tbuckley/cabot-search huggingface dataset:
Examining the influence of early life socioeconomic position on pulmonary function across the life span: where do we go from here?
Authors: B Jackson
Journal: Thorax (2004)

A further step in the process of developing better service and standards of care for patients with COPD T he full version of the new NICE guidelines on the management of chronic obstructive pulmonary disease (COPD) is published as a supplement to this issue of Thorax. 1 These guidelines have been developed for the National Institute for Clinical Excellence (NICE) by the National Collaborating Centre for Chronic Conditions (NCC-CC) based at the Royal College of Physicians, London with the involvement of
Reoperation, Myocardial Infarction and Mortality after Transurethral and Open Prostatectomy: A Nation-Wide, Long-Term Analysis of 23,123 Cases
Authors: Stephan Madersbacher, Jakob Lackner, Clemens Brössner, Michaela Röhlich, Igor Stancik, Manfred Willinger, Georg Schatzl
Journal: European Urology (2005)
Twenty-Two Years of Phase III Trials for Patients With Advanced Non–Small-Cell Lung Cancer: Sobering Results
Authors: Oscar S. Breathnach, Boris Freidlin, Barbara Conley, Mark R. Green, David H. Johnson, David R. Gandara, Michael O’Connell, Frances A. Shepherd, Bruce E. Johnson
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the changes in clinical trials and outcomes of patients with advanced-stage non–small-cell lung cancer (NSCLC) treated on phase III randomized trials initiated in North America from 1973 to 1994. PATIENTS AND METHODS: Phase III trials for patients with advanced-stage NSCLC were identified through a search of the National Cancer Institute’s Cancer Therapy Evaluation Program database from 1973 to 1994, contact with Cooperative Groups, and by literature search of MEDLINE. Patients with advanced NSCLC treated during a similar time interval were also examined in the SEER database. Trends were tested in the number of trials, in the number and sex of patients entered on the trials, and in survival over time. RESULTS: Thirty-three phase III trials were initiated between 1973 and 1994. Twenty-four trials (73%) were initiated within the first half of this period (1973 to 1983) and accounted for 5,359 (64%) of the 8,434 eligible patients. The median number of patients treated per arm of the trials rose from 77 (1973 to 1983) to 121 (1984 to 1994) (P &lt; .001). Five trials (15%) showed a statistically significant difference in survival between treatment arms, with a median prolongation of the median survival of 2 months (range, 0.7 to 2.7 months). CONCLUSION: Analysis of past trials in North America shows that the prolongation in median survival between two arms of a randomized study was rarely in excess of 2 months. Techniques for improved use of patient resources and appropriate trial design for phase III randomized therapeutic trials with patients with advanced NSCLC need to be developed.
Clustering of Adverse Drug Events: Analysis of Risk Factors for Cerebellar Toxicity With High-Dose Cytarabine
Authors: H. M. Jolson, L. Bosco, M. G. Bufton, B. B. Gerstman, S. S. Rinsler, E. Williams, B. Flynn, W. D. Simmons, B. V. Stadel, G. A. Faich, C. Peck
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Cerebellar toxicity is a severe, therapy-limiting adverse reaction of cytarabine given in high doses. The Food and Drug Administration received a report of an increased frequency of cerebellar toxicity at the University of Wisconsin Hospital and Clinics after a switch from the product (Cytosar-U) manufactured by The Upjohn Co., Kalamazoo, Mich., to the generic form made by Quad Pharmaceuticals, Inc., Indianapolis, Ind. Purpose : To compare the incidence of cerebellar toxicity in Quad-treated patients with Upjohn-treated patients, a record-based cohort study was conducted at the University of Wisconsin Hospital and Clinics between January 1986 and August 1989. Methods : The incidence of cerebellar toxicity was studied in 63 leukemia patients according to the manufacturer of the product received (34 Upjohn only, 25 Quad only, and four both manufacturers). The relative risk of cerebellar toxicity was adjusted for other known risk factors. Results : Patients in the manufacturer-defined treatment groups did not differ significantly with respect to age, sex, type of leukemia, disease stage, calculated creatinine clearance, presence of abnormal liver function tests, or total dose received. The crude relative risk of cerebellar toxicity comparing the Quad product with the Upjohn product was 5.0 (95% confidence interval = 1.8–13.7). Adjustment for potential confounders did not alter the association. Other risk factors for cerebellar toxicity, independent of manufacturer, were age greater than 50 years, type of leukemia, disease stage, total dose greater than or equal to 20 g/m, abnormal pretreatment liver function, and reduced creatinine clearance. Conclusion : This study found a significantly higher incidence of cerebellar toxicity with high-dose cytarabine manufactured by Quad Pharmaceuticals when compared with the incidence of cerebellar toxicity with the Upjohn product. Further research at independent institutions would be necessary to allow generalization of this finding. In addition, our findings suggest that a dose reduction in high-dose cytarabine therapy may be indicated for patients with reduced glomerular filtration rates. [J Natl Cancer Inst 84: 500–505, 1992]
Myeloid-derived suppressor cells in pancreatic cancer: more than a hidden barrier for antitumour immunity?
Authors: Tim F Greten
Journal: Gut (2014)

