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Biomedical subjects

M W Smith

Publications and source records attributed to M W Smith.

At least 271 records · Page 15Linked to original sources
PubMed1980

A sodium-indpendent low affinity transport system for neutral amino acids in rabbit ileal mucosa.

1. The kinetic parameters for serine, alanine and methionine uptake by rabbit ileal mucosa have been determined in the absence of Na. 2. Uptake of all three amino acids took place through a single mediated system. The apparent Km values of serine, alanine and methionine for this system were equal to their respective apparent K1 values (approximately 89, 75 and 23 mM respectively). 3. Autoradiography was used to measure the cellular location of alanine uptake by rabbit ileum. Approximately 80% of the total uptake took place in the upper third of each villus. This uptake was reduced by 75% either by removal of Na or addition of serine. The proportional distribution of Na-dependent and Na-independent alanine uptakes along the villus was found to be equal. 4. The kinetic properties of the low affinity uptake mechanism for neutral amino acids, seen in the absence of Na, were virtually identical with those of one of the uptake mechanisms seen previously in the presence of Na. 5. The low affinity uptake mechanism appears to be Na-independent. It is suggested that the Na-coupled uptake of amino acid takes place through the high affinity system.

Alanine↗
PubMed1980

Delayed development of amiloride-sensitive sodium transport in lamb distal colon.

1. Na transport has been measured in vitro across distal colons taken from fetal and early post-natal lambs. 2. The mucosal to serosal Na flux fell by half during the first three weeks of post-natal life. Similar falls were recorded for measured short-circuit current and open-circuit voltage. The net transport of Na, measured isotopically at all stages of development, corresponded approximately to that calculated from measurements of short-circuit current. 3. The serosal to mucosal flux of Na was approximately half the mucosal to serosal flux at all stages in development. 4. Amiloride affected neither the short-circuit current nor the mucosal to serosal flux of Na measured during the first five days of post-natal life. The short-circuit current of an increasing proportion of distal colons (30-70%) began to show some sensitivity to amiloride during the second to third week of post-natal life. Sensitivity of the short-circuit to inhibition by amiloride appeared to be fully developed in the 8-week-old lamb colon. 5. The serum concentration of aldosterone was high at birth. It then fell rapidly to levels approaching those found in fetuses in the last week of pregnancy. The serum concentration of cortisol was two orders of magnitude higher than for aldosterone. Changes in cortisol concentration during development paralleled those for aldosterone. 6. There appears to be no aldosterone-induced change in Na transport across lamb distal colon during the first week of post-natal development. Comparisons are made between this situation and that found in the neonatal pig, where aldosterone acts to increase Na reabsorption immediately after birth. Possible reasons for this species difference are discussed.

Aldosterone↗
PubMed1980

Different pathways for lysine transport across neonatal pig intestine.

1. Undirectional fluxes of lysine, presented free and in the form of a dipeptide, have been measured in vitro using the small intestines of pigs taken during the first 2 weeks of post-natal life. 2. The concentration dependence of free lysine transfer to the serosal surface of new-born pig intestine (Jms) can be described as the sum of a saturable (Km 0.2 mM; Jm 3 n- mole cm-2 in-1) and a non-saturable (1.0 n-mole cm-2 min-1 mM-1) component. 3. The dipeptide isoleucyl-lysine was hydrolysed completely during transfer to the serosal surface of intestines taken at all stages of development. The concentration dependence of peptide-derived lysine transfer can be described as if it took place through a single saturable process (Km 5 mM; Jm 27 n-mole cm-2 min-1). 4. The mucosa to serosa transfer of free lysine fell to a half and that of peptide-derived lysine fell to a quarter, during the first 8 days of post-natal life. The decline in peptide-derived lysine transport correlated with changes in peptide hydrolase activity, measured in homogenates of intestinal mucosa using isoleucyl-lysine as substrate. 5. The new-born pig intestine transported lysine derived from isoleucyl-lysine twice as quickly as from lysyl-isoleucine. Lysine and isoleucine did not inhibit the transfer of isoleucine and lysine derived from isoleucyl-lysine. The transport of lysine, but not isoleucine, from isoleucyl-lysine took place more quickly than from equimolar solutions of the free amino acids. 6. It is suggested from these results that lysine and isoleucyl-lysine use different pathways when crossing the intestinal mucosa. Attempts are made to assess the probable contributions made by these pathways to the total absorption of lysine taking place during neonatal development.

