tbuckley/cabot-search huggingface dataset:
Reduced spontaneous apoptosis in peripheral blood neutrophils during exacerbation of COPD
Authors: M.W.R. Pletz, M. Ioanas, A. de Roux, O. Burkhardt, H. Lode
Journal: European Respiratory Journal (2004)

A major feature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is the accumulation of activated neutrophils in the bronchial tree. This phenomenon can be explained by an increased migration and/or by a prolonged survival due to an inhibition of spontaneous apoptosis. The aim of this study was to assess the apoptotic behaviour of peripheral blood neutrophils in COPD patients during an acute exacerbation. Thirty-six hospitalised COPD patients with an acute exacerbation and 10 healthy volunteers were included. Blood samples were obtained at admission, after 3–5 days and at discharge. Spontaneous apoptosis of isolated neutrophils was measured based on Annexin V‐PE binding and nuclear morphology after culturing for 18 h. At admission, significantly lower rates of spontaneous apoptosis were noted in COPD patients compared with healthy volunteers (mean±sd 31±13% versus 44±18%). The mean percentages of apoptotic neutrophils were 31±13% at admission, 39±15% after 3–5 days and 47±18% at discharge. There was a statistically significant difference between the rates of spontaneous apoptosis on the first day and at discharge. Neither forced expiratory volume in one second &lt;35% predicted, smoking habit, corticosteroid therapy nor evidence of bacterial infection showed any influence on the spontaneous apopotosis in this study. In conclusion, during acute exacerbations of chronic obstructive pulmonary disease, neutrophil granulocytes show a reduced spontaneous apoptosis that increases progressively after treatment and clinical remission. This raises the question of the importance of neutrophil apoptosis in the development and resolution of exacerbations of chronic obstructive pulmonary disease.
Predialysis Systolic BP Variability and Outcomes in Hemodialysis Patients
Authors: Tariq Shafi, Stephen M. Sozio, Karen J. Bandeen-Roche, Patti L. Ephraim, Jason R. Luly, Wendy L. St. Peter, Aidan McDermott, Julia J. Scialla, Deidra C. Crews, Navdeep Tangri, Dana C. Miskulin, Wieneke M. Michels, Bernard G. Jaar, Charles A. Herzog, Philip G. Zager, Klemens B. Meyer, Albert W. Wu, L. Ebony Boulware
Journal: Journal of the American Society of Nephrology (2014)

BP variability (BPV) is an important predictor of outcomes in the general population, but its association with clinical outcomes in hemodialysis patients is not clear. We identified 11,291 patients starting dialysis in 2003-2008 and followed them through December 31, 2008 (median=22 months). Predialysis systolic BPV was assessed over monthly intervals. Outcomes included factors associated with BPV, mortality (all-cause and cardiovascular), and first cardiovascular event (cardiovascular death or hospitalization). Patients' mean age was 62 years, 55% of patients were men, and 58% of patients were white. Modifiable factors associated with higher BPV included obesity, higher calcium-phosphate product levels, and lower hemoglobin concentration; factors associated with lower BPV included greater fluid removal, achievement of prescribed dry weight during dialysis, higher hemoglobin concentration, and antihypertensive regimens without β-blockers or renin-angiotensin system blocking agents. In total, 3200 deaths occurred, including 1592 cardiovascular deaths. After adjustment for demographics, comorbidities, and clinical factors, higher predialysis BPV was associated with increased risk of all-cause mortality (hazard ratio [HR], 1.18; 95% confidence interval [95% CI] per 1 SD increase in BPV, 1.13 to 1.22), cardiovascular mortality (HR, 1.18; 95% CI, 1.12 to 1.24), and first cardiovascular event (HR, 1.11; 95% CI, 1.07 to 1.15). Results were similar when BPV was categorized in tertiles and patients were stratified by baseline systolic BP. In summary, predialysis systolic BPV is an important, potentially modifiable risk factor for death and cardiovascular outcomes in incident hemodialysis patients. Studies of BP management in dialysis patients should focus on both absolute BP and BPV.
Dilated cardiomyopathy is associated with reduced expression of the cardiac sodium channel Scn5a
Authors: M HESSE, C KONDO, R CLARK, L SU, F ALLEN, C GEARYJOO, S KUNNATHU, D SEVERSON, A NYGREN, W GILES
Journal: Cardiovascular Research (2007)