Myeloid-derived suppressor cells (MDSC) represent an immune cell subset with profound immune suppressor function. Initially described in 1978 as natural suppressor cells, this cell type has gained significant attention in recent years not only among tumour immunologists but also among medical oncologists interested both in developing new immune-based antitumour strategies and trying to understand how conventional non-immunological therapies affect antitumour immune responses.1 MDSC represent a mixture of immature cell types that accumulate in tumour-bearing mice and patients with cancer. Tumour-derived factors block the maturation of myeloid cells at different stages, leading to accumulation of these cells in tumours, as well as in the periphery. At least two different subsets of MDSC have been described in mice and men: monocytic and polymorphonuclear granulocytic MDSC, which can be identified as CD14+HLA-DRlo/neg and linnegCD11b+HLA-DRneg in patients2 and as CD11b+Ly6G+ Ly6Clow or CD11b+Ly6Gneg Ly6Chi in mice.3

An accumulation of MDSC has been described in multiple models of pancreatic cancer. We have been able to demonstrate an accumulation of MDSC in mice with premalignant lesions.4 Similarly, an accumulation of MDSC, regulatory T cells and tumour-associated macrophages has been described in KC mice, …
Salt in Hypertension and the Effects of Diuretics
Authors: Edward D. Freis
Journal: The Annual Review of Pharmacology and Toxicology (1979)

Shortly after hypertension was recognized as a clinical disorder Ambard & Beaujard (1) in 1904 proposed that it was due to a failure to adapt to an excess of salt in the diet. In this country Allen (2) was the first to carry out careful dietary studies showing that severe restriction of salt in the diet reduced blood pressure in about 60% of hypertensive patients. Allen, like the French before him, believed that hypertension was due to an unknown renal defect with respect to the excretion of salt. His work was not generally accepted, however, and it was not until 25 years later that the dietary treatment of hypertension was finally popularized by Kempner (3) with his so-called rice-and-fruit diet. Whereas Kempner believed the antihyperten­ sive effect of the diet was due primarily to protein restriction it was later demonstrated conclusively by Murphy (4) and by Watkin et al (5) that it was due to the extremely low sodium content of the diet. These clinical reports called attention to the importance of salt in the maintenance of hypertension, which in recent years has received additional strong support from epidemiological studies.
Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice I. Xenotropic virus.
Authors: S K Datta, N Manny, C Andrzejewski, J André-Schwartz, R S Schwartz
Journal: The Journal of Experimental Medicine (1978)

