tbuckley/cabot-search huggingface dataset:
Altered phenotype of blood dendritic cells in patients with acute pneumonia
Authors: Katharina Dreschler, Kai Bratke, Sebastian Petermann, Petra Thamm, Michael Kuepper, J. Christian Virchow, Marek Lommatzsch
Journal: European Respiratory Journal (2011)

Background: Dendritic cells (DCs) play a key role in the host defense against inhaled pathogens. However, the phenotype of blood DCs in patients with acute respiratory infections is unknown.

Objective: To investigate the number and the expression of function-associated molecules of blood DCs in patients with acute infectious pneumonia.

Methods: Sixteen patients with an acute pneumonia and 19 controls without pneumonia were included in the study. The number as well as the expression of function-associated molecules of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) were analysed in peripheral blood using four-colour flow cytometry.

Results: Elevated concentrations of procalcitonin (median: 0.55 ng/ml) and the rapid response to antibiotic treatment suggested a bacterial origin of the pneumonia in the patients. Total mDC (median: 27% of the controls) and pDC counts (median: 53% of the controls) were markedly reduced in patients with pneumonia, as compared to controls. Percentages of blood mDCs, but not pDCs, were negatively correlated with serum concentrations of c-reactive protein (CRP). Patients with pneumonia were characterised by a significantly increased expression of Fc gamma receptors (CD32 and CD64) on mDCs and the Toll-like receptor 9 (TLR9) in pDCs.

Conclusions: Circulating DCs are markedly reduced in patients with pneumonia, and characterised by an upregulation of molecules recognising pathogen-associated molecular patterns (PAMPs) and opsonised antigens.
Deafness from Dihydrostreptomycin
Authors: F. Savy
Journal: BMJ (1951)

REPORTS OF SOCIETIESMEDICALBJURNAL experience many cases could be treated in the surgery which at present come to hospital.In that way the clinical acti--vities of the general practitioner would be extended.Revising the Tonsil Waiting-list Dr. J. P. KIEs had recently gone over a large tonsil wait- ing-list, some of the children on which had been waiting for two or three years for operation.On re-examining the -children he had found that about 30% had no clinical indica- tion for tonsillectomy, 30% required operation, and in the remaining cases operation would not be justified until after further investigations. (Similar figures were given later in the meeting by a consultant.)Dr. Kies considered that too much attention was paid to the indications for tonsill- -ectomy and not enough to those against it.Among the latter he mentioned persistent colds, enlargement of tonsils, allergy, and fussy parents.Dr. H. A. WARE described a group practice in an agri- cultural region of England, in which he was also responsible for the oto-rhino-laryngology at the hospitals.He agreed with all the previous speakers that students were not given enough instruction in that branch of medicine.The whole-
Haemopoietic stem-cell transplantation with antibody-based minimal-intensity conditioning: a phase 1/2 study
Authors: Karin C Straathof, Kanchan Rao, Matthias Eyrich, Geoff Hale, Prudence Bird, Eleanor Berrie, Lucinda Brown, Stuart Adams, Paul G Schlegel, Nicholas Goulden, H Bobby Gaspar, Andrew R Gennery, Paul Landais, EG Davies, Malcolm K Brenner, Paul A Veys, Persis Jal Amrolia
Journal: The Lancet (2009)
Clonal relationship between precursor T-lymphoblastic leukaemia/lymphoma and Langerhans-cell histiocytosis
Authors: Andrew L Feldman, Frank Berthold, Robert J Arceci, Carlos Abramowsky, Bahig M Shehata, Karen P Mann, Stephen J Lauer, Jon Pritchard, Mark Raffeld, Elaine S Jaffe
Journal: The Lancet Oncology (2005)
VISUALIZATION OF EGYPT 101 VIRUS IN THE MOUSE'S BRAIN AND IN CULTURED HUMAN CARCINOMA CELLS BY MEANS OF FLUORESCENT ANTIBODY
Authors: Wilbur Fiske Noyes
Journal: The Journal of Experimental Medicine (1955)

