tbuckley/cabot-search huggingface dataset:
Destructive pulmonary disease due to mixed anaerobic infection
Authors: O. Seriki, A. Adeyokunnu, T. O. De La Cruz
Journal: Thorax (1970)

Pulmonary infection is one of the commonest infections in childhood and is responsible for considerable mortality and morbidity, especially in Nigeria. Most infections are caused by <i>Staphylococcus pyogenes, Streptococcus pneumoniae,</i> and <i>Haemophilus influenzae,</i> though occasionally other organisms such as <i>Klebsiella pneumoniae,</i> coliform, and salmonella are responsible. Rarely does one encounter mixed infection with <i>Clostridium welchii,</i> coliform, and anaerobic streptococci organisms which are the causative organisms in the case reported here. The child presented with features of a bronchopneumonia and empyema, and was later shown to have destructive lung disease due to unusual organisms. This diagnosis was reached on the basis of the radiological finding and bacteriological examination of the sputum. The child was treated with appropriate antibiotics and postural drainage and, when the condition had improved, was subjected to thoracotomy and excision of the diseased lung. He made an uneventful recovery.
Mobilization of Bone Marrow–Derived Cells Enhances the Angiogenic Response to Hypoxia Without Transdifferentiation Into Endothelial Cells
Authors: Thomas J. O’Neill, Brian R. Wamhoff, Gary K. Owens, Thomas C. Skalak
Journal: Circulation Research (2005)

Bone marrow-derived cells (BMCs) have been implicated as a modifiers of vascular growth either directly by transdifferentiation into endothelial cells (ECs) or indirectly through growth factor release. To examine these possibilities under physiological conditions, we developed a model of hypoxia-mediated angiogenesis in the mouse spinotrapezius muscle. This allows whole-mount analysis; therefore, the morphology and location of BMCs within the vascular network may be observed along with differentiation markers. We exposed bone marrow transplant chimeric mice to hypoxia and treated a subset with granulocyte macrophage colony-stimulating factor. Exposure to hypoxia caused an 13% increase in capillary density relative to control. Hypoxia did not increase the overall number of muscle-resident BMCs, but did increase the number of rounded BMCs by 25%. There was no discernable BMC contribution to the endothelium, although some BMCs assumed a pericyte morphology around capillaries. Granulocyte macrophage colony-stimulating factor treatment further increased the number of round BMCs within the muscle and caused a 23% increase in angiogenesis. The results of this study suggest a potentially beneficial action of BMCs during hypoxia through paracrine release of growth factors but not transdifferentiation into ECs.
A Phase I Trial of Combined Ridaforolimus and MK-2206 in Patients with Advanced Malignancies
Authors: Shilpa Gupta, Guillem Argilés, Pamela N. Munster, Antoine Hollebecque, Olav Dajani, Jonathan D. Cheng, Ruixue Wang, Ann Swift, Alessandra Tosolini, Sarina A. Piha-Paul
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The PI3K/Akt/mTOR signaling pathway is aberrantly activated in many cancers. Combining ridaforolimus, an mTOR inhibitor, with MK-2206, an Akt inhibitor, may more completely block the PI3K pathway and inhibit tumor growth. Experimental Design: This phase I study assessed dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of oral ridaforolimus plus oral MK-2206 in patients with advanced solid tumors. Efficacy was evaluated in patients with biomarker-identified estrogen receptor–positive breast cancer (low RAS gene signature and high Ki67 index) or castration-resistant prostate cancer (PTEN deficiency) with PI3K pathway addiction. Results: Thirty-five patients were enrolled: 11 patients in part A (three breast cancer) and 24 biomarker-eligible patients in part B (16 breast cancer, eight prostate cancer). One patient with breast cancer from part A was also found to be biomarker-eligible when tested after she had clinical response. The MTD was 10 mg/d ridaforolimus 5 d/wk + 90 mg/wk MK-2206; 1 of 17 patients experienced DLT (grade 3 rash) at this dose. The most common adverse events at MTD were rash (44.4%), stomatitis (38.9%), diarrhea (27.8%), and decreased appetite (27.8%). By investigator assessment, 2 of 16 (12.5%) evaluable patients with breast cancer had partial response; by central assessment, 2 of 14 (14.3%) evaluable patients had complete response. Two patients had durable stable disease (SD) for 416 and 285 days, respectively. No patients with prostate cancer responded; one patient had SD for ≥6 months. Conclusions: Combination ridaforolimus and MK-2206 showed promising activity and good tolerability in heavily pretreated patients with hormone-positive and -negative breast cancer exhibiting PI3K pathway dependence. Clin Cancer Res; 21(23); 5235–44. ©2015 AACR.
Urokinase-Type Plasminogen Activator Receptor Is Involved in Mediating the Apoptotic Effect of Cleaved High Molecular Weight Kininogen in Human Endothelial Cells
Authors: Dian J. Cao, Yan-Lin Guo, Robert W. Colman
Journal: Circulation Research (2004)

