Different types of segmental sclerosing glomerular lesions in six experimental models of proteinuria

From 133 to 615 glomeruli were examined in sections of kidneys from each of 60 animals, representing six rodent models of proteinuria. Particular attention was paid to the position of segmental lesions. Lewis rats given sheep anti-rat glomerular basement membrane antibodies had lesions almost exclusively at the glomerulo-tubular junction. Wistar rats on a diet of 24 per cent casein or with subtotal nephrectomy and a diet of 24 per cent soya had lesions mainly at the hilum. Wistar rats given bovine serum albumin had global lesions but virtually no segmental lesions. Wistar rats given puromycin aminonucleoside had lesions at the glomerulo-tubular junction and global mesangial abnormalities shortly after the treatment but later developed segmental lesions at all parts of the glomerulus. Untreated BUF/Mna rats had lesions at the glomerulo-tubular junction early in life but later had lesions at all parts of the glomerulus. Untreated NZB/NZW hybrid mice had various types of glomerulonephritis and also had lesions at the glomerulo-tubular junction. These findings showed that (1) segmental lesions at the glomerulo-tubular junction, or glomerular tip, occur in experimental animals, a fact not previously reported, and these tip changes are a common feature in several different models of proteinuria; (2) hilar segmental lesions are seen in conditions with hyperfiltration of protein; and (3) segmental lesions at various parts of the glomerulus are seen in some models of proteinuria and probably indicate late effects of random toxic damage to the glomerulus. Thus, there are at least three different types of segmental glomerular lesions in experimental animals--tip, hilar, and random--with different morphology and pathogenesis. It is likely that these findings can be extended to human renal diseases with segmental glomerular lesions. This will help to clarify the controversial and unsatisfactory term focal segmental glomerulosclerosis.     

Glomerular sclerosis in Wistar rats: analysis of its variable occurrence after unilateral nephrectomy.

Individual differences in susceptibility to the development of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) were studied in rats after unilateral nephrectomy. A total of 20 male Wistar rats underwent unilateral nephrectomy at 3 months of age. Glomerular number in the removed kidney ranged from 17,000 to 32,700 with a mean value of 25,997 (n = 19). At death 30 weeks later, the incidence of glomeruli with FSGHS in the remaining kidney varied from 0 to 20% with a mean of 4.4%. However, the percentage of glomeruli with FSGHS and the degree of proteinuria did not correlate either with glomerular number per kidney (left and right kidneys were shown to be equivalent for glomerular number) or with glomerular volume on killing. The occurrence of FSGHS correlated significantly with mean protein excretion (P less than 0.01) and serum cholesterol levels (P less than 0.01). In conclusion, in the rat a relatively low number of nephrons in the kidneys does not increase susceptibility to the development of FSGHS.     

Glomerular sclerosis in Wistar rats: analysis of its variable occurrence after unilateral nephrectomy

Individual differences in susceptibility to the development of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) were studied in rats after unilateral nephrectomy. A total of 20 male Wistar rats underwent unilateral nephrectomy at 3 months of age. Glomerular number in the removed kidney ranged from 17,000 to 32,700 with a mean value of 25,997 (n = 19). At death 30 weeks later, the incidence of glomeruli with FSGHS in the remaining kidney varied from 0 to 20% with a mean of 4.4%. However, the percentage of glomeruli with FSGHS and the degree of proteinuria did not correlate either with glomerular number per kidney (left and right kidneys were shown to be equivalent for glomerular number) or with glomerular volume on killing. The occurrence of FSGHS correlated significantly with mean protein excretion (P less than 0.01) and serum cholesterol levels (P less than 0.01). In conclusion, in the rat a relatively low number of nephrons in the kidneys does not increase susceptibility to the development of FSGHS.     

