tbuckley/cabot-search huggingface dataset:
Circulating Deoxyribonucleic Acid As Prognostic Marker in Non–Small-Cell Lung Cancer Patients Undergoing Chemotherapy
Authors: Oliver Gautschi, Colette Bigosch, Barbara Huegli, Monika Jermann, Arthur Marx, Eveline Chassé, Daniel Ratschiller, Walter Weder, Markus Joerger, Daniel C. Betticher, Rolf A. Stahel, Annemarie Ziegler
Journal: Journal of Clinical Oncology (2004)

Purpose Circulating cell-free DNA is present in increased amounts in the blood of cancer patients, but the clinical relevance of this phenomenon remains unclear. We conducted a clinical study to assess the value of circulating DNA as a prognostic marker in patients with non–small-cell lung cancer (NSCLC). Patients and Methods A standard protocol for the quantification of circulating DNA by real-time polymerase chain reaction was set up and validated at two oncology units. One hundred eighty-five informed patients with NSCLC and 46 healthy controls were included in the study. DNA concentrations were determined in paired plasma and serum samples and analyzed for a relationship with leukocyte counts and lactate dehydrogenase (LDH) levels. DNA concentrations in healthy controls and in patients were compared, and cutoff levels for plasma and serum DNA were determined. Patient survival was analyzed relative to baseline DNA concentrations, and the relationship between tumor responses and changes in DNA concentrations was assessed in patients receiving chemotherapy. Results We found a significant correlation between increased plasma DNA concentrations and elevated LDH levels (P = .009), advanced tumor stage (P &lt; .003), and poor survival (P &lt; .001). Tumor progression after chemotherapy was significantly (P = .006) associated with increasing plasma DNA concentrations. Serum DNA concentrations strongly correlated (P &lt; .001) with leukocyte counts. Conclusion Our data demonstrate that quantification of plasma DNA is an accurate technique amenable to standardization, which might complement current methods for the prediction of patient survival. This approach might be considered for evaluation in large prospective studies.
Adrenocortical Carcinoma Is a Lynch Syndrome–Associated Cancer
Authors: Victoria M. Raymond, Jessica N. Everett, Larissa V. Furtado, Shanna L. Gustafson, Chelsy R. Jungbluth, Stephen B. Gruber, Gary D. Hammer, Elena M. Stoffel, Joel K. Greenson, Thomas J. Giordano, Tobias Else
Journal: Journal of Clinical Oncology (2013)

Adrenocortical carcinoma (ACC) is an endocrine malignancy with a poor prognosis. The association of adult-onset ACC with inherited cancer predisposition syndromes is poorly understood. Our study sought to define the prevalence of Lynch syndrome (LS) among patients with ACC.One hundred fourteen patients with ACC were evaluated in a specialized endocrine oncology clinic and were prospectively offered genetic counseling and clinical genetics risk assessment (group 1). In addition, families with known mismatch repair (MMR) gene mutations that were recorded in the University of Michigan Cancer Genetics Registry were retrospectively reviewed for the presence of ACC (group 2). ACC tumors from patients with LS were tested for microsatellite instability and immunohistochemistry (IHC) to evaluate for MMR deficiency.Ninety-four (82.5%) of 114 patients with ACC underwent genetic counseling (group 1). Three individuals (3.2%) had family histories suggestive of LS. All three families were found to have MMR gene mutations. Retrospective review of an additional 135 MMR gene-positive probands identified two with ACC (group 2). Four ACC tumors were available (group 1, 3; group 2, 1). All four tumors were microsatellite stable; three had IHC staining patterns consistent with germline mutation status.The prevalence of LS among patients with ACC is 3.2%, which is comparable to the prevalence of LS in colorectal and endometrial cancer. Patients with ACC and a personal or family history of LS tumors should be strongly considered for genetic risk assessment. IHC screening of all ACC tumors may be an effective strategy for identifying patients with LS.
NOTE ON LOBAR PNEUMONIA FOLLOWING MEASLES
Authors: F. C. Bottomley
Journal: BMJ (1905)

2uxA '37 Finding after a lapse of a week no amelioration of the symptoms, Dr. Jefferiss asked the writer to see the case with him, and here is what was found: the child lay on her back, the breathing was frequent and shallow, and the cheeks had a pink flush; the skin was hot and dry.Inspection showed the right side to be motionless.The heart's apex was in the normal position.Vocal fremitus was increased all over *he right lung, and the percussion note was so dull from apex to base as almost to warrant the designation of " flat."The dullness below was indistinguishable from the liver dullness.There was very high pitched tubular breathing over the entire lung, with whispering pectoriloquy.No rdles of any kind.The left lung was normal throughout, the breathing therein wvas puerile, and for some distance outside the vertebral column the tubular breathing and voice sounds from the
Diagnosis of Legionnaires' disease. An update of laboratory methods with new emphasis on isolation by culture
Authors: J. J. Zuravleff
Journal: JAMA (1983)