The relationship between expression of xenotropic virus and the development of autoimmunization was studied in the progeny of crosses between New Zealand Black (NZB) and SWR mice. The (F1 X SWR) and F2 progeny segregated into three phenotypes: high-virus, low-virus, and virus-negative; F1 and (F1 X NZB) progeny were always high-virus. Autoantibodies, immune deposit nephritis and lymphomas developed in the progeny of these crosses. The virological phenotype of the animal could be dissociated from the presence of either autoantibodies or nephritis. For example, mice that expressed titers of virus as high as the NZB parent failed to develop signs of autoimmunization, even up to 24 mo of age. By contrast, some (F1 X SWR) and F2 mice that expressed low titers of virus developed autoimmune disease. Furthermore, a proportion of virus-negative mice produced autoantibodies and were found to have typical immune deposit nephritis. No viral antigens could be detected in the renal lesions of such virus-negative animals. By contrast with the dissociation between expression of virus and occurrence of nephritis, the presence of antibodies to DNA correlated with the development of renal lesions. We conclude that the genes that determine the expression of infectious xenotropic virus in NZB mice segregate independently from those that are involved in the autoimmune disease of these animals.
Macrolide therapy in asthma: limited treatment, long-term improvement
Authors: D. L. Hahn
Journal: European Respiratory Journal (2009)

Macrolide therapy in asthma: limited treatment, long-term improvementTo the Editors:As part of their interesting review of long-term macrolide therapy in chronic inflammatory airway diseases, CROSBIE and WOODHEAD [1] cite eight randomised double-blind placebocontrolled trials of macrolide therapy in asthma.Most were small, and all were short-term (none .12weeks).Some positive effects were noted; mechanisms proffered included both anti-inflammatory and antimicrobial (including against Chlamydia pneumoniae).
Racial Differences in Urinary Potassium Excretion
Authors: Sharon Turban, Edgar R. Miller, Brett Ange, Lawrence J. Appel
Journal: Journal of the American Society of Nephrology (2008)

Racial differences in potassium (K) intake and urinary K excretion may contribute to the higher BP observed in black compared with white individuals. Although black individuals typically consume less dietary K than white individuals, the lower urinary K excretion observed in black individuals may reflect more than differences in intake. In this study, data from the Dietary Approaches to Stop Hypertension (DASH) trial (413 white and black participants) were used to evaluate urinary K excretion in black and white individuals with similar K intake. At screening, mean urinary K excretion was higher in white than black individuals (mean Δ = 645 mg/d for white minus black individuals, adjusted for age, gender, and weight; P < 0.001). After a 3-wk run-in period during which all participants received a low-K control diet, a significant racial difference remained (mean Δ = 201 mg/d, adjusted for age, gender, and caloric intake; P < 0.001). Participants were then randomly assigned to continue the control diet or switch to a high-K diet (either a high fruit/vegetable diet or the DASH diet) for 8 wk. At the end of intervention, the mean difference in urinary K in white compared with black individuals after adjustment for age, gender, and caloric intake was −6 mg/d (P = 0.95) in the control group, 163 mg/d in the fruits/vegetables group (P = 0.39), and 903 mg/d in the DASH group (P < 0.001). Racial differences in urinary K excretion seem to reflect more than intake differences; further studies are needed to understand their potential impact on clinical outcomes.
High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas.
Authors: J A Fagin, K Matsuo, A Karmakar, D L Chen, S H Tang, H P Koeffler
Journal: Journal of Clinical Investigation (1993)

