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M L Gardner

Publications and source records attributed to M L Gardner.

52 records · Page 3Linked to original sources
PubMed1978

Responding maintained under fixed-interval and fixed-time schedules of electric shock presentation.

Following initial histories under a schedule of electric shock postponement, lever pressing in squirrel monkeys was maintained under fixed-interval and fixed-time schedules of electric shock presentation. No difference in either rate or pattern of responding was obtained when these schedules were presented as components of a multiple schedule. When they were presented singly for long periods of time, the fixed-interval schedule consistently maintained a higher response rate than the fixed-time schedule. The pattern of responding under both schedules was similar, typically consisting of a pause at the beginning of each interval followed by either a steady or a positively accelerating rate of responding. The results suggest that the response-shock dependency is of critical importance in the maintenance of high rates of responding under schedules of electric shock presentation, and support the general view that such responding may be conceptualized as operant behavior under control of many of the same variables that control responding under comparable schedules of food or water reinforcement.

Journal Article↗
PubMed1977

The computation of saturable and linear components of intestinal and other transport kinetics.

1. Published data for absorption kinetics have been fitted by non-linear regression to (i) a single Michaelis-Menten function, (ii) a Michaelis-Menten function plus a linear term and (iii) a sum of two Michaelis-Menten functions. A series of criteria have been drawn up to establish the goodness of fit in each case. 2. In 17 out of 35 cases the Michaelis-Menten function was the "best fit". In nine cases the "best-fit" model also included a linear term, but never was the sum of two Michaelis-Menten functions accepted to be the "best-fit" model. 3. Linearity of a Lineweaver-Burk plot was of unreliable diagnostic value in assessing goodness of fit. 4. Since the fit of a Michaelis-Menten function was often poor, simulated data sets with error were used to study the influence of experimental design etc. on Michaelis-Menten parameter estimation. 5. Precision of estimation of Km is increased by increasing the number of data points, reducing their variance, increasing the data range and by straddling Km in the observations. For a given constant number of observations there is no advantage in using replicate observations at few concentrations or single values at relatively many concentrations, or in using single values rather than means. 6. The caution necessary in interpretation of kinetic models is emphasized.

Animals↗
PubMed1977

The absorption of phenformin and its effects on glucose and water absorption in isolated perfused rat small intestine.

The effects of phenformin on glucose and water absorption from isolated perfused rat small intestine were studied. Luminal phenformin inhibited glocose and water absorption progressively as its concentration was increased from 0-1-1-0 mg.ml-1. At 0-5 mg phenformin ml-1, inhibition increased with time of exposure to phenformin up to 15 min and thereafter remained constant. Arterial infusion of phenformin (1-0 mg-ml-1) produced less inhibition of glucose and water absorption. The site of phenformin's action appeared to be intracellular. Phenformin absorption from a luminal perfusate (0-5 mg-ml-1) was measured. Although it was rapidly absorbed (22 microgram.cm intestine-1.h-1) from the lumen, less than 2 microgram.cm-1.h-1 appeared at the serosal surface of the intestine. In subsequent phenformin-free perfusion, only 25% of the absorbed phenformin was recovered in the luminal and serosal effluents.

Animals↗
PubMed1977

Metabolic energy dependence of glucose, water and sodium absorption in the presence and absence of 'downhill' sodium gradients across isolated rat small intestine.

1. Absorption of glucose and water was studied in isolated perfused rat small intestine with arterial infusion under normal conditions and with a 'downhill' sodium gradient across the mucosa. 2. The effects of metabolic inhibitors, iodoacetate phenformin and dinitrophenol, on absorption were determined in the presence of normal and 'downhill' sodium gradients. 3. Glucose absorption was inhibited by each inhibitor, and the inhibition was independent of the direction of the sodium gradient. 4. Net sodium flux across the mucosa was also inhibited under 'downhill' sodium gradient conditions. 5. The simultaneous and parallel inhibition of both glucose and sodium transport is consistent with, but does not prove, the sodium gradient theory.

Animals↗
PubMed1976

A diurnal rhythm in the absorption of glucose and water by isolated rat small intestine.

