tbuckley/cabot-search huggingface dataset:
AUTOLOGOUS IMMUNE COMPLEX NEPHRITIS INDUCED WITH RENAL TUBULAR ANTIGEN
Authors: Richard J. Glassock, Thomas S. Edgington, J. Ian Watson, Frank J. Dixon
Journal: The Journal of Experimental Medicine (1968)

The pathogenetic mechanism involved in a form of experimental allergic glomerulonephritis induced by immunization of rats with renal tubular antigen has been investigated. A single immunization with less than a milligram of a crude renal tubular preparation, probably containing less than 25 microg of the specific nephritogenic antigen, is effective in the induction of this form of chronic membranous glomerulonephritis. In the nephritic kidney autologous nephritogenic tubular antigen is found in the glomerular deposits along with gamma-globulin and complement. When large amounts of antigen are injected during induction of the disease the exogenous immunizing antigen can also be detected in the glomerular deposits. It appears that this disease results from the formation of circulating antibodies capable of reacting with autologous renal tubular antigen(s) and the deposition of these antibodies and antigen(s) plus complement apparently as immune complexes in the glomeruli. This pathogenetic system has been termed an autologous immune complex disease and the resultant glomerulonephritis has been similarly designated.
Factors influencing duration of exposure with symptoms and costs of occupational asthma
Authors: D. Miedinger, J-L. Malo, H. Ghezzo, J. L'Archevêque, M-V. Zunzunegui
Journal: European Respiratory Journal (2010)

The most important factor for the prognosis of occupational asthma is the length of exposure with symptoms prior to removal from exposure. We wanted to identify factors, including socioeconomic status, that can influence the delay in submitting a claim to a medicolegal agency after the onset of asthmatic symptoms, and to confirm that this delay is associated with worse respiratory prognosis and higher direct costs. This is a cross-sectional study of subjects who claimed compensation for occupational asthma at the Workers' Compensation Board of Quebec, Canada. Data were collected at re-evaluation ∼2.5 yrs after diagnosis. Information on the number of years with symptoms and removal from exposure was obtained from the medicolegal file. 60 subjects were included in the study. Being older, having a revenue of &gt;30,000 Canadian dollars and having occupational asthma due to high molecular weight agents were all positively associated with the number of years of exposure with symptoms before removal from exposure. Subjects with persistent airway hyperresponsiveness at follow-up had a higher number of years with symptoms. Experiencing symptoms in the workplace for &lt;1 yr generated lower direct costs. These findings might help in surveillance programmes that could be preferentially targeted for these subgroups of workers.
Prospective Randomized Trial of Low- Versus High-Dose Radiation Therapy in Adults With Supratentorial Low-Grade Glioma: Initial Report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group Study
Authors: E. Shaw, R. Arusell, B. Scheithauer, J. O’Fallon, B. O’Neill, R. Dinapoli, D. Nelson, J. Earle, C. Jones, T. Cascino, D. Nichols, R. Ivnik, R. Hellman, W. Curran, R. Abrams
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To compare survival and toxicity in adult patients treated with low-dose (50.4 Gy/28 fractions) versus high-dose (64.8 Gy/36 fractions) localized radiation therapy (RT) for supratentorial low-grade astrocytoma, oligodendroglioma, and mixed oligoastrocytoma. PATIENTS AND METHODS: From 1986 to 1994, 203 eligible/analyzable patients were randomized: 101 to low-dose RT, 102 to high-dose RT. Almost half were younger than 40 years, and 95% had grade 2 tumors. Histologic subtype was astrocytoma (or mixed oligo-astrocytoma with astrocytoma dominant) in 32% of patients and oligodendroglioma (or oligoastrocytoma with oligodendroglioma dominant) in 68%. Tumor diameter was less than 5 cm in 35% of patients, and 41% of tumors showed some degree of contrast enhancement. Extent of resection was gross total in 14% of patients, subtotal in 35%, and biopsy only in 51%. RESULTS: At the time of the present analysis, 83 patients (41%) are dead, and median follow-up is 6.43 years in the 120 who are still alive. Survival at 2 and 5 years is nonsignificantly better with low-dose RT; survival at 2 and 5 years was 94% and 72%, respectively, with low-dose RT and 85% and 64%, respectively, with high-dose RT (log rank P = .48). Multivariate analysis identified histologic subtype, tumor size, and age as the most significant prognostic factors. Survival is significantly better in patients who are younger than 40 years and in patients who have oligodendroglioma or oligo-dominant histology. Grade 3 to 5 radiation neurotoxicity (necrosis) was observed in seven patients, with one fatality in each treatment arm. The 2-year actuarial incidence of grade 3 to 5 radiation necrosis was 2.5% with low-dose RT and 5% with high-dose RT. CONCLUSION: This phase III prospective randomized trial of low- versus high-dose radiation therapy for adults with supratentorial low-grade astrocytoma, oligodendroglioma, and oligoastrocytoma found somewhat lower survival and slightly higher incidence of radiation necrosis in the high-dose RT arm. The most important prognostic factors for survival are histologic subtype, tumor size, and age. The study design of the ongoing intergroup trial in this population will be discussed.
Nonrecombining Genes in a Recombination Environment: The Drosophila "Dot" Chromosome
Authors: J. R. Powell, K. Dion, M. Papaceit, M. Aguade, S. Vicario, R. C. Garrick
Journal: Molecular Biology and Evolution (2010)

