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Biomedical subjects

J M Hanson

Publications and source records attributed to J M Hanson.

At least 55 records · Page 3Linked to original sources

Pharmacologic effects of 4-chlorophenol in rats: comparison to clofibrate.

4-Chlorophenol (4-CP) is an identified trace contaminant in commercial clofibrate preparations and the pharmacologic effects of 4-CP have not yet been widely established. We have examined the dose-dependent effects of oral 4-CP and clofibrate administration on selected hepatic parameters and on serum glucose, cholesterol, and triglyceride concentrations in male rats. 4-CP treatment (0.00125-0.08 mmol/kg, twice a day) of rats for 2 weeks increased hepatic microsomal protein (20-30%) and cytochrome P-450 (20-190%) contents without changing liver/body weight ratios. Both 4-CP (0.0025 mmol/kg body wt, twice a day) and CPIB (0.4 mmol/kg body wt, twice a day) treatment to rats for 2 weeks caused significant elevations in microsomal cytochrome P-450 content and in the maximal activities of ethylmorphine, aminopyrine, and benzphetamine N-demethylase, but not in the activity of zoxazolamine 6-hydroxylase. With the same dose of 4-CP, time-dependent increases in hepatic microsomal protein, cytochrome P-450, and the activity of benzphetamine N-demethylase were observed for a 4-week period, and the induction of hepatic microsomal benzphetamine N-demethylase activity by 4-CP was associated with an increased enzyme synthesis. 4-CP treatment produced a marked morphologic change in liver cell ultrastructure, including a proliferation of mitochondria and endoplasmic reticulum at lower 4-CP doses. A clustering of intracellular organelles (mitochondria and endoplasmic reticulum) and a foamy cytoplasm were seen at doses greater than 0.01 mmol/kg, twice a day for 2 weeks, and at 0.0025 mmol/kg, twice a day for greater than 4 weeks. The effects of 4-CP and clofibrate on fasting blood glucose and fasting serum lipid levels were also monitored throughout an 8-week period. Both 4-CP (0.005 mmol/kg body wt, twice a day) and clofibrate (0.2 mmol/kg body wt, twice a day) produced significant elevations in fasting serum glucose levels, but this dosage of 4-CP did not alter serum lipid and lipoprotein parameters, whereas clofibrate significantly reduced serum total cholesterol and high density lipoprotein cholesterol levels. These results lead us to conclude that 4-CP does not contribute to the antilipidemic effects of clofibrate.

Animals↗

Noninvasive testing of cerebral perfusion reserve prior to coronary artery bypass graft surgery.

Cerebral perfusion reserve testing using fluorine-18-fluoromethane and positron emission tomographic brain scanning to define cerebral blood flow abnormalities was performed in 5 patients being considered for combined coronary and carotid reconstructive surgery. Blood flow testing during normocapnia and following hypercapnia was utilized in these patients to determine the hemodynamic significance of known extracranial carotid artery occlusive lesions. Reserve diminution in 2 of these patients prompted combined surgery, whereas normal reserve values in the other 3 prompted coronary surgery alone. Results obtained in this preliminary series show how preoperative noninvasive testing of cerebral perfusion reserve adds to the diagnostic evaluation of patients with widespread vascular disease.

Brain↗

Adrenoceptor function in atopic dermatitis: in vitro and in vivo observations.

Impaired beta-adrenergic and enhanced alpha-adrenergic reactivity have been implicated in the pathogenesis of atopic dermatitis. We have measured the elevation of cyclic AMP in peripheral blood leukocytes in response to isoprenaline, histamine and prostaglandin E2, in the presence and absence of a phosphodiesterase inhibitor. An impaired response to beta-adrenergic stimulation was demonstrated in subjects with atopic dermatitis but impaired responses were also observed with histamine and prostaglandin E2. In vivo, both noradrenaline and salbutamol caused significant inhibition of the histamine-induced weal response in atopic and normal subjects. However, there was no significant difference between the two groups when alpha- and beta-adrenoceptor responses were compared.

Adrenergic alpha-Agonists↗

Effects of non-steroidal anti-inflammatory drugs on lymphocyte activation.

Guinea-pig lymph node lymphocytes were stimulated with mitogen (phytohaemagglutinin) in vitro and lymphocyte activation was measured by tritiated thymidine incorporation (DNA synthesis). Inclusion of non-steroidal anti-inflammatory drugs (NSAIDs) in the culture medium at therapeutic concentrations, frequently exerted an inhibitory effect. Such inhibition could not be attributed to the ability of these drugs to inhibit cyclo-oxygenase or lipoxygenase enzymes. Inhibition by salicylates was not associated with cytotoxic or cytopathic effects, since inhibition was only evident when the drugs were included in the early phase of culture. Other NSAIDs exhibited varying degrees of toxicity, which in some instances may account for observed inhibition. The effects on lymphocyte activation of selective inhibitors of pathways of arachidonic acid metabolism, do not support the proposition that the generation of prostaglandins, thromboxanes, leukotrienes or related compounds is an obligatory step during lymphocyte activation.

Animals↗

Mononuclear leukocyte cyclic adenosine monophosphate responses in psoriasis are normal.

It has been proposed that immune dysfunction in psoriasis is a consequence of aberrant cyclic nucleotide metabolism. We have examined cyclic AMP responses to isoprenaline, histamine, and prostaglandin E2 in peripheral blood mononuclear leukocytes from patients with psoriasis, in the presence and absence of a potent cyclic AMP phosphodiesterase inhibitor. Stimulated and basal cyclic AMP levels in mononuclear leukocytes from psoriatics did not differ from those observed in mononuclear leukocytes from normal subjects, irrespective of the stimulant employed, either in the presence or in the absence of the phosphodiesterase inhibitor. These findings do not support the hypothesis that psoriasis is associated with either impaired beta-adrenergic reactivity or a more generalized abnormality of mononuclear leukocyte cyclic nucleotide metabolism.

