tbuckley/cabot-search huggingface dataset:
Fibromuscular Dysplasia of the Renal Artery
Authors: Christoph Caliezi, Peter Reber
Journal: New England Journal of Medicine (2006)

During a routine preoperative checkup before a planned hysterectomy, a healthy 31-year-old woman was noted to have an elevated blood pressure of 230/130 mm Hg, mild headache without chest pain, shortness of breath, and proteinuria. Her serum creatinine level was 1.0 mg per deciliter (88 μmol per liter; normal range, 0.5 to 0.9 mg per deciliter [44 to 80 μmol per liter]), and an electrocardiogram showed signs of left ventricular hypertrophy. Antihypertensive treatment with 20 mg of enalapril per day and 100 mg of metoprolol per day was started and led to a drop in blood pressure to 120/75 mm . . .
ECZEMA, ITS DEFINITION AND ITS AETIOLOGY.*
Authors: H. G. ADAMSON
Journal: British Journal of Dermatology (1935)

Journal Article ECZEMA, ITS DEFINITION AND ITS ÆTIOLOGY. Get access H. G. ADAMSON H. G. ADAMSON Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 47, Issue 12, 1 December 1935, Pages 497–501, https://doi.org/10.1111/j.1365-2133.1935.tb10244.x Published: 01 December 1935
Toll-like receptor 4 deficiency causes pulmonary emphysema
Authors: Xuchen Zhang, Peiying Shan, Ge Jiang, Lauren Cohn, Patty J. Lee
Journal: Journal of Clinical Investigation (2006)

TLRs have been studied extensively in the context of pathogen challenges, yet their role in the unchallenged lung is unknown. Given their direct interface with the external environment, TLRs in the lungs are prime candidates to respond to air constituents, namely particulates and oxygen. The mechanism whereby the lung maintains structural integrity in the face of constant ambient exposures is essential to our understanding of lung disease. Emphysema is characterized by gradual loss of lung elasticity and irreversible airspace enlargement, usually in the later decades of life and after years of insult, most commonly cigarette smoke. Here we show Tlr4–/– mice exhibited emphysema as they aged. Adoptive transfer experiments revealed that TLR4 expression in lung structural cells was required for maintaining normal lung architecture. TLR4 deficiency led to the upregulation of what we believe to be a novel NADPH oxidase (Nox), Nox3, in lungs and endothelial cells, resulting in increased oxidant generation and elastolytic activity. Treatment of Tlr4–/– mice or endothelial cells with chemical NADPH inhibitors or Nox3 siRNA reversed the observed phenotype. Our data identify a role for TLR4 in maintaining constitutive lung integrity by modulating oxidant generation and provide insights into the development of emphysema.
An increased calcium accumulation in ATP‐depleted red cells of the patients with paroxysmal nocturnal hemoglobinuria
Authors: Masaoo Shimoda, Yoshihito Yawata
Journal: American Journal of Hematology (1985)

Abstract A marked increase in calcium (Ca) uptake (85.5 ± 39.0 nmoles/ml RBC/2 hr) was observed in ATP‐depleted red cells of patients with paroxysmal nocturnal hemoglo‐binuria (PNH) as compared to ATP‐depleted normal red cells (8.0 ± 2.0). The extent of increased Ca uptake in the PNH red cells was related to the extent of increased sensitivity to complement, as judged by the sugar water test (p &lt; 0.001) and the acidified serum test (p &lt; 0.001), and inversely correlated to the decreased activity of red cell acetylcholinesterase (p &lt; 0.01). The results may indicate that increased calcium uptake in PNH red cells is a possible intrinsic defect of the red cell membranes in the disorder.
Role of bile in non-specific defence mechanisms of the gut.
Authors: T Kalambaheti, G N Cooper, G D Jackson
Journal: Gut (1994)

