tbuckley/cabot-search huggingface dataset:
Is Private Health Care the Answer to the Health Problems of the World's Poor?
Authors: Kara Hanson, Lucy Gilson, Catherine Goodman, Anne Mills, Richard Smith, Richard Feachem, Neelam Sekhri Feachem, Tracey Perez Koehlmoos, Heather Kinlaw
Journal: PLoS Medicine (2008)

The global burden of disease falls disproportionately upon the world's low-income countries, which are often struggling with weak health systems. Both the public and private sector deliver health care in these countries, but the appropriate role for each of these sectors in health system strengthening remains controversial. This debate examines whether the private sector should step up its involvement in the health systems of low-income countries.
Treatment of Burkitt's/Burkitt-like lymphoma in adolescents and adults: a 20-year experience from the Norwegian Radium Hospital with the use of three successive regimens
Authors: S. Smeland, A.K. Blystad, S.O. Kvaløy, I.M. Ikonomou, J. Delabie, G. Kvalheim, J. Hammerstrøm, G.F. Lauritzsen, H. Holte
Journal: Annals of Oncology (2004)
INVOLVEMENT OF ADRENERGIC FACTORS IN THE EFFECTS OF BACTERIAL ENDOTOXIN
Authors: James T. Gourzis, Murray W. Hollenberg, Mark Nickerson
Journal: The Journal of Experimental Medicine (1961)

The possible involvement of adrenergic mechanisms in the effects of Escherichia coli endotoxin was investigated in several preparations. Appropriate pretreatment of rabbits with E. coli endotoxin significantly increased pressor responses to epinephrine and norepinephrine as compared to untreated controls. Exposure of isolated rabbit aorta strips to E. coli endotoxin in a medium containing whole blood or cellular constituents of blood significantly increased the response to epinephrine. Endotoxin had no effect on responses to epinephrine in ritro when plain Krebs-Ringer solution was used. Pretreatment with reserpine or phenoxybenzamine (dibenzyline) protected rabbits and mice against the acute lethal effects of E. coli endotoxin. The time period intervening between reserpine or dibenzyline administration and challenge by endotoxin precluded a direct antiendotoxic action of these agents. In addition, incubation of dibenzyline with endotoxin in vitro, under conditions which would favor reaction, did not decrease the toxicity of the latter. These results indicate that peripheral adrenergic mechanisms are intimately involved in the effects of E. coli endotoxin and support the concept that deleterious effects of endotoxin in shock probably are due to exaggeration of existing vasoconstriction in an already compromised organism.
Cytomegalovirus immunoevasin reveals the physiological role of “missing self” recognition in natural killer cell dependent virus control in vivo
Authors: Marina Babić, Michal Pyzik, Biljana Zafirova, Maja Mitrović, Višnja Butorac, Lewis L. Lanier, Astrid Krmpotić, Silvia M. Vidal, Stipan Jonjić
Journal: The Journal of Experimental Medicine (2010)

Cytomegaloviruses (CMVs) are renowned for interfering with the immune system of their hosts. To sidestep antigen presentation and destruction by CD8+ T cells, these viruses reduce expression of major histocompatibility complex class I (MHC I) molecules. However, this process sensitizes the virus-infected cells to natural killer (NK) cell–mediated killing via the “missing self” axis. Mouse cytomegalovirus (MCMV) uses m152 and m06 encoded proteins to inhibit surface expression of MHC I molecules. In addition, it encodes another protein, m04, which forms complexes with MHC I and escorts them to the cell surface. This mechanism is believed to prevent NK cell activation and killing by restoring the “self” signature and allowing the engagement of inhibitory Ly49 receptors on NK cells. Here we show that MCMV lacking m04 was attenuated in an NK cell– and MHC I–dependent manner. NK cell–mediated control of the infection was dependent on the presence of NK cell subsets expressing different inhibitory Ly49 receptors. In addition to providing evidence for immunoevasion strategies used by CMVs to avoid NK cell control via the missing-self pathway, our study is the first to demonstrate that missing self–dependent NK cell activation is biologically relevant in the protection against viral infection in vivo.
Targeting HER-2/<i>neu</i>in Early Breast Cancer Development Using Dendritic Cells with Staged Interleukin-12 Burst Secretion
Authors: Brian J. Czerniecki, Gary K. Koski, Ursula Koldovsky, Shuwen Xu, Peter A. Cohen, Rosemarie Mick, Harvey Nisenbaum, Terry Pasha, Min Xu, Kevin R. Fox, Susan Weinstein, Susan G. Orel, Robert Vonderheide, George Coukos, Angela DeMichele, Louis Araujo, Francis R. Spitz, Mark Rosen, Bruce L. Levine, Carl June, Paul J. Zhang
Journal: Cancer Research (2007)

