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R Verani

Publications and source records attributed to R Verani.

At least 19 recordsLinked to original sources
PubMed2006

Expression of the Wnt inhibitor Dickkopf-1 is required for the induction of neural markers in mouse embryonic stem cells differentiating in response to retinoic acid.

Cultured mouse D3 embryonic stem (ES) cells differentiating into embryoid bodies (EBs) expressed several Wnt isoforms, nearly all isotypes of the Wnt receptor Frizzled and the Wnt/Dickkopf (Dkk) co-receptor low-density lipoprotein receptor-related protein (LRP) type 5. A 4-day treatment with retinoic acid (RA), which promoted neural differentiation of EBs, substantially increased the expression of the Wnt antagonist Dkk-1, and induced the synthesis of the Wnt/Dkk-1 co-receptor LRP6. Recombinant Dkk-1 applied to EBs behaved like RA in inducing the expression of the neural markers nestin and distal-less homeobox gene (Dlx-2). Recombinant Dkk-1 was able to inhibit the Wnt pathway, as shown by a reduction in nuclear beta-catenin levels. Remarkably, the antisense- or small interfering RNA-induced knockdown of Dkk-1 largely reduced the expression of Dlx-2, and the neuronal marker beta-III tubulin in EBs exposed to RA. These data suggest that induction of Dkk-1 and the ensuing inhibition of the canonical Wnt pathway is required for neural differentiation of ES cells.

Animals↗
PubMed2001

Concomitant inhibition of Janus kinase 3 and calcineurin-dependent signaling pathways synergistically prolongs the survival of rat heart allografts.

The cytoplasmic localized Janus tyrosine kinase 3 (Jak3) is activated by multiple cytokines, including IL-2, IL-4, and IL-7, through engagement of the IL-2R common gamma-chain. Genetic inactivation of Jak3 is manifested as SCID in humans and mice. These findings have suggested that Jak3 represents a pharmacological target to control certain lymphoid-derived diseases. Using the rat T cell line Nb2-11c, we document that tyrphostin AG-490 blocked in vitro IL-2-induced cell proliferation (IC(50) approximately 20 microM), Jak3 autophosphorylation, and activation of its key substrates, Stat5a and Stat5b, as measured by tyrosine/serine phosphorylation analysis and DNA-binding experiments. To test the notion that inhibition of Jak3 provides immunosuppressive potential, a 7-day course of i.v. therapy with 5-20 mg/kg AG-490 was used to inhibit rejection of heterotopically transplanted Lewis (RT1(l)) heart allografts in ACI (RT1(a)) recipients. In this study, we report that AG-490 significantly prolonged allograft survival, but also acted synergistically when used in combination with the signal 1 inhibitor cyclosporin A, but not the signal 3 inhibitor, rapamycin. Finally, AG-490 treatment reduced graft infiltration of mononuclear cells and Stat5a/b DNA binding of ex vivo IL-2-stimulated graft infiltrating of mononuclear cells, but failed to affect IL2R alpha expression, as judged by RNase protection assays. Thus, inhibition of Jak3 prolongs allograft survival and also potentiates the immunosuppressive effects of cyclosporin A, but not rapamycin.

Animals↗
PubMed1999

Changing patterns in the histopathology of idiopathic nephrotic syndrome in children.

BACKGROUND: It is widely accepted that minimal change nephrotic syndrome (MCNS) is the most common cause of nephrosis in children. Recent studies have demonstrated an increasing incidence of focal segmental glomerulosclerosis (FSGS) in adults. METHODS: To determine possible changes in the etiology of childhood nephrosis, the clinical charts of 152 pediatric patients diagnosed with idiopathic nephrotic syndrome between 1978 and 1997 were reviewed. Histopathological diagnosis was available in 105 patients. RESULTS: MCNS was present in 35% of all biopsies, whereas FSGS was observed in 31%. Even if we assume that all patients without a histological diagnosis had MCNS (presumptive MCNS), the total incidence of MCNS (biopsy proven + presumptive) in our population was only 55%. We observed a dramatic increase in the incidence of FSGS during recent years. Before 1990, FSGS was diagnosed in 23% of all renal biopsies but increased to 47% afterward (P = 0.02). This pattern was observed in all ethnic groups. In African Americans, there was a trend for an increase in the incidence of FSGS from 38% before 1990 to 69% after 1990. A similar trend was observed in Caucasians (from 20 to 45%) and Hispanics (from 8 to 33%) Hispanics had the highest incidence of MCNS (biopsy proven + presumptive: 73%), followed by Caucasians (53%) and African Americans (37%). The mean age for presentation of nephrotic syndrome in African Americans (8.0 +/- 0.9 years) was higher than in Caucasians (4.1 +/- 0.05) and Hispanics (3.3 +/- 0.5). CONCLUSIONS: Our study showed that the incidence of FSGS in children with idiopathic nephrotic syndrome has increased recently. Furthermore, in African American children. FSGS is the most common cause of nephrotic syndrome. These findings may have significant implications in the management of childhood nephrotic syndrome.

