Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00080 (Leaf)
 21,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The morphology and development of junctional complexes between blastomeres of the preimplantation rabbit embryo were investigated using several approaches. Electron microscopic examination of embryos stained en bloc with uranyl acetate, and the study of junction permeability using horseradish peroxidase and lanthanum nitrate provided information on structure, intermembrane spacing and permeability of the junctional complexes. In addition, the freeze fracture technique was used with day 5 and day 6 blastocysts, since the large size of these embryos facilitated use of this method. These experiments showed that although rudimentary junctions were present between blastomeres of the early cleavage stages, effective tight junctions were not present until the blastocyst stage. Electron microscopic examination of thin sections revealed apical foci of membrane approximation or "fusion" between trophoblast cells by day 4. Freeze fracturing revealed a lattice of interconnecting ridges (on the A face) and grooves (on the B face) in the apical region between trophoblast cells of the day 5 blastocyst. This lattice formed a continuous band along the apical margin of each cell, and therefore constituted a zonula occludens. The zonula occludens of the day 5 blastocyst averages 2-3 ridges per lattice, while day 6 blastocysts had lattices that averaged 5-6 ridges. Also seen in the freeze fracture replicas from the day 5 and day 6 blastocysts were local accumulations of intramembranous particles on the A face. These particles were often observed in aggregates similar to those of previously described gap junctions. It could not be determined whether these small regions of particles were true gap junctions or a possible primitive form of gap junction because the complementary pitted surfaces (B face pits) were not demonstrated.
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PMID:Junctional complexes in the preimplantation rabbit embryo. 4 78

Investigation into the vascularization of the Ganglion spirale of the rat showed an irregular, loose network of capillaries, with a somewhat denser vacularization of the marginal areas of the ganglion; the horseradish peroxidase benzidine test according to Sugar was used to demonstrate the vessels. At least of the blood supply of the ganglion is effected via the vessels which run parallel to the nerve fibres through the osseous canals from the modiolus into the Rosenthal canal. The density of vascularization of the Ganglion spirale is surprisingly small, namely 1.89% by volume. The comparative figure for the Ganglion spirale, also measured by means of stereological methods, is approximately 6.8% by volume, whilst the vessels in the Nervus cochlearis occupy 2.1% by volume. The vascularization density of the ganglion corresponds roughly to that of the Cortex cerebri. Electro-microscopical tests have shown that there are unfenestrated capillaries with a small number of pinocytotic vesicles. Possible conclusions as to the permeability of the capillaries are discussed in the paper. The blood supply of the Ganglion spirale has so far received only little attention. In the case of internal ear diseases of vascular genesis, attention is mainly given to changes in the vessels of the lateral wall of the cochlea. Experimental findings, however, show the high sensitivity of the nervous apparatus of the cochlea in the case of disturbed blood supply.
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PMID:[Vascularization of the ganglion spirale cochleae of the rat (author's transl)]. 7 71

Two fractions of gastric mucosal membranes obtained by Ficoll-sucrose density gradient centrifugation were studied by a variety of techniques to localize the polypeptides. Gel electrophoresis showed the presence of five major polypeptides and several minor ones. Only one of these, 82,000 daltons, was available for iodination in the intact tissue. The two membrane fractions differed in their accessibility to peroxidase. The denser fraction showed two major defined iodination peaks at 82,000 and 102,000 daltons. Freeze-thawing and iodinating with 131-I produced additional labeling of peaks as well as relabeling the 82,000-dalton component, showing it was accessible from both sides of the membrane. The two major components were also sensitive to cross-linking, the 102,000 polypeptide being especially sensitive to --SH oxidation. Proteolysis with trypsin removed both components in the denser membrane fraction, in addition to inhibiting the K+-ATPase and K+-p-nitrophenylphosphatase of that fraction. Phosphorylation with [gamma-32-P]ATP labeled the 102,000-dalton component and K+, HCO3- minus and p-nitrophenylphosphate reduced the level of labeling. Hence the 102,000 region contains a subunit of the ATPase, is readily iodinated in inside-out vesicles, and is the most available for interpeptide S--S cross-linking.
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PMID:Characterization of gastric mucosal membranes. VIII. The localization of peptides by iodination and phosphorylation. 16 6