Dilated cardiomyopathy (DCM) leads to dilation of the cardiac chambers and congestive heart failure. Recent reports have associated mutations in the SCN5A gene, which codes for the major cardiac sodium channel Nav1.5, with DCM. Although DCM is the most common form of cardiomyopathy, no animal studies have established this functional connection.We have produced transgenic mice that ectopically express the transcriptional repressor Snail in heart. These animals display severe DCM, ECG abnormalities, conduction defects, revealed by voltage-sensitive dye imaging, and significantly reduced voltage-gated sodium current as measured by patch clamping. There is a concomitant decrease in expression of the major cardiac sodium channel gene Scn5a, which we show by gene reporter assays and electrophoretic mobility shift assays is a direct target of Snail.Our findings indicate that a decrease in Scn5a expression and significant reduction in sodium current can result in DCM, and support the hypothesis that some mutations in the human SCN5A gene can lead to DCM.
Effects of Acetylstrophanthidin on Isolated Veins of the Dog
Authors: DAVID BRENDER, CAMERON G. STRONG, JOHN T. SHEPHERD
Journal: Circulation Research (1970)

Acetylstrophanthidin, 1.0 to 10.0 µg/ml, caused contraction of strips of the lateral saphenous vein of the dog in an organ bath at 37°C. The superior mesenteric vein, which exhibited spontaneous activity in the organ bath, responded to acetylstrophanthidin with an almost immediate increase in tension and an increased frequency of contractions; this was followed by a sustained contraction which had the same time lag as the contraction of a saphenous vein strip from the same dog. In strips from both veins, the contraction was depressed by cooling and augmented by warming, an effect opposite to that seen with norepinephrine-induced contractions. A latent period of 10 to 60 minutes preceded the contraction of the saphenous vein; during this time, the vein showed increased reactivity to added norepinephrine, 5-hydroxytryptamine, acetylcholine, barium chloride, increased bath concentration of K + , and decreased bath concentration of Na + . The increased reactivity and contraction still occurred after catecholamine depletion of the vein by chronic lumbar sympathectomy and in umbilical veins, which are devoid of adrenergic nerves. In addition to its direct constrictor action on cutaneous and mesenteric veins, acetylstrophanthidin sensitized cutaneous veins to vasoactive agents and to changes in ionic environment. These actions did not depend on the presence of norepinephrine in the veins.
G Protein βγ Subunits Stimulate p114RhoGEF, a Guanine Nucleotide Exchange Factor for RhoA and Rac1
Authors: Jiaxin Niu, Jasmina Profirovic, Haiyun Pan, Rita Vaiskunaite, Tatyana Voyno-Yasenetskaya
Journal: Circulation Research (2003)

Rho GTPases integrate the intracellular signaling in a wide range of cellular processes. Activation of these G proteins is tightly controlled by a number of guanine nucleotide exchange factors (GEFs). In this study, we addressed the functional role of the recently identified p114RhoGEF in in vivo experiments. Activation of endogenous G protein-coupled receptors with lysophosphatidic acid resulted in activation of a transcription factor, serum response element (SRE), that was enhanced by p114RhoGEF. This stimulation was inhibited by the functional scavenger of Gbetagamma subunits, transducin. We have determined that Gbetagamma subunits but not Galpha subunits of heterotrimeric G proteins stimulated p114RhoGEF-dependent SRE activity. Using coimmunoprecipitation assay, we have determined that Gbetagamma subunits interacted with full-length and DH/PH domain of p114RhoGEF. Similarly, Gbetagamma subunits stimulated SRE activity induced by full-length and DH/PH domain of p114RhoGEF. Using in vivo pull-down assays and dominant-negative mutants of Rho GTPases, we have determined that p114RhoGEF activated RhoA and Rac1 but not Cdc42 proteins. Functional significance of RhoA activation was established by the ability of p114RhoGEF to induce actin stress fibers and cell rounding. Functional significance of Rac1 activation was established by the ability of p114RhoGEF to induce production of reactive oxygen species (ROS) followed by activation of NADPH oxidase enzyme complex. In summary, our data showed that the novel guanine nucleotide exchange factor p114RhoGEF regulates the activity of RhoA and Rac1, and that Gbetagamma subunits of heterotrimeric G proteins are activators of p114RhoGEF under physiological conditions. The findings help to explain the integrated effects of LPA and other G-protein receptor-coupled agonists on actin stress fiber formation, cell shape change, and ROS production.
Pulmonary hypertension in antisynthetase syndrome: prevalence, aetiology and survival
Authors: Baptiste Hervier, Alain Meyer, Céline Dieval, Yurdagul Uzunhan, Hervé Devilliers, David Launay, Matthieu Canuet, Laurent Têtu, Christian Agard, Jean Sibilia, Mohamed Hamidou, Zahir Amoura, Hilario Nunes, Olivier Benveniste, Philippe Grenier, David Montani, Eric Hachulla
Journal: European Respiratory Journal (2013)