A prospective clinical study of 40 cases of legionnaires' disease combined with serial laboratory examinations enabled us to present an update as well as new recommendations concerning the use of diagnostic tests for legionnaires' disease. Transtracheal aspirate specimens are the optimal specimen for recovery of<i>Legionella pneumophila</i>by culture as well as the most sensitive method for early diagnosis. In addition, with recent improvements in culture media and methodology,<i>L pneumophila</i>can now be readily isolated from sputum. Examination of respiratory specimens by direct immunofluorescence (DFA) is useful, but the sensitivity is much less than that of culture. The yield from DFA examination directly correlates with the number of<i>L pneumophila</i>recoverable by cultural methods; thus, the DFA test result may be negative in an early or mild case of legionnaires' disease. Antibody titers were elevated in 27% of cases within one week of onset of pneumonia and may, therefore, be useful in early diagnosis in selected patients. (<i>JAMA</i>1983;250:1981-1985)
Amino acid residues required for binding of lymphocyte function-associated antigen 3 (CD58) to its counter-receptor CD2.
Authors: L Osborn, E S Day, G T Miller, M Karpusas, R Tizard, S C Meuer, P S Hochman
Journal: The Journal of Experimental Medicine (1995)

Efficient activation and regulation of the cellular immune response requires engagement of T cell accessory molecules as well as the antigen-specific T cell receptor. The lymphocyte function-associated antigen (LFA) 3 (CD58)/CD2 accessory pathway, one of the first discovered, has been extensively characterized in terms of structure and function of the CD2 molecule, which is present on all T lymphocytes and natural killer cells of the human immune system. The binding site of human CD2 for LFA-3 has been localized to two epitopes on one face of the first immunoglobulin (Ig)-like domain of this two-domain, Ig superfamily molecule. Human LFA-3 is genetically linked and is 21% identical in amino acid sequence to CD2, suggesting that this adhesive pair may have evolved from a single ancestral molecule. We have aligned the amino acid sequences of LFA-3 and CD2 and mutagenized selected amino acids in the first domain of LFA-3 that are analogous to those implicated in the binding site of CD2. The data show that K30 and K34, in the predicted C-C' loop, and D84, in the predicted F-G loop of LFA-3, are involved in binding to CD2, suggesting that two complementary sites on one face of the first domain of each molecule bind to each other.
Evaluation of pemetrexed (Alimta, LY231514) as second-line chemotherapy in persistent or recurrent carcinoma of the cervix: the CERVIX 1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) Group
Authors: D. Lorusso, G. Ferrandina, S. Pignata, M. Ludovisi, R. Viganò, S. Scalone, P. Scollo, E. Breda, A. Pietragalla, G. Scambia
Journal: Annals of Oncology (2009)
Response to Open Peer Commentaries on “Relative Versus Absolute Standards for Everyday Risk in Adolescent HIV Prevention Trials: Expanding the Debate”
Authors: Jeremy Snyder, Cari L. Miller, Glenda Gray
Journal: The American Journal of Bioethics (2011)

The authors of this letter comment on the responses to an article that focuses on expanding the debate over use of a relative standard of risk for adolescent involvement in HIV vaccine trials. It addresses each response and provides explanations for the raised concerns.
Enhanced expression of mRNA for Krüppel-like factor 5 in CD34+ cells of the bone marrow in rheumatoid arthritis: Figure 1
Authors: S Hirohata, Y Miura, T Tomita, H Yoshikawa
Journal: Annals of the Rheumatic Diseases (2009)

