Intracytoplasmic giant cross-striated fibrils in giant cell fibroblastoma.
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Biomedical subjects
Publications and source records attributed to A H Yang.
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Hepatic arteritis is a rare complication in systemic lupus erythematosus (SLE). Information about its clinical manifestations is still very limited. Elevated serum r-glutamyl transpeptidase and alkaline phosphatase levels, but without elevated bilirubin and transaminase levels, were found in the present report to be the clinical presentation of hepatic arteritis. This clinical picture originally suggested a disease of the biliary tree. Hepatic arteritis must be included in the differential diagnosis of biliary tract disorders in SLE.
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We report a 20-year-old female with severe hypertension, hypokalemia, hyperaldosteronism and elevated level of plasma renin activity (PRA). The clinical diagnosis of renin secreting tumor of left kidney was made before surgery by the lateralization of plasma renin activity via selective renal venous blood sampling and CT scan of kidney. Prompt normalization of blood pressure and decrease of PRA and aldosterone levels were found after surgical removal of the tumor. The pathological findings showed a juxtaglomerular cell tumor.
The effect of cyclosporin (CS) on intrinsic glomerular level of antioxidants in puromycin aminonucleoside (PAN) nephrosis was examined. A single intravenous dose of PAN (50 mg/kg body weight) given to Sprague-Dawley rats resulted in marked proteinuria. Ten days after PAN injection, the rats were treated with daily intraperitoneal injection of CS (10 mg/kg body weight/day) for 10 days. PAN-treated rats without CS treatment (PAN rats) had significantly lower activities of glomerular superoxide dismutase (SOD) and catalase (CAT) than normal rats (p < 0.05, respectively). When compared with PAN rats, CS-treated PAN rats had significantly less proteinuria and higher activities of glomerular SOD and CAT (p < 0.01 and p < 0.05, respectively). Significant elevation of glomerular malondialdehyde (MDA) level characteristic of PAN rats was absent in CS-treated PAN rats. Moreover, segmental sclerosis with capsular adhesion, hyalinosis, epithelial cell foot process fusion and microvillous transformation seen in PAN rats were apparently attenuated in CS-treated PAN rats. When compared with normal rats, rats receiving CS only had a significantly higher CAT activity and MDA level (p < 0.01 and p < 0.05, respectively). Assessment of glomerular reduced glutathione revealed no significant differences among PAN rats, CS-treated PAN rats, normal rats, and rats receiving only CS. These data indicate that glomerular antioxidant enzyme activities are modulated by CS.
Cystic partially differentiated nephroblastoma is a rare neoplasm occurring mainly in children with distinctive pathological features set between those of classic nephroblastoma and multilocular cysts. The amount of its constituent components including blastema, stroma and epithelium varies greatly. It shows a spectrum of differentiation pattern indicating the possibility of maturation of Wilms' tumor. We present a case with typical features of cystic partially differentiated nephroblastoma with a brief review of literature.
Silver-binding nucleolar organizer region (AgNOR) and nuclear grade were histologically assessed in 112 renal cell carcinomas. Nuclear grade was better capable of stratification than AgNOR in terms of survival prediction. It also had prognostic significance when total metastatic rates were evaluated. Although higher mean AgNOR numbers were constantly associated with higher nuclear grades, two arbitrary classifications of AgNOR (less than 1.5, 1.5-3.5, greater than 3.5; less than 2, 2-3, greater than 3) failed to resolve the survival difference.
Tailgut cyst, an unusual presacral lesion, is lined by a variety of epithelial types including squamous, columnar, transitional and cuboidal epithelium. Disorganized fascicles of smooth muscle may be seen in the cystic wall. Tailgut cysts are usually multiloculated, and often afflict adult women. In rare cases, adenocarcinoma arises within the tailgut cyst. We present a carcinoid tumor developing from the tailgut cyst. The tumor cells grow in ribbon and festoon patterns and are positive for argyrophilic granules. Immunostains for neuron-specific enolase are also positive. Ultrastructurally, dense-core, membrane-bounded neurosecretory granules are present.
