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Biomedical subjects

D R Peterson

Publications and source records attributed to D R Peterson.

At least 19 recordsLinked to original sources
PubMed1998

Glutamine transport by the blood-brain barrier: a possible mechanism for nitrogen removal.

Glutamine and glutamate transport activities were measured in isolated luminal and abluminal plasma membrane vesicles derived from bovine brain endothelial cells. Facilitative systems for glutamine and glutamate were almost exclusively located in luminal-enriched membranes. The facilitative glutamine carrier was neither sensitive to 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid inhibition nor did it participate in accelerated amino acid exchange; it therefore appeared to be distinct from the neutral amino acid transport system L1. Two Na-dependent glutamine transporters were found in abluminal-enriched membranes: systems A and N. System N accounted for approximately 80% of Na-dependent glutamine transport at 100 microM. Abluminal-enriched membranes showed Na-dependent glutamate transport activity. The presence of 1) Na-dependent carriers capable of pumping glutamine and glutamate from brain into endothelial cells, 2) glutaminase within endothelial cells to hydrolyze glutamine to glutamate and ammonia, and 3) facilitative carriers for glutamine and glutamate at the luminal membrane may provide a mechanism for removing nitrogen and nitrogen-rich amino acids from brain.

Animals↗
PubMed1998

Relevance of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis.

Mammalian nephrogenesis begins by the reciprocal interaction of the ureteric bud with the undifferentiated mesenchyme. The mesenchyme differentiates into an epithelial phenotype with the development of the glomerulus and proximal and distal tubules. At the same time, the mesenchyme stimulates the branching morphogenesis of the ureteric bud that differentiates into the collecting ducts. These inductive interactions and differentiation events are modulated by a number of macromolecules, including the extracellular matrix (ECM), integrin receptors, and cell adhesion molecules. Many of these macromolecules exhibit spatiotemporal developmental regulation in the metanephros. Some are expressed in the mesenchyme, whereas others appear in the ureteric bud epithelia. The molecules expressed in the mesenchyme or at the epithelial:mesenchymal interface may serve as ligands while those in the epithelia serve as the receptors. In such a scenario the ligand and the receptor would be ideally suited for epithelial:mesenchymal paracrine/juxtacrine interactions that are also influenced by RGD sequences and Ca2+ binding domains of the ECM proteins and their receptors. This review addresses the role of such interactions in metanephric development.

Animals↗
PubMed1998

Isolation of rat fibrillin-1 cDNA and its relevance in metanephric development.

The role of fibrillin-1 in metanephrogenesis was investigated. Fibrillin-1 cDNA was isolated from the rat kidney cDNA library and sequenced, and its spatiotemporal expression was studied. It had approximately 88% homology with human fibrillin-1 and had Ca2+ binding epidermal growth factor-like domains, transforming growth factor-beta binding protein motifs, and an RGD binding site. Northern blot analysis revealed an approximately 10-kb transcript, and fibrillin-1 expression was developmentally regulated. In situ hybridization and immunofluorescence studies indicated that at day 15 of gestation, fibrillin-1 is expressed in the metanephric mesenchyme. At day 18, its expression was confined to nascent blood vessels and glomeruli, and it increased in the newborn and neonatal kidneys. Immunoprecipitation revealed an approximately 300-kDa band by SDS-PAGE. Treatment with fibrillin-1 antisense oligodeoxynucleotide induced marked dysmorphogenesis of the embryonic metanephroi. Concomitantly, the fibrillin-1 mRNA, antibody reactivity in the metanephroi, and fibrillin-1-specific radioincorporation were reduced. These data indicate that, like alphavbeta3 integrin, a known morphogen and a putative receptor of fibrillin-1, the fibrillin-1 modulates events related to early organogenesis and possibly also the vascularization of the rat kidney.

Amino Acid Sequence↗
PubMed1997

Glucose transport by isolated plasma membranes of the bovine blood-brain barrier.

Luminal and abluminal endothelial plasma membrane vesicles were isolated from bovine cerebral microvessels, the site of the blood-brain barrier. Glucose transport across each membrane was measured using a rapid-filtration technique. Glucose transport into luminal vesicles occurred by a stereospecific energy-independent transporter [Michaelis-Menten constant (K(m)) = 10.3 +/- 2.8 (SE) mM and maximal velocity (Vmax) = 8.6 +/- 2.0 nmol.mg protein(-1).min-1]. Kinetic analysis of abluminal vesicles also showed a transport system with characteristics similar to the luminal transporter (K(m) = 12.5 +/- 2.3 mM and Vmax = 10.0 +/- 1.0 nmol.mg protein-1.min-1). These functional, facilitative glucose transporters were symmetrically distributed between the luminal and abluminal membrane domains, providing a mechanism for glucose movement between blood and brain. The studies also revealed a Na-dependent transporter on the abluminal membrane with a higher affinity and lower capacity than the facilitative transporters (K(m) = 130 +/- 20 microM and Vmax = 1.59 +/- 0.44 nmol.mg protein-1.min-1. The abluminal Na-dependent glucose transporter is in a position to transport glucose from the brain extracellular fluid into the endothelial cells of the blood-brain barrier. The functional significance of its presence there remains to be determined.

