tbuckley/cabot-search huggingface dataset:
The Human Bone Marrow Response to Acute Air Pollution Caused by Forest Fires
Authors: WAN C. TAN, DIWEN QIU, BENG L. LIAM, TZE P. NG, SZU H. LEE, STEPHAN F. van EEDEN, YULIA D'YACHKOVA, JAMES C. HOGG
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Atmospheric pollution increases cardiopulmonary morbidity and mortality by unexplained mechanisms. Phagocytosis of fine particles (PM10) by rabbit alveolar macrophages elevates white blood cells (WBC) by releasing precursors from the bone marrow and this could contribute to the pathogenesis of cardiopulmonary disease. The present study examined the association between acute air pollution caused by biomass burning and peripheral WBC counts in humans. Serial measurements of the WBC count made during the 1997 Southeast Asian Smoke-haze (Sep 29, Oct 27) were compared with a period after the haze cleared (Nov 21, Dec 5) using peripheral blood PMN band cells to monitor marrow release. The results showed that indices of atmospheric pollution were significantly associated with elevated band neutrophil counts expressed as a percentage of total polymorphonuclear leukocytes (PMN), with maximal association on zero and 1 lag day for PM10 and 3, and 4 lag days for SO2 (p value < 0.000). We conclude that atmospheric pollution caused by biomass burning is associated with elevated circulating band cell counts in humans because of the increased release of PMN precursors from the marrow. We speculate that this response contributes to the pathogenesis of the cardiorespiratory morbidity associated with acute air pollution.
Targeting Folate Receptors to Treat Invasive Urinary Bladder Cancer
Authors: Deepika Dhawan, José A. Ramos-Vara, James F. Naughton, Liang Cheng, Philip S. Low, Ryan Rothenbuhler, Christopher P. Leamon, Nikki Parker, Patrick J. Klein, Iontcho R. Vlahov, Joseph A. Reddy, Michael Koch, Linda Murphy, Lindsey M. Fourez, Jane C. Stewart, Deborah W. Knapp
Journal: Cancer Research (2012)

Abstract Folate receptors (FR) may be of use for targeted delivery of cytotoxic drugs in invasive urothelial carcinoma (iUC), for which improved therapy is needed. FR expression and function in iUC were explored and the antitumor activity and toxicity of a folate-targeted vinblastine conjugate were evaluated in dogs with naturally occurring iUC, an excellent model for human iUC. FR immunohistochemistry was carried out on iUC and normal human and dog bladder tissues together with nuclear scintigraphy in dogs to monitor iUC folate uptake. Dose escalation of a folate-targeted vinblastine compound, EC0905, was conducted in dogs with biopsy-confirmed, FR-positive iUC. FRs were detected by immunohistochemistry (PU17) in most primary iUC and many nodal and lung metastases from dogs, and scintigraphy confirmed folate uptake in both primary and metastatic lesions. The maximum tolerated dose of EC0905 in dogs was 0.25 mg/kg IV weekly, with neutropenia at higher doses. Tumor responses included partial remission (≥50% reduction in tumor volume) in five dogs and stable disease (&amp;lt;50% change in tumor volume) in four dogs. Immunoreactivity to PU17 was similar in humans (78% of primary iUC, 80% of nodal metastases). Less immunoreactivity to mab343 (22% of cases) occurred. FR-β was noted in 21% of human iUC cases. Our findings suggest folate-targeted therapy holds considerable promise for treating iUC, where FR-β may be important in addition to FR-α. Cancer Res; 73(2); 875–84. ©2012 AACR.
Loss of immunoreactivity for RTI40, a type I cell-specific protein in the alveolar epithelium of rat lungs with bleomycin-induced fibrosis
Authors: R Koslowski, LG Dobbs, KW Wenzel, D Schuh, M Muller, M Kasper
Journal: European Respiratory Journal (1998)