The development and progression of thyroid tumors is signaled by phenotype-specific mutations of genes involved in growth control. Molecular events associated with undifferentiated thyroid cancer are not known. We examined normal, benign, and malignant thyroid tissue for structural abnormalities of the p53 tumor suppressor gene. Mutations were detected by single-strand conformation polymorphisms of PCR-amplified DNA, using primers bracketing the known hot spots on either exons 5, 6, 7, or 8. The prevalence of mutations was as follows: normal thyroid 0/6; follicular adenomas 0/31; papillary carcinomas 0/37; medullary carcinomas 0/2; follicular carcinomas 1/11; anaplastic carcinomas 5/6; thyroid carcinoma cell lines 3/4. Positive cases were confirmed by direct sequencing of the PCR products. All five anaplastic carcinoma tissues and the anaplastic carcinoma cell line ARO had G:C to A:T transitions leading to an Arg to His substitution at codon 273. In both tumors and cell lines, examples of heterozygous and homozygous p53 mutations were identified. The only thyroid carcinoma cell line in which p53 mutations were not detected in exons 5-8 had markedly decreased p53 mRNA levels, suggesting the presence of a structural abnormality of either p53 itself or of some factor controlling its expression. The presence of p53 mutations almost exclusively in poorly differentiated thyroid tumors and thyroid cancer cell lines suggests that inactivation of p53 may confer these neoplasms with aggressive properties, and further loss of differentiated function.
Promoter Hypermethylation of Resected Bronchial Margins
Authors: Mingzhou Guo, Michael G. House, Craig Hooker, Yu Han, Elizabeth Heath, Edward Gabrielson, Stephen C. Yang, Stephen B. Baylin, James G. Herman, Malcolm V. Brock
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Histologically positive bronchial margins after resection for non-small cell lung cancer are associated with shortened patient survival due to local recurrence. We hypothesized that DNA promoter hypermethylation changes at bronchial margins could be detected in patients with no histological evidence of malignancy and that they would reflect epigenetic events in the primary tumor. Experimental Design: Bronchial margins, primary tumor, bronchoalveolar fluid, and paired nonmalignant lung were obtained from 20 non-small cell lung cancer patients who underwent a lobectomy or greater resection. Disease-specific recurrence was the primary end point. The methylation status of p16, MGMT, DAPK, SOCS1, RASSF1A, COX2, and RARβ was examined using methylation-specific polymerase chain reaction. Results: All malignancies had methylation in at least one locus. Concordance of one gene with an identical epigenetic change in the tumor or bronchial margin was observed in 85% of patients. Only one patient had methylation at the bronchial margin for a gene that was not methylated in the corresponding tumor. Median time to recurrence was 37 months (range, 5–71 months). There were two local recurrences and five metastases. There were no significant correlations between DNA methylation in tumor, margins, or bronchoalveolar fluid specimens and either regional recurrence or distant metastases. Conclusions: Histologically negative bronchial margins of resected non-small cell lung cancer exhibit frequent hypermethylation changes in multiple genes. These hyper-methylation abnormalities are also present in the primary tumor and thus may represent a field defect of preneoplastic changes that occurs early in carcinogenesis.
Aminoacridine-precipitable polyuronide (AAPP) excretion in rheumatoid arthritis: preliminary results.
Authors: T Bitter
Journal: Annals of the Rheumatic Diseases (1969)

encouraging but far less dramatic than in the animal".Carl Pearson and his colleagues give an interesting account of the aortic ring lesions in relapsing poly- chondritis.These papers are all presented in a well-produced and abundantly illustrated book with a clear and well laid-out text.Since many of the communica- tions take the form of a review, it is a pity that, although most of the papers are accompanied by adequate references which should prove useful in themselves, the discussions which followed the papers have been omitted.Many readers will be left with the feeling that this is what they would have most liked to read if they had not been able to attend the Congress.Events in rheumatology are moving faster than the publishers-there was an interval of 2 years between this Conference and its publication, which is much too long.MICHAEL MASON Aids and Adaptations.Published by the Occupa- tional Therapy Department of the Canadian Arthritis and Rheumatism Society.1969.Pp. 55, 41 figs.($2.)This handbook contains the designs of a number of simple aids and adaptations suitable for the arthritic patient, together with instructions as to how they can be assembled.One ofits main features is the number of excellent line drawings.A word of caution is needed if books like this are to be used like a sales catalogue by the patients themselves.They are not a substitute for the careful assessment of the needs of each individual, but nonetheless this booklet should prove a useful source of ideas for those doctors and therapists anxious to provide as comprehensive a service as possible for their arthritic patients.
Structure and specificity of T cell receptors expressed by potentially pathogenic anti-DNA autoantibody-inducing T cells in human lupus.
Authors: A Desai-Mehta, C Mao, S Rajagopalan, T Robinson, S K Datta
Journal: Journal of Clinical Investigation (1995)

