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Biomedical subjects

G W Scott

Publications and source records attributed to G W Scott.

At least 19 recordsLinked to original sources
PubMed2000

Self-regulation phenomena in bacterial reaction centers. I. General theory.

A model for light-induced charge separation in a donor-acceptor system of the reaction center of photosynthetic bacteria is described. This description is predicated on a self-regulation of the flow of photo-activated electrons due to self-consistent, slow structural rearrangements of the macromolecule. Effects of the interaction between the separated charges and the slow structural modes of the biomolecule may accumulate during multiple, sequential charge transfer events. This accumulation produces non-linear dynamic effects on system function, providing a regulation of the charge separation efficiency. For a biomolecule with a finite number of different charge-transfer states, the quasi-stationary populations of these states with a localized electron on different cofactors may deviate from a Lagmuir law dependence with actinic light intensity. Such deviations are predicted by the model to be due to light-induced structural changes. The theory of self-regulation developed here assumes that light-induced changes in the effective adiabatic potential occur along a slow structural coordinate. In this model, a "light-adapted" conformational state appears when bifurcation produces a new minimum in the adiabatic potential. In this state, the lifetime of the charge-separated state may be quite different from that of the "dark-adapted" conformation. The results predicted by this theory agree with previously obtained experimental results on photosynthetic reaction centers.

Darkness↗
PubMed1996

Ag(I)-binding to phytochelatins.

Phytochelatins (PCs) are glutathione-derived peptides with the general structure (gamma-Glu-Cys)nGly, where n varies from 2 to 11. A variety of metal ions such as Cu(II), Cd(II), Pb(II), Zn(II), and Ag(I) induce PC synthesis in plants and some yeasts. It has generally been assumed that the inducer metals also bind PCs. However, very little information is available on the binding of metals other than Cu(I) and Cd(II) to PCs. In this paper, we describe the Ag(I)-binding characteristics of PCs with the structure (gamma-Glu-Cys)2Gly, (gamma-Glu-Cys)3Gly, and (gamma-Glu-Cys)4Gly. The Ag(I)-binding stoichiometries of these three peptides were determined by (i) UV/VIS spectrophotometry, (ii) luminescence spectroscopy at 77 K, and (iii) reverse-phase HPLC. The three techniques yielded similar results. ApoPCs exhibit featureless absorption in the 220-340 nm range. The binding of Ag(I) to PCs induced the appearance of specific absorption shoulders. The titration end point was indicated by the flattening of the characteristic absorption shoulders. Similarly, luminescence at 77 K due to Ag(I)-thiolate clusters increased with the addition of graded Ag(I) equivalents. The luminescence declined when Ag(I) equivalents in excess of the saturating amounts were added to the peptides. At neutral pH, (gamma-Glu-Cys)2Gly, (gamma-Glu-Cys)3Gly, and (gamma-Glu-Cys)4Gly bind 1.0, 1.5, and 4.0 equivalents of Ag(I), respectively. The Ag(I)-binding capacity of (gamma-Glu-Cys)2Gly and (gamma-Glu-Cys)3Gly was increased at pH 5.0 and below so that Ag(I)/-SH ratio approached 1.0. A similar pH-dependent binding of Ag(I) to glutathione was also observed. The increased Ag(I)-binding to PCs at lower pH is of physiological significance as these peptides accumulate in acidic vacuoles. We also report lifetime data on Ag(I)-PCs. The relatively long decay-times (approximately 0.1-0.3 msec) accompanied with a large Stokes shift in the emission band are indicative of spin-forbidden phosphorescence.

Amino Acid Sequence↗
PubMed1991

Electrical activity of canine gallbladder.

Our aims were to describe the myoelectrical activity in the single very thin layer of muscle of the canine gallbladder. The study was performed on 22 freshly removed canine gallbladders. Electrical activity was studied by the single sucrose-gap method and contractility of the tissue was measured simultaneously using a force transducer. The strips (15 x 1 mm) from different regions of gallbladder (fundus, corpus, neck) were cut in longitudinal, circular and oblique axes. The sucrose-gap apparatus together with connecting tubes, solutions and electrodes were kept at 37 degrees C and the initial tension applied to the tissue was set to 1 g. In 82.7% of recordings, spontaneous myoelectrical activity consisted of regular rhythmic changes in membrane potential similar to slow waves recorded in intestinal tissue. The overall mean frequency was 11.4 +/- 5.2 (mean +/- SD) cycles per min: 11.1 +/- 4.4 cycles per min in fundus, 11.9 +/- 6.2 cycles per min in corpus and 10.8 +/- 3.8 cycles per min in the neck of the gallbladder. In 84.2% of cases electrical activity correlated with mechanical activity and preceded it. No significant differences were seen between the electrical patterns in strips with different orientations or from the different regions of the gallbladder.