Adolescent↗
PubMed1995

[Transurethral resection of the prostate: when?].

Over a period of 5 years (from 1989 to 1993) 410 patients with benign prostatic hypertrophy (BPH) were treated by transurethral resection of the prostate (TURP). A retrospective study was conducted by the Authors to evaluate indications, surgical approaches and results. The Authors' experience is compared with literature reports.

Humans↗
PubMed1994

Intracytoplasmic lumina in a case of bilaterally multifocal renal oncocytomas.

We report a case of bilaterally multifocal renal oncocytomas in a patient with chronic renal disease and a long history of hypertension. Histologic study of the multiple oncocytic neoplasms with hematoxylin-eosin, periodic acid-Schiff, trichrome, and colloidal iron stains revealed novel, intracytoplasmic lumina, which were accentuated by immunoperoxidase staining with high-molecular-weight cytokeratin, epithelial membrane antigen, and Arachis hypogaea lectin. Ultrastructural studies demonstrated multiple microvilli lining the intracytoplasmic lumina. We also review the literature on bilaterally multifocal oncocytomas.

Adenoma, Oxyphilic↗
PubMed1993

Congenital mesoblastic nephroma: an immunohistochemical and lectin study.

Eight cases of congenital mesoblastic nephroma (CMN) were examined. Three CMNs were of the classical (typical) variant, two were cellular (atypical), and three showed a mixed pattern. A panel of nephron segment-specific tubular epithelial markers (the lectins Tetragonolobus purpureas, Phaseolus vulgaris erythroagglutinin, and Arachis hypogaea and antibodies to epithelial membrane antigen, cytokeratin, and Tamm-Horsfall protein) were used to differentiate epithelial structures within the tumor. Antibodies against vimentin, desmin, and muscle-specific actin were used as mesenchymal markers. A monoclonal antibody to the long (embryonic) form of polysialic acid (PSA) on the neural cell adhesion molecule was used as a putative renal oncodevelopmental marker. An antibody to proliferating cell nuclear antigen also was applied, which revealed increased proliferative rate in cellular CMNs. In addition to clearly entrapped native renal tubules, CMNs contain tubular structures with immature, dysplastic epithelium and occasional epithelial cell clusters embedded deep within the tumor. These immature tubules and clusters express distal nephron, including collecting duct markers and, occasionally, vimentin and PSA. We propose that these primitive tubules and epithelial structures may originate from the ureteric bud. An epithelial differentiation of the tumor cells also is possible. In one pure cellular CMN and two mixed CMNs the cellular component showed diffuse staining for PSA. The PSA (neural cell adhesion molecule) expression of the cellular component suggests that CMN may originate from the uninduced nephrogenic mesenchyme.

Child↗
PubMed1993

Effect of atrial natriuretic peptide on urine flow and glomerular filtration during acute renal allograft rejection.

The effect of exogenous atrial natriuretic peptide (ANP) on urine excretion and glomerular filtration rate (GFR) during acute renal allograft rejection was evaluated in a canine model. Eight animals underwent simultaneous allotransplantation and unilateral native nephrectomy. No preoperative or postoperative immunosuppressive therapy was given. Acute renal function studies were performed on the allografts and companion, native kidneys following surgical exposure and mobilization on the third postoperative day. At reexploration, the allografts were found to be grossly enlarged (138 +/- 10 gm.) and contained moderate-to-marked perivascular interstitial infiltration. Glomerular filtration rate, determined by measurement of urinary inulin clearance, was significantly reduced from prenephrectomy baseline values (19 +/- 4 ml. per minute versus 32 +/- 5 ml. per minute, p < .05). During a 30 minute, intravenous ANP infusion, allograft urine flow rates increased from 1.4 +/- 0.5 ml. per minute to 3.3 +/- 0.4 ml. per minute (p < .01), and GFR increased from 19 +/- 4 ml. per minute to 24 +/- 4 ml. per minute (p < .05). During ANP infusion, mean arterial pressure declined from 136 +/- 7 mm. Hg to 116 +/- 7 mm. Hg (p < .05), and the hematocrit remained unchanged. These observations are consistent with previously described, ameliorative effects of ANP in other models of acute ischemic renal injury and provide an experimental basis for more extended studies examining the potential usefulness of ANP as adjunctive therapy in the treatment of acute renal allograft rejection.

