tbuckley/cabot-search huggingface dataset:
Cell specific effects of glucocorticoid treatment on the NF-kappa Bp65/Ikappa Balpha system in patients with Crohn's disease
Authors: K Thiele, A Bierhaus, F Autschbach, M Hofmann, W Stremmel, H Thiele, R Ziegler, P P Nawroth
Journal: Gut (1999)

<h3>BACKGROUND/AIMS/PATIENTS</h3> Glucocorticoid treatment is known to reduce nuclear factor-kappa B (NF-κB)p65 binding activity and activation in lamina propria cells of patients with Crohn's disease. However, lamina propria cells of glucocorticoid treated patients did not show increased expression of IκBα, and the hypothesised upregulation of IκBα by glucocorticoid treatment has not yet been shown in vivo. To investigate whether cells other than lamina propria localised mononuclear cells contribute to increased IκBα, resection gut specimens from patients matched for Crohn's disease activity index (CDAI) with or without glucocorticoid treatment were studied, and changes in the NF-κB/IκBα system were determined in the lamina propria as well as in underlying submucosal and endothelial cells. <h3>METHODS</h3> Changes in the NF-κB/IκBα system were determined by immunohistochemistry, electrophoretic mobility shift assay, and western blot analysis in resected gut specimens from patients matched for CDAI and van Hees index with or without long term glucocorticoid treatment. <h3>RESULTS</h3> Resection gut specimens from patients with Crohn's disease under glucocorticoid treatment had significantly lower nuclear NF-κBp65 levels in mononuclear, epithelial, and endothelial cells than samples from CDAI and van Hees index matched patients not having glucocorticoid treatment. Nuclear NF-κBp65 showed a strong positive correlation with both the CDAI (<i>r</i> = 1 for both groups) and the van Hees index (<i>r</i> = 0.605 for untreated and <i>r</i> = 0.866 for glucocorticoid treated specimens). Lower nuclear translocation of NF-κBp65 in the glucocorticoid treated group was paralleled by higher IκBα levels in vascular endothelial cells, but not in infiltrating mononuclear cells. <h3>CONCLUSION</h3> A comparison of resection gut specimens from untreated and treated CDAI matched patients with Crohn's disease showed downregulation of NF-κB binding activity and NF-κBp65 expression and cell specific induction of endothelial IκBκ expression in the glucocorticoid treated group. As the two groups showed similar disease activity (CDAI, van Hees index), the activation of the NF-κBp65/IκBα system must be only part of the inflammatory cascade leading to the clinical appearance of Crohn's disease.
Transferrin receptor mediates uptake and presentation of hepatitis B envelope antigen by T lymphocytes.
Authors: A Franco, M Paroli, U Testa, R Benvenuto, C Peschle, F Balsano, V Barnaba
Journal: The Journal of Experimental Medicine (1992)

Human activated T lymphocytes expressing class II molecules are able to present only complex antigens that bind to their own surface receptors, and thus can be captured, internalized, and processed through the class II major histocompatibility complex processing pathway. We have used the antigen-presenting T cell system to identify the viral receptor used by hepatitis B virus (HBV) to enter cells, as well as the sequence of HB envelope antigen (HBenvAg) involved in this interaction. Results show that both CD4+ and CD8+ T clones can process and present HBenvAg to class II-restricted cytotoxic T lymphocytes and that the CD71 transferrin receptor (TfR) is involved in efficient HBenvAg uptake by T cells. Moreover, we provide evidence that the HBenvAg sequence interacting with the T cell surface is contained within the pre-S2 region. Since TfR is also expressed on hepatocytes, it might represent a portal of cellular entry for HBV infection. This system of antigen presentation by T cells may serve as a model to study both lymphocyte receptors used by lymphocytotropic viruses and viral proteins critical to bind them.
First-Line Treatment With Epirubicin and Vinorelbine in Metastatic Breast Cancer
Authors: Patrizia Vici, Giuseppe Colucci, Vittorio Gebbia, Antonella Amodio, Francesco Giotta, Franca Belli, Francesca Conti, Nicola Gebbia, Giuseppe Pezzella, Maria Rosaria Valerio, Mario Brandi, Salvatore Pisconti, Ernesto Durini, Diana Giannarelli, Massimo Lopez
Journal: Journal of Clinical Oncology (2002)

