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Helen Liapis

Publications and source records attributed to Helen Liapis.

31 records · Page 2Linked to original sources
PubMed2003

Biology of congenital obstructive nephropathy.

Congenital obstructive nephropathy is a common disease affecting fetuses and young children. The kidney shows profound morphologic and functional changes. The physiologic developmental kidney program is disturbed in the most advanced cases, arguing for altered temporal/spatial expression of genes which control normal nephrogenesis. Major regulators of mesenchymal-epithelial transformation and collecting duct and tubular development such as WT1 and Sall1 are decreased with obstruction. Additional candidate genes include GDNF/cRET, LIM1 and Pax2. Excessive apoptosis is an undisputed mechanism in these processes, mediated by decreased expression of apoptosis inhibiting genes (Bcl-2, HGF, IGF, BMP7), and overexpression of pro-apoptotic genes like Bax and TGF-beta. Renin and AT2R implicated in renal vascular development are decreased. Numerous extracellular matrix genes including Matrilysin are altered. The emerging theories of the biology of congenital obstructive nephropathy suggest new targets for therapeutic interventions with profound implications for these children.

Animals↗
PubMed2002

Systemic amyloidosis associated with pleomorphic sarcoma of the spleen and remission of nephrotic syndrome after removal of the tumor.

We report a case of a 57-year-old woman who was diagnosed with a systemic AA amyloidosis associated with a pleomorphic sarcoma of the spleen. Although the association and causality between chronic inflammatory states and systemic AA amyloidosis have been well established, the evidence linking solid malignancies to reactive AA amyloidosis is scarce. Our patient had a significant systemic amyloid deposition including biopsy-proven renal and cardiac AA amyloidosis. Subsequent evaluation uncovered the presence of a large splenic mass, which was treated by splenectomy. Histologically the splenic tumor was classified as pleomorphic sarcoma. The removal of the tumor resulted in a marked decline in proteinuria, stable renal and cardiac functions, and symptomatic improvement at 1-year follow-up. Based on the noted improvements, we speculate that the pleomorphic sarcoma of the spleen caused secondary amyloidosis in our case. Stromal tumors, although rare, may be associated with and should be considered in the differential diagnosis of the cause of AA amyloidosis.

Amyloidosis↗
PubMed2002

Histopathology, ultrastructure, and clinical phenotypes in thin glomerular basement membrane disease variants.

Recent genetic studies indicate that Alport syndrome and thin glomerular basement membrane disease (TMD) may both be due to COL4A3, COL4A4, and COL4A5 mutations, but there is continuing uncertainty concerning the diagnosis and management of patients without classic family history and symptoms. We examined kidney pathology and collagen alpha 3 to alpha 5(IV) expression in a series of 16 patients who presented with overlapping signs between TMD and Alport nephritis. All patients presented with hematuria, and 11 also had proteinuria, of whom 5 had nephrotic range proteinuria. Only 9 had family history of hematuria. In 9 of 16 (60%) we found premature glomerulosclerosis in the renal biopsies. Three of 16 had predominantly wide, lamellated glomerullar basement membranes (GBM), and in these, alpha 3 to alpha 5(IV) was absent in glomeruli or skin, diagnostic of Alport nephritis. One patient (12) had a very wide GBM with intramembranous lucencies but no lamellation. Skin biopsy was collagen alpha 5(IV) positive. Nine of 16 patients had predominantly thin GBM by electron microscopy, and 3 had thin and slightly lamellated GBM. Collagen alpha 3 to alpha 5(IV) expression in the kidney or skin biopsy was present in all of the latter 12 patients. Three patients had end-stage renal disease, 7 patients had hypertension, and 1 patient had chronic renal failure. We found that of the 16 patients with presumed TMD, 3 had X-linked Alport nephritis, 2 appeared to have autosomal recessive Alport nephritis, and the remaining patients had either an Alport or a TMD variant. The latter had histologic and/or clinical evidence of progressive renal disease, including premature glomerulosclerosis, hypertension, sustained proteinuria, and either thin or slight GBM lamellation focally, and preserved alpha 3 to alpha 5(IV) expression. These patients have a TMD variant, but an Alport variant with a potentially transmissible severe defect different from benign hematuria cannot be excluded.

