tbuckley/cabot-search huggingface dataset:
Keratinocyte growth factor improves alterations of lung permeability and bronchial epithelium in allergic rats
Authors: I. Tillie-Leblond, P. Gosset, R. Le Berre, A. Janin, T. Prangère, A. B. Tonnel, B. P. H. Guery
Journal: European Respiratory Journal (2007)

Chronic allergic asthma is associated with marked inflammatory reaction, microvascular leakage and epithelium injury. As previously shown in a rat model of chronic asthma, these alterations increase lung permeability and distal airway fluid clearance. Keratinocyte growth factor (KGF) has been shown to induce epithelial cell proliferation and to protect from acute lung injuries. Therefore, the current authors evaluated the potential role of KGF treatment on lung permeability and airway inflammation in rats with chronic asthma. KGF (1 mg x kg(-1)) was administered intravenously before the last ovalbumin (OVA) challenge in sensitised rats. Permeability was assessed by the leak of radiolabelled albumin from the alveolar and systemic compartments. Histopathological analysis was also performed. Treatment with KGF decreased the leak of both markers and decreased the level of extravascular lung water in sensitised rats challenged with OVA. KGF treatment also reduced the inflammatory cell number in bronchoalveolar lavage fluid but not in bronchial mucosa. KGF markedly limited the allergen-induced alterations in epithelium integrity and the expression of the intercellular junction proteins beta-catenin and zonula occludens protein-1. In conclusion, keratinocyte growth factor administration markedly limits lung permeability and airway inflammation, an effect associated with a decrease in epithelium alterations during chronic allergic asthma. These data open new prospects in the therapeutic strategy of asthma.
Proteomics Technologies and Challenges
Authors: William C.S. Cho
Journal: Genomics Proteomics & Bioinformatics (2007)

Abstract Proteomics is the study of proteins and their interactions in a cell. With the completion of the Human Genome Project, the emphasis is shifting to the protein compliment of the human organism. Because proteome reflects more accurately on the dynamic state of a cell, tissue, or organism, much is expected from proteomics to yield better disease markers for diagnosis and therapy monitoring. The advent of proteomics technologies for global detection and quantitation of proteins creates new opportunities and challenges for those seeking to gain greater understanding of diseases. High-throughput proteomics technologies combining with advanced bioinformatics are extensively used to identify molecular signatures of diseases based on protein pathways and signaling cascades. Mass spectrometry plays a vital role in proteomics and has become an indispensable tool for molecular and cellular biology. While the potential is great, many challenges and issues remain to be solved, such as mining low abundant proteins and integration of proteomics with genomics and metabolomics data. Nevertheless, proteomics is the foundation for constructing and extracting useful knowledge to biomedical research. In this review, a snapshot of contemporary issues in proteomics technologies is discussed.
Die Liquordiagnostik in Klinik und Praxis
Journal: JAMA (1935)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Blockade of CD40/CD40 ligand interactions attenuates skin fibrosis and autoimmunity in the tight-skin mouse
Authors: K Komura, M Fujimoto, K Yanaba, T Matsushita, Y Matsushita, M Horikawa, F Ogawa, K Shimizu, M Hasegawa, K Takehara, S Sato
Journal: Annals of the Rheumatic Diseases (2007)

To assess the association of CD40/CD40 ligand (CD40L) interactions with the development of skin fibrosis and autoimmunity in tight-skin (TSK/+) mouse, which is a mouse model for human systemic sclerosis.Newly born TSK/+ mice were treated with murine anti-CD40L monoclonal antibody (100 microg intraperitoneally weekly). Hypodermal thickness of 8-week-old female mice (defined as the thickness of a subcutaneous loose connective tissue layer beneath the panniculus carnosus) was measured under a light microscope. All skin sections were taken from the para-midline, upper back region. Serum anti-topoisomerase I autoantibody levels, serum immunoglobulin levels and plasma soluble CD40L levels were determined by enzyme-linked immunosorbent assay. For analysis of lymphocyte surface molecules, single cell suspensions of lymphocytes were stained by monoclonal antibodies. Proliferation of TSK/+ B cells and fibroblasts to anti-CD40 antibodies was assessed by the uptake of [3H]-labelled thymidine and bromodeoxyuridine, respectively.The blockade of CD40/CD40L interactions by anti-CD40L monoclonal antibody significantly reduced cutaneous fibrosis (65%) and anti-topoisomerase I autoantibody in TSK/+ mice. Anti-CD40L monoclonal antibody also normalised B lymphocyte abnormal activation in TSK/+ mice, demonstrated by hyper-gamma-globulinaemia. Furthermore, augmented CD40/CD40L interactions in TSK/+ mice were suggested by upregulated expression of CD40L on CD4(+) T cells, elevated plasma soluble CD40L levels. The hyperresponsiveness to CD40 stimulation was also observed in TSK/+ B cells and fibroblasts.Cutaneous fibrosis and autoimmunity in TSK/+ mice are closely correlated with CD40/CD40L interactions.
Death and Children: A Guide for Educators, Parents and Caregivers
Authors: W. Foster Eich
Journal: JAMA (1986)

