tbuckley/cabot-search huggingface dataset:
Analysis of multicentric Castleman's disease (MCD) with pulmonary lesions
Authors: Soichiro Ikushima, Yasuhiro Terasaki, Akira Hebisawa, Takeshi Johko, Fumikazu Sakai, Norihiro Nishimoto, Takashi Ogura, Yasunori Ohta, Haruyuki Ishii, Shoko Matsui, Hiroshi Yamamoto, Yasunori Ichimura, Masuo Ujita, Tetsuharu Kawamura, Masashi Bando, Hiroshi Ishimoto, Shinyu Izumi, Norihiko Hata, Keisuke Tomii, Isoko Owan, Hiroshi Kimura, Yuko Komase, Yasuo Matsuzawa, Machiko Arita, Akira Shiraki
Journal: European Respiratory Journal (2013)

Background   MCD is a systemic lymphoproliferative disease that often involves pulmonary lesions. Few studies have combined analyses of clinical, radiological, and pathological (CRP) data relating to this rare disease.   Aim   We aimed to identify the CRP features of this disease via a multicenter retrospective study.   Methods   We enrolled 40 patients who had MCD with pulmonary involvement throughout Japan.   Results   The average age at diagnosis was 47 years (men, 13; women, 12). The patients were admitted with symptoms of cough (48%), dyspnea (24%), and fever (18%). Laboratory findings revealed elevated serum levels of IL-6 (24.1 pg/mL), KL6 (736.7 U/mL), CRP (6.68 mg/dL) and IgG4 (394.1 mg/dL). Common radiologic findings included presence of ground glass attenuation (96%), centrilobular nodules (92%), septal thickening (72%), bronchovascular thickening (64%), and cysts (64%).  From the pathological point of view, all specimens showed lesions characteristic of marked lymphoplasmacytic accumulation with lymphoid follicles and lymphatic distribution of foci of dense fibrosis. Small cystic lesions were found in 4 lung samples, but no obstructive vasculitis was observed. The mean IgG4+/IgG+ plasma cell ratio was 22%. A pulmonary function test revealed progressive obstructive airflow limitation. Steroid therapy was successful in preventing progression in just 33% of cases, but tocilizumab was successful in 67%. Three patients died due to respiratory failure with progression of diffuse cystic lesions.   Conclusion   The clinical course of pulmonary involvement of MCD varies from stable disease to progressive obstructive impairment. Tocilizumab appears to be more effective than steroid therapy in controlling the disease.
Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma.
Authors: G Gahrton, S Tura, P Ljungman, J Bladé, L Brandt, M Cavo, T Façon, A Gratwohl, A Hagenbeek, P Jacobs
Journal: Journal of Clinical Oncology (1995)

PURPOSE To analyze prognostic factors for allogeneic bone marrow transplantation (BMT) in multiple myeloma. PATIENTS AND METHODS One hundred sixty-two reports of allogeneic matched sibling-donor transplants in multiple myeloma received by the European Group for Blood and Marrow Transplantation (EBMT) registry between 1983 and early 1993 were analyzed for prognostic factors. End points were complete remission, survival, and duration of complete remission. RESULTS Following BMT, 44% of all patients and 60% of assessable patients entered complete remission. The overall actuarial survival rate was 32% at 4 years and 28% at 7 years. The overall relapse-free survival rate of 72 patients who were in complete remission after BMT was 34% at 6 years. Favorable pretransplant prognostic factors for survival were female sex (41% at 4 years), stage I disease at diagnosis (52% at 4 years), one line of previous treatment (42% at 4 years), and being in complete remission before conditioning (64% at 3 years). The subtype immunoglobulin A (IgA) myeloma and a low beta 2-microglobulin level (&lt; 4 g/L) also tended to have a favorable prognostic impact. The most important post-transplant prognostic factor was to enter a complete remission. Grade III to IV graft-versus-host disease (GVHD) was associated with poor survival. CONCLUSION Patients with a low tumor burden who respond to treatment before BMT and are transplanted after first-line therapy have the best prognosis following BMT.
Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity
Authors: Alison M. Paterson, Scott B. Lovitch, Peter T. Sage, Vikram R. Juneja, Youjin Lee, Justin D. Trombley, Carolina V. Arancibia-Cárcamo, Raymond A. Sobel, Alexander Y. Rudensky, Vijay K. Kuchroo, Gordon J. Freeman, Arlene H. Sharpe
Journal: The Journal of Experimental Medicine (2015)

