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Helen Liapis

Publications and source records attributed to Helen Liapis.

At least 19 recordsLinked to original sources
PubMed2007

Pathology and immunology of lupus glomerulonephritis: can we bridge the two?

Aberrant immune responses underwrite lupus glomerulonephritis and may contribute to glomerular cell proliferation and inflammation. Recent studies provide evidence that apoptotic immune cells may initiate immune events leading to tissue damage. Nucleosomes within apoptotic particles are recognized by B cells and other antigen presenting cells and represent the most likely inciting antigen for autoantibody production. Some of these antibodies are nephritogenic depending on fine structural composition and antigen recognition in the circulation or on renal cells. Deficient complement components contribute to reduced clearance of circulating and native kidney apoptotic cells. This review summarizes current concepts in lupus immune pathogenesis and attempts to bridge immunology to pathology of lupus glomerulonephritis.

Animals↗
PubMed2006

Microarray interrogation of human metanephric mesenchymal cells highlights potentially important molecules in vivo.

Many molecules have been implicated in kidney development, often based on experimental animal studies with organ cultures and cell lines. There are very few studies, however, that have directly addressed equivalent living human embryonic tissues. We generated renal mesenchymal cell lines from normal human metanephroi and used a microarray strategy to define changes in gene expression after stimulation with growth factors which enhance nephrogenesis in rodents. Changes were observed in 1) genes modulating diverse general cellular processes, such as matrix metalloproteinase 1 and stanniocalcin 1; 2) genes previously implicated in organogenesis e.g., sprouty 4 and midline 1; and 3) genes involved in blood vessel growth, including angiopoietin 1 and 4. Expression of these same genes was subsequently confirmed in vivo. Our novel data have identified several previously unhighlighted genes that may be implicated in differentiation programs within early human nephrogenesis.

Cell Line↗
PubMed2006

Glucose tolerance normalization following transplantation of pig pancreatic primordia into non-immunosuppressed diabetic ZDF rats.

Pancreas or pancreatic islet transplantation in humans is limited by organ availability, and success of the latter is negatively impacted upon by tissue loss post-transplantation and limited potential for expansion of beta cells. A way to overcome the supply and expansion problems is to xenotransplant embryonic tissue. Previously, we have shown that beta cells originating from embryonic day (E) 28 (E28) pig pancreatic primordia transplanted into the mesentery of streptozotocin-diabetic (type 1) Lewis rats engraft without the need for host immune-suppression and normalize glucose tolerance. Here we show long-term engraftment of pig beta cells within liver, pancreas and mesenteric lymph nodes post-transplantation of E28 pig pancreatic primordia into diabetic ZDF rats, a model for type 2 diabetes. Porcine insulin is present in circulation after an oral glucose load. Glucose tolerance is normalized in transplanted ZDF hosts and insulin sensitivity restored in formerly diabetic ZDF males. Release of porcine insulin in vitro from tissue originating in transplanted rats occurs within 1 min of glucose stimulation characteristic of first-phase secretion from beta cells. Of potential importance for application of this transplantation technology to treatment of type 2 diabetes in humans and confirmatory of our previous findings in Lewis rats, no host immunosuppression is required for engraftment of E28 pig pancreatic primordia.

Animals↗
PubMed2005

Catastrophic antiphospholipid syndrome in a 14-year-old child.

Antiphospholipid syndrome (APS) is an autoimmune disease. Less than 1% of patients with APS present with life-threatening catastrophic APS (CAPS). We report here a case of CAPS in a young girl with cardiac, gastrointestinal and renal involvement. Although the management was complicated, the outcome was better than expected. We suggest that CAPS be included in the differential diagnosis of acute renal failure in children with multi-organ involvement and prolonged phospholipid-dependent coagulation time and promptly treated with immunomodulating agents and anticoagulants.

Acute Kidney Injury↗
PubMed2005

Normalization of glucose post-transplantation of pig pancreatic anlagen into non-immunosuppressed diabetic rats depends on obtaining anlagen prior to embryonic day 35.

Embryonic day (E) 28 (E28) pig pancreatic anlagen (PPA) transplanted into the omentum of non-immunosuppressed steptozotocin-diabetic Lewis rats normalize levels of circulating glucose within 2-4 weeks. Following transplantation formerly diabetic rats have porcine insulin, but no rat insulin detectable in circulation. At 3 weeks post-E28 PPA transplantation, bits of insulin-positive tissue are observed amidst host omental fat, but by 6 weeks only individual alpha and beta cells remain. In contrast, E35 PPA transplantation does not normalize glucose and 6 weeks post-implantation of E35 PPA transplanted tissue is rejected. In contrast to E28 PPA, no trace of implanted renal tissue is detectable post implantation of E28 pig renal anlagen (PRA) in non-immunosuppressed non-diabetic rats or in streptozocin-diabetic rats previously transplanted with E28 PPA. In the latter, normoglycemia is maintained post-PRA transplantation. We conclude that normalization of glucose levels following transplantation of PPA into non-immunosuppressed Lewis rats depends on obtaining the anlagen before E35 and that prior successful engraftment of E28 PPA as reflected by normalization of glucose, does not permit successful engraftment of E28 PRA.

