bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasensitive time-resolved immunofluorometric assay of prostate-specific antigen in serum and preliminary clinical studies
Authors: Yu H , Diamandis E P 
Published: January 2020

Abstract
We developed an ultrasensitive method for measuring prostate-specific antigen (PSA) in serum. The assay includes a capture monoclonal anti-PSA antibody coated to microtiter wells, a biotinylated rabbit polyclonal detection antibody, and alkaline phosphatase (ALP)-labeled streptavidin. The activity of ALP is measured with the substrate diflunisal phosphate; the released diflunisal forms highly fluorescent complexes with Tb(3+)-EDTA that are quantified with microsecond time-resolved fluorometry. The assay is precise and accurate and correlates well with the established Hybritech Tandem-PSA kit. Its distinguishing feature is extreme sensitivity (lowest limit of detection is 0.002 micrograms/L or 2 x 10(6) PSA molecules per assay). This is the most sensitive PSA assay reported thus far; we used it to quantify PSA in patients who had undergone radical prostatectomy. Many patients had &lt; 0.01 micrograms/L PSA in their serum. This method could have important clinical applications in postsurgical early detection of relapse or residual prostate cancer, as recently suggested in the literature (Clin Chem 1992;38:1930-2).
Carbohydrate-deficient transferrin quantified by HPLC to determine heavy consumption of alcohol
Authors: Jeppsson J O , Kristensson H , Fimiani C 
Published: January 2020

Abstract
We developed a new fully automated ion-exchange chromatographic method for quantitating carbohydrate-deficient transferrin (CDT) on a Mono Q column. Quantitation relies on the selective absorbance of the iron-transferrin complex at 460 nm. Transferrin isoforms deficient in sialic acid, with pIs 5.7 and 5.9, can easily be separated and quantitated as a percentage of the total transferrin. This method has been applied to samples from teetotalers, occasional drinkers, patients with recent heavy alcohol consumption, and patients during detoxification. The sensitivity of the method was 55% in patients reporting 40-70 g daily ethanol consumption and nearly 100% in heavily intoxicated patients (70-500 g daily consumption). The half-life of the dominating pI 5.7 isoform in this group was 9.5 (+/- 1) days during detoxification. A CDT value &gt; 0.8% is a highly specific marker for alcohol abuse and is greatly superior to other currently available biological markers.
Apolipoprotein E polymorphism in a healthy Swedish population: variation of allele frequency with age and relation to serum lipid concentrations
Authors: Eggertsen G , Tegelman R , Ericsson S , Angelin B , Berglund L 
Published: January 2020

Abstract
We analyzed blood samples from 407 healthy Swedish individuals, 244 men and 163 women, ages 17 to 86 years, for apolipoprotein (apo) E isoforms and serum triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol. Parallel genotyping by means of polymerase chain reaction (PCR)-amplified DNA was performed in 200 subjects. Identical results were obtained by genotyping and phenotyping in 95% of all subjects analyzed. The apo E allelic frequencies were 7.8% for epsilon 2, 71.9% for epsilon 3, and 20.3% for epsilon 4. Compared with other Caucasian populations, the present population had a high relative allelic frequency of epsilon 4. The epsilon 4 frequency decreased with increasing age and was significantly lower in individuals &gt; 60 years of age (14.7%). When controlling for age and sex, there were strong correlations between total serum and LDL cholesterol and the various epsilon alleles. The epsilon 4 and epsilon 3 alleles correlated positively with serum cholesterol and the epsilon 4 allele correlated positively with LDL cholesterol. In contrast, HDL cholesterol and serum triglycerides did not show any correlation to the allele types. Thus, the results demonstrate a considerable age variation of the epsilon allele frequency among healthy Swedes and an influence of apo E alleles on serum and LDL cholesterol concentrations.
Dietary nutrient intakes and slight albuminuria in people at least 40 years old
Authors: Metcalf P A , Baker J R , Scragg R K , Dryson E , Scott A J , Wild C J 
Published: January 2020