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of T cell responses. Germline Ctla4 deficiency is lethal, making investigation of the function of CTLA-4 on mature T cells challenging. To elucidate the function of CTLA-4 on mature T cells, we have conditionally ablated Ctla4 in adult mice. We show that, in contrast to germline knockout mice, deletion of Ctla4 during adulthood does not precipitate systemic autoimmunity, but surprisingly confers protection from experimental autoimmune encephalomyelitis (EAE) and does not lead to increased resistance to MC38 tumors. Deletion of Ctla4 during adulthood was accompanied by activation and expansion of both conventional CD4+Foxp3− (T conv) and regulatory Foxp3+ (T reg cells) T cell subsets; however, deletion of CTLA-4 on T reg cells was necessary and sufficient for protection from EAE. CTLA-4 deleted T reg cells remained functionally suppressive. Deletion of Ctla4 on T reg cells alone or on all adult T cells led to major changes in the Ctla4 sufficient T conv cell compartment, including up-regulation of immunoinhibitory molecules IL-10, LAG-3 and PD-1, thereby providing a compensatory immunosuppressive mechanism. Collectively, our findings point to a profound role for CTLA-4 on T reg cells in limiting their peripheral expansion and activation, thereby regulating the phenotype and function of T conv cells.
Rituximab-Dependent Cytotoxicity by Natural Killer Cells
Authors: Sébastien Dall’Ozzo, Sophie Tartas, Gilles Paintaud, Guillaume Cartron, Philippe Colombat, Pierre Bardos, Hervé Watier, Gilles Thibault
Journal: Cancer Research (2004)

Abstract The FCGR3A gene dimorphism generates two allotypes: FcγRIIIa-158V and FcγRIIIa-158F. The genotype homozygous for FcγRIIIa-158V (VV) is associated with higher clinical response to rituximab, a chimeric anti-CD20 IgG1 used in the treatment of B lymphoproliferative malignancies. Our objective was to determine whether this genetic association relates to rituximab-dependent cytotoxicity mediated by FcγRIIIa/CD16a+ cells. The number of CD16+ circulating monocytes, T cells, and natural killer (NK) cells in 54 donors was first shown to be unrelated to FCGR3A polymorphism. We then demonstrated that FcγRIIIa-158V displays higher affinity for rituximab than FcγRIIIa-158F by comparing rituximab concentrations inhibiting the binding of 3G8 mAb (anti-CD16) with VV NK cells and NK cells homozygous for FcγRIIIa-158F (FF). VV and FF NK cells killed Daudi cells similarly after FcγRIIIa engagement by saturating concentrations of rituximab or 3G8. However, the rituximab concentration resulting in 50% lysis (EC50) observed with NK cells from VV donors was 4.2 times lower than that observed with NK cells from FF donors (on average 0.00096 and 0.00402 μg/ml, respectively, P = 0.0043). Finally, the functional difference between VV and FF NK cells was restricted to rituximab concentrations weakly sensitizing CD20. This study supports the conclusion that FCGR3A genotype is associated with response to rituximab because it affects the relationship between rituximab concentration and NK cell-mediated lysis of CD20+ cells. Rituximab administration could therefore be adjusted according to FCGR3A genotype.
Selectins: initiators of leucocyte adhesion and signalling at the vascular wall
Authors: Rodger P. McEver
Journal: Cardiovascular Research (2015)

