tbuckley/cabot-search huggingface dataset:
Absorption and distribution of xenobiotics.
Authors: F G Standaert
Journal: Environmental Health Perspectives (1988)

Extrapolation of pharmacokinetic data between species has been simplified by the advent of more sensitive methods of analysis of chemicals in body tissues and by the capability of inexpensive computers to perform complex calculations. These new methods enable investigators to observe the rates at which target tissues reach equilibrium in different species and to develop mathematical models of these processes. The evaluation of physiological pharmacokinetics from classical or compartmental kinetics is improving the ability to project the long-term behavior of chemicals in body fluids and organs based on independently derived physical, chemical, and physiological constants obtained from simple chemical reactions, tissue culture experiments, or short-term animal studies. Accurate prediction of chemical behavior by such models gives support to hypothetical mechanisms of distribution and accumulation, while significant deviations from predicted behavior signal the existence of previously unsuspected pathways. These techniques permit the simulation of the impact of linear, nonlinear, and saturation kinetics on chemical behavior; the prediction of integrated tissue exposure; and the mapping of the sequence of alternate metabolic pathways that lead to toxicity or detoxification. The discussion will identify the research needs for improving extrapolations between species.
Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: an efficacy assessment
Authors: Kathleen M Daddario-DiCaprio, Thomas W Geisbert, Ute Ströher, Joan B Geisbert, Allen Grolla, Elizabeth A Fritz, Lisa Fernando, Elliott Kagan, Peter B Jahrling, Lisa E Hensley, Steven M Jones, Heinz Feldmann
Journal: The Lancet (2006)
Effects of Cytostatic Drugs and 40.5°C Hyperthermia on Human Bone Marrow Progenitors (CFU-C) and Human Clonogenic Tumor Cells Implanted Into Mice<xref ref-type="fn" rid="FN2">2</xref>
Authors: H A Neumann, H H Fiebig, G W Löhr, R Engelhardt
Journal: JNCI Journal of the National Cancer Institute (1985)

Human spontaneous tumors after surgical resection were implanted into NMRI nude mice. Clonogenic cells from these tumors (4 malignant melanomas, 2 squamous cell carcinomas of the lung, and 1 small cell carcinoma of the lung) were cultured in a methylcellulose monolayer assay. Dose-response curves with 7 cytostatic drugs (doxorubicin, bleomycin, dactinomycin, cisplatin, vincristine, vinblastine, and melphalan) were assessed at 37°C and after a 2-hour pulse at 40.5°C. In addition, bone marrow cells (CFU-C) were plated in the same assay. Dose-response curves were assessed with the same drugs under the same conditions. Hyperthermic treatment without drugs did not alter the colony formation of tumor and bone marrow cells. Bone marrow samples from different donors showed homogeneous response patterns; the tumor probes revealed sensitivity patterns typical for each tumor. In 13 of 48 tumor-drug combinations a thermal enhancement of the drug effects was observed, whereas there was no significant difference between normothermic and hyperthermic cultures in the bone marrow cultures. A comparison of colony and bone marrow dose-response curves suggested that a hyperthermic enhancement can occur in single cases. However, this phenomenon seems to be due to individual properties of the tumor.
Hemodynamic response during lower body negative pressure
Authors: G Ligtenberg, P J Blankestijn, H A Koomans
Journal: Journal of the American Society of Nephrology (1998)

Sudden dialysis-related hypotension is characterized by paradoxical vasodilation, suggestive of sympathoinhibition. A similar hypotensive reaction can be evoked by lower body negative pressure (LBNP), which thus allows the study of the numerous factors involved in dialysis hypotension separately. This article examines the influence of changes in volume status on the hemodynamic response to LBNP (45 mmHg up to the iliac crest, maximum 60 min) in 12 healthy subjects. LBNP caused a decrease in cardiac index and pulse pressure, and an increase in heart rate and total peripheral resistance, most of which developed within the first 3 min of LBNP. Six subjects developed sudden hypotension characterized by vasodilation after 9 +/- 4 min of LBNP. After saline expansion (25 ml/kg), which increased blood volume by approximately 8%, five subjects endured LBNP for the full 60 min. However, after 60 min of LBNP, the circulatory parameters suggested a similar critical situation as that observed before presyncope in their first experiment. The other six subjects endured the full 60 min of LBNP. After furosemide-induced volume reduction associated with 1.6 +/- 0.2 kg weight loss and approximately 7% blood volume reduction, five of them developed vasodilatory presyncope after 17 +/- 5 min of LBNP. Comparison of presyncopal and nonpresyncopal experiments within subjects, as well as between subjects, showed that the early (3 min) response to LBNP was different: Despite similar decreases in cardiac index, the values for systolic pressure, pulse pressure, peripheral resistance, and stroke volume were lower, and the heart rate was higher in the experiments ending in presyncope. It is concluded that the volume status is a determinant of the tolerance to LBNP, probably by affecting the vasoconstrictive response. By inference, this study suggests that the vasoconstrictive response to the hemodynamic stress of hemodialysis is also influenced by the volume status.
Diabetes Care in the U.S. and Canada
Authors: Gillian L. Booth, Bernard Zinman, Donald A. Redelmeier
Journal: Diabetes Care (2002)

