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R Rej

Publications and source records attributed to R Rej.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1986

Subchronic oral toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the guinea pig: comparisons with a PCB-containing transformer fluid pyrolysate.

In contrast to the well-characterized acute toxicity of the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in the guinea pig, the effects of prolonged po exposure in this species are unknown. The present report describes the results of administration to guinea pigs of 2,3,7,8-TCDD in the feed at levels of 0, 2, 10, 76, or 430 ppt for up to 90 days. Additional aims were to examine recovery following prolonged 2,3,7,8-TCDD exposure in the guinea pig and to generate data to facilitate comparison of the previously reported toxicity of a transformer fluid pyrolysate with that of pure 2,3,7,8-TCDD. Animals receiving 430 ppt 2,3,7,8-TCDD exhibited body weight loss, thymic atrophy, liver enlargement, and 60% mortality by Day 46 (males) and by Day 60 (females), when surviving animals in this group were sacrificed. Total 2,3,7,8-TCDD consumption was approximately 1.3 and 1.9 micrograms/kg, respectively. Animals receiving 76 ppt 2,3,7,8-TCDD for 90 days (total 0.44 microgram/kg) exhibited a decreased rate of body weight gain and increased relative (to body) liver weights. Male animals also displayed a reduction in relative thymus weights and elevated serum triglycerides, while females exhibited hepatocellular cytoplasmic inclusion bodies and lowered serum alanine aminotransferase activities. Toxic effects were generally similar to those observed after acute 2,3,7,8-TCDD administration. No dose-related alterations were seen in animals receiving either 10 ppt (total 0.06 micrograms/kg) or 2 ppt (total 0.01 micrograms/kg) for 90 days, establishing a no-observed-effect level of approximately 0.65 ng 2,3,7,8-TCDD/kg/day. In the recovery study, groups of guinea pigs were administered 430 ppt 2,3,7,8-TCDD for 11, 21, or 35 days and then allowed to recover for an additional 79, 69, or 55 days, respectively. Treatment-related mortality in each group was 0, 10, and 70%, respectively, by Day 90. An effective LD50 of 0.8 microgram 2,3,7,8-TCDD/kg for prolonged exposure was calculated on the basis of these results, a value lower than those previously reported from this laboratory for acute exposure. The results also suggested a possible lowering of the body weight "set point" following 2,3,7,8-TCDD exposure. Comparison of the present findings with those previously reported for a transformer fluid pyrolysate containing a mixture of polychlorinated aromatic species indicated both a greater variety of toxic effects and flatter dose-response relationships for the pyrolysate in the guinea pig.

Administration, Oral↗
PubMed1985

Effects of temperature on measurement of alkaline phosphatase activity.

We examined the effects of temperature on the activity and steady-state kinetic properties of alkaline phosphatase (EC 3.1.3.1). Purified isoenzymes from human liver, intestine, and placenta were used, as was human serum, and the enzyme from porcine kidney. Phosphatase activity was estimated by two different assay techniques. For all isoenzymes, apparent Michaelis constants for the substrate 4-nitrophenyl phosphate decreased with increased temperature; Km at 37 degrees C was typically half that determined at 25 degrees C. All enzymes of human origin exhibited similar linear Arrhenius relationships over the range examined, 20-37 degrees C (Ea of 30-36 kJ X mol-1). The porcine kidney enzyme obeyed an Arrhenius relationship that was slightly, but significantly, different from the isoenzymes of human origin. Temperature relationships based upon Arrhenius behavior and individual activity measurements are presented. For human alkaline phosphatases, they differed by no more than 10%.

Alkaline Phosphatase↗
PubMed1985

Mitochondrial enzymes in human serum: comparative determinations of glutamate dehydrogenase and mitochondrial aspartate aminotransferase in healthy persons and patients with chronic liver diseases.

