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V E Torres

Publications and source records attributed to V E Torres.

At least 37 records · Page 2Linked to original sources
PubMed1998

New insights into polycystic kidney disease and its treatment.

Major advances in the understanding of the genetics and pathogenesis of autosomal dominant polycystic kidney disease have occurred within the past year. The proteins encoded by the PKD1 and PKD2 genes, polycystin 1 and polycystin 2, are membrane proteins, capable of interacting physically in vitro, and are likely components of a complex signalling pathway. The majority of PKD1 and PKD2 mutations so far identified are unique inactivating mutations dispersed over the entire genes. Immunohistochemical studies have shown that polycystin 1 and polycystin 2 are developmentally regulated and are overexpressed in polycystic kidneys. The cysts probably result from clonal expansions of single cells. The demonstration of loss of heterozygosity for PKD1 and the absence of immunoreactive polycystin 1 in approximately 20% of the cysts supports a two-hit tumor suppressor gene model of cystogenesis. Regardless of the nature of the initial pathogenic mechanism, the cysts in autosomal dominant polycystic kidney disease are accompanied by partial dedifferentiation of the epithelial cells, disregulation of epithelial cell proliferation, expression of a secretory phenotype, and disarray of cell matrix interactions which leads to interstitial inflammation and matrix accumulation. Recent observations in animal models of inherited polycystic kidney disease have implicated oxidative stress in its pathogenesis. These downstream pathogenetic events have been targeted for intervention, and an increasing number of studies have demonstrated that the course of polycystic kidney disease in rodents can be altered by environmental and pharmacological interventions. Nevertheless, these experimental observations cannot be extrapolated to human autosomal dominant polycystic kidney disease. The recent generation of mice with PKD1 or PKD2 targeted mutations will help to bridge this gap.

Animals↗
PubMed1998

Hepatic lymphangiomatosis mimicking polycystic liver disease.

Hepatic lymphangiomatosis is a rare disorder characterized by cystic dilatation of the lymphatic vessels in the hepatic parenchyma. It can occur in the liver alone, in the liver and spleen, or in multiple organs. Clinically, diagnosis can be difficult because of the rarity and protean manifestations of this disorder. We describe a 53-year-old woman with hepatic lymphangiomatosis in whom polycystic liver disease had been previously diagnosed. In addition, we review 12 cases of hepatic, splenic, and hepatosplenic lymphangiomatosis with or without systemic lymphangiomatosis and discuss the differential diagnosis.

Cysts↗
PubMed1997

Expression of polycystin in mouse metanephros and extra-metanephric tissues.

The presence of messenger RNA for the mouse homologue of the polycystic kidney disease 1 gene (PKD1) was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) methods in mouse embryo messenger RNA. A single locus for the PKD1 gene was detected on mouse chromosome 17 by fluorescent in situ hybridization. Immunoprecipitation of proteins from [35S] methionine-labeled mouse metanephric explants with an anti-polycystin antibody (Pc1) revealed high molecular weight bands, the highest being > 400 kDa. Immunoperoxidase staining of mouse embryos with Pc1 revealed expression of polycystin as early as day 8 gestation. The expression was seen in epithelial cells of the ureteric bud, in condensing blastemal cells of the developing metanephros and, subsequently, in cells of the nascent tubules. In addition, Pc1 immunoreactivity was seen in hepatocytes and biliary epithelium, cardiac and skeletal muscle, neural tissue, gut, and bronchial epithelium. In post-natal and adult mouse kidney and liver persistent slight to moderate immunoreactivity was observed. Immunofluorescent studies of cultured 13-day mouse metanephroi revealed polycystin expression in ureteric bud epithelium, early glomerular structures (that is, condensates, S-shaped and comma-shaped bodies) and in proximal and distal tubular epithelia. These data indicate that the mouse has a single gene homologous to human PKD1 on chromosome 17, and polycystin is expressed in a variety of tissues during embryonic development.