Once, few books were written about death. Death, like sex in the Victorian era, was a taboo subject. Friends passed away and patients expired. Now, things have changed; friends and patients can die, and many books are written about death. It is fashionable.  But there is still little material dealing with death and children. Somehow, we seem to be able to face death in adults, but the death of a child is much harder to accept.  Only recently have chapters about the terminally ill child been added to pediatric textbooks, and even now not all include such a chapter. Pediatricians are not usually very good at handling their feelings about a patient's death, either; I have known internists to needle us about how hard we take the death of a patient. I have also noticed that oncologists trained in internal medicine usually are not eager to help manage cancer in
808-2 Creatine kinase-MB elevation after coronary stenting in lesions with ruptured plaque
Authors: Kenichi Fujii, Yoshio Kobayashi, Gary S Mintz, David Jacoboff, Hideo Takebayashi, Takenori Yasuda, Issam Moussa, Roxana Mehran, George Dangas, Alexandra J Lansky, Edward Kreps, Michael Collins, Gregg W Stone, Martin B Leon, Jeffrey W Moses
Journal: Journal of the American College of Cardiology (2004)
Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses
Authors: Denis Gaucher, René Therrien, Nadia Kettaf, Bastian R. Angermann, Geneviève Boucher, Abdelali Filali-Mouhim, Janice M. Moser, Riyaz S. Mehta, Donald R. Drake, Erika Castro, Rama Akondy, Aline Rinfret, Bader Yassine-Diab, Elias A. Said, Younes Chouikh, Mark J. Cameron, Robert Clum, David Kelvin, Roland Somogyi, Larry D. Greller, Robert S. Balderas, Peter Wilkinson, Giuseppe Pantaleo, Jim Tartaglia, Elias K. Haddad, Rafick-Pierre Sékaly
Journal: The Journal of Experimental Medicine (2008)

Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity, including complement, the inflammasome, and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (modular immune in vitro construct [MIMIC] system), by the coordinated up-regulation of transcripts for specific transcription factors, including STAT1, IRF7, and ETS2, which are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional, and persistent immune response that integrates all effector cells of the immune system.
Noninvasive ventilation and the potential risk of transmission of infection
Authors: A. Singh, P. J. Sterk
Journal: European Respiratory Journal (2008)

To the Editors: 

In their exhaustive review on noninvasive ventilation (NIV) in acute respiratory failure, Ambrosino and Vagheggini 1 do not mention the potential risk of transmitting infections during its application.

Noninvasive positive-pressure ventilation (NPPV) is becoming increasingly used in patients with acute respiratory failure caused by a wide range of infectious aetiologies such as human-adapted avian influenza, aspergillosis and varicella 2–4, in order to avoid intubation or as a bridge to invasive mechanical …
Differential Effect of Doxorubicin and Zoledronic Acid on Intraosseous versus Extraosseous Breast Tumor Growth <i>In vivo</i>
Authors: Penelope D. Ottewell, Blandine Deux, Hannu Mönkkönen, Simon Cross, Robert E. Coleman, Philippe Clezardin, Ingunn Holen
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Breast cancer patients with bone metastases are commonly treated with chemotherapeutic agents such as doxorubicin and zoledronic acid to control their bone disease. Sequential administration of doxorubicin followed by zoledronic acid has been shown to increase tumor cell apoptosis in vitro. We have therefore investigated the antitumor effects of clinically relevant doses of these drugs in a mouse model of breast cancer bone metastasis. Experimental Design: MDA-MB-231/BO2 cells were injected via the tail vein into athymic mice. Tumor-induced osteolytic lesions were detected in all animals following X-ray analysis 18 days after tumor cell inoculation (day 18). Mice were administered saline, 100 μg/kg zoledronic acid, 2 mg/kg doxorubicin, doxorubicin and zoledronic acid simultaneously, or doxorubicin followed 24 h later by zoledronic acid. Doxorubicin-treated animals received a second injection on day 25. Tumor growth in the marrow cavity and on the outside surface of the bone was measured as well as tumor cell apoptosis and proliferation. The effects of treatments on bone were evaluated following X-ray and μCT analysis. Results: Sequential treatment with doxorubicin followed by zoledronic acid caused decreased intraosseous tumor burden, which was accompanied by increased levels of tumor cell apoptosis and decreased levels of proliferation, whereas extraosseous parts of the same tumors were unaffected. Administration of zoledronic acid, alone or in combination with doxorubicin, resulted in significantly smaller tumor-induced osteolytic lesions compared with control or doxorubicin-treated animals. Conclusions: This is the first study to show that sequential treatment with clinically relevant doses of doxorubicin, followed 24 h later by zoledronic acid, reduces intraosseous but not extraosseous growth of BO2 breast tumors. Our results suggest that breast cancer patients with metastatic bone disease may benefit from sequential treatment using doxorubicin and zoledronic acid.
Germinal Center Initiation, Variable Gene Region Hypermutation, and Mutant B Cell Selection without Detectable Immune Complexes on Follicular Dendritic Cells
Authors: Lynn G. Hannum, Ann M. Haberman, Shannon M. Anderson, Mark J. Shlomchik
Journal: The Journal of Experimental Medicine (2000)

