tbuckley/cabot-search huggingface dataset:
Cancer Causes Cardiac Atrophy and Autophagy in a Sexually Dimorphic Manner
Authors: Pippa F. Cosper, Leslie A. Leinwand
Journal: Cancer Research (2010)

Approximately one-third of cancer deaths are caused by cachexia, a severe form of skeletal muscle and adipose tissue wasting that affects men more than women. The heart also undergoes atrophy in cancer patients, but the mechanisms and the basis for apparent sex differences are unclear. In a mouse colon-adenocarcinoma model, cancer causes a loss of cardiac mass due to a decrease in cardiac myocyte size that is associated with reduced levels of all sarcomeric proteins. Unlike skeletal muscle cachexia, atrophic hearts do not upregulate the ubiquitin-proteasome system or its activity but increase autophagy. Thus, cancer causes cardiac atrophy by a mechanism distinct from that in skeletal muscle. Male tumor-bearing mice have a more severe phenotype than females, including greater cardiac mass loss and mortality, a more robust pro-inflammatory response to the tumor, and greater cardiac autophagy. In females, estrogen protects against cancer-induced cardiac atrophy and body weight loss by signaling through its receptor. Sex differences in cardiac atrophy need to be considered during the treatment of patients suffering from chemotherapy-induced cardiomyopathy to prevent exacerbation of cardiac dysfunction.
Ex vivo exposure to carbon monoxide prevents hepatic ischemia/reperfusion injury through p38 MAP kinase pathway
Authors: Farin Amersi, Xiu-Da Shen, Dean Anselmo, Judy Melinek, Suhasani Iyer, Daniel J. Southard, Masamichi Katori, Hans-Dieter Volk, Ronald W. Busuttil, Roland Buelow, Jerzy W. Kupiec-Weglinski
Journal: Hepatology (2002)

A direct role of carbon monoxide (CO), an effector-signaling molecule during heme oxygenase-1 (HO-1) catalysis of heme, in the protection against hepatic ischemia/reperfusion (I/R) injury needs to be established. This study was designed to determine the effects and downstream mechanisms of CO on cold I/R injury in a clinically relevant isolated perfusion rat liver model. After 24 hours of cold storage, rat livers perfused ex vivo for 2 hours with blood supplemented with CO (300 parts per million) showed significantly decreased portal venous resistance and increased bile production, as compared with control livers perfused with blood devoid of CO. These beneficial effects correlated with improved liver function (serum glutamic oxaloacetic transaminase levels) and diminished histological features of hepatocyte injury (Banff's scores). The CO-mediated cytoprotective effects were nitric oxide synthase- and cyclic guanine monophosphate-independent, but p38 mitogen-activated protein kinase (MAPK)-dependent. Moreover, adjunctive use of zinc protoporphyrin, a competitive HO-1 inhibitor, has shown that exogenous CO could fully substitute for endogenous HO-1 in preventing hepatic I/R insult. This study performed in a clinically relevant ex vivo cold ischemia model is the first to provide the evidence that HO-1-mediated cytoprotection against hepatic I/R injury depends on the generation of, and can be substituted by, exogenous CO. The p38 MAPK signaling pathway represents the key downstream mechanism by which CO prevents the I/R insult. In conclusion, regimens that employ exogenous CO should be revisited, as they may have potential applications in preventing/mitigating I/R injury, and thus expanding the liver donor pool for clinical transplantation.
Cost-minimization analysis of a phase III trial comparing concurrent versus sequential radiochemotherapy for locally advanced non-small-cell lung cancer (GFPC-GLOT 95–01)
Authors: A. Vergnenegre, C. Combescure, P. Fournel, S. Bayle, C. Gimenez, P.J. Souquet, H. Lena, M. Perol, J.Y. Delhoume
Journal: Annals of Oncology (2006)
1066-193 Endovascular stent-graft placement for nonsurgical repair of descending aortic perforations: Acute and follow-up results
Authors: Dierk Scheinert, Andrej Schmidt, Susanne Scheinert, Sven Bräunlich, Hans Krankenberg, Giancarlo Biamino, Friedrich Mohr
Journal: Journal of the American College of Cardiology (2004)
CD81/CD9 tetraspanins aid plasmacytoid dendritic cells in recognition of hepatitis C virus-infected cells and induction of interferon-alpha
Authors: Shuye Zhang, Karen Kodys, Gregory J. Babcock, Gyongyi Szabo
Journal: Hepatology (2012)