Cleaved high molecular weight kininogen (HKa) has been shown to inhibit in vivo neovascularization and induce apoptosis of endothelial cells. We have shown that HKa-induced apoptosis correlated with its antiadhesive effect and was regulated by extracellular matrix (ECM) proteins. In this study, we identified the urokinase-type plasminogen activator receptor (uPAR) as a target of HKa activity at the endothelial cell surface. Anti-uPAR antibodies blocked the apoptotic effect of HKa. Further studies revealed that uPAR formed a signaling complex containing integrin alpha(v)beta3 or alpha5beta1, caveolin, and Src kinase Yes in endothelial cells. HKa physically disrupted the formation of this complex in a manner that paralleled its apoptotic effect. For the first time, our results provide a mechanistic explanation for the previous observation that HKa selectively induces apoptosis of endothelial cells grown on vitronectin, but not cells grown on fibronectin. These data also resolve the controversial role of uPAR in mediating the apoptotic and antiadhesive activities of HKa.
Controlled trial of disodium cromoglycate in chronic persistent ulcerative colitis.
Authors: N A Buckell, S R Gould, D W Day, J E Lennard-Jones, A M Edwards
Journal: Gut (1978)

Oral disodium cromoglycate (200 mg qds) has been tested in 26 patients with ulcerative colitis that was resistant to medical treatment. In a double-blind crossover trial disodium cromoglycate and placebo were added to conventional treatment in random order, each for four weeks. There was no significant difference in therapeutic effect between disodium cromoglycate and placebo.
Contempo '81. Ethics
Authors: R. M. Veatch
Journal: JAMA (1981)

This last year saw a major development in professionally articulated statements of ethics for physicians. The American Medical Association's House of Delegates adopted the first major revision of its Principles of Ethics since 1957. The newly adopted principles continue the tradition begun in 1847 when the AMA, meeting in Philadelphia, first adopted a code governing the professional conduct of its members. It has undergone four previous revisions since then. The original purpose of the current effort to revise the principles was to modernize the language, eliminate reference to gender, and reach an appropriate understanding of the relation between professional principles and contemporary society. An Ad Hoc Committee, working for two years under the chairmanship of New Jersey surgeon James S. Todd, MD, dealt simultaneously with controversial issues in the public eye, such as the ethics of advertising and chiropractic, and more subtle, fundamental issues, such as the relationship of the
Histamine-releasing factor: a possible future therapeutic target for asthma and allergy
Authors: Victoria Elizabeth Beasley
Journal: Thorax (2012)

