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Biomedical subjects

T Lee

Publications and source records attributed to T Lee.

At least 343 records · Page 19Linked to original sources

Differentiation of asymptomatic patients from symptomatic patients by the slope of the forced vergence fixation disparity curve.

Eighty-nine optometry students were divided into an asymptomatic group and a symptomatic group on the basis of a case history. A forced vergence fixation disparity (FD) curve was generated for each subject using a Disparometer (Vision Analysis, Columbus, Ohio). Slopes were calculated for each curve. In addition, each curve was labeled steep or flat based on a previously determined cutoff point of -0.96 min/delta (Sheedy, 1980). Steep curves did not correlate well with symptomatic patients, whereas flat curves did not correlate well with asymptomatic patients. An independent t-test found no significant difference between the two groups.

Fixation, Ocular↗

Hemoglobin North Chicago (beta 36 [C2] proline----serine): a new high affinity hemoglobin.

Hemoglobin North Chicago, beta 36 [C2] Pro----Ser is a new high oxygen affinity hemoglobin variant. It was discovered in a 52-year-old male with erythrocytosis since age 20 who had been treated with different regimens for polycythemia vera including several courses of 32P. The variant is electrophoretically silent with normal stability and increased oxygen affinity (P50 16.6 mm Hg at 37 degrees C, pH 7.4). Characterization of the structure of hemoglobin North Chicago involved the use of HPLC, secondary ion mass spectral analysis of the tryptic peptides and conventional fingerprinting. Hemoglobin North Chicago manifested bizarre hydrophobicity of its beta-chains, as demonstrated by reverse phase HPLC and Triton X-100 electrophoresis. This behavior is not expected from the substitution of proline to serine. Proline residue beta 36 [C2] is one of the invariant residues of the beta-chains of all known mammals and most vertebrates. This residue is involved in the alpha 1 beta 2 contacts of hemoglobin molecule and its substitution to serine is possibly associated with conformational changes and alteration of hemoglobin function.

Amino Acid Sequence↗

An unusual case of sacrococcygeal teratoma and a short review.

While sacrococcygeal teratoma presents typically at birth as a mass lesion, we had a case of late presentation with the classical triad of urinary retention, constipation and weakness of legs. Interesting enough, a tuft of hair together with a small lump was noted at birth and an associated small meningocoele was found at operation. We review the literature with regard to pathogenesis, clinical features, differential diagnosis, malignant change and treatment of the tumour.

Constipation↗

Increased biosynthesis of platelet-activating factor in activated human eosinophils.

1-Alkyl-2-lyso-sn-glycero-3-phosphocholine:acetyl-CoA acetyltransferase catalyzes the conversion of biologically inactive lysophospholipid to bioactive platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) by an acetylation reaction. The activity of this enzyme in eosinophils isolated from patients with eosinophilia is stimulated (up to 4-fold) in a dose-, time-, and Ca2+/Mg2+-dependent manner after exposure to the eosinophil chemotactic factor of anaphylaxis (ECF-A), C5a, formyl-methionylleucylphenylalanine (fMLP), or ionophore A23187. The three naturally occurring chemotactic factors (ECF-A, C5a, and fMLP) cause a rapid and transient increase of enzyme activity, with a maximum at 1 or 3 min, whereas ionophore A23187 maintains an elevated level for up to 15 min. The activity of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine acetylhydrolase, an enzyme that catalyzes the breakdown of PAF to lyso-PAF, is not affected by C5a, fMLP, or ionophore A23187. The presence of PAF in eosinophils was established by demonstrating the lipid nature of the compound, the RF value being identical with that of synthetic 1-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine on thin layer chromatograms, and by its ability to induce serotonin release from rabbit platelets. Furthermore, ECF-A, C5a, fMLP, and ionophore A23187 all induce the secretion of PAF from eosinophils. These findings suggest that the generation and release of PAF could be a consequence of eosinophil chemotactic activation and may thus function in inflammatory and allergic reactions in which eosinophils participate.

Acetyltransferases↗

Loxapine and clozapine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain.