Animals↗
PubMed1990

Gallbladder contractility and gallstone formation in the Richardson Ground Squirrel.

The pathogenesis of cholesterol cholelithiasis in man is probably multifactorial and the mechanism by which gallbladder stasis occurs in gallstone patients has not been studied in detail. In the present study, time-dependent changes in gallbladder motility of the Richardson Ground Squirrels were investigated. 100 of animals were examined for their contractile responses of gallbladders to CCK-OP and Ach in vitro. Also, biochemical changes of serum and bile were investigated. There were no significant differences in motility of gallbladders to CCK-OP or Ach between control and cholesterol-fed animals. The results of this study indicate that gallbladder muscle contractility remains unchanged during the dietary induction of cholesterol gallstones in the Richardson Ground Squirrel.

Acetylcholine↗
PubMed1988

Characterization of lipid accumulation in the gallbladder mucosa of the ground squirrel fed a lithogenic diet.

Richardson's ground squirrels (Spermophilus richardsonii) of both sexes were fed a 2 per cent cholesterol-enriched diet for intervals of 12, 18, and 24 h; 3, 5, and 7 days; and 2, 3, 10, and 20 weeks. It was shown that free (unesterified) cholesterol, phospholipid, and cholesterol ester accumulated in specific regions of the gallbladder mucosa during cholelithiasis. Electron microscopy revealed the presence of lipids inter- and intracellularly as early as 12 h after ingestion. By 7 days, lipids were seen in dilated endoplasmic reticulum, as well as in supranuclear and basal regions of epithelial cells. Histochemical localization revealed free cholesterol in dilated endoplasmic reticulum and residual bodies at the ultrastructural level. Neutral lipid was observed by light microscopy in the supranuclear and basal regions of the cells. In 10- and 20-week treated animals, lipid droplets were also seen in the lamina propria and macrophages. The lesion induced by cholesterol ingestion persisted throughout the experimental period, and while different from that in human tissue, it was similar to those observed in experimental canine cholesterosis.

Animals↗
PubMed1987

Periodic gallbladder contraction maintains bile acid circulation during the fasting period: a canine study.

Using a canine model we have studied the relationship between the interdigestive cycle in the small intestine, motility changes in the biliary tract and bile acid output into the duodenum from direct hepatic secretion and gallbladder emptying. Under anaesthesia catheters were inserted into the gallbladder, common bile duct and duodenum, and electrodes were attached to the small intestine in five dogs. These animals were subsequently studied conscious and fasting. A double marker technique was used to measure bile acid output from the gallbladder and liver while pressure in the gallbladder and common bile duct and electrical activity in the small intestine were monitored. Four complete interdigestive cycles were recorded in each dog. Output of bile acids from the gallbladder fluctuated with the phases of the cycle: being lowest in phase I (3.9 +/- 0.7 mumol/min); increasing significantly (P less than 0.005) in phase II (9.8 +/- 1.0 mumol/min); remaining elevated in phase III (13.9 +/- 1.7 mumol/min); and falling significantly (P less than 0.05) in phase IV (8.4 +/- 1.8 mumol/min). In contrast, hepatic secretion of bile acids directly into the duodenum remained fairly constant. Intraluminal pressure in the biliary tract paralleled the fluctuation in gallbladder bile acid output, being significantly increased (P less than 0.05) in phases II and III. Periodic contraction of the gallbladder would, therefore, appear to be the principal mechanism for the phasic output of bile during fasting.

Animals↗
PubMed1987

Morphological observations on the gallbladder of ground squirrels fed a lithogenic diet.

Richardson's ground squirrels (Spermophilus richardsonii) of both sexes were fed a 2 per cent cholesterol-enriched rat chow diet for intervals of 1, 2, 10 and 20 weeks. Light microscopy and 3H-thymidine autoradiography revealed an increase in cell proliferation prior to the occurrence of macroscopically visible stones, but in the presence of crystals and microliths. Transmission electron microscopy studies showed that columnar epithelial cells undergo mitosis rather than basal cells and that oedematous cells were extruded from the epithelial sheet. Transmission and scanning electron microscopy studies on gallbladders of animals fed the lithogenic diet for 10 and 20 weeks revealed damaged epithelial cells either singly or in groups. Neighbouring cells often slide under the basal aspects of cells being extruded. Hypertrophy, hyperplasia, Rokitansky-Aschoff sinuses, thickening of the lamina propria around the muscle bundles and inflammatory cells in the lamina propria began to occur about the time macroscopically visible stones were present. The epithelium of the Richardson's ground squirrel gallbladder is damaged more slowly than that of other animal models by a cholesterol-enriched, lithogenic diet and may more accurately reflect changes occurring in human cholecystitis.

