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Biomedical subjects

L R Drewes

Publications and source records attributed to L R Drewes.

At least 73 records · Page 4Linked to original sources
PubMed1977

Blood-brain amino acid transport and content during anoxia and reoxygenation.

The isolated dog brain preparation was used to investigate the dynamics of cerebral amino acid metabolism during perfusion with anoxic blood (PO2 less than 10 mmHg). Significant uptake of histidine and lysine, as determined by arteriovenous (A-V) differences in whole blood samples, was observed during 30 min of cerebral anoxia. The A-V differences determined from plasma samples indicated that uptake of histidine and efflux of glutamic acid and proline had occurred. Nitrogen balance in the preparation appeared to be maintained. Thirty minutes of anoxic perfusion resulted in increased tissue concentrations of five essential amino acids (methionine, histidine, leucine, lysine, and valine) and a decreased tissue level of the essential amino acids threonine and phenylalanine. Taurine, gamma-aminobutyric acid, alanine, glycerophosphoethanolamine and phosphoethanolamine also increased, whereas the aspartic acid concentration declined. When aerobic perfusion was resumed, the total pool of essential amino acids continued to increase and was nearly twice normal after 120 min of reperfusion. The combined concentration of asparagine and glutamine, serine, alpha-aminobutyric acid, and cystathionine also increased during postanoxic perfusion. Only taurine and phenylalanine concentrations returned toward normal.

Amino Acids↗
PubMed1977

Nutrient transport systems in dog brain.

The cerebral circulation of the dog was isolated and an extracorporeal system was used to perfuse the brain with diluted blood. Transport of blood-borne substances was investigated by measurement of arteriovenous (a-v) differences (net transport) and by the indicator dilution method (unidirectional influx). The net movement of amino acids between blood and brain was qualitatively and quantitatively different when measured by whole blood a-v differences than when measured by plasma a-v differences. This result suggests that erythrocytes are involved in the movement of amino acids between the blood and brain, a finding similar to that observed in other vascular beds (Elwyn et al. Am. J. Physiol. 222: 13338 1972). The transport of 13 different blood-borne substances was investigated at normal and elevated solute concentrations using the indicator dilution method. Saturable processes were observed for the unidirectional transport of tyrosine, tryptophan, L-dopa, free palmitic acid, adenine, thymine, adenosine, and guanosine. However, the blood-brain interface did not appear to contain a carrier for dopamine, folic acid, cyanocobalamin, guanine, hypoxanthine, and free oleic acid.

Adenine↗
PubMed1976

The characteristics of glucose transport across the blood brain barrier and its relation to cerebral glucose metabolism.

The evidence suggests that glucose transport across the blood brain barrier (BBB) in the dog is normally not a rate-limiting step in cerebral metabolism; however, transport may become rate-limiting under conditions of extreme hypoglycemia or anoxia. Studies on the mechanism of glucose transport from blood to brain do not at this time permit us to distinguish between active transport and facilitated diffusion; however, a decrease in the rate of unidirectional transport during anoxia suggests that an energy-dependent process may be involved. In spite of this evidence, glucose transport across the BBB is similar to the facilitated diffusion of glucose into the red cell in terms of the structural requirements of the glucose molecule, the pattern of inhibition by phlorizin, phloretin and cytochalasin B, and the lack of sensitivity to Na+ or insulin.

Animals↗
PubMed1976

Relationship of cerebral oxygen uptake to EEG frequency in isolated canine brain.

