bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced detection of hematogenous circulating prostatic cells in patients with prostate adenocarcinoma by using nested reverse transcription polymerase chain reaction assay based on prostate-specific membrane antigen
Authors: Loric S , Dumas F , Eschwege P , Blanchet P , Benoit G , Jardin A , Lacour B 
Published: January 2020

Abstract
We report the development of a new sensitive nested reverse transcription-polymerase chain reaction (RT-PCR) assay, using primers derived from the prostate-specific membrane antigen (PSM) cDNA sequence, to detect an hematogenous spread of prostate adenocarcinoma cells. In 60 patients with a biopsy-proven prostate cancer, PSM and PSA RT-PCR detected circulating prostate cells in 40 and 20 patients, respectively. In pT4 M+ and pT3 M+ disease patients, nested PSM primers detected cells in 28 of 33 patients (85%), whereas nested PSA primers detected cells in 17 of 33 (51%). In patients with organ-confined cancer spread (pT2a and pT2b patients) before radical prostatectomy, nested PSM RT-PCR detected circulating prostatic epithelial cells in 6 of 17 patients (35%), which suggests that an hematogenous spread of prostate cells may occur early in prostate cancer history. Altogether, these results suggest that the detection of PSM-expressing cells in blood may predict the development of cancer in patients without clinically apparent prostate cancer. Nevertheless, the potential application and the clinical significance of detection of hematogenous prostate cells through the use of nested PSM primers need an extensive longitudinal study.
Automated assay of oxygen radical absorbance capacity with the COBAS FARA II
Authors: Cao G , Verdon C P , Wu A H , Wang H , Prior R L 
Published: January 2020

Abstract
Reactive oxygen species are of interest in biology and medicine because of evidence relating them to aging and disease processes. A relatively simple but sensitive and reliable method for quantifying the oxygen radical absorbance capacity (ORAC) of antioxidants in biological tissues has been automated for use with the COBAS FARA II centrifugal analyzer with a fluorescence-measuring attachment. In this assay, beta-phycoerythrin (beta-PE) is used as an indicator protein, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a peroxyl radical generator, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) as a calibrator for antioxidant activity. This assay is unique because the reaction goes to completion so that both inhibition time and inhibition degree are considered in quantifying ORAC (micromoles of Trolox equivalent per liter or per gram of tissue). This method can be used not only for serum but also other tissue and food samples and is suitable for application to a range of nutritional and clinical conditions.
Significance of individual sensitivity to chemicals: elucidation of host susceptibility by use of biomarkers in environmental health research
Authors: Cullen M R , Redlich C A 
Published: January 2020

Abstract
Biomarker research has become the predominant theme for study of human dose-host-response relations to environmental chemicals. Increasing interest has been focused on identifying markers for host susceptibility, with mixed results. Efforts to identify markers for host variability in carcinogenic risk, on the basis of theoretical knowledge of carcinogen metabolism, have been disappointing. New work in the area of acquired risk modifiers, such as nutritional status, is theoretically attractive, but results have been limited. Impressive achievements have been made in the area of immunological variability, which may elucidate the molecular basis of as well as provide practical biomarkers for several diseases. The problem of multiple chemical sensitivities, on the other hand, has proved refractory to biomarker research, reflecting inadequate knowledge of the mechanism and inappropriate application of biomarker methods.
Variability in DNA repair and individual susceptibility to genotoxins
Authors: Kyrtopoulos S A 
Published: January 2020

Abstract
DNA repair is an important mechanism of cellular protection from the effects of genotoxic chemicals. Although extensive evidence from studies in experimental systems indicates that variation in DNA repair can significantly influence susceptibility to genotoxins, corresponding studies in human populations are so far limited, mainly because of methodological difficulties. One system, using observations of the accumulation and repair of DNA damage in cancer patients treated with alkylating cytostatic drugs, has provided useful information for assessing the effects of interindividual variation in DNA repair activity on the induction of genotoxic effects in humans. The most detailed studies of this kind have been carried out on patients with cancer (i.e., Hodgkin disease, malignant melanoma) treated with the methylating cytostatic drugs procarbazine or dacarbazine; these studies have provided detailed information on dose-response relationships. They have also demonstrated the protective role of the repair enzyme O6-alkylguanine-DNA alkyltransferase against the accumulation of the premutagenic methylated DNA lesion O6-methylguanine in patients' DNA. Given the strong evidence that exposure of the general population to environmental methylating agents may be extensive, as indicated by the frequent discovery of methylated DNA adducts in human DNA, data on DNA damage and repair in alkylating drug-treated patients and their modulation by host factors may prove useful in efforts to assess the possible carcinogenic risks posed by exposure to environmental methylating agents.
Assessment of immunotoxic effects in humans
Authors: Descotes J , Nicolas B , Vial T 
Published: January 2020

