Total Glomerular Volume Research Articles

Combination treatment with an ET(A)-receptor blocker and an ACE inhibitor is not superior to the respective monotherapies in attenuating chronic transplant nephropathy in a 'Fisher-to-Lewis' rat model.

Specific endothelin A (ET(A))-receptor blockade and ACE inhibition attenuate chronic transplant nephropathy (CTN) in the 'Fisher-to-Lewis' rat model. It is unknown (i) which of both pharmacological interventions attenuates CTN more effectively and (ii) whether combination therapy exerts additive nephroprotection. We compared (i) the effects of specific ET(A)-receptor blockade with LU 302146 (30 mg/kg bw/day) and ACE inhibition with trandolapril (0.3 mg/kg bw/day) and (ii) the effect of a combination therapy of both drugs on the development of CTN. Kidneys of Fisher rats were orthotopically grafted to Lewis rats. Untreated 'Fisher-to-Lewis' allografts served as controls (TX). All animals received low-dose cyclosporin A (1.5 mg/kg body weight) for 10 days post-transplant to inhibit early acute rejection episodes. The duration of the experiment was 36 weeks. Blood pressure (BP) was measured every other week by tail plethysmography. Indices of glomerulosclerosis (GS), tubulointerstitial and vascular damage, number of glomeruli, total glomerular volume and mean glomerular volume were measured using morphometric and stereological techniques, respectively. Albuminuria, blood chemistry and haematology were measured at the end of the experiment. LU 302146 did not affect systolic BP. In contrast, trandolapril and combination treatment significantly reduced systolic BP. Histological signs of CTN were almost completely prevented by LU 302146 and trandolapril as compared to TX, e.g. GS=0.8+/-0.08 and 0.9+/-0.20 vs 1.8+/-0.21* (arbitrary unit; *P<0.001 vs treated groups). Allograft weight was significantly lower in treated vs TX animals. Trandolapril and combination therapy, but not LU 302146 alone, abrogated glomerular hypertrophy, i.e. mean glomerular volume: TX 2.22+/-0.43, trandolapril 1.61+/-0.38**, LU 302146 2.22+/-0.11, trandolapril+LU 302146 1.78+/-0.28* (microm(3); *P<0.05 vs control and LU 302146, **P<0.01 vs control and LU 302146). Albuminuria was lower in treated compared to TX animals. Combination therapy did not confer additional benefit compared to the respective monotherapies. We conclude that ET(A)-receptor blockade abrogates GS, tubulointerstitial and vascular damage in the 'Fisher-to-Lewis' model of CTN to a similar extent as ACE inhibition. However, only ACE inhibition inhibits glomerular hypertrophy. In contrast to ACE inhibition, the effect of ET(A)-receptor blockade is independent of BP. This finding is consistent with the notion that ET(A)-receptor mediated events play a partly BP-independent role in the genesis of CTN. Combination therapy exerts no additive nephroprotection.

Compensatory renal growth after unilateral nephrectomy in the ovine fetus.

Unilateral nephrectomy of the adult animal results in compensatory renal growth but does not involve formation of new nephrons. It is not clear whether compensatory growth can occur during the period of active nephrogenesis in utero and if so, whether more nephrons can be formed. Male ovine fetuses (n = 20) underwent unilateral nephrectomy (n = 10) or sham nephrectomy (n = 10) at 100 d of gestation (term, 150 d). After 27 to 34 d, ewes and fetuses were killed and the right kidney of each fetus was removed and weighed. The wet weight of the right kidney was greater in the unilaterally nephrectomized fetuses (16.3 +/- 1.3 g compared with 12.2 +/- 0.7 g; mean +/- SEM, P < 0.05) as was the kidney to body weight ratio (5.2 +/- 0.3 g/kg compared with 3.8 +/- 0.2 g/kg; P < 0.001). Nephron number in the right kidney was estimated by an unbiased stereologic technique. There was a 45% increase in the number of nephrons in the kidneys from unilaterally nephrectomized animals compared with the kidneys from sham-operated animals (530,763 +/- 37,136 nephrons in the unilaterally nephrectomized group compared with 365,672 +/- 36,016 nephrons in the sham-operated group; P < 0.01). Mean glomerular volume was lower in the unilaterally nephrectomized group; however, total glomerular volume per kidney was not different between groups. This study demonstrates that there is a significant amount of compensatory growth and nephron endowment in a remaining kidney after unilateral nephrectomy during the period of active nephrogenesis in the sheep. This is the first time such events have been shown to occur in utero.