Overexpression of HER-2/neu (c-erbB2) is associated with increased risk of recurrent disease in ductal carcinoma in situ (DCIS) and a poorer prognosis in node-positive breast cancer. We therefore examined the early immunotherapeutic targeting of HER-2/neu in DCIS. Before surgical resection, HER-2/neu(pos) DCIS patients (n = 13) received 4 weekly vaccinations of dendritic cells pulsed with HER-2/neu HLA class I and II peptides. The vaccine dendritic cells were activated in vitro with IFN-gamma and bacterial lipopolysaccharide to become highly polarized DC1-type dendritic cells that secrete high levels of interleukin-12p70 (IL-12p70). Intranodal delivery of dendritic cells supplied both antigenic stimulation and a synchronized preconditioned burst of IL-12p70 production directly to the anatomic site of T-cell sensitization. Before vaccination, many subjects possessed HER-2/neu-HLA-A2 tetramer-staining CD8(pos) T cells that expressed low levels of CD28 and high levels of the inhibitory B7 ligand CTLA-4, but this ratio inverted after vaccination. The vaccinated subjects also showed high rates of peptide-specific sensitization for both IFN-gamma-secreting CD4(pos) (85%) and CD8(pos) (80%) T cells, with recognition of antigenically relevant breast cancer lines, accumulation of T and B lymphocytes in the breast, and induction of complement-dependent, tumor-lytic antibodies. Seven of 11 evaluable patients also showed markedly decreased HER-2/neu expression in surgical tumor specimens, often with measurable decreases in residual DCIS, suggesting an active process of "immunoediting" for HER-2/neu-expressing tumor cells following vaccination. DC1 vaccination strategies may therefore have potential for both the prevention and the treatment of early breast cancer.
Sequencing a mouse acute promyelocytic leukemia genome reveals genetic events relevant for disease progression
Authors: Lukas D. Wartman, David E. Larson, Zhifu Xiang, Li Ding, Ken Chen, Ling Lin, Patrick Cahan, Jeffery M. Klco, John S. Welch, Cheng Li, Jacqueline E. Payton, Geoffrey L. Uy, Nobish Varghese, Rhonda E. Ries, Mieke Hoock, Daniel C. Koboldt, Michael D. McLellan, Heather Schmidt, Robert S. Fulton, Rachel M. Abbott, Lisa Cook, Sean D. McGrath, Xian Fan, Adam F. Dukes, Tammi Vickery, Joelle Kalicki, Tamara L. Lamprecht, Timothy A. Graubert, Michael H. Tomasson, Elaine R. Mardis, Richard K. Wilson, Timothy J. Ley
Journal: Journal of Clinical Investigation (2011)

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). It is characterized by the t(15;17)(q22;q11.2) chromosomal translocation that creates the promyelocytic leukemia-retinoic acid receptor α (PML-RARA) fusion oncogene. Although this fusion oncogene is known to initiate APL in mice, other cooperating mutations, as yet ill defined, are important for disease pathogenesis. To identify these, we used a mouse model of APL, whereby PML-RARA expressed in myeloid cells leads to a myeloproliferative disease that ultimately evolves into APL. Sequencing of a mouse APL genome revealed 3 somatic, nonsynonymous mutations relevant to APL pathogenesis, of which 1 (Jak1 V657F) was found to be recurrent in other affected mice. This mutation was identical to the JAK1 V658F mutation previously found in human APL and acute lymphoblastic leukemia samples. Further analysis showed that JAK1 V658F cooperated in vivo with PML-RARA, causing a rapidly fatal leukemia in mice. We also discovered a somatic 150-kb deletion involving the lysine (K)-specific demethylase 6A (Kdm6a, also known as Utx) gene, in the mouse APL genome. Similar deletions were observed in 3 out of 14 additional mouse APL samples and 1 out of 150 human AML samples. In conclusion, whole genome sequencing of mouse cancer genomes can provide an unbiased and comprehensive approach for discovering functionally relevant mutations that are also present in human leukemias.
Phenotypic Heterogeneity and Associations of Two Aldose Reductase Gene Polymorphisms With Nephropathy and Retinopathy in Type 2 Diabetes
Authors: Ying Wang, Maggie C.Y. Ng, Shao-Chin Lee, Wing-Yee So, Peter C.Y. Tong, Clive S. Cockram, Julian A.J.H. Critchley, Juliana C.N. Chan
Journal: Diabetes Care (2003)

