bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic components of carcinogenesis
Authors: Schmandt R , Mills G B 
Published: January 2020

Abstract
Many of the genes encoding growth factors, growth factor receptors, enzymes, and other effector molecules that regulate normal cell growth are designated protooncogenes. Oncogenes, those genes associated with cellular transformation, differ from their protooncogenic progenitors by being mutated, overexpressed, or expressed at inappropriate times or locations in the cell. One of the activities of growth factors is to prime cells to undergo programmed cell death, which is characterized by a series of morphologic changes called apoptosis. In normal cells, specific mediators must be activated or suppressed to bypass programmed cell death. In tumor cells, either the pathways leading to apoptosis are not functional or the mediators that normally "rescue" cells from this fate are overexpressed or constitutively activated. In addition to the biochemical pathways that drive cell division, there are others that limit cell proliferation; these, designated tumor suppressors, anti-oncogenes, or recessive oncogenes, must be inactivated in normal cells to allow passage through the cell cycle and cell proliferation. In contrast to oncogenes, which are overexpressed or activated in tumors, tumor-suppressor genes are frequently inactivated in tumor cells, either by mutation or deletion. Thus, in normal cells a series of checks and balances must be overcome to allow initiation and continuation of cell division. In tumors, these processes are aberrant, resulting in increased rates of cell division, increases in the proportion of cells in the cell cycle, or increased survival of activated cells. Therefore, tumor cells frequently accumulate genomic alterations, which may result in the activation of a particular array of oncogenes, the inactivation of specific tumor-suppressor genes, and the bypassing of programmed cell death. Trials of antitumor agents that act by exploiting the overexpression of oncogenes in tumors and of the biochemical pathways by which they mediate cell proliferation are currently underway.
Screening for cancer: is it cost effective?
Authors: Schwartz M K 
Published: January 2020

Abstract
Screening is defined as the presumptive identification of unrecognized disease or defect by the application of tests, examinations, or other procedures that can be applied rapidly and carried out in the general population or in individuals at high risk. When considering immunochemical or biochemical cancer markers, it might be more appropriate to describe these tests as risk-factor monitors and introduce the concept of two interpretations of these tests: in asymptomatic populations as indicators of probability of cancer, and in patients with previously treated cancer as predictors of recurrence despite initial treatment described as "curative." The successes of screening with alpha-fetoprotein for hepatocellular carcinoma and with catechol metabolites in neuroblastoma are discussed. The major emphasis will be the possible use of CA 125 and prostate-specific antigen (PSA) in risk-factor assessment of ovarian cancer and prostate cancer, respectively. It is important to understand in what context a PSA value &gt; 10 micrograms/L indicates a 67% probability of cancer.
Circadian pharmacodynamics of anticancer therapies
Authors: Hrushesky W J 
Published: January 2020

Abstract
Circadian variation in drug metabolism and tissue sensitivity to drugs affects their activity and toxicity. A growing body of data suggests that therapy may be improved and toxicity reduced by administering antineoplastic agents at carefully selected times of the day. Here I briefly review molecular, cellular, and organismic time-keeping mechanisms as well as cytokinetic, pharmacokinetic, and pharmacodynamic data, which support the predictable and exploitable nonlinear dynamic relation between dose and effect that occurs each day.
Therapeutic drug monitoring in cancer management
Authors: Galpin A J , Evans W E 
Published: January 2020

Abstract
Several anticancer drugs display characteristics that make them suitable candidates for therapeutic drug monitoring (TDM), including substantial pharmacokinetic variability and a narrow therapeutic index. However, concentration-effect relationships (pharmacodynamics) of most antineoplastic agents have not been well defined, thus limiting the widespread clinical application of TDM for cancer chemotherapy. Strategic incorporation of pharmacokinetic studies during phase I-III clinical trials should facilitate the identification of concentration-effect relationships and the definition of clinically useful levels of treatment intensity. We review representative clinical studies that have defined pharmacodynamic relationships for methotrexate, teniposide, etoposide, carboplatin, and mercaptopurine. Given that TDM has impacted positively on the clinical use of many drugs belonging to other therapeutic classes, and that pharmacodynamic correlations have been identified in several recent studies of anticancer drugs, we consider implementation of TDM a rational strategy for optimizing the use of selected antineoplastics.
Serum phospholipases A2 in inflammatory diseases
Authors: Nevalainen T J 
Published: January 2020