Adolescent↗
PubMed2002

Differential NF1, p16, and EGFR patterns by interphase cytogenetics (FISH) in malignant peripheral nerve sheath tumor (MPNST) and morphologically similar spindle cell neoplasms.

Malignant peripheral nerve sheath tumors (MPNSTs) are diagnostically challenging neoplasms for which sensitive and specific immunohistochemical markers are lacking. Although limited to date, previous studies have suggested that NF1 (17q), NF2 (22q), p16 (9p), and EGFR (7p) alterations may be involved in MPNST tumorigenesis. To determine whether specific genetic changes differentiate between MPNST and morphologically similar neoplasms, we assessed these chromosomal regions in 22 MPNSTs (9 NF1-associated, 13 sporadic), 13 plexiform neurofibromas, 5 cellular schwannomas, 8 synovial sarcomas, 6 fibrosarcomas, and 13 hemangiopericytomas by 2-color FISH. NF1 deletions, often in the form of monosomy 17, were found in MPNSTs (76%). neurofibromas (31%), hemangiopericytomas (17%), and fibrosarcomas (17%), but not in synovial sarcomas or cellular schwannomas. NF1 losses were encountered more frequently in MPNSTs versus other sarcomas (p < 0.001), as were p16 homozygous deletions (45% vs 0%; p < 0.001), EGFR amplifications (26% vs 0%; p = 0.006), and polysomies for either chromosomes 7 (53% vs 12%; p = 0.003) or 22 (50% vs 4%; p < 0.001). Hemizygous or homozygous p16 deletions were detected in 75% of MPNSTs, but not in benign nerve sheath tumors (p < 0.001). Thus, FISH analysis identifies relatively specific genetic patterns that may be useful in selected cases, for which the differential diagnosis includes low- or high-grade MPNST.

Cytogenetic Analysis↗
PubMed2002

The effects of sevelamer hydrochloride and calcium carbonate on kidney calcification in uremic rats.

The control of serum phosphorus (P) and calcium-phosphate (Ca x P) product is critical to the prevention of ectopic calcification in chronic renal failure (CRF). Whereas calcium (Ca) salts, the most commonly used phosphate binders, markedly increase serum Ca and positive Ca balance, the new calcium- and aluminum-free phosphate binder, sevelamer hydrochloride (RenaGel), reduces serum P without altering serum Ca in hemodialysis patients. Using an experimental model of CRF, these studies compare sevelamer and calcium carbonate (CaCO(3)) in the control of serum P, secondary hyperparathyroidism (SH), and ectopic calcifications. 5/6 nephrectomized rats underwent one of the following treatments for 3 mo: uremic + high-P diet (U-HP); UHP + 3% CaCO(3) (U-HP+C); UHP + 3% sevelamer (U-HP+S). Sevelamer treatment controlled serum P independent of increases in serum Ca, thus reducing serum Ca x P product and further deterioration of renal function, as indicated by the highest creatinine clearances. Sevelamer was as effective as CaCO(3) in the control of high-P-induced SH, as shown by similar serum PTH levels, parathyroid (PT) gland weight, and markers of PT hyperplasia. Also, both P binders elicited similar efficacy in reducing the myocardial and hepatic calcifications induced by uremia. However, sevelamer caused a dramatic reduction of renal Ca deposition (29.8 +/- 8.6 micro g/g wet tissue) compared with both U-HP (175.5 +/- 45.7 micro g/g wet tissue, P < 0.01) and the U-HP+C (58.9 +/- 13.7 micro g/g wet tissue, P < 0.04). Histochemical analyses using Von Kossa and Alizarin red S staining of kidney sections confirmed these findings. The high number of foci of calcification in the kidney of uremic controls (108 +/- 25) was reduced to 33.0 +/- 11.3 by CaCO(3) and decreased even further with sevelamer (16.4 +/- 8.9, P < 0.02 versus CaCO(3)). Importantly, the degree of tubulointerstitial fibrosis was also markedly lower in U-HP+S (5%) compared with either U-HP+C (30%) or U-HP (50%). It is concluded that in experimental CRF in rats, despite a similar control of serum P and SH, sevelamer is more effective than CaCO(3) in preventing renal Ca deposition and tubulointerstitial fibrosis, including better preservation of renal function. These findings cannot be extrapolated to human disease, and further studies in patients are necessary to determine the benefits of either P binder.

