tbuckley/cabot-search huggingface dataset:
Frequency of expressed immunoglobulin light chain genes in lipopolysaccharide-stimulated BALB/c spleen cells.
Authors: D Zhu, I Lefkovits, G Köhler
Journal: The Journal of Experimental Medicine (1984)

Variants of four hybridoma lines secreting antibodies specific for either trinitrophenyl (TNP) or sheep erythrocytes (SRBC) were isolated which have lost either the specific heavy (H) chain or the specific light (L) chain. They were fused to lipopolysaccharide-stimulated mouse spleen cells and the resulting secondary hybridomas were screened for the restoration of the original antibody specificity. Antibody activity was 37 times more frequently restored with fusion lines donating H chain than with those donating L chain. We obtained a variety of different (spleen cell derived) L chains in association with one H chain and one specificity. We found that those L chains originally associated with a given H chain were rescued most often. Their frequencies were 1:74 and 1:490 for an anti-SRBC- and an anti-TNP-restoring kappa L chain, respectively. Two most commonly observed V-J kappa combinations in one anti-SRBC complementation group were detected with a 5- and 30-fold reduced frequency in two anti-TNP groups, indicating somatic diversification of kappa chains. It is shown that the Sp7/HK line resumes anti-TNP activity with a mutated, non-germline lambda 1 chain, which was found in 30% of lambda 1-expressing hybridomas.
Does extensive genotyping and nasal potential difference testing clarify the diagnosis of cystic fibrosis among patients with single-organ manifestations of cystic fibrosis?
Authors: Chee Y Ooi, Annie Dupuis, Lynda Ellis, Keith Jarvi, Sheelagh Martin, Peter N Ray, Leslie Steele, Paul Kortan, Tanja Gonska, Ruslan Dorfman, Melinda Solomon, Julian Zielenski, Mary Corey, Elizabeth Tullis, Peter Durie
Journal: Thorax (2013)

<h3>Background</h3> The phenotypic spectrum of cystic fibrosis (CF) has expanded to include patients affected by single-organ diseases. Extensive genotyping and nasal potential difference (NPD) testing have been proposed to assist in the diagnosis of CF when sweat testing is inconclusive. However, the diagnostic yield of extensive genotyping and NPD and the concordance between NPD and the sweat test have not been carefully evaluated. <h3>Methods</h3> We evaluated the diagnostic outcomes of genotyping (with 122 mutations included as disease causing), sweat testing and NPD in a prospectively ascertained cohort of undiagnosed patients who presented with chronic sino-pulmonary disease (RESP), chronic/recurrent pancreatitis (PANC) or obstructive azoospermia (AZOOSP). <h3>Results</h3> 202 patients (68 RESP, 42 PANC and 92 AZOOSP) were evaluated; 17.3%, 22.8% and 59.9% had abnormal, borderline and normal sweat chloride results, respectively. Only 17 (8.4%) patients were diagnosable as having CF by genotyping. Compared to sweat testing, NPD identified more patients as having CF (33.2%) with fewer borderline results (18.8%). The level of agreement according to kappa statistics (and the observed percentage of agreement) between sweat chloride and NPD in RESP, PANC and AZOOSP subjects was 'moderate' (65% observed agreement), 'poor' (33% observed agreement) and 'fair' (28% observed agreement), respectively. The degree of agreement only improved marginally when subjects with borderline sweat chloride results were excluded from the analysis. <h3>Conclusions</h3> The diagnosis of CF or its exclusion is not always straightforward and may remain elusive even with comprehensive evaluation, particularly among individuals who present at an older age with single-organ manifestations suggestive of CF.
Ventilatory effects of aerosol gentamicin.
Authors: M B Dally, S Kurrle, A B Breslin
Journal: Thorax (1978)

