tbuckley/cabot-search huggingface dataset:
Effects of platelet activating factor on airway calibre, airway responsiveness, and circulating cells in asthmatic subjects.
Authors: K F Chung, P J Barnes
Journal: Thorax (1989)

The effects of inhaled platelet activating factor were compared with those of inhaled methacholine (control) on airway calibre, airway responsiveness to methacholine and isoprenaline, and circulating cells in eight subjects with mild, stable asthma. Platelet activating factor was given in six doses at 15 minute intervals and airway response measured as change in partial expiratory flow at 30% of vital capacity (Vp30). Platelet activating factor caused a fall in Vp30, the mean (SEM) maximum percentage fall being 28.9 (4.2) five minutes after the first dose (12 micrograms) and 50.9 (8.0) after the second dose (24 micrograms). Tachyphylaxis occurred, however, with the four subsequent doses of inhaled platelet activating factor. There was transient neutropenia after the first dose, from a mean of 3.6 (0.2) x 10(9) to 2.2 (0.5) x 10(9) neutrophils/l; this response also showed tachyphylaxis with subsequent doses. The mean PC40 (the concentration of methacholine needed to cause a 40% fall in Vp30) was unchanged one, three, and seven days after administration of platelet activating factor. There was no significant correlation between baseline PC40 methacholine and the maximal fall in Vp30 after either the first (12 micrograms) or the second dose (24 micrograms) of platelet activating factor. The control challenge with methacholine produced a degree of bronchoconstriction similar to that of platelet activating factor but was not associated with any significant change in bronchial responsiveness or in circulating cells. The bronchodilator response to inhaled isoprenaline measured three days after inhalation of platelet activating factor and of methacholine was similar after the two challenges. Thus asthmatic subjects who are hyperresponsive to methacholine show a similar bronchoconstrictor response to platelet activating factor, as has been observed in normal subjects; overall this did not cause airway hyperresponsiveness to methacholine.
Decreased Expression of the Cardiac LIM Domain Protein MLP in Chronic Human Heart Failure
Authors: Oliver Zolk, Pico Caroni, Michael Böhm
Journal: Circulation (2000)

Background —The cardiac LIM domain protein MLP, a member of the cysteine-rich protein family, is an essential regulator of cardiac muscle development. Mice with a disruption of the MLP gene resemble the morphological and clinical picture of dilated cardiomyopathy and heart failure in humans. We investigated whether altered MLP expression is significant for the pathogenesis of human heart failure. Methods and Results —Immunohistochemistry and in situ hybridization confirmed the expression of MLP protein and mRNA in human cardiomyocytes. Western blot analysis revealed that the MLP peptide was present in the contractile protein fraction but not in the cytosolic or membrane fraction and that the binding of MLP to myofibrils required functional zinc finger domains. MLP immunoreactivity was decreased ≈50% ( P &lt;0.05) in the left ventricular myocardium of patients with chronic heart failure due to dilated or ischemic cardiomyopathy compared with non-failing donor hearts. MLP mRNA expression, as assessed by Northern blot experiments, was not significantly different between failing and non-failing control hearts, which suggests that decreased MLP synthesis or increased MLP protein turnover, rather than a decreased number of RNA transcripts, may play a role. Conclusions —Because MLP may promote myofibril assembly, the down-regulation of this adapter protein might play an essential role in myofibril derangement or impaired myofibril rearrangement in the failing human myocardium.
Efficacy, safety, and immunogenicity of a Vero-cell-culture-derived trivalent influenza vaccine: a multicentre, double-blind, randomised, placebo-controlled trial
Authors: P Noel Barrett, Gregory Berezuk, Sandor Fritsch, Gerald Aichinger, Mary Kate Hart, Wael El-Amin, Otfried Kistner, Hartmut J Ehrlich
Journal: The Lancet (2011)
TREATMENT OF PSORIASIS WITH TAR BATHS
Authors: ERIK A. KNUDSEN
Journal: British Journal of Dermatology (1963)

