tbuckley/cabot-search huggingface dataset:
Tissue Platinum Concentration and Tumor Response in Non–Small-Cell Lung Cancer
Authors: Eric S. Kim, J. Jack Lee, Guangan He, Chi-Wan Chow, Junya Fujimoto, Neda Kalhor, Stephen G. Swisher, Ignacio I. Wistuba, David J. Stewart, Zahid H. Siddik
Journal: Journal of Clinical Oncology (2012)

Purpose Platinum resistance is a major limitation in the treatment of advanced non–small-cell lung cancer (NSCLC). Reduced intracellular drug accumulation is one of the most consistently identified features of platinum-resistant cell lines, but clinical data are limited. We assessed the effects of tissue platinum concentrations on response and survival in NSCLC. Patients and Methods We measured total platinum concentrations by flameless atomic absorption spectrophotometry in 44 archived fresh-frozen NSCLC specimens from patients who underwent surgical resection after neoadjuvant platinum-based chemotherapy. Tissue platinum concentration was correlated with percent reduction in tumor size on post- versus prechemotherapy computed tomography scans. The relationship between tissue platinum concentration and survival was assessed by univariate and multicovariate Cox proportional hazards regression model analysis and Kaplan-Meier analysis. Results Tissue platinum concentration correlated significantly with percent reduction in tumor size (P &lt; .001). The same correlations were seen with cisplatin, carboplatin, and all histology subgroups. Furthermore, there was no significant impact of potential variables such as number of cycles and time lapse from last chemotherapy on platinum concentration. Patients with higher platinum concentration had longer time to recurrence (P = .034), progression-free survival (P = .018), and overall survival (P = .005) in the multicovariate Cox model analysis after adjusting for number of cycles. Conclusion This clinical study established a relationship between tissue platinum concentration and response in NSCLC. It suggests that reduced platinum accumulation might be an important mechanism of platinum resistance in the clinical setting. Further studies investigating factors that modulate intracellular platinum concentration are warranted.
Inducible nitric oxide synthase activation after ischemia/reperfusion contributes to myocardial dysfunction and extent of infarct size in rabbits: evidence for a late phase of nitric oxide-mediated reperfusion injury
Authors: S Wildhirt
Journal: Cardiovascular Research (1999)

Background: Ischemia/reperfusion (I/R) leads to the induction of inducible nitric oxide synthase. The present study investigated the effects of selective and continuous inhibition of iNOS on myocardial performance, infarct size and histomorphological changes after I/R in rabbits. Methods and Results: Ischemia/reperfusion (I/R) was induced by occlusion of the circumflex coronary artery for 30 min followed by 48 h of reperfusion. Sham animals (group A) served as control. Three groups were subjected to I/R: (B) placebo; (C) aminoguanidine (AMG; 10 mg/kg bolus) given prior to and 48 h after I/R to test its acute effects; (D) AMG (300 mg/kg/day sc) to test effects of continuous treatment. Hemodynamics, myocardial blood flow, infarct size, iNOS activity, cGMP levels, immunohistochemical analysis of iNOS expression and AMG tissue levels were determined.Continuous AMG treatment improved myocardial performance (hemodynamics and blood flow) compared to placebo group. iNOS was highest in placebo-treated animals. AMG tissue levels were highest in tissues affected by I/R. Infarct size (% of the circumflex region) was significantly smaller in group D when compared to group B. Conclusions: This is the first study showing that activation of myocardial iNOS isozyme during 48 h of reperfusion contributes to a late phase of I/R-induced injury in rabbits. Selective and continuous modulation of iNOS by AMG over this time period exerts protective effects with respect to myocardial performance, coronary blood flow, cellular infiltration and reduction of infarct size; this may be a novel therapeutic approach in the clinical situation to limit irreversible myocardial injury associated with ischemia and reperfusion.
Age-dependent changes in TDP-43 levels in a mouse model of Alzheimer disease are linked to Aβ oligomers accumulation
Authors: Antonella Caccamo, Andrea Magrí, Salvatore Oddo
Journal: Molecular Neurodegeneration (2010)

