tbuckley/cabot-search huggingface dataset:
Prevention of Rabbit Acute Lung Injury by Surfactant, Inhaled Nitric Oxide, and Pressure Support Ventilation
Authors: ZHAO-HUI ZHOU, BO SUN, KE LIN, LIE-WEI ZHU
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Improvement of pulmonary perfusion and blood oxygenation and prevention of acute lung injury (ALI) may rely on ventilation strategy. We hypothesized that application of a combined surfactant, inhaled nitric oxide (iNO), and pressure support ventilation (PSV) should more effectively protect the lungs from injury. Anesthetized and intubated adult rabbits weighing 2.8 ± 0.3 kg were allowed to breathe room air while receiving oleic acid intravenously (60 μ l/kg). Within 90 min this caused a reduction of PaO2 from 94 ± 7 to 48 ± 3 mm Hg and dynamic lung compliance (Cdyn) from 1.59 ± 0.22 to 0.85 ± 0.10 ml/cm H2O/kg (both p < 0.01), and increase of intrapulmonary shunting (Q˙ s/Q˙ t) from 9.4 ± 1.2 to 27 ± 5% (p < 0.05). PSV was subsequently applied with 3 cm H2O of continuous positive airway pressure and Fi O2 of 0.3, and the animals were randomly allocated to four groups, receiving: (1) PSV only (Control, n = 10); (2) iNO at 20 ppm (NO, n = 9); (3) surfactant phospholipids at 100 mg/kg (Surf, n = 8); and (4) surfactant at 100 mg/kg and iNO at 20 ppm (SNO, n = 8). PSV level was varied to maintain a tidal volume of 8 to 10 ml/kg for another 12 h or until early animal death. Five animals in the SNO, three each in the NO and Surf group, and one in the Control group survived 12 h (SNO versus Control, p < 0.05). The NO, Surf, and SNO groups had significantly improved mean PaO2 ( > 70 mm Hg, p < 0.05), and reduced Q˙ s/Q˙ t (15, 19, and 17%, respectively, p < 0.05) at 6 and 12 h, but not in the Control group. The SNO group had the highest values of Cdyn at 12 h, alveolar aeration and disaturated phosphatidylcholine-to-total protein ratio in bronchoalveolar lavage fluid, and the lowest wet-to-dry lung weight ratio and lung injury score (p < 0.05). The results indicate that early alleviation of ALI by surfactant, iNO, and PSV is due to synergistic effects, and only PSV in this model had limited effects. Zhou Z-H, Sun B, Lin K, Zhu L-W. Prevention of rabbit acute lung injury by surfactant, inhaled nitric oxide, and pressure support ventilation.
DNAX Accessory Molecule-1 Mediated Recognition of Freshly Isolated Ovarian Carcinoma by Resting Natural Killer Cells
Authors: Mattias Carlsten, Niklas K. Björkström, Håkan Norell, Yenan Bryceson, Thorbald van Hall, Bettina C. Baumann, Mikael Hanson, Kjell Schedvins, Rolf Kiessling, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
Journal: Cancer Research (2007)

Abstract Although natural killer (NK) cells are well known for their ability to kill tumors, few studies have addressed the interactions between resting (nonactivated) NK cells and freshly isolated human tumors. Here, we show that human leukocyte antigen class Ilow tumor cells isolated directly from patients with advanced ovarian carcinoma trigger degranulation by resting allogeneic NK cells. This was paralleled by induction of granzyme B and caspase-6 activities in the tumor cells and significant tumor cell lysis. Ovarian carcinoma cells displayed ubiquitous expression of the DNAX accessory molecule-1 (DNAM-1) ligand PVR and sparse/heterogeneous expression of the NKG2D ligands MICA/MICB and ULBP1, ULBP2, and ULBP3. In line with the NK receptor ligand expression profiles, antibody-mediated blockade of activating receptor pathways revealed a dominant role for DNAM-1 and a complementary contribution of NKG2D signaling in tumor cell recognition. These results show that resting NK cells are capable of directly recognizing freshly isolated human tumor cells and identify ovarian carcinoma as a potential target for adoptive NK cell–based immunotherapy. [Cancer Res 2007;67(3):1317–25]
Interaction of Deleted in Liver Cancer 1 with Tensin2 in Caveolae and Implications in Tumor Suppression
Authors: Judy Wai Ping Yam, Frankie Chi Fat Ko, Chung-Yiu Chan, Dong-Yan Jin, Irene Oi-Lin Ng
Journal: Cancer Research (2006)

