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Biomedical subjects

M C Henderson

Publications and source records attributed to M C Henderson.

At least 55 records · Page 3Linked to original sources
PubMed1990

Immunological characterization of constitutive isozymes of cytochrome P-450 from rainbow trout. Evidence for homology with phenobarbital-induced rat P-450s.

Immunoglobulin G fractions (IgGs), isolated from rabbits immunized against hepatic cytochrome P-450 isozymes were used to investigate the immunochemical homology among trout P-450s and between trout and rat P-450s. The antigens used for immunization were five constitutive trout P-450s (LMC1 to LMC5), one beta-naphthoflavone (BNF)-inducible trout P-450 (LM4b), and one phenobarbital-induced rat P4500IIB1 (PB-B). In the enzyme-linked immunosorbent assay (ELISA), strong cross-reactivity was observed between anti-LMC2 IgG and P-450 LMC1, and between anti-LMC3 IgG and P-450 LMC4. There was little or no cross-reactivity of anti-LMC5 IgG with other trout P-450s. Trout P-450 LM4b was not recognized by any of the antibodies against constitutive trout P-450s. Antibodies to P-450 LMC1 and P450 LMC2 cross-reacted strongly with rat P450IIB1 and with proteins of PB-induced rat liver microsomes. Rat P450IA1 (BNF-B) did not cross-react with anti-LMC1 or anti-LMC2 IgG. These cross-reactions were essentially confirmed by immunoblot (Western blot) analysis. Western blots of PB-induced rat liver microsomes probed with anti LMC1 revealed two major immunoreactive proteins in the P-450 region, one of which co-migrated with rat P450IIB1. P450IIB1 itself cross-reacted strongly with anti-LMC1 IgG. In control rats, a single protein band cross-reacted poorly with anti-LMC1 IgG. Antibodies to LMC1 and LMC2 did not cross-react with rat P450IA1 in Western blots. The antigenic epitopes in rat P450IIB1 recognized by anti-LMC1 IgG and anti-LMC2 IgG are probably not located at or near the active site of the enzyme since these antibodies did not inhibit benzphetamine N-demethylase activity of P450IIB1 or of PB-induced rat liver microsomes. In general, our results demonstrate: (1) the presence of a significant homology between LMC1 and LMC2, and between constitutive trout P-450 (LMC1) and PB-induced rat P-450 (P450IIB1); and (2) distant homology between constitutive trout P-450s and constitutive rat P-450s or BNF-induced rat P-450s.

Animals↗
PubMed1990

Sexually deviant behavior and schizotypy: a theoretical perspective with supportive data.

Sexual offenses against adults and children continue to increase annually. Although theory and research have helped explain the personality functioning and motivation of sexual offenders, most treatment approaches have been found to have high recidivism rates and have failed to address the heterogeneity of sex offender populations. In the present paper, we utilize the growing literature on schizotypic personality organization to describe a subgroup of sex offenders. Data from the sex offender personality literature which indicates signs of thought disturbances among some sex offenders are reviewed in the context schizotypy. We conclude that treatment programs which address the heterogeneity of sex offenders and employ interventions to treat cognitive disturbances will likely result in greater efficacy.

Humans↗
PubMed1990

Influence of the Ah locus on the humoral immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: evidence for Ah-receptor-dependent and Ah-receptor-independent mechanisms of immunosuppression.

There are conflicting reports in the literature regarding the role of the Ah locus in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) immunotoxicity. The present studies have utilized two congenic strains of C57Bl/6 mice that differ only at this locus to assess its influence on TCDD-induced suppression of antibody responses. Mice were given a single oral dose of TCDD 2 days prior to challenge with sheep red blood cells (SRBC) or trinitrophenyl-lipopolysaccharide (TNP-LPS). The subsequent dose-dependent effects of TCDD on the amount of antibody produced by splenic plasma cells were measured using the hemolytic antibody isotope release assay. In addition, the relative importance of the Ah genotype of lymphoid versus nonlymphoid tissue was examined in adoptive transfer experiments. Aryl hydrocarbon hydroxylase (AHH) activity was significantly induced in Ahbb mice by a dose of 0.5 micrograms/kg TCDD and maximally induced by a dose of 2 micrograms/kg. Ahdd mice required 10-fold higher doses of TCDD to induce comparable levels of AHH. The degree of thymic involution and liver hypertrophy induced by TCDD was also influenced by the Ah genotype of the animals. Both Ahbb and Ahdd mice exhibited dose-dependent suppression of the anti-TNP response following TCDD exposure. The ID50 was 7.0 micrograms/kg in Ahbb mice and 30.8 micrograms/kg in Ahdd mice. Suppression of the antibody response to SRBC was also dependent on the Ah locus. The ID50 in Ahbb mice was 0.6 micrograms/kg TCDD. However, an apparent biphasic dose response for suppression of the anti-SRBC response in Ahdd mice suggested the involvement of an Ah-independent component of suppression as well. In adoptive transfer studies, lymphocytes were identified as an Ah-dependent component of the response. The Ah-independent component of the response was not identified, and could be either lymphoid or nonlymphoid in nature. The possibility that T helper cells represent the Ah-independent component is discussed.

