tbuckley/cabot-search huggingface dataset:
Antibiotics with a selective aerobic or anaerobic spectrum have different therapeutic activities in various regions of the colon in interleukin 10 gene deficient mice
Authors: F Hoentjen
Journal: Gut (2003)

Background and aims: Multiple rodent models implicate resident intestinal bacteria in the pathogenesis of chronic immune mediated intestinal inflammation. Specific pathogen free (SPF) interleukin 10 gene deficient (IL-10−/−) mice develop colitis, which does not occur in the germ free (GF) state. We investigated whether broad or narrow spectrum antibiotics affect onset and progression of disease in various regions of IL-10−/− mice. Methods: Metronidazole, ciprofloxacin, vancomycin-imipenem (50 mg/kg/day), or water (control) was administered orally before (prevention) or two weeks after (treatment) colonisation of GF IL-10−/− mice with SPF bacteria. After four weeks, colonic histology scores and cytokine production by colonic explants were determined. Caecal and colonic contents were collected for quantitative bacterial analysis. Results: In the prevention study, all antibiotics decreased inflammation in the caecum and colon. However, in the treatment study, ciprofloxacin and vancomycin-imipenem decreased caecal inflammation, and reduced Escherichia coli and Enterococcus faecalis concentrations, whereas only vancomycin-imipenem lowered direct microscopic bacterial counts. In contrast, metronidazole and vancomycin-imipenem reduced colonic injury and eliminated anaerobic bacteria, including Bacteroides spp. Conclusions: Both narrow and broad spectrum antibiotics can prevent disease but treatment of established colitis is more selective. Ciprofloxacin is most effective in the treatment of caecal inflammation, metronidazole preferentially treats the colon, whereas vancomycin-imipenem definitively treats both regions. These results suggest that subsets of aerobic or anaerobic bacteria show regional differences in their capacity to mediate experimental colitis in IL-10−/− mice.
Alveolar fibroblasts in acute lung injury: biological behaviour and clinical relevance
Authors: C Quesnel, L Nardelli, P Piednoir, V Leçon, J Marchal-Somme, S Lasocki, L Bouadma, I Philip, P Soler, B Crestani, M Dehoux
Journal: European Respiratory Journal (2009)

Although fibroblasts are key cells in the lung repair/fibrosis process, their characteristics are poorly studied in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The aims of our study were to: 1) determine the biological behaviour of alveolar fibroblasts during ALI; and 2) to evaluate the clinical relevance of positive alveolar fibroblast culture from patients with ALI/ARDS. Cells were cultured from bronchoalveolar lavage (BAL) obtained from 68 critically ill, ventilated patients: ALI n = 17; ARDS n = 31; and ventilated controls n = 20. Patients were followed for 28 days and clinical data was recorded. We studied proliferation, migration and collagen-1 synthesis capacities of fibroblasts. Cells expressing fibroblast markers were cultured from BAL obtained in six (35%) ALI patients and six (19%) ARDS patients, but never from ventilated controls. Alveolar fibroblasts exhibited a persistent activated phenotype with enhanced migratory and collagen-1 production capacities, with hyporesponsiveness to prostaglandin E<sub>2</sub> compared to normal lung fibroblasts (p≤0.04). Positive fibroblast culture was associated with both an increased collagen-1 concentration and monocyte/macrophage percentage in BAL fluid (p≤0.01), and with a reduced duration of mechanical ventilation (p&lt;0.001). We conclude that activated alveolar fibroblasts can be cultured either in ALI or ARDS and that their presence might reflect the initiation of the organising phase of ALI.
Outcome of allogeneic stem cell transplantation in adults with common variable immunodeficiency
Authors: Marta Rizzi, Carla Neumann, Adele K. Fielding, Reinhard Marks, Sigune Goldacker, James Thaventhiran, Michael D. Tarzi, Michael Schlesier, Ulrich Salzer, Hermann Eibel, Klaus Warnatz, Jürgen Finke, Bodo Grimbacher, Hans-Hartmut Peter
Journal: Journal of Allergy and Clinical Immunology (2011)
Dietary Genistein Inhibits Metastasis of Human Prostate Cancer in Mice
Authors: Minalini Lakshman, Li Xu, Vijayalakshmi Ananthanarayanan, Joshua Cooper, Chris H. Takimoto, Irene Helenowski, Jill C. Pelling, Raymond C. Bergan
Journal: Cancer Research (2008)

