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Biomedical subjects

E Holtzman

Publications and source records attributed to E Holtzman.

At least 73 records · Page 4Linked to original sources
PubMed1981

Calcium accumulation in intracellular compartments of frog retinal rod photoreceptors.

The accumulation of calcium in the rod cells of isolated frog retinas was studied by methods involving the pretreatment of tissue with saponin, which reduces the permeability barrier posed by the plasma membrane, and the inclusion of a Ca2+ trapping agent, oxalate, in incubation media. X-ray microanalysis using an analytical transmission electron microscope was employed to verify the presence of calcium in the deposits produced by these methods. Ca2+ was found to accumulate in the rough endoplasmic reticulum (ER) and the agranular reticulum of the myoid region and in the presynaptic terminals of the rods. At least one aspect of this accumulation appears to depend upon the presence of ATP.

Animals↗
PubMed1981

Uptake of horseradish peroxidase by presynaptic terminals of bipolar cells and photoreceptors of the from retina.

The uptake of horseradish peroxidase (HRP) into synaptic vesicles of presynaptic terminals in the inner and outer plexiform layers of isolated frog retinas was studies by electron microscopy. Uptake into the terminals of bipolar cells was found to be enhanced by exposure of the preparations to elevated concentrations of potassium ions, and by exposure to aspartic acid or glutamic acid. Glycine had much less effect on the terminals. These results suggest that HRP uptake may prove useful in monitoring some aspects of the responses of inner plexiform layer cells to conditions of physiological interest. Uptake into photoreceptor terminals was also enhanced by elevated potassium concentrations; the effects of the amino acids were complex.

Amino Acids↗
PubMed1981

Science, philosophy, and society: some recent books.

The essay discusses a number of issues developed in several recent books on philosophical and ethical problems in the natural sciences, both pure (especially biology) and applied (especially medicine). The scaffolding of the discussion can be outlined as follows: Science is most coherently portrayed as a set of activities through which societies deal with a distinctive, but continually evolving set of interwoven practical, empirical, and conceptual problems. Consequently, approaches which attempt to delineate universal features of "scientific methods" or to depict the sciences as providing an approximation to an "objective" view of reality are much less enlightening than are analyses rooted directly in concrete scientific history and in the actual interplay of science with other social configurations. However, scientists are granted some meaningful autonomy in exercising their "curiosity" and there is a real sense in which scientific ideas and activities do possess momentum of their own. In other words, as is also true for other spheres, such as the arts, it is important not to fall into mechanical viewpoints which treat the movement of science as simply a derivative of forces generated elsewhere.

Biological Evolution↗
PubMed1980

Quantitative analysis of exocytosis and endocytosis in the hydroosmotic response of toad bladder.

This study concerns the timing and magnitude of exocytosis and endocytosis in the granular cells of toad bladder during the hydroosmotic response to antidiuretic hormone. Granule exocytosis at the luminal cell surface is extensive within 5 min of the administration of a physiological dose of hormone. Hydroosmosis becomes detectable during this time period. The amount of membrane added to the luminal surface by exocytosis during 60 min of exposure to hormone can be of the same order of magnitude as the extent of the luminal plasma membrane. Endocytosis, demonstrated by peroxidase uptake from the luminal surface, becomes extensive during the period 15-45 min after hormone administration. Thus, maximal endocytic activity occurs later than the period of most extensive exocytosis and seems to correlate with the onset of the decline in water movement. The amount of membrane retrieved from the luminal surface by endocytosis during 60 min of stimulation is at least three quarters of that added by exocytosis. The bulk membrane movement in ADH stimulated preparations does not require the presence of an osmotic gradient. Colchicine inhibits the hydroosmotic response, the exocytosis of granules, and endocytosis at the luminal surface. These results strengthen our view that the bulk circulation of membrane at the cell surface, via exocytosis and endocytosis, is closely related to the permeability changes occurring at the surface.

Animals↗
PubMed1980

The effect of chlorthalidone on serum lipids and lipoproteins.

The effect of chlorthalidone treatment on serum lipids and lipoproteins was investigated in 21 hypertensive patients. Chlorthalidone caused an increase in total serum and low density lipoprotein (LDL) cholesterol, but not in high density lipoprotein (HDL) cholesterol. Serum and lipoprotein triglycerides also increased. Our findings suggest that chlorthalidone increases serum concentrations of "atherogenic" lipoproteins (LDL and VLDL), and possibly decreases the levels of a "beneficial" lipoprotein, namely HDL. Thus, the use of this medication may increase a major atherosclerosis risk factor.