Bronchial provocation tests with gentamicin solution, 40 mg/ml, and with the drug vehicle solution alone were carried out in 29 subjects aged 19 to 66 years. There were 18 subjects with bronchial asthma, four with chronic bronchitis, four with primary carcinoma of the lung, and three with no chest disease. Two millilitres of each of the two test solutions was given to each subject, in duplicate, via a nebuliser driven by a Bird Mark 8 respirator. Ventilatory function (FEV1 and VC) was measured before and after each inhalation, and changes were expressed as percentage variations from baseline. Seven subjects, all from the asthmatic group, developed at least one immediate FEV1 fall of 20% or more. The reactions ranged up to 71% and occurred to both test solutions. There was a trend towards greater reactions to the vehicle. In two subjects pretreatment with salbutamol and sodium cromoglycate did not modify these reactions. In three of the seven, inhalation of 2 ml normal saline produced FEV1 falls of 25% to 30%, but these falls were not as great as each subject9s reactions to the test solutions. Skin prick tests using the gentamicin solution were negative in all subjects. These results show that substantial obstructive reactions may occur in some asthmatic subjects after inhalation of gentamicin. The reactions appear to be non-immunological in nature and may be due to an irritant effect of the drug vehicle.
Protoporphyrin hepatopathy. Effects of cholic acid ingestion in murine griseofulvin-induced protoporphyria.
Authors: M B Poh-Fitzpatrick, J A Sklar, C Goldsman, J H Lefkowitch
Journal: Journal of Clinical Investigation (1983)

Short-term effects of cholic acid ingestion on hepatic accumulation, fecal excretion, and blood levels of protoporphyrin were studied in vivo in griseofulvin-induced protoporphyric mice. Experimental mice that received feed with 2% griseofulvin and 0.5% cholic acid were compared with control mice that received feed with 2% griseofulvin for 4 wk. Five mice from each group were assessed each week for liver and blood porphyrin levels. Fecal protoporphyrin was compared weekly in the total pooled output of each population. Mean protoporphyrin levels were significantly lower for liver (P less than 0.0001), erythrocytes (P less than 0.05), and plasma (P less than 0.05), and higher for feces (P less than 0.001) for the mice that were fed cholic acid. Microscopic protoporphyrin deposits, inflammation, necrosis, and dysplasia were more severe in livers of control mice. A second experimental design compared four regimens in the feed given to all mice after 1-wk induction with 2% griseofulvin: (a) 0.5% cholic acid, (b) no adulterant, (c) 2% griseofulvin and 0.5% cholic acid, and (d) 2% griseofulvin. No difference in protoporphyrin removal from livers of mice in groups 1 and 2 was observed after 1 and 2 wk of these regimens. The apparent reduction in hepatic protoporphyrin content in mice of group 3 as compared with group 4 at weeks 2 and 3 was not significant at P less than 0.05. These data suggest that in selected circumstances, hepatic protoporphyrin secretion may be enhanced in protoporphyric disease states by bile salt supplementation.
Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer
Authors: Mary-Clare Cathcart, Kathy Gately, Robert Cummins, Elaine Kay, Kenneth J O'Byrne, Graham P Pidgeon
Journal: Molecular Cancer (2011)

Abstract Background Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro , providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease. Methods TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB 2 ) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression. Results TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB 2 levels were increased in protein ( p &lt; 0.05) and plasma ( p &lt; 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma ( p &lt; 0.001) and female patients ( p &lt; 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis. Conclusion TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.
Early effect of screening programmes on incidence and mortality rates of colorectal cancer
Authors: Manuel Zorzi, Ugo Fedeli
Journal: Gut (2014)

We thank Logan and Halloran for their interest in our study1 and admit that we were equally surprised at the early impact of screening programmes on colorectal cancer mortality rates.2 

With respect to incidence trends, rates peaked during the prevalence round and showed a sharp reduction below the prescreening values within 5 years of screening set-up.2 These results are in line with the few evidences in the literature that evaluated the effect of population screening programmes based on the faecal occult …
Opposing Functions of the T Cell Receptor Kinase ZAP-70 in Immunity and Tolerance Differentially Titrate in Response to Nucleotide Substitutions
Authors: Owen M. Siggs, Lisa A. Miosge, Adèle L. Yates, Edyta M. Kucharska, Daniel Sheahan, Tomas Brdicka, Arthur Weiss, Adrian Liston, Christopher C. Goodnow
Journal: Immunity (2007)
Composition of Human Thrombus Assessed by Quantitative Colorimetric Angioscopic Analysis
Authors: Kenneth G. Lehmann, Robert J. van Suylen, Jeane Stibbe, Cornelis J. Slager, Jan A. Oomen, Arthur Maas, Carlo di Mario, Pim deFeyter, Patrick W. Serruys
Journal: Circulation (1997)