Abstract Dietary genistein has been linked to lower prostate cancer (PCa) mortality. Metastasis is the ultimate cause of death from PCa. Cell detachment and invasion represent early steps in the metastatic cascade. We had shown that genistein inhibits PCa cell detachment and cell invasion in vitro. Genistein-mediated inhibition of activation of focal adhesion kinase (FAK) and of the p38 mitogen-activated protein kinase (MAPK)–heat shock protein 27 (HSP27) pathway has been shown by us to regulate PCa cell detachment and invasion effects, respectively. To evaluate the antimetastatic potential of genistein, we developed an animal model suited to evaluating antimetastatic drug efficacy. Orthotopically implanted human PC3-M PCa cells formed lung micrometastasis by 4 weeks in &amp;gt;80% of inbred athymic mice. Feeding mice dietary genistein before implantation led to blood concentrations similar to those measured in genistein-consuming men. Genistein decreased metastases by 96%, induced nuclear morphometric changes in PC3-M cells indicative of increased adhesion (i.e., decreased detachment) but did not alter tumor growth. Genistein increased tumor levels of FAK, p38 MAPK, and HSP27 “promotility” proteins. However, the ratio of phosphorylated to total protein trended downward, indicating a failure to increase relative amounts of activated protein. This study describes a murine model of human PCa metastasis well suited for testing antimetastatic drugs. It shows for the first time that dietary concentrations of genistein can inhibit PCa cell metastasis. Increases in promotility proteins support the notion of cellular compensatory responses to antimotility effects induced by therapy. Studies of antimetastatic efficacy in man are warranted and are under way. [Cancer Res 2008;68(6):2024–32]
Preventing In-Facility Pressure Ulcers as a Patient Safety Strategy
Authors: Nancy Sullivan, Karen M. Schoelles
Journal: Annals of Internal Medicine (2013)

Complications from hospital-acquired pressure ulcers cause 60 000 deaths and significant morbidity annually in the United States. The objective of this systematic review is to review evidence regarding multicomponent strategies for preventing pressure ulcers and to examine the importance of contextual aspects of programs that aim to reduce facility-acquired pressure ulcers. CINAHL, the Cochrane Library, EMBASE, MEDLINE, and PreMEDLINE were searched for articles published from 2000 to 2012. Studies (any design) that implemented multicomponent initiatives to prevent pressure ulcers in adults in U.S. acute and long-term care settings and that reported pressure ulcer rates at least 6 months after implementation were selected. Two reviewers extracted study data and rated quality of evidence. Findings from 26 implementation studies (moderate strength of evidence) suggested that the integration of several core components improved processes of care and reduced pressure ulcer rates. Key components included the simplification and standardization of pressure ulcer–specific interventions and documentation, involvement of multidisciplinary teams and leadership, use of designated skin champions, ongoing staff education, and sustained audit and feedback.
Working in a multidisciplinary team: need it be so difficult?
Authors: G. Salmon
Journal: BMJ (1994)

The tensions that can exist between members of a multidisciplinary team have recently become apparent to me. As part of a rotational training scheme in psychiatry I am working with people with learning disabilities. As in many branches of psychiatry a multidisciplinary team exists to serve the needs of the patients in the hospital setting as well as in the community. The difficulties are, however, different in these two settings.

In the community team, assessments and follow up tend to be provided by the professional whose special skills are most likely to be needed. When I took up the post I was advised that the initial assessment of a new patient was ideally made by two professionals visiting jointly. In this way a more accurate assessment of needs could be made and an appropriate care package drawn up. This does not seem to happen in practice. I have never been asked to accompany anyone, nor have I been successful in arranging joint visits to patients that I have been allocated. An attempt to suggest the joint assessment of a new patient with another team member brought a written reply that “it would not be suitable.” I do not know whether this referred to the patient, the other professional, me, …
The Interaction of Hageman Factor and Immune Complexes
Authors: Charles G. Cochrane, Kirk D. Wuepper, Barbara S. Aiken, Susan D. Revak, Hans L. Spiegelberg
Journal: Journal of Clinical Investigation (1972)