Animals↗
PubMed1987

Contractility of human gallbladder muscle in vitro.

This study examined the effects of transmural nerve stimulation, acetylcholine, adrenoceptor agonists and several peptides on the contractility of strips of human gallbladder in vitro. Acetylcholine caused concentration-related contractions of the tissues and the sensitivity to acetylcholine was similar in gallbladders with mild and severe chronic cholecystitis. Noradrenaline and adrenaline relaxed gallbladder strips, probably via beta 2-adrenoceptor stimulation. Transmural nerve stimulation always caused contractions, but in the presence of atropine inhibitory responses were demonstrable and these were antagonized by propranolol. There was no evidence of non-adrenergic inhibitory neural responses. Of the peptides tested, only cholecystokinin octapeptide (CCK-OP), gastrin, pentagastrin, substance P and caerulein caused contractions. Responses to CCK-OP, gastrin and pentagastrin were antagonized by dibutyryl cyclic GMP. Hormones which had no effect upon human gallbladder strips included motilin, secretin, bombesin, neurotensin, glucagon, vasopressin, VIP and somatostatin. Considerable differences therefore exist between human tissues and those from experimental animals with respect to the direct actions of neural and hormonal stimuli on gallbladder contractility.

Electric Stimulation↗
PubMed1987

Bronchodilators: beta 2 agonists versus theophylline.

Beta 2 agonists are best administered by inhalation since this route provides maximum therapeutic effect with minimum side effects. Plasma levels are lower and muscle cramps, tachycardia and tremor less common. Inhalation may be carried out by use pressurised inhalers (with various modification if necessary), by a Rotahaler with Salbutamol powder, and by nebulisers. All have their uses. Apart from their immediate bronchodilator effect, it is customary to give Beta 2-agonists routinely before inhalation beclomethasone, and there is evidence that regular use of Beta 1-agonists has a useful suppressive effect. In severe chronic asthma high doses may be indicated and be effective where conventional doses have failed. The introduction of reliable sustained-release preparation of theophylline and its derivatives together with plasma assays theophylline levels has enabled therapy to be optimal and side effects to be lessened. The therapeutic range is a plasma concentration of 10-20 mg/l. There are large individual variations in hepatic clearance of theophylline, which may also be influenced by age, liver disease, drugs and viral infections. Theophyllines are less effective as bronchodilators than Beta 2-agonists but in chronic severe asthma have a place for their additive effect. They are used most frequently to suppress nocturnal asthma and early morning wheezing.

Adrenergic beta-Agonists↗
PubMed1987

Ultrastructural observations on the gallbladder of Richardson's ground squirrel (Spermophilus richardsonii).

The gallbladder of Richardson's ground squirrel shares many structural similarities with numerous other species, including the mouse, rabbit and man. Dark cells exhibit a condensed cytoplasm but contain all the typical organelles of light cells, although their total complement appears reduced. Edematous cells extruded from the epithelial lining were replaced through mitosis or had their space occupied by adjacent cells. Specializations of the basal plasma membrane and underlying basal lamina form peg-and-socket interdigitations, and desmosomes were observed on the lateral cell boundaries down to the level of the basal lamina. The latter remain intact during active water resorption while the former disappear. Adrenergic nerve fibers were observed intramuscularly and beneath the basal lamina. Random interepithelial migration of leucocytes was also observed. Some of these observations help to elucidate controversial issues whereas others have been previously unreported and may be species-dependent.

Animals↗
PubMed1987

Experimental cholelithiasis in the ground squirrel.

Richardson's ground squirrels of both sexes were fed a 2% cholesterol-enriched rat chow diet for various intervals from 6 hours through 20 weeks. Bile was withdrawn from the organs and analyzed biochemically to obtain a lithogenic index. The remaining luminal contents were rinsed from the resected organs and examined by light and scanning electron microscopy. Gallbladder tissue was fixed and examined in a similar fashion to observe the luminal aspect of the epithelial sheet. Scanning electron microscopy revealed increased mucus secretion before precipitation of rhomboidal cholesterol monohydrate crystals from the lithogenic bile. The crystals grew by appositional layering into microliths and then by aggregation into mulberry-shaped stones. Mucus hypersecretion continued to be a common epithelial observation throughout the study. Five days after introduction of the diet, a thick discontinuous sludge-like layer was observed overlying large regions of the epithelial sheet. In later stages, this material was observed embedding cholesterol crystals into the surface aspect of the stone. By 20 weeks many stones were approximately 2 mm in diameter and were accompanied by large numbers of various sized concrements. The nature of the cholesterol crystals and stone formation pattern closely resembled that reported for humans. The ground squirrel fulfills all criteria required to be regarded as an excellent animal model and is well suited for continued study into the role of the epithelial cell during cholesterol cholelithiasis.

