tbuckley/cabot-search huggingface dataset:
Cell and cytokine markers in COPD
Authors: R A STOCKLEY
Journal: Thorax (2000)

We read with interest the paper by Dr Wedzicha and colleagues on cell and cytokine measurements in exacerbations of COPD.1 We feel there are two factors which are worthy of comment. The authors described their patients as being predominantly those with chronic bronchitis. They presented with an exacerbation that consisted of the cardinal features described by Anthonisen and colleagues—namely, combinations of increased breathlessness, increased sputum volume, and increased sputum purulence.2 In view of the fact that increased sputum purulence is a feature of exacerbations, we are surprised at the lack of increase in neutrophils seen in the exacerbations described in the paper. Even if half the patients did not have purulent sputum, we would have expected to have seen an overall increase in the number of neutrophils in the samples …
Angiotensin II–Induced Growth Responses in Isolated Adult Rat Hearts
Authors: Heribert Schunkert, Jun-ichi Sadoshima, Torsten Cornelius, Yutaka Kagaya, Ellen O. Weinberg, Seigo Izumo, Günter Riegger, Beverly H. Lorell
Journal: Circulation Research (1995)

Abstract Cardiac myocyte hypertrophy often occurs in response to both hemodynamic and neurohumoral factors. To study whether activation of the renin-angiotensin system by itself may induce a cardiac growth response, the acute effects of angiotensin II on cardiac protein synthesis were studied in isolated rat hearts. New protein synthesis in isolated buffer-perfused adult rat hearts was measured by incorporation of [ 3 H]phenylalanine into cardiac proteins during a 3-hour perfusion protocol. Angiotensin II (1×10 −8 mol/L), administered alone or in combination with the α 1 -blocker prazosin (1×10 −7 mol/L), stimulated protein synthesis in both ventricles. The rate of [ 3 H]phenylalanine incorporation into cardiac proteins was 3.9-fold ( P &lt;.005) and 2.6-fold ( P &lt;.01) higher in angiotensin II–perfused (n=6) than in vehicle-perfused (n=6) left and right ventricles, respectively. The induction of new protein synthesis by angiotensin II was blocked by the angiotensin II type 1 (AT 1 ) receptor antagonist losartan (1×10 −7 mol/L, n=5). To study the pathways of angiotensin signal transduction, protein kinase C (PKC)-ε as well as cardiac c- fos and c- jun mRNA levels were analyzed. Angiotensin II (1×10 −8 mol/L, n=20) resulted in a transient translocation of PKC-ε from the cytosol to the cellular membrane. However, compared with phorbol ester stimulation (phorbol 12-myristate 13-acetate [PMA], 1×10 −7 mol/L; n=20), angiotensin II effects on PKC translocation were significantly less pronounced and required a more prolonged stimulation. There was no effect of angiotensin II in concentrations from 10 −9 to 10 −6 mol/L (n=22) on c- fos and c- jun mRNA levels in intact adult rat hearts studied over a time course from 15 to 120 minutes of perfusion. In contrast, norepinephrine (10 −6 mol/L, n=6), phorbol ester (PMA, 10 −7 mol/L; n=5), and calcium ionophore (A23187, 2.5×10 −6 mol/L; n=5) infusion as well as elevated left ventricular systolic wall stress (n=6) were all followed by a threefold to fourfold induction of cardiac c- fos and c- jun mRNA levels ( P &lt;.005) compared with respective angiotensin II–infused or vehicle-infused rat hearts (n=12). In contrast, administration of angiotensin II in concentrations &gt;10 −9 mol/L caused a significant induction of c- fos in adult and neonatal cardiac myocytes. In conclusion, angiotensin II acutely stimulates protein synthesis in cultured adult isolated perfused rat hearts. Angiotensin II–activated signal transduction appears to involve AT 1 receptors and activation of PKC. However, further downstream signaling mechanisms remain elusive, since angiotensin II may stimulate protein synthesis in the adult intact heart without preceding c- fos and c- jun proto-oncogene induction.
Mutations of the VHL tumour suppressor gene in renal carcinoma
Authors: J.R. Gnarra, K. Tory, Y. Weng, L. Schmidt, M.H. Wei, H. Li, F. Latif, S. Liu, F. Chen, F.-M. Duh, I. Lubensky, D.R. Duan, C. Florence, R. Pozzatti, M. M. Walther, N.H. Bander, H.B. Grossman, H. Brauch, S. Pomer, J.D. Brooks, W.B. Isaacs, M.I. Lerman, B. Zbar, W.M. Linehan
Journal: Nature Genetics (1994)
HOMICIDE IN THE UNITED STATES.
Authors: PAUL BARTHOLOW
Journal: JAMA (1896)