The effects of hyperfiltration on serum sickness glomerulonephritis in rats

The effects of hyperfiltration induced due to unilateral nephrectomy on immunologically induced glomerular injuries were studied. Glomerulonephritis was induced in rats by sensitizing them with egg albumin as an antigen. Unilateral nephrectomy did not affect the removal rate of the antigen from the glomeruli in the rats, but accelerated the rate of the glomerular injuries after cessation of the immunologically induced glomerular inflammation. The histopathological features were characterized by sclero-adhesive lesions with aneurysmal dilatation and hyalinosis of the glomerular capillaries. The parietal epithelial cells extended from the Bowman's capsule with matrices to cover the denuded basement membrane and formed adhesions. The neighboring capillaries collapsed, and the sclero-adhesive lesions progressed. These findings indicate that hyperfiltration at the capillary level did not accelerate the recovery from glomerulonephritis, but induced glomerular sclerosis with adhesions and deteriorated the trivial glomerular injuries to produce similar focal segmental lesions.     

The Effects of Hyperfiltration on Serum Sickness Glomerulonephritis in Rats

The effects of hyperfiltration induced due to unilateral nephrectomy on immunologically induced glomerular injuries were studied. Glomerulonephritis was induced in rats by sensitizing them with egg albumin as an antigen. Unilateral nephrectomy did not affect the removal rate of the antigen from the glomeruli in the rats, but accelerated the rate of the glomerular injuries after cessation of the immunologically induced glomerular inflammation. The histopathological features were characterized by sciero-adhesive lesions with aneurysmal dilatation and hyalinosis of the glomerular capillaries. The parietal epithelial cells extended from the Bowman's capsule with matrices to cover the denuded basement membrane and formed adhesions. The neighboring capillaries collapsed, and the sclero-adhesive lesions progressed. These findings indicate that hyperfiltration at the capillary level did not accelerate the recovery from glomerulonephritis, but induced glomerular sclerosis with adhesions and deteriorated the trivial glomerular injuries to produce similar focal segmental lesions.     

Mesangial lesions and focal glomerular sclerosis in the aging rat.

The pathogenesis of focal glomerular sclerosis (FGS) and its relation to proteinuria and idiopathic nephrotic syndrome are unknown. Urine protein excretion in Sprague-Dawley rats increased with age. Fifty per cent of 12-month and 90 per cent of 24-month-old animals were proteinuric (greater than 20 mg. per day). Heavily proteinuric old rats manifested biochemical changes characteristic of nephrotic syndrome without significant loss of renal function. Three-month, 6-month, and nonproteinuric 12-month-old animals had mesangial deposits of IgM in occasional lobules of some glomeruli and slight mesangial hyperplasia. Four proteinuric 12-month-old rats had diffuse 4+ deposits of IgM in the mesangium of most glomeruli, basement membrane thickening and epithelial cell foot process fusion without FGS. The mesangial IgM deposits eluted in acid buffer and did not fix complement. Six proteinuric 12-month-old rats had focal and segmental areas of glomerular sclerosis with adhesions to Bowman's capsule, foamy cells, intraluminal eosinophilic deposits and capillary wall wrinkling and collapse. These lesions were more advanced in 24-month-old animals. Nonproteinuric 24-month-old rats did not have detectable FGS. Mesangial uptake of colloidal carbon was normal in proteinuric and nonproteinuric animals without FGS. Mesangial uptake of colloidal carbon was normal in proteinuric and nonproteinuric animals without FGS and reduced in proteinuric animals with FGS. In the aging rat the development of proteinuria and mesangial IgM deposition apparently precede development of a focal sclerotic glomerular lesion with histologic and ultrastructural features similar to FGS in man. The generalized impairment of mesangial phagocytic function in proteinuric rats with FGS suggests that this lesion may result from mesangial overload and dysfunction consequent to the persistent increase in glomerular permeability and proteinuria.     