Abstract
The immunotoxic effects of chemicals are varied and markedly different depending on the underlying pathogenesis, namely, direct immunotoxicity (including immunosuppression, immunodepression, and immunostimulation), hypersensitivity, and autoimmunity. A large number of immunological endpoints and functional assays have been proposed for use as biomarkers of immunotoxicity, but they often lack sensitivity or are poorly standardized, so that their relevance in assessing immunotoxic effects in humans is at best ill established. Examining sentinel immunopathological events in individuals with a defined history of chemical exposure is another approach, presumably more cost-effective at the present time. A multicenter collaboration is mandated, however, because these events are rare. We expect that progress in new technologies, e.g., molecular biology, will provide the sensitive and reliable biomarkers of immunotoxicity that are currently lacking.
Detection of prostatic cells in peripheral blood: correlation with serum concentrations of prostate-specific antigen
Authors: Jaakkola S , Vornanen T , Leinonen J , Rannikko S , Stenman U H 
Published: January 2020

Abstract
We have studied the expression of prostate-specific antigen (PSA) mRNA by reverse transcriptase-polymerase chain reaction in peripheral blood of 25 patients with cancer of the prostate (CAP), four with benign prostatic hyperplasia (BPH), two with renal stones, three with other types of cancer, and six healthy male and three female controls. Expression of mRNA specific for a certain tissue in peripheral blood is thought to indicate the presence of circulating cancer cells and metastatic spread of a tumor originating from this tissue. We detected PSA mRNA in 9 of 18 CAP patients with metastatic disease but in none of 7 patients without metastases. Negative results in patients with metastatic disease were associated with successful endocrine therapy and low concentrations of serum PSA, and the correlation between serum concentrations of PSA and the presence of PSA mRNA in peripheral blood was statistically significant. PSA mRNA was not found in patients with BPH, other types of cancer, or in healthy controls. Thus the occurrence of PSA mRNA in peripheral blood is associated with metastatic CAP.
Three assays for glycohemoglobin compared
Authors: Turpeinen U , Karjalainen U , Stenman U H 
Published: January 2020

Abstract
Using 123 specimens, we compared the concordance of three different methods for determining glycohemoglobin (GHb): the Diamat (Bio-Rad Laboratories), an automated analyzer measuring HbA1c by cation-exchange chromatography; an assay with the IMx analyzer (Abbott Laboratories), based on boronate affinity binding; and an HPLC method measuring HbA1c by cation-exchange chromatography on a PolyCAT A column (PolyLC Inc.). The Pearson's correlation coefficient between PolyCAT A and Diamat was 0.900 +/- 0.038 (mean +/- 2 SD) and between PolyCAT A and IMx, 0.857 +/- 0.042. However, up to twofold differences were seen in some samples. The proportion of GHb was consistently lower with the PolyCAT A method than with the other two assays, apparently because of better separation of HbA1c from nonglycated coeluting forms of Hb. The difference in glycation percentage between the PolyCAT A and Diamat methods is 2-3% over the whole concentration range. These results point to the limitations of Diamat as a reference method to be used to calibrate other methods for determining HbA1c. Further, a switch from one method to another is likely to cause considerable problems in the clinical follow-up of certain patients.
Two bone alkaline phosphatase assays compared with osteocalcin as a marker of bone formation in healthy elderly women
Authors: Bouman A A , Scheffer P G , Ooms M E , Lips P , Netelenbos C 
Published: January 2020

Abstract
Serum bone alkaline phosphatase (ALP; EC 3.1.3.1) was measured with a wheat germ agglutinin (WGA) precipitation assay and with a new IRMA in a group of healthy elderly women. Both assays were correlated with serum total ALP activity and with osteocalcin. The two bone ALP assays have comparable within- and between-run imprecisions (WGA assay within-run CVs 2.6-5.4% and between-run, 4.0-5.1%; IRMA within-run CV 5.0% and between-run, 3.2%). Comparison of the WGA precipitation assay (x) with the IRMA (y) demonstrated a correlation coefficient of 0.87 [Deming regression equation: y = (0.58 +/- 0.02)x - (4.62 +/- 0.45); n = 101; Sy/x = 1.26; P &lt; 0.001). Correlation studies with osteocalcin and total ALP showed correlation coefficients (all P &lt; 0.001) of 0.34 and 0.65, respectively, for the WGA precipitation assay and of 0.36 and 0.68, respectively, for the IRMA. We conclude that the two bone ALP assays have similar imprecision and that neither can be given preference over the other as a marker of bone turnover.
Prostate-specific antigen immunoreactivity in amniotic fluid
Authors: Yu H , Diamandis E P 
Published: January 2020

