tbuckley/cabot-search huggingface dataset:
Allogeneic Stem-Cell Transplantation in Patients With Waldenström Macroglobulinemia: Report From the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Authors: Charalampia Kyriakou, Carmen Canals, Jan J. Cornelissen, Gerard Socié, Roel Willemze, Norbert Ifrah, Hildegard T. Greinix, Didier Blaise, Eric Deconinck, Augustin Ferrant, Anton Schattenberg, Jean-Luc Harousseau, Anna Sureda, Norbert Schmitz
Journal: Journal of Clinical Oncology (2010)

Allogeneic stem-cell transplantation (alloSCT) is a curative therapeutic option for patients with low-grade lymphoid malignancies. Information regarding alloSCT in Waldenström macroglobulinemia (WM) is limited. This study presents the long-term outcome of a large series of patients with WM treated with alloSCT.A total of 86 patients received allograft by using either myeloablative (MAC; n = 37) or reduced-intensity conditioning (RIC; n = 49) regimens and were retrospectively studied. The median age was 49 years (range, 23 to 64 years); 47 patients had received three or more previous lines of therapy, and eight patients had experienced failure on a prior autologous stem-cell transplantation. A total of 59 patients (68.6%) had chemotherapy-sensitive disease at the time of alloSCT. Median follow-up of the surviving patients was 50 months (7 to 142 months).Nonrelapse mortality (NRM) at 3 years was 33% for MAC and 23% for RIC. The overall response rate was 75.6%. The relapse rates (RRs) at 3 years were 11% for MAC and 25% for RIC. Fourteen patients received donor lymphocyte infusions (DLIs) for disease relapse. PFS and OS at 5 years were 56% and 62% for MAC and 49% and 64% for RIC, respectively. The occurrence of chronic graft-versus-host disease (cGVHD) was associated with a higher NRM and a lower RR, leading to an improvement in PFS.alloSCT can induce durable remissions in a selected population of young and heavily pretreated patients with WM. The low RR, the achievement of additional disease responses after DLIs, and the lower RR in patients developing cGVHD suggest the existence of a clinically relevant graft-versus-WM effect.
Regulatory T cells in human and angiotensin II-induced mouse abdominal aortic aneurysms
Authors: Y. Zhou, W. Wu, J. S. Lindholt, G. K. Sukhova, P. Libby, X. Yu, G.-P. Shi
Journal: Cardiovascular Research (2015)

AimsRegulatory T cells (Tregs) protect mice from angiotensin II (Ang-II)-induced abdominal aortic aneurysms (AAA). This study tested whether AAA patients are Treg-insufficient and the Treg molecular mechanisms that control AAA pathogenesis.
Secretable Chaperone Grp170 Enhances Therapeutic Activity of a Novel Tumor Suppressor, <i>mda-7</i>/IL-24
Authors: Ping Gao, Xiaolei Sun, Xing Chen, Yanping Wang, Barbara A. Foster, John Subjeck, Paul B. Fisher, Xiang-Yang Wang
Journal: Cancer Research (2008)

Abstract Melanoma differentiation–associated gene-7 (mda-7)/interleukin-24 (IL-24) is a cancer-specific, apoptosis-inducing gene with broad-spectrum antitumor activity, making it an ideal candidate for a novel cancer gene therapy. A systemic and sustained antitumor immune response generated at the time of initial molecular-targeted therapy would provide additional clinical benefits in cancer patients, resulting in improved prevention of tumor recurrence. In this study, we explored the therapeutic efficacy of intratumoral delivery of a nonreplicating adenoviral vector encoding mda-7/IL-24 (Ad.mda-7) and a secretable form of endoplasmic reticulum resident chaperone grp170 (Ad.sgrp170), a potent immunostimulatory adjuvant and antigen carrier. Intratumoral administration of Ad.mda-7 in combination with Ad.sgrp170 was more effective in controlling growth of TRAMP-C2 prostate tumor compared with either Ad.mda-7 or Ad.sgrp170 treatment. Generation of systemic antitumor immunity was shown by enhanced protection against subsequent tumor challenge and improved control of distant tumors. The combined treatments enhanced antigen and tumor-specific T-cell response, as indicated by increased IFN-γ production and cytolytic activity. Antibody depletion suggests that CD8+ T cells may be involved in the antitumor effect of the dual molecule–targeted therapies. Therefore, introducing immunostimulatory chaperone grp170 in situ strongly promotes the “immunogenic” cell death when delivered to the mda-7/IL-24–induced apoptotic tumor cells, indicating that an improved anticancer efficacy may be achieved by concurrently targeting both tumor and immune compartments. Given multiple undefined antigens present endogenously within prostate cancer, these data provide a rationale for combining sgrp170-based vaccine strategy with mda-7/IL-24–targeted cancer therapy to induce durable systemic immunity. [Cancer Res 2008;68(10):3890–8]
Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study
Authors: C. E Koro
Journal: BMJ (2002)