Antisynthetase syndrome is characterised by the association of interstitial lung disease and myositis with different anti-tRNA-synthetase antibodies. The occurrence, aetiology and prognosis of pulmonary hypertension have not yet been evaluated. Among 203 consecutive patients, transthoracic echocardiogram and right heart catheterisation results were retrospectively analysed in the light of clinico-biological, morphological and functional parameters. Definitions of pulmonary hypertension were based on the European Society of Cardiology/European Respiratory Society 2009 guidelines, with severe pulmonary hypertension being defined by a mean pulmonary arterial pressure &gt;35 mmHg. Pulmonary hypertension was suspected by transthoracic echocardiogram in 47 (23.2%) cases, corresponding to pulmonary hypertension “possible” (n=27, 13.3%) or “likely” (n=20, 9.9%). Right heart catheterisation was performed in 21 patients, excluding pulmonary hypertension in five and confirming pre-capillary pulmonary hypertension in 16 (7.9%). Although related to interstitial lung disease in all cases, pre-capillary pulmonary hypertension was severe in 13 (81.3%) patients (mean± sd pulmonary arterial pressure 46±9 mmHg), frequently associated with low cardiac index (mean± sd 2.3±0.8 L·min −1 ·m −2 ) and high forced vital capacity/diffusing capacity of the lung for carbon monoxide ratio (2.5±0.6). Pulmonary hypertension was significantly associated with a lower survival rate (p&lt;0.001), with a 3-year survival rate of 58%. The occurrence of pulmonary hypertension in antisynthetase syndrome is significant and dramatically worsens the prognosis. Although systematically associated with interstitial lung disease, pulmonary hypertension was usually severe, suggesting a specific pulmonary vascular involvement.
Experiments in the Acceleration of Wound Healing
Authors: W. G. Waugh
Journal: BMJ (1940)

X RAYS IN GAS GANGRENE ME RTISINAL 249 unusual fatality gives rise to the question whethei the simpler and less heroic measures for the treatment of an abrasion are not freer from risk of this infection.Excision and closure of the wound would appear to produLce a suitable nidus for the development of anaerobic organisms.If such an event can occur in a patient having the advantage of hospital treatment and observation, the relative rarity of such untoward results in street accidents is surprising.That it can-occur should be borne in mind by all who treat casualties, so that a careful watch may
Protagonist: Should we eradicate Helicobacter pylori before long term antireflux therapy?
Authors: J Labenz
Journal: Gut (2001)

Helicobacter pylori infection invariably induces chronic active gastritis which can give rise to serious consequences such as peptic ulcer and gastric malignancies. Generally accepted indications for treatment are H pylori associated peptic ulcer disease and early stages of low grade mucosa associated lymphoid tissue lymphoma of the stomach. In contrast, treatment of H pylori in patients with gastro-oesophageal reflux disease (GORD) requiring long term treatment with a proton pump inhibitor (PPI) has not yet been put on a scientific footing. In support of this indication in patients with GORD and no associated ulcer disease, the following theoretical arguments might be advanced.

In contrast, treatment of H pylori in patients with gastro-oesophageal reflux desease (GORD) requiring long term treatment with a proton pump inhibitor (PPI) has not yet been put on a scientific footing. In support of this indication in patients with GORD and no associated ulcer disease, the following theoretical arguments might be advanced.

(1)
:    H pylori is involved in the pathogenesis of GORD so that eradication of this organism would lead to an improvement in, or even elimination of, GORD.
(2)
:   Eradication of H pylori infection is associated with an improvement in the effectiveness of treatment with PPI in patients with GORD.
(3)
:   PPI treatment of GORD carries a higher risk in patients with H pylori infection than in H pylori negative patients, and this risk can be eliminated by eradication of the infection.



