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T Gessner

Publications and source records attributed to T Gessner.

At least 37 records · Page 2Linked to original sources
PubMed1983

A comparison of self-devaluation and somatic suggestion content in depressive mood manipulation.

The Velten Mood Induction Procedure (VMIP), often used to manipulate depressive mood, has its effectiveness attributed to the self-devaluative content of its statements; this finding supports cognitive theories of depression. Recent research has suggested that somatic content is more important than self-devaluation content in producing depressive mood variations. To study this using the VMIP, a neutral condition and two modified depression conditions were used: Somatic and self-devaluation (N = 302). The results indicate that self-devaluative statements resulted in significantly more depressed affect than neutral Ss, but no more than somatic statements; this latter group, however, did not differ from neutral Ss. The results of the previous research indicating the importance of the somatic suggestion manipulations as having more influence than negative self-evaluative statements is questioned.

Adult↗
PubMed1983

A simplified method for determination of daunorubicin, adriamycin, and their chief fluorescent metabolites in human plasma by high-pressure liquid chromatography.

A simple method was developed for the routine monitoring of daunorubicin (DR) or adriamycin (ADR) and of their chief fluorescent metabolites in plasma of cancer patients. The plasma samples were treated with ethanol: hydrochloric acid mixture, following which the drug and its metabolites, released to the 40,000 g supernatant, were analyzed by HPLC. A mu-bondapak-phenyl column was used and an isocratic mobile phase consisting of acetonitrile in 0.1 M ammonium-formate buffer at pH 4.0. Average recovery of all the tested compounds within the concentration range of 17-3,450 pmol/ml plasma was 108 +/- 5% (mean +/- SD). The method was applied to analyses of plasma samples of several patients treated with DR or ADR. At 3 h after treatment with a DR dose of 45 mg/m2 or 60 mg/m2, daunorubicinol was the major metabolite and its concentrations were 46-270 or 85-305 pmol/ml, respectively; the unchanged drug was present at concentrations of 16-99 or 30-101 pmol/ml, respectively. Deoxydaunorubicinolone and deoxydaunorubicinone were detected at concentrations ranging from 0 to 89 pmoles/ml in the plasma of some patients. Plasma of patients treated with ADR (30 mg/m2) contained adriamycinol as the main detectable metabolite, but at 3 h after treatment its concentration was usually lower than that of the unchanged drug (22 +/- 9 vs 53 +/- 16 pmol/ml). Traces of 7-deoxyaglycones were detected in some plasma samples.

Chromatography, High Pressure Liquid↗
PubMed1983

Formation of glucuronide, sulphate and glutathione conjugates of benzo[a]pyrene metabolites in hepatocytes isolated from inbred strains of mice.

Metabolism of benzo[a]pyrene (BP) was studied in mouse hepatocytes isolated from uninduced animals of C57BL/6 Jacobs (B6) and C3Hf/HeHa (C3) inbred strains. Conjugates with sulphate, glucuronate and glutathione were the major products of BP biotransformation in the intact cells. Their formation was measured by determining the radioactivity incorporated from [3H]BP into the appropriate metabolite, after separation on silica gel t.l.c. plates. The conjugates were identified by their susceptibility to the action of specific degrading enzymes, arylsulphatase, beta-glucuronidase and gamma-glutamyltransferase. Effects of inhibitors of conjugation were also examined. D-Galactosamine and diethyl maleate caused approximately 50% inhibition of the formation of glucuronide and glutathione derivatives of BP, respectively. The effect of salicylamide was less specific, besides an 88% decrease in sulphation of BP metabolites, a 40% decrease in the formation of glutathione conjugates was observed in the presence of this inhibitor. In hepatocytes of B6 mouse, all the above three types of BP conjugates were formed in almost equimolar quantities. The total formation of BP conjugates was 42% higher in B6 hepatocytes than in those of C3 strain. The most significant difference (1.7-fold) was in the production of BP glucuronides, despite an absence of observable differences between these mouse strains in the activity of microsomal UDP-glucuronosyltransferase and in the rate of 1-naphthol conjugation in isolated hepatocytes. Simultaneously, 2.5-fold higher accumulation of unconjugated BP metabolites was observed in the hepatocyte suspension of B6 than C3 strain and a 1.4-fold higher activity of aryl hydrocarbon hydroxylase in hepatic microsomes of this strain. The unconjugated metabolites of BP were separated into four major fractions by h.p.l.c. The retention times of the metabolites corresponded to trans 9,10-diol; trans 7,8-diol; 9-hydroxy- and 3-hydroxy-BP. Despite quantitative differences between B6 and C3 strains of mice in BP metabolism, the same degree of covalent binding of BP metabolites to cellular DNA, was observed. The results indicate a relatively high capacity of hepatocytes from uninduced mice for conjugation of BP metabolites. Hepatocytes isolated from various strains of mice, should be useful in elucidating the role of numerous factors in metabolism and biologic activity of BP and related carcinogens.

