tbuckley/cabot-search huggingface dataset:
A murine model of CF lung disease
Authors: D McKeon
Journal: Thorax (2004)

▴ Mall M, Grubb BR, Harkema JR, et al . Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice. Nature Med2004;10:487–93 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] CFTR null mice do not develop spontaneous pulmonary disease and the mechanistic link between altered ion transport and the pathogenesis of CF has remained unclear. In this paper, Mall et al have generated transgenic mice that overexpress the ENaC epithelial Na+ channel and … [1]: {openurl}?query=rft.jtitle%253DNature%2Bmedicine%26rft.stitle%253DNat%2BMed%26rft.aulast%253DMall%26rft.auinit1%253DM.%26rft.volume%253D10%26rft.issue%253D5%26rft.spage%253D487%26rft.epage%253D493%26rft.atitle%253DIncreased%2Bairway%2Bepithelial%2BNa%252B%2Babsorption%2Bproduces%2Bcystic%2Bfibrosis-like%2Blung%2Bdisease%2Bin%2Bmice.%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fnm1028%26rft_id%253Dinfo%253Apmid%252F15077107%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1038/nm1028&link_type=DOI [3]: /lookup/external-ref?access_num=15077107&link_type=MED&atom=%2Fthoraxjnl%2F59%2F9%2F817.atom [4]: /lookup/external-ref?access_num=000221242400026&link_type=ISI
Prescribing of -adrenoceptor antagonists in asthma: an observational study
Authors: D. R. Morales, B. Guthrie, B. J. Lipworth, P. T. Donnan, C. Jackson
Journal: Thorax (2011)

<h3>Background</h3> β-Antagonists have recently been proposed for the treatment of chronic asthma; however, concerns regarding risk of acute bronchoconstriction in clinical trials remain. <h3>Objective</h3> To determine the frequency of oral β-blocker prescribing in patients with asthma and associations with severe asthma exacerbations requiring oral steroids in patients with active asthma defined by prior asthma-related medication use. <h3>Methods</h3> Patients with asthma registered on 31 March 2007 and all asthma-related medications from the preceding 2 years were identified from anonymised clinical data from one-third of Scottish general practices. The main outcome measure was the relative incidence of active asthma patients receiving oral steroids following a new oral β-antagonist prescription. <h3>Results</h3> Of the 53 994 adult patients identified with asthma 1527 (2.8%; 95% CI 2.69% to 2.97%) patients were prescribed an oral β-antagonist of which 441 (28.9%, 95% CI 26.7% to 31.2%) had active asthma and received a new β-blocker prescription. The average number of patients prescribed rescue steroids at baseline in 367 patients with sufficient follow-up was 3.4 (0.9%) patients every 2 weeks. Rescue steroids were prescribed to 3 (0.8%) patients in the first 2 weeks and to 3 (0.8%) patients in the second 2 weeks following the new oral β-antagonist (incidence rate ratio (IRR) 0.87, 95% CI 0.25 to 2.99 and IRR 0.89, 95% CI 0.26 to 2.97, respectively). No significant difference was found following stratification for β-antagonist selectivity. <h3>Conclusion</h3> These results suggest that prescribing new oral β-blockers for the purpose of investigating potentially beneficial effects of chronic treatment would not lead to large increases in patients treated with oral steroids acutely in general practice.
High-mobility group box 1 is involved in the initial events of early loss of transplanted islets in mice
Authors: Nobuhide Matsuoka, Takeshi Itoh, Hiroshi Watarai, Etsuko Sekine-Kondo, Naoki Nagata, Kohji Okamoto, Toshiyuki Mera, Hiroshi Yamamoto, Shingo Yamada, Ikuro Maruyama, Masaru Taniguchi, Yohichi Yasunami
Journal: Journal of Clinical Investigation (2010)