OBJECTIVE—To compare the glycemic control of patients with type 1 diabetes treated in the U.S. and Canada. RESEARCH DESIGN AND METHODS—A large multicenter randomized clinical trial conducted in the U.S. and Canada was analyzed. Patients with type 1 diabetes, screened from 1983 to 1989 for enrollment in the Diabetes Control and Complications Trial (DCCT), were categorized as treated in the U.S. (n = 2,604) or Canada (n = 245). HbA1c levels were compared between U.S. and Canadian patients, both before and after adjustment for predictors of HbA1c. RESULTS—In general, volunteers screened for the DCCT were highly educated and following healthy lifestyles. Canadians were somewhat younger (25 vs. 27 years of age, P = 0.002), less likely to be college educated (62 vs. 71%, P = 0.002), more likely to receive care through a family doctor (41 vs. 28%, P = 0.001), and had a higher frequency of out-patient visits (4 vs. 3 per year, P = 0.004). Despite these differences in health care delivery, the mean HbA1c at baseline was identical in the two countries (8.9 vs. 9.0, P = 0.40). Adjustment for demographic, lifestyle, and clinical predictors of HbA1c yielded similar findings (9.0 vs. 9.2, P = 0.15). Equal percentages of American and Canadian patients who were screened ultimately entered the trial (21 vs. 19%, P = 0.20), and those randomized to conventional care achieved similar mean HbA1c levels (9.1 vs. 9.2, P = 0.50). CONCLUSIONS—Differences in care delivery patterns do not yield large differences in glycemic control for patients with type 1 diabetes who were recruited in the U.S. and Canada for a large randomized trial.
HEMOLYTIC ACTION OF A STAPHYLOCOCCUS DUE TO A FAT-SPLITTING ENZYME
Authors: Marion L. Orcutt, Paul E. Howe
Journal: The Journal of Experimental Medicine (1922)

A staphylococcus was isolated from milk which is hemolytic with horse blood only in the presence of fat. Similar results were obtained with two other strains of staphylococci. The hemolysis is the result of the action of a fatty acid (or soap) upon the red blood cells. The fatty acid is formed by the action of a lipase elaborated by the staphylococcus. The corpuscles of different animals show slight variations in the ease with which they are hemolyzed by the staphylococcus. Attention is called to the desirability of testing for lipases in the study of staphylococci or of hemolysis.
Depression and unintended pregnancy in the National Longitudinal Survey of Youth: a cohort study
Authors: D. C Reardon
Journal: BMJ (2002)

Psychological maladjustments after abortion are significantly associated with a history of depression.1 It has been suggested that prior psychological state is equally predictive of subsequent depression among women with unintended pregnancies regardless of whether they abort or carry to term.1 To examine this hypothesis we examined the National Longitudinal Study of Youth begun in 1979 with a nationwide cohort of 12 686 American youths aged 14-21.

The outcome variable of interest, depression, was assessed in 1992 for a subset of 4463 women using the Center for Epidemiological Studies depression (CES-D) scale scored by professional interviewers. This 20 item scale has good test-retest reliability among diverse population subgroups. In 1992 women were also asked whether their first delivered pregnancy had been the result of an intended pregnancy. Women who responded “yes” or “didn't …
Can immunoglobulin C(H)1 constant region domain modulate antigen binding affinity of antibodies?
Authors: O Pritsch, G Hudry-Clergeon, M Buckle, Y Petillot, J P Bouvet, J Gagnon, G Dighiero
Journal: Journal of Clinical Investigation (1996)

