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T Lee

Publications and source records attributed to T Lee.

At least 379 records · Page 21Linked to original sources
PubMed1980

Neurochemical and behavioral evidence for a selective presynaptic dopamine receptor agonist.

A new dopamine analog, 6,7-dihydroxy-2-dimethylaminotetralin (TL-99), was compared to apomorphine in three tests of dopaminergic function in the central nervous system. The tests, performed on rats, included production of changes in locomotor activity (involving both presynaptic and postsynaptic receptors), inhibition of dopa accumulation (quantifying presynaptic receptor activity), and the rotation model (quantifying postsynaptic receptor activation). Apomorphine was efficacious at both presynaptic and postsynaptic receptors, whereas TL-99 was much more efficacious at the presynaptic receptor. This result indicates not only that differences exist between presynaptic and postsynaptic dopamine receptors, but also that these differences may be exploited in the design of selective dopamine agonists.

Animals↗
PubMed1980

Dopaminergic activity of cis-trans isomers of benzhydro[f]quinoline analogs.

A comparison of the biological activity of isomers with varying alkyl substitutions on the heterocyclic nitrogen of benzhydro[f]quinoline derivatives was made. The secondary amines did not inhibit adrenergic transmission. The trans-isomer of the secondary amine was 0.5 as active as norepinephrine when evaluated for positive chronotropic action in anesthetized cats. The trans-isomers of the N-alkyl derivatives produce inhibition of responses produced by stimulation of cardioaccelerator nerves with doses of 1--5 mumol/kg. Likewise potent emetic activity (dog) and rotational behavior (rat) was observed with the N-alkyl derivatives when administered subcutaneously. The cis-isomers were much less active. The neuronal inhibitions in cats were antagonized by haloperidol 100 micrograms/kg, except the cis-isomer of the N-ethyl derivate which required phentolamine, 2 mg/kg. In general, the transisomers were more potent in contracting the isolated rabbit aorta. This response appeared to be mediated through an alpha-adrenergic mechanism since phentolamine blocked these responses. The trans-isomer TL-305 was effective in relaxing methacholine contracted guinea-pig trachea through a beta-adrenergic mechanism since propranolol blocked this response.

Animals↗
PubMed1980

Association of HLA-DRw4 with rheumatoid arthritis in black and white patients.

The HLA-A, B, C, and DR antigens were typed in 35 black and 35 white Americans with rheumatoid arthritis. The frequency of HLA-DRw4 was increased in both the black and white patient patient groups compared to the race-matched control groups. DRw4 was found in 45.7% of the black patients compared to 14.3% of the black controls (corrected P value < 0.035) and DRw4 was found in 71.4% of the white patients compared to 40.0% of the white controls (corrected P value < 0.035). These data indicate that immunogenetic factors related to DRw4 are important in the development of rheumatoid arthritis in American blacks as well as whites.

Adult↗
PubMed1980

Occurrence of unusual hexadecenoate fatty acids in hepatoma lipids.

Cis-hexadecenoates isolated from rat liver and hepatoma 7288CTC lipids were analyzed for positional isomers by ozonolysis and capillary gas liquid chromatography. In addition to the delta 6, delta 7, delta 9 and delta 11 isomers found in both tissues, the hepatoma neutral and polar lipids contained relatively high percentages of delta 12 and delta 14 hexadecenoates that were virtually absent from liver. The occurrence of these unusual fatty acids may result from an error in lipid metabolism in the hepatoma.

Animals↗
PubMed1980

Effect of methyl 2-hexadecynoate on hepatic fatty acid metabolism.

