tbuckley/cabot-search huggingface dataset:
CUMBERLAND INFIRMARY: PAST, PRESENT, AND FUTURE
Authors: N. Maclaren
Journal: BMJ (1925)

IN 1828 Carlisle was a very different city from what it is to- day.At that time only a few years had passed since a broad turreted wall had enclosed the city.On the south stood the citadel with its frowning barbicans, and on the north the castle with its battled towers and donjon keep.The gates of * Presidential address (abridged) delivered to the Border Counties Rranch of the British Medical Association on July 10th, 1925.were admitted annually.At Whitehaven thert, was also a dis- pensary and fever house; nearly 3,000 patients were annually
Myeloid Expression of Adenosine A2A Receptor Suppresses T and NK Cell Responses in the Solid Tumor Microenvironment
Authors: Caglar Cekic, Yuan-Ji Day, Duygu Sag, Joel Linden
Journal: Cancer Research (2014)

Abstract High concentrations of adenosine in tumor microenvironments inhibit antitumor cytotoxic lymphocyte responses. Although T cells express inhibitory adenosine A2A receptors (A2AR) that suppress their activation and inhibit immune killing of tumors, a role for myeloid cell A2ARs in suppressing the immune response to tumors has yet to be investigated. In this study, we show that the growth of transplanted syngeneic B16F10 melanoma or Lewis lung carcinoma cells is slowed in Adora2af/f–LysMCre+/− mice, which selectively lack myeloid A2ARs. Reduced melanoma growth is associated with significant increases in MHCII and IL12 expression in tumor-associated macrophages and with &amp;gt;90% reductions in IL10 expression in tumor-associated macrophages, dendritic cells (DC), and Ly6C+ or Ly6G+ myeloid-derived suppressor cells (MDSC). Myeloid deletion of A2ARs significantly increases CD44 expression on tumor-associated T cells and natural killer (NK) cells. Depletion of CD8+ T cells or NK cells in tumor-bearing mice indicates that both cell types initially contribute to slowing melanoma growth in mice lacking myeloid A2A receptors, but tumor suppression mediated by CD8+ T cells is more persistent. Myeloid-selective A2AR deletion significantly reduces lung metastasis of melanomas that express luciferase (for in vivo tracking) and ovalbumin (as a model antigen). Reduced metastasis is associated with increased numbers and activation of NK cells and antigen-specific CD8+ T cells in lung infiltrates. Overall, the findings indicate that myeloid cell A2ARs have direct myelosuppressive effects that indirectly contribute to the suppression of T cells and NK cells in primary and metastatic tumor microenvironments. The results indicate that tumor-associated myeloid cells, including macrophages, DCs, and MDSCs all express immunosuppressive A2ARs that are potential targets of adenosine receptor blockers to enhance immune killing of tumors. Cancer Res; 74(24); 7250–9. ©2014 AACR.
Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide.
Authors: D S Marks, J A Vita, J D Folts, J F Keaney, G N Welch, J Loscalzo
Journal: Journal of Clinical Investigation (1995)

Endothelium-derived relaxing factor is important for vascular homeostasis and possesses qualities that may modulate vascular injury, including vasodilation, platelet inhibition, and inhibition of smooth muscle proliferation. S-nitrososerum albumin is a naturally occurring adduct of nitric oxide (NO) with a prolonged biologic half-life and is a potent vasodilator and platelet inhibitor. Given the avidity of serum albumin for subendothelial matrix and the antiproliferative effects of NO, we investigated the effects of locally delivered S-nitroso-bovine serum albumin (S-NO-BSA) and a polythiolated form of bovine serum albumin (pS-BSA) modified to carry several S-nitrosothiol groups (pS-NO-BSA) on neointimal responses in an animal model of vascular injury. Locally delivered S-NO-BSA bound preferentially to denuded rabbit femoral vessels producing a 26-fold increase in local concentration compared with uninjured vessels (P = 0.029). pS-NO-BSA significantly reduced the intimal/medial ratio (P = 0.038) and did so in conjunction with elevations in platelet (P < 0.001) and vascular cGMP content (P < or = 0.001). pS-NO-BSA treatment also inhibited platelet deposition (P = 0.031) after denuding injury. Comparison of BSA, S-NO-BSA, pS-NO-BSA, and control revealed a dose-response relationship between the amount of displaceable NO delivered and the extent of inhibition of neointimal proliferation at 2 wk (P < or = 0.001). Local administration of a stable protein S-nitrosothiol inhibits intimal proliferation and platelet deposition after vascular arterial balloon injury. This strategy for the local delivery of a long-lived NO adduct has potential for preventing restenosis after angioplasty.
Prognostic factors of hepatocellular carcinoma in the west: A multivariate analysis in 206 patients
Authors: Xavier Calvet, Jordi Bruix, Pere Ginés, Concepció Bru, Manel Sole, Ramón Vilana, Joan Rodés
Journal: Hepatology (1990)