Bone marrow (BM) CD34+ cells in rheumatoid arthritis (RA) have abnormal capacities to respond to tumour necrosis factor alpha (TNFα) and to differentiate into fibroblast-like cells producing matrix metalloproteinase type 1, suggesting that BM CD34+ progenitor cells might generate type B synoviocytes.1 Of note, RA BM CD34+ cells show enhanced expression of nuclear factor kappa B1 (NFκB1) (p50), the silencing of which resulted in the prevention of fibroblast-like cell differentiation.2 Kruppel-like factor 5 (KLF-5), a zinc finger-containing transcription factor, activates many genes, including platelet-derived growth factor (PDGF) A/B, plasminogen activator inhibitor-1, inducible nitric oxide synthase and vascular endothelial growth factor receptors.3 4 KLF-5 has been shown to cooperate with NFκB1 to activate PDGF-A gene expression,4 5 which might be involved in synovial fibroblast-like cell proliferation.6 We explored KLF-5 messenger RNA expression in RA BM CD34+ cells to delineate the mechanism …
Hypotension and Resistance to Lipopolysaccharide-Induced Shock in Transgenic Mice Overexpressing Adrenomedullin in Their Vasculature
Authors: Takayuki Shindo, Hiroki Kurihara, Koji Maemura, Yukiko Kurihara, Tomoyuki Kuwaki, Taro Izumida, Naoto Minamino, Ki-Hwan Ju, Hiroyuki Morita, Yoshio Oh-hashi, Mamoru Kumada, Kenji Kangawa, Ryozo Nagai, Yoshio Yazaki
Journal: Circulation (2000)

Background —Adrenomedullin (AM) is a vasodilating peptide involved in the regulation of circulatory homeostasis and in the pathophysiology of certain cardiovascular diseases. To determine the extent to which chronic AM overproduction affects circulatory physiology under normal and pathological conditions, we used a preproendothelin-1 promoter to establish transgenic mouse lines overexpressing AM in their vasculature. Methods and Results —Transgenic mice overexpressing AM mainly in vascular endothelial and smooth muscle cells exhibited significantly lower blood pressure (BP) and higher plasma cGMP levels than their wild-type littermates. Blockade of NO synthase with N G -monomethyl- l -arginine elevated BP to a greater degree in AM transgenic mice, offsetting the BP difference between the 2 groups. Despite their lower basal BP, administration of bacterial lipopolysaccharide elicited smaller declines in BP and less severe organ damage in AM transgenic mice than in wild-type mice. Furthermore, the 24-hour survival rate after induction of lipopolysaccharide shock was significantly higher in the transgenic mice. Conclusions —A chronic increase in vascular AM production reduces BP at least in part via an NO-dependent pathway. In addition, smaller responses to LPS in transgenic mice suggest that AM is protective against the circulatory collapse, organ damage, and mortality characteristic of endotoxic shock.
Gender Rears Its Ugly Head Again
Authors: E. Ward Gilman
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The interesting exchange between Fletcher<sup>1</sup>and Iverson<sup>2</sup>on the subject of gender meaning "sex" has been brought to my attention. I would like to clarify some apparent confusion about the definition of<i>gender</i>and<i>sex</i>in<i>Webster's Ninth New Collegiate Dictionary</i>. "Sex" is given as the first sense of gender; there is no reciprocal mention of gender at the definition of<i>sex</i>because sex is not used in the sense of gender. The date (14c) on the entry for gender means that it has been used in the meaning "sex" since the 14th century. Its grammatical meaning has also been in use since the same century. Both meanings have coexisted and have been listed in dictionaries down to the present day. Around the turn of the century, dictionary editors began labeling the "sex" sense humorous or colloquial, but by the middle of this century, it
Allowing or Causing: Another Look
Authors: K. DANNER CLOUSER
Journal: Annals of Internal Medicine (1977)

If "allowing to die" is really different from "causing to die," it is so on a much more subtle level than is generally thought. Efforts to compare the two by locating "cause" have been mistaken. What is really at issue is the location of moral responsibility. The physician has an obligation to save and is remiss if he does not try. The layman does not and is not. But as saving turns into pointless torture, the physician's obligation recedes, and he (ethically) becomes a layman. There is a range within which this turning point would take place for each of us, and the value of a "living will" can be seen as a means for each of us to specify that point for himself.
Modulation of norepinephrine release by ATP-dependent K+-channel activators and inhibitors in guinea-pig and human isolated right atrium
Authors: K Oe
Journal: Cardiovascular Research (1999)

