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Biomedical subjects

J W Robinson

Publications and source records attributed to J W Robinson.

At least 109 records · Page 6Linked to original sources

Alterations in the dog renal tubular epithelium during normothermic ischemia.

Dog kidneys were subjected to one, two, or three hours' normothermic ischemia in situ and were then excised for biochemical and histological evaluation. The uptake of para-aminohippurate (PAH) by cortical slices progressively decreased with prolongation of the ischemia, but active transport was never abolished. Glycine uptake and oxygen consumption were only reduced to a modest extent by the ischemia. The intracellular ion levels were drastically altered, with loss of potassium and gain of sodium and chloride, and considerable increases in tissue water were observed. Acid phosphatase was liberated by the whole organ into the venous blood and by the incubated slices into the incubation medium, but both biochemical and histochemical techniques showed that the total quantity of the enzyme in the cells was hardly changed. The histochemical reaction product was localized exclusively in the lysosomes. Morphological damage was slight after one or two hours' ischemia, but more pronounced after three hours, when some cells were seen to be detached from the basement membrane. These relatively minor changes seem insufficient to predict the ultimate fate of the organ after ischemia.

Acid Phosphatase↗

Functional and structural characteristics of the jejunum and ileum in the dog and the rat.

The dog jejunum is a much denser tissue than the ileum, with a greater weight per unit length and higher proportion of mucosal tissue. Morphometric analysis reveals longer and wider villi, deeper crypts and larger enterocytes in the jejunal mucosa. Uptake of phenylalanine or beta-methyl-glucoside by tissue slices in vitro is slightly greater in jejunal than in ileal tissue. The levels of acid phosphatase and alkaline phosphatase in the individual enterocytes are significantly greater in the jejunum, according to quantitative histochemical analysis. The absorption of water, sodium, potassium, chloride and glucose in vivo is significantly smaller in the jejunal than in ileal loops, particularly when expressed in terms of unit mucosal weight. Sodium and water absorptions are stimulated by glucose at both sites, but the stimulation is significantly greater in the ileum. Opposite results have been obtained in rats where the transport of phenylalannie in vitro is greater in the ileum, but water, electrolyte and glucose absorption in vivo is greater in the jejunum.

Acid Phosphatase↗

The roles on intraluminal oxygen and glucose in the protection of the rat intestinal mucosa from the effects of ischaemia.

Rat ileal loops were subjected to 15 minutes ischaemia by clamping both mesenteric and collateral vessels, after which the functional capacity of their mucosae was assessed according to their ability to accumulate phenylalanine "in vitro". Groups of intestines were rinsed before being subjected to ischaemia. Independent and additive protective effects were observed when the rinsing buffer was oxygenated and/or when it contained glucose. Indeed, an oxygenated, glucose-containing buffer afforded full protection to the mucosa, whereas a nitrogenated, glucose-free buffer had no action.

Animals↗

Enhanced non-electrolyte uptake in vitro by the dog jejunal mucosa in the cholera-toxin-induced secretory phase.

A characteristic secretory response in the dog jejunumis observed following three hours' perfusion with cholera toxin. When this mucosa in the secretory phase is examined in vitro, the steady-state accumulation of phenylalanine and beta-methyl-glucoside is considerably enhanced. Since the initial rates of influx of these substrates are unchanged and the tissue ion contents are the same as normal, it is concluded that the increase in steady-state uptake may be attributed to a change in the rate of efflux of the substrates across the baso-lateral membrane of the cell. This change might be related to the reported collapse of the intercellular channels when the intestine is in a secretory state.

Animals↗

The consequences of ischaemia after mechanical obstruction of the dog ileum.

A mechanical obstruction was produced in the dog ileum, and four days later, loop of intestine above and below the occlusion were subjected to one hour's ischaemia. This led to widespread morphological and functional damage of the epithelium, indistinguishable from the response of the normal intestine. The recovery of the mucosa of both loops after the ischaemia followed exactly the same pattern as when there was no occlusion superimposed: The transport capacity for phenylalanine in vitro was entirely restored, whereas that of beta-methyl-glucoside, together with oxygen consumption and lactate production, remained depressed; morphometric examination revealed that the recuperating mucosa had smaller villi, shorter crypts and smaller epithelial cells than the contiguous untouched tissue. These results suggest that the regenerative potential of the crypts could not be obliterated by one hour's ischaemia, either in the presence of a noxious obstruction fluid above the occlusion, or in the atrophic mucosa below it.