Angioscopy surpasses other diagnostic tools, such as angiography and intravascular ultrasound, in detecting arterial thrombus. This capability arises in part from the unique ability of angioscopy to assess true color during imaging. In practice, hardware-induced chromatic distortions and the subjectivity of human color perception substantially limit the theoretic potential of angioscopic color. We used a novel application of tristimulus colorimetry to quantify thrombus color to both aid in its detection and assess its composition.A series of human thrombus models were constructed in vitro. Spatial homogeneity was ensured by light and electron microscopy. Quantitative colorimetric angioscopic analysis demonstrated excellent measurement reproducibility (mean difference, 0.07% to 0.17%), unaffected by illuminating light intensity (coefficient of variation, 0.21% to 3.67%). Colorimetric parameters C1 and C2 were strongly correlated (r=.99, P<.0001) with thrombus erythrocyte concentration. Principal components analysis transformed these parameters into a single value, the thrombus erythrocyte index, with little (0.06%) loss of content. Measured and predicted concentrations were similar (mean difference, 0.16 erythrocytes per 1 ng). Randomly ordered images were also subjected to visual analysis by three experienced angioscopists, with suboptimal levels of both intraobserver (mean kappa=0.63) and interobserver (mean kappa=0.48) agreement. In addition, visual ranking resulted in a Kendall rank coefficient of 0.72 to 0.76 versus a perfect 1.00 from quantitative measurement.Quantitative colorimetric angioscopic analysis provides a new, objective, and reproducible analytic tool for assessing angioscopic images of human thrombus. Even under ideal circumstances, experienced angioscopists do a poor job of assessing color (and therefore composition) of human thrombi. This technique can, for the first time, provide quantitative information of thrombus composition during routine diagnostic imaging.
Developing Nations Face Challenges as Breast Cancer Rises
Authors: V. Brower
Journal: JNCI Journal of the National Cancer Institute (2011)

Patients suspected of having breast cancer at a public clinic in Mexico City returned an average of seven times before receiving a definitive diagnosis; those diagnosed waited more than 6 months on average for treatment. In eastern Nigeria, 30% of women with symptoms of breast cancer refused biopsies, and more than half declined surgery when their
The effects of respiratory infections, atopy, and breastfeeding on childhood asthma
Authors: W.H. Oddy, N.H. de Klerk, P.D. Sly, P.G. Holt
Journal: European Respiratory Journal (2002)

The objectives of the present study were to quantify the association of atopy and respiratory infections with asthma, and exclusive breastfeeding with respiratory illness, atopy and asthma in children. A cohort study of 2,602 children enrolled prior to birth and followed prospectively, provided data on respiratory illness, the method of feeding in the first year of life, as reported on a prospective diary card, and current asthma at the age of 6 yrs (defined as doctor-diagnosed asthma with wheeze in the last year or cough without a cold, and currently taking either preventer or reliever asthma medication), as reported by parental questionnaire. Atopy was defined by a positive skin-prick test assessed at the age of 6 yrs. Wheezing lower respiratory illness (LRI) in the first year of life, particularly multiple episodes of wheezing LRI, increased the risk for current asthma in both nonatopic (odds ratio (OR) 4.10, p⪕0.0005) and atopic children (OR 9.00, p⪕0.0005), but did not increase the risk for atopy. In contrast, up to three upper respiratory tract infections demonstrated a negative association and four or more a positive risk for current asthma in unadjusted (p=0.006) and adjusted (p=0.057) analysis. Following adjustment, exclusive breastfeeding for &lt;4 months was associated with an increased risk for current asthma (OR 1.36, 95% confidence interval 1.00–1.85, p=0.047). Wheezing lower respiratory illness in the first year of life and atopy are independently associated with increased risk for current asthma at the age of 6 yrs, suggesting that their effects are mediated via different causal pathways and that these risk factors are multiplicative when they operate concomitantly within individual children. Exclusive breastfeeding protects against asthma via effects on both these pathways, as well as through other as yet undefined mechanisms.
Response criteria for NHL: Importance of ‘normal’ lymph node size and correlations with response rates
Authors: A.J. Grillo-López, B.D. Cheson, S.J. Horning, B.A. Peterson, W.D. Carter, C.L. Varns, D.L. Klippenstein, C.D. Shen
Journal: Annals of Oncology (2000)
Brahma-related gene 1 (Brg1) epigenetically regulates CAM activation during hypoxic pulmonary hypertension
Authors: Dewei Chen, Fei Fang, Yuyu Yang, Jian Chen, Gang Xu, Yong Xu, Yuqi Gao
Journal: Cardiovascular Research (2013)

