tbuckley/cabot-search huggingface dataset:
Shikonin-enhanced cell immunogenicity of tumor vaccine is mediated by the differential effects of DAMP components
Authors: Tien-Jen Lin, Hsin-Ting Lin, Wei-Ting Chang, Pradeep Mitapalli. S, Pei-Wen Hsiao, Shu-Yi Yin, Ning-Sun Yang
Journal: Molecular Cancer (2015)

The tumor cell lysate-pulsed, dendritic cell (DC)-based cancer vaccine approaches are being actively evaluated for application to cancer immunotherapy, hopefully at a personalized medicine base. There is apparently an emerging technical problem however, the lack of highly efficacious potency in activation of patient's DCs for T-cell priming and the associated process for presenting tumor immunogenicity. One strategy to address this is to consider the manipulation of the tumor immunogenic cells death (ICD) complex ex-vivo for maximal activation of DC efficacy. In our previous study we showed that phytochemical shikonin (SK) can drastically enhance ICD activity in mouse tumor cells treated ex-vivo, and the resultant tumor cell lysate (TCL) can effectively augment such SK-TCL pulsed DC vaccine activity in vivo in anti-tumor activities. In this study, we investigated the specifics and the multi-functional effects of various damaged associated molecular pattern (DAMP) components of the ICD complex for their participation, roles and potential cross talks in activating DCs, as measured by five different functional assays. Among three DAMPs tested, HSP70 and CRT mediate a key role in SK-TCL-induced DC immunity for both CD4+ and CD8+ T cell proliferations in vitro. HSP70 is the most important component, followed by CRT, then HMGB1 in facilitating DC immunity on suppressing metastasis of mouse 4 T1 mammary tumors and prolonging survival in test mice. Only HSP70, but not CRT or HMGB1, is effective for the suppression of both granulocytic and monocytic MDSC populations in vivo. Both HSP70 and HMGB1, but not CRT, are essential in activating the expression of three key ICD molecules-associated receptors on test DCs. Each of the three test ICD proteins can exhibit a distinguishable pattern in stimulating the expression of four key chemokines in test DCs. Our findings on the differential roles or effect of various ICD components in activating vaccinated DCs may help formulate new strategies for future cancer vaccine designs.
Treatment of Multifocal Primary Cutaneous B-Cell Lymphoma: A Clinical Follow-Up Study of 29 Patients
Authors: Marcel W. Bekkenk, Maarten H. Vermeer, Marie-Louise Geerts, Ed M. Noordijk, Freerk Heule, Pieter C. van Voorst Vader, Willem A. van Vloten, Chris J.L.M. Meijer, Rein Willemze
Journal: Journal of Clinical Oncology (1999)

Although patients with primary cutaneous B-cell lymphoma (CBCL) and localized skin lesions are generally treated with radiotherapy and have an excellent prognosis, the clinical behavior and optimal treatment of CBCL presenting with multifocal skin lesions are less well defined. In this study, we evaluated the clinical behavior of and results of treatment for multifocal CBCL in 29 patients, and we formulated therapeutic guidelines.The study group included 16 patients with primary cutaneous follicular center-cell lymphoma (PCFCCL), eight with primary cutaneous immunocytoma (PCI), and five with primary cutaneous large B-cell lymphoma presenting on the legs (PCLBCL of the leg).Only one of the 24 patients with multifocal PCFCCL or PCI developed extracutaneous disease, and no patient died from lymphoma (median follow-up, 54 months). In patients with PCFCCL, treatment with either multiagent chemotherapy (nine patients) or radiotherapy directed toward all skin lesions (five patients) proved equally effective in terms of complete remission, relapse, and survival. In contrast, all five patients with PCLBCL of the leg developed extracutaneous disease, and four of the five died from systemic lymphoma, 8 to 36 months (median, 21 months) after diagnosis.The results of these preliminary studies suggest that patients with PCFCCL or PCI presenting with multifocal skin lesions have the same excellent prognosis that patients with localized PCFCCL or PCI have and that radiotherapy directed toward all skin lesions is as effective as multiagent chemotherapy. Patients with PCLBCL of the leg have a more unfavorable prognosis, particularly patients presenting with multifocal skin lesions. This last group should always be treated with multiagent chemotherapy.
Assisted dying—time for a full and fair debate
Authors: Fiona Godlee
Journal: BMJ (2015)