Objective: The aim of this study was to show, whether ATP sensitive K+ channels (KATP channels), are involved in the modulation of norepinephrine (NE) release from the sympathetic nerves innervating the guinea-pig and human right atrium. Methods: The resting and stimulation-evoked release of [3H]norepinephrine ([3H]NE) was measured from the isolated guinea-pig and human right atrium and the effect of activators and inhibitors of ATP sensitive K+ channels was studied. Results: Cromakalim (30–300 μM), a KATP channel-agonist decreased concentration-dependently the stimulation-evoked release of NE from the guinea-pig atrium, an effect, antagonized by glibenclamide, a KATP channel-antagonist (30 μM). Diazoxide (30–300 μM), another activator of the KATP channels reduced the resting release of NE, and also attenuated the evoked release at a single concentration (100 μM), and this latter action was also counteracted by glibenclamide (30 μM). Pinacidil, increased dose-dependently the resting and stimulation-evoked release of NE in a glibenclamide-sensitive manner and reversed the inhibitory effect of cromakalim (100 μM), suggesting that it acts as an antagonist. Glibenclamide (30–300 μM), by itself enhanced the stimulation-evoked release of [3H]NE, and also increased the resting release of NE. On the other hand, 5-hydroxydecanoate, an ischemia-selective inhibitor of cardiac KATP channels did not change NE release. Adenosine, (30–300 μM), an A1-receptor agonist, clonidine (3 μM), an α2-adrenoceptor agonist and oxotremorine, a muscarinic receptor agonist (30 μM) all reduced the evoked release of [3H]NE, but these effects were not modified by glibenclamide (300 μM), indicating that neuronal adenosine (A1), adrenergic (α2) and muscarinic (M3) receptors do not act on KATP channels. In the human right atrium, cromakalim, and diazoxide did not affect significantly the release of [3H]NE. However, glibenclamide (30–300 μM) and pinacidil (30–300 μM) enhanced dose-dependently the evoked-release of NE, and pinacidil also augmented the resting release. Conclusions: Our results indicate that sympathetic nerve endings of the human and guinea-pig atrium are endowed with ATP-sensitive K+ channels. These channels responded to agonists and antagonists under the experimental conditions applied and they could modulate the release of NE thereby affecting the autonomic control of cardiac function under various physiological and pathophysiological conditions.
Fibrinogen Is a Marker for Nephropathy and Peripheral Vascular Disease in Type 1 Diabetes
Authors: Richard L. Klein, Steven J. Hunter, Alicia J. Jenkins, Deyi Zheng, Andrea J. Semler, Jennifer Clore, W. Timothy Garvey
Journal: Diabetes Care (2003)

ABSTRACT— We examined whether plasma fibrinogen levels and the β-fibrinogen gene G−455→A polymorphism were related to microvascular or macrovascular disease in patients (n = 909) with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/ EDIC). Univariate regression showed that fibrinogen levels were correlated with BMI (r = 0.15; P &amp;lt; 0.0001), HbA1c (r = 0.11; P = 0.0014), total cholesterol (r = 0.17; P &amp;lt; 0.0001), and LDL cholesterol (r = 0.16; P &amp;lt; 0.0001) in all patients. In men, but not women, waist-to-hip ratio (r = 0.20; P &amp;lt; 0.0001) and triglycerides (r = 0.13; P = 0.0047) also became powerful predictors of fibrinogen level; in women, but not men, fibrinogen was correlated with both diastolic (r = 0.16; P = 0.0011) and systolic (r = 0.11; P = 0.0241) blood pressure. Fibrinogen was correlated with urinary albumin excretion rates in men (r = 0.13; P = 0.0033), but not in women. In both sexes, however, the development of proteinuria (albumin excretion &amp;gt;300 mg/24 h) was accompanied by 1.5-fold increment in plasma fibrinogen compared with patients with normal excretion or microalbuminuria. In addition, high fibrinogen levels were associated with a lower average ankle-brachial index in women (r = −0.13; P = 0.0075), but not men. Multiple regression analyses demonstrated that plasma fibrinogen was independently correlated with high albumin excretion rate in men, and with low average ankle-brachial index in women. Fibrinogen was not correlated with the severity of retinopathy. Carotid artery intima-medial thickness was not correlated with fibrinogen, and the G−455→A polymorphism in the 5′ promoter region of the β-fibrinogen gene did not influence circulating fibrinogen levels. However, the presence of the more common G−455 allele was associated with greater intima-medial thickness in the internal carotid artery (ANCOVA P = 0.045). Last, hyperfibrinogenemia in type 1 diabetes is associated with components of the insulin resistance syndrome trait cluster, and the association is influenced by sex.
Radium-226-Contaminated Drinking Water: Hypothesis on an Exposure Pathway in a Population with Elevated Childhood Leukemia
Authors: Wolfgang Hoffmann, A. Kranefeld, Inge Schmitz-Feuerhake
Journal: Environmental Health Perspectives (1993)