Ultrastructural studies of the mouse aorta and its endothelial pinocytosis in diet-induced arteriosclerosis

In mice fed on an atherogenic diet for 4 to 8 months, the aortas were examined by transmission and scanning electron microscopy. After 8 months of being fed a high cholesterol diet, the animals developed aortic intimal lesions composed mainly of proliferated modified smooth muscle cells with an increase of connective tissues. Scanning electron microscopy showed changes in aortic luminal surface consisting primarily of altered distribution of microvilli. Quantitative analysis of these changes showed a statistically significant (P less than 0.001) increase in cholesterol-fed animals compared with controls and a significant (P less than 0.001) difference between at 4 months and at 8 months in cholesterol-fed mice. Ultrastructural study on the uptake of protein tracer, horseradish peroxidase (HRP), by aortic endothelial cells in vitro was performed. The uptake of HRP was essentially the same for controls and cholesterol-fed mice at 4 months, but a statistically significant (P less than 0.005) increased uptake of HRP was observed at 8 months. Additional mice were subjected to nephrectomy with DOCA administration for 4 months along with a cholesterol-feeding. These animals showed a 2-fold increase in HRP-uptake compared with nephrectomized mice without a cholesterol-feeding. These results suggest that the enhanced pinocytotic activity of aortic endothelial cells in vitro, especially in hypertensive condition, and altered distribution of microvilli might be correlated to the arteriosclerotic process.     

ULTRASTRUCTURAL STUDIES OF THE MOUSE AORTA AND ITS ENDOTHELIAL PINOCYTOSIS IN DIETINDUCED ARTERIOSCLEROSIS

In mice fed on an atherogenic diet for 4 to 8 months, the aortas were examined by transmission and scanning electron microscopy. After 8 months of being fed a high cholesterol diet, the animals developed aortic intimal lesions composed mainly of proliferated modified smooth muscle cells with an increase of connective tissues. Scanning electron microscopy showed changes in aortic luminal surface consisting primarily of altered distribition of microvilli. Quantitative analysis of these changes showed a statistically significant (P<0.001) increase in cholesterol-fed animals compared with controls and a significant (P<0.001) difference between at 4 months and at 8 months in cholesterol-fed mice. Ultrastructural study on the uptake of protein tracer, horseradish peroxidase (HRP), by aortic endothelial cells in vitro was performed. The uptake of HRP was essentially the same for controls and cholesterol-fed mice at 4 months, but a statistically significant (P<0.005) increased uptake of HRP was observed at 8 months. Additional mice were subjected to nephrectomy with DOCA administration for 4 months along with a cholesterol-feeding. These animals showed a 2-fold increase in HRP-uptake compared with nephrectomized mice without a cholesterol-feeding. These results suggest that the enhanced pinocytotic activity of aortic endothelial cells in vitro , especially in hypertensive condition, and altered distribution of microvilli might be correlated to the arteriosclerotic process.     

内源性睾酮在雄性高脂血症大鼠早期动脉粥样硬化形成中的作用

目的：研究内源性睾酮对雄性高脂血症大鼠早期动脉粥样硬化形成的影响及其作用机制。方法：雄性Ｗｉｓｔａｒ大鼠随机均分为正常对照组,高脂对照组,高脂去势组（切除双侧睾丸及副睾）。实验时间１２周。结果：高脂去势组与高脂对照组相比,血浆总胆固醇（ＴＣ）,甘油三酯（ＴＧ）浓度相差不明显,低密度脂蛋白（ＨＤＬ）水平较高,低密度脂蛋白（ＬＤＬ）＋极低密度脂蛋白（ＶＬＤＬ）水平较低,血浆脂质过氧化物（ＬＰＯ）水平较     

Induction of glomerulosclerosis by dietary lipids. A functional and morphologic study in the rat

