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Biomedical subjects

M W Smith

Publications and source records attributed to M W Smith.

At least 289 records · Page 16Linked to original sources

The ultrastructure of the neonatal pig colon.

The neonatal pig colon has several unique structural and developmental features. At birth it has a variable population of epithelial cells which in their arrangement on villus-like protrusions and in their capability for protein uptake into large preformed supranuclear vacuoles closely resemble neonatal ileal cells. Such villus-like protrusions and vacuolated cells are not present in the 2-day-old piglet. On the first day after birth absorptive epithelial cells which lack supranuclear vacuoles transiently accumulate a large number of lipid droplets, each separated from the cytoplasm only by a proteolipid interface. None of the much smaller lipid droplets bounded by a unit membrane of the smooth endoplasmic reticulum and characteristic of normal small intestinal fat uptake were ever seen in these cells. Very few of the large lipid drops remain on the second day after birth. This initial capacity of the colon for protein and lipid uptake never reappears. The pattern of colonic amino acid transport also changes markedly in the first four days of independent life and this may be correlated with the observation that the absorptive cells at birth have microvilli which are twice the length of those on similar cells at and after two days old. These morphological results are discussed in terms of implied functional changes in the neonatal period.

Amino Acids↗

Discrimination between different entry mechanisms for neutral amino acids in rabbit ileal mucosa.

1. Influx of neutral and basic amino acids into the mucosal epithelium of the rabbit ileum was measured in the presence of high and low concentrations of Na. Uptake measured at an amino acid concentration of 1 mM varied from 10 to 16 nmole . cm-2 . min-1. Removal of Na inhibited the uptake of short-chain amino acids more than long-chain amino acids. 2. Inhibition of uptake of glycine, alanine, leucine and phenylalanine by a selection of non-radioactive amino acids was found to follow a particular pattern. Long-chain amino acids inhibited the uptake of all test amino acids; short-chain amino acids inhibited preferentially the uptake of glycine. 3. The maximum inhibition serine could cause to the uptake of other amino acids was found to vary. Serine inhibited completely the uptake of glycine but a portion of uptake of long-chain amino acids was found to persist, even in the presence of high concentrations of serine. This is taken as evidence for the presence of an amino acid uptake mechanism having no affinity for serine. 4. The apparent affinities of neutral amino acids for the serino-inhibitable system (system 1) varied from about 0.5 mM (for long-chain amino acids) to about 3 mM (for short-chain amino acids). The total uptake of individual amino acids by system 1 was essentially similar when compared at an amino acid concentration of 1 mM. 5. The serine-resistant uptake of neutral amino acids (system 2) constituted up to two fifths of total uptake for long-chain amino acids, measured at amino acid concentrations of 1mM. The affinities of long-chain amino acids for system 2 is thought to be less than for system 1. Serine appears not to interact with system 2. 6. A second component to serine uptake was found to be related linearly to the concentration of serine in the medium. A similar component may contribute to the total uptake of phenylalanine. The possibility that such a component could arise as a space marker artifact is discussed. 7. An independent kinetic analysis of phenylalanine uptake by rabbit ileal mucosa showed that it could not be accounted for on the basis of a single entry system. However uptake could be described kinetically, assuming two systems of mediated entry to be present. The possible presence of a third non-saturable component to uptake does not affect these conclusions. 8. It is concluded that least two systems exist for the mediated entry of neutral amino acids into rabbit ileal mucosa. This fact should be taken into account in any future mechanistic interpretation of carrier-mediated amino acid transport in the small intestine.

Amino Acids↗

Some lesions observed in calves born to cows exposed to the virus of infectious bovine rhinotracheitis in the last trimester of gestation.

Sixteen pregnant cows were challenged with infectious bovine rhinotracheitis virus intranasally. One had a mummified fetus, four aborted, one calf was stillborn, two live fetuses were taken at the abattoir and eight calves were born alive. Of the eight born alive, five were dead by 12 days of age. Four of these had the usual lesions of infectious bovine rhinotracheitis as well as lesions in the intestine and peritoneum and two of the four had a fibrinous pneumonia thought to be caused by aspiration of milk. The lesions, results of virus isolation and fluorescent antibody testing are recorded in these four calves. Attention is drawn to the intestinal lesions, the peritonitis and fibrinous pneumonia and the ease with which the underlying infectious bovine rhinotracheitis infection may be overlooked.

Abortion, Veterinary↗

Villus growth and cell replacement in the small intestine of the neonatal pig.

Cells produced in the crypts of newborn pig ileum migrate onto villi during development. There is little or no corresponding loss of cells from villus tips during the first week of postnatal life. Villus growth during this period is largely responsible for the slow rate of cellular renewal seen to take place.

Animals↗

Studies on the pathogenesis of ischemic cell injury. XI. P/O ratio and acceptor control.

