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Biomedical subjects

E Lee

Publications and source records attributed to E Lee.

At least 397 records · Page 22Linked to original sources
PubMed1987

Gastrointestinal ulcer formation in rabbits immunized with prostaglandin E2.

Circulating prostaglandin E2 antibodies were produced in 12 rabbits immunized with prostaglandin E2-thyroglobulin conjugate and ulcers occurred in 10, usually in the stomach and less often in the small intestine. Immunization of rabbits with both prostaglandin E2 and 6-keto prostaglandin F1 alpha significantly increased the number of gastric ulcers compared with rabbits immunized with prostaglandin E2 alone. Gastrointestinal ulceration in prostaglandin E2-immunized rabbits was not prevented by oral enprostil. Gastrointestinal ulcers occurred as early as 6 wk after beginning immunization and often perforated with resulting fatality. Neither prostaglandin E2 antibodies nor ulcers developed in rabbits immunized with thyroglobulin vehicle (controls). Passive immunization of unimmunized rabbits with prostaglandin E2-hyperimmune plasma led to acute gastric ulcers within 9 days, whereas passive transfer of nonimmune plasma did not produce ulcers. This latter finding suggests that prostaglandin E2 antibodies per se were responsible for ulcer formation.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Effect of indomethacin on gastric mucosal prostaglandins in humans. Correlation with mucosal damage.

We evaluated in healthy human beings the effect of indomethacin on gastric mucosal prostaglandin concentration and on gastric mucosal damage in a placebo-controlled study. Prostaglandin E2, prostaglandin F2 alpha, and 6-keto prostaglandin F1 alpha concentrations of gastric mucosal biopsy specimens, obtained endoscopically, were measured by radioimmunoassay. Mean prostaglandin concentration of the antrum and fundus was similar. In both regions there was considerable intersubject variability in prostaglandin concentration. Repeated 50-mg oral doses of indomethacin for 4 days reduced mean prostaglandin F2 alpha and E2 concentration by 50.2% and 69.4%, respectively, in the fundus and by 40.0% and 49.7% in the antrum, but this led to no significant mucosal damage when assessed endoscopically or histologically. A single 100-mg oral dose of indomethacin reduced mean prostaglandin F2 alpha and prostaglandin E2 concentration by 81.4% and 60.9% in the fundus and by 64.2% and 57.5% in the antrum and also induced significant mucosal injury in both regions when assessed endoscopically. However, there was no correlation between degree of suppression of prostaglandin concentration by indomethacin and endoscopic evidence of mucosal damage.

Administration, Oral↗
PubMed1987

Gastroduodenal ulceration following active immunization with prostaglandin E2 in dogs. Role of gastric acid secretion.

In this study we present evidence to suggest that gastroduodenal mucosal defects may occur in gastric fistula dogs actively immunized with PGE2-thyroglobulin conjugate. One of four PGE2-immunized dogs developed a chronic pyloroduodenal ulcer with penetration into the pancreas and the other three had endoscopic evidence of gastric and/or duodenal erosions. In contrast, no gastroduodenal mucosal defects were seen in control dogs immunized with thyroglobulin alone. Occurrence of gastroduodenal ulcers or erosions was temporally related to formation of specific antibody to PGE2 suggesting that PGE2 antibody may be responsible for lesion formation. An increase in gastric acid secretion was not observed in PGE2-immunized dogs. Thus, it is likely that mucosal defects occur as a result of an impairment of PGE2-mediated mucosal defense mechanisms. Since gastroduodenal lesions can be visualized by endoscopy, the dog may prove to be useful in studying the role of endogenous PG in ulcer diseases.

Animals↗
PubMed1987

Selective operative approach for diagnosis and treatment of anterior mediastinal masses.

