Search PubMed⌕ Search

Biomedical subjects

C H Walker

Publications and source records attributed to C H Walker.

At least 91 records · Page 5Linked to original sources

The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain.

The effects of hyperthyroidism or hypothyroidism, alone or in combination with the tricyclic antidepressant desmethylimipramine (DMI), on brain beta-adrenergic and serotonin (5HT2) receptors were studied in adult male Sprague-Dawley rats. Intraperitoneal administration of T3 or T4 for 7 days increased the number of cortical beta-adrenergic and 5HT2 receptors. These increases were significant at levels of 250 micrograms/kg or above for both hormones. Neither thyroidectomy nor "reverse" T3 (rT3) (500 micrograms/kg) produced an effect on either receptor type. The down-regulation of beta-adrenergic receptors produced by daily subcutaneous injections of 20 mg/kg of DMI for 7 days was partially offset by concurrent administration of T4, whereas the down-regulation of 5HT2 receptors produced by the drug was not affected by concurrent administration of either T3 or T4. Hypothyroidism (thyroidectomy) did not significantly affect the adaptation of these receptor populations to DMI. As regards brain regions other than cortex, T4 (250 micrograms/kg) produced the same changes in hippocampus as in cortex, while thyroidectomy decreased beta-adrenergic receptors only in the cerebellum. Thyroxine also elevated 5HT2 receptors in the hippocampus; thyroidectomy caused a significant decrease in 5HT2 receptors in the striatum.

Animals↗

Hepatic metabolism of cyclodiene insecticides by constitutive forms of cytochrome P-450 from lower vertebrates.

1. Multiple forms of cytochrome P-450 were separated from the hepatic microsomes of untreated male rats, pigeons (Columbia livia), razorbills (Alca torda), puffins (Fratercula arctica), and rainbow trout (Salmo gairdnerii), using anion exchange chromatography and DEAE-cellulose. 2. In some cases cytochrome P-450 forms were further purified on hydroxylapatite and carboxymethyl-sephadex columns. 3. Considerable differences in the distribution of forms between these five species were evident from elution profiles on DEAE cellulose, and on analysis of the cytochrome P-450 containing pools by SDS-PAGE. 4. The metabolism of two organochlorine compounds, aldrin and the dieldrin analogue HCE, were studied in (a) intact microsomes and (b) reconstituted systems containing cytochrome P-450, from each of the five species. 5. In spite of their close structural similarity, significant differences were found between the two substrates in the distribution of catalytic activity between the cytochrome P-450 isozymes of each species.

Aldrin↗

Activities and toxicological significance of hepatic microsomal enzymes of the kestrel (Falco tinnunculus) and sparrowhawk (Accipiter nisus).

Activities of hepatic microsomal monooxygenase and epoxide hydrolase in sparrowhawks and kestrels were determined using organochlorine substrates. Monooxygenase activities were low in the kestrel and very low in the sparrowhawk compared to those in the male rat, down to environmentally realistic substrate concentrations. Epoxide hydrolase activities were very low in both species. These activities are discussed in relation to feeding ecology and susceptibility to organochlorine pollutants.

Animals↗

Modulation of gamma-aminobutyric acid uptake of rat brain synaptosomes by thyroid hormones.

The effects of thyroid hormones on gamma-aminobutyric acid (GABA) uptake were compared in homogenates and purified synaptosomes from rat cerebral cortex. L-triiodothyronine (T3) and L-thyroxine (T4), but not reverse T3(rT3), blocked GABA uptake in homogenates when hormone and labeled GABA were added to the system simultaneously. Similar effects were obtained when homogenates were preincubated with hormone and washed to remove free hormone before addition of GABA. A competitive inhibitor of neuronal GABA uptake, diaminobutyric acid (DABA), blocked GABA uptake when added with GABA, but not after preincubation and washing. In purified synaptosomes, T3, T4, and rT3 blocked GABA uptake when added simultaneously with GABA and also after preincubation and washing before addition of GABA, thus indicating that binding of hormones had occurred. Other experiments suggested that hormone binding was not at the GABA recognition site and that the effect of T4 was not dependent on conversion to T3.

Animals↗

Association of infant alimentary and respiratory illness with parental smoking and other environmental factors.

The incidences of alimentary and respiratory illnesses were observed during the first year of life in 1565 infants born in Tayside during 1980. Significant correlations (p less than 0.05) were found between each of these outcomes and parental smoking, maternal age, social class, method of infant feeding, and heating fuels. Multiple logistic regression indicated a significant independent effect of parental smoking was related separately to alimentary and to respiratory outcomes, the relative risks being of similar strength.

Age Factors↗

Low A-esterase activity in serum of patients with fish-eye disease.