Abstract
We studied the relation between diet and slight albuminuria in 5416 people, ages 40 years and over, who participated in a health screening survey of a local workforce. Degree of albuminuria showed log-linear univariate relations with dietary protein, cholesterol, and sodium intakes, and negative log-linear univariate relations with dietary fiber and polyunsaturated to saturated fat (P/S) ratio. After adjusting for age, gender, and ethnicity, the relative risk (95% confidence interval) for slight albuminuria was significantly increased in people reporting dietary cholesterol consumption &gt; 226 mg/day compared with people reporting consumption &lt; or = 226 mg/day [1.32 (1.02, 1.70)], and significantly reduced in people reporting dietary fiber consumption &gt; 26 g/day compared with people reporting consumption &lt; or = 26 g/day [0.74 (0.58, 0.95)]. There was no significant effect of dietary protein, P/S ratio, or salt intake. We conclude that risk of slight albuminuria is increased by consumption of dietary cholesterol and reduced by consumption of dietary fiber.
FK506 (tacrolimus), a novel immunosuppressant in organ transplantation: clinical, biomedical, and analytical aspects
Authors: Wallemacq P E , Reding R 
Published: January 2020

Abstract
The macrolide immunosuppressant FK506 (tacrolimus) is a powerful and selective anti-T-lymphocyte agent that was discovered in 1984. This agent, isolated from the fungus Streptomyces tsukubaensis, has a mechanism of action similar to that of cyclosporine. Experimental data were first published in 1987, and clinical trials were started 2 years later in Pittsburgh. The drug has a potent hepatotrophic effect, which could explain its success in liver transplantation. Particularly encouraging results were obtained in liver allograft recipients, suggesting a lower risk/benefit ratio than with other immunosuppressants. However, recent data show that the drug is not devoid of toxicity (mainly nephrotoxicity), which should the percent the need for careful blood monitoring. Several methods of analysis have been described, some satisfactory, others inadequate for routine monitoring. There is still a lack of specific methods to determine routinely the parent drug concentrations in biological fluids for clinical pharmacokinetics purposes. Despite greater experience in therapeutic drug monitoring, the correlation between FK506 concentrations and efficacy or toxicity is still unclear. More investigations are required to better understand and determine the appropriate use of FK506 in organ transplantation and treating autoimmune diseases.
Artificial neural networks in diagnosis of thyroid function from in vitro laboratory tests
Authors: Sharpe P K , Solberg H E , Rootwelt K , Yearworth M 
Published: January 2020

Abstract
We studied the potential benefit of using artificial neural networks (ANNs) for the diagnosis of thyroid function. We examined two types of ANN architecture and assessed their robustness in the face of diagnostic noise. The thyroid function data we used had previously been studied by multivariate statistical methods and a variety of pattern-recognition techniques. The total data set comprised 392 cases that had been classified according to both thyroid function and 19 clinical categories. All cases had a complete set of results of six laboratory tests (total thyroxine, free thyroxine, triiodothyronine, triiodothyronine uptake test, thyrotropin, and thyroxine-binding globulin). This data set was divided into subsets used for training the networks and for testing their performance; the test subsets contained various proportions of cases with diagnostic noise to mimic real-life diagnostic situations. The networks studied were a multilayer perceptron trained by back-propagation, and a learning vector quantization network. The training data subsets were selected according to two strategies: either training data based on cases with extreme values for the laboratory tests with randomly selected nonextreme cases added, or training cases from very pure functional groups. Both network architectures were efficient irrespective of the type of training data. The correct allocation of cases in test data subsets was 96.4-99.7% when extreme values were used for training and 92.7-98.8% when only pure cases were used.
Synthetic peptide-based immunoassay for amino-terminal propeptide of type I procollagen: application for evaluation of bone formation
Authors: Linkhart S G , Linkhart T A , Taylor A K , Wergedal J E , Bettica P , Baylink D J 
Published: January 2020

Abstract
Serum biochemical markers are powerful tools for the evaluation of bone turnover. In this study, we developed a radioimmunoassay, using a synthetic peptide for the N-terminal fragment of human type I [alpha 1(I)] procollagen (N-PCP). A 14-amino acid peptide was synthesized from the amino terminus and used to generate antibodies in rabbits. The synthetic peptide was used as standard and tracer in the assay. Both native type I amino procollagen (PINP), which was purified from skin fibroblasts, and human serum displaced tracer binding in parallel with the synthetic peptide. The range for measurement of N-PCP in serum was 0.7 to 30 micrograms/L (0.21-9.18 nmol/L). In a sample of 17 normal adults and 13 children (ages 9-16 years) there was a strong correlation between serum N-PCP determined by this assay and both skeletal alkaline phosphatase isoenzyme and osteocalcin, markers of bone formation. Serum concentrations of N-PCP in a group of normal children were eightfold higher than concentrations in normal adults, with no overlap between the two groups. N-PCP also correlated with C-terminal type I procollagen determined with a commercially available kit (r = 0.92).
Beta-N-terminal glycohemoglobins in subjects with common hemoglobinopathies: relation with fructosamine and mean erythrocyte age
Authors: Martina W V , Martijn E G , van der Molen M , Schermer J G , Muskiet F A 
Published: January 2020

