Search PubMed⌕ Search

Biomedical subjects

P Madsen

Publications and source records attributed to P Madsen.

At least 55 records · Page 3Linked to original sources
PubMed1998

The carboxy-terminal domain of the receptor-associated protein binds to the Vps10p domain of sortilin.

Binding of the receptor-associated protein (RAP) to the newly identified putative sorting receptor, sortilin, was analyzed by surface plasmon resonance analysis of recombinant RAP and sortilin domains and compared with binding to megalin and low density lipoprotein receptor-related protein (LRP). The data show that the RAP-binding site in sortilin is localized in the cysteine-rich lumenal part homologous to yeast vacuolar protein-sorting 10 protein (Vps10p), and the sortilin-binding site in RAP is localized in the carboxy-terminal domain III of the three homologous domains in RAP. Whereas sortilin bound only RAP domain III, megalin and LRP bound all RAP domains with the functional affinity order: domain III >domain I > domain II.

Adaptor Proteins, Vesicular Transport↗
PubMed1998

Characterization of glycerol uptake and glycerol kinase activity in rat hepatocytes cultured under different hormonal conditions.

Glycerol uptake and glycerol kinase activity were studied in primary cultures of rat hepatocytes in the presence of either 1 nM insulin, 1 nM glucagon, or 100 nM dexamethasone, alone or in combination in the culture medium. Glycerol uptake exhibited saturation kinetic with K(m) values (microM) and Vmax (nmol/min x mg protein) ranging from 250-402, and 7.9-10.1, respectively. The corresponding K(m) and Vmax values for glycerol kinase activity were 36-46 and 8.7-12.7. Using the metabolic uncoupler 2,4-dinitrophenol, glycerol uptake and the cellular content of glycerol phosphorylated metabolites were reduced 33% and 43%, respectively, whereas no decrease in the cellular content of glycerol was seen. The glycerol analogues monoacetin, monobutyrin and dihydroxypropyl dichloroacetate were able in a concentration-dependent manner to inhibit glycerol uptake into hepatocytes with the two latter having IC50 values of approximately 1 mM. Moreover, it was demonstrated that the three glycerol analogues were substrates for glycerol kinase, which indicates a competitive mode of inhibition. The kinetic parameters for these substrates were calculated by using glycerol kinase from Candida Mycoderma. Monobutyrin was found to be 4 times lees efficient as substrate compared to the other substrates. Overall, these results indicate that independently of the culture conditions, glycerol uptake is the rate-limiting step in glycerol metabolism, and that the investigated glycerol analogues are metabolized via the same route as glycerol.

2,4-Dinitrophenol↗
PubMed1998

EF-hands at atomic resolution: the structure of human psoriasin (S100A7) solved by MAD phasing.

BACKGROUND: The S100 family consists of small acidic proteins, belonging to the EF-hand class of calcium-binding proteins. They are primarily regulatory proteins, involved in cell growth, cell structure regulation and signal transduction. Psoriasin (S100A7) is an 11.7 kDa protein that is highly upregulated in the epidermis of patients suffering from the chronic skin disease psoriasis. Although its exact function is not known, psoriasin is believed to participate in the biochemical response which follows transient changes in the cellular Ca2+ concentration. RESULTS: The three-dimensional structure of holmium-substituted psoriasin has been determined by multiple anomalous wavelength dispersion (MAD) phasing and refined to atomic resolution (1.05 A). The structure represents the most accurately determined structure of a calcium-binding protein. Although the overall structure of psoriasin is similar to those of other S100 proteins, several important differences exist, mainly in the N-terminal EF-hand motif that contains a distorted loop and lacks a crucial calcium-binding residue. It is these minor differences that may account for the different specificities among members of this family. CONCLUSIONS: The structure of human psoriasin reveals that this protein, in contrast to other S100 proteins with known structure, is not likely to strongly bind more than one calcium ion per monomer. The present study contradicts the idea that calcium binding induces large changes in conformation, as suggested by previously determined structures of apo forms of S100 proteins. The substitution of Ca2+ ions in EF-hands by lanthanide ions may provide a general vehicle for structure determination of S100 proteins by means of MAD phasing.

Calcium↗
PubMed1998

Expression of recombinant psoriasis-associated fatty acid binding protein in Escherichia coli: gel electrophoretic characterization, analysis of binding properties and comparison with human serum albumin.