We measured the activities of two mitochondrial enzymes, the mitochondrial form of aspartate aminotransferase (EC 2.6.1.1) and glutamate dehydrogenase (EC 1.4.1.2), in the serum of apparently healthy persons (n = 84) and patients suffering from chronic liver diseases (n = 43). The distribution of activities for glutamate dehydrogenase, but not mitochondrial aspartate aminotransferase, was sex-dependent. The upper limits of the reference intervals (99th percentile) at 37 degrees C were 3.2 U/L for mitochondrial aspartate aminotransferase, 6.4 U/L for glutamate dehydrogenase (women), and 11.0 U/L for glutamate dehydrogenase (men); there was a weak correlation between the activities of both mitochondrial enzymes (r = 0.439). In patients with chronic liver diseases we found a greater increase in the activity of glutamate dehydrogenase than of mitochondrial aspartate aminotransferase and the correlation between the two mitochondrial enzymes was stronger. The diagnostic sensitivity and specificity of either mitochondrial enzyme was less than that of total aspartate aminotransferase, alanine aminotransferase (EC 2.6.1.2), or gamma-glutamyltransferase (EC 2.3.2.2).

Adult↗
PubMed1984

Subchronic exposure of mice to Love Canal soil contaminants.

The health hazard potential of soil collected from the surface of the Love Canal chemical dump site in Niagara Falls, New York, was assessed in 90-day exposure studies. Female CD-1 mice were exposed to two concentrations of the volatile components of 1 kg of soil with and without direct soil contact. Control mice were identically housed but without soil. The soil was replaced weekly and 87 compounds were detected in the air in the cages above fresh and 7-day-old soil as analyzed by gas chromatography/mass spectrometry. The concentration of many of these compounds decreased during the 7-day exposure cycle. Histopathologic, hematologic, and serum enzyme studies followed necropsy of all mice. There was no mortality of mice exposed for up to 90 days under any condition. Thymus and spleen weights relative to body weight were increased after 4 weeks of exposure by inhalation but not after 8 or 12 weeks of exposure. alpha-, beta-, and delta- Benzenehexachlorides , pentachlorobenzene, and hexachlorobenzene were detected in liver tissue from these animals. Mice exposed to 5- to 10-fold elevated concentration of volatiles had increased body and relative kidney weights. There was no chemically induced lesion in any animal exposed only to the volatile soil contaminants. Mice exposed by direct contact with the soil without elevated volatile exposure had increased body (10%) and relative liver weights (169%). Centrolobular hepatocyte hypertrophy, which involved 40 to 70% of the lobules, was observed in all mice in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Air↗
PubMed1984

Measurement of aminotransferases: Part 1. Aspartate aminotransferase.

Aminotransferases are ubiquitous enzymes of mammalian cells and several are of important diagnostic use. The application of aspartate aminotransferase activity measurements in serum from individuals suffering from myocardial infarction brought about a new dimension in clinical laboratory testing in the 1950s. This review focuses on measurement techniques for aspartate aminotransferase and their application (a subsequent article will review other aminotransferases). Assay techniques measuring enzyme activity are direct spectrophotometric measurements, manometric techniques, assays using dye substances, coupled enzyme techniques, and radiometric procedures. Of these procedures, the one employing malate dehydrogenase and NADH is the most important and is covered in particular detail. The estimation of the mitochondrial isoenzyme of aspartate aminotransferase is also of clinical interest, in particular for estimating severity of disease or in specific applications (e.g., chronic alcoholism). Methods reviewed for estimation of this enzyme are electrophoresis, chromatography, differential kinetic behavior, and immunochemical separation. Determination of the enzyme protein by techniques independent of its catalytic activity are also reviewed.

Animals↗
PubMed1984

Distribution of cytosolic and mitochondrial aspartate aminotransferase in normal, ischemic, and necrotic myocardium. An immunohistochemical study.