The activity of HDL-associated paraoxonase in the lipoprotein fraction of serum from two patients with fish-eye disease (FED) was only 11% of the mean value for control subjects. Similarly, concentrations of apolipoproteins A-I and A-II in the serum of FED subjects were only 10% of those in normal subjects. Thus the ratio of enzyme activity to A-I and A-II is virtually the same in these two groups of subjects. This suggests that paraoxonase activity of the lipoprotein fraction is associated with one or both of these apolipoproteins.

Apolipoprotein A-I↗

Polyamines contribute to calcium-stimulated release of aspartate from brain particulate fractions.

The calcium-stimulated release of several neurotransmitters has been studied in crude synaptosomal preparations following accumulation of various radioactively labeled neurotransmitters or their precursors. The high affinity uptake of D-aspartate, gamma-aminobutyric acid (GABA) and dopamine was not modulated in the presence of 5 mM of difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase (ODC). Depolarization-induced calcium influx caused release of labeled compounds. In the case of D-aspartate, this process was inhibited by DFMO. This major inhibition was completely reversed in the presence of 0.5 mM putrescine, the product of ODC-mediated catabolism of ornithine. This effect could not be shown for the depolarization-related release of dopamine, GABA or acetylcholine. In our preparation, a direct effect of the depolarizing medium upon levels of synaptosomal ODC could not be demonstrated, and the 50 mM K+-stimulated entry of 45Ca into the synaptosomal fraction was not inhibited by DFMO. These data suggest that polyamines are involved in the regulation of neurotransmitter release within certain classes of neurons.

Animals↗

The hydration of sterically hindered epoxides by epoxide hydrolase of the rat and rabbit.

The hydration of the sterically-hindered epoxides dieldrin (HEOD) (1,2,3,4, 10,10-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-exo-1,4-endo-5,8- dimethanonaphthalene) and MME (1,2,3,4,9,9-hexachloro-1,4,4a,5,8,8a-hexahydro-6-methyl-6,7 epoxy 1,4-methanonaphthalene) was studied in pig and rabbit liver microsomes, and in apparently homogeneous preparations of epoxide hydrolase purified from liver microsomes of the rat and rabbit. A non-hindered substrate, HEOM (1,2,3,4,9,9-hexachloro-1,4,4a,5,6,7,8,8a-octahydro exo-6,7 epoxy-1,4 methano naphthalene) was used to assay both the enzyme preparations and the microsomes for epoxide hydrolase activity. The purified enzymes had more stable activity when incorporated into suspensions of phospholipid derived from rat liver microsomes than when used alone, so this preparation was used for long-term incubation with HEOD and MME. Activity towards the three substrates followed the sequence HEOM much greater than MME much much greater than HEOD, in the approximate ratios 1.5 X 10(6):10(4) activity towards dieldrin being only 0.0065-0.052 pmol/mg prot/min. The sole product of MME hydration was identified as a trans diol. The only product identified in the case of HEOD hydration by microsomes or enzyme preparations was the trans diol so there was no evidence for a significant metabolic pathway through the cis diol which is mediated by epoxide hydralase.

Animals↗

Distribution of paraoxon hydrolytic activity in the serum of patients after myocardial infarction.

The activity of paraoxonase in serum was found to be bimodally distributed, both in a control group and in a group of patients who had suffered myocardial infarction. Activity in the myocardial infarct group was significantly lower than in the control group. Low paraoxonase activity in serum may provide an indication of susceptibility to the development of coronary heart disease.

Aryldialkylphosphatase↗

The Tayside infant morbidity and mortality study: effect on health of using gas for cooking.

The relation between respiratory illness and the use of gas for cooking was examined from data on 1565 infants born to mothers who were primigravidas living in Dundee in 1980. Episodes of, and admissions to hospital for, respiratory illness were recorded during the first year of life. Both admissions and episodes were more common in infants from families using gas for cooking or heating than in infants from families using any other type of cooking or heating, but the differences were not significant. Results from this and other studies show that there is probably a small relation between respiratory illness and the use of gas appliances without a flue. To show convincingly whether such a relation exists might require a survey of 18 000-23 000 subjects. Respiratory illness was, however, strongly and positively related to parental smoking, a finding that is often made even in small studies.

Adolescent↗

The separation of sheep and human serum "A"-esterase activity into the lipoprotein fraction by ultracentrifugation.

Using sheep and human serum the relationship between centrifugation time and yield of total lipoprotein, HDL-cholesterol and "A"-esterase in lipoprotein was studied employing different centrifuge rotors. More rapid separation of these components was obtained with a vertical rotor than with an angled rotor. The procedures commonly employed for lipoprotein separation gave low yields of lipoprotein "A"-esterase and HDL-cholesterol. The separation of sheep serum "A"-esterase into the lipoprotein fraction was not in phase with that of HDL-cholesterol and the pattern of separation was different from that in human serum. These results provide further evidence that serum "A"-esterase activity is associated with different species of HDL-particle.