PURPOSE: This phase II multicenter trial was aimed at investigating the activity of epirubicin-vinorelbine combination as first-line chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS: Ninety-seven patients with metastatic breast cancer and no prior exposure to anthracyclines received the following regimen: epirubicin 100 mg/m 2 by intravenous (IV) bolus infusion on day 1 plus vinorelbine 25 mg/m 2 by 30-minute IV infusion on days 1 and 5, every 3 weeks for up to eight cycles. All patients also received granulocyte colony-stimulating factor (G- CSF) on days 7 to 12 of every cycle. RESULTS: Objective responses, confirmed at least 4 weeks after the first documentation, were observed in 65 out of 92 assessable patients (70.6%; 95% CI, 62% to 80%). Disease remained stable in 17 patients (18.5%). Responses were observed in all disease sites, being 94% in soft tissue, 60% in bone, and 66% in visceral disease. Median time to response, median duration of response, median time to progression, and median overall survival were 2, 9, 10, and 26 months, respectively. The dose-limiting toxicity was neutropenia, which was grade 4 in 36% of the patients, and was accompanied by fever in 26% of the cases. Grade 3 to 4 mucositis was encountered in 28% of the patients. Other toxicities were mild to moderate. No cardiotoxicity was observed. CONCLUSION: The epirubicin-vinorelbine combination with G-CSF support has been shown in this study to be highly active as first-line treatment of metastatic breast cancer patients, with significant although transient toxicity. This justifies further evaluation in the neoadjuvant setting and in early-stage breast cancer.
Primary Graft Function, Metabolic Control, and Graft Survival After Islet Transplantation
Authors: Marie-Christine Vantyghem, Julie Kerr-Conte, Laurent Arnalsteen, Geraldine Sergent, Frederique Defrance, Valery Gmyr, Nicole Declerck, Violeta Raverdy, Brigitte Vandewalle, Pascal Pigny, Christian Noel, Francois Pattou
Journal: Diabetes Care (2009)

OBJECTIVE To investigate the influence of primary graft function (PGF) on graft survival and metabolic control after islet transplantation with the Edmonton protocol. RESEARCH DESIGN AND METHODS A total of 14 consecutive patients with brittle type 1 diabetes were enrolled in this phase 2 study and received median 12,479 islet equivalents per kilogram of body weight (interquartile range 11,072-15,755) in two or three sequential infusions within 67 days (44-95). PGF was estimated 1 month after the last infusion by the beta-score, a previously validated index (range 0-8) based on insulin or oral treatment requirements, plasma C-peptide, blood glucose, and A1C. Primary outcome was graft survival, defined as insulin independence with A1C < or =6.5%. RESULTS All patients gained insulin independence within 12 days (6-23) after the last infusion. PGF was optimal (beta-score > or =7) in nine patients and suboptimal (beta-score < or =6) in five. At last follow-up, 3.3 years (2.8-4.0) after islet transplantation, eight patients (57%) remained insulin independent with A1C < or =6.5%, including seven patients with optimal PGF (78%) and one with suboptimal PGF (20%) (P = 0.01, log-rank test). Graft survival was not significantly influenced by HLA mismatches or by preexisting islet autoantibodies. A1C, mean glucose, glucose variability (assessed with continuous glucose monitoring system), and glucose tolerance (using an oral glucose tolerance test) were markedly improved when compared with baseline values and were significantly lower in patients with optimal PGF than in those with suboptimal PGF. CONCLUSIONS Optimal PGF was associated with prolonged graft survival and better metabolic control after islet transplantation. This early outcome may represent a valuable end point in future clinical trials.
A case of cutaneous acral sarcoidosis with response to allopurinol
Authors: F. Antony, A.M. Layton
Journal: British Journal of Dermatology (2000)