Age Factors↗
PubMed1997

Neonatal presentation of autosomal dominant polycystic kidney disease with a maternal history of tuberous sclerosis.

BACKGROUND: Childhood presentation of polycystic kidney disease has been reported with tuberous sclerosis complex (TSC). Recently some such cases have been shown to be due to combined deletion of the PKD1 and TSC2 genes, which lie close together on chromosome 16. The phenomenon of anticipation, whereby disease presentation occurs at a progressively earlier age in each generation, has been suggested to occur in autosomal dominant polycystic kidney disease (ADPKD). We have carried out a genetic study of a family in which these issues became clinically relevant. Neonatal presentation of polycystic kidneys occurred in an individual with a maternal family history of epilepsy and features of TSC without renal cystic disease. METHODS: Detailed historical and clinical profiles were gathered for three generations of the maternal and paternal families. Both parents underwent renal ultrasound scanning. Genomic DNA was obtained from affected and unaffected individuals from the maternal family and used for linkage analysis to gene loci for TSC. RESULTS: Renal cysts were not present in the mother by ultrasound. Linkage to TSC2 was found for members of the maternal family with clinical features of TSC. While a diagnosis of TSC was confirmed in her mother the child was found not to have inherited the disease-related allele. The father was found to have asymptomatic bilateral polycystic kidneys consistent with ADPKD. The presence of ADPKD in other paternal relatives could not be confirmed. CONCLUSIONS: The index case was found to have paternally inherited ADPKD with unusually early presentation. While at risk for concomitant maternal inheritance of TSC this diagnosis was ruled out by linkage analysis studies. The ability to clarify the true nature of a complex inherited condition greatly facilitates future management and counselling. The mechanisms underlying phenotypic heterogeneity in ADPKD remain to be clearly defined and are the subject of ongoing investigation.

Female↗
PubMed1997

Cystic kidney diseases.

The goal of understanding the primary defects that lead to renal cystic diseases has proved to be an elusive one, despite 3 decades of physiologic and genetic investigation. Within the past 2 years the genes responsible for type 1 and type 2 autosomal dominant polycystic kidney disease have been identified. The process of defining the normal distribution and functions of the proteins encoded by these genes as well as the precise pathophysiology of cystogenesis is underway. For other major hereditary cystic kidney diseases, chromosomal localization or gene identification has also been achieved in recent years. Mouse and rat models of renal cystic disease continue to be a rich source of new data on the effect of genetic and environmental modifying factors on disease progression as well as serving as a preliminary testing ground for novel approaches to management such as gene therapy and early dietary modification. Ongoing clinical research continues to better define the renal and extra-renal manifestations of autosomal dominant polycystic and other renal cystic diseases. It is likely that a clearer understanding of the pathophysiology of these diseases will provide important insights into the processes that control tissue development and growth, and cellular differentiation.

Animals↗
PubMed1997

Vascular expression of polycystin.

Autosomal dominant polycystic kidney disease (AD-PKD) is predominantly caused by mutations of the gene PKD1, which encodes a large protein, polycystin, of unknown function. A variety of arterial abnormalities occur with increased prevalence in ADPKD patients. Using an antiserum against the nonduplicated region of the polycystin protein, immunostaining of vascular smooth muscle cells was detected in normal adult elastic arteries. Partial digestion of tissue slices with nonspecific proteases greatly enhanced this staining. Similar enhancement was seen with specific elastase digestion. Immunostaining for smooth muscle actin was not affected by elastase. Antiserum preadsorbed with peptide antigen gave no staining. In specimens of intracranial aneurysms, aortic dissections, and dolichoectatic arteries from thirteen patients with ADPKD, immunostaining of variable intensity for polycystin was demonstrated in arterial smooth muscle cells and myofibroblasts, along with disruption of elastic laminae. Further elastase digestion did not significantly alter staining patterns. Intracranial aneurysms from patients without ADPKD also showed a variable degree of immunostaining with polycystin antisera in the same distribution. The expression of polycystin in arterial smooth muscle suggests a direct pathogenic role for ADPKD-related mutations in the arterial complications of this disease.