Rate of recombination is a powerful variable affecting several aspects of molecular variation and evolution. A nonrecombining portion of the genome of most Drosophila species, the "dot" chromosome or F element, exhibits very low levels of variation and unusual codon usage. One lineage of Drosophila, the willistoni/saltans groups, has the F element fused to a normally recombining E element. Here, we present polymorphism data for genes on the F element in two Drosophila willistoni and one D. insularis populations, genes previously studied in D. melanogaster. The D. willistoni populations were known to be very low in inversion polymorphism, thus minimizing the recombination suppression effect of inversions. We first confirmed, by in situ hybridization, that D. insularis has the same E + F fusion as D. willistoni, implying this was a monophyletic event. A clear gradient in codon usage exists along the willistoni F element, from the centromere distally to the fusion with E; estimates of recombination rates parallel this gradient and also indicate D. insularis has greater recombination than D. willistoni. In contrast to D. melanogaster, genes on the F element exhibit moderate levels of nucleotide polymorphism not distinguishable from two genes elsewhere in the genome. Although some linkage disequilibrium (LD) was detected between polymorphic sites within genes (generally <500 bp apart), no long-range LD between F element loci exists in the two willistoni group species. In general, the distribution of allele frequencies of F element genes display the typical pattern of expectations of neutral variation at equilibrium. These results are consistent with the hypothesis that recombination allows the accumulation of nucleotide variation as well as allows selection to act on synonymous codon usage. It is estimated that the fusion occurred ∼20 Mya and while the F element in the willistoni lineage has evolved "normal" levels and patterns of nucleotide variation, equilibrium may not have been reached for codon usage.
Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallel-group study
Authors: Marc L Decramer, Kenneth R Chapman, Ronald Dahl, Peter Frith, Gilles Devouassoux, Carlos Fritscher, Ray Cameron, Muhammad Shoaib, David Lawrence, David Young, Danny McBryan
Journal: The Lancet Respiratory Medicine (2013)
Association of the P-Glycoprotein Transporter MDR1 C3435T Polymorphism with the Susceptibility to Renal Epithelial Tumors
Authors: Michael Siegsmund, Ulrich Brinkmann, Elke Scha[Combining Acute Accent]ffeler, Gregor Weirich, Matthias Schwab, Michel Eichelbaum, Peter Fritz, Oliver Burk, Jochen Decker, Peter Alken, Uwe Rothenpieler, Reinhold Kerb, Sven Hoffmeyer, Hiltrud Brauch
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Except for hereditary disease, genetic factors that contribute to the development of renal epithelial tumors are unknown. There is a possibility that the <i>MDR1</i> encoded plasma membrane transporter P-glycoprotein (PGP) influences the risk of development of renal neoplasms. PGP is known to be involved in uptake, binding, transport, and distribution of xenobiotics. There is evidence that the <i>MDR1</i><sup><i>C3435T</i></sup> polymorphism drives expression and modulates disease risk. In an explorational case-control study, constitutional genotype frequencies were established at <i>MDR1</i><sup><i>C3435T</i></sup> of 537 healthy control subjects and compared with those of 212 patients with renal epithelial tumors. There were 179 clear cell renal cell carcinoma (CCRCC) and 33 tumors collectively assigned as non-CCRCC. In a second study, genotypes of another 150 healthy control subjects and 50 patients with three non-CCRCC types (26 papillary RCC, 11 chromophobe RCC, and 13 renal oncocytic adenoma) were compared. PCR-restriction fragment length polymorphism–based analysis of constitutional DNA, and statistical analysis were applied. PGP expression was analyzed by quantitative immunohistochemistry. The explorational study showed a significant association between T allele frequency and the occurrence of tumors (<i>P</i> = 0.007). When tumors were histopathologically distinguished into frequent CCRCC and less frequent non-CCRCC, both patient groups contributed to this effect with a seemingly strong influence by the latter (<i>P</i> = 0.0419). The second study established the T allele as a risk factor especially for non-CCRCC (<i>P</i> = 0.0005) with the highest risk for homozygote TT allele carriers (<i>P</i> &lt; 0.0001). Independently, <i>MDR1</i><sup><i>C3435T</i></sup> genotype associated variations in PGP expression were shown in normal renal parenchyma with a 1.5-fold difference of median values (TT, 1.9; CC, 2.8; <i>P</i> = 0.0065). The data provide evidence for PGP to influence the susceptibility to develop renal epithelial tumors by virtue of its <i>MDR1</i><sup><i>C3435T</i></sup> polymorphism and changes in expression. Especially T and TT carriers are at risk for developing non-CCRCC, <i>i.e.,</i> papillary and chromophobe RCC as well as oncocytic adenomas.
Identification of <i>cis</i> Elements in the Cardiac Troponin T Gene Conferring Specific Expression in Cardiac Muscle of Transgenic Mice
Authors: Q. Wang, C. D. Sigmund, J. J.-C. Lin
Journal: Circulation Research (2000)