Clinical and experimental data indicate that glomerular function and morphology may be influenced by plasma lipids. In familial lecithin-cholesterol-acyltransferase (LCAT) deficiency and in Fabry's disease, lipids accumulate in glomeruli and are assumed to induce sclerosis. The present study was undertaken to examine if dietary lipids could exert effects on the glomeruli of normal, unilaterally nephrectomized rats, and of rats with two-kidney, one clip (2-K,1C) hypertension. In rats with two kidneys on a diet rich in fat and cholesterol, cholesterol concentrations in very low density lipoproteins increased. In these rats the number of glomeruli with sclerotic foci was significantly higher than in rats on a low fat, cholesterol free diet. After 6 months on the diet the percentage of glomeruli with sclerosis (SC) was 13.2 +/- 4.1 (N = 9) in rats with a cholesterol diet and 1.8 +/- 0.6 (N = 11) in control rats (p less than 0.05). The fat and cholesterol diet exacerbated glomerular lesions in the remnant kidney model of uninephrectomized rats. The sclerosis in rats with only one kidney was 38.2 +/- 9.5 (N = 6) on a cholesterol diet compared with 8.7 +/- 3.0 (N = 6) in control rats after 6 months (p less than 0.05). After 3 to 4 months on a fat rich diet cholesterylester was increased in isolated glomeruli. The composition of the dietary lipids influenced the development of glomerular lesions. A linseed oil diet that is rich in unsaturated fatty acids, especially linolenic acid, did not cause major plasma lipid abnormalities and was accompanied by a low sclerosis (1.2 +/- 0.3; N = 9) for rats with two kidneys. In rats with chronic 2-K, 1C hypertension the percentage of glomeruli with partially sclerosed tufts in the unclipped kidney was significantly higher on a fat and cholesterol diet (F) than on a control diet (N) (SC: diet F 31.0 +/- 4.0, N = 13; diet N 12.2 +/- 2.6, N = 12; P less than 0.05). In the clipped kidney, protected against the arterial hypertension, only an increased number of glomeruli with mesangial expansion was noted in rats with the cholesterol diet. Glomerular hemodynamic factors seem to play an important pathogenetic role in the induction of glomerular sclerosis by a lipid rich diet. The fact that dietary lipids can aggravate glomerular lesions in states of arterial hypertension and nephron loss may have implications for the progression of renal disease in humans.     

Up-regulation of macrophage colony-stimulating factor (M-CSF) and migration inhibitory factor (MIF) expression and monocyte recruitment during lipid-induced glomerular injury in the exogenous hypercholesterolaemic (ExHC) rat

Although macrophages play an important role in lipid-induced glomerular injury, we know little of the mechanisms by which hyperlipidaemia induces monocyte recruitment. This study investigated the role of M-CSF and macrophage MIF in monocyte recruitment during the development of lipid-induced glomerular injury in the susceptible ExHC rat strain. Groups of five ExHC rats were fed a high cholesterol diet (HCD) containing 3% cholesterol, 0.6% sodium cholate and 15% olive oil, and killed after 3 days, 1, 2 or 6 weeks. Control animals were killed on day 0 or after 6 weeks on a normal diet. Animals were hypercholesterolaemic 3 days after the induction of the HCD, but showed no change in plasma triglycerides over the 6-week period. Glomerular macrophage accumulation was first evident at 1–2 weeks and increased up to week 6, when macrophage-derived foam cells were seen in almost all glomeruli, and segmental lesions and mild proteinuria were also evident. Combined in situhybridization and immunohistochemistry staining demonstrated that, coincident with the induction of hypercholesterolaemia on day 3, there was marked up-regulation of M-CSF and MIF mRNA expression by intrinsic glomerular cells (mostly mesangial cells and podocytes) which preceded monocyte recruitment. There was a highly significant correlation between the number of M-CSF and MIF-positive cells and glomerular macrophage accumulation over the 6-week period. Although some glomerular macrophages and foam cells exhibited M-CSF and MIF expression, the major source of these molecules was intrinsic glomerular cells. No local macrophage proliferation was observed during the development of glomerular lesions. In conclusion, hypercholesterolaemia caused marked up-regulation of M-CSF and MIF expression by intrinsic glomerular cells, which correlated with monocyte recruitment and the development of lipid-induced glomerular injury. This is the first study to implicate local synthesis of MIF in the pathogenesis of lipid-induced lesions.     

Focal segmental glomerular hyalinosis and/or sclerosis in rats with congenital unilateral hydronephrosis.