Islet transplantation for the treatment of type 1 diabetes mellitus is limited in its clinical application mainly due to early loss of the transplanted islets, resulting in low transplantation efficiency. NKT cell-dependent IFN-gamma production by Gr-1(+)CD11b(+) cells is essential for this loss, but the upstream events in the process remain undetermined. Here, we have demonstrated that high-mobility group box 1 (HMGB1) plays a crucial role in the initial events of early loss of transplanted islets in a mouse model of diabetes. Pancreatic islets contained abundant HMGB1, which was released into the circulation soon after islet transplantation into the liver. Treatment with an HMGB1-specific antibody prevented the early islet graft loss and inhibited IFN-gamma production by NKT cells and Gr-1(+)CD11b(+) cells. Moreover, mice lacking either of the known HMGB1 receptors TLR2 or receptor for advanced glycation end products (RAGE), but not the known HMGB1 receptor TLR4, failed to exhibit early islet graft loss. Mechanistically, HMGB1 stimulated hepatic mononuclear cells (MNCs) in vivo and in vitro; in particular, it upregulated CD40 expression and enhanced IL-12 production by DCs, leading to NKT cell activation and subsequent NKT cell-dependent augmented IFN-gamma production by Gr-1(+)CD11b(+) cells. Thus, treatment with either IL-12- or CD40L-specific antibody prevented the early islet graft loss. These findings indicate that the HMGB1-mediated pathway eliciting early islet loss is a potential target for intervention to improve the efficiency of islet transplantation.
DERMAL ANGIOLYMPHOID HYPERPLASIA WITH EOSINOPHILIA VERSUS PSEUDOPYOGENIC GRANULOMA
Authors: EZZAT KANDIL
Journal: British Journal of Dermatology (1970)

SUMMARY.– A case of multiple nodules of the left ear clinically misdiagnosed as granuloma faciale was found to show the histological features characteristic of subcutaneous angiolymphoid hyperplasia with eosinophilia as described by Wells and Whimster (1969). It is suggested that subcutaneous angiolymphoid hyperplasia with eosinophilia and pseudopyogenic granuloma, as described by Wilson Jones and Bleehen (1969), could represent the same disease process taking place at different tissue levels.
The SleepStrip<sup>TM</sup>: an apnoea screener for the early detection of sleep apnoea syndrome
Authors: T. Shochat, N. Hadas, M. Kerkhofs, A. Herchuelz, T. Penzel, J.H. Peter, P. Lavie
Journal: European Respiratory Journal (2001)

Sleep apnoea syndrome (SAS) is a largely undiagnosed and prevalent disorder. It is associated with cardiovascular morbidity as well as excessive daytime sleepiness and poor quality of life. In the present study the SleepStrip TM , a novel screening device is introduced, which is low cost and easy to use and is aimed for widespread use. The results of three independent validation studies, which compared the SleepStrip TM score (Sscore) against “gold standard” polysomnographically-determined apnoea/hypopnoea index (AHI), are reported both separately and combined. Four hundred and two patients suspected of SAS underwent full polysomnography recordings concomitantly with the use of the SleepStrip TM . For all samples combined, the correlation between AHI and Sscore was r=0.73, sensitivity and specificity values ranged from 80–86% and 57–86% respectively, and the area under the curve derived from receiver-operating characteristic curves ranged from 0.81–0.92 at varying AHI thresholds. Though not intended as a substitute for polysomnography, the SleepStrip TM may provide initial screening information, which may be useful in both clinical and experimental settings.
Negative transcriptional regulation of human interleukin 2 (IL-2) gene by glucocorticoids through interference with nuclear transcription factors AP-1 and NF-AT.
Authors: F Paliogianni, A Raptis, S S Ahuja, S M Najjar, D T Boumpas
Journal: Journal of Clinical Investigation (1993)

IL-2 gene transcription is affected by several nuclear proteins. We asked whether dexamethasone (Dex) and cyclosporin A (CsA) inhibit IL-2 gene transcription by interfering with the activity of nuclear proteins that bind to the IL-2 promoter. Nuclear extracts from primary human T lymphocytes were analyzed by electrophoretic DNA mobility shift assays. Both Dex and CsA inhibited the binding of transcription factors AP-1 and NF-AT, but not of NF-kB and OCT-1/OAF, to their corresponding sites on the IL-2 gene promoter. To correlate changes in nuclear factor binding in vitro with transcriptional activity in vivo and define the structural requirements for IL-2 promoter repression, we used transient DNA transfections. Jurkat cells were transfected with plasmids containing either the intact IL-2 promoter or its AP-1, NF-AT, and NF-kB motifs. Dex inhibited the IL-2 promoter and the AP-1, but not the NF-AT and NF-kB plasmids. In contrast, CsA inhibited the IL-2 promoter and the NF-AT, but not the AP-1 and NF-kB plasmids. These results suggest that in human T lymphocytes both Dex and CsA inhibited IL-2 gene transcription through interference with transcription factors AP-1 and NF-AT. We propose that, while maximum inhibition may involve interaction with both transcription factors, AP-1 is the primary target of Dex.
Prognosis of Women With Metastatic Breast Cancer by <i>HER2</i> Status and Trastuzumab Treatment: An Institutional-Based Review
Authors: Shaheenah Dawood, Kristine Broglio, Aman U. Buzdar, Gabriel N. Hortobagyi, Sharon H. Giordano
Journal: Journal of Clinical Oncology (2009)