We retrospectively reviewed the records of 41 patients with an isolated anterior mediastinal mass to identify whether the traditional surgical approach of resection for both diagnosis and therapy is the optimal approach to these tumors. In addition to plain chest radiographs, clinical evaluation included computed tomography (CT) in 23 and gallium scintigraphy in 23. The initial intervention was attempted excisional therapy in 16 and mediastinoscopy for biopsy in 25. Pathological diagnoses included lymphoma (13), thymoma (11), germ cell tumor (6), carcinoid (2), bronchogenic carcinoma (2), and other benign processes (7). Based on histological findings, nonoperative therapy was the most appropriate treatment in 61%. The clinical selection of the surgical approach was not aided by patient age, symptoms, or findings on CT. The gallium scan was positive in 13 of 15 patients for whom nonoperative therapy was appropriate, and was normal in 7 of 8 for whom excision was indicated. Mediastinoscopy is useful in the diagnosis of anterior mediastinal masses, and may eliminate unnecessary thoracotomy, especially when a gallium scan is positive.

Adolescent↗
PubMed1987

Effect of cetirizine, a new histamine H1 antagonist, on airway dynamics and responsiveness to inhaled histamine in mild asthma.

Cetirizine, a major human metabolite of hydroxyzine, preserves the histamine H1-antagonist activity of the parent compound but poorly penetrates the blood-brain barrier, thus minimizing sedative and anticholinergic effects. In 10 young (mean age 27.7 years) subjects with mild asthma (FEV1 greater than 70% predicted), we evaluated the bronchodilator and protective efficacy of 5, 10, and 20 mg of cetirizine against bronchospasm induced by histamine inhalation (0.03 to 20 mg/ml) in comparison with placebo and hydroxyzine, 25 mg, using a random, double-blind crossover design. The provocative concentration of histamine causing a 20% decline in FEV1 for all 10 subjects from the postdiluent control value was more than fourfold greater after each active drug than after placebo. Cetirizine, 5 to 20 mg, provided significantly greater protection against histamine-induced bronchospasm than hydroxyzine (p less than 0.001); moreover, a dose-dependent protective effect was noted with cetirizine. Significant bronchodilation was also found: at 60 minutes, FEV1 increased significantly after all active antihistamines compared to placebo and after 20 mg of cetirizine compared to hydroxyzine (p less than 0.05). FEV1 increased significantly at 120 minutes after hydroxyzine and after cetirizine in both the 20 and 10 mg doses compared to placebo (p less than 0.05). We conclude that in subjects with mild asthma, orally administered cetirizine provides significant dose-dependent protection against histamine-induced bronchoconstriction, which in the doses studied is superior to that produced by the parent compound, hydroxyzine. In addition, cetirizine in 5 to 20 mg doses causes acute bronchodilation. These results suggest a possible role of cetirizine in asthma therapy.

Administration, Inhalation↗
PubMed1987

Induction of anionic glutathione transferases in rat liver by propylthiouracil.

The treatment of rats with propylthiouracil (PTU) resulted in an induction of not only cationic but also anionic glutathione (GSH) transferases. DE-52 column chromatography of the anionic GSH transferases divided into five main peaks (I-V). Peaks I-IV had a high activity toward 1-chloro-2,4-dinitrobenzene (CDNB). Peak V, which is a new form of the enzyme, showed high activity to ethacrynic acid. PTU induced peaks I and V, whereas phenobarbital increased the activity of only peak I.

Animals↗
PubMed1986

Propylthiouracil, a selective inhibitor of NADH-cytochrome b5 reductase.

Propylthiouracil inhibited the activity of NADH-cytochrome b5 reductase of rat liver microsomes using potassium ferricyanide as electron acceptor. On the other hand, NADPH-cytochrome P-450 reductase activity was not affected by the compound. NADH-supported reduction of cytochrome b5 was also inhibited by propylthiouracil in the reconstituted system consisting of cytochrome b5 and partially purified NADH-cytochrome b5 reductase.

Animals↗
PubMed1986

ESR studies on the oxidation of N,N-dimethyl-p-anisidine and its analogues catalyzed by myeloperoxidase.

