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H J Gundersen

Publications and source records attributed to H J Gundersen.

At least 73 records · Page 4Linked to original sources
PubMed1987

Quantitative changes of cerebral neocortical structure in insulin-treated long-term streptozocin-induced diabetes in rats.

The brains of rats with streptozocin-induced diabetes treated with a low-dose insulin regimen (1 IU/day) were studied with morphometric techniques. After 1 yr of diabetes, brain weight decreased slightly (1350 +/- 71 vs. 1521 +/- 55 mg, 2P less than .01) as did the volume of the neocortex (498 +/- 36 vs. 567 +/- 40 mm3, 2P less than .05). A significant loss of neocortical neurons occurred (38 +/- 2 X 10(6) vs. 46 +/- 3 X 10(6), 2P less than .01), and the length of the capillary network in the neocortical tissue shortened disproportionately (405 +/- 102 vs. 631 +/- 47 m, 2P less than .01), leading to increased diffusion distance. The mechanisms underlying cerebral loss in this model are unknown, but abnormalities of the vascular supply with prolongation of the route of diffusion might play a role.

Animals↗
PubMed1987

Advanced diabetic glomerulopathy. Quantitative structural characterization of nonoccluded glomeruli.

Quantitative ultrastructural data were obtained from kidney biopsy material of 12 long-term insulin-dependent diabetics. All patients had overt diabetic nephropathy with increased urinary albumin excretion and reduced glomerular filtration rate. Renal clearance of 51Cr-EDTA was in the range of 16-50 ml X min-1 X 1.73 m-2. All patients received antihypertensive treatment. A combined light- and electron-microscope study was performed. A significant proportion of the glomeruli was totally occluded (mean 36%, range 24-67%). Structural data presented relate only to the open, still-functioning glomeruli. Comparison with data previously obtained showed that the thickness of the peripheral basement membrane [647 nm, coefficient of variation (C.V.) 0.22] was more than twice the normal value (310 nm, C.V. 0.08); the width of epithelial foot processes (352 nm, C.V. 0.07) was significantly greater than in normal biopsies (224 nm, C.V. 0.06); and the mean volume of the open glomeruli was markedly increased compared with normal and clearly exceeded that in the early diabetic hypertrophy. Total mesangial volume and total basement membrane material per open glomerulus were increased by 277 and 614%, respectively. However, capillary length and surface per open glomerulus were similar to those observed in early diabetic hypertrophy. These findings suggest that a late glomerular hypertrophy with preservation of capillary surface occurs as a compensatory phenomenon, prolonging renal survival for diabetic nephropathy patients.

Adolescent↗
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

Stereological estimates of nuclear volume correlated with histopathological grading and prognosis of bladder tumour.

The aim of this retrospective study is to provide morphometric data which make grading of urinary bladder tumours objective and reproducible by stereological estimation of nuclear volume using the principle of estimating of the volume of particles of arbitrary shape. The study includes 92 specimens: 12 from normal bladder mucosa, and 80 from bladder tumours (15 grade I, 45 grade II, 19 grade III and one grade IV according to Bergkvist et al. 1965). After standard fixation, embedding, sectioning and hematoxylin-eosin staining, an unbiased estimate of the mean volume of nuclei sampled with a change proportional to the volume: (Formula: see text) was calculated. Here l0 is the length of the intercept through a test point hitting a nucleus measured in a random direction through the test point. The weighted means of nuclear volume in bladder tumours are spread over a wide range and show a strong correlation with the Bergkvist grade. Moreover, the relationship between the weighted mean volume of nuclei in bladder tumours and the prognosis is very good. Only one of 35 patients with a mean nuclear volume below 300 micron 3 died of bladder cancer whereas 18 of 19 patients with a mean nuclear volume above 500 micron 3 developed invasives tumours or died of their disease. This simple and fast estimate of nuclear volume seems to provide objective data of high prognostic value.

Adult↗
PubMed1986

The impact of recent stereological advances on quantitative studies of the nervous system.

The usefulness of a number of new stereological principles for unbiased estimation of particle number and sizes and sampling of particles is illustrated together with a novel principle for unbiased estimation of anisotropic surfaces. The examples include descriptions of estimators of neurone and synapse number and sizes, synapse gradients, neurone point patterns in three-dimensional space, capillary surface area, and perikarya volumes. A major advantage of the methods is the possibility to carry out the estimation procedures in specified, well-characterized regions or layers of the brain. Some general statistical and stereological problems are briefly discussed.