The production of potentially pathogenic anti-DNA autoantibodies in SLE is driven by special, autoimmune T helper (Th) cells. Herein, we sequenced the T cell receptor (TCR) alpha and beta chain genes expressed by 42 autoimmune Th lines from lupus patients that were mostly CD4+ and represented the strongest inducers of such autoantibodies. These autoimmune TCRs displayed a recurrent motif of highly charged residues in their CDR3 loops that were contributed by N-nucleotide additions and also positioned there by the recombination process. Furthermore, Th lines from four of the five patients showed a marked increase in the usage of the V alpha 8 gene family. Several independent Th lines expressed identical TCR alpha and/or beta chain sequences indicating again antigenic selection. 10 of these Th lines could be tested further for antigenic specificity. 4 of the 10 pathogenic anti-DNA autoantibody-inducing Th lines responded to the non-histone chromosomal protein HMG and two responded to nucleosomal histone proteins; all presented by HLA-DR molecules. Another Th line responded to purified DNA more than nucleosomes. Thus, these autoimmune Th cells of lupus patients respond to charged epitopes in various DNA-binding nucleoproteins that are probably processed and presented by the anti-DNA B cells they selectively help.
Reversal of the Adynamic Bone Disorder and Decreased Vascular Calcification in Chronic Kidney Disease by Sevelamer Carbonate Therapy
Authors: Suresh Mathew, Richard J. Lund, Frank Strebeck, Kimberly S. Tustison, Theresa Geurs, Keith A. Hruska
Journal: Journal of the American Society of Nephrology (2006)

A model of chronic kidney disease (CKD)-induced vascular calcification (VC) that complicates the metabolic syndrome was produced. In this model, the metabolic syndrome is characterized by severe atherosclerotic plaque formation, hypertension, type 2 diabetes, obesity, and hypercholesterolemia, and CKD stimulates calcification of the neointima and tunica media of the aorta. The CKD in this model is associated the adynamic bone disorder form of renal osteodystrophy. The VC of the model is associated with hyperphosphatemia, and control of the serum phosphorus both in this animal model and in humans has been preventive in the development of VC. This article reports studies that demonstrate reduction of established VC by the addition of sevelamer carbonate to the diets of this murine metabolic syndrome model with CKD. Sevelamer, besides normalizing the serum phosphorus, surprisingly, reversed the CKD-induced trabecular osteopenia. Sevelamer therapy increased osteoblast surfaces in the metaphyseal trabeculae of the tibia and femur. It also increased osteoid surfaces and, importantly, bone formation rates. In addition, sevelamer was found to be effective in decreasing serum cholesterol levels. These results suggest that sevelamer may have important actions in decreasing diabetic and uremic vasculopathy and that sevelamer carbonate may be capable of increasing bone formation rates that are suppressed by diabetic nephropathy.
Characterization of Ascaris lumbricoides Tropomyosin: Use of Recombinant Protein to Investigate IgE Antibody Responses
Authors: A.B.R. Santos, G.C. Arruda, A.S. Zampolo, M.C. Rodrigues, V.P.L. Ferriani, C. Oliver, M.S. Palma, V.S. Sales, L.K. Arruda
Journal: Journal of Allergy and Clinical Immunology (2007)
Resolution of the two components of macrophage inflammatory protein 1, and cloning and characterization of one of those components, macrophage inflammatory protein 1 beta.
Authors: B Sherry, P Tekamp-Olson, C Gallegos, D Bauer, G Davatelis, S D Wolpe, F Masiarz, D Coit, A Cerami
Journal: The Journal of Experimental Medicine (1988)

A number of macrophage-derived mediators have been implicated in the vascular changes of inflammation. We recently reported the isolation of a novel monokine, macrophage inflammatory protein 1 (MIP-1), which causes local inflammatory responses in vivo, and induces superoxide production by neutrophils in vitro. Purified native MIP-1 comprises two peptides with very similar physical characteristics. We report here the resolution of MIP-1 into component peptides by SDS-hydroxylapatite chromatography, and compare the NH2-terminal sequences of the two peptides, now referred to as MIP-1 alpha and MIP-1 beta. A synthetic oligonucleotide probe pool corresponding to the NH2-terminal amino acid sequence of MIP-1 beta was used to isolate a cDNA clone containing its coding sequence. The sequence codes for a 109 amino acid-long polypeptide, of which 69 amino acids correspond to the mature product. Comparison of this MIP-1 beta cDNA with our previously cloned MIP-1 alpha sequence reveals that the MIP-1 peptides, members of a growing family of potential inflammatory mediators, are distinct but highly homologous (58.9% sequence identity) products of different genes.