Journal clubHistamine-releasing factor: a possible future therapeutic target for asthma and allergy Mast cells and basophils are key players in the IgE-dependent allergic response.These cells trigger an inflammatory cascade by secreting numerous preformed pro-inflammatory chemical mediators such as histamine, proteases and cytokines into the blood.Histamine-releasing factor (HRF), found in nasal, skin blister and bronchoalveolar lavage fluids, is a protein secreted by macrophages that can stimulate histamine, interleukin 4 and IL-3 production from IgE-sensitised basophils and mast cells.Despite considerable efforts, research has failed to identify a HRF receptor.However, HRF is known to have intracellular and extracellular functions, with the latter implicated in late-phase allergic reactions and chronic inflammation.This study identified a subset of IgE and IgG antibodies as HRF-interacting molecules in vitro.Through complex molecular research techniques it was confirmed that HRF together with HRF-reactive IgE triggered mast cell activation in vitro, confirming its pro-inflammatory role.Specific HRF inhibitor peptides were also characterised.Through several different intricate experiments these peptides were found to suppress passive cutaneous anaphylaxis and mast cell-dependent airway inflammation and substantially reduce allergic airway inflammation.These findings provide further clarification that HRF promotes allergic inflammation in the skin and lung via an immediate hypersensitivity reaction.The authors conclude that HRF could be a future novel therapeutic target for asthma and allergy.However, this development may be reliant on the discovery of a specific HRF receptor.Furthermore, the additional intracellular activities of HRF are extensive and more specific research related to these functions may also be essential.
Essentialism gives way to motivation
Authors: Adele E. Goldberg
Journal: Behavioral and Brain Sciences (2009)

Abstract The recognition that contentful universals are rare and often “banal” does not undermine the fact that most non-universal but recurring patterns of language are amenable to explanation. These patterns are sensical or motivated solutions to interacting and often conflicting factors. As implied by the Evans &amp; Levinson's (E&amp;L's) article, linguistics would be well served to move beyond the essentialist bias that seeks universal, innate, unchanging categories with rigid boundaries.
Diathermy Dissection of the Gall-bladder
Authors: R. J. M. Love
Journal: BMJ (1947)

MEDICAL JOURtNALtest meal revealed no free acid.There were no obvious abnormalities of the stomach and gall-bladder on x-ray examination.Dietetic treatment was given.On Feb. 23, 1946, he reported again at the out-patient department.He had been free from symptoms for seven months, but during the preceding few weeks he had renewed attacks of pain, mostly after milk and porridge.Once more there was no abnormality of the gall-bladder.He was completely free of symptoms after some days of complete rest and frequent small meals with little fat and without milk. ConclusionsFrom a total of 220 extirpations of the gall-bladder and 174 resections of the stomach over a period of 3* years it was observed that gallstones occurred on six occasions shortly after a resection.As a result we believe that it is necessary, when patients complain of pain after resection, to look for the cause in the gall-bladder rather than the anastomosis.Some arguments support the view that the Billroth II type of operation may further the formation of gallstones.
Relation Between Autonomic Function and Blood Glucose in the Nondiabetic Range
Authors: Johan D. Lefrandt, Marieke C. Mulder, Eelke Bosma, Andries J. Smit, Klaas Hoogenberg
Journal: Diabetes Care (2001)

We agree with Marfella et al. (1) that increased free radical generation could very well be a common denominator of the mechanisms by which elevations in blood glucose influence baroreflex sensitivity (BRS) in healthy subjects, as we have proposed (2). Free radicals influence Na+-K+-ATPase enzyme activity and intracytosolic free Ca2+ content at the cellular level as well as …
How prominent are patient-reported outcomes in clinical trials of dermatological treatments?
Authors: A.P. Townshend, C-M. Chen, H.C. Williams
Journal: British Journal of Dermatology (2008)

Journal Article How prominent are patient‐reported outcomes in clinical trials of dermatological treatments? Get access A.P. Townshend, A.P. Townshend Centre of Evidence‐Based Dermatology, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar C‐M. Chen, C‐M. Chen GSF – National Research Centre for Environment and Health, Institute of Epidemiology, Neuherberg, Germany Search for other works by this author on: Oxford Academic Google Scholar H.C. Williams H.C. Williams Centre of Evidence‐Based Dermatology, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, U.K. Correspondence: Hywel C. Williams. E‐mail: Hywel.williams@nottingham.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 5, 1 November 2008, Pages 1152–1159, https://doi.org/10.1111/j.1365-2133.2008.08799.x Published: 01 November 2008
Differential Macrophage Polarization in Male and Female BALB/c Mice Infected With Coxsackievirus B3 Defines Susceptibility to Viral Myocarditis
Authors: Kang Li, Wei Xu, Qiang Guo, Zhenggang Jiang, Ping Wang, Yan Yue, Sidong Xiong
Journal: Circulation Research (2009)