Journal Article A case of cutaneous acral sarcoidosis with response to allopurinol Get access F. Antony, F. Antony Department of Dermatology, Harrogate District Hospital, Lancaster Park Road, Harrogate, North Yorkshire HG2 7SX, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.M. Layton A.M. Layton Department of Dermatology, Harrogate District Hospital, Lancaster Park Road, Harrogate, North Yorkshire HG2 7SX, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Pages 1052–1053, https://doi.org/10.1046/j.1365-2133.2000.03500.x Published: 01 May 2000
Mechanical Ventilation with Heated Humidifiers or Heat and Moisture Exchangers: Effects on Patient Colonization and Incidence of Nosocomial Pneumonia
Authors: Didier Dreyfuss, Kamel Djedaïni, Isabelle Gros, Laurence Mier, Geneviève Le Bourdellés, Yves Cohen, Philippe Estagnasié, François Coste, Yves Boussougant
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The contribution of ventilator circuit bacterial contamination to the occurrence of ventilator-associated pneumonia remains controversial. In a previous study, we found that the incidence of pneumonia was identical with ventilator circuit changes every 48 h and with no ventilator circuit changes. The present study prospectively assessed whether keeping ventilator circuits clean with a heat and moisture exchanger exhibiting antimicrobial barrier properties affects patient colonization and the incidence of nosocomial pneumonia in patients receiving mechanical ventilation for more than 48 h. Consecutive patients were randomly allocated to humidification with either a heat and moisture exchanger (Group 1, n = 61) or a heated humidifier (Group 2, n = 70). In both groups, no circuit changes were performed throughout ventilatory support. Duration of mechanical ventilation was identical in both groups (10 ± 8.6 d (range: 2 to 47) in Group 1 and 12.5 ± 14.2 d [range: 2 to 85] in Group 2). The incidence of pneumonia (positive quantitative culture of protected brush specimen) was similar in both groups (6/61 and 8/70 in Groups 1 and 2, respectively; p = 0.8), as was duration of ventilation prior to pneumonia (9 ± 5.9 versus 8.2 ± 5.7 d; p = 0.8). Ventilator tubing contamination was considerably reduced with the use of a heat and moisture exchanger. In contrast, bacterial colonization of the pharynx and trachea was identical in both groups. These results suggest that circuit colonization plays little or no role in the occurrence of ventilator-associated pneumonia, provided usual maintenance precautions are applied. It also indirectly confirms our previous finding that during mechanical ventilation with a heated humidifier, circuits need not be changed except between patients. Although it failed to reduce the incidence of pneumonia, the use of a heat and moisture exchanger may allow reduction of the number of septic procedures linked to circuit management during mechanical ventilation as well as substantial savings in care provider time.
Localized Xanthomas in Lymphedema
Authors: E. G. Thorne
Journal: JAMA (1970)

<h3>To the Editor.—</h3> Wooling and co-workers recently described a case of localized xanthomas associated with lymphedema (<b>211</b>:1372, 1970) which was similar to a case briefly mentioned by Polano in a recent review article.<sup>1</sup>Polano described a young man with lymphedema in whom the xanthomas disappeared after treatment with compression. Polano proposed that the xanthomas were caused by abnormal lipid supply to the skin induced by the lymph stasis. The improvement with compression may be attributed to a decrease in the high lipid lymph flow to the skin.
Lack of Insulin Receptor Substrate-2 Causes Progressive Neointima Formation in Response to Vessel Injury
Authors: Tetsuya Kubota, Naoto Kubota, Masao Moroi, Yasuo Terauchi, Tsuneo Kobayashi, Katsuo Kamata, Ryo Suzuki, Kazuyuki Tobe, Atsushi Namiki, Shinichi Aizawa, Ryozo Nagai, Takashi Kadowaki, Tetsu Yamaguchi
Journal: Circulation (2003)

Insulin resistance is associated with atherosclerosis, but its mechanism is unknown. It has been reported that insulin receptor substrate (IRS)-1 deficient (IRS-1-/-) mice showed insulin resistance without type 2 diabetes, whereas the IRS-2 deficient (IRS-2-/-) mice showed insulin resistance with type 2 diabetes.We investigated neointima formation in the IRS-1-/- and IRS-2-/- mice at 8 and 20 weeks. The IRS-2-/- mice showed much greater neointima formation than the IRS-1-/- and wild-type mice at 8 weeks. At 20 weeks, the IRS-2-/- mice had greater neointima formation than the IRS-1-/- mice, which showed more enhanced neointima formation than the wild-type mice. The IRS-1-/- and IRS-2-/- mice had dyslipidemia, hypertension, and insulin resistance. The IRS-2-/- mice had more metabolic abnormalities than the IRS-1-/- mice at 8 and 20 weeks. IRS-2 expression was detected, but IRS-1 expression was not detected in the vessels.The neointima formation in the IRS-1-/- and IRS-2-/- mice appears to be related to abnormalities induced by the altered metabolic milieu in insulin-resistant states. Moreover, because neointima formation was much greater in the IRS-2-/- mice than in the IRS-1-/- mice at 8 and 20 weeks, it is suggested that a lack of IRS-2 renders the vasculature more susceptible to injury in the abnormal metabolic milieu, and IRS-2 may have a protective effect on neointima formation. We conclude that IRS-2 is protective and retards the development of neointima formation in insulin-resistant states.
Ischemic Heart Disease Events Triggered by Short-Term Exposure to Fine Particulate Air Pollution
Authors: C. Arden Pope, Joseph B. Muhlestein, Heidi T. May, Dale G. Renlund, Jeffrey L. Anderson, Benjamin D. Horne
Journal: Circulation (2006)

