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R Rej

Publications and source records attributed to R Rej.

At least 19 recordsLinked to original sources
PubMed1996

Propylthiouracil treatment reduces long-term potentiation in area CA1 of neonatal rat hippocampus.

Rat pups were made hypothyroid by exposure to propylthiouracil in drinking water beginning at 1 week of age, and the degree of long-term potentiation (LTP) in hippocampal area CA1 determined from brain slices of animals ranging in age from 2 to 6 weeks. Serum T3 levels were less than 20% of that of age matched controls after 3 weeks of treatment, and remained at that level. Relative to the age-matched controls, LTP was reduced significantly after 2 weeks of treatment. These observations are consistent with the conclusion that LTP magnitude is a reflection of cognitive function, which is known to be depressed in hypothyroid conditions in both animals and man.

Administration, Oral↗
PubMed1994

Human ventricular myosin light chain isotype 1 as a marker of myocardial injury.

A monoclonal enzyme immunoassay for measuring human ventricular myosin light chain isotype 1 (HVMLC1) in serum has been developed. To evaluate the method in patients with suspected myocardial injury, we studied 51 patients (16 acute myocardial infarction (AMI), 19 unstable angina pectoris (UAP), 9 stable angina pectoris, 3 nonischemic heart disease, 4 hip surgery patients), and 190 controls (blood donors). Serial blood-samples were drawn from patients; a single blood-sample from controls. The diagnostic value of the HVMLC1 assay was compared with total creatine kinase (CK), CKMB activity, CKMB mass concentration, lactate dehydrogenase isoenzyme 1 (LD1), troponin T (TnT) and mitochondrial-aspartate aminotransferase (m-ASAT). The detection limit of HVMLC1 was 0.4 microgram/l (linear range 0-20 micrograms/l). Sera from 190 reference persons did not contain detectable levels of HVMLC1 (< 0.4 microgram/l; 99% percentile). The coefficients of variation were 13% (1.0 microgram/l) and 3.1% (17.7 micrograms/l). Cross-reactivity with myosin from skeletal muscle was seen. Times to peak value were: CK 19.3 +/- 2.0, LD1 43.4 +/- 3.2, HVMLC1 72.9 +/- 7.0, and m-ASAT 67.3 +/- 5.6 h. Time-curves of HVMLC1 and m-ASAT were similar, whereas time-curves for HVMLC1 and TnT were quite different in most cases. Peak value of HVMLC1 was five times higher than CK peak value and eight times that of LD1. HVMLC1 appeared in the blood within hours after the onset of chest pain and in the majority remained for more than a week after AMI. Among patients with UAP 16% (3/19) had elevated HVMLC1 in serum, whereas elevated TnT was seen in 26% (5/19) and elevated CKMB mass in 26% (5/19). We conclude that the new HVMLC1 assay offers a sensitive diagnosis of myocardial injury. It is characterized by a wide diagnostic time window. The similarity of the HVMLC1 and m-ASAT curves indicates that it may be used to estimate the extent of myocardial necrosis.

Adult↗
PubMed1993

Accurate enzyme activity measurements. Two decades of development in the commutability of enzyme quality control materials.

Commercial serum preparations are integral components of both internal and external quality control programs for enzyme activity measurements. However, properties of these materials may differ significantly from those of clinical specimens. Differences from clinical specimens may include the following: species origin of the enzyme; isoenzyme form(s); integrity of the molecular species; matrix of the solution; processes such as lyophilization; and addition of preservatives. There are also significant differences among methods measuring the activity of a single enzyme including a diversity of compounds that may serve as substrate(s); variable cofactor or metal supplementation; and differences in the substrate concentration(s), buffer substances, pH, and temperature. The measured response to each of these variations in assay technique may differ among these types of specimens. To be acceptable, quality control materials must have properties similar to those of clinical specimens. Thus, the concept of commutability that we originated and first applied to enzyme activity measurements remains useful, and its further application to the problem of "matrix effects" is reviewed here. Multivariate display techniques are applied to the specific examples of aspartate aminotransferase, alpha-amylase, and alkaline phosphatase to judge the commutability of quality control materials for these enzymes.

Bias↗
PubMed1992

Application of clinical laboratory measurements to issues of environmental health.