Renal function and structure in albuminuric type 2 diabetic patients without retinopathy.

In type 2 diabetic patients without retinopathy the cause of albuminuria is heterogeneous and our knowledge of the relationship between kidney structure and function in these patients is limited. Therefore, a long-term study evaluating the structural-functional relationship in albuminuric type 2 diabetic patients without retinopathy was performed. Mesangial volume of total glomerular volume (Vv (mes/glom)), fractional area of focal interstitial fibrosis and tubular atrophy of cortical area (FF) and percentage of sclerosed glomeruli (S/G) were measured on kidney biopsies from 49 type 2 diabetic patients without retinopathy. Glomerular filtration rate (GFR) was determined at least 3 times (median 8 (range 3-20)) in each patient. Patients were followed for 7.0 (1.1-17) years. Albuminuria and blood pressure were measured every 3-6 months. Biopsies revealed diabetic glomerulopathy (DG-group) in 69% of the patients (27 male/7 female) and normal glomerular structure (n=9) or glomerulonephritis (n=6) were found in 31% (13 male/2 female) (NDG-group). In the DG-group GFR decreased from 97+/-5 to 66+/-5 ml/min/1.73 m(2) (mean+/-SE) (P<0.001), with a rate of decline in GFR of 5.3+/-0.8 ml/min/year and in the NDG-group from 93+/-7 to 74+/-11 ml/min/1.73 m(2) (P<0.01), with a rate of decline in GFR of 3.2+/-0.9 ml/min/year, P=0.09 between groups. Mean arterial blood pressure decreased from 109+/-2 to 100+/-2 mm Hg (P<0.001) (DG-group) and remained unchanged in the NDG-group. An association between Vv (mes/glom) and rate of decline in GFR was revealed mainly in the NDG-group (DG-group; r=0.31, P=0.07 and NDG-group; r=0.74, P<0.01). Furthermore, the rate of decline in GFR seemed to be associated with FF in the NDG group (r=0.48, P=0.07). Percentage of S/G was not associated with the rate of decline in GFR. Vv (mes/glom) was associated with mean albuminuria during follow-up in the DG group; r=0.38, P<0.03 (NDG group; r=0.51, P=0.09). Albuminuria was an independent predictor of the rate of decline in GFR in both groups (DG-group; r=0.40, P<0.05 and NDG-group; r=0.61, P<0.01). Our study revealed a tendency to a faster rate of decline in GFR in the DG-group compared to the much smaller NDG-group, characterized by marked heterogeneity of the underlying kidney lesions and rate of GFR loss. A large mesangial volume fraction was associated with increased albuminuria and loss in GFR. Albuminuria acted as a progression promoter in both groups.

Cell Adhesion Molecule Expression in Murine Lupus-Like Nephritis Induced by Lipopolysaccharide

Background: Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM) are thought to play important roles in leukocyte recruitment to the kidney. We therefore chose to study mesangial cell adhesion molecule expression in vitro, and the role of these molecules in experimental lupus-like nephritis. Methods and Results: When cultured murine mesangial cells were stimulated with interferon-γ (IFγ) and tumor necrosis factor-α (TNFα), mRNA levels for ICAM-1 and VCAM markedly increased. These molecules were detected at the cell surface by flow cytometry. Since lipopolysaccharide (LPS) stimulates TNFα and IFγ production in vivo, we treated mice with Streptococcus minnesota LPS in order to study renal adhesion molecule expression. LPS treatment induced mesangial proliferative glomerulonephritis characterized by leukocyte infiltration, and increases in total glomerular cellularity, volume and matrix area. mRNA levels for ICAM-1 and VCAM were increased in the kidneys of LPS-treated versus control mice. ICAM-1 and VCAM molecules were constitutively expressed in renal vascular endothelium. At 3 and 5 weeks, this vascular staining intensified, and some ICAM-1 and VCAM expression was induced in the glomerular mesangium. ICAM-1 and VCAM induction occurred early and correlated in time with leukocyte infiltration. Conclusion: Interactions between cell adhesion molecules expressed by intrinsic glomerular cells and infiltrating leukocytes play a role in the initiation of LPS-induced lupus-like nephritis. These observations are potentially relevant to the understanding and treatment of certain types of human glomerulonephritis.

