tbuckley/cabot-search huggingface dataset:
Topical application of St John’s wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells
Authors: C.M. Schempp, B. Winghofer, R. Lüdtke, B. Simon-Haarhaus, E. Schöpf, J.C. Simon
Journal: British Journal of Dermatology (2000)

St John's wort (Hypericum perforatum) is a traditional herbal medicine that is used for the topical treatment of superficial wounds, burns and dermatitis. The characteristic metabolites of St John's wort are the photodynamic active plant pigment hypericin and the phloroglucin-derivative hyperforin. To date, no studies on immunomodulatory properties of topical preparations of St John's wort have been performed. Here, we investigated the alloantigen presenting function of human epidermal cells (EC) exposed to Hypericum ointment in vivo in a mixed EC lymphocyte reaction (MECLR). The effect of Hypericum ointment was compared with the immunosuppressive effect of solar-simulated radiation (SSR). Subsequently, we tested purified hyperforin in vivo and in vitro in a MECLR to evaluate its possible contribution to the effect of the Hypericum ointment. Furthermore, we assessed the effect of hyperforin on the proliferation of peripheral blood mononuclear cells (PBMC) in vitro. Compared with untreated skin, treatment with Hypericum ointment resulted in a significant suppression of the MECLR (P ≤ 0·001) that was similar to the effect of SSR. The combination of Hypericum ointment plus SSR was not significantly different from either treatment alone. EC isolated from skin treated with the hyperforin containing ointment also showed a reduced capacity to stimulate the proliferation of allogeneic T cells (P ≤ 0·001). Similarly, in vitro incubation of EC with hyperforin suppressed the proliferation of alloreactive T cells (P ≤ 0·001). Furthermore, hyperforin inhibited the proliferation of PBMC in a dose-dependent manner, without displaying pronounced toxic effects as determined by Trypan blue staining. The results demonstrate an inhibitory effect of Hypericum extract and of its metabolite hyperforin on the MECLR and on the proliferation of T lymphocytes that may provide a rationale for the traditional treatment of inflammatory skin disorders with Hypericum extracts.
Long-term using of omalizumab in children with atopic severe persistent non-controlled asthma
Authors: Leyla Namazova-Baranova, Elena Vishneva, Anna Alekseeva, Anna Tomilova, Kamilla Efendieva, Julia Levina, Natalya Voznesenskaya, Tatyana Kulichenko
Journal: European Respiratory Journal (2013)

Omalizumab (Omab) is a medication for treatment severe persistent atopic asthma in children older 6 y. There is few published data examining long-term Omab using in children.  We report the experience of long-term treatment in school age children with difficult-to-treat asthma. Open-label observation study analyzed the efficacy and tolerability of Omab.  Methods: Medical files of 53 children treated with Omab were reviewed and 4 treated with Omab during 48-49 (mean 48.5 mo) were chosen for report.  The following data were recorded, at baseline and after 48.5 months of Omab treatment: maintenance therapy, PFTs values, symptom scores, control level (GINA), allergic features.  Results: The characteristics of these 4 patients were: mean age of the beginning of Omab therapy - 13.2 y, 50% boys, initial maintenance therapy was ICS (mean daily dose: 1000µg fluticasone) with LABA, asthma symptom control questionnaires (mean ACT: 8, mean ACQ 22.5), mean FEV1 70.75%, mean PEF 68.7%. 100% had allergic rhinitis, 25% atopic dermatitis and 50% food allergy.  After long-term Omab therapy following indices significantly improved: maintenance ICS doses (mean 337.5 µg fluticasone) with LABA, symptom scores (mean ACT: 18, mean ACQ 12.5), PFTs values (mean FEV1 103.5%, mean PEF 100.5%). Rescue medication requirement reduced on 80%, mean number of unscheduled medical contacts attributable to asthma exacerbation was significantly decreased. Patients or parents reported no significant adverse effects.  Conclusions: Omalizumab improves control in children with atopic severe non-controlled asthma, reduces the rate exacerbations and asthma-related hospitalizations and reduces doses of maintenance and rescue medication.
Mechanism of Genetic Resistance to Friend Virus Leukemia in Mice. V. Relevance of &lt;italic&gt;Fv-3&lt;/italic&gt; Gene in the Regulation of in Vivo Immunosuppression&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: V Kumar, P Resnick, J W Eastcott, M Bennett
Journal: JNCI Journal of the National Cancer Institute (1978)