Animals↗
PubMed2005

Three cases of hemolytic uremic syndrome in ovarian cancer patients treated with combination gemcitabine and pegylated liposomal doxorubicin.

BACKGROUND: Hemolytic uremic syndrome (HUS) is a rare coagulation disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute uremia. Reports have described this fatal syndrome in association with cytotoxic agents. To our knowledge, no case reports of HUS in ovarian cancer patients receiving treatment with combination gemcitabine and pegylated liposomal doxorubicin (PLD) have been reported. CASE REPORTS: Three patients with recurrent ovarian carcinoma each developed profound hypertension and peripheral edema while receiving combination gemcitabine and PLD. The first patient had rapid hemolysis, thrombocytopenia, renal failure and respiratory distress. The other patients experienced slowly progressive renal failure and mild hematologic abnormalities. Two of the three patients had favorable outcomes. CONCLUSION: The reported incidence of gemcitabine-induced HUS is rare. Clinicians should suspect HUS if blood pressure elevation or peripheral edema develop.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Thrombotic microangiopathy associated with the hypereosinophilic syndrome.

BACKGROUND: Hypereosinophilic syndrome (HES), defined as persistent marked eosinophilia of unknown origin complicated by end organ damage, is thought to be due to activation of eosinophils and release of substances that are toxic to various cells and tissues. An association between hypereosinophilia and kidney damage is not well documented. METHODS: We describe two patients with the HES, acute renal failure, and thrombocytopenic hemolytic anemia. Renal biopsy pathology and immunohistochemistry for activated eosinophils were performed. RESULTS: Renal biopsy revealed glomerular thrombosis, proliferative arteritis, and glomerular and tubulointerstitial eosinophil infiltrates. Ultrastructurally, subendothelial glomerular fibrin deposits and numerous luminal platelets characteristic of thrombotic microangiopathy (TMA) were present. Abundant degranulated eosinophils were localized in glomeruli and the interstitium. Immunofluorescence with specific antibody to eosinophil granule major basic protein (MBP) showed striking extracellular MBP deposition within glomeruli, a marker of eosinophil degranulation. Both patients developed TMA. High-dose glucocorticoids achieved sustained decrease of blood eosinophils and improvement of renal function. CONCLUSION: To our knowledge these are the first documented cases of TMA associated with HES. We propose that products released from degranulated eosinophils caused endothelial injury and microvascular thrombosis. Recognition of this serious renal complication associated with blood eosinophilia should prompt early diagnosis and treatment.

Acute Kidney Injury↗
PubMed2005

Progressive accumulation of lanthanum in the liver of normal and uremic rats.

BACKGROUND: The loss of renal function in chronic kidney disease (CKD) patients leads to a variety of metabolic disturbances that promote the development of secondary hyperparathyroidism (SH) and bone disease. One of these alterations, hyperphosphatemia, is a persistent problem in patients with CKD and is an important factor in the development and severity of SH as well as coronary artery and cardiac valve calcification. To help control serum phosphorus (P), phosphate binders are used to minimize intestinal absorption of P in these patients. Since the use of aluminum- and calcium-based phosphate binders can result in severe side effects, other phosphate binders have been proposed. One of these is lanthanum (La) carbonate. METHODS: Since there is some controversy as to the degree La is absorbed by the intestine, whether it is deposited in tissues, and what effect its prolonged use would have in patients with chronic renal failure, we studied normal and uremic rats fed a control diet or a diet with La carbonate (1.5% elemental La) for 45, 90, or 110 days. RESULTS: As expected, plasma creatinine increased after the induction of uremia and continued to increase with time. At 45 and 90 days, dietary La produced a reduction in plasma P in normal rats (N + La) [45 days: 3.15 +/- 0.35 vs. normal control (NC) 4.41 +/- 0.15 mg/dL, P < 0.01; 90 days: 3.20 +/- 0.30 vs. 4.09 +/- 0.15 mg/dL, P < 0.05], but not at 110 days. Plasma P was initially lower (45 days) in both groups of La-treated rats (U + La: 3.47 +/- 0.28 vs. UC: 4.91 +/- 0.27 mg/dL, P < 0.01), but was not at 90 and 110 days. Whole blood La content was not increased in rats fed the La diet and is, therefore, not a good indicator of the La content of tissue. La was increased in kidney, femur, and especially liver in normal and uremic rats fed the La diet. Uremia markedly enhanced tissue accumulation of La (liver, 110 days: N + La: 849 +/- 152 vs. U + La: 2676 +/- 479 ng/g wet wt, P < 0.01), which increased in a time-dependent manner. The increase in La in the liver of normal rats was 44-fold compared to control and 98-fold in the liver of uremic rats compared to uremic control. CONCLUSION: La accumulates in tissues, most strikingly in the liver, and renal failure accelerates the accumulation. While this was a relatively short-term study, La accumulation increased in a time-dependent manner. The effect of long-term La treatment on patients with chronic renal insufficiency needs to be evaluated.