Abstract
Phospholipase A2 (EC 3.1.1.4; PLA2) is detected in serum by determination of either the catalytic activity of the enzyme or the concentration of the enzyme protein by immunoassays. The most sensitive methods for determining PLA2 catalytic activity are radiometric assays, with a substrate of synthetic phospholipid (e.g., phosphatidylcholine or phosphatidylethanolamine) containing a 14C- or 3H-labeled fatty acid at the sn-2-position. Membranes of autoclaved Escherichia coli grown in the presence of radioactive oleic acid may also be used as a substrate. The released fatty acids are separated from the unreacted substrate and quantified by liquid scintillation counting. PLA2 catalytic activities are increased in serum in sepsis, acute pancreatitis, peritonitis, multiple injuries, rheumatoid arthritis, and other arthropathies. Immunoassays--radioimmunoassay, enzyme-linked immunosorbent assay, or time-resolved fluoroimmunoassay--are based on the use of either polyclonal or monoclonal antibodies to purified PLA2s. Specific assays have been developed for both pancreatic group I PLA2 (PLA2-I) and nonpancreatic group II PLA2 (PLA2-II). The cellular source of PLA2-I in serum is the pancreatic acinar cell. Increased serum PLA2-I values have been reported in acute pancreatitis, pancreatic cancer, and abdominal trauma. Increased PLA2-II values are found in conditions involving inflammation, e.g., sepsis, infections, acute pancreatitis, various forms of arthritis, cancer, complications of pregnancy, and postoperative states. Good correlations have been found in serum samples between the catalytic activity of PLA2 and the concentration of PLA2-II but not PLA2-I. PLA2-II may represent an acute-phase protein. The cellular source of the PLA2-II in serum is unknown; it is present in large amounts in cartilage and Paneth cells, prostatic gland cells, seminal fluid, lacrimal gland cells, and tears, but cannot be demonstrated by immunohistochemical or immunochemical methods in inflammatory cells.
Predicting behavior of an enzyme-linked immunoassay model by using commercially available neural network software
Authors: Vertosick F T , Rehn T 
Published: January 2020

Abstract
Setting up new immunoassays can be a laborious and expensive task. A relatively new form of multivariate analysis known as neural networks can be applied to this problem with potential savings in reagents and technician time. Neural network software programs for personal computers are now available. We applied one such software package (Brainmaker) to a model ELISA system for measuring human serum albumin. Random combinations of four variable ELISA conditions (antigen concentration, primary and secondary antibody titers, and time for chromagen development) were used to train a three-layered feed-forward network. The trained network was then used to predict measured absorbances as a function of the four input variables in separate cross-validation sets. The network adequately predicted the effect of the input variables on the absorbance produced. With use of such methods, optimal conditions for the linear dependence of absorbance on antigen concentration can be evaluated on the computer rather than in the laboratory, with subsequent savings of time and money.
Antibodies to casein kinase II in sera of patients with mixed connective tissue disease: evaluation with recombinant proteins
Authors: Wiemann C , Bodenbach L , Pyerin W 
Published: January 2020

Abstract
In this study we determined the prevalence of autoantibodies against casein kinase II (CKII) in patients positive for anti-70K marker antibodies, which is indicative of mixed connective tissue disease. An anti-CKII ELISA was established with the use of bacterially expressed recombinant CKII proteins. Eight out of 52 anti-70K-positive sera (15%) were positive for anti-CKII antibodies, which recognized preferentially the CKII alpha subunit. All control sera (n = 52) were anti-CKII negative. Thus, the occurrence of anti-CKII antibodies may be of value for differential diagnosis.
Optimal collection and storage conditions for catecholamine measurements in human plasma and urine
Authors: Boomsma F , Alberts G , van Eijk L , Man in 't Veld A J , Schalekamp M A 
Published: January 2020

