Search PubMed⌕ Search

Biomedical subjects

W Kriz

Publications and source records attributed to W Kriz.

At least 73 records · Page 4Linked to original sources
PubMed1994

Podocyte damage is a critical step in the development of glomerulosclerosis in the uninephrectomised-desoxycorticosterone hypertensive rat.

The progressive renal disease model of chronic uninephrectomy-desoxycorticosterone-trimethylacetate (UNX-DOCA) hypertension is associated with mesangial proliferation as a major disease mechanism. A detailed structural analysis of the alterations in glomerular structure which accompany the development of sclerosis in this model has not been made. Male Munich-Wistar rats underwent UNX, received weekly injections of the aldosterone agonist DOCA and 1% sodium chloride as drinking solution and were compared with sham operated controls (CON). Thirty eight days after onset, UNX animals had an albuminuria of 183 +/- 180 mg/day versus 0.38 +/- 0.22 mg/day in CON. Kidneys were fixed by total body perfusion and renal tissue processed for light and electron-microscopy. Superficial and deep total glomerular volume increased from 2.18 +/- 0.15 (deep: 2.57 +/- 0.24) 10(6) microns 3 in CON to 3.98 +/- 0.81 (deep: 3.95 +/- 0.63) 10(6) microns 3 in UNX. In addition to overall tuft hypertrophy, structural analysis revealed severe destruction of tuft architecture with mesangial expansion and/or capillary ballooning, leading to local tuft enlargements. Podocytes overlying the expanded areas appeared unable to adapt to cover the increased tuft surfaces. They developed severe lesions in cell architecture leading to denudation of glomerular basement membrane (GBM)-areas. "Naked" GBM appears to represent a nidus for hyalinosis, thrombosis and synechia formation, which progresses to segmental sclerosis. In the UNX-DOCA model of chronic glomerular hypertension local mesangial expansion was frequently encountered but no evidence was found that mesangial proliferation and matrix production proceeded to sclerosis. The crucial damage to the glomerulus in this model would appear to be attributable to podocyte failure, with the resultant GBM denudation triggering synechia formation, hyalinosis and ultimately glomerulosclerosis.

Animals↗
PubMed1994

Characterization of the Han:SPRD rat model for hereditary polycystic kidney disease.

The Han:SPRD rat model for inherited polycystic kidney disease (PKD) was characterized (clinical parameters, morphology, immunohistochemistry and in situ hybridization). Homozygous animals died of uremia after three to four weeks with severe cystic transformation of virtually all nephrons and collecting ducts (serum urea: 616 +/- 195 mg/dl; kidney-to-body weight ratio: > 20%). In heterozygotes, slow progression of the disease led to death between the 12th and 21st month (median: 17 months; serum urea levels above 200 mg/dl). Kidney enlargement was moderate, and cysts were restricted to the cortex and outer medulla. Immunohistochemical markers showed that approximately 75% of the cysts were derived from the proximal tubule. Cystic transformation started in the proximal tubule with a sharp onset of basement membrane alteration and a loss of epithelial differentiation restricted to small focal areas. In these areas, alpha 1(IV) collagen and laminin B1 mRNA were enhanced as revealed by isotopic and non-isotopic in situ hybridization. Fibroblasts underlying the affected tubular portions were involved in matrix overexpression resulting in subepithelial accumulation of immunoreactive collagen IV and laminin. In later stages of cystic transformation distal nephron segments were affected as well. A reversal in epithelial polarity as judged from Na,K-ATPase-immunoreactivity was not observed. Renal immunoreactive renin-status was significantly decreased. Hematocrit was lowered in heterozygotes (40.4 +/- 5.8 vol% compared to 46.7 +/- 1.99 vol% in controls; P < 0.05) and total renal EPO mRNA was reduced to 36 +/- 14% of the mean value of control animals, whereas serum EPO levels were not significantly altered. We conclude that the Han:SPRD rat is a useful model for the study of human ADPKD since both diseases are similar in several aspects. The model is particularly suitable for the study of epithelial-mesenchymal interactions at the beginning of tubular cystic transformation.

Animals↗
PubMed1994

A role for podocytes to counteract capillary wall distension.