Journal Article TREATMENT OF PSORIASIS WITH TAR BATHS Get access ERIK A. KNUDSEN ERIK A. KNUDSEN Department of Skin and Venereal Diseases, University of Copenhagen Medical School, Rigshospitalet, Copenhagen, Denmark (Chief: Professor G. Asboe‐Hansen, M.D.) Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 75, Issue 11, 1 November 1963, Pages 428–433, https://doi.org/10.1111/j.1365-2133.1963.tb13538.x Published: 01 November 1963
Androgen-Regulated SPARCL1 in the Tumor Microenvironment Inhibits Metastatic Progression
Authors: Paula J. Hurley, Robert M. Hughes, Brian W. Simons, Jessie Huang, Rebecca M. Miller, Brian Shinder, Michael C. Haffner, David Esopi, Yasunori Kimura, Javaneh Jabbari, Ashley E. Ross, Nicholas Erho, Ismael A. Vergara, Sheila F. Faraj, Elai Davicioni, George J. Netto, Srinivasan Yegnasubramanian, Steven S. An, Edward M. Schaeffer
Journal: Cancer Research (2015)

Prostate cancer is a leading cause of cancer death in men due to the subset of cancers that progress to metastasis. Prostate cancers are thought to be hardwired to androgen receptor (AR) signaling, but AR-regulated changes in the prostate that facilitate metastasis remain poorly understood. We previously noted a marked reduction in secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) expression during invasive phases of androgen-induced prostate growth, suggesting that this may be a novel invasive program governed by AR. Herein, we show that SPARCL1 loss occurs concurrently with AR amplification or overexpression in patient-based data. Mechanistically, we demonstrate that SPARCL1 expression is directly suppressed by androgen-induced AR activation and binding at the SPARCL1 locus via an epigenetic mechanism, and these events can be pharmacologically attenuated with either AR antagonists or HDAC inhibitors. We establish using the Hi-Myc model of prostate cancer that in Hi-Myc/Sparcl1(-/-) mice, SPARCL1 functions to suppress cancer formation. Moreover, metastatic progression of Myc-CaP orthotopic allografts is restricted by SPARCL1 in the tumor microenvironment. Specifically, we show that SPARCL1 both tethers to collagen in the extracellular matrix (ECM) and binds to the cell's cytoskeleton. SPARCL1 directly inhibits the assembly of focal adhesions, thereby constraining the transmission of cell traction forces. Our findings establish a new insight into AR-regulated prostate epithelial movement and provide a novel framework whereby SPARCL1 in the ECM microenvironment restricts tumor progression by regulating the initiation of the network of physical forces that may be required for metastatic invasion of prostate cancer.
SPAK Differentially Mediates Vasopressin Effects on Sodium Cotransporters
Authors: Turgay Saritas, Aljona Borschewski, James A. McCormick, Alexander Paliege, Christin Dathe, Shinichi Uchida, Andrew Terker, Nina Himmerkus, Markus Bleich, Sylvie Demaretz, Kamel Laghmani, Eric Delpire, David H. Ellison, Sebastian Bachmann, Kerim Mutig
Journal: Journal of the American Society of Nephrology (2013)

Activation of the Na+-K+-2Cl−-cotransporter (NKCC2) and the Na+-Cl−-cotransporter (NCC) by vasopressin includes their phosphorylation at defined, conserved N-terminal threonine and serine residues, but the kinase pathways that mediate this action of vasopressin are not well understood. Two homologous Ste20-like kinases, SPS-related proline/alanine-rich kinase (SPAK) and oxidative stress responsive kinase (OSR1), can phosphorylate the cotransporters directly. In this process, a full-length SPAK variant and OSR1 interact with a truncated SPAK variant, which has inhibitory effects. Here, we tested whether SPAK is an essential component of the vasopressin stimulatory pathway. We administered desmopressin, a V2 receptor–specific agonist, to wild-type mice, SPAK-deficient mice, and vasopressin-deficient rats. Desmopressin induced regulatory changes in SPAK variants, but not in OSR1 to the same degree, and activated NKCC2 and NCC. Furthermore, desmopressin modulated both the full-length and truncated SPAK variants to interact with and phosphorylate NKCC2, whereas only full-length SPAK promoted the activation of NCC. In summary, these results suggest that SPAK mediates the effect of vasopressin on sodium reabsorption along the distal nephron.
Randomized phase III trial of vinblastine, bleomycin, and cis-dichlorodiammine-platinum versus dacarbazine in malignant melanoma.
Authors: S D Luikart, G T Kennealey, J M Kirkwood
Journal: Journal of Clinical Oncology (1984)

