tbuckley/cabot-search huggingface dataset:
Immunopathology of interleukin (IL) 2-deficient mice: thymus dependence and suppression by thymus-dependent cells with an intact IL-2 gene.
Authors: S Krämer, A Schimpl, T Hünig
Journal: The Journal of Experimental Medicine (1995)

Interleukin (IL) 2-deficient mice develop a fatal immunopathology characterized by lymphoadenopathy, splenomegaly, T cell infiltration of the bone marrow, loss of B cells, anemia, and inflammation of the gut. The thymus dependence of these disease symptoms was tested by introducing the IL-2 mutation into athymic mice. With the exception of an increase in CD8+ intrahepatic alpha/beta T cells, IL-2 deficiency had no detectable effect on leukocyte composition or health of athymic mice, indicating a key role for thymus-derived T cells in the initiation of disease and demonstrating that B cell development and survival are independent of IL-2. In adoptive transfer studies, lymph node and spleen cells from euthymic IL-2-deficient mice induced disease in athymic mice with an intact IL-2 gene, suggesting that thymus-independent IL-2-expressing cells are unable to control the development of immune pathology. Both IL-2+ and IL-2-/- bone marrow cells repopulated the thymus and the peripheral T cell compartment of the recombination activator gene 2-deficient recipients, and chimeras that had received IL-2-deficient bone marrow developed immune pathology. Disease development was, however, fully or at least partially prevented when 30% of the bone marrow inoculum was derived from mice able to express IL-2. These results demonstrate that the IL-2 deficiency syndrome depends on the intrathymic differentiation of T cells carrying the IL-2 mutation, and that the abnormal activation of IL-2-deficient lymphocytes can be controlled by thymus-derived but not thymus-independent lymphocytes.
Phase I trial of sorafenib in patients with recurrent or progressive malignant glioma
Authors: L. B. Nabors, J. G. Supko, M. Rosenfeld, M. Chamberlain, S. Phuphanich, T. Batchelor, S. Desideri, X. Ye, J. Wright, S. Gujar, S. A. Grossman
Journal: Neuro-Oncology (2011)

Sorafenib is an inhibitor of multiple kinases that has demonstrated antiproliferative and antiangiogenic activity in a number of in vitro and in vivo model systems. A phase I study was conducted to determine the maximum tolerated dose (MTD) of sorafenib in patients with recurrent malignant glioma. Sorafenib was given orally, twice a day (BID), continuously in 28-day cycles. The dose was escalated in 2 groups of patients stratified by use of enzyme-inducing antiseizure drugs (±EIASDs). Dose-limiting toxicity (DLT) was defined as any grades 3–4 nonhematological toxicity, grade 4 hematological toxicity, and febrile neutropenia. The number of evaluable patients enrolled in the +EIASD and −EIASD arms were 23 and 24, respectively. DLTs were predominantly dermatological and gastrointestinal effects, as observed in previous clinical trials of sorafenib. The MTD was 600 mg BID for patients receiving EIASDs and 800 mg BID for those who were not. The plasma pharmacokinetics of sorafenib were not significantly affected by the concurrent administration of EIASDs. The MTD of sorafenib given orally BID on a continuous basis was established as 600 mg BID in patients with malignant glioma who were concurrently receiving EIASDs and 800 mg BID in those who were not. Further evaluation is warranted of sorafenib at the recommended MTD against recurrent or progressive malignant glioma in combination with other molecularly targeted drugs or in the newly diagnosed setting concurrent with chemoradiation.
Proteoglycan 4 Expression Protects Against the Development of Osteoarthritis
Authors: Merry Z. C. Ruan, Ayelet Erez, Kilian Guse, Brian Dawson, Terry Bertin, Yuqing Chen, Ming-Ming Jiang, Jason Yustein, Francis Gannon, Brendan H. L. Lee
Journal: Science Translational Medicine (2013)

Proteoglycan 4 protects from age-related and posttraumatic osteoarthritis development.
Pulmonary function and symptoms in workers exposed to wood dust.
Authors: M H Shamssain
Journal: Thorax (1992)