Rat glomerular cells were grown either in or on fibrin clots prepared from rat plasma to assess the effect of native fibrin on the growth of glomerular epithelial and mesangial cells. Progressive fibrinolysis was observed in glomerular explant cultures without epsilon-aminocaproic acid (EACA), an inhibitor of plasminogen activation. The lytic areas extended as the cell number of glomerular explant outgrowths increased. Glomerular cultures containing 0.5% EACA showed complete inhibition of fibrinolysis. Under this condition, the glomerular outgrowths developed only when the glomerular explants were seeded on the surface of fibrin matrix. While the explants were embedded in the fibrin matrix, few cells could grow out of explants. The more prosperous growth of glomerular epithelial cells in the lytic areas and the lack of intimate binding of glomerular epithelial cell membrane with fibrin fibers implied that fibrin might hinder the outgrowth of glomerular epithelial cells. The mesangial cells, whether growing on the surface of or embedded in the fibrin matrix, showed no fibrinolytic activity. Inhibition of fibrinolysis did not alter the growth pattern of mesangial cells. In addition, mesangial cells exhibited extensive binding of fibrin fibers on their cell surface and developed conspicuous arborization of their cell processes. These features suggested a close affinity between mesangial cells and fibrin matrix. These experiments have addressed our attention to the particular roles of the visceral epithelial cells and mesangial cells in the pathogenesis of fibrin-related glomerulonephritis.
Twenty-one consecutive cases of gastrointestinal spindle cell stromal tumors (SCSTs) were studied histologically and immunohistochemically. They consisted of 18 smooth muscle tumors, 2 neurilemmomas (schwannomas), and 1 unclassified malignant tumor designated as stromal sarcoma. Slender, spindle and wavy nuclei with palisading associated with peripheral tumor aggregation of lymphocytes are the pathological hallmarks of neurilemmoma. With peroxidase-antiperoxidase method, antibodies to Glial Fibrillary Acidic Protein (GFAP), Leu-7, S-100, desmin and HHF35 were applied. Antibodies to Leu-7 and GFAP could only be demonstrated in neurilemmomas (2 cases). Antibody to S-100 was observed strongly in 2 neurilemmomas and 1 stromal sarcoma, and focally in a leiomyoma, while the other SCSTs were negative. One neurilemmoma disclosed focal positivity of desmin. Six of 10 leiomyomas revealed varied degrees of positive staining of desmin and HHF35. One epithelioid leiomyoma, two leiomyosarcomas and five smooth muscle tumors of undetermined malignant potential (STUMP) disclosed no immunoreactivity. The study suggests that panel of immunostaining should be applied. Coexpression of GFAP, Leu-7 and S-100 as well as negative staining of HHF35 is characteristic of neurilemmoma. On the contrary, coexpression of desmin and HHF35 while negative for GFAP, S-100 and Leu-7 are suggestive of smooth muscle tumor. In poorly differentiated SCST, histological features and immunostains are always disappointing. Diagnosis of those tumors as stromal tumor is more appropriate or electron microscopic observation should be included for accurate classification.
Malignant haemangiopericytoma was grown in vitro to assess the histogenesis of the tumour. Disaggregated tumour cells maintained in serum-supplemented Waymouth's MB 752/1 medium showed monolayers of homogeneous spindle cells. Post-confluent cultures exhibited hillocks or plaques of multilayer growth within which considerable amount of basal lamina-like material and fibrillar matrix were present between cells. Delicate basal laminae were also expressed on cell surfaces facing matrix material. Other consistent features were attenuated cytoplasmic processes, desmosome-like junctions, abnormal mitochondria and a paucity of intracellular filaments. The three-dimensional organization of tumour cells with concomitant expression of differentiated phenotype in vitro has significant implications on the cell of origin and differentiation process of haemangiopericytoma.
