Determination of membrane thickness distribution from orthogonal intercepts

Jensen, Eva B. Vedel; Gundersen, Hans Jørgen G.; Østerby, Ruth

doi:10.1111/j.1365-2818.1979.tb00149.x

Cited by 350 publications

(205 citation statements)

References 12 publications

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“…BMT was measured in randomised fields at a final magnification of ×62,000 from the same sections described above. BMT was measured applying the orthogonal intercept method as previously described [12]. About 60 measurements were performed per glomerulus and BMT is given as a harmonic mean.…”

Section: Methodsmentioning

confidence: 99%

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

et al. 2007

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Aims/hypothesis An increasing amount of evidence indicates that mannose-binding lectin (MBL) plays a role in the development of diabetic nephropathy. The main objective of the study was to analyse whether MBL influences the effects of diabetes on the kidneys. Materials and methods In one group of wild-type mice and in one group of MBL double knockout mice we induced diabetes by the use of streptozotocin as a model of type 1 diabetes. Two groups of non-diabetic mice, wild-type and MBL knockout, were also included. By two-way ANOVA we evaluated if MBL modulated the effects of diabetes by testing the interaction between diabetes and MBL. Results MBL interacted with the effects of diabetes on three outcome measures: kidney weight (p<0.001), urinary albumin excretion (p=0.001) and the expression of collagen IVα1 (Col4a1) mRNA (p=0.002). This means that the effects that diabetes normally has on these parameters were significantly modified by MBL. MBL showed a tendency to interact with the effects of diabetes on glomerular basement membrane thickness and total mesangial volume (p=0.065 and p=0.063, respectively). Glomerular volume and total mesangial volume were significantly smaller in animals lacking MBL than in wild-type animals (p=0.006 and p=0.047, respectively). Conclusions/interpretation These findings, for the first time, show that the degree of kidney alteration as a consequence of diabetes is modified by MBL. These findings support a pivotal role of MBL in the development of diabetic kidney disease.

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Section: Methodsmentioning

confidence: 99%

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

et al. 2007

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“…The method was a modification (Dische, 1992) of the orthogonal intercept procedure of Jensen et al (1979). GBM measurements were carried out on acellular glomeruli from 11 groups of animals, including 4 BB/DR groups, 4 BB/DP h groups, and 3 BB/DP n groups.…”

Section: Morphometrymentioning

confidence: 99%

Significant glomerular basement membrane thickening in hyperglycemic and normoglycemic diabetic‐prone BB Wistar rats

et al. 2004

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The diabetic-prone BioBreeding Wistar rat (BB/DP) is an autoimmune model of insulindependent diabetes mellitus. Approximately 80 -90% of the animals are hyperglycemic (BB/ DP h ) by 90 -120 days of age while those that do not become diabetic in adolescence (BB/DP n ) remain normoglycemic for life. Likewise, rats in the diabetes-resistant (BB/DR) strain are normoglycemic. Although renal morphological studies have been carried out in this model, ultrastructural observations of age-and diabetes-related extracellular matrix (ECM) changes, including glomerular basement membrane (GBM) morphometry, are not available. Moreover, possible renal changes in the relatively uncommon BB/DP n control animals have not been reported. The current electron microscopic study was carried out to investigate temporal changes in detergent-treated acellular ECM in BB/DP h rats at 2 weeks, 3 months, 6 months, and 1 year postonset of moderate hyperglycemia. Age-matched BB/DR and BB/DP n control animals were also examined. Our data demonstrate age-and diabetes-related alterations in mesangial matrix distributions and GBM widths and show for the first time significant increases in GBM thickening in both hyperglycemic (BB/DP h ) and normoglycemic (BB/DP n ) rats when compared to age-matched BB/DR controls. Surprisingly, the rate of increase is greatest in BB/DP n animals. Although the pathogenesis of diabetic basement membrane disease is not completely understood, GBM thickening is widely regarded as a morphological consequence of hyperglycemia. However, data in the current investigation show that ECM alterations, including significantly increased GBM thickness, may occur in genetically diabetic animals in the absence of hyperglycemia. © 2004 Wiley-Liss, Inc. Key words: diabetes; glomerular basement membrane thickness; BB Wistar ratsThe BioBreeding Wistar rat (BB rat) is an autoimmune model of insulin-dependent diabetes mellitus (IDDM) discovered in 1974 in a colony of pathogen-free Wistar rats (Chappel and Chappel, 1983). Like human IDDM, the onset of clinical symptoms in diabetes-prone (BB/DP) BB rats appear during adolescence, generally between 60 and 120 days of age (Butler et al., 1983;Chappel and Chappel, 1983). These are characterized by rapid weight loss, polyuria, polydipsia, ketonuria, and finally death unless exogenous insulin is administered (Chappel and Chappel, 1983;Like and Rossini, 1984). The incidence of diabetes through 120 days of age is 60 -90% in most colonies and averaged 86% in a viral antibody-free NIH colony in Worcester, Massachusetts (Crisa et al., 1992). The diabetes exhibited by BB rats is not attributed to a single dominant or recessive gene, but the etiology seems to include a genetic component (Chappel and Chappel, 1983).

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“…Electronmicrographs with a total magnification of 44,000 times from a minimum of two glomeruli per kidney were used for the measurement of GBM thickness by the orthogonal intercept method [9], GBM area, and the number of anionic sites expressed as # / l x m 2.…”

Section: Morphometrymentioning

confidence: 99%

Reduced number of anionic sites is associated with glomerular basement membrane thickening in the diabetic BB-rat

Chakrabarti

Sima

1989

Diabetologia

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Summary. Glomerular basement membranes of diabetic and age-and sex-matched non-diabetic BB rats were studied morphometrically and ultrastructurally using a quantitative histochemical technique employing the cationic dye cuprolinic blue. Six months of diabetes resulted in a significant reduction in the density of anionic sites associated with increased thickness of the glomerular basement membrane. These findings suggest that loss of anionic sites may be an important mechanism in the genesis of glomerular basement membrane dysfunction in diabetes.

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Determination of membrane thickness distribution from orthogonal intercepts

Cited by 350 publications

References 12 publications

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

Significant glomerular basement membrane thickening in hyperglycemic and normoglycemic diabetic‐prone BB Wistar rats

Reduced number of anionic sites is associated with glomerular basement membrane thickening in the diabetic BB-rat

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