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Biomedical subjects

C M Lee

Publications and source records attributed to C M Lee.

At least 343 records · Page 19Linked to original sources
PubMed1981

Synthesis and biological properties of enzyme-resistant analogues of substance P.

Six analogues of substance P were synthesized with the aim of developing a metabolically stable peptide that would retain the biological activity of substance P. A recently isolated and characterized substance-P-degrading enzyme from human brain with a high specificity for substance P described in the preceding paper in this journal was used as a model for the enzymatic inactivation of substance P. The synthetic analogues were designed to protect the peptide bonds on the carboxyl side of residues 6, 7 and 8 of substance P, which represent the sites of cleavage by substance-P-degrading enzyme. To test for increased enzymatic resistance, the analogues were incubated with the enzyme, the digests were separated on a high-performance liquid chromatography reverse-phase column and the peptide fragments were collected and identified by amino acid analysis. Of the analogues described, an heptapeptide analogue of residues 5-11, less than Glu-Gln-Phe-MePhe-MeGly-Leu-MetNH2, showed almost complete resistance both towards substance-P-degrading enzyme and to degradation on exposure to rat hypothalamic slices. This analogue was about a third as potent as substance P in competing for binding to receptor sites for this peptide in rat brain membranes and a tenth as potent in eliciting contractions of the guinea pig ileum. The peptides were synthesized using the solid-phase technique with polydimethylacrylamide as a solid support and the coupling was achieved with pre-formed symmetrical anhydrides in dimethylacetamide. Fluorenylmethyloxycarbonyl was used as an alpha-amino protecting group in conjunction with t-butyloxycarbonyl as an epsilon-amino protecting group. Ammoniolytic cleavage from the resin was followed by stepwise elution from an SP-Sephadex column, deprotection with trifluoroacetic acid and chromatography on a Bio-Rex 70 ion-exchanger. The peptides were finally purified on a semi-preparative reverse-phase column.

Animals↗
PubMed1980

Regulation of neuropeptide release.

The demonstration of depolarization-induced release of substance P, Met- and Leu-enkephalin, somatostatin, neurotensin, vasoactive intestinal polypeptide and cholecystokinin-like material from various regions of rat brain in vitro supports the hypothesis that these and other neuropeptides may act as neurotransmitters. In each case the stimulus-evoked release, but not the basal release, of peptide was dependent on the presence of calcium ions in the external medium. The stimulus-evoked release of substance P from nerve terminals in rat substantia nigra may be regulated by presynaptic gamma-aminobutyric acid (GABA) receptors. The possible existence of presynaptic opiate receptors on substance P-containing sensory nerve terminals may offer an explanation for the analgesic effects of opiates at spinal cord level, and for the existence of enkephalin neurons in substantia gelatinosa. Capsaicin releases substance P from spinal cord nerve terminals and may impair their function, while having no effect on substance P neurons in supraspinal regions. The possibility of cosecretion of peptide and amine products from the same cells is discussed.

Animals↗
PubMed1980

Specific binding of 3H-substance P to rat brain membranes.

The undecapeptide substance P is a putative neurotransmitter in the mammalian central nervous system (CNS), and may be associated with pain fibres in the spinal cord. Radiolabelled derivatives of other neuropeptides have been used to demonstrate specific interactions with receptor sites on brain membranes, and this approach has now been explored with substance P. We have now prepared [4-3H-Phe8]-substance P and we find that it binds reversibly to a saturable population of sites in rat brain particulate fractions. Scatchard analysis of concentration-dependent saturation of binding indicates a single population of non-interacting sites with a high affinity (Kd=0.38 nM) and a low density (Bmax=27.2 fmol per mg protein). Kinetic analyses indicate an apparent dissociation equilibrium constant of 0.46 nM. A variety of neurotransmitter amines and amino acids, and other peptides do not compete at the substance P sites, but structurally related peptides or shorter C-terminal fragments of substance P are active. The rank order of potency of these substance P-related peptides agrees with that reported for their effects in depolarizing spinal cord neurones. The regional distribution of the specific binding sites for 3H-substance P parallels that of substance P immunoreactivity, being high in the hypothalamus and low in the cerebellum and cerebral cortex. The characteristics of the 3H-substance P binding sites are consistent with those expected for substance P receptors.

Animals↗
PubMed1980

Axonal transport of neuropeptides in the cervical vagus nerve of the rat.