Animals↗

Species variations in the metabolism of liposoluble organochlorine compounds by hepatic microsomal monooxygenase: comparative kinetics in four vertebrate species.

Liposoluble organochlorine compounds were used as substrates in a kinetic study of the hepatic microsomal monooxygenases of the male rat, feral pigeon (Columbia livia), frog (Rana pipiens) and rainbow trout (Salmo gairdnerii). Substrate concentrations were taken down to environmentally realistic levels. Lineweaver-Burk plots gave straight lines for both aldrin (HHDN) and the dieldrin analogue HCE. For both substrates activities followed the order rat greater than feral pigeon greater than trout over the entire concentration range. The metabolism of PCB isomers in microsomes from these uninduced animals was very slow. These results give evidence of cytochrome P-450 forms which can metabolize organochlorine compounds at low substrate concentrations.

Animals↗

Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities.

Evidence for the existence in rat and rabbit liver of two microsomal epoxide hydrolases with radically different substrate specificities was obtained, one with a broad specificity (EHb), whilst the other catalyzed the hydrolysis of cholesterol 5 alpha,6 alpha-oxide (EHch), a reaction taken as diagnostic since it was not observed with pure fractions of EHb. The two enzymes were physically separated by immunoprecipitation using antibodies which had been raised against EHb purified to apparent homogeneity. The substrate specificity of the two enzymes is radically different and mutually complementary. Cholesterol 5 alpha,6 alpha-oxide has a trisubstituted oxirane ring. All epoxides of this nature tested to date were not, or very poor, substrates of EHb. The two enzymes can also effectively be discriminated by inhibitors, in that 5 alpha,6 alpha-imino-5 alpha-cholestane-3 beta-ol potently inhibits EHch but not EHb whilst 1,1,1-trichloropropene oxide has the opposite specificity. The cytosolic EH did not significantly contribute to the catalysis of the hydrolysis of cholesterol 5 alpha,6 alpha-oxide.

Animals↗

Partial purification and properties of sheep serum "A'-esterases.

Using paraoxon and pirimiphos-methyl as substrates, much of the "A'-esterase activity of sheep serum was found to be in the high-density lipoprotein (HDL) fraction. A method was developed for the partial purification of "A'-esterases by the preparation of a lipoprotein fraction, followed by preparative polyacrylamide gel electrophoresis. The properties of the partially purified preparations of "A'-esterase were studied. Although four different preparations all contained a major protein unit, which resembled the core protein of HDL, there was evidence of differences between preparations with regard to substrate specificity, suggesting the existence of multiple enzyme forms. Gel filtration of serum samples indicated that paraoxonase activity is expressed by proteins with mol. wts greater than 200,000, strongly suggesting that the "A'-esterase activity of the lipoprotein fraction is present in one or more forms of HDL2. The dependence of "A'-esterase activity upon Ca2+ and the problem of esterase classification are discussed.

Animals↗

Control enzyme levels in the plasma, brain and liver from wild birds and mammals in Britain.

Brain from 47 avian and 17 mammalian species and the liver from 19 avian and 7 mammalian species has been examined for acetyl cholinesterase and nitrophenyl acetate esterase activities. Plasma from 27 avian and 7 mammalian species has been examined for acetyl cholinesterase, cholinesterase, nitrophenyl acetate esterase, glutamate, oxaloacetate transaminase, glutamate pyruvate transaminase, glutamate dehydrogenase, sorbitol dehydrogenase and lactate dehydrogenase activities. The studies have revealed that variations in enzyme activities occur between species but that there are discernible trends within families. The results indicate that comprehensive control enzyme data is necessary in order to assess the effects of exposure to agricultural chemicals in wildlife.

Alanine Transaminase↗

Special and intensive care baby units and nurse staffing in the UK.

A review of neonatal special and intensive care units in the UK in 1980-81 shows that although the number of cot/incubator units provided for special care conforms with current recommendations, there is a contrasting shortfall of 40% in cot/incubator units for intensive care. Admission policies are vague, vary considerably, and not all units are engaged in the type of care for which they are officially intended. Many units would admit fewer babies if the number and level of expertise of nursing staff in postnatal wards was improved. Rationalisation and redistribution of facilities seems advisable. The number of trained nurses falls far short of those recommended. Almost 21% of units had no formal staffing establishment, and of those that did less than half were filled. The total number of nurses of all ranks and experience failed to reach recommended levels, as did the ratio of trained staff to 'others'. Recruitment of nurses to this specialty is slow and the high turnover rate endangers maintenance of high standards and continuity of patient care.

Education, Nursing, Diploma Programs↗