Abstract —To investigate the underlying mechanism regulating cardiac gene expression, transgenic mice carrying the rat cardiac troponin T proximal promoter (−497 bp from the transcriptional start site) fused to a LacZ or chloramphenicol acetyltransferase ( CAT ) reporter gene were analyzed. The LacZ expression pattern throughout development was very similar to that of the endogenous cardiac troponin T gene. Within this promoter, a high degree of sequence homology was found at 2 sites, modules D (−335 to −289 bp) and F (−249 to −209 bp). Both regions contain at least a TCTG(G/C) direct repeat and an A/T-rich site, whereas only the F module has a muscle enhancer factor 2 (MEF2)-like motif. No significant decrease in CAT transgene expression was observed when only the MEF2 core sequence was mutated. However, when the MEF2 core sequence and its flanking TCTGG site were mutated (Mut5), CAT transgene expression was significantly decreased in the heart, and ectopic expression of the transgene was also observed. When mutations were introduced into this promoter to destroy all upstream TCTG(G/C) direct repeats in the D module (MutD), CAT expression remained cardiac specific, but the expression level was dramatically decreased. Relaxation of cardiac-specific transgene expression became even more severe in transgenic mice carrying double mutations (Mut[D+5]). In addition, CAT activity in the heart was nearly abolished. These results suggest that D and F modules have an additive function in determining the level of expression in the heart and only the F module confers cardiac-specific expression.
Effects of fibrinogen derivatives upon the inflammatory response. Studies with human fibrinopeptide B.
Authors: R M Senior, W F Skogen, G L Griffin, G D Wilner
Journal: Journal of Clinical Investigation (1986)