The effect of depriving the intestine of bile for 48 hours was studied to determine any influence on various parameters of innate immunity in the gastrointestinal tract. Groups of rats were prepared by bile duct cannulation (with or without fluid replacement) or bile duct ligation. Normal and sham operated animals were used for comparing the thickness of the mucus layer and the cells contained therein, enumeration of goblet cells, and measurement of villus size. Histological examination indicated that the intestinal tissues of treated and control rats were similar. Though villus size and numbers of goblet cells were unaffected, a significant reduction occurred in the thickness of the mucus blanket in the duodenal regions of rats deprived of bile, and there were significantly lower numbers of mucus associated enterocytes and lymphocytes, suggesting a lower turnover rate of the epithelium. The balance of the bacterial populations in the caecum and intestine was altered by bile deprivation-increased numbers of coliform organisms were found in both regions. The range of factors, including antibodies and other known constituents, present in bile may contribute to the maintenance of tissue integrity and influence the balance in indigenous bacterial populations in the intestine. Disturbance of the host's biliary system and concomitant effects on the microbial flora may weaken the overall processes of defence in the intestine.
The Problem of the Final M.B., B.S.Lond
Authors: C. S. Staddon
Journal: BMJ (1938)

An intrachromosomal duplication containing the <i>PMP22</i>gene is associated with the human hereditary peripheral neuropathy Charcot-Marie-Tooth disease type 1A, and PMP22 overexpression as a consequence of increased <i>PMP22</i> gene dosage has been suggested as causative event in this frequent disorder of peripheral nerves. We have generated transgenic mice that carry additional copies of the <i>pmp22</i> gene to prove that increased PMP22 gene dosage is sufficient to cause PNS myelin deficiencies. Mice carrying approximately 16&nbsp;and 30&nbsp;copies of the <i>pmp22</i> gene display a severe congenital hypomyelinating neuropathy as characterized by an almost complete lack of myelin and marked slowing of nerve conductions. Affected nerves contain an increased number of nonmyelinating Schwann cells, which do not form onion bulbs but align in association with axons. The mutant Schwann cells are characterized by a premyelination-like state as indicated by the expression of embryonic Schwann cell markers. Furthermore, continued Schwann cell proliferation is observed into adulthood. We hypothesize that Schwann cells are impaired in their differentiation into the myelinating phenotype, leading to a disorder comparable to severe cases of hereditary motor and sensory neuropathies. Our findings, combined with the analysis of heterozygous and homozygous PMP22-deficient mice, indicate that aberrant <i>pmp22</i> gene copy numbers cause various forms of myelination defects.
The Diabetes Educator's Role in Teaching the Diabetic Patient
Authors: Jacqueline D Dudley
Journal: Diabetes Care (1980)

Diabetes educators have become a necessary cost-effective addition to the health care team whose efforts are directed toward the improvement of the total care provided to the diabetic patient. The role of the nurse educator in clinical practice and in hospital teams is a new approach to improving the quality of patient education. The nurse educator has specific responsibilities in the evaluation of each diabetic patient. An assessment of not only what that individual knows about his illness and where his educational needs lie but also of each person's readiness to learn. Whereas the physician's contact time with each diabetic patient is limited, the nurse educator has the time to spend with the patient and family. One must listen to what each individual has to say about his diabetes and other problems and to start the teaching-learning process. The nurse educator must be skilled in this teaching-learning process and have a good background and understanding of diabetes, including diabetes complications and problems. Very importantly, the educator must have the capability and the responsibility to evaluate the effectiveness of the teaching and learning that are done. This evaluation provides proof that better education of the diabetic patient does provide improvement in patient self-care through a better understanding of his illness. Proper care and management reduce the frequency of office visits, telephone calls, and hospitalization. Finally, the educator must interpret, for eah diabetic patient, the research being done, and, when possible, encourage diabetic patients to become involved themselves, for they are the ones who reap the benefits from diabetes research.
CONTROL OF SUPPURATION IN THE ANTERIOR SEGMENT OF THE EYE.BY THE INSERTION OF IODOFORM INTO THE ANTERIOR CHAMBER.
Authors: E. C. ELLETT
Journal: JAMA (1903)