Murders are of very great frequency in this country. The number reported last year was 10,500, an enormous figure! We might, if there were not some reasons against it, take this number as the annual average, which in most countries is a fairly constant quantity. But here, owing to some conditions that I shall endeavor to particularize, the amount of homicide in any year, taken as a standard, does not give us the least reason for predicting that the succeeding year will be marked by a similar number of murders, neither many more nor less. In 1885, for instance, the homicides reported numbered 1,808; in 1890, 4,290; in 1894, 9,800, and I have just mentioned 10,500 in 1895. That is to say, there was nearly six times as much homicidal crime reported last year as in 1885, an increase almost in arithmetical ratio. In a word, the population loses every
Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci
Authors: John B. Harley, Marta E. Alarcón-Riquelme, Lindsey A. Criswell, Chaim O. Jacob, Robert P. Kimberly, Kathy L. Moser, Betty P. Tsao, Timothy J. Vyse, Carl D. Langefeld, Swapan K. Nath, Joel M. Guthridge, Beth L. Cobb, Daniel B. Mirel, Miranda C. Marion, Adrienne H. Williams, Jasmin Divers, Wei Wang, Summer G. Frank, Bahram Namjou, Stacey B. Gabriel, Annette T. Lee, Peter K. Gregersen, Timothy W. Behrens, Kimberly E. Taylor, Michelle Fernando, Raphael Zidovetzki, Patrick M. Gaffney, Jeffrey C. Edberg, John D. Rioux, Joshua O. Ojwang, Judith A. James, Joan T. Merrill, Gary S. Gilkeson, Michael F. Seldin, Hong Yin, Emily C. Baechler, Quan Zhen Li, Edward K. Wakeland, Gail R. Bruner, Kenneth M. Kaufman, Jennifer A. Kelly
Journal: Nature Genetics (2008)
Hyperlipemic Xanthomatosis with Associated Osseous Granuloma
Authors: Henry J. Koch, John S. Lewis
Journal: New England Journal of Medicine (1956)

THE xanthomatoses have been divided by most authors into two groups, depending on the serum cholesterol concentration.Those exhibiting a high cholesterol in the serum are thought to result from an imbalance of cholesterol production and disposition. Secondary to the hypercholesterolemia, there may be a deposition of cholesterol in the skin, tendons, blood vessels and reticuloendothelial system. The clinical types of xanthomatoses seen in this group are usually classified according to organ-system involvement.The second group has a normal cholesterol concentration and includes such entities as xanthoma disseminatum of the skin, osseous xanthoma and the Schüller-Christian syndrome.1 Here, the fundamental . . .
A flow cytometric study of the significance of DNA aneuploidy in cutaneous lesions
Authors: JULIA A. NEWTON, R.S. CAMPLEJOHN, D.H. MCGIBBON
Journal: British Journal of Dermatology (1987)

Aneuploidy has not to date been demonstrated in any entirely benign condition and thus is held to be implicit of neoplasia. DNA flow cytometry can be used to detect DNA aneuploidy rapidly. A technique has been developed to make possible flow cytometric analysis of formalin-fixed skin. The technique was validated by study of benign and pre-malignant dermatoses. Further studies were performed on skin conditions of questionable malignant potential. DNA aneuploidy was demonstrated in lichen sclerosus et atrophicus. Flow cytometry was unable to distinguish keratoacanthomas from squamous cell carcinomas.
Brother of man with CJD fights to get his treatment reinstated
Authors: C. Dyer
Journal: BMJ (2010)

The brother of a man with sporadic Creutzfeldt-Jakob disease (CJD) has launched a legal action at the Court of Protection in London to try to get his treatment with pentosan polysulphate reinstated after his infusion pump malfunctioned.

The patient, named only as AVS, was given a diagnosis of CJD in May 2008 and a prognosis of only three or four weeks of life, according to papers filed with the court by his brother, CS. But he is still alive two and half years later, after being given pentosan polysulphate from June 2008 until the pump failed in August 2010.