OBJECTIVE—We investigated the phenotypic features of diabetic microvascular complications and their association with a (CA)n microsatellite and a C/T polymorphism at the 5′ region of the aldose reductase gene (ALR2) in a consecutive cohort of 738 Chinese type 2 diabetic patients. RESEARCH DESIGN AND METHODS—Of the entire patient cohort, 392 were free of diabetes complications, or uncomplicated, 159 had diabetic nephropathy, 66 had diabetic retinopathy, and 121 had both diabetic nephropathy and retinopathy. Nephropathy was defined as urinary albumin excretion rate (AER) ≥20 μg/min and albumin-to-creatinine ratio ≥3.5 mg/mmol in two urine collections. Retinopathy was defined by the presence of hemorrhages, exudates, laser marks, and fibrous proliferation or by a history of vitrectomy. (CA)n and C/T polymorphisms were examined by PCR followed by capillary electrophoresis and digestion with BfaI, respectively. RESULTS—In the whole cohort, patients with diabetic retinopathy (n = 187) had higher blood pressure and lower BMI, while those with diabetic nephropathy (n = 280) had higher blood pressure, waist-to-hip ratio, and lipid profile than those without the respective complications. The z+6 carriers of the (CA)n polymorphism were less common in patients with diabetic retinopathy than those without diabetic retinopathy (n = 551) (4.3 vs. 9.3%, P = 0.04). The CT/TT carriers had a higher AER than the CC carriers (30.2 ×/÷ 7.2 vs. 21.9 ×/÷ 6.9 μg/min, P = 0.03). Further subgroup analysis was performed after excluding uncomplicated patients with &amp;lt;5 years disease duration. The group with both diabetic nephropathy and retinopathy had higher frequencies of the z-2 allele (25.7 vs. 16.9%, P = 0.03) and T allele (26.4 vs. 18.5%, P = 0.04) and a lower frequency of the z+6 allele (1.7 vs. 5.5%, P = 0.054) than the uncomplicated group. Multiple logistic regression analysis confirmed that z-2 carrying (odds ratio 2.6, 95% CI 1.20–5.83, P = 0.02) and CT/TT genotypes (OR 2.5, 95% CI 1.19–5.19, P = 0.02) were independent predictors for both diabetic nephropathy and retinopathy. CONCLUSIONS—Chinese type 2 diabetic patients exhibited phenotypic differences in terms of risk factors for both diabetic nephropathy and diabetic retinopathy. Both the z-2 allele of (CA)n polymorphism and T allele of ALR2 were independently associated with severe diabetic microvascular complications.
30-days mortality in patients admitted with COPD
Authors: Jakob Kjaergaard, Lone Braagaard, Jon Torgny Wilcke, Jørgen Balslev Jørgensen, Philip Tønnesen
Journal: European Respiratory Journal (2012)

Introduction:  The aim of this study was to describe 30-days mortality after hospital admission for COPD.   Methods:  This is a retrospective study of all patients with the diagnosis of COPD as a primary diagnosis or co-diagnosis admitted to a tertiary pulmonary treatment unit, Department of Respiratory Medicine, Gentofte Hospital, Denmark in 2010. The 30-days mortality is compared to the Danish National Indicator Project (NIP).   Results:  67 (15.1%) died out of 442 patients admitted with COPD within a period of 30-days after hospital admission, compared to 10% at the national level, odds ratio 1.51 (1.15 – 1.99). Mean age was 82.2 years, 55.2% were women and average BMI was 20.7. They had an average admission rate at 2.89 admissions in a period of 12 months prior to the inclusion date. Out of the 67, 23 (34.3%) received non-invasive ventilation (NIV) or respirator treatment at the respiratory unit or the intensive care unit. In 4 (5.9%) cases COPD was neither the cause of admission nor the cause of death, in further 18 (26.9%) cases COPD was not the cause of admission and 5 (7.5%) patients was wrongly diagnosed with COPD.   Conclusion:  The 30-days mortality is significantly higher at Department of Respiratory Medicine at Gentofte Hospital. Possible explanations are a selection of hospitalization of more severe cases of COPD since the department has a unique outgoing COPD-treatment unit, which treats the milder exacerbations at home. Furthermore a mortality increase due to a selection of high risk patients with complications, comorbidities and pulmonary cancer in a tertiary unit. In conclusion, the crude 30-days mortality needs further data interpretation if to be used as a measurement for quality of treatment for patients admitted with COPD.
Glutamic acid decarboxylase 67-reactive T cells: a marker of insulin-dependent diabetes.
Authors: M C Honeyman, D S Cram, L C Harrison
Journal: The Journal of Experimental Medicine (1993)

