tbuckley/cabot-search huggingface dataset:
Dynein Light Chain 1 Contributes to Cell Cycle Progression by Increasing Cyclin-Dependent Kinase 2 Activity in Estrogen-Stimulated Cells
Authors: Petra den Hollander, Rakesh Kumar
Journal: Cancer Research (2006)

Progression of hormone-responsive cancers is characterized by deregulation of the cell cycle and cytoskeleton signaling. In addition, development of breast and endometrial cancer is influenced by the stimulatory action of estrogen. Up-regulation of dynein light chain 1 (DLC1), a component of cytoskeleton signaling, was recently found to promote tumorigenesis. The purpose of our study was to determine the role that DLC1 up-regulation plays in cell cycle progression. To achieve this goal, we used human breast ductal carcinoma ZR-75 cells overexpressing DLC1 as a model system. We found that ZR-75 cells with up-regulated DLC1 were hypersensitive to estrogen-dependent growth stimulation and that DLC1 had an accelerating effect on the G(1)-S transition and stimulated cyclin-dependent kinase 2 (Cdk2) activity. To better understand the promotion of the G(1)-S transition by DLC1, we sought to identify new DLC1-interacting proteins with roles in cell cycle regulation. Using a modified proteomic strategy, we identified two such DLC1-interacting proteins: Cdk2 and Cip-interacting zinc finger protein 1 (Ciz1). DLC1 was verified to interact with Cdk2 and Ciz1 in vivo. We also showed that down-regulation of DLC1 and Ciz1 reduced both Cdk2 activity and cell cycle progression of breast cancer ZR-75 and MCF-7 and endometrial Ishikawa cancer cells. Further, we showed that overexpression of DLC1 is accompanied by a reduction of nuclear p21(WAF1). These findings suggest that interactions among DLC1, Cdk2, and Ciz1 play a regulatory role in cell cycle progression of cancer cells presumably by influencing the levels of nuclear p21(WAF1).
A Bioluminescent Transposon Reporter-Trap Identifies Tumor-Specific Microenvironment-Induced Promoters in <i>Salmonella</i> for Conditional Bacterial-Based Tumor Therapy
Authors: Kelly Flentie, Brandon Kocher, Seth T. Gammon, Deborah V. Novack, Jeffrey S. McKinney, David Piwnica-Worms
Journal: Cancer Discovery (2012)

Salmonella specifically localize to malignant tumors in vivo, a trait potentially exploitable as a delivery system for cancer therapeutics. To characterize mechanisms and genetic responses of Salmonella during interaction with living neoplastic cells, we custom-designed a promoterless transposon reporter containing bacterial luciferase. Analysis of a library containing 7,400 independent Salmonella transposon insertion mutants in coculture with melanoma or colon carcinoma cells identified five bacterial genes specifically activated by cancer cells: adiY, yohJ, STM1787, STM1791, and STM1793. Experiments linked acidic pH, a common characteristic of the tumor microenvironment, to a strong, specific, and reversible stimulus for activation of these Salmonella genes in vitro and in vivo. Indeed, a Salmonella reporter strain encoding a luciferase transgene regulated by the STM1787 promoter, which contains a tusp motif, showed tumor-induced bioluminescence in vivo. Furthermore, Salmonella expressing Shiga toxin from the STM1787 promoter provided potent and selective antitumor activity in vitro and in vivo, showing the potential for a conditional bacterial-based tumor-specific therapeutic.Salmonella, which often encounter acidic environments during classical host infection, may co-opt evolutionarily conserved pathways for tumor colonization in response to the acidic tumor microenvironment. We identified specific promoter sequences that provide a platform for targeted Salmonella-based tumor therapy in vivo.
Elastin and collagen accumulation in rabbit ascending aorta and pulmonary trunk during postnatal growth. Correlation of cellular synthetic response with medial tension.
Authors: D Y Leung, S Glagov, M B Mathews
Journal: Circulation Research (1977)

Absolute and relative quantities of elastin, collagen, and DNA in anatomically defined segments of rabbit ascending aorta (AA) and pulmonary trunk (PT) were compared at intervals from birth to 2 months of age. Identical in size, weight, and composition at birth, the vessels maintained similar lengths and diameters at each age but diverged markedly in weight and scleroprotein content after 1 week. By 2 months, 3 times as much elastin and 1.7 times as much collagen had accumulated in the AA as compared to the PT. By contrast, the increase in total DNA content was the same for both segments. Differences in total fibrous protein accumulation, total elastin accumulation, and elastin content relative to DNA paralleled differences in estimated total medial tangential tension. Proportions of elastin and collagen relative to dry weight increased markedly only between 4 and 2 weeks of age and not thereafter despite continuing rapid growth, steadily increasing medial tension, and increasing total scleroprotein content. Thus, medial cells were capable of adapting their quantitative scleroprotein synthetic response to differences in medial tension throughout growth but established a fixed qualitative response within 2 weeks.
Resistin Is an Inflammatory Marker of Atherosclerosis in Humans
Authors: Muredach P. Reilly, Michael Lehrke, Megan L. Wolfe, Anand Rohatgi, Mitchell A. Lazar, Daniel J. Rader
Journal: Circulation (2005)

