tbuckley/cabot-search huggingface dataset:
Mediator release after nasal aspirin provocation supports different phenotypes in subjects with hypersensitivity reactions to NSAIDs
Authors: P. Campo, P. Ayuso, M. Salas, M. C. Plaza, J. A. Cornejo-García, I. Doña, M. J. Torres, N. Blanca-López, G. Canto, J.-L. Guéant, M. Sanak, M. Blanca
Journal: Allergy (2013)

Background Multiple NSAID-induced urticaria/angioedema (MNSAID-UA) is an entity well differentiated from aspirin-exacerbated respiratory disease (AERD), although no detailed phenotype analysis has yet been performed. The objective was to evaluate the functional characteristics of MNSAID-UA subjects by analyzing the response to nasal lysine–aspirin challenge and measurement of nasal inflammatory mediator release compared with AERD subjects and controls. Methods The study included 85 subjects with confirmed hypersensitivity to NSAIDs (≥3 episodes with >2 different NSAIDs or positive drug provocation) with either cutaneous (MNSAID-UA, n = 25) or respiratory manifestations (AERD, n = 60) and 30 tolerant controls (15 aspirin-tolerant asthmatic patients and 15 healthy controls). Nasal lavages at 0, 15, 60, and 120 min after lysine–aspirin challenge were analyzed for ECP, tryptase, PGE2, PGD2, LTD4, and LTE4. Results Lysine nasal challenge was positive in 80% of the AERD cases but positive only in 12% of the MNSAID-UA group. MNSAID-UA subjects showed no changes in nasal ECP, whereas subjects with AERD had increased levels of ECP, with the highest peak at 15 min after challenge (P < 0.05). Tryptase levels were higher in AERD compared with MNSAID-UA and controls with the highest release of tryptase at 60 min (P < 0.05). Significant increases in PGD2, LTD4, and LTE4 were observed in AERD (at 60 min for PGD2, LTD4, and LTE4) but not in MNSAID-UA or control subjects (P < 0.05). Conclusions Data support the observation that MNSAID-UA, although sharing a common response with AERD to COX inhibitors, seems to have a distinctive phenotype, based on the response to nasal challenge and the release of inflammatory mediators.
Rho-Associated Protein Kinase Contributes to Early Atherosclerotic Lesion Formation in Mice
Authors: Ziad Mallat, Andrea Gojova, Vincent Sauzeau, Valérie Brun, Jean-Sébastien Silvestre, Bruno Esposito, Régine Merval, Hervé Groux, Gervaise Loirand, Alain Tedgui
Journal: Circulation Research (2003)

Members of the Rho family of small GTPases have been recently implicated in inflammatory signaling. We examined the effect of in vivo inhibition of Rho kinase on atherogenesis in mice. Low-density lipoprotein receptor (LDLR) knockout (KO) mice fed a cholate-free high-fat diet received daily intraperitoneal injection of saline (n=8, control group) or Y-27632 (30 mg/kg, n=9), a specific Rho kinase inhibitor. After 9 weeks, Y-27632 treatment resulted in significant in vivo inhibition of Rho kinase activity (P=0.004). Body weights, arterial blood pressures, and plasma cholesterol levels were comparable in both groups. Atherosclerotic lesion size in the aortic sinus and thoracic aorta of mice treated with Y-27632 was reduced by respectively 35% and 29% in comparison with the saline-treated animals (P=0.006 and P=0.03, respectively). This was associated with a significant reduction in T lymphocyte accumulation (P=0.035) and expression of p65 subunit of NF-kappaB within plaques (P<0.05). In vitro, treatment with Y-27632 inhibited p65 phosphorylation and degradation of IkappaBalpha in mouse peritoneal macrophages and significantly inhibited concanavalin A-induced proliferation of spleen-derived T cells (P<0.001). In conclusion, inhibition of Rho kinase significantly limits early atherosclerotic plaque development in the LDLR KO mice. This study identifies Rho kinase inhibitors as potential candidates for the treatment of atherosclerosis.
Effect of glucocorticoids on rectal transport in normal subjects and patients with ulcerative colitis.
Authors: G I Sandle, J P Hayslett, H J Binder
Journal: Gut (1986)