The invasive properties of human renal cell carcinoma were tested on a gel-like reconstituted basement membrane matrix extracted from Engelbreth-Holm-Swarm transplantable mouse tumor (Matrigel). Both high-grade (Fuhrmans's nuclear grade III) and low-grade (Fuhrman's nuclear grade I) renal carcinoma cells as well as normal human renal tubular cells were seeded onto a thin-layered, full-strength gel (1-2 mm). The normal tubular cells migrated to form small irregular colonies interconnected by polygonal networks of cell cords and grew along the surface contour of the gel. No evidence of distortion, dissolution, or invasion of underlying gel was observed but a thin layer of electron dense lamina was found to form underneath the cells. The noninvasive morphology was observed to have lasted for more than 3 weeks. On the contrary, both low-grade and high-grade carcinoma cells formed individual colonies and invaded the underlying matrix by developing invasion buds and subsequently cords or tubule-like structures of variable length. No basement-membrane-like electron dense deposit was observed at the cell-matrix interface. The observation that the mean invasion depth was higher in high nuclear grade carcinoma has significant implications on the association between invasiveness and nuclear grade. The findings that cancer cells closely contacted the surrounding matrix and reorganized the matrix in the immediate vicinity provided additional evidence of cell-matrix interaction.
The activities of three antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase, were monitored in isolated guinea pig glomeruli and primary or subcultured glomerular epithelial cells. Cell injury was assessed by morphologic studies and by measurement of cellular lipid peroxidation (levels of malondialdehyde). Antioxidant enzyme activities were very different in cultured cells than in parent glomeruli. The possible effect of culture substrates (tissue culture plastic, bovine corneal endothelial [BCE] cell basement membrane, and PF-HR-9 endodermal cell basement membrane) on antioxidant enzyme status, cell morphology, and lipid peroxidation was also assessed. Glomerular epithelial cells cultured on the BCE cell basement membrane substrate survived longer and showed less lipid peroxidation than cells cultured on plastic or the HR-9 substrate. Cells cultured on a plastic substrate had substantially less glutathione peroxidase activity than cells cultured on either BCE or HR-9 basement membranes.
The activities of three antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase, were monitored in isolated human renal adenocarcinoma tissues and in cultured human renal adenocarcinoma cells. The results were compared to the activities of these enzymes in the proposed cell of origin, isolated human proximal tubular tissues, and cultured proximal tubular epithelial cells. Strong modulation of these enzymes by culture conditions was observed in normal cells but not in carcinoma cells. Low levels of cellular lipid peroxidation, as assessed by levels of malondialdehyde (MDA), were observed in adenocarcinoma cells under the culture conditions tested with one exception: greatly elevated MDA was observed in renal adenocarcinoma cells grown on plastic in serum-free, chemically defined medium. This increased lipid peroxidation correlated with a loss of cell viability under these conditions.
Kidney cortical tubular cells, mainly proximal tubular cells, isolated from human kidney and grown either on a basement membrane substrate in chemically defined medium or on plastic in serum-supplemented medium, had substantial proliferative potential and could be propagated for more than 10 generations or 8 passages before senescence. Basement membrane produced on a plastic substrate by the HR-9 endodermal cell line could replace serum supplementation in promoting tubular cell growth. Tubular cells grown on an HR-9 basement membrane substrate exhibited stable epithelial morphology over an extended period of time; in the presence of 5% serum they differentiated into organized structures such as hemicysts and cell cords. Cells grown on plastic failed to differentiate and gradually degenerated. Tubular cells on HR-9 basement membrane were characterized by densely packed microvilli, abundant rough endoplasmic reticulum and free polysomes, basal cell membrane interdigitations, a well-developed endocytotic apparatus, and conspicuous junctional complexes--all features of the proximal tubular cell. Compared with cells on plastic substrate, there were higher levels of the brush border enzymes gamma-glutamyl transpeptidase, L-leucine aminopeptidase, and alkaline phosphatase in cells maintained on an HR-9 basement membrane substrate, further supporting the conclusion that a basement membrane substrate promoted differentiation of tubular cells. These data and morphological observations indicate that a basement membrane substrate can promote growth and both functional and morphologic differentiation of human kidney tubular cells.