Animals↗
PubMed2002

Reduced renin expression and altered gene transcript profiles in multicystic dysplastic kidneys.

PURPOSE: Some patients with multicystic dysplasia experience hypertension in infancy which can be clinically improved with simple nephrectomy. Little is known of the role of renin in multicystic dysplasia and therefore, we studied renin expression in nonhypertensive multicystic dysplasia and compared it with hypertensive multicystic dysplasia. Additionally, global gene transcript profiles were studied in nonhypertensive multicystic dysplasia. MATERIALS AND METHODS: Tissue from 12 patients with multicystic dysplasia without hypertension and 2 patients with hypertensive multicystic dysplasia were compared to normal metanephric mid-term and neonatal kidneys. Renin expression was studied by immunohistochemistry. CD-68, a marker for macrophages, was applied to slides previously stained with renin. GeneChip (Affymetrix, Southern Oaks, California) microarray analysis was performed using total RNA from 2 nonhypertensive multicystic dysplastic kidneys and normal newborn kidney as control. RESULTS: Strong renin staining was present in arteries and arterioles in normal early metanephric kidneys and concentrated in juxtaglomerular cells in neonatal kidneys. Renin was variably decreased in arterioles in multicystic dysplasia and was ectopically expressed in interstitial cells. Renin positive interstitial cells co-expressed CD-68 antigen identifying these cells as macrophages. Ectopic renin production was more pronounced in hypertensive multicystic dysplasia. GeneChip hybridization showed a 60 to 200-fold decrease in expression of renin transcript in multicystic dysplasia relative to normal kidney, concordant with immunohistochemical results. Altered expression of several other candidate transcripts was also identified. CONCLUSIONS: Dramatic renin decrease in multicystic dysplasia suggests that it may participate in the development of dysplastic vessels. Pronounced ectopic renin expression by macrophages in multicystic dysplasia associated with hypertension may be linked to hypertension in multicystic dysplasia. Several other candidate genes whose altered expression may be associated with the pathophysiology of multicystic dysplasia provide intriguing molecular targets for future study.

Antigens, CD↗
PubMed2002

Microvessel formation from mouse embryonic aortic explants is oxygen and VEGF dependent.

To delineate the roles of O(2) and vascular endothelial growth factor (VEGF) in the process of angiogenesis from the embryonic aorta, we cultured mouse embryonic aorta explants (thoracic level to lateral vessels supplying the mesonephros and metanephros) in a three-dimensional type I collagen gel matrix. During 8 days of culture under 5% O(2), but not room air, the addition of VEGF to explants stimulated the formation of CD31-positive, Flk-1-positive, Gs-IB(4)-positive structures in a concentration-dependent manner. Electron microscopy showed the structures to be capillary-like. VEGF-induced capillary-like structure formation was inhibited by sequestration of VEGF via addition of soluble Flt-1 fusion protein or anti-VEGF antibodies. Expression of Flk-1, but not Flt-1, was increased in embryonic aorta cultured under 5% O(2) relative to room air. Our data suggest that low O(2) upregulates Flk-1 expression in embryonic aorta in vitro and renders it more responsive to VEGF.

Animals↗
PubMed2002

Diagnostic dilemmas in atypical postinfectious glomerulonephritis.

