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J C Cook

Publications and source records attributed to J C Cook.

At least 73 records · Page 4Linked to original sources
PubMed1990

Creatine kinase: race-gender differences in patients hospitalized for suspected myocardial infarction.

Race-gender differences in creatine kinase values were studied in 647 consecutive patients admitted for suspected myocardial infarction. The lowest value in a serial set for each patient was used for group comparisons. Significant differences were found between Hispanic females and black males, using standard values. Using log creatine kinase values, significant differences were found among blacks, Caucasians, and Hispanics. Males had higher log creatine kinase values than females, but no differences were found between sexes within racial groups. Body surface area differences (significant between males and females) did not explain all of the racial-gender differences found. Reexamination of ranges of normality, taking into account race-gender differences, is strongly supported by these data.

Asian People↗
PubMed1989

Characterization of a specific binding protein for 2,3,7,8-tetrachlorodibenzo-p-dioxin in human thymic epithelial cells.

Specific toxic and biochemical responses elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in human thymic epithelial (TE) cells in culture are mediated by the TCDD receptor protein. Characterization of the physicochemical properties of the TCDD receptor in cytosol fractions from cultured human TE cells indicates that this protein is similar, but not identical, to the extensively studied receptor species present in mouse and rat liver. The human TCDD receptor sediments at 9.1 S on sucrose density gradients at 0 degrees, undergoes a temperature-dependent conversion at 20 degrees to a species sedimenting at 10.7 S, and partially dissociates in the presence of 0.4 M KCl, as judged by the appearance of a peak sedimenting at 5 S. Both the temperature- and salt-dependent changes in the observed physical properties of the human TCDD receptor are inhibited by sodium molybdate. Two molybdate-stabilized binding species can be resolved from TCDD specific binding isotherms to human TE cytosol. Under identical conditions, only a single TCDD specific binding component was detected in cytosol fractions from both mouse and rat liver. Mixing cytosol prepared from human TE cells with hepatic cytosol fractions from C57BL/6 mice revealed the presence of a heat-labile, trypsin-sensitive factor in human TE cells that inhibits TCDD specific binding to the murine hepatic receptor. Molybdate stabilized the mouse receptor against the actions of this human inhibitory factor. Molybdate also may stabilize the human TCDD receptor, as indicated by the 2- to 3-fold increase in total TCDD specific binding measured in human TE cytosol fractions in the presence of this metallo-oxyanion.

Adolescent↗
PubMed1987

An in vitro model for studying the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to human thymus.

A coculture system of human thymic epithelial (HuTE) cells and thymocytes (T lymphocyte precursors) has been established and characterized as an in vitro model for assessing the potential toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to human thymus. HuTE cells in culture were responsive to TCDD as judged by induction of the cytochrome P1-450 monooxygenase activities, 7-ethoxycoumarin O-deethylase (ECOD) and 7-ethoxyresorufin O-deethylase (EROD). Measurement of the responsiveness of thymocytes cocultured on TCDD-pretreated HuTE monolayers to the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA) indicated that TCDD can act directly on HuTE cells to suppress thymocyte maturation (at a concentration of 10 nM, TCDD produced a 25 to 50% inhibition of thymocyte responsiveness to Con A and PHA). Both the induction of cytochrome P1-450 monooxygenase activity (EC50 values approximately 1 nM) and immunosuppressive responses elicited by TCDD in HuTE cells were concentration-dependent and stereospecific (as judged by the relative activities of chlorinated dibenzo-p-dioxin and dibenzofuran isomers), indicating involvement of the Ah receptor which was detected in all HuTE strains examined. Initial characterization of these Ah receptor-mediated responses in several strains of HuTE cells indicated marked interstrain differences in maximally inducible ECOD and EROD activities which did not appear to directly correlate with measured concentrations of the cytosolic Ah receptor, and in certain strains examined, differences in sensitivity and magnitude were observed for TCDD-evoked immunotoxic responses but not always for the induction response. These data on the actions of TCDD on cultured HuTE cells suggest that human thymus is a target for TCDD and related halogenated aromatic compounds. In HuTE cells, measurement of either the Ah receptor concentration or of marker responses such as the induction of cytochrome P1-450 alone cannot provide an accurate quantitative assessment of susceptibility to TCDD-induced thymus toxicity.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1987

Immunosuppression following exposure to 7,12-dimethylbenz[a]anthracene (DMBA) in Ah-responsive and Ah-nonresponsive mice.