Adult↗
PubMed1980

Ultrastructural localization of alpha-OH acid oxidase in peroxisomes with the CeCl3 technique.

alpha-OH acid oxidase activity was demonstrated in peroxisomes of glutaraldehyde-fixed tissues using the CeCl3 cytochemical method. For kidney, alpha-OH butyrate or alpha-OH valerate were used as substrates. These substrates gave much less reaction product in liver peroxisomes. Liver peroxisomes were more reactive with glycolate as substrate. Glycolate gave little or no reaction product in kidney peroxisomes. alpha-keto-glutarate inhibited activity of the enzyme with alpha-OH butyrate as substrate.

Alcohol Oxidoreductases↗
PubMed1979

Ultrastructural localization of D-amino acid oxidase in microperoxisomes of the rat nervous system.

A recently developed procedure for the localization of D-amino acid oxidase (D-AAO) has been used to investigate the distribution of this enzyme in rat nervous tissue. Initial studies were carried out on kidney to validate the methods. The cytochemically demonstrable enzyme in kidney is inhibited by kojic acid, a known competitive D-AAO inhibitor. Omission of the catalse inhibitor, aminotriazole, from the cytochemical medium produces a marked diminution of D-AAO reaction product in kidney peroxisomes. This would be expected if catalase and D-AAO are present in the same particles. In brain, kojic acid-inhibitable D-AAO is demonstrable in numerous bodies within astrocytes especially in the cerebellum, a brain region known from biochemistry to contain particularly high levels of the oxidase. In preparations incubated for catalase, far fewer positive bodies are seen in the cerebellum. Moreover, omission of aminotriazole has little evident effect on the D-AAO reaction. Thus, the oxidase-containing cerebellar bodies may be relatively poor in catalse. In contrast, several nervous system cell types that contain relatively numerous catalase-positive bodies, contain none with detectable D-AAO. Such heterogeneity of peroxisome enzyme content is in accord with reports from biochemical studies of brain.

Animals↗
PubMed1978

Microperoxisomes in the central nervous system of the postnatal rat.

The distribution of catalase-containing microperoxisomes was studied in the central nervous system of rats during the early postnatal period when the processes of myelination and cell differentiation are active. The regions selected for study included a region previously found in adult animals to contain substantial numbers of reactive microperoxisomes, as well as areas where few such bodies were seen. Microperoxisomes were relatively numerous in all areas during the first two postnatal weeks; at later times they occurred less frequently, or, in some areas, were almost entirely absent. In early postnatal CNS, catalase-positive microperoxisomes were found in all cell types in all regions studied. Neurons of both cerebrum and cerebellum contained catalase-positive microperoxisomes during the first two postnatal weeks; few such neuronal bodies are found in these areas after the third postnatal week. During the period of active myelination, catalase-positive microperoxisomes were found in oligodendrocyte cell bodies, and also in oligodendrocyte processes associated with forming myelin sheaths in all areas. In several areas during the first 3 postnatal weeks, catalase-positive bodies were seen in synaptic terminals, a location where they are seldom observed in mature tissue. Cells of postnatal choroid plexus also were found to contain modest numbers of reactive microperoxisomes.

Age Factors↗
PubMed1978

Binding of antibodies to acetylcholine receptors in Electrophorus and Torpedo electroplax membranes.

Antisera against purified acetylcholine receptors from the electric tissues of Torpedo californica and of Electrophorus electricus were raised in rabbits. The antisera contain antibodies which bind to both autologous and heterologous receptors in solution as shown by an immunoprecipitation assay. Antibodies in both types of antisera bind specifically to the postjunctional membrane on the innervated surface of the intact electroplax from Electrophorus electric tissue as demonstrated by an indirect immunohistochemical procedure using horseradish peroxidase conjugated to anti-rabbit IgG. Only anti-Electrophorus receptor antisera, however, cause inhibition of the receptor-mediated depolarization of the intact Electrophorus electroplax. The lack of inhibition by anti-Torpedo receptor antibodies, which do bind, suggests that the receptor does not undergo extensive movement during activity. The binding of anti-Torpedo antibodies to receptor-rich vesicles prepared by subcellular fractionation of Torpedo electric tissue was demonstrated by both direct and indirect immunohistochemical methods using ferritin conjugates. These vesicles can be conveniently collected and prepared for electron microscopy on Millipore filters, a procedure requiring only 25 micrograms of membrane protein per filter. In addition, it was possible to visualize the binding of anti-Torpedo receptor antibodies directly, without ferritin. These anti-Torpedo receptor antibodies, however, do not inhibit the binding of acetylcholine or of alpha-neurotoxin to receptor in Torpedo microsacs but do inhibit binding of alpha-neurotoxin to Torpedo receptor in Triton X-100 solution. It is likely that the principal antigenic determinants on receptor are at sites other than the acetylcholine-binding sites and that inhibition of receptor function, when it occurs, may be due to a stabilization by antibody binding of an inactive conformational state.