Resistin, a plasma protein, induces insulin resistance in rodents. Recent reports suggest that circulating levels of resistin are elevated in obese and insulin-resistant rodents and humans. Whereas rodent resistin is made in adipocytes, macrophages are a major source of human resistin. Given the convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and atherosclerosis in humans.We examined whether plasma resistin levels were associated with metabolic and inflammatory markers, as well as with coronary artery calcification (CAC), a quantitative index of atherosclerosis, in 879 asymptomatic subjects in the Study of Inherited Risk of Coronary Atherosclerosis. Resistin levels were positively associated with levels of inflammatory markers, including soluble tumor necrosis factor-alpha receptor-2 (P<0.001), interleukin-6 (P=0.04), and lipoprotein-associated phospholipase A2 (P=0.002), but not measures of insulin resistance in multivariable analysis. Resistin levels also were associated (odds ratio and 95% confidence interval in ordinal regression) with increasing CAC after adjustment for age, sex, and established risk factors (OR, 1.23 [CI, 1.03 to 1.52], P=0.03) and further control for metabolic syndrome and plasma C-reactive protein (CRP) levels (OR, 1.25 [CI, 1.04 to 1.50], P=0.01). In subjects with metabolic syndrome, resistin levels further predicted CAC, whereas CRP levels did not.Plasma resistin levels are correlated with markers of inflammation and are predictive of coronary atherosclerosis in humans, independent of CRP. Resistin may represent a novel link between metabolic signals, inflammation, and atherosclerosis. Further studies are needed to define the relationship of resistin to clinical cardiovascular disease.
Down regulation of interleukin 1beta production in human osteoarthritic synovial tissue and cartilage cultures by aminoguanidine
Authors: I Shirazi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To evaluate the effect of aminoguanidine (AG) on de novo interleukin 1β (IL1β), nitric oxide (NO), and interleukin 1 receptor antagonist (IL1ra) production by osteoarthritic human synovial tissue and articular cartilage cultures. <h3>METHODS</h3> Synovial tissue and cartilage, obtained during surgery from 29 patients undergoing total knee or hip replacement for osteoarthritis, were cut into small pieces and cultured in the presence or absence of lipopolysaccharide (LPS) and test materials. IL1β, IL1ra, and NO were determined in culture media. The inducible nitric oxide synthase inhibitor, AG, was added to cultures in various concentrations (0.3–3 mmol/l). <h3>RESULTS</h3> In synovial tissue cultures AG (0.3, 1, and 3 mmol/l) decreased LPS (1 μg/ml) stimulated IL1β and NO release in the media in a dose dependent manner (p&lt;0.05 at 1 mmol/l and p&lt;0.05 at 0.3 mmol/l, respectively). In articular cartilage cultures AG (0.3, 1, and 3 mmol/l) decreased LPS (1 μg/ml) stimulated IL1β and NO release in the media in a dose dependent manner (p&lt;0.05 at 1 mmol/l and p&lt;0.01 at 0.3 mmol/l, respectively). Hydrocortisone (5 μg/ml) also significantly decreased LPS stimulated IL1β release in media of synovial tissue and cartilage cultures and NO in media of synovial cultures. AG (0.3, 1, and 3 mmol/l) decreased LPS (1 μg/ml) stimulated IL1ra levels in media of synovial tissue cultures in a dose dependent manner (p&lt;0.05 at 1 mmol/l) but increased LPS (1 μg/ml) stimulated IL1ra release in media of cartilage cultures (p&lt;0.01 at 3 mmol/l). The NO donor, nitroprusside (10, 30, 100, and 300 μg/ml) stimulated IL1β release in media of synovial tissue cultures in a dose dependent manner (p&lt;0.01 at 100 μg/ml). AG and nitroprusside at the concentrations used had no toxic effect on human synovial cells. <h3>CONCLUSIONS</h3> NO synthase inhibitors may modulate osteoarthritis and articular inflammatory processes not only by decreasing NO synthesis but also by their effects on ILβ and IL1ra production.
CASE OF GUN-SHOT WOUND: WITH OBSERVATIONS
Authors: H. B. Norman
Journal: BMJ (1855)