We utilized immunoperoxidase methods to study the distribution of both cytosolic or soluble(s) and mitochondrial (m) aspartate aminotransferase (AspAT) in normal, ischemic, and necrotic myocardium. Human myocardium was obtained from autopsy (n = 9) and surgery (n = 6). Cardiac tissue from 26 dogs with experimental myocardial infarction induced by closed-chest balloon occlusion and four dogs with myocardial ischemia without necrosis induced by a 50% reduction in left main coronary artery flow for 3 hours were studied. Duration of occlusion was 45 minutes (n = 1), 3 hours (n = 11), 5 to 6 hours (n = 10), or 15 to 24 hours (n = 4). Highly purified m- and s-AspAT and specific antibodies were prepared in our laboratory. In all cases, control experiments were performed. Microscopically normal human and dog myocardium uniformly stained for m- and s-AspAT. Necrotic myocardium from patients with infarcts showed markedly reduced immunostaining. In those dogs with myocardial necrosis, all dogs with coronary occlusion of 5 to 24 hours, and eight of 11 dogs with 3-hour occlusions, immunostaining was significantly reduced for both s- and m-AspAT in regions confirmed to be necrotic by triphenyl tetrazolium chloride and hematoxylin and eosin staining. Myocardial necrosis was confirmed in the 3-hour infarcts by electron microscopy. In the four dogs with a 50% reduction in left main flow for 3 hours, and one dog with a 45-minute coronary occlusion, ischemia was demonstrated by glycogen loss in period acid-Schiff-stained sections but there was no evidence of necrosis by electron microscopy or triphenyl tetrazolium chloride staining and there was no loss of immunostaining evident for s- or m-AspAT. Thus, s- and m-AspAT were visualized in normal and ischemic myocardium with decreased staining in necrotic tissue using immunoperoxidase techniques. Loss of both s- and m-AspAT can be demonstrated in human myocardium and in experimental canine myocardium as early as 3 hours after coronary occlusion and appears to be specific for irreversible myocardial injury. No depletion of isoenzyme can be detected by immunohistochemical techniques in tissue that is ischemic but not necrotic. Furthermore, by these immunoperoxidase techniques, loss of s- and m-AspAT from necrotic myocardium appears to be simultaneous.

Animals↗
PubMed1983

Subchronic oral toxicity in guinea pigs of soot from a polychlorinated biphenyl-containing transformer fire.

We have previously described the acute po toxicity in guinea pigs of soot from a transformer fire at the State Office Building in Binghamton, New York. The soot was determined to contain polychlorinated biphenyls, biphenylenes, dibenzodioxins, and dibenzofurans. The present study evaluates soot toxicity in guinea pigs receiving 0, 0.2, 1.9, 9.3, or 46.3 ppm soot in the feed for 90 days or 231.5 ppm for 32 days. At 231.5 ppm, body weight loss, thymic atrophy, bone marrow depletion, skeletal muscle and gastrointestinal tract epithelial degeneration, and fatty infiltration of hepatocytes were observed. Mortality had reached 35% by Day 32 (when survivors were killed), with total soot consumption of approximately 400 mg/kg. At 46.3 or 9.3 ppm soot, a reduced rate of body weight gain was observed, and at 46.3 ppm, the mortality by Day 90 was 30%. Relative (to body) thymus weights were decreased in both groups, while relative spleen weights were increased at 46.3 ppm soot only. Salivary gland interlobular duct squamous metaplasia and focal lacrimal gland adenitis were detected histopathologically, while bone marrow depletion was noted only in females at the higher dose. Diminished serum alanine aminotransferase (ALT) activity in both sexes and decreased serum sodium levels in male and potassium levels in female animals were detected at both dose levels. decreased gamma-glutamyl transferase activity and red blood cell count and elevated serum creatinine and triglycerides were observed only in animals fed 46.3 ppm soot. At 1.9 ppm soot, salivary gland duct metaplasia was observed in both sexes, along with decreased relative thymus weights, ALT activity, and serum sodium levels in male animals only. No effects attributable to soot exposure were noted in animals receiving 0.2 ppm soot for 90 days. Total average soot consumption for male and female animals in the 0.2, 1.9, 9.3, and 46.3 ppm dosage groups was 1.2, 12, 55, and 275 mg/kg, respectively. Although many of the observed effects were typical of acute exposure of guinea pigs to the Binghamton soot or to polychlorinated aromatic hydrocarbons in general, salivary gland duct metaplasia has not been previously reported. Toxic effects of this subchronic exposure were observed at lower total doses than with acute exposure, although variations in absorption due to the effects of different vehicles (aqueous in the acute study versus the feed in this study) could account for some or all of this difference.

Administration, Oral↗
PubMed1983

Immunochemical quantitation of isoenzymes of aspartate aminotransferase and lactate dehydrogenase.