Infection with the Friend murine leukemia virus complex (F-MuLV) suppressed humoral antibody synthesis in vivo and lymphocyte mitogenesis in vitro. Both these effects of F-MuLV were under host genetic control. In vitro suppression of lymphocyte mitogenesis was regulated by a single autosomal gene called Fv-3 that is dominant for susceptibility. Genetic analyses, with the use of the susceptible DBA/2 and resistant B10.D2/n parents, their F1, intercross, and backcross progeny, indicated that a single autosomal gene dominant for susceptibility regulated the in vivo susceptibility to immunosuppression by F-MuLV. Individual [(DBA/2xB10.D2)F1xB10.D2] mice were typed both for susceptibility to F-MuLV-induced suppression of lymphocyte mitogenesis in vitro (an Fv-3 function) and susceptibility to immunosuppression by F-MuLV in vivo. Such an analysis indicated that the same mice that were susceptible or resistant to immunosuppression in vivo were susceptible or resistant to suppression of lymphocyte mitogenesis in vitro. Spearman's rank analysis of the data also indicated that the in vivo and in vitro immunosuppressive effects of F-MuLV were correlated with and not independent of each other. Thus Fv-3, which regulates the effect of F-MuLV on lymphocytes in vitro, also appears to regulate the effect of F-MuLV on antibody-forming cells in vivo.
High Court rules that Health Research Authority acted unlawfully over trial transparency:
Authors: Clare Dyer
Journal: BMJ (2015)

The Health Research Authority acted unlawfully in giving “misleading” and “confusing” messages to companies carrying out early stage clinical trials about new rules on publicly registering trials, a High Court judge has ruled.1

Mr Justice Jay said that the authority’s public utterances “fail the public law test of certainty and transparency,” which ensures that those who are required to comply with rules can be sure of exactly what requirements they must meet.

The ruling followed a legal challenge by Richmond Pharmacology, a clinical research organisation, to the authority’s transparency requirements on companies carrying out phase I trials, which test the safety and tolerability of new medicines.

The case initially involved broader issues, but it was narrowed down to an argument by Richmond that the authority was …
Mycobacterium avium genotype is associated with the therapeutic response to lung infection
Authors: T. Kikuchi, Y. Kobashi, T. Hirano, N. Tode, A. Santoso, T. Tamada, S. Fujimura, Y. Mitsuhashi, Y. Honda, T. Nukiwa, M. Kaku, A. Watanabe, M. Ichinose
Journal: Clinical Microbiology and Infection (2013)

Factors that can interfere with the successful treatment of Mycobacterium avium lung infection have been inadequately studied. To identify a potent predictor of therapeutic responses of M. avium lung infection, we analyzed variable number tandem repeats (VNTR) at 16 minisatellite loci of M. avium clinical isolates. Associations between the VNTR profiling data and a therapeutic response were evaluated in 59 subjects with M. avium lung infection. M. avium lung infection of 30 subjects in whom clarithromycin-containing regimens produced microbiological and radiographic improvement was defined as responsive disease, while that of the remaining 29 subjects was defined as refractory disease. In phylogenetic analysis using the genotypic distance aggregated from 16-dimensional VNTR data, 59 M. avium isolates were divided into three clusters, which showed a nearly significant association with therapeutic responses (p 0.06). We then subjected the raw 16-dimensional VNTR data directly to principal component analysis, and identified the genetic features that were significantly associated with the therapeutic response (p <0.05). By further analysis of logistic regression with a stepwise variable-selection, we constructed the highest likelihood multivariate model, adjusted for age, to predict a therapeutic response, using VNTR data from only four minisatellite loci. In conclusion, we identified four mycobacterial minisatellite loci that together were associated with the therapeutic response of M. avium lung infections.
Adjuvant aminoglutethimide for postmenopausal patients with primary breast cancer: analysis at 8 years.
Authors: A L Jones, T J Powles, M Law, A Tidy, D Easton, R C Coombes, I E Smith, J A McKinna, A Nash, H T Ford
Journal: Journal of Clinical Oncology (1992)