Transactive response DNA-binding protein 43 (TDP-43) is the pathological protein found in frontotemporal lobar degeneration with ubiquitin positive inclusions and in amyotrophic lateral sclerosis. In diseased tissue, TDP-43 translocates from its physiological nuclear location into the cytoplasm, where it accumulates. Additionally, C-terminal fragments of TDP-43 accumulate in affected brain regions and are sufficient to cause TDP-43 mislocalization and cytoplasmic accumulation in vitro. TDP-43 also accumulates in 30% of Alzheimer disease (AD) cases, a finding that has been highly reproducible. The role of TDP-43 in AD and its relation with Aβ and tau pathology, the two neuropathological hallmarks of AD, remains to be elucidated.Here we show that levels of TDP-43 and its ~35 kDa C-terminal fragment are significantly increased in the 3×Tg-AD mice, an animal model of AD that develops an age-dependent cognitive decline linked to the accumulation of Aβ and tau. We also report that the levels of TDP-43 and its C-terminal fragment correlate with the levels of soluble Aβ oligomers, which play a key role in AD pathogenesis. Notably, genetically reducing Aβ42 production restores the levels of TDP-43 and its ~35 kDa C-terminal fragment to control levels.These data suggest a possible relation between Aβ oligomers and TDP-43.
Novel technology for detection of genomic and transcriptional alterations in pancreatic cancer
Authors: C. Wallrapp, F. Müller-Pillasch, A. Micha, C. Wenger, M. Geng, S. Solinas-Toldo, P. Lichter, M. Frohme, J.D. Hoheisel, G. Adler, T.M. Gress
Journal: Annals of Oncology (1999)
Pulsed dye laser treatment in lupus erythematosus telangiectoides
Authors: M. Nunez, P. Boixeda, K.S. Miralles, R.F. Misa, A. Ledo
Journal: British Journal of Dermatology (1995)

Journal Article Pulsed dye laser treatment in lupus erythematosus telangiectoides Get access M. Nunez, M. Nunez Servicio de Dermatologia, Hospital Ramon y Cajal, Universidad de Alacalá, 28034 Madrid, Spain Search for other works by this author on: Oxford Academic Google Scholar P. Boixeda, P. Boixeda Servicio de Dermatologia, Hospital Ramon y Cajal, Universidad de Alacalá, 28034 Madrid, Spain Search for other works by this author on: Oxford Academic Google Scholar K.S. Miralles, K.S. Miralles Servicio de Dermatologia, Hospital Ramon y Cajal, Universidad de Alacalá, 28034 Madrid, Spain Search for other works by this author on: Oxford Academic Google Scholar R.F. de Misa, R.F. de Misa Servicio de Dermatologia, Hospital Ramon y Cajal, Universidad de Alacalá, 28034 Madrid, Spain Search for other works by this author on: Oxford Academic Google Scholar A. Ledo A. Ledo Servicio de Dermatologia, Hospital Ramon y Cajal, Universidad de Alacalá, 28034 Madrid, Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 133, Issue 6, 1 December 1995, Pages 1010–1011, https://doi.org/10.1111/j.1365-2133.1995.tb06945.x Published: 01 December 1995
Autoregulation of mariner transposase activity by overproduction and dominant-negative complementation
Authors: A. R. Lohe, D. L. Hartl
Journal: Molecular Biology and Evolution (1996)

Genetic studies of the mariner transposable element Mos1 have revealed two novel types of regulatory mechanisms. In one mechanism, overproduction of the wild-type transposase reduces the overall level of transposase activity as assayed by the excision of a nonautonomous mariner target element. This mechanism is termed overproduction inhibition (OPI). Another mechanism is observed in a class of hypomorphic missense mutations in the transposase. In the presence of wild-type Mos1 transposase, these mutations exhibit dominant-negative complementation (DNC) that antagonizes the activity of the wild-type transposase. We propose that these regulatory mechanisms act at the level of the transposase protein subunits by promoting the assembly of oligomeric forms, or of mixed-subunit oligomers, that have reduced activity. We suggest that these regulatory mechanisms may apply generally to mariner-like elements (MLEs). Overproduction inhibition may help explain why the MLE copy number reaches very different levels in different species. Dominant-negative complementation may help explain why most naturally occurring copies of MLEs have been mutationally inactivated.
Characteristics of Recurrent Ventricular Fibrillation Associated With Inferolateral Early Repolarization
Authors: Michel Haïssaguerre, Frederic Sacher, Akihiko Nogami, Nohiriro Komiya, Anne Bernard, Vincent Probst, Sinikka Yli-Mayry, Pascal Defaye, Yoshifusa Aizawa, Robert Frank, Roberto Mantovan, Riccardo Cappato, Christian Wolpert, Antoine Leenhardt, Luc de Roy, Hein Heidbuchel, Isabel Deisenhofer, Thomas Arentz, Jean-Luc Pasquié, Rukshen Weerasooriya, Meleze Hocini, Pierre Jais, Nicolas Derval, Pierre Bordachar, Jacques Clémenty
Journal: Journal of the American College of Cardiology (2009)
Teaching Psychosomatic Approaches as a Basis of Clinical Medicine
Authors: Tetsuya Nakagawa, Yufiro Ikemi
Journal: Psychotherapy and Psychosomatics (1979)