To quantify the association between olanzapine and diabetes.Population based nested case-control study.United Kingdom based General Practice Research Database comprising 3.5 million patients followed between 1987 and 2000.19 637 patients who had been diagnosed as having and treated for schizophrenia. 451 incident cases of diabetes were matched with 2696 controls.Diagnosis and treatment of diabetes.Patients taking olanzapine had a significantly increased risk of developing diabetes than non-users of antipsychotics (odds ratio 5.8, 95% confidence interval 2.0 to 16.7) and those taking conventional antipsychotics (4.2, 1.5 to 12.2). Patients taking risperidone had a non-significant increased risk of developing diabetes than non-users of antipsychotics (2.2, 0.9 to 5.2) and those taking conventional antipsychotics (1.6, 0.7 to 3.8).Olanzapine is associated with a clinically important and significant increased risk of diabetes.
Severe Renal Mass Reduction Impairs Recovery and Promotes Fibrosis after AKI
Authors: Aaron J. Polichnowski, Rongpei Lan, Hui Geng, Karen A. Griffin, Manjeri A. Venkatachalam, Anil K. Bidani
Journal: Journal of the American Society of Nephrology (2014)

Preexisting CKD may affect the severity of and/or recovery from AKI. We assessed the impact of prior graded normotensive renal mass reduction on ischemia-reperfusion–induced AKI. Rats underwent 40 minutes of ischemia 2 weeks after right uninephrectomy and surgical excision of both poles of the left kidney (75% reduction of renal mass), right uninephrectomy (50% reduction of renal mass), or sham reduction of renal mass. The severity of AKI was comparable among groups, which was reflected by similarly increased serum creatinine (SCr; approximately 4.5 mg/dl) at 2 days, tubule necrosis at 3 days, and vimentin-expressing regenerating tubules at 7 days postischemia-reperfusion. However, SCr remained elevated compared with preischemia-reperfusion values, and more tubules failed to differentiate during late recovery 4 weeks after ischemia-reperfusion in rats with 75% renal mass reduction relative to other groups. Tubules that failed to differentiate continued to produce vimentin, exhibited vicarious proliferative signaling, and expressed less vascular endothelial growth factor but more profibrotic peptides. The disproportionate failure of regenerating tubules to redifferentiate in rats with 75% renal mass reduction associated with more severe capillary rarefaction and greater tubulointerstitial fibrosis. Furthermore, initially normotensive rats with 75% renal mass reduction developed hypertension and proteinuria, 2–4 weeks postischemia-reperfusion. In summary, severe (>50%) renal mass reduction disproportionately compromised tubule repair, diminished capillary density, and promoted fibrosis with hypertension after ischemia-reperfusion–induced AKI in rats, suggesting that accelerated declines of renal function may occur after AKI in patients with preexisting CKD.
Part-Time Residency Training
Authors: Ethel Weinberg
Journal: JAMA (1969)

In order to make medicine a more feasible career choice for women and in order to increase the level of training and, therefore, the quality of practice, it is important to decrease the scheduling rigidity of standard residency training programs. The steadily increasing numbers of women in medical school makes the problem more pressing at this time. This communication reports the result of a survey of the specialty boards concerning the acceptability of part-time training. In most cases the boards will consider this kind of training on an individual basis. Part-time specialty training does merit a trial.
Poxvirus Decapping Enzymes Enhance Virulence by Preventing the Accumulation of dsRNA and the Induction of Innate Antiviral Responses
Authors: Shin-Wu Liu, George C. Katsafanas, Ruikang Liu, Linda S. Wyatt, Bernard Moss
Journal: Cell Host & Microbe (2015)