Exposure to wood dust can cause a variety of lung problems, including chronic airflow obstruction.Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory ratio (FEV1/FVC x 100), forced expiratory flow (FEF), forced mid expiratory flow (FMF), peak expiratory flow (PEF), and respiratory symptoms (cough, phlegm, breathlessness, wheezing, and nasal symptoms) were recorded in 145 non-smoking workers (77 male, 68 female) exposed to wood dust in a furniture factory in Umtata, Republic of Transkei, and 152 non-smoking control subjects (77 male, 75 female) from a bottling factory with a clean environment.After adjustment for age and standing height the forced expiratory indices were significantly lower in the exposed male workers than in the control subjects. FEF and PEF in the exposed men were 81.3% and 89.4% of predicted values and were lower than other indices. FVC in exposed men showed a significant inverse correlation with exposure (expressed in number of years of employment). The FVC was reduced by 26 ml per year of employment. The proportion of men with an FEV1/FVC below 70 was higher in exposed workers than in control subjects and higher in the exposed workers with more years of employment. The exposed workers had more respiratory symptoms than the control subjects, the prevalence, especially of cough and nasal symptoms, increasing with the increase in the number of years of employment.Workers exposed to pine and fibre dust have more respiratory symptoms and a greater risk of airflow obstruction.
Investigation About Risk Factors of Profound Neutropenia by Amrubicin Hydrochloride Therapy for Small Cell Lung Cancer
Authors: C. Imai, R. Kurimoto, E. Sakaida, Y. Tada, I. Sekine, T. Suzuki, H. Nakasa, N. Ariyoshi, Y. Takiguchi, I. Ishii
Journal: Annals of Oncology (2013)
1α,25-Dihydroxyvitamin D3 promotes CD200 expression by human peripheral and airway-resident T cells
Authors: Sarah Dimeloe, David F Richards, Zoe L Urry, Atul Gupta, Victoria Stratigou, Sophie Farooque, Sejal Saglani, Andrew Bush, Catherine M Hawrylowicz
Journal: Thorax (2012)

<h3>Background</h3> CD200, a cell-surface immunoglobulin-like molecule expressed by immune and stromal cells, dampens the pro-inflammatory activity of tissue-resident innate cells via its receptor, CD200R. This interaction appears critical for peripheral immune tolerance, particularly in the airways where excessive inflammation is undesirable. Vitamin D contributes to pulmonary health and promotes regulatory immune pathways, therefore its influence on CD200 and CD200R was investigated. <h3>Methods</h3> CD200 and CD200R expression were assessed by qPCR and immunoreactivity of human lymphoid, myeloid and epithelial cells following 1α,25-dihydroxyvitamin D3 (1α,25VitD3) exposure in vitro and in peripheral T cells following 1α,25VitD3 oral ingestion in vivo. The effect of 1α25VitD3 was also assessed in human airway-resident cells. <h3>Results</h3> 1α25VitD3 potently upregulated CD200 on peripheral human CD4+ T cells in vitro, and in vivo there was a trend towards upregulation in healthy, but not asthmatic individuals. CD200R expression was not modulated in any cells studied. CD200 induction was observed to a lesser extent in CD8+ T cells and not in B cells or airway epithelium. T cells isolated from the human airway also responded strongly to 1α25VitD3 to upregulate CD200. <h3>Conclusions</h3> The capacity of 1α,25-dihydroxyvitamin D3 to induce CD200 expression by peripheral and respiratory tract T cells identifies an additional pathway via which vitamin D can restrain inflammation in the airways to maintain respiratory health.
Early impairment of hepatitis C virus specific T cell proliferation during acute infection leads to failure of viral clearance
Authors: A Folgori
Journal: Gut (2006)

<b>Background and aims:</b> Cellular mediated immunity (CMI) is thought to play a key role in resolution of primary hepatitis C virus (HCV) infection. However, CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses are also generated during acute infection in individuals who become chronic, suggesting that they developed a defective CMI. The aim of this study was to verify if and when such immune dysfunction is established by measuring the breadth, magnitude, function, and duration of CMI in a large cohort of subjects during the natural course of acute HCV infection. <b>Methods:</b> CMI was comprehensively studied by prospective sampling of 31 HCV acutely infected subjects enrolled at the onset of infection and followed for a median period of one year. <b>Results:</b> Our results indicated that while at the onset of acute HCV infection a measurable CMI with effector function was detected in the majority of subjects, after approximately six months less than 10% of chronically infected individuals displayed significant CMI compared with 70% of subjects who cleared the virus. We showed that progressive disappearance of HCV specific T cells from the peripheral blood of chronic patients was due to an impaired ability to proliferate that could be rescued in vitro by concomitant exposure to interleukin 2 and the antigen. <b>Conclusion:</b> Our data provide evidence of strong and multispecific T cell responses with a sustained ability to proliferate in response to antigen stimulation as reliable pharmacodynamic measures of a protective CMI during acute infection, and suggest that early impairment of proliferation may contribute to loss of T cell response and chronic HCV persistence.
Disease Amelioration With Tocilizumab in a Treatment-Resistant Patient With Neuromyelitis Optica
Authors: Bernd C. Kieseier, Olaf Stüve, Thomas Dehmel, Norbert Goebels, Verena I. Leussink, Anne K. Mausberg, Marius Ringelstein, Bernd Turowski, Orhan Aktas, Gerald Antoch, Hans-Peter Hartung
Journal: JAMA Neurology (2012)