Monitoring of biochemical constituents in serum is an important component in revealing potential toxicity in humans and experimental animals due to exposure to a variety of xenobiotic agents. The relative toxicity of pure compounds, usually at large doses, has helped elucidate the mode of action of these compounds and their relative risk. However, most actual cases of environmental exposure present an extensive range of components and the potential for synergistic or inhibitory interactions. In this paper we review two such environmental cases: The Love Canal chemical dump site in Niagara Falls, NY, and the transformer fire at the State Office Building in Binghamton, NY. We focus on the clinical laboratory measurements obtained in these studies (including serum glucose, triglycerides, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, lactate dehydrogenase, sodium and potassium), their usefulness, limitations, and application to such cases. Significant alterations in serum triglyceride and alanine aminotransferase levels were found in guinea pigs due to exposure to dioxins. These two tests were useful in estimating the 'equivalent' concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin in complex chemical mixtures.

Alkaline Phosphatase↗
PubMed1992

How good are clinical laboratories? An assessment of current performance.

The Clinical Laboratory Improvement Act of 1967 and Amendments of 1988 (CLIA '67 and CLIA '88) were enacted to ensure that clinical laboratories within the U.S. provide a quality of service that meets clinical needs for good patient care. Approved proficiency-testing programs are to judge the quality of laboratory testing by promulgated performance criteria. We examine the quality of analytical results reported in 1991 to the New York State Department of Health Proficiency Testing program in light of these criteria and analytical goals, based on medical usefulness. Analytical performance is examined for cholesterol, potassium, sodium, calcium, glucose, aspartate aminotransferase, digoxin, and theophylline. In general, proposed CLIA '88 performance standards are compatible with the current state of practice for the population of laboratories examined. Exceptions appear to be digoxin and sodium (failure rate exceeding average) and most therapeutic substances (low failure rate). Sources of analytical bias relative to an accuracy-based target value must be characterized as method-, laboratory-, or matrix-dependent if regulatory programs are to achieve the objective of improving analytical accuracy across all testing sites.

Chemistry, Clinical↗
PubMed1991

The nature of calibrators in immunoassays: are they commutable with test samples? Must they be?

Immunoassay systems require calibration protocols that are normally more sophisticated than many analytical techniques in routine clinical use. Calibrators used in such assays may differ significantly from the analyte in clinical specimens. Differences in the properties of calibrators, or reference materials, from those of clinical specimens may include: species origin of the calibrator for an analyte; integrity of the molecular species; matrix of the calibration solution; addition of preservative agents. Owing to the large number of potential differences in the properties of calibrators and those of serum specimens that may affect immunoassay results, the concept of commutability that we originated and first applied to enzyme activity measurements can readily be applied to immunoassay determinations. We specifically examined the properties of calibration materials in nine commercial immunoassay tests for human thyrotropin. Significant non-commutability of materials was demonstrated. The measured results obtained with authentic patient sera differed by a factor of approximately two fold between the techniques exhibiting the lowest and greatest numeric results. Considerably larger intermethod biases were found for calibration materials. Multivariate analysis revealed that the patient sera formed a highly focussed pattern. The calibration materials for one instrument system also focussed in this group. Other calibrators formed three foci indicating similar patterns of commutability within each of the three groups. Clustering was independent of the amount of thyrotropin in the patient specimens, but appeared to be concentration-dependent for at least some of the calibrators. Thus the availability of a common calibration material appears feasible, but not presently available in many commercial products. A processed human serum, a candidate material for use in our proficiency testing program, was projected in the same cluster as authentic patient sera indicating that this material has intermethod properties identical to patient sera (i.e. fully commutable).

Humans↗
PubMed1990

Effects of exercise on serum amino-transferase activity and pyridoxal phosphate saturation in Thoroughbred racehorses.

Aminotransferase activities were measured in the serum of two- to three-year-old Thoroughbred fillies and colts during a four week period of peak training for flat racing. Aspartate aminotransferase (AspAT, EC 2.6.1.1), mitochondrial aspartate aminotransferase (m-AspAT) and alanine aminotransferase (AlaAT, EC 2.6.1.2) activities in serum were measured and the relative proportions of apoenzyme and holoenzyme were determined. The aminotransferase activities were increased only slightly immediately following exercise. This small and immediate post exercise increase in activity did not vary greatly over the period of peak training. Measured in the presence of exogenous pyridoxal 5'-phosphate, mean enzyme activities (iu/litre at 30 degrees C) before exercise were: AspAT, 291; m-AspAT, 13; AlaAT, 18. After exercise they were: AspAT, 317; m-AspAT, 16; AlaAT, 23. Nearly all of the AspAT activity was present in the holoenzyme form (94 per cent holoenzyme) indicating excellent vitamin B6 status in these animals. Paradoxically, the AlaAT in serum from the same highly trained Thoroughbred horses was poorly saturated with pyridoxal phosphate, with nearly half of the AlaAT in most horses present in the inactive apoenzyme form (61 per cent that of holoenzyme). It is critical therefore, that exogenous pyridoxal phosphate be included in aminotransferase assays to determine the amounts of enzyme release into the peripheral circulation.