The applicability of immunochemical techniques to the determination of aspartate aminotransferase (AspAT, EC 2.6.1.1) and lactate dehydrogenase (LDH, EC 1.1.1.27) isoenzymes in human serum are reviewed. In the case of AspAT, the human enzymes of mitochondrial (m-AspAT) and cytosolic (s-AspAT) origin were purified to homogeneity from liver and erythrocytes respectively and used to prepare isoenzyme-specific anti-sera in rabbits. Immunoprecipitation and immunoinhibition assays using partially purified antibodies or monovalent Fab fragments were found to provide better accuracy and precision than column chromatographic, electrophoretic, or differential kinetic techniques. A variety of immunochemical techniques were examined for the determination of enzyme protein including radioimmunoassay, turbidimetric procedures, and an assay using the indium slide technique. In the last, purified isoenzyme was absorbed as a monolayer to the surface of an indium metal film upon glass. The enzyme retains immunological reactivity, allowing the specific binding of antibody at the surface. The minimum detectable concentration by this technique is greater than 50 micrograms/L of enzyme protein; results suggest that normal and patient sera contain considerably more immunologically reactive s- and m-AspAT than catalytically active enzyme.

Aspartate Aminotransferases↗
PubMed1983

Analogues of hycanthone and lucanthone as antitumor agents.

Hycanthone analogues (5 and 6) containing 7-substituted hydroxyl groups were prepared and evaluated as antitumor agents. These compounds were significantly more active than the corresponding unsubstituted derivatives. The 7-hydroxylated 4-(hydroxymethyl)-9H-xanthen-9-ones, 11 and 12, were also active antitumor agents. However, the 7-hydroxy-9H-xanthen-9-one counterparts of the 7-hydroxylucanthones were totally devoid of antitumor activity. Results obtained thus far are consistent with the hypothesis that 4-hydroxymethyl substituents in the 9H-xanthen-9-one and 9H-thioxanthen-9-one series are required for antitumor activity.

Animals↗
PubMed1982

Ring-hydroxylated analogues of lucanthone as antitumor agents.

A series of ring-alkoxylated and ring-hydroxylated analogues of lucanthone was prepared and tested for antitumor activity. The most biologically interesting members of this group were the 7-hydroxylucanthone derivatives, 50 and 51, which gave T/C values in the NCI P-388 antitumor screen of 188 and 265, respectively. The apparent association constants and delta Tm values for a number of analogue-DNA complexes were determined to ascertain whether there was any quantitative correlation with biological activity. The most that can be said is that intercalation may be a necessary but far from sufficient condition for antitumor activity.

Animals↗
PubMed1982

Nitro and amino derivatives of lucanthone as antitumor agents.

A group of nitro and amino derivatives of lucanthone was prepared and tested for antitumor activity. Reaction of 1-chloro-4-methyl-7-nitrothioxanthenone and N,N-diethylethylenediamine gave the 7-amino analogue (11) directly, accompanied by 7-amino-1-chloro-4-methylthioxanthenone. The antitumor activity of 11 was inferior to that of lucanthone and 7-hydroxylucanthone. The most active compound in the series was the nitro compound 1. In the P-388 lymphocytic leukemia screen it showed a T/C = 178 at 200 mg/kg.

Animals↗
PubMed1982

Emulsions of perfluorinated compounds for use in quality control of blood gas analyses.

We prepared emulsions of perfluorinated compounds and examined their utility as liquid matrixes for tonometry in quality control of blood pH and gas analyses. Emulsions of perfluorotributylamine and perfluorodecalin, prepared by sonication, consisted largely of particles not exceeding 0.2 micrometer in diameter. Unlike most aqueous solutions these materials were not easily contaminated by room air and can be reliably used for tonometry liquids. Results for pCO2 and pO2 agreed well with calculated values. Average day-to-day coefficients of variation for emulsions of perfluorotributylamine were 2.9% for pH (within the range 7.11-7.60), 4.4% for pCO2 (2.88-9.17 kPa), and 1.6% for pO2 (7.76-40.67 kPa).

Blood Gas Analysis↗