The psoriasis-associated fatty acid binding protein (PA-FABP, also known as FABP5) is a novel keratinocyte protein that is highly up-regulated in psoriatic plaques (P. Madsen, H. H. Rasmussen, H. Leffers, B. Honoré and J. E. Celis, J. Invest. Dermatol. 1992, 99, 299-305). Here we have expressed PA-FABP in Escherichia coli as a fusion protein containing an NH2-terminal hexa-His tag followed by a factor Xa cleavage site. The recombinant protein was expressed at a level of about 30% of the soluble proteins and was purified to homogeneity using a simple two-step protocol consisting of affinity chromatography on Ni2+-nitrilotriacetic acid agarose followed by gel filtration. The recombinant protein was then digested with factor Xa and characterized by two-dimensional gel electrophoresis. The ability of PA-FABP to bind saturated fatty acids ranging from 6 to 16 carbons was determined directly by dialysis and compared to human serum albumin (HSA). The results showed that PA-FABP binds multiple molecules of the fatty acids hexanoate (C6:0), octanoate (C8:0), decanoate (C10:0) and laurate (C12:0), all with a K1 of about 10(4) M(-l), and myristate (C14:0) with a K1 of 4.4 X 10(5) M(-l). Palmitate (C16:0) also bound strongly with multiple molecules. Due to the very low solubility of palmitate its affinity to PA-FABP was measured relatively to HSA and found to be 8.1 times lower. At ligand/protein ratios below 1, all fatty acids bound to PA-FABP with about one to three orders of magnitude lower affinity than to HSA. The difference in the fatty acid binding properties of the two proteins may reflect differences in their three-dimensional structures, which in the case of PA-FABP consists mainly of beta-sheets while HSA contains predominantly alpha-helices.

Albumins↗
PubMed1998

Muscle metabolism from near infrared spectroscopy during rhythmic handgrip in humans.

The rate of metabolism in forearm flexor muscles (MO2) was derived from near-infrared spectroscopy (NIRS-O2) during ischaemia at rest rhythmic handgrip at 15% and 30% of maximal voluntary contraction (MVC), post-exercise muscle ischaemia (PEMI), and recovery in seven subjects. The MO2 was compared with forearm oxygen uptake (VO2) [flow x (oxygen saturation in arnterial blood-oxygen saturation in venous blood, SaO2 - SvO2)], and with the 31P-magnetic resonance spectroscopy-determined ratio of inorganic phosphate to phosphocreatine (P(I):PCr). During ischaemia at rest, the fall in NIRS-O2 was more pronounced [76 (SEM 3) to 3 (SEM 1)%] than in SvO2 [71 (SEM 3) to 59 (SEM 2)%]. During the handgrip, NIRS-O2 was lower at 30% compared to 15% MVC [58 (SEM 3) v.s. 67 (SEM 3)%] while the SvO2 was similar [29 (SEM 3) v.s. 31 (SEM 4)%]. Accordingly, MO2 as well as P(I):PCr increased twofold, while VO2 increased only 30%. During PEMI after 15% and 30% MVC, NIRS-O2 fell to 9 (SEM 1)% and "0", but the use of oxygen by forearm muscles was not reflected in SvO2. During reperfusion after PEMI, the peak NIRS-O2 was lowest after intense exercise, while for SvO2 the reverse was seen. The discrepancies between NIRS-O2 and SvO2, and therefore between the estimates of the metabolic rate, would suggest significant limitations in sampling venous blood which is representative of the flexor muscle capillaries. In support of this contention, SvO2 and venous pH decreased during the first seconds of reperfusion after PEMI. To conclude, NIRS-O2 of forearm flexor muscles closely reflected the exercise intensity and the metabolic rate determined by magnetic resonance spectroscopy but not that rate derived from flow and the arterio-venous oxygen difference.

Adult↗
PubMed1998

The influence of PaO2, pH and SaO2 on maximal oxygen uptake.