Poxvirus replication involves synthesis of double-stranded RNA (dsRNA), which can trigger antiviral responses by inducing phosphorylation-mediated activation of protein kinase R (PKR) and stimulating 2′5′-oligoadenylate synthetase (OAS). PKR inactivates the translation initiation factor eIF2α via phosphorylation, while OAS induces the endonuclease RNase L to degrade RNA. We show that poxvirus decapping enzymes D9 and D10, which remove caps from mRNAs, inhibit these antiviral responses by preventing dsRNA accumulation. Catalytic site mutations of D9 and D10, but not of either enzyme alone, halt vaccinia virus late protein synthesis and inhibit virus replication. Infection with the D9-D10 mutant was accompanied by massive mRNA reduction, cleavage of ribosomal RNA, and phosphorylation of PKR and eIF2α that correlated with a ∼15-fold increase in dsRNA compared to wild-type virus. Additionally, mouse studies show extreme attenuation of the mutant virus. Thus, vaccinia virus decapping, in addition to targeting mRNAs for degradation, prevents dsRNA accumulation and anti-viral responses.
IL-17–induced CXCL12 recruits B cells and induces follicle formation in BALT in the absence of differentiated FDCs
Authors: Henrike Fleige, Sarina Ravens, Georgios Leandros Moschovakis, Jasmin Bölter, Stefanie Willenzon, Gerd Sutter, Susanne Häussler, Ulrich Kalinke, Immo Prinz, Reinhold Förster
Journal: The Journal of Experimental Medicine (2014)

Ectopic lymphoid tissue, such as bronchus-associated lymphoid tissue (BALT) in the lung, develops spontaneously at sites of chronic inflammation or during infection. The molecular mechanisms underlying the neogenesis of such tertiary lymphoid tissue are still poorly understood. We show that the type of inflammation-inducing pathogen determines which key factors are required for the formation and maturation of BALT. Thus, a single intranasal administration of the poxvirus modified vaccinia virus Ankara (MVA) is sufficient to induce highly organized BALT with densely packed B cell follicles containing a network of CXCL13-expressing follicular DCs (FDCs), as well as CXCL12-producing follicular stromal cells. In contrast, mice treated with P. aeruginosa (P.a.) develop BALT but B cell follicles lack FDCs while still harboring CXCL12-positive follicular stromal cells. Furthermore, in IL-17–deficient mice, P.a.-induced BALT largely lacks B cells as well as CXCL12-expressing stromal cells, and only loose infiltrates of T cells are present. We show that Toll-like receptor pathways are required for BALT induction by P.a., but not MVA, and provide evidence that IL-17 drives the differentiation of lung stroma toward podoplanin-positive CXCL12-expressing cells that allow follicle formation even in the absence of FDCs. Taken together, our results identify distinct pathogen-dependent induction and maturation pathways for BALT formation.
Aerosol delivery from spacers in wheezy infants: a daily life study
Authors: HM Janssens, EM Heijnen, VM de Jong, WC Hop, WP Holland, JC de Jongste, HA Tiddens
Journal: European Respiratory Journal (2000)

The aims of this study were to assess and compare dose delivery and dose variability of pressurized metered dose inhalers (pMDI)/spacers in wheezy infants in daily life and to investigate factors influencing aerosol delivery. In an open randomized crossover study in 25 wheezy infants aged 5-26 months, a metal spacer (Nebuchamber), a detergent coated (DC) and a non-detergent coated (nonDC) plastic spacer (Babyhaler) were tested at home for 7 days each. Budesonide (200 microg b.i.d) was administered via a Nebuchamber or fluticasone (125 microg b.i.d) via a Babyhaler. Aerosol was trapped in filters, positioned between the spacer and face mask. Cooperation was scored on diary cards. Electrostatic charge (ESC) of the spacers was measured. Evaluations of the administration technique were made from video recordings. Median (range) dose delivery of the filters expressed as per cent (%) of nominal dose, was 34% (3-59), 23% (1-49), and 41% (12-55) for the Nebuchamber, nonDC-Babyhaler, and DC-Babyhaler respectively. Considerable dose variability was found, median (range) within-subject dose variability, expressed as coefficient of variation, for the Nebuchamber (49% (15-249)) was significantly higher when compared with both nonDC- (36% (12-325)) and DC-Babyhalers (27% (10-122)), for which dose variabilities were similar. Detergent coating was effective to reduce electrostatic charge, and to increase dose delivery, but had no effect on dose variability. Bad cooperation was an important cause for high dose variability for all spacers (r=0.5-0.6, p&lt;0.02). Many mistakes were made during the administration procedure.
Expression of Fatty Acid Amide Hydrolase (FAAH) in Human, Mouse, and Rat Urinary Bladder and Effects of FAAH Inhibition on Bladder Function in Awake Rats
Authors: Frank Strittmatter, Giorgio Gandaglia, Fabio Benigni, Arianna Bettiga, Patrizio Rigatti, Francesco Montorsi, Christian Gratzke, Christian Stief, Giorgia Colciago, Petter Hedlund
Journal: European Urology (2011)
Declining Second Primary Ovarian Cancer After First Primary Breast Cancer
Authors: Sara J. Schonfeld, Amy Berrington de Gonzalez, Kala Visvanathan, Ruth M. Pfeiffer, William F. Anderson
Journal: Journal of Clinical Oncology (2013)

