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Biomedical subjects

K E Williams

Publications and source records attributed to K E Williams.

67 records · Page 4Linked to original sources

Trypan blue: identification and teratogenic and oncogenic activities of its coloured constituents.

Three coloured substances frequently present as contaminants in commercial samples of trypan blue have been identified as those monoazo dyes in which 4-amino-3,3'-dimethyl-biphenyl, 4-amino-3,3'-dimethyl-4'-hydroxy-biphenyl or omicroc-tolidine are coupled to H-acid. These dyes have been synthesized and, together with purified samples of trypan blue, tested for teratogenic activity in mice and oncogenic activity in rats. Unpurified trypan blue was both teratogenic and oncogenic; purified trypan blue, was teratogenic but only weakly oncogenic; the monoazo dyes possessed neither activity. It is concluded that the main blue component of trypan blue is the teratogenic principle and that some as yet unidentified component of the purple fraction either is the main oncogenic principle or potentiates the action of the blue component.

Animals↗

A quantitative study of pinocytosis and lysosome function in experimentally induced lysosomal storage.

The highly pinocytic epithelial cells of the visceral yolk sac from 17.5-day rat conceptuses were used as a model in which to induce engorgement of the vacuolar system by direct accumulation of substances that are not hydrolysed by lysosomal enzymes. The ultra-structural appearances of these cells in pregnant animals that 24-48h before had received intraperitoneal injections of Triton WR-1339, polyvinylpyrrolidone, dextran or sucrose revealed gross abnormalities that were confined to the vacuolar system; in comparison with normal tissue the number, and in some cases the size, of vacuoles was increased, leading to close packing within the apical cytoplasm and distortion of the normal rounded shape. By culturing yolk sacs in vitro, rates of ingestion of 125I-labelled polyvinylpyrrolidone and of 125I-labelled bovine serum albumin were determined, together with the rate of digestion of the labelled protein. The rates of exocytosis of 125I-labelled polyvinylpyrrolidone and of lysosomal enzymes were also determined. No significant differences between normal and highly vacuolated tissues were found. Apparently marked vacuolation of these cells by these agents is without significant effect on pinocytosis, exocytosis or intralysosomal proteolysis.

Acetylglucosaminidase↗

Inhibition of pinocytosis in rat yolk sac by trypan blue.

Day 17.5 yolk sacs from rats injected with partially denatured 125I-labeled bovine serum albumin (I-BSA) were cultured in vitro by a raft technique. The rates of release of [125I]iodotyrosine were similar in control yolk sacs and in yolk sacs from rats preinjected with trypan blue. Day 17.5 rat yolk sacs were also cultured in medium containing I-BSA. Following pinocytic uptake the substrate was degraded intracellularly and [135I]iodotyrosine released into the medium. Trypan blue, when present in the medium in concentrations above 100 mug/ml, inhibited pinocytosis of I-BSA and so decreased the rate of [125I]iodotyrosine production. Trypan blue similarly decreased the rate of pinocytic uptake of 125I-labeled polyvinylpyrrolidone. Pinocytic uptake of macromolecules was not decreased in yolk sacs from rats pretreated with trypan blue. The relevance of these results to the mechanism of teratogenic action of trypan blue is discussed. It is proposed that if trypan blue in teratogenic doses similarly inhibits pinocytosis by the yolk sac during the organogenetic period teratogenesis might result from a transient interruption in the flow of metabolites through the yolk sac to the embryo.

Animals↗

Quantitative studies of pinocytosis. I. Kinetics of uptake of (125I)polyvinylpyrrolidone by rat yolk sac cultured in vitro.

A method is described for the in vitro culture of 17.5-day rat visceral yolk sac. Tissue survival was good as judged by light and electron microscopy. The rate of pinocytic uptake of 125I-labeled polyvinylpyrrolidone by the tissue was constant both within and between experiments. Within the concentration range 0.15-24 mug/ml, the 125I-labeled polyvinylpyrrolidone neither stimulated nor inhibited pinocytosis. The system offers many advantages in the quantitative study of the physical basis of pinocytosis.

Animals↗

Quantitative studies of pinocytosis. II. Kinetics of protein uptake and digestion by rat yolk sac cultured in vitro.