The study purpose was to evaluate aminoglutethimide (AG) as adjuvant therapy in patients with primary node-positive breast cancer in a randomized double-blind placebo-controlled trial.In a multicenter trial, 354 postmenopausal women with early breast cancer and histologically confirmed positive axillary lymph nodes were randomized after surgery to received aminoplac. Patients were prescribed either AG 250 mg four times per day and hydrocortisone 20 mg twice per day or placebos of identical appearance for 2 years.After a median follow-up of 8.1 years, there has been no overall benefit for AG in terms of either event-free survival or overall survival (OS). However, the results are consistent with interim analyses with a significantly improved event-free survival for patients who received AG for up to 4 years, although this benefit subsequently disappears. Similarly, there is an improved OS for patients who received AG for up to 4 years, but this also subsequently disappears. There was a marginal advantage for estrogen receptor (ER)-positive patients who received AG (n = 74; P = .054). There was no difference in the sites of relapse. There was a significant increase in toxicity for patients who received AG.The lack of survival benefit with long-term follow-up for AG may indicate that aromatase inhibitors have less of an impact on early breast cancer than tamoxifen and may imply different biologic mechanisms of action.
Quality Indicators in the Management of Bladder Cancer
Authors: Jeffrey S. Montgomery, David C. Miller, Alon Z. Weizer
Journal: Journal of the National Comprehensive Cancer Network (2013)

Bladder cancer is predominantly seen in elderly patients. With the aging United States population, the incidence and prevalence of bladder cancer are on the rise, heightening the relevance of this disease as a public health issue. Despite having one of the greatest average cancer treatment costs per patient, improvements in disease-specific survival have been subtle. Clinical guidelines based predominantly on expert opinion and randomized controlled studies offer some guidance, but adherence to these guidelines is lacking. Building awareness of quality indicators to optimize patient care represents an opportunity to improve bladder cancer outcomes. Although quality indicators exist for other disease states, widely accepted quality indicators for the management of bladder cancer have not yet been established. This article proposes an initial set of quality indicators for both non–muscle-invasive and muscle-invasive bladder cancer based on established clinical guidelines and the available literature.
A common group I intron between a plant parasitic fungus and its host.
Authors: H Nishida, J Sugiyama
Journal: Molecular Biology and Evolution (1995)

The self-splicing RNAs known as group I introns exist in many organisms, but their distribution is difficult to explain. We hypothesize that group I introns have been transferred between a parasite and its host. We describe here the discovery of a common group I intron sequence between a plant-parasitic fungus, Protomyces inouyei, and its host, Youngia japonica. It strongly supports our theory that the group I intron had been transferred from the host plant to the parasitic fungus in the course of evolution.
Cryptogenic fibrosing alveolitis: pathogenetic mechanisms and therapeutic approaches
Authors: PL Haslam
Journal: European Respiratory Journal (1990)

Cryptogenic fibrosing alveolitis: pathogenetic therapeutic approaches Cellular immune responses in the lung of h VIliCrl:i~n.npneumonitis Evidence in bronchoalveolar lavage for third type reactions in hypersensitivity pneumonitis Inflammation and immune reactions in interstitial (lLD) associated with inorganic dust exposure Inflammatory and immune reactions associated with dust exposure: comparison between patients with and c linical lung involvement Airway inflammation and late asthmatic reactions Bronchoalveolar lavage in allergic asthma Role of bronchoalveolar lavage in the investigation mediated defence mechanisms against lung cancer Lung defence mechanisms against infection Role of bronchoalveolar lavage in the assessment o~ pulmonary complications following bone marrow a transplantation Pulmonary toxicity induced by chemical agents Clinical usefulness of bronchoalveolar lavage
Respiratory muscle training in impaired elderly: Threshold loading versus Pranayama breathing exercises
Authors: Maria dels Àngels Cebriài Iranzo, David Alan Arnall, Celedonia Igual Camacho, José Manuel Tomás
Journal: European Respiratory Journal (2012)