Animals↗
PubMed1982

Absence of seasonal variation in antipyrine metabolism.

The induced activity of aryl hydrocarbon hydroxylase (AHH), measured by the metabolism of benzo[a]pyrene to fluorescent products in cultured human lymphocytes, shows a strong seasonal variation. The in vivo metabolism of antipyrine, which is also catalyzed by microsomal cytochrome P-450-dependent monooxygenases, has been reported to be correlated with AHH inducibility in human lymphocytes. To determine whether antipyrine metabolism also showed seasonal changes, we measured antipyrine half-life (t 1/2) in 10 nonsmokers and eight smokers at the two times of the year that correspond to the high and low peaks of inducible AHH activity as measured in lymphocytes. The mean antipyrine t 1/2 determined in all 18 subjects in summer was almost identical to that found in winter (mean +/- SEM = 10.90 +/- 0.65 and 10.96 +/- 0.78 hr). AHH activity in cultured human lymphocytes from the nonsmoking subjects was determined in control and 3-methylcholanthrene-induced cells to obtained inducibility ratios of 4.2 +/- 0.56 (SEM) in the summer and 1.4 +/- 0.14 (SEM) in winter. These results indicate that the seasonal variation in AHH inducibility in human lymphocytes is not reflected by a corresponding seasonal variation in antipyrine metabolism in vivo.

Adult↗
PubMed1982

Nuclear membrane-bound UDPglucuronosyltransferase of rat liver.

Some properties of rat liver nuclear membrane-bound UDPglucuronosyltransferase were compared with those of the endoplasmic reticulum bound enzyme. The activity of nuclear membrane-bound UDPglucuronosyltransferase was stimulated only about 1.5-fold by Lubrol WX. Under the same conditions microsomal UDPglucuronosyltransferase was, as usual, highly activated (up to 10-fold), when 4-nitrophenol was the acceptor of glucuronic acid. Specific activities of the detergent-activated enzyme were similar in microsomal and nuclear membrane preparations, when the following aglycone substrates were used: 4-methylumbelliferone, 4-nitrophenol, 1-naphthol, phenolphthalein, and testosterone. Apparent Km values for UDP-glucuronic acid ranged between 0.15-0.25 mM for glucuronidation of 4-nitrophenol and 1-naphthol, by either Lubrol WX activated or non-activated, nuclear membrane-bound UDPglucuronosyltransferase. These values were comparable to those found for detergent activated microsomal enzyme. The results show a similarity in behavior of detergent-activated UDPglucuronosyltransferase regardless of subcellular membrane source and, therefore, suggest the association of the same glucuronosyltransferase with nuclear membrane and endoplasmic reticulum. A possible significance of the presence of high activity of this enzyme in nuclear membrane is discussed.

Animals↗
PubMed1982

Enzymatic properties of human glucuronyltransferase and a sensitive method for its assay in a stable B lymphocyte cell line.