Animals↗
PubMed1996

Role of oxoproline in the regulation of neutral amino acid transport across the blood-brain barrier.

Regulation of neutral amino acid transport was studied using isolated plasma membrane vesicles derived from the bovine blood-brain barrier. Neutral amino acids cross the blood-brain barrier by facilitative transport system L1, which may allow both desirable and undesirable amino acids to enter the brain. The sodium-dependent amino acid systems A and Bo,+ are located exclusively on abluminal membranes, in a position to pump unwanted amino acids out. gamma-Glutamyl transpeptidase, the first enzyme of the gamma-glutamyl cycle, is an integral protein of the luminal membrane of the blood-brain barrier. We demonstrate that oxoproline, an intracellular product of the gamma-glutamyl cycle, stimulates the sodium-dependent systems A and Bo,+ by 70 and 20%, respectively. Study of system A showed that 2 mM oxoproline increased the affinity for its specific substrate N-methylaminoisobutyrate by 50%. This relationship between the activity of the gamma-glutamyl cycle and system A transport may provide a short term regulatory mechanism by which the entry of potentially deleterious amino acids (i.e. neurotransmitters or their precursors) may be retarded and their removal from brain accelerated.

Amino Acids↗
PubMed1996

Gentamicin inhibits carrier-mediated dipeptide transport in kidney.

The effect of gentamicin on transport of pyroglutamylhistidine (pGlu-His) was examined in rabbit renal brush-border membrane vesicles (BBMV). Gentamicin, an aminoglycoside antibiotic, is limited in its usage because of nephrotoxicity characterized in part by transport defects in the proximal tubule. Since there is no information regarding the effects of gentamicin on renal peptide carriers, uptake of [3H]pGlu-His was measured in BBMV following either in vivo or in vitro exposure to the antibiotic. One hour after in vivo administration, the maximal rate (Vmax) for pGlu-His transport was significantly reduced in isolated membrane vesicles washed free of the drug, but the apparent Michaelis constant (Km) was unaltered. Coincubation of membranes with gentamicin during measurements of pGlu-His uptake had a similar effect, causing a significant decrease in the Vmax but not the Km of transport. The addition of 5 mM magnesium to the uptake medium prevented the in vitro but not the in vivo effect. The data indicate that high doses of gentamicin inhibit the capacity but not the affinity of dipeptide transport in the kidney, prior to morphological changes which typify acute tubular necrosis. The in vitro effect is rapid and involves a direct action of gentamicin on the brush-border membrane. The in vivo experiments show that toxicity may be prolonged and remains following removal of the drug from the renal brush border.

Animals↗
PubMed1995

Biochemical discrimination between luminal and abluminal enzyme and transport activities of the blood-brain barrier.

Luminal and abluminal membrane vesicles derived from bovine brain endothelial cells, the site of the blood-brain barrier, were fractionated in a discontinuous Ficoll gradient. A mathematical analysis was developed to determine the membrane distribution of membrane marker enzyme activities as well as the ratio of luminal to abluminal membrane in each fraction of the gradient. The results of this analysis indicate that gamma-glutamyl transpeptidase and amino acid transport system A are located on the luminal and abluminal membranes, respectively. Conversely, 5'-nucleotidase and alkaline phosphatase activities are evenly distributed between both membranes. Although Na+/K(+)-ATPase activity is primarily located on the abluminal membrane, approximately 25% of the activity is of luminal origin. Na+/K(+)-ATPase activities associated with each membrane showed different ouabain sensitivities, suggesting that different isoenzymes are located in luminal and abluminal membranes. The analytical procedure used in this study provides a quantitative means to determine the distribution of marker enzymes and transport proteins in partially purified membrane vesicle populations.

5'-Nucleotidase↗
PubMed1995

Neutral amino acid transport characterization of isolated luminal and abluminal membranes of the blood-brain barrier.