DH, the consultant neurologist at an …
Effect of Insulin Sensitizer Therapy on Amino Acids and Their Metabolites
Authors: Brian A. Irving, Rickey E. Carter, Mattias Soop, Audrey Weymiller, Husnain Syed, Helen Karakelides, Sumit Bhagra, Kevin R. Short, Laura Tatpati, Rocco Barazzoni, K. Sreekumaran Nair
Journal: Metabolism (2015)
ACUTE ASCENDING MYELITIS FOLLOWING A MONKEY BITE, WITH THE ISOLATION OF A VIRUS CAPABLE OF REPRODUCING THE DISEASE
Authors: Albert B. Sabin, Arthur M. Wright
Journal: The Journal of Experimental Medicine (1934)

A case of acute ascending myelitis which followed the bite of an apparently normal Macacus rhesus monkey is described. The clinical course as well as the pathological changes has been studied and found to be suggestive of a virus cause for the disease. The absence of perivascular demyelinization removes the case from the realm of acute disseminated encephalomyelitis and establishes it more or less definitely as a primary acute infectious myelitis. An extremely important feature of the pathological picture of this disease has been the presence of focal necrosis in the viscera (spleen, adrenals, regional lymph nodes). Attempts to transmit the disease to Macacus rhesus monkeys, dogs, mice, and guinea pigs, employing glycerinated organs from the human case, proved unsuccessful. By the inoculations of rabbits the presence of a strongly neurotropic, filtrable virus was demonstrated in the patient's brain, cord, and spleen. Following intracutaneous injection of it as derived either from brain and cord or spleen, an experimental disease develops in rabbits which strikingly resembles the human disease in the character of the local lesion, the incubation period, development of urinary retention, and flaccid paralysis of the posterior extremities with cephalad progression, death by respiratory failure, and finally by the occurrence of focal necrosis in the spleen, adrenals, and liver. In attempting to establish the identity of this virus, (the B virus), a consideration of its biological properties excludes the viruses of poliomyelitis, rabies, vaccinia, Virus III disease of rabbits, and the other viruses which are known to produce similar intranuclear inclusion bodies, except perhaps herpes. Although the relationship between the B virus and the virus of herpes must still be determined by cross-immunity tests it has been shown to possess certain properties which warrant consideration of it as a distinct entity.
All because of the mast cell: blocking the angiotensin receptor-1 should be better than inhibiting ACE (theoretically)
Authors: Bernhard F. Becker
Journal: Cardiovascular Research (2011)

In cardiovascular disease, especially hypertension, chronic heart failure, and atherosclerosis, angiotensin II (Ang II) is generally a culprit while nitric oxide exerts beneficial effects. Accordingly, inhibiting angiotensin-converting enzyme (ACE) has become established as one of the most successful therapeutic options in the treatment of chronic cardiovascular disorders. However, an estimated 20–40% of patients do not respond to and/or tolerate ACE inhibition.1 The introduction of drugs selectively blocking Ang II receptors of type 1 (ARBs) has definitely brought some relief from unwanted side effects. In the paper by Company et al. , appearing in the current issue of Cardiovascular Research ,2 reasons are now given for why one should expect ARBs to be even more beneficial than ACE inhibitors in all cardiovascular conditions with an inflammatory component.

The reasoning and evidence are compelling and centre on the fact that the mast cell enzyme chymase is able to generate Ang II independently of the activity of ACE. In experiments conducted on the mouse cremaster muscle microcirculation, the authors show that degranulating mast cells release chymase in amounts great enough to circumvent the functional protection otherwise provided by an ACE inhibitor under non-inflammatory conditions. In contrast, stimulated mast cells lose much of their microcirculatory destabilizing potential if an ARB is applied instead …
Multi-Tasking RGS Proteins in the Heart
Authors: Evan L. Riddle, Raúl A. Schwartzman, Meredith Bond, Paul A. Insel
Journal: Circulation Research (2005)

Regulator of G-protein-signaling (RGS) proteins play a key role in the regulation of G-protein-coupled receptor (GPCR) signaling. The characteristic hallmark of RGS proteins is a conserved approximately 120-aa RGS region that confers on these proteins the ability to serve as GTPase-activating proteins (GAPs) for G(alpha) proteins. Most RGS proteins can serve as GAPs for multiple isoforms of G(alpha) and therefore have the potential to influence many cellular signaling pathways. However, RGS proteins can be highly regulated and can demonstrate extreme specificity for a particular signaling pathway. RGS proteins can be regulated by altering their GAP activity or subcellular localization; such regulation is achieved by phosphorylation, palmitoylation, and interaction with protein and lipid-binding partners. Many RGS proteins have GAP-independent functions that influence GPCR and non-GPCR-mediated signaling, such as effector regulation or action as an effector. Hence, RGS proteins should be considered multifunctional signaling regulators. GPCR-mediated signaling is critical for normal function in the cardiovascular system and is currently the primary target for the pharmacological treatment of disease. Alterations in RGS protein levels, in particular RGS2 and RGS4, produce cardiovascular phenotypes. Thus, because of the importance of GPCR-signaling pathways and the profound influence of RGS proteins on these pathways, RGS proteins are regulators of cardiovascular physiology and potentially novel drug targets as well.
Secrets about Patients
Authors: John F. Burnum
Journal: New England Journal of Medicine (1991)