Animal Feed↗
PubMed2004

Congenital bilateral renal arteriovenous malformation: an unrecognized cause of renal failure.

Congenital renal arteriovenous malformations (AVM) are very rare abnormal communications between arteries and veins. These lesions are almost always unilateral, predominantly in the right kidney, and usually asymptomatic until adulthood. We present a unique case of bilateral renal AVM in a 10-year-old white boy who developed renal failure requiring renal transplantation. Microscopic sections of an atrophic right and a slightly larger left kidney with tortuous and dilated hilar vessels showed elaborate derangement of arteries and veins insinuating between lobules. Glomeruli were diffusely enlarged with increased number of capillary loops. Glomerular basement membrane reduplication and fibrinoid necrosis was focally noted. Electron microscopy demonstrated absence of electron-dense deposits or mesangial interposition excluding membranoproliferative glomerulonephritis. We believe that the glomerular lesions are secondary to congenital renal arteriovenous malformation. To our knowledge, bilateral arteriovenous malformation in infancy is not previously described.

Arteriovenous Malformations↗
PubMed2004

Hemolytic uremic syndrome presenting after treatment of endodermal sinus tumor.

BACKGROUND: Hemolytic uremic syndrome is a rare multisystem disorder that is caused by infections, preeclampsia, autoimmune disorders, or oral contraceptive agents, and rarely in association with different cancers and chemotherapeutic agents. CASE: A 34-year-old woman who presented for evaluation of a pelvic mass received a diagnosis of International Federation of Gynecology and Obstetrics (FIGO) stage 1c endodermal sinus tumor at laparotomy. Three months after receiving 3 courses of bleomycin, etoposide, and cisplatinum, she presented with renal failure, thrombocytopenia, anemia, and severe hypertension. Cancer-associated hemolytic uremic syndrome was diagnosed, and the patient was treated with plasmaphoresis, blood transfusion, and hemodialysis. CONCLUSION: Cancer-associated hemolytic uremic syndrome has a high mortality rate; thus, prompt diagnosis is critical to survival.

Abdominal Pain↗
PubMed2004

Matrilysin (MMP-7) expression in renal tubular damage: association with Wnt4.

BACKGROUND: Matrilysin, a secreted matrix metalloproteinase and target gene of Wnt signaling, functions in epithelial repair and host defense, but no role in renal injury has been described. METHODS: Matrilysin expression was assessed in human kidney specimens by immunohistochemistry, and in experimental renal injury in mice by immunohistochemistry, Northern blotting, and RNase protection assays (RPA). A relationship to Wnt4, which is also induced in renal injury, was determined by RPA and in situ hybridization. RESULTS: Matrilysin was not detected in the normal human renal tubular epithelium by immunohistochemistry. However, prominent staining was detected in sections from autosomal-dominant polycystic kidney disease in the cyst lining epithelium, atrophic tubules, and cyst micropolyps, and from hydronephrosis in dilated and atrophic tubules. Matrilysin expression was also induced by acute folic acid nephropathy and unilateral ureteral obstruction (UUO) in the mouse, and expression increased as acute injury progressed to tubulointerstitial fibrosis. Matrilysin staining was primarily localized to epithelium of distal tubule/collecting duct origin in both human and murine renal disease. Wnt signaling can induce matrilysin expression, and we found that the pattern of matrilysin expression during progression of renal fibrosis in the mouse after UUO or folic acid nephropathy, and in the jck model of murine polycystic kidney disease, closely paralleled that of Wnt4. CONCLUSION: These observations suggest that matrilysin may have a role in renal tubular injury and progression of tubulointerstitial fibrosis, and that Wnt4 may regulate matrilysin expression in the kidney.