Acid Phosphatase↗

Effect of different bathing media on the short-circuit current across the intestine of the rat and guinea-pig.

The changes in short-circuit current occurring when one or both solutions bathing the intestine of rat or guinea-pig mounted in flux chambers were recorded. The results with the guinea-pig can be explained in terms of diffusion potentials arising from the ionic replacements, and an electrogenic sodium pump, sensitive to ouabain, in the contraluminal membrane of the cell. In the rat, the situation is more complicated, and the enterocyte probably possesses an electrogenic sodium pump in the brush-border membrane.

Animals↗

Effect of (+)-catechin on renal and intestinal transport.

The ability of dog renal cortex slices to accumulate beta-methyl-glucoside or glycine is enhanced by the flavonoid (+)-catechin at a concentration of 3.5 mM. This stimulatory effect is apparently due to a decreased rate of efflux of either substrate. On the other hand, the uptake of p-amino-hippuric acid and N1-methyl-nicotinamide is inhibited by (+)-catechin. The drug at the same concentration is without action on amino-acid transport by guinea-pig intestine in vitro.

Aminohippuric Acids↗

Differential effects of harmaline and ouabain on intestinal sodium, phenylalanine and beta-methyl-glucoside transport.

Harmaline inhibits both the Na+ -K+ -ATPase activity and the uptake of L-phenylalanine in guinea-pig intestinal mucosa. The latter effect is not a direct consequence of the former, since higher concentrations are needed to inhibit the enzyme than the influx into the mucosa; Furthermore the uptake is still sensitive to harmaline when the Na+ -K+ -ATPase has been fully inhibited by ouabain. Harmaline can inhibit L-phenylalanine influx at a concentration at which it does not affect intracellular ion concentrations. Ouabain, however, inhibits the uptake of L-phenylalanine only after a 30 min preincubation period, when the intracellular sodium concentration reached the extracellular level. Harmaline also interferes with the influx of beta-methyl-D-glucoside in the mucosa of the dog colon. Addition of harmaline at the mucosal face of the tissue suppresses all net transport of sodium and chloride ions and L-phenylalanine across the mucosa. Thus the same mode of action appears to apply in both the guinea-pig ileum and the dog colon.

Adenosine Triphosphatases↗

The functional response of the dog ileum to one hour's ischaemia.

1. The function and structure of dog ileal mucosa was examined immediately after arterial ischaemia for 1 h and 1, 3 or 7 days after the trauma. 2. Immediately after the ischaemia, there was a net movement of water and ions into a luminal perfusate in vivo. One day later, there was no net movement of water and electrolytes but net absorption returned on the third day. 3. Active transport of phenylalanine or beta-methylglucoside by mucosal strips in vitro was abolished immediately after the trauma but was largely restored 1 day later. There was a close correlation between glucose absorption in vivo and beta-methylglucoside uptake in vitro. 4. Morphological study revealed pronounced desquamation of enterocytes immediately after the trauma. The regenerating mucosa had shorter villi and crypts, and lower enzyme activities assessed histochemically 1 day later. Most parameters had returned to normal by the third post-operative day.

Acid Phosphatase↗

Morphology and function of the dog ileum after mechanical occlusion.

1. Complete mechanical occlusion of the ileum was produced in dogs and the loops above and below the obstruction were examined functionally and morphologically 4 or 7 days later. 2. The intraluminal pressure in the occluded loop never exceeded 8 cm water. 3. The mucosa above the obstruction secreted water and ions into the lumen in vivo, though it absorbed glucose normally. Mucosal slices also absorbed amino acids and monosaccharides normally in vitro. 4. The mucosa below the obstruction absorbed ions and glucose in vivo and non-electrolytes in vitro to a slightly smaller extent than normal intestine. 5. The morphological changes above the occlusion included shorter, plumper villi and shorter crypts, a reduction in histochemically stainable brush-border enzymes, but an increase in acid phosphatase. Below the obstruction, there was atrophy of the villi and crypts and reductions in all enzymes studied. 6. The results suggest that the mucosa above the occlusion possesses an intact and almost normal epithelial layer, but that it has been stimulated to secrete in vivo, presumably by intraluminal factors. Below the obstruction, true atrophy of the mucosa has promptly developed.