Perinatal ANG II programs adult blood pressure, glomerular number, and renal function in rats.

ANG II is known to be important in normal renal development, but the long-term consequences of a suppressed renin-angiotensin system (RAS) during the developmental period are not completely understood. This study tested the hypothesis that the RAS in the developing animal is important in long-term regulation of renal function and arterial pressure. Newborn Sprague-Dawley rat pups were given the ANG II AT1 receptor antagonist losartan (25 mg . kg-1 . day-1 sc) for the first 12 days of postnatal life (Los). Body weights at weaning (22 days) were significantly reduced in Los (53.4 +/- 3.2 vs. 64.5 +/- 3.6 g in controls); however, at the time of study (approximately 22 wk), body weights and the kidney-to-body weight ratios were not different. In chronically instrumented conscious animals, glomerular filtration rate and effective renal plasma flow were reduced by 27 and 20%, respectively, in Los; the filtration fraction was not different. Maximal urine concentrating ability was also reduced in Los (1,351 +/- 45 vs. 2,393 +/- 52 mosmol/kg in controls). Mean arterial pressure was significantly higher in Los (134 +/- 3 vs. 120 +/- 1 mmHg). The number of glomeruli per kidney was reduced by 42% in Los, but the total glomerular volume was unchanged. Thus perinatal blockade of ANG II AT1 receptors results in fewer but enlarged glomeruli, reduced renal function, and an increased arterial pressure in adulthood. These data indicate that perinatal ANG II, acting via AT1 receptors, plays an important role in renal development and long-term control of renal function and arterial pressure. Physiological conditions that cause suppression of the RAS in the developing animal may have long-term consequences for renal function and blood pressure.

Effect of GH/IGF-I deficiency on long-term renal changes and urinary albumin excretion in diabetic dwarf rats.

Growth hormone (GH) and insulin-like growth factor I (IGF-I) may play a role in early diabetic renal and glomerular growth and in the later development of experimental diabetic kidney disease. Rats from a genetic GH/IGF-I-deficient dwarf rat strain were made streptozotocin diabetic and were compared with nondiabetic dwarf rats. GH/IGF-I-intact rats with and without diabetes served as controls. After 6 mo of diabetes, kidney weight and total glomerular volume increased significantly in GH/IGF-I-intact diabetic rats compared with the nondiabetic GH/IGF-I-intact rats (P < 0.05), whereas the diabetic dwarf rats had insignificant changes compared with dwarf control rats. By the end of the study, urinary albumin excretion (UAE) increased from similar base levels of approximately 15-20 micrograms/24 h to 473 +/- 52 (SE) micrograms/24 h in GH/IGF-I-intact diabetic rats compared with 151 +/- 32 micrograms/24 h in diabetic dwarf rats (P < 0.01). In conclusion, isolated GH/IGF-I deficiency reduces the degree of renal and glomerular hypertrophy and the increase in UAE after 6 mo of experimental diabetes in GH/IGF-I-deficient rats.

Podocyte loss and progressive glomerular injury in type II diabetes.

Kidney biopsies from Pima Indians with type II diabetes were analyzed. Subjects were classified clinically as having early diabetes (n = 10), microalbuminuria (n = 17), normoalbuminuria, despite a duration of diabetes equal to that of the subjects with microalbuminuria (n = 12), or clinical nephropathy (n = 12). Subjects with microalbuminuria exhibited moderate increases in glomerular and mesangial volume when compared with those with early diabetes, but could not be distinguished from subjects who remained normoalbuminuric after an equal duration of diabetes. Subjects with clinical nephropathy exhibited global glomerular sclerosis and more prominent structural abnormalities in nonsclerosed glomeruli. Marked mesangial expansion was accompanied by a further increase in total glomerular volume. Glomerular capillary surface area remained stable, but the glomerular basement membrane thickness was increased and podocyte foot processes were broadened. Broadening of podocyte foot processes was associated with a reduction in the number of podocytes per glomerulus and an increase in the surface area covered by remaining podocytes. These findings suggest that podocyte loss contributes to the progression of diabetic nephropathy.

