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Biomedical subjects

J L Dorner

Publications and source records attributed to J L Dorner.

At least 19 recordsLinked to original sources

Assessment of corticosteroid-induced alkaline phosphatase isoenzyme as a screening test for hyperadrenocorticism in dogs.

Quantitative determination of the corticosteroid-induced isoenzyme of alkaline phosphatase (CAP) was evaluated as a screening test for hyperadrenocorticism (HAC) in dogs. A series of 40 dogs with HAC (CAP range, 96 to 14,872 U/L), 30 clinically normal dogs (CAP range, 0 to 38 U/L), and 80 dogs with various diseases (non-HAC) and without history of exogenous glucocorticoid exposure for a minimum of 60 days (CAP range, 0 to 1163 U/L) were used to evaluate the test. Sensitivity and specificity of CAP was calculated at various cutoff points for absolute CAP activity and for CAP activity expressed as a percentage of total alkaline phosphatase activity. A cutoff point of 90 U/L was selected as optimal for use of this assay as a screening test for HAC. A prevalence survey then was done of all canine serum samples submitted to our diagnostic laboratory over a 3-month period, to calculate the predictive values of a positive and a negative test result in a clinical population and to determine the relative frequency and magnitude of CAP activity in dogs that had received glucocorticoids. The predictive values of a positive and a negative test result at the 90 U/L cutoff value were 21.43% (95% confidence limits, 8.3 to 40.95%) and 100% (95% confidence limit > 96%), respectively. It was concluded that CAP isoenzyme activity, determined by routine biochemical analysis by an automated levamisole-inhibition assay, could function as a screening test for HAC; however, the predictive value of a positive test result was too low to recommend the assay as a diagnostic test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocortical Hyperfunction↗

Safety of L-tryptophan for pigs.

Epidemic eosinophilia-myalgia syndrome (EMS) associated with excess L-tryptophan (Trp) consumption in humans has been declared a major public health problem. The EMS problem has not been observed in pigs, nor has comprehensive pathology associated with EMS in humans been described. Experiments were therefore conducted to evaluate the pathology and effects of excess dietary L-Trp for finishing (79 to 119 kg) pigs and to determine an LD50 of Trp for pigs. In Exp. 1, addition of .1 or 1% Trp to corn-soybean meal diets had no effect on growth performance or leukocyte and relative eosinophil counts or on plasma aspartate transferase, creatine phosphokinase, and lactate dehydrogenase activities. Likewise, untoward pathological effects of Trp feeding were not observed in the animals under study. In Exp. 2, supplementing the basal diet with 0, 2, and 4% Trp caused linear (P less than .05) decreases in weight gain, feed intake, and gain:feed ratio. Mortality could not be produced by acute oral dosing in the LD50 study (Exp. 3), wherein Trp doses between 2.00 and 5.71 g/kg of BW were administered by stomach tube. Vomiting occurred at oral doses greater than 5.71 g/kg of BW. These results suggest that oral ingestion of Trp in pigs is safe and that pigs can tolerate considerable excesses of Trp.

Administration, Oral↗

Haptoglobin and ceruloplasmin as determinants of inflammation in dogs.

Assay procedures for determining serum haptoglobin concentration and ceruloplasmin oxidase activity in dogs were validated, and reference values were established. Serum haptoglobin concentration is reported as milligrams per deciliter of cyanmethemoglobin binding capacity, whereas serum ceruloplasmin oxidase activity was determined by use of p-phenylenediamine as substrate. Both assays were used to analyze serum samples from 288 dogs. In each dog's case record, clinical history and final diagnosis were evaluated to determine whether the dog had an inflammatory condition. Complete blood cell counts were performed in 265 dogs, using simultaneously collected blood samples. Plasma fibrinogen concentration was determined for 161 dogs. A positive correlation (P less than 0.01) for serum haptoglobin concentration and for ceruloplasmin oxidase activity, compared with WBC counts, segmented neutrophil and band neutrophil counts, and plasma fibrinogen concentration. Ceruloplasmin oxidase activity and haptoglobin concentration were up to 6 times more sensitive than fibrinogen concentration or leukocyte counts in detecting inflammation. Specificity of ceruloplasmin oxidase activity was comparable to fibrinogen concentration and leukocyte counts, whereas haptoglobin concentration was found to be slightly less specific. Specificity of haptoglobin concentration improved slightly (from 0.82 to 0.88) when dogs with a history of glucocorticoid administration were excluded from analysis. Predictive value of a negative test result (haptoglobin concentration less than 125 mg/dl; ceruloplasmin oxidase activity less than 20 IU/L) and predictive value of a positive test result for haptoglobin concentration and ceruloplasmin activity were comparable to or better than fibrinogen concentration or various oxidase leukocyte counts in detection of inflammation in a variety of disease conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of glucocorticoids on alkaline phosphatase, alanine aminotransferase, and gamma-glutamyltransferase in cultured dog hepatocytes.