Abstract
Improvements in methodologies for measuring concentrations of catecholamines (CA) have led to an increasing use of these compounds as markers in the screening of patients and in long-term clinical trials. Because of the associated logistical problems, we have investigated the unresolved question of optimal conditions for sample preparation and for storage of plasma and urine samples. Results show that blood should be centrifuged within 1 h after collection; the use of a refrigerated centrifuge is not necessary. Once plasma is prepared, CA are stable for 1 day at 20 degrees C, 2 days at 4 degrees C, 1 month at -20 degrees C (or 6 months with added glutathione), and up to 1 year at -70 degrees C. CA are stable at 4 degrees C for 1 month in unpreserved urine and for 4 months in urine preserved with EDTA and sodium metabisulfite. In acidified urine, CA were nearly unchanged after 1 year at 4 and -20 degrees C.
Europium(III) trisbipyridine cryptate label for time-resolved fluorescence detection of polymerase chain reaction products fixed on a solid support
Authors: Lopez E , Chypre C , Alpha B , Mathis G 
Published: January 2020

Abstract
We report a method for the nonradioactive detection of specific amplified target DNA, based on a new long-lived fluorescent label, europium(III) trisbipyridine cryptate [TBP-(Eu3+)]. After a polymerase chain reaction with a set of nested primers, microtiter affinity-collected hybrids were recognized by a TBP(Eu3+)-labeled antibody. The particular structure of the label containing the energy transfer units (bipyridine moieties) enables direct fluorescence measurement on the solid phase. Moreover, its stability and long lifetime contribute to the enhancement of the signal-to-noise ratio. The usefulness of this new label is illustrated by the detection of human papillomavirus type 16 DNA in clinical smears.
Coronary artery disease risk predicted by plasma concentrations of high-density lipoprotein cholesterol, apolipoprotein AI, apolipoprotein B, and lipoprotein(a) in a general Chinese population
Authors: Wu J H , Kao J T , Wen M S , Wu D 
Published: January 2020

Abstract
We measured lipid and lipoprotein concentrations in blood samples from control subjects and patients with coronary artery disease (CAD) in Taiwan. We found significant differences (P &lt; 0.01) in the concentrations of high-density lipoprotein cholesterol (HDLC), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)]. Concentrations of HDLC &lt; 350 mg/L, ApoAI &lt; 900 mg/L, ApoB &gt; 800 mg/L, and Lp(a) &gt; 200 mg/L occurred, respectively, 2.8, 5.2, 1.7, and 2.3 times more frequently in the patients than in the control group. If one considers HDLC at &lt; 350 mg/L, ApoAI at &lt; 900 mg/L, ApoB at &gt; 800 mg/L, and Lp(a) at &gt; 200 mg/L as separate risk factors for CAD, the ratio of individual patients to control subjects having 4, 3, 2, 1, or 0 risk factors was [symbol: see text] 9.4, 2.1, 0.2, 0.2, respectively. Individuals displaying three or more risk factors were found 15 times more frequently in the CAD group than in the control group. These risk factors may be used clinically for the prediction and prevention of CAD in the general population.
Hepatic and lipoprotein lipases selectively assayed in postheparin plasma
Authors: Henderson A D , Richmond W , Elkeles R S 
Published: January 2020

Abstract
Sensitive, reliable procedures are reported for the selective assay of lipoprotein lipase (LPL) and hepatic lipase (HL) in postheparin plasma samples. LPL is inhibited in the HL assay by inclusion of 0.76 mol/L sodium chloride in the substrate. In the LPL assay, specificity is attained by pretreating the sample with sodium dodecyl sulfate, which selectively denatures HL. This LPL method was validated by direct comparison with a procedure in which HL is inactivated by an antiserum to human HL. We used the described assays to quantify LPL and HL activity in 32 normal adults, demonstrating a clear sex difference for both enzymes. On average, the men displayed higher HL and lower LPL activities than did the women.
Transcriptional activation of the estrogen receptor
Authors: Wei L L 
Published: January 2020