Abstract Deleted in liver cancer 1 (DLC1) is a recently identified tumor suppressor gene frequently underexpressed in hepatocellular carcinoma (HCC). DLC1 encodes a Rho GTPase-activating protein domain that exhibits growth-suppressive activity in HCC cell lines. Our recent finding has revealed that inhibition of Rho-mediated actin stress fiber formation by DLC1 is associated with its growth inhibitory activity. In the present study, we identified tensin2 as the novel binding partner of DLC1. Tensin2 belongs to a new family of focal adhesion proteins that play key roles in cytoskeleton organization and signal transduction. Dysregulation of tensin proteins has previously been implicated in human cancers. Tensin2 is highly expressed in human liver. Introduction of tensin2 into HCC cell lines with low expression of tensin2 caused significant growth inhibition and induction of apoptosis. Tensin2 directly interacted with DLC1 in vitro and in vivo. Both proteins localized to punctate structures in the cytoplasm. Sequence analysis of DLC1 and tensin2 identified caveolin-1 binding motif in both proteins. In vivo immunoprecipitation study confirmed that both proteins indeed interacted with endogenous caveolin-1, which is the major structural component of caveolae. Our findings presented here suggest a new model for the action of DLC1 in hepatocytes, whereby DLC1-tensin2 complex interacts with Rho GTPases in caveolae to effect cytoskeletal reorganization. (Cancer Res 2006; 66(17): 8367-72)
The role of antigen form and function in the primary and secondary intestinal immune responses to cholera toxin and toxoid in rats
Authors: NF Pierce
Journal: The Journal of Experimental Medicine (1978)