Recognition of hepatitis C virus (HCV)-infected hepatocyes and interferon (IFN) induction are critical in antiviral immune response. We hypothesized that cell-cell contact between plasmacytoid dendritic cells (pDCs) and HCV-infected cells was required for IFN-α induction through the involvement of cell-surface molecules. Coculture of human peripheral blood mononuclear cells (PBMCs) with genotype 1a full-length (FL) HCV genomic replicon cells or genotype 2a Japanese fulminant hepatitis type 1 (JFH-1) virus-infected hepatoma cells (JFH-1), and not with uninfected hepatoma cells (Huh7.5), induced IFN-α production. Depletion of pDCs from PBMCs attenuated IFN-α release, and purified pDCs produced high levels of IFN-α after coculture with FL replicons or JFH-1-infected cells. IFN-α induction by HCV-containing hepatoma cells required viral replication, direct cell-cell contact with pDCs, and receptor-mediated endocytosis. We determined that the tetraspanin proteins, CD81 and CD9, and not other HCV entry receptors, were required for IFN-α induction in pDCs by HCV-infected hepatoma cells. Disruption of cholesterol-rich membrane microdomains, the localization site of CD81, or inhibition of the CD81 downstream molecule, Rac GTPase, inhibited IFN-α production. IFN-α induction involved HCV RNA and Toll-like receptor (TLR) 7. IFN-α production by HCV-infected hepatoma cells was decreased in pDCs from HCV-infected patients, compared to healthy controls. We found that preexposure of healthy PBMCs to HCV viral particles attenuated IFN-α induction by HCV-infected hepatoma cells or TLR ligands, and this inhibitory effect could be prevented by an anti-HCV envelope glycoprotein 2–blocking antibody. Conclusion: Our novel data show that recognition of HCV-infected hepatoma cells by pDCs involves CD81- and CD9-associated membrane microdomains and induces potent IFN-α production. (HEPATOLOGY 2013;58:940–949)
Tele-assistance in chronic respiratory failure patients: a randomised clinical trial
Authors: M. Vitacca, L. Bianchi, A. Guerra, C. Fracchia, A. Spanevello, B. Balbi, S. Scalvini
Journal: European Respiratory Journal (2008)

Chronic respiratory patients requiring oxygen or home mechanical ventilation experience frequent exacerbations and hospitalisations with related costs. Strict monitoring and care have been recommended. The aim of the present study was to primarily evaluate reduction in hospitalisations and, secondly, exacerbations, general practitioner (GP) calls and related cost-effectiveness of tele-assistance (TA) for these patients. A total of 240 patients (101 with chronic obstructive pulmonary disease (COPD)) were randomised to two groups: an intervention group entered a 1-yr TA programme while controls received traditional care. No anthropometric and clinical differences were found between groups both in baseline and in mortality (18% for TA, 23% for controls). Compared with controls, the TA group experienced significantly fewer hospitalisations (-36%), urgent GP calls (-65%) and acute exacerbations (-71%). Only COPD patients, as a separate group, had fewer hospitalisations, emergency room admissions, urgent GP calls or exacerbations. Each patient referred to staff a mean± sd 36±25 times. After deduction of TA costs, the average overall cost for each patient was 33% less than that for usual care. In chronic respiratory failure patients on oxygen or home mechanical ventilation, a nurse-centred tele-assistance prevents hospitalisations while it is cost-effective. The chronic obstructive pulmonary disease group seems to have a greater advantage from tele-assistance.
The MR imaging diagnosis of liver diseases using gadoxetic acid: Emphasis on hepatobiliary phase
Authors: Woo Kyoung Jeong, Young Kon Kim, Kyoung Doo Song, Dongil Choi, Hyo Keun Lim
Journal: Clinical and Molecular Hepatology (2013)

Hepatocyte specific contrast agents including gadoxetic acid and gadobenate dimeglumine are very useful to diagnose various benign and malignant focal hepatic lesions and even helpful to estimate hepatic functional reservoir. The far delayed phase image referred to as the hepatobiliary phase makes the sensitivity of detection for malignant focal hepatic lesions increased, but specificity of malignant diseases, including hepatocellular carcinoma, metastasis and cholangiocarcinoma, characterization remained to be undetermined. Keywords: Magnetic resonance imaging; Gadoxetic acid; Focal hepatic lesion; Hepatocellular carcinoma; Metastasis; Focal nodular hyperplasia
Suppression of metalloproteinase biosynthesis in human alveolar macrophages by interleukin-4.
Authors: S Lacraz, L Nicod, B Galve-de Rochemonteix, C Baumberger, J M Dayer, H G Welgus
Journal: Journal of Clinical Investigation (1992)