Influence of arterial oxygen pressure (PaO2) and pH on haemoglobin saturation (SaO2) and in turn on O2 uptake (VO2) was evaluated during ergometer rowing (156, 276 and 376 W; VO2max, 5.0 L min-1; n = 11). During low intensity exercise, neither pH nor SaO2 were affected significantly. In response to the higher work intensities, ventilations (VE) of 129 +/- 10 and 155 +/- 8 L min-1 enhanced the end tidal PO2 (PETO2) to the same extent (117 +/- 2 mmHg), but PaO2 became reduced (from 102 +/- 2 to 78 +/- 2 and 81 +/- 3 mmHg, respectively). As pH decreased during maximal exercise (7.14 +/- 0.02 vs. 7.30 +/- 0.02), SaO2 also became lower (92.9 +/- 0.7 vs. 95.1 +/- 0.1%) and arterial O2 content (CaO2) was 202 +/- 3 mL L-1. An inspired O2 fraction (F1O2) of 0.30 (n = 8) did not affect VE, but increased PETO2 and PaO2 to 175 +/- 4 and 164 +/- 5 mmHg and the PETO2-PaO2 difference was reduced (21 +/- 4 vs. 36 +/- 4 mmHg). pH did not change when compared with normoxia and SaO2 remained within 1% of the level at rest in hyperoxia (99 +/- 0.1%). Thus, CaO2 and VO2max increased to 212 +/- 3 mL L-1 and 5.7 +/- 0.2 L min-1, respectively. The reduced PaO2 became of importance for SaO2 when a low pH inhibited the affinity of O2 to haemoglobin. An increased F1O2 reduced the gradient over the alveolar-arterial membrane, maintained haemoglobin saturation despite the reduction in pH and resulted in increases of the arterial oxygen content and uptake.

Adult↗
PubMed1998

Contribution of pH, diprotonated phosphate and potassium for the reflex increase in blood pressure during handgrip.

The relative importance of pH, diprotonated phosphate (H2PO4-) and potassium (K+) for the reflex increase in mean arterial pressure (MAP) during exercise was evaluated in seven subjects during rhythmic handgrip at 15 and 30% maximal voluntary contraction (MVC), followed by post-exercise muscle ischaemia (PEMI). During 15% MVC, MAP rose from 92 +/- 1 to 103 +/- 2 mmHg, [K+] from 4.1 +/- 0.1 to 5.1 +/- 0.1 mmol L-1, while the intracellular (7.00 +/- 0.01 to 6.80 +/- 0.06) and venous pH fell (7.39 +/- 0.01 to 7.30 +/- 0.01) (P < 0.05). The intracellular [H2PO4-] increased 8.4 +/- 2 mmol kg-1 and the venous [H2PO4-] from 0.14 +/- 0.01 to 0.16 +/- 0.01 mmol L-1 (P < 0.05). During PEMI, MAP remained elevated along with the intracellular [H2PO4-] as well as a low intracellular and venous pH. However, venous [K+] and [H2PO4-] returned to the level at rest. During 30% MVC handgrip, MAP rose to 130 +/- 3 mmHg, [K+] to 5.8 +/- 0.2 mmol L-1, the intracellular and extracellular [H2PO4-] by 20 +/- 5 mmol kg-1 and to 0.20 +/- 0.02 mmol L-1, respectively, while the intracellular (6.33 +/- 0.06) and venous pH fell (7.23 +/- 0.02) (P < 0.05). During post-exercise muscle ischaemia all variables remained close to the exercise levels. Analysis of each variable as a predictor of blood pressure indicated that only the intracellular pH and diprotonated phosphate were linked to the reflex elevation of blood pressure during handgrip.

Adult↗
PubMed1998

Near-infrared spectrophotometry determined brain oxygenation during fainting.

During orthostatic hypotension we evaluated whether presyncopal symptoms relate to a reduced brain oxygenation. Nine subjects performed 50 degrees head-up tilt for 1 h and eight subjects were followed during 2 h of supine rest and during 1 h of 10 degrees head-down tilt. Cerebral perfusion was assessed by transcranial Doppler determined middle cerebral artery blood velocity (MCA vmean), while brain blood oxygenation was assessed by near-infrared spectrophotometry determined concentration changes for oxygenated (delta HbO2) and deoxygenated haemoglobin and brain cell oxygenation by the oxidized cytochrome c concentration (delta CytO2). During head-up tilt, six volunteers developed presyncopal symptoms and mean arterial pressure (88 (78-103) to 68 (57-79) mmHg; median and range), heart rate (96 (72-111) to 65 (50-107) beats min-1), MCA vmean (59 (51-82) to 41 (29-56) cm s-1), delta HbO2 (by -5.3 (-3.0 to -14.8) mumol l-1) and delta CytO2 were reduced (by -0.2 (-0.1 to -0.4) mumol l-1; P < 0.05). During tilt down the cardiovascular variables recovered immediately and delta HbO2 increased to 2.2 (-0.9-12.0) mmol L-1 above the resting value and also delta CytO2 recovered. In the nonsyncopal head-up tilted subjects as in the controls, blood pressure, heart rate, MCA vmean and brain oxygenation indices remained stable. The results suggest that during orthostasis, presyncopal symptoms relate not only to cerebral hypoperfusion but also to reduced brain oxygenation.

