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Biomedical subjects

J G Swift

Publications and source records attributed to J G Swift.

35 records · Page 2Linked to original sources

The structure of tight junctions between uterine luminal epithelial cells at different stages of pregnancy in the rat.

The ultrastructure of tight junctions between uterine luminal epithelial cells of the pregnant rat was studied by the freeze-fracture technique. On day 5 of pregnancy, the day of implantation, the region of tight junctions extended three times as far down the lateral cell membrane as on day 1 of pregnancy, and the strands of the complex interlinked more frequently. These observations suggest that tight junctions on day 5 may be more efficient in preserving the contents of the uterine lumen from dilution or escape than at earlier times of pregnancy.

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The dual effect of rubidium ions on potassium efflux in depolarized frog skeletal muscle.

The effects of external Rb+ on the efflux of 42K+ from whole frog sartorius muscles loaded with 305 mM K+ and 120 mM Cl- were studied. K+ efflux is activated by [Rb+]o less than about 40 mM according to a sigmoid relation similar to that for activation by [K+]o. At [Rb+]o greater than 40 mM, K+ efflux declines, although at [Rb+]o = 300 mM it is still greater than at [Rb+]o = 0 mM. For low concentrations, the increment in K+ efflux over that in K+-and Rb+-free solution, delta K, is described by the relation delta k = a[X+]on, for both K+ and Rb+. The value of a is larger for Rb+ than for K+, while the values of n are similar; the activation produced by a given [Rb+]o is larger than that by an equal [K+]o for concentrations less than about 40 mM. Adding a small amount of Rb+ to a K+-containing solution has effects on K+ efflux which depend on [K+]o. At low [K+]o, adding Rb+ increases K+ efflux, the effect being greatest near [K+]o = 30 mM and declining at higher [K+]o; at [K+]o above 40 mM, addition of Rb+ decreases K+ efflux. At [K+]o above 75 mM, where K+ efflux is largely activated, Rb+ reduces K+ efflux by a factor b, described by the relation b = 1/(1+c[Rb+]o). Activation is discussed in terms of binding to at least two sites in the membrane, and the reduction in K+ efflux by Rb+ at high [K+]o in terms of association with an additional inhibitory site.

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Reflexive gap junctions on uterine luminal epithelial cells.

Freeze-fracture electron microscopy has been used to search for reflexive gap junctions on apical projections of uterine epithelial cells in the rat. These structures were found in 5 of 6 animals in the study and consisted of from 15 to over 70 intramembranous particles which ranged in size from 7 to 9 nm. Some suggestions on the function of these enigmatic junctions are discussed.

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Changes in the fine structure of the apical plasma membrane of endometrial epithelial cells during implantation in the rat.

In previous work we have shown that ovarian hormones, when injected into ovariectomized rats, alter the fine structure of the plasma membrane of endometrial epithelial cells. In this paper freeze-fractures have been used to study the apical plasma membrane of endometrial epithelial cells of rats during the period of blastocyst implantation of normal pregnancy. On day 1 of pregnancy there were 2354 +/- 114 intramembranous particles (IMPs) per micrometer2 of membrane. The particles were spherical and randomly distributed. On day 5 of pregnancy IMP density rose to 2899 +/- 289 per micrometer2 and some rod-shaped particles were also visible. By day 6 of pregnancy IMP density had risen to 4014 +/- 206 per micrometer2 and there were more rod-shaped IMPs than before. In addition, on day 6 IMPs were also present as rows of particles and some gap-junction-like arrays of particles were also seen. Our findings indicate that there are fine-structural alterations in the apical plasma membrane of endometrial epithelial cells, the site of first contact between maternal and embryonic cells, during the period of early pregnancy. The findings are discussed in the light of suggested mechanisms of blastocyst attachment to the uterine epithelium at implantation.

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Effects of ovarian hormones on cell membranes in the rat uterus. II. Freeze-fracture studies on tight junctions of the lateral plasma membrane of the luminal epithelium.

Freeze-fracture techniques have been used to study tight junctions on the lateral plasma membrane of cells of the luminal epithelium of the rat uterus under various hormonal regimes. Tight junctions from ovariectomized control rats extended some 0.5 micron down the lateral membrane and the junctional strands often formed a network of closely packed, circular compartments. Following treatment of rats with estrogen for 3 days the tight junctional region still extended 0.5 micron down the lateral membrane, but the strands ran more parallel to the apical surface. They did not enclose circular compartments. After treatment with progesterone, either alone or with estrogen in such a way as to condition the ovariectomized uterus for implantation, a third pattern of junctional organization emerged. In these animals the junctional region extended 1.1 micron down the lateral membrane and the strands frequently crosslinked, enclosing compartments of varying and irregular size and shape. Our observations suggest that ovarian hormones could regulate the contents of the uterine lumen by altering the structure and extent of the tight junctions which connect the epithelial cells enclosing the lumen.

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Unidirectional flux ratio for potassium ions in depolarized frog skeletal muscle.