PURPOSE The purpose of this study was to determine whether trastuzumab improves prognosis of women with metastatic human epidermal growth factor receptor 2 (HER2)/neu -positive breast cancer beyond that of women with HER2/neu-negative disease. PATIENTS AND METHODS Two thousand ninety-one women with metastatic breast cancer diagnosed from 1991 to 2007, with known HER2/neu status and who had not received trastuzumab in the adjuvant setting, were identified. Disease was classified into the following three groups: HER2/neu negative, HER2/neu positive without first-line trastuzumab treatment, and HER2/neu positive with first-line trastuzumab treatment. Overall survival (OS) was estimated using the Kaplan-Meier product-limit method and compared between groups with the log-rank test. Cox proportional hazards models were used to determine associations between OS and HER2/neu status after controlling for patient characteristics. Results One hundred eighteen patients (5.6%) had HER2/neu-positive disease without trastuzumab treatment, 191 (9.1%) had HER2/neu-positive disease and received trastuzumab treatment, and 1,782 (85.3%) had HER2/neu-negative disease. Median-follow-up was 16.9 months. One-year survival rates among patients with HER2/neu-negative disease, HER2/neu-positive disease and trastuzumab treatment, and HER2/neu-positive disease and no trastuzumab treatment were 75.1% (95% CI, 72.9% to 77.2%), 86.6% (95% CI, 80.8% to 90.8%), and 70.2% (95% CI, 60.3% to 78.1%), respectively. In a multivariable model, women with HER2/neu-positive disease who received trastuzumab had a 44% reduction in the risk of death compared with women with HER2/neu-negative disease (hazard ratio [HR] = 0.56; 95% CI, 0.45 to 0.69; P < .0001). This HR varied with time and was significant for the first 24 months and not significant after 24 months. CONCLUSION Our results show that women with HER2/neu-positive disease who received trastuzumab had improved prognosis compared with women with HER2/neu-negative disease.
Intermittent Hypoxia in Rats Increases Myogenic Tone Through Loss of Hydrogen Sulfide Activation of Large-Conductance Ca <sup>2+</sup> -Activated Potassium Channels
Authors: Olan Jackson-Weaver, Daniel A. Paredes, Laura V. Gonzalez Bosc, Benjimen R. Walker, Nancy L. Kanagy
Journal: Circulation Research (2011)

Myogenic tone, an important regulator of vascular resistance, is dependent on vascular smooth muscle (VSM) depolarization, can be modulated by endothelial factors, and is increased in several models of hypertension. Intermittent hypoxia (IH) elevates blood pressure and causes endothelial dysfunction. Hydrogen sulfide (H(2)S), a recently described endothelium-derived vasodilator, is produced by the enzyme cystathionine γ-lyase (CSE) and acts by hyperpolarizing VSM.Determine whether IH decreases endothelial H(2)S production to increase myogenic tone in small mesenteric arteries.Myogenic tone was greater in mesenteric arteries from IH than sham control rat arteries, and VSM membrane potential was depolarized in IH in comparison with sham arteries. Endothelium inactivation or scavenging of H(2)S enhanced myogenic tone in sham arteries to the level of IH. Inhibiting CSE also enhanced myogenic tone and depolarized VSM in sham but not IH arteries. Similar results were seen in cerebral arteries. Exogenous H(2)S dilated and hyperpolarized sham and IH arteries, and this dilation was blocked by iberiotoxin, paxilline, and KCl preconstriction but not glibenclamide or 3-isobutyl-1-methylxanthine. Iberiotoxin enhanced myogenic tone in both groups but more in sham than IH. CSE immunofluorescence was less in the endothelium of IH than in sham mesenteric arteries. Endogenouse H(2)S dilation was reduced in IH arteries.IH appears to decrease endothelial CSE expression to reduce H(2)S production, depolarize VSM, and enhance myogenic tone. H(2)S dilatation and hyperpolarization of VSM in small mesenteric arteries requires BK(Ca) channels.
Progress towards in Vivo Use of siRNAs
Authors: Mark A. Behlke
Journal: Molecular Therapy (2006)

RNA interference (RNAi) has been extensively employed for in vivo research since its use was first demonstrated in mammalian cells 10 years ago. Design rules have improved, and it is now routinely possible to obtain reagents that suppress expression of any gene desired. At the same time, increased understanding of the molecular basis of unwanted side effects has led to the development of chemical modification strategies that mitigate these concerns. Delivery remains the single greatest hurdle to widespread adoption of in vivo RNAi methods. However, exciting advances have been made and new delivery systems under development may help to overcome these barriers. This review discusses advances in RNAi biochemistry and biology that impact in vivo use and provides an overview of select publications that demonstrate interesting applications of these principles. Emphasis is placed on work with synthetic, small interfering RNAs (siRNAs) published since the first installment of this review which appeared in 2006.
Dyslipidemia and the Metabolic Syndrome
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2004)

This is the third in a series of articles on presentations at the American Diabetes Association Annual Meeting, Orlando, Florida, 4–8 June 2004.