Animals↗
PubMed1990

Role of the Ah locus in suppression of cytotoxic T lymphocyte activity by halogenated aromatic hydrocarbons (PCBs and TCDD): structure-activity relationships and effects in C57Bl/6 mice congenic at the Ah locus.

Previous studies have shown that the generation of cytotoxic T lymphocytes (CTL) following allogeneic tumor challenge is suppressed in Ah-responsive C57Bl/6 mice treated with a single oral dose of the toxic, Ah receptor-binding 3,4,5,3',4',5'-hexachlorobiphenyl (HxCB). The present studies have examined the specific role of the Ah receptor in this immunotoxic response by utilizing HxCB isomers of known, varied affinity for the Ah receptor as well as by comparing effects of high-affinity Ah receptor ligands (3,4,5,3',4',5'-HxCB and 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]) on the CTL response of mice that differ only at the Ah locus, that is, Ah-responsive (Ahbb) and Ah-nonresponsive (Ahdd) congenic C57Bl/6 mice. Correlative changes in thymic weight, serum corticosterone (CS) levels, and spleen cellularity were also measured. The potency of HxCB congeners (3,4,5,3',4',5'-; 2,3,4,5,3',4'-; 2,4,5,2',4',5'-) and 2,3,7,8-TCDD to suppress the CTL response, to reduce spleen cellularity, to cause thymic atrophy, and to elevate serum CS levels was directly correlated with the binding affinity of the congener for the Ah receptor. Furthermore, these parameters of immunotoxicity in Ahdd C57Bl/6 mice were significantly more resistant to alterations induced by either 3,4,5,3',4',5'-HxCB or 2,3,7,8-TCDD as compared to Ahbb C57Bl/6 mice. These results strongly support an Ah receptor-dependent immunotoxic mechanism in suppression of the CTL response following acute exposure to halogenated aromatic hydrocarbons.

Animals↗
PubMed1989

Purification and characterization of hepatic steroid hydroxylases from untreated rainbow trout.

Purification of cytochrome P450 from liver microsomes of untreated juvenile male rainbow trout yielded five fractions designated LMC1 to LMC5. All fractions, except LMC4 and LMC5, appeared homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and showed minimum molecular weights of 50,000 (LMC1), 54,000 (LMC2), 56,000 (LMC3), 58,000 (LMC4), and 59,000 (LMC5). Specific contents ranged from 2.8 (LMC3) to 14.9 (LMC5) nmol heme/mg protein. The catalytic activity of LMC1, LMC2, and LMC5 toward various substrates was examined. LMC2 exhibited the highest estradiol 2-hydroxylase activity and progesterone 16 alpha-hydroxylase activity. LMC2 also was most active in the metabolic activation of aflatoxin B1 (AFB1). In contrast, LMC5 was most active in catalyzing the 6 beta- and 16 beta-hydroxylation of testosterone and the 6 beta-hydroxylation of progesterone. LMC1 showed the highest lauric acid hydroxylase activity. The three isozymes tested had low activity (for LMC2 and LMC5) or no activity (for LMC1) toward benzphetamine or benzo[a]pyrene. Polyclonal antibodies to all five isozymes were raised in rabbits and the antibodies were used to examine the contribution of the P450s to microsomal enzyme activities. The results of microsomal enzyme inhibition studies with polyclonal antibodies showed that anti-LMC2 IgG significantly inhibited the oxidative metabolism of testosterone, lauric acid, AFB1, and benzphetamine. Anti-LMC5 IgG inhibited the oxidation of progesterone, estradiol, benzo[a]pyrene, and benzphetamine. Anti-LMC1 IgG slightly inhibited the microsomal hydroxylation of lauric acid. Anti-LMC3 and anti-LMC4 IgG did not inhibit any of the measured microsomal enzyme activities. These findings suggest that individual constitutive isozymes of trout cytochrome P450 have well-defined contributions to the microsomal metabolism of steroids, fatty acids, and xenobiotics.

