tbuckley/cabot-search huggingface dataset:
A novel homozygous 62-bp insertion in<i>ECM1</i>causes lipoid proteinosis in a multigeneration Pakistani family
Authors: M. Nasir, A. Latif, M. Ajmal, M. Ismail, A. Hameed
Journal: British Journal of Dermatology (2009)

Journal Article A novel homozygous 62‐bp insertion in ECM1 causes lipoid proteinosis in a multigeneration Pakistani family Get access M. Nasir, M. Nasir Institute of Biomedical and Genetic Engineering, GPO Box 2891, 24‐Mauve Area, G‐9/1, Islamabad, Pakistan Search for other works by this author on: Oxford Academic Google Scholar A. Latif, A. Latif Leprosy Hospital, Rawalpindi, Pakistan Search for other works by this author on: Oxford Academic Google Scholar M. Ajmal, M. Ajmal Institute of Biomedical and Genetic Engineering, GPO Box 2891, 24‐Mauve Area, G‐9/1, Islamabad, Pakistan Search for other works by this author on: Oxford Academic Google Scholar M. Ismail, M. Ismail Institute of Biomedical and Genetic Engineering, GPO Box 2891, 24‐Mauve Area, G‐9/1, Islamabad, Pakistan Search for other works by this author on: Oxford Academic Google Scholar A. Hameed A. Hameed Institute of Biomedical and Genetic Engineering, GPO Box 2891, 24‐Mauve Area, G‐9/1, Islamabad, Pakistan Correspondence: Abdul Hameed. E‐mail: ahameed0786@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue 3, 1 September 2009, Pages 688–690, https://doi.org/10.1111/j.1365-2133.2009.09275.x Published: 01 September 2009
Cisplatin and Gemcitabine Treatment for Malignant Mesothelioma: A Phase II Study
Authors: M. J. Byrne, J. A. Davidson, A. W. Musk, J. Dewar, G. van Hazel, M. Buck, N. H. de Klerk, B. W.S. Robinson
Journal: Journal of Clinical Oncology (1999)

PURPOSE: We performed a phase II study of combined cisplatin 100 mg/m 2 , given intravenously on day 1, and gemcitabine 1,000 mg/m 2 , given intravenously on days 1, 8, and 15 of a 28-day cycle for six cycles among patients with advanced measurable pleural mesothelioma. PATIENTS AND METHODS: Pleural tumor was measured at three levels on computed tomographic scans at study entry and before the second, fourth, and sixth cycles and every 2 months thereafter to disease progression. Of the 21 patients treated, 19 were male; the median age was 62 years (range, 46 to 74 years); 62% had epithelial tumors; and 18 were classified as tumor-node-metastasis system stage III or IV. Ninety-four cycles were given (median, six; mean, 4.5 per patient), with a mean relative dose intensity of cisplatin 96.7% and gemcitabine 82.5%. RESULTS: Best objective responses achieved were as follows: complete response, no patients; partial response, 10 patients (complete response + partial response, 47.6% [95% confidence interval, 26.2% to 69.0%]); no change, nine patients; and progressive disease, two patients. Median response duration was 25 weeks, progression-free survival was 25 weeks, and overall survival was 41 weeks. Nine of the 10 responders (90%) and three of nine patients with no change had significant symptom improvement. Serial measurements of vital capacity were performed on three of the responders; all showed a significant increase during the time of remission. Toxicity was mainly gastroenterologic and hematologic. Grade 3 nausea and vomiting occurred in 33% of patients, grade 3 leukopenia in 38%, grade 3 thrombocytopenia in 14%, and grade 4 thrombocytopenia in 19%. CONCLUSION: Combined cisplatin and gemcitabine is an active combination in malignant mesothelioma and produces symptomatic benefit in responding patients.
Hemolytic anemia and acute renal failure associated with temafloxacin‐dependent antibodies
Authors: Robert B. Maguire, David F. Stroncek, Eric Gale, Martha Yearlsey
Journal: American Journal of Hematology (1994)