To investigate the prognostic factors in Western patients with hepatocellular carcinoma, 206 patients with confirmed diagnoses of hepatocellular carcinoma were studied in terms of survival. All patients were diagnosed between 1983 and 1987. A multivariate survival analysis (Cox regression model) using clinical, biochemical, ultrasonographical and pathological data obtained at diagnosis disclosed that bilirubin (p = 0.0001), ascites (p = 0.0001), toxic syndrome (defined by the presence of weight loss &gt; 10% premorbid weight, malaise and anorexia) (p = 0.009), blood urea nitrogen (p = 0.025), tumor size (p = 0.001), γ-glutamyltranspeptidase (p = 0.0006), age (p = 0.0005), serum sodium (p = 0.003) and presence of metastases (p = 0.002) were independent predictors of survival. According to the contribution of each of these factors to the final model, a prognostic index was constructed allowing division of patients in different groups according to their relative risk of death: RRD = EXP (Age × 0.03 + Ascites × 0.8281 + BUN × 0.0137 + Serum sodium × (− 0.0538) + γ-Glutamyltranspeptidase × 0.0019 + Bilirubin × 0.0734 + Tumor size × 0.33 + Toxic syndrome × 0.4965 + Metastases × 0.55). These results facilitate the stratification of hepatocellular carcinoma patients to design and evaluate future controlled trials. (HEPATOLOGY 1990;12:753-760).
EVOLUTION OF MEDICAL EDUCATION IN THE ARMY.
Authors: PHILIP F. HARVEY
Journal: JAMA (1907)

The recognition of the vital relation that a well organized and trained sanitary personnel bears to the efficiency of an army in the field has been of slow growth and there is yet an inadequate appreciation of that relationship in certain quarters, notwithstanding the awful lessons taught by sanitary unreadiness in many wars of recent times. It would appear that there is still cherished a belief among many otherwise well informed persons that in the event of war an abundant number of skilled physicians and surgeons would be available for duty with troops. That is true, but the essential prerequisites of military training for the military physician is lost sight of. The well equipped military surgeon must understand, in addition to his purely professional duties, the complex subjects of medical administration, including the customs of the service; the hygiene of posts and camps; the service of the front and rear,
Direct Effects of Salicylate on Renal Function in the Dog
Authors: A. Quintanilla, R. H. Kessler
Journal: Journal of Clinical Investigation (1973)

Sodium salicylate was administered to anesthetized dogs in doses sufficient to produce concentrations in plasma comparable to those common in human salicylate toxicity. Salicylate administration increased the rates of excretion of water, sodium, and chloride in the urine. Salicylate administration also increased the rate of excretion of potassium so that its clearance often exceeded that of creatinine. This enhancement of potassium excretion was dissociated from the alkalosis that accompanies salicyate toxicity. Administration of 5% CO(2) in inspired gas did not attenuate the excretion of potassium; injection of salicylate into one renal artery caused a unilateral kaliuresis. Phosphate excretion increased progressively after administration of salicylate. On several occasions the clearance of phosphate equalled that of creatinine. Salicylate reduced renal tubular glucose reabsorption. When salicylate was injected into a renal artery, a glycosuria occurred ipsilaterally at filtered loads of glucose far below the reabsorptive capacity of the dog kidney. Salicylate administration also was associated with early elevation of glucose, phosphate, and potassium concentration in plasma. Salicylate administration reduced the content of adenosine triphosphate in the renal medulla. Salicylate was concentrated within the medulla between 1.5 and 3 times that of the cortex, a gradient equal to that for chloride.
Interstitial Pneumonia in Angio-Immunoblastic Lymphadenopathy with Dysproteinemia
Authors: Michael D. Iseman, Marvin I. Schwarz, Ray E. Stanford
Journal: Annals of Internal Medicine (1976)