Abstract
We examined whether the 33-kDa serine protease prostate-specific antigen (PSA) is present in amniotic fluid and, if so, whether its concentration changes with gestational age. Analyzing 115 amniotic fluids with a highly sensitive immunofluorometric procedure, we found PSA in all the amniotic fluids examined and established that its concentration increases with increasing gestational age from 11 to 21 weeks, decreasing at delivery. PSA in amniotic fluid is present predominantly in the free (33 kDa) form; a minor fraction (&lt; 20%) is present bound to alpha 1-antichymotrypsin. No significant correlation was seen between PSA and alpha-fetoprotein (AFP) in amniotic fluid or maternal serum in samples with high AFP. Amniotic fluid PSA was also measurable by two different established methods for PSA. Pregnant women had higher concentrations of serum PSA than nonpregnant women. The highest PSA concentration in amniotic fluid was associated with a pregnancy that was complicated by the Rhesus incompatibility syndrome but the source of the PSA was not established. From recent literature reports, and the association of PSA with prostate and breast tumors, we think PSA may serve as a growth factor regulator in cancer and in normal fetal development during pregnancy.
Coenzyme Q: potentially useful index of bioenergetic and oxidative status of spermatozoa
Authors: Angelitti A G , Colacicco L , Callà C , Arizzi M , Lippa S 
Published: January 2020

Abstract
The concentration of coenzyme Q10 (CoQ10), a key intermediate of the mitochondrial respiratory chain, was determined in spermatozoa of 13 fertile subjects, 8 potentially fertile patients, and 12 infertile patients. CoQ10 concentrations were significantly higher (P &lt; 0.001) in infertile patients than in fertile and potentially fertile subjects. The difference between potentially fertile and fertile subjects was also significant (P &lt; 0.001). We propose that a decrease in consumption of CoQ10 in both infertile and potentially fertile populations is due to an autoregulatory mechanism of ATP production.
Changes in serum lipoprotein(a) and lipids during treatment of hyperthyroidism
Authors: Kung A W , Pang R W , Lauder I , Lam K S , Janus E D 
Published: January 2020

Abstract
Because of suggestions that thyroid hormones modulate serum lipoprotein(a) [Lp(a)] concentration, we evaluated prospectively the serial changes of serum Lp(a), measured as apolipoprotein(a) [apo(a)], and other lipoproteins in 40 subjects with hyperthyroidism treated with radioactive iodine (RAI) therapy. Hyperthyroid patients had lower (P &lt; 0.001) concentrations of apo(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apo B, but higher apo A-I concentrations compared with age-matched controls [geometric mean (range)]; apo(a) 81 (17-614) vs 187 (17-1808 IU/L): TC 4.07 +/- 0.8 vs 5.22 +/- 1.00 mmol/L (mean +/- SD); LDL-C 2.47 +/- 0.89 vs 3.40 +/- 0.88 mmol/L; HDL-C 1.05 +/- 0.33 vs 1.24 +/- 0.34 mmol/L; apo B 0.66 +/- 0.23 vs 1.13 +/- 0.34 g/L, and apo A-I 2.07 +/- 0.42 vs 1.46 +/- 0.28 g/L, respectively. Euthyroidism was associated with normalization of serum TC, LDL-C, and apo B within 1 month of treatment. However, apo(a) required 4 months to normalize, and HDL-C and apo A-I were still abnormal 6 months after RAI. Serum apo(a), TC, LDL-C, and apo B were negatively correlated with serum thyroxine (T4), free thyroxine index, and triiodothyronine (T3) and positively correlated with thyrotropin during the transitional period from hyperthyroidism to euthyroidism. Parallel changes of these lipoproteins and thyroid hormones were also observed after treatment of hyperthyroidism. In conclusion, thyroid hormones do modulate lipoproteins, particularly Lp(a). The delay in normalization of apo(a) but not LDL suggests an effect on apo(a) production rather than on LDL removal.
Lipoprotein(a) in childhood: relation with other atherosclerosis risk factors and family history of atherosclerosis
Authors: Bailleul S , Couderc R , Rossignol C , Fermanian J , Boutouchent F , Farnier M A , Etienne J 
Published: January 2020