After lung injury, the epithelial cells lining the alveolar surface in rat lung show an altered distribution of several membrane proteins. Pulmonary fibrosis was induced by intratracheal administration of bleomycin into the lung of rats and the distribution of RTI40, a recently detected alveolar epithelial type I cell antigen, was examined, as well as the relationship between RTI40 and a type I cell-specific antigen recognized by the monoclonal antibody MEP-1 and the type I cell-binding lectin Bauhinia purpurea in serial sections and double stainings. Loss of RTI40 protein was observed in fibrotic lungs, particularly in areas with obliteration of alveoli. Pre-embedding immunoelectron microscopy confirmed this observation by detection of RTI40 protein in the alveolar lumen. Western blot analysis revealed elevated levels of RTI40 in the bronchoalveolar fluid of bleomycin-treated rats with a maximum at day 7 after treatment. Twenty-eight days after bleomycin application, the bronchoalveolar fluid contained three times the amount of RTI40 x mg protein(-1) of control lungs, as determined by semiquantitative dot blot. These results suggest RTI40 as a tool for the evaluation of alveolar epithelial type I cell behaviour during re-epithelialization processes.
The Prevalence of Cutaneous Manifestations in Young Patients With Type 1 Diabetes
Authors: Miloš D. Pavlović, Tatjana Milenković, Miroslav Dinić, Milan Mišović, Dragana Daković, Slađana Todorović, Zorana Đaković, Radoš D. Zečevi, Radoje Doder
Journal: Diabetes Care (2007)

OBJECTIVE—The aim of the study was to assess the prevalence of cutaneous disorders and their relation to disease duration, metabolic control, and microvascular complications in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS—The presence and frequency of skin manifestations were examined and compared in 212 unselected type 1 diabetic patients (aged 2–22 years, diabetes duration 1–15 years) and 196 healthy sex- and age-matched control subjects. Logistic regression was used to analyze the relation of cutaneous disorders with diabetes duration, glycemic control, and microvascular complications. RESULTS—One hundred forty-two (68%) type 1 diabetic patients had at least one cutaneous disorder vs. 52 (26.5%) control subjects (P &amp;lt; 0.01). Diabetes-associated skin lesions were found in 81 (38%) patients. Acquired ichthyosis, rubeosis faciei, diabetic hand, and necrobiosis lipoidica were seen in 22 vs. 3%, 7.1 vs. 0%, 2.3 vs. 0%, and 2.3 vs. 0% of type 1 diabetic and control subjects, respectively. The frequency of cutaneous reactions to insulin therapy was low (–2.7%). The prevalence of fungal infections in patients and control subjects was 4.7% and 1.5%, respectively. Keratosis pilaris affected 12% of our patients vs. 1.5% of control subjects. Diabetic hand was strongly (odds ratio 1.42 [95% CI 1.11–1.81]; P &amp;lt; 0.001), and rubeosis faciei weakly (1.22 [1.04–1.43]; P = 0.0087), associated with diabetes duration. Significant association was also found between acquired ichthyosis and keratosis pilaris (1.53 [1.09–1.79]; P &amp;lt; 0.001). CONCLUSIONS—Cutaneous manifestations are common in type 1 diabetic patients, and some of them, like acquired ichthyosis and keratosis pilaris, develop early in the course of the disease. Diabetic hand and rubeosis faciei are related to disease duration.
Impaired tracheobronchial clearance in bronchiectasis.
Authors: D C Currie, D Pavia, J E Agnew, M T Lopez-Vidriero, P D Diamond, P J Cole, S W Clarke
Journal: Thorax (1987)

Tracheobronchial clearance was measured by a radioaerosol technique in 12 patients with bronchiectasis, seven patients with chronic obstructive lung disease expectorating mucoid sputum daily (group X), eight patients with chronic obstructive lung disease but negligible sputum expectoration (group Y), and 10 healthy subjects. The patients with bronchiectasis all expectorated purulent sputum daily (mean wet weight 47 g/day), had reduced forced expiratory volume in one second (FEV1) (mean 47.5% predicted), and were unable to avoid coughing during the six hour observation period. None of the patients with bronchiectasis or the healthy subjects were current smokers. There were five current smokers in group X and six in group Y. The mean FEV1 in group X was 41% predicted and in group Y 52% predicted, both values similar to that of the patients with bronchiectasis. Tracheobronchial clearance in the first six hours after inhalation of radioaerosol was significantly (p less than 0.01) slower in patients with bronchiectasis than in matched healthy subjects despite more proximal deposition of radioaerosol (p = 0.01) and more coughing (p less than 0.01) in the former. Tracheobronchial clearance in patients with bronchiectasis was impaired to a similar degree to that in patients with chronic obstructive lung disease but no bronchiectasis.
Motor responses to experimental Achilles tendon pain
Authors: Marius Henriksen, Jens Aaboe, Thomas Graven-Nielsen, Henning Bliddal, Henning Langberg
Journal: British Journal of Sports Medicine (2010)

