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Biomedical subjects

L Diamond

Publications and source records attributed to L Diamond.

At least 127 records · Page 7Linked to original sources
PubMed1978

Active bronchial anaphylaxis in the rat: inhibition by tiaramide.

Intravenous administration of the benzothiazoline derivative tiaramide hydrochloride, to rats actively sensitized to ovalbumin, inhibited immunologic lung reactions in a dose-related manner. Methysergide also inhibited anaphylactic lung reactions. Serotonin, but not other chemical mediators, produced changes in pulmonary mechanics qualitatively similar to those produced by the sensitizing antigen. The bronchoconstrictive action of serotonin was blocked by methysergide and tiaramide. The latter drug also inhibited bronchoconstriction induced by methacholine. The results implicate serotonin as the primary mediator of the respiratory component of systemic anaphylaxis in the rat: however, the mechanism by which tiaramide inhibits anaphylactic bronchoconstriction remains to be elucidated.

Anaphylaxis↗
PubMed1978

Formation of 7,12-dimethylbenz[alpha] anthracene-DNA adducts in 7,8-benzoflavone-treated hamster embryo cells.

Pretreatment of secondary cultures of Syrian hamster embryo cells with 7,8-benzoflavone (7,8-BF) inhibited both the metabolism of 7,12-dimethylbenz[alpha] anthracene (DMBA) and the formation of DMBA-DNA adducts. The DMBA-deoxyribonucleoside adducts from 7,8-BF-treated cultures had the same elution profiles on Sephadex LH-20 columns as those from cultures exposed to DMBA alone, but 7,8-BF-treated cultures contained smaller amounts of DMBA-DNA adducts per mg DNA. As the concentration of 7,8-BF was increased, the decrease in the amount of DMBA-DNA adducts per mg DNA was logarithmic with respect to the decrease in the amount of DMBA metabolized. The results suggest that more than one metabolic step is required for the binding of DMBA to DNA in hamster embryo cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Congenital hypoplastic anemia (Diamond-Blackfan syndrome) terminating in acute myelogenous leukemia.

A 31-yr-old female with congenital hypoplastic anemia (Diamond-Blackfan syndrome) whose long course terminated in acute myelogenous leukemia is described. In contrast to Fanconi anemia, malignant transformation rarely occurs in congenital hypoplastic anemia. This patient's diagnosis of congenital hypoplastic anemia is supported by her clinical course, absence of renal abnormalities, a negative family history for hematologic disorders, normal chromosome studies, failure of her skin fibroblasts to transform in culture with SV-40 virus, macrocytic erythrocyte indices, erythrocyte enzyme studies, and bone marrow findings. Only two other cases of malignancy have been reported in patients with congenital hypoplastic anemia. The development of malignancy in these patients suggests that malignant transformation may be a concern in the long-term progression of congenital hypoplastic anemia.

Adult↗
PubMed1978

Metabolism of tritium-labeled 12-O-tetradecanoylphorbol-13-acetate by cells in culture.

The metabolism of [20-3H]-12-O-tetradecanoylphorbol-13-acetate ([3H]TPA) was studied in human and hamster cell cultures. Within 2 to 3 days after its addition to growing or confluent cultures of hamster embryo fibroblasts, no unchanged [3H]TPA remained in the medium as determined by thin-layer chromatography of the chloroform phase obtained by extraction of the medium with chloroform:methanol:H2O. In contrast, little or no metabolism of [3H]TPA occurred under identical conditions in cultures of human fibroblasts. The major metabolite formed from [3H]TPA in hamster cell cultures was [3H]phorbol-13-acetate. with both hamster and human cells, virtually all cell-associated radioactivity was unchanged [3H]TPA.

Animals↗
PubMed1978

The effects of exogenous norepinephrine on ventilatory mechanics in the rat.