Abstract
Almost all breast cancer tumors progress to a hormone-resistant state. Evidence is presented that the existence of mutant estrogen receptors may explain some hormone-resistant phenotypes. Breast tumor cells bearing a mutant receptor that is constitutively active and does not bind hormone would have unregulated cell growth and thus appear to be hormone-independent. Alternatively, breast cancer cells may contain estrogen receptors that are transcriptionally inactive but when co-expressed with wild-type receptors render normal estrogen receptors inactive. These cells would be considered estrogen receptor-positive but would be hormone-resistant. The hormone-resistant phenotype could be further complicated by the finding that other nonreceptor proteins may also modulate the transcriptional activity of estrogen receptors. These findings, if substantiated in vivo, could add to the complexity of the hormone-resistant phenotype. Different strategies of treatment will need to be developed to effectively treat the various subtypes of hormone-resistant breast tumors.
c-myc oncogene expression in estrogen-dependent and -independent breast cancer
Authors: Shiu R P , Watson P H , Dubik D 
Published: January 2020

Abstract
We demonstrate that c-myc gene expression is essential for growth of breast cancer cells. It also plays an important role in the progression of human breast cancer. c-myc gene amplification may be important for cancer cell invasion, but perhaps not essential for nodal metastasis. We also provide compelling evidence that the c-myc oncogene is an estrogen target gene in hormone-responsive breast cancer. Hormonal progression of breast cancer could be brought about by the enhanced expression of the c-myc gene, with gene amplification and enhanced c-myc mRNA stability being two major mechanisms involved.
Automated assay of methylmalonic acid in serum and urine by derivatization with 1-pyrenyldiazomethane, liquid chromatography, and fluorescence detection
Authors: Schneede J , Ueland P M 
Published: January 2020

Abstract
Determination of methylmalonic acid (MMA) in serum has been established as an accurate test for the diagnosis of cobalamin deficiency. We describe here the development and performance of a liquid-chromatographic assay of MMA in blood and urine. The assay is based on our recent finding that one of the carboxylic acid moieties of some short-chain dicarboxylic acids reacts with the fluorogenic reagent 1-pyrenyldiazomethane in an aqueous medium, whereas the other remains underivatized (Anal Chem 1992; 63:315-9). The pH-dependent ionization of the free carboxylic acid group of 1-pyrenylmethyl monoesters permits retention on anion-exchange columns, which are used for solid-phase extraction. The analysis is done with a cyanopropyl column coupled in series with an octadecyldimethylsilyl column. Solid-phase extraction and sample injection are carried out automatically by a Gilson ASPEC sample processor. The assay response varies linearly with MMA concentration in the range 0.1-1000 mumol/L in serum. The within-day and between-day CVs are 2.8-10.9%, and the detection limit of 5 fmol injected (approximately 20 nmol/L in serum) is sufficiently low to determine MMA in serum (mean 0.187 mumol/L, SD 0.084, range 0.044-0.431, n = 44) and urine from healthy subjects.
A theoretical evaluation of linearity
Authors: Kroll M H , Emancipator K 
Published: January 2020

Abstract
The measure of linearity is an important part of the evaluation of a method. According to the NCCLS guidelines (Document EP6-P), results of a linearity experiment are fit to a straight line and judged linear either by visual evaluation, which is subjective, or by the lack-of-fit test. This approach depends on the precision of the method, is not necessarily conclusive, and fails to be quantitative. We define linearity as a measure of how well a first-order (linear) polynomial fits the data compared with a higher-order (nonlinear) polynomial. The major property of a linear polynomial is that the first derivative is a constant. The nonlinearity of a method can be measured by the difference between these two polynomials (first-order and higher-order) at specific values or, as an average, the root-mean difference. This approach is independent of the precision of the assay and is conclusive, quantitative, and objective.
New insight into the comparative power of quality-control rules that use control observations within a single analytical run
Authors: Parvin C A 
Published: January 2020

Abstract
The error detection characteristics of quality-control (QC) rules that use control observations within a single analytical run are investigated. Unlike the evaluation of QC rules that span multiple analytical runs, most of the fundamental results regarding the performance of QC rules applied within a single analytical run can be obtained from statistical theory, without the need for simulation studies. The case of two control observations per run is investigated for ease of graphical display, but the conclusions can be extended to more than two control observations per run. Results are summarized in a graphical format that offers many interesting insights into the relations among the various QC rules. The graphs provide heuristic support to the theoretical conclusions that no QC rule is best under all error conditions, but the multirule that combines the mean rule and a within-run standard deviation rule offers an attractive compromise.
Simultaneous quantification of mannitol, 3-O-methyl glucose, and lactulose in urine by HPLC with pulsed electrochemical detection, for use in studies of intestinal permeability
Authors: Kynaston J A , Fleming S C , Laker M F , Pearson A D 
Published: January 2020

