Biomedical subjects
Publications and source records attributed to H Stolte.
The glomerular epithelial cells of the Atlantic hagfish (Myxine glutinosa) lack a slit diaphragm which is replaced by filaments. The epithelial cells show numerous occluding junctions (maculae and fasciae occludentes), septate desmosome-like junctions and desmosomes. The present findings are compared with available data on developing and mature glomerular epithelial cells of mammals.
Male rats are widely used for comparative investigations in renal physiology and pathology. However, they demonstrate a striking physiological proteinuria which must be considered if protein excretion is one parameter in the description of a model. Electrophoretic differentiation of urinary proteins shows that the major portion of male urinary protein consists of low molecular weight proteins which are strain-, sex- and age-dependent. The excretion of these proteins depends mainly on sex hormones and only to a lesser degree on kidney function. The excretion of albumin is a sensitive indicator to detect glomerular permeability changes, mainly because the tubular transport maximum is restricted and because the concentration difference between glomerular ultrafiltrate and plasma is very large, so that a small increase in permeability may cause a greatly elevated albumin excretion. Therefore, selective determination of albumin, e.g., by electrophoretic separation, is indispensable to estimate the renal permeability. Complicating the evaluation of experimental results, spontaneous kidney disease (progressive glomerulonephritis or glomerulosclerosis) develops in aging rats. Therefore, long-term studies in rats should be avoided because this spontaneous kidney disease with concomitant changes in protein excretion might interfere with experimental results.
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The permeability of the glomerular filtration barrier with respect to molecular size could best be studied by substances which are neither secreted nor reabsorbed and have a mean molecular weight of about 40,000--80,000 daltons. Uncharged molecules are preferred because the charge definitely influences the glomerular filtration. Several such substances are available; however, in most permeability studies labelled PVP, mainly 125I- or 131I-PVP, and dextrans have been applied. Gel filtration and binding studies with 125I-PVP have demonstrated that this substance should not be used because of unspecific binding of radioactive material. The application of dextran gives more reliable results. Disadvantages, however, include the large amounts which must be administered and some cases of intolerance, particularly in rats. Therefore, experiments with dextran seem feasible in some species but not in others. Ficoll, a synthetic polysucrose, is better tolerated than dextran but still causes allergic reactions in susceptible animals.
A variety of sex-dependent urinary proteins of low molecular weight, absent in females and in castrated males, can be identified in male rats by disc electrophoresis. In the urine of male rats of age 5.5 months, albumin comprises only 1-2% of the total protein. Albumin excretion increases greatly with age and associated kidney disease. Total protein excretion, however, stays the same or even decreases slightly as the rat ages, due to a loss of low molecular weight, sex-dependent, proteins. These are virtually absent in senescent rats (38 months of age), although total protein excretion rises tenfold in these animals due to high molecular weight plasma proteins passing into the urine; the glomerular filtration rate decreases to 70% of the value measured at 5.5 months of age.
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This report describes 3 cases of yellow nail syndrom. The examination either did not reveal lymphedemas or only transitory edemas were found. But both typical changes of nails and chronic inflammation of the respiratory tract were found. Remarkably enough, two of our patients showed a decrease in serum immunoglobulin M (IgM). Both patients had a most serious disorder of the respiratory tract. In the form of a table this report contains a survey of the literature published hitherto about the combinations of symptoms of yellow nail syndrom occurring most frequently.
Glomerular albumin filtration was investigated in the isolated perfused rat kidney and compared with in vivo experiments. Applying micropuncture techniques, we obtained samples from the glomerulus or adjacent early proximal convoluted tubules (EPT) of cortical nephrons and analyzed them for albumin using ultramicrodisc electrophoresis. By determining albumin in glomerular filtrate, we could calculate the sieving coefficient (EPTalb/Palb) directly. The control in vivo value was 0.27 +/- 0.05 X 10(-3) (N = 11). In the isolated perfused rat kidney, the sieving coefficient was 2.1 +/- 0.8 X 10(-3), N = 18 (30 g/liter albumin in perfusate) and 2.3 +/- 0.8 X 10(-3), N = 13 (50 g/liter albumin in perfusate), which is approximately eight times the control in vivo value. With elevated renal venous pressure (20 cm H2O), it increased further to 5.4 +/- 1.6 X 10(-3), N = 8. In all experiments, GFR and proximal transit times were similar to the in vivo controls. Although no major morphologic changes could be detected in any instance, the albumin filtration was greatly elevated. These data confirm the role of a functional barrier in the prevention of glomerular albumin filtration.
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For uraemic diabetics the loss of insulin by dialysis with highly permeable membranes has clinical relevance. We investigated renal handling (in isolated perfused rat kidneys) of insulin and c-peptide and their dialytic clearances and sieving coefficients using cuprophan and polyacrylonitrile membranes. Rat kidney catabolic clearances were five times (insulin) and 12 times (c-peptide) greater than urinary clearances and twice inulin clearance. Cuprophan membrane was found to be virtually impermeable for both hormones. Polyacrylonitrile sieving coefficients were 0.3 (insulin) and 0.4 (c-peptide). Both hormones are filtered as well as tubularly and peritubularly catabolised in the kidney. Insulin removal during dialysis and haemofiltration with polyacrylonitrile membranes has to be considered in treating uraemic diabetics.