Recent reports suggest that the immunotoxicity of certain polycyclic aromatic hydrocarbons is associated with the Ah locus in mice. To test whether immunosuppression mediated by 7,12-dimethylbenz[a]anthracene (DMBA) is regulated by the Ah locus, several endpoints of immune function were measured in Ah-responsive B6C3F1 and Ah-nonresponsive DBA/2N and in Ah-congenic C57BL/6J (responsive B6-AhbAhd and nonresponsive B6-AhdAhd) mice dosed sc with up to 100 micrograms/g DMBA in corn oil. Some groups of B6C3F1 and DBA/2N mice were exposed to 100 micrograms/g benzo[a]pyrene (B(a)P) or 1 nmol 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for determination of hepatic microsomal monooxygenase activity. The body weights of all mice were unaffected by DMBA exposure, but thymus weights and spleen cellularity were decreased. Antibody plaque-forming cells (PFC) measured 4 days after iv sheep erythrocyte (SRBC) immunization were suppressed 99% in B6C3F1 and 96% in DBA/2 mice. Antibody PFC after in vitro immunization to SRBC were similarly suppressed 98% in both B6-AhbAhd and B6-AhdAhd Ah-congenic mice exposed to 100 micrograms/g DMBA. Responses to the T-cell mitogens concanavalin A and phytohemagglutinin were significantly suppressed in both B6C3F1 and DBA/2N strains, as was mitogenesis to bacterial lipopolysaccharide. The unidirectional mixed lymphocyte responses of the congenic strains were suppressed 76% in B6-AhbAhd and 85% in B6-AhdAhd, cytotoxic lymphocyte generation was suppressed 68% in B6-AhbAhd and 78% in B6-AhdAhd. The overall differences between immunosuppressive responses in splenocytes from B6-AhbAhd and B6-AhdAhd congenics were not significant. Induction of cytochrome P1-450, a marker of Ah responsiveness, was determined by 7-ethoxycoumarin O-deethylase monooxygenase activity in hepatic microsomes or splenocytes. This monooxygenase activity was not significantly increased in either B6C3F1 or DBA/2 mice exposed to DMBA, whereas B(a)P and TCDD exposure significantly induced enzyme activity in B6C3F1 hepatocytes. These data suggest that DMBA has an immunosuppressive action on murine splenocytes which is independent of the Ah locus and associated induction of cytochrome P1-450 xenobiotic-metabolizing enzymes.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Ah receptor: relevance of mechanistic studies to human risk assessment.

Studies of the toxic actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in numerous animal models and in human and animal cells in culture have established that the most characteristic pathologic lesions produced by this compound result from events initiated by the interaction of TCDD with a specific intracellular receptor protein, the Ah receptor. Although most research on the interaction of TCDD with the Ah receptor has focused on establishing involvement of this receptor complex in specific toxic responses, recent application of modern cell and molecular biology techniques is yielding new insights into the mechanism(s) of signal transduction. Elucidation of these mechanisms is essential for understanding the molecular basis of the cell and species specificity which is a hallmark of TCDD toxicity. This knowledge should provide the framework for development of a more toxicologically relevant risk assessment model.

Animals↗
PubMed1986

Sequence analyses of adipokinetic hormones II from corpora cardiaca of Schistocerca nitans, Schistocerca gregaria, and Locusta migratoria by fast atom bombardment mass spectrometry.

Structures of the second adipokinetic hormones (AKH II's) from three locust species have been assigned by fast atom bombardment mass spectrometry. The AKH II hormone is identical in two Schistocerca species, S. nitans and S. gregaria, but is different in Locusta migratoria. Both AKH II's are related to red pigment-concentrating hormone (RPCH) from prawns, Schistocerca AKH II being [Thr6]-RPCH and Locusta AKH II being [Ala6]-RPCH. Schistocerca AKH II is also bioactive in Locusta individuals.

Amino Acid Sequence↗
PubMed1986

Cytochrome P-450 induction by 3-methylcholanthrene and its antagonism by 2,2-dimethyl-5-t-butyl-1,3-benzodioxole.