Accumulations of the neuropeptides substance P (SP), somatostatin (ST), and vasoactive intestinal polypeptide (VIP) proximal to a crush in the cervical vagus nerve of the rat have been measured using sensitive radioimmunoassays. Each of the peptides was rapidly transport towards the peripheral terminals of vagal afferent fibres, with average rates of flow ranging from 0.8 to 2.7 mm h-1. In the rabbit vagus nerve, SP was transported with an average rate of 4 mm h-1, which is more than double the rate for this peptide in the rat. Double crush experiments in rabbit vagus nerves indicated that the rapidly transported proportion of the total content of SP in the nerve free was about 34%. From this, the rate of transport of SP in the rapidly transported pool in the rabbit vagus nerve can be calculated to be 12 mm h-1 (280 mm day-1). Since such double crush experiments were not possible in the rat, it is not clear whether the different average rates of transport of SP in the rat and the rabbit reflect real differences in the rate of rapid transport in the two species. In common with rapid axonal transport of other neurotransmitters, the transport of SP and ST in the rat vagus nerve was blocked by colchicine, a drug that disrupts microtubules.

Animals↗
PubMed1979

Separation of human brain angiotensin-converting enzyme from enkephalin-degrading activity.

Angiotensin-converting enzyme and enkephalin-degrading enzyme activities were solubilized and purified from a particulate fraction of human diencephalon. Converting enzyme activity and enkephalin-degrading activity elute in different fractions following ion exchange chromatography on DEAE-cellulose, suggesting that they are different enzymes. Both enzymes were purified further by ion exchange chromatography on hydroxylapatite and by gel filtration on Sephadex G-200. The purified enzymes had markedly different sensitivities to known inhibitors of angiotensin-converting enzyme. The data do not support the hypothesis that angiotensin-converting enzyme and enkephalin degrading-enzyme are identical.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1979

Immunobiology of schistosomiasis.

Although malaria and hookworm disease appear to be on the decline, another dreaded parasitic disease-schistosomiasis-is on the increase. Presently, the number of infected individuals with schistosomes is estimated to be 250 million, and even though only a small proportion of them become sick and die, schistosomiasis remains a medical problem of great significance. The high incidence of infection of man with Schistosoma mansoni, Schistosoma japonicum or Schistosoma haematobium, as well as the chronic debilitating diseases produced, places these organisms among the world's most important infectious agents. This paper discusses the nature of immunity to schistosomiasis.

Adult↗
PubMed1979

The interaction of nutrition and infection: a succinct review.

Malnutrition combined with susceptibility to infection threatens the health and survival of a large portion of the world's population. Of the many components of the host-parasite relation, nutrition has not received the attention it deserves. There has been increasing activity in recent years on the elucidation of the role nutritional factors play in the behavior of both host and parasite.This paper reviews the effects vitamins exert on the course of parasitic infections.

Animals↗
PubMed1979

Immunobiology of malaria.

Malaria, the number one disease in the world, is caused by intracellular protozoans belonging to the Subphylum, Sporozoa; Suborder, Haemosphoridia; and Family, Plasmodiidae. The four classical organisms producing disease in man are Plasmodium vivax, P. falciparum, P. malariae, and P. ovale. Although malaria has been known to man for centuries, attempts are still being made to control and eliminate its devastating effects in tropical and subtropical areas of the world. Current active interest in malarial immunology and immunopathology derives from two main facts: (1) that human malaria is still one of the chief health problems in a broad tropical and subtropical zone in which lie most of the developing countries; and (2) most of the seminal leads in basic immunology are being applied to malarial immunology, either directly in human patients, or using laboratory animals as test objects.This paper addresses the nature of malarial immunity and target organs in malarial pathology.

Adult↗
PubMed1978

Electron microscopy observations on Trypanosoma brucei: freeze-cleaving and thin-sectioning study of the apical part of the flagellar pocket.

Observations on the apical part of the flagellar pocket of Trypanosoma brucei using the freeze-cleaving and thin-sectioning techniques of electron microscopy are reported. The flagellar pocket is shown as a flask-shaped depression in the body, continuous with the pellicle and flagellar sheath. The membranes of the apical part of the pocket on the flanged side of the body compress the flagellar sheath, forming part of a "neck region". This region is completed on the broad body side of the flagellar pocket when it embraces the flagellar sheath. The possible role of the neck region in the dynamic function of pinocytosis is discussed.

Animals↗