This report describes studies of the mucosal antitoxic response in rats after enteric administration of several forms of cholera toxin or toxoid, proteins which differ primarily in their ability to bind to cell membranes and activate cellular adenyl cyclase. These two characteristics appeared to markedly enhance the local primary response to these antigens. A single dose of toxoid lacking these features was ineffective in local priming even though it was absorbed and induced a systemic immune response. Single dose mucosal priming occurred only with preparations which bind to cell membranes and was enhanced by those which also activate cellular adenyl cyclase. In contrast, single-dose mucosal boosting was best accomplished by materials with these properties but was also seen with a toxoid lacking both of these functions. The property of membrane binding appears to be most advantageous in mucosal priming, perhaps by increasing effective trapping of absorbed antigen in unprimed mucosal lymphoid tissue, whereas the ability to activate adenyl cyclase appears to enhance primary and secondary type responses about equally. Combinations of crude toxoid and toxin were also more effective in mucosal priming than purified materials, a finding which is unexplained. A single dose of this combination induced mucosal priming which was fully developed in 2 wk, undiminished after 4 too, and only modestly diminished after 8 mo, thus demonstrating relatively prolonged memory in the IgA mucosal immune system. Effective two-dose local immunizing regimens were developed, and it was shown that there was no correlation between the mucosal and systemic secondary antitoxin responses provoked by these regimens.
Enhanced Delivery of Cisplatin to Intraperitoneal Ovarian Carcinomas Mediated by the Effects of Bortezomib on the Human Copper Transporter 1
Authors: Danielle D. Jandial, Salman Farshchi-Heydari, Christopher A. Larson, Gregory I. Elliott, Wolfgang J. Wrasidlo, Stephen B. Howell
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The copper transporter 1 (CTR1) is a major influx transporter for platinum drugs. However, the accumulation of cisplatin in human ovarian carcinoma cells is limited by the fact that cisplatin triggers the down-regulation and proteasomal degradation of CTR1, thereby limiting its own uptake. We sought to determine whether proteasome inhibition using bortezomib would prevent human CTR1 (hCTR1) degradation and increase platinum accumulation in ovarian cancer cells. Experimental Design: The effects of bortezomib on human hCTR1 expression and cisplatin accumulation were measured by Western blot, flow cytometric, and confocal digital imaging analyses. Platinum accumulation was measured by inductively coupled plasma mass spectrometry and bortezomib concentrations by liquid chromatography/mass spectrometry. Results: Bortezomib blocked the cisplatin-induced down-regulation of hCTR1 in a concentration-dependent manner and increased cisplatin uptake 1.6- to 2.4-fold. Median effect analysis showed a combination index of 0.37 at 50% cell kill, indicating a high level of synergy. The effect of bortezomib was muted in cells lacking both alleles of CTR1, showing that bortezomib was working primarily through its effect on blocking hCTR1 degradation. I.p. administration of bortezomib produced a peritoneal/plasma area under the curve ratio of 252 in a murine model. I.p. administration of bortezomib before i.p. cisplatin increased platinum accumulation in peritoneal tumors by 33% (P = 0.006). Conclusions: Proteasomal inhibition prevented cisplatin-induced down-regulation of hCTR1 in ovarian cancer cells and enhanced drug uptake and cell killing in a synergistic manner. Bortezomib shows a large pharmacologic advantage when administered i.p. There is a strong rationale for the combined i.p. administration of bortezomib and cisplatin.
Effectiveness of simulation based training in patient safety - Validation study for Georges patient safety in simulation tool
Authors: Shairana Naleem, Hannah Robinson, Indranil Chakravorty
Journal: European Respiratory Journal (2014)

The Georges Patient Safety in Simulation Tool (GPSS) was developed to assess 4 domains: DI -clinical decision making,DII- prescribing, DIII-communication-escalation and D IV-team-working. The assessment criteria was based on the Acute Care Assessment Tool of the JRCPTB and scoring on the Royal College of Physicians. The pilot study in 2011-12 in 48 core medical trainees in SW London demonstrated a baseline score of 22 and that majority of candidates failed to meet the pre-determined threshold for safe patient management. Clinical decision making and prescribing improved with training but only modest change was seen in communication and team-working.

Design

The course was redesigned to include enhanced aspects of situational awareness, delegation, team-management and handover. The structure of baseline assessment of all candidates, followed by 4 learning scenarios concluding with an assessment scenario, was retained with 2 assessors and single blinding. This was implemented in 2012-13 cohort and the impact analysed in a further 20 trainees.

Results

The baseline scores were similar to 2011-12 cohort as 22.4 (SD 8.9) and this improved to 34.4 (SD 6.8) at the end of the simulation based training. The effect sizes Cohen's d and (correlation) of each domain were DI 1.13 (0.49), DII 1.01 (0.45), DIII 1.11 (0.49) and D IV 1.75 (0.66) with total scores 1.51 (0.6).

Conclusion

The GPSS demonstrated internal consistency and reliability in measuring the impact of simulation based learning in improving patient safety domains and results were consistent with 2011-12 data with additional improvements seen in communication and team-working and may be used in other learners.
Association of Early Kidney Allograft Failure with Preformed IgA Antibodies to β 2-Glycoprotein I
Authors: Jose M. Morales, Jose Angel Martinez-Flores, Manuel Serrano, Maria José Castro, Francisco Javier Alfaro, Florencio García, Miguel Angel Martínez, Amado Andrés, Esther González, Manuel Praga, Estela Paz-Artal, Antonio Serrano
Journal: Journal of the American Society of Nephrology (2014)