Myocardial infiltrating macrophages play an important role in the pathogenesis of viral myocarditis in male BALB/c mice following coxsackievirus B3 (CVB3) infection. Interestingly, comparable macrophage numbers were observed in the myocardium of female mice during acute myocarditis.Given CVB3 infection causes severe myocarditis in male but not female mice, we postulated that macrophages infiltrating the myocardium of female mice may display distinct functional properties that contribute to differential susceptibility to CVB3 myocarditis.Here, we found that myocardial infiltrating macrophages from CVB3-infected male mice expressed high levels of classically activated macrophages (M1) markers, including inducible nitric oxide synthase, interleukin-12, tumor necrosis factor-alpha, and CD16/32, whereas those of females showed enhanced expression of arginase 1, interleukin-10, macrophage mannose receptor (MMR) and macrophage galactose type C-type lectin (MGL) that were associated with alternatively activated macrophage (M2) phenotype. Moreover, distinct myocardial-derived cytokines were found to play a critical role in differential macrophage polarization between sexes after CVB3 infection. Adoptive transfer of ex vivo programmed M1 macrophages, as expectedly, significantly increased myocarditis in both male and female mice. Strikingly, transfer of M2 macrophages into susceptible male mice remarkably alleviated myocardial inflammation by modulating local cytokine profile and promoting peripheral regulatory T cell (Treg) differentiation.Taken together, this study may facilitate the understanding of the mechanism underlying gender bias in susceptibility to CVB3 myocarditis and the development of therapeutic strategies based on macrophage polarization for inflammatory heart disease.
S128 Analysis of volatile biomarkers within exhaled breath for the diagnosis of pneumonia
Authors: P. R. Boshier, V. Mistry, J. R. Cushnir, S. Curtis, S. Elkin, O. M. Kon, N. Marczin, G. B. Hanna
Journal: Thorax (2010)

<h3>Introduction</h3> Whilst pneumonia is a common condition affecting both medical and surgical patients there is currently no definitive diagnostic test. One novel approach may be through the non-invasive analysis of volatile metabolites within exhaled breath, released either by pathogens or host cells. The objective of this study was to delineate the metabolic phenotype of the exhaled breath of patients with community acquired (CAP) and post-operative pneumonia. <h3>Methods</h3> Breath samples were collected from patients with a confirmed diagnosis of CAP (n=26). Targeted analysis of six prominent breath metabolites was performed by selected ion flow tube-mass spectrometry. Metabolites found to be significantly different in the breath of CAP patients were subsequently investigated in patients undergoing both major abdominal and thoracoabdominal surgery (n=40). Receiver operating characteristic (ROC) analysis of putative pneumonia biomarkers was performed in an independent cohort of patients with suspected CAP (n=21). A diagnosis of pneumonia was established through fulfilment of pre-defined radiological, microbiological, haematological and clinical criteria. <h3>Results</h3> Compared to healthy controls, CAP patients had significantly lower breath levels of hydrogen cyanide (6 vs 14ppb, p=0.001) and isoprene (72 vs 111ppb, p=0.014). Patients who developed postoperative pneumonia (n=8) had significantly lower levels of hydrogen cyanide within their breath compared to both those patients who had an uncomplicated recovery (4 vs 13ppb, p=0.008) and healthy controls. Whilst patients who underwent thoracoabdominal compared to abdominal surgery had higher breath levels of isoprene at both 96 (114 vs 176ppb, p=0.02) and 168 h (119 vs 176ppb, p=0.02) following surgery, this did not correlate with the onset of pneumonia. ROC analysis of hydrogen cyanide and isoprene are displayed in Abstract S128 Figure 1. In both medical and surgical patients there was no significant change in the levels of other examined breath metabolites: acetone, ethanol, propanol and acetic acid. <h3>Conclusions</h3> Results provide evidence that the levels of several prominent breath metabolites, which are potentially related to bacterial activity and lung injury, are significantly altered in patients with this disease. Breath analysis may therefore provide a novel, non-invasive and reliable strategy for the diagnosis of pneumonia.
The role of taurine in the pathogenesis of the cardiomyopathy of insulin-dependent diabetes mellitus
Authors: Julius D Militante, John B Lombardini, Stephen W Schaffer
Journal: Cardiovascular Research (2000)