Animals↗
PubMed1986

Estimation of surface area from vertical sections.

'Vertical' sections are plane sections longitudinal to a fixed (but arbitrary) axial direction. Examples are sections of a cylinder parallel to the central axis; and sections of a flat slab normal to the plane of the slab. Vertical sections of any object can be generated by placing the object on a table and taking sections perpendicular to the plane of the table. The standard methods of stereology assume isotropic random sections, and are not applicable to this kind of biased sampling. However, by using specially designed test systems, one can obtain an unbiased estimate of surface area. General principles of stereology for vertical sections are outlined. No assumptions are necessary about the shape or orientation distribution of the structure. Vertical section stereology is valid on the same terms as standard stereological methods for isotropic random sections. The range of structural quantities that can be estimated from vertical sections includes VV, NV, SV and the volume-weighted mean particle volume vV, but not LV. There is complete freedom to choose the vertical axis direction, which makes the sampling procedure simple and 'natural'. Practical sampling procedures for implementation of the ideas are described, and illustrated by examples.

Animals↗
PubMed1986

Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R. Thompson.

This paper deals with isolated, countable items, often termed particles, in three-dimensional space. Its substance is the unbiased stereological estimation of the number, height, surface and volume of such particles without any assumptions about their shape. The full range of estimators is described, some of them for the first time, some in an improved form, several in more than one version, and all of them under the single, absolute requirement that one can in fact identify what one is quantifying on sections. In terms of the minimal number of sections for the analysis, the estimators may be classified as follows: On a single section it is possible to estimate vV, the mean volume of particles in the volume-weighted or 'sieving'-distribution. On two parallel sections, separated by a known distance, estimators exist of particle number and of all mean sizes (height, surface and volume) in the ordinary number distribution, as well as of SDN(v), the standard deviation in the number distribution of particle volumes. If the containing space is relatively transparent the sections may be two optical sections within one thick physical section. On a stack of parallel sections, at least as high as the largest particle, and separated by known distances, one can get twelve mean sizes and twelve distributions of individual sizes: all combinations of three sizes: height, surface and volume in four different types of distributions: number, height, surface and volume. Fulfilling the sampling requirements of the above two estimation principles it has been shown very recently that by combining them one may even estimate mean sizes and number of arbitrary particles in a stack of sections with constant but unknown separation. Finally, a unique, unbiased estimator of the total number of items in a specimen is described for the use of which one need not measure the distance between sections, nor their thickness, nor the volume of the specimen, nor assume anything about shrinkage/swelling, sectioning compression or lost caps. It is the fractionator.

Animals↗
PubMed1985

The pupillary response to light in type 1 (insulin-dependent) diabetes.

The pupillary response to light was examined by infrared television-videopupillography in 93 Type 1 (insulin-dependent) diabetic patients (aged 25-42 years, duration of diabetes 0-32 years), and 37 control subjects (aged 26-41 years) with techniques ensuring equality of stimulus and retinal sensitivity, and allowing a detailed computerized calculation of the various parameters of the response. There was no difference in latency time or constriction time between diabetic patients and control subjects. The diabetic patients had a smaller initial pupil size (p = 0.012) and a smaller response amplitude (p less than 0.001) than the control subjects, and these two parameters were correlated to each other (r = 0.49, p less than 0.000001) and inversely correlated to the duration of diabetes (r = 0.26, p = 0.013 and r = 0.29, p = 0.0051, respectively). As a group, the diabetic patients had a relative response amplitude that was similar to that of the control subjects. However, more detailed analysis showed that the diabetic patients with pupil size in the normal range had a small, but significant, reduction in relative response amplitude (p = 0.0021). The maximal velocities of constriction and re-dilatation were reduced in the diabetic patients (p less than 0.001 in either case), but both parameters were intimately correlated to the response amplitude (r = 0.91, p less than 0.000001, and r = 0.79, p less than 0.000001, respectively), and this relationship was identical in the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodation, Ocular↗
PubMed1985

Stereological estimation of the volume-weighted mean volume of arbitrary particles observed on random sections.