1. Glucose and water absorption by isolated small intestine from rats which have had unrestricted access to food is 50-60% higher at night than during the daytime. 2. When the feeding time is restricted to 06.00-09.00 hr G.M.T. glucose and water absorption rates in the period from 3 to 7 hr after withdrawal of food are almost as high as the rates observed at night-time in the animals with unrestricted feeding. 3. These changes in absorption rates appear to be associated with feeding time and not with the pattern of illumination.

Animals↗
PubMed1976

Absorption from a mixture of seventeen free amino acids by the isolated small intestine of the rat.

Absorption and secretion from a mixture of seventeen free amino acids has been measured in isolated perfused rat small intestine. 2. The absorption rate of an amino acid from this mixture is proportional to its concentration in the perfusate and independent of its chemical constitution. The constant of proportionality is the same as that previously observed when the perfusate contained peptides as well as amino acids. 3. Amino acids are concentrated, on average, sixfold during passage across the mucosa, and the free amino acid composition of the secretion into the tissue fluid is very similar to that of the luminal perfusate. 4. Peptides do not appear to be added to the tissue fluid during absorption of free amino acids. 5. It is concluded that the mechanisms for absorption of free amino acids are in general independent of those for absorption of peptides.

Amino Acids↗
PubMed1975

Transport of deutherium oxide across isolated rat small intestine.

1. Transport of deuterium oxide from a luminal perfusate containing 1% D2O was studied in Fisher & Gardners (1974) isolated preparation of perfused rat small intestine. 2. The kinetics of appearance of D2O in the intestinal secretion at the serosal surface fitted well to a single exponential function. 3. The steady-state concentration of D2O in this secretion was not significantly different from the concentration in the luminal perfusate. 4. The total tissue water contained D2O at a concentration, on average, 5% lower than that in the luminal perfusate. 5. There is no evidence to suggest discrimination in transport across the intestinal mucosa between H2O and D2O. 6. The kinetics of wash-in of D2O to intestinal secretion show that the ratio of flux out of the lumen to reflux back to the lumen is 1-38;1.

Animals↗
PubMed1975

Absorption of amino acids and peptides from a complex mixture in the isolated small intestine of the rat.

Amino acid and peptide absorption from a pancreatic digest of casein at low concentration by an isolated preparation of perfused rat small intestine has been measured. 2. The rate of absorption of each amino acid (free or peptide-bound) is closely proportional to its concentration in the perfusate; this implies a constant Vmax/Km ration for all amino acids in the mixture. 3. There is a high correlation between the compositions of luminal perfusate and secretion into the tissue fluid (apart from the content of glutamic and aspartic acids and alanine). 4. The concentrations of each free amino acid are, on average, 9 times as great in secretion as in lumen; the total peptide-N concentration in secretion is approximately 4 times that in the lumen. 5. The rate of absorption of each free amino acid is highly negatively dependent on the rate of absorption of that amino acid in peptide-bound form, in addition to being positively dependent on the perfusate concentration of free amino acid. 6. While peptide-bound proline appears to be well absorbed, free proline liberated by hydrolysis appears to pass back into the lumen as well as into the tissue fluid. Substantial back flux of hydrolysis products may occur for all amino acids. 7. About one-third of the amino acids appearing in the secretion on the serosal surface are peptide-bound. 8. The rate of absorption of peptides appears to determine the rate of their hydrolysis which probably occurs mainly after entry into the mucosal cells.

Amino Acids↗
PubMed1974

A kinetic approach to the study of absorption of solutes by isolated perfused small intestine.

1. A new technique has been developed for making serial measurements of water and solute absorption from the lumen of isolated small intestine.2. The isolated intestine is perfused in a single pass with a segmented flow of slugs of liquid separated by bubbles of oxygen-carbon dioxide mixture. Simultaneous collections are made of effluent from the lumen and of the fluid which is transported across the mucosa. This latter fluid appears to be a fair sample of the tissue fluid.3. Conditions in the lumen can be changed within less than 5 min. The effects of two or more treatments applied to the same segment of intestine can be determined and the time course of a change in luminal conditions.4. The rate of appearance of solutes on the serosal side depends on the rate of water absorption, and changes exponentially towards a steady state. The rate constant is a function of tissue fluid volume.5. In the steady state the concentration of glucose in the tissue fluid is 71 mM when the luminal concentration is 28 mM, and is 45 mM when the luminal concentration is 8.3 mM.6. For solutes such as glucose for which reflux from tissue fluid to lumen is small relative to flux from lumen to tissue fluid, the time of attainment of a steady state in secretion is usually 50-60 min.7. For solutes such as sodium for which the reflux is relatively high, the steady state may be reached in 15-20 min.8. The K(m) for glucose absorption (14-19 mM) is much lower than is found with unsegmented flow perfusion.9. These findings emphasize problems in interpreting results from other types of intestinal preparation.10. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium concentration is reduced abruptly. In contrast the rate of glucose absorption falls suddenly when the luminal glucose concentration is reduced abruptly. This suggests that glucose absorption is not directly dependent on luminal sodium ions.