A patient presented with characteristic historical, physical, and laboratory findings of angio-immunoblastic lymphadenopathy with dysproteinemia. This newly described entity apparently represents a nonneoplastic proliferation of the B-lymphocyte system with immunoblastic transformation of many lymphocytes and excessive production of immunoglobulins. It is associated with fever, sweats, weight loss, skin rash, lymphadenopathy, splenomegaly, hepatomegaly, and characteristic histologic features of the involved lymph nodes. Noteworthy in the patient reported here are the extent and course of radiographically and clinically evident pulmonary involvement and the biopsy documentation of an interstitial pneumonia marked by histopathologic changes closely resembling those found in the lymph nodes, with immunohistologic demonstration of immunoglobulins in the alveolar walls.
Inhaled particles in human disease and animal models: use of electron beam instrumentation.
Authors: A R Brody
Journal: Environmental Health Perspectives (1984)

The mineral pneumoconioses (lung disease caused by inhalation of inorganic dust) have been an important disease entity for centuries. In the last several decades, the electron microscope has been used to elucidate the distribution and identification of inhaled minerals, to aid in establishing etiologic factors, and less commonly, to determine the basic biologic mechanisms through which inhaled minerals cause lung disease. In this section, I review the instrumentation and tissue preparation currently used to address some modern problems in particle-induced lung disease. For example, human pneumoconioses of undetermined etiology can be clarified by electron microscopy and X-ray energy spectrometry. In addition, the initial deposition patterns of asbestos and silica are demonstrated in animal models, and the contributions of electron microscopy in establishing the initial lesions of asbestosis are described.
Antibody Response in Infants to the Poliomyelitis Component of a Quadruple Vaccine
Authors: I. B. Hillary, P. N. Meenan, A. P. Goffe, G. J. Knight, A. D. Kanarek, T. M. Pollock
Journal: BMJ (1962)

ORAL POLIOMYELITIS VACCINATION BJuA vaccinated regions was initiated in November, 1958, and repeated random collections of stool specimens were made throughout 1959 and 1960.In 1958-9 a total of 2,322 specimens was collected in the four vaccinated regions, and 2,964 specimens in 10 non-vaccinated provinces; in 1960 a total of 7,486 stool specimens was collected from healthy children throughout the whole country.At least three important observations can be made from the results gained hitherto. (1)The initial spread of viruses which foUows their mass introduction into the child population is self-limited, and the attenuated strains (Sabin) do not appear to persist in a community longer than a few months. (2)There is no evidence that the attenuated viruses spread beyond the regions into which they had been introduced. (3)An extraordinarily reduced spread of polioviruses could be demonstrated at the peak of the season, after the nationwide use of oral vaccine in the spring of 1960.We are indebted to many co-workers without whose help this programme, completion of surveillance, could not have been carried out.
Anaphylaxis and IgE Antibodies to Galactose-Alpha-1,3-Galactose (alphaGal): Insight from the Identification of Novel IgE ab to Carbohydrates on Mammalian Proteins
Authors: S COMMINS, S LUCAS, J HOSEN, S SATINOVER, L BORISH, T PLATTSMILLS
Journal: Journal of Allergy and Clinical Immunology (2008)
Therapeutic retraction of the foreskin in childhood
Authors: R J Brereton
Journal: BMJ (1983)

3 7h1 4 ng/ml), normal range 7-30 nmol/l (2 0-8 7 ng/ml)) (unpublished data).In view of these observations and the fact that seven of our patients without obstructive jaundice had subnormal testosterone con- centrations, we think it unlikely that impaired hepatic function secondary to obstructive jaundice could account for our findings.
Disposable instrument issue affects lots of doctors too
Authors: E. Willis
Journal: BMJ (2008)