Acceptor control index, P/O ratio and inner membrane permeability were examined in isolated mitochondria following periods of renal ischemia for 15, 30, 60, 120, and 240 min. It was noted that the P/O ratio remained unchanged until 1-2 h after the onset of ischemia. A similar change was noted in the contraction rate of isolated ischemic mitochondria after swelling in KCl and addition of ATP+Mg2+. Both changes are probably indications of a basic membrane alteration which correlates with the occurrence of irreversibility of cell injury. In contrast, the swelling rate in KCl and the acceptor control index are altered almost simultaneously with the onset of ischemia. Therefore, acceptor control index and the rate of swelling are affected prior to the point of irreversible cell injury. They are not, therefore, good as indicators of irreversible changes in the inner membrane of mitochondria leading to the "point-of-no-return."

Animals↗

Studies on the pathogenesis of ischemic cell injury. VI. Accumulation of calcium by isolated mitochondria of ischemic rat kidney cortex.

Mitochondria isolated from rat kidney subject to in vitro ischemia at various time intervals demonstrated a continuous decline of the ability to accumulate calcium following a high initial stable phase of accumulation of calcium which is dependent both on ATP and respiration. This decline occurs during the reversible phase of cell injury and appears to be a sensitive indicator of membrane changes in a binding and/or transport protein or of other membrane permeability characteristics. The morphology of mitochondrial densities related to calcium accumulation in mitochondria varied. Any form of calcium accumulation, resulted in marked swelling of mitochondria. Control renal mitochondria in sucrose were highly condensed. Partially inhibited calcium accumulation in the presence of phosphate was also associated with numerous small spheric or punctate deposits in close relationship to the inner membrane. Uninhibited calcium accumulation resulted in the formation of needle-like structures radiating from such inner membrane associated sites.

Adenosine Triphosphate↗

Studies on the pathogenesis of ischemic cell injury. VII. Proton gradient and respiration of renal tissue cubes, renal mitochondrial and submitochondrial particles following ischemic cell injury.

Electron transport in tissue cubes, isolated mitochondria and submitochondria particles were examined as a function of ischemic time. It was found that electron transport remains active in all systems beyond the 2 hour ischemic time interval. The NADH stimulated respiration, however, declined after 2 hours of ischemia in ASU (Ammonia-Sephadex-Urea) particles followed by respiration with matrix-located dehydrogenases tested by substrates such as glutamate, alpha-ketoglutarate and pyruvate plus malate. Succinate dependent respiration remains active at control levels. In contrast proton gradient reveals changes in two phases: Phase A is characterized by gradually increasing gradient without valinomycin and by a rapidly declining gradient with valinomycin in the medium. Phase B is characterized by a declining proton gradient with or without valinomycin. It is suggested that the alteration of the proton gradient between 1 and 2 hours ischemia is an important factor contributing to irreversible cell injury.

Animals↗

Endocytosis and immunoglobulin transport across the small intestine of the new-born pig.

1. Measurements of porcine and human IgG transport across the small intestine of the new-born pig have been made in vivo and related to the amount of endocytosis taking place.2. The amount of immunoglobulins transported, following intraduodenal administration to conscious animals, is directly related to the degree of endocytosis which these proteins produce. Administration of protein in amounts sufficient to cause a maximal endocytotic response causes saturation of the protein transporting process.3. Absorption of small amounts of human IgG from the small intestine can be accelerated by the addition of sow colostrum or porcine IgG in quantities sufficient to stimulate endocytosis. These effects disappear when the amount of human IgG administered is itself sufficient to fully stimulate endocytosis.4. Preferential transport of porcine over human IgG can be demonstrated when both are given as a single solution to individual pigs. The degree of preference is, however, small in relation to the total amount of immunoglobulin transported.5. The initial formation of endocytotic vacuoles in the pig intestine seems, unlike the situation in rats and mice, to provide a major route for the trans-cellular movement of macromolecules including immunoglobulins. Present evidence suggests that, though sow colostrum can on occasion stimulate such transport, it does so merely by acting as a protein-containing solution to increase the amount of endocytosis taking place.

Animals↗

Cell replacement and changing transport function in the neonatal pig colon.

1. Measurements of intracellular methionine concentration in pig colon, following in vitro incubation in methionine containine medium, have been carried out during the first 10 days of post-natal life. 2. The new-born pig colon concentrates methionine within its mucosa. Autoradiography of 3H-labelled phenylalanine shows it to be accumulated to greatest extent in cells located in the surface epithelium. 3. The ability of the colonic mucosa to concentrate methionine disappears during the first few days of post-natal life. 4. Radioactive thymidine, injected at birth, shows cell mitosis to be confined to the lower third of each colonic crypt. Labelled cells later migrate out of the crypts on to the surface epithelium. The cell replacement time is 105 h. 5. The time course for the fall in the ability of the pig colon to actively accumulate methionine corresponds to that predicted if cells synthesized from birth were unable to transport this amino acid. 6. The ability of the new-born pig colon to transport amino acids, though transient, may be physiologically important. The nature of the signal which changes the physiological function of cells synthesized post-natally remains to be determined.

Age Factors↗