Animals↗
PubMed2004

Pleomorphic rhabdomyosarcoma of the anterior abdominal wall following multimodality treatment for carcinoma of the rectum.

Postradiation sarcomas are rare, and the most commonly reported ones are malignant fibrous histiocytoma, osteosarcoma, angiosarcoma, fibrosarcoma, malignant peripheral nerve sheath tumor, and high-grade pleomorphic sarcoma, not otherwise specified. There are a few case reports of postradiation rhabdomyosarcomas following treatment of retinoblastoma, breast cancer, endometrial adenocarcinoma, and Hodgkin's disease. Secondary neoplasms following radiation and surgical treatment of rectal adenocarcinomas have not been reported in the English literature. We report a case of pleomorphic rhabdomyosarcoma of the anterior abdominal wall following treatment of rectal carcinoma, and we review the literature.

Abdominal Wall↗
PubMed2003

Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy.

BACKGROUND: Bone morphogenic protein-7 (BMP-7), an essential developmental renal morphogen, is a secreted differentiation factor of the adult collecting duct. It activates receptors in the collecting duct, distal nephron, proximal tubule, and glomerulus. BMP-7 is therapeutic in tubulointerstitial nephritis raising the question of broader efficacy in chronic kidney disease (CKD). METHODS: Diabetes was induced in 200 g rats by a single dose of streptozotocin. After 16 weeks, glomerular hypertrophy and proteinuria were established, and therapy with BMP-7 (10, 30, or 100 microg/kg intravenously twice a week), enalapril (20 mg/kg), or vehicle was begun and continued until 32 weeks. Kidney weight, glomerular filtration rate (GFR), urine albumin excretion, blood pressure, pathology, and BMP-7 expression were measured. RESULTS: Diabetic vehicle-treated rats developed renal insufficiency by 32 weeks (GFR, 0.34 +/- 0.02 mL/min/100 g body weight vs. 0.55 +/- 0.02 in normal). In the diabetic BMP-7 high-dose-treated rats, GFR was preserved (0.70 +/- 0.08, P < 0.01 vs. vehicle), and higher than diabetic enalapril-treated rats (0.58 +/- 0.06). Kidney weights of vehicle-treated animals were not affected, but were reduced in all of the treatment groups (P < 0.001). Proteinuria was reversed to normal by BMP-7 in a dose-dependent manner. The reduction in proteinuria by the intermediate dose of BMP-7 was similar to the effect of enalapril therapy. Glomerular area and interstitial volume were significantly decreased in the BMP-7 and enalapril-treated animals. Glomerular sclerosis was prevented by BMP-7 therapy more effectively than by enalapril. Enalapril controlled hypertension throughout the course of therapy while BMP-7 did not affect blood pressure until the final 4 weeks of therapy. Diabetic vehicle-treated rats lost BMP-7 expression in the kidney. BMP-7 and enalapril therapy restored BMP-7 expression at high levels. CONCLUSION: BMP-7 partially reversed diabetic-induced kidney hypertrophy, restoring GFR, urine albumin excretion, and glomerular histology toward normal. Restoration of BMP-7 expression was associated with a successful repair reaction and a reversal of the ill-fated injury response.

Albuminuria↗
PubMed2003

Sevelamer hydrochloride attenuates kidney and cardiovascular calcifications in long-term experimental uremia.

BACKGROUND: In chronic renal failure (CRF), hyperphosphatemia and an elevated calcium-phosphate product are associated with vascular calcification and increased cardiovascular morbidity and mortality. Previous data have demonstrated that 3-month treatment of uremic rats with sevelamer was associated with less nephrocalcinosis compared to calcium carbonate (CaCO3), despite similar control of serum phosphorus, calcium-phosphorus product (Ca x P product), and secondary hyperparathyroidism. There was no evidence of aortic calcification after 3 months of uremia (J Am Soc Nephrol 13:2299-2308, 2002). The present studies explore the influence of sevelamer and CaCO3 on cardiovascular and kidney calcifications in long-term experimental uremia over 6 months. METHODS: Normal and 5/6 nephrectomized rats (U) were fed a high phosphorus (HP) diet for 6 months. Two phosphate binders, CaCO3 and sevelamer, were administered and their influence on hyperphosphatemia, secondary hyperparathyroidism, kidney/myocardial/aortic calcification, and renal function was compared. RESULTS: All uremic rats began the study with the same degree of renal failure. Sevelamer was as effective as CaCO3 in reducing serum phosphorus, Ca x P product, and attenuating secondary hyperparathyroidism. Despite similar serum cholesterol levels, rats in the U-HP + sevelamer group had markedly lower calcium deposition in the myocardium and aorta (myocardium, 72 +/- 4 microg/g wet tissue; aorta, 736 +/- 156 microg/g wet tissue) compared to rats in either the U-HP + CaCO3 group (myocardium, 179 +/- 48, P < 0.05; aorta, 1308 +/- 343, P < 0.05) or the U-HP group (myocardium, 98 +/- 10, NS; aorta, 2150 +/- 447, P < 0.05). Dual immunohistochemical analysis for calcium and endothelial cell markers demonstrated that myocardial calcium deposition was intravascular within capillaries. Furthermore, calcium deposition in the kidney of uremic rats treated with sevelamer (582 +/- 111 microg/g wet tissue) was lower than that found in uremic rats treated with CaCO3 (1196 +/- 180 microg/g wet tissue). Sevelamer-treated rats had less deterioration in renal function with an associated lower serum creatinine, higher creatinine clearance, and less proteinuria. There was no difference in overall mortality between the three experimental groups. CONCLUSION: In long-term experimental CRF, in addition to controlling serum phosphorus and secondary hyperparathyroidism as efficiently as CaCO3, treatment with the phosphate-binder sevelamer attenuates vascular and kidney calcification.