A recent epidemiological survey on childhood malignant disease in the region of Ellweiler, Rheinland-Pfalz, Germany, revealed a significantly increased incidence of childhood leukemia, but observed incidences of lymphoma and solid tumors were normal. Established risk factors such as individual exposure to chemicals as well as hereditary genetic disorders were ruled out in interviews with the patients or their families. The general population in the region, however, is subjected to considerable doses of ionizing radiation due to high levels of external gamma radiation and high activities of indoor radon. Radiation-specific chromosome aberrations were found in one of two healthy siblings and one father of leukemia patients as well as in any of three probands living in houses with high indoor radon activities. Radon and natural gamma radiation, however, cannot explain the geographical pattern of the cases. Four out of seven cases were observed in two particular villages near a uranium processing plant. The drinking water of these villages partly came from a small river that was contaminated with radium-226 washed out from the dumps of the uranium plant. Only sparse measurements of 226Ra are available, but derived red bone marrow doses for children in the two villages obtained from a simple radio-ecological model show the significance of the drinking water pathway. Prenatal 226Ra exposure of fetuses due to placental transfer and accumulation may have led to significant doses and may explain the excess cases of childhood leukemia in the region even in quantitative terms.
THE ROLE OF LIVER AND SPLEEN IN THE METABOLISM OF INTRAVENOUSLY INJECTED FAT IN RABBITS
Authors: J. Van Den Bosch, E. Evrard, A. Billiau, J. V. Joossens, P. De Somer
Journal: The Journal of Experimental Medicine (1961)

The uptake of intravenously injected coconut oil emulsion by the liver and spleen was investigated by gas-liquid chromatography in normal, triton-injected, and hypercholesterolemic rabbits. The lauric and myristic acids from this emulsion, almost absent in the tissues of normal animals, were used as marked acids. In normal rabbits only the liver took up a quantitatively important fraction of the injected fat. The uptake by the spleen appears to be due to a different mechanism than that of the liver. In rabbits given triton the liver was incapable of taking up large quantities of fat, while the uptake in the spleen was undisturbed. 12 hours after injection the plasma, liver, and spleen of normal animals contained only 14 per cent of the dose. With animals given triton 71 per cent of the injected dose was recovered, most of it in the plasma. Hypercholesterolemic rabbits cleared an injected fat emulsion and took fat into the liver at the same rate as the controls. When triton is injected 6 hours after the administration of the emulsion, the fat taken up in the liver reappears in the plasma.
Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease
Authors: Anna J. James, Lovisa E. Reinius, Marri Verhoek, Anna Gomes, Maciej Kupczyk, Ulf Hammar, Junya Ono, Shoichiro Ohta, Kenji Izuhara, Elisabeth Bel, Juha Kere, Cilla Söderhäll, Barbro Dahlén, Rolf G. Boot, Sven-Erik Dahlén
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels.To examine serum chitotriosidase activity and YKL-40 levels in patients with asthma and chronic obstructive pulmonary disease (COPD) and evaluate clinically relevant factors that may affect chitinase levels, including genetic variability, corticosteroid treatment, disease exacerbations, and allergen exposure.Serum chitotriosidase (CHIT1) activity and YKL-40 (CHI3L1) levels, as well as the CHIT1 rs3831317 and CHI3L1 rs4950928 genotypes, were examined in subsets of patients with mild to moderate asthma (n = 76), severe asthma (n = 93), and COPD (n = 64) taking part in the European multicenter BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) study. Blood was obtained at baseline, before and after a 2-week oral steroid intervention, up to six times during a 1-year period, and during exacerbations. Baseline chitinase levels were also measured in 72 healthy control subjects. The effect of allergen inhalation on blood and sputum YKL-40 levels was measured in two separate groups of patients with mild atopic asthma; one group underwent repeated low-dose allergen challenge (n = 15), and the other underwent high-dose allergen challenge (n = 16).Serum chitotriosidase and YKL-40 were significantly elevated in patients with asthma and those with COPD compared with healthy control subjects. Genotype and age strongly affected both YKL-40 and chitotriosidase activity, but associations with disease remained following adjustment for these factors. Correlations were observed with lung function but not with other biomarkers, including exhaled nitric oxide, blood eosinophils, periostin, and IgE. Generally, acute exacerbations, allergen-induced airway obstruction, and corticosteroid treatment did not affect circulating chitinase levels.YKL-40 and chitotriosidase are increased in asthma and more so in COPD. The data in the present study support these substances as being relatively steroid-insensitive, non-T-helper cell type 2-type biomarkers distinctly related to chronic inflammatory disease processes.