Acid Phosphatase↗

A glycoprotein precipitate in the blood vessels of kidneys stored in cold homologous blood.

Dog kidneys were stored three hours at 4 degrees C in heparinized homologous blood. Their histological examination revealed the presence of a homogeneous precipitate in the glomerular capillaries and afferent and efferent arterioles, and histochemical analysis indicated that it consisted of glycoprotein. It is tentatively suggested that the substance is cryoglobulin, a conclusion supported by the disappearance of the deposit on reimplantation of the kidney.

Animals↗

[Adaptive changes in intestinal mucosa of the small intestine as a result of intraluminal stress].

Under physiological conditions, the intestinal mucosa is the site of a delicate balance between cell proliferation in the crypt region and cell desquamation at the villus tips. This balance can be deranged by a number of endogenous or exogenous factors, oneof which is the intraluminal contents. This review discusses the effects of different modifications of the luminal milieu on the structure and function of the mucosa. Following intestinal resection or loop transposition, the contents reaching the remnant or the transposed loop differ markedly from those with which they come into contact under normal conditions. Hyperplasia without zonal transformation then develops in the experimental loop. The villi do not become wider, and changes in the strucutre of the epithelium are not observed. There are conflicting resutls in the literature concerning the enzyme activities in the individual enterocytes resulting from this hyperplasia. However, the epithelium its functionally immature, since transport capacities measured in vitro are reduced. On the other hand, the hyperplasia of the mucosa is such that absorptive capacities in vivo, when expressed in terms of intestinal length, are larger than normal. When the intestine is subjected to prolonged infusion of lactic acid, the enterocytes are damaged and increased exfoliation results. A similar result is obtained in the blind-loop syndrome, where the accumulation of bile acids and bacteria provides the stress responsible for the destruction of the enterocytes, and in non-tropical spure, where the epithelium is attacked by noxious peptides in the diet. The first consequence of the accelerated desquamation is epithelial hyperplasia without zonal transformation, though the enterocytes are damaged - in contrast to those of the resected intestine - and apparently possess reduced enzyme activities. If the application of the stress is continued, a stage is reached in which the cell proliferation does not suffice to counteract the cell loss at the villus tips. Then a zonal transformation occurs whereby, despite the lengthened crypts, the villi become shorter and wider until, in extreme cases, the mucosa is completely devoid of villi. The transport capacity in vitro and in vivo - even when expressed in terms of unit-length is reduced, and good correlations exist between the reduction in function and the diminution in surface area of the intestine. In a self-emptying blind loop, the intestine is devoid of all contact with nutritional material. Under these circumstances, hypoplasia of the mucosa develops in which the enterocytes appear unchanged, though in extreme cases they may possess reduced enzyme levels, and the absorption capacity in vivo is consequently reduced.

Adaptation, Physiological↗

Protection of the intestinal mucosa during ischaemia by intraluminal perfusion.

The function of the intestinal mucosa immediately after one hour's ischaemia was examined by means of tests in vivo and in vitro. During the ischaemia, the intestinal loop was perfused with media of different compositions, in an attempt to assess which provided the best protection of the epithelium from the deleterious effects of the ischaemia. The absorption of water, ions and glucose was then monitored in vivo, and the uptake of phenylalanine and beta methyl-glucoside by slices of mucosa was determined in vitro. The unprotected mucosa loses all active transport capacity in vitro following one hour's ischaemia, and is the site of a pronounced loss of water and ions into the lumen in vivo. Glucose absorption in vivo is also abolished. If the loop is perfused during the ischaemia with glucose-containing Krebs bicarbonate buffer, much of the transport capacity in vitro is retained; the loss of ions and water is prevented, and glucose absorption in vivo occurs. Perfusion during the ischaemia with other media, such as isotonic mannitol, Krebs bicarbonate buffer, or Ringer-lactate solution, results in a marked protection of the mucosa, in comparison with the unperfused loop, but the effects are not as pronounced as those of the glucose-containing buffer. It is concluded that the act of perfusing the intestine is the most beneficial factor, but that the presence of glucose in the perfusate does afford added protection.

Animals↗