Although ovarian cancer incidence rates have declined in the United States, less is known of ovarian cancer trends among survivors of breast cancer. Therefore, we examined second primary ovarian cancers after first primary breast cancer.Data were obtained from the Surveillance, Epidemiology, and End Results program (1973 to 2008). Standardized incidence ratios (SIRs) were calculated as the observed numbers of ovarian cancers among survivors of breast cancer compared with the expected numbers in the general population. Absolute rates were measured as the incidence rates for second primary ovarian cancer by year of diagnosis of the first primary breast cancer adjusted for age of breast cancer diagnosis and years since diagnosis.SIRs for second primary ovarian cancer were elevated over the entire study period (SIR, 1.24; 95% CI, 1.2 to 1.3), whereas the absolute rates declined with an estimated annual percentage change near 1% (-1.34% to -0.09% per year). Secular trends for second ovarian cancers were similar after estrogen receptor (ER) -positive and ER-negative breast cancers, whereas the age-specific patterns varied significantly by ER expression (P for interaction < .001). The largest SIR was among women age less than 50 years with ER-negative breast cancer (SIR, 4.35; 95% CI, 3.5 to 5.4).Persistently elevated SIRs along with decreasing absolute rates over the entire study period suggest that ovarian cancers in both the general population and survivors of breast cancer are declining in parallel, possibly because of common risk factor exposures. Analytic studies are needed to further assess the parallel overall trends and the age-specific interaction by ER expression.
Recombinant Interleukin-2 and Adoptive Immunotherapy Alternated With Dacarbazine Therapy in Melanoma: A National Biotherapy Study Group Trial
Authors: R. O. Dillman, R. K. Oldham, N. M. Barth, R. Birch, J. Arnold, W. H. West
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Recombinant Interleukin-2 and Adoptive Immunotherapy Alternated With Dacarbazine Therapy in Melanoma: A National Biotherapy Study Group Trial Get access Robert O. Dillman, Robert O. Dillman Hoag Cancer CenterNewport Beach, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert K. Oldham, Robert K. Oldham Biological Therapy InstituteFranklin, Tenn Search for other works by this author on: Oxford Academic PubMed Google Scholar Neil M. Barth, Neil M. Barth Hoag Cancer CenterNewport Beach, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert Birch, Robert Birch National Biotherapy Study Group (NBSG), Central OfficeFranklin, Tenn Search for other works by this author on: Oxford Academic PubMed Google Scholar Jerri Arnold, Jerri Arnold National Biotherapy Study Group (NBSG), Central OfficeFranklin, Tenn Search for other works by this author on: Oxford Academic PubMed Google Scholar William H. West William H. West Baptist Memorial HospitalMemphis, Tenn Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 16, 15 August 1990, Pages 1345–1349, https://doi.org/10.1093/jnci/82.16.1345 Published: 15 August 1990 Article history Received: 06 March 1990 Revision received: 24 May 1990 Accepted: 05 June 1990 Published: 15 August 1990
Silica exposure among male current smokers is associated with a high risk of developing ACPA-positive rheumatoid arthritis
Authors: Patrik Stolt, Abqariyah Yahya, Camilla Bengtsson, Henrik Källberg, Johan Rönnelid, Ingvar Lundberg, Lars Klareskog, Lars Alfredsson
Journal: Annals of the Rheumatic Diseases (2009)