Serum antibody (Ab) can play several roles during B cell immune responses. Among these is to promote the deposition of immune complexes (ICs) on follicular dendritic cells (FDCs). ICs on FDCs are generally thought to be critical for normal germinal center (GC) formation and the development and selection of memory B cells. However, it has been very difficult to test these ideas. To determine directly whether FDC-bound complexes do indeed function in these roles, we have developed a transgenic (Tg) mouse in which all B lymphocytes produce only the membrane-bound form of immunoglobulin M. Immune Tg mice have 10,000-fold less specific Ab than wild-type mice and lack detectable ICs on FDCs. Nonetheless, primary immune responses and the GC reaction in these mice are robust, suggesting that ICs on FDCs do not play critical roles in immune response initiation and GC formation. Moreover, as indicated by the presence and pattern of somatic mutations, memory cell formation and selection appear normal in these IC-deficient GCs.
Observations on the Responses of Rats with Spontaneous Hypertension and Control Rats to Pressor Drugs and to Hexamethonium
Authors: E. L. Phelan, I. Eryetishir, F. Horace Smirk
Journal: Circulation Research (1962)

The establishment, by selective breeding, of a colony of rats with a high incidence of spontaneous hypertension has been confirmed by a kymographic technique with femoral artery cannulation. The reaction of rats to several pressor drugs has been altered by selective breeding. In both control and inherited hypertensive rats, the initial level of the blood pressure prior to administration of the drug influences the magnitude of the responses to several pressor drugs but not to norepinephrine. If hypertensives are compared only with other hypertensives and controls with other controls, it is clear that high preinjection pressures have an inhibiting effect on the pressor responses to biologically and synthetically prepared angiotensin, to vasopressin, and possibly lessen also the responses to s-methyl iso -thiourea. When under experimental conditions the blood pressures of rats with inherited hypertension have fallen into the upper range of control rat blood pressures, the responses to epinephrine, vasopressin, s-methyl iso -thiourea and biological angiotensin are greater in the hypertensives than in the controls. The difference in the case of synthetic angiotensin is not statistically significant. In the case of norepinephrine, the responses are equal. Hexamethoniun reduced the blood pressures of inherited hypertensive and control rats to the same level.
Using susceptibility-weighted imaging to determine response to combined anti-angiogenic, cytotoxic, and radiation therapy in patients with glioblastoma multiforme
Authors: J. M. Lupo, E. Essock-Burns, A. M. Molinaro, S. Cha, S. M. Chang, N. Butowski, S. J. Nelson
Journal: Neuro-Oncology (2013)

The goal of this study was to investigate whether the amount of hypointense signal on susceptibility-weighted imaging within the contrast-enhancing lesion (%SWI-h) on the pretreatment scan could determine response in patients with newly diagnosed glioblastoma multiforme who received external beam radiation therapy with concomitant anti-angiogenic therapy (enzastaurin) and cytotoxic chemotherapy (temozolomide). Twenty-five patients were imaged before therapy (postsurgical resection) and scanned serially every 2 months until progression. Standard clinical MR imaging and SWI were performed on a 3T scanner. %SWI-h was quantified for each patient's pretreatment scan. Time to progression and death were used to characterize patients into non-, immediate-, and sustained-response groups for both events. Cox proportional hazards models were used to assess the association between %SWI-h and both progression-free survival (PFS) and overall survival (OS). Classification and regression tree analysis were used to determine optimal cutoffs on which to split %SWI-h. For both death- and progression-based response categories, %SWI-h was significantly higher in sustained responders than in nonresponders. Cox model coefficients showed an association between %SWI-h and PFS and OS, both in univariate analysis (PFS: hazard ratio [HR] = 0.966, 95% confidence interval [CI] = 0.942–0.988; and OS: HR = 0.945, 95% CI = 0.915–0.976) and when adjusting for baseline KPS, age, sex, and resection extent (PFS: HR = 0.968, 95% CI = 0.940 –0.994; and OS: HR = 0.943, 95% CI = 0.908 –0.976). A cutoff value of 38.1% significantly differentiated patients into 2 groups based on censored OS and into non- and intermediate-response categories based on time to progression. These early differences suggest that SWI may be able to predict which patients would benefit most from similar combination therapies and may assist clinicians in making important decisions about patient care.
A phase I study of systemic sorafenib in combination with isolated limb infusion with melphalan (ILI-M) in patients (pts) with locally advanced in-transit melanoma
Authors: N. McMahon, G. M. Beasley, G. Sanders, C. Augustine, J. Padussis, A. Coleman, M. A. Selim, B. Peterson, M. S. Brady, D. S. Tyler
Journal: Journal of Clinical Oncology (2009)