A randomized phase III study was carried out in 57 patients with metastatic melanoma treated with either dacarbazine (DTIC) given intravenously (IV) daily for 10 days using light protection, or a combination of vinblastine IV on days 1 and 2, bleomycin by continuous IV infusion during days 1-5, and cisplatin by IV infusion on day 5 (VBD). Objective response rates were similar: 14% for dacarbazine and 10% for VBD. However, dacarbazine responses were associated with a trend toward longer progression-free intervals and longer survival. Toxicity was significantly greater in the VBD arm, and fatal in two patients. Dacarbazine was also associated with severe toxicity by the 10-day light-protected schedule used here. VBD is not as effective as previously reported, and dacarbazine remains a standard of therapy for metastatic melanoma.
Endothelial cells augment T cell interleukin 2 production by a contact-dependent mechanism involving CD2/LFA-3 interaction.
Authors: C C Hughes, C O Savage, J S Pober
Journal: The Journal of Experimental Medicine (1990)

We have demonstrated that endothelial cells (EC) augment IL-2 production by PHA-stimulated PBMC or purified CD4+ T cells and that the increase is apparent both in the amount of soluble IL-2 secreted and in the level of specific mRNA detectable by Northern blot hybridization. The ability of EC to affect levels of IL-2 cannot be reproduced by soluble factors, including the cytokines IL-1, IL-6, IFN-gamma, or TNF, conditioned medium from resting EC or IL-1, IFN-gamma- or TNF-treated EC, or from resting PBMC + EC cultures. Separation of the EC and PBMC by a Transwell membrane demonstrated that cell contact was required for augmentation of IL-2 synthesis and that this effect was unlikely to be mediated by a short-lived soluble signal. The cell-cell interaction required the ligand pair CD2/LFA-3, since augmentation could be inhibited by antibodies to these structures. Antibodies to ICAM-1, LFA-1, CD4, and MHC class II were without effect. A contact-dependent pathway involving CD2/LFA-3 interactions also may be used by EC to augment IL-2 production from T cells stimulated more specifically through the TCR/CD3 complex with antibody OKT3. This pathway provides a proliferative advantage to T cells stimulated with OKT3 in the presence of EC and may also be involved in the proliferative response of resting T cells to allogeneic class II MHC-expressing EC. We propose that EC augmentation of T cell IL-2 synthesis may be critical in the ability of EC to elicit primary T cell antigen responses and may have consequences for the development of localized cell-mediated immune reactions.
Prevalence of CD44+/CD24−/low Cells in Breast Cancer May Not Be Associated with Clinical Outcome but May Favor Distant Metastasis
Authors: Benny K. Abraham, Peter Fritz, Monika McClellan, Petra Hauptvogel, Maria Athelogou, Hiltrud Brauch
Journal: Clinical Cancer Research (2005)

Breast cancer is composed of phenotypically diverse populations of cancer cells. The ability to form breast tumors has been shown by in vitro/in vivo studies to be restricted to epithelial tumor cells with CD44(+)/CD24(-/low) characteristics. Validation of these findings with respect to detection in clinical samples, prognosis, and clinical relevance is in demand.We investigated breast cancer tissues for the prevalence of CD44(+)/CD24(-/low) tumor cells and their prognostic value. The study included paraffin-embedded tissues of 136 patients with and without recurrences. In addition, a breast cancer progression array with normal, carcinoma in situ, and carcinoma tissues was analyzed. We applied double-staining immunohistochemistry for the detection of CD44(+)/CD24(-/low) cells. Evaluation was by microscopic pathologic inspection and automated image analysis.CD44(+)/CD24(-/low) cells ranged from 0% to 40% in normal breast and from 0% to 80% in breast tumor tissues. The prevalence of CD44(+)/CD24(-/low) tumor cells in 122 tumors was < or =10% in the majority (78%) of cases and >10% in the remainder. There was no significant correlation between CD44(+)/CD24(-/low) tumor cell prevalence and tumor progression. Although recurrences of tumors with high percentages of CD44(+)/CD24(-/low) tumor cells were mainly distant, preferably osseous metastasis, there was no correlation with the event-free and overall survival. There was no influence on the response to different treatment modalities.Our findings suggest that the prevalence of CD44(+)/CD24(-/low) tumor cells in breast cancer may not be associated with clinical outcome and survival but may favor distant metastasis.
Effect of Angiotensin II Receptor Blockage on Osteopontin Expression and Calcium Oxalate Crystal Deposition in Rat Kidneys
Authors: Tohru Umekawa, Yuji Hatanaka, Takashi Kurita, Saeed R. Khan
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Hyperoxaluria leads to calcium oxalate (CaOx) crystallization and development of tubulointerstitial lesions in the kidneys. Treatment of hyperoxaluric rats with angiotensin II (Ang II) type I receptor blocker (ARB) reduces lesion formation. Because Ang II mediates osteopontin (OPN) synthesis, which is involved in both macrophage recruitment and CaOx crystallization, it was hypothesized that ARB acts via OPN. Hyperoxaluria was induced in 10-wk-old male Sprague-Dawley rats, and they were treated with ARB candesartan. At the end of 4 wk, kidneys were examined for crystal deposits, ED-1–positive cells, and expression of OPN mRNA. PCR was used to quantify OPN, renin, and angiotensin-converting enzyme (ACE) mRNA in kidneys. RIA was used to determine renal, plasma, and urinary OPN; plasma renin; Ang II and ACE; and renal Ang II. For evaluating oxidative stress, malondialdehyde was measured. Urinary calcium, oxalate, creatinine, and albumin were also determined. Despite similar urinary calcium and oxalate levels, kidneys of hyperoxaluric rats on candesartan had fewer CaOx crystals, fewer ED-1–positive cells, reduced OPN expression, and reduced malondialdehyde than hyperoxaluric rats. Urinary albumin excretion and serum creatinine levels improved significantly on candesartan treatment. mRNA for OPN, renin, and ACE were significantly elevated in hyperoxaluric rats. OPN synthesis and production increased with hyperoxaluria but to a lesser extent in candesartan-treated hyperoxaluric rats. These results show for the first time that oxalate can activate the renal renin-angiotensin system and that oxalate-induced upregulation of OPN is in part mediated via renal renin-angiotensin system.
Searching for the Autoimmune Thyroid Disease Susceptibility Genes: From Gene Mapping to Gene Function
Authors: Yaron Tomer, Terry F. Davies
Journal: Endocrine Reviews (2003)

