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Biomedical subjects

C J Morgan

Publications and source records attributed to C J Morgan.

At least 91 records · Page 5Linked to original sources
PubMed1985

Production of a monoclonal antibody directed against the nerve growth factor receptor from sympathetic membranes.

Spleen cells from BALB/c mice immunized with a plasma membrane-enriched fraction from rabbit sympathetic ganglia were fused with the mouse myeloma NS1. A hybrid clone was obtained that produced monoclonal antibody directed against the receptor for nerve growth factor (NGF). The antibody, identified as IgG, was able to immunoprecipitate solubilized NGF receptor in the presence or absence of bound NGF. The antibody bound specifically to sympathetic membranes with high affinity but did not affect the binding of 125I-NGF to its receptor in sympathetic or sensory neurons or PC12 cells.

Animals↗
PubMed1984

Chemical crosslinking of the mononuclear phagocyte specific growth factor CSF-1 to its receptor at the cell surface.

The cell surface receptor for CSF-1 has been identified by affinity labeling intact mouse bone marrow-derived macrophages and intact cells of the murine J774.2 and BAC1 lines, which differ in their specific CSF-1 binding capacities and biological responses. The receptor, labeled by crosslinking to 125I-CSF-1 with disuccinimidyl suberate, is a polypeptide of approximately 165,000 molecular weight, irrespective of cell type.

Affinity Labels↗
PubMed1984

Nerve growth factor: mechanism of action.

Although the detailed mechanism of action of NGF as it occurs in vivo still requires considerable clarification, a model in which NGF is generated by end organs of responsive neurons and interacts with these neurons to provide trophic stimulation and maintenance of viability seems highly plausible. The demonstration of NGF synthesis by these cells, including the details of the process, is required, and information regarding the events following the formation of the hormone-receptor complex at the plasma membrane must be obtained. However, the contribution of internalization and the possible role of the internalized receptor as a second messenger for generating the long-term effects of the hormone are particularly appealing. Any findings with NGF will almost certainly provide additional important insights into other polypeptide growth factors, particularly those substances found in the neurotrophic subset.

Affinity Labels↗
PubMed1984

Magnetic resonance imaging. Part I--physical principles.

Magnetic resonance (MR) imaging is the most complex imaging technology available to clinicians. Whereas most imaging technologies depict differences in one, or occasionally two, tissue characteristics, MR imaging has five tissue variables-spin density, T(1) and T(2) relaxation times and flow and spectral shifts-from which to construct its images. These variables can be combined in various ways by selecting pulse sequences and pulse times to emphasize any desired combination of tissue characteristics in the image. This selection is determined by the user of the MR system before imaging data are collected. If the selection is not optimal, the imaging process must be repeated at a cost of time and resources. The optimal selection of MR imaging procedures and the proper interpretation of the resultant images require a thorough understanding of the basic principles of MR imaging. Included in this understanding should be at least the rudiments of how an MR imaging signal is produced and why it decays with time; the significance of relaxation constants; the principles of scanning methods such as saturation recovery, inversion recovery and spin echo; how data obtained by these methods are used to form an image, and how the imaging data are complied by multi-slice and volumetric processes. In selecting an MR imaging unit, information about different magnet designs (resistive, superconductive and permanent) is useful. Although no bioeffects are thought to be associated with an MR imaging examination, some knowledge of the attempts to identify bioeffects is helpful in alleviating concern in patients.

Humans↗
PubMed1984

Magnetic resonance imaging. Part II--Clinical applications.

Magnetic resonance (MR) imaging is the most promising new technology to appear in the clinical imaging arena since the advent of x-ray transmission computed tomography in the early 1970s. Five independent tissue characteristics (spin density, spin-lattice and spin-spin relaxation times, flow and spectral shift information) are accessible to MR imaging, and their relative influence in the magnetic resonance image can be varied by appropriate selection of pulse sequences and pulse times. All major organ systems appear to be amenable to MR imaging, and some are revealed with superior definition compared with their appearance in images obtained by alternate imaging technologies. Of particular interest is the superior contrast resolution in MR images of the brain and spinal cord, and the absence of bone- and motion-induced artifacts in images of the abdomen and pelvis. Applications of MR imaging to the heart and great vessels are just developing, as are new types of contrast agents for use in MR imaging. In vivo chemical spectroscopic measurements by magnetic resonance are heralded by some investigators as the most significant contribution that magnetic resonance will make ultimately to clinical diagnosis. At present, the number of MR imaging units is extremely low, and clinical studies are proceeding at a slow rate. Nevertheless, it is possible to provide a preliminary evaluation of the usefulness of MR imaging in a variety of clinical applications. This article is such an evaluation, tempered by the acknowledgement that much additional work remains to be done.