Adult↗
PubMed1998

Cholinergic blockade and the mesenteric artery response to head-up tilt-induced central hypovolaemia.

The influence of muscarinic blockade on the superior mesenteric artery (SMA) response to head-up tilt (HUT) was assessed by Doppler ultrasound in eight healthy adults pretreated with i.v. glycopyrron. During supine rest, cholinergic blockade increased heart rate from 58 +/- 3 to 106 +/- 6 beats min-1 (mean +/- SE) and mean arterial pressure from 81 +/- 3 to 97 +/- 4 mmHg (P < 0.01) and it reduced the cardiac stroke volume from 89 +/- 6 to 59 +/- 7 ml (P < 0.01) with no significant effect on the SMA diameter and blood flow velocities. HUT provoked a further increase in heart rate to 134 +/- 5 beats min-1 (P < 0.01) and a reduction in stroke volume to 45 +/- 4 ml (P < 0.01). The early diastolic velocity increased from -51 +/- 4 to 6 +/- 8 cm s-1 during the normotensive stage of HUT and further to 21 +/- 9 cm s-1 during the hypotensive stage with a reduction in mean arterial pressure from 97 +/- 4 to 73 +/- 7 mmHg (P < 0.01) but, in contrast to control HUT (without cholinergic blockade), the end-diastolic velocity did not change significantly. Maintenance of blood velocity and diameter in spite of an increase in arterial pressure at rest indicates increased SMA impedance. Likewise, during hypovolaemia, a glycopyrron-induced inhibition in diastolic velocity supports an increase in SMA impedance. The results indicate cholinergic vasorelaxing influence on the superior mesenteric artery both at rest and during normotensive central hypovolaemia.

Adult↗
PubMed1998

The sella turcica in children with lumbosacral myelomeningocele.

The purpose of the present study was to analyze the morphology of the sella turcica in children born with myelomeningocele. Profile radiographs from 16 children (nine females and seven males) born with myelomeningocele were analysed. The contour of the anterior wall of the sella turcica in myelomeningocele patients, instead of following the normal cranio-caudal direction, was always in an obliquely antero-posterior direction. The sella turcica thus appeared broad cranially with a diverging anterior wall, or with both diverging anterior and posterior walls. This appearance gave and impression of a wide sella turcica in myelomeningocele with less depth than normal. The investigation has drawn attention to the fact that congenital malformations in the axial skeleton, even though, as in the case of myelomeningocele, they are located far from the cranial base, may have manifested themselves in the cranial base as well. The pathogenetic relationship between these manifestations is to be found in the early embryonic structure, the notochord. With the concept of embryological developmental fields, defined as areas with a common developmental origin, such as the notochordal field involved in myelomeningocele, new ways seem to be emerging for an improvement of aetiologically based diagnosis and treatment.

Adolescent↗
PubMed1998

Distortion product otoacoustic emissions stimulated through bone conduction.

OBJECTIVE: To demonstrate the viability of bone conduction as a novel method for stimulation of distortion product otoacoustic emissions (DPOAEs). DESIGN: DPOAEs were recorded from a single ear of 23 normally hearing adults using bone and air conduction for the delivery of stimulus tones. Exploration of the input-output function was performed by varying stimulus frequency and magnitude. RESULTS: Bone-stimulated emissions demonstrated similar characteristics to those obtained through standard air transmission techniques. Characteristic nonlinear DPOAE growth was found as the magnitude of the higher frequency stimulus tone, L2, was increased monotonically with other parameters fixed. Bilateral stimulation due to using bone conduction did not saturate the mechanisms of emission suppression. Emission magnitude was not altered substantially by occlusion of the ear canal. CONCLUSION: Bone conduction can be used successfully to elicit DPOAEs. Absolute comparison of air- and bone-stimulated DPOAEs was difficult because of imprecise calibration of the bone conductors for each individual and particular placement. Properties unique to bone conduction, such as simultaneous bilateral stimulation and reduction of stimulus magnitude in the ear canal, may make bone conduction attractive for clinical measurement of DPOAEs.

