tbuckley/cabot-search huggingface dataset:
Early Plus Delayed Hirudin Reduces Restenosis in the Atherosclerotic Rabbit More Than Early Administration Alone
Authors: Leonard M. Thome, Lawrence W. Gimple, Brian G. Bachhuber, Coleen A. McNamara, Michael Ragosta, S. David Gertz, Eric R. Powers, Gary K. Owens, John E. Humphries, Ian J. Sarembock
Journal: Circulation (1998)

Background —A 2-hour infusion of r-hirudin at the time of balloon angioplasty limits restenosis in atherosclerotic rabbits. Because thrombin activity in the vessel wall after angioplasty remains high for 48 to 72 hours, we hypothesized that a second infusion of hirudin at 24 hours would reduce restenosis more than early treatment alone. Methods and Results —Femoral atherosclerosis was induced in 35 rabbits by air desiccation injury and a high-cholesterol diet. At the time of angioplasty, rabbits were randomly assigned to 1 of 4 groups: controls: heparin bolus, saline infusion at 24 hours; early hirudin: hirudin bolus+2 hours’ infusion, saline infusion at 24 hours; delayed hirudin: heparin bolus, hirudin infusion±bolus at 24 hours; and early+delayed hirudin: hirudin bolus+2 hours’ infusion, hirudin infusion±bolus at 24 hours. Rabbits were euthanized after 28 days. The early+delayed hirudin treatment group had less loss of minimal lumen diameter by angiography at 28 days. By histomorphometry, cross-sectional area narrowing by plaque was least in the early+delayed treatment group compared with controls ( P =0.0001), early hirudin ( P =0.01), or delayed hirudin ( P =0.001). The early+delayed hirudin group also had a significant reduction in absolute plaque area and an improvement in lumen area compared with the other groups. No differences were observed between treatment groups with respect to the cross-sectional area encompassed by the internal or external elastic laminae. Conclusions —Combined early+delayed administration of hirudin significantly reduces angiographic restenosis and cross-sectional area narrowing by plaque compared with early or late treatment alone. These results suggest that restenosis after balloon angioplasty is markedly influenced by thrombin-mediated events not only occurring early but also extending beyond the first 24 hours in this model.
Exhaled nitric oxide: a new lung function test.
Authors: P J Barnes, S A Kharitonov
Journal: Thorax (1996)

Exhaled nitric oxide: a new lung function test Nitric oxide (NO) is produced by many cells within the respiratory tract and endogenous NO may play an important signalling role in the physiological control ofairway function and in the pathophysiology of airway diseases.'3Endo- genous NO is generated from the amino acid L-arginine by the enzyme NO synthase (NOS), of which three distinct isoforms exist.4Constitutive isoforms are found in endo- thelial cells (ecNOS or type III) and neurons (nNOS, type I) and are activated by a rise in intracellular calcium, usually in response to physiological stimuli.A third isoform (iNOS, type II) is induced in several cell types by exposure to pro- inflammatory cytokines and endotoxin and its induction is blocked by glucocorticoids.All three isoforms have been detected in the human respiratory tract."Gustafsson and colleagues first showed that NO can be detected in the exhaled air of animals and normal human subjects9 and this has subsequently been confirmed in many studies.""'5Furthermore, the concentration of exhaled NO is increased in patients with inflammatory diseases of the airways such as asthma" 1216 and bronchiectasis.'7This suggests that exhaled NO may provide a non-invasive means of monitoring inflammation in the respiratory tract and the measurement of exhaled NO has attracted in- creasing interest.However, interpretation of exhaled NO measurements may be difficult and there is a wide variation in the reported levels of NO in exhaled air, suggesting that technical factors are important.How is NO in exhaled air measured?Most studies have measured NO in exhaled air by chemi- luminescence and detection depends on the photochemical reaction between NO and ozone generated in the analyser.'8 Several NO analysers are now commercially available but may need to be converted for online measurement of NO in exhaled air.Most analysers are sensitive to <1 part per billion (ppb) of NO and this is adequate for studies of exhaled air.The specificity of exhaled NO measurements by chemiluminescence has recently been confirmed using gas chromatography-mass spectrometry."5NO may be de-
Tamoxifen-induced hair colour change
Authors: J.P. Hampson, A. Donnelly, M.S. Lewis-Jones, J.K. Pye
Journal: British Journal of Dermatology (1995)