Focal segmental glomerular hyalinosis and/or sclerosis (FSHS) was observed in five Wistar-Imamichi rats with congenital unilateral hydronephrosis (CUH rats). Marked proteinuria (164.9 +/- 138.4 mg/day) was observed in the CUH rats. Immunoperoxidase staining for IgM, C3 and IgG was positive in the glomeruli, showing in a focal, segmental pattern that corresponded to the areas of FSHS seen by light microscopy. These glomerular findings were extremely similar to those of human focal glomerular sclerosis (FGS). FSHS was found to be common to both the hydronephrotic kidney and the contralateral kidney without hydronephrosis. Morphometry revealed that the glomerular area of the juxtamedullary glomeruli was greater than that of superficial glomeruli in control rats (11,037 micron2 vs. 6,847 microns2). On the other hand, glomerular hypertrophy was observed in non-sclerotic glomeruli of CUH rats (superficial glomeruli; 12,477-16,123 microns2, juxtamedullary glomeruli; 14,635-18,418 microns2). Also, a decreased in the number of glomeruli within the range 1.8-4.1 per unit area (1 mm2) was seen in CUH rats compared with control rats (mean 4.4). These results suggest that the increased rate of development of FSHS is based on hyperfiltration in the remaining functional nephrons.     

Number of glomeruli in normal and hypertrophied kidneys of mice and guinea-pigs.

1. In mice and guinea-pigs, the number of glomeruli was counted in kidneys during normal growth and in hypertrophy induced by unilateral nephrectomy. 2. In mice, the number of glomeruli increased sharply during the first 2 weeks in life, and more slowly afterwards. Unilateral nephrectomy, when performed during this period of natural increase, induced the formation of supplementary nephrons in the contralateral kidney. 3. In guinea-pigs, the number of glomeruli was almost complete at birth. No evidence of a supplementary increase in the number of nephrons was found in hypertrophied kidneys following unilateral nephrectomy. 4. These results, together wit previous data obtained in the rat, suggest that the ability to induce new nephrons after unilateral nephrectomy in different species would depend more on the state of kidney maturity at birth than on differences in the renal mechanisms which lead to hypertrophy.     

Relationship of dietary intake to the development of glomerulosclerosis in obese Zucker rats

Obese Zucker rats are hyperphagic and develop premature glomerulosclerosis. The purpose of this study was to find out the effects of restriction of dietary intake on this glomerulosclerosis. The obese and lean male Zucker rats were fed with restricted amounts of balanced diet for periods of 40 and 50 weeks, sacrificed, and the body weight, the light and ultrastructural alterations of glomeruli, and the serum levels of blood urea nitrogen, triglyceride, and cholesterol were examined. Obese and lean male rats of identical ages were fed ad libitum with the diet and studied similarly. The dietary restriction significantly lessened the development of the glomerulosclerosis in obese rats, while those on the nonrestricted diet manifested an advanced glomerulosclerosis. The dietary restriction, however, did not normalize the obesity nor correct the elevated serum lipid level to the range of lean control rats. The spontaneous glomerular lesions of the obese rats were characterized by segmental mesangial expansion, disappearance of podocytes and endothelia, and obliteration of capillary lumina. The lean rats maintained essentially normal renal morphology. A similar study on the renal morphology done in female Zucker rats also revealed a preventive effect of dietary restriction on the development of glomerulosclerosis. In conclusion, there is a strong association between the glomerulosclerosis and the hyperphagia of the obese Zucker rats, both in males and females, and the emergence of this lesion is preventable to a significant degree.     

Experimental canine atherosclerosis and its prevention. The dietary induction of severe coronary, cerebral, aortic, and iliac atherosclerosis and its prevention by safflower oil.

