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E Johnsson

Publications and source records attributed to E Johnsson.

48 records · Page 3Linked to original sources

Reduced permselectivity in isolated perfused rat kidneys following small elevations of glomerular capillary pressure.

A modified rat kidney preparation was used to explore how changes in hydrostatic pressure affect the permselective properties of the glomerular capillary bed. The maximally vasodilated kidneys of 18 rats were perfused with albumin solutions (16.7 g l-1) at different flow rates and hence arterial pressures (PA). One kidney in each rat was exposed to pressure elevations with the other kidney serving as a control perfused at constant PA of about 100 mmHg. Both the vascular resistance to flow and the glomerular filtration rate (GFR 34.6 +/- 2.9 ml min-1 100 g-1) were similar in the two kidneys at equal PA and remained constant throughout the experiment. The ratio of albumin clearance over GFR (theta) was initially around 0.4% at constant PA and gradually increased during 1.5 h to reach 0.7% at the end of the experiment. A direct increase of PA from 100 to 200 mmHg for 15 min resulted in a calculated increase of the effective glomerular filtration pressure gradient of 10-15 mmHg and in a two-fold increase of theta when measured at an identical PA of 100 mmHg. Albumin clearance was almost fully normalized within 20 min similar to that observed in e.g. skeletal muscle. However, the glomerular capillary barrier seemed to be far more sensitive to elevations of hydrostatic pressure than other capillary walls which require capillary pressure increments of 60 mmHg in order to induce similar reversible changes in permeability. Therefore, we conclude that an elevated PGC per se induces changes of glomerular permselectivity, which may have important pathophysiological implications during conditions of proteinuria.

Albumins↗

The nucleotide sequence of the mitochondrial DNA molecule of the grey seal, Halichoerus grypus, and a comparison with mitochondrial sequences of other true seals.

The sequence of the mtDNA of the grey seal, Halichoerus grypus, was determined. The length of the molecule was 16,797 base pairs. The organization of the molecule conformed with that of other eutherian mammals but the control region was unusually long due to the presence of two types of repeated motifs. The grey seal and the previously reported harbor seal, Phoca vitulina, belong to different but closely related genera of family Phocidae, true (or earless) seals. In order to determine the degree of differences that may occur between mtDNAs of closely related mammalian genera, the 2 rRNA genes, the 13 peptide coding genes, and the 22 tRNA genes of the 2 species were compared. Total nucleotide difference in the peptide coding genes was 2.0-6.1%. The range of conservative difference was 0.0-1.5%. In the inferred peptide sequences the amino acid difference was 0.0-4.5%, and the difference with respect to chemical properties of amino acids was 0.0-3.0%. A gene that showed a limited degree of difference in one mode of comparison did not necessarily show a corresponding limited difference in another mode. The ratio for differences in codon positions 1, 2, and 3 was approximately 2.7:1:16. The corresponding ratio for conservative differences was approximately 1.8:1.1:1. The evolutionary separation of the two species was calculated to have taken place 2-2.5 million years ago. This dating gives the figure approximately 8 x 10(-9) as the mean rate of substitution per site and year in the entire mtDNA molecule. Comparison with the cytochrome b gene of the Hawaiian monk seal and the Weddell seal suggested that the lineage of these two species and that of the grey and harbor seals separated approximately 8 million years ago.

Animals↗

Addition of purified orosomucoid preserves the glomerular permeability for albumin in isolated perfused rat kidneys.

The serum protein, orosomucoid has been shown to be essential for the maintenance of normal capillary permeability in several different organs, including the kidney. Thus, the clearance of albumin was found to be almost fivefold higher in the absence of orosomucoid in a previous study on isolated rat kidneys, perfused with either of two commercially available human albumin solutions of similar composition, but differing in their content of orosomucoid (0.21 g l-1 vs. < 0.005 g l-1). The following experiments were performed in order to verify the hypothesis that this effect on glomerular permselectivity was due to orosomucoid per se and not to other ingredients in the two solutions. Both kidneys of 12 rats were isolated and perfused with identical albumin solutions without orosomucoid, but with the addition of purified orosomucoid (0.25 g l-1) to one of the kidneys. No significant differences in vascular resistance, urine flow or glomerular filtration rate (GFR), which was found to be 27 +/- 2 ml min-1 100 g-1, were observed between the two groups of kidneys. The fractional clearance of albumin (theta) was initially similar for both kidneys (0.0022 +/- 0.0002). In the absence of orosomucoid, theta gradually increased to 0.0076 +/- 0.0013 after 1 h of perfusion compared to 0.0040 +/- 0.0006 for the kidneys with orosomucoid added to the perfusate (P < 0.001, n = 12). We conclude that the plasma glycoprotein orosomucoid indeed plays an important role in regulating the dynamic properties of the glomerular capillary wall by reducing the permeability towards macromolecules such as albumin.