Chronic administration of loxapine or clozapine in rats for 4 weeks or 10 weeks did not produce enhancement of striatal dopamine receptor density. However, there was a marked reduction (50-60%) of cortical serotonin receptor density associated with clozapine or loxapine administration. Acute doses of clozapine or loxapine produced the same potent effect. The possibility that these two antipsychotic drugs act via the serotonin system in the brain is proposed.

Animals↗

6-Hydroxy-4-[2-(di-n-propylamino)ethyl]indole: synthesis and dopaminergic actions.

The title compound was proposed to be a biologically active metabolite of a dopaminergic agent, 4-[2-(di-n-propylamino)ethyl]indole. This proposed metabolite was synthesized by a multistep sequence beginning with methyl 3,5-dinitro o-toluate, and involving the Batcho-Leimgruber modification of the Reissert indole synthesis. The target compound exhibited high potency/activity in vivo in a cat cardioaccelerator nerve assay and in vitro in an isolated cat atrium assay. It manifested maximal pharmacological effect less than 5 min after intravenous administration in cats, as compared with a 20-min lag time following intravenous administration of the nonoxygenated congener. These pharmacological data are consistent with the proposal that the target compound is a metabolite of 4-[2-(di-n-propylamino)ethyl]indole.

Animals↗

The effect of 16, 16-dimethyl prostaglandin E2 on experimental bile reflux pancreatitis in the opossum.

Pharmacological attempts to alter the course of experimental pancreatitis in the opossum were made using synthetic 16, 16-dimethyl prostaglandin E2 (16, 16-dm PGE2). Anatomically, the opossum has an elongated ampulla resulting in a supraduodenal pancreatic duct-common bile duct junction allowing for bile reflux pancreatitis to be produced by ligating the distal common bile duct. Preliminary evaluation demonstrated that at 72 hours common bile duct ligation distal to the pancreatic duct orifice produced pancreatitis comparable in severity to that produced by a Pfeffer loop. When the oppossum distal common bile duct was ligated, serum amylase concentrations progressively increased from control values of 182 +/- 43 to 742 +/- 62 Somogyi units/dl at 5 hours. Administration of 0.2 microgram-kg-1-min-1 16, 16-dm PGE2 significantly decreased the hyperamylasemia associated with bile reflux pancreatitis and, in addition, decreased the pancreatic gland weights when compared to control values. Subsequent evaluation of the administration of 75 micrograms-kg-1 16, 16-dm PGE2 every 12 hours for 72 hours to opossums with distal common bile duct ligation demonstrated no significant differences in serum amylase concentrations when compared to control values. Histologic evaluation of the pancreas glands at 72 hours demonstrated increased glandular integrity when the pancreas glands from the opossums receiving 16,16-dm PGE2 were compared to the glands subjected to distal common bile duct ligation alone. This report identifies several favorable characteristics in the course of experimental pancreatitis associated with the administration of a synthesis PGE analog at the onset of the inflammatory process.(ABSTRACT TRUNCATED AT 250 WORDS)

16,16-Dimethylprostaglandin E2↗

TL-350, an ergoline derivative with dopamine receptor agonist properties.

Intravenous and intraduodenal injection of a new ergoline derivative, TL-350, produced dose-dependent inhibition of heart rate increase produced by cardioaccelerator nerve stimulation in anesthetized cats. ID50 values of TL-350 were 0.019 and 0.047 mumol/kg after i.v. and intraduodenal injection, respectively. This inhibition was reversed by either sulpiride (0.15 mumol/kg i.v.) or haloperidol (0.13 mumol/kg i.v.) but not by yohimbine (0.14 mumol/kg i.v.). TL-350 did not change isoproterenol-induced tachycardia and hypotensive responses. TL-350 caused dose-dependent decrease of arterial blood pressure and heart rate in anesthetized cats. Haloperidol (0.13 mumol/kg i.v.) prevented the hypotensive and bradycardic effects of the compound. TL-350 also produced concentration-dependent inhibition of heart rate responses to transmural stimulation of isolated cat right atria. IC50 value was 0.026 microM. Dopaminergic antagonists, haloperidol and sulpiride, antagonized the inhibitory effect of TL-350 in in vitro experiments. TL-350 did not stimulate presynaptic alpha-2 adrenergic receptors in rat vas deferens and guinea-pig ileum. TL-350 induced rotation for 3 hr in rats with unilateral denervated caudate nucleus. The compound was 0.5 as potent as apomorphine. In [3H]dopamine binding assays using rat caudate tissue, TL-350 had approximately the same activity as apomorphine in displacing the radioligand. It was concluded that TL-350 is a selective dopamine receptor agonist without possessing alpha and beta adrenergic receptor stimulating activity.