Animals↗
PubMed1986

A scanning electron-microscopic study of the muscle layer of the canine gallbladder.

A connective tissue digestion and removal technique utilizing collagenase and hyaluronidase incubation followed by treatment with 8 N hydrochloric acid successfully revealed the muscular components within the gallbladder wall of the dog, allowing three-dimensional visualization with the scanning electron microscope. The muscle adjacent to the serosa appeared as a homogeneous layer with few discontinuities. In contrast to this were the more superficial muscle layers which were arranged as a meshwork of interlacing smooth muscle bundles of various size, the interstices of which were filled with cellular connective tissue. These gaps in the muscle layer varied in size, becoming larger as the muscle bundles tapered out just below the mucosal aspect of the gallbladder wall.

Animals↗
PubMed1986

Effects of age, gender and female sex hormones upon contractility of the human gallbladder in vitro.

Age, gender and female sex hormones are thought to influence contractility of the gallbladder. Surgically removed gallbladders with gallstones and mild chronic cholecystitis from three groups of patients (males and premenopausal and postmenopausal females) were studied. Strips were incubated in Krebs solution, in Krebs containing 0.2 per cent ethanol-propylene glycol solvent (solvent controls) or in Krebs solution containing progesterone (0.1, 1.0 and 10.0 micromolar) or 17-beta-estradiol (0.1 and 1.0 micromolar). Concentration response curves were obtained for acetylcholine and octapeptide of cholecystokinin and the maximum contraction and median effective dose values were recorded. Steroid receptor levels in the wall of the gallbladder were also estimated. In gallbladders from males, the sensitivity to acetylcholine increased significantly with age. However, in gallbladders from premenopausal women, there was a significant decrease in sensitivity to acetylcholine and cholecystokinin with age. Progesterone (1 and 10 micromolar) reduced the spontaneous rhythmic contractions of the strips by 35 +/- 8 and 65 +/- 8 per cent, respectively, and also reduced the maximum contraction of gallbladders from postmenopausal females to acetylcholine. Estradiol-17 beta had no effect upon the contractility of the gallbladder. The results of additional studies showed that the human gallbladder is estrogen and progesterone receptor negative. The sensitivity of the gallbladder to neurohormonal stimulation varies with age and gender. These results indicate that short term exposure to female sex hormones has an inhibitory effect upon gallbladder contractility. The inhibitory effects of short term exposure to progesterone seen in this study are probably nonspecific in nature.

Acetylcholine↗
PubMed1984

Effects of prostaglandins on motility of gallbladders removed from patients with gallstones.

Prostaglandins (PGs) affect smooth-muscle contractility and are also involved in the inflammatory reaction. They may therefore affect gallbladder motility in cholecystitis. The contractile effects of PGs were recorded in organ baths on strips from 63 fresh, surgically removed human gallbladders. Spontaneous rhythmic contractions were reduced or abolished by indomethacin, which inhibits endogenous PG synthesis. In strips with chronic cholecystitis, concentration-dependent contractions were produced by PGF2, PGB2 and PGD2; the responses to PGE1 and PGE2 were sometimes variable but there were concentration-dependent contractions after treatment of the strips with indomethacin. The majority of strips with acute cholecystitis responded poorly to PGs even after pretreatment with indomethacin. We concluded from this preliminary study that PGs could affect gallbladder motility and that indomethacin probably reduces the endogenous production of PGs in the gallbladder.

Cholelithiasis↗
PubMed1984

The effects of vasoactive intestinal polypeptide on the motility of human and guinea pig gallbladder.

The effects of several preparations of vasoactive intestinal polypeptide (VIP) on the motility of strips of human and guinea pig gallbladder were investigated in vitro. VIP (10(-12) to 10(-6) M) had no measurable effects on the spontaneous activity, resting tone or cholecystokinin-octapeptide induced tone of human gallbladder strips. However, VIP (10(-12) to 10(-6) M) caused biphasic effects on the tone of guinea pig gallbladder strips. At low concentrations (10(-12) to 10(-10) M) contractions were observed that became smaller at higher concentrations (10(-9) to 10(-8) M). At still higher concentrations (10(-7) to 10(-6) M) relaxations were elicited. It appears that VIP is not as potent a relaxant of gallbladder muscle as first described. Human gallbladder tissue was totally unresponsive to the VIP preparations tested.

Animals↗