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Biomedical subjects

S Abraham

Publications and source records attributed to S Abraham.

At least 217 records · Page 12Linked to original sources

Relationship of malic enzyme activity to fatty acid synthesis and the pathways of glucose catabolism in developing rat liver.

The rates of fatty acid synthesis and the activity of several enzymes involved in lipid and carbohydrate metabolism were determined in livers from fetal, suckling, weanling and maternal rats. An estimate of the proportion of glucose catabolized via the pentose phosphate cycle and the Embden-Meyerhoff pathway was made using 14C- and 3H-labeled glucose. The contribution of pentose phosphate cycle-generated reducing equivalents to fatty acid synthesis was assessed using glucose-3-3H. Developmental changes in the activity of hepatic malic enzyme were not related to developmental changes in the rate of fatty acid synthesis as might be expected if this enzyme functioned to provide NADPH for fatty acid synthesis. Malic enzyme activity did not correlate with pentose phosphate cycle activity or with utilization for fatty acid synthesis of NADPH generated via this pathway.

Acetates↗

Does rigidity in structure of muscarinic agonists and antagonists reflect drug specificity?

The present work is an attempt to elucidate: (1) whether highly rigid structural analogs of acetylcholine are still capable of activating the muscarinic receptor; (2) whether such analogs, be they agonists or antagonists, discriminate among the various ACh-mediated functions, thereby providing a tool for the study of a possible receptor heterogeneity; (3) whether structural rigidity is a significant factor in the kinetics of drug-receptor interaction. To this end, we investigated some properties of drugs in the spiro-(1,3-dioxolane-4,3')-quinuclidine system (SDQ) which embodies the muscarinic pharmacophore in a framework of utmost rigidity. Wherever possible, these properties were compared with those of a closely related but more flexible analog. Variation in effect between members of a rigid-flexible pair or among drugs of varying rigidity is considered to reflect varying affinities towards various sites of action. 2-Methyl-spiro-(1,3-dioxolane-4,3')-quinuclidine (AF-30) is a weak but selective muscarinic agonist. It can be viewed as a highly rigid version of 3-acetoxyquinuclidine (3-AcQ) and it can be used as a probe for detection of heterogeneity among muscarinic receptors. AF-30 is equipotent with 3-AcQ in causing tremors (mice), but has 1/17th the activity of 3-AcQ in the guinea-pig ileum, 1/30th in lowering blood pressure (cats) and 1/10th in inducing analgesia (mice). 2-Diphenylmethyl-spiro(1,3-dioxolane-4',3)-quinuclidine (AF-41) and 2.2-diphenyl-spiro-(1,3-dioxolane-4,3')-quinuclidine (AF-32 are potent antagonists and possess KD values in the same range as those of the more flexible congener 3-diphenylacetoxy-quinuclidine (AF-43) and atropine (0.6--2 nM) but with koff = 0.1 msec-1 (AF-41) and koff = 1 msec-1 (AF-43) (carp atrium). Thus, duration of drug action of drug action at the receptor is a function of structural rigidity in the drug molecule, termination of action being fastest with the flexible molecules. Differences in rigidity among various antagonists also find expression in an unequal distribution of potencies in various tests; thus the rigid antagonists differentiate between two central effects in mice, viz., prevention of oxotremorine-induced tremors and fall from the rotating rod by a factor of 1:20 (especially AF-41 versus AF-43), whereas the more flexible antagonists (AF-43, atropine or even 3-quinuclidinyl-benzilate) do not show such as a selectivity. The existence of heterogenous muscarinic receptors can be inferred from data presented. Both theoretical and practical implications are discussed.

Acetylcholine↗

Microcomplement fixation and particle size of chicken lipoproteins.

Conformational changes of the lipoproteins of chicken serum and egg yolk were studied with the use of microcomplement fixation. Egg yolk very low density lipoproteins and serum total low density lipoproteins were separated by 2% agarose gel chromatography into four and five fractions, respectively, with different average particle diameters. A correlation between percent complement fixed at equivalence and particle diameter was noted. Thus, smaller particles fixed less complement. The shortening of the radius of curvature could alter the steric fit of apolipoprotein with antibody and, as a consequence, reduce complement fixation. The patterns obtained after delipidation of very low density lipoproteins indicate a general distortion of apolipoprotein conformation supporting the view that lipids are essential for maintaining the conformation of these apolipoproteins. On the other hand, the general conformation of the high density apolipoproteins does not appear to depend on lipid content. It has been reported that lipids restrain the free movement of these apolipoproteins. After delipidation, the greater degree of freedom allowed the apolipoprotein may increase the strength of the antigen-antibody union and therefore an increase in complement fixation is observed. These studies demonstrate the applicability of quantitative microcomplement fixation to the eludication of lipoprotein structure and function.

Animals↗

Identification of mouse mammary adipose cells by membrane antigens.

Antisera produced to mammary adipose cells from midpregnant BALC/c females can be used to distinguish mammary adipose cells from mammary epithelial cells and fibroblasts. The mammary adipose membrane antigen detected by indirect immunofluorescence was found in adipose cells from (a) mammary glands of virgin, midpregnant and lactating mice; (b) mammary fat pads that had been surgically cleared of glandular elements; and (c) epididymis. In all tissues, this cell-surface antigen was removed by the enzymatic action used to dissociate the cells from the tissues and was shown to be fully restored when cells were cultured for 48 hr.