Brain Diseases↗
PubMed1983

Does naloxone always act as an opiate antagonist?

Evidence for the ability of the opiate antagonist naloxone to block a variety of metabolic effects exerted by morphine and non-opiate drugs is reviewed. Naloxone prevents or reverses the following effects in the rat: (a) the chronic morphine-induced increase in liver [NADPH]; (b) the consequent chronic morphine-induced inhibition of liver tryptophan pyrrolase activity; (c) the resultant chronic morphine-induced enhancement of brain 5-hydroxytryptamine synthesis; (d) the similar effects on liver and brain tryptophan metabolism exerted chronically by other drugs of dependence (ethanol, nicotine and phenobarbitone); (e) the acute ethanol-induced increase in the hepatic [NADH]/[NAD] ratio. Naloxone also (f) inhibits basal and stimulated lipolysis in fed and 24hr-starved rats. This leads to prevention of (g) the consequent increase in the availability of circulating free tryptophan, and (h) the resultant tryptophan-mediated decrease in liver 5-aminolaevulinate synthase activity. The question of how many of these effects involve changes in endogenous opiates or at opiate receptors is not clearly understood at present and thus merits investigation. However, because most of the above effects are explained on biochemical grounds, and in view of evidence from behavioural and pharmacological studies [see (1)], the possibility must be considered that many of the actions of naloxone may be unrelated to its opiate-receptor-antagonistic properties.

Animals↗
PubMed1982

Tryptophan pyrrolase in haem regulation. The mechanisms of enhancement of rat liver 5-aminolaevulinate synthase activity by starvation and of the glucose effect on induction of the enzyme by 2-allyl-2-isopropylacetamide.

1. Rat liver tryptophan pyrrolase activity is enhanced by a hormonal-type mechanism during the first 2 days of starvation and by a substrate-type mechanism during the subsequent 2 days. 5-Aminolaevulinate synthase activity is also enhanced during the first 2 days of starvation, but returns thereafter to values resembling those observed in the fed rat. Treatments that prevent or reversé the enhancement of tryptophan pyrrolase activity in 24-48h-starved rats also abolish that of 5-aminolaevulinate synthase activity. Starvation of guinea pigs, which does not enhance the pyrrolase activity, also fails to alter that of the synthase. It is suggested that the decrease in 5-aminolaevulinate synthase activity in 72-96h-starved rats represents negative-feedback repression of synthesis, possibly involving tryptophan participation, whereas the enhancement observed in 24-48h-starved animals is caused by positive-feedback induction secondarily to increased utilization of the regulatory-haem pool by the newly synthesized apo-(tryptophan pyrrolase). 2. Glucose, fructose and sucrose abolish the 24h-starvation-induced increases in rat liver tryptophan pyrrolase and 5-aminolaevulinate synthase activities. Cortisol reverses the glucose effect on 5-aminolaevulinate synthase activity, presumably by enabling pyrrolase to re-utilize the regulatory-haem pool after induction of synthesis of this latter enzyme. 3. The impaired ability of 2-allyl-2-isopropylacetamide to enhance markedly 5-aminolaevulinate synthase activity in 24h-starved rats treated with glucose is associated with a failure of the porphyrogen to cause loss of tryptophan pyrrolase haem. Cortisol restores the ability of the porphyrogen to destroy tryptophan pyrrolase haem and to enhance markedly 5-aminolaevulinate synthase activity, presumably by enhancing tryptophan pyrrolase synthesis and, thereby, its re-utilization of the regulatory-haem pool. It is tentatively suggested that 2-allyl-2-isopropylacetamide destroys the above pool only after it has become bound to (or utilized by) apo-(tryptophan pyrrolase).

5-Aminolevulinate Synthetase↗
PubMed1982

Tryptophan and tryptophan pyrrolase in haem regulation. The role of lipolysis and direct displacement of serum-protein-bound tryptophan in the opposite effects of administration of endotoxin, morphine, palmitate, salicylate and theophylline on rat liver 5-aminolaevulinate synthase activity and the haem saturation of tryptophan pyrrolase.