In 1897 Ostwalt introduced a method of combating purulent inflammation of the anterior segment of the eye by inserting iodoform into the anterior chamber, and he also showed that when this was done on a normal eye it was not followed by any bad effects. The method has been occasionally referred to, but in the available literature only three allusions to it could be found. Ostwalt<sup>1</sup>again experimented with it in 1901 by placing ro[ill]s of iodoform in the anterior chamber of a rabbit's eye, and "some time later" injecting a culture of staphylococcus or streptococcus. Purulent inflammation was prevented, but not having the original paper at hand, the facts as quoted from the abstract are vague to the point of uselessness. Romer<sup>2</sup>reports the use of it in three cases. In two cases of staphylococcus infection of the anterior chamber its use was followed by a cure
Potassium Supplementation in Hypertensive Patients with Diuretic-Induced Hypokalemia
Authors: Norman M. Kaplan, Alfred Carnegie, Philip Raskin, Jo Ann Heller, Marcia Simmons
Journal: New England Journal of Medicine (1985)

Changes in potassium balance have been found to have variable effects on the blood pressure of animals, and the administration of potassium supplements has been reported to lower the blood pressure of normokalemic hypertensive patients. To assess the effect of potassium repletion in hypokalemic hypertension, we administered either potassium chloride, 60 mmol per day, or placebo tablets, each for six weeks, in a randomized, double-blind, crossover trial to 16 hypertensive patients who had diuretic-induced hypokalemia and who continued to take a constant amount of diuretic. We selected patients whose control serum potassium levels were below 3.5 mmol per liter. In association with an average rise in the serum potassium concentration of 0.56 mmol per liter, the mean blood pressure fell by an average of 5.5 mm Hg (P = 0.004), with at least a 4 mm Hg fall observed in 9 of the 16 patients. The fall in blood pressure correlated with a fall in plasma renin activity (r = 0.568, P = 0.043) but not with changes in plasma aldosterone levels or other variables. We conclude that short-term potassium supplementation that ameliorates diuretic-induced hypokalemia may induce a significant fall in blood pressure. (N Engl J Med 1985; 312:746–9.)
French multicentric validation of <i>ALK</i> rearrangement diagnostic in 547 lung adenocarcinomas
Authors: Sylvie Lantuejoul, Isabelle Rouquette, Hélène Blons, Nolwenn Le Stang, Marius Ilie, Hugues Begueret, Valerie Grégoire, Paul Hofman, Audrey Gros, Stephane Garcia, Nathalie Monhoven, Mojgan Devouassoux-Shisheboran, Audrey Mansuet-Lupo, Françoise Thivolet, Martine Antoine, Jean-Michel Vignaud, Frederique Penault-Llorca, Françoise Galateau-Sallé, Anne McLeer-Florin
Journal: European Respiratory Journal (2015)

Anaplastic lymphoma kinase ( ALK ) gene rearrangements in lung adenocarcinoma result in kinase activity targetable by crizotinib. Although fluorescence in situ hybridisation (FISH) is the reference diagnostic technique, immunohistochemistry (IHC) could be useful for pre-screening. Diagnostic yields of ALK IHC, FISH and quantitative reverse transcriptase PCR performed in 14 French pathology/molecular genetics platforms were compared. 547 lung adenocarcinoma specimens were analysed using 5A4 and D5F3 antibodies, two break-apart FISH probes and TaqMan kits. Clinicopathological data were recorded. 140 tumours were ALK rearranged (FISH with ≥15% of rearranged cells) and 400 were ALK FISH negative (&lt;15%). FISH was not interpretable for seven cases. ALK patients were young (p=0.003), mostly females (p=0.007) and light/nonsmokers (p&lt;0.0001). 13 cases were IHC negative but FISH ≥15%, including six cases with FISH between 15% and 20%; eight were IHC positive with FISH between 10% and 14%. Sensitivity and specificity for 5A4 and D5F3 were 87% and 92%, and 89% and 76%, respectively. False-negative IHC, observed in 2.4% of cases, dropped to 1.3% for FISH &gt;20%. Variants were undetected in 36% of ALK tumours. Discordances predominated with FISH ranging from 10% to 20% of rearranged cells and were centre dependent. IHC remains a reliable pre-screening method for ALK rearrangement detection.
Mechanical efficiency of stunned myocardium is modulated by increased afterload dependency
Authors: Dongsheng Fan, Loe Kie Soei, Loes MA Sassen, Rob Krams, Pieter D Verdouw
Journal: Cardiovascular Research (1995)