Adolescent↗
PubMed1997

Aggravation of polycystic kidney disease in Han:SPRD rats by buthionine sulfoximine.

The administration of ammonium chloride or of sodium or potassium bicarbonate has marked effects on the development of polycystic kidney disease (PKD) in Han:SPRD rats. Because of the possibility that these effects are mediated by changes in redox metabolism, the aim of this study was to determine whether depletion of glutathione, the most abundant and important cellular thiol and scavenger of reactive oxygen species, would affect the development of PKD in this animal model. +/+ and cy/+ Han:SPRD rats were treated with: (1) L-buthionine(S,R)-sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase, the rate-limiting enzyme for the synthesis of glutathione; (2) glutathione monoethyl ester (GME), a compound that is known to increase the intracellular levels of glutathione; or (3) BSO and GME. Treatment with these drugs was started at 3 wk of age, and the animals were killed at 6 or 8 wk of age. Renal levels of oxidized glutathione were significantly higher in cy/+ than in +/+ rats, whereas no significant differences in reduced glutathione were detected. The administration of BSO caused a marked reduction in the levels of glutathione. The administration of GME caused a significant increase in the levels of glutathione at 2 h, but not at 12 h, after the administration. The increase in the renal levels of glutathione 2 h after the administration of GME was less in the rats treated with BSO than in the rats not receiving this drug, indicating that in part the increase in glutathione level was due to de novo synthesis. BSO-induced glutathione depletion was accompanied by a marked aggravation of the renal cystic disease, as reflected by kidney weights, histological scores, and plasma urea concentrations. However, the administration of GME did not lessen the cystic disease and did not reverse the effects of BSO. The transient effect of GME administration and the simultaneous increases in the levels of cysteine and oxidized glutathione, in addition to reduced glutathione, may explain the lack of protection by GME. These data support the notion that changes in redox metabolism may affect the development of PKD.

Animals↗
PubMed1997

Intracranial arterial dolichoectasia in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder with a variety of cardiovascular manifestations. This study presents a group of patients with ADPKD who had intracranial arterial dolichoectasia. One hundred seventy-eight ADPKD patients were screened with magnetic resonance angiography, 40 ADPKD patients had conventional angiography, and 98 ADPKD patients underwent a brain autopsy. For comparison, 360 patients without ADPKD who had magnetic resonance angiography and conventional angiography or brain autopsy were also studied. The prevalence of asymptomatic intracranial arterial dolichoectasia was 2.2% (4 of 178), 2.5% (1 of 40), and 2.0% (2 of 98) in the three ADPKD groups, respectively. None of the patients without ADPKD had intracranial arterial dolichoectasia. In addition to the seven patients with asymptomatic disease, two ADPKD patients with vertebrobasilar dolichoectasia had posterior circulation ischemic symptoms. The mean age of the nine patients (five men and four women) was 56.6 yr (range, 41 to 67 yr). The posterior circulation was involved in five patients, the anterior circulation was involved in two patients, and both were involved in two patients. Arterial dissection was believed to have caused middle cerebral artery dolichoectasia in one patient, and intracranial arterial dissections were strongly suspected in two other patients. Six of the nine patients with intracranial arterial dolichoectasia had additional vascular manifestations of ADPKD. Some patients with ADPKD are at an increased risk of developing intracranial arterial dolichoectasia and dissections. Recognizing this association is important because (1) it may be a cause of stroke; (2) it may mimic a saccular aneurysm on radiographic studies; and (3) it suggests that the arteriopathy of ADPKD may be more generalized than previously believed.

Adult↗
PubMed1996

Follow-up of intracranial aneurysms in autosomal dominant polycystic kidney disease by magnetic resonance angiography.