Introduction: In the older elderly, the respiratory function may be seriously compromised when the decrease of respiratory muscle (RM) strength coexists with comorbidity and immobility syndrome.  The aim of this study was to determine the effectiveness of RM training using the Threshold IMT device, or Pranayama breathing exercises vs. a control group in impaired elderly. Our general hypothesis was that RM training would improve RM function among this population.  Methods: Institutionalized elderly, who were unable to walk, were allocated randomly into three groups: a control group and two experimental groups (Threshold and Pranayama). Experimental groups performed a supervised interval-based training protocol, either through respiratory threshold loading or Pranayama breathing exercises, which lasted six weeks (5 days per week). Maximum respiratory pressures (MIP and MEP) and Maximum Voluntary Ventilation (MVV) were measured at four time points: pre-training, intermediate, post-training and follow-up (weeks 0, 4, 7 and 10, respectively).  Results: Seventy-one residents (90% female, mean age 85) completed the study: Control (n=24); Threshold (n=23); Pranayama (n=24). There was a significant treatment effect on the MIP (F6,204= 6,755, p  Conclusion: Pranayama training group works differently and significantly better than the other two groups, and may be therefore, a powerful alternative to general exercise conditioning in order to improve RM function (strength and endurance) in the elderly population with a significant loss of mobility and exercise capacity.
CD40 Ligation Enhances IL-15 Production by Tubular Epithelial Cells
Authors: MICHAL WEILER, LEONID KACHKO, CIDIO CHAIMOVITZ, CEES VAN KOOTEN, AMOS DOUVDEVANI
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Interleukin-15 (IL-15) is a potent T-cell growth factor and activator. Acute rejection of kidney allografts strongly correlated with elevated IL-15 mRNA in the graft. A role in the rejection process is also suggested for the interaction between CD40 ligand (CD154) expressed on membranes of activated T cells and its receptor (CD40). The effect of CD40 ligation on IL-15 production in human tubular epithelial cells (TEC) was investigated. TEC were co-cultured with a cell line genetically engineered to express CD154. CD154-expressing cells (CD40L cells) bind to TEC. Addition of the CD40L cells to the TEC culture resulted in elevated IL-15 levels. This enhanced production was not observed with control cells, when anti-CD154 antibody was added, and when direct contact between CD40L-cells and TEC was prevented with the use of a Trans-well system. CD40 activation resulted in a twofold increase of IL-15 mRNA transcripts as measured by reverse transcription-PCR and a concordant elevation in IL-15 protein production as measured by specific enzyme-linked immunosorbent assay. The intensity of activation by CD154 was linearly dependent on cell number, reaching plateau when the effector/target-ratio was 1:1. The increase of IL-15 levels was similar to that produced by stimulation with interferon-γ (IFN-γ). Combination of IFN-γ and activation with CD154 resulted in an additive effect. To conclude, activated T cells may enhance IL-15 expression in two ways: by secreting IFN-γ and by cell to cell contact using CD154. Each signal alone induces IL-15 in similar magnitudes, and both signals are additive. Because IL-15 is a major T-cell activator, this interaction may contribute to graft rejection.
Abstract 15326: Transient Extracellular Acidification at the Onset of Reperfusion Decreases Cardiac Injury by Inhibiting Complex I Activity in the Murine Heart
Authors: Aijun Xu, Qun Chen, Ying Hu, Edward J Lesnefsky
Journal: Circulation (2011)

Reversible inhibition of complex I at the onset of reperfusion (REP) decreases cardiac injury in buffer perfused hearts. Complex I activity is decreased when mitochondria are exposed to an acid med...
Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8+ T cells that induce GVHD without antileukemic effects
Authors: Kate H. Gartlan, Kate A. Markey, Antiopi Varelias, Mark D. Bunting, Motoko Koyama, Rachel D. Kuns, Neil C. Raffelt, Stuart D. Olver, Katie E. Lineburg, Melody Cheong, Bianca E. Teal, Mary Lor, Iain Comerford, Michele W. L. Teng, Mark J. Smyth, James McCluskey, Jamie Rossjohn, Brigitta Stockinger, Glen M. Boyle, Steven W. Lane, Andrew D. Clouston, Shaun R. McColl, Kelli P. A. MacDonald, Geoffrey R. Hill
Journal: Blood (2015)
Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors
Authors: Aurore Morello, Michel Sadelain, Prasad S. Adusumilli
Journal: Cancer Discovery (2015)