This study discusses the differential diagnosis of atypical postinfectious glomerulonephritis (PIGN) which may mimic a great variety of glomerular diseases. These include mild mesangial and/or endocapillary glomerulonephritis (GN) focal segmental glomerulosclerosis (FSGS) with diffuse IgM mesangial deposits, crescentic GN with C3 hump-like deposits, focal mesangiocapillary GN superimposed on endocapillary pattern, membranous GN with diffuse exudative changes, crescentic GN with microabscesses, and postinfectious glomerulonephritis with anti-GBM linear deposits.

Antigen-Antibody Complex↗
PubMed2002

Diabetic glomerulopathy: unusual patterns and dual disease.

Diabetic glomerulopathy is a well-recognized consequence of both type I and type II diabetes. Occasionally, pathologic diagnosis may be challenging for the pathologist. These circumstances include atypical light microscopy or diabetic change with a second superimposed glomerulopathy (dual disease). We have compiled a selection of 12 renal biopsies from diabetic patients that show either an unusual pattern of nephropathy or "dual disease," as well as 2 cases in which the patient had no history of diabetes but had renal biopsies exhibiting changes consistent with diabetic nephropathy. The salient diagnostic features are discussed. To accurately assess these biopsies, immunofluorescence and electron microscopy become essential, and a broadened differential diagnosis must be considered.

Diabetic Angiopathies↗
PubMed2002

Glomerular injury associated with hepatitis C infection: a correlation with blood and tissue HCV-PCR.

Membranoproliferative glomerulonephritis, with or without cryoglobulinemia, and membranous glomerulonephritis are the best characterized glomerulonephropathies associated with hepatitis C virus (HCV) infection. Other more unusual patterns of glomerular injury, including IgA nephropathy, focal segmental glomerulosclerosis, crescentic glomerulonephritis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, and thrombotic microangiopathy, have also been associated with HCV infection, but primarily on an anecdotal basis. It remains uncertain whether the patterns of glomerular injury seen in HCV infected patients, particularly the unusual patterns, represent a disease process specifically related to HCV infection or whether they represent nonspecific patterns of injury due to other causes that happen to occur in HCV-infected patients. We examine this issue by reviewing the epidemiological and pathological evidence in the literature that either supports or refutes a specific relationship between HCV and the pattern of glomerular injury. We also include our experience with 31 HCV-infected patients. In addition, the pathogenesis of HCV-associated glomerulonephropathies is discussed with an emphasis on the significance of detecting HCV in renal biopsies by reverse transcriptase-polymerase chain reaction.

AIDS-Associated Nephropathy↗
PubMedDate not supplied

Intraperitoneal transplantation of pancreatic anlagen.

To determine whether embryonic pancreatic anlagen transplanted to an intraperitoneal site in adult hosts grow, differentiate, and function, we implanted pancreas from embryonic day (E) 12.5 Lewis rat embryos into the omentum of adult Lewis rats or C57Bl/6J mice. E12.5 pancreatic anlagen were relatively undifferentiated except for the presence of condensing tubuloacinar cords. By 2 weeks after implantation, pancreatic anlagen transplanted into rats had enlarged and differentiated such that islets of Langerhans that stained positive for insulin could be delineated. Continued differentiation, as reflected by the presence of "ductal" islets connected to the duct epithelium, was observed at 6 weeks after implantation. At 15 weeks after implantation, "mature" islets had separated from the ducts. Electron microscopy showed eccentric dense bodies within clear vacuoles consistent with insulin granules. Little or no acinar tissue was present in developed anlagen. Within 5 weeks of pancreatic anlagen transplantation, levels of glucose in rats rendered diabetic by an injection of streptozotocin were normalized compared with levels in nontransplanted diabetic controls. Rat pancreatic anlagen underwent growth and development in the peritoneum of C57Bl/61 mice that received costimulatory blocking agents but not in the absence of costimulatory blockade. We concluded that whole E12.5 pancreatic anlagen undergo growth, differentiation, and function after intraperitoneal placement. Implantation of the embryonic pancreas, a "cellular" transplant, is followed by selective differentiation of islet compared with acinar components.

Animals↗