Background: Angiotensin 1 converting enzyme (ACE) inhibitors reduce morbidity and mortality after coronary artery bypass graft surgery (CABG). This benefit may result from an anti-inflammatory action. Objective: To examine the effect of ACE inhibition on interleukin 6 (IL-6) concentrations after CABG. Patients and methods: 161 patients undergoing elective first time CABG were recruited, of whom 41 (25%) were receiving ACE inhibitor treatment; 21 patients with confounding postoperative complications were excluded. After these exclusions there were 33 patients (24%) on ACE inhibitor treatment. Plasma IL-6 was measured preoperatively and again six hours after CABG. Results: Baseline IL-6 concentrations (geometric mean (SEM)) were non-significantly lower among the patients receiving ACE inhibitors (3.7 (0.1) <i>v</i> 4.3 (0.1) pg/ml, p = 0.12). Overall, post-CABG IL-6 concentrations increased significantly (mean rise 177 (12) pg/ml, p &lt; 0.0005). This response was blunted among ACE inhibitor treated patients. Median increases in IL-6 concentrations were 117 <i>v</i> 193 pg/ml, for treated <i>v</i> non-treated patients, respectively (Kruskal–Wallis, p = 0.02), with peak postoperative IL-6 concentrations lower among the subjects receiving ACE inhibitors than in untreated subjects (142 (19) <i>v</i> 196 (13) pg/ml, p = 0.02). The effect of ACE inhibitors remained significant after multivariate analysis (p = 0.018). Conclusions: ACE inhibitor treatment is associated with a reduction in IL-6 response to CABG. The data suggest that this class of drug may have a direct anti-inflammatory effect, which could explain some of its clinical benefit.
Effects of thrombomodulin and coagulation Factor Va-light chain on protein C activation in vitro.
Authors: H H Salem, N L Esmon, C T Esmon, P W Majerus
Journal: Journal of Clinical Investigation (1984)

Protein C activation by thrombin is significantly accelerated by the endothelial cell surface protein thrombomodulin, Factor Va, or its light chain. In this study we have compared the activation of protein C in the presence of either cofactor and examined the possibility that thrombomodulin and Factor Va-light chain act together to regulate protein C activation by thrombin. At all concentrations of protein C used, thrombomodulin was 20 times more efficient than Factor Va-light chain in accelerating protein C activation by thrombin. Protein C treated with chymotrypsin to remove the amino-terminal 41 amino acids that contain the gamma-carboxyglutamyl residues was activated by the thrombin-thrombomodulin complex at an identical rate to native protein C, whereas the modified protein C was activated by Factor Va-light chain and thrombin at only 5% of the rate obtained by using native protein C. Increasing concentrations of Factor Va-light chain, greater than or equal to 30 nM, inhibited thrombin-thrombomodulin catalyzed protein C activation with complete inhibition observed at 90 nM Factor Va-light chain. On the other hand, increasing thrombomodulin concentrations did not inhibit protein C activation by Factor Va-light chain and thrombin. These reactions in solution mimic, in part, those obtained on endothelial cells where protein C lacking the gamma-carboxyglutamyl domain is activated poorly and Factor Va-light chain at concentrations greater than 50 nM inhibited the activation of native protein C. The results of this study suggest that thrombomodulin and Factor Va-light chain may act in concert to regulate protein C activation by thrombin.
Pathological Cardiac Hypertrophy Alters Intracellular Targeting of Phosphodiesterase Type 5 From Nitric Oxide Synthase-3 to Natriuretic Peptide Signaling
Authors: Manling Zhang, Eiki Takimoto, Dong-ik Lee, Celio X.C. Santos, Taishi Nakamura, Steven Hsu, Aiyang Jiang, Takahiro Nagayama, Djahida Bedja, Yuan Yuan, Philip Eaton, Ajay M. Shah, David A. Kass
Journal: Circulation (2012)

Background In the normal heart, phosphodiesterase type 5 (PDE5) hydrolyzes cGMP coupled to nitric oxide– (specifically from nitric oxide synthase 3) but not natriuretic peptide (NP)–stimulated guanylyl cyclase. PDE5 is upregulated in hypertrophied and failing hearts and is thought to contribute to their pathophysiology. Because nitric oxide signaling declines whereas NP-derived cGMP rises in such diseases, we hypothesized that PDE5 substrate selectivity is retargeted to blunt NP-derived signaling. Methods and Results Mice with cardiac myocyte inducible PDE5 overexpression (P5 + ) were crossed to those lacking nitric oxide synthase 3 (N3 − ), and each model, the double cross, and controls were subjected to transaortic constriction. P5 + mice developed worse dysfunction and hypertrophy and enhanced NP stimulation, whereas N3 − mice were protected. However, P5 + /N3 − mice behaved similarly to P5 + mice despite the lack of nitric oxide synthase 3–coupled cGMP generation, with protein kinase G activity suppressed in both models. PDE5 inhibition did not alter atrial natriuretic peptide–stimulated cGMP in the resting heart but augmented it in the transaortic constriction heart. This functional retargeting was associated with PDE5 translocation from sarcomeres to a dispersed distribution. P5 + hearts exhibited higher oxidative stress, whereas P5 + /N3 − hearts had low levels (likely owing to the absence of nitric oxide synthase 3 uncoupling). This highlights the importance of myocyte protein kinase G activity as a protection for pathological remodeling. Conclusions These data provide the first evidence for functional retargeting of PDE5 from one compartment to another, revealing a role for natriuretic peptide–derived cGMP hydrolysis by this esterase in diseased heart myocardium. Retargeting likely affects the pathophysiological consequence and the therapeutic impact of PDE5 modulation in heart disease.
Basic Principles of Transport Across Cell Membranes.
Authors: I. S. Edelman
Journal: Annals of Internal Medicine (1962)

