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Biomedical subjects

G S Johnson

Publications and source records attributed to G S Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1986

Factor VIII complex in canine plasma after submaximal treadmill exercise.

Exercise-induced changes in the plasma concentrations of coagulation factor VIII and von Willebrand factor were evaluated, using 8 random-source adult dogs that exercised on a treadmill for 5 to 10 minutes (mean running time = 8.3 minutes). Maximum treadmill speeds attained by the dogs were 11 to 18 km/hr, and the mean of the maximum individual speeds was 14.3 km/hr. Maximum heart rates of individual dogs during exercise were 190 to 250 beats/min with a mean of 218 beats/min (a 2.4-fold increase over the mean preexercise rate). Exercise did not induce significant increases in plasma concentrations of factor VIII coagulant activity, coagglutinin co-factor activity, or factor VIII-related antigen. Results indicated that submaximal exercise does not induce increases in plasma concentrations of coagulation factor VIII or von Willebrand factor in the dog.

Animals↗
PubMed1986

Prekallikrein deficiency in a family of miniature horses.

Two sibling miniature horses, a male and a female, had a normal 1-stage prothrombin time and a prolonged activated-partial thromboplastin time (APTT). The addition of as little as 5% of a normal equine plasma pool to the plasma samples of both horses shortened their prolonged APTT to within normal limits. Coagulation factor analysis revealed deficiencies in factor XII (12 and 13 U/dl, control population 77 to 128 U/dl), when determined with a feline factor XII-deficient plasma substrate, but normal concentrations (119 and 96 U/dl) when a human factor XII-deficient plasma substrate was used. Deficiencies of another factor, prekallikrein, were detected with a human prekallikrein-deficient plasma substrate (16 and 6 U/dl, control population 70 to 173 U/dl). Other intrinsic coagulation factors were present in normal concentrations. The APTT was measured with plasma from the 2 horses after various incubation periods (1 to 15 minutes) with a contact activator before the addition of Ca ions. With incubation times of greater than or equal to 10 minutes, the APTT of both horses were essentially the same as that of the normal equine plasma pool. Several family members of the 2 prekallikrein-deficient miniature horses appeared to be heterozygous carriers of the prekallikrein deficiency.

Animals↗
PubMed1986

Effect of internal hemorrhage on fibrin(ogen) degradation products in canine blood.

To determine effects of internal hemorrhage on fibrin(ogen) degradation products, blood was pumped from catheters in the jugular veins of 7 anesthetized dogs into extravascular sites in the same dogs. Blood (25 ml/kg of body weight) was transported into their peritoneal cavities (3 dogs) or into the muscle of the pelvic limbs (4 dogs). Blood samples were obtained periodically from these dogs for 4 days after the injections were given. Fibrin(ogen) degradation products (FDP) could not be detected in any of these samples by standard procedures with a commonly used clinical assay, based on the agglutination of antibody-coated latex beads. Even when the assay was modified to make it 2.5 times as sensitive, FDP was not detected. Seemingly, extravascular blood from internal hemorrhage is unlikely to supply enough FDP to the circulating blood to produce clinically important increases in FDP concentrations.

Agglutination Tests↗
PubMed1985

Retinoic acid-induced expression of tissue transglutaminase in human promyelocytic leukemia (HL-60) cells.

Addition of retinoic acid to human promyelocytic leukemia cells results in a dramatic increase in cellular transglutaminase activity. This increase is due to the induction of a specific intracellular transglutaminase, tissue transglutaminase. Retinoic acid-induced expression of tissue transglutaminase is potentiated by analogues of cyclic AMP. The induction of the enzyme can be detected within 6 h of the addition of the retinoid to the cell and results in increases of the enzyme of at least 50-fold. The induction of HL-60 transglutaminase is a specific response of the cells to retinoic acid and is not seen with other agents that induce HL-60 differentiation. We believe that the induction of tissue transglutaminase is a useful index of the early events in retinoid-regulated gene expression in both normal and transformed cells.

Acyltransferases↗
PubMed1985

Endogenous ADP ribosylation of high mobility group proteins 1 and 2 and histone H1 following DNA damage in intact cells.