Previous studies in this laboratory have shown 2,2-dimethyl-5-t-butyl-1,3-benzodioxole (DBBD) to antagonize 3-methylcholanthrene induction of cytochrome P-450 in Dub:ICR mice yet have no effect on phenobarbital induction. In the present experiments, C57BL/6 mice, an Ah responsive strain, produced a similar response under the same experimental conditions. The hypothesis that DBBD, although not a cytochrome P-450 inducer, competes with 3-methylcholanthrene for binding to the Ah receptor was tested. Using sucrose density gradients, the Ah receptor was measured in hepatic cytosol from Dub:ICR and C57BL/6 male mice. DBBD was unable to displace either 2,3,7,8-tetra-chlorodibenzo-p-dioxin or 3-methylcholanthrene from the Ah receptor, in vitro. However, in in vivo experiments, DBBD treatment of Dub:ICR mice caused Ah receptor depression at 6 and 24 hr with complete recovery in between, while 3-methylcholanthrene treatment caused a 2-fold Ah receptor reduction at 2 hr followed by complete recovery after 12 hr. When 3-methylcholanthrene and DBBD were coadministered, the depression of the Ah receptor was additive. DBBD-pretreated mice had a 2.25-fold reduction in Ah receptor level, effectively blocking the ability of 3-methylcholanthrene to increase the cytochrome P-450 content and either benzo[a]pyrene hydroxylase or ethoxyresorufin O-deethylase activities. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed that 3-methylcholanthrene induction of cytochrome P-450 was inhibited by DBBD pretreatment. Hence, although DBBD does not displace 3-methylcholanthrene from the Ah receptor in vitro, it does antagonize 3-methylcholanthrene induction of cytochrome P-450 and also reduces the amount of available receptor in vivo. This interaction may be due either to antagonism or to downregulation of the Ah receptor.

Animals↗
PubMed1986

Induction of cytochrome P-450 in congenic C57BL/6J mice by isosafrole: lack of correlation with the Ah locus.

Isosafrole induction of cytochrome P-450 was compared in congenic strains of C57BL/6J mice, one of which expresses normal levels of the Ah receptor [B6(Ahb)], and another that does not contain a measurable receptor concentration [B6(Ahd)]. Using sucrose gradient analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) binding, an Ah receptor concentration of 69.1 +/- 3.8 fmol/mg protein was measured in the hepatic cytosol from B6(Ahb) mice, while no receptor could be detected in the cytosol from B6(Ahd) mice. Isosafrole treatment (75 mg/kg X 3 days) increased the total hepatic microsomal cytochrome P-450 content to the same extent in the two congenic strains. The level of microsomal monooxygenase induction in the isosafrole-treated B6(Ahd) mice was greater than that of B6(Ahb) mice for ethylmorphine N-demethylase and isosafrole metabolite-complex formation, the latter a measure of cytochrome P2-450. In the case of 7-ethoxycoumarin O-deethylase only the isosafrole-treated B6(Ahd) mice had elevated microsomal activity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) also revealed a similar induction pattern for the two congenic strains, following isosafrole treatment. Thus, the isosafrole treated B6(Ahd) mice produced an equivalent or slightly larger induction of cytochrome P-450 than the B6(Ahb) mice, suggesting that there is no direct role for the Ah receptor in the regulation of these cytochrome P-450 monooxygenase activities by isosafrole.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1985

Patency rate of bifurcated aortic grafts: comparative analysis of woven versus knitted prostheses in the same patient.

To investigate the difference in patency rate between woven and knitted aortofemoral or aortoiliac prosthetic grafts, a special vascular prosthesis was manufactured with one limb of the graft knitted and the other, woven. The prosthesis was implanted in 143 consecutive patients with occlusive aortoiliac arteriosclerotic disease or aneurysms. Detailed statistical analysis failed to reveal any difference in the patency rate between the woven and knitted limbs of the grafts during an observation period ranging from one month to two years.

Aged↗
PubMed1984

2,2-Dimethyl-5-t-butyl-1,3-benzodioxole: an unusual inducer of microsomal enzymes.

Our previous studies have shown that 2,2-dimethyl-5-t-butyl-1,3-benzodioxole (DBBD), a methylenedioxyphenyl (MDP) analog in which the methylene hydrogens have been replaced by methyl groups, does not form an inhibitory complex with cytochrome P-450 nor induce this cytochrome. However, in the present experiments, DBBD-treated male Dub:ICR mice showed an increase in NADPH-dependent cytochrome c (P-450) reductase and epoxide hydrolase activity. This separation of cytochrome P-450 induction from the induction of epoxide hydrolase and NADPH-dependent cytochrome c (P-450) reductase appears to be unique among inducers of xenobiotic metabolizing enzymes. In similar experiments, mice were treated with phenobarbital + DBBD or 3-methylcholanthrene + DBBD and the following parameters were measured: cytochrome P-450 content; NADPH-dependent reduction of cytochrome c; ethylmorphine and benzphetamine N-demethylase; 7-ethoxycoumarin O-deethylase; benzo[a]pyrene hydroxylase; and ethoxyresorufin O-deethylase. The microsomal proteins were examined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE). Phenobarbital + DBBD treatment gave results which did not differ significantly from those obtained with phenobarbital alone. In contrast, cytochrome P-450 content and benzo[a]pyrene hydroxylase and ethoxyresorufin O-deethylase activities were less in mice treated with 3-methylcholanthrene + DBBD than in animals treated with 3-methylcholanthrene alone. SDS-PAGE confirmed that induction of cytochrome P-450 by 3-methylcholanthrene was reduced by DBBD, suggesting that the latter compound may be an antagonist to the Ah cytosolic receptor.