Background— Recent evidence suggests that long-term exposure to particulate air pollution contributes to pulmonary and systemic oxidative stress, inflammation, progression of atherosclerosis, and risk of ischemic heart disease and death. Short-term exposure may contribute to complications of atherosclerosis, such as plaque vulnerability, thrombosis, and acute ischemic events. These findings are inconclusive and controversial and require further study. This study evaluates the role of short-term particulate exposure in triggering acute ischemic heart disease events. Methods and Results— A case-crossover study design was used to analyze ischemic events in 12 865 patients who lived on the Wasatch Front in Utah. Patients were drawn from the cardiac catheterization registry of the Intermountain Heart Collaborative Study, a large, ongoing registry of patients who underwent coronary arteriography and were followed up longitudinally. Ambient fine particulate pollution (particles with an aerodynamic diameter ≤2.5 μm; PM 2.5 ) elevated by 10 μg/m 3 was associated with increased risk of acute ischemic coronary events (unstable angina and myocardial infarction) equal to 4.5% (95% confidence interval, 1.1 to 8.0). Effects were larger for those with angiographically demonstrated coronary artery disease. Conclusions— Short-term particulate exposures contributed to acute coronary events, especially among patients with underlying coronary artery disease. Individuals with stable presentation and those with angiographically demonstrated clean coronaries are not as susceptible to short-term particulate exposure.
Effect of omeprazole and sucralfate on prepyloric gastric ulcer. A double blind comparative trial and one year follow up.
Authors: H T Sorensen, H H Rasmussen, I Balslev, S Boesby, J Bone, A Kruse, S N Rasmussen
Journal: Gut (1994)

This study compared healing rates, relief of symptoms, frequency of adverse events, and proportion of patients in remission after one year follow up in 104 patients with active prepyloric ulcer during treatment with 40 mg omeprazole once daily or 2 g sucralfate twice daily, using a randomised double blind controlled trial. Healing rates after two, four, and six weeks were (omeprazole/sucralfate) 49%/23%; 83%/59%; 90%/70% respectively. After two weeks, omeprazole was more efficient than sucralfate in relief of daytime and nocturnal epigastric pain, nausea, and heartburn. The proportion of patients in remission after one year follow up was significantly higher in the omeprazole group (p &lt; 0.01). Of the healed patients ulcers recurred in 36% in the omeprazole group and in 46% in the sucralfate group. It is concluded that the ulcer healing rate was higher and symptom relief was more pronounced in the omeprazole group compared with the sucralfate group, and that more patients were still in remission after a one year follow up period.
The good doctor
Authors: L. Farrell
Journal: BMJ (2002)

How do you define the good doctor? How do you solve a problem like Maria? Being kind and compassionate is all very well but we need more, the rage to achieve, the pride not to accept defeat; like Milton's Satan, our vices are indistinguishable from our virtues. The qualities demanded are multiple, and they fluctuate with time and circumstances.

Jennie had an unusual form of high spirited and happy dementia, and just as I arrived at the farm she was …
Neuroendocrine-Immune System Interactions and Autoimmunity
Authors: R L Wilder
Journal: Annual Review of Immunology (1995)