Journal Article Tamoxifen‐induced hair colour change Get access J.P. Hampson, J.P. Hampson Maelor Hospital Croesnewydd Road, Wrexham, M.S.L Clwyd LL13 7TD, U.K. Search for other works by this author on: Oxford Academic Google Scholar A. Donnelly, A. Donnelly Maelor Hospital Croesnewydd Road, Wrexham, M.S.L Clwyd LL13 7TD, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.S. Lewis‐Jones, M.S. Lewis‐Jones Maelor Hospital Croesnewydd Road, Wrexham, M.S.L Clwyd LL13 7TD, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.K. Pye J.K. Pye Maelor Hospital Croesnewydd Road, Wrexham, M.S.L Clwyd LL13 7TD, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 132, Issue 3, 1 March 1995, Pages 483–484, https://doi.org/10.1111/j.1365-2133.1995.tb08690.x Published: 01 March 1995
1.67 Interaction between fibroblasts and T lymphocytes is needed for IL-17 secretion and Th17 differentiation requires T cell activation
Authors: Mélissa Noack, N’Diémé Thiam, Pierre Miossec
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives </h3> Rheumatoid arthritis (RA) and Psoriasis are chronic inflammatory diseases, both characterised by an immune cell infiltrate, notably Th17 cells and a migration of blood derived mononuclear cells that interact with fibroblasts (synoviocytes or skin fibroblasts) and this promotes cell proliferation. In this context, the aim of our work is to study and compare the interactions between fibroblasts and peripheral blood mononuclear cells (PBMC) on cytokine production with focus on the effect of cell contact on IL-17 pathway, in order to differentiate intracellular expression from secretion of IL-17. <h3>Materials and Methods </h3> A co-culture system with synoviocytes or skin fibroblasts and PBMC was developed. Fibroblasts were cultured overnight in 96 well plate and normal PBMC were seeded at a 1:5 ratio for 24 h, in the presence or not of activation with PHA. Transwell system was used to study cell-cell contact effect. Supernatants were collected and IL-6, IL-1β and IL-17 production measured by ELISA. Extracellular (CD3, CD4) and intracellular (IL-17) staining of PBMC was analysed by flow cytometry. <h3>Results </h3> Interaction between synoviocytes or skin fibroblasts and PBMC was sufficient to induce IL-6 and IL-1β production. Flow cytometry analysis showed no difference in the percentage of Th17 cells in activated-PBMC alone or cultured with synoviocytes (3.21% vs. 4.70%, respectively, p = 0.42), indicating that Th17 differentiation requires only T cell activation but not cell-cell contact. Conversely IL-17 production was highly increased only in co-cultures (activated-PBMC in co-cultures (338.31 pg/ml) vs. activated-PBMC alone (26.49 pg/ml, p = 0.0002). Transwell experiments confirm that contact between fibroblasts and PBMC was critical for IL-17 secretion, as no detection was observed in transwell system. Therefore IL-17 secretion, in addition to T cell activation, requires interaction between cells. T cell activation is required to Th17 differentiation but the interaction between cells promotes IL-17 secretion. <h3>Conclusions</h3> The interaction between PBMC and fibroblasts (synoviocytes or skin fibroblasts) alone induces IL-6 and IL-1β production. T cell activation is required for Th17 differentiation but both PBMC activation and cell interaction with fibroblasts are needed to have high IL-17 secretion. This applies in particular to the pathogenesis of RA and psoriasis.
Amino Acid Metabolism Conflicts with Protein Diversity
Authors: Teresa Krick, Nina Verstraete, Leonardo G. Alonso, David A. Shub, Diego U. Ferreiro, Michael Shub, Ignacio E. Sánchez
Journal: Molecular Biology and Evolution (2014)

The 20 protein-coding amino acids are found in proteomes with different relative abundances. The most abundant amino acid, leucine, is nearly an order of magnitude more prevalent than the least abundant amino acid, cysteine. Amino acid metabolic costs differ similarly, constraining their incorporation into proteins. On the other hand, a diverse set of protein sequences is necessary to build functional proteomes. Here, we present a simple model for a cost-diversity trade-off postulating that natural proteomes minimize amino acid metabolic flux while maximizing sequence entropy. The model explains the relative abundances of amino acids across a diverse set of proteomes. We found that the data are remarkably well explained when the cost function accounts for amino acid chemical decay. More than 100 organisms reach comparable solutions to the trade-off by different combinations of proteome cost and sequence diversity. Quantifying the interplay between proteome size and entropy shows that proteomes can get optimally large and diverse.
Effects of Immunosympathectomy on Development of High Blood Pressure in Genetically Hypertensive Rats
Authors: DAVID W. J. CLARK
Journal: Circulation Research (1971)