We have introduced our idea of psychosomatic approach as a basis of clinical medicine and the present state of psychosomatic teaching and training in our department as well as in other university hospitals in Japan. In teaching and training medical students and postgraduates, we aim at producing psychosomatically minded clinical physicians. For this purpose, multidisciplinary and teamwork approaches in cooperation with paramedicals are needed.
Guidelines for the diagnosis of tick-borne bacterial diseases in Europe
Authors: P. Brouqui, F. Bacellar, G. Baranton, R.J. Birtles, A. Bjoërsdorff, J.R. Blanco, G. Caruso, M. Cinco, P.E. Fournier, E. Francavilla, M. Jensenius, J. Kazar, H. Laferl, A. Lakos, S. Lotric Furlan, M. Maurin, J.A. Oteo, P. Parola, C. Perez-Eid, O. Peter, D. Postic, D. Raoult, A. Tellez, Y. Tselentis, B. Wilske
Journal: Clinical Microbiology and Infection (2004)
Tidal Volume Reduction for Prevention of Ventilator-induced Lung Injury in Acute Respiratory Distress Syndrome
Authors: LAURENT BROCHARD, FRANÇOISE ROUDOT-THORAVAL, ERIC ROUPIE, CHRISTOPHE DELCLAUX, JEAN CHASTRE, ENRIQUE FERNANDEZ-MONDÉJAR, EVA CLÉMENTI, JORDI MANCEBO, PHILLIP FACTOR, DIMITRI MATAMIS, MARCO RANIERI, LLUIS BLANCH, GIUSEPPE RODI, HERVÉ MENTEC, DIDIER DREYFUSS, MIGUEL FERRER, CHRISTIAN BRUN-BUISSON, MARTIN TOBIN, FRANÇOIS LEMAIRE
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Because animal studies have demonstrated that mechanical ventilation at high volume and pressure can be deleterious to the lungs, limitation of airway pressure, allowing hypercapnia if necessary, is already used for ventilation of acute respiratory distress syndrome (ARDS). Whether a systematic and more drastic reduction is necessary is debatable. A multicenter randomized study was undertaken to compare a strategy aimed at limiting the end-inspiratory plateau pressure to 25 cm H2O, using tidal volume (Vt) below 10 ml/kg of body weight, versus a more conventional ventilatory approach (with regard to current practice) using Vt at 10 ml/kg or above and close to normal PaCO2 . Both arms used a similar level of positive end-expiratory pressure. A total of 116 patients with ARDS and no organ failure other than the lung were enrolled over 32 mo in 25 centers. The two groups were similar at inclusion. Patients in the two arms were ventilated with different Vt (7.1 ± 1.3 versus 10.3 ± 1.7 ml/kg at Day 1, p < 0.001) and plateau pressures (25.7 ± 5.0 versus 31.7 ± 6.6 cm H2O at Day 1, p < 0.001), resulting in different PaCO2 (59.5 ± 15.0 versus 41.3 ± 7.6 mm Hg, p < 0.001) and pH (7.28 ± 0.09 versus 7.4 ± 0.09, p < 0.001), but a similar level of oxygenation. The new approach did not reduce mortality at Day 60 (46.6% versus 37.9% in control subjects, p = 0.38), the duration of mechanical ventilation (23.1 ± 20.2 versus 21.4 ± 16.3 d, p = 0.85), the incidence of pneumothorax (14% versus 12%, p = 0.78), or the secondary occurrence of multiple organ failure (41% versus 41%, p = 1). We conclude that no benefit could be observed with reduced Vt titrated to reach plateau pressures around 25 cm H2O compared with a more conventional approach in which normocapnia was achieved with plateau pressures already below 35 cm H2O.
RECIPROCAL EFFECTS OF CONCOMITANT INFECTIONS
Authors: Louise Pearce
Journal: The Journal of Experimental Medicine (1928)

Experiments are reported in which it was shown, first, that the effectiveness of the reaction to experimental syphilis was increased in rabbits immune to vaccine virus, the ensuing disease being less severe than in control animals. It was further shown that a comparable modification of the syphilitic reaction occurred in rabbits inoculated intratesticularly with a mixture of Treponema pallidum and vaccine virus, and it was suggested that this result was due to the influence of a vaccinal immunity and to the local effect of the vaccinal reaction. It was pointed out that the manner in which two concomitant experimental infections are induced is of significance in determining the character of the host's reaction.
Cystinuria With Hyperuricemia
Authors: C. Robert Meloni
Journal: JAMA (1967)