The intravenous injection into mice of small volumes (less than 0.1 ml) of peroxidatic enzymes of molecular weight of 40 000 daltons or greater results in little if any penetration of these probe molecules into endothelial junctions. The injection of cytochrome c (12 000 daltons), on the other hand, results in the localization of this tracer in some but not all endothelial junctions. When horseradish peroxidase (EC 1.11.1.7) is injected in a large volume of saline (0.5 ml), reaction product is present in endothelial junctions and basement membrane, but is prevented from entering the alveolar space by zonulae occludentes between epithelial cells. These experiments indicate that although endothelial junctions, under physiological conditions, are largely impermeable to molecules the size of horseradish peroxidase, and presumably most serum proteins, they are labile and susceptible to stretching if intravascular pressure is increased. Freeze-fracture studies show that pulmonary capillary endothelial junctions are composed of one or at the most two strands which show areas of discontinuity. Epithelial junctions, by contrast, are composed of a continuous, complex network of anastomosing fibres. These observations confirm physiological experiments which indicate that it is the pulmonary epithelium rather than the endothelium which determines the permeability properties of the alveolar-capillary membrane to lipid-insoluble molecules. Bidirectional pinocytic transport is an additional mechanism whereby lipid-insoluble molecules are transported across both endothelial and epithelial layers. The relative contribution of this transport mechanism to the total amount transported remains to be established.
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PMID:Ultrastructural basis for alveolar-capillary permeability to protein. 18 Dec 20

Tight junctions (zonulae occludentes) create a pericellular barrier to the diffusion of large molecules in non-keratinizing mammalian epithelia. However, in cornifying epithelia such as the epidermis, the importance of tight-junctional elements versus secreted intercellular lipid for barrier function is uncertain. In an attempt to resolve this question, we compared membrane structure in the stratum granulosum and stratum corneum of epidermis, esophagus, and vagina of newborn and adult humans and mice under both normal and various experimental conditions. We incubated pieces of epidermis in organ culture and infused tissues with lanthanum or horseradish peroxidase in vivo and in vitro. All were processed for electron microscopy of freeze-fracture replicas or thin sections. Lanthanum seeped outward to the stratum granulosum in all tissues examined--further apical migration was halted by lamellar-body contents in skin. A similar pattern of intercellular lamellar lipid deposition and membrane structure occurred in all epithelia studied. Freeze-fracture replicas of these obstructive regions revealed occasional, incomplete junctional strands (particularly in moist epithelia) and abundant lamellar material, but complete zonulae occludentes were never encountered. A possible relationship between moisture and tight junction formation was further suggested by organ culture experiments during which brief incubations stimulated an increase in the number of junctional strands and diminished numbers of lamellar bodies. We conclude that, in the epithelia studied, the deposition of secreted lamellar body contents forms the barrier to water-soluble tracer loss: tight-junctional elements are either absent or too fragmentary to constitute an effective barrier.
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PMID:Membrane alterations during cornification of mammalian squamous epithelia: a freeze-fracture, tracer, and thin-section study. 33 80