Fibrin formation and turnover are intimately associated with inflammation and wound healing. To explore whether fibrin(ogen)-derived peptides exert direct effects upon cells involved in inflammation and tissue repair we examined the capacity of human fibrinopeptide B (hFpB), a thrombin-derived proteolytic cleavage product of the fibrinogen B beta-chain, to stimulate neutrophils (PMN), monocytes, and fibroblasts. hFpB caused directed cell migration of PMN and fibroblasts that was optimal at approximately 10(-8) M. This chemotactic activity was blocked by preincubating hFpB with antiserum to hFpB. hFpB was not chemotactic for monocytes. The chemotactic potency of hFpB for PMN was equivalent to that of anaphylatoxin from the fifth component of human complement (C5a), leukotriene B4 (LTB4), and formyl-methionyl-leucyl-phenylalanine (fMLP), and for fibroblasts its chemotactic activity was comparable to that of platelet-derived growth factor. hFpB did not interact with PMN receptors for C5a, LTB4, or fMLP as (a) desensitization with 10(-7) M hFpB abolished chemotaxis to hFpB but had no effect upon chemotaxis to C5a, LTB4, or fMLP and (b) induction of chemotactic responses to fMLP and LTB4 in neutrophilic leukemic cells (HL-60 cells) by incubation with dimethylsulfoxide did not extend to hFpB. Like fMLP, hFpB caused a rapid, dose-dependent increase in PMN cytoskeletal associated actin, but unlike fMLP, hFpB did not cause PMN aggregation, release of lysosomal enzymes (lysozyme and beta-glucuronidase), or the production of superoxide anion. These results suggest that hFpB may have a role in recruiting PMN and fibroblasts at sites of fibrin deposition and turnover. The capacity of hFpB to cause PMN chemotaxis without causing concurrent release of lysosomal enzymes or the production of superoxide anion is further evidence for the complexity of PMN responses to chemotactic agents.
Mechanism of vascular hyperresponsiveness in the spontaneously hypertensive rat.
Authors: L T Lais, M J Brody
Journal: Circulation Research (1975)

Hyperresponsiveness of resistance vessels has been described in various vascular beds of spontaneously hypertensive rats perfused with artificial medium. This change has been attributed to altered vascular dimensions secondary to the development of hypertension. To test the possibility that true changes in sensitivity might contribute independently to vasoconstrictor hyperresponsiveness in spontaneously hypertensive rats, threshold vasoconstrictor doses of norepinephrine and barium chloride were determined in denervated hindquarters of rats perfused at constant flow with autologous blood. Threshold constrictor responses to norepinephrine were elicited in the hypertensive rats at concentrations averaging less than one-third that required in controls. Threshold vasoconstrictor concentrations of barium were not significantly different between the two groups. The ratio of norepinephrine/barium sensitivity was also significantly elevated in the hypertensive group. These data suggest that in the presence of a full humoral complement, excitability (barium sensitivity) in resistance vessels of spontaneously hypertensive rats is not altered, whereas the smooth muscle is hypersensitive to norepinephrine. Thus, it appears that changes in sensitivity as well as altered vascular geometry are important in the production of vascular hyperresponsiveness in the spontaneously hypertensive rat.
Terminal deoxynucleotidyl transferase is found in prothymocytes
Authors: AE Silverstone, H Cantor, G Goldstein, D Baltimore
Journal: The Journal of Experimental Medicine (1976)

Terminal deoxynucleotidyl transferase is an enzyme which has the unique property of polymerizing polydeoxynucleotides onto a primer in the absence of a template (1,2). This enzyme is found both in the thymus and the bone marrow of birds, rodents, and humans (3-7). Whether the marrow cells that contain terminal transferase are related to thymocytes, or are on a separate pathway of differentiation, is not yet known (7,8). To determine the lineage of the murine bone marrow cells that have terminal transferase, we have investigated whether these cells have the antigen Thy-1 induced on the cells by treatment with thymopoietin (9). Thymopoietin is known to induce a set of characteristic T-cell markers including the Thy-1 alloantigen on the surface of a subpopulation of bone marrow cells committed to T-cell differentiation (prothymocytes) (10). Destruction of Thy- 1-positive cells after exposure to thymopoietin allows elimination of a substantial fraction of those bone marrow cells that can repopulate an irradiated thymus (11). We find that such an elimination after induction with the thymic polypeptide removes a substantial amount of terminal transferase from the bone marrow cell population, suggesting that at least one-half of the marrow cells bearing this enzyme are related to those found in the thymus.
Phase I/IIa Study of Cisplatin and Gemcitabine As Induction Chemotherapy Followed by Concurrent Chemoradiotherapy With Gemcitabine and Paclitaxel for Locally Advanced Non–Small-Cell Lung Cancer
Authors: Stephen G. Divers, Sharon A. Spencer, Delicia Carey, Elizabeth M. Busby, Mark D. Hyatt, Francisco Robert
Journal: Journal of Clinical Oncology (2005)

