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R Osterby

Publications and source records attributed to R Osterby.

At least 73 records · Page 4Linked to original sources
PubMed1986

The cortical distribution pattern of diabetic glomerulopathy.

In advanced diabetic nephropathy, all nephrons are affected. However, glomerulopathy shows some variation in severity. The aim of this study was to see whether the distribution of glomerular lesions bears any relationship to known renal anatomical/functional organization. Autopsy material from 12 long-term Type 1 (insulin-dependent) diabetic patients was collected retrospectively. Sections presenting the whole depth of cortex were subdivided into 3 zones of equal width. Two parameters were estimated in the deep and the superficial zones separately: in open glomeruli, the volume of red-stained (PAS-positive) material as a fraction of the total glomerular volume, and the number of occluded glomeruli as a fraction of the total number. The results show that the volume fraction of red-stained (PAS-positive) material, as well as the frequency of occluded glomeruli, are similar in the superficial and the deep zone. In addition, the spatial distribution of occluded glomeruli was tested for randomness. The occluded glomeruli are not randomly distributed, but show clustering. Furthermore, they tend to be located in columns perpendicular to the kidney surface, a tendency which cannot be explained by the general tendency for glomeruli to show such an arrangement. We conclude that it is unlikely that the combined structural and functional differences that exist between the superficial and deep glomeruli play a major role in the development of diabetic glomerulopathy. The kidney topology influences the process of glomerular occlusion. Several a priori, plausible mechanisms for the process are discussed.

Adult↗
PubMed1986

Structural changes in the diabetic kidney.

Diabetic glomerulopathy is characterized by a very slow development of basement membrane (BM) accumulation, manifested as thickening of the peripheral BM and increased volume of the mesangial BM-like material (BMLM) with mesangial expansion. The initiation of the process is probably at the onset of diabetes since the BM thickening is detectable after a few years. The BM accumulations at the two sites (PBM and BMLM) in the glomerular tuft are considered as two different expressions of a fundamental BM abnormality. The two locations present different conditions for quantitation, may have a different biochemical make-up, and immediate functional implications of the abnormalities may differ as well. In the long run, however, the two in concert lead to the ultimate solidification of the glomerular tuft with loss of capillary surface. The end-stage is glomerular closure, with elimination of glomerular function. A very close correlation has been found between the total remnant surface area of the glomerular capillaries and the level of GFR. Along with the classical changes of the diabetic glomerulopathy, changes in glomerular size are detectable. In early diabetes during the stages of glomerular hyperfunction, hypertrophy develops acutely at the onset of diabetes, leading to an increase in capillary surface corresponding to the increase in filtration rate. In the advanced stages when glomerular closure involves a proportion of the nephrons compensatory hypertrophy develops, thereby probably helping to preserve capillary surface for a period of time. The exact mechanisms that may influence these developments are not known, but underlying them all are the metabolic abnormalities of diabetes.

Albuminuria↗
PubMed1985

Stereology of the rat kidney during compensatory renal hypertrophy.

Different renal structures were studied during the initial phases of compensatory renal hypertrophy. Four days after unilateral nephrectomy, kidney weight had increased by 31%, total glomerular volume by 17%, and glomerular filtration surface by 10%. After 24 days, kidney weight had increased by 44%, glomerular volume by 24%, and filtration area by 22%. The proximal tubules increased their cell volume and diameter significantly after four days (30% and 11%), but tubular length did not increase until later. We conclude that during compensatory renal hypertrophy glomerular growth is less pronounced than tubular growth, and that the increase in filtration surface area is not sufficient to explain the increased glomerular filtration rate after nephrectomy. Proximal tubules initially grow transversally and only later on longitudinally, the two growth phases possibly corresponding to cellular hypertrophy and hyperplasia.

Adaptation, Physiological↗
PubMed1984

Quantitative studies of glomerular ultrastructure in human and experimental diabetes.