1. The increase in the haem saturation of rat liver tryptophan pyrrolase caused by tryptophan administration was previously shown to be associated with a decrease in 5-aminolaevulinate synthase activity. 2. It is now shown that similar reciprocal effects are caused by palmitate and salicylate, both of which increase tryptophan availability to the liver by direct displacement of the serum-protein-bound amino acid. 3. The reciprocal effects on the former two parameters caused by endotoxin and morphine are associated with an increase in liver tryptophan concentration produced by a lipolysis-dependent, non-esterified fatty acid-mediated, displacement of the serum-protein-bound amino acid. 4. All these changes and those caused by another lipolytic agent, theophylline, are prevented by the beta-adrenoceptor-blocking agent propranolol and by the opiate-receptor antagonist naloxone, whose anti-lipolytic nature is demonstrated. 5. High correlation coefficients have been obtained for one or more pairs of the following parameters: serum non-esterified fatty acid concentration, free serum tryptophan concentration, liver tryptophan concentration, liver 5-aminolaevulinate synthase activity, liver holo-(tryptophan pyrrolase) activity and the haem saturation of liver tryptophan pyrrolase. 6. It is suggested that liver tryptophan concentration may play an important role in the regulation of 5-aminolaevulinate synthase synthesis, and that the latter may be subject to control by changes in lipid metabolism and may be influenced by pharmacological agents that affect tryptophan disposition. 7. Preliminary evidence suggests that tryptophan may be bound in the liver and that such a possible binding may control its availability for its hepatic functions.

5-Aminolevulinate Synthetase↗
PubMed1981

Identification of a nerve growth factor receptor protein in sympathetic ganglia membranes by affinity labeling.

Membranes from adult rabbit superior cervical ganglia, cross-linked to membrane-bound 125I-labeled nerve growth factor (NGF) by the photoreactive agent hydroxysuccinimidyl-p-azidobenzoate, were found to contain two labeled components with apparent Mr = 143,000 and Mr = 112,000. At high concentrations of the cross-linker, minor amounts of a Mr = 300,000 affinity labeled product were also observed. The affinity labeled species exhibit the characteristics expected of membrane receptors for NGF. The inhibition of specific 125I-NGF binding to membranes by increasing concentrations of unlabeled NGF parallels the inhibiton of the affinity labeling of these components. Insulin, insulin-like growth factor I, multiplication stimulating activity, and epidermal growth factor do not inhibit the affinity labeling reaction. Membrane preparations of various non-neuronal tissues do not show any detectable specific cross-linking to 125I-NGF. The affinity labeled species of superior cervical ganglia are proteins and contain intrapeptide disulfide bridges compacting their molecular structure. Peptide mapping experiments indicate a close structural relationship between the Mr = 143,000- and the Mr = 112,000-labeled proteins, suggesting a transformation of the former into the latter by limited proteolysis. The results suggest that the Mr = 143,000 affinity labeled protein represents a native NGF receptor component.

Affinity Labels↗
PubMed1981

Tryptophan pyrrolase in haem regulation. The mechanism of the opposite effects of tryptophan on rat liver 5-aminolaevulinate synthase activity and the haem saturation of tryptophan pyrrolase.

1. Administration of tryptophan to starved rats causes a rapid decrease in liver 5-aminolaevulinate synthase activity associated with an increase in the haem saturation of tryptophan pyrrolase. Both effects are maximally produced at 30 min by a 100 mg/kg body wt. dose of tryptophan. 2. Pb2+ prevents both effects. 3. Prevention by allopurinol or benserazide of the tryptophan-induced increase in the haem saturation of tryptophan pyrrolase renders this haem available for further repression of synthase synthesis. 4. The opposite effects on synthase activity and pyrrolase saturation with haem caused by administration of 5-aminolaevulinate, but not those by that of haematin, are potentiated by tryptophan. 5. It is suggested that tryptophan decreases 5-aminolaevulinate synthase activity and causes the initial increase in the haem saturation of tryptophan pyrrolase by enhancing the conversion of 5-aminolaevulinate into haem by a process requiring protein synthesis.

5-Aminolevulinate Synthetase↗
PubMed1980

Tryptophan pyrrolase in haem regulation. The relationship between the depletion of rat liver tryptophan pyrrolase haem and the enhancement of 5-aminolaevulinate synthase activity by 2-allyl-2-isopropylacetamide.