9065 Background: Sorafenib is a multi-kinase inhibitor that may also enhance the cytotoxicity of concurrently administered chemotherapy. In a preclinical model of regionally advanced melanoma, the combination of systemic Sorafenib and regional melphalan led to augmented tumor responses. Methods: A Phase I multicenter study was performed to evaluate the safety and pharmacokinetics (PK) of systemic Sorafenib in combination with ILI-M in patients with measurable in-transit melanoma of the extremity. Sorafenib dose escalation cohorts consisted of 200mg, 300mg, and 400mg administered systemically twice daily for one week prior and one week after a standard dose ILI-M corrected for ideal body weight. Tumor biopsies pre-therapy and pre-ILI were obtained to assess molecular changes associated with Sorafenib pretreatment. Response was defined at 3 months using RECIST. Results: Nine pts with high disease burden, including 7 previous ILI-M alone failures, have been treated; 3 in the first cohort and 6 in the second cohort. There were no grade 5 toxicities. Four patients had CTCAE Grade 4 toxicities including neutropenia (2), CPK elevation (1), and skin ulceration (1). In the remaining 5 patients, there were no &gt;grade 3 toxicities. The maximally tolerated dose (MTD) has not yet been defined. Initial in field response determination in 6 of the 9 patients out at least 3 months includes 2 partial responses and 4 disease progressions. Conclusions: Systemic Sorafenib administered pre and post ILI-M is a well tolerated, novel targeted therapy approach to regionally advanced melanoma. An additional 10 patients will be enrolled to define the MTD. Correlation of response with drug PK, Sorafenib downregulation of pErk and Mcl1, and a melphalan resistance signature is in progress. No significant financial relationships to disclose.
The Role of a Combined Regimen With Intravesical Chemotherapy and Hyperthermia in the Management of Non-muscle-invasive Bladder Cancer: A Systematic Review
Authors: Rianne J.M. Lammers, J. Alfred Witjes, Brant A. Inman, Ilan Leibovitch, Menachem Laufer, Ofer Nativ, Renzo Colombo
Journal: European Urology (2011)
ALLOANTISERUM-INDUCED INHIBITION OF IMMUNE RESPONSE GENE PRODUCT FUNCTION
Authors: Ethan M. Shevach, Ira Green, William E. Paul
Journal: The Journal of Experimental Medicine (1974)

It has been previously demonstrated that alloantisera can specifically block the activation of T lymphocytes by antigens, the response to which is linked to the presence of histocompatibility (H) types against which the alloantisera are directed. Thus, strain 13 anti-2 serum can inhibit the activation of (2 x 13)F1 T lymphocytes by a DNP derivative of a copolymer of L-glutamic acid and L-lysine (DNP-GL), an antigen the response to which is controlled by a 2-linked Ir gene. It was proposed that alloantisera can inhibit T-lymphocyte antigen recognition through interference with the activity of immune response (Ir) gene products. In order to further study whether the inhibitory antibodies within the alloantisera are directed against H antigens or against the products of the Ir genes, we have examined whether the anti-2 serum can inhibit the function of an Ir gene (the L-glutamic acid and L-alanine [GA] gene), which is normally linked to strain 2 H genes when this gene occurs in an outbred animal lacking strain 2 H genes. In the majority of cases, the anti-2 serum was capable of inhibiting the in vitro proliferative response to GA of T cells derived from animals that were GA+2+, but the serum had little if any effect on the GA response of T cells from GA+2- animals. Furthermore, an antiserum prepared in strain 13 animals against the lymphoid cells of a GA+2- outbred animal was devoid of inhibitory activity on the GA response of cells from a (2 x 13)F1, while an antiserum prepared in strain 13 animals against the lymphoid cells of a GA+2+ outbred animal was capable of specifically inhibiting the response to GA. It thus appears that the inhibition of the GA response by the anti-2 serum is primarily mediated via antibodies directed toward strain 2 H antigens rather than antibodies specific for the product of the GA Ir gene. The mechanism of alloantiserum induced suppression of Ir gene function would then be by steric interference with the Ir gene product on the cell surface, rather than by direct binding to it. This conclusion implies that the products of both the H genes and the Ir genes are physically related on the cell surface. The implications of such a relationship in terms of the fluid-mosaic model of the lymphocyte surface are discussed.