Animals↗
PubMed1989

Endemic fluorosis with spinal cord compression. A case report and review.

We report a case of spinal cord compression in a Mexican immigrant due to vertebral osteosclerosis from chronic fluoride intoxication. Endemic fluorosis is acquired through drinking water. Groundwater sources with high fluoride content occur worldwide. The epidemiology, metabolism, and clinical features of fluorosis are reviewed. Greater physician awareness of this entity is important to identify correctly patients with this unusual and potentially devastating clinical disorder.

Aged↗
PubMed1987

Effects of polychlorinated biphenyls on porphyrin synthesis and cytochrome P-450-dependent monooxygenases in small intestine and liver of Japanese quail.

The effects of acute exposure to polychlorinated biphenyls (PCBs) on porphyrin synthesis and cytochrome P-450-dependent monooxygenases in the small intestine and liver were studied in male Japanese quail. The birds were dosed orally with the PCB mixture, Aroclor 1242, or the individual PCB isomers, 2,4,2',4'-tetrachlorobiphenyl (2-TCB) and 3,4,3',4'-tetrachlorobiphenyl (3-TCB), and were killed 48 h later. All the PCB compounds caused a significant increase in porphyrin content and delta-aminolevulinic acid synthetase (ALA-S) activity in the small intestine and liver. Increases in porphyrins were greater in the small intestine than in liver. However, a smaller increase in ALA-S activity occurred in the small intestine than in liver, suggesting that ALA-S induction is not a major mechanism for the increased porphyrin content of small intestine. All the test compounds significantly increased the cytochrome P-450 content of liver. In the small intestine, cytochrome P-450 content was increased by Aroclor 1242 and 2-TCB but not by 3-TCB. The activity of 7-ethoxyresorufin O-deethylase, however, was increased by all test compounds in both liver and small intestine. In contrast, there was a striking difference between small intestine and liver in the induction of 7-ethoxycoumarin O-deethylase (ECOD) activity by Aroclor 1242. In the liver, ECOD activity was unchanged or decreased, but in the small intestine, ECOD activity increased linearly with dose. No tissue difference in ECOD activity was observed after treatment with 2-TCB or 3-TCB. These findings suggest that acute exposure to a given PCB results in marked differences between small intestine and liver in porphyrin metabolism and in the induction of cytochrome P-450 isozymes and associated monooxygenases.

Animals↗
PubMed1986

Regional blood flow responses to stimulation of the subthalamic locomotor region.

Recent studies have suggested that descending central command from an area in the diencephalon (subthalamic locomotor region - STLR) is involved in the control of ventilation, arterial pressure and heart rate during exercise. The purpose of this study was to determine if electrical activation of the STLR in anesthetized cats elicits changes in regional blood flow and vascular resistances similar to those evoked by exercise. Therefore, organ blood flows (radioactive microsphere technique), arterial pressure (AP), heart rate (HR), and respiratory output (quantified from phrenic nerve activity) were recorded during resting conditions and during STLR stimulation. Stimulation of the subthalamic locomotor region produced increases in AP, HR and respiratory output similar to those reported previously. These changes were accompanied by increased blood flow to the heart, diaphragm and limb skeletal muscles. A concomitant decrease occurred in blood flow to the kidneys. In addition, the vascular resistances of the intestines, gallbladder and stomach increased. These vascular and respiratory responses are similar to those occurring during static exercise in conscious cats.

Animals↗
PubMed1986

Effects of hypothalamic lesions on the cardiorespiratory responses to muscular contraction.