In a previous study of the changes in glomerular structure in the isolated perfused kidney (IPK), perfusion at high pressures lead to an enlargement of the glomerular tuft and to the formation of giant capillaries. The present paper analyzes the morphological and dimensional changes of the peripheral glomerular capillary wall under these circumstances. The enlargement of glomerular capillaries at high pressure perfusion was accompanied by a considerable increase in the surface area of the glomerular basement membrane (GBM). The podocyte as well as the endothelial layer perfectly adapted to the acute challenge in covering increasing GBM area. The interdigitating foot process pattern showed up in an ideal arrangement. The capillary wall expansion was associated with a significant increase in total pericapillary slit area. Compared to the corresponding low pressure groups (65 mm Hg, without and with the application of vasodilators) the slit area increased in the high pressure groups (105 mm Hg, without and with vasodilator) by approximately 50 and 75%, respectively. This increase of the slit area was mainly due to an increase in slit length; the slit width remained fairly constant. These findings indicate that the pericapillary wall is distensible based on a distensibility of the GBM. We suggest that the contractile apparatus of podocyte foot processes regulates the expansion of the GBM.

Animals↗
PubMed1993

Cultured rat mesangial cells contain smooth muscle alpha-actin not found in vivo.

A monoclonal antibody against smooth muscle alpha-actin (SM alpha-actin) was used to study the expression of SM alpha-actin in kidney sections and mesangial cell (MC) cultures. In the tissue sections, indirect immunofluorescence revealed intense labeling of vascular smooth muscle cells and precapillary pericytes for SM alpha-actin. Glomerular cells including MC were negative, with the exception of scattered smooth muscle cells in the wall of the intraglomerular segment of the efferent arteriole. In contrast, in MC cultures 50 to 95% of the cells displayed bright fluorescence. Immunoreactivity for SM alpha-actin first appeared 3 days after explanation of glomeruli and increased until the primary culture reached subconfluence. In each subculture (1 to 10) expression of SM alpha-actin was weak on day 1 and pronounced at subconfluence. Growth arrest of subconfluent cultures for 1 to 7 days in serum-free medium did not alter the percentage of cells positive for SM alpha-actin. However, exposure of MC to serum-free medium beginning on the first day of subculture curtailed expression of SM alpha-actin. Double-labeling with antibodies against proliferating cell nuclear antigen and SM alpha-actin revealed SM alpha-actin-positive filaments in both replicating and resting cells. In summary, our results demonstrate that some process or processes associated with cell proliferation and cell growth of MC are accompanied by de novo expression of SM alpha-actin. The relevance to the contractile behavior of the difference in SM alpha-actin expression under in vitro and in vivo conditions is unknown.

Actins↗
PubMed1992

The glomerular mesangium: capillary support function and its failure under experimental conditions.

We present a structural analysis of the ability of the biomechanical unit consisting of mesangium and glomerular basement membrane to maintain normal capillary architecture in the face of mechanical challenges due to high intraglomerular pressures. Capillary support function may be considered in terms of the stabilization of local form (development of wall tension against capillary dilation) and global form (centripetal fixation of capillary loops to maintain higher order form). The pathologic consequences of the loss of this support are illustrated by way of experimental models of mechanical mesangial failure. Such failure may express itself as mesangial widening, increased transmesangial macromolecule "traffic," ballooning of capillary segments, and unfolding of capillary loops. Mechanisms are described by which these structural changes may lead to segmental glomerular sclerosis.

Animals↗
PubMed1992

Glomerular damage after uninephrectomy in young rats. I. Hypertrophy and distortion of capillary architecture.

Uninephrectomy (UNX) results in a higher incidence of focal glomerular sclerosis (FGS) in young rats than it does in adults. The reason for this higher susceptibility in young animals is not fully understood, but this does suggest that UNX in young rats may represent a particularly promising model in which to study the development of FGS. In the present study 10-day-old rats were subjected to UNX. After 4, 12 and 24 weeks, glomerular hypertrophy, structural lesions and function were analyzed in comparison with sham-operated controls. Up to the twelfth week, remnant kidney growth and glomerular growth proceeded in parallel; thereafter, kidney growth ceased, whereas glomerular growth continued undiminished. Twenty-four weeks after UNX, glomerular tuft volume in experimental animals exceeded that in controls by 80%. Twelve weeks after surgery, total GFR in UNX rats was approximately 80% of that in controls, a value maintained until the end of the observation period. Twenty-four weeks after surgery, heavy proteinuria was present in UNX animals. Structural abnormalities in glomeruli of UNX animals were already encountered 12 weeks after surgery; they were present to a much lesser extent in controls. In UNX animals these proceeded to the FGS stage by the end of the observation period. Three major groups of glomerular lesions were observed: (1) changes in the width and shape of glomerular capillaries. (2) changes in podocyte structure, and (3) tuft adhesions to Bowman's capsule with or without segmental sclerosis. The structural changes are analyzed in this and an accompanying paper [1]. The present paper deals with the widespread formation of irregular, giant capillary loops. They occur predominantly at the tuft periphery with a clear predilection for the vascular pole region. They are not a result of compensatory growth, but rather an expansion of single capillaries due to failure of the mesangium. Local disconnection of the mesangium from its anchoring points at the GBM leads to bulging and "coalescence" of capillary loops, resulting in abnormally-shaped vascular channels. This process is associated with a rearrangement of the corresponding mesangium. In our view, the appearance of dilated capillaries represents a local event pivotal to the development of more severe lesions, such as tuft adhesions and FGS.