Achilles tendinopathies are characterised by pain and reduced function, and heavy-load exercises have been shown to be effective in the treatment of painful chronic Achilles tendinopathies. However, basic information is needed on how the biomechanics and neuromuscular control of the exercise are affected by Achilles tendon pain.The authors aimed to determine the effects of experimental Achilles tendon pain on motor function during one-legged weight bearing ankle plantar and dorsal flexion exercises.In a crossover study, with 16 healthy subjects tested on two different days separated by 1 week, three-dimensional ground reaction forces, ankle joint kinematics and surface electromyography (EMG) of the lower leg muscles were recorded during one-legged full weight-bearing ankle plantar (concentric) and dorsal (eccentric) flexion exercises. Measurements were done before, during and after either experimental Achilles tendon pain or a non-painful control condition. Pain was induced by intratendinous injections of hypertonic saline with isotonic saline injections as control. Joint kinematics, ground reaction force frequency contents and average EMG amplitudes were calculated.Compared with the control condition experimental Achilles tendon pain reduced the EMG activity in agonistic, synergistic and antagonistic muscles, and increased the ground reaction force frequency content around 10 Hz, during both eccentric and concentric movement phases.These data show that experimental Achilles tendon pain causes widespread and reduced motor responses with functional effects on the ground reaction force.
Association of <i>TXNDC5</i> gene polymorphisms and susceptibility to nonsegmental vitiligo in the Korean population
Authors: K-H. Jeong, M-K. Shin, Y-K. Uhm, H-J. Kim, J-H. Chung, M-H. Lee
Journal: British Journal of Dermatology (2009)

Journal Article Association of TXNDC5 gene polymorphisms and susceptibility to nonsegmental vitiligo in the Korean population Get access K‐H. Jeong, K‐H. Jeong Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar M‐K. Shin, M‐K. Shin Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar Y‐K. Uhm, Y‐K. Uhm Pharmacology, Kohwang Medical Research Institute, School of Medicine, Kyunghee University, 1 Hoeki‐Dong, Dongdaemun‐Ku, Seoul 130‐702, Korea Search for other works by this author on: Oxford Academic Google Scholar H‐J. Kim, H‐J. Kim Pharmacology, Kohwang Medical Research Institute, School of Medicine, Kyunghee University, 1 Hoeki‐Dong, Dongdaemun‐Ku, Seoul 130‐702, Korea Search for other works by this author on: Oxford Academic Google Scholar J‐H. Chung, J‐H. Chung Pharmacology, Kohwang Medical Research Institute, School of Medicine, Kyunghee University, 1 Hoeki‐Dong, Dongdaemun‐Ku, Seoul 130‐702, Korea Search for other works by this author on: Oxford Academic Google Scholar M‐H. Lee M‐H. Lee Departments of Dermatology Mu‐Hyoung Lee. E‐mail:mhlee@khmc.or.kr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 4, 1 April 2010, Pages 759–764, https://doi.org/10.1111/j.1365-2133.2009.09574.x Published: 01 April 2010
Stable disease after high dose interleukin-2 (HD IL-2) immunotherapy: observations on long term survival and clinical benefit of additional HD IL-2
Authors: Howard L Kaufman, Sandra Aung, Michael Morse, Michael Wong, James Lowder, Gregory Daniels, David McDermott
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Patients with stable disease (SD) following cancer treatment have traditionally not been considered responders. We, and others, have previously shown that SD is an important response criteria in cancer patients treated with HD IL-2 immunotherapy [[1][1]–[5][2]]. Here we
TUBERCULOSIS IN LIMEWORKERS
Authors: W. J. B. Selkirk
Journal: BMJ (1908)

TUBERCULOSIS IN LIMEWORKERS.L MEDIOAL JOURA I493 and more self-centred and hypochondriacal, and at the same time not infrequently he ceases to have any real feeling of his social duties and responsibilities.He is organized selfishness.Such I have seen pass gradually into what I would call mental paralysis.Another somewbat similar type is that in which a first attack of insanity has changed the whole mental horizon, 'so that the objects in life seem altered.The girl who was a cheerful companionable person now becomes isolated, neglecting her old friends and making no new ones.
Control of Very Low-Density Lipoprotein Secretion by N-Ethylmaleimide-Sensitive Factor and miR-33
Authors: Ryan M. Allen, Tyler J. Marquart, Jordan J. Jesse, Ángel Baldán
Journal: Circulation Research (2014)