Animals↗
PubMed1980

Antibiotic resistance and its transfer among clinical and nonclinical Klebsiella strains in botanical environments.

A total of 183 isolates of Klebsiella from drinking water, market vegetables, wood, sawdust, industrial effluents, and human and animal origin were examined for susceptibility to 10 antibacterial agents. Incidence of resistance to two or more antibiotics tested was: 65% of the human clinical isolates, 59% among bovine mastitis, and 24% among the nonclinical isolates. The five different multiple resistance patterns among nonclinically derived Klebsiella were also found among the human and bovine mastitis isolates. Statistical analyses revealed that patterns of resistance among Klebsiella isolates from drinking water, market vegetables, and industrial effluents were highly correlated with each other and with resistance patterns of human clinical isolates. Antibiotic resistance was transferred between Klebsiella growing in two habitat-simulated environments (growing radish plants and aqueous sawdust suspensions). Transconjugants were detected in 5 of 21 and 6 of 21 mating pairs, respectively. Average transconjugants/donor ranged from 10(-3) to 10(-6) in Penassay broth, from 10(-6) to 10(-7) on radish plants, and from 10(-5) to 10(-8) in sawdust suspensions. Although antibiotic resistance transfer under simulated environmental conditions can occur, regrowth of clinical strains is probably the major cause for the widespread occurrence of antibiotic-resistant Klebsiella in the nonclinical environment.

Anti-Bacterial Agents↗
PubMed1980

The role of calcium in cell injury. A review.

The role of calcium in cell injury is currently under investigation in many laboratories. It appears that movement of calcium between extra- to intracellular compartments and between various intracellular compartments plays a key role in determining many important reactions of cells both to lethal and sublethal injuries of diverse types as well as in adaptive new steady states. Prevention and/or modification of calcium movements has implication for the control of cell population growth, the prevention of cancer, and the retrieval of victims of shock, myocardial infarction and stroke. Regardless of what type of initial injury occurs, for example ischemia or direct cell membrane damage, the cell undergoes calcium accumulation either by impaired energy metabolism and/or plasmalemmal alterations. This elevated intracellular calcium concentration is responsible for cytoskeletal modifications which alter cell shape, the activation of phospholipases which results in perpetuation of membrane damage and finally, mitochondrial calcification. Although such changes have been partially characterized biochemically and morphologically, some obscure points continue to need clarification. The importance of determing the event(s) responsible for cell death is directly related to the potential capability of their manipulation. Therefore, this could result in the development and/or modification of pharmacologic interventions for the control and prevention of many human diseases. It is the purpose of this paper to review the present state of the art regarding the role of calcium in cell injury, to put it into perspective concerning organelle changes from the standpoint of morphology, and to indicate the present and future role of analytical microscopy in furthering the understanding of these processes.

Animals↗
PubMed1979

Sodium dependence of neutral amino acid uptake into rabbit ileum.

Alanine uses two mediated pathways to enter the rabbit ileal mucosa. Present results suggest that one of them (Km = 4.1 mM) is fully dependent on sodium in the mucosal medium, while the other (Km = 91 mM) is sodium-independent. Similar results are obtained for methionine and serine. Reinterpretation of previous alanine/sodium coupling coefficients suggests that two sodium ions per alanine molecule are transported via the high affinity system.

Alanine↗
PubMed1979

Different mechanisms for neutral amino acid uptake by new-born pig colon.

1. Mucosal amino acid uptake by pig proximal colon, measured independently for fourteen different amino acids each used at a concentration of 1 mM, ranged from 0.6 to 8.6 n-mole. cm(-2). min(-1) in the new-born to 0 to 0.3 n-mole. cm(-2). min(-1) in the 2-day-old animal. Long chain amino acids entered the mucosa of new-born pig proximal colon much more readily than did short chain amino acids.2. Glycine was used extensively to inhibit the uptake of other neutral amino acids. The degree of maximal inhibition produced depended on the amino acid used. The relative inability of glycine to inhibit the uptake of long chain amino acids suggested that these compounds could cross the brush border on a carrier inaccessible to glycine. The glycine-sensitive uptake remained more or less constant for all amino acids tested (1-2 n-mole.cm(-2).min(-1)); the glycine-insensitive uptake varied from 0 to 7 n-mole.cm(-2).min(-1) (glycine and methionine respectively).3. It is suggested that at least two mechanisms exist for the entry of neutral amino acids into pig proximal colon, one showing specificity for hydrophobic amino acids and the other having broad specificity. The mechanism responsible for the uptake of long chain essential amino acids predominates over the less specific mechanism.4. These results are discussed in relation to previous work carried out on the rabbit ileum where two similar systems for neutral amino acid entry have been shown to be present. Both tissues transport hydrophobic amino acids on their own specific carrier at approximately the same rate; the ability of the pig colon to transport amino acids on the broad specificity carrier is eight times less than in the rabbit ileum. The possibility is raised that this system is subject to regulation.