CYSTINURIA is intrinsically a nonfatal metabolic abnormality with variable morbidity. The morbidity associated with this disorder is directly related to the relative insolubility of cystine and the resulting formation of cystine stones in the urinary tract. Since concurrent chronic disease has rarely been reported in association with cystinuria, it seemed appropriate to record observations on four of six cystinuric patients who had hyperuricemia, normal renal function, and family backgrounds of hyperuricemia. These six cases of cystinuria comprise our experience with the disease. <h3>Methods and Materials</h3> The cyanide nitroprusside test<sup>1</sup>was used to test for urinary cystine. Urinary two-dimensional thinlayer chromatograms for amino acids, modified from Fahmy et al,<sup>2</sup>were examined for the presence of lysine, cystine, arginine, and ornithine. Serum and urinary uric acid were measured by the uricase method of Liddle et al. By this method, any value over 6.5 mg/100 ml indicates hyperuricemia.<sup>3</sup>The families
Regulation of colony stimulating factor-1 expression and ovarian cancer cell behavior in vitro by miR-128 and miR-152
Authors: Ho-Hyung Woo, Csaba F László, Stephen Greco, Setsuko K Chambers
Journal: Molecular Cancer (2012)

Colony stimulating factor-1 (CSF-1) plays an important role in ovarian cancer biology and as a prognostic factor in ovarian cancer. Elevated levels of CSF-1 promote progression of ovarian cancer, by binding to CSF-1R (the tyrosine kinase receptor encoded by c-fms proto-oncogene). Post-transcriptional regulation of CSF-1 mRNA by its 3’ untranslated region (3’UTR) has been studied previously. Several cis-acting elements in 3’UTR are involved in post-transcriptional regulation of CSF-1 mRNA. These include conserved protein-binding motifs as well as miRNA targets. miRNAs are 21-23nt single strand RNA which bind the complementary sequences in mRNAs, suppressing translation and enhancing mRNA degradation. In this report, we investigate the effect of miRNAs on post-transcriptional regulation of CSF-1 mRNA in human ovarian cancer. Bioinformatics analysis predicts at least 14 miRNAs targeting CSF-1 mRNA 3’UTR. By mutations in putative miRNA targets in CSF-1 mRNA 3’UTR, we identified a common target for both miR-128 and miR-152. We have also found that both miR-128 and miR-152 down-regulate CSF-1 mRNA and protein expression in ovarian cancer cells leading to decreased cell motility and adhesion in vitro, two major aspects of the metastatic potential of cancer cells. The major CSF-1 mRNA 3’UTR contains a common miRNA target which is involved in post-transcriptional regulation of CSF-1. Our results provide the evidence for a mechanism by which miR-128 and miR-152 down-regulate CSF-1, an important regulator of ovarian cancer.
Phenotype of airway epithelial cells suggests epithelial to mesenchymal cell transition in clinically stable lung transplant recipients
Authors: C Ward
Journal: Thorax (2005)

<b>Background:</b> Obliterative bronchiolitis in chronic rejection of lung allografts is characterised by airway epithelial damage and fibrosis. The process whereby normal epithelium is lost and replaced by fibroblastic scar tissue is poorly understood, but recent findings suggest that epithelial cells can become fibroblasts through epithelial-mesenchymal transition (EMT). It is hypothesised that EMT occurs in lung allografts and plays a potential role in airway remodelling. <b>Methods:</b> Sixteen stable lung transplant recipients underwent bronchoscopy with bronchoalveolar lavage (BAL), endobronchial biopsies, and bronchial brushings. Biopsy sections were stained for the fibroblast marker S100A4. Brushings were cultured on collagen, stained with anti-S100A4, and examined for further EMT markers including matrix metalloproteinase (MMP) zymographic activity and epithelial invasion through collagen coated filters. <b>Results:</b> A median 15% (0–48%) of the biopsy epithelium stained for S100A4 in stable lung transplant recipients and MMP-7 co-localisation was observed. In non-stimulated epithelial cultures from lung allografts, S100A4 staining was identified with MMP-2 and MMP-9 production and zymographic activity. MMP total protein and activity was increased following stimulation with transforming growth factor (TGF)-β<sub>1</sub>. Non-stimulated transplant epithelial cells were invasive and penetration of collagen coated filters increased following TGF-β<sub>1</sub> stimulation. <b>Conclusions:</b> This study provides evidence of EMT markers in lung allografts of patients without loss of lung function. The EMT process may represent a final common pathway following injury in more common diseases characterised by airway remodelling.
Sirolimus Therapy in Infants with Severe Hyperinsulinemic Hypoglycemia
Authors: Senthil Senniappan, Sanda Alexandrescu, Nina Tatevian, Pratik Shah, Ved Arya, Sarah Flanagan, Sian Ellard, Dyanne Rampling, Michael Ashworth, Robert E. Brown, Khalid Hussain
Journal: New England Journal of Medicine (2014)