Adipose Tissue↗

The influence of environmental salinity, temperature, ionizing irradiation and yellow or silver stage on lipid metabolism in the gills of the european eel (Anguilla anguilla).

1. The influence of temperature on the incorporation of [32P]phosphate and [14C]acetate into gill lipids in vivo depends also on environmental salinity. 2. Ionizing irradiation (1000 r) results in a relatively enhanced incorporation of [32P]phosphate into phosphatidyl choline and of [14C]acetate into triglycerides and wax esters in vivo. 3. When gill tissue is removed from the animal and incubated in vitro, a pronounced dependence of lipid metabolism on previous environmental salinity is not observed.

Acclimatization↗

The trabecular wall of Schlemm's canal: a study of the effects of pilocarpine by scanning electron microscopy.

The scanning electron microscope was used to study the endothelium lining the trabecular wall of Schelemm's canal in 10 human eyes enucleated in treatment of choroidal melanomas. The eyes of 5 patients had been treated before enucleated with pilocarpine drops, and the remaining 5 were untreated and served as controls. In the pilocarpine-treated tissue there was an increased prominence of cellular bulges in the endothelial monolayer, and the endothelial pores were both larger and more frequent than in the untreated eyes. By the use of Poiseuille's formula it was calculated that the resistance offered by the pore system to the drainage of aqueous in the pilocarpine-treated group was approximately one-ninth of that in the control series.

Choroid Neoplasms↗

Mass action and acridine orange staining: static and flow cytofluorometry.

We present results involving an approach to acridine orange staining of intact cells based on basic physicochemical considerations. We show by static microfluorometry of several in vitro and in vivo cell lines that the important parameters for such staining are the molar ratio (Formula: see text), and molar concentration of acridine orange. Differential nuclear DNA and cytoplasmic RNA staining are totally controlled by these two parameters. We show this by a physicochemical model of cell-dye interaction. Finally, we use the method to study the growth parameters of complex in vivo cell populations by automated multiparameter flow microfluorometry. We have explored also, both by static and flow systems, the effect on AO-cell staining of various cell pretreatments such as Triton X-100 and chelating agents.

Acridine Orange↗

The effects of topical pilocarpine on the morphology of the outflow apparatus of the baboon (Papio cynocephalus).

The morphology of the outflow system of the baboon (Papio cynocephalus) was studied by light microscopy and transmission electron microscopy in tissue from eyes treated with topical pilocarpine. In one group of five animals the intraocular pressure (IOP) was maintained at 18 mm /g in both the experimental and the control eye of each baboon for the duration of the experiment. The endothelial meshwork was more distended, and there was a significantly greater number of giant vacuoles in the lining endothelium of Schlemm's canal in the pilocarpine-treated eyes than in the corresponding controls. However, in another series of animals, IOP was not maintained, and the differences between the treated and untreated eyes was much less striking. There appeared to be little evidence that the increase in vacuolation was produced by the direct action of pilocarpine on the endothelium of Schlemm's canal; more likely, it was a consequence of an increased passage of fluid through the drainage system. In addition, we have been able to show that (1) the mode of primary fixation can produce partial reversal of the pilocarpine effect and (2) the mechanical manipulation which is required to determine outflow facility has a deleterious effect on the morphology of the outflow tissues.

Animals↗

A light microscopic study of the effects of testicular hyaluronidase on the outflow system of a baboon (Papio cynocephalus).

An attempt was made to investigate the effects of hyaluronidase on the morphology of the baboon outflow system. The eyes of six adult baboons provided the material for this histological study. For each animal the IOP in both eyes was maintained at 18 mm Hg, and 150 IU of testicular hyaluronidase were introduced into one eye and a control solution into the other. It was observed by light microscopy that the outer meshwork was more distended in the hyaluronidase-treated outflow system than in the corresponding controls. Further, it was found from a quantitative analysis that the incidence of giant vacuoles in the endothelium of Schlemm's canal was greater in the experimental than the control eye of each animal. The difference between the vacuole counts in the experimental and control eyes was significant in five of the six animals. These preliminary findings provide morphological evidence which indicates that there is a hyaluronidase-sensitive barrier to aqueous outflow in the baboon drainage system.

Animals↗

Associations between the cells of the walls of Schlemm's canal.

The associations between the cells of the corneoscleral and trabecular walls of Schlemm's canal from the three primate species human, baboon and rhesus monkeys were examined by transmission electron microscopy. Small gap junctions and occluding junctions modify the lateral borders between the canalicular endothelial cells. The endothelial monolayer on the corneoscleral aspect of Schlemm's canal is separated from several layers of fibrobasts by a continuous basement membrane. The fibroblasts are embedded in a dense collagenous matrix and at the regions of cellular association, modifications are restricted to simple maculae adhaerentes. The endothelial monolayer on the trabecular aspect of Schlemm's canal does not have a continuous basement membrane but maintains its association with the underlying endothelial meshwork by means of process connections. In the endothelial meshwork, the native meshwork cells link with each other by gap junctions and maculae adhaerentes.

Adolescent↗

Serum lipoprotein concentrations in cystic fibrosis.

Two major classes of lipoproteins, low density and high density, are decreased in the serum of patients with cystic fibrosis; major apoproteins are also decreased. Since essential fatty acids and certain fat-soluble vitamins depend on lipoproteins for transport in the serum, knowledge of lipoprotein levels in cystic fibrosis patients could prove valuable in understanding (i) the basis for the abnormally low serum levels of these fatty acids and vitamins and (ii) the effects of therapies involving these molecules.

Adolescent↗