Abstract Quinine‐ingestion has been associated with immune‐mediated recurrent pancytopenia, hemolysis, and renal failure. The structure of fluoroquinolone antibiotics is similar to the structure of quinine. Over a 3 month period, three patients at our institution developed hemolysis and renal failure following ingestion of the fluoroquinolone antibiotic temafloxacin. Two of the three patients required hemodialysis. Following withdrawal from the drug, the hemolysis resolved and the renal function eventually returned to normal in all three patients. One patient also had a transient mild thrombocytopenia. Sera from all three patients were tested for drug‐dependent antibodies to red blood cells, platelets, and neutrophils. Temafloxacin‐dependent red cell antibodies were detected in one patient, and temafloxacin‐dependent red cell and neutrophil antibodies were detected in a second patient. No temafloxacin‐dependent antibodies were detected in the third patient. Sera from all three patients were also tested for quinine and quinidine‐dependent antibodies to red cells, platelets, and neutrophils. Sera from the patient without temafloxacin‐dependent red cell antibodies reacted with red cells in the presence of quinine. These results suggest that, at least in some patients, the toxicities associated with temafloxacin are immune mediated. © 1994 Wiley‐Liss, Inc.
Combining Radioimmunotherapy with Antihypoxia Therapy 2-Deoxy-<scp>d</scp>-Glucose Results in Reduction of Therapeutic Efficacy
Authors: Jason L.J. Dearling, Uzma Qureshi, Richard H.J. Begent, R. Barbara Pedley
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The efficacy of solid tumor radioimmunotherapy is reduced by heterogeneous tumor distribution of the radionuclide, with dose mainly deposited in the normoxic region and by the relative radioresistance of hypoxic tumor cells. In an attempt to overcome these challenges, radioimmunotherapy was combined with 2-deoxy-d-glucose (2DG), a hypoxia-selective cytotoxic inhibitor of glucose metabolism. Experimental Design: In vitro toxicity of 2DG in LS174T cultures was tested using a colony-forming assay. The effect of combining 2DG with radioimmunotherapy in vivo was tested by administering radiolabeled anti–carcinoembryonic antigen antibody ([131I]A5B7 IgG1 whole monoclonal) to nude mice bearing s.c. LS174T tumors, followed by 10 daily injections of 2DG (2.0 g/kg). Tumors were measured to assess therapeutic efficacy. Results: Data from in vitro studies confirmed 2DG cytotoxicity in this cell line. Greater toxicity was observed under standard laboratory conditions and in hypoxic cultures than at intermediate, physiologically relevant levels of glucose and oxygen. Alone, 2DG had no effect on in vivo tumor growth (P = 0.377 compared with saline-treated controls). Combination of radioimmunotherapy with 2DG reduced the therapeutic effect of radioimmunotherapy (e.g., 150 μCi 131I alone mean survival time, 48.33 ± 16.83 days; combined with 2DG, 30.67 ± 5.62 days, P = 0.038). Conclusions: The combination investigated had a detrimental effect on survival. It is suggested that a cellular metabolic response to more aggressive therapy, previously reported in vitro, caused this. The results of this study have implications for the clinical application of combined cancer therapies with an antimetabolic modality component.
Initiate Insulin by Aggressive Titration and Education (INITIATE)
Authors: Hannele Yki-Järvinen, Leena Juurinen, Michael Alvarsson, Tord Bystedt, Ian Caldwell, Melanie Davies, Sanni Lahdenperä, Gil Nijpels, Markku Vähätalo
Journal: Diabetes Care (2007)

Insulin is often postponed for years because initiation is time-consuming. We sought to compare initiation of insulin individually and in groups with respect to change in A1C and several other parameters in type 2 diabetic patients.A randomized (1:1), multicenter, two-arm, parallel design study with a recruiting period of up to 14 weeks and a 24-week treatment period. Either in groups of 4-8 or individually, using the same personnel and education program, 121 insulin-naive type 2 diabetic patients with an A1C of 7.0-12.0% were randomized to initiate bedtime insulin glargine. The patients visited the treatment center before and at the time of insulin initiation and at 6, 12, and 24 weeks. Patients self-adjusted the insulin dose to achieve a fasting plasma glucose 4.0-5.5 mmol/l.At 24 weeks, mean +/- SE A1C had decreased from 8.7 +/- 0.2 to 6.9 +/- 0.1% in those treated individually and from 8.8 +/- 0.2 to 6.8 +/- 0.1% in those in groups (not significant [NS]). Insulin doses averaged 62 +/- 5 IU and 56 +/- 5 IU at 24 weeks (NS), respectively. The frequency of hypoglycemia was similar. The total time (visits and phone calls) spent in initiating insulin in the patients in groups (2.2 +/- 0.1 h) was 48% less than in those treated individually (4.2 +/- 0.2 h). Diabetes treatment satisfaction improved significantly in both sets of patients.Similar glycemic control and treatment satisfaction can be achieved by initiating insulin in groups and individually. Starting insulin in groups takes one-half as much time as individual initiation.
Surface air plasma-induced cell death and cytokine release of human keratinocytes in the context of psoriasis
Authors: S.Y. Zhong, Y.Y. Dong, D.X. Liu, D.H. Xu, S.X Xiao, H.L. Chen, M.G. Kong
Journal: British Journal of Dermatology (2015)