Although the switch process is frequently associated with affinity maturation, the constant region is not assumed to play a role in Ag-Ab binding. In the present work, we demonstrate that two clonally related human monoclonal Igs sharing identical V(H) and V(L) sequences, but expressing different isotypes (IgA1kappa(PER) and IgG1kappa(PER)), bind tubulin with significantly different affinities. This difference was mainly accounted for by a disparity in the association rate constants. These results suggest that affinity maturation of this clone could be achieved through class switching in the absence of further somatic mutations. Since the differences observed were found at the Fab level, they also suggest a role for the C(H)1 domain in structuring the Ag-binding site into a more kinetically competent form.
Passive Smoke Effects on Cough and Airways in Young Guinea Pigs
Authors: Jesse P. Joad, Paul A. Munch, John M. Bric, Samuel J. Evans, Kent E. Pinkerton, Chao-Yin Chen, Ann C. Bonham
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Children raised with extended exposure to environmental tobacco smoke (ETS) experience increased cough and wheeze. This study was designed to determine whether extended ETS exposure enhances citric acid–induced cough and bronchoconstriction in young guinea pigs via a neurokinin-1 (NK-1) receptor mechanism at the first central synapse of lung afferent neurons, the nucleus tractus solitarius. Guinea pigs were exposed to ETS from 1 to 6 weeks of age. At 5 weeks of age, guide cannulae were implanted bilaterally in the medial nucleus tractus solitarius at a site that produced apnea in response to the glutamate agonist D,L-homocysteic acid. At 6 weeks of age, either vehicle or a NK-1 receptor antagonist, SR 140333, was injected into the nucleus tractus solitarius of the conscious guinea pigs who were then exposed to citric acid aerosol. ETS exposure significantly enhanced citric acid–induced cough by 56% and maximal Penh (a measure of airway obstruction) by 43%, effects that were attenuated by the NK-1 receptor antagonist in the nucleus tractus solitarius. We conclude that in young guinea pigs extended exposure to ETS increases citric acid–induced cough and bronchoconstriction in part by an NK-1 receptor mechanism in the nucleus tractus solitarius.
Suppressor T Cells in Human Diseases
Authors: Clare Baecher-Allan, David A. Hafler
Journal: The Journal of Experimental Medicine (2004)

Although central and peripheral tolerance are important for the regulation of human immune responses to self- and microbial antigens, an important role of suppressor CD4(+) CD25(+) T cells is suggested from the recent investigations of human autoimmune diseases and HIV. These new data provide increasing evidence that altered function of CD4(+) CD25(+) T cells may be an important factor in a wide range of human inflammatory and infectious diseases.
When acquired thrombophilia mattered
Authors: J S Hammond
Journal: Gut (2005)

Management of acute pancreatitisNo account of the complications of acute pancreatitis (Gut 2005;54:426-36) would be complete without mention of diabetic ketoacidosis as an association, which is either fortuitous or one which exists as a complication in its own right.Recognition of this association has been inhibited by the complicated relationship between diabetic ketoacidosis, acute abdominal pain, and hyperamylassaemia, notwithstanding the
Heavy chain variable region. Multiple gene segments encode anti-4-(hydroxy-3-nitro-phenyl)acetyl idiotypic antibodies.
Authors: M E Boersch-Supan, S Agarwal, M E White-Scharf, T Imanishi-Kari
Journal: The Journal of Experimental Medicine (1985)

The hapten (4-hydroxy-3-nitrophenyl)acetyl (NP), when conjugated to carrier proteins, elicits a characteristic idiotypic response (NPb) in C57BL/6 mice. The response can be divided serologically into two distinct NPb-positive groups of antibodies. The first group consists of four crossreacting subgroups (I-IV), the second of two subgroups (V, VI). Some antibodies of subgroups I and II have been shown to express the unmutated heavy chain variable region (VH) germline gene 186.2. Antibodies of subgroups V and VI crossreact extensively with the NPa-positive antibodies of BALB/c mice. We sequenced heavy chain complementary DNA from eight hybridomas producing anti-NP antibodies. Six of these belong to subgroups V and VI, and two were NPa-positive hybridomas of BALB/c origin. All sequences were homologous to each other, and differed by approximately 80 basepairs from the 186.2 C57BL/6 germline VH gene. From our sequence and Southern blot analyses we suggest: (a) the NPb idiotypic response is the product of several VH germline genes, (b) some of these genes are very homologous to the gene coding for the BALB/c NPa idiotype, and might represent the C57BL/6 allelic forms of this gene, (c) the diversity regions of NPb and NPa-positive antibodies are diverse in length and amino acid composition, except for the first residue, which is always tyrosine, (d) all four heavy chain joining region gene segments are expressed without mutation. We discuss our data in terms of diversity in the germline VH gene repertoire, as well as diversity created by gene segment-joining events and somatic mutation.
Quantitative Detection of p53 Mutations in Plasma DNA from Tobacco Smokers
Authors: Nobutoshi Hagiwara, Leah E. Mechanic, Glenwood E. Trivers, Helen L. Cawley, Masataka Taga, Elise D. Bowman, Kensuke Kumamoto, Peijun He, Mark Bernard, Saira Doja, Masao Miyashita, Takashi Tajiri, Koji Sasajima, Tsutomu Nomura, Hiroshi Makino, Ken Takahashi, S. Perwez Hussain, Curtis C. Harris
Journal: Cancer Research (2006)