Membrane vesicles can be obtained from epimastigote forms of Trypansoma cruzi by incubating cells with either cross-linking reagents or acid pH. Acetate, phtalate or citrate, at pH 4.0, but not at higher pH values, were able to induce plasma membrane vesiculation. Vesicles have been purified by sucrose density centrifugation and their membrane origin was demonstrated by the following criteria: (a) Vesicles are 5--10 times richer in protein-bound iodine when they are prepared from cells previously labeled with 131I by the lactoperoxidase catalyzed reaction. (b) Electron microscopy of vesiculating cells shows physical continuity between cell plasma membrane and vesicle membrane. (c) Antibodies prepared against purified vesicles are able to agglutinate epimastigote forms of T. cruzi with sera dilutions up to 1 : 256 to 1 : 512. (d) Freeze-fracture studies of the purified vesicles have shown images of faces P and E compatible with known images of the intact cell plasma membrane. Typical preparations of acetate vesicles present the following characteristics: total carbohydrate : protein=1.5--2.0; orcinol : protein-0.07 and absence of diphenylamine reaction. Vesicles contain 0.2--0.5% and 0.3--1.0% of the total homogenate protein and carbohydrate, respectively. The presence of 10 major protein bands and 30--50-fold enrichment of the four sugar-containing macromolecules present in epimastigote forms of T. cruzi have been demonstrated in these preparations.
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PMID:Plasma membrane vesicles isolated from epimastigote forms of Trypanosoma cruzi. 36 44

In early embryonic development of the tobacco horn moth no blood-brain barrier is present, as shown by the unimpeded entry of exogenous tracers into the nervous system. However, later on, just before hatching, lanthanum and horseradish peroxidase (HRP) are unable to move inwardly beyond the level of the perineurium, which is the morphological site of the blood--brain barrier in the adult moth, as well as in other insects. Freeze-fracture studies indicate that in the early embryo, 10 nm particles are scattered about in the perineurial membrane PF, either as separate entities or as short linear arrays. By hatching or just before, however, the 10 nm particles have become aligned into lengthy linear aggregates as PF ridges with EF grooves. These would appear to be the simple, arthropod-form of tight junction, and are presumed to be the basis of the perineurial blood-brain barrier. At about the same time, gap junctional elements appear both between adjacent perineurial cells and between glial cells. In both cell types, the gap junctions form from free 13 nm EF particles which gradually become aligned or clumped into strands and aggregates which ultimately coalesce to form first irregular masses and then the macular plaques typical of mature gap junctions. Many of the latter stages are coincident with the hatching of a motile larvae, so that the perineurial and glial cells are by this stage coupled via the channels of the gap junctional particles. They are therefore able to undergo both ionic and metabolic exchange and cooperation during larval life, in addition to being able to respond to hormonal substances in an integrated way. During the 5 larval instars more gap junctions form as the perineurial layer grows thicker. These junctions become more regular in outline and their particles more tightly packed; these larval structures are compared with junctions found in the adult which tend to be more extensive but otherwise similar. Since no septate junctions are apparent during Manduca embryonic or larval life when the blood-brain barrier forms, nor in adults, the results of this report support the contention that it is the tight junctions rather than septate ones which form the basis of permeability barriers in this, and probably other, arthropod systems.
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PMID:Intercellular junctions and the development of the blood-brain barrier in Manduca sexta. 44 42

The anatomical basis of the blood-brain barrier in the American chameleon, Anolis carolinensis, is the system of tight intercellular junctions that occurs between apposed endothelial cells of brain capillaries. Under normal physiological conditions, capillaries in the brain cortex of these animals remain sealed by interendothelial zonulae occludentes and, consequently, escape of exogenous tracer proteins such as horseradish peroxidase (HRP) into the extracellular compartment of the central nervous system is prevented. Systemic injection of 2.7 mg of D-glucose into chameleons results in increased brain capillary permeability, as evidenced by escape of HRP or Trypan blue into the intercellular spaces of central neuropil. Freeze-fracture analysis of brain capillary endothelia of glucose-hyperglycemic lizards revealed no alteration of the ridge and groove construction of endothelial tight junctions, indicating that although the blood-brain interface becomes leaky during severe hyperglycemia, the capillary zonulae occludentes are not affected. Evidence obtained in this study strongly supports the notion that the increased capillary permeability is the result of amplified transendothelial transport. The effect is manifest as and facilitated by the formation of chains of pinocytotic vesicles derived from the luminal surface of the endothelial cells, which fuse to create open trans-endothelial conduits. It is likely that formation of open channels that traverse brain capillary endothelial cells, as a response to hyperglycemia, could allow temporarily unrestricted passage of a wide range of molecules, some potentially toxic, into the CNS extracellular milieu. This is the first report to unequivocally document with freeze-cleave techniques, that abnormally elevated levels of blood sugar can affect blood-brain interface permeability. This finding suggests that similar consequences may be expected to result from diabetic hyperglycemia in humans.
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PMID:The effect of hyperglycemia on brain capillary permeability in the lizard, Anolis carolinensis. A freeze-fracture analysis of blood-brain barrier pathology. 46 26