Abstract
Amounts of beta-N-terminal glycohemoglobins (HbX1c), serum fructosamine, and erythrocyte polyamines were determined in nondiabetic adults with HbAA, HbAC, HbAS, HbCC, HbSC, HbSS, and HbS/hereditary persistent HbF (HPFH). The groups did not differ in fructosamine concentrations. Mean (95% confidence limits) HbX1c percentages were: 4.4 (4.1-4.8) for HbA1c in HbAA, 4.3 (3.9-4.8) for HbA1c in HbAC, 4.1 (3.6-4.6) for HbC1c in HbAC, 4.4 (4.0-4.7) for HbA1c in HbAS, 2.6 (range: 2.3-3.8) for HbC1c in HbCC, 2.0 (1.5-2.4) for HbS1c in HbSC, 0.9 (0.6-1.3) for HbS1c in HbSS, and 1.3 (range: 0.8-2.4) for HbS1c in HbS/HPFH. There was a nonlinear inverse relation between HbX1c and erythrocyte polyamines, indicating that HbX1c percentage decreases with decreasing mean erythrocyte age. We conclude that amounts of HbX1c in subjects with heterozygous hemoglobinopathies should be expressed as a percentage of HbX0 + HbX1c, not total hemoglobin. Interpretation of HbX1c in subjects with a decreased erythrocyte half-life is difficult; measurement of fructosamine seems a suitable alternative.
Fast lipoprotein chromatography: new method of analysis for plasma lipoproteins
Authors: März W , Siekmeier R , Scharnagl H , Seiffert U B , Gross W 
Published: January 2020

Abstract
Fast lipoprotein chromatography (FLPC) is a novel method for quantifying lipoproteins. Plasma proteins are separated by fast-flow gel filtration. Lipoproteins are detected by post-column derivatization with an enzymatic cholesterol reagent. FLPC resolves very-low-, low-, and high-density lipoproteins (VLDL, LDL, and HDL, respectively) and completely separates apolipoprotein Al- and apolipoprotein B-containing lipoproteins. CVs for VLDL-cholesterol, LDL-cholesterol, and HDL-cholesterol are 5.8%, 2.0%, and 1.9%, respectively. We compared FLPC with a combined ultracentrifugation and precipitation method and obtained correlation of r = 0.979, 0.978, and 0.933 for VLDL-cholesterol, LDL-cholesterol, and HDL-cholesterol, respectively. Triglyceride concentrations up to 9.00 g/L did not interfere with the quantification of lipoproteins by FLPC. We conclude that FLPC is a precise and reliable method for the analysis of plasma lipoproteins that complements conventional techniques.
Electrochemical assay system with single-use electrode strip for measuring lactate in whole blood
Authors: Shimojo N , Naka K , Uenoyama H , Hamamoto K , Yoshioka K , Okuda K 
Published: January 2020

Abstract
We have developed an assay system for measuring lactate in whole blood, consisting of a single-use strip of an enzyme-coated electrode and a small meter. The electrode strip is made of three plastic films: a cover sheet, a spacer, and an insulation layer printed with electrodes that are coated with lactate oxidase (EC 1.1.3.x) and ferricyanide as an electron mediator. The meter measures the magnitude of the anodic current of the reduced mediator by the enzymatic reaction and displays the lactate concentration 60 s after a blood sample (5 microL) is applied. The calibration curve was linear up to 20 mmol/L, and the between-run CVs at three concentrations were 1.7-8.4%. Lactate concentrations determined by this method (y) in blood samples from healthy individuals before and after exercise agreed with the results obtained by the conventional enzymatic method (x): y = 0.97x - 0.3, Sy/x = 0.7. This assay provides a rapid and convenient test for measuring blood lactate concentrations.
Clinical utility and validation of emerging biochemical markers for mammary adenocarcinoma
Authors: Werner M , Faser C , Silverberg M 
Published: January 2020