Glucocorticoid(GC)-induced hepatopathy in the dog is characterized by abnormal liver morphology and increases in serum alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), and the liver alkaline phosphatase isoenzyme (LALP) and by the appearance of an unusual isoenzyme of alkaline phosphatase known as the corticosteroid-induced alkaline phosphatase isoenzyme (CALP). It has not been shown whether the increases in serum ALT, GGT, and LALP are as a result of an increase in production of these enzymes or as a result of the GC-induced hepatocellular swelling and possible membrane alterations. Also, it has been assumed that the mechanism of production of CALP is via GC-induced gene derepression and de novo protein synthesis; however, this hypothesis has not been directly tested. Using isolated dog hepatocytes maintained in a confluent monolayer culture in the presence and absence of GC or cyclic AMP, no statistical increase in serum ALT, GGT, or LALP was observed. A combination of GC and cyclic AMP also caused no statistical increase in ALT and GGT; however, we demonstrate that these conditions clearly stimulated the de novo synthesis of LALP. These conditions do not induce the synthesis of CALP as determined by a sensitive immunoassay. The data obtained using this in vitro model suggest that the primary mechanism(s) of the in vivo increase of serum ALT and GGT in GC treated dogs may be other than that of de novo protein synthesis. Likewise, in vitro production of CALP may be a mechanism more complex than the conditions tested in this study.

Alanine Transaminase↗

Purification and comparison of corticosteroid-induced and intestinal isoenzymes of alkaline phosphatase in dogs.

Corticosteroid-induced alkaline phosphatase (CALP) and intestinal alkaline phosphatase (IALP) from dogs were purified to homogeneity, as determined by polyacrylamide gel electrophoresis. Purification involved an un-interrupted system using DEAE-cellulose, concanavalin A-agarose, and monoclonal antibody affinity columns. The monoclonal antibody was prepared by use of IALP as the antigen. The 2 isoenzymes were compared, using molecular weight determinations, amino acid analyses, peptide mapping, N-terminal sequencing of the first 10 amino acids, carbohydrate analyses, and recognition by anti-IALP monoclonal antibody. The data indicated that canine IALP and CALP are identical with regard to recognition by monoclonal antibody and N-terminal amino acid sequence, nearly identical in amino acid content and peptide maps, but different in carbohydrate content. It was concluded that CALP is a product of the same gene as IALP and that differences in glycosyl transferase activities between liver and intestines or the presence of glycosidase activities in or around the intestinal mucosae result in the marked difference in carbohydrate content.

Adrenal Cortex Hormones↗

A Technique for Automated Quantification of Canine Glucocorticoid-induced Isoenzyme of Alkaline Phosphatase.

A sensitive assay for the corticosteroid-induced alkaline phosphatase isoenzyme (CAP), adaptable to most clinical chemistry autoanalyzers, is described and validated. This assay is based on the greater than 98% inhibition of liver alkaline phosphatase isoenzyme (LAP) activity with 4.2 mM levamisole, as compared to the 42% inhibition of CAP activity. Analysis of serum with total alkaline phosphatase (AP) activity within the reference range, resulted in a reference range of 0 to 19 U/L for CAP activity. Analysis of serum from 160 clinical patients with AP activity above the reference range, revealed 73% with increased CAP activity ranging from 20 to 7,000 U/L. The diagnostic significance of this increased CAP activity is discussed.

Journal Article↗

Disseminated meningeal tumor in a dog.

A 6-year-old Golden Retriever was referred for evaluation of hind limb paresis and generalized weakness. Neurologic examination revealed multifocal cervical and lumbosacral spinal disease. Radiography and myelography failed to identify a lesion. Cerebrospinal fluid was markedly cellular and had a high protein concentration, consistent with myelitis or a neoplastic process. The dog did not improve with medical management. Gross and histologic examination of the brain and spinal cord revealed a thick meningeal surface characterized by polymorphic histiocytic-like cells to multinucleate giant cells. The neoplastic process was considered to be a disseminated meningeal polymorphic cell sarcoma.

Animals↗

Subcellular location of corticosteroid-induced alkaline phosphatase in canine hepatocytes.

Dogs received either 4 mg/kg of prednisone or sterile saline daily for 32 days. Serum samples were assayed every 4 days for total alkaline phosphatase (ALP) and corticosteroid-induced ALP isoenzyme (CIALP) activity. The initial and major increase of serum ALP was attributed to the liver isoenzyme of ALP (LALP), however, CIALP began to increase by day 8 and was significantly increased by day 24. Prior to treatment and on day 32, sections of liver from control and prednisone-treated dogs were stained for ALP activity after blocking the staining activity of LALP with levamisole. The staining activity of CIALP was compared to the staining activity of LALP in liver sections from control dogs and from dogs in which the bile duct was ligated. It was determined that CIALP was located in that area of the hepatocyte membranes which comprise the bile canaliculi.

Adrenal Cortex Hormones↗

Alterations in selected serum biochemical constituents in equids after induced hepatic disease.