s1 April 1962Basic Principles of Transport Across Cell Membranes.I. S. Edelman, M.D.I. S. Edelman, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-697_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTransport of water and solute across cell membranes is described in terms of the chemical characteristics of the passengers, the properties of the cell membranes constituting the passages and the sources of energy needed to effect observed flows. The distinction between passive and active transport is based on the concept that if the force producing the flow resides in the external solutions, that is, concentration gradients, pressure gradients, electrical gradients, or thermal gradients, it is passive; whereas if it arises in the boundary or membrane and is derived from chemical bond energy, it is active. Applications of these concepts to... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: I. S. Edelman, M.D.Affiliations: San Francisco, Calif. (BS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1962Volume 56, Issue 4Page: 697-697KeywordsAttentionCell membranes ePublished: 1 December 2008 Issue Published: 1 April 1962 PDF downloadLoading ...
Lower prevalence of asthma and atopy in Turkish children living in Germany
Authors: M Kabesch, W Schaal, T Nicolai, E von Mutius
Journal: European Respiratory Journal (1999)

Ethnic origin has been reported to affect the prevalence of atopic diseases in several studies in different parts of the world. However, little is known about the prevalence of asthma and atopy in immigrants living in Europe. The objective of this study was to evaluate the prevalence of asthma and atopy in Turkish children living in Germany and to investigate the role of ethnic origin on the development of asthma and atopy in this population. In a cross-sectional survey the prevalence of physician-diagnosed asthma, atopy, skin-prick tests and bronchial hyperresponsiveness (BHR) to cold dry air challenge was assessed in 7,445 school children aged 9-11 yrs, living in Munich, south Germany. Questionnaires were distributed to the parents for self-completion and children underwent skin prick tests and cold air hyperventilation challenge. The Turkish children showed a significantly lower prevalence of asthma (5.3 versus 9.4%, p&lt;0.05) than their German peers. Furthermore, atopy, as assessed by skin prick tests (24.7 versus 36.7%, p&lt;0.001) and BHR (3.9 versus 7.7%, p&lt;0.001), was less common in Turkish children. In multivariate regression models controlling for potential explanatory factors, Turkish origin still showed a significantly lower risk of developing asthma, atopic sensitization and BHR. The prevalence of childhood asthma was therefore shown to be lower in Turkish children living in Germany than in Turkey. These findings suggest that the lower prevalence of asthma and allergy in Turkish children living in Germany might be attributable to a selection bias affecting the parents of these children, as healthy individuals may have decided to come to Germany for work.
Primary Lymphoma of the Lung
Authors: Lloyd K. Mark
Journal: JAMA (1977)

PRIMARY lymphoma of the lung is an uncommon yet distinct entity, histologically indistinguishable from secondary or metastatic lymphoma but biologically and behaviorally different.<sup>1</sup>It starts extranodally within the lymphatic tissues of the lung, spreads slowly by contiguity, produces few or no symptoms, and usually can be cured. The following case illustrates primary lymphoma of the lung. <h3>Report of a Case</h3> During a routine investigation, a 59-year-old man was found to have an abnormal chest x-ray film. He denied any symptoms, had smoked a pipe for many years, and considered himself in good health. Results of physical examination, routine and customary laboratory studies, and bronchoscopy were normal. Frontal and lateral roentgenograms of the chest showed a homogeneous, poorly marginated density confined to the right middle lobe (Figure). Tomograms of the lung showed a normal, patent, tracheobronchial tree and an air bronchogram within the right middle lobe. Studies of the sputum