Abstract
The clinical utilities of the emerging biochemical markers for mammary adenocarcinoma CA 15-3, CA 549, CA M26, CA M29, and MCA (mucin-like carcinoma-associated antigen) were assessed by a formal rating according to six desirable marker characteristics. All five indicators similarly have good specificities but limited sensitivities. As a consequence, these markers mainly meet just two desirable criteria: their frequency and degree of expression reflect tumor burden and prognosis, and they may correlate with therapeutic results. The validation of these assay properties by clinical trials was evaluated by another rating system, designed to assess proband sample selection, restrictions on allowable observations, and choice of statistical descriptors. By these benchmarks, the estimates of the prior probabilities of test outcome (sensitivity and specificity) are reasonably definitive, but conclusive judgments about the posterior probabilities of test outcome ("predictive values") and about values and costs associated with testing are not possible. Three approaches to enhance the limited clinical utility of biochemical breast cancer markers are considered: shifts of the diagnostic decision threshold, marker panels, and sequential testing. However, none of these strategies improves the described performance characteristics.
Serum tumor markers for patient monitoring: a case-oriented approach illustrated with carcinoembryonic antigen
Authors: Fritsche H A 
Published: January 2020

Abstract
The effectiveness of patient monitoring with serum tumor markers is improved when the patient's pretreatment baseline is established, regular serial testing is performed, and a clinically significant change of the marker is determined on the basis of objective criteria. Attention must be directed to (a) ensuring long-term assay precision, (b) timing specimen collection to avoid misinterpretation of paradoxical increases (induced by chemotherapy, surgery, or radiation), (c) noting changes in the production or clearance mechanisms of the marker, and (d) recognizing the variability of site-response in patients who have multiple locations of metastatic disease. Clinical decisions to alter therapy should not be based only on tumor marker measurements. In the absence of other clinical data, a tumor marker abnormality should be confirmed with serial samples collected at a time interval dictated by the half-life of the marker. Serial tumor marker testing can improve cancer patient care, especially when effective salvage therapies are available.
Reimbursement of tumor marker tests
Authors: Logue L J 
Published: January 2020

Abstract
The diffusion of new technology is significantly affected by coverage and reimbursement decisions. A variety of agencies (public and private) make decisions as to which technologies or treatments will be covered and what the levels of reimbursement will be. Recently, these agencies' coverage decisions have tended to be strongly affected by whether a technology is cost raising or cost reducing. Historically, a common effect of medical innovation has been improved quality of health care but with a corresponding increase in cost of delivery. The Medicare program has significant influence on the coverage policies of public and private third-party payers. This influence is especially visible in coverage and reimbursement decisions for cancer-related diagnostic procedures and systems. Coverage for these procedures and systems is not widespread because payers have not been convinced of the clinical usefulness of the assays. The industry must take the responsibility of working through the issues surrounding coverage and reimbursement of cancer-related diagnostic procedures with the payers. The ability to successfully negotiate payment for assays requires knowledge of Medicare coverage policies and a grasp of the reimbursement system.
The FDA's perspective on the evaluation of tumor marker tests
Authors: Aziz K J , Maxim P E 
Published: January 2020

Abstract
Cancer marker tests are often proposed for three intended uses: screening, diagnosis, and monitoring. For each intended use, performance characteristics need to be well defined. The utility of a marker in a given setting depends heavily on two predominant performance characteristics--sensitivity and specificity. These parameters must be established with respect to the intended clinical use of the marker. The value of the marker in a particular situation also depends on the effectiveness of therapy for the malignancy. In reviewing a cancer marker test, the US Food and Drug Administration focuses on both the proposed intended use statement and the clinical utility of the marker. The sponsor is expected to provide specific claims data in support of the safety and effectiveness of the device through well-designed and -executed clinical studies. Several cancer markers are already available. In the future, new markers are anticipated that may greatly expand the range of usefulness in cancer diagnosis screening and monitoring.
Perspectives on the future of cancer markers
Authors: Bast R C 
Published: January 2020