Glutamic acid decarboxylase (GAD) has been shown to be a target of autoantibodies in insulin-dependent diabetes (IDD). Two forms of GAD, with molecular weights of 67,000 and 65,000, have been cloned from separate genes. As pancreatic islet beta cell destruction DD is an autoimmune process mediated by T cells, we sought to determine if recombinant GAD67 was recognized by T cells in IDD subjects and particularly their first-degree relatives with islet cell antibodies known to be at risk for IDD. The central regions of human islet and brain GAD67 (amino acids 208-404) were cloned as fusion proteins with glutathione-S-transferase (GST). Proliferation of peripheral blood T cells in the presence of recombinant GAD67 was significantly higher in both at-risk relatives and recent-onset IDD subjects than in other autoimmune disease subjects and human histocompatibility leukocyte antigen (HLA)-matched healthy controls. Thus, 12 of 29 (41%) at-risk relatives and 11 of 29 (38%) recent-onset IDD subjects responded to GAD67, compared with 1 of 7 (14%) other autoimmune disease subjects and 1 of 23 (4%) HLA-matched controls. T cell responses to GST alone or to tetanus toxoid were not different between the groups. These findings demonstrate that GAD67 is a target autoantigen of T cells in IDD and suggest the possibility that GAD-reactive T cells may delineate asymptomatic subjects at increased risk for IDD.
Synergy between adjuvant arthritis and collagen-induced arthritis in rats.
Authors: J D Taurog, S S Kerwar, R A McReynolds, G P Sandberg, S L Leary, M L Mahowald
Journal: The Journal of Experimental Medicine (1985)

Adjuvant arthritis (AA) in rats is susceptible to cell-mediated passive transfer. Collagen-induced arthritis (CIA) in rats is susceptible to passive transfer with antibody to type II collagen. We report here the development of strikingly severe arthritis in Lewis rats as the result of synergy between passively transferred antibody to type II collagen from rats with CIA and concanavalin A (Con A)-stimulated lymph node or spleen cells from syngeneic rats with AA. Similar synergy was seen in rats with AA given anticollagen antibody, in rats with CIA given Con A-stimulated adjuvant spleen cells, and in rats actively immunized with CII and complete Freund's adjuvant. The synergistic process caused a very severe polyarthritis, characterized by marked swelling and erythema in all the joints of the distal extremities, with histologic and radiographic evidence of early, extensive erosion of articular cartilage. Synergy was apparent if the lymphoid cells from AA rats were given up to 1 mo after a single injection of anticollagen antibody. No synergy was seen when normal rat immunoglobulin or anti-ovalbumin antibody was substituted for anticollagen antibody, when Con A-stimulated lymphoid cells from normal rats or donors with CIA were used, or when Con A-stimulated AA lymphoid cells were irradiated before transfer. Synergy between separate immune effector mechanisms may represent a general phenomenon in the pathogenesis of inflammatory joint disease.
The Treatment of Consumption by the Oil of Cinnamon
Authors: J. H. Thompson
Journal: BMJ (1896)

developed.During the last 3 months of life exophthalmos very slight, and thyroid enlargement only moderate.VI. Female, aged 46.Fatal at the end of 4 years.RECOVERY.vii.Female, aged 40 in i896.I first saw this patient when liouse physician atthe ManchesterRoyalInflimary. in I884.Exophthalmos, thyroidenlargement and palpitation were then all exceedingly well inarked.CEdema of the leg.Symptoms noted 2 years previously.I examined the patient at her own home in April, I896, that is 14 years after the onset of the disease.There was then no enlargement of the thyroid, no exophthalmos.no in- creased freauency of the heart beats, the pulse was slow, rather feeble and irregular.She stated that at times she suffered from palpitation.There was no cedema.viii.Female.Thyroid enlargement, palpitation, exophthalmos, eyelids remained open duringsleep.About four years later these symptoms were all slight.Von Graefe's symptoms was present but not well marked.The patient gradually improved, and g years after the onset all thc symptoms had disappeared.ix. Female.Slight case.At the end of years, I found on examin- ation of the patient at her own liolmie, that all the symptoms had dis- appeared.x. Male.Slight case.His friends state that the symptoms disappeared.He died of appendicitis and peritonitis 8 years after the onset of tlie: symptoms of exophthalmic gottre.Dr. F. C. Bottomley kindly informed me that no indications of exophthalmic goitre were noticed during the patient's last illness.xi. Female.Slight case.The exophitlalmos soon disappeared.Then the patient suffered from several attacks of rheumatism.Nine years later, on examination, I found the physical signs of mitral stenosis.Exopltlialmos, goitre, and palpitation had all disappeared.RECOVERY ALMOST COMPLETE.
Preoperative endoscopic ultrasound-guided fine needle aspiration does not impair survival of patients with resected pancreatic cancer
Authors: Saowanee Ngamruengphong, Kristi M Swanson, Nilay D Shah, Michael B Wallace
Journal: Gut (2015)