Hyperinsulinemic hypoglycemia is the most common cause of severe, persistent neonatal hypoglycemia. The treatment of hyperinsulinemic hypoglycemia that is unresponsive to diazoxide is subtotal pancreatectomy. We examined the effectiveness of the mammalian target of rapamycin (mTOR) inhibitor sirolimus in four infants with severe hyperinsulinemic hypoglycemia that had been unresponsive to maximal doses of diazoxide (20 mg per kilogram of body weight per day) and octreotide (35 μg per kilogram per day). All the patients had a clear glycemic response to sirolimus, although one patient required a small dose of octreotide to maintain normoglycemia. There were no major adverse events during 1 year of follow-up.
A new noninvasive quantification of renal blood flow with N-13 ammonia, dynamic positron emission tomography, and a two-compartment model.
Authors: B C Chen, G Germano, S C Huang, R A Hawkins, H W Hansen, M J Robert, D B Buxton, H R Schelbert, I Kurtz, M E Phelps
Journal: Journal of the American Society of Nephrology (1992)

In order to determine if dynamic positron emission tomography (PET) and N-13 ammonia can be used to quantitate regional RBF (rRBF) noninvasively, six anesthetized dogs were examined with PET imaging after an iv bolus administration of 5 mCi of N-13 ammonia. Renal time activity curves and the arterial input function were derived from regions of interest drawn over the renal cortex and abdominal aorta, respectively. For calculation of rRBF, less than 120 s of the initial data were used to minimize contamination by plasma metabolites of N-13 radioactivity. rRBF was quantitated with a two-compartment model, and the results were compared with simultaneously acquired microsphere blood flow measurement. Fourteen experiments were performed in six dogs, and four regions of interest on renal cortex were selected on each PET image. RBF derived from dynamic PET imaging with N-13 ammonia was linearly related to microsphere (MS) values (rRBF = 1.06 x MS - 0.17; r = 0.91). Mean rRBF in the canine experiments was 4.0 mL/min/g. The results indicate that dynamic N-13 ammonia renal PET can provide noninvasively quantitative rRBF.
Circulating carcinoembryonic antigen (CEA): Relationship to clinical status of patients with inflammatory bowel disease
Authors: A. H. Rule, C. Goleski-Reilly, D. B. Sachar, J. Vandevoorde, H. D. Janowitz
Journal: Gut (1973)

Plasma levels of circulating carcinoembryonic antigen (CEA) were measured by zirconyl phosphate gel radioimmunoassay in 112 patients with chronic inflammatory bowel disease. The levels were then related to category, extent, duration, and severity of disease, as well as to the ages and surgical status of the patients. The distribution of CEA levels and their mean values were significantly raised over the levels in 33 normal control subjects, and were similar among patients with ulcerative colitis compared with those with granulomatous bowel disease. Positive values were defined as those in excess of 2.5 ng/ml. Positive assays occurred in 42% of ulcerative colitis patients, in 38% of Crohn's disease patients, and in 40% of the total group with inflammatory bowel disease. Among normal control subjects, only 3% were positive. Among inflammatory bowel disease patients, positive CEA assays occurred more frequently with more severe disease, more extensive anatomical involvement, younger ages, and shorter duration of disease. Those patients who had undergone total colectomy showed levels of circulating CEA and frequency of CEA positivity similar to those of an age-matched normal control group. Levels of CEA did not correspond with known cancer risk factors in patients with inflammatory bowel disease. Although rising or persisting plasma CEA values unrelated to severity and extent of disease may indicate an unfavourable prognosis in cancer, this study shows that a single CEA value in patients with chronic inflammatory bowel disease is not a reliable indicator of cancer risk.
The social matrix reloaded: An attachment perspective on Carpendale & Lewis
Authors: Howard Steele
Journal: Behavioral and Brain Sciences (2004)

The "new" theory of Carpendale & Lewis (C&L) needs be compared with existing elaborated and tested models concerning the social origins underpinning the sense of being a person with thoughts and feelings in relation to others. Illustrations are provided from contemporary attachment theory and research in the context of questioning the potential legacy of Piaget as a theorist of social relationships.