DOCTORS are often given information about a patient by family members or others and asked to keep it secret from the patient. Deciding what to do after being told such a secret can be a troubling, guilt-provoking experience for practitioners. Are we not sworn to keep patients fully informed of everything we know about them, both out of respect for their autonomy and to help them make choices about their care? There is also the uncomfortable possibility that the information confided may be unreliable, or that we may find we are being manipulated for the benefit of the confider, not . . .
Relationship of Antihypertensive Treatment Regimens and Change in Blood Pressure to Risk for Heart Failure in Hypertensive Patients Randomly Assigned to Doxazosin or Chlorthalidone: Further Analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial
Authors: Barry R. Davis
Journal: Annals of Internal Medicine (2002)

Background: The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial reported that treatment initiated with doxazosin compared with chlorthalidone doubled the risk for heart failure in high-risk hypertensive patients (relative risk, 2.04 [95% CI, 1.79 to 2.32]). Patients assigned to doxazosin therapy had a mean in-trial systolic/diastolic blood pressure 3/0 mm Hg higher than that in patients assigned to chlorthalidone. Sixty-eight percent (6167 of 9061) of the former patients and 59% (9081 of 15 256) of the latter patients were given additional medications to achieve a target blood pressure of less than 140/90 mm Hg. Objective: To ascertain the influence of open-label antihypertensive drugs and subsequent blood pressure on relative risk for heart failure. Design: Randomized, double-blind, active-controlled clinical trial. Setting: 623 sites in the United States and Canada. Patients: Hypertensive patients 55 years of age or older with at least one additional risk factor for cardiovascular disease. Intervention: Chlorthalidone (12.5 to 25 mg/d) or doxazosin (2 to 8 mg/d) for a planned follow-up of 4 to 8 years. Measurements: Data on blood pressure, medication, and incident heart failure (treated outside hospital, hospitalized, or fatal) from February 1994 through December 1999. Results: After the treatment groups were categorized as having no exposure to open-label medications (monotherapy) or exposure to open-label therapy, the relative risk for heart failure with doxazosin versus chlorthalidone was 3.10 (CI, 2.51 to 3.82) and 1.42 (CI, 1.20 to 1.69), respectively. After adjustment for follow-up systolic/diastolic blood pressure, the overall relative risk was 2.00 (CI, 1.72 to 2.32). Conclusion: In high-risk patients with hypertension, the higher risk for heart failure while taking doxazosin compared with chlorthalidone is attenuated but not eliminated by adding other antihypertensive drugs. The small observed difference in systolic blood pressure does not explain this increased risk. *For a complete list of members of the ALLHAT Collaborative Research Group, see JAMA. 2000; 283:1973-5.
Molecular basis of bortezomib resistance: proteasome subunit β5 (PSMB5) gene mutation and overexpression of PSMB5 protein
Authors: Ruud Oerlemans, Niels E. Franke, Yehuda G. Assaraf, Jacqueline Cloos, Ina van Zantwijk, Celia R. Berkers, George L. Scheffer, Kabir Debipersad, Katharina Vojtekova, Clara Lemos, Joost W. van der Heijden, Bauke Ylstra, Godefridus J. Peters, Gertjan L. Kaspers, Ben A. C. Dijkmans, Rik J. Scheper, Gerrit Jansen
Journal: Blood (2008)
Intravascular Ultrasound Findings During Episodes of Drug-Eluting Stent Thrombosis
Authors: Fernando Alfonso, Alfonso Suárez, María J. Pérez-Vizcayno, Raul Moreno, Javier Escaned, Camino Bañuelos, Pilar Jiménez, Esther Bernardo, Dominick J. Angiolillo, Rosana Hernández, Carlos Macaya
Journal: Journal of the American College of Cardiology (2007)
Rare De Novo and Transmitted Copy-Number Variation in Autistic Spectrum Disorders
Authors: Dan Levy, Michael Ronemus, Boris Yamrom, Yoon-ha Lee, Anthony Leotta, Jude Kendall, Steven Marks, B. Lakshmi, Deepa Pai, Kenny Ye, Andreas Buja, Abba Krieger, Seungtai Yoon, Jennifer Troge, Linda Rodgers, Ivan Iossifov, Michael Wigler
Journal: Neuron (2011)
Exercise for Degenerative Arthritis of the Spine
Authors: James F. Fries
Journal: JAMA (1993)