The neutral amino acid carrier composition of luminal and abluminal membranes of the blood-brain barrier has been studied using isolated membrane vesicles. Phenylalanine was carried almost exclusively by a high affinity (Km = 10 +/- 2 microM), Na(+)-independent amino acid transport system, presumably L1 system, that was found to be symmetrically distributed between luminal and abluminal membranes. Inhibition of phenylalanine uptake was used to determine the affinities (Ki values) toward leucine (17 +/- 3 microM), tryptophan (8 +/- 1), 2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid (BCH) (11 +/- 2), alanine (628 +/- 117), and glutamine (228 +/- 51). Alanine was found to be transported by two Na(+)-dependent transport systems that were located exclusively on the abluminal membrane. Kinetic and inhibition experiments indicated that one of these activities was due to system A, which is probably the main route for Na(+)-dependent alanine transport (Km = 0.6 +/- 0.2 mM) under physiological conditions. The other Na(+)-dependent activity was attributed to a B(o,+)-like system based on its sensitivity toward BCH. This latter system showed greater affinity for large neutral amino acids. The affinities of these two transport systems for several other amino acids were also studied.

Alanine↗
PubMed1995

The reflective educator.

Since the Boulder conference on training in clinical psychology in 1949, at least 13 national conferences have been convened to examine issues in training for practice in psychology, all based on the assumption that extensive training is required to develop professional skills in psychotherapy, psychodiagnosis, and related professional functions. This assumption is challenged by a large body of research that fails to show any relationship between training and efficacy in common forms of practice. Educators of professional psychologists are urged to heed the challenge closely and examine its implications critically. At the same time, educators of researchers in psychology are encouraged to examine common assumptions about the nature of practice in psychology and to consider conceptions of professional work that emphasize reflection in action and disciplined inquiry, rather than psychotherapy and psychodiagnosis, as defining features. Education for practice is neither science nor art, but a profession in itself. When the educational process is approached from this vantage point, novel opportunities for systematic investigation emerge. Decisive studies of the appropriate kind have yet to be done.

Curriculum↗
PubMed1995

Nephrotic syndrome and acute renal failure associated with hepatitis A virus infection.

Acute renal failure has been documented in association with hepatitis A virus (HAV) infection. This report describes a temporal relationship between HAV infection and immune complex mesangial proliferative glomerulonephritis associated with nephrotic syndrome. Animal experimental data have already shown that this is indeed a histological lesion associated with HAV infection. This case report is the first English documentation associating HAV infection with immune complex mesangial proliferative glomerulonephritis.

Acute Kidney Injury↗
PubMed1993

Parameter sensitivity of a model of viral epidemics simulated with Monte Carlo techniques. IV. Parametric ranges and optimization.

A model is presented of the spread of influenza into and within a nursing home. To use this model for studies involving surveillance and vaccine efficacy, it is necessary to estimate optimal ranges of a group of parameters. Attempts to do so by manual methods proved unsatisfactory. Initial use of the methods presented in the previous three papers of this series led to points that were also unsatisfactory. However, by noting which parameters were placed at the outer surface of the chosen hypervolume, it was possible to choose new ranges and to select an optimal point in hyperspace that satisfied the epidemiologically preselected characteristics.

Community-Acquired Infections↗
PubMed1992

Neutral amino acid transport by the blood-brain barrier. Membrane vesicle studies.

Endothelial cell membranes, the site of the blood-brain barrier, were obtained from the capillaries of cow brain. The luminal and abluminal membranes were separated by centrifugation on a discontinuous Ficoll gradient. Electron microscopy revealed that the membrane preparations consisted almost entirely of sealed vesicles. The release of latent enzyme activity showed that both membrane preparations were primarily right side out. Radiolabeled L-phenylalanine uptake by luminal vesicles was proportional to membrane protein concentration, with less than 10% binding. Transport was by a high affinity carrier (Km 11.8 +/- 0.1 microM, asymptotic standard error) that showed little or no stereospecificity, and was independent of Na+ or H+ gradients. Transport was inhibited by L-tryptophan, L-leucine, 2-aminobicyclo[2,2,1]heptane-2-carboxylate and D-phenylalanine, but not by N-(methylamino)-isobutyrate. Abluminal membranes showed an additional component in which a Na+ gradient accelerated the transport of both phenylalanine and N-(methylamino)-isobutyrate. These studies demonstrate the utility of membrane vesicles as a model to characterize the transport properties of the distinct membranes of the polar endothelial cells that form the blood-brain barrier.

Amino Acids↗
PubMed1992

Activation of proximal tubular Na(+)-H+ exchange by angiotensin II.

Stimulation of Na(+)-H+ exchange by angiotensin II (ANG II) was characterized in renal proximal tubular cells. Rabbit proximal nephron segments were incubated in the presence or absence of ANG II (5 x 10(-10) M), after which brush-border membrane vesicles (BBMV) were isolated and assayed for Na(+)-H+ antiporter activity using the acridine orange technique. Both the affinity (for sodium) and capacity of the carrier were elevated significantly (P less than 0.05) within 15 min of incubation with ANG II. To determine whether the stimulation of transport capacity involved a change in Na(+)-H+ antiporter density in the luminal membrane, binding of tritiated 5-(N-methyl-N-isobutyl)amiloride ([3H]MIA) was measured in BBMV derived from control and ANG II-treated nephron segments, following maximal stimulation. This demonstrated a significant (P less than 0.05) increase in the maximal specific binding (Bmax) of [3H]MIA binding in the ANG II-treated group compared with control, of a magnitude sufficient to account for the observed change in maximal velocity (Vmax). The data indicate that the Vmax effect is caused by an apparent increase in the number (density) of active Na(+)-H+ carriers present in the luminal membrane. Finally, to test the possibility that the observed kinetic change involves an exocytic mechanism, the effect of colchicine on ANG II-stimulated antiporter activity was examined. The increase in Vmax due to ANG II was blocked by the addition of 0.5 mM colchicine to the incubation medium, whereas colchicine alone had no significant effect on the Vmax of Na(+)-H+ kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1992