Effects of induced cholestasis and hepatocellular necrosis and of fasting on serum biochemical constituents including bile acids, IgA, bilirubin, alkaline phosphatase, gamma-glutamyltransferase (GGT), arginase, and the clearance of sodium sulfobromophthalein were studied in 4 groups of equids. The reference value for serum bile acids, as determined by an enzymatic colorimetric procedure for horses and ponies was 5.94 +/- 2.72 mumol/L, there being no statistical difference for horses and ponies. Sample collection at time of feeding had no effect on serum bile acid concentration. Seemingly, serum bile acids, arginase, and GGT were the most sensitive indicators of cholestasis and/or hepatocellular necrosis and would form an essential minimum effective battery of tests to diagnose and prognose hepatic disease in equids. These tests provided a measure of hepatobiliary transport function (bile acids), cell necrosis (arginase), and cholestasis (GGT and bile acids).

Alkaline Phosphatase↗

Diagnostic value of intestinal alkaline phosphatase in horse serum.

Antiserum directed against equine intestinal Alkaline Phosphatase (ALP) was produced in rabbits and used to develop a sensitive and quantitative assay for the detection of intestinal ALP in equine serum. This assay was then used to measure the half-life of intravenously injected intestinal ALP and to determine if the intestinal ALP was present in normal horse sera, sera from horses presented for lesions not involving the gastrointestinal tract and sera from horses presented with lesions involving the gastrointestinal tract. The results suggest that intestinal ALP is not likely to appear in equine serum even when gastrointestinal disease is present and, therefore, appears to be of no diagnostic value.

Journal Article↗

Effect of in vitro Hemolysis on Values for Certain Porcine Serum Constituents.

Serum consistuents were determined for 14 healthy pigs after the addition of hemolysates containing 54, 133, 215 and 400 mg/dl of hemoglobin to serum. Of sixteen chemical procedures considered, changes (P<0.0005) in creatinine, total protein, Pi, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), Ca, K, aspartate aminotransferase (AST), total bilirubin and albumin values occurred following the addition of a hemolysate containing 400 mg/dl of hemoglobin. Changes (P<0.0005) were also observed in certain serum constituents when hemolysates containing 54, 133 and 215 mg/dl of hemoglobin were added.

Journal Article↗

Intestinal alkaline phosphatase-like properties of horse kidney alkaline phosphatase.

Two isoenzymes of alkaline phosphatase from horse kidney were identified by cellulose acetate electrophoresis. Horse kidney alkaline phosphatase was similar to horse intestinal alkaline phosphatase, in regard to both antigenicity and response to levamisole inhibition, but different from horse liver alkaline phosphatase. This study suggests that horse kidney alkaline phosphatase is an expression of the intestinal gene locus and not the hepatic gene locus.

Alkaline Phosphatase↗

Immunoassay for the steroid-induced isoenzyme of alkaline phosphatase in the dog.

Antiserum directed against the steroid-induced alkaline phosphatase (ALP) isoenzyme of the dog was produced in rabbits. This antiserum was used to develop a sensitive and quantitative assay for the detection of the steroid-induced ALP isoenzyme in the serum of dogs. This antiserum was also used to enhance the electrophoretic separation of the steroid-induced and hepatic ALP isoenzymes.

Adrenal Cortex Hormones↗

Comparison of the steroid-induced, intestinal, and hepatic isoenzymes of alkaline phosphatase in the dog.

The steroid-induced, intestinal, and hepatic isoenzymes of canine alkaline phosphatase (ALP) were compared, using antibodies against the steroid-induced ALP isoenzyme, heat inactivation, phenylalanine inhibition, prednisolone inhibition, and Michaelis constant determinations. The results indicate that the steroid-induced and intestinal ALP isoenzymes are similar and indicate that the steroid-induced isoenzyme might be a product of the same gene that controls the intestinal isoenzyme.

Adrenal Cortex Hormones↗

Sub-acute toxicity of hexachlorobenzene in female beagles, including electroencephalographic changes.

Adult female beagles were given oral HCB for 21 days. Subdividing the dose resulted in greater accumulation of HCB in fat and seemed to enhance toxic effects. Subjecting the animals to a 10-day period of food restriction immediately following 21 days of dosing further increased residues, but obscured any differences due to dosing regimen. Liver and hepatocyte enlargement, as well as physiologic changes in the central nervous system, were HCB-induced. Weight loss and various hematological changes were equivocal, with dietary stress and HCB probably contributing to the changes to varying degrees. A dose of 50 mg/kg/day of HCB for 21 days must be considered at least minimally toxic to female beagles.

Animals↗

Alkaline phosphatase and alkaline phosphatase isoenzymes in the cat.

Feline alkaline phosphatase and alkaline phosphatase isoenzymes have been studied in tissue and serum. Alkaline phosphatase from various organs was quantitated and then subjected to cellulose acetate electrophoresis. The effects of bile duct ligation, prednisolone treatment and phenobarbital treatment on serum alkaline phosphatase was measured. The diagnostic importance of feline serum alkaline phosphatase levels is discussed in light of the results of this and other studies.

Journal Article↗