The purpose of this study was to assess the value of magnetic resonance angiography (MRA) in the follow-up of patients with autosomal dominant polycystic kidney disease (ADPKD) and saccular intracranial aneurysms (ICA), the risk of MRA-defined growth of asymptomatic incidental ICA, and the rate of development of MRA-defined de novo ICA in these patients. Between 1989 and 1995, 15 asymptomatic incidental ICA measuring 1.5 to 6.5 mm in diameter, three symptomatic aneurysms, and one asymptomatic concurrent aneurysm were detected by MRA in this study in 18 patients from 15 families. Four-vessel cerebral angiography in the three patients with symptomatic ICA and autopsy in one patient with an asymptomatic incidental ICA did not reveal additional aneurysms undetected by MRA. Thirty MRA studies were obtained in 10 of the 15 patients with incidental ICA during a cumulative clinical follow-up of 500 months (mean, 33.3; range, 0 to 65 months). The cumulative interval between the initial and the last MRA was 306 months (mean, 30.6; range, 14 to 51 months). No change in aneurysmal size or development of de novo aneurysms was detected. Eight MRA studies were obtained in the three patients with symptomatic ICA during a cumulative clinical follow-up of 130 months (mean, 43.3; range, 23 to 64 months). The cumulative interval between the first and the last MRA was 95 months (mean, 31.7; range, 15 to 49 months). Development of de novo aneurysms was not detected. These results indicate that MRA is an appropriate technique to follow small asymptomatic incidental ICA in patients with ADPKD and that the risk for rapid growth of these aneurysms is low. Although the results of this study should be viewed as preliminary, they do not suggest a higher rate of development of de novo aneurysms or a higher frequency of multiple aneurysms in patients with ADPKD and ICA as compared with patients with sporadic ICA in the general population.

Adult↗
PubMed1996

Laparoscopic marsupialization of symptomatic polycystic kidney disease.

PURPOSE: Although laparoscopic unroofing of simple renal cysts has proved to be an effective form of therapy, its use for treatment of multiple renal cysts or symptomatic autosomal dominant polycystic kidney disease only recently has been investigated. MATERIALS AND METHODS: The results of laparoscopic marsupialization of symptomatic renal cysts in 13 patients was determined 12 to 28 months postoperatively by assessing subjective pain relief, and comparing preoperative and postoperative computerized tomography (CT). Eight patients had autosomal dominant polycystic kidney disease. Multiple dominant (more than 3 cm.) cysts were marsupialized in 11 patients and 1 dominant cyst was treated in 2. RESULTS: Of 13 patients with symptomatic renal cysts and 8 with autosomal dominant polycystic kidney disease 8 (62%) and 4, respectively, were pain-free 12 to 28 months postoperatively. Two patients had persistent pain, while 3 had recurrent pain 7 to 16 months postoperatively. All 5 patients had persistent or recurrent dominant cysts on followup CT. Followup CT demonstrated resolution or a significant decrease of the largest and all or all but 1 of the other dominant cysts in 6 of 7 pain-free patients. Intraoperative ultrasound detected unidentified cysts during an open and laparoscopic procedure. No deleterious effects on serum creatinine were observed. CONCLUSIONS: Laparoscopic marsupialization is a safe, relatively successful technique for providing persistent pain relief in patients with autosomal dominant polycystic kidney disease. Although the 2-year pain-free rate approaches the 62% rate reported for open surgical cyst resection, continued efforts to improve current laparoscopic techniques are clearly indicated. Persistence or recurrence of dominant cysts on CT correlated with persistent or recurrent symptoms. Intraoperative ultrasound is effective in identifying dominant cysts.

Adult↗
PubMed1996

Immunolocalization of polycystin in human tissues and cultured cells.

The gene PKD I, which is mutated in type I autosomal dominant polycystic kidney disease (ADPKD 1), encodes a large protein of novel structure and unknown function and distribution that has been named polycystin. To gain better insight into polycystin function, we raised a panel of antisera against synthetic peptide antigens derived from the unique portion of the predicted polycystin sequence. Antisera were used to immunolocalize the protein in a variety of normal human fetal, childhood, and adult tissues as well as kidney and liver tissue from individuals with ADPKD 1, the genetically distinct ADPKD 2, and acquired renal cystic disease (ARCD). Subcellular localization studies were carried out on human cultured cell lines of renal epithelial origin. In normal tissues, polycystin expression was noted in renal tubular epithelial cells from 20 weeks gestation to 4 years postpartum, and in hepatocytes and biliary epithelium up to 4 years, but not in adult kidney or liver. Expression also was present in fetal and childhood pancreas, myocardium, bowel, and adrenal medulla. In cell lines of renal epithelial origin, immunofluorescence and immunoelectron-microscopical studies showed localization of polycystin epitopes to the peripheral cytoplasm. Kidney and liver from four unrelated adults with known ADPKD 1 showed strong staining, which was not seen in kidney and liver from one adult with ADPKD 2 or in kidney from three patients with ARCD. We conclude that polycystin is expressed in renal tubular epithelial cells as well as a variety of other cell types during development and growth but is absent or weakly expressed in adult kidney and liver. Overexpression of polycystin epitopes within affected tissue may be a specific feature of some or all cases of ADPKD 1.

Adult↗
PubMed1995

Liver resection and cyst fenestration in the treatment of severe polycystic liver disease.

BACKGROUND/AIMS: There is limited information on treatment options for massive, highly symptomatic polycystic liver disease. The aim of the study was to analyze the immediate and long-term outcome of combined liver resection and fenestration. METHODS: Information was abstracted from medical records. Follow-up was obtained by mailed questionnaire. Liver volume was quantified by computed tomography. RESULTS: Thirty-one patients underwent liver resection and fenestration between July 1985 and June 1993. Mean liver volume was 9357 mL before and 3567 mL after surgery. There was one death from postoperative intracerebral bleed. Eighteen patients experienced complications, usually transient pleural effusions or transient ascites. Twenty-eight of 29 surviving patients with adequate follow-up have experienced immediate and sustained relief of symptoms and improvement in quality of life. After median follow-up of 2.4 years (range, 0.2 to 7.9 years), most patients have not had clinically significant enlargement of the liver. Sequential computed tomography scans before and after surgery suggest that hepatic enlargement in the age range of the patients in the study mainly resulted from the expansion of existing cysts rather than from the development of new cysts. CONCLUSIONS: Selected patients with severe symptomatic polycystic liver disease and favorable anatomy benefit from liver resection and fenestration with acceptable morbidity and mortality. The extent of hepatic resection and fenestration is important for the long-term effectiveness of this procedure.

Adult↗
PubMed1995

Continuous epithelial cell lines from ADPKD liver cysts exhibit characteristics of intrahepatic biliary epithelium.

We have produced continuous cell lines using retroviral transduction of SV40 large T antigen into epithelial cells removed from the lumen of liver cysts from four female patients with autosomal dominant polycystic kidney disease (ADPKD). Liver cyst-derived epithelial (LCDE) cell lines are grown in a hormonally supplemented medium in the presence of lethally irradiated NIH/3T3 fibroblast coculture. LCDE cells maintain their epithelial appearance and are positive for the biliary-specific markers cytokeratin 7 and 19 and gamma-glutamyl transpeptidase while being negative for hepatocyte markers. SV40 large T antigen is localized to the cell nucleus. LCDE cells have been grown continuously for periods exceeding 12 mo and 25 passages (170 population doublings). LCDE cells exhibit intracellular pH regulatory pathways that, with one exception, are similar to those found in normal intrahepatic biliary epithelium. These LCDE cell lines exhibit impaired alkalinization in response to Cl- substitution. This finding is suggestive of decreased function or abundance of a Cl-/HCO3- anion exchanger and could account for the failure of ADPKD hepatic cysts to secrete HCO3- in response to secretin.

3T3 Cells↗