Cerebral oxygen uptake was correlated with electroencephalographic (EEG) frequency and amplitude in 87 isolated canine brains. Group I (71 brains) was perfused with diluted blood and Group II (16 brains) was perfused with whole blood equilibrated with oxygen at various partial pressures. The EEG's were classified as follows: A, highest frequency greater than or equal to 17 Hz, alpha (8-13 Hz) amplitude less than 50 muv, delta (less than or equal to 3.5 Hz), amplitude less than 100 muv; B, highest frequency greater than or equal to 17 Hz, alpha amplitude greater to or equal to 50 muv, and/or delta amplitude greater than or equal to 100 muv. C, highest frequency 8-16 Hz, alpha amplitude greater than or equal to 25 muv, and delta amplitude greater than 100 muv, D, highest frequency 0.5-16 Hz, alpha, if present, amplitude less than 25 muv, and/or delta amplitude less than 100 muv, and E, highest frequency 0-16 Hz, alpha, if present, amplitude less than 10 muv, and/or delta amplitude less than 15 muv. The Group I oxygen uptakes in ml/100 g of brain per min+/-SE for the five EEG classifications were A, 4.39+/-0.06, B, 4.13+/-0.08, C, 3.76+/-0.09, D, 3.40+/-0.12, and E, 2.55+/-0.06, whereas the corresponding Group II values were A, 4.64+/-0.22, B, 4.28+/-0.15, C, 3.82+/-0.24, D, 3.39+/-0.40, and E, 1.38+/-0.42. As the EEG deteriorates, cerebral oxygen uptake tends to decrease in a significant and parallel manner in both the diluted and whole blood groups.

Animals↗
PubMed1975

Inhibition of glucose transport into brain by phlorizin, phloretin and glucose analogues.

An indicator dilution technique with 22Na+ as the intravascular marker was used to measure unidirectional transport of D-[6-3H]glucose from blood into the isolated, perfused dog brain. 18 compounds which are structurally related to glucose were tested for their ability to inhibit glucose transport. The data suggest that no single hydroxyl group is absolutely required for glucose transport, but rather that glucose binding to the carrier probably occurs through hydrogen bonding at several sites (hydroxyls on carbons 1, 3, 4 and 6). In addition, alpha-D-glucose has higher affinity for the carrier than does beta-D-glucose. A separate series of experiments demonstrated that phlorizin and phloretin are competitive inhibitors of glucose transport into brain; however, phloretin is partially competitive and inhibits at lower concentrations than does phlorizin. Inhibition by phlorizin and phloretin is mutually competitive, indicating that these compounds compete for binding to the glucose carrier. Comparison with the results reported in the literature for similar studies using the human erythrocyte demonstrates a fundamental similarity between glucose transport systems in the blood-brain barrier and erythrocyte.

Animals↗
PubMed1975

Accelerative exchange diffusion kinetics of glucose between blood and brain and its relation to transport during anoxia.

An earlier study showed that unidirectional glucose transport from blood to brain decreases during perfusion with anoxic blood (Betz, A. L., Gilboe, D. D. and Drewes, L. R. (1974) Brain Res. 67, 307-316). Brain glucose levels also decrease during anoxia. Therefore, the present study was designed to investigate whether the decreased transport might be the result of decreased accelerative exchange diffusion when brain glucose levels are low. The rate of undirectional transport into brain (v) of D-[6-3H]glucose was studied in 22 isolated, perfused dog brains by means of an indicator dilution technique using 22Na as the intravascular reference. The kinetics of transport were determined over a range of blood glucose concentrations (S1) at each of five different brain glucose levels (S2). The existence of accelerative exchange diffusion for glucose was indicated by a decrease in the intercept (increase of apparent V) of a double reciprocal plot (1/v versus 1/S1) as S2 increased. This phenomenon is consistent with a model for facilitated diffusion in which the mobility of the loaded carrier is greater than that of the unloaded carrier. Although the data predict a decrease in glucose transport during anoxia, the predicted decrease (5%) is less than the observed decrease (35%). It is concluded that the simple mobile-carrier model for facilitated diffusion cannot, by itself, describe all properties of blood-brain glucose transport.

Animals↗
PubMed1975

In vivo biosynthesis of peptidophosphogalactomannan in Penicillium charlesii.