N,N-Dimethyl-p-anisidine (DMA) was used as a substrate to differentiate between the direct, or chloride-independent, and the indirect, or chloride-dependent, pathways characteristic of myeloperoxidase (donor: hydrogen-peroxide oxidoreductase, EC 1.11.1.7). The chemical oxidation by sodium hypochlorite and the horseradish peroxidase-catalyzed oxidation by H2O2 were also investigated for a comparison. The chemical oxidation of DMA by NaOCl (DMA/NaOCl = 1) gave the p-N,N-dimethylaminophenoxy radical at pH 5 and 7. p-Benzoquinone and formaldehyde were determined as stable end-products. On the other hand, the cation radical of DMA was detected and p-benzoquinone was not obtained in the horseradish peroxidase-H2O2-Cl- system. In the presence of Cl- the myeloperoxidase-catalyzed oxidation at pH 5 gave nearly the same result as did the oxidation by NaOCl, whereas in the absence of Cl- the result of the oxidation was similar to that of the horseradish peroxidase-catalyzed oxidation, except for a low yield of formaldehyde formation, which was ascribed to the decomposition of H2O2 by the catalase activity of myeloperoxidase. Although the myeloperoxidase-catalyzed oxidation of DMA at pH 7 in the presence of Cl- gave only the cation radical of DMA, a fairly large amount of p-benzoquinone was obtained as a product. This result indicates that the indirect chloride-dependent oxidation is also operating at pH 7. The reaction mechanism for the myeloperoxidase-catalyzed oxidation of DMA is proposed.

Aniline Compounds↗
PubMed1986

Propylthiouracil inducible glutathione transferases. Selective induction of ligandin (glutathione transferase 1-1).

Repeated administration of propylthiouracil (PTU) resulted in an increase in glutathione (GSH) transferases activity in rat liver cytosol toward various substrates except for epoxy(p-nitrophenoxy)propane. The enzyme from rat treated with PTU showed high activity with 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid. GSH transferases were separated into five forms by CM-Sephadex C-50 column chromatography to detect which isozymes were induced by PTU treatment. Although the activity of the unretained fraction obtained from the column was slightly increased by PTU treatment, the treatment markedly elevated the activity of GSH transferase 1-1. On the other hand, the activities of GSH transferases 1-2, 3-3 and 2-2 were little changed. In addition, an analysis of GSH transferase 1-1 from CM-Sephadex C-50 using SDS-PAGE confirmed that it comprised the 1-1 homodimer. This fraction was then further purified by passing it through a hydroxylapatite column and the partially purified GSH transferase 1-1 from rats treated with PTU was found to have the same characteristics as the control, e.g. the same Km values for GSH and CDNB and the same substrate spectrum. It was concluded that PTU specifically induced GSH transferase 1-1 among the cationic transferases.

Animals↗
PubMed1986

Inhibition of hepatic glutathione transferases by propylthiouracil and its metabolites.

The effects of propylthiouracil (PTU) and its metabolites on the activity of GSH transferases were examined using rat liver cytosol. PTU inhibited the enzyme activity toward both CDNB and DCNB in a concentration-dependent manner. At the concentration of 10 mM, PTU caused 25% inhibition, which was the maximum effect. PTU derivatives such as propyluracil and thiouracil showed the same effect as the parent compound. On the other hand, S-oxides of PTU such as PTU-SO2 and PTU-SO3, which were chemically synthesized by the oxidation of PTU, were more potent inhibitors of GSH transferases than the parent PTU. A significant inhibition was observed at a concentration of 0.1 mM of PTU S-oxides. At a concentration of 10 mM the S-oxides caused an 80% inhibition of the enzyme activity. PTU inhibited the transferase activity by competing with GSH but the S-oxides of PTU acted by another mechanism. In contrast to the effect on GSH transferases, PTU-SO3 had a weak inhibitory effect on GSH peroxidase activity. Thus, oxidation of PTU leads to products which are potent inhibitors of GSH transferases.