Acoustic Stimulation↗
PubMed1998

Tolerance to head-up tilt and suspension with elevated legs.

OBJECTIVE: Orthostatic hypotension is usually a benign event. However, some patients are disabled by frequent syncopal events, and vertical transportation during helicopter rescue, for example, may even be fatal. Normal orthostatic tolerance is poorly defined, so we evaluated the response to 50 degrees head-up tilt. Also, the effect of leg elevation was examined in order to establish the influence of venous return, and a fatal accident associated with orthostasis is reported. METHODS: There were 79 volunteers who were subjected to 50 degrees head-up tilt, and 9 subjects performed 1 h of suspension by double strops placed around the thorax and knee bends, respectively. The time to presyncope and changes in BP, heart rate, thoracic electrical impedance, central venous pressure and central venous and muscle oxygen saturations were measured. RESULTS: Head-up tilt resulted in hypotension, bradycardia and presyncopal symptoms in 69 subjects within 1 h (87%; half time 27 min), but during suspension with elevated legs in only one subject (11%; p < 0.02). In presyncopal subjects the central blood volume was reduced as reflected by an elevated thoracic electrical impedance and reduced central venous and muscle oxygen saturations. CONCLUSIONS: During 50 degrees head-up tilt, half of 79 subjects near-fainted within 27 min, whereas elevation of the legs secured venous return to the heart and prevented presyncopal symptoms. The high rate of near-fainting in normal subjects should be taken into account during evaluation of patients with syncope, and it emphasizes the use of a position that secures venous return during transportation.

Adult↗
PubMed1997

Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography.

Receptor-associated protein (RAP) is an endoplasmic reticulum/Golgi protein involved in the processing of receptors of the low density lipoprotein receptor family. A approximately 95-kDa membrane glycoprotein, designated gp95/sortilin, was purified from human brain extracts by RAP affinity chromatography and cloned in a human cDNA library. The gene maps to chromosome 1p and encodes an 833-amino acid type I receptor containing an N-terminal furin cleavage site immediately preceding the N terminus determined in the purified protein. Gp95/sortilin is expressed in several tissues including brain, spinal cord, and testis. Gp95/sortilin is not related to the low density lipoprotein receptor family but shows intriguing homologies to established sorting receptors: a 140-amino acid lumenal segment of sortilin representing a hitherto unrecognized type of extracellular module shows extensive homology to corresponding segments in each of the two lumenal domains of yeast Vps10p, and the extreme C terminus of the cytoplasmic tail of sortilin contains the casein kinase phosphorylation consensus site and an adjacent dileucine sorting motif that mediate assembly protein-1 binding and lysosomal sorting of the mannose-6-phosphate receptors. Expression of a chimeric receptor containing the cytoplasmic tail of gp95/sortilin demonstrates evidence that the tail conveys colocalization with the cation-independent mannose6-phosphate receptor in endosomes and the Golgi compartment.

Adaptor Proteins, Vesicular Transport↗
PubMed1997

Influence of Naloxone on the cellular immune response to head-up tilt in humans.

To evaluate a possible role for beta-endorphin in the stress-induced modulation of natural killer (NK) cells, immunologically competent blood cells were followed in eight male volunteers administered either Naloxone or saline (control) during head-up tilt maintained until the appearance of presyncopal symptoms (PS). The PS appeared more rapidly with Naloxone compared to control [5.7 (SEM 1.1) vs 22.3 (SEM 5.1) min; P = 0.01]. The NK cell activity increased threefold during PS partly due to an increase in CD16+ and CD56+ NK cells in blood. In support, NK cell activity boosted with interferon-alpha and interleukin 2 rose in parallel with unboosted NK cell activity and NK cell concentration and activities returned to the baseline level after 105 min. The total lymphocyte count and the concentrations of CD3+, CD4+, CD8+, CD16+, and CD56+ cells increased during PS. Head-up tilt also induced an increase in plasma adrenaline concentration during control PS and a rise in plasma cortisol and adrenocorticotropic hormone concentrations up to 30 min thereafter, whereas no significant changes were found in plasma concentrations of noradrenaline, growth hormone, or beta-endorphin. The results would indicate an influence of endorphin on the increase in plasma adrenaline concentration during head-up tilt and at the same time contra-indicate a significant role for adrenaline in the provocation of PS. The influence of head-up tilt on plasma beta-endorphin was too small to influence the modulation of the cellular immune system.