Background: Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system in which aberrant antibody responses to the astrocytic water channel aquaporin 4 have been described.Experimental evidence is emerging that NMO is partly driven by the proinflammatory cytokine interleukin 6 (IL-6), which propagates the survival of disease-specific B cell subclasses, and deviates CD4 ϩ T helper cell differentiation toward IL-17-producing T helper 17 cells.Tocilizumab is a recombinant humanized monoclonal antibody against the IL-6 receptor approved for treatment of rheumatoid arthritis.Objectives: To study clinical and paraclinical effects of tocilizumab in a patient with NMO.Design: Case report.
Delivery of medication by breath-actuated nebulizer (BAN) is similar when used with differing inhalation / exhalation ratios: A contrast to breath enhanced nebulizer (BEN) behavior
Authors: Jason Suggett, Nagel Mark, Doyle Cathy, Ali Rubina, Jolyon Mitchell
Journal: European Respiratory Journal (2014)

RATIONALE:  BANs only deliver medication during inhalation. BENs continue to deliver aerosol (at a lower rate) during exhalation. If the inspiratory/expiratory (I/E) ratio of a patient decreases in obstructive lung disease, drug delivery efficiency by BEN may reduce. We compared the delivery of a corticosteroid by both types of nebulizer in a lab study.   METHODS:  These nebulizer/table-top compressor systems (n=5/group) were evaluated: (a) AeroEclipse®-XL BAN/ Ombra® (TMI); (b) LC-Plus® BEN/Pari Boy®; (c) LC-Sprint® BEN/Pari Boy® SX (PARI Respiratory Equipment); (d) SideStream® Plus BEN/Inspiration® Elite (Philips Respironics). Each device was evaluated with 2 x 2.0-mL fill of 0.25 mg/mL budesonide (AstraZeneca). The nebulizer was connected to a simulator (ASL5000, IngMar Medical) mimicking adult (tidal volume=500-ml) tidal breathing, with I/E ratios of 1:1, 1:2 or 1:3. Emitted aerosol was captured by filter at 1-minute intervals until sputtering to determine total mass budesonide delivered ( TM bud  ), as percentage of  TM bud   at I/E ratio=1:1. Budesonide assay was undertaken by HPLC-UV spectrophotometry.   RESULTS:  Average  TM bud   at extended I/E ratios as percentage of  TM bud   are in the Table.   CONCLUSIONS:  More consistent dose delivery was achieved by BAN. Clinicians should be aware of the opportunity to more confidently titrate patients to the lowest effective dose. The risk of potential under-dosing as disease progresses is also removed.
INTERACTIONS BETWEEN HORMONES AND CHEMICALS IN BREAST CANCER
Authors: Stephen H. Safe
Journal: The Annual Review of Pharmacology and Toxicology (1998)

Development of breast cancer in women is dependent on diverse factors, including genetic predisposition, exposure to both exogenous and endogenous chemicals, which can modulate initiation, promotion and progression of this disease, and the timing of exposure to these agents. Several compounds--including 16 alpha-hydroxyestrone (16 alpha-OHE1), catecholestrogens, and aromatic amines--have been proposed as initiators of mammary carcinogenesis in humans; however, their role as genotoxins is unconfirmed. Lifetime exposure to estrogens has been established as an important risk factor for breast cancer, and it has been suggested that xenoestrogens may directly add to the hormonal risk or indirectly increase risk by decreasing 2-hydroxyestrone (2-OHE1)/16 alpha-OHE1 metabolite ratios. Results of recent studies suggest that chemical-induced modulation of 2-OHE1/16 alpha-OHE1 metabolite ratios is not predictive of xenoestrogens or mammary carcinogens. Moreover, based on current known dietary intakes of natural and xenoestrogenic/antiestrogenic chemicals, it is unlikely that xenoestrogens contribute significantly to a woman's overall lifetime exposure to estrogens. More information is required on the identities and serum levels of both natural and xenoendocrine active compounds, their concentrations in serum, and the mammary gland and levels of these compounds at critical periods of exposure.
Effect of altitude on spirometric parameters and the performance of peak flow meters.
Authors: A. J. Pollard, N. P. Mason, P. W. Barry, R. C. Pollard, D. J. Collier, R. S. Fraser, M. R. Miller, J. S. Milledge
Journal: Thorax (1996)