Normal and hepatoma bearing rats were fed a low level of methyl 2-hexadecynoate in a low fat diet for one month. The effect of the acetylenic acid on lipid metabolism as derived from mass analysis of lipid classes, fatty acids and positional monoene isomers isolated from the major lipid classes of liver and hepatoma has been assessed. Methyl 2-hexadecynoate caused a 25% decrease in body weight and the appearance of essential fatty acid deficiency symptoms within one week. Non-tumor-bearing animals contained a seven-fold increase in all neutral lipid classes, except cholesterol, while host animals did not contain fatty livers. The apparent protective effect of the host animal by the hepatoma also resulted in only marginal changes in the fatty acid and positional monoene isomers from host liver and hepatoma lipids. In contrast to host liver and hepatoma, methyl 2-hexadecynoate caused a massive accumulation of palmitate and hexadecenoates with a concomitant decrease in stearate and octadecenoates in most of the lipid classes from non-tumor-bearing animals. These changes were accompanied by a shift from the higher molecular weight triglycerides to lower molecular weights corresponding to carbon number 48. The high concentrations of hexadecenoates consisted predominantly of the delta 9 isomer. Despite the high concentrations of cis delta 9 hexadecenoate, precursor of cis delta 11 octadecenoate (vaccenate), total vaccenate levels of the five major lipid classes were lower than control values. All of these data strongly suggest that long-chain 2-ynoic acids inhibit elongation of saturated and monoene fatty acids.

Animals↗
PubMed1980

HLA serological cross-reactivity: HLA-B15 has two public antigens.

On the basis of their serologic cross-reactivity, HLA antigens can be organized into cross-reactive groups or CREG's. We have recently defined immunochemically two public alloantigenic determinants X and Y which can account for the serological cross-reactivity of the B7-CREG and B5-CREG, respectively. One of the smaller of these CREG's consists of HLA-B15 and B17. Using microcytotoxicity testing, a fluoresceinated Protein A binding assay, and chemical immunoprecipitation techniques, we have defined a new public alloantigenic determinant, tentatively designated "Z," which is present on the 44,000 dalton glycoprotein chains of HLA-B15 and HLA-B17, but distinct from the B15 and B17 determinants. Since HLA-B15 is also a member of the B5-CREG, and therefore bears allodeterminant Y, this report constitutes the first immunochemical demonstration of two public determinants, Y and Z, on a single HLA-B molecule, HLA-B15.

Absorption↗
PubMed1980

Congeners of the beta conformer of dopamine derived from cis- and trans-octahydrobenzo[f]quinoline and trans-octahydrobenzo[g]quinoline.

The so-called beta conformer of dopamine has been proposed to be involved in agonist--receptor interactions at several sites in the dopaminergic nervous system. Further to evaluate this proposal, rigid congeners of the beta conformer derived from linearly and angularly annelated octahydrobenzoquinolines have been synthesized. Certain N-alkylated trans-angularly annelated systems exhibited unusually potent and highly selective dopamine-like effects in an assay on a cardioaccelerator nerve preparation in the cat, but these compounds were inactive in a variety of assays for CNS effects. These compounds present a clear separation of CNS effects from some potent peripheral effects.

Animals↗
PubMed1980

Congeners of the alpha conformer of dopamine derived from octahydrobenz[h]isoquinoline.

Two synthetic paths have been investigated for the preparation of cis and trans 8,9-dioxygenated octahydrobenz[h]isoquinoline ring systems. A sequence involving intramolecular Diels--Alder cyclization of a ring-opened intermediate product of a benzocyclobutene derivative was more satisfactory. The trans-fused isomers of the title compounds are frozen congeners of the alpha conformer of dopamine, isomeric with certain other tricyclic heterocycles which elicit a high degree of dopamine agonist activity. However, the present series of compounds exhibited a very low potency in an assay for dopamine-like actions. A possible reason for this inactivity has been suggested.

Animals↗
PubMed1980

Role of the papillary muscle in opening and closure of the mitral valve.

Dimensional changes of the left ventricular anterolateral papillary muscle of six open-chest dogs were measured continuously throughout the cardiac cycle in order to evaluate the role of the papillary muscle in opening and closing of the mitral valve. Dimensional changes were measured with ultrasonic dimension gauges. Maximal shortening and maximal elongation of the papillary muscle followed maximal shortening and elongation of a segment of the free wall of the left ventricle by 65 +/- 6 (SE) ms. Maximal elongation of the papillary muscle occurred 25 +/- 2 ms after the onset of ejection. Maximal shortening of the papillary muscle occurred 68 +/- 5 ms after the aortic incisura and 10 +/- 2 ms after the crossover of left ventricular and left atrial pressure. The papillary muscle shortened 14 +/- 4%. The percentage of papillary muscle shortening that occurred after the aortic incisura was 39 +/- 7%, and the percentage of shortening that occurred after the crossover of left ventricular and left atrial pressure was 3 +/- 1%. The observed shortening of the papillary muscle throughout left ventricular isovolumic relaxation suggests that the papillary muscle may have a role in opening the mitral valve. Conversely, elongation of the papillary muscle in the late portion of diastole appears necessary to permit proper closure of the mitral valve leaflets.

