plasma BH 4 was associated with lower vasorelaxations in response to acetylcholine ( P &lt;0.05). Furthermore, an inverse association was observed between plasma and vascular biopterins ( P &lt;0.05 for both saphenous veins and internal mammary arteries). High vascular (but not plasma) BH 4 was associated with reduced total and N G -nitro- l -arginine methyl ester–inhibitable superoxide, suggesting improved eNOS coupling. Finally, plasma but not vascular biopterin levels were correlated with plasma C-reactive protein levels ( P &lt;0.001). Conclusions— An inverse association exists between plasma and vascular biopterins in patients with coronary artery disease. Vascular but not plasma BH 4 is an important determinant of eNOS coupling, endothelium-dependent vasodilation, and superoxide production in human vessels, whereas plasma biopterins are a marker of systemic inflammation.
Progression and Remission of Renal Disease in the Lupus Nephritis Collaborative Study
Authors: Andrew S. Levey, Shu-Ping Lan, Howard L. Corwin, Balakuntalam S. Kasinath, John Lachin, Eric G. Neilson, Lawrence G. Hunsicker, Edmund J. Lewis
Journal: Annals of Internal Medicine (1992)

Objective: To describe the clinical course of severe lupus nephritis and to identify the risk factors for progression to renal failure among patients treated with prednisone and short-term courses of low-dose oral cyclophosphamide. Design: Ancillary analyses of data from the Lupus Nephritis Collaborative Study (LNCS). Setting: University hospital medical centers (14). Patients: The 86 patients who participated in the LNCS (mean follow-up, 136 weeks [2.6 years]) and a subgroup of 63 patients with follow-up of more than 48 weeks (mean follow-up, 160 weeks [3.1 years]). Measurements: Initial clinical and pathologic features, response to therapy within 48 weeks, and subsequent clinical events, including development of renal failure. Main Results: Renal failure developed in 18 patients (21%). An observed elevation in serum creatinine concentration was the only initial feature predictive of subsequent renal failure. Mean (± SD) initial serum creatinine levels were higher in patients who subsequently developed renal failure (244 ± 134 μmol/L [2.76 ± 1.52 mg/dL] compared with 163 ± 103 μmol/L [1.85 ± 1.17 mg/dL]; P= 0.007). The risk for renal failure was higher among patients with initial serum creatinine levels greater than 106 ¼mol/L (1.2 mg/dL) (29% compared with 6.5%; P = 0.014). Response to therapy (defined as resolution of initial serum creatinine elevations within 48 weeks) refined the prognosis based on initial serum creatinine determinations. The risk for subsequent renal failure was higher among patients who failed to respond to therapy within 48 weeks (30% compared with 0%; P = 0.015). By comparison, 9% of patients with normal initial serum creatinine levels progressed to renal failure after 48 weeks. Conclusions: Initial serum creatinine levels and responses to initial therapy with prednisone and short-term cyclophosphamide, as used in the LNCS, can guide further therapy. Patients with normal initial serum creatinine levels or resolution of initial serum creatinine elevations within 48 weeks have a low risk for renal failure and may not require long-term treatment with cyclophosphamide.
INSULIN TREATMENT OF POSTOPERATIVE (NONDIABETIC) ACIDOSIS
Authors: WILLIAM THALHIMER
Journal: JAMA (1923)

The possibility of treating various types of nondiabetic acidosis with insulin must have occurred to many, since insulin causes such a rapid disappearance of diabetic acidosis. We have treated three cases of postoperative acidosis with insulin,<sup>1</sup>causing almost immediate cessation of vomiting and ketosis; and although this is an extremely small number of cases, they are worthy of publication because, with the widespread interest in insulin therapy, our results may stimulate others to investigate in this field. The improvement in Cases 1 and 2 was quite as rapid and as dramatic as is caused by insulin in diabetic coma. In Case 3 the improvement was not as rapid at first with a small dose of insulin, but the condition rapidly cleared up with larger doses. <h3>REPORTS OF CASES</h3><h3>Case 1.</h3> —Mrs. F., aged 35 years, was operated on for a fibromyoma of the uterus, May 12, 1923, a supravaginal
A Lecture ON SOME OF THE LESS COMMON ASPECTS OF PNEUMONIA: Delivered to the York Medical Society
Authors: T. Oliver
Journal: BMJ (1910)

PNEUMONIA is no longer regarded as a local inflammation 43f the lungs attended or followed by a rise of temperature, but rather as the localized expression of a constitutional state and due to the operations of-a micro-organism.Speaking generally, it is a striking fact that although a specific micro-organism is the recognized cause of a partioulax disease, and that without the microbe the malady is impossible, yet something more than the preseno of the micro-organism in the body is required to explain disease.Tubercle bacilli, for example, may be present in the body without giving rise to symptoms.People harbour Eberth's bacillus for years, and go about in apparent health spreading typhoid fever, although they -themselves are not suffering from the fever.The pneumococcus is, present in the mouth in fully 25 per cent. of men