Newborn male rats from the New Zealand colony with genetic hypertension (hypertensive rats) and from a normotensive colony (controls) were immunosympathectomized by injections of antiserum to nerve growth factor. Blood pressure of immunosympathectomized hypertensive rats aged 63 days (128±2 mm Hg) was significantly less ( P &lt;.001) than that of untreated hypertensive rats (176±3 mm Hg) of the same age. Pressure of immunosympathectomized controls aged 63 days (107±2 mm Hg) was significantly less ( P &lt;.001) than that of untreated controls (126±1 mm Hg) at the same age. Pressure thereafter remained near these levels. In immunosympathectomized rats, ganglion blockade with supramaximal doses of hexamethonium still induced a lar51ge fall in pressure which was significantly lower than in untreated rats. The combination of immunosympathectomy and hexamethonium brought the pressure of hypertensive rats and controls down to the same level (68 mm Hg). The pressor response to intravenous norepinephrine was greater in immunosympathectomized than in untreated rats. Resistance to flow in perfused mesenteric arteries from immunosympathectomized hypertensive rats was significantly less ( P &lt;.05) than in arteries from untreated hypertensive rats. Hearts of immunosympathectomized hypertensive rats were significantly lighter ( P &lt;.01) than those of untreated hypertensive rats. Heart rates of hypertensive or control rats were not altered by immunosympathectomy.
Ebola: epidemic echoes and the chronicle of a tragedy foretold
Authors: Mark Honigsbaum
Journal: The Lancet (2014)

Victims lying in the gutter shunned by passers-by as fluids leak from their ravaged bodies; arbitrary quarantines and angry clashes between armed troops and terrified slum-dwellers; heroic tales of bravery and medical sacrifice; and, for the survivors and returning health workers, the ongoing taint of stigma and fear. Ebola, like other epidemics, seems to draw on a familiar store of images and metaphors—of parasites and hot zones, desperate patients, and intrepid disease detectives. The dramatic arc of the epidemic from progressive revelation, to crisis and recrimination, seems to conform to a classic three-act Greek tragedy.
Chest Pain and Palpitations
Authors: Russell J. Everett, Mary N. Sheppard, David C. Lefroy
Journal: Circulation (2013)

This case highlights the importance of considering a wide differential diagnosis in a young patient with chest pain and an abnormal ECG. Rarer causes of myocarditis such as GCM should be sought in patients who develop ventricular arrhythmias or high-grade heart block because the treatment is different and dramatically influences outcome. Our patient is the first reported case of GCM and a concurrent diagnosis of tuberculosis. It is most likely that the histological appearance of GCM was due to the presence of mycobacterial infection within the myocardium, and we believe that effective antituberculous therapy has led to resolution of the GCM without the need for continued long-term immunosuppression.
New studies of the excitatory sodium currents in heart muscle.
Authors: H A Fozzard, C T January, J C Makielski
Journal: Circulation Research (1985)

After decades of frustration with inadequate methods, cardiac electrophysiologists have developed new techniques for superior control of membrane potential by use of single cells, and they have begun careful study of cardiac Na+ currents. Direct recordings of the behavior of single Na+ channels have been made by the newly developed patch clamp technique. Biochemists have made excellent progress purifying and characterizing the Na+ channel proteins, and there has been some initial success in reconstituting these partially purified channels into lipid bilayers, where their function can be studied. Even at this early stage of development of these new techniques, several conclusions are warranted: The cardiac Na+ currents are not accurately described by the original Hodgkin-Huxley mathematical formulation, making undesirable the further use of this model for study of cardiac excitation and conduction. We need to keep an open mind as to the kinetic behavior of Na+ channels, until the newer experimental techniques provide a more complete picture. Although the cardiac Na+ channel strongly resembles Na+ channels in other excitable tissues, important differences remain, reinforcing the idea that the detailed molecular structure of the cardiac Na+ channel will be different from its close relatives in other excitable cells. The density of Na+ channels in heart cell membranes is much less than in nerve and fast twitch skeletal muscle. The Na+ channels are the focus of action of many drugs and pathological processes. The tools are at hand for a complete description of the Na+ channel, including its gating and its molecular structure. We can expect considerable progress in this decade.
Pemetrexed and carboplatin plus bevacizumab for advanced non-squamous non-small cell lung cancer (NSCLC): Preliminary results
Authors: J. D. Patel, T. A. Hensing, V. Villafor, E. Hart, P. Bonomi
Journal: Journal of Clinical Oncology (2007)