Abstract
The relation between lipoprotein(a) [Lp(a)], apolipoprotein (apo) E phenotypes, cholesterol, triglycerides, apo A-I, apo B, and a family history of atherosclerosis or risk factors was studied in 2- and 4-year-old French Caucasian children (n = 499). Lp(a) concentrations were distributed in a typical skewed manner and were found to be an independent lipid variable. The distribution of apo E phenotypes did not differ by gender. Cholesterol and apo B were under apo E phenotype control; Lp(a) was not. A significant positive relation was found between Lp(a) concentrations and the number of parental risk factors. Children whose grandparents had a history of cardiovascular disease had Lp(a) concentrations shifted towards higher values. Measurement of Lp(a) in children may help to identify those at an increased risk of atherosclerotic disease, especially when their parents have at least two relevant risk factors.
Effect of the number of apolipoprotein(a) kringle 4 domains on immunochemical measurements of lipoprotein(a)
Authors: Marcovina S M , Albers J J , Gabel B , Koschinsky M L , Gaur V P 
Published: January 2020

Abstract
Lipoprotein(a) [Lp(a)] has been measured in numerous clinical and epidemiological studies by a variety of immunochemical methods. However, little, if any, consideration has been given to the confounding effect of the size heterogeneity of apolipoprotein(a) [apo(a)] on the measurement of Lp(a). We developed three direct-binding enzyme-linked immunosorbent assays (ELISAs) with detecting antibodies of different specificities to evaluate the effect of apo(a) size on Lp(a) measurement. The three assays used the same monoclonal antibody to capture the apo(a)-containing particles and were calibrated (in nanomoles per liter) with a serum containing apo(a) with 21 kringle 4 domains. Using all three ELISAs, we measured Lp(a) in a group of 723 subjects selected to have a single apo(a) band, as determined by a high-resolution phenotyping system. Essentially identical results were obtained by the two methods that measured Lp(a) by use of either a polyclonal antibody against apo B or a monoclonal antibody against apo(a) that does not recognize the kringle 4 type 2 repeats. In contrast, the ELISA using a monoclonal antibody specific for apo(a) kringle 4 type 2 repeats overestimated Lp(a) concentration in samples containing apo(a) with more than 21 kringle 4 domains and underestimated Lp(a) samples containing apo(a) with fewer than 21 kringle 4 domains. Thus, these differences in Lp(a) values varied as a function of apo(a) size. We conclude that antibody specificity and apo(a) size heterogeneity can significantly affect Lp(a) measurements.
Laboratory methods and quality assurance in the Cardiovascular Health Study
Authors: Cushman M , Cornell E S , Howard P R , Bovill E G , Tracy R P 
Published: January 2020

Abstract
The Cardiovascular Health Study is an observational cohort study of risk factors for cardiovascular disease in 5201 participants, ages &gt; or = 65 years. We report the methods and quality-assurance results for blood procurement, processing, shipping, storage, and sample analysis used during the first examination period (May 1989-June 1990). The most frequent difficulty in phlebotomy and processing was the requirement of more than one venipuncture (in 2.6% of the participants). The CVs for control materials ranged from 0.93% for glucose to 10.7% for insulin; most were &lt; 4%. In addition to standard quality-assurance methods, we applied two other methods: technical error calculation for replicates, and weighted linear regression to assess time trend in results of control materials. After outliers were excluded, technical error values ranged from 1.7 for uric acid to 18.8 for insulin. Factor VII and factor VIII had slight trends over the 12-month analysis period. Results of quality-assurance analyses used to resolve problems were successful, thereby improving the second laboratory examination.
1H NMR determination of urinary betaine in patients with premature vascular disease and mild homocysteinemia
Authors: Lundberg P , Dudman N P , Kuchel P W , Wilcken D E 
Published: January 2020