Summary Background Cold atmospheric plasma (CAP) has shown promise for wound healing, although little is understood of the underpinning mechanisms. Little has been reported so far of its potential use in the treatment of immune-mediated diseases such as psoriasis. Objectives To study CAP-induced cell death and cytokine release in human keratinocytes as a first assessment of possible CAP use for psoriasis. Methods Using a CAP generator free of energetic ions, we observed its effects on keratinocytes in terms of morphology, cell viability and apoptosis, intracellular and mitochondrial reactive oxygen species (ROS), lysosomal integrity and mitochondrial membrane potential; and on secretion and expression of eight cytokines at protein and gene levels. Results CAP-induced reduced cell viability, apoptotic death and production of intracellular and mitochondrial ROS in dose-dependent manner. Mitochondrial dysfunction and lysosomal leakage were found in CAP-treated cells. It also induced release of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF), and enhanced the mRNA expression of IL-1β, IL-6, IL-8, IL-10, TNF-α, interferon-γ and VEGF. By contrast, IL-12 declined monotonically. Conclusions The results suggest that with appropriate control of its dose, physical plasma could induce cell death via apoptotic pathways and enable simultaneous reduction in IL-12. These effects may be used to suppress keratinocyte hyperproliferation and to target T-cell activation to control amplification of inflammation. This provides an initial basis for further studies of CAP as a potential therapeutic option for inflammatory and immune-related diseases in dermatology, including psoriasis.
Mechanisms of exercise intolerance in Global Initiative for Chronic Obstructive Lung Disease grade 1 COPD
Authors: Jordan A. Guenette, Roberto C. Chin, Sicheng Cheng, Paolo B. Dominelli, Natya Raghavan, Katherine A. Webb, J. Alberto Neder, Denis E. O’Donnell
Journal: European Respiratory Journal (2014)

The purpose of this study was to determine if a dissociation existed between respiratory drive, as estimated by diaphragmatic electromyography (EMG di ), and its pressure-generating capacity during exercise in mild chronic obstructive pulmonary disease (COPD) and whether this, if present, had negative sensory consequences. Subjects meeting spirometric criteria for mild COPD (n=16) and age and sex-matched controls (n=16) underwent detailed pulmonary function testing and a symptom limited cycle test while detailed ventilatory, sensory and respiratory mechanical responses were measured. Compared with controls, subjects with mild COPD had greater ventilatory requirements throughout submaximal exercise. At the highest equivalent work rate of 60 W, they had a significantly higher: total work of breathing (32±17 versus 16±7 J·min −1 ; p&lt;0.01); EMG di (37.3±17.3 versus 17.9±11.7% of maximum; p&lt;0.001); and EMG di to transdiaphragmatic pressure ratio (0.87±0.38 versus 0.52±0.27; p&lt;0.01). Dyspnoea–ventilation slopes were significantly higher in mild COPD than controls (0.17±0.12 versus 0.10±0.05; p&lt;0.05). However, absolute dyspnoea ratings reached significant levels only at high levels of ventilation. Increased respiratory effort and work of breathing, and a wider dissociation between diaphragmatic activation and pressure-generating capacity were found at standardised work rates in subjects with mild COPD compared with controls. Despite these mechanical and neuromuscular abnormalities, significant dyspnoea was only experienced at higher work rates.
A Mouse Model of Arterial Gene Transfer
Authors: Giuseppe Vassalli, Ramtin Agah, Renli Qiao, Christina Aguilar, David A. Dichek
Journal: Circulation Research (1999)