Animals↗
PubMed2003

CMV infection of the renal allograft is much more common than the pathology indicates: a retrospective analysis of qualitative and quantitative buffy coat CMV-PCR, renal biopsy pathology and tissue CMV-PCR.

BACKGROUND: Quantitative blood polymerase chain reaction (PCR) for cytomegalovirus (CMV) is used to direct therapy in kidney transplant patients, but cytomegalic inclusions are rarely found in allograft renal biopsies even with an elevated serum creatinine and apparent CMV disease. The relationship between quantitative blood CMV and renal allograft pathology is unknown. METHODS: Thirteen biopsy samples were available for analysis from patients suspected of CMV disease, who had a buffy coat CMV-PCR drawn within 2-5 days of a renal allograft biopsy for an elevated creatinine. All were evaluated for CMV pathologically, by light microscopy, immunohistochemistry, in situ hybridization and tissue PCR. RESULTS: Qualitative and quantitative buffy coat CMV-PCR were positive in 10/13 (77%) patients. Tissue CMV-PCR was positive in five (50%) biopsies, including two with CMV inclusions and three with no inclusions. Quantitative buffy coat CMV-PCR levels did not correlate with detection of CMV inclusions in renal tissue. Paradoxically, quantitative buffy coat CMV-PCR was low (239 and 538 copies/microg of DNA) when CMV inclusions were detected. All five biopsies with acute rejection were associated with CMV viraemia and two of the five with allograft CMV inclusions. A quantitative buffy coat CMV-PCR of <100 copies/microg of DNA ruled out disease with CMV inclusions. CONCLUSIONS: CMV nephropathy is much more common than previously reported when sensitive techniques are used for detection in tissue. Acute rejection and CMV viraemia occur commonly together in patients at risk for CMV. Quantitative buffy coat CMV-PCR does not correlate with the presence of CMV inclusions. These findings have implications for management of patients who have elevated serum creatinine and are at risk for CMV disease.

Biopsy↗
PubMed2003

Cytomegalovirus disease after prophylaxis with oral ganciclovir in renal transplantation: the importance of HLA-DR matching.

This study assessed the incidence of cytomegalovirus (CMV) disease and associated outcomes after oral ganciclovir prophylaxis in renal transplantation. A retrospective analysis was performed of all adult renal transplant recipients at a single transplant center transplanted between August 16, 1996, and December 31, 2000. CMV disease prophylaxis included ganciclovir 1000 mg orally thrice daily prescribed for 90 d in D-/R+ cases and 180 d in D+/R- and D+/R+ cases. Forty (9.1%) of 470 patients studied were diagnosed with CMV disease, which varied significantly by CMV serostatus and number of HLA-DR matches. The highest incidence of disease, 26.2%, was in D+/R- patients with zero HLA-DR matches. Five-year graft survival was 56.8% with CMV disease compared with 79.1% without (P < 0.001). Five-year graft survival with CMV disease was 75.9% with one or two HLA-DR matches versus 16.2% with zero HLA-DR matches (P < 0.001). CMV remains an important factor in long-term graft survival after oral ganciclovir prophylaxis. However, we have observed that the adverse impact of CMV disease on graft survival is apparent only in patients with zero HLA-DR matches. These results call for the development of new CMV disease prophylaxis and treatment strategies in patients with zero HLA-DR matches. In addition, organ allocation policies discouraging combining CMV-seropositive donors and zero HLA-DR matches may be worth consideration.

Administration, Oral↗