H pylori infection interferes with the regulation of gastric acid secretion. The effect of eradication therapy on acid secretion is closely linked to the type of gastritis before treatment. In the case of duodenal ulcer patients with antrum dominant gastritis, acid hypersecretion normalises within some months, while in the case of gastric ulcer patients with more severe corpus gastritis, acid hyposecretion disappears within a few weeks.1 It is conceivable, although not yet unequivocally proved in patients with confirmed GORD, that treatment of H pylori can lead to an improvement in, or the healing of, GORD (at least in individual cases). To date, the literature contains …
EGF Receptor-Targeted Synthetic Double-Stranded RNA Eliminates Glioblastoma, Breast Cancer, and Adenocarcinoma Tumors in Mice
Authors: Alexei Shir, Manfred Ogris, Ernst Wagner, Alexander Levitzki
Journal: PLoS Medicine (2005)

Background Glioblastoma multiforme (GBM) is the most lethal form of brain cancer. With the available treatments, survival does not exceed 12–14 mo from the time of diagnosis. We describe a novel strategy to selectively induce the death of glioblastoma cells and other cancer cells that over-express the EGF receptor. Using a non-viral delivery vector that homes to the EGF receptor, we target synthetic anti-proliferative dsRNA (polyinosine-cytosine [poly IC]), a strong activator of apoptosis, selectively to cancer cells. Methods and Findings Poly IC was delivered by means of a non-viral vector: 25kDa polyethylenimine-polyethyleneglycol-EGF (PEI25-PEG-EGF). EGFR-targeted poly IC induced rapid apoptosis in the target cells in vitro and in vivo. Expression of several cytokines and "bystander killing" of untransfected tumor cells was detected in vitro and in vivo. Intra-tumoral delivery of the EGFR-targeted poly IC induced the complete regression of pre-established intracranial tumors in nude mice, with no obvious adverse toxic effects on normal brain tissue. A year after treatment completion the treated mice remain cancer-free and healthy. Similarly, non-viral delivery of poly IC completely eliminated pre-established breast cancer and adenocarcinoma xenografts derived from EGFR over-expressing cancer cell lines, suggesting that the strategy is applicable to other EGFR-over-expressing tumors. Conclusion The strategy described has yielded an effective treatment of EGFR over-expressing GBM in an animal model. If this strategy is translated successfully to the clinical setting, it may actually offer help to GBM patients. Moreover the elimination of two additional EGFR over-expressing cancers in vivo suggests that in principle this strategy can be applied to treat other tumors that over-express EGFR.
Cortical plasticity: A proposed mechanism by which genomic factors lead to the behavioral and neurological phenotype of autism spectrum and psychotic-spectrum disorders
Authors: Lindsay M. Oberman, Alvaro Pascual-Leone
Journal: Behavioral and Brain Sciences (2008)

Abstract Crespi &amp; Badcock (C&amp;B) hypothesize that biases toward expression of paternally or maternally imprinted genes lead to the symptoms of autism spectrum disorders (ASD) and psychotic-spectrum disorders (PSD), respectively. We suggest that such genetic risk factors may act by inducing abnormalities in developmental and learning-related plasticity. We provide preliminary evidence of abnormal plasticity in ASD and suggest transcranial magnetic stimulation as a useful tool to investigate as well as influence cortical plasticity.
Inflammatory Cytokines Interleukin-6 and Oncostatin M Induce Plasminogen Activator Inhibitor-1 in Human Adipose Tissue
Authors: G. Rega, C. Kaun, T.W. Weiss, S. Demyanets, G. Zorn, S.P. Kastl, S. Steiner, D. Seidinger, C.W. Kopp, M. Frey, R. Roehle, G. Maurer, K. Huber, J. Wojta
Journal: Circulation (2005)

Background— Adipose tissue is a prominent source of plasminogen activator inhibitor-1 (PAI-1), the primary physiological inhibitor of plasminogen activation. Increased PAI-1 expression acts as a cardiovascular risk factor, and plasma levels of PAI-1 strongly correlate with body mass index (BMI). Elevated serum levels of interleukin-6 (IL-6), an inflammatory cytokine and a member of the glycoprotein 130 (gp130) ligand family, are found in obese patients and might indicate low-grade systemic inflammation. Another gp130 ligand, oncostatin M (OSM), upregulates PAI-1 in cardiac myocytes, astrocytes, and endothelial cells. We used tissue explants and primary cultures of preadipocytes and adipocytes from human subcutaneous and visceral adipose tissue to investigate whether IL-6 and OSM affect PAI-1 expression in fat. Methods and Results— Human subcutaneous and visceral adipose tissue responded to treatment with IL-6 and OSM with a significant increase in PAI-1 production. Human preadipocytes were isolated from subcutaneous and visceral adipose tissue. Adipocyte differentiation was induced by hormone supplementation. All cell types expressed receptors for IL-6 and OSM and produced up to 12-fold increased levels of PAI-1 protein and up to 9-fold increased levels of PAI-1 mRNA on stimulation with IL-6 and OSM. AG-490, a janus kinase/signal transducer and activator of transcription inhibitor, abolished the OSM-dependent PAI-1 induction almost completely. Conclusions— We have for the first time established a link between the gp130 ligands, the proinflammatory mediators IL-6 and OSM, and the expression of PAI-1 in human adipose tissue. Thus, we speculate that IL-6 and OSM, by upregulating PAI-1 in adipose tissue, can contribute to the increased cardiovascular risk of obese patients.
Interpretation in Consultations With Immigrant Patients With Cancer: How Accurate Is It?
Authors: Phyllis N. Butow, David Goldstein, Melaine L. Bell, Ming Sze, Lynley J. Aldridge, Sarah Abdo, Michelle Tanious, Skye Dong, Rick Iedema, Janette Vardy, Ray Ashgari, Rina Hui, Maurice Eisenbruch
Journal: Journal of Clinical Oncology (2011)