, , be eom with dsk disese that is anotber tiou.It is ut y tat you may not put him ain In a good state of healt, ad prevet the more sious and complicated disea which sometimes follow.May persons, know, have deuied the possibility of curing constitutional syphilis at all; some say that it is never erdicated.Now, that it is never eradicated if the patient does not undergo a proper treatment, namely, sweating during and concurrent with the application of internal medicinas, I am quite prepared to admit; but that it may be eradicated by the means I pro- pose, I am no less certain Birminghan, April 18i5.
Competitive Interaction Between Fibroblast Growth Factor 23 And Asymmetric Dimethylarginine in Patients With CKD
Authors: Giovanni Tripepi, Barbara Kollerits, Daniela Leonardis, Mahamut Ilker Yilmaz, Maurizio Postorino, Danilo Fliser, Francesca Mallamaci, Florian Kronenberg, Carmine Zoccali
Journal: Journal of the American Society of Nephrology (2014)

Both fibroblast growth factor 23 (FGF-23) and asymmetric dimethylarginine (ADMA) are associated with progression of CKD. We tested the hypothesis that ADMA and FGF23 are interactive factors for CKD progression in a cohort of 758 patients with CKD in Southern Europe (mean eGFR±SD, 36±13 ml/min per 1.73 m(2)) and in a central European cohort of 173 patients with CKD (MMKD study, mean eGFR, 64±39 ml/min per 1.73 m(2)). In the first cohort, 214 patients had renal events (decrease in eGFR of >30%, dialysis, or kidney transplantation) during a 3-year follow-up. Both intact FGF-23 and ADMA predicted the incidence rate of renal events in unadjusted and adjusted analyses (P<0.001). There was a strong competitive interaction between FGF-23 and ADMA in the risk of renal events (P<0.01 in adjusted analyses); the risk associated with raised ADMA levels was highest in patients with low FGF-23 levels. These results were confirmed in the MMKD cohort, in which FGF-23 level was again an effect modifier of the relationship between plasma ADMA level and renal events (doubling of baseline serum creatinine, dialysis, or kidney transplantation) in the adjusted analyses (P<0.01). Furthermore, in the MMKD cohort there was a parallel, independent competitive interaction between symmetric dimethylarginine level and c-terminal FGF-23 level for the risk for renal events (P=0.001). These findings indicate that the association of ADMA level with the risk of CKD progression is modified by FGF-23 level and provide further evidence that dysregulation of the nitric oxide system is involved in CKD progression.
Phase I Study of the Taxane BMS-188797 in Combination with Carboplatin Administered Every 3 Weeks in Patients with Solid Malignancies
Authors: Mayer N. Fishman, Christopher R. Garrett, George R. Simon, Alberto A. Chiappori, Richard M. Lush, William R. Dinwoodie, J. Joseph Mahany, Anne M. Dellaportas, Alan Cantor, Ashwin Gollerki, Marvin B. Cohen, Daniel M. Sullivan
Journal: Clinical Cancer Research (2006)

BMS-188797 is one of several novel taxanes in ongoing clinical development. It has superior activity in experimental tumor models when compared with paclitaxel. BMS-188797 has a single C-4 modification, a 4-desacetyl-4-methylcarbonate, compared with paclitaxel.We did a phase I study, in which a fixed dose of carboplatin was combined with a dose escalation schedule of BMS-188797, both administered once every 3 weeks, in patients with advanced solid malignancies.Thirty patients were treated, 11 at the proposed recommended phase II dose. The dose-limiting toxicity was myelosuppression. There was a linear relationship between administered dose of BMS-188797 and the measured area under the curve (AUC). There was significant interpatient variability of BMS-188797 AUC at the maximum tolerated dose. Two radiographic partial responses were observed: one patient with duodenal adenocarcinoma and one patient with esophageal adenocarcinoma (time on study, 19 and 30 weeks, respectively).The recommended phase II dose for BMS-188797 and carboplatin administered on a once-every-3 week schedule is carboplatin AUC = 5 mg min/mL and BMS-188797 at a dose of 135 mg/m(2).
Anaerobic bacteria in cystic fibrosis: pathogens or harmless commensals?
Authors: A. M. Jones
Journal: Thorax (2011)