Establishment of an inflammatory milieu following elevated leukocyte adhesion to the vascular endothelium, which is mediated by transcriptional activation of cell adhesion molecules (CAMs), contributes to the pathogenesis of chronic hypoxia-induced pulmonary hypertension (HPH). The epigenetic switch that dictates CAM transactivation in response to hypoxia in endothelial cells leading up to HPH is not fully appreciated. We report here that brahma-related gene 1 (Brg1) and brahma (Brm), two catalytic components of the mammalian chromatin remodelling complex, were induced in cultured endothelial cells challenged with hypoxia in vitro as well as in pulmonary arteries in an animal model of HPH. Over-expression of Brg1/Brm enhanced, while the depletion of Brg1/Brm attenuated, CAM transactivation and adhesion of leukocytes. Endothelial-specific deletion of Brg1/Brm ameliorated vascular inflammation and HPH in mice. Chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that hypoxia up-regulated the occupancies of Brg1 and Brm on CAM promoters in a nuclear factor κB (NF-κB) -dependent manner. Finally, Brg1 and Brm activated CAM transcription by altering the chromatin structure surrounding the CAM promoters. Our data suggest that Brg1 provides the crucial epigenetic link to hypoxia-induced CAM induction and leukocyte adhesion that engenders endothelial malfunction and pathogenesis of HPH. As such, targeting Brg1 in endothelial cells may yield promising strategies in the intervention and/or prevention of HPH.
The Brussels' experience of more than 5 years of clinical preimplantation genetic diagnosis
Authors: M. Vandervorst
Journal: Human Reproduction Update (2000)

This paper describes the 5 years' experience of preimplantation genetic diagnosis (PGD) at the Brussels Free University. Our first PGD was carried out in February 1993. Up to October 1998, we carried out 183 PGD cycles on fresh cleavage embryos of 92 couples for 25 different conditions. Patients were treated for autosomal recessive (n = 39), autosomal dominant (n = 65) and X-linked recessive (n = 47) monogenic disorders as well as for autosomal structural aberrations (n =10), sex chromosome numerical and structural aberrations (n = 21) and a combination of the two latter (n = 1). Specific diagnosis was carried out by polymerase chain reaction (n = 108). Fluorescence in-situ hybridization was used for sexing (n = 64) and structural aberrations (n = 11). We transferred 1.6 ± 1.1 embryos per cycle, resulting in an implantation rate of 12.0% per replaced embryo. Ongoing pregnancies were achieved in 29 cycles, i.e. 23 singletons, five twins and one dichorionic triplet with an acardius acranius. The ongoing pregnancy rates per cycle, per transfer and per couple were 16.4, 19.9 and 31.5% respectively. While 28 ongoing pregnancies resulted in the births of 34 infants, one pregnancy was terminated after misdiagnosis. The results of 24 PGD were confirmed by prenatal diagnosis or after birth while no information was available in four pregnancies. Our series demonstrates that PGD is a feasible technique by which to avoid the birth of genetically affected children to couples at risk.
Induced First-Trimester Abortion and Risk of Mental Disorder
Authors: Trine Munk-Olsen, Thomas Munk Laursen, Carsten B Pedersen, Øjvind Lidegaard, Preben Bo Mortensen
Journal: New England Journal of Medicine (2011)