Abstract
Urinary N,N,N-trimethylglycine (betaine) and N,N-dimethylglycine (DMG) have been identified and quantified for clinical purposes by proton nuclear magnetic resonance (1H NMR) measurement in previous studies. We have assessed these procedures by using both one-dimensional (1-D) and 2-D NMR spectroscopy, together with pH titration of urinary extracts to help assign 1H NMR spectral peaks. The betaine calibration curve linearity was excellent (r = 0.997, P = 0.0001) over the concentration range 0.2-1.2 mmol/L, and CVs for replicate betaine analyses ranged from 7% (n = 10) at the lowest concentration to 1% (n = 9) at the highest. The detection limit for betaine was &lt; 15 mumol/L. Urinary DMG concentrations were substantially lower than those of betaine. Urinary betaine and DMG concentrations measured by 1H NMR spectroscopy from 13 patients with premature vascular disease and 17 normal controls provided clinically pertinent data. We conclude that 1H NMR provides unique advantages as a research tool for determination of urinary betaine and DMG concentrations.
Essential and toxic element concentrations in fresh and formalin-fixed human autopsy tissues
Authors: Bush V J , Moyer T P , Batts K P , Parisi J E 
Published: January 2020

Abstract
The concentrations of five essential elements and six potentially toxic elements were determined in seven organs collected at autopsy from 30 human subjects. Elemental analyses were carried out by graphite furnace atomic absorption spectroscopy, and inductively coupled plasma emission spectroscopy, and inductively coupled plasma mass spectroscopy, and concentrations in fresh and formalin-fixed tissues were compared. Formalin-fixation long-term storage has little effect on most element concentrations in tissue, except for Al and Mn, which changed with prolonged storage in formalin. The kidney and liver contained the greatest concentrations of toxic elements compared with other organs, whereas the essential elements were uniformly distributed among all organs. There was no more than a 10-fold difference in the tissue concentration of the elements studied among the organs, except for the concentration of Fe in liver, and Ca and Mg in bone. We also demonstrate that these elements are homogeneously distributed in tissues.
Pharmacodynamic assessment of mycophenolic acid-induced immunosuppression by measuring IMP dehydrogenase activity
Authors: Langman L J , LeGatt D F , Yatscoff R W 
Published: January 2020

Abstract
Pharmacodynamic monitoring of the biological effect of immunosuppressive drugs provides an alternative to traditional therapeutic drug monitoring. We chose this method to investigate mycophenolic acid (MPA), an immunosuppressive drug that mediates its effect by inhibition of IMP dehydrogenase (IMPDH), a key enzyme in the de novo biosynthesis of purines. Using an assay developed for measuring IMPDH activity in whole blood, we found the concentration of MPA required for 50% inhibition of enzyme activity to be in the range of 2.0-5.0 mg/L for both human and rabbit blood. The amount of enzyme activity in whole blood depended on the concentration of the leukocytes, was unaffected by the type of anticoagulant used, and was stable in blood specimens stored for as long as 48 h at 4 degrees C. An inverse relationship was found between plasma MPA concentrations and IMPDH activity in rabbits administered a single dose of RS-61443, the prodrug of MPA. Maximal inhibition of IMPDH activity (by approximately 60%) occurs at peak concentrations of MPA; as the concentration of the drug decreases postdose, the enzyme activity gradually increases with little or no inhibition being observed 24 h postdose.
Analytical artifacts in hematocrit measurements by whole-blood chemistry analyzers
Authors: Stott R A , Hortin G L , Wilhite T R , Miller S B , Smith C H , Landt M 
Published: January 2020

Abstract
Compact analyzers suited to near-patient testing estimate hematocrit by measuring the conductivity of undiluted blood. We evaluated the accuracy of hematocrit determination of one such analyzer (Instrumentation Laboratory BGE analyzer) against an automated cell counter (EPC) and packed cell volume (PCV) microhematocrit. When specimens (n = 34) from outpatient and ward patients were analyzed with all three methods, the BGE analyzer correlated well with both EPC and PCV hematocrit determinations (BGE = 1.00 PCV + 0.3%, S(y)/x = 2.0%), suggesting that all three methods are similar in performance for most patients. However, a patient with increased plasma osmolality showed significant decreases in BGE and PCV hematocrits relative to the EPC method. The differences in hematocrit measurements could be reproduced by adding solutes to blood in vitro or by modifying the plasma osmolality of rats in vivo. Samples from patients undergoing cardiac surgery, whose blood had large changes in protein concentration, showed discrepancies between hematocrits by conductivity and other methods; similar effects could be produced by changes in protein concentration or in vitro addition of polyethylene glycol. We conclude that conductivity measurements provide accurate hematocrit results for physiologically normal subjects but not for some intensive-care and surgical patients.