To study the interaction of lymphocytes and macrophages in the control of extracellular matrix turnover, we determined the effects of several soluble T cell products on mononuclear phagocyte production of metalloproteinases. Cytokines including IL-2, IL-4, IL-6, tumor necrosis factor alpha (TNF alpha), GM-CSF, and IFN-gamma were each tested for capacity to modulate macrophage metalloproteinase and tissue inhibitor of metalloproteinases (TIMP) expression. The addition of IL-4 to cells cultured under basal conditions caused a dose-dependent suppression in the release of 92-kD type IV collagenase without affecting TIMP production. 92-kD enzyme secretion was inhibited by 50% with 1-2 ng/ml of IL-4 and by 90% with 10 ng/ml of IL-4. When cells were first exposed to killed Staphylococcus aureus to induce metalloproteinase production, IL-4 potently blocked the stimulated release of both interstitial collagenase and 92-kD type IV collagenase, again without effect upon TIMP. Metabolic labeling experiments and Northern hybridizations demonstrated that IL-4 exerted its action at a pretranslational level. Furthermore, IL-4 possessed the capacity to inhibit metalloproteinase expression even in the relatively immature peripheral blood monocyte. As reported previously (Shapiro, S. D., E. J. Campbell, D. K. Kobayashi, and H. G. Welgus. 1990. J. Clin. Invest. 86:1204), IFN-gamma suppressed constitutive macrophage production of 92-kD type IV collagenase. Despite the frequent antagonism observed between IL-4 and IFN-gamma in other systems, the combination of these two agents lowered metalloproteinase biosynthesis dramatically, whereas IL-4 opposed the IFN-gamma-stimulated production of cytokines (IL-1 and TNF alpha). IL-6 had only minimal effect upon metalloproteinase production, but appeared to specifically augment TIMP release. In summary, cytokines released by activated T cells may profoundly reduce the capacity of the macrophage to mediate extracellular matrix degradation.
Molecular Insights into Segmentation along the Proximal–Distal Axis of the Nephron
Authors: Raphael Kopan, Hui-Teng Cheng, Kameswaran Surendran
Journal: Journal of the American Society of Nephrology (2007)

The structure of a mammalian kidney is parsed into large collections of polarized nephrons, and each segment is home to a diverse community of cells that specialize in renal endocrine and excretory functions. Early developmental lengthening and diversification of nephron segments along a proximal--distal axis initiate all subsequent facets of tubular growth and function. Morphogenic cues and biochemical interactions that are critical to this process are starting to emerge. The underlying principles of regional cell signaling and transcriptional control organizing early segmentation are the subject of this review.
Development of colon cancer after liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis
Authors: Hidefumi Higashi, Katsuhiko Yanaga, J. Wallis Marsh, Andreas Tzakis, Saduro Kakizoe, Thomas E. Starzi
Journal: Hepatology (1990)

Between February 26, 1981, and July 30, 1987, 36 patients underwent orthotopic liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis. Three of the 36 recipients died within 3 mo because of graft nonfunction or surgical complications. The other 33 (92%) lived for at least 1 yr. Two of the 33 died after 12 and 14 mo, respectively, of recurrent cholangiocarcinoma that was not diagnosed before transplantation. Four other patients died of recurrent liver failure (three cases) or immunoblastic sarcoma (one case) after 14, 21, 36 and 44 mo. Twenty-seven (75%) of the patients are still alive 23 to 81 mo after transplantation. Two patients have been diagnosed as having colorectal cancer 11 and 21 mo respectively, after transplantation, for an overall incidence of 5.6% (2 of 36) and a corrected incidence of 6.5% (2 of 31) if the three early deaths and two later deaths caused by cholangiocarcinomas are excluded. It is not known whether colorectal malignancies were present but undetected at the time of transplantation or whether they developed afterward. It is clear that patients who undergo liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis should have careful follow-up of the colon, including colonoscopy and multiple biopsies of the colorectal mucosa. Whether proctocolectomy should be considered prophylactically after liver transplantation is an unresolved issue.(HEPATOLOGY 1990;11:477–480.)
Allergenic cross‐reactivity of yeasts
Authors: A. Koivikko, K. Kalimo, E. Nieminen, J. Savolainen, M. Viljanen, M. Viander
Journal: Allergy (1988)