On the day he had chosen to die, Henri Bataille sat on his hospital bed with his wife and children around him. “Thank you for allowing me to go the way I want to go,” he told them. As a doctor in Belgium, Bataille had often felt powerless to help his own patients who were dying in pain (doi:10.1136/bmj.h4385). When he developed bone metastases secondary to prostate cancer, he registered for a physician assisted death, legal in Belgium since 2002. His daughter Veronique, also a doctor, explains, “I think that it was because he knew exactly when he was going to go that he had four or five hours of amazing …
S91 Mouse Melanoma Sublines Following Total &lt;italic&gt;In Vitro&lt;/italic&gt; Versus Alternate &lt;italic&gt;In Vivo&lt;/italic&gt; Passages&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Jewel Plummer Cobb, Anne McGrath
Journal: JNCI Journal of the National Cancer Institute (1972)

Two lines from one S91 mouse melanoma specimen, carried over 23 months solely in vitro (B line) or alternately also in vivo (BV line), showed differences in growth rates, plating efficiencies, and cell-aggregation patterns. When seeded at low cell densities, B cells grew faster and had higher plating efficiencies than BV cells. Pigmented aggregates were large enough to be seen macroscopically in BV cultures but were microscopic in B cultures. Both lines maintained their pigment-producing capacity and had large numbers of (3,4-dihydroxyphenyl)alanine DOPA-positive melanized cells that increased in number after each initial transfer. Neither long-term culture nor in vivo passages altered the pigment-forming capacity or tumor-producing capacity of either line, as judged by the formation of pigmented melanomas when cells were injected into mice.
Bone Marrow Versus Peripheral Blood Progenitor Cells CD34 Selection in Patients With Non-Hodgkin's Lymphomas: Different Levels of Tumor Cell Reduction. Implications for Autografting
Authors: M. Lopez, F.M. Lemoine, H. Firat, L. Fouillard, J.P. Laporte, S. Lesage, F. Isnard, J. Stachowiak, F. Ferrer-Le Coeur, P. Morel, A. Najman, L. Douay, N.C. Gorin
Journal: Blood (1997)
Phase II trial investigating the effects of zoledronate and dexamethasone in hormone resistant prostate cancer
Authors: O. Din, J. Horsman, N. James, K. Wood, P. Kirkbride
Journal: Journal of Clinical Oncology (2007)

15629 Background: Response rates to second line therapy in hormone resistant prostate cancer have been shown to be relatively low. Current options of management include dexamethasone, zoledronate or more recently, cytotoxic chemotherapy. Many trials have studied their effects as monotherapy. The aim of this study is to assess the efficacy and safety of the combination of zoledronate and dexamethasone in these patients. Methods: 20 patients were identified in 2004–2005. All had histologically confirmed prostatic adenocarcinoma and biochemically confirmed hormone resistance. All patients had bone metastases as confirmed on radionuclide imaging. Treatment consisted of 6 cycles of zoledronate at a dose of 4 mg, given at 4 weekly intervals, in combination with dexamethasone 2–4 mg once a day. Calcium/vitamin D supplementation was given throughout the zoledronate treatment. Data was collected prospectively on serum PSA, quality of life and pain score. Results: Of the 20 patients in the study, 11 completed the full 24 weeks of treatment. Reasons for not completing the study included disease progression, treatment toxicity, fracture and death. The overall response rate, as defined by an initial fall of serum PSA of more than 50%, was 35% (7 out of 20 patients). In those who responded, the sustained fall in PSA, during the trial period, lasted on average 3.0 months. Conclusion: This study has demonstrated clinically significant effects on tumour response for the combination of zoledronate and dexamethasone in hormone resistant prostate carcinoma. With the emergence of newer chemotherapeutic agents, this combination could be used as an effective, but less toxic alternative. No significant financial relationships to disclose.
Intestinal Calcium Absorption and Serum Vitamin D Metabolites in Normal Subjects and Osteoporotic Patients
Authors: J. C. Gallagher, B. Lawrence Riggs, John Eisman, Alan Hamstra, Sara B. Arnaud, Hector F. Deluca
Journal: Journal of Clinical Investigation (1979)