In the current immunosuppressive therapy era, vessel thrombosis is the most common cause of early graft loss after renal transplantation. The prevalence of IgA anti-β2-glycoprotein I antibodies (IgA-aB2GPI-ab) in patients on dialysis is elevated (>30%), and these antibodies correlate with mortality and cardiovascular morbidity. To evaluate the effect of IgA-aB2GPI-ab in patients with transplants, we followed all patients transplanted from 2000 to 2002 in the Hospital 12 de Octubre prospectively for 10 years. Presence of IgA-aB2GPI-ab in pretransplant serum was examined retrospectively. Of 269 patients, 89 patients were positive for IgA-aB2GPI-ab (33%; group 1), and the remaining patients were negative (67%; group 2). Graft loss at 6 months post-transplant was significantly higher in group 1 (10 of 89 versus 3 of 180 patients in group 2; P=0.002). The most frequent cause of graft loss was thrombosis of the vessels, which was observed only in group 1 (8 of 10 versus 0 of 3 patients in group 2; P=0.04). Multivariate analysis showed that the presence of IgA-aB2GPI-ab was an independent risk factor for early graft loss (P=0.04) and delayed graft function (P=0.04). There were no significant differences regarding patient survival between the two groups. Graft survival was similar in both groups after 6 months. In conclusion, patients with pretransplant IgA-aB2GPI-ab have a high risk of early graft loss caused by thrombosis and a high risk of delayed graft function. Therefore, pretransplant IgA-aB2GPI-ab may have a detrimental effect on early clinical outcomes after renal transplantation.
MOPP Versus ABVD and Low-Dose Versus High-Dose Irradiation in Hodgkin's Disease at Intermediate and Advanced Stages: Analysis of a Meta-Analysis by Clinicians
Authors: Jean Marie Andrieu, Ugur Yilmaz, Pierre Colonna, M. Loeffler, O. Brosteanu, D. Hasenclever
Journal: Journal of Clinical Oncology (1999)
Associations between white blood cell count, lung function, respiratory illness and mortality: the Busselton Health Study
Authors: A.L. James, M.w Knuiman, M.l Divitini, A.W. Musk, G. Ryan, H.c Bartholomew
Journal: European Respiratory Journal (1999)

An independent association between reduced levels of lung function and increased mortality from nonrespiratory causes has been observed in a number of studies. Since the total white blood cell count (WBC) has been related to both death from coronary heart disease and to levels of lung function, the relationship between these parameters was examined in subjects from the Busselton Health Surveys. Questionnaires regarding respiratory and cardiac illness and smoking habits were administered and total WBC, forced expiratory volume in one second (FEV1) and forced vital capacity measured in 2,105 males and 2,186 females at their initial attendance at a Busselton Health Survey in 1969, 1972 or 1975. Mortality follow-up to 1995 was completed. Multiple linear regression showed that smoking, increasing age, reduced FEV1 (% predicted) and a history of bronchitis were associated with increased WBC. Reduction of FEV1 (% pred) by 20%, a history of dyspnoea and an increase in WBC of 1,300 cells x mL(-1) were predictive of increased mortality from all causes or coronary heart disease by approximately 20, 100 and 10% respectively, independent of smoking. Removing WBC from the regression model did not significantly change the relationship between FEV1 and mortality. The study shows that the white blood cell count, forced expiratory volume in one second and dyspnoea are independently related to mortality in both males and females and that the effect of forced expiratory volume in one second on mortality is not explained by the white blood cell count.
Novel mutations in the EDAR gene in two Pakistani consanguineous families with autosomal recessive hypohidrotic ectodermal dysplasia
Authors: M. Naeem, D. Muhammad, W. Ahmad
Journal: British Journal of Dermatology (2005)