BACKGROUND: Portable peak flow meters are used in clinical practice for measurement of peak expiratory flow (PEF) at many different altitudes throughout the world. Some PEF meters are affected by gas density. This study was undertaken to establish which type of meter is best for use above sea level and to determine changes in spirometric measurements at altitude. METHODS: The variable orifice mini-Wright peak flow meter was compared with the fixed orifice Micro Medical Microplus turbine microspirometer at sea level and at Everest Base Camp (5300 m). Fifty one members of the 1994 British Mount Everest Medical Expedition were studied (age range, 19-55). RESULTS: Mean forced vital capacity (FVC) fell by 5% and PEF rose by 25.5%. However, PEF recorded with the mini-Wright peak flow meter underestimated PEF by 31%, giving readings 6.6% below sea level values. FVC was lowest in the mornings and did not improve significantly with acclimatisation. Lower PEF values were observed on morning readings and were associated with higher acute mountain sickness scores, although the latter may reflect decreased effort in those with acute mountain sickness. There was no change in forced expiratory volume in one second (FEV1) at altitude when measured with the turbine microspirometer. CONCLUSIONS: The cause of the fall in FVC at 5300 m is unknown but may be attributed to changes in lung blood volume, interstitial lung oedema, or early airways closure. Variable orifice peak flow meters grossly underestimate PEF at altitude and fixed orifice devices are therefore preferable where accurate PEF measurements are required above sea level.
The airway microbiome in patients with severe asthma: Associations with disease features and severity
Authors: Yvonne J. Huang, Snehal Nariya, Jeffrey M. Harris, Susan V. Lynch, David F. Choy, Joseph R. Arron, Homer Boushey
Journal: Journal of Allergy and Clinical Immunology (2015)

BackgroundAsthma is heterogeneous, and airway dysbiosis is associated with clinical features in patients with mild-to-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown.ObjectiveWe sought to evaluate relationships between the bronchial microbiome and features of severe asthma.MethodsBronchial brushings from 40 participants in the Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) study were evaluated by using 16S ribosomal RNA–based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between patients with severe asthma and previously studied healthy control subjects (n = 7) and patients with mild-to-moderate asthma (n = 41).ResultsIn patients with severe asthma, bronchial bacterial composition was associated with several disease-related features, including body mass index (P < .05, Bray-Curtis distance-based permutational multivariate analysis of variance; PERMANOVA), changes in Asthma Control Questionnaire (ACQ) scores (P < .01), sputum total leukocyte values (P = .06), and bronchial biopsy eosinophil values (per square millimeter, P = .07). Bacterial communities associated with worsening ACQ scores and sputum total leukocyte values (predominantly Proteobacteria) differed markedly from those associated with body mass index (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ scores and bronchial epithelial gene expression of FK506 binding protein (FKBP5), an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophil values and Proteobacteria. No taxa were associated with a TH2-related epithelial gene expression signature, but expression of TH17-related genes was associated with Proteobacteria. Patients with severe asthma compared with healthy control subjects or patients with mild-to-moderate asthma were significantly enriched in Actinobacteria, although the largest differences observed involved a Klebsiella genus member (7.8-fold increase in patients with severe asthma, adjusted P < .001).ConclusionsSpecific microbiota are associated with and may modulate inflammatory processes in patients with severe asthma and related phenotypes. Airway dysbiosis in patients with severe asthma appears to differ from that observed in those with milder asthma in the setting of inhaled corticosteroid use.
Non-risk-adapted surveillance for patients with stage I nonseminomatous testicular germ-cell tumors: diminishing treatment-related morbidity while maintaining efficacy
Authors: C. Kollmannsberger, C. Moore, K.N. Chi, N. Murray, S. Daneshmand, M. Gleave, B. Hayes-Lattin, C.R. Nichols
Journal: Annals of Oncology (2009)
Intercellular adhesion molecule 3, a third adhesion counter-receptor for lymphocyte function-associated molecule 1 on resting lymphocytes.
Authors: A R de Fougerolles, T A Springer
Journal: The Journal of Experimental Medicine (1992)