Endogenous ADP ribosylation of nonhistone high-mobility group (HMG) proteins and histone H1 was studied in cultured mouse mammary tumor cells following treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). MNNG treatment of cells caused a rapid and transient increase in ADP ribosylation of histone H1 and HMG 1 and 2, whereas (ADP-ribose)n on HMG 14 and 17 was not affected. 3-Aminobenzamide, an inhibitor of (ADP-ribose)n synthetase, prevented the increase in ADP ribosylation of histone H1 and HMG 1 and 2. This inhibitor enhanced the cell-killing effect of MNNG, but had no significant effect on the removal of methylated purines. The preferential increase in ADP ribosylation of HMG 1 and 2 and histone H1 may be necessary for cell recovery from DNA damage.

Adenosine Diphosphate Ribose↗
PubMed1985

Coagulation of plasma from the chicken (Gallus domesticus): phospholipids influence clotting rates induced by components from Russell's viper venom.

Added phospholipid failed to accelerate chicken-plasma coagulation, induced by high concentrations of crude Russell's viper venom; however, similarly induced coagulation of canine and human plasma proceeded more rapidly when phospholipid was added. Phospholipid reduced clotting times of canine, human and also chicken plasma when partially purified factor X-activating enzyme from Russell's viper venom was the inducing agent. In the absence of added phospholipid, preincubation of chicken plasma with factor V-activating enzyme from Russell's viper venom accelerated factor X-activating-enzyme-induced coagulation. Preincubation of chicken plasma with the factor V-activating enzyme slowed factor X-activating-enzyme-induced coagulation in the presence of added phospholipid.

Animals↗
PubMed1985

Detection of von Willebrand's Disease in Dogs with a Rapid Qualitative Test, Based on Venom-Coagglutinin-Induced Platelet Agglutination.

A rapid, qualitative blood test was developed to identify potential bleeders among dogs that are von Willebrand's disease suspects. The test, based on venom coagglutinin-induced agglutination of formalin-fixed washed platelets, was compared to the more lengthy electroimmunoassay for factor VIII-related antigen. The 2 tests were performed on plasma samples from 82 dogs, including 68 Doberman pinschers. The 39 plasma samples that were found to be "clinically normal" by the new test had factor VIII-related antigen concentrations ranging from 32% to 192% of that in a pool of normal canine plasma samples. Plasma samples from the 43 dogs that tested as "potential bleeders" by the new test had factor VIII-related antigen concentrations from 4% to 38%. All 43 "potential bleeders" were Doberman pinschers. Shortly after being evaluated by the new test, 46 of the dogs underwent invasive diagnostic, therapeutic, or cosmetic procedures. Excessive hemorrhage was encountered in 40% of the 25 dogs that tested as "potential bleeders. " In contrast, only 5% of the 21 dogs that tested as "clinically normal" exhibited abnormal bleeding.

Journal Article↗
PubMed1985

Hemorrhage from the cosmetic otoplasty of Doberman Pinschers with von Willebrand's disease.

The hemorrhagic tendencies of 23 Doberman Pinscher pups were observed during cosmetic otoplasty and were ranked by a +1 to +4 grading system (+1 = least hemorrhage, and +4 = most hemorrhage). A second estimate of the hemostatic competencies of these dogs was made by counting the gauze sponges used in the otoplasties. Factor VIII-related antigen concentrations and coagglutinin cofactor concentrations were measured in plasma samples from blood drawn not more than 30 hours before the surgical procedures were done. The factor VIII-related antigen concentrations were between 9% and 147% of the concentration in a normal plasma pool, and the coagglutinin cofactor concentrations were between 1% and 165%, indicating that some of these dogs had von Willebrand's disease. The hemorrhagic tendencies of 12 pups were graded +1. This group had a mean antigen concentration of 75% (min-max, 38% to 147%) and a mean coagglutinin cofactor concentration of 89% (min-max, 42% to 165%). These were significantly greater than the antigen and cofactor concentrations of the grades +2 (n = 5), +3 (n = 3), or +4 (n = 3) dogs. Significant differences were not found when antigen concentrations of the grade +2 dogs (mean, 16%; min-max, 11% to 22%), grade +3 dogs (mean, 13%; 12% to 16%), and grade +4 dogs (mean, 11%; 9% to 12%) were compared with each other, nor were significant differences seen among the coagglutinin cofactor concentrations of the grade +2 dogs (mean, 7%; min-max, 1% to 11%), grade +3 dogs (mean, 6%, 4% to 8%), and grade +4 dogs (mean, 5%; 2% to 9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Maturation of human promyelocytic leukemia cells induced by nicotinamide: evidence of a regulatory role for ADP-ribosylation of chromosomal proteins.