The selectins are transmembrane, Ca(2+)-dependent lectins that mediate leucocyte rolling on vascular surfaces, the first adhesive step during inflammation and immune surveillance. Leucocytes express L-selectin, activated platelets express P-selectin, and activated endothelial cells express E- and P-selectin. Rolling involves force-regulated, rapidly reversible interactions of selectins with a limited number of glycosylated cell surface ligands. Rolling permits leucocytes to interact with immobilized chemokines that convert β2 integrins to high-affinity conformations, which mediate arrest, post-arrest adhesion strengthening, and transendothelial migration. However, rolling leucocytes also transduce signals through selectin ligands, the focus of this review. These signals include serial activation of kinases and recruitment of adaptors that convert integrins to intermediate-affinity conformations, which decrease rolling velocities. In vitro, selectin signalling enables myeloid cells to respond to suboptimal levels of chemokines and other agonists. This cooperative signalling triggers effector responses such as degranulation, superoxide production, chemokine synthesis, and release of procoagulant/proinflammatory microparticles. In vivo, selectin-mediated adhesion and signalling likely contributes to atherosclerosis, arterial and deep vein thrombosis, ischaemia-reperfusion injury, and other cardiovascular diseases.
Association between obstructive sleep apnea (OSA) and depression and the effect of continuous positive airway pressure (CPAP) treatment
Authors: Amro M. El-Sherbini, Adel Salah Bediwy, Ashraf El-Mitwalli
Journal: European Respiratory Journal (2012)

Background:  Obstructive sleep apnea (OSA) is a relatively common disorder which has a negative impact on the psychological well-being of affected individuals.   Objective:  To assess the association between OSA and depression as well as the effect of treatment with continuous positive airway pressure (CPAP).   Methods:  A total of 37 newly diagnosed individuals with OSA underwent an overnight polysomnography and were assessed using the Epworth Sleepiness Scale (ESS), the Hamilton Depression Rating Scale (HDRS), and the Structured Clinical Interview for  Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition . Patients were assessed before and after 2 months of CPAP use.   Results:  Of the 37 patients included in the study, 21 (56.7%) had clinically relevant depression as indicated by a score .10 on the HDRS and eleven patients (29.7%) met the diagnostic criteria for a major depressive episode using the Structured Clinical Interview. Scores on the HDRS were correlated with the Apnea Hypoxia Index, ESS scores, and oxygen saturation. Patients showed a significant reduction in depressive symptoms and improvement in ESS scores after CPAP treatment.   Conclusion:  Patients with OSA should be screened carefully for depressive disorders. CPAP should be tried first before starting other treatment modalities for depression.
LSC 2013 abstract - Pulmonary senescence in chronic obstructive pulmonary disease is primarily mediated by persistent DNA double strand breaks
Authors: Manish Kumar, Nobert Weissman, Werner Seeger, Robert Voswinckel
Journal: European Respiratory Journal (2013)

Introduction:  Chronic obstructive pulmonary disease or COPD is an age associated disease that occurs after a prolonged period of cigarette smoking. Deregulated repair, tissue degeneration and lung regression are the hallmarks of COPD. Cellular senescence is a signal transduction program leading to irreversible cell cycle arrest. The growth arrest can be triggered by many different mechanisms including recognition by cellular sensors of DNA double-strand breaks leading to the activation of cell cycle checkpoint responses and recruitment of DNA repair foci. We propose COPD to be a disease of premature lung senescence and aim to decipher markers of DNA damage, repair and senescence in animal models of smoke induced emphysema as well as in smokers with and without COPD.   Results:  Cellular senescence could be successfully assessed by staining for β-galactosidase and evaluation of senescence associated heterochromatin foci (SAHF), reflecting condensed chromatin, in the nuclei. DNA double strand breaks and cell cycle arrest could be demonstrated by up regulated 53-BP1, γH2AX and p21.  In vitro, senescence of lung fibroblasts could be induced by 100uM H 2 O 2  as well as by 1% cigarette smoke extract. PBMC derived Circulating fibrocytes were rather stimulated in growth by H 2 O 2  than driven towards senescence.  Paraffin lung sections from Smoked Mice and Human COPD samples were investigated for markers of senescence, DNA damage and repair. Our results indicate that the senescence in case of COPD is primarily driven by the persistent DNA double-strand breaks due to prolonged cigarette smoking.
Characterization of Nonrandom Chromosomal Gains and Losses in Multiple Myeloma by Comparative Genomic Hybridization
Authors: Juan C. Cigudosa, Pulivarthi H. Rao, M. Jose Calasanz, M. Dolores Odero, Joseph Michaeli, Suresh C. Jhanwar, R.S.K. Chaganti
Journal: Blood (1998)
Immunization of melanoma patients with a MAGE-3 peptide combined with IFNa
Authors: J.-F. Baurain, N. Van Baren, C. Uyttenhove, V. Brichard, J.-P. Machiels, C. Gerard, T. Boon, P. G. Coulie
Journal: Journal of Clinical Oncology (2004)