The antigens of the Egypt virus have been detected by means of the fluorescent antibody technique in the neurons of the brain and spinal cord, in both sensory and motor areas, of infected mice. The antigens have also been observed in infected human epidermoid carcinoma cells in culture. In both cases the antigens occurred in the cytoplasm of the cells exclusively. In the early stages of infection the antigen was localized about the nucleus of the human cultured cells. In some cases the staining of the antigens produced a sponge-like effect, probably because of the numerous vacuoles of lipid material. The antigens were observed in the protoplasmic connections between cells and they probably served as a main route of spread of the agent in these human cell cultures. The number of cells initially infected and showing antigen was proportional to the amount of virus added, and titration with one substrain of cells proved much more sensitive than intracerebral titration in the mouse.
Role of the Microenvironment for Radiosensitization by Patupilone
Authors: Carla Rohrer Bley, Wolfram Jochum, Katrin Orlowski, Polina Furmanova, Van Vuong, Paul M.J. McSheehy, Martin Pruschy
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The combined treatment modality of ionizing radiation (IR) and the clinically relevant microtubule-stabilizing compound patupilone (epothilone B, EPO906) is a promising approach for anticancer therapy. Here, we investigated the role of the tumor microenvironment for the supra-additive in vivo response in tumor xenografts derived from patupilone-sensitive and patupilone-resistant non-small cell lung cancer cells. Experimental Design: The treatment response to a combined regimen of patupilone and IR was investigated in vitro and in tumor xenografts derived from wild-type A549 and A549.EpoB40 cells, which are resistant to patupilone due to a β-tubulin mutation. Results: In both A549 and A549.EpoB40 cells, proliferative activity and clonogenicity were reduced in response to IR, whereas patupilone, as expected, inhibited proliferation of the mutant cell line with reduced potency. Combined treatment with patupilone and IR induced a cytotoxic effect in vitro in an additive way in A549 cells but not in the tubulin-mutated, patupilone-resistant A549.EpoB40 cells. A supra-additive tumor growth delay was induced by combined treatment in xenografts derived from A549 cells but not in xenografts derived from A549.EpoB40 cells. Histologic analysis revealed a significant decrease in tumor cell proliferation (Ki-67) and microvessel density and a treatment-dependent change of tumor hypoxia in A549 but not A549.EpoB40 xenografts. Conclusions: Using a genetically defined patupilone-sensitive and patupilone-resistant tumor model, we here showed that the major cytotoxic effect of the combined treatment modality of IR and patupilone is directed against the tumor cell compartment. The induced antiangiogenic effect derives indirectly from the tumor cell.
ES‐62 Protects Against Collagen‐Induced Arthritis by Resetting Interleukin‐22 Toward Resolution of Inflammation in the Joints
Authors: Miguel A. Pineda, David T. Rodgers, Lamyaa Al‐Riyami, William Harnett, Margaret M. Harnett
Journal: Arthritis & Rheumatology (2014)