Objective To study the association between silica exposure, separately as well as combined with smoking, and the risk of developing rheumatoid arthritis (RA) with or without the presence of antibodies against citrullinated peptide antigens (ACPA). Methods This Swedish population based case–control study analysed 577 incident RA cases and 659 randomly selected controls, all men aged 18–70 years, included during May 1996 to May 2006. Self-reported silica exposure, defined as exposure to stone dust, rock drilling or stone crushing and cigarette smoking was registered. ACPA status among cases was analysed. Results Silica-exposed subjects were found to have a moderately increased risk of ACPA-positive RA (odds ratio (OR) adjusted for age and residency=1.67 (95% CI 1.13 to 2.48), but not of ACPA-negative RA (OR=0.98 (95% CI 0.57 to 1.66)), compared with subjects unexposed to silica. Subjects exposed to rock drilling were found to have a somewhat more markedly increased risk of ACPA-positive RA (OR=2.34 (95% CI 1.17 to 4.68)). A high risk of developing ACPA-positive RA was observed among silica-exposed current smokers (OR=7.36 (95% CI 3.31 to 16.38)), exceeding the risk expected from the separate effects of silica exposure and current smoking, indicating an interaction between these exposures (attributable proportion due to interaction=0.60 (95% CI 0.26 to 0.95)). Conclusion Silica exposure combined with smoking among men is associated with an increased risk of developing ACPA-positive RA. These results suggest that different inhalation exposures may interact in the aetiology of ACPA-positive RA.
End-Tidal Carbon Dioxide Monitoring During Cardiopulmonary Resuscitation
Authors: A. Randolph Garnett
Journal: JAMA (1987)

The end-tidal carbon dioxide (CO<sub>2</sub>) concentration has been found to correlate with cardiac output during and after cardiopulmonary resuscitation (CPR) in animal models. We monitored end-tidal CO<sub>2</sub>values continuously during cardiac resuscitation in 23 humans while ventilation was held constant with a computercontrolled CPR Thumper. This report focuses on ten of the 23 patients who experienced return of spontaneous circulation (ROSC) during monitoring. There was no significant difference in the end-tidal CO<sub>2</sub>value of patients without ROSC (1.8% ±0.9%) and the end-tidal CO<sub>2</sub>value of patients before ROSC in patients who had ROSC (1.7%± ±0.6%). The end-tidal CO<sub>2</sub>concentration increased immediately in all patients who had ROSC, from 1.7% ±0.6% to 4.6% ±1.4%, then gradually returned to a new baseline (3.1% ± 0.9%). Change in the end-tidal CO<sub>2</sub>value was often the first clinical indicator that ROSC had occurred. Our findings suggest that end-tidal CO<sub>2</sub>monitoring may provide clinically useful information that can be used to guide therapy during CPR. (<i>JAMA</i>1987;257:512-515)
Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse
Authors: Emmanuelle Clappier, Bastien Gerby, François Sigaux, Marc Delord, Farah Touzri, Lucie Hernandez, Paola Ballerini, André Baruchel, Françoise Pflumio, Jean Soulier
Journal: The Journal of Experimental Medicine (2011)

Genomic studies in human acute lymphoblastic leukemia (ALL) have revealed clonal heterogeneity at diagnosis and clonal evolution at relapse. In this study, we used genome-wide profiling to compare human T cell ALL samples at the time of diagnosis and after engraftment (xenograft) into immunodeficient recipient mice. Compared with paired diagnosis samples, the xenograft leukemia often contained additional genomic lesions in established human oncogenes and/or tumor suppressor genes. Mimicking such genomic lesions by short hairpin RNA–mediated knockdown in diagnosis samples conferred a selective advantage in competitive engraftment experiments, demonstrating that additional lesions can be drivers of increased leukemia-initiating activity. In addition, the xenograft leukemias appeared to arise from minor subclones existing in the patient at diagnosis. Comparison of paired diagnosis and relapse samples showed that, with regard to genetic lesions, xenograft leukemias more frequently more closely resembled relapse samples than bulk diagnosis samples. Moreover, a cell cycle– and mitosis-associated gene expression signature was present in xenograft and relapse samples, and xenograft leukemia exhibited diminished sensitivity to drugs. Thus, the establishment of human leukemia in immunodeficient mice selects and expands a more aggressive malignancy, recapitulating the process of relapse in patients. These findings may contribute to the design of novel strategies to prevent or treat relapse.