The effects of intravenous administration of norepinephrine on ventilatory mechanics were assessed in the anesthetized, spontaneously breathing rat. Pulmonary resistance, dynamic compliance and functional residual capacity remained unchanged during a 10-min infusion period. After paralysis, repetition of the norepinephrine infusion caused an increase in static deflation recoil pressure at lung volumes above the tidal range but maximum expiratory flow rates at corresponding lung volumes were not increased indicating an elevation in the resistance of upstream airways. Flow rate responses to low density gas breathing were not enhanced by norepinephrine suggesting peripheral airways narrowing as the cause of the increased upstream resistance. Isoproterenol protected animals against serotonin-induced bronchoconstriction whereas norepinephrine augmented the response to serotonin. It is concluded that in intact rats norepinephrine increases the flow-resistive properties of peripheral airways, does not measurably alter the caliber of central airways and possesses no discernible bronchodilator activity. The effects of norepinephrine on small airways appear to be secondary to changes in pulmonary hemodynamics rather than the result of direct stimulation of alpha adrenoceptors in airway smooth muscle.

Airway Resistance↗
PubMed1978

Formation of glucuronic acid conjugates of 7,12-dimethylbenz(a)anthracene phenols in 7,12-dimethylbenz(a)anthracene-treated hamster embryo cell cultures.

Secondary cultures of hamster embryo cells exposed to 0.5 nmol [G-3H]7,12-dimethylbenz(a)anthracene (DMBA) per ml medium metabolized more than 90% of the DMBA within 48 hr. Samples of medium were extracted with chloroform, methanol, and water. The chloroform phases contained about one-third of the DMBA metabolites; the major chloroform-extractable metabolite was 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene. Beta-glucuronidase treatment of the aqueous methanol-soluble metabolites converted almost one-half of them to chloroform-soluble metabolites, of which more than 80% were identified as phenolic derivatives of DMBA. Similar metabolite profiles were obtained by treating the medium with beta-glucuronidase before chloroform extraction. Separation of the methyl group-hydroxylated derivatives of DMBA from the phenolic derivatives was accomplished by high-pressure liquid chromatography. Small amounts of hydroxymethyl derivatives were detected only in the chloroform-extractable material, whereas DMBA phenols were the major component of the beta-glucuronidase-released mateirla. These results indicate that the major pathway of DMBA metabolism in hamster embryo cells is oxidation of the aromatic rings and not oxidation of the methyl groups.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

The effect of ion pair formation on the antimuscarinic activity of methantheline.

The quaternary ammonium compound, methantheline, was found to antagonize acetylcholine induced contractions in isolated guinea pig ileum by a mechanism which did not conform to the criteria for either competitive or non-competitive inhibition. Enhancement of the lipid solubility of methantheline by formation of an ion pair with trichloracetate failed to influence its cholinergic inhibitory activity. The results suggest that in the guinea pig ileum a) an intracellular site of action does not exist for methantheline and b) the membrane receptors for methantheline most likely are located in an aqueous environment.

Acetylcholine↗
PubMed1977

Relationship of aryl hydrocarbon hydroxylase activity to benzo(a)pyrene-metabolizing activity of cells in culture.

The basal level of aryl hydrocarbon hydroxylase (AHH) activity was high in cultures of low passage hamster embryo (HE) cells but AHH inducibility by benz(a)-anthracene (BA) was low; in R72/3 rat liver cells, basal activity was low and inducibility was high. The metabolism of 3H--benzo(a)pyrene was similar in cultures of BA-induced R72/3 cells and uninduced HE cells. Thus, low AHH inducibility may not always be an indication of the cells' absolute hydrocarbonmetabolizing capacity.

Aryl Hydrocarbon Hydroxylases↗
PubMed1977

Tumor promoters inhibit spontaneous differentiation of Friend erythroleukemia cells in culture.

Clones of Friend erythroleukemia cells, characterized by the presence of 40-70% benzidine-positive cells synthesizing hemoglobin in the absence of inducing drugs, were treated with several phorbol diesters with a known range of tumor-promoting activity on mouse skin. Good correlation was found between the reported tumor-promoting activity of a particular phorbol diester and its ability to inhibit spontaneous erythroid differentiation in culture. The inhibition of differentiation by 12-O-tetradecanoyl-phorbol-13-acetate, the most active tumor promoter, was maximum after 4 days of treatment; this inhibition was reversed by removal of the phorbol diester no matter how long the period of treatment. Unlike control cells, which gradually revert to a population with a low percentage of benzidine-positive cells, cells treated with 12-O-tetradecanoyl-phorbol-13-acetate retained a high potential for spontaneous differentiation.