The parasitic worm-derived immunomodulator ES-62 protects against disease in the mouse collagen-induced arthritis (CIA) model of rheumatoid arthritis (RA) by suppressing pathogenic interleukin-17 (IL-17) responses. The Th17-associated cytokine IL-22 also appears to have a pathogenic role in autoimmune arthritis, particularly in promoting proinflammatory responses by synovial fibroblasts and osteoclastogenesis. The present study was undertaken to investigate whether the protection against joint damage afforded by ES-62 also reflects suppression of IL-22.The role(s) of IL-22 was assessed by investigating the effects of neutralizing anti-IL-22 antibodies and recombinant IL-22 (rIL-22) on proinflammatory cytokine production, synovial fibroblast responses, and joint damage in mice with CIA in the presence or absence of ES-62.Neutralization of IL-22 during the initiation phase abrogated CIA, while administration of rIL-22 enhanced synovial fibroblast responses and exacerbated joint pathology. In contrast, after disease onset anti-IL-22 did not suppress progression, whereas administration of rIL-22 promoted resolution of inflammation. Consistent with these late antiinflammatory effects, the protection afforded by ES-62 was associated with elevated levels of IL-22 in the serum and joints that reflected a desensitization of the synovial fibroblast responses. Moreover, neutralization of IL-22 during the late effector stage of disease prevented ES-62-mediated desensitization of synovial fibroblast responses and protection against CIA.IL-22 plays a dual role in CIA, being pathogenic during the initiation phase while acting to resolve inflammation and joint damage during established disease. Harnessing of the tissue repair properties of IL-22 by ES-62 highlights the potential for joint-targeted therapeutic modulation of synovial fibroblast responses and consequent protection against bone damage in RA.
Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis
Authors: K. Vähävihu, M. Ala-Houhala, M. Peric, P. Karisola, H. Kautiainen, T. Hasan, E. Snellman, H. Alenius, J. Schauber, T. Reunala
Journal: British Journal of Dermatology (2010)

Narrowband ultraviolet B (NB-UVB) is a routine treatment for psoriasis and atopic dermatitis (AD) but its effect on vitamin D balance is not well studied.To examine whether NB-UVB treatment in winter improves vitamin D balance in psoriasis and AD, and to study the effects of NB-UVB on antimicrobial peptide and cytokine expression in the skin.Eighteen adult patients with psoriasis, 18 with AD and 15 healthy subjects received a total of 15 NB-UVB exposures on the whole body, given three times a week. Serum calcidiol (25-hydroxyvitamin D) was measured by radioimmunoassay. Antimicrobial peptide and cytokine expression in skin lesions was examined by real-time quantitative polymerase chain reaction.At onset 16 (89%) patients with psoriasis, 17 (94%) patients with AD and eight (53%) healthy subjects had vitamin D insufficiency (calcidiol < 50 nmol L(-1)). NB-UVB treatment significantly increased (P < 0.001) serum calcidiol. The increase was 59.9 nmol L(-1) (95% confidence interval, CI 53.5-66.9) in psoriasis, 68.2 nmol L(-1) (95% CI 55.4-80.1) in AD and 90.7 nmol L(-1) (95% CI 63.8-123.4) in healthy subjects. Psoriasis Area and Severity Index and SCORAD improved significantly (P < 0.001) but no correlation to the increase of serum calcidiol was found. Cathelicidin and human beta-defensin 2 (HBD2) expression was high in skin lesions of psoriasis. After six NB-UVB treatments cathelicidin increased further while HBD2 expression decreased. A similar trend was observed in AD lesions. NB-UVB caused a marked but nonsignificant decrease of interleukin (IL)-1beta and IL-17 in psoriasis lesions.The present study shows that in addition to a significant improvement of psoriasis and AD, NB-UVB treatment effectively corrects vitamin D insufficiency. It also increases cathelicidin and decreases HBD2 levels in healing skin lesions of psoriasis and AD. This effect might be mediated by improved vitamin D balance and the local cytokine network.
495 ARE LIVER TRANSPLANT HIV-1 INFECTED PATIENTS AT RISK TO DEVELOP HIV-1 DRUG RESISTANCE?
Authors: E. Teicher, D. Desbois, E. Dussaix, M. Figueroa, T. Antonini, J.-C. Duclos Vallée, D. Samuel, D. Vittecoq
Journal: Journal of Hepatology (2010)
Venous Thromboembolism Associated With Long-Term Use of Central Venous Catheters in Cancer Patients
Authors: Melina Verso, Giancarlo Agnelli
Journal: Journal of Clinical Oncology (2003)