Abstract In lung tumors, the p53 tumor suppressor gene is commonly mutated with a characteristic mutation spectrum. The amount of and alterations in plasma DNA, such as mutations in p53, were associated with several cancers. Few studies used quantitative methods of high sensitivity. Previously, we observed p53 mutations in the noncancerous tissue that differed from those in lung tumors using the highly sensitive p53 mutation load assay. Based on our observation of an increased p53 mutation load in nontumorous lung tissue in smokers, we hypothesized that plasma DNA may contain mutant p53 indicative of tobacco smoke exposure and will be an effective biomarker of lung cancer or smoking exposure. We modified the p53 mutation load assay to detect mutations at p53 codons 248 and 249, common mutations in lung cancer, in plasma DNA samples with a sensitivity of 1:5,000. The assay was applied to a set of lung cancer cases (n = 39), hospital controls (n = 21), and population controls (n = 20) from a larger study. Controls were selected to consist of equal numbers of both ever and never smokers. The p53 mutation load (mutated p53 copies per total number of p53 copies) was associated with smoking (P = 0.06), but not with lung cancer (P = 0.59). Most of the individuals with p53 mutations observed in plasma DNA were ever smokers and the p53 mutation load was higher in those who smoked for longer durations (P = 0.04). In summary, we were able to detect p53 mutations in plasma DNA from healthy individuals and our data suggest that p53 mutations in plasma DNA may be a marker of carcinogen exposure from tobacco smoke. (Cancer Res 2006; 66(16): 8309-17)
Genomics in Sudden Cardiac Death
Authors: Dan E. Arking, Sumeet S. Chugh, Aravinda Chakravarti, Peter M. Spooner
Journal: Circulation Research (2004)

Sudden cardiac death (SCD) remains a public health problem of major magnitude. Contrary to earlier expectations, and despite decreased overall cardiac mortality, SCD rates appear to be rising in concert with escalating global prevalence of coronary disease and heart failure, the two major conditions predisposing to SCD. With the exception of the implantable defibrillator, there are few effective approaches to SCD prevention and even fewer clues concerning patient phenotypes predisposed to life-threatening arrhythmias. Clinical variables such as ejection fraction predict mortality but are not sensitive enough to identify many high SCD risk patients. The predictive power of autonomic dysregulation and markers such as lipid levels, hypertension, diabetes, and smoking is quite low in subclinical heart disease, the population in which the majority of SCDs occur. This review addresses advances in genomic science applicable to the SCD public health problem in both rare and common forms of heart disease. These include novel bioinformatic approaches to both identify candidate genes/pathways and identify previously unknown functional genetic elements, as well as methods to comprehensively screen these elements. We also discuss the possibility of applying high-density genome-wide SNP analyses to examine genetic contributions to arrhythmia susceptibility in community-based, case-control studies of common forms of SCD. The development of novel strategies to identify contributors to susceptibility in common cardiac phenotypes is most likely to lead to new and relevant therapeutic targets for SCD.
Dominant missense mutations in ABCC9 cause Cantú syndrome
Authors: Magdalena Harakalova, Jeske J T van Harssel, Paulien A Terhal, Stef van Lieshout, Karen Duran, Ivo Renkens, David J Amor, Louise C Wilson, Edwin P Kirk, Claire L S Turner, Debbie Shears, Sixto Garcia-Minaur, Melissa M Lees, Alison Ross, Hanka Venselaar, Gert Vriend, Hiroki Takanari, Martin B Rook, Marcel A G van der Heyden, Folkert W Asselbergs, Hans M Breur, Marielle E Swinkels, Ingrid J Scurr, Sarah F Smithson, Nine V Knoers, Jasper J van der Smagt, Isaac J Nijman, Wigard P Kloosterman, Mieke M van Haelst, Gijs van Haaften, Edwin Cuppen
Journal: Nature Genetics (2012)
Myostatin
Authors: Jochen Springer, Volker Adams, Stefan D. Anker
Journal: Circulation (2010)

