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Biomedical subjects

J Raskova

Publications and source records attributed to J Raskova.

53 records · Page 3Linked to original sources
PubMed1984

Glomerular hemodynamics and vascular structure in uremia: a network analysis of glomerular path lengths and maximal blood transit times computed for a microvascular model reconstructed from subserial ultrathin sections.

The dimensions of individual capillary segments were determined from a glomerular model constructed on the basis of electron micrographs of subserial ultrathin sections of kidney tissue from a rat made chronically uremic by subtotal nephrectomy. Hemodynamic calculations used computer programs for node pressure analysis and for the determination of path lengths and transit times from afferent to efferent arteriole. The afferent arteriole divided into five primary capillary segments. Three of these carried 84% of the flow through 632 paths, which accounted for 54% of the capillary endothelial area. Their mean path length was 520.97 micron, mean of segment numbers per path 17.66, and mean transit time 0.50 sec. The remaining two capillary segments carried 16% of the flow and led to paths accounting for the remaining 46% of the capillary area. The number of paths from the afferent arteriole through these two segments was 21,244. Mean path length from the initial node through these two segments was 852.18 micron, mean of segment numbers per path 29.62, and mean transit time 20.76 sec. The most striking difference between the two sets of paths was in transit time. This asymmetry would tend to reduce the filtration surface and the Kf (hydraulic conductance x filtering surface area) by causing early filtration pressure equilibrium in much of the capillary network, and suggests an intrinsic glomerular aspect of chronic renal insufficiency.

Animals↗
PubMed1983

Vesicular diffusion and thermal forces.

The concept that an endothelial vesicular shuttle serves much if not all the function of the large pores of the microcirculation for macromolecular transport has been current for 2 decades. Morphologists have expended much ingenuity in the study of plasmalemmal vesicles by the use of nonenzymatic and enzymatic tracers combined with electron microscopy. Several theoretical models of vesicular transport have been suggested, all of which assume vesicular migration by Brownian or thermal motion. Two such models based on simple diffusion are described, and more recent models in which vesicular diffusion is constrained by long-range hydrodynamic interaction with the plasmalemma are discussed. Theoretical models agree in predicting a vesicular transport time of the order of seconds. Only recently has experimental evidence appeared that tends to corroborate such predictions. Reports that frog mesenteric capillary endothelium fixed with formaldehyde-glutaraldehyde contains very few (approximately 1%) free vesicles are at variance with many in vivo tracer studies and inconsistent with the shuttle theory. It is possible that aldehyde fixation gives a poor representation of the state of the endothelium in vivo. It would seem that more instantaneous methods of fixation, such as rapid freezing, combined with tracer studies and serial sectioning, may be required to resolve this contradiction.

Biological Transport, Active↗
PubMed1983

T cell subsets and cellular immunity in end-stage renal disease.

The T lymphocyte population was studied by immunofluorescent staining with monoclonal antibodies and laser flow cytometry in the blood of 50 patients with end-stage renal disease undergoing long-term maintenance intermittent hemodialysis. The absolute number of T cells was lower in patients receiving dialysis for more than one year (p less than 0.001), as was the absolute count of helper T cells (p less than 0.005). In patients under 30 years of age, the absolute number of helper T cells was markedly reduced, whereas the number of suppressor/cytotoxic T lymphocytes was not changed. In patients between the ages of 30 and 60 years, both helper and suppressor cells were significantly reduced. In patients over 60 years of age, only the number of helper T cells was reduced. The in vitro response of patients' lymphocytes was reduced both in the mixed lymphocyte reaction (p less than 0.01) and after phytohemagglutinin stimulation (p less than 0.001). Natural killer cytotoxicity of patients' peripheral blood mononuclear cells, however, was unaffected.

Adolescent↗
PubMed1983

Humoral inhibitors of the immune response in uremia. V. Induction of suppressor cells in vitro by uremic serum.

The mechanism of inhibition of mixed lymphocyte reaction (MLR) by serum of chronically uremic rats has been studied. The inhibitory activity of the serum has been associated with a discrete subset of very low density lipoproteins (VLDL) of Sf 100-400. The degree of the inhibitory activity of uremic serum correlates with the severity of uremia. Spleen cells from normal rats incubated for 20 hours with uremic serum or its VLDL fraction suppress the response of control syngeneic cells in the MLR. Induction of such suppressor activity does not require cell proliferation because it is not inhibited by mitomycin C. although the exact identity of the induced suppressor cells has not been established, they may be macrophages. The suppressor activity of induced spleen cells can be markedly reduced by filtration of spleen cells on glass wool or on nylon wool columns. Reconstruction experiments show that the adherent cell fraction of spleen cells exposed to uremic serum suppresses the response of the nonadherent fraction of control spleen cells. These results indicate that the immunosuppressive effects of rat uremic serum in vitro involve the induction of suppressor cells.

Animals↗
PubMed1980

Ultrastructure of the glomerular basement membrane of rats with proteinuria due to subtotal nephrectomy.