Several reports suggest that antisense oligonucleotides against miR-33 might reduce cardiovascular risk in patients by accelerating the reverse cholesterol transport pathway. However, conflicting reports exist about the impact of anti-miR-33 therapy on the levels of very low-density lipoprotein-triglycerides (VLDL-TAG).We test the hypothesis that miR-33 controls hepatic VLDL-TAG secretion.Using therapeutic silencing of miR-33 and adenoviral overexpression of miR-33, we show that miR-33 limits hepatic secretion of VLDL-TAG by targeting N-ethylmaleimide-sensitive factor (NSF), both in vivo and in primary hepatocytes. We identify conserved sequences in the 3'UTR of NSF as miR-33 responsive elements and show that Nsf is specifically recruited to the RNA-induced silencing complex following induction of miR-33. In pulse-chase experiments, either miR-33 overexpression or knock-down of Nsf lead to decreased secretion of apolipoproteins and TAG in primary hepatocytes, compared with control cells. Importantly, Nsf rescues miR-33-dependent reduced secretion. Finally, we show that overexpression of Nsf in vivo increases global hepatic secretion and raises plasma VLDL-TAG.Together, our data reveal key roles for the miR-33-NSF axis during hepatic secretion and suggest that caution should be taken with anti-miR-33-based therapies because they might raise proatherogenic VLDL-TAG levels.
Characterization of Cytokine/Chemokine Profiles of Severe Acute Respiratory Syndrome
Authors: Yong Jiang, Jun Xu, Chengzhi Zhou, Zhenguo Wu, Shuqing Zhong, Jinghua Liu, Wei Luo, Tao Chen, Qinghe Qin, Peng Deng
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

There is currently no optimal treatment or effective drug for severe acute respiratory syndrome (SARS), because the immunopathologic mechanism is poorly understood.To explore the immune mechanism underlying the pathogenesis of SARS, we studied the expression profile of cytokines/chemokines in the blood and the immunopathology of the lung and lymphoid tissues.Fourteen cytokines/chemokines in the blood of 23 patients with SARS were dynamically screened, using a bead-based multiassay system. Reverse transcription-polymerase chain reaction was performed to amplify mRNA. Histopathology of the lung and lymphoid tissues at autopsy was examined, using methods of immunohistochemistry and double immunofluorescence staining.Interferon-inducible protein-10 (IP-10) was markedly elevated in the blood during the early stage of SARS, and remained at a high level until convalescence. Moreover, IP-10 was highly expressed in both lung and lymphoid tissues, where monocyte-macrophage infiltration and depletion of lymphocytes were observed. The levels of interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 were concomitantly increased in the blood of the patients with superinfection, and the mRNAs for these cytokines were also increased in lung tissues.Induction of IP-10 is a critical event in the initiation of immune-mediated acute lung injury and lymphocyte apoptosis during the development of SARS. Superinfection after the immune injury is the main cause of death. The prompt elevation of interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 is a sign of superinfection, indicating a high risk of death.
Immunobiology of Fibrinogen. EMERGENCE OF NEOANTIGENIC EXPRESSIONS DURING PHYSIOLOGIC CLEAVAGE IN VITRO AND IN VIVO
Authors: Edward Plow, Thomas S. Edgington
Journal: Journal of Clinical Investigation (1973)

Physiological degradation of fibrinogen by plasmin leads to a recognized series of intermediate and stable terminal cleavage fragments and is associated with complex modulation and progressive loss of native antigenic expressions. Early in association with progressive plasmin cleavage, a stable cleavage-associated neoantigen, present in the D-fragment region of the molecule, is exposed in vitro and can be recognized by competitive inhibition radioimmunoassay with specific antiserum. It is demonstrated that there is an approximate equimolar expression of the cleavage-associated neoantigen. fg-D(neo), on the X-, Y-, and D-fragments and no recognizable (< 10(-3)) expression by fibrinogen or by the E-fragment. The X-fragment contains two D regions in respect to total D-fragment-associated antigenic expressions but unitary expression of fg-D(neo) is observed. The Y-fragment appears to contain one D-fragment region in respect to total D-fragment-associated antigens and exhibits close to unitary expression of fg-D(neo). Terminal cleavage digests containing the D- and E-fragments exhibit more than 10-fold greater native fibrinogen antigenic expression than the sum of the constituent fragments. This suggests the presence of a non-covalently associated native complex of the D- and E-fragments, and implies contiguity of the D- and E-fragments in the native fibrinogen molecule. The cleavage-associated neoantigen, fg-D(neo), is also generated in vivo and is generically demonstrable in the plasma of patients with various forms of in vivo fibrinolysis. These studies offer a precise immunochemical system, based upon defined molecular events, for the investigation of physiological and pathophysiological cleavage of fibrinogen. By contrast with other approaches to the assay of in vitro or in vivo cleavage of fibrinogen, assay of the cleavage-associated neoantigen fg-D(neo) is specific, sensitive, directly yields the molar concentration of all cleavage fragments except E, and is directly applicable to plasma.
The INPULSIS enigma: exacerbations in idiopathic pulmonary fibrosis
Authors: Samy Suissa, Pierre Ernst
Journal: Thorax (2014)