2606 Background: Melanoma patients with lymph node metastasis at diagnosis have a less than 60% survival rate at 5 years. Interferon-a (IFNa) is used as adjuvant treatment for such patients, even though recent studies showed no increase in survival. Vaccination with tumor-specific MAGE peptides may induce tumor regression in 10–20% of metastatic melanoma patients, mostly those with only subcutaneous or lymph node metastases. However, cytolytic T lymphocyte (CTL) responses to the vaccine antigens have been observed only in half of the patients with tumor regression. We examined whether IFNa could serve as an adjuvant to induce CTL responses against tumor-specific peptides in mice and in melanoma patients without evidence of disease. Methods and Results: No detectable CTL responses can be observed in DBA/2 mice vaccinated with 50 ug of peptide P1A, which is carried on mastocytoma cells P815, injected subcutaneously without adjuvant. In the presence of immunological adjuvant AS02B (QS21/MPL from GlaxoSmithKline Biologicals), CTL responses are observed in 1/10 mice. However, 9/10 mice mount a detectable anti-P1A CTL response when IFNa (100.000 units/days for 3 days) is added to the peptide and AS02B. We have conducted a pilot trial in 6 melanoma patients with no evidence of disease. They received 300 ug of peptide MAGE-3.A1, encoded by gene MAGE-A3 and presented by HLA-A1, associated with ten millions units of IFNa, followed by IFNa alone on days 2 and 3. Vaccinations included six injections every 2 weeks. Blood samples collected before vaccination and two weeks after the last injection, were tested for the presence of anti-MAGE-3.A1 CD8 T cells. None of the six patients mounted a detectable anti-MAGE-3.A1 CTL response. Conclusions: Our results suggest that IFNa does not help to mount a detectable CTL response to a MAGE peptide injected alone. We now wish to associate peptide, the adjuvant AS02B, and IFNa, the full combination which proved immunogenic in mice. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Biologicals
Precision Medicine in Breast Cancer Care
Authors: Allison W. Kurian, Christopher R. Friese
Journal: JAMA Oncology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Clinical characteristics and outcome of Pneumocystis carinii pneumonia in HIV-infected and otherwise immunosuppressed patients
Authors: S Ewig, T Bauer, C Schneider, A Pickenhain, L Pizzulli, U Loos, B Luderitz
Journal: European Respiratory Journal (1995)

The factors contributing to unequal mortality rates following Pneumocystis carinii pneumonia (PCP) in different groups at risk are poorly understood. We therefore compared the first episodes of PCP without prophylaxis in human immunodeficiency virus infected (HIV) and otherwise immunosuppressed patients in this retrospective study. A total of 58 HIV-infected and 16 otherwise immunosuppressed patients were analysed. The comparison included epidemiological, clinical, laboratory, radiological and microbiological data, as well as therapy and clinical course. A prognostic analysis was performed using a logistic regression model. The mortality was significantly different in the two groups (HIV group 17 versus non-HIV group 50%). Renal transplant patients had a higher survival rate as compared to malignancy or collagen vascular disease as underlying diseases at risk. Acute respiratory failure was more common in the non-HIV group. Variables found to be significantly associated with lethal outcome in univariate analysis were alveolar to arterial pressures difference for oxygen (P(A-a),O2), haemoglobin, platelet count, total protein, serum albumin, and gamma-globulins in the HIV-group, and serum albumin in the non-HIV group. In the multivariate analysis of the HIV group, platelet count and gamma-globulins remained independent prognostic factors. In conclusion, in the HIV-group, mortality is closely related to the severeness of PCP as well as to the severeness of the acquired immune deficiency syndrome (AIDS) disease. In the non-HIV group, malignancy and collagen vascular disease as underlying conditions at risk account for the high mortality rate. Its severeness was mainly reflected by serum albumin, which represented the only variable found to be significantly associated with death in both groups.
Blurred vision and myopic shift in Puumala virus infections are independent of disease severity
Authors: G. Theiler, B. Langer-Wegscheider, I. Zollner-Schwetz, T. Valentin, M. Hönigl, W. Schnedl, R. Krause
Journal: Clinical Microbiology and Infection (2012)