7601 Background: Pemetrexed in combination with carboplatin has been shown to have promising activity and favorable toxicity profile in NSCLC. Bevacizumab has been shown to improve response rates and survival in pts with advanced non-squamous NSCLC when combined with carboplatin and paclitaxel. This study of pemetrexed and carboplatin plus bevacizumab was designed to evaluate the toxicity profile and to estimate the activity of the regimen in this pt population. Methods: Eligibility required that pts were chemotherapy-naive, had stage IIIB (effusion)/IV non-squamous NSCLC, PS 0–1, with no evidence of CNS metastases. Pts received pemetrexed 500 mg/m 2 over 10 minutes, carboplatin AUC 6 over 30 minutes, and bevacizumab 15 mg/kg over 30–90 minutes on a 21-day cycle for 6 cycles. Pts with SD or PR received pemetrexed 500 mg/m 2 and bevacizumab 15 mg/kg every 21 days until disease progression or toxicity. All pts received folic acid, vitamin B12 and steroid prophylaxis. Results: From 8/05 to 9/06, 39 pts (of planned 50) were enrolled: 20 M/19 F; median age 64 (range 41 - 80). One pt enrolled and subsequently refused treatment. Median number of cycles was 6 (range 1–22), and 25/38 (66%) completed at least 6 cycles of therapy. There was no grade 4 hematological toxicity. Grade 3 hematological toxicities were anemia (5%, N=2) and thrombocytopenia (3%, N=1). The most common grade 3/4 non-hematological toxicities included proteinuria (3%, N=1, gr 3), venous thrombosis (3%, N=1, gr 3), infection (3%, N=1, gr 4), and diverticulitis (11%: 8%, N=3, gr 3/3%, N=1, gr 4). 1 pt with diverticulitis experienced bowel perforation that required surgical intervention. The trial was temporally suspended and the group of pts with diverticulitis was analyzed separately. The only risk factor identified was previous history of diverticulitis. One CR, 20 PRs were observed for an overall response rate of 55% (95%, CI 43–75%). Conclusions: Treatment with pemetrexed and carboplatin plus bevacizumab in pts with advanced non-squamous NSCLC is feasible with an acceptable toxicity profile. The encouraging activity justifies further development of this regimen. However, pts with a prior history of diverticulitis should be excluded until this observation can be investigated further. No significant financial relationships to disclose.
Lithium in Manic-Depressive Illness
Authors: R. J. KERRY, G. OWEN
Journal: American Journal of Psychiatry (1968)

Treatment with lithium carbonate has stabilized a group of patients with long-standing manic-depressive illness. These are patients who have shown large total body water and weight changes and serum sodium changes during the different phases of the illness. The authors feel that lithium may be useful in the biochemical study of these illnesses as well as in their treatment.
Downstream Shift in Sodium Pump Activity along the Nephron during Acute Hypertension
Authors: CLARA E. MAGYAR, YIBIN ZHANG, NIELS-H. HOLSTEIN-RATHLOU, ALICIA A. MCDONOUGH
Journal: Journal of the American Society of Nephrology (2001)

Acute hypertension rapidly inhibits proximal tubule (PT) Na,K-ATPase activity and sodium reabsorption 30 to 40%, increasing sodium and volume delivery to the thick ascending loop of Henle (TALH) and macula densa, providing the error signal for tubuloglomerular feedback. The hypothesis was tested in rats that an acute increase in sodium and volume delivery to the TALH would acutely increase outer medulla Na,K-ATPase activity. Flow to the TALH was increased by either (1) elevating BP (102 to 160 mmHg) for 5 min by constricting arteries (hypertension) or (2) inhibiting PT sodium and volume reabsorption with the carbonic anhydrase inhibitor benzolamide: 2 mg/kg in 300 mM NaHCO3 at 50 μl/min for 5 to 7 min. Both stimuli increased urine output and lithium clearance three- to four-fold and increased basolateral Na,K-ATPase activity about 40%. In homogenates, acute hypertension increased medullary Na,K-ATPase activity from 20 ± 3.5 to 27 ± 6.4 μmol Pi/mg protein per h while decreasing renal cortex activity from 10.9 ± 0.9 to 6.5 ± 0.7. Hypertension and benzolamide also doubled medullary alkaline phosphatase activity. As chronic hypertension develops in the young spontaneously hypertensive rat, medullary Na,K-ATPase activity similarly increases. In conclusion, there is a rapid activation of medullary Na,K-ATPase activity during acute hypertension that can be explained by the increase in sodium and volume flow to the region independent of hypertension. That is, the glomerulotubular balance response in the loop of Henle is accompanied by increased Na,K-ATPase activity. The rapid, downstream shift in Na,K-ATPase activity during acute hypertension contributes the driving force for activating TGF (by inhibition in the PT) and minimizes changes in distal sodium delivery (by activation in the TALH).
Metabolic Syndrome as a Risk Factor for Cardiovascular Disease, Mortality, and Progression of Diabetic Nephropathy in Type 1 Diabetes
Authors: Lena M. Thorn, Carol Forsblom, Johan Wadén, Markku Saraheimo, Nina Tolonen, Kustaa Hietala, Per-Henrik Groop
Journal: Diabetes Care (2009)