Abstract The autoimmune thyroid diseases (AITD) are complex diseases that are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility, in combination with external factors (e.g., dietary iodine), is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been used to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g., human leukocyte antigen, cytotoxic T lymphocyte antigen-4) and thyroid-specific genes (e.g., TSH receptor, thyroglobulin). Most likely these loci interact, and their interactions may influence disease phenotype and severity. It is hoped that in the near future additional AITD susceptibility genes will be identified and the mechanisms by which they induce AITD will be unraveled.
Symptomatic hiatus hernia: a study of the pyloro-duodenal region and the rationale of vagotomy in its treatment.
Authors: H W Burge, A M Gill, C D MacLean, R H Lewis
Journal: Thorax (1966)

The association of duodenal ulceration and symptomatic hiatus hernia, with or without peptic oesophagitis, is well recognized.Casten, Bernhang
Atypical pulmonary carcinoid tumour in a 28-year-old nonsmoker with Prader-Willi syndrome
Authors: I. Nenekidis, G.T. Stathopoulos, V. Anagnostakou, A. Kokkori, P. Dedeilias, J. Kokotsakis, M. Argiriou, C. Zisis
Journal: European Respiratory Journal (2011)

Atypical pulmonary carcinoid tumour
Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy
Authors: F. Liu, L. Chen, D.-M. Yu, L. Deng, R. Chen, Y. Jiang, L. Chen, S.-Y. Huang, J.-L. Yu, Q.-M. Gong, X.-X. Zhang
Journal: Gut (2011)