Albumins↗

The complete mitochondrial DNA sequence of the harbor seal, Phoca vitulina.

The nucleotide sequence of the mitochondrial DNA (mtDNA) of the harbor seal, Phoca vitulina, was determined. The total length of the molecule was 16,826 bp. The organization of the coding regions of the molecule conforms with that of other mammals, but the control region is unusually long. A considerable portion of the control region is made up of short repeats with the motif GTACAC particularly frequent. The two rRNA genes and the 13 peptide-coding genes of the harbor seal, fin whale, cow, human, mouse, and rat were compared and the relationships between the different species assessed. At ordinal level the 12S rRNA gene and 7 out of the 13 peptide-coding genes yielded a congruent topological tree of the mtDNA relationship between the seal, cow, whale, human, and the rodents. In this tree the whale and the cow join first, and this clade is most closely related to the seal.

Amino Acid Sequence↗

An isolated perfused rat kidney preparation designed for assessment of glomerular permeability characteristics.

The aim of the present investigation was to modify the widely used isolated perfused rat kidney preparation to make it more suitable for studies of glomerular permeability to macromolecules. Both kidneys were perfused in situ using separate pumps in two of each other independent systems with Tyrode-solution containing human serum albumin (18.2 g l-1). Sodium nitroprusside was administered to induce dilatation and to maintain constant vascular resistance (PRU100) during the experiments. The addition of sodium nitroprusside decreased vascular resistance from 0.17 +/- 0.05 to 0.09 +/- 0.02 mmHg min-1 100 g-1 ml-1 and increased urine flow and glomerular filtration rate. The temperature of the perfusate was reduced from 37 degrees C to 8 degrees C to inhibit tubular reabsorption of protein and fluid, resulting in a urine to plasma concentration ratio of [51Cr]EDTA of 1.26 +/- 0.07. Furosemide reduced the urine to plasma concentration ratio for [51Cr]EDTA further to 1.15 +/- 0.02 and increased glomerular filtration rate. Moreover, by performing the studies at low temperatures (8 degrees C) in the presence of sodium nitroprusside and furosemide it was possible to achieve low and stable albumin fractional clearance values close to those prevailing in vivo. Thus, the described technique, allowing simultaneous perfusions of both kidneys with different solutions, pressures and flows, seem to be well suited for studies of macromolecular transport across glomerular capillaries.

Animals↗

Raised plasma concentrations of endothelin-1 and -3 in marmosets with acute aortic stenosis: no relation to the renin-angiotensin system.

Plasma levels of endothelin (ET), plasma renin activity (PRA) and angiotensin II (Ang II) were measured in anaesthetized marmosets exposed to acute aortic stenosis proximal to the renal arteries. In vehicle experiments, ET rose from 5 +/- 2 to 38 +/- 4 pg ml-1, PRA from 5 +/- 2 to 99 +/- 21 ng ml-1 h-1 and Ang II from 21 +/- 4 to 213 +/- 76 pg ml-1. Administration of renin inhibitor and angiotensin converting enzyme inhibitor reduced PRA and Ang II to control levels, while the plasma levels of ET increased further (51 +/- 10 and 71 +/- 16 pg ml-1, respectively). During aortic stenosis the two isoforms ET-1 and ET-3 appeared in the circulation, while in conscious control animals only ET-1 was found. It is concluded that the increased plasma levels of ET in our primate model could not be ascribed to the increased circulating levels of PRA and Ang II.

Acute Disease↗

Myogenic responsiveness in rat hindquarter vessels during constant-flow and constant-pressure perfusion in vitro; effects of various potassium concentrations and of endothelial nitrous oxide blockade.