Properties of lymphocyte glucuronyltransferase were studied in homogenates of SN1006 cells. A sensitive assay procedure for lymphocyte glucuronyltransferase was developed utilizing radioactive testosterone as the acceptor substrate and TLC for separation of the metabolite. The method is capable of detecting picomolar quantities of the product. The enzyme activity exhibited a broad pH optimum, and was subject to activation by the detergent Lubrol WX and Mn++ ions. The activity conformed to the Michaelis-Menten kinetics giving apparent Km values of 0.8 mM and 11 microM, for UDPGA and testosterone, respectively. 4-Methylumbelliferone, a-naphthol and p-nitrophenol behaved as competitive inhibitors of testosterone glucuronidation. The results indicate that the method could be used for genetic studies of human lymphocyte glucuronyltransferase, and that the enzyme is of consequence in detoxication of exogenous as well as endogenous substrates.

B-Lymphocytes↗
PubMed1982

Body residue and metabolism of adriamycin and daunorubicin in control and phenobarbital-pretreated mice.

1. Metabolism of adriamycin (ADR) and daunorubicin (DR) was investigated in DBA/2Ha mice after i.p. injection and compared with that in phenobarbital-pretreated animals. At 24 h after drug administration 83% of ADR and 67% of DR derived fluorescence were recovered from cadavers and excreta. Destruction of anthracyclines in excreta to non-fluorescent materials could be partly responsible for the low recoveries. 2. ADR was metabolized to a limited extent in mice. At 24 h 70% dose was detected as the unchanged drug and only 13% as its deoxyaglycones. 3. DR was metabolized more extensively. At 24 h 29% of the dose was as the unchanged drug, while 32% was present as daunorubicinol (DROL) and 16% as aglycones. Phenobarbital did not significantly affect these parameters. 4. In phenobarbital-pretreated mice there was a marked increase in the amount of ADR or DR aglycones in the liver, and a decrease in the levels of unchanged ADR or DR.

Animals↗
PubMed1982

Re-investigation of the presence of UDP-glucuronosyltransferase in rat liver mitochondria.

Specific activities of UDP-glucuronosyltransferase and glucose-6-phosphatase, a marker enzyme of endoplasmic reticulum, were measured in mitochondria and microsomes. In mitochondria the specific activity of UDP-glucuronosyltransferase represented only 7-11% of that found in microsomes, when measured in the presence of various aglycone substrates, including 4-nitrophenol, 4-methylumbelliferone, 1-naphthol, phenolphthalein, testosterone and 17 beta-estradiol. Similarly, the specific activity of glucose-6-phosphatase in mitochondrial preparations was about 80% of that found in microsomes. In conclusion, it seems that in rat liver the UDP-glucuronosyltransferase activity associated with mitochondrial fractions reflects the presence of membrane fragments derived from endoplasmic reticulum, rather than mitochondrial location of this enzyme.

Animals↗
PubMed1982

On the functional heterogeneity of UDP-glucuronyl transferase of mouse liver microsomes.

Fractionation of sodium cholate solubilized microsomes from mouse liver on Sepharose CL-48 yielded three protein peaks with UDP-glucuronyltransferase activities. Of these three peaks, only peak II contained activities towards all the substrates tested: p-nitrophenol, 1-naphthol, morphine, testosterone and estrone. These glucuronyltransferase activities could not be dissociated by further chromatography on DEAE-Sepharose CL-6B and isoelectric focusing. The results show the presence of a functional form of glucuronyltransferase with a wide substrate specificity, and indicate that in addition, other forms with narrower studied specificities may also be present in mouse liver microsomes.

Animals↗
PubMed1981

Substrate specificity of human UDP-glucuronyltransferase in cultured lymphocytes.