The cellular and molecular physiology and pathology of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) are mostly studied and understood through the use of animal models. Fundamental differences between the IDDM and NIDDM animal models may help to explain the etiology behind diabetic cardiomyopathy, one of the most severe complications of IDDM. Experimental rat models of IDDM exhibit a characteristic increase in tissue levels of taurine in the heart, a change that is not seen in NIDDM rats. This article deals with the causes and possible consequences of this observation which may contribute to the development of diabetic cardiomyopathy. Modulation of pyruvate dehydrogenase (lipoamide) (PDH; EC 1.2.4.1) activity was found to be a possible mode for taurine involvement. PDH is a mitochondrial protein and is the rate-limiting step in the generation of acetyl CoA from glycolysis. In IDDM, PDH activity is decreased through a mechanism that includes the stimulation of the de novo synthesis of a kinase activator protein (KAP) which phosphorylates PDH and inactivates the enzyme. This lesion does not occur in NIDDM rat hearts. Taurine is known to inhibit the phosphorylation of PDH in vitro, and in taurine-depleted rats PDH phosphorylation is known to increase. Thus, the increased levels of taurine in the diabetic heart may be inhibiting this phosphorylation which in turn may be stimulating the synthesis of KAP through a negative feedback process. The main argument for this theory would be the lack of change in both the taurine levels and the activity of PDH in the NIDDM rat model.
Delayed Development of Ventricular Ectopic Rhythms following Experimental Coronary Occlusion
Authors: A. SIDNEY HARRIS
Journal: Circulation (1950)

Following aseptic occlusion of the anterior descending artery of the dog's heart ectopic ventricular tachycardia develops after a latency of four and one-half to eight hours, and persists for two to four days. Large gross infarcts are found in all hearts. The duration of latency of onset of major ectopic activity approximates the minimal period of ischemia required to produce histologic signs of necrosis. It is suspected that products or processes of necrosis have excitatory effects on tissues bounding the ischemic zone. Evidences concerning various possible excitatory factors are briefly reviewed.
[47] THE LONG TERM BENEFITS OF BARIATRIC SURGERY CORRELATED TO INSULIN RESISTANCE: A PROSPECTIVE STUDY WITH 5 YEARS OF FOLLOW UP
Authors: A. Hollebecque, L. Arnalsteen, A. Louvet, E. Leteurtre, S. Dharancy, F. Gonzalez, V. Canva, P. Deltenre, F. Pattou, P. Mathurin
Journal: Journal of Hepatology (2007)
Some facts and thoughts: p73 as a tumor suppressor gene in the network of tumor suppressors
Authors: Lakshmanane Boominathan
Journal: Molecular Cancer (2007)

The question of whether p73 is a tumor suppressor gene, is not yet answered with full confidence. The lack of spontaneous tumor formation in p73 null mice and infrequent p73 mutations seen in a variety of cancers analyzed would straightaway negate its role as a primary tumor suppressor gene. However, accumulating evidence suggest that p73 gene and its target genes are hypermethylated in the cancer of lymphoid origin. Here I discuss some facts and thoughts that support the idea that p73 could still be a tumor suppressor gene. The tumor suppressor network in which p73 appears to be a participant involves E2F1, JunB, INK4a/p16, ARF/p19, p57kip2 and BRCA1. Knock out of each gene in E2F-1-p73-JunB-p16INK4a network of tumor suppressor proteins result in lymphoma/leukemia formation. Further, I tried to explain why lymphomas are not seen in p73 null mice and why p73 gene is not prone to frequent mutation.
(15) Congenital ichthyosiform erythroderma
Authors: A. Navaratnam, G.A. Hodgson
Journal: British Journal of Dermatology (1973)

Journal Article (15) Congenital ichthyosiform erythroderma Get access A. Navaratnam, A. Navaratnam Department of Dermatology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar G.A. Hodgson G.A. Hodgson Department of Dermatology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue s9, 1 July 1973, Pages 64–67, https://doi.org/10.1111/j.1365-2133.1973.tb03448.x Published: 01 July 1973