Abstract —We developed a murine model of arterial gene transfer and used it to test the role of antigen-specific immunity in the loss of adenovirus-mediated transgene expression. Adenoviral vectors encoding either β-galactosidase (β-gal) or green fluorescent protein were infused to the lumen of normal common carotids of CD-1 and C57BL/6 mice and atherosclerotic carotids of Apoe −/− mice. At 3 days after gene transfer, significant reporter gene expression was detected in all strains. Transgene expression was transient, with expression undetectable at 14 days. Next, a β-gal–expressing vector was infused into carotids of ROSA26 mice (transgenic for, and therefore tolerant of, β-gal) and RAG-2 −/− mice (deficient in recombinase-activating gene [RAG]-2 and therefore lacking in antigen-specific immunity). β-Gal expression was again high at 3 days but declined substantially (&gt;90%) by 14 days. In vivo labeling with bromodeoxyuridine revealed that carotid endothelial proliferation was increased dramatically by the gene-transfer procedure alone, likely leading to the loss of episomal adenoviral DNA. Gene transfer to normal and atherosclerotic mouse carotids can be accomplished; however, elimination of antigen-specific immune responses does not prevent the early loss of adenovirus-mediated transgene expression. Efforts to prolong adenovirus-mediated transgene expression in the artery wall must be redirected. These efforts will likely include strategies to avoid the consequences of increased cell turnover. Nevertheless, despite the brevity of expression, this mouse model of gene transfer to normal and severely atherosclerotic arteries will likely be useful for investigating the genetic basis of vascular disease and for developing gene therapies. The full text of this article is available at http://www.circresaha.org.
Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function
Authors: Leif E. Sander, Sara Dutton Sackett, Uta Dierssen, Naiara Beraza, Reinhold P. Linke, Michael Müller, J. Magarian Blander, Frank Tacke, Christian Trautwein
Journal: The Journal of Experimental Medicine (2010)

Acute-phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a mouse model of polymicrobial sepsis, we show that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6 family cytokines, strongly increased mortality despite normal bacterial clearance. Hepatic gp130 signaling through STAT3 was required to control systemic inflammation. Notably, hepatic gp130–STAT3 activation was also essential for mobilization and tissue accumulation of myeloid-derived suppressor cells (MDSCs), a cell population mainly known for antiinflammatory properties in cancer. MDSCs were critical to regulate innate inflammation, and their adoptive transfer efficiently protected gp130-deficient mice from sepsis-associated mortality. The hepatic APPs serum amyloid A and Cxcl1/KC cooperatively promoted MDSC mobilization, accumulation, and survival, and reversed dysregulated inflammation and restored survival of gp130-deficient mice. Thus, gp130-dependent communication between the liver and MDSCs through APPs controls inflammatory responses during infection.
Increased expression of the interleukin-8 gene by alveolar macrophages in idiopathic pulmonary fibrosis. A potential mechanism for the recruitment and activation of neutrophils in lung fibrosis.
Authors: P C Carré, R L Mortenson, T E King, P W Noble, C L Sable, D W Riches
Journal: Journal of Clinical Investigation (1991)

Neutrophil migration into the airspaces of the lung is thought to contribute to the alveolar damage and subsequent fibrosis in idiopathic pulmonary fibrosis (IPF). Interleukin 8 (IL-8), a monocyte- and macrophage-derived cytokine, displays potent chemotactic and activating properties towards neutrophils and thus may contribute to the pathogenesis of IPF. The objective of this investigation was to quantify the spontaneous expression of IL-8 transcripts by alveolar macrophages from normal healthy volunteers and individuals with IPF. A quantitative assay employing reverse transcription of mRNA and the polymerase chain reaction was utilized. The level of IL-8 mRNA in alveolar macrophages was found to be significantly elevated in individuals with lone IPF or with lung fibrosis associated with connective tissue disorders compared to normal healthy controls. Moreover, the level of IL-8 mRNA in the 23 individuals with IPF correlated with the number of neutrophils per milliliter in their bronchoalveolar lavage (BAL) and with the degree of disease severity. In addition, the level of IL-8 protein in BAL was found to reflect the pattern of IL-8 mRNA expression by alveolar macrophages. These data suggest that IL-8 derived from alveolar macrophages may significantly contribute to neutrophil involvement in the pathogenesis of IPF.
Effect of plyometric training on sand versus grass on muscle soreness and jumping and sprinting ability in soccer players
Authors: F M Impellizzeri, E Rampinini, C Castagna, F Martino, S Fiorini, U Wisloff
Journal: British Journal of Sports Medicine (2007)