The acute effects of single pharmacological doses of glucocorticoid hormones on net electrolyte and water transport and electrical potential difference (pd) in the rectum was studied in control subjects and in patients with either active or inactive ulcerative colitis, using a dialysis technique. Compared with 17 control subjects, nine patients with active ulcerative colitis exhibited marked decreases in net sodium absorption and rectal pd, while these transport parameters were normal in six patients with inactive ulcerative colitis. Intravenous administration of hydrocortisone hemisuccinate (100 mg) resulted five hours later in significant and quantitatively similar increases in net sodium and water absorption and pd in nine control subjects, seven patients with active ulcerative colitis, and six patients with inactive ulcerative colitis. Intravenous administration of methylprednisolone phosphate (40 mg) to eight control subjects produced increases in net sodium and water absorption and pd five hours later, which did not differ significantly from those produced by hydrocortisone; methylprednisolone induced similar changes in two patients with active ulcerative colitis. These results indicate that single pharmacological doses of glucocorticoids stimulate acute increases in rectal sodium and water absorption in control subjects and in patients with acute ulcerative colitis. The ability of systemically administered glucocorticoids to reduce diarrhoea in ulcerative colitis may therefore be related to direct effects on distal colonic sodium and water transport, as well as to their better known anti-inflammatory action.
When Do HIV-Infected Women Disclose Their HIV Status to Their Male Partner and Why? A Study in a PMTCT Programme, Abidjan
Authors: Hermann Brou, Gérard Djohan, Renaud Becquet, Gérard Allou, Didier K Ekouevi, Ida Viho, Valériane Leroy, Annabel Desgrées-du-Loû
Journal: PLoS Medicine (2007)

Background In Africa, women tested for HIV during antenatal care are counselled to share with their partner their HIV test result and to encourage partners to undertake HIV testing. We investigate, among women tested for HIV within a prevention of mother-to-child transmission of HIV (PMTCT) programme, the key moments for disclosure of their own HIV status to their partner and the impact on partner HIV testing. Methods and Findings Within the Ditrame Plus PMTCT project in Abidjan, 546 HIV-positive and 393 HIV-negative women were tested during pregnancy and followed-up for two years after delivery. Circumstances, frequency, and determinants of disclosure to the male partner were estimated according to HIV status. The determinants of partner HIV testing were identified according to women's HIV status. During the two-year follow-up, disclosure to the partner was reported by 96.7% of the HIV-negative women, compared to 46.2% of HIV-positive women (χ2 = 265.2, degrees of freedom [df] = 1, p < 0.001). Among HIV-infected women, privileged circumstances for disclosure were just before delivery, during early weaning (at 4 mo to prevent HIV postnatal transmission), or upon resumption of sexual activity. Formula feeding by HIV-infected women increased the probability of disclosure (adjusted odds ratio 1.54, 95% confidence interval 1.04–2.27, Wald test = 4.649, df = 1, p = 0.031), whereas household factors such as having a co-spouse or living with family reduced the probability of disclosure. The proportion of male partners tested for HIV was 23.1% among HIV-positive women and 14.8% among HIV-negative women (χ2 = 10.04, df = 1, p = 0.002). Partners of HIV-positive women who were informed of their wife's HIV status were more likely to undertake HIV testing than those not informed (37.7% versus 10.5%, χ2 = 56.36, df = 1, p < 0.001). Conclusions In PMTCT programmes, specific psychosocial counselling and support should be provided to women during the key moments of disclosure of HIV status to their partners (end of pregnancy, weaning, and resumption of sexual activity). This support could contribute to improving women's adherence to the advice given to prevent postnatal and sexual HIV transmission.
Emergency Psychiatric Ambulance Services in the USSR
Authors: E. FULLER TORREY
Journal: American Journal of Psychiatry (1971)

In 1965 psychiatrists in the Soviet Union began an experiment in emergency psychiatric ambulance services. This system has the following advantages: Immediate treatment is provided; physicians rather than police bring patients to the hospital; information can be gathered from "significant others" at the crisis scene; and feldshers (medical workers) assist psychiatrists. The author raises several questions about the provision of emergency psychiatric services in the United States and concludes that we have much to learn from psychiatrists abroad.
Small, Dense Low-Density Lipoprotein Particles as a Predictor of the Risk of Ischemic Heart Disease in Men
Authors: Benoiˆt Lamarche, Andre´ Tchernof, Sital Moorjani, Bernard Cantin, Gilles R. Dagenais, Paul J. Lupien, Jean-Pierre Despre´s
Journal: Circulation (1997)