Long-term central venous catheters (CVCs) have considerably improved the management of cancer patients because they facilitate chemotherapy, transfusions, parenteral nutrition, and blood sampling. However, the use of long-term CVCs, especially for chemotherapy, has been associated with the occurrence of upper-limb deep venous thrombosis (UL-DVT). The incidence of clinically overt UL-DVT related to CVCs has been reported to vary between 0.3% and 28.3%. The incidence of CVC-related UL-DVT screened by venography reportedly varies between 27% and 66%. The incidence of clinically overt pulmonary embolism (PE) in patients with CVC-related UL-DVT ranges from 15% to 25%, but an autopsy-proven PE rate of up to 50% has been reported. Vessel injury caused by the procedure of CVC insertion, venous stasis caused by the indwelling CVC, and cancer-related hypercoagulability are the main pathogenetic factors for CVC-related venous thromboembolism (VTE). Several studies have assessed the benefit of the prophylaxis of UL-DVT after CVC insertion in cancer patients. According to the results of these studies, prophylaxis with low molecular weight heparin or a low fixed dose of warfarin has been recently proposed. However, the limitations of the experimental design of the prophylactic studies do not allow definitive recommendations. The recommended therapy for UL-DVT associated with CVC is based on anticoagulant therapy with or without catheter removal. This review focuses on the epidemiology, pathogenesis, diagnosis, prevention, and treatment of VTE in cancer patients with long-term CVC.
Phase I Study of 30-Minute Infusion of Carfilzomib As Single Agent or in Combination With Low-Dose Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma
Authors: Kyriakos P. Papadopoulos, David S. Siegel, David H. Vesole, Peter Lee, Steven T. Rosen, Naseem Zojwalla, Joseph R. Holahan, Susan Lee, Zhengping Wang, Ashraf Badros
Journal: Journal of Clinical Oncology (2014)

Purpose Carfilzomib is an irreversible inhibitor of the constitutive proteasome and immunoproteasome. This phase I study evaluated the maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of carfilzomib administered as a 30-minute intravenous (IV) infusion. Safety and efficacy of carfilzomib as a single agent or in combination with low-dose dexamethasone were assessed. Patients and Methods Patients with relapsed and/or refractory multiple myeloma (MM) were administered single-agent carfilzomib on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Cycle one day 1 and 2 doses were 20 mg/m 2 , followed thereafter by dose escalation to 36, 45, 56, or 70 mg/m 2 . Additionally, carfilzomib was combined with low-dose dexamethasone (40 mg/wk). Results Thirty-three patients were treated with single-agent carfilzomib. Dose-limiting toxicities in two patients at 70 mg/m 2 were renal tubular necrosis and proteinuria (both grade 3). The MTD was 56 mg/m 2 . Nausea (51.5%), fatigue (51.5%), pyrexia (42.4%), and dyspnea and thrombocytopenia (each 39.4%) were the most common treatment-related toxicities. Overall response rate (ORR) was 50% (56-mg/m 2 cohort). Increasing carfilzomib dosing from 20 to 56 mg/m 2 resulted in higher area under the plasma concentration-time curve from time zero to last sampling and maximum plasma concentration exposure with short half-life (range, 0.837 to 1.21 hours) and dose-dependent inhibition of proteasome chymotrypsin-like activity. In 22 patients treated with 45 or 56 mg/m 2 of carfilzomib plus low-dose dexamethasone, the ORR was 55% with a safety profile comparable to that of single-agent carfilzomib. Conclusion Carfilzomib administered as a 30-minute IV infusion at 56 mg/m 2 (as single agent or with low-dose dexamethasone) was generally well tolerated and highly active in patients with relapsed and/or refractory MM. These data have provided the basis for the phase III randomized, multicenter trial ENDEAVOR.
Phorbol ester-induced downregulation of CD4 is a multistep process involving dissociation from p56lck, increased association with clathrin-coated pits, and altered endosomal sorting.
Authors: A Pelchen-Matthews, I J Parsons, M Marsh
Journal: The Journal of Experimental Medicine (1993)