<h3>Objective</h3> To investigate the evolution of hepatitis B virus (HBV) quasispecies (QS) within the reverse transcriptase (RT) region during the early stage of entecavir treatment and its impact on virological response, and to compare evolutionary patterns under different selective pressures. <h3>Methods</h3> 31 patients with chronic hepatitis B receiving entecavir (17 responders and 14 partial responders according to the HBV DNA levels at week 48) and 25 patients receiving lamivudine (14 responders and 11 non-responders) as controls were included. An average of 26 clones (2892 total from both groups) spanning the RT region per sample was sequenced. <h3>Results</h3> QS complexity and diversity, in addition to alanine aminotransferase and HBV DNA levels, were comparable between responders and partial responders at baseline. However, QS complexity in responders at week 4 was statistically lower than that in partial responders at the nucleotide level (0.6494 vs 0.7723, p=0.039). Net changes in diversity as well as the viral nucleotide substitution rate of responders were higher than those of partial responders, and both correlated with virological responses at both week 48 and the final visit (mean: 28 months). A preliminary model of QS evolution variables predicted 16 of 17 responders and 13 of 14 partial responders in the entecavir group. Despite significant differences between responders to entecavir and responders to lamivudine at week 4, the characteristics of QS were quite similar between partial responders to entecavir and non-responders to lamivudine. <h3>Conclusions</h3> The evolutionary patterns of HBV RT QS differ between responders and partial responders during the early stage of entecavir treatment. Characteristics of HBV QS evolution during the first 4 weeks contribute to the prediction of long-term virological responses. The similar patterns of HBV RT QS in partial responders and non-responders receiving different nucleoside analogues may imply a novel mechanism of drug resistance, which warrants further investigation.
Serologic diagnosis of tuberculosis by combining Ig classes against selected mycobacterial targets
Authors: Ralf Baumann, Susanne Kaempfer, Novel N. Chegou, Wulf Oehlmann, André G. Loxton, Stefan H.E. Kaufmann, Paul D. van Helden, Gillian F. Black, Mahavir Singh, Gerhard Walzl
Journal: Journal of Infection (2014)
Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression.
Authors: P Hammel, C Haioun, M T Chaumette, P Gaulard, M Divine, F Reyes, J C Delchier
Journal: Journal of Clinical Oncology (1995)

PURPOSE The treatment of low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphoma with prominent gastric expression is controversial. Total gastrectomy has been proposed, but is associated with significant morbidity. The aim of this monocentric study was to assess the efficacy of continuous oral chemotherapy with a single alkylating agent. PATIENTS AND METHODS Twenty-four consecutive patients, 13 men and 11 women, were studied. Their mean age was 51 years (range, 22 to 79). Low-grade B-cell MALT lymphoma was diagnosed by histologic and immunohistologic examination of endoscopic biopsies. Seventeen patients had stage I disease and seven stage IV disease, with lung and gastric involvement. Two of these seven patients also had bone marrow involvement. The alkylating agent (cyclophosphamide or chlorambucil) was administered orally and daily for periods of 12 to 24 months. RESULTS The median follow-up time was 45 months (range, 14 months to 14 years). Complete remission was obtained in 18 patients (75%) after a median treatment duration of 12 months. Five patients relapsed; two of them were successfully re-treated, and one died of MALT lymphoma that had transformed into large-cell lymphoma. Chemotherapy was stopped after 24 months for six patients who only achieved a partial remission; two of them required further treatment for progressive disease (surgery for a small-bowel localization in one case and cyclophosphamide rechallenge in the other). Nine patients had neutropenia that required a reduced chemotherapy dosage. CONCLUSION In low-grade MALT lymphoma with prominent gastric expression, continuous monochemotherapy may constitute an efficient alternative to gastrectomy, regardless of disease stage.
FOXO Transcription Factors Control E2F1 Transcriptional Specificity and Apoptotic Function
Authors: Igor Shats, Michael L. Gatza, Beiyu Liu, Steven P. Angus, Lingchong You, Joseph R. Nevins
Journal: Cancer Research (2013)

The transcription factor E2F1 is a key regulator of proliferation and apoptosis but the molecular mechanisms that mediate these cell fate decisions remain unclear. Here, we identify FOXO transcription factors as E2F1 target genes that act in a feed-forward regulatory loop to reinforce gene induction of multiple apoptotic genes. We found that E2F1 forms a complex with FOXO1 and FOXO3. RNAi-mediated silencing of FOXO impaired E2F1 binding to the promoters of cooperative target genes. A FOXO3 mutant insensitive to inactivation by survival kinases rescued the inhibitory effect of growth factor signaling on E2F1-mediated transcription and apoptosis. The E2F1/FOXO axis is frequently blocked in cancer, as evidenced by the specific downregulation of the FOXO-dependent E2F1 transcriptional program in multiple cancer types and by the association of a reduced E2F1/FOXO transcriptional program with poor prognosis. HDAC and phosphoinositide 3-kinase (PI3K) inhibitors were identified as specific activators of E2F1/FOXO transcription, acting to enhance E2F1-induced apoptosis in a FOXO3-dependent manner. Notably, combining the histone deacetylase inhibitor vorinostat with a PI3K inhibitor led to enhanced FOXO-dependent apoptosis. Collectively, our results identify E2F1/FOXO cooperation as a regulatory mechanism that places E2F1 apoptotic activity under the control of survival signaling. Therapeutic reactivation of this tumor suppressive mechanism may offer a novel broad-acting therapy for cancer.