Animals↗
PubMed1977

Pulmonary mechanics in normal rats.

A versatile, whole-body pressure, or volume plethysmographic system for the study of pulmonary mechanics in anesthetized, tracheotomized rats has been described. Lung volumes and lung compliance values were in good agreement with those previously reported. Pulmonary resistance and chest wall compliance values were lower than those previously reported. Total dynamic compliance remained independent of respiratory frequency between 40 and 320 breaths/min. Flow-limiting behavior was demonstrated from a series of imposed forced expiratory maneuvers of graded effort. With a deflation pressure of 30 cmH2O, the effort-independent range of maximum flow extended to 40-50% of vital capacity. Maximal flow-static recoil pressure relationships were essentially linear over the effort independent portion of the flow-volume curve. Substitution of a low-density gas mixture (80% He-20% O2) for air resulted in increased forced expiratory flow rates but the magnitude of the response was considerably less than that which has been reported in man.

Airway Resistance↗
PubMed1977

Serum creatine phosphokinase activity in asthma.

Serum creatine phosphokinase activity was measured in 2 groups of asthmatics. The first group consisted of 12 asthmatics followed as outpatients for periods of up to 16 months. Serum creatine phosphokinase activity increased in 8 patients and correlated with the severity of subjective symptoms and objective measurement of airway obstruction, as represented by the forced expiratory volume in 1 second. In the second group, consisting of 5 asthmatic patients studied during hospitalization for acute exacerbations of asthma, serum creatine phosphokinase activity was increased on admission in all the patients and decreased as symptoms and airway obstruction improved and alveolar ventilation decreased. Analysis of creatine phosphokinase isoenzymes showed the increase in every instance to be due entirely to skeletal muscle isoenzyme. The results of additional laboratory tests and further evaluation suggested that the increased serum creatine phosphokinase activity was not derived from the myocardium and was not related to parenteral therapy, specific drugs, hyperthermia, or hyperkalemia. The increase in serum creatine phosphokinase during exacerbations of asthma is probably derived from respiratory muscles, owing to the increased work of breathing.

Airway Obstruction↗
PubMed1977

Survival differences exhibited by normal and transformed rat liver epithelial cell lines in the aggregate form.

Normal and transformed rat liver epithelial cell lines exhibited differences in the ability to survive in the aggregate form. Normal rat liver epithelial cells in the aggregate form underwent a rapid decline in the number of viable cells, while counterpart transformed epithelial cells exhibited an ability to survive and proliferate in the aggregate form. This survival ability was found to correlate with colony formation in soft agar and tumorigenicity in nude mice. Cell survival in the aggregate form could possibly serve as a criterion for in vitro transformation of epithelial cells derived from rat liver.

Cell Aggregation↗
PubMed1977

Ornithine decarboxylase induction and DNA synthesis in hamster embryo cell cultures treated with tumor-promoting phorbol diesters.

The effects of tumor-promoting phorbol diesters on ornithine decarboxyalse (ODC) activity and DNA synthesis in normal and chemically transformed hamster embryo fibroblasts (HEF) in culture were studied. Only those phorbol diesters with promoting activity in mouse skin induced ODC in HEF. ODC was induced in both cell types by 12-O-tetradecanoyl-phorbol-13-acetate (TPA); maximal induction occurred 4 to 6 hr after the addition of the promoter to the medium of confluent cultures and was greater in transformed cells than in normal cells. The extent of induction in transformed cells treated with 0.016 to 1.6 micron TPA was dose dependent. The cellular concentrations of the polyamines, particularly putrescine, also increased after TPA treatment. The addition of TPA to confluent cultures of either normal or transformed HEF did not produce an increase in cell number or the percentage of [3H]thymidine- labeled nuclei and did not stimulate the incorporation of [3H]thymidine. ODC also was induced by adding fresh medium to the cultures. When both fresh medium and TPA were added, the effect of the medium was markedly potentiated in transformed, but not in normal, cells. These experiments demonstrate that tumor promoters specifically induce ODC in HEF without increasing the rate of DNA synthesis and that normal and transformed HEF differ in the levels of ODC activity attained after exposure to promoters.

Carboxy-Lyases↗