Adult↗

Circulating beta-adrenoceptor blocking factors in asthma.

The hypothesis that a generalized defect in beta-adrenoceptor function characterized asthma and atopy has been proposed by Szentivanyi. Such a defect may be intrinsic to the beta-adrenoceptor mechanism or could be attributed to circulating factors which interfere with the binding of catecholamines to beta-adrenoceptors. This study shows that sera from a proportion of the asthmatic population studied contain beta-adrenoceptor blocking activity and that the degree of inhibition correlates with some of the clinical indices of asthma.

Adrenal Cortex Hormones↗

The late reaction following bronchial provocation with house dust mite allergen. Dependence on arachidonic acid metabolism.

The involvement of arachidonic acid metabolism in early and late bronchial reactions has been studied in four asthmatic subjects sensitive to Dermatophagoides pteronyssinus. Pre-treatment with either indomethacin (an inhibitor of the cyclo-oxygenase pathway) or benoxaprofen (an inhibitor of both cyclo-oxygenase and lipoxygenase pathways) failed to affect the amplitude, but did produce some foreshortening of the early response to allergen. If benoxaprofen is an effective inhibitor of SRS-A formation in vivo, then these observations question the role of SRS-A as a spasmogen in allergen-induced bronchospasm. Both drugs were effective inhibitors of the late reaction, implying involvement of cyclo-oxygenase products (endoperoxides, prostaglandins or thromboxanes) in the genesis of a late response to allergen.

Adolescent↗

Fatty acid content and composition of infant formulas and cereals.

The lipid content and fatty acid composition of commercial infant formulas and cereals were determined. The lipid content of formulas ranged from 3 to 7 percent by weight and provided from 30 to 47 percent of the total calories supplied by the formula. The fatty acd distribution in several formulas was similar to that of fat in human milk. Linoleic acid, ranging from 13 to 53 percent, supplied from 5.7 to 24 percent of total calories. The infants' requirements for linoleic acid (2.7 percent of total calories) would be adequately satisfied by any of the commercial formulas. No significant level of trans fatty acid isomers was found in any commercial formula. Infant cereals had low levels of fat, with 21 to 49 percent of the fatty acids being linoleic acid.

Edible Grain↗

The structures of some peptides from bee venom.

The sequences are given of two peptides (secapin and melittin F) whose isolation from the venom of the common European honey bee (Apis mellifera) has previously been described [Gauldie et al. (1976) Eur. J. Biochem. 61, 369--376]. Some structural studies on the known peptide 401 (MCD peptide) are described. The positions of the two disulphide bridges in peptide 401 have been determined by (an essentially) novel method.

Amino Acid Sequence↗

Leucocyte chemotactic activity in the parallel bioassay of guinea--pig lymphokines.

This paper describes the application of parallel bioassay to determine the extent to which the leucocyte chemotactic activity of guinea-pig lymphokine preparations is associated with their lymphocyte mitogenic, inflammatory (increased vascular permeability) and macrophage migration inhibitory activities. A convenient test of chemotactic activity was devised whereby Coulter counter determinations were made of the number of peritoneal exudate cells passing through a Nuclepore membrane into the medium of the lower (test) compartment of a chemotaxis chamber. Symmetrical parallel line (2+2) dose assays were used to obtain potency ratio estimates of the chemotactic activity of seven lymphokine preparations whose mitogenic, inflammatory and migration inhibitory activities were already known. Statistical analysis of the results revealed a clear dissociation of chemotactic activity from mitogenic and migration inhibitory activities; but with six of the seven lymphokine preparations, a marked similarity was revealed between their chemotactic and inflammatory activities. Cytological studies showed that although the lymphokine preparations were chemotactic for different cell types, there was a preferential migration of neutrophils and the smaller mononuclear cells. The demonstration by parallel bioassay of an association between the ability of lymphokine preparations to increase vascular permeability in vivo and to promote chemotaxis of leucocytes in vitro is viewed in relation to the possible role of lymphokine in inflammatory processes.

Animals↗

Anti-inflammatory property of 401 (MCD-peptide), a peptide from the venom of the bee Apis mellifera (L.).

1 Peptide 401, a potent mast cell degranulating factor from bee venom, substantially inhibited the oedema provoked by subplantar injection of carrageenin or intra-articular injection of turpentine in the rat. The ED(50) of 401 was c. 0.1 mg/kg. The anti-inflammatory effect was assessed by measurement of the increased (125)I-albumin content of an injected site in comparison with an uninjected contralateral site.2 Peptide 401 also suppressed the increased vascular permeability due to intradermal injection of various smooth muscle spasmogens (histamine, bradykinin, 5-hydroxytryptamine (5-HT), and prostaglandins).3 Other comparable mast cell degranulating agents (48/80 and melittin) showed little evidence of anti-inflammatory activity when tested at comparable dosage on turpentine arthritis and carrageenin oedema.4 The anti-inflammatory effects were not abolished by pretreatment with mepyramine and methysergide, which abolished the increased vascular permeability produced by local injection of 401.5 The anti-inflammatory action of 401 was not affected by regional denervation or pretreatment with phenoxybenzamine, and was reduced but not abolished by adrenalectomy.6 Measurement of skin temperature, fractional extraction of (86)Rb and blood flow in perfused mesentery gave no evidence that the anti-inflammatory action of 401 was due to reduced tissue perfusion.7 It is concluded that 401 may exert its anti-inflammatory action directly by making the vascular endothelium anergic to phlogistic stimuli.

Adrenalectomy↗