Rat liver tryptophan pyrrolase haem is maximally depleted at 30 min after administration of a 400 mg/kg dose of 2-allyl-2-isopropylacetamide. This depletion lasts for 24 h, by which time 5-aminoleevulinate synthase activity becomes maximally enhanced. 2. though the above maximum depletion of pyrrolase haem (at 0.5h) is also produced by a 100 mg/kg dose of the porphyrogen, this does not enhance synthase activity at 24 h. It and smaller doses, however, cause a smaller but earlier enhancement of synthase activity (maximum at 2 h) and produce a similarly short-lived deplation of pyrrolase haem. 3. The depletion of pyrrolase haem and the enhancement of synthase activity by the porphyrogen are inhibited by compound SKF 525-A and phenazine methosulphate, and are potentiated by nicotinamide but not by phenobarbitone. Phenazine methosulphate and nicotinamide also exert opposite effects on hexobarbital sleeping-time. 4. 2-Allyl-2-isopropylacetamde also the depletes pyrrolase haem in vitro. It does so in liver homogenates of control rats in the presence, and in those of phenobarbitone-treated rats in the absence of added NADPH. 5. A discussion of the present results in relation to previous work with other haemoproteins suggests that, whereas cytochrome P-450 (haem) is primarily involved in the production of the active (porphyrogenic) metabolite(s) of 2-allyl-2-isopropylacetamide, the haem pool used by tryptophan pyrrolase may play an important role in the effects of this compound on haem biosynthesis.

5-Aminolevulinate Synthetase↗
PubMed1980

Tryptophan pyrrolase in haem regulation. The mechanism of the permissive effect of cortisol on the enhancement of 5-aminolaevulinate synthase activity by 2-allyl-2-isopropylacetamide in the adrenalectomized-rat liver.

The decreased ability of 2-allyl-2-isopropropylacetamide to enhance liver 5-amino-laevulinate synthase activity in the adrenalectomized rat is not associated with a marked depletion of the already low amount of tryptophan pyrrolase haem. Cortisol permits the porphyrogen markedly to enhance synthase activity by rendering it capable of causing a stronger depletion of pyrrolase haem, presumably as result of hormonal induction of pyrrolase synthesis.

5-Aminolevulinate Synthetase↗
PubMedDate not supplied

Tryptophan metabolism in alcoholism. Tryptophan but not excitatory amino acid availability to the brain is increased before the appearance of the alcohol-withdrawal syndrome in men.

Tryptophan (Trp) metabolism and disposition and excitatory and other amino acid concentrations were determined in alcohol-dependent subjects in relation to the alcohol-withdrawal syndrome (AWS). Parameters were examined in 12 alcohol-dependent male subjects, undergoing elective upper digestive tract tumour resection, and 12 age-, gender-, and medication-matched controls on three occasions: pre-operatively, post-operatively, and immediately before (i.e. within 24 h of) the appearance of the AWS. No significant differences were observed between controls and alcoholic subjects on the first or second of these occasions. On the third occasion, within 24 h of the appearance of the AWS, alcoholics showed a dramatic elevation (117%) in free serum Trp concentration and a consequent increase (111%) in the ratio of [free Trp]/[competing amino acids], which is an accurate predictor of Trp entry into the brain. Increases were also observed on this third occasion in concentrations of total Trp (49%), cortisol (123%), and norharman (137%). Concentrations of glutamate, glycine, aspartate, serine, and taurine did not differ significantly within or between the control and alcohol-dependent groups of subjects on any of the three occasions. The possible significance of the Trp and related metabolic changes in relation to the behavioural features of the AWS is discussed.

Alcoholism↗
PubMedDate not supplied

Rat liver tryptophan pyrrolase activity and gene expression during alcohol withdrawal.

Rat liver tryptophan (Trp) pyrrolase activity and gene expression were studied in relation to the alcohol-withdrawal syndrome (AWS). Both activity and gene expression were enhanced after withdrawal of ethanol-containing liquid diets and the time-course of these changes mirrored that of development and intensity of the behavioural disturbances of the AWS. By contrast, no correlation was observed between the AWS-induced behaviour and changes in activity of another hepatic glucocorticoid-inducible enzyme, tyrosine aminotransferase, and a negative correlation was noted between behaviour and the gene expression of this latter enzyme and also of that of the hepatic glucocorticoid receptor. We suggest that the metabolic consequences of activation of liver Trp pyrrolase during alcohol withdrawal may play a role in the behavioural features of the AWS.

Animals↗