<h3>Objective</h3> Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) allows preoperative tissue confirmation of malignancy, but fear of tumour cell dissemination along the needle track has limited its use. We hypothesised that if tumour cell dissemination occurs with EUS-FNA, survival after complete resection would be impaired. We aimed to evaluate the association of preoperative EUS-FNA with long-term outcomes of patients with resected pancreatic cancer. <h3>Design</h3> Using the linked Surveillance, Epidemiology, and End Results (SEER)–Medicare data, we identified patients with locoregional pancreatic cancer who underwent curative intent surgery from 1998 to 2009. The patients who received EUS-FNA within the peridiagnostic period were included in the EUS-FNA group. Patients who did not receive EUS evaluation or who underwent EUS without FNA were included in the non-EUS-FNA group. Overall survival and pancreatic cancer-specific survival were compared after controlling for relevant covariates. <h3>Results</h3> A total of 2034 patients with pancreatic cancer were included (90% pancreatic adenocarcinoma). Of these, 498 (24%) patients were in EUS-FNA group. Patients with multiple comorbidities and more recent diagnosis were more likely to receive EUS-FNA. In multivariate analysis, after controlling for age, race, gender, tumour histology, tumour stage, tumour grade, tumour location, SEER site, year of diagnosis, undergoing percutaneous aspiration/biopsy, Charlson Comorbidity Index, radiation and chemotherapy, EUS-FNA was marginally associated with improved overall survival (HR 0.84, 95% CI 0.72 to 0.99), but did not affect cancer-specific survival (HR 0.87, 95% CI 0.74 to 1.03). <h3>Conclusions</h3> Preoperative EUS-FNA was not associated with increased risk of mortality. These data suggest that EUS-FNA can be safely performed for the work-up of suspicious pancreatic lesions.
Porcine transcriptome analysis based on 97 non-normalized cDNA libraries and assembly of 1,021,891 expressed sequence tags
Authors: Jan Gorodkin, Susanna Cirera, Jakob Hedegaard, Michael J. Gilchrist, Frank Panitz, Claus B. Jørgensen, Karsten Scheibye-Knudsen, Troels Arvin, Steen Lumholdt, Milena Sawera, Trine Green, Bente J Nielsen, Jakob H Havgaard, Carina Rosenkilde, Jun-Jun Wang, Heng Li, Ruiqiang Li, Bin Liu, Songnian Hu, Wei Dong, Wei Li, Jun Qing Yu, Jian Wang, Hans-Henrik Stærfeldt, Rasmus Wernersson, Lone B Madsen, Bo Thomsen, Henrik Hornshøj, Zhan Bujie, Xuegang Wang, Xuefei Wang, Lars Bolund, Søren Brunak, Huanming Yang, Christian Bendixen, Merete Fredholm
Journal: Genome biology (2007)

Knowledge of the structure of gene expression is essential for mammalian transcriptomics research. We analyzed a collection of more than one million porcine expressed sequence tags (ESTs), of which two-thirds were generated in the Sino-Danish Pig Genome Project and one-third are from public databases. The Sino-Danish ESTs were generated from one normalized and 97 non-normalized cDNA libraries representing 35 different tissues and three developmental stages. Using the Distiller package, the ESTs were assembled to roughly 48,000 contigs and 73,000 singletons, of which approximately 25% have a high confidence match to UniProt. Approximately 6,000 new porcine gene clusters were identified. Expression analysis based on the non-normalized libraries resulted in the following findings. The distribution of cluster sizes is scaling invariant. Brain and testes are among the tissues with the greatest number of different expressed genes, whereas tissues with more specialized function, such as developing liver, have fewer expressed genes. There are at least 65 high confidence housekeeping gene candidates and 876 cDNA library-specific gene candidates. We identified differential expression of genes between different tissues, in particular brain/spinal cord, and found patterns of correlation between genes that share expression in pairs of libraries. Finally, there was remarkable agreement in expression between specialized tissues according to Gene Ontology categories. This EST collection, the largest to date in pig, represents an essential resource for annotation, comparative genomics, assembly of the pig genome sequence, and further porcine transcription studies.