Objective: Oxygen consumption (MVO,) of stunned myocardium is relatively high compared to, and poorly correlated with, systolic contractile function.The aim of this study was to investigate whether an increased afterload dependency, induced by the decreased contractility of the stunned myocardium, contributes to the large variability in the mechanical efficiency data.Methods: In 13 anaesthetised open thorax pigs undergoing two cycles of 10 min occlusion of left anterior descending coronary artery and 30 min reperfusion, segment shortening, the slope of end systolic pressure segment length relationship (E,,), external work (EW, derived from the area inside the left ventricular pressure segment length loop), the efficiency of energy conversion (EET, =EW/PLA X lOO%, where PLA = total pressure-segment length area), mechanical efficiency (EW/MVO& and their dependency on left ventricular end systolic pressure (P,,) were determined before and after induction of stunning, and during subsequent inotropic stimulation with dobutamine (1 and 3 pg.kg-'.min-'over 15 min).Results: The stunning protocol not only caused significant decreases in segment shortening, external work, energy conversion efficiency, and EWA4V02 but also increased the afterload dependency of these variables.Before stunning an increase in P,, from 100 to 160 mm Hg decreased segment shortening from 18(SEM I)% to 14(2)% (P > 0.05) and increased external work from 206( 18) to 254(32) mm Hg.mm (P < 0.05).After induction of stunning the same increase in P,, caused a decrease in segment shortening from 9.5( 1.8)% to -4.6(2.1)%(P<O.O5) and in external work from 149(21) to -1 l(l0) mm Hg.mm (P<O.O5).The afterload dependency of the PLA was not altered by stunning, but the afterload dependency of energy conversion efficiency increased, since efficiency decreased from 67(3)% to 59(5)% as P,, was increased from 100 to 160 mm Hg before stunning, but from 57(5) to -7(5)% after,induction of stunning (P < 0.05).Furthermore, the same increase in P,, resulted in an 8% decrease of EW/MV02 before stunning and 107% after induction of stunning.Infusion of dobutamine not only restored segment shortening, external work, energy conversion efficiency, and EW/MVO> of the stunned myocardium, but also attenuated their afterload dependency to prestunning levels.Conclusions: Myocardial stunning increases the afterload dependency of segment shortening, external work, energy conversion efficiency, and mechanical efficiency, which can be attenuated by inotropic stimulation with dobutamine.However, the decrease in left ventricular end systolic pressure, which accompanies the induction of stunning.counteracts the decrease in these variables.These two mechanisms can explain most of the reported scatter il'mechanical efficiency.
Targeting Intracellular Oncoproteins with Antibody Therapy or Vaccination
Authors: Ke Guo, Jie Li, Jing Ping Tang, Cheng Peow Bobby Tan, Cheng William Hong, Abdul Qader O. Al-Aidaroos, Leyon Varghese, Caixia Huang, Qi Zeng
Journal: Science Translational Medicine (2011)

Antibody-based therapies have better specificity and thus improved efficacy over standard chemotherapy regimens, which result in extended survival and improved quality of life for cancer patients. Because antibodies are viewed as too large to access intracellular locations, antibody therapy has traditionally targeted extracellular or secreted proteins expressed by cancer cells. However, many oncogenic proteins are found within the cell (such as intracellular phosphatases/kinases and transcription factors) and have therefore not been pursued for antibody therapies. Here, we explored the possibility of antibody therapy or vaccination against intracellular proteins. As proofs of concept, we selected three representative intracellular proteins as immunogens for tumor vaccine studies: PRL-3 (phosphatase of regenerating liver 3), a cancer-associated phosphatase; EGFP (enhanced green fluorescent protein), a general reporter; and mT (polyomavirus middle T), the polyomavirus middle T oncoprotein. A variety of tumors that expressed these intracellular proteins were clearly inhibited by their respective exogenous antibodies or by antigen-induced host antibodies (vaccination). These anticancer activities were reproducibly observed in hundreds of C57BL/6 tumor-bearing mice and MMTV-PymT transgenic breast tumor mice. Our in vivo data suggest that immunotherapies can target not only extracellular but also intracellular oncoproteins.
Cytotoxic interactions of cardioactive cationic amphiphilic compounds in primary rat hepatocytes in culture
Authors: Subhankar Bandyopadhyay, James E. Klaunig, Pitambar Somani
Journal: Hepatology (1990)