A stereological estimator of the weighted mean volume of particles of arbitrary shape is described. This unbiased estimator is based on simple point-sampling of linear intercept lengths. The complete absence of shape assumptions effectively breaks the long-standing 'convexity-barrier': the only requirement here is that individual particles can be unambiguously identified by their profiles on random sections. Practical details of the simple estimation procedure and an example with very irregular particles are reported. Finally, an estimator of the variance of the weighted distribution of particle volume is discussed. This estimator is also valid for particles of arbitrary shape. For any mixture of ellipsoids (spheres, oblates, prolates and triaxial ellipsoids) the estimator is reduced to a simple function of measurements of diameters in the section plane.

Animals↗
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↗
PubMed1985

Evidence for hyperplasia in mesenteric resistance vessels of spontaneously hypertensive rats using a three-dimensional disector.

Cellular dimensions in mesenteric resistance vessels from 10 spontaneously hypertensive rats and 10 Wistar-Kyoto rats have been determined using a random volume with an unbiased counting rule as the counting unit (the disector). With this method, vessels first were mounted on a myograph. Media thickness (spontaneously hypertensive rats, 11.3 micron; Wistar-Kyoto rats, 8.6 micron; P less than 0.01), lumen diameter (spontaneously hypertensive rats, 178 micron; Wistar-Kyoto rats, 194 micron; P greater than 0.1), and maximum active wall tension response (spontaneously hypertensive rats, 3.2 N/m; Wistar-Kyoto rats, 2.5 N/m; P less than 0.05) were determined. After fixation, serial sections normal to the long axis of the smooth muscle cells were made. In each vessel, the disector was a defined volume of the vessel wall (volume ca. 25 X 10(3) micron3) which was contained in about eight of these sections. The number of nuclei within the disector was counted using an unbiased, three-dimensional counting rule. On the basis that cells were mononuclear (an assumption that was tested), the ratio of this number divided by disector volume equaled the numerical cellular density. Measurement of the fraction of media taken up by smooth muscle cells then gave mean cell volume (spontaneously hypertensive rats, 563 micron3; Wistar-Kyoto rats, 615 micron3; P greater than 0.1). From the myograph measurements, the number of cells per unit length (spontaneously hypertensive rats, 10.4/micron; Wistar-Kyoto rats, 7.4/micron; P less than 0.05) and maximum force production per cell (spontaneously hypertensive rats, 5.1 microN; Wistar-Kyoto rats, 5.7 microN; P greater than 0.1) could then be calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Reconstruction of the formative site in iliac trabecular bone in 20 normal individuals employing a kinetic model for matrix and mineral apposition.

A stereologic procedure for the reconstruction of matrix and mineralized bone growth curves at formative sites in trabecular bone is presented. Iliac crest bone biopsies obtained from twenty normal individuals after tetracycline double-labeling were investigated histomorphometrically. Corresponding values for osteoid width and apparent distance between bone markers and width of mineralized bone walls were classified using a sector plotting system. Observed structure widths were converted to three-dimensional structure thicknesses by a stereologic unfolding procedure. Osteoid thickness, calcification rate, and fractional labeling of osteoid varied characteristically with increasing wall thickness and permitted the construction of curves describing the time-dependent variations in matrix and wall thicknesses. The mean thickness of completed walls was 61.9 +/- 1.5 micron (SE), and the mean bone formation period (Sigma f) was 145 days (124-168; 95% confidence interval.). The initial appositional rates for bone matrix (2.1 microns3/microns2/day) (1.4-2.9) and bone mineral (1.1 micron3/micron2/day) (0.4-1.9) declined gradually toward zero at the end of Sigma f. The initial mineralization lag time was 15 days (12-24) and increased to a maximum of 27 days during the first 45% of Sigma f. Thereafter, it decreased gradually toward zero. The height of the osteoblast nuclei gradually declined from 6.7 +/- 0.5 micron at the start of bone formation to 1.2 +/- 0.1 micron at the end. The study demonstrates that it is possible to reconstruct growth curves for trabecular bone walls based on three-dimensional values for structure thicknesses using different sections for light and fluorescence microscopy and avoiding classification according to osteoblastic nuclear morphology.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
PubMed1984

Diabetic macroangiopathy. Medial calcifications, narrowing, rugosities, stiffness, norepinephrine depletion and reduced blood flow capacity in the leg arteries.