Intestinal calcium absorption assessed by a double-isotope method, decreased significantly with aging in 94 normal subjects (r = −0.22, P < 0.025). In 52 untreated patients with postmenopausal osteoporosis, calcium absorption was significantly lower than normal when either age or habitual calcium intake was used as a covariable (P < 0.001). Serum 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in 44 normal subjects and 27 osteoporotic patients. For all normals, calcium absorption and serum 1,25(OH)2D were positively correlated (r = 0.50, P < 0.001). In nonelderly normal subjects (ages 30-65 yr), dietary calcium intake correlated inversely with both calcium absorption (r = −0.39, P < 0.01) and with serum 1,25(OH)2D (r = −0.50, P < 0.01). Both osteoporotic patients and elderly normal subjects (ages 65-90 yr) differed from nonelderly normals in that these correlations were not present. In addition although serum 25-OH-D was normal, serum 1,25(OH)2D was significantly decreased in both osteoporotic patients and elderly normals (P < 0.001). In osteoporotic patients, calcium absorption increased significantly (P < 0.001) after 7 d administration of a small dose (0.4 μg/d) of synthetic 1,25(OH)2D3. In osteoporotics mean serum immunoreactive parathyroid hormone was either normal (COOH-terminal assay) or low (NH2-terminal assay) relative to age-matched controls, and mean serum phosphate was increased.
Cancer Incidence by Marital Status: U.S. Third National Cancer Survey2
Authors: V. L. Ernster, S. T. Sacks, S. Selvin, N. L. Petrakis
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Cancer Incidence by Marital Status: U.S. Third National Cancer Survey Get access V. L. Ernster, V. L. Ernster 3Department of Epidemiology and International Health, University of California, San Francisco, Calif. 94143. Search for other works by this author on: Oxford Academic PubMed Google Scholar S. T. Sacks, S. T. Sacks 3Department of Epidemiology and International Health, University of California, San Francisco, Calif. 94143. Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Selvin, S. Selvin 4Department of Biomedical and Environmental Health Sciences, University of California, Berkeley, Calif. 94720. Search for other works by this author on: Oxford Academic PubMed Google Scholar N. L. Petrakis N. L. Petrakis 3Department of Epidemiology and International Health, University of California, San Francisco, Calif. 94143. 5Incidence data in the form of Third National Cancer Survey (TNCS) public use tapes were provided by Dr. John L. Young, Jr., Biometry Branch, National Cancer Institute. The authors also acknowledge the efforts of Dr. Deane W. Merrill, computer scientist, who facilitated processing of the TNCS and census tapes. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 3, September 1979, Pages 567–585, https://doi.org/10.1093/jnci/63.3.567 Published: 01 September 1979 Article history Received: 29 August 1978 Accepted: 22 February 1979 Published: 01 September 1979
Blood eosinophilia and the number of exacerbations in COPD patients
Authors: David Price, Anna Rigazio, Dirkje Postma, Alberto Papi, Bruselle Guy, Alvar Agusti, Antonio Anzueto, Claus Vogelmeier, Dermot Ryan, Daryl Freeman, Mike Thomas, Ian Pavord, Mona Bafadhel, Nicolas Roche, Rupert Jones, Ted Popov, Emilio Pizzichini, Alison Chisholm, Marjan Kerkhof
Journal: European Respiratory Journal (2014)

Background: There are limited data on the relevance of blood eosinophilia in COPD.

We studied the prospective relationship between eosinophilia at steady state and the subsequent number of COPD exacerbations.

Methods: Data was taken from 13,780 general practice patients with a doctor diagnosis of COPD, blood eosinophil counts measured at steady state (> 4 weeks prior or after an exacerbation) and a 1 year subsequent follow-up, identified from the Optimum Patient Care Research Database. Rate Ratios (RR) were calculated using Quasi-Poisson regression.

Results: Blood eosinophilia (≥ 0.5 x 109 /litre) was found in 10% of COPD patients, 37% of whom had ≥ 1 exacerbations. COPD patients with eosinophilia had a significantly higher rate of exacerbations than patients with normal values. The association was only significant in ex-smokers (53% of the population) and never-smokers (12%). No association was found in current smokers (35%) and in patients without maintenance treatments (28%). Within the subgroup of 4,785 COPD patients not currently smoking and using inhaled corticosteroids at baseline and follow-up year, patients with blood eosinophilia had a 24% higher exacerbation rate than patients without eosinophilia (RR=1.24 (1.10,1.41), adjusted for GOLD grade and host factors). Excluding patients with a record of asthma ever (42%) did not change this association.