Background Hypohidrotic ectodermal dysplasia (HED) is a human heritable disorder characterized by sparse hair, a lack of sweat glands and malformation of teeth. There are X-linked, autosomal recessive and autosomal dominant forms of this disorder. Mutations in the EDA gene cause X-linked HED and mutations in either the EDAR or the EDARADD genes cause autosomal forms of HED. Objectives To identify pathogenic mutations in two consanguineous Pakistani families (A and B) with 11 affected individuals demonstrating the autosomal recessive form of HED. Methods Genotyping of 17 members of the two families, including eight affected and nine unaffected individuals, was carried out by using polymorphic markers D2S293, D2S1893 and D2S1891, which are closely linked to the EDAR gene on chromosome 2q11-q13. To screen for mutations in the EDAR gene, all of its exons and splice junctions were polymerase chain reaction amplified from genomic DNA and sequenced directly in an ABI Prism 310 automated sequencer. Results Genotyping results showed linkage in both the Pakistani families to the EDAR locus. Sequence analysis of the EDAR gene identified two novel mutations in the families: a missense mutation (G382S) in family A and a 4-bp deletion (718delAAAG) in family B. Conclusions We describe novel mutations in the EDAR gene in two Pakistani families affected with the autosomal recessive form of HED. Our findings extend the body of evidence that supports the importance of the ectodysplasin A1 isoform receptor, a member of the tumour necrosis factor receptor family, in the development of ectodermal appendages.
Unifocal psoriatic arthritis development in identical twins following site specific injury: evidence supporting biomechanical triggering events in genetically susceptible hosts
Authors: Jennifer Ng, Ai Lyn Tan, Dennis McGonagle
Journal: Annals of the Rheumatic Diseases (2015)

There have been reports suggesting that trauma or ‘deep Koebner phenomenon’ can precipitate the development of psoriatic arthritis (PsA).1 Both psoriasis and PsA have strong genetic associations, but there are no studies or reports on any potential interaction between environmental injury and genetics in the development of PsA. We describe the cases of identical twins with psoriasis who each developed PsA of the respective right and left second toes following foot injury.

A 54-year-old woman with a 15-year history of psoriasis kicked a table leg with her right foot. Thereafter, she developed pain and swelling of the second toe. X-ray of the foot did not show any fractures. An ultrasound showed marked synovitis of the right second toe with associated plantar plate rupture. She subsequently had surgical repair of the plantar plate, but the pain and swelling persisted. …
The Pathology of Honeycomb Lung
Authors: A. G. Heppleston
Journal: Thorax (1956)

recognized though apparently uncommon condition, which, according to earlier accounts, occurred especially in children (Sharkey, 1894; Tooth, 1897; Fletcher, 1901; Bernstein, 1905).Such lungs were described by Fowler and Godlee (1898) as having a worm-eaten or honeycomb appearance.Sharkey
INHIBITION OF ESCHERICHIA COLI BY p-AMINOBENZOIC ACID AND ITS REVERSAL BY p-HYDROXYBENZOIC ACID
Authors: Bernard D. Davis
Journal: The Journal of Experimental Medicine (1951)

p-Aminobenzoic acid (PABA) exerts three metabolic effects on E. coli: it acts as a normal vitamin at low concentrations, as a source of another vitamin, p-hydroxybenzoic acid (POB), at moderate concentrations, and as a growth inhibitor at high concentrations (150 to 1600 microg./ml.). The inhibition is competitively reversed by POB in 1/100 the concentration of PABA. The inhibition is also reversed to a limited extent by shikimic acid and compound X, precursors of POB. p-Nitrobenzoic acid is an inhibitory competitor of both POB and PABA. The retardation of growth produced by PABA and other competitive analogues of POB (p-nitrobenzoic acid; 4,4'-dihydroxydiphenyl sulfone; phenosulfazole) is converted to complete bacteriostasis by the addition of L-aspartic acid in a remarkably low concentration (1 microg./ml.)) without change in the competitive ratio with POB. The mechanism underlying this synergism is not clear. In contrast to wild type, mutants that require POB not only are inhibited by much lower concentrations of the above analogues, but also show inhibition by weaker competitors of POB such as p-hydroxybenzenesulfonamide, p-chlorobenzoic acid, and p-fluorobenzoic acid.
Subcorneal pustular dermatosis in dogs and in human beings: Comparative aspects
Authors: Kathleen M. Kalaher, Danny W. Scott
Journal: Journal of the American Academy of Dermatology (1990)