Abstract
The percentage of an oral dose of mannitol, 3-O-methyl glucose, and lactulose excreted in urine is used in noninvasive investigation of active and passive intestinal mucosal transport. We developed a high-pressure liquid-chromatographic method involving anion exchange and pulsed electrochemical detection that allows the simultaneous determination of all three sugar probes in urine. Sample preparation is simple: diluting, mixing with internal standard (melibiose), and desalting. With use of a Dionex 250 x 40 mm Carbopac PA-1 column and elution with an isocratic mixture of 120 mmol/L NaOH and 0.5 mmol/L zinc acetate, all sugars were resolved within 10 min. The standard curve of the method is linear to the following concentrations: mannitol 125 mg/L, 3-O-methyl glucose 300 mg/L, and lactulose 40 mg/L. The minimal detectable concentration of lactulose is 0.4 mg/L. Analytical recovery of the sugars is between 89.0% and 99.5%. The precision of estimation (CV) ranges from 1.76% to 5.6% overall. Reference intervals were established from results for 28 healthy children. The method is adaptable for the study of carbohydrates at low concentrations in other biological fluids.
Relation of lipoprotein(a) in 11- to 19-year-old adolescents to parental cardiovascular heart disease
Authors: Vella J C , Jover E 
Published: January 2020

Abstract
We studied several risk factors in relation to parental cardiovascular heart disease: total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I, apo B, and lipoprotein(a) [Lp(a)] were determined in 322 serum samples (43 from subjects with and 279 without parental cardiovascular heart disease). The distribution of Lp(a) concentrations in our young population was similar to that of other white populations, i.e., markedly skewed, with higher frequencies at low values. As compared with children whose parents did not report cardiovascular heart disease, those with affected parents had a higher mean Lp(a) (0.23 vs 0.18 g/L; P &lt; 0.05). Moreover, 42% of the children with parental cardiovascular heart disease, but only 19% of those with no parental cardiovascular heart disease, exhibited Lp(a) values &gt; 0.30 g/L. These results suggest not only that Lp(a) is an important risk factor for cardiovascular heart disease, but also that Lp(a) is more strongly related to the risk of cardiovascular heart disease than are HDL- and LDL-cholesterol and apo A-I and B.
Cocaine and benzoylecgonine in saliva, serum, and urine
Authors: Schramm W , Craig P A , Smith R H , Berger G E 
Published: January 2020

Abstract
We studied the feasibility of using saliva to detect cocaine and benzoylecgonine. Saliva was collected as an ultrafiltrate directly in the mouth with an osmotic device. We analyzed by immunoassay matched samples of urine, blood, and salivary ultrafiltrate from 69 patients who had used cocaine within 24 h of sample collection. Cocaine concentrations were 4.9 times higher in saliva than in serum; benzoylecgonine concentrations were 2.5 times higher in serum. Seven urine and two serum samples had undetectable concentrations of cocaine, but all 69 saliva samples were positive for the drug. For benzoylecgonine detection, all urine samples were positive and three serum and one saliva sample were negative. We also analyzed 43 samples of saliva by gas chromatography/mass spectrometry: all were positive for benzoylecgonine, whereas 40 were positive for cocaine. We conclude that simultaneous measurement of cocaine and benzoylecgonine in saliva is suitable in screening for recent cocaine use.
Testosterone concentration is increased in whole saliva, but not in ultrafiltrate, after toothbrushing
Authors: Schramm W , Smith R H , Craig P A , Grates H E 
Published: January 2020

Abstract
The concentration of testosterone in whole saliva is significantly increased (by 9%) after toothbrushing. In ultrafiltrates of saliva collected at the same time as the whole saliva, testosterone concentrations after toothbrushing were unchanged. In 88% of the 162 whole-saliva specimens, but not in the ultrafiltrates, we also measured higher hemoglobin concentrations after toothbrushing. We conclude that the increase of testosterone in whole saliva after toothbrushing can be attributed to a protein-bound fraction. For analytes that are bound to serum proteins, salivary measurements can give spurious results. This problem can be avoided by using as a diagnostic medium an ultrafiltrate of saliva collected directly in the mouth.