Glomerular dimensions in spontaneously hypertensive rats

A reduction in glomerular number and/or size has been implicated in the development of hypertension. This study investigated whether differences in glomerular number and/or size occur during the development of hypertension in the spontaneously hypertensive rat (SHR) and whether angiotensin II is responsible for any glomerular differences. SHR (n=6) and Wistar-Kyoto (WKY) rats (n=6) were administered the angiotensin II type I receptor antagonist TCV-116 from 4 to 10 weeks of age. At 10 weeks of age, the kidneys from these rats and those from untreated SHR (n=6) and WKY rats (n=6) controls were perfusion fixed at physiological pressures and analysed using unbiased stereological techniques. There were no significant differences in glomerular number, glomerular volume or total glomerular volume between SHR and WKY rats. Treatment of SHR with TCV-116 significantly lowered systolic blood pressure but had no significant effect on glomerular number or volume or total glomerular volume. Treatment of WKY rats with TCV-116 reduced systolic blood pressure, body weight, glomerular volume and total glomerular volume; however, total glomerular volume per body weight of treated WKY rats was not significantly different from that of untreated WKY rats. There were no differences in glomerular number or volume in SHR compared with WKY rats at 10 weeks of age. We therefore conclude that glomerular changes are not responsible for the development of hypertension in SHR. Angiotensin II, via the type 1 receptor, does not contribute to glomerular growth during the development of hypertension in the SHR.

Effects of maternal uninephrectomy on the development of the proximal tubule in fetal rat kidney: morphometrical study.

The kidneys of fetal rats from uninephrectomized mothers were investigated morphometrically on days 18, 20, and 22 of gestation. Maternal uninephrectomy was performed on day 5. On days 20 and 22, the proximal tubular cell height in fetuses from uninephrectomized mothers was significantly lower than that in fetuses from sham-operated mothers. The luminal diameter, length and total volume of the proximal tubule were significantly larger in fetuses from uninephrectomized mothers than in those from sham-operated mothers. The total glomerular volume of mature type in fetuses from uninephrectomized mothers was significantly larger than that in fetuses from sham-operated mothers. On day 18, maternal uninephrectomy caused no significant difference in any kind of parameters used for the proximal tubule, but induced an increase in the total glomerular volume of immature type. These results suggest that maternal uninephrectomy stimulates morphological development of the proximal tubule in the fetal kidney.

Effect of octreotide on experimental diabetic renal and glomerular growth: importance of early intervention.

IGF-I acts as a renotropic factor in early streptozotocin-induced diabetes. Somatostatin analogue (octreotide) treatment initiated at the onset of diabetes prevents kidney IGF-I accumulation and renal growth. Seven days of octreotide treatment initiated after 3, 5, 7 or 9 days of untreated diabetes was investigated. Diabetic renal hypertrophy was followed by renal hyperplasia. Compared with placebo-treated diabetic rats, the earliest octreotide intervention was followed by a greater reduction in renal growth compared with intervention later on (days 3 to 10, 12%; days 5 to 12, 10%; days 7 to 14, 9%; days 9 to 16, 6%; P < 0.05). Octreotide treatment was unable to reduce protein accumulation and kidney DNA increase consistently. No difference in glomerular volume fraction or total glomerular volume was observed between placebo- and octreotide-treated diabetic rats. Octreotide treatment was followed by reduced kidney and serum IGF-I especially following early intervention, while no effect over that of diabetes was observed in the later intervention periods. The results confirm the notion that initial renal IGF-I accumulation is a prerequisite for early diabetic kidney hypertrophy in rats and show that delayed octreotide treatment cannot reverse renal and glomerular growth which is already manifest.