An in vitro constant-flow, alternatively constant-pressure, perfusion method for studying microvascular myogenic responsiveness in otherwise intact rat hindquarters was used to explore how three types of influences affect the pressure-flow induced enhancements of myogenic tone: (1) Changes of potassium concentration over the range 2-50 mmol; (2) Whether myogenic responsiveness, which is fairly weak during these conditions of high shear rates, is enhanced by blockade of endothelial prostacyclin and nitrous oxide formation; (3) Whether some of the drawbacks of the constant-flow technique, like rapid edema formation, is offset by a constant-pressure variant. The result can be summed up as follows. (1) Myogenic responsiveness is also during in vitro conditions markedly influenced by even modest potassium concentration changes around the physiological resting level, e.g. showing a fourfold difference between potassium concentrations of 2.5-4.5 mmol. It was entirely suppressed above 7-8 mmol potassium concentration but also when potassium concentration values above 20 mmol increasingly depolarize and constrict the resistance vessels. (2) While blockade of prostacyclin synthesis was without effect, suppression of endothelial nitrous oxide production could increase myogenic responsiveness up to fourfold, suggesting that shear-stress dependent release of this agent serves to suppress myogenic activity. These effects were, however, quite variable suggesting that also other endothelial inhibitory influences are involved. (3) The constant-pressure variant reduces some of the methodological drawbacks, particularly the oedema formation which can be further reduced by increasing perfusate colloid osmotic pressure. However, interferences by the mentioned, partly unknown endothelial mechanisms still tend to suppress myogenic responsiveness to a varying extent, which hampers quantitative analyses particularly of other inhibitory influences.

Animals↗

A note on the errors of using venous congestion in intact rats for determinations of microvascular permeability.

The established ideas of transcapillary exchange have recently been challenged based on studies in intact rats. In vivo measurements of net fluid flux and albumin clearance in muscle (and skin) have given estimates of the reflection coefficient (sigma) for albumin of 0.98-0.99 compared to the sigma value of 0.90 obtained by most other techniques. This discrepancy has vast consequences for the understanding of the transcapillary passage of macromolecules. A sigma for albumin near unity implies that there is virtually no coupling between protein and fluid transfer as induced by, for example, increases in vascular hydrostatic pressures. However, there are several assumptions inherent in the seemingly straight-forward experiments on intact rats, and in the present study we tested the hypothesis that occlusion of the femoral vein by ligation induces only moderate and transient increments of venous pressure (PV). During control conditions PV was 6.3 mmHg and pressure increased to 12.8 mmHg immediately following venous occlusion. However, PV declined with time and after 30 minutes of occlusion the capillary hydrostatic pressure was only increased by 3.0 mmHg. Calculations of the capillary filtration coefficient gave completely unrealistic values, close to those of maximally vasodilated skeletal muscle. The findings suggest that data obtained from intact rats, albeit important and interesting, should be evaluated with great care due to possible experimental errors in the in vivo approaches. In particular, the technique of estimating sigma for albumin in intact rats must be subjected to modifications before allowing any reliable conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Dose-dependent reduction of bone inductive properties by ethylene oxide.

Sterilisation of demineralised bone matrix with ethylene oxide has been claimed to destroy the ability of bone matrix to induce new bone formation on intramuscular implantation. Other workers have routinely used ethylene oxide sterilised bone matrix for assays in rodents without detrimental effects. We studied the effects of various lengths of exposure to ethylene oxide gas, and found that bone induction properties are destroyed in a dose-dependent manner. After a short exposure, bone induction properties were moderately diminished. However, this short ethylene oxide treatment did not kill Bacillus subtilis spores. A sterilisation procedure that killed these spores rendered the implants incapable of bone-induction.

Animals↗

Electrophysiological and mechanical characteristics of isolated hearts from spontaneously hypertensive (SHR) and normotensive (WKY) rats on very high- and low-sodium diets.

Electrophysiological, mechanical, dimensional and coronary flow characteristics were studied on papillary strips and on isolated hearts, from spontaneously hypertensive (SHR) and normotensive (WKY) rats respectively, which from 5 to 15 weeks of age had been on either 'low' (LNa, 0.5 mmol 100 g-1 food), control (CNa, 5) 'high' (HNa, 50) or 'very high' (vHNa, 120) sodium diets. With respect to cardiac electrophysiological characteristics, contractility, and maximal stroke volume capacity only minor, if any, differences were observed between the various Na diet groups, both in WKY and SHR. This is in accordance with our earlier findings concerning vascular smooth muscle, where a largely unchanged sensitivity and responsiveness to, for example, noradrenaline was noted. Further, only to the extent that the various Na diets had also caused changes in average blood pressure levels, adaptations of cardiac and coronary resistance vessel design were observed, in general agreement with our earlier findings in other preparations and experimental designs. The largely unaffected functional characteristics of cardiac as well as vascular effector cells, despite 240-fold long-term variations in sodium intake, are in sharp contrast to the marked changes that have been shown to affect the adrenergic nerves, as here chronic low-Na intakes cause reductions of transmitter release/impulse, and vice versa at high Na intakes. This latter type of change seems to be by far the most important functional deviation affecting cardiovascular control during long-term alterations of sodium intake, as it can markedly affect both cardiac and vascular influences on haemodynamics, even though the respective effector functions seem to be surprisingly little influenced directly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