Sudden infant death syndrome and maternal smoking.

Data from Missouri for the period 1980 to 1985 suggest a dose-response relationship between smoking during pregnancy and the incidence of sudden infant death syndrome (SIDS). However, data from the National Institute of Child Health and Human Development SIDS Cooperative Epidemiological Study did not support a dose-response relationship. Neither the Missouri data nor the Cooperative Study data support a relationship between the age of occurrence of SIDS and smoking during pregnancy.

Age Factors↗
PubMed1991

Multiple carriers for dipeptide transport: carrier-mediated transport of glycyl-L-proline in renal BBMV.

To determine whether multiple carriers are responsible for luminal uptake of glycyl-L-proline (Gly-Pro) in the renal proximal tubule, transport of Gly-[3H]Pro was measured in brush-border membrane vesicles (BBMV). A Line-weaver-Burk analysis of Michaelis-Menten kinetics revealed the presence of two carriers: a lower affinity, higher capacity carrier (Km = 1.3 x 10(-2) M; Vmax = 4.6 x 10(-8) mol.mg-1.min-1) and a higher affinity, lower capacity carrier (Km = 2.7 x 10(-7) M; Vmax = 7.8 x 10(-13) mol.mg-1.min-1). The dipeptides Gly-Sar, beta Ala-His, and pyroGlu-His competitively inhibited the low-affinity carrier. No effect on the Km or Vmax of Gly-Pro transport in this range was seen in the presence of the dipeptides Gly-Gly or cycloHis-Pro. The high-affinity carrier exhibited a different inhibition spectrum. Competitive inhibition of Gly-Pro transport was demonstrated for the dipeptides Gly-Gly and Gly-Sar. However, none of the other peptides tested above altered Gly-Pro transport in the high-affinity range, including pyroGlu-His, which is transported by a high-affinity carrier. At both low (4 x 10(-8) M) and high (4 x 10(-3) M) concentrations, uptake of Gly-Pro was stimulated in the presence of an inwardly directed H+ gradient but was unaffected by the presence of an inward Na+ gradient. In addition, measurements in the presence of valinomycin and an outwardly directed K+ gradient strongly suggest that H(+)-stimulated uptake at both concentrations is electrogenic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Long-term neurologic outcome in psychogenic water drinkers with severe symptomatic hyponatremia: the effect of rapid correction.

PURPOSE: The purpose of our study was to ascertain the safety of rapidly correcting acute symptomatic hyponatremia in psychogenic water drinkers, particularly in regard to any delayed adverse neurologic sequelae. PATIENTS AND METHODS: We reviewed the medical records of all known psychogenic water drinkers (34) in our hospital from 1977 to 1989. Using seizure as a marker of severity, we identified 13 patients having a total of 27 episodes associated with severe hyponatremia. We evaluated the charts of those patients in detail to assess the mode of treatment, rate of correction, and long-term neurologic outcome. None of the patients experienced respiratory arrest before treatment, which was initiated within 2 hours of seizure. RESULTS: For all 27 episodes, the initial serum sodium level (mean +/- SE) was 110.9 +/- 1.2 mmol/L, and the rate of correction (mean +/- SE) was 1.65 +/- 0.2 mmol/L/hour. All but one episode were corrected "rapidly" (initial correction rate of 0.7 or more mmol/L/hour) to 120 to 130 mmol/L within 12 hours. The absolute change in the serum sodium level was 15.1 +/- 1.2 mmol/L in 12 hours, 21.6 +/- 1.4 mmol/L in 24 hours, and 25.9 +/- 1.4 mmol/L in 48 hours. In no instance did therapy induce hypernatremia. All patients recovered immediately after treatment. There was no clinical or radiologic evidence of adverse neurologic sequelae immediately after treatment or after 6 years of follow-up. CONCLUSION: In this series of male psychogenic water drinkers, early "rapid" correction of acute symptomatic hyponatremia by raising the serum sodium level 15 mmol/L in 12 hours while maintaining an absolute change in the serum sodium level of 26 mmol/L within 48 hours produced no long-term neurologic sequelae.

Adult↗