Animals↗
PubMed1992

Glomerular damage after uninephrectomy in young rats. II. Mechanical stress on podocytes as a pathway to sclerosis.

In a preceding study [1], we showed that within six months after UNX in young rats, glomeruli in the remnant kidney undergo a sequence of serious changes which finally lead to focal segmental glomerulosclerosis (FGS). The formation of abnormally-shaped capillary channels was shown to result from local mesangial failure and is considered to be a nidus for the development of more severe lesions. In the present paper, the development of characteristic lesions in podocyte structure is described and analyzed. Concomitant with overall glomerular growth after UNX, a pronounced hypertrophy of podocytes was observed, while the mean number of podocytes per glomerulus did not change. It appears that podocytes cannot sustain the same degree of growth as the tuft as a whole; podocyte hypertrophy is soon followed by maladaptive changes which eventually lead to cell destruction. The following sequence of pathologic changes can be suggested: cell bodies enlarge in volume and area associated with a dramatic attenuation to cytoplasmic sheets. Primary processes are thinned out and frequently extend to remote capillaries. As a whole, the capillary area served by a single podocyte is dramatically enlarged. Furthermore, the expanding cytoplasmic sheets (derived from podocyte cell bodies) cover an increasingly large proportion of the outer capillary surface, that is, of the filtration area. Consequently, an increasing amount of filtrate is delivered into the subcellbody space. Obstruction of the efflux of this filtrate into the urinary space causes bulging of the overlying cytoplasmic sheets into pseudocysts. Podocytes overlying abnormally-shaped and dilated capillary channels are generally the most seriously affected. Tuft hypertrophy, pseudocyst formation and local capillary expansion cause wide-spread apposition of podocytes to Bowman's capsule. Appositions are a prerequisite for the development of tuft adhesion. Local detachment of a podocyte from the GBM in those areas allows access of parietal cells to the GBM. In early adhesions the connection of the tuft to Bowman's capsule is established by single parietal cells which attach to both the GBM and the basement membrane of Bowman's capsule. An adhesion is considered as a nidus for segmental sclerosis; as the adhesion progresses, the related tuft regions turn into sclerosis. In the present model FGS develops exclusively in areas of tuft adhesion.

Animals↗
PubMed1992

Expression of nitric oxide synthase in kidney macula densa cells.

The distribution of nitric oxide synthase (NOS), the enzyme by which NO is generated from L-arginine, was investigated in rat kidney. The indirect immunofluorescence technique using a polyclonal antibody against type I NOS was applied, followed by the histochemical NADPH diaphorase staining technique on the same sections in order to demonstrate the enzymatic activity of NOS. Macula densa cells were strongly stained by both techniques, demonstrating abundant NOS in the cytoplasm of these cells. In addition, these findings were confirmed by nonradioactive in situ hybridization, thus demonstrating the corresponding messenger RNA in macula densa cells as well. Our findings provide the morphological basis for a possible role of NO as a mediator substance in signal transfer from distal tubular fluid to glomerular arterioles.

Amino Acid Oxidoreductases↗
PubMed1992

Morphometric analysis of kidney hypertrophy in rats after chronic potassium depletion.

Hypertrophic kidney growth in K depletion was analyzed morphometrically in rats fed a K-free diet for 18 days. K excretion decreased rapidly to less than 1% of control, creatinine clearance decreased, and urinary concentrating ability was impaired. Kidney weight in K-depleted rats was 30% higher than in controls. Growth of individual kidney zones was not uniform; hypertrophy of the inner stripe (IS) of the outer medulla was most prominent. Among tubules the most striking enlargement was seen in the outer medullary collecting duct (CD); hypertrophy and hyperplasia of both CD cells and intercalated (IC) cells occurred in the same proportion. In the IS, both luminal and basolateral membrane area per unit tubule length doubled in IC cells and increased 1.2- and 1.7-fold, respectively, in CD cells. Despite overall kidney growth, epithelial volume of thick ascending limb (TAL) per tubule length was unchanged in IS and cortex and only slightly increased in outer stripe. The increased membrane area of CD epithelium in the IS is consistent with previously reported increases in activity of enzymes involved in active reabsorption of K+ and Na+.