Severe atherosclerotic lesions were produced without thyroid suppression in seven out of eight dogs by feeding semisynthetic diets containing 5 per cent cholesterol and 16 per cent hydrogenated coconut oil for 12 to 14 months. Occlusive plaques were located in the coronary arteries and major cerebral arteries as well as in the aorta and iliac vessels. The lesions were characterized by an intense sclerotic reaction to areas of lipid deposition and foam cell accumulation in the intima. The diet induced a rapid elevation of plasma-free and esterfied cholesterol, triglyceride, and phospholipid, and the extent of aortic atherosclerosis was shown to be partially dependent on mean plasma cholesterol concentration. A second group of eight dogs were fed a diet identical with the first except for the replacement of 4 per cent hydrogenated coconut oil by 4 per cent safflower oil. Despite receiving the same amounts of dietary cholesterol and fat, this second group of dogs was completely protected from the atherogenic process. Plasma lipids became only slightly elevated and no induced atherosclerotic lesions were found at autopsy. Circulating thyroid hormone concentrations were similar between the two groups of dogs and the thyroid glands had a normal morphology in both groups.     

Spontaneous hypertension and hypertensive renal disease in the fawn-hooded rat.

The fawn-hooded (FH) rat, a strain characterized by a platelet storage-pool disease, developed focal and segmental glomerulosclerosis at the age of 2-3 months (males) and approximately 6 months (females). Male animals died spontaneously at 11-13 months, and females at 15 months of age, both with overt malignant nephrosclerosis. During the first half year of life focal glomeruli showed depositions of IgG, IgA, IgM, C3 and fibrinogen in a segmental pattern and mainly in mesangial areas. Mesangial IgG and IgA were already demonstrable at the age of 5 weeks. On electron microscopy no electron-dense deposits suggestive of immune complexes were found. Mean arterial blood pressure in 5.5-month-old male FH rats was increased compared with that of matched Wistar rats. One-year-old FH rats had severe hypertension. The presumed relationship between the hypertension, the renal lesions and the blood platelet defect is discussed.     

Spontaneous hypertension and hypertensive renal disease in the fawn-hooded rat

The fawn-hooded (FH) rat, a strain characterized by a platelet storage-pool disease, developed focal and segmental glomerulosclerosis at the age of 2-3 months (males) and approximately 6 months (females). Male animals died spontaneously at 11-13 months, and females at 15 months of age, both with overt malignant nephrosclerosis. During the first half year of life focal glomeruli showed depositions of IgG, IgA, IgM, C3 and fibrinogen in a segmental pattern and mainly in mesangial areas. Mesangial IgG and IgA were already demonstrable at the age of 5 weeks. On electron microscopy no electron-dense deposits suggestive of immune complexes were found. Mean arterial blood pressure in 5.5-month-old male FH rats was increased compared with that of matched Wistar rats. One-year-old FH rats had severe hypertension. The presumed relationship between the hypertension, the renal lesions and the blood platelet defect is discussed.     

The effects of coadministration of dietary copper and zinc supplements on atherosclerosis, antioxidant enzymes and indices of lipid peroxidation in the cholesterol-fed rabbit

It has previously been shown that dietary copper can modulate the extent of atherosclerosis in the thoracic aorta of cholesterol-fed rabbits. The metabolism of copper and zinc are closely related, and it has been hypothesized that the balance of dietary copper to zinc may be important in determining coronary risk. Hence, we have investigated the interaction between dietary copper and zinc in atherogenesis in the New Zealand White rabbit. Juvenile male rabbits were randomly allocated to eight groups. Four groups were fed a normal chow diet with zinc (0.5%, w/w), copper (0.2%, w/w), copper plus zinc or neither in their drinking water for 12 weeks. Four other groups were fed a diet containing 0.25-1% (w/w) cholesterol plus zinc, copper, both or neither. Serum cholesterol of individual animals was maintained at approximately 20 mmol/l. Integrated plasma cholesterol levels were similar for all groups receiving cholesterol and significantly higher than those in the chow-fed groups (P < 0.001). Aortic copper concentrations were higher in the animals receiving cholesterol diets with copper compared to rabbits receiving normal chow and copper (P < 0.001). Aortic zinc content was significantly higher in cholesterol-fed rabbits supplemented with zinc alone or with copper than in those fed cholesterol alone (P < 0.001). Plasma ceruloplasmin concentrations were significantly higher in groups receiving cholesterol, irrespective of their trace element supplementation (P < 0.001). However, trace element supplementation increased the level significantly (P < 0.05). Trace element supplements did not appear to affect erythrocyte superoxide dismutase in the cholesterol-fed animals; however, zinc supplementation was associated with a significant increase in the enzyme in chow-fed animals (P < 0.05). The activity of the enzyme per mg of protein in aortic tissue was higher in animals receiving copper in the presence of cholesterol (P < 0.05) but not significantly so in its absence. Dietary trace element supplementation in cholesterol-fed animals was associated with a significant reduction in aortic lesion area. Plasma thiobarbituric acid-reactive substances and FOX concentrations were both significantly higher in the cholesterol-fed rabbits compared with the animals that fed on a chow diet (P < 0.001), and these were reduced significantly by dietary copper or zinc supplementation (P < 0.001). Hence, dietary supplements of copper or zinc at the doses used both inhibited aortic atherogenesis in the cholesterol-fed rabbits, although there was no significant additional effect when given in combination.     