Inhibition of renal ornithine decarboxylase activity fails to reduce kidney size and urinary albumin excretion in diabetic rats with manifest kidney hypertrophy

Formation of polyamines has previously been shown to play an important role for initial kidney growth in experimental diabetes, as treatment of diabetic rats with a selective ornithine decarboxylase (ODC) inhibitor, initiated immediately after diabetes induction, abolishes the initial kidney growth. In order to investigate the role of polyamine formation for the maintenance of diabetic kidney hypertrophy, ODC inhibition was initiated after manifest kidney hypertrophy had occurred. The kidney weight in diabetic rats was significantly larger than in control rats after a diabetes duration of 7, 14, 50 and 71 days and the total glomerular volume was increased in kidneys from diabetic rats after a diabetes duration of 71 days. Renal activity of ODC was increased in diabetic rats throughout the study period of 71 days. Treatment of diabetic rats with the selective ODC inhibitor di-fluoro-methyl-ornithine (DFMO) was maintained for two periods (days 7–14 and days 50–71). DFMO treatment had no effect on 24-h food consumption, blood glucose concentration or body weight. However, despite almost total inhibition of the kidney ODC activity, there was no effect on kidney growth or total glomerular volume in the DFMO treated diabetic rats compared to placebo treated diabetic rats. Finally, the urinary albumin excretion was markedly increased in diabetic rats with no effects of ODC-inhibition. In conclusion, inhibition of ODC initiated in diabetic rats with manifest kidney enlargement had no effect on renal size, glomerular volume or urinary albumin excretion. These findings together with our previous findings indicate that the role of polyamines in diabetic kidney enlargement is restricted to the first week after diabetes induction.

Prevention of glomerular hypertrophy and glomerulosclerosis in Milan normotensive rats by low-protein diet, but not by low-dose captopril treatment.

Milan normotensive rats, which spontaneously develop marked proteinuria (PU) and glomerulosclerosis (GS), were either kept on a normal-protein diet, a normal-protein diet with additional low-dose captopril (CAP), which did not affect blood pressure, or on a low-protein diet. After 8 months PU (79 +/- 25 mg/day) GS (3 +/- 2%) and total glomerular volume (TGV; 27.9 +/- 2.9 mm3/kidney) were significantly lower (p < 0.05) in the low-protein diet group than in both the normal-protein group (PU 583 +/- 210 mg/day, GS 12 +/- 5%, TGV 34.6 +/- 8 mm3/kidney) and the low-CAP group (PU 611 +/- 224 mg/day, GS 16 +/- 6%, TGV 41.8 +/- 8.6 mm3/kidney). In conclusion, the development of glomerular hypertrophy and GS in Milan normotensive rats was reduced by the low-protein diet, but not by low-CAP treatment.

Number and size of renal glomeruli in spontaneously hypertensive rats

A reduced number of nephrons, whether acquired or congenital, as has been observed in certain inbred rat strains, may lead to systemic hypertension. The present study estimated the total number of glomeruli and mean glomerular size in kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Unbiased stereological methods were used on immersion-fixed kidneys from 12-week-old male SHR (n = 9) and age-matched WKY rats (n = 11). The total number of glomeruli was significantly reduced in the SHR compared with in the WKY rats. Sclerotic glomeruli were not found in either group. No significant difference in mean glomerular volume was observed, but the total glomerular volume was reduced by 25% in the SHR compared with in the WKY rats. SHR have fewer glomeruli than WKY rats, but of similar size, resulting in a reduced total glomerular volume in adult SHR. These findings are consistent with the hypothesis that the kidney plays an important role in the pathogenesis of genetic hypertension.

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.

Development of the proximal tubule of the fetal rat kidney : Morphometry and ultrastructural findings

The development of the kidney in fetal rats was investigated morphometrically and ultrastructurally. Both the length and volume of the proximal tubule increased with age. The total volume of functional glomeruli increased markedly from fetal day 20 onward. The ratio of total glomerular volume to total proximal tubular volume decreased with age and was less than 1 from fetal day 20 onward. The cells of the proximal tubule had numerous microvilli on their free surfaces and vacuoles in the apical region of the cytoplasm after fetal day 20. These findings indicate that the relative growth of the proximal tubule has exceeded that of the glomeruli by fetal day 20, and that increased filtration induces both the growth and the differentiation of the proximal tubule during development of the fetal rat kidney.

Measurement of albumin reflection coefficient with isolated rat glomeruli.