We have studied the role of ADP-ribosylation of chromosomal proteins in the regulation of myeloid cell maturation using the HL-60 cell line as a model. Nuclei isolated from this human promyelocytic leukemia cell line contained (ADP-ribose)n synthetase activity, whereas little or no enzymatic activity was detectable in normal human blood neutrophils. Furthermore, the activity of (ADP-ribose)n synthetase was decreased in HL-60 cells when they were induced to mature with retinoic acid (RA). To determine whether reduced (ADP-ribose)n synthetase activity is simply a result of induced maturation or whether it is a necessary precedent event for the maturation process, we evaluated the effects of nicotinamide (NAm) and its methyl derivative, N'-methylnicotinamide (N'-Met-NAm), agents which decrease ADP-ribosylation. Treatment of HL-60 cells with these drugs caused the cells to undergo maturation and to acquire certain of the morphologic, functional, and biochemical characteristics of normal neutrophils. N'-Met-NAm was more potent than NAm in inducing maturation; at a concentration of 0.8 mM, it caused greater than 80% of the cells to mature, whereas a tenfold greater concentration of NAm was required to induce a similar degree of maturation. NAm and N'-Met-NAm also potentiated the maturation of HL-60 cells induced by RA. Exposure of cells to noninducing concentrations of these compounds caused a leftward shift in the dose-response curve for RA; maturation was observed at 10(-11) M RA in the presence of either 2 mM NAm or 0.2 mM N'-Met-NAm while 10(-9) M RA was required to induce maturation in their absence. A leftward shift in the dose response curve for maturation in the presence of low doses of NAm or N'-Met-NAm did not occur with another inducer, dimethyl formamide (DMF). Two enzymes, NAD glycohydrolase and tissue transglutaminase, that are abundant in macrophages, were induced by RA but not by NAm. N'-Met-NAm decreased by about 75% the amount of endogenous (ADP-ribose)n in a selected fraction of chromosomal proteins which included histone H1 and the nonhistone high mobility group proteins. The results of this study support the concept that ADP-ribosylation of chromosomal proteins influences the regulation of human myeloid cell maturation.

Acyltransferases↗
PubMed1984

A pyrophosphatase which degrades NAD+ is located on the external surface of cultured fibroblasts: evidence that NAD+ is not extruded during treatment with N-methyl-N'-nitro-N-nitrosoguanidine.

The Harvey sarcoma virus-transformed derivative of normal rat kidney cells contains a very large membrane-associated NAD+ pyrophosphatase activity. Exogenous NAD+ was metabolized into NMN, demonstrating that the enzyme was located, at least in part, on the external surface of the cell. This external location of the pyrophosphatase was used to evaluate possible extrusion of NAD+ during treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG); i.e., extruded NAD+ would be degraded to NMN. NAD+ levels quickly decreased following MNNG addition. The nicotinamide moiety of degraded NAD+ was accounted for as nicotinamide in the culture medium, and no NMN was detectable. Thus, NAD+ was not extruded during MNNG treatment. Additional studies were done to determine which enzyme system was responsible for the rapid fall in NAD+ in these cells. MNNG treatment increased (ADP-rib)n synthetase activity; moreover, this increase in activity was sufficient to account for the loss in intracellular NAD+. Also, the decrease in NAD+ during treatment with MNNG was prevented by 3-aminobenzamide, an agent which inhibited (ADP-rib)n synthetase but not NAD+ glycohydrolase or pyrophosphatase. MNNG had no effect on NAD+ glycohydrolase or pyrophosphatase activities. The results are consistent with the proposal that NAD+ is not extruded but rather is rapidly metabolized by the nuclear (ADP-rib)n synthetase during MNNG treatment.

Animals↗
PubMed1984

Activated partial thromboplastin time of owl monkey (Aotus trivirgatus) plasma.