The phorbol ester phorbol myristate acetate (PMA) induces a rapid downregulation of CD4 from the surface of T cells and lymphocytic cell lines, as well as from CD4-transfected nonlymphoid cells. Here we have studied the mechanisms of this phorbol ester-induced CD4 modulation. Using HeLa-CD4 or NIH-3T3-CD4 cells, in which the endocytosis of CD4 is not influenced by the protein tyrosine kinase p56lck, we show that PMA enhanced the uptake of CD4, increasing the rate of CD4 endocytosis three to five-fold, and doubling the proportion of CD4 found inside the cells. Trafficking of a CD4 mutant lacking the major portion of the cytoplasmic domain, as well as fluid phase endocytosis were not affected by PMA treatment. Studies in which clathrin-coated pits were disrupted through the use of hypertonic media indicated that both the constitutive and PMA-induced CD4 uptake occurred through coated vesicles. Electron microscopy demonstrated directly that PMA increases the association of CD4 with coated pits. Immunofluorescent staining of internalized CD4 showed that PMA also diverted CD4 from the early endosome-plasma membrane recycling pathway to a mannose 6-phosphate receptor-containing late endosomal compartment. In lymphoid or p56lck-expressing transfected cells, these effects were preceded by the PMA-induced dissociation of CD4 and p56lck, which released CD4 and made possible increased endocytosis and altered intracellular trafficking. Together these results indicate that phorbol esters have multiple effects on the normal endocytosis and trafficking of CD4, and suggest that phosphorylation may influence the interaction of CD4 with coated pits.
Rigid bronchoscopy under intravenous general anaesthesia with oxygen Venturi ventilation.
Authors: D J Godden, R F Willey, R J Fergusson, D J Wright, G K Crompton, I W Grant
Journal: Thorax (1982)

In a study of 100 patients undergoing rigid bronchoscopy under intravenous general anaesthesia with oxygen Venturi ventilation no major complications were observed. Minor complications included one adverse reaction to alphaxalone-alphadolone acetate (Althesin), one prolonged episode of laryngeal spasm after removal of the bronchoscope, and subsequent muscle pain attributed to suxamethonium in 36 patients. The last complication occurred significantly less frequently (p less than 0 . 025) in those patients who were pretreated with a small dose of a non-depolarising neuromuscular blocking agent. Serial arterial blood gas sampling in 10 patients showed adequate ventilation during bronchoscopy, but carbon dioxide retention developed in nine cases immediately after the bronchoscope was withdrawn. With adequate precautions, however, the procedure is safe and well tolerated, even in patients with severe impairment of respiratory function.
D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease
Authors: Kim Tieu, Celine Perier, Casper Caspersen, Peter Teismann, Du-Chu Wu, Shi-Du Yan, Ali Naini, Miquel Vila, Vernice Jackson-Lewis, Ravichandran Ramasamy, Serge Przedborski
Journal: Journal of Clinical Investigation (2003)

Parkinson disease (PD) is a neurodegenerative disorder characterized by a loss of the nigrostriatal dopaminergic neurons accompanied by a deficit in mitochondrial respiration. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes dopaminergic neurodegeneration and a mitochondrial deficit reminiscent of PD. Here we show that the infusion of the ketone body d-beta-hydroxybutyrate (DbetaHB) in mice confers partial protection against dopaminergic neurodegeneration and motor deficits induced by MPTP. These effects appear to be mediated by a complex II-dependent mechanism that leads to improved mitochondrial respiration and ATP production. Because of the safety record of ketone bodies in the treatment of epilepsy and their ability to penetrate the blood-brain barrier, DbetaHB may be a novel neuroprotective therapy for PD.
Reproducibility of bone mineral density measurement in daily practice
Authors: M C Lodder
Journal: Annals of the Rheumatic Diseases (2004)