The application of molecular non-culture-based techniques designed for characterising bacterial communities, such as 16S rRNA gene profiling by terminal restriction fragment length polymorphisms (T-RFLPs) or pyrosequencing, has provided new insights into the microbiology of cystic fibrosis (CF) lung disease.1–3 Studies have revealed that rather than being dominated by a single or small numbers of microorganisms, the CF lung is populated by a much more diverse polymicrobial community, including facultative anaerobic bacterial species. Analyses of CF airway samples by strict anoxic culture and culture-independent molecular methods have demonstrated that the anaerobic species can be repeatedly isolated, suggesting that their presence is persistent rather than transient, and are present in numbers comparable with those of the typical aerobic bacterial pathogens.1–9 The anaerobes present often represent those that usually colonise the oropharynx. The relative abundance of anaerobes in samples, and differences in composition of anaerobic species between mouthwash specimens and sputum samples, suggests that they are not oral contaminants but do truly originate from the lower respiratory tract.5 9 10 That anaerobes are present in the CF lung is perhaps not surprising. There is a steep oxygen gradient within the CF airway, with regions of hypoxia within mucus plugs. During chronic infection, the major CF pathogen, Pseudomonas aeruginosa , adapts to these conditions by increasing alginate production, forming biofilms and changing to an anaerobic metabolism.11 Regions of anoxia in a warm, humid, nutrient-rich environment combined with a defective mucociliary clearance mechanism may allow obligate anaerobic bacteria to colonise or infect the CF lung. Although there is compelling evidence that obligate anaerobic species are …
Observations of ventilation during resuscitation in a canine model.
Authors: N C Chandra, K G Gruben, J E Tsitlik, R Brower, A D Guerci, H H Halperin, M L Weisfeldt, S Permutt
Journal: Circulation (1994)

BACKGROUND Fear of infection limits the willingness of laymen to do cardiopulmonary resuscitation (CPR). This study assessed the time course of change in arterial blood gases during resuscitation with only chest compression (no ventilation) in an effort to identify the time for which ventilation could be deferred. METHODS AND RESULTS Aortic pressures and arterial blood gases were monitored in seven 20- to 30-kg dogs in ventricular fibrillation (VF) at 2-minute intervals during chest compression alone (no ventilation) at 80 to 100 compressions per minute. Before the induction of ventricular fibrillation, all animals were intubated and ventilated with room air, 10 mL/kg. The endotracheal tube was removed when VF was induced. Pre-VF arterial pH, PCO2, and O2 saturation were (mean +/- SEM) 7.39 +/- 0.02, 27.0 +/- 1.5 mm Hg, and 97.5 +/- 0.5%, respectively, with aortic pressures being 143.2 +/- 5.7/116.2 +/- 4.6 mm Hg. At 4 minutes of chest compression alone, the corresponding values were 7.39 +/- 0.03, 24.3 +/- 3.1 mm Hg, and 93.9 +/- 3.0%, with an arterial pressure of 48.1 +/- 7.7/22.6 +/- 3.9 mm Hg. Mean minute ventilation during the fourth minute of CPR, measured with a face mask-pneumotachometer, was 5.2 +/- 1.1 L/min. CONCLUSIONS These data suggest that in the dog model of witnessed arrest, chest compression alone during CPR can maintain adequate gas exchange to sustain O2 saturation &gt; 90% for &gt; 4 minutes. The need for immediate ventilation during witnessed arrest should be reexamined.
A SERIES OF CONSECUTIVE OPERATIONS ON THE MASTOID
Authors: J. A. Gibb
Journal: BMJ (1928)