Animals↗
PubMed1992

[Adolescents and computers: attitude, personality and motive for interaction].

This empirical study was undertaken to clarify controversial points emanating from previous theoretical and empirical papers dealing with apparently negative consequences on the personality development of young people who have at least a causal working-acquaintance with computers. We tested 174 persons of both sexes (age: 14-18 years) with a "Computer-Attitude-Questionnaire" and the "Mehrdimensionaler Persönlichkeitstest für Jugendliche" (Schmidt, 1981; "Multidimensional-Personality-Test"). A subgroup of 63 persons who have access to and do avail themselves of computers on a regular basis (as leisure-time activity) also answered the "Computer-Motive-Questionnaire". Statistical analyses revealed that the personality test-values of young people with a positive attitude toward computers range within the test-norm. The data for these people describe them as stress resistant, emotionally stable, well-balanced, sociable, achievement-oriented, and less aggressive.

Adolescent↗
PubMed1991

Glomerular injury in analbuminemic rats after subtotal nephrectomy.

Progressive proteinuria has been suggested not just to reflect but also to contribute to the development of focal glomerular sclerosis. Development of proteinuria and glomerular lesions was examined up to 18 weeks after 3/4 nephrectomy in Sprague-Dawley (SDR) rats and an analbuminemic SDR variant (NAR). Nephrectomy led to a significantly lesser degree of proteinuria in NAR (42 +/- 14 SD mg/day) than in SDR (140 +/- 54 mg/day), consistent with the fact that 50-60% of urinary protein in SDR after nephrectomy is serum albumin. Nevertheless at 18 weeks NAR showed a significantly higher frequency of moderate and severe glomerular lesions than SDR. We conclude that, in this model, proteinuria itself is not a major cause of progressive glomerular injury.

Animals↗
PubMed1991

Podocytes in glomerulus of rat kidney express a characteristic 44 KD protein.

We describe a new monoclonal antibody (MAb) directed against glomerular visceral epithelial cells (podocytes), generated by immunization with isolated rat kidney glomeruli. In immunoblotting experiments this MAb (IgG1 subclass) reacted with a 44 KD protein. In cryostat sections of normal rat kidney the MAb stained glomerular podocytes; therefore, we called the antigen pp44 (podocyte protein 44 KD). On 0.5-micron cryostat sections the signal could be more precisely ascribed to the podocyte foot processes, whereas the cell bodies appeared virtually unreactive. On ultra-thin frozen sections pp44 was found within the cytoplasm of podocyte foot processes at their origin from their parent processes. The podocyte cell membrane was not labeled. All other parts of the nephron were unreactive. An additional but weaker immunoreaction was found in the arterial endothelium; the endothelia of other vessels (peritubular capillaries, veins) were negative. In human kidney anti-pp44 revealed the same staining pattern as in rat kidney. The expression of pp44 was also studied in newborn rat kidney. The early stages of glomerular development (renal vesicle, S-shaped body) were negative. pp44 first appeared during the capillary loop stage, i.e., when formation of podocyte foot processes commences. In comparing the present results with published data, pp44 is clearly different from other antigens thus far described in podocytes. From the results of this investigation we conclude that pp44 represents a novel cytoplasmic protein of podocytes. Our data suggest a cytoskeletal role for pp44 in preserving the complex architecture of podocytes. This idea is confirmed by the simultaneous appearance of foot processes and anti-pp44 immunoreactivity during glomerular development.

Animals↗
PubMed1991

Branching and confluence pattern of glomerular arterioles in the rat.

In addition to the usual division of the glomerular tuft into lobules, a subdivision into an afferent and an efferent capillary domain is made. Immediately after entering the glomerulus the afferent arteriole splits into superficially located branches which supply the lobules. The capillaries of each lobule first run towards the urinary pole; these parts of each lobule establish the afferent domain. The capillaries of each lobule running back towards the vascular pole establish the efferent domain. The afferent domain represents the major part of the tuft; it has the shape of an incomplete globe with a deep depression on one side within which the efferent domain is situated. The efferent arteriole is established inside the glomerular tuft within the efferent capillary domain. Generally tributaries from each lobule converge to form the intraglomerular segment of the efferent arteriole, which leaves the tuft by passing through the mesangium of the glomerular stalk. At this site the intraglomerular segment of the efferent arteriole is fully surrounded by the mesangium; consequently, it is exposed to the intramesangial pressure.

Animals↗