Immigrants with cancer often have professional and/or family interpreters to overcome challenges communicating with their health team. This study explored the rate and consequences of nonequivalent interpretation in medical oncology consultations.Consecutive immigrant patients with newly diagnosed with incurable cancer, who spoke Arabic, Cantonese, Mandarin, or Greek, were recruited from the practices of 10 medical oncologists in nine hospitals. Their first two consultations were audio taped, transcribed, translated into English and coded.Thirty-two of 78 participants had an interpreter at 49 consultations; 43% of interpreters were family, 35% professional, 18% both a professional and family, and 4% a health professional. Sixty-five percent of professional interpretations were equivalent to the original speech versus 50% for family interpreters (P= .02). Seventy percent of nonequivalent interpretations were inconsequential or positive; however, 10% could result in misunderstanding, in 5% the tone was more authoritarian than originally intended, and in 3% more certainty was conveyed. There were no significant differences in interpreter type for equivalency of interpretations.Nonequivalent interpretation is common, and not always innocuous. Our study suggests that there may remain a role for family or telephone versus face-to-face professional interpreters.careful communication between oncologists and interpreters is required to ensure optimal communication with the patient.
Preoperative Mitomycin, Ifosfamide, and Cisplatin Followed by Esophagectomy in Squamous Cell Carcinoma of the Esophagus: Pathologic Complete Response Induced by Chemotherapy Leads to Long-Term Survival
Authors: S.J. Darnton, V.R. Archer, D.D. Stocken, P.J. Mulholland, A.G. Casson, D.R. Ferry
Journal: Journal of Clinical Oncology (2003)

Squamous cell carcinoma of the esophagus remains an aggressive disease with a poor prognosis, even after curative-intent surgery. This article analyzes the impact of preoperative chemotherapy with mitomycin, ifosfamide, and cisplatin (MIC) on a cohort of 68 patients.From 1988 to 1994, 68 patients with potentially operable squamous cell carcinoma of the esophagus were entered onto two phase II trials of neoadjuvant chemotherapy with mitomycin 6 mg/m2, ifosfamide 3 g/m2, and cisplatin 50 mg/m2 and received between two and four cycles of treatment at 3-weekly intervals. Two patients were removed from the analysis when they were found to have malignancy other than squamous cell carcinoma of the esophagus.Forty (61%) of 66 patients had a radiologic response to chemotherapy (18 complete responses and 22 partial responses), and 52 (79%) of 66 patients went on to have the primary tumor resected. There were nine pathologic complete responders, seven of whom remain fit and well after at least 60 months of follow-up. The overall median survival was 12.4 months (95% confidence interval, 9.6 to 18.8 months). The complete response and node-negative patients survived significantly longer than those in other categories (log-rank chi2 = 18.8; P <.001): on average 13 months longer than the node-positive or nonresected category (22.0 v 9.4 months). The toxicity of the regimen was low.MIC is an easily administered, well-tolerated, and efficacious regimen as neoadjuvant therapy for patients with squamous cell carcinoma of the esophagus. These results warrant further investigation.
Developmental Hypertension, Nephrogenesis, and Mother's Milk
Authors: Susan P. Bagby
Journal: Journal of the American Society of Nephrology (2007)

Compelling epidemiologic and experimental evidence indicates that early-life experiences shape risk for disease in later life. Infants who are born smaller, reflecting a slower growth trajectory in utero , experience higher incidences of hypertension, obesity, diabetes, and renal disease as adults