The possible interaction of Hageman factor from human or rabbit plasma with a variety of immunologic reactants was studied. Evidence of an interaction was not obtained and neither binding of radiolabeled Hageman factor to immune aggregates nor depletion of the Hageman factor from the supernate was observed. Cleavage of the labeled Hageman factor molecule into its 30,000 molecular weight-active fragments was not detectable after incubation with immune complexes. Isolated Hageman factor was far more sensitive to activation than Hageman factor in plasma or serum. There was no consistent activation of isolated Hageman factor by immunologic reactants as determined by conversion of prekallikrein to its enzymatic form or by shortening of the clotting time of factor XII-deficient plasma. A variety of immunologic stimuli were tested: (a) antigen-antibody complexes in soluble or precipitated form; (b) particulate antigen-antibody complexes, i.e., zymosan-anti-zymosan in which a surface was presented for activation; (c) human IgM-IgG and IgG-IgG (rheumatoid factor) complexes; (d) immune aggregates consisting of heat or bis-diazotized benzidine-aggregated myeloma proteins of all human immunoglobulin classes and subclasses: IgG(1,2,3,4), IgA, IgD, IgM, and IgE. Absorption with immune aggregates did not reduce the quantity of Hageman factor in solution, nor was the Hageman factor bound to the precipitates. The presence of plasma or serum with immune aggregates did not generate activity of the Hageman factor. The only preparations of immunoglobulins capable of activating Hageman factor were found to be contaminated with bacteria. These bacteria, upon isolation, activated Hageman factor.
Alcohol-induced Pain in Hodgkin's Disease
Authors: J. G. de Winter
Journal: BMJ (1953)

RABBIT SERUM CONTAINING SPECIFIC AGGLUTININ BRDI reached us, reporting the preparation of sera which precipitate foetal haemoglobin specifically from aqueous solutionsThe relation of these precipitins to our agglutinin remains to be determined.Chernoff reports that in one normal pregnant woman 2% of the total haemoglobin was present in the foetal form, whereas in twelve others the percentage was below 0.85, the upper limit in normal adults being 1.3.Since we have shown.cord red cells to produce agglutinin in rabbits and the American authors have demonstrated foetal haemoglobin to be antigenic, it will be important to consider the possible consequences of transplacental introduction of such materials into the circulation of human mothers. SummaryBy the injection into rabbits of human cord blood cells, an antiserum has been prepared which agglutinates specifically the red cells of cord blood and of newborn infants.We are grateful to Dr. R. R. A. Coombs for the supply of goat anti-rabbit-globulin serum and to the medidal and nursing staff of the Department for Midwifery and Diseases of Women, St. Bartholomew's Hospital, for making available blood samples and helping in their collection.One of us (H.L.) thanks the Medical Research Council for a grant towards expenses.
Serum‐induced basophil CD63 expression by means of a tricolour flow cytometric method for the <i>in vitro</i> diagnosis of chronic urticaria
Authors: A. Frezzolini, A. Provini, P. Teofoli, D. Pomponi, O. De Pità
Journal: Allergy (2006)

Background: Functional autoantibodies against the α ‐chain of the high‐affinity IgE receptor (Fc ɛ RI α ) identify a subset of patients with chronic urticaria (CU) due to autoreactivity, as assessed by an in vivo positive response to autologous serum skin test (ASST). We performed a study to standardize the serum‐induced basophil activation assay by flow cytometry (FCM) using a new tricolour method, assessing the diagnostic performance of this test in discriminating between ASST+ and ASST− CU patients. Methods: Sera of 64 CU patients (22 ASST+ CU and 42 ASST− CU) and 10 healthy subjects were tested for their ability to induce basophil CD63 expression when incubated with whole blood of both atopic (D A ) and non‐atopic donors (D NA ). Using a triple‐labelled strategy with anti‐CD123, anti‐HLA‐DR and anti‐CD63 antibodies, CD63+ basophils were identified on a selected population of CD123+ HLA‐DR‐ cells. In 3 ASST+ CU patients who underwent cyclosporine therapy, the assay was performed before and after treatment. Results: The ASST+ CU sera resulted in a significant higher induction of basophil CD63 expression compared with ASST− CU and healthy donors sera; when whole blood from D A was used, sensitivity and specificity of the assay were 95.5% and 90.5% respectively. ASST+ CU serum activity was significantly decreased during cyclosporine A treatment, in parallel with clinical remission. Conclusions: Chronic urticaria serum‐induced CD63 expression assay performed on D A whole blood by means of our tricolour FCM method could be the most useful tool for identification of a subset of patients with autoimmune CU and may become a promising tool also for monitoring treatment efficacy.
Anticipation in familial Crohn’s disease
Authors: B Grandbastien, M Peeters, D Franchimont, C Gower-Rousseau, D Speckel, P Rutgeerts, J Belaïche, A Cortot, R Vlietinck, J-F Colombel
Journal: Gut (1998)