The major exocellular glycopeptide (peptidophosphogalactomannan) produced by Penicillum charlesii first appears in the culture filtrate when the growth medium is nearly depleted of NH4+. The extent of incorporation of exogenously supplied radioactive precursors (D-[U-14C] GLUCOSE, L-[U-14C]threonine and NaH2(32)PO4) into peptidophosphogalactomannan suggests that approximately 20% of the total quantity of peptidophosphogalactomannan is assembled from constituents taken from the growth medium before NH4+ starvation and that the remainder is assembled from constituents in the medium during NH4" starvation. In the absence of NH4+, an increase in dry weight continues until the medium is depleted of glucose. However, peptidophosphogalactomannan accumulation proceeds until after glucose is depleted and growth is halted. These data suggest that peptidophosphogalactomannan is a product of cellular turnover.

Galactose↗
PubMed1975

Exocellular glycopeptide from a Penicillium charlesii mutant incapable of growth on D-galactose.

The compositions of exocellular saccharide-containing polymers from six mutants of Penicillium charlesii incapable of growing on galactose were investigated. The polymers from the mutants contain a much smaller percentage of galactose than that reported for the peptidophosphogalactomannan (PPGM) from the wild-type organism (Gander et al. 1974). A polymer containing only one galactosyl residue per 49 mannosyl residues was investigated in detail. This polymer is a glycopeptide (peptidomannan) with an amino acid composition similar to that of peptidophospogalactomannan and a mass of about 23,000 daltons. Treatment of peptidomannan with 0.4 N NaOH releases mannan, mannopentaose, mannotetraose, mannotriose, mannobiose, and mannose residues, which are attached to the peptide by O-glycosidic linkage to seryl and threonyl groups. The quantity of glycerol and threitol, derived from mannosyl and internal galactofuranosyl residues, respectively, following Smith degradation, showed that peptidomannan contains 2 mol of internal galactofuranosyl residues per mol of polymer. The polymer contains only 3 mol of (1 yields 5)-linked galactofuranosyl residues per mol of polymer, as described by analysis of the methylation products. Methylation analysis also indicates that the polysaccharide contains primarily (1 yields 2)-linked (67.5%) and (1 yields 6)-linked (20.2%) mannopyranosyl residues. However, acetolysis of the polymer suggests that 37% of the residues are (1 yields 6)-linked. Mannopentaose, mannotetraose, mannotriose, mannobiose, and mannose in a molar ratio of 0.30:0.11:0.15:0.39:0.06, respectively, are released by acetolysis. This result is similar to that obtained with peptidophosphogalactomannan. We conclude that the occurrence of large numbers of galactofuranosyl residues in the major extracellular glycopeptide is not an obligatory requirement for glycopeptide formation.

Amino Acids↗
PubMed1975

Kinetics of unidirectional leucine transport into brain: effects of isoleucine, valine, and anoxia.

The rate of unidirectional uptake, v, of L-[4,5-3H]leucine was studied in 17 isolated dog brains by means of an indicator-dilution technique using 22Na as the intravascular reference. The arterial leucine concentration was varied in increments by adding unlabeled leucine to the blood and v was determined after each change. The valine and isoleucine concentrations were varied independently to permit evaluation of their effect on leucine transport. A preliminary analysis indicated that both valine and isoleucine are competitive inhibitors. Therefore, all data were fitted to an equation that describes Michaelis-Menten kinetics in the presence of two competitive inhibitors. These calculations yielded an apparent Km for leucine transport of 1.58 mM plus or minus .28 SE, a V max of 0.323 mumol/g per min plus or minus .035 SE, and an apparent K i for inhibition of leucine transport of 1.76 mM plus or minus .34 SE for valine and 0.73 mM plus or minus .14 SE for isoleucine. In four isolated brains perfused with blood having a constant leucine level, indicator-dilution injections were made before, and at 1, 5, and 10 min after the start of perfusion with anoxic blood. These findings showed that, unlike glucose transport (Brain Res. 67: 307-316, 1974), the rate of lucine transport is unaffected by 10 min of anoxia.

Animals↗