Animals↗
PubMed1974

Dependence of intestinal glucose absorption on sodium, studied with a new arterial infusion technique.

1. A new preparation of isolated rat jejunum plus ileum (ca. 100 cm) is described in which a saline infusate is pumped into the superior mesenteric artery, the superior mesenteric vein having been ligated.2. The arterial infusate washes out the tissue spaces: the lumen is perfused in a single pass with a segmented flow as by Fisher & Gardner (1974).3. At an arterial infusion rate of 3 ml./min, steady states are set up in the tissue fluid within 10-15 min: the compositions of the fluids bathing both sides of the mucosa can therefore be controlled.4. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium is replaced by choline abruptly while the tissue fluid sodium is maintained at 144 m-equiv/l. by arterial infusion.5. The rate of glucose absorption from the lumen is unaffected by replacement of sodium in the arterial infusate by choline.6. Ouabain (10(-4) M) in an arterial infusate containing sodium 144 m-equiv/l. causes inhibition of glucose and water absorption from the lumen. There is no effect of ouabain when the arterial infusate contains sodium, 0 or 72 m-equiv/l.7. Arterial ouabain does not reverse the effects of depletion of luminal sodium. Simultaneous removal of luminal sodium and application of arterial ouabain causes faster inhibition of glucose absorption than does either treatment alone.8. Glucose absorption is more likely to depend on rate of efflux of sodium from mucosal cell to tissue fluid than on a sodium gradient at the brush border or on intracellular sodium concentration.

Animals↗
PubMedDate not supplied

Elemental diets in the repair of small intestinal damage.

We have investigated the possible benefits of elemental diets, especially a diet supplemented with L-glutamine, on maintenance of intestinal absorptive function in rat small intestine damaged by 5-fluorouracil. Although a standard rat diet sustained better body growth in control rats, each of the elemental diets and the diet containing intact casein in place of hydrolyzed casein was beneficial in promoting less body weight loss during the 3 d after 5-fluorouracil injection. The same significant benefit was seen in absorptive activity measured in small intestine in vitro 3 d after the cytotoxic injury. Glutamine supplementation, however, did not confer any significant advantages, although it did cause significant elevation of muscle glutamine pools. This elevation was substantially less than the corresponding increase in muscle glycine content after dietary supplementation with glycine.

Animals↗
PubMedDate not supplied

Can elemental diets reduce the intestinal toxicity of 5-fluorouracil?

In order to test the hypothesis that elemental diets protect the intestinal mucosa against 5-fluorouracil toxicity, we have estimated water absorption, cytoplasmic peptide hydrolase activities, and mucosal DNA contents in isolated intestines from rats fed on one of three elemental diets or a standard diet and injected with 5-fluorouracil. Water absorption rates were significantly increased when rats, not injected with 5-fluorouracil, were fed on Flexical or Vivonex-HN. However, water absorption was severely impaired 3 days after administration of 5-fluorouracil and none of the elemental diets alleviated this impairment of absorption. Cytoplasmic peptide hydrolase activities and mucosal DNA contents were also severely decreased after 5-fluorouracil injection, the changes observed being independent of the diet. Also, none of the elemental diets reduced the body weight losses observed after 5-fluorouracil administration. Although the effects of the sodium salt of 5-fluorouracil on body weight and food intakes were much less severe than those of the Tris salt the two salts had identical effects on intestinal absorption even when an elemental diet was used. Although there was a smaller incidence of diarrhea after 5-fluorouracil administration when the rats had been fed on one of the elemental diets, diet B, the results do not support the suggestion that elemental diets might reduce the intestinal toxicity of 5-fluorouracil.

Animals↗