Subcorneal pustular dermatosis is a rare disorder in dogs and in human beings. A retrospective study of 13 cases of canine subcorneal pustular dermatosis indicates that many of the clinicopathologic features of this disease are similar in both species. In both the condition is characterized by a variably pruritic, sterile, pustular eruption that is resistant to antibiotics and glucocorticoids. The therapeutic response to dapsone is not uniformly successful in either species, and the disorder tends to be chronic and recurrent.
STI571: A Paradigm of New Agents for Cancer Therapeutics
Authors: Michael J. Mauro, Michael O’Dwyer, Michael C. Heinrich, Brian J. Druker
Journal: Journal of Clinical Oncology (2002)

STI571 exemplifies the successful development of a rationally designed, molecularly targeted therapy for the treatment of a specific cancer. This article reviews the identification of Bcr-Abl as a therapeutic target in chronic myelogenous leukemia and the steps in the development of an agent to specifically inactivate this abnormality. Issues related to clinical trials of molecularly targeted agents are discussed, including dose selection, optimizing therapy, and predicting response, as are possible mechanisms of resistance to STI571. Lastly, the potential use of STI571 in other malignancies and the translation of this paradigm to other malignancies are explored.
Fetal Lead Exposure at Each Stage of Pregnancy as a Predictor of Infant Mental Development
Authors: Howard Hu, Martha María Téllez-Rojo, David Bellinger, Donald Smith, Adrienne S. Ettinger, Héctor Lamadrid-Figueroa, Joel Schwartz, Lourdes Schnaas, Adriana Mercado-García, Mauricio Hernández-Avila
Journal: Environmental Health Perspectives (2006)

BackgroundThe impact of prenatal lead exposure on neurodevelopment remains unclear in terms of consistency, the trimester of greatest vulnerability, and the best method for estimating fetal lead exposure.ObjectiveWe studied prenatal lead exposure's impact on neurodevelopment using repeated measures of fetal dose as reflected by maternal whole blood and plasma lead levels.MethodsWe measured lead in maternal plasma and whole blood during each trimester in 146 pregnant women in Mexico City. We then measured umbilical cord blood lead at delivery and, when offspring were 12 and 24 months of age, measured blood lead and administered the Bayley Scales of Infant Development. We used multivariate regression, adjusting for covariates and 24-month blood lead, to compare the impacts of our pregnancy measures of fetal lead dose.ResultsMaternal lead levels were moderately high with a first-trimester blood lead mean (± SD) value of 7.1 ± 5.1 μg/dL and 14% of values ≥10 μg/dL. Both maternal plasma and whole blood lead during the first trimester (but not in the second or third trimester) were significant predictors (p < 0.05) of poorer Mental Development Index (MDI) scores. In models combining all three trimester measures and using standardized coefficients, the effect of first-trimester maternal plasma lead was somewhat greater than the effect of first-trimester maternal whole blood lead and substantially greater than the effects of second- or third-trimester plasma lead, and values averaged over all three trimesters. A 1-SD change in first-trimester plasma lead was associated with a reduction in MDI score of 3.5 points. Postnatal blood lead levels in the offspring were less strongly correlated with MDI scores.ConclusionsFetal lead exposure has an adverse effect on neurodevelopment, with an effect that may be most pronounced during the first trimester and best captured by measuring lead in either maternal plasma or whole blood.