Five quantitative studies performed to disclose and measure diabetic abnormalities in the leg arteries are reported and briefly discussed. A medial as well as an intimal disease was found in the diabetic leg arteries. Thus roentgenological medial calcification correlated to glucose intolerance in older non-diabetics and to diabetes duration in young insulin dependent diabetics. An intimal roughness was disclosed by arteriography in young insulin-dependent diabetic patients. The roughness grew worse the longer the diabetes persisted. The development of this abnormality did not take place simultaneous with the medial calcification, but was closely connected with another disclosed abnormality, a uniform arterial narrowing, quite unlike the well known abrupt narrowing in older patients. The existence of a uniform arterial narrowing in diabetic patients was confirmed by ultrasonography and the use of this technique further revealed arterial stiffness as a long-term diabetic phenomenon. A functional abnormality of the leg arteries of diabetic patients was disclosed by measurement of the postischemic peak blood flow in the leg in a 45 degree feet-down position. A vast destruction of the autonomic nerves of the peripheral arteries was demonstrated by measurement of the norepinephrine content post mortem in long-term diabetic patients. The results reported suggest a specific element in the large-vessel disease of diabetic patients.

Adult↗
PubMed1983

Sampling problems in an heterogeneous organ: quantitation of relative and total volume of pancreatic islets by light microscopy.

In stereological studies analysis of sampling variances is used for optimizing the sampling design. In organs with a heterogeneous distribution of the phase of interest the analysis of sampling variances can be undertaken only if the observed variance between sections is distributed into the fraction which is due to random variation and the fraction which is due to the heterogeneity. In the present example (pancreatic islet volume estimated by light microscopic point-counting) the density of islets showed a linear increase along the axis of the organ. By analysis of sampling variances it was calculated that the most efficient number of sections (cut perpendicular to the organ) was considerably lower when the isolated contribution from the random variation was considered. The total islet volume was obtained by the product of the fractional islet volume and the pancreatic weight. Analysis of sampling variances of the total islet volume was performed by including the variance contribution from the individual pancreatic weights to the variance of the group mean total islet volume. Due to a negative correlation between the fractional volume and organ weight the total islet volume in the group of animals was more precisely estimated than the fractional islet volume. The methods used for dealing with the heterogeneity of the organ and for estimating sampling variances of total structural quantities generalize to a large number of stereological studies in biology.

Analysis of Variance↗
PubMed1983

Ultrastructural lesions in lightmicroscopically defined types of glomerulonephritis. A blind and semiquantitative study.

Current classification of glomerulonephritis (GN) is based primarily on light microscopical (LM) histopathological criteria. The aim of the present study was to investigate the occurrence and severity of a number of electron microscopical (EM) lesions in different LM defined classes of GN in order to determine the degree of homogeneity of these classes and the degree of specificity of various EM lesions seen in GN. The analysis was performed using a blind, systematic and semiquantitative method and applied on 91 consecutive biopsies from patients with GN as well as on 11 reference biopsies. Most of the EM lesions were not restricted to a single or a few light microscopically defined classes of GN. EM lesions having direct LM counterparts used as classification criteria were generally present with high scores in the corresponding LM classes but were also present in other types of GN. When the EM-findings were compared with our original classification of the 91 biopsies it was found that about 13% of all biopsies were classified erroneously using only LM. Thus, the groups obtained with the presently used LM classification system are quite heterogenous with respect to ultrastructure and probably with respect to pathogenesis. On the other hand, it appears that many ultrastructural lesions display a more or less continuous spectrum of changes which therefore are difficult to use for classification purposes.

Biopsy↗
PubMed1983

The effect of heating and central cooling on serum TSH, GH, and norepinephrine in resting normal man.

The effects of central cooling and exterior heating on serum concentrations of thyrotropin (TSH), growth hormone (GH), and norepinephrine were studied in 10 normal males under resting conditions. Cooling was induced by ingestion of ice while the subjects were immersed in water of a temperature prone to elicit only minor cutaneous thermal reflexes. TSH and thyroid hormones changed neither during cooling nor during heating. Cooling induced a virtually complete suppression of GH-secretion whereas heating had the opposite effect: pronounced increase, also without previous cooling. Plasma norepinephrine rose by a factor of 2.5 and 1.7 during cooling and heating, respectively. It is concluded that the pituitary-thyroid system does not take part in short-term thermoregulation in man--as opposed to the situation in some smaller mammals. The mechanisms and the physiological role of the GH-responses to cooling and heating are as yet unknown, but the latter stimulus is an advantageous tool in clinical and pathophysiological studies of pituitary function as it is both safe and convenient.

Adult↗