Yeast allergen extracts of Candida albicans, C. pseudotropicalis, C. krusei, C. parapsilosis, C. tropicalis, C. guilliermondi, C. humicola, C. norwegica, C. utilis, Cryptococcus albidus, Geotrichum candidum, Pityrosporon pachydermatis, P. ovale, Rhodotorula minuta, R. rubra, Saccharomyces cerevisiae, Torulopsis glabrata and Trichosporon cutaneum were investigated regarding their common allergenic properties. The enzyme immunoassay (EIA) using rabbit anti Candida albicans antiserum showed remarkable immunological cross‐reactivity only between the Candida species. However, there was a significant multiple sensitivity to the extracts of C. albicans, C. utilis, Cr. albidus, R. rubra , and S. cerevisiae in skin prick testing in atopic patients, suggesting the possible presence of one or more common skin reactive allergens.
The biosynthesis of human hemoglobin A1c. Slow glycosylation of hemoglobin in vivo.
Authors: H F Bunn, D N Haney, S Kamin, K H Gabbay, P M Gallop
Journal: Journal of Clinical Investigation (1976)

Hemoglobin A1c, the most abundant minor hemoglobin component in human erythrocytes, is formed by the condensation of glucose with the N-terminal amino groups of the beta-chains of Hb A. The biosynthesis of this glycosylated hemoglobin was studied in vitro by incubating suspensions of reticulocytes and bone marrow cells with [3H]leucine or 59Fe-bound transferrin. In all experiments, the specific activity of Hb A1c was significantly lower than that of Hb A, suggesting that the formation of Hb A1c is a posttranslational modification. The formation of Hb A1c in vivo was determined in two individuals who were given an infusion of 59Fe-labeled transferrin. As expected, the specific activity of Hb A rose promptly to a maximum during the 1st week and remained nearly constant thereafter. In contrast, the specific activity of Hb A1c and also of Hbs A1a and A1b rose slowly, reaching that of Hb A by about day 60. These results indicate that Hb A1c is slowly formed during the 120-day life-span of the erythrocyte, probably by a nonenzymatic process. Patients with shortened erythrocyte life-span due to hemolysis had markedly decreased levels of Hb A1c.
Quantitation of Harvey &lt;italic&gt;ras&lt;/italic&gt; p21 Enhanced Expression in Human Breast and Colon Carcinomas
Authors: P H Hand, V Vilasi, A Thor, N Ohuchi, J Schlom
Journal: JNCI Journal of the National Cancer Institute (1987)

Molecular studies have demonstrated increased expression of the Harvey (Ha) ras oncogene in human breast and colon carcinomas. With the use of a direct-binding liquid competition radioimmunoassay (RIA), capable of providing truly quantitative analysis of the 21,000-dalton (p21) ras oncogene and protooncogene products, absolute levels of Ha-ras p21 have been determined in human breast and colon carcinomas, benign lesions, and/or their respective normal tissues. Enhanced Ha-ras expression was documented in 66% of breast and 100% of colon carcinomas as compared with their normal counterparts, with levels in breast carcinomas ranging from 10.1 to 50.4 pg ras p21/micrograms protein and those in colon carcinomas ranging from 18.4 to 51.7 pg ras p21/micrograms protein. Some dysplastic lesions of the breast and colon also contained elevated Ha-ras p21. Relative levels of Ha-ras p21 expression, detected by competition RIA, correlated with percent Ha-ras p21-positive cells as determined by immunohistochemical assays. By use of liquid competition RIA and immunohistochemical assays, it has been shown that levels of ras p21 expression did not always correlate between primary and metastatic colon lesions of the same patient. The use of the quantitative RIA and semiquantitative immunohistochemical assays, in concert with cDNA probes for identification of specific ras point-mutated oncogenes or protooncogenes, may now provide the means for definitive quantitative analyses of ras p21 in human carcinomas and benign lesions.
Familial Carbohydrate Intolerance and Hypoglycemia
Authors: M Cornblath
Journal: Annual Review of Medicine (1966)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Follow-up studies of children born after frozen sperm donation
Authors: J. Lansac
Journal: Human Reproduction Update (2001)