The ultrastructural effects of dark, light, and low temperature were investigated in the cone cell endings of the red-eared turtle (Pseudemys scripta elegans). Thin sections revealed that in dark-adapted retinas maintained at 22 degrees C, the neural processes which contact the cone cells at the invaginating synapses penetrated deeply into the photoreceptor endings. When dark-adapted retinas were illuminated for 1 h at 22 degrees C, the invaginating processes were apparently extruded from the synaptic endings. On the other hand, 1-h exposure to a temperature of 4 degrees C in the dark caused the invaginating processes to become much more strikingly inserted than at room temperature. A morphometric analysis showed that the ratio between the synaptic surface density of the endings and their total surface density decreased in the light and increased in the dark and cold. Freeze-fracturing documented fusion of synaptic vesicles with the presynaptic membrane in all conditions tested. These observations suggest that the changes in configuration of the pedicles in the light, dark, and cold reflect a different balance between addition and retrieval of synaptic vesicle membrane from the plasmalemma; in the dark, the rate of vesicle fusion is increased, whereas in the cold, membrane retrieval is blocked. When the eyecups were warmed up and illuminated for 30-45 min after cold exposure, a striking number of vacuoles and cisterns appeared in the cytoplasm and coated vesicles were commonly seen budding from the plasmalemma. 60-90 min after returning to room temperature, the endings had reverted to their normal configuration, and the vast majority of vacuoles, cisterns, and coated vesicles had disappeared. When horseradish peroxidase was included in the incubation medium, very few synaptic vesicles were labeled at the end of the period of cold exposure. 30-45 min after returning to 22 degrees C, vacuoles and cisterns contained peroxidase, whereas most synaptic vesicles were devoid of reaction product. 2 h after returning to 22 degrees C, coated vesicles, vacuoles, and cisterns had disappeared and a number of synaptic vesicles were labeled. These experiments suggest that vacuoles, cisterns, and coated vesicles mediate the retrieval of the synaptic vesicle membrane that has been added to the plasmalemma during cold exposure.
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PMID:Membrane recycling in the cone cell endings of the turtle retina. 73 Jul 68

Pulmonary capillary permeability was studied in 10 normal anesthetized dogs using horseradish peroxidase (HRP) as tracer. Physiological studies involved measurement of left ventricular, pulmonary arterial, and wedge pressures, and of right lymphatic duct (RLD) and thoracic duct lymph flows. Plasma and interstitial oncotic pressures were calculated from protein measurements. After 1 h of lymph collection, HRP was injected intravenously at three total dose levels, low (20-30 mg/kg), medium (55 mg/kg), and high (110-120 mg/kg) as a bolus followed by smaller doses over 1.5-3 h. HRP was measured colorimetrically in plasma and lymph and appeared in the first RLD lymph sample collected at all dose levels. Electron microscopic studies to examine the passage of HRP from plasma to RLD, while less sensitive in that HRP was seen only at the high dose, showed that it crossed pulmonary capillaries under normal physiological conditions. Freeze-cleaving studies suggest this may have occurred through pathways in the interendothelial space caused by discontinuities in the junctional strands of tight junctions.
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PMID:Pulmonary capillary permeability to HRP in dogs: a physiological and morphological study. 83 71


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