Guinea pig glomeruli were grown in vitro for 22 days in a serum-free medium composed of Waymouth's MB 752/1 supplemented with sodium pyruvate, nonessential amino acids, antibiotics, insulin, transferrin, selenium, triiodothyronine, and fibronectin (FN), and sequential morphologic and quantitative studies of cell outgrowth were performed. Glomeruli grown in serum-free medium showed preservation of glomerular visceral epithelial cells but extensive necrosis of endocapillary cells (endothelial and mesangial cells). Morphologic analysis demonstrated progressive morphologic changes in cultured glomerular cells; however, most cell types observed in culture appeared to grow from the epithelial side of the glomerular basement membrane. Mitosis was a prominent component of glomerular cell outgrowth in vitro, and total DNA increased slightly during glomerular culture. FN was required for glomerular cell outgrowth, and studies using FN fragments demonstrated that the carboxy-terminal portion of FN was required for whole glomerular attachment. These results are used to develop a model for glomerular cell outgrowth in vitro.
Adult guinea pig glomeruli were grown in vitro either in serum or in a chemically defined medium. Glomeruli were plated either directly into plastic flasks or into plastic flasks that had been coated with the extracellular matrix produced by the PF-HR-9 mouse teratocarcinoma endodermal cell line. Both the composition of the medium and the nature of the culture substrate affected whole glomerular attachment and the type of cells produced in culture. Quantitative studies demonstrated selection of cell types by different culture conditions. Three colony types, each composed of distinctive cell types, could be identified by morphological features. The cells constituting two of these colony types were epithelial in nature, but they were identified as different epithelial types by both histochemical and ultrastructural criteria. Previous studies suggested that one epithelial cell type was derived from the glomerular visceral epithelial cell. This study demonstrates that this cell type could be selectively grown in defined medium on plastic. A second cell type showed several features of renal tubular epithelial cells, including histochemical staining for catalase, cell surface microvilli and cilia, and formation of hemicysts and structures that resembled tubules after prolonged periods in culture. To demonstrate that the 'glomerulus-derived' tubular cells were indeed tubular epithelium, we isolated purified renal cortical tubules (greater than 99% pure) and cultured them on the HR-9 matrix in a serum-free chemically defined medium. The resultant outgrowths had morphological properties identical to those of the glomerulus-derived tubular cells. It seems likely that small tubular fragments attached to a minority of the glomeruli are the source of these glomerulus-derived tubular cells. Neither epithelial cell type could be subcultured on plastic, but both could be passaged on the HR-9 matrix. A third cell type, the spindle-shaped cell, was easily propagated on both plastic and the HR-9 matrix. The origin of this cell type is not clear. Our results demonstrate the important effect of culture conditions on the selection, growth and differentiation of kidney cell types in vitro.
BACKGROUND/AIM: Nephropathy after ingestion of Chinese herbs is known as a rapidly progressive form of interstitial renal fibrosis after a slimming regimen containing aristolochic acid that was identified first in Belgium. Intake of traditional Chinese herbal medicines is very popular in Taiwan. So we looked for similar cases in our hospital. METHODS: From 1994 to 1998, we observed 20 Taiwanese patients who underwent renal biopsy for rapidly progressive renal failure of unknown origin. The medical history of these patients gave no clue to the origin of renal impairment, except for the administration of Chinese herbs before the development of renal failure in all cases. RESULTS: Although these patients took herbal medications from various sources for different purposes, their renal biopsy specimens showed strikingly similar histological patterns: extensive paucicellular interstitial fibrosis and tubular atrophy, but the glomeruli were apparently intact. They also had similar clinical features, such as a nearly normal blood pressure, obvious anemia, insignificant edema, low-grade proteinuria, and glucosuria. The renal function declined rapidly in most cases; 15 patients underwent dialysis within 3 months of renal biopsy, and 7 patients received emergency dialysis when they first came to our hospital. On clinical and morphological grounds, the nephropathy in our patients appears similar to Chinese herb nephropathy. CONCLUSIONS: Because of the diversity of the herbal regimens used, in addition to aristolochic acid, other unidentified phytotoxins may also play a role in this particular disease entity. There is a strong relation between rapidly progressive interstitial renal fibrosis and the consumption of Chinese herbs.