Chimeric antigen receptors (CAR) are synthetic receptors that target T cells to cell-surface antigens and augment T-cell function and persistence. Mesothelin is a cell-surface antigen implicated in tumor invasion, which is highly expressed in mesothelioma and lung, pancreas, breast, ovarian, and other cancers. Its low-level expression in mesothelia, however, commands thoughtful therapeutic interventions. Encouragingly, recent clinical trials evaluating active immunization or immunoconjugates in patients with pancreatic adenocarcinoma or mesothelioma have shown responses without toxicity. Altogether, these findings and preclinical CAR therapy models using either systemic or regional T-cell delivery argue favorably for mesothelin CAR therapy in multiple solid tumors.Recent success obtained with adoptive transfer of CAR T cells targeting CD19 in patients with refractory hematologic malignancies has generated much enthusiasm for T-cell engineering and raises the prospect of implementing similar strategies for solid tumors. Mesothelin is expressed in a wide range and a high percentage of solid tumors, which we review here in detail. Mesothelin CAR therapy has the potential to treat multiple solid malignancies.
Prevention and treatment of CME after cataract surgery11The following letters address an article that appeared in the March 1998 issue of the Journal:Rossetti L, Chaudhuri J, Dickersin K. Medical prophylaxis and treatment of cystoid macular edema after cataract surgery: the results of a meta-analysis.(Ophthalmology 1998;105:397–405)
Authors: David Miller
Journal: Ophthalmology (1998)
Amish Study, I: Affective disorders among the Amish, 1976-1980
Authors: Janice A. Egeland, Abram M. Hostetter
Journal: American Journal of Psychiatry (1983)

The authors review the goals, methods, sample, and selected epidemiologic findings from a collaborative study of affective disorders among the Amish. This culturally and genetically homogeneous population (N = 12,500) constitutes an excellent research setting for psychiatric epidemiologic and genetic study. Alcoholism, drug abuse, and sociopathy did not complicate the study because they are culturally prohibited. During 1976-1980, 112 active cases of mental illness were identified; 71% received diagnoses of major affective disorder. Equal numbers of men and women received diagnoses of unipolar illness, and slightly more men than women were diagnosed as having bipolar illness.
Indian smokers: A faster downhill course?
Authors: B.V. Murali Mohan, P. Asha, Kedar Hibare, Ranganath Ramanjaneya
Journal: European Respiratory Journal (2011)

Introduction:  The deleterious effects of tobacco smoke on lung function are well known even among asymptomatic smokers. We hypothesized that the addition of pollution and undernutrition in a developing country would cause declines in lung function at lower levels of tobacco use than usually described.   Methods:  We compared the spirometry of 249 asymptomatic smokers and 143 healthy never smokers in Bangalore, India. Smoking was quantified using the smoking index (cigarette years = cigarettes/day X years smoked). To adjust for differences in demographics between groups, we compared spirometric values as percentage of predicted (ECCS reference equations; race correction factor - 87%).   Results:  Compared with never smokers, smokers with even a smoking index    Conclusions:  In an Indian population, the effects of cigarette smoke on lung function are seen earlier than is usually described; this may reflect greater susceptibility to cigarette smoke or the additive environmental effect including air pollution and undernutrition. The cause effect relationship needs to be worked out, but it is clear that it is never too early to quit smoking.
Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: The role of noninvasive ventilation
Authors: Fabio Di Stefano, Vittoria Conti, Marta Di Nicola, Angelo Petroianni, Claudio Terzano
Journal: European Respiratory Journal (2012)

Hypercapnic COPD exacerbation in patients with comorbidities is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV).  Methods.  Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO 2  and PaCO 2  and blood lactate were checked at the 1 st , 2 nd , 6 th  and 24 th  hours after starting NIV.   Results.  Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p=0.026), with durations of 45.1±9.8, 36.2±8.9 and 53.3±4.1 hours, respectively (p=0.016). The duration of ventilation was associated with higher blood lactate (p Conclusions . Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV.