Biomedical subjects

H Liapis

Publications and source records attributed to H Liapis.

At least 37 records · Page 2Linked to original sources

PubMed1998

K-Cl cotransporter expression in the human kidney.

The K-Cl cotransporter protein KCC1 is a membrane transport protein that mediates the coupled, electroneutral transport of K and Cl across plasma membranes. The precise cell type(s) in the kidney that express the K-Cl cotransporter have remained unknown. The aim of the present investigation was to define the distribution of KCC1 mRNA in the human kidney. We used in situ hybridization with a nonradioactive digoxigenin-labeled riboprobe. We identified abundant KCC1 mRNA expression in the epithelial cells throughout the distal and proximal renal tubular epithelium. The transporter was also expressed in glomerular mesangial cells and endothelial cells of the renal vessels. These findings suggest that the K-Cl cotransporter may have an important role in transepithelial K and Cl reabsorption.

Carrier Proteins↗

PubMed1998

A human forkhead/winged-helix transcription factor expressed in developing pulmonary and renal epithelium.

Members of the forkhead/winged-helix transcription factor family play crucial roles during vertebrate development. A human hepatocyte nuclear factor/forkhead homolog (HFH)-4 cDNA encoding a 421-amino acid protein was isolated from a human fetal lung cDNA library. By Southern blot analysis of human-rodent somatic cell hybrid genomic DNA, the human HFH-4 gene localizes to chromosome 17q23-qter. This is the locus of another forkhead/winged-helix gene, the interleukin enhancer binding factor gene. RNA blot analysis revealed a 2.5-kilobase human HFH-4 transcript in fetal lung, kidney, and brain as well as in adult reproductive tissues, lung, and brain. By in situ hybridization, HFH-4 expression is associated with differentiation of the proximal pulmonary epithelium, starting during the pseudoglandular stage of human lung development. During human renal morphogenesis, HFH-4 is expressed in the developing epithelial cells of the ureteric duct, glomerulus, and epithelial vesicles. The unique pattern of HFH-4 expression during human fetal development suggests a role for this forkhead/winged-helix factor during pulmonary and renal epithelial development.

Amino Acid Sequence↗

PubMed1997

North American opossum Didelphis virginiana as a fetal nephrotoxicity model: histologic and ultrastructural assessment of uranyl nitrate (UN)-induced damage.

We have used our opossum model of fetal nephrotoxicity to investigate uranyl nitrate-induced morphologic changes in the developing kidney. The present study establishes a renal dose response curve for the uranyl nitrate (UN). We find that pups treated with nonlethal doses of UN do not demonstrate growth retardation compared to saline-treated controls. The kidneys of UN-treated pups are heavier than the control animals, an effect less apparent the longer the pups are followed. A low dose of 60 mg/kg of UN administered to small pups causes slight histologic derangement but nevertheless more change than the same dose administered to larger more mature pups. Using a dose of 100 mg/kg of UN that effectively causes nonfatal renal disruption, we examined the kidneys from 4 to 42 days following injection. We find that tubular dilation and epithelial necrosis starts soon after treatment (day 4) and reaches its maximum during the second and third week (11 and 22 days). Architectural restoration appears complete by the end of the third week. By electron microscopy, UN induces sequential structural damage with loss of proximal tubule brush border, epithelial necrosis with intact basement membranes and regeneration at 4, 11, and 22 days. Residual tubular mitochondrial damage is present at 42 days in spite of histologically normal tubules. No apparent lesions are seen in glomeruli. Fibroblastic interstitial proliferation in UN-treated kidneys at 11 days is not followed by appreciable fibrosis when assessed at 22 and 42 days. As the structural changes caused by 100 mg/ml UN administration in fetal opossum kidneys are reversible, this is a useful model to study the molecular mediators responsible for this form of renal damage and repair.

Animals↗

PubMed1997

Recurrent ovarian tumor with low malignant potential and cardiac metastasis.

BACKGROUND: Up to 20% of ovarian epithelial tumors are classified as being of low malignant potential. Most of these low malignant potential tumors are detected at an early stage and have an excellent prognosis. This is a report of a woman with cardiac metastasis from an ovarian low malignant potential tumor. CASE: This case describes a 53-year-old woman who presented with congestive heart failure and was found to have a recurrent stage III ovarian tumor of low malignant potential. A transesophageal echocardiogram revealed compression of the inferior vena cava and a mass encompassing the right atrium. Findings at autopsy confirmed a low malignant potential ovarian tumor thrombus involving the inferior vena cava and right atrium. CONCLUSION: Ovarian low malignant potential tumors can metastasize in an aggressive manner. A transesophageal echocardiogram may be useful when the diagnosis of cardiac tumor thrombus is considered.

Carcinoma↗

PubMed1997

Expression of alpha(v)beta3 integrin is less frequent in ovarian epithelial tumors of low malignant potential in contrast to ovarian carcinomas.

Ovarian tumors of low malignant potential (LMPs) histologically lack invasion and have excellent prognosis in contrast to invasive carcinomas. Integrins are heterodimeric adhesion molecules thought to play a role in cell migration and tumor progression. The alpha(v)beta3 integrin in particular mediates melanoma invasion in vitro and promotes neoplastic angiogenesis, facilitating breast cancer metastasis. In addition, alpha(v)beta3 expression has been detected in ovarian cancer cell lines and in a limited number of human ovarian cancer samples. The distribution pattern of this integrin in LMPs is not known. We examined tissue sections from 19 LMPs and 31 ovarian carcinomas for alpha(v)beta3, in addition to alpha5beta1 and alpha2beta1 integrins, which have been shown to be expressed in ovarian cancer cell lines. Variable immunoreactivities of alpha5beta1 and alpha2beta1 were detected in both LMPs and ovarian carcinomas. Most (74.2%) ovarian carcinomas were alpha(v)beta3 positive, whereas only 36.8% of LMPs were positive, which is statistically significant (P = .009). These results establish the distribution pattern of alpha2beta1, alpha5beta1, and alpha(v)beta3 integrins in LMPs. The biological significance of the less frequent expression of alpha(v)beta3 in LMPs compared with carcinomas of the ovary needs further elucidation.

Adult↗

PubMed1997

Primary intrathyroidal paraganglioma with metachronous carotid body tumor: report of a case and review of the literature.

A case of primary intrathyroidal paraganglioma is reported, and the light microscopic and immunohistochemical findings are described. Primary paragangliomas of the thyroid region are extremely uncommon and are therefore often confused clinically and histopathologically with more common intrathyroidal mass lesions. The diagnostic difficulties are underscored by the present case, which was misdiagnosed twice, firstly as a medullary thyroid carcinoma and secondly as a follicular thyroid carcinoma. Immunohistochemistry may be very helpful in arriving at the correct diagnosis. The case was further complicated by a second neck mass contralateral to the original thyroid nodule, which was interpreted as consistent with metastasis. The second lesions was proved angiographically and histologically to be a carotid body paraganglioma.

Adult↗

PubMed1997

Primitive neuroectodermal tumor of the kidney--another enigma: a pathologic, immunohistochemical, and molecular diagnostic study.

Primitive neuroectodermal tumor (PNET), the second most common type of sarcoma in the first two decades of life, rarely presents as an organ-based neoplasm. Rather, it is seen typically in the soft tissues of the chest wall and paraspinal region. We report a case of primary PNET of the kidney in a 17-year-old girl who presented with abdominal pain, hematuria, and an abdominal mass. Nodules and sheets of monotonous-appearing primitive round cells and the formation of rosettes focally were the principal microscopic features. The tumor cells were uniformly immunoreactive for vimentin, cytokeratin, neuron-specific enolase, and 013 (CD99). In addition, the characteristic translocation of PNET and Ewing sarcoma, t(11;22)(q24;q12), was detected by polymerase chain reaction (PCR). Eight previous examples of renal PNET have been reported in the literature in the past 2 years, but only three of these cases have had complete immunohistochemical evaluation with the demonstration of 013 positivity. To our knowledge the present case is the only one to date demonstrating the recurrent translocation t(11;22)(q24;q12) by PCR. Assuming that the previous cases in the literature are bona fide examples of PNET, the kidney may be another site of predilection for this usual soft-tissue neoplasm. We are once again confronted with the dilemma about the nature of the progenitor cell.

12E7 Antigen↗

PubMed1997

Expression of bcl-2 and bax in regenerating rat renal tubules following ischemic injury.

To define potential roles for bcl-2 and bax in adult kidney as regulators of regeneration, their expressions were characterized postischemic injury. A 2.1-fold increase in levels of renal bcl-2 mRNA occurred within 24 h of injury relative to levels in kidney of sham-operated control rats. The levels of bcl-2 mRNA remained elevated for 3 days but returned to baseline by day 5 postischemia. In situ hybridization of kidneys from sham-operated rats demonstrated faint expression of bcl-2 mRNA localized diffusely throughout the nephron. After renal injury, the expression of bcl-2 mRNA was markedly enhanced in regenerating proximal tubule cells relining the basement membrane. Immunohistochemistry showed a similar localization for bcl-2 protein. Levels of bax mRNA in kidney were elevated beginning at 24 h postischemia and remained elevated for 7 days postinjury. Bax mRNA and bax protein were colocalized to regenerating proximal tubules postischemia and were prominently expressed in papillary proliferations. We conclude that the expressions of bcl-2 and bax in kidney are enhanced in a predictable pattern following acute ischemic injury. Our findings suggest that these regulators of apoptosis play key roles in the process of repair of the damaged proximal tubule postischemia.

Animals↗

PubMed1997

Increased expression of platelet-derived growth factor A and collagenous matrix proteins in congenital multicystic renal dysplasia.

The expression of platelet-derived growth factor A (PDGF-A), and its spatial and temporal relationship to interstitial collagens in kidneys with congenital multicystic dysplasia using in situ hybridization, have been examined. Seventeen dysplastic kidneys (16 weeks to 7 months) and 20 normal age-matched controls were used in the study. Increased PDGF-A mRNA was detected in dysplastic compared to normal kidneys in all age groups including extensively fibrotic postnatal kidneys. An abundant PDGF-A mRNA signal was seen within the epithelial cells of cystically dilated or dysplastic tubules and within interstitial fibroblasts and disorganized primitive mesenchyme. A comparable amount of PDGF-A protein was detected by Western blotting. Procollagen I and III mRNA were increased in fibroblasts surrounding cystic and dysplastic tubules. We conclude that tubular epithelial production of PDGF-A may induce collagenous matrix production by adjacent fibroblasts, while marked up-regulation of PDGF-A by interstitial cells may be responsible for sustainable fibrogenic effects in the fetal kidney contributing to renal maldevelopment.

Collagen↗

PubMed1997

Detection of integrins in formalin-fixed, paraffin-embedded tissues.

Integrins are heterodimeric transmembrane receptors, which are expressed in many cells. In vitro experiments have demonstrated that integrins may be important in tumor progression and organ development. The functions of integrins were previously studied in cell cultures and their tissue expression was detected by immunofluorescence or immunoperoxidase in frozen sections. The purpose of this study was to determine the optimal conditions for detection of integrins in formalin-fixed, paraffin-embedded tissues. We utilized microwave heating and enzyme digestion in routinely processed, surgically removed tissues. Our results demonstrate that integrins can be reliably detected in archival material. This approach will facilitate further investigation of the role played by integrins in human malignancies and in developmental processes.

Formaldehyde↗

PubMed1996

Human blood-mobilized hematopoietic precursors differentiate into osteoclasts in the absence of stromal cells.

Osteoclastogenesis is a complex process that is facilitated by bone marrow stromal cells (SCs). To determine if SCs are an absolute requirement for the differentiation of human hematopoietic precursors into fully mature, osteoclasts (OCs), CD34+ cells were mobilized into the peripheral circulation with granulocyte colony-stimulating factor, harvested by leukapheresis, and purified by magnetic-activated cell sorting. This procedure yields a population of CD34+ cells that does not contain SC precursors, as assessed by the lack of expression of the SC antigen Stro-1, and that differentiates only into hematopoietic cells. We found that CD34+, Stro-1- cells cultured with a combination of granulocyte/macrophage colony-stimulating factor, interleukin 1, and interleukin 3 generated cells that fulfill current criteria for the characterization of OCs, including multinucleation, presence of tartrate-resistant acid phosphatase, and expression of the calcitonin and vitronectin receptors and of pp60c-src tyrosine kinase. These OCs also expressed mRNA for the noninserted isoform of the calcitonin receptor and excavated characteristic resorption pits in devitalized bone slices. These data demonstrate that accessory SCs are not essential for human osteoclastogenesis and that granulocyte colony-stimulating factor treatment mobilizes OC precursors into the peripheral circulation.

Acid Phosphatase↗

PubMed1996

Integrin alpha V beta 3 expression by bone-residing breast cancer metastases.

Breast cancer metastasis to bone is a multistep process requiring attachment of tumor cells to the bone and bone marrow environment. The precise adhesion molecules involved in skeletal homing of breast cancer to bone are unknown but likely include integrins. We investigated the expression of vitronectin receptor (alpha V beta 3) by breast cancer cells residing in bone because this heterodimer mediates osteoclast-bone recognition. We used immunohistochemistry and in situ hybridization in a systematic study of 22 bone biopsies containing breast cancer metastases and available samples of corresponding primary tumors and normal breast and compared alpha V beta 3, alpha 2 beta 1, and alpha B beta 5 integrin expression. The results showed that alpha V beta 3 was strongly expressed by normal breast epithelium and was decreased in some and strongly expressed in other primary invasive breast carcinomas. In contrast, this integrin heterodimer was abundant in all breast cancer cells metastatic to bone. In situ hybridization revealed high levels of steady-state mRNA corresponding to sites of protein expression; alpha 2 beta 1 was weakly expressed in both primary and metastatic tumors, and alpha V beta 5 was not detected. Our results showed an overexpression of alpha V beta 3 by bone-residing breast cancer cells and suggest either subclonal selection of alpha V beta 3-expressing tumor cell populations or upregulation of alpha V beta 3 in the bone microenvironment.

Biomarkers, Tumor↗

PubMed1995

The Ivemark syndrome: prenatal diagnosis of an uncommon cystic renal lesion with heterogeneous associations.

Renal dysplasia has been reported in association with a number of anatomical abnormalities, including pancreatic dysgenesis and hepatic anomalies. The combination of renal, hepatic, and pancreatic dysplasia (RHPD), also known as Ivemark syndrome, is rare and uniformly fatal. We report here the gross and histological findings in 4 cases of combined RHPD, 2 of which were detected by prenatal ultrasonography. Evaluation of these 4 and the other 20 reported cases shows that combined RHPD has considerable variability in the histological findings and in organ involvement. In addition, nearly half were associated with anomalies in other organ systems, and 11 of the 24 were familial. In this study, ultrasonographic and histological abnormalities were seen as early as 18.5 weeks gestation in 1 case.

Abnormalities, Multiple↗

PubMed1995

Endothelin-1 release by erythropoietin involves calcium signaling in endothelial cells.

We investigated the effects of recombinant human erythropoietin (rHuEPO) on intracellular calcium ([Ca2+]i) and whether these changes regulate both endothelin-1 (ET-1) protein release and ET-1 messenger RNA (mRNA) production in bovine pulmonary arterial endothelial cells (BPAEC). rHuEPO (3.3 U/ml) induced [Ca2+]i increases from a basal level of 54 +/- 12.2 (SE) to 147 +/- 21.1 nM (p < 0.001), in fura-2-loaded BPAEC. In the presence of nifedipine (10 microM), the increases in [Ca2+]i were significantly reduced. Furthermore, when extracellular calcium ([Ca2+]o) was reduced (200 microM), there was a significant reduction in [Ca2+]i increase after stimulation with rHuEPO. Incubation of BPAEC with rHuEPO for 4 h increased ET-1 levels in the culture supernatant from 44.7 +/- 5.3 to 85 +/- 7.6 pg/ml (p < 0.001). However, when the cells were treated with rHuEPO and nifedipine, the ET-1 levels were decreased, as compared to levels resulting from treatment with rHuEPO alone (41 +/- 6.1 vs. 85 +/- 7.6 pg/ml, p < 0.001, respectively). rHuEPO also induced a fourfold increase in the level of the preproET-1 mRNA as compared with control. PreproET-1 mRNA was diminished in the presence of nifedipine and rHuEPO and rHuEPO can increase [Ca2+]i in BPAEC, and this increase may be related to the stimulation of ET-1 synthesis and release.

Animals↗

PubMed1995

Insulin-like growth factor improves renal architecture of fetal kidneys with complete ureteral obstruction.

Others have previously demonstrated that the administration of insulin-like growth factor-I accelerates recovery from ischemic acute tubular necrosis in the rat kidney. We investigated the effect of insulin-like growth factor-I on the histology of unilaterally obstructed kidneys in the pouch young of the North American opossum, Didelphis virginiana. In this model complete unilateral ureteral obstruction reliably induces statistically significant degrees of caliceal dilatation, tubular cystic change, and cortical and medullary fibrosis in kidneys examined 1 week after the creation of complete obstruction. Cortical and medullary inflammation is also increased after 1 week of obstruction in this model but not to a degree that is statistically different than control (sham operated) animals. We administered insulin-like growth factor-I to opossum pups with complete unilateral obstruction created at a length of 5 cm. (age 25 days, human equivalent 18 to 20 weeks). Insulin-like growth factor-I (400 mcg/kg.) was injected subcutaneously on the day of operation and again on days 2 and 4 postoperatively. The animals were sacrificed 1 week after obstruction and the formalin fixed, paraffin embedded kidneys were assessed histologically. In the obstructed kidney insulin-like growth factor-I ameliorated the development of fibrosis (cortical and medullary) and caliceal dilatation such that these characteristics did not differ significantly from those of sham operated animals. Tubular cystic change in the obstructed kidneys was also decreased by insulin-like growth factor-I administration but not to significant levels. Insulin-like growth factor-I treatment in obstructed animals resulted in significantly more inflammation (cortical and medullary) than in the sham operated animals. We also administered insulin-like growth factor-I to normal pups with no other intervention. These insulin-like growth factor-I treated pups did not differ from sham pups for any characteristic studied. Our study suggests that there is protective effect of insulin-like growth factor-I on renal architecture when administered in the setting of experimental fetal ureteral obstruction.

Animals↗

PubMed1994

Effects of experimental ureteral obstruction on platelet-derived growth factor-A and type I procollagen expression in fetal metanephric kidneys.

Complete ureteral obstruction in fetal opossum kidneys has been used as an experimental method to induce tubulointerstitial damage and interstitial fibrosis. However, the molecular events underlying extracellular matrix deposition are currently unknown. Cytokines such as platelet-derived growth factor (PDGF) are considered possible participants in these processes. In this study we used a marsupial model of ureteral obstruction to examine the expression of PDGF-A and type I procollagen mRNAs by in situ hybridization. Complete unilateral ureteral obstruction was performed in six animals at midtrimester human equivalent. Obstructed kidneys, as well as the contralateral and age-matched sham kidneys, were harvested at 1, 3, 5, 10, and 20 days post obstruction. Morphological assessment of the obstructed kidneys harvested between 1 and 5 days post obstruction showed mild tubulocystic changes, interstitial fibrosis, and inflammation compared with controls. Kidneys harvested at days 10 and 20 showed moderate tubulointerstitial damage compared with kidneys harvested after 1 and 5 days. PDGF-A mRNA signal of low abundance was detected within renal interstitial cells, urothelial cells of the pelvis, and focally within epithelial cells of immature distal convoluted tubules in non-obstructed kidneys. Type I procollagen mRNA expression was spatially co-distributed with PDGF-A-expressing interstitial cells. PDGF-A and type I procollagen signal intensities in obstructed kidneys harvested 10 and 20 days post obstruction were increased several fold compared with controls and kidneys harvested 1-5 days post obstruction. Both PDGF-A and type I procollagen mRNA increases correlated with morphological features of tubulointerstitial damage. Our results suggest that PDGF-A may participate in this form of fetal kidney damage.

Animals↗

PubMed1993

In situ localization of parathyroid hormone-like protein and mRNA in intraepithelial neoplasia and invasive carcinoma of the uterine cervix.

Parathyroid-like protein (PLP), or parathyroid hormone-related peptide, is a well-recognized mediator of paraneoplastic hypercalcemia (humoral hypercalcemia of malignancy syndrome). In this study we examined the expression of PLP by 40 invasive squamous cell carcinomas (SCCs) of the cervix and selected carcinomas of nonsquamous histology. Using a polyclonal antibody to human PLP, 93% of SCCs, including two tumors from patients with humoral hypercalcemia of malignancy syndrome, showed moderate to strong cytoplasmic immunoperoxidase staining for PLP. The strongest staining often was observed in areas of invasion associated with stromal desmoplasia. The small number of weak or negatively stained SCCs were all poorly differentiated tumors. Although native uninvolved squamous epithelium showed weak to moderate staining of the superficial layers, there was variable or full-thickness immunostaining in areas of dysplasia. Normal endocervical glands and stroma as well as cervical adenocarcinomas and neuroendocrine carcinomas were negative. In situ hybridization studies showed abundant PLP mRNA within SCC in patients with hypercalcemia. However, PLP mRNA was of relatively low abundance in tumors of normocalcemic patients. Ultrastructural studies showed cytoplasmic, membrane-bound, granular inclusions in tumor cells from the hypercalcemic patients. Our data suggest that increased PLP gene transcription contributes to the increased production of PLP and the pathogenesis of humoral hypercalcemia of malignancy syndrome.

Adult↗

PubMed1993

Expression of parathyroidlike protein in normal, proliferative, and neoplastic human breast tissues.

Parathyroidlike peptide (PLP), or parathyroid hormone-related protein, is a protein of uncertain biological function that is structurally homologous to parathyroid hormone. Immunohistochemical studies have identified aminoterminal epitopes of PLP in breast carcinomas, but not in normal breast. In the present studies, immunohistochemistry and in situ hybridization were performed to evaluate further expression of PLP in normal, proliferative, and neoplastic breast tissues. Using a polyclonal antibody that recognizes epitopes within the middle and carboxyl-terminal domains of PLP, immunoreactive protein was detected within the cytoplasm of lobular and ductal epithelial cells in all normal and fibrocystic breast tissues from 74 patients. The intensity of cytoplasmic staining was increased in association with lactation, adenosis, and simple or atypical ductal hyperplasia and decreased in atrophic lobules. Cytoplasmic reactivity was also observed in 69% (56 of 81) of breast adenocarcinomas. Expression of immunoreactive PLP was inversely correlated with tumor stage and extent of nodal involvement at the time of diagnosis. However, there was no significant correlation with tumor grade, patient age, or hormone receptor status. In situ hybridization studies confirmed the epithelial expression of PLP messenger RNA in PLP-positive normal and neoplastic breast tissue. Interestingly, tumor-associated calcifications were identified in 43% of PLP-positive carcinomas, but in only 12% of PLP-negative carcinomas (P < 0.007). Our results suggest that PLP plays some role in the normal differentiated function of mammary epithelial cells and are consistent with the hypothesis that expression of this protein influences local calcium metabolism.

Adolescent↗