Pinocytic uptake of 125I-labeled bovine serum albumin by 17.5-day rat visceral yolk sac cultured in vitro has been examined. Uptake was followed by intracellular digestion and, after an initial period, the content of radioactivity in the tissue itself remained constant during the incubation. Radiolabel was returned to the culture medium predominantly as (125I)iodotyrosine; exocytosis of undigested protein did not occur. The rate of uptake of labeled protein, which was constant within an experiment and reproducible between experiments, was much higher than that of a nondigestible macromolecule, 125I-labeled polyvinylpyrrolidone. The higher rate of uptake was a consequence of the protein entering the cells chiefly by adsorption to the plasma membrane being internalized; 125I-labeled albumin did not stimualte, nor did 125I-labeled polyvinylpyrrolidone inhibit pinocytosis. Different preparations of 125I-labeled albumin had characteristically different rates of uptake, probably reflecting differences in affinity for plasma membrane receptors. The physiological significance of the findings is discussed.

Animals↗

Digestion of an exogenous protein by rat yolk-sac cultured in vitro.

Yolk-sacs were removed from 17.5-day pregnant rats injected 2-5h previously with (125)I-labelled bovine serum albumin. The specific activities of acid phosphatase and acid proteinase, and the specific radioactivities (trichloroacetic acid-insoluble and trichloroacetic acid-soluble) were measured in subcellular fractions prepared by homogenization and differential centrifugation. The conversion of acid-insoluble into acid-soluble radioactivity within cultured tissue was followed and the nature of the liberated products was investigated by gel chromatography. The results are consistent with the protein entering lysosomes and being digested there. The radiolabel was released chiefly as free iodotyrosine.

Acid Phosphatase↗

Glycogen metabolism in the rat visceral yolk sac. I. Glycogen content and gestational age.

The glycogen content of the rat visceral yolk sac was determined between 13.5 and 20.5 days of gestation by the best available colorimetric method. The concentration of glycogen in the tissue increased ten-fold between 13.5 and 18.5 days, to reach a value similar to that for mammalian muscle, but then decreased by 50 per cent between 18.5 and 20.5 days. Determination of the iodine-iodide spectra and fractionation of the glycogen particles by a novel sodium citrate centrifugation method indicated broad similarities between the structures of glycogen particles, isolated by a mild phenol-water method, from the yolk sac and the liver of the rat. However, the proportion of 'high'-molecular-weight glycogen in the yolk sac increases between 18.5 and 20.5 days, as a result of the preferential loss of 'low'-molecular-weight glycogen, so that at term the proportion approaches that found in liver glycogen.

Animals↗

Microscopic evidence of silent inflammation in grossly normal fallopian tubes with ectopic pregnancy.

A normal laparoscopic examination of the pelvis in an infertile patient is usually considered sufficient evidence of normal tubal function. Twelve of 27 tubal ectopic pregnancies which occurred over a 4-year period in patients attending an infertility clinic were in patients with a previously "normal" laparoscopy. In eight patients, salpingectomy was performed, and the whole tube was available for examination by a single pathologist. The eight fallopian tubes, thoroughly examined histologically, all had evidence of ongoing, low-grade salpingitis or postinflammatory endosalpingeal disorganization in areas away from the ectopic pregnancy. These findings suggest that laparoscopy does not exclude significant microscopic tubal disease in at least some women with an apparently normal pelvis, and that this may be a cause of ectopic pregnancy and perhaps "idiopathic" infertility.

Fallopian Tubes↗

Bacterial meningitis in Navojo Indians.

An analysis of 219 confirmed cases of bacterial meningitis among Navajo Indians during a 5-year period, July 1, 1968, through June 30, 1973, revealed that 56 percent were caused by Haemophilus influenzae, 26 percent by Neisseria meningitidis, 6 percent by Mycobacterium tuberculosis, and 6 percent by other organisms. The annual incidence of H. influenzae meningitis (17.7 per 100,000 persons) and that of pneumococcal meningitis (8.0 per 100,000) were much higher than the rates for these diseases reported from other population groups. The annual incidence of meningococcal meningitis (2.0 per 100,000) was similar to that found elsewhere. There was an ususual concentration of cases during the first year of life; 78 percent of H. influenzae, 64 percent of pneumococcal, and 50 percent of meningococcal meningitis occurred during this time. However, bacterial meningitis during the first month of life was not frequent (0.29 per 1,000 live births). Case fatality rates were similar to those reported for other population groups.

Adolescent↗