Recent studies suggest that some T and B lymphocyte cell lines bind to the integrin lymphocyte function-associated molecule 1 (LFA-1) chiefly through a pathway independent of its two known counter-receptors, intercellular adhesion molecules (ICAMs)-1 and -2. A monoclonal antibody (mAb) was raised that, in combination with blocking mAb to ICAM-1 and ICAM-2, can completely inhibit binding of these cell lines to purified LFA-1. This third ligand, designated ICAM-3 based on its functional relatedness to ICAM-1 and -2, is a highly glycosylated protein of 124,000 Mr. It is well expressed on all leukocytes and absent from endothelial cells. In assays of adhesion of resting lymphocytes to purified LFA-1, ICAM-3 is by far the most functionally important ICAM, implying an important role for ICAM-3 in the generation of immune responses.
Post‐transfusion thrombocytopenic purpura: A case report
Authors: Jean E. Howard, Alan B. Glassberg, Herbert A. Perkins
Journal: American Journal of Hematology (1976)

Abstract Post‐transfusion thrombocytopenic purpura (PTTP) is a rare syndrome which was first brought to widespread attention by Shulman et al. Eighteen cases have been reported. The present report describes an additional patient, a multiparous female who developed petechiae 7 days after blood transfusion. The patient's serum contained anti‐PI A1 antibodies and her own platelets were PI A1 ‐negative. She was treated with prednisone and recovered spontaneously without exchange transfusion of whole blood or plasma.
Superficial granulomatous pyoderma associated with chronic osteomyelitis
Authors: E. Bassi, S. Matthews, R. Cerio
Journal: British Journal of Dermatology (2005)

Journal Article Superficial granulomatous pyoderma associated with chronic osteomyelitis Get access E. Bassi, E. Bassi Department of Dermatology, The Royal London Hospital Trust, Whitechapel, London E1 1BB, U.KClinica Dermatologica dell'Università di Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy Elisa Bassi, Via Poma 7, 27100 Pavia, Italy E‐mail: elisa_bassi@yahoo.it Search for other works by this author on: Oxford Academic Google Scholar S. Matthews, S. Matthews Oldchurch Hospital, Waterloo Road, Romford RM7 0BE, U.K Search for other works by this author on: Oxford Academic Google Scholar R. Cerio R. Cerio Department of Dermatology, The Royal London Hospital Trust, Whitechapel, London E1 1BB, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 3, 1 September 2005, Pages 684–686, https://doi.org/10.1111/j.1365-2133.2005.06822.x Published: 01 September 2005
Metabolic Effects of Plasmin Digests of Human Growth Hormone in the Rat and Man
Authors: John B. Mills, Charles R. Reagan, Daniel Rudman, Jack L. Kostyo, P. Zachariah, Alfred E. Wilhelmi
Journal: Journal of Clinical Investigation (1973)

As a first step in our study of structure-function relationships among primate and non-primate growth hormones, human growth hormone (hGH) was subjected to the limited digestive activity of human plasmin. The lyophilized whole digest, containing less than 2% of unchanged hormone, had an average of 2.3 new amino-terminal groups per mole. The digest had the same potency as the native hormone (a) in causing weight gain in hypophysectomized rats; (b) in stimulating somatomedin production in hypophysectomized rats; (c) in stimulating upake of [(3)H]leucine into isolated diaphragm of hypophysectomized rats; (d) in accelerating transport of [(14)C]alpha-aminoisobutyric acid into isolated diaphragm of hypophysectomized rats; (e) in stimulating uptake of [3-0-methyl-(14)C]glucose by isolated adipose tissue of hypophysectomized rats; (f) in accelerating conversion of [(14)C]glucose to (14)CO(2) by isolated epididymal adipose tissue of hypophysectomized rats. The digest also caused glucosuria in partially pancreatectomized rats treated with dexamethasone. These metabolic actions of plasmin-digested hGH in the array of animal tests were confirmed by comparable effects elicited in 11 human subjects (nine pituitary-deficient children and adolescents and two nondeficient adults). A single injection of the plasmin digest caused an increase in plasma free fatty acids and a fall in plasma amino acids. Seven daily injections caused positive balances of nitrogen, phosphorous, sodium, and potassium, gain in body weight, and in two of three subjects impairment of glucose tolerance. The potency of the plasmin digest in producing these metabolic effects in man was comparable to that of native hGH.Thus, 2-3 bonds in the hGH molecule can be cleaved by plasmin without impairing the hormone's growthpromoting, anabolic, diabetogenic, and adipokinetic actions for rat and man.