Conclusion: Blood eosinophilia occurs in stable (mostly treated) COPD patients and is associated with a higher exacerbation risk, especially in non-smokers receiving maintenance treatment. The inhibitory effect of current cigarette smoking on the relationship between blood eosinophilia and COPD exacerbations has to be further explored.
Caring for Children with Drug-Resistant Tuberculosis
Authors: James A. Seddon, Jennifer J. Furin, Marianne Gale, Hernan Del Castillo Barrientos, Rocío M. Hurtado, Farhana Amanullah, Nathan Ford, Jeffrey R. Starke, H. Simon Schaaf
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Section:ChooseTop of pageAbstract <<MethodologyTreatment InitiationRegimen Design and Treatm...Management of Comorbid Co...Morbidity Associated With...Treatment MonitoringAdverse EventsPromoting AdherenceInfection ControlMultidisciplinary CareDR-TB Definitions in Chil...ConclusionsReferencesCITING ARTICLES
Repeated embolization and fibrinolysis inhibition induce chronic thromboembolic pulmonary hypertension in rabbits
Authors: Rozenn Quarck, Alicja Ronisz, Marion Delcroix
Journal: European Respiratory Journal (2013)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe disease characterized by unresolved and organized thrombi obstructing pulmonary arterial bed, resulting in pulmonary hypertension and right heart failure. Since CTEPH is notoriously underdiagnosed and its pathogenesis poorly understood, developing animal models is a major challenge. Our aim was to develop a chronic model of CTEPH in rabbits.

CTEPH was induced in adult male New Zealand rabbits by performing 5 weekly embolizations of autologous blood clots, with (n=5) or without (n=5) administration of tranexamic acid, a fibrinolysis inhibitor. Saline replaced clots in the control group (n=5). Right ventricular systolic pressure (RVSP) was monitored by telemetry. Right heart catheterization was performed 12 weeks after the first embolization, before animal sacrifice. RV hypertrophy, plasma endothelin-1 (ET-1) and lung vessel morphometry were analyzed.

Acute embolization with tranexamic acid resulted in a 46% increase in RVSP. Repeated embolization with tranexamic acid increased systolic RVSP by 28% (p≤0.05), as well as mean pulmonary arterial pressure, pulmonary vascular resistance, RV/(LV+S) ratio and plasma ET-1 by 31%, 71%, 21% and 34%, respectively, compared to control rabbits. Distal pulmonary artery remodeling was also observed.

We have shown a significant increase in RVSP, accompanied by persistently increased mPAP and PVR, and RV hypertrophy after repeated embolization and fibrinolysis inhibition in rabbits, together with remodeling of proximal and distal pulmonary arteries.
Prediction of disease risk using common genetic variants
Authors: David J. Hunter
Journal: Clinical Cancer Research (2010)

Abstract A frequently proposed application of knowledge on inherited predisposition to cancers is the possibility that susceptible individuals could be targeted for enhanced surveillance, lifestyle advice, or chemoprevention, and thus have reduced risk of diagnosis or mortality from cancer. Action based on knowledge of mutations in high penetrance genes such as BRCA1 in breast cancer, or hMSH2 and colorectal cancer has become established practice in high risk clinics. With the advent of genome-wide association studies (GWAS) dozens of common genetic variants (mostly SNPs) have been discovered to be associated with cancer at various sites, with approximately 30 discovered for prostate cancer alone. In general, the relative risks associated with these risk variants are an order of magnitude or more less than those associated with high penetrance gene mutations, and thus, the risk information contributed by a single common risk variant contributes minimally to risk prediction. However, when cumulated into multi-SNP risk scores, large relative risks are predicted for the small number of persons in the tail of the risk distribution (i.e. those who have inherited mostly risk variants as opposed to “protective” variants). For this small number of people, the estimated relative risks approach those for the high penetrance single gene mutations, but at this stage of our knowledge the risk scores are unstable and may change as more common variants are discovered. For the majority of people, with either modestly elevated or modestly reduced predicted risks, the clinical application of this knowledge is even less secure. However, combinations of risk variants have been shown at some cancer sites to be at least as predictive as available risk scores based on demographic and lifestyle factors. As more variants are discovered, the predictive value of these risk scores will increase, and thus the clinical utility of the information should be rigorously tested.
Cord blood vitamin D concentrations are unrelated to atopy and wheeze in 2 diverse birth cohort studies
Authors: Cynthia M. Visness, Megan T. Sandel, George O'Connor, James E. Gern, Katy F. Jaffee, Robert A. Wood, Meyer Kattan, Gordon R. Bloomberg, Amy Dresen, Peter J. Gergen, Diane R. Gold, Robert F. Lemanske, Victoria Rajamanickam, Carlos A. Camargo, Daniel J. Jackson
Journal: Journal of Allergy and Clinical Immunology (2015)
Practical guidelines are important
Authors: A. Van Es, A.-M. Raat, G. De Wildt
Journal: BMJ (1996)