Hepatocytes from adult male Sprague–Dawley rats were isolated by the two–stage collagenase perfusion technique; 1 × 10 6 cells/plate were incubated in primary cell culture in Leibovitz's L–15 medium for 24 hr with or without various concentrations (12.5 to 400 μmol/L) of cardioactive cationic amphiphilic compounds such as propranolol, verapamil, sotalol, atenolol and procainamide. Propranolol and verapamil caused a significant release of lactate dehydrogenase (used as cytotoxic index in this study) in the culture media in a concentration–dependent manner, with LC 50 values of 220 ± 10 and 224 ± 7 μmol/L, respectively. Atenolol, sotalol and procainamide had no effect on lactate dehydrogenase release. Electron microscopy of the hepatocytes showed that subtoxic concentrations of propranolol (12.5 to 125 μmol/L) and verapamil (12.5 to 100 μmol/L) induced multilamellar inclusion bodies after 24 hr of incubation. The two higher concentrations of propranolol (50 and 125 μmol/L) and 100 μmol/L of verapamil produced a significant decrease in the percentage of volume density of the mitochondria as quantitated by morphometrical analysis. An unusual feature of the electron microscopical changes with propranolol and verapamil was the presence of mitochondria within the multilamellar inclusion bodies. When these two drugs were used together or with subtoxic concentrations of amiodarone or desethylamiodarone, release of lactate dehydrogenase was significantly enhanced. No correlation was evident between the cytotoxic response and the volume density of cellular inclusions in hepatocytes treated with different concentrations of propranolol, verapamil, amiodarone or desethylamiodarone. Sotalol, atenolol and procainamide in concentrations up to 400 μmol/L did not produce any ultrastructural changes in hepatocytes after 24 hr of incubation. These results show that (a) cationic amphiphilic structure per se is not the only requirement for induction of multilamellar inclusions, (b) propranolol and verapamil can induce the formation of multilamellar inclusion bodies and cause a concentration–dependent release of lactate dehydrogenase from hepatocytes and (c) combination of different cationic amphiphiles in subtoxic concentrations can enhance cytotoxicity and increase the volume density of multilamellar inclusions. (Hepatology 1990;12:48-58).
Low density lipoproteins in human plasma make vascular smooth muscle cells resistant to growth inhibition by heparin
Authors: P Underwood
Journal: Cardiovascular Research (2000)

Vascular smooth muscle cell hyperplasia plays a role in atherosclerosis and restenosis. While heparin has shown promise as an inhibitor of smooth muscle cell proliferation in vitro and in some animal models, it has failed to reduce restenosis in clinical trials. We have previously shown that human smooth muscle cells grown in the presence of human serum are heparin resistant, whereas in the presence of bovine serum they are heparin sensitive. In this report, we demonstrate that the heparin resistance factor is present in human plasma as well as serum, and characterise it further.Human vascular smooth muscle cells were cultured as explants from the media of redundant adult internal mammary or umbilical cord arteries. They were tested for sensitivity to heparin at 100 microg/ml in the growth medium, in the presence of foetal bovine serum, human-plasma-derived serum, human whole blood serum, or fractions derived from these.In the presence of foetal bovine serum, heparin inhibited cell proliferation, while human-plasma-derived or whole blood sera conveyed heparin resistance. This activity was contained within the fraction of plasma/serum which bound to heparin Sepharose, and the sub-fraction which was retained by a membrane filter of molecular weight cut off of 100000. All the heparin resistance in this latter fraction was supplied by lipoproteins. LDL prepared directly from human plasma conveyed similar heparin resistance to the lipoproteins from the above sub-fraction.LDL in human plasma/serum conveys resistance to the anti-proliferative effects of heparin upon vascular smooth muscle cells. This activity may interfere with potential therapeutic effects of heparin as an anti-restenosis agent.
Getting to grips with hand eczema: measuring skin disease severity objectively
Authors: C.R. Charman, J.S. English
Journal: British Journal of Dermatology (2005)

Journal Article Getting to grips with hand eczema: measuring skin disease severity objectively Get access British Journal of Dermatology, Volume 152, Issue 2, 1 February 2005, Pages 199–201, https://doi.org/10.1111/j.1365-2133.2005.06420.x Published: 01 February 2005