Subtotal nephrectomy in the rat gives rise to progressive proteinuria, glomerular hypertrophy, and glomerulosclerosis. The proteinuria antedates significant ultrastructural lesions demonstrable by conventional techniques; its mechanism is obscure. In this article it is shown that proteinuria in this system is not accompanied by evident changes in the ultrastructural distribution of anionic sites in the glomerular basement membrane, as determined by organ perfusion with two cationic probe molecules. It is suggested that the proteinuria may reflect a change in the steric aspect of glomerular ultrafilration, in which the loss of renal mass imposes a significant rise in capillary pressure in a structure whose capillaries are peculiar in the high pressures they normally sustain and in their lack of mechanical support from the interstitium. It is suggested that a sustained rise in capillary pressure overcomes the rigidity of the glomerular basement membrane, so that its pore size increases and proteinuria results from basement membrane failure.

Animals↗
PubMed1979

Humoral inhibitors of the immune response in uremia. II. Further characterization of an immunosuppressive factor in uremic serum.

The serum of Lewis rats with chronic renal insufficiency (induced by subtotal nephrectomy) contains a nondialyzable inhibitor of the mixed lymphocyte reaction. Fractionation of uremic serum by gel filtration on Sephadex G-200 shows that the inhibitory activity elutes with an apparent molecular weight of greater than 200,000 daltons. To establish the possible relationship of the uremic inhibitor to known immunosuppressive components of normal serum, uremic serum was further fractionated on a DEAE cellulose column. The inhibitory activity elutes in 10 mM sodium phosphate at pH 8.0. This fraction contains both alpha-macroglobulin and IgG. The inhibitory activity of this fraction is completely inactivated by treatment with 2-mercaptoethanol, indicating that the inhibitor is a protein. The inhibitory activity is partially inactivated by periodate treatment, suggesting that it may be a glycoprotein. To determine whether or not the inhibitory factor is an immunoregulatory alpha-macroglobulin, or an immune complex, the uremic serum was fractionated by affinity chromatography procedures, which do not induce artifactual inhibitory properties in control serum. The alpha-macroglobulin was removed by affinity chromatography on a column of Con A-Sepharose; its removal had no effect on the inhibitory activity of serum in the mixed lymphocyte reaction. To examine the possibility that immune complexes may be the uremic inhibitor, the serum was fractionated by affinity chromatography on Protein A-Sepharose or by adsorption to a suspension of Staphylococcus aureus, cowan I. Neither of the two latter procedures had any effect on the inhibitory activity of uremic serum. So far all of our findings indicate that the immunosuppressive factor of uremic serum is distinct from two major immunoregulatory factors, alpha-macroglobulin and immune complexes.

Animals↗
PubMed1978

Humoral inhibitors of the immune response in uremia. I. Effect of serum and of the supernatant of spleen cultures from uremic rats on the mixed lymphocyte reaction.

The effects of the serum of rats with experimentally induced chronic renal failure and of the supernatant of cultured spleen cells obtained from these animals were tested in the mixed lymphocyte reaction (MLR). Serum of uremic rats with blood urea nitrogen levels greater than 35 mg. per 100 ml. and supernatant of spleen cultures from animals with blood urea nitrogen levels greater than 60 mg. per 100 ml. were found to be inhibitory to the MLR. The inhibitory activity of uremic serum was directly correlated with blood urea nitrogen levels. The inhibitory activities both of uremic serum and of the supernatant of cultured uremic spleen cells were further studied and compared. Dialysis in vitro does not remove the suppressing effect of serum or of supernatant on the MLR. Irreversible inhibition of the MLR is observed after 48 hours' exposure to the serum or to the supernatant; this inhibition occurs whether the MLR culture is exposed during the first 48 hours or last 48 hours of incubation. In some uremic rats the inhibitory activity of the serum disappears or is weakened after splenectomy, despite a continued rise in blood urea nitrogen levels.

Animals↗
PubMed1978

A stereologic study of glomerular hypertrophy in the subtotally nephrectomized rat.

Subtotal nephrectomy in the rat is followed by glomerular hypertrophy, glomerulosclerosis, and, ultimately, renal failure. To gain more insight into this sequence, we have made a morphometric study of the glomerular changes following subtotal nephrectomy in the rat during the period of functional compensation before glomerulosclerosis appears. We found a twofold increase in glomerular volume as compared with controls 2 weeks after operation (to approximately 2 X 10(6) cu mu) followed by a linear increase to approximately 5 X 10(6) cu mu at 21 weeks. The rate of increase in glomerular volume in controls did not significantly exceed that of body weight. The volume increase after subtotal nephrectomy is a true hypertrophy, since other morphometric parameters expressed per unit glomerular volume (surface and length densities) were approximately 80% of control values at 2 weeks and constant thereafter. Glomerular hypertrophy up to 21 weeks is accompanied by a stable BUN and a gradually increasing proteinuria. We conclude that glomerular hypertrophy in this system is a pathologic rather than a compensatory process and suggest that it may represent a counter-productive response to hemodynamic changes serving to increase the glomerular filtration rate.

Animals↗
PubMed1976

A decrease in cell-mediated immunity in uremia associated with an increase in activity of suppressor cells.