1. This study establishes the presence of UDP-glucuronyltransferase activity for non-steroidal as well as steroidal substrates, in cultured human B-lymphocytes. Glucuronidation of alpha-naphthol and testosterone was demonstrated in homogenates of two cell lines, SN1006 and RPMI-1788, and that of phenolphthalein, 4-methylumbelliferone, p-nitrophenol and estradiol in the cell line with the higher glucuronyltransferase activity, SN1006. 2. Kinetic studies of testosterone glucuronidation in homogenates of both cell lines revealed a similarity in the behaviour of glucuronyltransferase of these cells. Thus, comparable apparent Km values for UDPGA (0.63 mM) and for testosterone (14 microgram) were observed, although apparent maximal velocities, Vmax, differed several-fold (3.0 versus 0.55 pmol/10(6) cells per min, in SN1006 and RPMI-1788 cells, respectively). 3. Kinetic studies of glucuronidation of testosterone, estradiol, phenolphthalein, alpha-naphthol, 4-methylumbelliferone, and p-nitrophenol yielded comparable apparent Km values for UDPGA (0.56-0.67 mM), suggesting that the same, or similar, glucuronyltransferase(s) catalyse(s) glucuronidation of this wide range of substrates in lymphocytes. This was reinforced by the observation of competitive inhibition of testosterone glucuronidation by alpha-naphthol (Ki 0.25mM), 4-methylumbelliferone (Ki 0.8mM) and p-nitrophenol (Ki 0.8 mM). Thus, lymphocyte glucuronyltransferase activity with a broad substrate specificity, for steroidal and non-steroidal aglycones, is indicated.

Cell Line↗
PubMed1981

Competition by meperidine for the organic cation renal excretory system.

Renal tubular excretory transport of meperidine was studied using the Sperber preparation in chickens. When urine samples from infused and uninfused kidneys were analyzed for meperidine by gas chromatography, meperidine was always present in greater amounts in the urine from the infused kidney, demonstrating active tubular excretion. Meperidine at an infusion rate of 1 mumole/min, also inhibited the excretion of the organic cations choline and acetylcholine, indicating occupation of the renal organic cation excretory system in the chicken.

Acetylcholine↗
PubMed1980

Mechanism for gastric accumulation of meperidine and effect of antacid.

The effect of hydrogen ion activity (pH) on the degree of meperidine sequestration in gastric contents was studied in 15 patients. Those patients with higher gastric juice cH+ (lower pH) showed greater accumulation with time. At a cH+ more than 10,000 nmol/l, (pH < 5) concentration usually reached 100 micrograms/ml within the 60-minute period after administration of 200 mg of meperidine. When cH+ was less than 100 nmol/l (pH > 7) gastric concentrations remained low, being only slightly greater than those of plasma. Oral administration of antacid may be a practical method for preventing sequestration of meperidine in gastric juice.

Adult↗
PubMed1980

High-pressure liquid chromatographic analysis of benzo(a)pyrene metabolism by human lymphocytes from donors of different aryl hydrocarbon hydroxylase inducibility and antipyrine half-lives.

With high-pressure liquid chromatography (HPLC), lymphocytes from six human donors were evaluated for their ability to metabolize benzo(a)pyrene (BP). Donors whose aryl hydrocarbon hydroxylase (AHH) inducibility ratios ranged from 2.4 to 4.6 and whose antipyrine plasma half-lives ranged from 8 to 17 hr were examined. The BP metabolites identified were: 7,8-dihydrodiol, quinones, and 9-hydroxy and 3-hydroxy phenols. HPLC profiles of BP metabolites elaborated by uninduced (control) and benz(a)anthracene-induced lymphocytes were qualitatively similar among the six donors. A good correlation (r = 0.79) was found between known AHH inducibility ratios for the donors, as determined by the conventional fluorometric AHH assay, and induction of BP phenol production quantitated from HPLC data. HPLC results also indicated that the induction of benzo(a)pyrene-7,8-dihydrodiol, the proposed proximate carcinogenic form of BP, did not parallel BP phenol induction. Furthermore, the data also indicated a good negative correlation between AHH inducibility and the measurements of plasma antipyrine or urinary 4-hydroxyantipyrine half-lives (r = -0.88 or -0.91), respectively.

Antipyrine↗
PubMed1979

Cognitive correlates of sex-role identification.

This study examined sex role and its relationship to several cognitive variables. No relationship between these variables and sex role but a significant difference between males and females was found for only a perceptual-motor speed task. These findings may indicate that sex role is unrelated to cognitive style as measured here.

Adult↗