Macromolecular permeability of the glomerular capillary has been inferred from the clearance of endogenous protein or infused macromolecules. Permeability is increased after treatment with polycations as well as after renal injury. It has previously been shown that the capillaries of glomeruli isolated from normal mammals expand or collapse in response to transcapillary albumin gradients and that the magnitude of the changes in capillary volume and in total glomerular volume are directly proportional to the applied oncotic gradients. In the experiments presented here, the volume responses of control glomeruli and of glomeruli treated with protamine (100 to 600 micrograms/mL for up to 60 min) were used to calculate the albumin reflection coefficient, sigma albumin, and the convectional permeability, P convectional albumin = (1 - sigma albumin), of the capillary wall. Sigma albumin for normal glomeruli was about 1 (P convectional albumin = 0); sigma albumin fell to a minimum of 0.2 +/- 0.1 (P convectional albumin = 0.8 +/- 0.1) after incubation with protamine sulfate (600 micrograms/mL) for 30 min. Retraction and fusion of podocyte foot processes and denudation of the underlying matrix was seen on scanning electron micrographs of protamine-treated glomeruli. These results confirm that it is possible to study macromolecular permeability of the glomerular capillary in vitro and to calculate sigma albumin independent of hemodynamic and systemic humoral influences. This method will permit the assessment of the effects of individual mediators of glomerular injury and the study of glomeruli from kidneys affected by experimentally induced or naturally occurring renal diseases.

Glomerular number and size in relation to age, kidney weight, and body surface in normal man.

The number and size of glomeruli in normal, mature human kidneys were estimated by a direct and unbiased stereological method, the fractionator. The number was 617,000 on average, and the mean size 6.0 M microns3. Both glomerular number and size showed significant negative correlation to age and significant positive correlation to kidney weight. Apparently, humans loose glomeruli with age. Body surface area correlated positively to kidney weight and total glomerular volume but not to number of glomeruli. Body surface area correlates significantly with metabolic rate (Robertson and Reid, Lancet, 1: 940-943, 1952). Thus, intraspecies adaptation of kidney filtration capacity to the metabolic demand is performed by changing the size of glomeruli, i.e., the number of glomeruli in individuals of a given species is independent of the metabolic rate.

Evaluation of projection patterns in the primary olfactory system of rainbow trout

Topographic projections are important for coding sensory information in the visual, auditory, and somatosensory systems but are of uncertain importance in the coding of olfactory information. We searched for topographic projections between olfactory receptor cells and the olfactory bulb of the rainbow trout Oncorhynchus mykiss. Anterograde axonal tracing with HRP revealed that the olfactory axons arising from discrete regions of the olfactory epithelium travel together within the olfactory nerve. The abrupt resorting and redistribution of these axons at the interface between the olfactory nerve and olfactory bulb imply that local cues control and organize axonal projections. The sites of termination of HRP-labeled axons in the glomerular layer could not be predicted from the location of their cell bodies in the periphery. Retrograde tracing with fluorescently labeled latex beads, injected into glomerular subregions as small as 1% of the total glomerular volume, labeled receptor cells dispersed throughout the olfactory epithelium. The distributions of labeled receptor cells were uncorrelated with the bulbar injection sites. Double-labeling experiments revealed that even widely separated sites in the glomerular layer receive axons from comingled populations of receptor cells. Hence, the evidence indicates that the spatial arrangement of olfactory receptor cells in the epithelium is not preserved in the termination of their axons in the olfactory bulb. We conclude that the primary olfactory in trout lacks point-to-point or regionally topographic organization and that the entire extent of the olfactory epithelium contributes axons to each region of the glomerular layer.

Effects of maternal bilateral ureteral ligation on the development of the proximal tubule of the kidney in fetal rats: Morphometry and electron microscopic study

Development of the proximal tubule in the fetal kidney was studied following ligation of both ureters of pregnant rats. The ligation was performed on days 15, 17, 19, and 21 of gestation and autopsy followed 24 hours after each operation. On fetal days 20 and 22, the proximal tubular length per unit volume (1 mm3) of whole kidney of the fetuses from the ligated mothers was significantly increased, while the ratio of total glomerular volume to total proximal tubular volume was remarkably decreased when compared to that of the fetuses from the non-ligated mothers. Apical vacuoles in proximal tubular cells were increased by the ligation on fetal days 20 and 22. These findings suggest that maternal bilateral ureteral ligation accelerates the growth and differentiation of the proximal tubule in fetal kidney, when the fetal kidney is functional in urine production.

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.