Acute Disease↗
PubMed1990

Proteinuria in cyclosporine-treated renal transplant recipients.

Of 704 renal transplant recipients receiving long-term cyclosporine immunosuppression, 71 patients experienced proteinuria greater than 1 g/24 hr beyond the first month posttransplant. Eight patients displayed transient proteinuria, defined as lasting less than 3 months. In most cases this condition was attributed to biopsy-proved acute rejection. The transient proteinuria cohort experienced good graft outcome--namely, 87.5% one-year and 52.5% five-year actuarial graft survivals, which was similar to that observed in patients without proteinuria. In contrast, 52.4% of the 63 patients with nontransient proteinuria experienced graft loss within a median time of 6.1 months. The one- and five-year actuarial graft survivals in patients with nontransient proteinuria were 75.3% and 37.5%, respectively. Among the 63 patients with nontransient proteinuria, histopathologic diagnosis included chronic rejection in 19, transplant glomerulopathy in 14, acute rejection in 9, glomerulonephritis (GN) in 7 including 2 cases of membranous GN, and nonspecific interstitial fibrosis in 10 cases. Despite the overall poor prognosis for graft survival among the entire cohort of patients with nontransient proteinuria, the seven with allograft GN maintained prolonged graft function. They showed an 83.3% five-year actuarial graft survival versus 31.2% in patients with other causes of proteinuria (P = 0.043). These results suggest that posttransplant proteinuria in CsA-treated renal transplant recipients arises primarily as a consequence of allograft rejection and portends a poor graft outcome.

Cyclosporins↗
PubMed1989

Renal cystic disease of infancy: results of histochemical studies. A report of the Southwest Pediatric Nephrology Study Group.

Histochemical techniques utilizing Tetragonolobus lotus (proximal tubules), Arachis hypogaea (distal nephron, i.e., distal convoluted tubules and collecting ducts), and antibodies against Tamm-Horsfall protein (thick ascending limbs of Henle) were used to determine the site of origin of renal cysts in five children with autosomal recessive polycystic kidney disease (ARPKD) and three patients with glomerulocystic disease (GCD) presenting in the 1st year of life. The findings support a distal nephron origin for the cysts in the children who had ARPKD, whereas the majority of cysts in the children with GCD were confirmed as having a glomerular origin. Tamm-Horsfall protein was identified in the cysts of both ARPKD and GCD; this finding suggests free communication between some of the cysts with the thick ascending limb of Henle. An unexpected finding was the frequent presence of cysts surrounded by muscle fibers. We suggest that these cysts are of collecting duct origin.

Child↗
PubMed1989

Effect of exogenous ANP on initial renal function following 24-hour cold preservation.

The impact of synthetic atrial natriuretic peptide (sANP) on renal function following cold ischemic injury was studied in a canine autotransplant model. Following a prenephrectomy inulin clearance determination (CIn), the left kidney was excised, flushed with Eurocollins solution, and cold-stored for 24 hours. Immediately following reperfusion and a 10 minute equilibration period, baseline CIn was measured over a 20-minute time interval (Collection Period I). Experimental animals (N = 11) then received 1 mcg/kg sANP by intravenous bolus followed by a continuous infusion at 0.3 mcg/kg/min for 30 minutes. CIn was measured throughout the infusion (Collection Period II). Normal saline was substituted for sANP in control animals (N = 11). CIn was also measured 24 hours following reimplantation in seven control and seven sANP-treated animals. Autograft inulin clearance increased from 0.32 +/- 0.11 ml/min during Period I to 2.5 +/- 0.6 ml/min during sANP infusion (P less than 0.01). This increase in CIn associated with ANP infusion was accompanied by increases in urine flow rate (V) (0.15 +/- 0.05 ml/min to 0.98 +/- 0.21 ml/min, P less than 0.01) and renal blood flow (RBF) measured by electromagnetic flow probe (85 +/- 17 ml/min to 171 +/- 13 ml/min, P less than 0.05). No significant changes in CIn, V, or RBF occurred in control animals between periods I and II. Although systemic blood pressure declined during sANP infusion, it did not decrease to an extent that compromised peripheral perfusion. CIn determined 24 hours after autograft reimplantation in the ANP-treated animals approximated or exceeded values determined during ANP infusion (Period II).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Granulomatous interstitial nephritis after a jejunoileal bypass: an ultrastructural and histochemical study.