The recently published INPULSIS studies, two duplicate randomised trials evaluating nintedanib in the treatment of idiopathic pulmonary fibrosis (IPF) over 1 year, reported effectiveness in terms of declining lung function, but inconsistent results on exacerbations of IPF.1 ,2 Indeed, in the prespecified pooled analysis of the two trials, the risk of an investigator-reported acute exacerbation was lower by 36% with nintedanib compared with placebo but not statistically significant (HR, 0.64; 95% CI 0.39 to 1.05; p=0.08). On the other hand, another prespecified analysis found that, after adjudication of these same investigator-reported exacerbations, the risk of a confirmed acute exacerbation was lower by 68% and statistically significant (HR, 0.32; 95% CI 0.16 to 0.65; p=0.001). Such differences in results for the same outcome may puzzle readers and even possibly arouse suspicion of selective or incorrect reporting, especially when the findings straddle the magic 5% conventional level of statistical significance. We believe such differences have a statistical explanation which shows how one result is biased and the other valid.

In this paper, we describe the phenomenon of treatment effect dilution, which can lead to false non-significant effects, using the INPULSIS trials as an illustration. We also provide a contrasting example to this phenomenon using, as an illustration, the case of the risk of pneumonia in trials of inhaled corticosteroids in COPD.

An acute exacerbation of IPF in the INPULSIS trials needed to meet the following criteria: ‘unexplained worsening or development of dyspnoea within the previous 30 days; new diffuse pulmonary infiltrates visualised on chest radiography, HRCT or both, or the development of parenchymal abnormalities with no pneumothorax or pleural effusion (new ground-glass opacities) since the preceding visit and exclusion of any known causes of acute worsening, including infection, left heart failure, PE and any identifiable cause of acute lung injury, in accordance …
Phase II-I-II Study of Two Different Doses and Schedules of Pralatrexate, a High-Affinity Substrate for the Reduced Folate Carrier, in Patients With Relapsed or Refractory Lymphoma Reveals Marked Activity in T-Cell Malignancies
Authors: Owen A. O'Connor, Steven Horwitz, Paul Hamlin, Carol Portlock, Craig H. Moskowitz, Debra Sarasohn, Ellen Neylon, Jill Mastrella, Rachel Hamelers, Barbara MacGregor-Cortelli, Molly Patterson, Venkatraman E. Seshan, Frank Sirotnak, Martin Fleisher, Diane R. Mould, Mike Saunders, Andrew D. Zelenetz
Journal: Journal of Clinical Oncology (2009)

Purpose To determine the maximum-tolerated dose (MTD) and efficacy of pralatrexate in patients with lymphoma. Patients and Methods Pralatrexate, initially given at a dose of 135 mg/m 2 on an every-other-week basis, was associated with stomatitis. A redesigned, weekly phase I/II study established an MTD of 30 mg/m 2 weekly for six weeks every 7 weeks. Patients were required to have relapsed/refractory disease, an absolute neutrophil greater than 1,000/μL, and a platelet count greater than 50,000/μL for the first dose of any cycle. Results The every-other-week, phase II experience was associated with an increased risk of stomatitis and hematologic toxicity. On a weekly schedule, the MTD was 30 mg/m 2 weekly for 6 weeks every 7 weeks. This schedule modification resulted in a 50% reduction in the major hematologic toxicities and abrogation of the grades 3 to 4 stomatitis. Stomatitis was associated with elevated homocysteine and methylmalonic acid, which were reduced by folate and vitamin B12 supplementation. Of 48 assessable patients, the overall response rate was 31% (26% by intention to treat), including 17% who experienced complete remission (CR). When analyzed by lineage, the overall response rates were 10% and 54% in patients with B- and T-cell lymphomas, respectively. All eight patients who experienced CR had T-cell lymphoma, and four of the six patients with a partial remission were positron emission tomography negative. The duration of responses ranged from 3 to 26 months. Conclusion Pralatrexate has significant single-agent activity in patients with relapsed/refractory T-cell lymphoma.