Background —Offspring with a family history of Crohn’s disease have an earlier age of onset than their parents. This might be due to genetic anticipation, characterised by earlier and/or more severe disease in subsequent generations. Aims —To investigate the possibility of genetic anticipation in affected parent-child pairs with Crohn’s disease from France and Belgium. Patients and methods —In a cohort of 160 multiply affected families with Crohn’s disease, 57 parent-first affected child pairs were detected. Clinical characteristics (age at diagnosis, disease extent, and type) of both parents and children were registered and compared. Results —Children were younger than their parents at diagnosis in 48/57 (84%) pairs. The median age at diagnosis was 16 years younger in children than in parents (p&lt;0.0001). However, the difference was related to the age at diagnosis in the parents and was not present in 12 parent-child pairs with an early age at diagnosis for the parents. In most cases, disease extent and type were not considered more severe in children than in parents. Parental sex affected neither age at diagnosis nor extent and type of disease in children. Conclusion —Patients in the second affected generation acquire their disease at an earlier time in life in some but not all familial cases of Crohn’s disease. Several explanations including genetic anticipation and environmental factors might explain this phenomenon.
Stimulation of a subset of normal resting T lymphocytes by a monoclonal antibody to a crossreactive determinant of the human T cell antigen receptor.
Authors: R D Bigler, D N Posnett, N Chiorazzi
Journal: The Journal of Experimental Medicine (1985)

A previous study from this laboratory described a monoclonal antibody, S511, that reacted with the T cell antigen receptor on a human T cell leukemia and also on 1-2% of circulating T lymphocytes in all normal individuals tested. The data presented in the present study demonstrate that, when normal T lymphocytes are cultured with or without irradiated non-T cells in the presence of soluble S511 antibody, a concentration- and time-dependent proliferation of the S511-reactive population occurred. Proliferation indices as high as 184 times greater than control were observed, which represents a major stimulatory effect on the initially minor S511+ subset. When S511+ cells were studied for evidence of prior activation, they were shown to be unresponsive to interleukin 2 (IL-2) unless exposed to S511 antibody, and were shown to be in the G0/G1 phase of the cell cycle. Thus, the S511 antibody activated resting normal T cells in a manner analogous to specific antigen binding to the T cell antigen receptor. The leukemic S511 molecule has been shown previously to differ from most other antigen receptors in the mobility of the two chains at 43 and 38 kD and the neutral isoelectric point of each chain. Expansion of reactive normal cells by S511-Sepharose permitted the development of IL-2-dependent T cell lines enriched for S511-bearing cells. The antigen receptor molecules on one such polyclonal S511-enriched T cell line were immunoprecipitated with S511 antibody and shown to have comparable mobility to that present on the leukemic cells, but to possess a greater heterogeneity of mobility. Thus, the leukemic cells and normal cells express similar T cell receptor molecules. The differences in the S511 T cell antigen receptor molecule possibly relate to differences in glycosylation or polypeptide structure.
Peptidylarginine Deiminase 4 Contributes to Tumor Necrosis Factor α–Induced Inflammatory Arthritis
Authors: Miriam A. Shelef, Jeremy Sokolove, Lauren J. Lahey, Catriona A. Wagner, Eric K. Sackmann, Thomas F. Warner, Yanming Wang, David J. Beebe, William H. Robinson, Anna Huttenlocher
Journal: Arthritis & Rheumatology (2014)

Peptidylarginine deiminase 4 (PAD4) is a citrullinating enzyme that has multiple associations with inflammation. In rheumatoid arthritis, PAD4 and protein citrullination are increased in inflamed joints, and anti-citrullinated protein antibodies (ACPAs) form against citrullinated antigens are formed. ACPA immune complexes can deposit in the joint and induce the production of tumor necrosis factor α (TNFα), a critical inflammatory cytokine in the pathogenesis of rheumatoid arthritis. Further, in other settings, TNFα has been shown to induce PAD4 activity and modulate antibody formation. We undertook this study to investigate whether TNFα and PAD4 may synergistically exacerbate autoantibody production and inflammatory arthritis.
Human CD14<sup>+</sup>CTLA-4<sup>+</sup>regulatory dendritic cells suppress T-cell response by cytotoxic T-lymphocyte antigen-4-dependent IL-10 and indoleamine-2,3-dioxygenase production in hepatocellular carcinoma
Authors: Yanmei Han, Zhubo Chen, Yuan Yang, Zhengping Jiang, Yan Gu, Yangfang Liu, Chuan Lin, Zeya Pan, Yizhi Yu, Minghong Jiang, Weiping Zhou, Xuetao Cao
Journal: Hepatology (2013)