Small bundles of frog skeletal muscle fibers were loaded with 305 mM K+ and 120 mM Cl-, and 42K+ tracer efflux and influx were measured as a function of external K+ concentration ([K+]o) at a resting potential of -2 mV. As [K+]o was lowered from 305 mM, efflux decreased along a markedly sigmoidal curve, reaching a constant nonzero value at low [K+]o. Influx varied linearly with [K+]o at low [K+]o and more steeply at higher [K+]o. The ratio of influx to efflux was described by the equation: influx/efflux = exp[-n(V - VK)F/RT] with n = 2 at high [K+]o, but the ratio approached this equation with n = 1 at low [K+]o. Efflux did not depend on [K+]o when the membrane potential was raised to +36 mV, whereas at low [K+]o decreasing the membrane potential to -19 mV further activated the efflux. The results are discussed in terms of an inwardly rectifying potassium channel with two or more activating sites within the membrane that bind K+ and are accessible from the external solution.

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Effects of ovarian hormones on cell membranes in the rat uterus. I. Freeze fracture studies of the apical membrane of the liminal epithelium.

Freeze fracture techniques have been used to study the apical membrane of cells of the luminal epithelium of the rat uterus under various hormonal regimes. In the ovariectomized but otherwise untreated rat, intramembranous particles (IMPs) occur at a density of 1395 +/- 122 per micron 2; they appeared spherical and uniformly distributed. After 3 days treatment with estrogen, no change in appearance or density was found, but 3 days of progesterone treatment produced a significant increase in IMP density to 1622 +/- 104. Treatment with progesterone, with an additional dose of estrogen on day 3, is known to produce an epithelium receptive to the implanting blastocyst. In these conditions, the IMP density rose to 3818 +/- 337: rod-shaped particles and aggregations of IMPs were seen, and some particle arrays resembling gap junctions, in addition to the isolated spherical particles.

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Membrane changes associated with mucus production by intestinal goblet cells.

Changes in the structural organization of membranes of mucous bodies and the plasma membrane that occur during mucus production in goblet cells of rat rectum have been studied by thin-section and freeze-fracture techniques. Immature mucous bodies are bounded by a trilaminar membrane and fracture faces of the membrane have randomly distributed intramembrane particles. During maturation, mucous bodies become packed tightly together and changes in the structure of their membranes include (1) fusion of apposing membranes of adjacent bodies to form a pentalaminar structure, (2) a reduction in the density of particles on membrane fracture faces, and (3) exclusion of particles from regions of membrane apposition. Some trilaminar membranes of mucous bodies fuse with the lumenal plasma membrane to form a pentalaminar structure. Sites of apposition between mucous body membranes and the lumenal plasma membrane are seen as particle-cleared bulges on fracture faces of the plasma membrane. Our results indicate that membrane reorganization associated with mucous production in goblet cells includes a reduction and redistribution of some membrane proteins and that membrane fusion occurs between portions of membranes from which proteins have been displaced.

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Theophylline action on sodium fluxes in frog striated muscle.

The action of theophylline on both sodium efflux and influx was measured using freshly isolated frog sartorius muscles. In normal Ringer's fluid, 2 mM theophylline increased sodium efflux by 35% whereas it decreased sodium influx by about 10%. The percent increase in sodium efflux produced by 2 mM theophylline was not significantly altered in sodium-free, lithium-containing solutions. Strophanthidin prevented the stimulation of sodium efflux by 2 mM theophylline in both normal, sodium-containing Ringer's fluid and sodium-free, lithium-containing solutions. Hence, the major effect of theophylline seems to be stimulation of active sodium transport and the enhanced rate of sodium exit induced by theophylline does not seem to require the presence of external sodium. An interesting and unexplained findings is that 2 mM theophylline, which does not produce a maximal stimulation of sodium efflux, prevents the increased sodium efflux induced by saturating doses of epinephrine.

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Apoptosis in liver damage produced by tunicamycin.

OBJECTIVE: To determine whether apoptosis contributes to hepatocyte loss in tunicamycin poisoning. DESIGN: Groups of four guinea pigs were given 400 microg/kg of tunicamycin subcutaneously and killed at 24 h intervals up to 72 h post-injection. Livers were examined by routine histological methods and ancillary techniques (TUNEL staining, endonuclease activation, caspase activity, and electron microscopy) to ascertain whether any hepatocyte injury was apoptotic. RESULTS: Many hepatocytes exposed to tunicamycin showed evidence of apoptosis in the form of nuclear karyorrhexis with chromatin margination and crescent formation, TUNEL-positivity, DNA laddering, elevated caspase activity and apoptotic body formation. CONCLUSION: Tunicamycin caused the death of many hepatocytes in the livers of guinea pigs by apoptosis.

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Exocytosis of neurosecretory granules in small cell undifferentiated carcinoma.

The tumor cells in the pleural effusions of a case of small cell undifferentiated carcinoma have been studied by light microscopy and by thin section and freeze-fracture electron microscopy. Evidence of exocytosis of neurosecretory granules from the tumor cells is presented. The tumor cells form clumps, with the cells joined by focal tight junctions and small desmosomes. These findings are discussed with reference to the neuroendocrine origin of these tumors and the role of the junctional complexes in the formation of tumor cell aggregates.

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