C achexia in chronic heart failure (HF) is a major clinical problem that is still underestimated for its impact on morbidity, mortality, and healthcare expenditures.The pathophysiology of cardiac cachexia is characterized by a catabolic/ anabolic imbalance.An important player in the development of muscle wasting and cachexia in HF may be myostatin.
Lung B cell-derived CXCL13 is critical for lymphoid follicle formation in chronic obstructive pulmonary disease
Authors: Eleni Litsiou, Maria Semitekolou, Ioannis Morianos, Aikaterini Tsoutsa, Panagiota Kara, Dimitra Rontogianni, Ion Belenis, Maria Konstantinou, Konstantinos Potaris, Georgina Xanthou, Spyros Zakynthinos, Maria Tsoumakidou
Journal: European Respiratory Journal (2012)

Lymphoid follicles (LFs) that have a similar organization to lymph nodes are found in small airways and alveoli in Chronic Obstructive Pulmonary Disease (COPD), but the mechanism of their development is unclear. During lymph node ontogeny lymphotoxin (LT)-expressing lymphoid-tissue inducer cells induce lymphokine production (mainly CXCL13) to LT-receptor-expressing stromal cells. Lymphokines attract haemopoietic cells leading to lymphoid organ development. We examined peripheral lung tissue from COPD patients with LFs (COPD-LF + ), without LFs (COPD-LF - ) and never-smokers. Lung CXCL13 was significantly increased in COPD-LF +  compared to COPD-LF -  and never-smokers and positively correlated to surface area of LFs. Immunostaining showed CXCL13 expression in B cell areas of LFs. Flow cytometry indicated that among lung cells, B cells have the highest expression for LT receptors. Ex-vivo, lipopolysaccharide (LPS) and a LT-receptor agonist induced CXCL13 production to whole lung cell cultures from COPD-LF + . The LPS induction of CXCL13 was decreased by neutralizing LT. Depletion of B cells from the cultures significantly decreased CXCL13 and LT. Isolated lung B cells showed high migration towards lung tissue homogenates from COPD-LF +  that was significantly decreased by CXCL13 neutralization. When isolated lung B cells were exposed to CXCL13, LT was significantly increased, indicating a positive feedback loop between LT and CXCL13. We propose that the initiating event to LF formation in CODP is B cell stimulation, leading to LT expression and CXCL13 production. CXCL13 positively feeds back LT, amplifying its levels and attracting more B cells that organize themselves into LFs.
Altered Biodistribution of Somatostatin Analogues After First Cycle of Peptide Receptor Radionuclide Therapy
Authors: Sofie Van Binnebeek, Christophe M. Deroose, Kristof Baete, Christelle Terwinghe, Bert Vanbilloen, Michel Koole, Karin Haustermans, Luc Mortelmans, Chris Verslype, Eric Van Cutsem, Alfons Verbruggen, Felix M. Mottaghy
Journal: Journal of Clinical Oncology (2011)
Impact of viral hepatitis on the outcome of patients after curative resection of hepato cellular carcinoma
Authors: R. C. Siriwardana, S. T. Fan, C. M. Lo, S. C. Chan
Journal: Gut (2011)

<h3>Introduction</h3> Hepatitis B (HBV) and C (HCV) viruses are closely linked with hepato cellular carcinoma (HCC). Virus induced tumour recurrence and hepatic parenchymal damage are major concerns after curative resection of HCC. <h3>Methods</h3> 781 Patients who underwent curative resection of HCC were divided in to three groups according their viral status (HBV=656, HCV=28, none hepatitis = 98). The baseline features and the survival of the groups were compared. Further they were divided according to background liver status as cirrhotics and none cirrhotics. In two groups HBV positive and negative patients were compared on the baseline features and survival. <h3>Results</h3> A higher number of HBV (56%, p&lt;0.001) and HCV (78%, p&lt;0.001) patients were cirrhotics and had poor liver function. None B/C patient9s median disease free survival (DFS) of 21.5 months and overall survival (OS) of 72 months was similar to DFS of 19 months and OS of 66 months (p=0.8 and 0.9 respectively) in HBV patients. HCV patients also had a similar DFS (26 months, p=0.7) and OS (66 months, p=0.64). When none cirrhotics (n=361) were taken separately, DFS in HBV positive cases was 18 months compared to 22 in others (p=0.68). On multivariate analysis HBV status was not affecting the OS (p=0.6) or DFS (p=0.6). In 393 cirrhotics, DFS was 18.5 months in HBV positive and 21.5 in none hepatitis patients (p=.0.5). The OS was 67.5 and 71 months in HBV and none hepatitis patients respectively (p=0.34). HBV status did not associate significantly with OS (p=0.3) or DFS (p=0.64). In 270 cirrhotic patients who developed recurrence, the treatment offered for recurrence or subsequent survival did not differ between HBV positive and negative patients. <h3>Conclusion</h3> Hepatitis B surface antigen positivity does not affect the recurrence, survival or the subsequent treatment of recurrence after curative resection of HCC.