Case-control studies have reported that patients with ischemic heart disease (IHD) have a higher proportion of small, dense LDL particles than do healthy control subjects. The extent to which the risk attributed to small LDL particles may be independent of concomitant variations in plasma lipoprotein-lipid concentrations remains to be clearly determined, however, particularly through prospective studies.Baseline characteristics were obtained in 2103 men initially free of IHD, among whom 114 developed IHD during a 5-year follow-up period. These 114 case patients were matched with healthy control subjects for age, body mass index, smoking habits, and alcohol intake. LDL peak particle diameter (PPD) was measured a posteriori in 103 case-control pairs by nondenaturing gradient gel electrophoresis of whole plasma. Conditional logistic regression analysis of the case-control status revealed that men in the first tertile of the control LDL-PPD distribution (LDL-PPD < or = 25.64 nm) had a 3.6-fold increase in the risk of IHD (95% CI, 1.5 to 8.8) compared with those in the third tertile (LDL-PPD > 26.05 nm). Statistical adjustment for concomitant variations in LDL cholesterol, triglycerides, HDL cholesterol, and apolipoprotein B concentrations had virtually no impact on the relationship between small LDL particles and the risk of IHD.These results represent the first prospective evidence suggesting that the presence of small, dense LDL particles may be associated with an increased risk of subsequently developing IHD in men. Results also suggest that the risk attributed to small LDL particles may be partly independent of the concomitant variation in plasma lipoprotein-lipid concentrations.
How did UK cigarette makers reduce tar to 10 mg or less?
Authors: Richard J O'Connor, K Michael Cummings, Gary A Giovino, Ann McNeill, Lynn T Kozlowski
Journal: BMJ (2006)

EDITOR—To try to reduce the harm caused by cigarette smoking, the European Commission established maximal values for tar (10 mg), nicotine (1 mg), and carbon monoxide (CO; 10 mg) per cigarette, as measured by the International Organization for Standardization (ISO) method, from 1 January 2004.1 The easiest way to reduce yields is by increasing filter ventilation,2 but this allows smokers easily to control the dose of smoke they can obtain, usually to facilitate increased intake from lower yield cigarettes.2 3 We compared yields and design features of 10 cigarette brands sold in the United Kingdom before and after the …
Interleukin 1 and lipopolysaccharide induce an inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells.
Authors: J J Emeis, T Kooistra
Journal: The Journal of Experimental Medicine (1986)

Human IL-1, recombinant murine IL-1 and E. coli LPS were found to be potent inducers of plasminogen activator (PA)-inhibitor activity, both in vivo, in rats, as well as in cultured human endothelial cells. In vivo, LPS rapidly and dose-dependently (0.01-1,000 micrograms/kg) increased plasma PA-inhibitor activity. Infusion of IL-1 into rats resulted in a small but significant increase in PA-inhibitor activity in rat plasma. Likewise, in cultured human umbilical vein endothelial cells, LPS and IL-1 induced increased synthesis of PA-inhibitor. We suggest that the induced rat plasma inhibitor might be of endothelial origin.
The risk of hepatitis B virus infection by transfusion in Kumasi, Ghana
Authors: Jean-Pierre Allain, Daniel Candotti, Kate Soldan, Francis Sarkodie, Bruce Phelps, Cristina Giachetti, Venkatakrishna Shyamala, Francis Yeboah, Margaret Anokwa, Shirley Owusu-Ofori, Ohene Opare-Sem
Journal: Blood (2003)
Self tolerance and localized autoimmunity. Mouse models of autoimmune disease that suggest tissue-specific suppressor T cells are involved in self tolerance.
Authors: O Taguchi, Y Nishizuka
Journal: The Journal of Experimental Medicine (1987)

Autoimmune diseases appeared frequently in adults in the prostate and stomach of C3.129 mice after thymectomy on day 3 (Tx-3) without any additional treatment. Lesions of both organs could be completely prevented by a single i.p. injection of spleen cells from syngeneic adult mouse on day 4. For prevention of prostatis, the most effective cell source was normal males (4 X 10(6); normal females or Orx-0 males were less effective as the cell source, and higher doses of cells (4 X 10(7)) were needed. In contrast, spleen cells (4 X 10(6)) from these three donors had equivalent capacity for the prevention of gastritis. Similar autoimmune prostatis developed at very high frequency when spleen cells (4 X 10(6)) from normal females or Orx-0 males, but not from normal males, were injected i.p. into C3.129 nu/nu mice at 4 d. However, no sign of prostatis was found in nu/+ recipients. Injection of a larger dose (4 X 10(7)) from the same donors was not effective for induction of prostatis. Gastritis could not be induced in nu/nu mice by this procedure. Injection of spleen cells from Tx-3 males or females was effective for induction of both prostatis and gastritis in nu/nu recipients. It was also shown that a T cell population (Thy-1.2+, Ig-) had the capacity to prevent and to induce autoimmune diseases. These results together strongly suggest a role for active tissue-specific suppressor T cells in self tolerance, and elimination of such T cell populations causes autoimmunity.
Effect of intra-articular inj-ction of radioactive colloids of erbium and yttrium on the growth of rabbit legs.
Authors: C Rebut-Bonneton, J C Roucayrol, F Delbarre
Journal: Annals of the Rheumatic Diseases (1975)