Bone mineral density (BMD) measurements are frequently performed repeatedly for each patient. Subsequent BMD measurements allow reproducibility to be assessed.To examine the reproducibility of BMD by dual energy x ray absorptiometry (DXA) and to investigate the practical value of different measures of reproducibility in a group of postmenopausal women.Ninety five women, mean age 59.9 years, underwent two subsequent BMD measurements of spine and hip. Reproducibility was expressed as smallest detectable difference (SDD), coefficient of variation (CV), and intraclass correlation coefficient (ICC). Sources of variation were investigated by multilevel analysis.The median interval between measurements was 0 days (range 0-45). The mean difference (SD) between the measurements (g/cm(2)) was -0.001 (0.02) and -0.0004 (0.02) at L1-4 and the total hip, respectively. At L1-4 and the total hip, SDD (g/cm(2)) was +/-0.05 and +/-0.04 and CV (%) was 1.92 and 1.59, respectively. The ICC at spine and hip was 0.99.Reproducibility in the postmenopausal women studied was good. In a repeated DXA scan a BMD change exceeding 2 radical 2CV (%), the least significant change (LSC), or the SDD should be regarded as significant. Use of the SDD is preferable to use of the CV and LSC (%) because of its independence from BMD and its expression in absolute units. Expressed as SDD, a BMD change of at least +/-0.05 g/cm(2) at L1-4 and +/-0.04 g/cm(2) at the total hip should be considered significant.
Remodeling of Ca2+-handling by atrial tachycardia: evidence for a role in loss of rate-adaptation
Authors: James Kneller, Hui Sun, Normand Leblanc, Stanley Nattel
Journal: Cardiovascular Research (2002)

Background: Loss of rate-dependent action potential (AP) duration (APD) adaptation is a characteristic feature of atrial tachycardia-induced remodeling (ATR). ATR causes sarcolemmal ion-channel remodeling (ICR) and changes in Ca2+-handling. The present studies were designed to quantify Ca2+-handling changes and then to apply a mathematical AP model to assess the contributions of Ca2+-handling abnormalities and ICR to loss of APD rate-adaptation. Methods: Indo-1 fluorescence was used to measure intracellular Ca2-transients and whole-cell patch-clamp to record APs in atrial myocytes from control dogs and dogs subjected to atrial pacing at 400/min for 6 weeks. A previously developed ionic model of the canine atrial AP was modified to reproduce measured Ca2+-transients of control and ATR myocytes. Results: In control, APD to 95% repolarization (APD95) decreased by 91 ms experimentally and by 88 ms in the model over the 1–6 Hz range. In ATR myocytes, APD95 failed to decrease over the 1–6 Hz range. Ca2+-handling abnormalities in ATR myocytes included slowed upstroke, decreased amplitude and strong single-beat post-rest potentiation. Unaltered Ca2+-handling properties included caffeine-releasable Ca2+-stores and Ca2+-transient relaxation before and after exposure to the sarcoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor cyclopiazonic acid (CPA). Including ICR alone in the model accounted for loss of APD50 rate-adaptation; however, KR alone reduced APD95 rate-adaptation by only 19% to 71 ms. When both ICR and Ca2+-handling changes were incorporated, APD95 rate-adaptation decreased to 6 ms, accounting for experimental observations. Conclusion: ICR alone does not fully account for loss of APD rate-adaptation with atrial remodeling: Ca2+-handling changes appear to contribute to this clinically significant phenomenon.
Re: CYP2D6 Genotype and Tamoxifen Response in Postmenopausal Women With Endocrine-Responsive Breast Cancer: The Breast International Group 1-98 Trial
Authors: Y. Nakamura, M. J. Ratain, N. J. Cox, H. L. Mcleod, D. L. Kroetz, D. A. Flockhart
Journal: JNCI Journal of the National Cancer Institute (2012)

Author(s): Nakamura, Yusuke; Ratain, Mark J; Cox, Nancy J; McLeod, Howard L; Kroetz, Deanna L; Flockhart, David A