A brief review is given of glomerular structural changes in diabetes mellitus and in rats with induced diabetes. The stereological methods for obtaining quantitative structural data are mentioned, and references are given to the underlying theories as well as to more detailed descriptions of the practical performance. In short-term diabetes a glomerular hypertrophy is found with increase in the surface area of the capillaries, in parallel with an increase in glomerular filtration. In long-term diabetes mellitus the picture is dominated by accumulations of basement membrane: thickening of the peripheral basement membrane and expansion of the mesangial regions which hold large amounts of basement membrane material. Rats with a moderate diabetes show the early hypertrophy as well as long-term basement membrane thickening. Severely diabetic rats develop basement membrane thickening but do not show the early hypertrophy, which is therefore not a necessary condition for basement membrane thickening to occur.

Adult↗
PubMed1983

Diabetic glomerulopathy. Structural characteristics of the early and advanced stages.

Studies of the glomerular structure in diabetes mellitus have helped to elucidate the basis for some functional abnormalities. The decline in glomerular filtration occurring in many long-term diabetics is a functional disorder of great clinical importance. Quantitative structural studies of the glomeruli in diabetics at different stages of disease are necessary to learn about the development of structural changes leading to the end-stage kidney disease. Preliminary results of a study of glomeruli from long-term diabetics with clinical nephropathy are compared with those obtained in control subjects and in diabetics within the first 5 yr of disease. In the long-term diabetics the peripheral basement membrane thickness was doubled. On the average, mesangial regions occupied nearly 60% of the total tuft volume as compared with 33% in the early stages. A marked accumulation of basement membrane material in the mesengial regions had taken place so that 85% of the total basement membrane material of the tufts (i.e., peripheral basement membrane in the capillary walls plus mesangial basement membrane-like material) was localized within the mesangial regions. In the early stages equal amounts were found at these two different sites. The distribution of the lesions within the kidney is under investigation in a light microscopic study of autopsy material from long-term diabetics with varying degrees of glomerulopathy. The severity of the diabetic glomerulopathy was quantitated separately within the superficial and the deep cortical zones. The results showed that there was no tendency toward increased severity in the deep glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Development of glomerular lesions in experimental long-term diabetes in the rat.

Exact parameters for relevant glomerular structures in the course of streptozotocin diabetes in rats with 1 to 18 months' duration were obtained with stereological methods. Renal cortical tissue from diabetic (D) and control animals (C) was processed for light- and electron microscopy and measurements were performed on systematically sampled glomeruli. The thickness of the basement membrane (BM) increased with age in both groups, but the rate of increase was 50% higher in D: 19 +/- 1.2 nm/month (mean +/- SD) vs. 13 +/- 0.9 nm/month, P = 0.0003. The time course of other structural quantities was characterized by the acute changes constituting the glomerular hypertrophy, earlier shown to develop within the first few days of diabetes. All these changes were confirmed in the present study: In the earliest phase the diabetic rats showed an increased total volume of glomeruli, mesangium, and mesangial BM material, as well as an increased surface of the capillary walls. However, none of these differences between the groups showed progression with increasing duration. Mesangial changes corresponding to those of the glomerulopathy in long-term diabetes were not demonstrable within the experimental period. The streptozotocin diabetic rat, therefore, is not useful as a model of advanced diabetic glomerulopathy. But the BM thickness follows the same predictable time course as in human diabetes insofar as moderately advanced cases are concerned. BM thickness is the parameter of choice when a potential effect of different variables on the development of diabetic glomerulopathy is under study.

Animals↗
PubMed1981

Acute renal hypertrophy in experimental diabetes: lack of effect of short-term growth hormone administration.

Normal and diabetic rats were given daily injections of human growth hormone for four days (5 mg per rat per day). Injected rats showed no differences from uninjected controls with respect to kidney weight or renal content of protein, RNA or DNA. Kidney weight increased by 7% after two days of diabetes and by 20% after four days, but growth hormone caused no augmentation of the hypertrophy. It is concluded that growth hormone plays no role in the initiation of diabetic renal hypertrophy.