Addition of Alcian Blue to the fixative reveals structural elements bearing negatively charged sites within the glomerular capillary wall of the rat kidney. According to previous research (review by Brenner et al., 1977), these charges represent one of the most important functional components of the glomerular filtration barrier. Alcian Blue also demonstrates negatively charged microfibrils (probably glycoproteins) of the mesangial matrix. Preliminary observations of glomeruli of lower vertebrates suggest that there is always a close correlation between the presence of microfibrils and mesangial cells.
Glomerular filtration and tubular uptake of plasma proteins have been studied in the rat using micropuncture techniques. 1. Under control conditions the glomerular capillary wall is an effective barrier, only 7.6 microgram/min x 100 g BW albumin have been measured as filtered load. Four to twelve hours after i.v. injection of anti-glomerular-basement membrane serum (anti-GBM-serum sieving coefficient phi and filtered load increased in a dose-dependent manner (phi albumin in controls = 0.27 x 10(-3), after injection of 0.5 ml Antiserum phi = 0.28 x 10(-3) and 1.0 ml Antiserum phi = 2.32 x 10(-3)). 2. The tubular reabsorption capacity is almost reached under control conditions and amounts to 5.6--10.7 microgram/min x 100 g BW for albumin. Only reduced GFR (0.36 +/- 0.07 ml/min x 100 g BW) and reduced tubular flow lead to increased tubular uptake under overload conditions (10.7 vs. 99.0 microgram albumin/min x 100 g BW). 3. Tubular reabsorption of so-called high-molecular-weight proteins seems to be a nonselective mechanism. The ratio Alb/Alb + Glob (89.9--93.1%) did not differ significantly at the individual puncture sites and in the final urine.
Renal micropuncture and microdissection techniques with ultramicro fluid analysis have been applied to evaluate single nephron function in the skate, Raja erinacea. We have divided the skate nephron into three proximal tubular segments (PTS I-III), three distal coilings (DC I-III), and a countercurrent loop system located between the proximal segments and the distal coilings. The collecting duct is the principal site of urinary dilution. Following exposure of the fish to 75% seawater for about 24 hours, the sodium concentration difference between the end collecting duct lumen and plasma is decreased sufficiently to account for the urinary dilution. The principal site for magnesium, phosphate and sulphate secretion appears to be PTS II. This segment is located on the ventral surface of the kidney. PTS II is also the main nephron site for reabsorption of sodium and chloride in excess of water.
The anatomy and ultrastructure of the lizard kidney (Sceloporus cyanogenys) have been studied by light and electron microscopy. The number of glomeruli was counted in serial sections and estimated to be 2,000 (in the two kidneys). Beginning with the glomerulus and Bowman's capsule the nephron segments are sequentially: (a) proximal tubule; (b) intermediate ciliated segment consisting of a proximal and distal part; (c) distal tubule, which can be divided into two segments, followed by (d) connecting tubule and (e) initial collecting duct. The initial collecting ducts from several nephrons open into the collecting duct. Tubular epithelium in this lizard has similarities to that of other reptiles. The lateral borders do not overlap like in mammals, but interdigitate by fingerlike projections. The length of the nephron segments was measured in disected tubules and the diameter was measured on light and electron micrographs. From these measurements estimates of inner tubular surface area were made. Together with data from physiological studies (Stolte et al., '76; Schmidt-Nielsen, '76) the estimated surface area was used to calculate transport rates per unit area across the epithelium. Comparisons of structure and transport rates per unit area across the epithelium. Comparisons of structure and transport rates were made between S. cyanogenys and other reptiles and mammals.
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The fine structure of the kidney (glomerulus and archinephric duct) of the hagfish. Myxine glutinosa (L.) was studied in thin sections and by freeze-fracture technique. The glomerular filtration barrier is similar to that of mammalian kidneys. However, endothelial fenestrations are relatively scanty and the basement membranes of endothelial cells and podocytes always appear separated by a layer of collagen fibrils and microfibrils often surrounding numerous and extended mesangial cells. Between podocytes and their processes maculae occludentes and peculiar junctions of another type occur. The zonulae occludentes between epithelial cells of the archinephric duct are composed of five or more strands, occasionally of only one or two.
The concentration of nine endogenous free L-alpha-amino acids (ALA, LEU, ILE, PHE, TYR, LYS, GLU, PRO, GLY) and of taurine were determined simultaneously along the nephron of the rat kidney using free-flow micropuncture techniques without altering plasma amino acid concentration or kidney function. The amount of each amino acid was determined after dansylation (14C-labelled dansyl-chloride) in the micropuncture sample followed by thinlayer chromatography. The main site of reabsorption is the proximal tubule. After 15-20% of the proximal tubule length the bulk of reabsorption has taken place (18.9 plus or minus 3.4% S.E. of the filtered load remaining). Net reabsorption continues to a small but significant extent along the distal nephron (disal tubule and collecting duct). Reabsorption of taurine is less rapid (% remaining of filtered load at the early proximal tubule 37.0 plus or minus 4.6%). The transtubular concentration ratio of all amino acids except taurine follows a homogeneous course. Under the experimental conditions of this study no distction with respect to different systems of reabsorption "neutral", "basic", "acidic", "imino-glycine") could be made.