Concern has been expressed about potential harm to women's mental health in association with having an induced abortion, but it remains unclear whether induced abortion is associated with an increased risk of subsequent psychiatric problems.We conducted a population-based cohort study that involved linking information from the Danish Civil Registration system to the Danish Psychiatric Central Register and the Danish National Register of Patients. The information consisted of data for girls and women with no record of mental disorders during the 1995-2007 period who had a first-trimester induced abortion or a first childbirth during that period. We estimated the rates of first-time psychiatric contact (an inpatient admission or outpatient visit) for any type of mental disorder within the 12 months after the abortion or childbirth as compared with the 9-month period preceding the event.The incidence rates of first psychiatric contact per 1000 person-years among girls and women who had a first abortion were 14.6 (95% confidence interval [CI], 13.7 to 15.6) before abortion and 15.2 (95% CI, 14.4 to 16.1) after abortion. The corresponding rates among girls and women who had a first childbirth were 3.9 (95% CI, 3.7 to 4.2) before delivery and 6.7 (95% CI, 6.4 to 7.0) post partum. The relative risk of a psychiatric contact did not differ significantly after abortion as compared with before abortion (P = 0.19) but did increase after childbirth as compared with before childbirth (P < 0.001).The finding that the incidence rate of psychiatric contact was similar before and after a first-trimester abortion does not support the hypothesis that there is an increased risk of mental disorders after a first-trimester induced abortion.
ZINC DERMATITIS: AN ADDITIONAL HAZARD IN THE AIRCRAFT INDUSTRY
Authors: Hal E. Freeman
Journal: JAMA (1942)

The salts of zinc, such as zinc chloride, are widely used in welding in large plane manufacturing, and reactions to these compounds have been reported. 1 However, no recorded instance of reaction to zinc has been found, and I have no previous knowledge of such allergic reaction.  Kirksite 2 is an alloy which is used in the foundry in the preliminary stages of die making. It is composed principally of zinc with a small admixture of aluminum and copper and a lesser amount of magnesium.  At this time of national emergency it seems desirable to record the following case, although it is readily acknowledged that such cases will be rarely encountered:  REPORT OF CASE  K. W. W., a man aged 33, was referred for dermatologic consultation by Dr. M. L. Loomis, of the Long Beach medical division of the Douglas Aircraft Company, Inc. The patient was of English descent. His
Further Studies of a Natriuretic Substance Occurring in Human Urine and Plasma
Authors: J. E. SEALEY, J. H. LARAGH
Journal: Circulation Research (1971)

Studies are presented which provide additional physiological and biochemical characterization of a natriuretic agent which has been identified in extracts of plasma and urine of human subjects. The natriuretic activity of active fractions was consistently demonstrable in normal hydropenic rats as well as in rats with congenital diabetes insipidus. The induced natriuresis usually developed slowly and could last for several hours. The natriuresis was not usually associated with increases in water or potassium excretion. It occurred without measurable changes in glomerular filtration rate or arterial blood pressure. Altogether, these results suggest that the substance acts to depress sodium reabsorption in the distal tubule.  In bioassays of similarly prepared fractions utilizing direct perfusion of the renal artery, an immediate and transient natriuresis has been consistently observed. This immediate response appears to be produced by a substance different from that responsible for the delayed and more prolonged natriuresis, because the immediate response was always associated with a rise in blood pressure in the assay animal. Also, the activity of the agent responsible for the immediate natriuresis did not fluctuate with changes in sodium balance in the experimental subjects. Contamination with this substance may explain the occasional immediate response observed in earlier assays. This experience points to the importance of monitoring blood pressure during assays for natriuretic agents.  Additional fractionation studies continue to suggest that the substance occurring in salt-loaded human subjects which causes the more delayed and prolonged natriuresis in assay animals appears to be of a molecular weight of from 10,000 to 50,000.
Endotoxin protein: a B-cell mitogen and polyclonal activator of C3H/HeJ lymphocytes.
Authors: B M Sultzer, G W Goodman
Journal: The Journal of Experimental Medicine (1976)

A cell wall protein that is ordinarily complexed to the lipopolysaccharide endotoxin in gram-negative bacteria has been separated by the use of aqueous phenol. The protein is active as a B-cell mitogen and polyclonal activator of murine lymphocytes including the C3H/HeJ strain which is a nonresponder to lipoplysaccharide or lipid A.