Acetylcholine↗
PubMed1976

Microperoxisome distribution in the central nervous system of the rat.

The distribution of microperoxisomes was studied in areas of the central nervous system having high concentrations of catecholaminergic neurons and in areas lacking this neuron type, using the alkaline DAB cytochemical method for catalase. Substantial numbers of microperoxisomes are found in neurons in the locus coeruleus and in nucleus A1 of the medulla, as well as in the substantia nigra, whereas few catalase-reactive bodies are seen in neurons of the cerebrum and cerebellum. The number of catalase-reactive microperoxisomes per unit area in the catecholaminergic neurons of the CNS is comparable to the number seen previously in neurons of the peripheral cervical sympathetic ganglia. Some spinal cord neurons also contain reactive microperoxisomes. Catalase-reactive microperoxisomes are numerous in oligodendrocytes of all areas studied, and in ependymal cells bordering the third and fourth ventricles. Astrocytes contain few reactive structures in the cytoplasm near the nucleus, but they are readily found in astrocytic processes and end-feet.

Animals↗
PubMed1976

Synaptic activity of frog retinal photoreceptors. A peroxidase uptake study.

The uptake of horseradish peroxidase (HRP) into membranous structures, detectable by light and electron microscopy, is used here to monitor the synaptic activity of photoreceptors of isolated frog retinas maintained in the dark or under various illumination conditions. The major findings are: (a) Neurotransmission from photoreceptor terminals seems to involve the same types of endocytic membrane-retrieval processes that occur at other nerve terminals. Presumably, the endocytic processes compensate for exocytic events associated with neurotransmission. The retrieved membrane is "recycled" to form vesicles. Some of these accumulate near the synaptic ribbons, perhaps indicating reutilization for exocytosis. On the other hand, some retrieved membrane evidently is degraded via multivesicular bodies that appear to undergo "retrograde" transport from the receptor synapses to the myoid regions. (b) Photoreceptor terminals take up much HRP in the dark. Steady illumination markedly decreases uptake by rods. Uptake by cones is notably reduced only at illumination intensities higher than those that have maximal effects on rods. (c) The decrease in rod HRP uptake with light is reversible when retinas are allowed to adapt to the dark, if the light exposures used were at intensities that bleach very little visual pigment. Such "recovery" is not observed after light exposures that bleach a considerable amount of visual pigment. The cones recover their dark levels of HRP uptake even after light exposures that bleach considerable amounts of visual pigment. The changes in HRP uptake that we observe parallel expectations for photoreceptor synaptic neurotransmission derived from indirect physiological evidence.

Animals↗
PubMed1975

Circulation and turnover of synaptic vesicle membrane in cultured fetal mammalian spinal cord neurons.

Intact neurons in cultures of fetal rodent spinal cord explants show stimulation-dependent uptake of horseradish peroxidase (HRP) into many small vesicles and occasional tubules and multivesicular bodies (MVB) at presynaptic terminals. Presynaptic terminals were allowed to take up HRP during 1 h of strychnine-enhanced stimulation of synaptic transmitter release and then "chased" in tracer-free medium either with strychnine or with 10 mM Mg++ which depresses transmitter release. Tracer-containing vesicles are lost from terminals under both chase conditions; the loss is more rapid (4-8 h) with strychnine than with 10 mM Mg++ (8-16 h). There is a parallel decrease in the numbers of labeled MVB's at terminals. Loss of tracer with 10 mM Mg++ does not appear to be due to the membrane rearrangements (exocytosis coupled to endocytosis) that presumably lead to initial tracer uptake; terminals exposed to HRP and Mg++ for up to 16 h show little tracer uptake into vesicles. Nor is the decrease likely to the due to loss of HRP enzyme activity; HRP is very stable in solution. During the chases there is a striking accumulation of HRP in perikarya that is far more extensive in cultures initially exposed to tracer with strychnine than 10 mM Mg++ regardless of chase conditions. Much of the tracer ends up in large dense bodies. These findings suggest that synaptic vesicle membrane turnover involves retrograde axonal transport of membrane to neuronal perikarya for further processing, including lysosomal degradation. The more rapid (4-8 h) loss of tracer-containing vesicles with strychnine may reflect vesicle membrane reutilization for exocytosis.

Axons↗