Alanine Transaminase↗
PubMed1990

Mitochondrial aspartate aminotransferase determined by "Fast Protein Liquid Chromatography".

We describe an improved separation of the isoenzymes of aspartate aminotransferase (EC 2.6.1.1), based on ion-exchange chromatography. Involving the "Fast Protein Liquid Chromatography" system (Pharmacia) with a MonoQ column, this rapid, reproducible method for quantifying the mitochondrial enzyme shows good resolution and sensitivity, and results correlate well with those by an established immunochemical method.

Aspartate Aminotransferases↗
PubMed1989

Transferrin and mitochondrial aspartate aminotransferase in young adult alcoholics.

Two recently proposed biochemical markers of alcoholism, namely, quantitation of plasma transferrin variant (Tf5.7) and the ratio of plasma mitochondrial aspartate aminotransferase (m-AspAT) to total AspAT (t-AspAT), were tested for their ability to detect young adult alcoholics. Another commonly used biochemical test, namely, activity of plasma gamma glutamyltransferase (GGT) was included as a comparison. Although mean values of GGT, TF5.7, total transferrin (Tftot), m-AspAT and t-AspAT in alcoholics were significantly higher than those in controls, there were too many overlapping values in each test between alcoholics and controls to render any of these tests suitable as a marker for young adult alcoholics. Depending on cut-off limits, the sensitivity of each test ranged from 0-52% and the specificity ranged from 80-97%. Moreover, the m-AspAT/t-AspAT and Tf5.7/Tftot ratios were not significantly different between alcoholics and controls. A stepwise linear discriminant function analysis of all the variables resulted in a slight increase in classification sensitivity (66%) but a decrease in specificity (77%). The relatively short duration (mean = 5.6 years) of heavy alcohol intake and the time elapsed (mean = 5.8 days) since the alcoholics last consumed alcohol very likely contributed to the low sensitivity. Young adults might also be more resilient with regard to the damaging biochemical effects of ethanol. Abnormal biochemical values might reverse to normal values much more quickly in young adult alcoholics than in those who are older and have more years of alcohol abuse.

Adolescent↗
PubMed1989

Treatment of infantile spasms with high-dose ACTH: efficacy and plasma levels of ACTH and cortisol.

Fifteen children with infantile spasms and a hypsarrhythmic EEG defined by EEG-videotelemetry monitoring received a regimen of high-dose (150 IU/m2/d) ACTH for their seizures. We carried out an endocrinologic evaluation before and after initiation of the ACTH and conducted a time course study of plasma ACTH and cortisol levels after ACTH dosing. Spasms were controlled and the EEG normalized in 14 of the 15 children. Prior to starting ACTH therapy all the patients had normal prolactin, insulin, cortisol, and ACTH levels in plasma and normal thyroid function. Although the pattern of rise of ACTH levels in plasma after ACTH dosing was similar in all the children, there was great individual variation in the absolute concentrations. However, both the pattern of rise and absolute level of cortisol in plasma after ACTH was highly predictable in all patients. Plasma cortisol rose rapidly within 1 hour of ACTH administration and continued a slower rise for 12 to 24 hours after the ACTH dose. High-dose ACTH therapy seems quite effective in infantile spasms, perhaps because of a sustained high level of plasma cortisol. This sustained plateau of cortisol may be more effective in controlling infantile spasms than the pulse effect expected with oral steroids or lower doses of ACTH.

Adrenocorticotropic Hormone↗
PubMed1989

Aminotransferases in disease.

Aspartate and alanine aminotransferases are two of the enzymes most frequently measured by the clinical laboratory. They are most commonly used in the differential diagnosis of various liver diseases where the ratio of the two enzymes provides additional clinical insight. AST is also useful in many cases for diagnosis, or estimating severity, of myocardial infarction. The mitochondrial isoenzyme of AST has a growing significance in the diagnosis of alcoholism and other conditions.

Alanine Transaminase↗
PubMed1988

A screening technique for monoclonal antibody production: application of an indium slide immunoassay.