Adult↗
PubMed1997

Mesenteric artery response to head-up tilt-induced central hypovolaemia and hypotension.

Superior mesenteric artery (SMA) blood flow and impedance were evaluated by duplex ultrasound during head-up tilt (HUT)-induced central hypovolaemia and hypotension in eight healthy volunteers. HUT induced a reduction in cardiac stroke volume from 88.8 +/- 6.3 to 64.7 +/- 6.3 ml (mean +/- SEM; P < 0.01) and an increase in thoracic electric impedance from 38.6 +/- 2.1 to 42.6 +/- 2.1 omega (P < 0.01) reflecting a reduced central blood volume. Maintained tilt provoked a 30% reduction in mean arterial pressure (from 87.1 +/- 3.3 to 63.4 +/- 3.6 mmHg: P < 0.01) and the appearance of presyncopal symptoms. During both the normotensive and the hypotensive phase of HUT, the SMA diameter (5.7 +/- 0.03 mm) and blood flow (514 +/- 75 ml min-1) did not change significantly, although the end-diastolic velocity increased from 9.7 +/- 4.8 to 39.7 +/- 4.0 cm s-1 (P < 0.01). The increase in diastolic velocity, despite a maintained or reduced arterial pressure, supports a reduction in the SMA impedance as it was reproduced during a meal test when a moderate reduction in mean arterial pressure (87 +/- 4 to 80 +/- 4 mm Hg; P = 0.04) was accompanied by a ninefold increase in the end-diastolic velocity (P < 0.01). The results indicate a reduction in the mesenteric vascular impedance to the extent that superior mesenteric artery blood flow is maintained during HUT-induced central hypovolaemia and hypotension.

Adult↗
PubMed1997

Adrenergic beta 1- and beta 1 + 2-receptor blockade suppress the natural killer cell response to head-up tilt in humans.

To evaluate stress-induced changes in blood leukocytes with emphasis on the natural killer (NK) cells, eight male volunteers were followed during three trials of head-up tilt with adrenergic beta 1- (metoprolol) and beta 1 + 2- (propranolol) blockade and with saline (control) infusions. The beta 1- and beta 1 + 2-receptor blockade did not affect the appearance of presyncopal symptoms, but the head-up tilt induced a transient lymphocytosis that was abolished by beta 1 + 2-receptor blockade but not by beta 1-receptor blockade. Head-up tilt also resulted in delayed neutrophilia, which was insensitive to beta-receptor blockade. Lymphocyte subset analysis revealed that the head-up tilt resulted in a twofold increase in the percentage and absolute number of CD3-/CD16+ and CD3-/CD56+ NK cells in peripheral blood and that this increase was partially blocked by metoprolol and abolished by propranolol. The NK cell activity on a per NK cell basis did not change during head-up tilt, indicating that the cytotoxic capability of NK cells recruited to circulation is unchanged. The data suggest that the head-up tilt-induced lymphocytosis was due mainly to CD16+ and CD56+ NK cells and that their recruitment to the blood was inhibited by beta 1- and especially beta 1 + 2-receptor blockade. Thus stress-induced recruitment of lymphocytes, and of NK cells in particular, is mediated by epinephrine through activation of beta-receptors on the lymphocytes.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1997

Endothelial cells of the human microvasculature express epidermal fatty acid-binding protein.

Epidermal fatty acid-binding protein (E-FABP), previously characterized in human keratinocytes, is a cytoplasmic protein of 15 kD that specifically binds fatty acids (FAs). Previous PAGE-immunoblotting studies indicated that several human tissues display an immunoreactive band with an electrophoretic mobility identical to that of E-FABP. The aim of this study was to determine in which cells, other than keratinocytes, E-FABP might be expressed. By immunohistochemistry, we show that E-FABP is expressed in endothelial cells of the microvasculature of the placenta, heart, skeletal muscle, small intestine, lung, and renal medulla. Interestingly, in lung, a tissue of endodermal origin, E-FABP staining was also localized to secretory cells, ie, Clara cells, goblet cells, and probably a subpopulation of pneumocytes. RNA isolated from cultured human umbilical vein and normal human dermal microvascular endothelial cells was analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR). Southern blotting and sequencing of the cloned RT-PCR products demonstrate that endothelial E-FABP is identical to keratinocyte E-FABP. These data suggest that E-FABP-mediated FA transport occurs at the level of the microvasculature in several FA target organs.

Base Sequence↗