A number of presentations at the June American Diabetes Association (ADA) meeting addressed aspects of lipid therapy of persons with diabetes. Brown et al. (abstract 929) reported the correlation between fasting lipids and HbA1c in 11,938 persons with diabetes in the Kaiser Permanente Northwest population. Comparing persons with no, one, and two high–cardiovascular disease (CVD) risk lipid abnormalities, HbA1c was 7.3, 7.5, and 7.9%, triglycerides 150, 210, and 381 mg/dl, and HDL 54, 40, and 37 mg/dl, respectively, suggesting association of poorer glycemic control with dyslipidemia in type 2 diabetes. Pladevall et al. (abstract 948) described trends in the management of dyslipidemia in patients with diabetes using a managed care database of 9,642 persons, 6,751 of whom were followed from 1997 to 2001. Lipid testing was performed in 37, 44, 51, 55, and 6% in 1997, 1998, 1999, 2000, and 2001, respectively. During this period, 19, 23, 28, 33, and 41% of patients were prescribed a lipid-lowering agent and the LDL cholesterol goal of <100 mg/dl was attained by 22%, 27%, 32%, 34%, and 37%, respectively, suggesting that important improvement has been made, although there is a great deal yet to be done in lipid treatment of persons with diabetes in the U.S.

Ronald Goldberg (Miami, FL) discussed LDL-targeted therapy, addressing the relationship between LDL cholesterol and CVD in diabetes, lessons learned from statin trials in diabetes, current guidelines for LDL-targeted therapy, and new data regarding the question of more rather than less statin, as well as special subgroups and obstacles to achieving goals. In the UKPDS (U.K. Prospective Diabetes Study), LDL levels were similar to those of persons without diabetes in men and slightly …
Hydrogels derived from central nervous system extracellular matrix
Authors: Christopher J. Medberry, Peter M. Crapo, Bernard F. Siu, Christopher A. Carruthers, Matthew T. Wolf, Shailesh P. Nagarkar, Vineet Agrawal, Kristen E. Jones, Jeremy Kelly, Scott A. Johnson, Sachin S. Velankar, Simon C. Watkins, Michel Modo, Stephen F. Badylak
Journal: Biomaterials (2012)
Caspase Induction and BCL2 Inhibition in Human Adipose Tissue
Authors: Francisco José Tinahones, Leticia Coín Aragüez, Mora Murri, Wilfredo Oliva Olivera, María Dolores Mayas Torres, Nuria Barbarroja, Ricardo Gomez Huelgas, Maria M. Malagón, Rajaa El Bekay
Journal: Diabetes Care (2012)

OBJECTIVE Cell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling. RESEARCH DESIGN AND METHODS The expression levels of initiator (CASP8/9) and effector (CASP3/7) caspases as well as antiapoptotic B-cell lymphoma (BCL)2 and inflammatory markers were assessed in visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with different degrees of obesity and without insulin resistance or diabetes. Adipose tissue explants from lean subjects were cultured with TNF-α or IL-6, and the expression of apoptotic and insulin signaling components was analyzed and compared with basal expression levels in morbidly obese subjects. RESULTS SAT and VAT exhibited increased CASP3/7 and CASP8/9 expression levels and decreased BCL2 expression with BMI increase. These changes were accompanied by increased inflammatory cytokine mRNA levels and macrophage infiltration markers. In obese subjects, CASP3/7 activation and BCL2 downregulation correlated with the IRS-1/2–expression levels. Expression levels of caspases, BCL2, p21, p53, IRS-1/2, GLUT4, protein tyrosine phosphatase 1B, and leukocyte antigen-related phosphatase in TNF-α– or IL-6–treated explants from lean subjects were comparable with those found in adipose tissue samples from morbidly obese subjects. These insulin component expression levels were reverted with CASP3/7 inhibition in these TNF-α– or IL-6–treated explants. CONCLUSIONS Body fat mass increase is associated with CASP3/7 and BCL2 expression in adipose tissue. Moreover, this proapoptotic state correlated with insulin signaling, suggesting its potential contribution to the development of insulin resistance.
Anti-angiogenic strategies and vascular targeting in the treatment of lung cancer
Authors: C.S. Brock, S.M. Lee
Journal: European Respiratory Journal (2002)