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. HCC-induced immunosuppression often leads to ineffectiveness of immuno-promoting therapies. Currently, suppressing the suppressors has become the potential strategy for cancer immunotherapy. So, figuring out the immunosuppressive mechanisms induced and employed by HCC will be helpful to the design and application of HCC immunotherapy. Here, we identified one new subset of human CD14+CTLA-4+ regulatory dendritic cells (CD14+DCs) in HCC patients, representing ˜13% of peripheral blood mononuclear cells. CD14+DCs significantly suppress T-cell response in vitro through interleukin (IL)-10 and indoleamine-2,3-dioxygenase (IDO). Unexpectedly, CD14+DCs expressed high levels of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1, and CTLA-4 was found to be essential to IL-10 and IDO production. So, we identified a novel human tumor-induced regulatory DC subset, which suppresses antitumor immune response through CTLA-4-dependent IL-10 and IDO production, thus indicating the important role of nonregulatory T-cell-derived CTLA-4 in tumor-immune escape or immunosuppression. Conclusions : These data outline one mechanism for HCC to induce systemic immunosuppression by expanding CD14+DCs, which may contribute to HCC progression. This adds new insight to the mechanism for HCC-induced immunosuppression and may also provide a previously unrecognized target of immunotherapy for HCC. (Hepatology 2014;59:567–579)
Chondronectin in human synovial fluid.
Authors: S Carsons, V J Horn
Journal: Annals of the Rheumatic Diseases (1988)

Chondronectin is a cartilage matrix protein that specifically mediates the attachment of chondrocytes to type II collagen. A monoclonal antibody to chondronectin was used in a competitive enzyme linked immunosorbent assay (ELISA) and Western blot assay to detect, measure, and characterise chondronectin in human synovial fluid. Chondronectin was detected in all 18 rheumatoid and 11 osteoarthritic synovial fluids examined. Chondronectin concentrations in synovial fluid were lower than those in plasma and correlated most strongly with concentrations of synovial fluid albumin and fibrinogen. These results suggest that synovial fluid chondronectin is in part derived from plasma. The role of chondronectin as a marker of cartilage destruction and potential mediator of pannus formation is discussed.
Erythroderma after autologous bone marrow transplantation modified by administration of cyclosporine and interferon gamma for breast cancer
Authors: Thomas D Horn, Viki Altomonte, Georgia Vogelsang, M.John Kennedy
Journal: Journal of the American Academy of Dermatology (1996)

Background: Allogeneic graft-versus-host disease is associated with decreased rates of tumor relapse. The addition of interferon gamma to cyclosporine, given to induce graft-versus-host disease after autologous bone marrow transplantation, increases the extent of the cutaneous eruption. Objective: Our purpose was to describe the clinical and histologic cutaneous changes in 10 patients with breast cancer who received interferon gamma to potentiate graft-versus-host disease after autologous bone marrow transplantation modified by cyclosporine. Methods: Ten women receiving autologous bone marrow transplantation modified by the administration of cyclosporine and interferon gamma were observed clinically with sequential biopsy of the skin weekly and at the time of cutaneous eruptions. Results: Erythroderma (stage 3) developed in five women after the first or second administration of interferon gamma. At least one skin biopsy specimen from 7 of the 10 women showed grade 2 changes of graft-versus-host reaction, including all patients with erythroderma. Epidermal intercellular edema was prominent in these specimens with expression of keratinocyte HLA-DR and intercellular adhesion molecule 1. Induction of keratinocyte HLA-DR and intercellular adhesion molecule 1 expression was not observed in specimens from normal skin during administration of interferon gamma. Conclusion: This protocol causes a more widely distributed cutaneous eruption, including erythroderma (50%), than autologous bone marrow transplantation and cyclosporine administration alone (3%). Whether it will affect survival is unknown.