Animals↗
PubMed1984

Structures of two cockroach neuropeptides assigned by fast atom bombardment mass spectrometry.

Amino acid sequences have been assigned to two cockroach neuropeptides (greater than Glu-Val-Asn-Phe-Ser-Pro-Asn-Trp-NH2, M I, and greater than Glu-Leu-Thr-Phe-Thr-Pro-Asn-Trp-NH2, M II) by application of fast atom bombardment mass spectrometry, including high resolution and linked scan (metastable) studies. The peptides show considerable homology with two other invertebrate neuropeptides, adipokinetic hormone (AKH, from a locust) and red pigment concentrating hormone (RPCH, from a prawn), whose fast atom bombardment spectra were also studied. M I and M II are thus members of a family of structurally-related invertebrate neuropeptides.

Amino Acid Sequence↗
PubMed1983

Induction of cytochrome P-450 by methylenedioxyphenyl compounds: importance of the methylene carbon.

Induction of hepatic microsomal cytochrome P-450 in Dub:ICR male mice treated with phenobarbital, 3-methylcholanthrene, safrole, isosafrole, 5-tert.-butyl-1,3-benzodioxole (BBD), 2-methyl-5-tert.-butyl-1,3-benzodioxole (MBBD), and 2,2-dimethyl-5-tert.-butyl-1,3-benzodiozole (DBBD) was evaluated by measuring the cytochrome P-450 content, Type II:Type 1 binding ratio, ethylisocyanide pH equilibrium point, biphenyl 2- and 4-hydroxylase, ethylmorphine N-demethylase, ethoxyresorufin O-deethylase, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Safrole and isosafrole treatment of mice produced a phenobarbital-type induction. BBD, but not MBBD and DBBD, induced cytochrome P-450 and formed a Type III metabolite-cytochrome P-450 complex, in vitro and in vivo. SDS-PAGE revealed that DBBD does induce proteins other than cytochrome P-450. These data suggest that the methylene carbon plays an important role in cytochrome P-450 induction.

Animals↗
PubMed1983

Factors associated with successful vaginal delivery after cesarean section.

To assess obstetric parameters that would predict successful vaginal delivery in patients with prior cesarean sections, the perinatal records of 579 such patients were reviewed. Sixty-six percent of the patients (385) had elective repeat cesarean sections. Of the 194 patients who attempted vaginal delivery, three-fourths (148) had success. Perinatal parameters that were statistically significant indicators of success included: nonrecurrent indication for cesarean section, vaginal delivery either prior or subsequent to cesarean section, duration of labor less than 24 hours prior to cesarean section, infant's birth weight less than 4,000 gm and cervical dilatation greater than 4 cm on admission for attempted vaginal delivery.

Birth Weight↗
PubMed1981

Pyochelin: novel structure of an iron-chelating growth promoter for Pseudomonas aeruginosa.

Pyochelin, an endogenous growth promoter that solubilizes ferric iron, has been isolated from Pseudomonas aeruginosa, including clinical strains. The structure of pyochelin has been assigned as 2-(2-o-hydroxyphenyl-2-thiazolin-4-yl)-3-methylthiazolidine-4-carboxylic acid and is of a different type from those previously assigned to siderophores (siderochromes) from bacteria. The assignment rests on 1H and 13C NMR data, high-resolution (including field desorption) mass spectrometry, and spectroscopic properties of synthetic model compounds. Pyochelin is presumed to be biosynthesized from salicylic acid and two moles of cysteine.

Growth Substances↗
PubMed1980

Field desorption mass spectrometry in structural studies of polyene macrolide antibiotics: isolation and early identification of a pentaene macrolide antibiotic.

Isolation of a pentaene macrolide antibiotic (NSC-277813) from Streptomyces griseus (FCRC-21) fermentation broth is described. Using field desorption mass spectrometry and high resolution field desorption mass spectrometry on the intact and derivatized antibiotic and degradation products, the antibiotic was identified as fungichromin. The application of field desorption mass spectrometry in the identification of polyene antibiotics is discussed.

Antibiotics, Antineoplastic↗