The graft-versus-host (GVH) reactivity of uremic and control spleen cells was studied by popliteal lymph node assay in the rat. The reaction evoked by cells from animals with severe uremia was conspicuously weaker than that evoked by control cells. The magnitude of the GVH reaction induced by control cells was directly proportional to dose, while with the uremic cells the same increases in dose led only to insignificant increases in the strength of the GVH reaction. When mixtures of syngeneic control and uremic cells were used, the GVH reactivity of the control cells was suppressed. The activity of uremic spleen cells can be enhanced (restored) by removal of the sub-population of cells adherent to glass wool. The GVH reaction induced by uremic cells so treated became directly proportional to dose. The removal of the adherent cell population from the uremic spleen cell suspension also led to the disappearance of the suppressor effect in mixtures of control and uremic cells. These results indicate that a decrease in GVH activity of rat uremic spleen cells is due to an increase in suppressor cell activity in the uremic spleen cell population.

Animals↗
PubMedDate not supplied

Effect of verapamil on the IL-2 binding to its active receptor and on the release of IL-2 receptor by activated PBMC.

In the present study we have examined the effect of a Ca2+ channel blocker (verapamil) on the binding of IL-2 to its biologically active receptor (IL-2R), as well as on the release of its soluble form (sIL-2R) by peripheral blood mononuclear cells (PBMC) stimulated by a variety of stimuli. In the same culture systems, cyclosporine A (CsA) was also used as an additional dissecting tool. PHA and the Ca2+ ionophore A23187 enhanced both the percentage of PBMC binding phycoerythrin-conjugated IL-2 (PE-IL-2) and the mean fluorescence intensity of this binding. A phorbol-ester (PMA), on the other hand, enhanced only slightly the proportion of PE-IL-2 binding cells. The two stimulatory combinations (PHA/PMA and A23187/PMA) also up-regulated the proportion of PE-IL-2 binding cells and the fluorescence intensity; the PHA/PMA combination was the most potent of all stimuli used. These two stimulatory combinations, and PHA alone, were also associated with maximal in vitro release of sIL-2R. Verapamil significantly down-regulated PE-IL-2 binding in all culture systems and it convincingly inhibited the release of sIL-2R. Furthermore, this mode of action of verapamil was concentration-dependent. CsA, on the other hand, inhibited the binding of PE-IL-2 to all stimulant-activated PBMC and had only a slight inhibitory effect on the in vitro release of sIL-2R. Our results indicate that there is a correlation between the binding of IL-2 to biologically active receptors on the surface of stimulant-activated PBMC and the release of the soluble form of IL-2R by the same cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMedDate not supplied

Multicenter randomized study of two once daily regimens in the initial management of community-acquired respiratory tract infections in 163 children: azithromycin versus ceftibuten.

In a randomized trial, we compared the efficacy and toxicity of azithromycin and ceftibuten once daily in the initial (empiric) therapy of proven or suspected community-acquired respiratory tract infections (CARTI) in 163 pediatric patients: 95.5% of those treated with azithromycin and 83.6% of those treated with ceftibuten were cured or improved. Streptococcus pneumoniae was more frequently eradicated in the azithromycin than in the ceftibuten group, whereas gram-negative bacilli were more susceptible to ceftibuten. Elimination rates for Staphylococcus aureus and Haemophilus influenzae were similar; adverse reactions did not differ in both arms. Thus, azithromycin was more effective but equally safe than ceftibuten in the initial therapy of pediatric CARTI.

Adolescent↗
PubMedDate not supplied

Evidence of mononuclear cell activation by hemodialysis.

The acute effects of hemodialysis (HD) on activation and function of mononuclear cells (MC) were studied in a model of in vitro HD. During the HD session, both cuprophan (CU) and polysulfone (PS) induced transcription of interleukin-2 receptor (IL-2R) mRNA. Expression of IL-2R on the cytoplasmic membrane, and release of soluble IL-2R (sIL-2R), however, did not change during HD, nor did responsiveness to IL-2. Polysulfone caused a slight reduction of the proliferative response to phypohemagglutinin, and of the release of sIL-2R. Hemodialysis did not induce IL-2 production, but induced IL-1 synthesis.

Humans↗
PubMedDate not supplied

Interleukin-1 kinetics in hemodialysis.

Interleukin-1 (IL-1) was measured in the plasma and in mononuclear cell (MC) lysates from patients on maintenance hemodialysis (HD) using either cuprophan (CU) or polysulfone (PS) membranes. Basal plasma levels of IL-1 in HD patients were significantly higher than those of uremic patients on conservative treatment or of healthy subjects. In 10 patients on conservative treatment, plasma levels of IL-1 increased significantly after 3 and 6 months of HD. During a single HD session, plasma IL-1 fell to 21% (CU) and 22% (PS) of pre-HD levels. Hemodialysis patients had a significantly higher intracellular IL-1 content than normal controls. During HD, a further increase was seen regardless of the membrane employed. A parallel in vitro study showed that IL-1 produced during HD requires at least 24 hours to be released, and that both CU and PS are able to bind and clear IL-1.

Adult↗