Abstract
More fundamental understanding of cell growth regulation will provide novel approaches for detecting, preventing, and treating different cancers. Activation of protooncogenes or loss of tumor-suppressor genes can have both prognostic and therapeutic importance. In epithelial ovarian cancer, poor prognosis is associated with continued expression or overexpression of tyrosine kinase growth factor receptors p170EGFR, p165fms, and p185erbB-2. Over-expression of erbB-2 (HER-2/neu) by breast and ovarian cancers already permits effective targeting of antibodies and immunotoxins. Ultimately, molecular analysis of individual cancers will guide the application of specific therapies to inhibit activated oncogenes or restore the function of tumor-suppressor genes. Circulating growth factors, oncogene products, and tumor-associated antigens may provide markers for earlier detection of some cancers. In epithelial ovarian cancer, concentrations of CA 125 can be increased 1-5 years before clinical diagnosis, and approximately 50% of patients with stage I disease have had an abnormal CA 125 concentration. Combining CA 125 with two novel markers--OVX1 and M-CSF--has retrospectively detected &gt; 98% of stage I ovarian cancers. Although the specificity of the three markers is insufficient for cost-effective screening, serum tests for them could prompt the performance of transvaginal sonography, substantially decreasing the number of sonograms required. Genetic markers in the germ line of patients at increased risk for certain cancers will almost certainly influence strategies for prevention or detection. In familial breast, and ovarian cancer, a locus on chromosome 17q tracks risk of cancer in a fraction of kindreds. How often germline abnormalities will be detected in patients with apparently sporadic cancer remains to be determined.
Mechanism of fructosamine assay: evidence against role of superoxide as intermediate in nitroblue tetrazolium reduction
Authors: Baker J R , Zyzak D V , Thorpe S R , Baynes J W 
Published: January 2020

Abstract
We studied the chemistry of the fructosamine assay for glycated serum proteins by using the model Amadori compound N alpha-formyl-N epsilon-fructoselysine (fFL), an analog of glycated lysine residues in protein. Free lysine was formed at approximately 70% yield during a standard 20-min incubation of fFL with alkaline nitroblue tetrazolium (NBT) at 37 degrees C. Although superoxide dismutase (SOD; EC 1.15.1.1) and catalase (EC 1.11.1.6) decreased the yield of the product, monoformazan dye (MF+), the yield of MF+ was slightly greater under anaerobic than aerobic conditions, excluding a role for superoxide as an intermediate in the reduction of NBT during the fructosamine assay. SOD added to diabetic patients' sera at physiological concentrations also caused a significant (approximately 50%) inhibition of MF+ formation. This inhibition was reduced by addition of nonionic detergents, which contain organic peroxide inhibitors of SOD, to the fructosamine reagent. Overall, these data indicate that the Amadori compound is the direct reductant of NBT in the fructosamine assay and that superoxide is not an intermediate in the reaction. The inhibitory effects of SOD and catalase are most likely the result of oxygen regeneration in the assay mixture.
Multiple forms of prostate-specific antigen in serum: differences in immunorecognition by monoclonal and polyclonal assays
Authors: Zhou A M , Tewari P C , Bluestein B I , Caldwell G W , Larsen F L 
Published: January 2020

Abstract
Prostate-specific antigen (PSA) in serum is primarily complexed with alpha 1-antichymotrypsin (alpha 1-ACT). However, 12-15% of prostate cancer (PCa) patients present with the predominant form being uncomplexed (free) PSA (Lilja et al., Clin Chem 1991;37:1618-24). We report that commercial immunoassays demonstrate variations in reactivity, especially to the uncomplexed form. We fractionated and analyzed commercial controls, PSA complexes prepared in vitro, and sera from patients with PCa or benign prostatic hyperplasia, using molecular sieve chromatography and Hybritech Tandem-R, Abbott IMx, and Ciba Corning ACS PSA assays. Peak integration of PCa samples demonstrated ACS:Tandem-R ratios of 1-1.3 for PSA/alpha 1-ACT complex. In contrast, ratios of uncomplexed peaks ranged from 2 to 4, suggesting a greater reactivity of the uncomplexed form in the ACS PSA assay. Discrepancies between assays, when PSA was measured in unfractionated sera, correlated directly with the percentage of the uncomplexed form. In controls, fractionation revealed the presence of uncomplexed PSA only, with ratios of ACS:Tandem-R and IMx:Tandem-R of 3:1 and 1.8:1, respectively. Immunoblots of PCa sera detected uncomplexed PSA (approximately 30 kDa) and PSA complexes of approximately 95 kDa (PSA/alpha 1-ACT) and &gt; 200 kDa, indicative of alpha 2-macroglobulin. Maximal recognition of all forms of PSA may be important for early detection of disease progression.