Puumala virus infection causes epidemic nephropathia (NE), a certain type of haemorrhagic fever with renal syndrome (HFRS). Myopic shift is considered a pathognomonic sign of NE and HFRS but rates of ocular involvement vary. The aim of the study was to evaluate whether clinical and laboratory findings are associated with ophthalmic involvement in NE in Austria. We found that blurred vision and myopic shift are frequent in Puumala virus infections in Austria but are independent of disease severity.
Hodgkin's Disease in English and African Children&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. Burn, J. N. P. Davies, O. G. Dodge, Birgitta C. Nias
Journal: JNCI Journal of the National Cancer Institute (1971)

The histologic classification of Hodgkin's disease based on the Rye Conference was applied to lesions in children in the Manchester region of England and to those in East Africa. It showed statistically significant differences in the distribution of types of lesions, with African children having many more lesions of the lymphocytic depletion type which has a less favorable prognosis. African children also differed significantly in this respect from French and Texan children. The reasons for this finding are obscure but may represent a less favorable reaction to the disease among African children.
Is Allergen Immunotherapy Effective in Asthma?
Authors: Michael J. Abramson, Robert M. Puy, John M. Weiner
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

A meta-analysis of clinical trials of allergen immunotherapy was undertaken to assess the efficacy of this controversial form of therapy in asthma. A computerized bibliographic search revealed 20 randomized placebo controlled double-blind trials of allergen immunotherapy for asthma. The results extracted included asthmatic symptoms, medication requirements, lung function, and bronchial hyperreactivity (BHR). Categorical outcomes were expressed as odds ratios and continuous outcomes as effect sizes. The combined odds of symptomatic improvement from immunotherapy with any allergen were 3.2 (95% CI 2.2 to 4.9). The odds for reduction in medication after mite immunotherapy were 4.2 (95% CI 2.2 to 7.9). The combined odds for reduction in BHR were 6.8 (95% CI 3.8 to 12.0). The mean effect size for any allergen immunotherapy on all continuous outcomes was 0.71 (95% CI 0.43 to 1.00), which would correspond to a mean 7.1% predicted improvement in FEV1 from immunotherapy. Although the benefits of allergen immunotherapy could be overestimated because of unpublished negative studies, an additional 33 such studies would be necessary to overturn these results. Allergen immunotherapy is a treatment option in highly selected patients with extrinsic (“allergic”) asthma.
Leukemia Induction in Mice by Moloney Virus From Long- and Short-Term Tissue Cultures, and Attempts to Detect a Leukemogenic Virus in Cultures From X-Ray-lnduced Leukemia&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Haim Ginsburg, Leo Sachs
Journal: JNCI Journal of the National Cancer Institute (1962)

The growth in vitro of Moloney leukemia virus (MLV) was studied in long- and short-term tissue cultures of mouse cells. Culture fluids were inoculated into animals, and the presence of virus was detected by the development of leukemia. MLV was successfully grown in 5, independently originating, long-term cultures of MLV-indueed leukemic cells, which were maintained on feeder layers of spleen cells. A high leukemogenic activity was recovered from these cultures in all tests made from 9 to 290 days in vitro. (Since MLV was recovered after infection of cultures containing only spleen feeder layers, the extent of virus production by the leukemic cells is still to be determined.) Successful passage of MLV was also obtained after infection of normal embryo and kidney cells. In the short-term experiments in vitro, MLV was recovered from 8-day-old cultures of spleen and thymus cells taken from virus-inoculated mice either with or without evident symptoms of leukemia. After inoculation into adult mice, but not after inoculation into baby mice, a higher leukemia incidence was induced at dilutions of 10−2 to 10−4 (in different experiments), than with undiluted virus stocks from the cultures. The leukemia induction by undiluted culture fluids was increased, after inoculation into adult mice, by frozen virus stocks heated at 37° C. In experiments with X-ray-induced leukemia, no leukemogenic virus was detected in cultures of leukemic cells from a primary and a transplanted radiation-induced leukemia, maintained on spleen feeder layers.