Animals↗
PubMed1980

Elevation of brain neuroleptic/dopamine receptors in schizophrenia.

To test the dopamine hypothesis of schizophrenia the authors measured specific 3H-neuroleptic/dopamine binding sites in three dopamin-rich regions of 59 postmortem normal human brains and 50 postmortem brains from schizophrenic patients using 3H-haloperidol and 3H-spiperone. The binding of 2 nM 3H-haloperidol and of 1 nM 3H-spiperone was significantly elevated in the brains from schizophrenic patients. The brain regions from patients who had no history of being treated with neuroleptic drugs also exhibited significantly higher binding of the 3H-neuroleptics. These results are compatible with the hypothesis that schizophrenia may be associated with an overactivity of postsynaptic dopamine receptors.

Adolescent↗
PubMed1980

Abnormal neuroleptic/dopamine receptors in schizophrenia.

In order to test the dopamine hypothesis of schizophrenia, the neuroleptic/dopamine receptors in three dopamine-rich regions of 53 postmortem normal human brains and 42 schizophrenic brains were measured using 3H-haloperidol and 3H-spiperone. The binding of 2 nM 3H-haloperidol was significantly elevated in the caudate nucleus (90 +/- 10%) and the putamen (61 +/- 6%) from schizophrenic brains. The binding of 1 nM 3H-spiperone was also elevated by 50 +/- 7% in schizophrenic caudate and 47 +/- 8% in the putamen. The nucleus accumbens from schizophrenic brains revealed an enhanced binding of 110 to 115%. In those schizophrenic patients who had no history of being treated with neuroleptic drugs the brain regions also exhibited significantly higher (29-80%) binding of 3H-neuroleptics. The results are compatible with the hypothesis that schizophrenia may be associated with an overactivity of postsynaptic dopamine receptors.

Adult↗
PubMed1979

Dopaminergic effects of non-hydroxylated rigid analogs of apomorphine.

A series of rigid analogs of apomorphine lacking aromatic hydroxyl substitutents were evaluated for dopaminergic properties. Three compounds, N-methyl-N-propyl-2-aminotetralin (Me-Pr-2-AT), N-N-dipropyl-2-aminotetralin (Di-pr-2-AT) and N,N-dipropyl-2-aminoindane (Di-Pr-2-AI) induced emesis in dogs, contralateral circling in unilaterally lesioned rats, and inhibited prolactin secretion. The induced circling responses, however, were attenuated by prior treatment with alpha-methyl-p-tyrosine methyl ester (AMPTME) and the compounds were weak inhibitors of 3-H-dopamine binding in calf caudate homogenates. The possibility that these agents may be metabolically activated in vivo is discussed.

Animals↗
PubMed1979

Rigid congeners of dopamine based on octahydrobenzo[f]quinoline: peripheral and central effects.

A series of cis- and trans-dihydroxycotahydrobenzo[f]quinoline congeners of dopamine has been prepared, in which the N substitutent is H, ethyl, or n-propyl. The trans isomers include the dopamine moiety held rigidly in an antiperiplanar diposition which is believed to be necessary for certian central and peripheral dopaminergic effects. The cis isomers are flexible molecules; the dopamine moiety lacks conformational integrity and it can exist in a conformation which is believed not to favor dopaminergic activity. The trans series of compounds was shown to possess a high level of central and peripheral dopaminergic effects, whereas the cis series was of low activity or was inert. These data further support previous proposals concerning stereochemical requirements for certain dopaminergic agonist activity.

Animals↗