Recent studies have suggested that descending central command from a hypothalamic site (subthalamic locomotor region) is involved in the control of the respiratory and cardiovascular systems during exercise. The purposes of this study were to determine if this hypothalamic area provides tonic drive to the cardiorespiratory systems and modulates the cardiorespiratory responses to static muscular contraction. Anesthetized cats were studied before and after bilateral electrolytic lesioning of the subthalamic locomotor region. Muscular contraction was evoked by stimulation of the L7-S1 ventral roots. Bilateral hypothalamic lesions produced a fall in resting levels for respiratory frequency, minute ventilation, heart rate and arterial pressure. The lesions did not alter the significant increases in arterial pressure and minute ventilation produced by muscular contraction. However, larger heart rate and respiratory frequency responses to muscular contraction occurred post-lesion. We conclude that this area of the hypothalamus provides tonic drive to the cardiorespiratory systems. Furthermore, the subthalamic locomotor region may participate in the modulation of some cardiorespiratory responses to neural feedback from contracting muscles.

Animals↗
PubMed1985

Dietary butylated hydroxyanisole reduces covalent binding of acetaminophen to mouse tissue proteins in vivo.

Covalent binding of acetaminophen (APAP) metabolites to mouse liver and kidney proteins was significantly decreased by prior consumption of diets containing 0.75% butylated hydroxyanisole (BHA). However, dietary BHA did not influence the covalent binding of APAP-derived radioactivity to liver microsomal protein in vitro. These findings suggest that BHA has no effect on monooxygenases involved in the conversion of APAP to reactive metabolites in vivo. The decreased covalent binding in vivo may be ascribed to the increased concentration of reduced glutathione (GSH) in liver and kidney following BHA consumption.

Acetaminophen↗
PubMed1984

Hexachlorobenzene-induced porphyria in Japanese quail. Effect of pretreatment with phenobarbital or beta-naphthoflavone.

In an effort to determine the role that metabolism by the cytochrome P-450 system plays in the development of hexachlorobenzene (HCB)-induced porphyria, Japanese quail were pretreated with either beta-naphthoflavone (BNF) or phenobarbital (PB) and then treated with HCB. PB or BNF pretreatment appeared to have no effect on the response of quail hepatic enzymes to HCB. There were no differences between the two groups in either the content of cytochrome P-450 or the activities of NADPH-cytochrome c reductase, glutathione transferase (microsomal or cytosolic), ethoxycoumarin-O-deethylase or ethoxyresorufin-O-deethylase following HCB treatment. These pretreatments did, however, markedly influence the development of porphyria in quail. BNF-treated birds had higher delta-aminolevulinic acid-synthetase (ALA-S) activities and developed porphyria much more rapidly than birds treated with HCB alone. Birds pretreated with PB did not exhibit porphyria even following 10 days of HCB. Although the ALA-S activities in this group were elevated slightly following HCB, they were about one-half of those seen in the BNF-pretreated HCB-treated group. These results may reflect a difference between the PB and BNF groups in the production of a porphyrogenic metabolite of HCB.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1984

Influence of tansy ragwort (Senecio jacobaea), dietary copper, and feed restriction on the subcellular distribution of minerals in rat liver.

Young male rats were pair-fed diets containing 0 or 5% tansy ragwort (TR), with each diet containing 0 or 50 micrograms/g copper. Other animals given TR-free diets were also maintained as ad libitum controls. After 5 weeks of feeding these diets, the rats were killed for the determination of the trace metal contents of liver fractions. TR with no dietary copper supplement increased the calcium content of all hepatic fractions except nuclei and debris, but had no effect on the subcellular concentrations of copper, zinc, or iron. When 50 micrograms/g copper was included in the TR diet, the subcellular distribution of copper, iron, and calcium was altered. This alteration was shown by an increase (as compared to pair-fed controls given copper-supplemented diet with no TR) in the copper content of all fractions except cytosol, the iron content of all fractions, and the calcium content of mitochondria, microsomes, lysosomes, and cytosol. Feed restriction (pair-fed versus ad libitum controls) using diets with no additional copper produced an increase in the copper and calcium contents of mitochondria; the copper, zinc, and calcium contents of cytosol; and the calcium content of lysosomes. Addition of 50 micrograms/g copper to the diets abolished these effects of feed restriction. These findings suggest that the subcellular distribution of copper, zinc, iron, and calcium in rat liver is subject to perturbation by pyrrolizidine alkaloid-containing diet, dietary copper, and feed restriction.

Animals↗
PubMed1984

Effects of chlorobenzenes on hepatic porphyrin and drug metabolism in chick embryo and day-old chick.