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AN EVALUATION OF INTRAVENOUS ETHER AS A TREATMENT FOR PSYCHIATRIC PATIENTS
Authors: DANIEL H. FUNKENSTEIN, LYDIA W. MEADE
Journal: American Journal of Psychiatry (1953)

1. Seventy-three committed patients diagnosed as having affective psychoses were divided at random into 3 treatment groups: one group received intravenous ether, one group intravenous saline, and a third group electric shock treatment. 2. Of the 37 patients who received intravenous ether 37.8% were scored as "improved"; 52.9% of the 17 patients who received intravenous saline were scored as "improved"; and 89.4% of the 19 patients who received electric shock treatment were so scored. A comparison of the results obtained following intravenous ether and intravenous saline showed statistically no significant difference. The improvement following electric shock treatment was significantly higher than that obtained following either intravenous ether or intravenous saline. 3. Twenty-two of the patients who failed to improve with intravenous ether were then given electric shock treatment, and 19 of these improved sufficiently to leave the hospital; 7 of the patients who failed to improve with intravenous saline were then given electric shock treatment and all 7 improved sufficiently to leave the hospital. A comparison of the results obtained by electric shock treatment alone with those obtained by a combination of ether and electric shock or saline and electric shock showed no differences considered significant by statistical methods. 4. Autonomic nervous system tests(6) showed that patients whose autonomic reaction was classified as "favorable" as far as electric shock treatment was concerned showed a higher rate of improvement with ether than did patients whose autonomic reaction would indicate a poor prognosis with electric shock treatment. However, the improvement rate in the "favorable" autonomic group cases was poor as compared with the expected improvement rate of similar cases treated with electric shock treatment. 5. It is concluded that intravenous ether as a treatment for affective psychoses showed no specific treatment effect that could not be obtained by intravenous saline, and that electric shock treatment was a much more efficacious treatment than ether in such cases.
Chronic urticaria: do urticaria nonexperts implement treatment guidelines? A survey of adherence to published guidelines by nonexperts
Authors: M. Ferrer, I. Jáuregui, J. Bartra, I. Dávila, A. del Cuvillo, J. Montoro, J. Mullol, A. Valero, J. Sastre
Journal: British Journal of Dermatology (2008)

Background Guidelines including level of evidence and grade of recommendation were recently published for chronic urticaria (CU). Objectives To describe the therapeutic approach in patients with CU, and to depict how recent guidelines are implemented in the daily practice of management of CU. Methods We performed a cross‐sectional multicentre study through a questionnaire answered by 139 specialists. In total, 695 patients were evaluated, mean ± SD age 42·3 ± 15 years, 62·1% women. Of the patients, 168 were treated by an allergist, 473 by a dermatologist and in 54 cases the specialist was not stated. The drug prescribed was the main variable, and χ2 and Fisher's tests were utilized for the statistical analysis. Results Nonsedating anti‐H1 antihistamines taken regularly were the most common drugs prescribed, followed by nonsedating anti‐H1 antihistamines taken as needed, corticosteroids, sedating antihistamines taken regularly, sedating antihistamines taken as needed, anti‐H2 antihistamines, leukotriene antagonists, ciclosporin and doxepin. Nonsedating antihistamines plus corticosteroids was the most frequent drug combination prescribed. When comparing between allergists and dermatologists we found a positive and significant correlation only between prescription of cetirizine, dexchlorfeniramine, leukotriene antagonists and anti‐H2 antihistamines and being treated by an allergist. A positive correlation was found with desloratadine and being seen by a dermatologist. We did not find any difference in CU management in the rest of the treatments studied. Conclusions It is surprising that a large amount of sedating antihistamines was prescribed. In many instances these were prescribed as needed. This fact could have a negative impact on urticaria control and patient satisfaction. It seems difficult for the nonexpert to differentiate between CU and any kind of physical urticaria.