The concept of an integrated bidirectionally regulated neuroendocrine-immune adaptive response to stress has strong experimental support. The quality and intensity of this coordinated response to stress varies depending upon age, gender, reproductive status, and other genetically determined factors as well as the types and magnitudes of environmental challenges. These factors and dysfunctional communication between the nervous, endocrine, and immune systems appear to contribute to the development of autoimmune diseases in the Lewis and BB rats, the OS chicken, and the NOD, MRL, NZB, NZW, and NZB/NZW F1 mice. Neuroendocrine-immune dysfunction also contributes to the pathogenesis of human autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, thyroid diseases, and others. This review highlights these concepts. It includes discussions on various aspects of the stress response, the hypothalamic-pituitary-adrenal and -gonadal axes, corticotropin releasing hormone, luteinizing hormone releasing hormone, interleukin-1 and -6, corticosteroids, estrogens, testosterone, dehydroepiandrosterone, growth hormone, prolactin, and thyroid hormone. The role of the nervous and endocrine systems in regulating thymopoiesis and T cell development is also emphasized.
The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice
Authors: Christina Schessl, Vijay P.S. Rawat, Monica Cusan, Aniruddha Deshpande, Tobias M. Kohl, Patricia M. Rosten, Karsten Spiekermann, R. Keith Humphries, Susanne Schnittger, Wolfgang Kern, Wolfgang Hiddemann, Leticia Quintanilla-Martinez, Stefan K. Bohlander, Michaela Feuring-Buske, Christian Buske
Journal: Journal of Clinical Investigation (2005)

The molecular characterization of leukemia has demonstrated that genetic alterations in the leukemic clone frequently fall into 2 classes, those affecting transcription factors (e.g., AML1-ETO) and mutations affecting genes involved in signal transduction (e.g., activating mutations of FLT3 and KIT). This finding has favored a model of leukemogenesis in which the collaboration of these 2 classes of genetic alterations is necessary for the malignant transformation of hematopoietic progenitor cells. The model is supported by experimental data indicating that AML1-ETO and FLT3 length mutation (FLT3-LM), 2 of the most frequent genetic alterations in AML, are both insufficient on their own to cause leukemia in animal models. Here we report that AML1-ETO collaborates with FLT3-LM in inducing acute leukemia in a murine BM transplantation model. Moreover, in a series of 135 patients with AML1-ETO-positive AML, the most frequently identified class of additional mutations affected genes involved in signal transduction pathways including FLT3-LM or mutations of KIT and NRAS. These data support the concept of oncogenic cooperation between AML1-ETO and a class of activating mutations, recurrently found in patients with t(8;21), and provide a rationale for therapies targeting signal transduction pathways in AML1-ETO-positive leukemias.
Isolation, Characterization, and use of Stem Cells from the CNS
Authors: F H Gage, J Ray, L J Fisher
Journal: Annual Review of Neuroscience (1995)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Measurement of overinflation by multiple linear regression analysis in patients with acute lung injury
Authors: AD Bersten
Journal: European Respiratory Journal (1998)

Strategies to optimize alveolar recruitment and prevent lung overinflation are central to ventilatory management of patients with acute lung injury (ALI). The recent description of overinflation using multilinear regression analysis of airway pressure (Paw) and flow (V') data allows a functional assessment of lung mechanics. However, this technique has not been studied in ALI patients. During 15 positive end-expiratory pressure (PEEP) trials in 10 ALI patients, respiratory elastance was partitioned into volume-independent (E1) and volume-dependent (E2VT) components, where Paw=(E1+E2VT)V+RrsV'+Po; where V is volume, VT is tidal volume, Rrs is respiratory resistance and Po is static recoil pressure at end-expiration (equivalent to total PEEP). Then, %E2 was calculated as (100E2VT)/(E1+E2VT); a measure of lung overinflation when %E2&gt;30%. Alveolar recruitment, assessed as a PEEP-induced increase in V&gt;50 mL at a constant Paw occurred in 14 of 15 trials (299+/-34 mL, mean+/-SEM), but was independent of the degree of lung inflation. Lung overinflation was common (six of 15 clinically set PEEP levels) and occurred despite a dynamic elastic distending pressure (Pel,dyn) &lt;30 cmH2O during 18 of 36 PEEP titrations. During a PEEP titration the resultant %E2 was directly related to delta(peak airway pressure-Po) (rs=0.86, p&lt;0.001) and delta(Pel,dyn-Po) (rs=0.89, p&lt;0.001). The 95% predictive intervals for a 2 cmH2O change in either driving pressure were %E2 values of 30.4-68.1% and 32.8-69.2%, respectively. Single or continuous measurement of %E2 (a measure of lung inflation) is a readily available method for titrating ventilatory parameters. Further, during a positive end-expiratory pressure titration a change in ventilatory driving pressure &gt; or =2 cmH2O is indicative of overinflation.