The effect of the intra-articular injection of radioactive erbium 169 and yttrium 90 on the growth of the leg in rabbits has been studied. I colloid state these isotopes are used clinically for synovial ablation. These beta emitters slow down bone growth in proportion to the amount of radioactivity injected. If the joint has previously been damaged by an inflammatory arthritis the effect of the radiation on the bone growth is reduced.
Endothelial injury in scleroderma.
Authors: M B Kahaleh, G K Sherer, E C LeRoy
Journal: The Journal of Experimental Medicine (1979)

Functional and structural vascular lesions have been observed in the organs involved in scleroderma. The etiology of these vascular changes is poorly understood. The ability to isolate, characterize, and maintain endothelial cells in vitro provides a target cell population to study endothelial damage in scleroderma. The present report describes the effect of scleroderma serum on endothelial, smooth muscle, and fibroblast cell types. Sera from patients with scleroderma (31/52) and Raynaud's syndrome (11/19) contain cytotoxic activity, specific for endothelial cells, which is nondialyzable, heat-stable, and elutes with albumin on gel-filtration chromatography.
Management of treatment-associated toxicites of anti-angiogenic therapy in patients with brain tumors
Authors: T. S. Armstrong, P. Y. Wen, M. R. Gilbert, D. Schiff
Journal: Neuro-Oncology (2012)

Anti-angiogenic therapies, including bevacizumab, are being used with increasing frequency in the management of malignant glioma. Common clinically significant toxicities include hypertension and proteinuria, poor wound healing, and the potential for thromboembolic events. Literature related to the use of bevacizumab in malignant glioma, reported toxicities in this patient population, and management of these toxicities was reviewed. Recommendations for assessment and management are provided. Anti-angiogenic therapies will continue to have a role in the treatment of malignant glioma. Further studies of the prevention, assessment, and management of these toxicities are warranted.
Hyperosmolality regulates endothelin release by Madin-Darby canine kidney cells.
Authors: H Schramek, G Gstraunthaler, C C Willinger, W Pfaller
Journal: Journal of the American Society of Nephrology (1993)

ET release by the renal epithelial Madin-Darby canine kidney (MDCK) cell line was investigated under isosmotic (300 mosmol/kg H2O; pH 7.4) and hyperosmotic (400, 500, or 600 mosmol/kg H2O) culture and assay conditions by the use of a specific and sensitive RIA. During isosmotic incubation, MDCK cells, which may be of collecting duct origin, secreted by far more ET into the cell culture supernatant (495.7 +/- 25.5 fmol.mg of protein-1.24 h-1) than did the proximal tubule-derived LLC-PK1 (2.42 +/- 0.20 fmol.mg of protein-1.24 h-1) and opossum kidney (3.12 +/- 0.47 fmol.mg of protein-1.24 h-1) cells. ET secretion by MDCK monolayers increased progressively within 24 h and then only slightly declined up to 48 h. Phosphoramidon (100 mumol/L) inhibited the constitutive ET synthesis in MDCK cells by 60%, indicating the participation of a phosphoramidon-sensitive ET-converting enzyme in the processing of bigET to ET in these cells. MDCK epithelia grown on filter inserts showed a clear polarity in their ET release. The baseline secretion of ET was 2.5 times higher to the basolateral than to the apical side, which might be in support of a predominantly basolateral action of the peptide. Short-term incubation of MDCK cells in hyperosmotic NaCl media for 24 h dose dependently decreased ET production. When urea was used as the solute to generate hyperosmolality, ET release by MDCK cells significantly increased. In contrast, when raffinose was added to increase osmolality to 500 mosmol/kg H2O, a decrease of ET production in a range similar to the effect of NaCl was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
Testing the Accelerator Hypothesis
Authors: M. Kibirige, B. Metcalf, R. Renuka, T. J. Wilkin
Journal: Diabetes Care (2003)