The generation of new blood vessels, angiogenesis, is important for tumour proliferation and metastasis. This involves a number of interacting processes and factors, such as growth factors and the receptor tyrosine kinases, matrix metalloproteinases and integrins. Studies have shown that tumour vascularity and the overexpression of growth factors and their receptors are of independent prognostic importance in different cancers, including lung cancer. The present article provides a background to angiogenesis and describes the potential targets for anti-angiogenic and vascular targeting strategies in cancer, focusing specifically on carcinoma of the lung. It also describes the anti-angiogenic drugs presently under phase I, II and III investigation and highlights some of the problems associated with the standard methodologies for assessing tumour response and drug efficacy using these agents.
PHENOTHIAZINE-INDUCED ACUTE PSYCHOTIC REACTION: THE "PSYCHOTOXICITY" OF A DRUG
Authors: DANIEL S. CHAFFIN
Journal: American Journal of Psychiatry (1964)

The literature is reviewed, and a case is presented of an acute psychotic reaction following the onset of phenothiazine therapy. The patient also suffered from loss of several sensory reactions and was considered a natural experiment in sensory deprivation. The author has speculated about the relationship between phenothiazine-induced toxic psychoses and sensory deprivation. The possibility is raised that phenothiazine drugs rather than having directly toxic effects on brain substance could produce acute brain syndromes through secondary effects on sensory input and perhaps through alteration of anxiety and agitation.
Reversibility of swallowing disfunction in tracheotomized patients
Authors: Piero Ceriana, Claudio Fracchia, Chiara Fassio, Claudio Cazzani, Barbara Cattani, Maria Dichiarante, Riccardo Bellazzi, Stefano Nava
Journal: European Respiratory Journal (2011)

Tracheotomized patients (Tp) are often dysphagic and videofluoroscopy (VF) represents the gold standard diagnostic technique. We wanted to evaluate with VF the swallowing function (SF) of a group of 80 Tp admitted to our centre: 48 (group N) were free from a chronic respiratory disease (CRD) and had been tracheotomized for a central nervous system hemorrhage or ischemia while the other 32 had been tracheotomized for the exacerbation of a CRD (group P). All patients were studied with VF twice: few days after admission (t0) and after the rehabilitation period (t1). The following aspects of SF were assessed: glottis elevation (E), epiglottis folding (EF), oral phase (OP), pharyngeal retention (PR), onset of reflex (OR), penetration (P) and inhalation (I). Every item was scored 1, 2 or 3 when it was judged, respectively, normal, slightly altered of abnormal. Differences in terms of categorical scores distributions between the two groups were tested with Pearson's chi square test, while t0 and t1 scores were compared separately for each group by Wilcoxon test to search for an improvement. At t0, Tp in group N exhibited better scores than Tp in group P with respect to EF, PR, P and I (p<0.02). At t1, Tp in group N had significantly improved their scores compared to t0 with respect to AE, EF, OP, PR, P and I (p<0.02), while Tp in group P improved only for I (p<0.01).

In conclusion, the presence of a CRD significantly impairs the SF, mainly for the disrupted coordination between swallowing and breathing. Even at the end of a rehabilitation course, Tp affected by a CRD exhibit limited improvement, while those suffering from previous cerebral ischemia or hemorrhage significantly improve their SF.
Investigation of peanut oral immunotherapy with CpG/peanut nanoparticles in a murine model of peanut allergy
Authors: Kamal D. Srivastava, Alyssa Siefert, Tarek M. Fahmy, Michael J. Caplan, Xiu-Min Li, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2016)
IMMUNOLOGICAL REACTIONS OF THE COXSACKIE VIRUSES
Authors: Joseph L. Melnick, Norman A. Clarke, Lisbeth M. Kraft
Journal: The Journal of Experimental Medicine (1950)

Maternal antibodies to the Coxsackie viruses (C virus) are conveyed to newborn mice through the colostrum and milk. of vaccinated mothers. No evidence for or against placental transmission of immunity was obtained. The immunity conferred on the young is type-specific. Immunity may be conferred to infants born of non-immune mice by allowing a suckling period of 24 to 48 hours with an immune mother. Immunity appears to be transferred through the milk for the duration of lactation. Strains of C virus can be typed by challenging infant mice born to mothers vaccinated with known types according to the outline presented above. Complement-fixing antibodies are also transferred from vaccinated mother mice to their offspring.