Animals↗
PubMed1981

Optimizing sampling efficiency of stereological studies in biology: or 'do more less well!'.

The aim of the sampling design for stereology is to obtain the maximal amount of quantitative structural information at a given total cost or effort. Principles of such optimal designs are discussed and methods for generating them are illustrated by a biological example. In general, the variation between different individuals--the biological variation--is the major determinant of overall efficiency, whereas the variation between single microscopic features is unimportant. It follows that the expenditure of time and/or money in order to increase the precision of the individual measurements is irrational in almost all studies where the emphasis is on the biological results.

Animals↗
PubMed1981

Irreversibility of glomerular basement membrane accumulation despite reversibility of renal hypertrophy with islet transplantation in early experimental diabetes.

A quantitative morphologic study of the glomeruli in rats after 4 wk of streptozotocin-induced diabetes showed a number of glomerular changes, as previously described. Of particular interest was the increase in the total amount of glomerular basement membrane material [from 0.94 +/- 0.13 (SD) mm3 to 1.26 +/- 0.14 mm3 per kidney]. This parameter did not change after 4 wk of normoglycemia following islet cell transplantation (1.19 +/- 0.17 mm3), nor was the total glomerular volume normalized. The contralateral kidney was weighed and used for estimating the total amounts of protein, RNA, and DNA. Four weeks of diabetes expectedly resulted in a 50% increase in kidney weight, and islet cell transplantation diminished this to 15% in excess of normal. The average cell size (protein/DNA ratio) paralleled the kidney size after diabetes and following transplantation. The average amount of RNA per cell (RNA/DNA) increased significantly after induction of diabetes and was totally normalized after transplantation. Kidney protein concentration (mg protein/mg kidney) remained constant throughout the experiment. Considering that a few weeks of diabetes provokes a large increase in basement membrane material, it is especially noteworthy that 1 mo of normoglycemia is quite insufficient to reverse the accumulation.

Animals↗
PubMed1980

Glomerular epithelial foot processes in normal man and rats. Distribution of true width and its intra- and inter-individual variation.

The width of individual glomerular epithelial foot processes appears very different on electron micrographs. A method for obtainining distributions of the true width of foot processes from that of their apparent width on electron micrographs has been developed based on geometric probability theory pertaining to a specific geometric model. Analyses of foot process width in humans and rats show a remarkable interindividual invariance implying rigid control and therefore great biological significance of foot process width or a derivative thereof. The very low inter-individual variation of the true width, shown in the present paper, makes it possible to demonstrate slight changes in rather small groups of patients or experimental animals.

Adolescent↗
PubMed1980

Fast accumulation of basement membrane material and the rate of morphological changes in acute experimental diabetic glomerular hypertrophy.

Renal glomerular structures have been studied during the initial phases of renal and glomerular hypertrophy in streptozotocin diabetic rats. -- After four days of diabetes significant increases were found in the following absolute structural quantities: the tuft volume (25%), the surface area (42%) and volume (46%) of peripheral basement membrane, and capillary luminal volume (29%). No further changes in these quantities took place over the succeeding 47 days. The geometry of the capillaries, however, changed over this period: at 4 days the total capillary length had increased significantly (32%) with an unchanged average cross sectional area, whereas at 47 days the length had reverted to normal, but average cross sectional area had increased (30%). The increased surface of filtering area may be the morphological counterpart of increased glomerular filtraton rate. The changes in glomerular volume were thus accompanied by changes in glomerular structural composition which after a few weeks returned to normal, in balance with the increased volume.

Aging↗
PubMed1980

Acute effects of insulin on plasma noradrenaline and the cardiovascular system.