OBJECTIVE—Previous reports have predicted greater risk of type 1 diabetes among people who were heavier as young children. The Accelerator Hypothesis predicts earlier onset in heavier people, without necessarily a change in risk, and views type 1 and type 2 diabetes as the same disorder of insulin resistance, set against different genetic backgrounds. Insulin resistance is a function of fat mass, and increasing body weight in the industrialized world has been accompanied by earlier presentation (i.e., acceleration) of type 2 diabetes. We wanted to establish whether increasing body weight was also asociated with the earlier presentation of type 1 diabetes, as the Accelerator Hypothesis would predict. RESEARCH DESIGN AND METHODS— The relationships between fatness and age at diagnosis were examined in context of birth weight, weight change since birth, weight at diagnosis, BMI at diagnosis, and BMI 12 months later in 94 children aged 1–16 years (49 boys and 45 girls) presenting for management of acute-onset type 1 diabetes. RESULTS—BMI standard deviation score (SDS) at diagnosis, weight SDS change since birth, and BMI SDS 12 months later were all inversely related to age at presentation (r = −0.39 to −0.40, P &amp;lt; 0.001). The boys were significantly fatter than the girls (BMI SDS 0.56 vs. −0.08, respectively; P = 0.006) and presented with diabetes at a significantly younger age (6.74 vs. 8.32 years, respectively; P &amp;lt; 0.05). The sex difference in age at diagnosis, however, disappeared when corrected for BMI (P = 0.31), suggesting that fatness or something related to it was the responsible factor. CONCLUSIONS—The data are consistent with the hypothesis that the age at presentation of type 1 diabetes is associated with fatness. The implications for prevention of type 1 diabetes may be important.
History of the treatment of rheumatoid arthritis.
Authors: F D Hart
Journal: BMJ (1976)

The severe and protracted inflammation that characterizes acute lung injury (ALI) is driven by the ongoing recruitment of neutrophils to the lung. Although much of the cytokine signaling responsible for the initial phase of ALI has been elaborated, relatively little is known about the mechanisms governing the recruitment of neutrophils from the bone marrow to the lung in the later period of this disease. Given its previously described chemoattractant effects on marrow neutrophils, we investigated whether stromal-derived factor-1 (SDF-1) (CXCL12) might participate in this later phase of recruitment. Using immunohistochemistry to examine both banked human lung specimens from patients with ALI and lungs from mice with LPS-induced pneumonitis, we found that pulmonary SDF-1 expression increases during ALI. We further determined that both lung SDF-1 protein expression and mRNA expression rise in a delayed but sustained pattern in this mouse model and that the major source of the increase in expression appears to be the lung epithelium. Lastly, we found that expression of the SDF-1 receptor CXCR4 rises in a similar temporal pattern on neutrophils in both the blood and airspace of LPS-injured mice and that Ab-mediated SDF-1 blockade significantly attenuates late but not early pulmonary neutrophilia in this model. These results implicate SDF-1 in neutrophil recruitment to the lung in the later period of acute lung injury and suggest a novel role for this cytokine in coordinating the transition from the inflammatory response to the initiation of tissue repair.
Matrix Metalloproteinase Inhibition After Myocardial Infarction
Authors: Esther E.J.M. Creemers, Jack P.M. Cleutjens, Jos F.M. Smits, Mat J.A.P. Daemen
Journal: Circulation Research (2001)

Increased activity of matrix metalloproteinases (MMPs) has been implicated in numerous disease processes, including tumor growth and metastasis, arthritis, and periodontal disease. It is now becoming increasingly clear that extracellular matrix degradation by MMPs is also involved in the pathogenesis of cardiovascular disease, including atherosclerosis, restenosis, dilated cardiomyopathy, and myocardial infarction. Administration of synthetic MMP inhibitors in experimental animal models of these cardiovascular diseases significantly inhibits the progression of, respectively, atherosclerotic lesion formation, neointima formation, left ventricular remodeling, pump dysfunction, and infarct healing. This review focuses on the role of MMPs in cardiovascular disease, in particular myocardial infarction and the subsequent progression to heart failure. MMPs, which are present in the myocardium and capable of degrading all the matrix components of the heart, are the driving force behind myocardial matrix remodeling. The recent finding that acute pharmacological inhibition of MMPs or deficiency in MMP-9 attenuates left ventricular dilatation in the infarcted mouse heart led to the proposal that MMP inhibitors could be used as a potential therapy for patients at risk for the development of heart failure after myocardial infarction. Although these promising results encourage the design of clinical trials with MMP inhibitors, there are still several unresolved issues. This review describes the biology of MMPs and discusses new insights into the role of MMPs in several cardiovascular diseases. Attention will be paid to the central role of the plasminogen system as an important activator of MMPs in the remodeling process after myocardial infarction. Finally, we speculate on the use of MMP inhibitors as potential therapy for heart failure.