Focal Segmental Glomerular Hyalinosis and/or Sclerosis in Rats with Congenital Unilateral Hydronephrosis

Focal segmental glomerular hyalinosis and/or sclerosis (FSHS) was observed in five Wistar-Imamichi rats with congenital unilateral hydronephrosis (CUH rats). Marked proteinuria (164.9+138.4mg/day) was observed in the CUH rats. Immunoperoxidase staining for IgM, C3 and IgG was positive in the glomerull, showing in a focal, segmental pattern that corresponded to the areas of FSHS seen by light microscopy. These glomerular findings were extremely similar to those of human focal glomerular sclerosis (FGS). FSHS was found to be common to both the hydronephrotic kidney and the contralateral kidney without hydronephrosis. Morphometry revealed that the glomerular area of the juxtamedullary glomeruli was greater than that of superficial glomeruli in control rats (11,037 μm² vs. 6,847 μm²). On the other hand, glomerular hypertrophy was observed in non-sclerotic glomeruli of CUH rats (superficial glomeruli; 12,477–16,123 μm², juxtamedullary glomeruli; 14,635–18,418 μm²). Also, a decreased in the number of glomeruli within the range 1.8-4.1 per unit area (1 mm²) was seen in CUH rats compared with control rats (mean 4.4). These results suggest that the increased rate of development of FSHS is based on hyperfiltration in the remaining functional nephrons. Acta Pathol Jpn 41: 653–660, 1991.     

Genesis of pulmonary foam cells in rats with diet-induced hyper beta-lipoproteinaemia

Hyper beta-lipoproteinaemia in rats was produced by feeding a standard diet to which was added excess cholesterol and cholic acid, with or without olive oil, for 4, 8, and 12 weeks. The beta-lipoprotein percentage in serum lipoprotein electrophoresis and lipid contents in very low density lipoprotein and low density lipoprotein fractions in these rats were significantly higher than in the control rats fed the standard diet only. The percentage of foamy monocytes (FMs) to the total number of blood monocytes (BMs) from mononuclear leucocyte fractions and percentage of pulmonary foam cells (PFCs) to the number of alveolar macrophages (AMs) from bronchopulmonary lavage fluids in the rats increased with the extension of the feeding period and were significantly higher than those in the controls. An increase in the percentage of PFCs was closely correlated with that of FMs in the rats. FMs and PFCs had cytoplasmic fine vacuoles proved to be neutral lipid and cholesterol. Histologically, PFCs made an appearance in the lungs of all the rats as early as 4 weeks after the start of feeding. The degree of the PFCs' development increased as the feeding period lengthened. When latex particles were injected intravenously into rats at feeding week 4, the percentage of latex-ingested AMs to the number of AMs in the rats was significantly higher than that of the controls at 4 and 8 days post-injection. The percentage of latex-ingested PFCs to the number of latex-ingested AMs increased with the lapse of a day after injection and was significantly higher than that of the controls at 2, 4, and 8 days post-injection. The present findings suggest that the foamy transformation of BMs and their migration into the pulmonary alveoli may be a potential mechanism of the PFCs' development in rats with hyper beta-lipoproteinaemia.