It is now known that insulin has marked acute effects on plasma noradrenaline and the cardiovascular system. These effects of insulin are not due to hypoglycemia and occur without changes in plasma adrenaline. Intravenous injection of insulin in juvenile diabetics increased plasma noradrenaline and heart rate and decreased glomerular filtration rate, renal and peripheral blood flow, and plasma volume. Urinary excretion rates of beta-2-microglobulin and urinary volume decreased after insulin, whereas urinary albumin excretion increased. When blood glucose was maintained by glucose infusion after insulin, glomerular filtration rate and renal blood flow remained unaltered whereas plasma noradrenaline, heart rate, and urinary albumin excretion increased and beta-2-microglobulin excretion decreased. Decreases in glomerular filtration rate and renal blood flow after insulin are thus due to the fall in blood glucose. Rise in albumin excretion after insulin is probably of glomerular origin and not caused by the fall in blood glucose or by changes in renal hemodynamics. In patients with long-term diabetic nephropathy and albuminuria, insulin decreased albumin excretion (probably due to renal vasoconstriction) and plasma noradrenaline did not increase. In alloxan-diabetic rabbits the increase in heart rate after insulin was not abolished by autonomic blockade. In short-term streptozotocin-diabetic rats, muscle capillary endothelial cells showed a reduced number of free micropinocytotic vesicles. The number was nearly normalized 1 hr after intramuscular injection of insulin. The mechanism of action of insulin on plasma noradrenaline, heart rate, plasma volume, and urinary albumin excretion is not known. The rise in plasma noradrenaline after insulin may be compensatory to hypovolemia or to antagonizing effects of insulin on some actions of noradrenaline. The findings in streptozotocin-diabetic rats suggest that insulin may be essential for the normal function of capillary endothelial cells.

Adult↗
PubMed1980

The rate of synthesis and breakdown of glomerular basement membrane material at the transition 'normal to diabetes' and 'diabetes to normal'.

A considerable enlargement of the renal glomeruli is present very early after the acute onset of juvenile diabetes mellitus. In the hypertrophied glomeruli the surface area of the capillary walls, the filtration surface, is increased, and thereby also the amount of basement membrane in the capillary wall. The rate of development of this type of diabetic basement membrane accumulation has been studied in streptozotocin diabetic rats with 4- and 47-day duration of diabetes. During the first 4 days a 40% increase in the total amount of peripheral basement membrane material occurs, whereas the following period up to 47 days shows no further change. The structural changes of the glomerular capillaries seen in conjunction with the basement membrane accumulation comprise an enlargement of the filtration surface and capillary luminal volume. In another experiment, 4-week diabetic animals were transplanted with pancreatic islets. The renal structures were studied quantitatively after 4 weeks of normalization. It was found that the increased amounts of basement membrane material were still present.

Animals↗
PubMed1980

Precise quantitation of glomerular basement membrane morphology.

Quantitative microscopical methods for studying the glomerular capillary basement membrane are described, mainly in terms of precision and overall experimental efficiency. The methods provide absolute data for basement membrane thickness, total surface and total volume, and for glomerular capillary dimensions, namely total length, total surface and average diameter, as well as for mesangial cell and matrix volumes. The impact of these methods on current research in glomerular structure and pathology is illustrated by results from a number of recent studies of human and experimental diabetes.

Animals↗
PubMed1980

A strong correlation between glomerular filtration rate and filtration surface in diabetic kidney hyperfunction.

The direct relationship between glomerular filtration surface and glomerulaf filtration rate was studied in a group of eight short term, young diabetics exhibiting a 50 per cent elevated glomerular filtration rate with a 2-fold variation within the group. A close correlation was obtained between glomerular filtration surface and glomerular filtration rate, r = 0.8. This supports the idea that the increase in glomerular capillary surface may be a main factor in diabetic kidney hyperfunction. The possible long term implications of the functional and morphologic abnormalities are discussed.

Adult↗