What, therefore, is the future of acute medical care in the NHS?How should we best train and supervise our junior medical staff?Should con- sultant physicians be brought reluctantly out of their subspecialty to deal with acute medical admissions?Are consultant physicians who sub- specialise in acute medical care needed?Medicine moves on, Calman's proposals are being imple- mented, and the systems and work patterns of the past may not be ideal for the future.
Determinant factors for bronchial ischemia after lung transplantation
Authors: Anne Olland, Nicola Santelmo, Pierre-Emmanuel Falcoz, Gilbert Massard
Journal: European Respiratory Journal (2011)

Objective:  Bronchial ischemia is a frequent problem encountered after lung transplantation. The resulting stenosis will delay functional recovery of the graft, reduce effective secretions drainage and lead to repetitive invasive endoscopy sessions before complete healing. The aim of our study was to identify risk factors for bronchial ischemia in a multi-centric study of single-lung transplantations.   Method:  With the agreement of 10 French centers, we recorded all single-lung transplantations performed between 1998 and 2008 especially 180 twinned recipients. According to that model, we compared characteristics of paired recipients presenting a discordant evolution of bronchial anastomosis. We recorded recipient age at the time of transplantation, respiratory disease and transplantation indication, nutritional state by body mass index (BMI), duration of cold ischemia, side of transplantation and immunosuppressive treatment. In our model, harvesting and graft preservation are identical in each pair.   Results:  Among 387 single lung-transplantations, 106 patients had an ischemic evolution of the bronchial anastomosis. Initial immunosuppressive treatment included tacrolimus for 32% of patients with an ischemic bronchus and for 14% of patients without ischemia (p   Discussion:  In our study, tacrolimus seems to increase risks of pathological ischemic process in the bronchus during post-operative period. Anti-proliferative properties of immunosuppressive drugs may impair early outcome of lung transplantation.
Effect of Protein A Immunoadsorption in Nephrotic Syndrome of Various Etiologies
Authors: VINCENT L. M. ESNAULT, DOMINIQUE BESNIER, ANGELO TESTA, PIERRE COVILLE, PIERRE SIMON, JEAN-FRANC[COMBINING CEDILLA]OIS SUBRA, MARIE A. P. AUDRAIN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Protein A immunoadsorption (IA) has proved effective in reducing proteinuria in patients with nephrotic syndrome after recurrence of focal and segmental glomerulosclerosis (FSGS) in kidney transplants. The effect of IA in nephrotic syndrome of other etiologies remains unknown. Nine patients with nephrotic syndrome secondary to membranous nephropathy (four cases), diabetes mellitus (one case), IgA nephropathy (two cases), and amyloidosis (two cases) had three to five IA of 2.5 plasma volumes over 4 to 8 d. Patients received no concomitant immunosuppressive treatment, and antihypertensive drugs were left unchanged. Proteinuria decreased from 12.64 ± 5.49 to 3.35 ± 2.2 g/24 h (mean ± SD) in all patients after three to five IA. Hematocrit decreased from 37.32 to 32.64% (12.5% hemodilution) and serum albumin from 25.43 to 18.6 g/L (26.4% decrease). Proteinuria returned to baseline levels within 1 mo, as described in recurrent FSGS following transplantation. When serum albumin balance was controlled by albumin infusion after IA in two patients, comparable decreases in proteinuria were observed. Therefore, IA is effective in producing short-term reduction of proteinuria in nephrotic syndromes related not only to FSGS but also to membranous and IgA nephropathies, diabetes mellitus, and amyloidosis, which suggests that IA removes a nonspecific circulating hemodynamic-altering or permeability-increasing factor.