Amino Acids↗
PubMed1979

Two-carrier influx of neutral amino acids into rabbit ileal mucosa.

1. The influx of serine, alanine and methionine across the brush border membrane of the rabbit ileal mucosa has been measured during short periods of incubation. 2. A kinetic analysis of the uptake data, assuming one mediated entry mechanism or one mediated entry mechanism plus a diffusion component to be present, does not provide an adequate explanation for the results obtained. Methionine inhibition of serine uptake provided direct evidence that the diffusive entry of serine into the rabbit ileum was small or non-existent. 3. Data taken from amino acid inhibition and substrate-uptake experiments, fitted simultaneously to a double hyperbolic model of amino acid uptake, give good agreement between predicted and experimental results. There is also good quantitative agreement between computer-derived kinetic constants in the present work and similar constants obtained previously using a different method of analysis. 4. Present work supports the general hypothesis that neutral amino acids use two mediated pathways to enter the rabbit ileal mucosa. The possible physiological significance of these results and their probable effect on currently held concepts of how amino acids cross the brush border membrane of the rabbit intestinal mucosa is discussed.

Alanine↗
PubMed1979

Post-natal development of amiloride sensitive sodium transport in pig distal colon.

1. Both electrophysiological properties and unidirectional Na and Cl fluxes have been determined across distal colons taken from pigs during early post-natal development. 2. The transmural potential difference (Vms) was 5 mV in the new-born and 10 mV in the 4 day old colon. The short circuit current (Scc) showed a three to sixfold increase during the first 10 days of post-natal life. The microvillar membrane potential (Vm) fell from about -45 mV in the new-born to -40 mV in the 4 day old colon. 3. Amiloride had no effect on Vms, Scc or Vm, measured in the new-born animal. It reduced Vms and Scc, caused a hyperpolarization of Vm and increased the microvillar membrane/basolateral membrane resistance ratio (Rm/Rs) in colons taken from older animals. 4. The Scc of distal colons taken from new-born and 1 day old pigs was only half that predicted from unidirectional measurements of Na flux. This discrepancy, which could not be completely accounted for by net CL absorption, disappeared in the older animals. 5. Net transport of Na doubled during the first 24 h of post-natal life. Part of this transport took place through an amiloride sensitive, non-electrogenic, pathway. 6. It is suggested that Na uses mainly a non-electrogenic pathway to cross the mucosa of the new-born pig. This pathway is replaced by an electrogenic amiloride sensitive mechanism in older animals. Aldosterone is thought to initiate these changes in Na tranport.

Amiloride↗
PubMed1979

Aldosterone induced changes in colonic sodium transport occurring naturally during development in the neonatal pig.

1. Serum concentrations of aldosterone in later fetal, 3-6 week old and adult pigs are of the order of 300 pg ml.-1. This increases to about 2000 pg ml.-1 in the period immediately after birth. 2. Canrenoate injected into pigs from birth onwards stops the increase in colonic short-circuit current, seen to take place normally during early postnatal development. Amiloride has little or no effect on the short-circuit current of colons taken from canrenoate injected pigs. 3. Canrenoate stops the post-natal increase in colonic Na influx (and therefore net transport) seen to occur under normal conditions. 4. There is in the neonatal pig distal colon a portion of Na transport which appears to be resistant to inhibition by amiloride or canrenoate. 5. There is a second portion of Na transport, increasing in importance as the piglets become older, which is electrogenic and which is electrogenic and which is inhibited by prior injection of canrenoate. It is assumed that this fraction of Na transport is influenced by aldosterone. 6. There is a third part of Na transport, maximal in colons taken from one day old animals, which appears to be non-electrogenic. This is also blocked by prior injection of canrenoate. 7. The physiological relevance of these findings is discussed.

Aging↗