We present a case of granulomatous interstitial nephritis and renal failure after a jejunoileal bypass for obesity. Improvement of the renal function occurred after reversal of the intestinal bypass. The renal biopsy showed an interstitial nephritis, oxalate crystal deposition and several aggregates of multinucleated giant cells related to the crystal material (granulomatous reaction). By ultrastructural and histochemical studies we demonstrated mitochondrial alterations in the tubular epithelial cells, and we suggested the proximal tubule origin of the giant cells. The association of the oxalate crystals with damaged tubules and giant cells suggests that the oxalate crystals are responsible for these alterations. The possibility of an associated immunological process as the cause of the interstitial nephritis cannot be excluded.

Acute Kidney Injury↗
PubMed1989

Bullous amyloidosis.

Amyloidosis may present with involvement of a variety of organ systems. Cutaneous involvement is a relatively common finding in patients with systemic amyloidosis. The occurrence of bullous skin lesions, however, is rare; only a few such cases have been previously reported. We describe a patient who presented with a subepidermal bullous skin disease initially thought to be bullous pemphigoid based on both clinical and histologic appearances. The patient subsequently developed the nephrotic syndrome. Biopsy specimens of the skin and kidney showed involvement of both organs with amyloid, and amyloid was later found in the spleen, heart, and nervous system. No subsequent evidence of myeloma was found in this patient. The clinical, histopathologic, immunofluorescent, and electron microscopic findings of systemic amyloidosis are discussed.

Amyloidosis↗
PubMed1988

Correlation of radionuclide and ultrasound studies with biopsy findings for diagnosis of renal transplant rejection.

The diagnosis of early renal transplant rejection is of the utmost importance to the transplant recipient. Unfortunately, such a diagnosis is often extremely difficult to make. In an attempt to clarify this issue we retrospectively evaluated 35 patients with the presenting diagnosis of rejection for the correlation of comparable radionuclide (RN) and ultrasound (US) examinations with biopsy findings. In 21 patients with heavy interstitial mononuclear cell infiltration, 22 of 23 serial RN studies within forty-eight hours of biopsy were positive for rejection. Only 3 of 14 comparable US studies were positive for rejection. When examinations performed within approximately fourteen days were evaluated, 7 of 11 RN studies were positive for rejection, while 2 of 9 comparable US studies were positive for rejection. However, in 14 patients with mild or no interstitial cellular infiltration, only 6 of 13 RN studies were positive, while all 4 US examinations were negative. In the group evaluated at approximately two weeks, 2 of 6 RN studies were positive, while 0 of 5 US studies were positive. We conclude that the serial RN study is more sensitive than US examination for the diagnosis of acute rejection. US, however, proved valuable in the identification of transplant complications (i.e., fluid collections, ascites, and hydronephrosis).

Biopsy↗
PubMed1988

Massive renal and retroperitoneal hemorrhage in a case of acquired renal cystic disease with atypical epithelial cell proliferation.

We present a case of acquired renal cystic disease in a patient with end-stage renal disease (ESRD) secondary to systemic lupus erythematosus who was dialysis dependent for 5 years. Renal hemorrhage and neoplastic transformation of the cyst epithelium are the two major complications of acquired renal cystic disease, and were present in this patient. The full clinical significance of the acquired renal cystic lesion is still unclear, although the possibility of renal tumors and massive renal and retroperitoneal hemorrhage should be considered in the long-term dialysis population.

Adult↗
PubMed1988

Renal glomerular and tubular abnormalities in glycogen storage disease type I.

Three children had renal histopathologic findings indicative of glycogen storage disease type I. Glomerular basement membrane (GBM) alterations were present in the three patients, particularly so in the two patients with proteinuria. Thickening, lamellation, and glycogen deposition were the characteristic alterations in the GBM. Glomerulosclerosis was prominent in one patient. We suggest that the GBM alteration is related to the glomerular sclerosis and that both are related to metabolic derangements of glycogen storage disease type I.

Adolescent↗