Animals↗

Selection and characterization of L1210 sublines resistant to teniposide (VM-26).

Two spectra of L1210 sublines with gradations of resistance to teniposide (VM-26) were selected by stepwise exposure of cultures to increasing concentrations of the drug. Cultures representing the first spectrum were from 20 times to 1200 times more resistant to VM-26 than were cultures of parental cells. At 24 hr after addition of 22 nM VM-26 to the medium, the growth of cultures of parental cells was inhibited by 50%. Increases in resistance to VM-26 among the sublines coincided with increases in population doubling times. When cells were transferred to drug-free medium, there was a sharp decrease in resistance over the first 10 days; the subsequent decline in resistance, over 2 to 4 months, correlated with a decrease in population doubling times. The second spectrum of resistant sublines arose from the first spectrum after the latter had been maintained for about 1 year on various selective concentrations of VM-26. Resistance to VM-26 by this second group of sublines was from 400 times to over 2000 times greater than that of the parental cell line. Doubling times for these resistant cell populations were similar to the normal rate of the parental cell line. Eight sublines were characterized by two chromosomes with homogeneously staining regions, while the remaining subline had a single chromosome with this anomaly. One of the regions appeared on a submetacentric chromosome in seven of the nine sublines, while the other was on an acrocentric chromosome. These observations indicate that a longer doubling time facilitated selection of increasingly resistant sublines but was not essential for the resistance of sublines in the second spectrum.

Animals↗

Flux of teniposide (VM-26) across the plasma membrane of teniposide-resistant sublines of L1210 cells.

The flux of teniposide (VM-26) across the cell membrane was compared for L1210 cells, nine VM-26-resistant L1210 sublines, and three partially revertant lines. The nine resistant sublines were maintained in medium with VM-26. A "zero-time," temperature-independent binding of VM-26 to cells, attributable to adsorption on the cell membrane or to solvation in the membrane, varied independently of the sensitivity of cell lines to the drug as measured by the extracellular concentration of drug required to inhibit growth of a subline by 50% at the end of 24 hr (IC50). The IC50 values varied from 22 nM VM-26 for parental cells to 45 microM VM-26 for the most resistant subline. After subtraction of the zero-time values, the initial rates of influx for VM-26 (extracellular concentration, 20.5 microM) and the apparent equilibrium constants for the flux of drug across the cell membrane correlated inversely with the logarithm of the IC50 values. Cellular steady-state levels of VM-26, initial rates of efflux of the drug, and cellular levels of nondiffusible drug varied independently of the IC50 values but in relation to each other. The efflux of VM-26 from the sublines was faster than from the parental cells at both 4 degrees and at 37 degrees. We conclude that resistance of L1210 cells to VM-26 is associated with changes in the flux of the drug across the cell membrane.

Animals↗

Intracoronary fibrinolytic therapy in acute myocardial infarction. Report of a prospective randomized trial.

We performed a randomized trial comparing intracoronary administration of streptokinase versus dextrose placebo within six hours after the onset of symptoms of acute myocardial infarction in 40 patients. The base-line clinical, hemodynamic, and angiographic findings were similar in the control and streptokinase-treated groups. Reestablishment of flow occurred in 12 of 20 patients treated with streptokinase and in 2 of 20 given placebo (P less than 0.05). Left ventricular function, angiographic ejection fraction, and regional wall motion, measured before and immediately after intervention, and serial radionuclide ejection fractions, measured at treatment, at 12 days, and at 5 months, were compared according to type of treatment (streptokinase vs. placebo) and outcome of therapy (reperfusion vs. no reperfusion). No statistically significant differences between groups were found. Thus, although streptokinase was more effective than placebo in achieving reperfusion, we detected no improvement of left ventricular function as a result of reestablished coronary flow.

Adult↗