To assess the predictive value of the metabolic syndrome in patients with type 1 diabetes.Patients were from the prospective Finnish Diabetic Nephropathy (FinnDiane) Study (n = 3,783): mean age 37 +/- 12 years and diabetes duration 23 +/- 12 years. Metabolic syndrome was defined according to World Health Organization (WHO), National Cholesterol Education Program (NCEP), and International Diabetes Federation (IDF) definitions. Follow-up time was median 5.5 years (interquartile range 3.7-6.7). Mortality data were complete, whereas morbidity data were available in 69% of the patients.The WHO definition was associated with a 2.1-fold increased risk of cardiovascular events and a 2.5-fold increased risk of cardiovascular- and diabetes-related mortality, after adjustment for traditional risk factors and diabetic nephropathy. The NCEP definition did not predict outcomes when adjusted for nephropathy but markedly added to the risk associated with elevated albuminuria alone (P < 0.001). The IDF definition did not predict outcomes.The metabolic syndrome is a risk factor, beyond albuminuria, for cardiovascular morbidity and diabetes-related mortality in type 1 diabetes.
Transgenic expression of mutant peroxisome proliferator–activated receptor γ in liver precipitates fasting–induced steatosis but protects against high-fat diet–induced steatosis in mice
Authors: Tomohiro Tanaka, Hiroaki Masuzaki, Ken Ebihara, Yoshihiro Ogawa, Shintaro Yasue, Hideo Yukioka, Hideki Chusho, Fumiko Miyanaga, Takashi Miyazawa, Muneya Fujimoto, Toru Kusakabe, Nozomi Kobayashi, Tatsuya Hayashi, Kiminori Hosoda, Kazuwa Nakao
Journal: Metabolism (2005)
Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies
Authors: O Krystufkova, T Vallerskog, S B. Helmers, H Mann, I Putova, J Belacek, V Malmstrom, C Trollmo, J Vencovsky, I E Lundberg
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To investigate serum levels of B cell activating factor (BAFF) in patients with myositis and correlate these to autoantibody profile, clinical phenotype and treatment. <h3>Methods:</h3> BAFF levels in sera from 49 patients with dermatomyositis, 44 with polymyositis, 6 with inclusion body myositis and 30 matched controls were measured by ELISA. Specific autoantibodies were detected by line blot and western blot assays. <h3>Results:</h3> Serum levels of BAFF were significantly higher in patients compared to healthy controls (p = 0.003). Patients with anti-Jo-1 autoantibodies had higher BAFF levels than control individuals (p&lt;0.003) or patients without any specific autoantibodies (p&lt;0.05). Patients with dermatomyositis had higher BAFF levels compared to polymyositis (p&lt;0.05). Patients with interstitial lung disease (ILD) had higher BAFF levels than patients without ILD (p&lt;0.05) or controls (p&lt;0.01) but this could be explained by presence of anti-Jo-1 autoantibodies. BAFF levels correlated with serum creatine kinase (CK) (rs = 0.365, p = 0.0005) but not with C-reactive protein (CRP) levels. A negative correlation of BAFF levels with glucocorticoid daily dose for all patients (rs = −0.292, p = 0.003) and with cumulative glucocorticoid doses in early myositis cases (rs = −0.659, p&lt;0.001) was recorded. <h3>Conclusion:</h3> Our finding of elevated serum levels of BAFF in patients with myositis with described phenotypes together with the correlations between levels of BAFF and CK and a negative correlation with dose of glucocorticoids, indicate that BAFF could be a potential therapeutic target in such cases.