A simple technique is described that is suitable for rapid screening of hybridoma microculture fluids for monoclonal antibody producing hybrids. The procedure measures increase in light scatter due to the antigen-antibody reaction on a surface of indium metal coated upon glass and does not require use of a labeled second antibody. Techniques minimizing nonspecific binding in such assays are presented. The procedure was used to screen hybridoma microculture fluids containing mouse monoclonal antibodies directed against human mitochondrial isoenzyme of aspartate aminotransferase (EC 2.6.1.1). The technique was compared to an enzyme-linked immunosorbent assay, and similar semi-quantitative results were found for sample cultures tested in the two procedures. The new screening procedure affords a simple screening assay without sacrificing sensitivity or specificity of standard methods.

Animals↗
PubMed1987

The absence of gamma-glutamyltransferase activity in transport-dependent methotrexate-resistant hepatoma cells.

A cell line derived from H35 hepatoma cells resistant to methotrexate (MTX) as a result of a defective transport system for MTX has been examined to determine how closely the variant resembles the parent cells with regard to other biochemical properties. The capacity of extracts of resistant cells to catalyze the poly-gamma-glutamylation of MTX was approximately twice as great as that of wild-type cell extracts. Evidence of similarity between wild-type and H35 R0.3 cells was derived from the equitoxic activity to both cell lines of nonclassical antifolates and other miscellaneous antineoplastics which act by a variety of mechanisms. Two phenotypic markers of hepatic cell function, alpha-aminoisobutyric acid (AIB) transport and tyrosine aminotransferase (TAT) activity inducibility, were present in both cell types, demonstrating the maintenance of these phenotypic properties in the H35 R0.3 cells. gamma-Glutamyltransferase (GGT, EC 2.3.2.2) activity differed in that it was present in wild-type cells and barely detectable in H35 R0.3 cells. The GGT activity reappeared in the H35 cells when they regained MTX sensitivity after incubation for 14-20 weeks in MTX-free media. Although defective MTX transport appeared to be correlated with the disappearance of GGT activity in an H35 variant cell line, no functional relationship between them is apparent at this time. It is possible that a lack of GGT activity may be evidence of a more differentiated phenotype in the transport-resistant cell line.

Aminoisobutyric Acids↗
PubMed1987

Quantitation of aspartate aminotransferase isoenzymes after electrophoretic separation.

A scheme for the quantitative detection of aspartate aminotransferase isoenzymes and multiple forms after electrophoretic separation is described. Glutamate generated from the aminotransferase reaction is quantitated by using the glutamate dehydrogenase/diaphorase-coupled enzyme system to form a formazan dye. Product inhibition of aspartate aminotransferase by oxaloacetate is prevented by including oxaloacetate decarboxylase in the overlay reagent. Results compare favorably with those of an immunochemical precipitation procedure. The method can also be used to detect quantitatively subforms and atypical forms (genetic variants, immunoglobulin-enzyme complexes) of aspartate aminotransferase.

Animals↗
PubMed1986

The effects of Love Canal soil extracts on maternal health and fetal development in rats.

The effects of a solvent extract of the surface soil of the Love Canal chemical dump site, Niagara Falls, New York, and of a natural extract, or leachate, which is drained from the canal for treatment, on the maternal health and fetal development were determined in rats. The solvent extract, which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2, 3,7,8-TCDD) at 170 ppb and numerous other chlorinated organic compounds with the primary identified components being the isomers of benzenehexachloride (BHC), was dissolved in corn oil and administered by gavage to pregnant rats at 0,25,75, or 150 mg crude extract/kg/day on Days 6-15 of gestation. A 67% mortality was observed at the highest dose. The rats were sacrificed on Day 20. Dose-related increases in relative liver weight accompanied by hepatocyte hypertrophy were observed at all dose levels. Fetal birthweight was decreased at 75 and 150 mg extract/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. Based on literature values for BHC, all of the observed toxicity could be accounted for by the BHC contaminants of the extract. The crude organic phase of the leachate was administered to pregnant rats at 0,10,100, or 250 mg/kg/day as described above. Maternal weight gain decreased at 100 and 250 mg/kg/day, accompanied by 5 and 14% maternal mortality, and 1 and 3 dead fetuses, respectively. Early resorptions and the percentage of dead implants increased whereas fetal birthweights were decreased at 250 mg/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. The primary components of the complex leachate by mass were tetrachloroethanes; however, 2,3,7,8-TCDD, which was present at 3 ppm, probably accounted for all the observed toxicity.

Abnormalities, Drug-Induced↗