Owl monkey plasma samples produced short, reproducible activated partial thromboplastin times, similar to those obtained with samples from many other mammalian species. This was an apparent contradiction to an earlier report of long irreproducible activated partial thromboplastin times from owl monkey samples. The discrepant data could not be explained by differences in anticoagulants (citrate or oxalate), assay reagents (partial thromboplastin with either diatomaceous earth or ellagic acid), or activation incubation times (2, 5, or 10 minutes); nor could they be explained by differences in the monkeys' sex, age or previous experimental exposure to Plasmodium falciparum malaria.

Animals↗
PubMed1983

ADP-ribosylation of chromosomal proteins and mouse mammary tumor virus gene expression. Glucocorticoids rapidly decrease endogenous ADP-ribosylation of nonhistone high mobility group 14 and 17 proteins.

The relationship between endogenous ADP-ribosylation of chromosomal proteins and glucocorticoid-regulated mouse mammary tumor virus gene expression was investigated in cultured mouse mammary tumor cells. It was observed that glucocorticoids quickly decreased endogenous (ADP-ribose)n on the nonhistone high mobility group (HMG) 14 and 17 proteins. The half-time for this loss was 8 and 17 min, respectively, for the two proteins. (ADP-ribose)n on HMG 1 and 2 and on histone H1 was less susceptible to hydrolysis during glucocorticoid treatment. The rapid loss of (ADP-ribose)n from HMG 14 and 17 occurred in the same time frame as the induction of mouse mammary tumor virus RNA synthesis by glucocorticoids in these cells (Young, H. A., Shih, T. Y., Scolnick, E. M., and Parks, W. P. (1977) J. Virol. 21, 139-149). 3-Amino-benzamide, a specific inhibitor of (ADP-ribose)n synthetase, increased mouse mammary tumor virus RNA levels with an accompanying decrease in endogenous ADP-ribosylation of HMG 14 and 17. These results show that a decrease in endogenous ADP-ribosylation of HMG 14 and 17 is a consequence of glucocorticoid action and suggest that loss of (ADP-ribose)n from these proteins may be an important event in mouse mammary tumor virus gene expression.

Adenosine Diphosphate Ribose↗
PubMed1983

Increased membrane-associated nucleoside diphosphate kinase activity as a possible basis for enhanced guanine nucleotide-dependent adenylate cyclase activity induced by picolinic acid treatment of simian virus 40-transformed normal rat kidney cells.

A biochemical analysis of an increase in guanine nucleotide-dependent adenylate cyclase activity induced by treatment of cultured SV40-transformed normal rat kidney cells with picolinic acid is described. In purified membranes from drug-treated cells with an ATP regenerating system in assay, GTP- and GTP plus hormone-stimulated adenylate cyclase activities were increased, whereas basal and NaF-stimulated cyclase activities, and steady state rate with guanosine 5'-(beta, gamma-imino)triphosphate were essentially unaltered by drug treatment. In assay systems devoid of ATP regenerating system, the drug-induced increase in cyclase activity was seen with GDP as well as with GTP, it being larger with GDP than with GTP in terms of activity ratio, whereas such an increase was not observed with their analogs, guanosine 5'-O-(2-thiodiphosphate) or guanosine 5'-(beta, gamma-imino)triphosphate. Guanosine 5'-(beta, gamma-imino)triphosphate-stimulated from drug-treated membranes became less sensitive to the inhibition by GDP as shown by a rightward shift in inhibition curve, but this shift could not be reproduced with guanosine 5'-O-(2-thiodiphosphate). From these results, it was concluded that altered guanine nucleotide metabolism in membranes was involved. Neither the amount of guanine nucleotide-binding protein nor its related functions including GTPase activity were changed by drug treatment. However, we observed in the drug-treated cell membranes, an increase in activity of nucleoside diphosphate kinase, an additional factor which has been proposed to play a role in regulating adenylate cyclase by replenishing GTP near the guanine nucleotide binding site (Kimura, N., and Shimada, N. (1983) J. Biol. Chem. 258, 2278-2283). The altered features of adenylate cyclase with the natural guanine nucleotides induced by drug treatment were explained as a result of this enhanced nucleoside diphosphate kinase activity associated with the membranes.

Adenylyl Cyclases↗
PubMed1983

ADP-ribosylation of nonhistone high mobility group proteins in intact cells.