The need to assess the health of children born after assisted reproductive technologies (ART) using frozen donor spermatozoa has been a major concern for the last decade. Most available published studies are confusing (since they are retrospective) and refer to small numbers of cases or involve a bias. Two prospective and large population-based studies have been published, one in France and the other in Australia. The general characteristics of children born after ART using frozen spermatozoa was unchanged in comparison with the general population (weight, prematurity, stillbirths, sex ratio). However, the rate of multiple pregnancy was increased, first in artificial insemination with donor semen (AID), where the use of hormonal treatment may be too heavily prescribed, and second in IVF with donor semen (IVF/D) where both the ovulation induction treatments and embryo transfer policy increase the rate of multiple pregnancies. As far as birth defects or chromosomal abnormalities are concerned, no difference has been observed from the general population. Finally, the use of frozen spermatozoa does not seem to affect the health of children conceived by AID or IVF/D. The psychosocial development of such infants is not as well known because of the confidentiality in many countries concerning sperm donation. However, the available information on the psychosocial development of these children up to the age of 8–10 years appears to be reassuring. Larger and longer studies are needed to answer such questions, particularly with regard to adulthood.
The Ion Channel ASIC2 Is Required for Baroreceptor and Autonomic Control of the Circulation
Authors: Yongjun Lu, Xiuying Ma, Rasna Sabharwal, Vladislav Snitsarev, Donald Morgan, Kamal Rahmouni, Heather A. Drummond, Carol A. Whiteis, Vivian Costa, Margaret Price, Christopher Benson, Michael J. Welsh, Mark W. Chapleau, François M. Abboud
Journal: Neuron (2009)
Effects of systemic steroids in patients with severe community-acquired pneumonia
Authors: C. Garcia-Vidal, E. Calbo, V. Pascual, C. Ferrer, S. Quintana, J. Garau
Journal: European Respiratory Journal (2007)

The benefit of systemic steroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) remains unclear. The present study aimed to evaluate the impact of corticosteroid treatment on mortality in patients with severe CAP. A retrospective, observational study of a cohort of patients hospitalised with severe CAP, classes IV and V of the Prognostic Severity Index score, was carried out. Information on epidemiological, clinical and laboratory data, and 30-day mortality was collected from medical charts. Of the 308 patients evaluated, 238 (77%) were treated with standard antimicrobial therapy and 70 (23%) received both antibiotics and systemic steroids. Clinical characteristics were similar between steroid and nonsteroid groups, except in the prevalence of male sex and the presence of chronic obstructive pulmonary disease. Systemic steroids were independently associated with a decreased mortality (odds ratio 0.287; 95% confidence interval 0.113-0.732), while severity of CAP (2.923; 1.262-6.770) was the only independent factor associated with increased mortality. Mortality decreased in the patients with severe CAP who received simultaneous administration of systemic steroids along with antibiotic treatment. Severity of community-acquired pneumonia remains the most important risk factor associated with increased mortality.
Adding Once-Daily Lixisenatide for Type 2 Diabetes Inadequately Controlled With Newly Initiated and Continuously Titrated Basal Insulin Glargine
Authors: Matthew C. Riddle, Thomas Forst, Ronnie Aronson, Leobardo Sauque-Reyna, Elisabeth Souhami, Louise Silvestre, Lin Ping, Julio Rosenstock
Journal: Diabetes Care (2013)

OBJECTIVE When oral therapy for type 2 diabetes is ineffective, adding basal insulin improves glycemic control. However, when glycated hemoglobin (HbA1c) remains elevated because of postprandial hyperglycemia, the next therapeutic step is controversial. We examined the efficacy and safety of lixisenatide in patients with HbA1c still elevated after initiation of insulin glargine. RESEARCH DESIGN AND METHODS This double-blind, parallel-group trial enrolled patients with HbA1c 7–10% despite oral therapy. Insulin glargine was added and systematically titrated during a 12-week run-in, after which candidates with fasting glucose ≤7.8 mmol/L and HbA1c 7–9% were randomized to lixisenatide 20 µg or placebo for 24 weeks while insulin titration continued. The primary end point was HbA1c change after randomization. RESULTS The randomized population (n = 446) had mean diabetes duration of 9.2 years, BMI 31.8 kg/m2, and daily glargine dosage of 44 units. HbA1c had decreased during run-in from 8.6 to 7.6%; adding lixisenatide further reduced HbA1c by 0.71 vs. 0.40% with placebo (least squares mean difference, –0.32%; 95% CI, –0.46 to –0.17; P &amp;lt; 0.0001). More participants attained HbA1c &amp;lt;7% with lixisenatide (56 vs. 39%; P &amp;lt; 0.0001). Lixisenatide reduced plasma glucose 2 h after a standardized breakfast (difference vs. placebo –3.2 mmol/L; P &amp;lt; 0.0001) and had a favorable effect on body weight (difference vs. placebo –0.89 kg; P = 0.0012). Nausea, vomiting, and symptomatic hypoglycemia &amp;lt;3.3 mmol/L were more common with lixisenatide. CONCLUSIONS Adding lixisenatide to insulin glargine improved overall and postprandial hyperglycemia and deserves consideration as an alternative to prandial insulin for patients not reaching HbA1c goals with recently initiated basal insulin.