Purpose This is a phase I/IIa study to assess tolerance of gemcitabine and paclitaxel with radiotherapy in locally advanced non–small-cell lung cancer after induction chemotherapy. Patients and Methods Fifty-seven patients with stage III non–small-cell lung cancer were treated with cisplatin 80 mg/m 2 on days 1 and 22 and gemcitabine 1,250 mg/m 2 on days 1, 8, 22, and 28. Chemoradiotherapy began on day 43 as follows: cohort 1 (n = 9), gemcitabine 300 mg/m 2 and paclitaxel 35 mg/m 2 weekly (except week 9); cohort 2 (n = 9), gemcitabine 150 mg/m 2 and paclitaxel 35 mg/m 2 weekly (except week 9); cohort 3 (n = 10) and the 25 phase IIa patients, gemcitabine 300 mg/m 2 and paclitaxel 135 mg/m 2 every 21 days. Patients were treated with three-dimensional thoracic radiotherapy concurrently to 60 Gy. Results Weekly chemotherapy resulted in grade 4 esophageal and grade 3 or higher pulmonary toxicities. Reduction in dose density (cohort 3) led to a tolerable toxicity profile and was chosen as the phase IIa regimen. The response rate to induction was 49%, with stable disease in 40% of the patients. The response rate after consolidation therapy was 75% (94% for weekly chemotherapy v 82% for every 3 weeks). Median survival was 23 months, and 3-year survival was 45% for eligible patients. Local relapse occurred in 20% of the patients. Performance status of more than 1 predicted for poor outcome, but baseline pulmonary function did not. Dosimetric parameters including V 15 , V 20 , V 30 (percent lung volume receiving ≥ 15, ≥ 20, and ≥ 30 Gy, respectively), and mean lung dose correlated with pulmonary toxicity. Conclusion Additional investigation with the 3-week schedule is warranted in patients with a good performance status based on the safety profile and preliminary efficacy data observed in this study.
Mechanism of action of extracorporeal photochemotherapy in chronic graft-versus-host disease
Authors: M. Fimiani, M. DI Renzo, P. Rubegni
Journal: British Journal of Dermatology (2004)

Chronic graft-versus-host disease (GvHD) affects 50% of long-term bone marrow transplant survivors and remains a cause of major long-term morbidity in these patients despite aggressive therapy. Extracorporeal photochemotherapy (ECP), considered as an effective treatment for patients with erythrodermic cutaneous T-cell lymphoma (CTCL), has recently been used successfully in the treatment of GvHD. One of the most intriguing aspects of ECP is its ability to induce two apparently opposite effects: activation of the immune system against neoplastic cells (as in CTCL) and downregulation of the activity of T-cell clones in autoimmune diseases (as in systemic sclerosis, systemic lupus erythematosus and pemphigus vulgaris) and autoallogeneic immune responses (as in GvHD and allograft rejection). Only a better and more complete understanding of the various mechanisms involved will enable this interesting new therapy to be made more effective and selective.
Polarization sensitive optical coherence tomography in the human eye
Authors: Michael Pircher, Christoph K. Hitzenberger, Ursula Schmidt-Erfurth
Journal: Progress in Retinal and Eye Research (2011)

Optical coherence tomography (OCT) has become a well established imaging tool in ophthalmology. The unprecedented depth resolution that is provided by this technique yields valuable information on different ocular tissues ranging from the anterior to the posterior eye segment. Polarization sensitive OCT (PS-OCT) extends the concept of OCT and utilizes the information that is carried by polarized light to obtain additional information on the tissue. Several structures in the eye (e.g. cornea, retinal nerve fiber layer, retinal pigment epithelium) alter the polarization state of the light and show therefore a tissue specific contrast in PS-OCT images. First this review outlines the basic concepts of polarization changing light-tissue interactions and gives a short introduction in PS-OCT instruments for ophthalmic imaging. In a second part a variety of different applications of this technique are presented in ocular imaging that are ranging from the anterior to the posterior eye segment. Finally the benefits of the method for imaging different diseases as, e.g., age related macula degeneration (AMD) or glaucoma is demonstrated.