Animals↗
PubMed1986

Clustering of extensive somatic mutations in the variable region of an immunoglobulin heavy chain gene from a human B cell lymphoma.

Following treatment of a human B cell lymphoma with an anti-idiotype antibody, a subpopulation of tumor cells remained that had lost the tumor-specific heavy chain idiotypic determinant. Nucleotide sequence analyses of eight independent heavy chain variable region isolates showed extensive point mutations, so that no two sequences were identical. Comparison of pretreatment and posttreatment sequences implicated an amino acid in CDR2 as being involved in the idiotypic determinant. Apparently the malignant B cells escaped the therapeutic effects of the anti-idiotype antibody through an ongoing process of somatic mutation in their immunoglobulin genes. Non-random clustering of amino acid replacements in CDR2 suggested that growth of the tumor may have been influenced by endogenous selective forces interacting with the tumor cell-surface immunoglobulin.

Amino Acid Sequence↗
PubMed1986

Psoralens potentiate ultraviolet light-induced inhibition of epidermal growth factor binding.

The psoralens, when activated by ultraviolet light of 320-400 nm (UVA light), are potent modulators of epidermal cell growth and differentiation. Previously, we reported that, in mammalian cells, these compounds bind to specific saturable high-affinity cellular receptor sites. In the present studies, we demonstrate that binding of psoralens to their receptors followed by UVA light activation is associated with inhibition of epidermal growth factor (EGF) receptor binding. Inhibition of EGF binding, which required UVA light, was rapid and dependent on the dose of UVA light (0.5-2.0 J/cm2), as well as the concentration of psoralens (10 nM to 1 microM). Higher doses of UVA light (2.0-6.0 J/cm2) by themselves were also inhibitory, indicating that psoralens potentiate the UVA-induced inhibition of EGF binding. A number of biologically active analogs of psoralen, including 8-methoxypsoralen, 5-methoxypsoralen, and 4,5',8-trimethylpsoralen, when activated by UVA light, were found to be inhibitors of binding. Inhibition of EGF binding by psoralens was observed in a variety of human and mouse cell culture lines known to possess psoralen receptors. In the epidermal-derived line PAM 212, at least two populations of receptors with different affinities for EGF were found. Psoralens and UVA light selectively inhibited binding to the higher-affinity EGF receptors, an effect analogous to that of the phorbol ester tumor promoters. As observed with phorbol esters, photoactivated psoralens appeared to inhibit EGF binding by an indirect mechanism. These data demonstrate that the psoralens and UVA light have direct biological effects on cell-surface membranes. Since EGF is a growth-regulatory peptide, the ability of psoralens and UVA light to inhibit EGF binding may underlie the biologic effects of these agents in the skin.

Cells, Cultured↗
PubMed1986

Association of the translocation (15;17) with malignant proliferation of promyelocytes in acute leukemia and chronic myelogenous leukemia at blastic crisis.

Cytogenetic studies were performed on nine patients with acute promyelocytic leukemia. Every patient had an identical translocation (15;17) or, in one case, a variant three-way rearrangement between chromosomes 7, 15, and 17. Another patient with chronic myelogenous leukemia was examined at the time of blastic crisis when the patient's bone marrow was infiltrated by hypergranular promyelocytes and blasts. Bone marrow cells contained a t(15;17) as well as a Ph1 chromosome. Only the latter abnormality was observed in the chronic phase of the disease. The translocation (15;17) was detected in all ten patients when bone marrow or peripheral blood cells were cultured for 24 hours prior to making chromosome preparations. However, the t(15;17) was not seen in three of these same cases when bone marrow cells were processed directly. These findings indicate that the t(15;17) is closely associated with acute proliferation of leukemic promyelocytes and that detection of this karyotypic defect may be influenced by the particular cytogenetic processing method used in different laboratories. An analysis of the banding pattern in the variant translocation provided additional evidence favoring chromosomal breakpoints at or very near the junction between bands 17q12 and 17q21 and at 15q22.

Bone Marrow↗