The ADP-ribosylation of nonhistone, high mobility group (HMG) proteins in intact cultured cells was investigated. Radioactively labeled adenosine was used as a precursor to detect (ADP-ribose)n on protein. A protein fraction enriched in HMG proteins and histone H1 was separated from RNA and DNA by CsCl density gradient centrifugation, 5% perchloric acid extraction, and CM-Sephadex C-50 column chromatography. Poly- and mono(ADP-ribose) were recovered following alkaline hydrolysis, and 5'-AMP and (2'-(5"-phosphoribosyl)-5'-AMP) were produced by phosphodiesterase treatment, indicating that the protein-bound radioactive material was (ADP-ribose)n. An average chain length of 1.5 to 1.8 was determined. Analysis of proteins by sodium dodecyl sulfate and acetic acid/urea polyacrylamide gel electrophoresis demonstrated that HMG 1, 2, 14, and 17 as well as histone H1 contained (ADP-ribose)n. Treatment of cells with 3-aminobenzamide, an inhibitor of (ADP-ribose)n synthetase, decreased endogenous ADP-ribosylation in both types of chromosomal proteins but that of HMG 14 and 17 was affected more.

Adenosine Diphosphate Ribose↗
PubMed1983

Nicotinamide and its derivatives increase growth hormone and prolactin synthesis in cultured GH3 cells: role for ADP-ribosylation in modulating specific gene expression.

To determine if changes in ADP-ribosylation of the chromosomal proteins can influence the expression of specific genes, the effects of compounds that influence this modification were investigated on the expression of the growth hormone (GH) and prolactin (Prl) genes in cultured rat pituitary (GH3) cells. The drugs tested, nicotinamide, N'-methylnicotinamide, 5-methylnicotinamide, 3-acetylpyridine, and 3-aminobenzamide, decrease ADP-ribosylation either by inhibiting (ADP-ribose)n synthetase and/or by decreaseing cellular levels of NAD+, the substrate for the enzyme. These drugs increased the synthesis of both GH and Prl and were synergistic in stimulating an increase in GH synthesis in response to triiodothyronine, a physiological regulator of GH synthesis. N'-methylnicotinamide, the most effective agent, was analyzed in detail; it increased the synthesis of both GH and Prl (maximally after 2 days) and increased their mRNAs in parallel; furthermore, this effect was reversible after drug removal. The effects of N'-methylnicotinamide were relatively specific for GH and Prl, since the synthesis of only a few other proteins was affected. These data suggest that changes in ADP-ribosylation can modulate the expression of specific genes.

Adenosine Diphosphate Ribose↗
PubMed1983

A Sensitive Autoradlographic Procedure for Factor VIII-Related Antigen in Canine Plasma.

A second-antibody autoradiographic technique was found to be suitable for visualization of precipitin arcs produced by the electroimmunoassay or crossed immunoelectrophoresis of factor VIII-related antigen in canine plasma. With the new autoradiographic procedure the electroimmunoassay was approximately ten times more sensitive than with the commonly used protein stain, Coomassie Blue R 250. Unlike earlier autoradiographic techniques, second-antibody autoradiography requires only commercially available reagents.

Journal Article↗
PubMed1983

Glucocorticoids increase GTP-dependent adenylate cyclase activity in cultured fibroblasts.

Glucocorticoid treatment of cultured fibroblasts increases intracellular cyclic AMP accumulation induced by isoproterenol or cholera toxin. This increase in agonist activity is not a direct action of glucocorticoids on cyclic AMP metabolism since about 2 days are necessary for maximal effect. Basal cyclic AMP levels are not changed. In membrane preparations, GTP-dependent adenylate cyclase activity is increased, basal adenylate cyclase activity is unchanged, and NaF-stimulated activity is decreased. The number of beta-adrenergic receptors is unchanged, but the affinity of receptor for the antagonist dihydroalprenolol is increased about 3-fold. This change in affinity is probably not responsible for the increased response to isoproterenol since the augmented response is noted at 0.1 mM isoproterenol, a concentration much larger than the apparent KD (about 5 nM). The results suggest that an alteration in some component in the GTP-dependent regulatory complex is responsible for the increase in agonist response.

Adenylyl Cyclases↗