Administration of monochlorobenzene (MCB), p-dichlorobenzene (DCB), or 1,2,4-trichlorobenzene (TCB) at single doses of 800 mg/kg produced an increase in the total porphyrin content of liver of day-old chicks. Porphyrinogenic activity was higher in DCB- and TCB-treated chicks than in MCB-treated chicks. Administration of any of these compounds to chick embryos (40 mg/egg) failed to produce an induction of liver porphyrins. TCB enhanced the excretion of porphyrin in bile of chicks but not of chick embryos. In day-old chicks TCB increased hepatic cytochrome P-450 levels and the activity of 7-ethoxyresorufin deethylase. However, 7-ethoxycoumarin deethylase activity was decreased while cytosolic glutathione S-transferase activity was unchanged. These results point out the differential response of chick embryos and day-old chicks to chlorobenzene-induced changes in porphyrin metabolism as well as the differential induction of microsomal monooxygenases in chicks by TCB.

Animals↗
PubMed1983

Protective role of dietary butylated hydroxyanisole against chemical-induced acute liver damage in mice.

Prior consumption of a diet containing the food antioxidant, butylated hydroxyanisole (BHA), by female mice prevented the development of or minimized the acute liver damage caused by monocrotaline, acetaminophen, or bromobenzene. In contrast, neither the incidence nor the severity of carbon tetrachloride-induced hepatotoxicity was affected by dietary BHA. Hepatotoxicity was judged by plasma alanine aminotransferase and aspartate aminotransferase levels, hepatic cytochrome P-450 content, and liver histology. The protective effect of BHA against acetaminophen-induced hepatotoxicity was not demonstrated in male mice. The observed protection by dietary BHA against acetaminophen- and bromobenzene-induced hepatotoxicity was associated with the increase of liver glutathione. It is concluded that the protective action of BHA is dependent upon the nature of the toxic agent.

Animals↗
PubMed1983

Differential induction of hepatic drug metabolizing enzymes in Japanese quail by 1,2,4-trichlorobenzene.

The effects of single oral administration of 1,2,4-trichlorobenzene (TCB), 200, 400, 800 or 1600 mg/kg, and of daily oral administration of TCB, 400 mg/kg, for 3 consecutive days, on components of the microsomal monooxygenase system, glutathione, and the activities of cytosolic glutathione S-transferase and microsomal epoxide hydrolase in Japanese quail liver were studied. Cytochromes P-450 and b5 contents of liver microsomes and the activities of 7-ethoxyresorufin deethylase (7-ERD) and glutathione S-transferase were significantly increased 1 day after administration of single doses of TCB. Liver GSH and 7-ethoxycoumarin deethylase (7-ECD) activity were unchanged. Microsomal epoxide hydrolase activity was significantly decreased at TCB doses above 400 mg/kg. Increases in cytochromes and activities of 7-ERD and glutathione S-transferase were also seen following the 3-day administration of TCB, 400 mg/kg. In addition, liver GSH and the activity of NADPH-cytochrome c reductase were significantly increased whereas 7-ECD was significantly decreased by the 3-day treatment. These findings indicate that in Japanese quail, TCB is an inducer of 7-ERD and glutathione S-transferase but not of 7-ECD and epoxide hydrolase.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1983

Studies on the porphyrinogenic action of 1,2,4-trichlorobenzene in birds.

The porphyrinogenic action of 1,2,4-trichlorobenzene (TCB) was examined in 17-day-old embryos, day-old chicks, 18-day-old chickens and adult Japanese quail. The quail was found to be the most sensitive species towards TCB induced porphyria whereas the chick embryo was totally non-responsive. The liver porphyrins of Japanese quail were increased in a dose-dependent manner 1 day after TCB. Elevation in porphyrin levels in quail was associated with comparable increases in delta-aminolevulinic acid synthetase (ALA-S) activity 1 day after TCB treatment. In contrast, ferrochelatase activity was found to be unchanged 1 day after TCB. Multiple administration of TCB produced only a slight increase in liver porphyrin levels and ALA-S activity in quail. However, there was a marked induction in ferrochelatase activity suggesting increased porphyrin turnover. Liver glutathione and glutathione S-transferase activity were also significantly increased following repeated administration of TCB in quail, which could indicate an enhancement of detoxication of reactive metabolites of TCB. Thus, it is suggested that the inability of low multiple doses of TCB to cause porphyria in Japanese quail may be related to the low responsiveness of ALA-S but high inducibility of ferrochelatase liver GSH and glutathione S-transferase.

Animals↗