TMta>J 49given every four houre.He was kept on boiled water with the occasionial addition of a little brandy.The two followinig days saw him steadily going downhill; there were nio physical signs in chest or abdomeni, no cough, nio vomiting; the bowels were opened two or three times daily, anid the motion,
Outcome of Patients with Interstitial Lung Disease Treated with Extracorporeal Membrane Oxygenation for Acute Respiratory Failure
Authors: Franziska C. Trudzinski, Franziska Kaestner, Hans-Joachim Schäfers, Sebastian Fähndrich, Frederik Seiler, Philip Böhmer, Oliver Linn, Ralf Kaiser, Hendrik Haake, Frank Langer, Robert Bals, Heinrike Wilkens, Philipp M. Lepper
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Patients with interstitial lung disease and acute respiratory failure have a poor prognosis especially if mechanical ventilation is required.Objectives: To investigate the outcome of patients with acute respiratory failure in interstitial lung disease undergoing extracorporeal membrane oxygenation (ECMO) as a bridge to recovery or transplantation.Methods: This was a retrospective analysis of all patients with interstitial lung disease and acute respiratory failure treated with or without ECMO from March 2012 to August 2015.Measurements and Main Results: Forty patients with interstitial lung disease referred to our intensive care unit for acute respiratory failure were included in the analysis. Twenty-one were treated with ECMO. Eight patients were transferred by air from other hospitals within a range of 320 km (linear distance) for extended intensive care including the option of lung transplant. In total, 13 patients were evaluated, and eight were finally found to be suitable for lung transplantation from an ECMO bridge. Four patients from external hospitals were de novo listed during acute respiratory failure. Six patients underwent lung transplant, and two died on the waiting list after 9 and 63 days on ECMO, respectively. A total of 14 of 15 patients who did not undergo lung transplantation (93.3%) died after 40.3 ± 27.8 days on ECMO. Five out of six patients (83.3%) receiving a lung transplant could be discharged from hospital.Conclusions: ECMO is a lifesaving option for patients with interstitial lung disease and acute respiratory failure provided they are candidates for lung transplantation. ECMO is not able to reverse the poor prognosis in patients that do not qualify for lung transplantation.
Transglutaminase Transcription and Antigen Translocation in Experimental Renal Scarring
Authors: TIMOTHY S. JOHNSON, N. JAMES SKILL, A. MEGUID EL NAHAS, SIMON D. OLDROYD, GRAHAM L. THOMAS, JULIE A. DOUTHWAITE, JOHN L. HAYLOR, MARTIN GRIFFIN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. It was recently demonstrated that renal tissue transglutaminase (tTg) protein and its catalytic product the ε(γ-glutamyl) lysine protein cross-link are significantly increased in the subtotal (5/6) nephrectomy model (SNx) of renal fibrosis in rats. It was proposed that the enzyme had two important physiologic functions in disease development; one of stabilizing the increased extracellular matrix (ECM) by protein crosslinking, the other in a novel form of tubular cell death. This study, using the same rat SNx model, demonstrates first by Northern blotting that expression of tTg mRNA when compared with controls is increased by day 15 (+70% increase, P < 0.05), then rises steadily, peaking at day 90 (+391%, P < 0.01), and remains elevated at 120 d (+205%, P < 0.05) when compared with controls. In situ hybridization histochemistry demonstrated that the tubular cells were the major site of the additional tTg synthesis. Immunohistochemistry on cryostat sections revealed a sixfold increase (P < 0.001) in ECM-bound tTg antigen at 90-d post-SNx, whereas in situ transglutaminase activity demonstrated by the incorporation of fluorescein cadaverine into cryostat sections indicated a 750% increase (P < 0.001) on day 90 in SNx animals. This increased activity was extracellular and predominantly found in the peritubular region. These results indicate that increased tTg gene transcription by tubular cells underlies the major changes in renal tTg protein reported previously in SNx rats, and that the presence of the ε(γ-glutamyl) lysine cross-links in the extracellular environment is the result of the extracellular action of tTg. These changes may be in response to tubular cell injury during the scarring process and are likely to contribute to the progressive expansion of the ECM in renal fibrosis.
Dynamic susceptibility contrast MRI measures of relative cerebral blood volume as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 multicenter trial
Authors: Kathleen M Schmainda, Zheng Zhang, Melissa Prah, Bradley S Snyder, Mark R Gilbert, A Gregory Sorensen, Daniel P Barboriak, Jerrold L Boxerman
Journal: Neuro-Oncology (2015)

The study goal was to determine whether changes in relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast (DSC) MRI are predictive of overall survival (OS) in patients with recurrent glioblastoma multiforme (GBM) when measured 2, 8, and 16 weeks after treatment initiation.Patients with recurrent GBM (37/123) enrolled in ACRIN 6677/RTOG 0625, a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide, consented to DSC-MRI plus conventional MRI, 21 with DSC-MRI at baseline and at least 1 postbaseline scan. Contrast-enhancing regions of interest were determined semi-automatically using pre- and postcontrast T1-weighted images. Mean tumor rCBV normalized to white matter (nRCBV) and standardized rCBV (sRCBV) were determined for these regions of interest. The OS rates for patients with positive versus negative changes from baseline in nRCBV and sRCBV were compared using Wilcoxon rank-sum and Kaplan-Meier survival estimates with log-rank tests.Patients surviving at least 1 year (OS-1) had significantly larger decreases in nRCBV at week 2 (P = .0451) and sRCBV at week 16 (P = .014). Receiver operating characteristic analysis found the percent changes of nRCBV and sRCBV at week 2 and sRCBV at week 16, but not rCBV data at week 8, to be good prognostic markers for OS-1. Patients with positive change from baseline rCBV had significantly shorter OS than those with negative change at both week 2 and week 16 (P = .0015 and P = .0067 for nRCBV and P = .0251 and P = .0004 for sRCBV, respectively).Early decreases in rCBV are predictive of improved survival in patients with recurrent GBM treated with bevacizumab.