The lower impact on the musculoskeletal system induced by plyometric exercise on sand compared to a firm surface might be useful to reduce the stress of intensified training periods or during rehabilitation from injury. The aim of this study was to compare the effects of plyometric training on sand versus a grass surface on muscle soreness, vertical jump height and sprinting ability.Parallel two-group, randomised, longitudinal (pretest-post-test) study.After random allocation, 18 soccer players completed 4 weeks of plyometric training on grass (grass group) and 19 players on sand (sand group). Before and after plyometric training, 10 m and 20 m sprint time, squat jump (SJ), countermovement jump (CMJ), and eccentric utilization ratio (CMJ/SJ) were determined. Muscle soreness was measured using a Likert scale.No training surface x time interactions were found for sprint time (p>0.87), whereas a trend was found for SJ (p = 0.08), with both groups showing similar improvements (p<0.001). On the other hand, the grass group improved their CMJ (p = 0.033) and CMJ/SJ (p = 0.005) significantly (p<0.001) more than players in the sand group. In contrast, players in the sand group experienced less muscle soreness than those in the grass group (p<0.001).Plyometric training on sand improved both jumping and sprinting ability and induced less muscle soreness. A grass surface seems to be superior in enhancing CMJ performance while the sand surface showed a greater improvement in SJ. Therefore, plyometric training on different surfaces may be associated with different training-induced effects on some neuromuscular factors related to the efficiency of the stretch-shortening cycle.
Ethanol in pancreatic juice after oral and intravenous administration.
Authors: I Gjorup, S Dueholm, B Andersen, F Burcharth
Journal: Gut (1990)

Six patients with a drain in the main pancreatic duct were studied. Ethanol was given orally with individually adjusted doses aiming at a blood value of 0.8/1000 (17.6 mmol/l). Concentrations of ethanol in venous blood and pancreatic juice were recorded for three hours. Similar studies were made when ethanol was administered as an intravenous priming dose followed by a maintenance infusion. After orally administered ethanol, pancreatic juice values were higher than those in blood for a short period of time. The relations between median concentrations and time were incongruous curves consistent with a significant treatment by time interaction. Intravenous administration resulted in a similar pattern, but the interaction was not statistically significant. These findings indicate that the human pancreas may secrete ethanol.
Differential Regulation and ATP Requirement for Caspase-8 and Caspase-3 Activation during CD95- and Anticancer Drug–induced Apoptosis
Authors: Davide Ferrari, Ania Stepczynska, Marek Los, Sebastian Wesselborg, Klaus Schulze-Osthoff
Journal: The Journal of Experimental Medicine (1998)

Apoptosis is induced by different stimuli, among them triggering of the death receptor CD95, staurosporine, and chemotherapeutic drugs. In all cases, apoptosis is mediated by caspases, although it is unclear how these diverse apoptotic stimuli cause protease activation. Two regulatory pathways have been recently identified, but it remains unknown whether they are functionally independent or linked to each other. One is mediated by recruitment of the proximal regulator caspase-8 to the death receptor complex. The other pathway is controlled by the release of cytochrome c from mitochondria and the subsequent ATP-dependent activation of the death regulator apoptotic protease-activating factor 1 (Apaf-1). Here, we report that both pathways can be dissected by depletion of intracellular ATP. Prevention of ATP production completely inhibited caspase activation and apoptosis in response to chemotherapeutic drugs and staurosporine. Interestingly, caspase-8, whose function appeared to be restricted to death receptors, was also activated by these drugs under normal conditions, but not after ATP depletion. In contrast, inhibition of ATP production did not affect caspase activation after triggering of CD95. These results suggest that chemotherapeutic drug–induced caspase activation is entirely controlled by a receptor-independent mitochondrial pathway, whereas CD95-induced apoptosis can be regulated by a separate pathway not requiring Apaf-1 function.