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F G Silva

Publications and source records attributed to F G Silva.

At least 37 records · Page 2Linked to original sources
PubMed1994

Renal interleukin-1 expression during endotoxemia and gram-negative septicemia in conscious rats.

Endotoxin-induced cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) are thought to contribute to the proinflammatory effects of endotoxin in gram-negative infections. Using a conscious rat model of sepsis, induced by intravenous challenge with LD95 doses of endotoxin (n = 24) or live Escherichia coli (E. coli) (n = 24), we examined frozen sections of kidney at various intervals for evidence of IL-1 alpha and TNF alpha expression. A transient glomerular endothelial IL-1 alpha expression was demonstrated at 30 and 90 min after initiation of the sepsis in both endotoxin and E. coli-treated animals using immunohistochemistry. The endothelial IL-1 alpha expression as determined by immunohistochemistry occurred at the same time as IL-1 alpha mRNA expression, as determined by Northern blot analysis. The glomerular endothelial IL-1 alpha expression coincided with a slight but significant increase in the number of the glomerular polymorphonuclear leukocytes as identified by naphthol AS-D chloroacetate esterase enzyme histochemical reaction. Glomerular endothelial IL-1 alpha expression was virtually absent by 180 and 360 min. No TNF alpha expression was detected in the renal tissues at any time interval. Neither alpha-naphthyl acetate esterase-positive nor acid phosphatase-positive monocytes/macrophages were identified in the glomeruli. Our findings provide direct in vivo evidence that the IL-1 alpha gene product is expressed locally in the kidney by glomerular endothelial cells in this septic rat model.

Animals↗
PubMed1994

Lack of suppressed renal thrombomodulin expression in a septic rat model with glomerular thrombotic microangiopathy.

BACKGROUND: The thrombomodulin-dependent protein C anticoagulant pathway plays a major physiologic role in the down-regulation of the coagulation process. In cell culture, inflammatory cytokines or endotoxin can down-regulate endothelial thrombomodulin (TM) suggesting that suppressed TM expression may contribute to thrombotic complications noted in Gram-negative sepsis. EXPERIMENTAL DESIGN: In the present study, we have examined TM expression in the kidneys of septic rats utilizing indirect immunofluorescence and have quantified TM antigen and TM activity in extracts of the same kidneys by enzyme-linked immunosorbent assays and protein C activation assays, respectively. Conscious Sprague-Dawley rats were injected intravenously with LD95 doses of live E. coli (N = 30), or endotoxin (N = 30). Control animals (N = 30) were injected with equivalent volumes of saline. The rats were killed 30, 90, 180, 360, and 720 minutes after the initiation of sepsis. RESULTS: Glomerular capillary thrombosis developed by 180 minutes in approximately half of the animals after the initiation of sepsis. We failed to demonstrate suppressed TM expression in the kidneys of septic animals using immunofluorescence. Neither enzyme-linked immunosorbent assays, nor protein C activation assays showed decreased levels in TM antigen expression or activity at different time points during the sepsis. CONCLUSIONS: These results indicate that suppressed TM expression does not contribute to the development of the glomerular capillary thrombosis in this septic rat model.

Animals↗
PubMed1994

Absence of association between cytomegalovirus infection and obliterative transplant arteriopathy in renal allograft rejection.

Cytomegalovirus (CMV) was recently identified, using in situ hybridization, in the coronary arteries of patients with cardiac transplant rejection, suggesting a role of CMV in the development of obliterative transplant arteriopathy in cardiac allografts. We sought to verify this observation by examining arteries in kidney transplants with intimal thickening due to chronic rejection. Eleven renal biopsies and 13 nephrectomies from 24 patients, all showing obliterative transplant arteriopathy, were collected for this study. Of these patients, six were seropositive for CMV before transplantation, three were identified as seropositive following renal transplantation, nine had no evidence of CMV infection, and clinical data were not available for an additional six patients. Paraffin-embedded renal sections were examined for the presence of CMV by immunohistochemistry in situ hybridization and polymerase chain reaction. By these methods, only one case (1/24) was demonstrated to have CMV infected cells in the renal interstitium, tubules, and glomeruli, but none (0/24) showed CMV to be located in any of the renal arteries or arterioles. Thus, our results suggest that obliterative transplant arteriopathy can occur in the absence of demonstrable CMV and is probably unrelated to direct CMV infection of the graft.

Adult↗
PubMed1993

Glomerular lesions in adolescents with gross hematuria or the nephrotic syndrome. Report of the Southwest Pediatric Nephrology Study Group.

We report clinical and pathological data in 56 adolescents presenting with gross hematuria (GH) and 65 presenting with idiopathic nephrotic syndrome (INS). IgA nephropathy (present in 52%) and other mesangial lesions were found in the majority of the 56 patients with GH. Many of these patients had complex urological procedures prior to consideration of a nephrological problem. This often led to significant delays in making the appropriate diagnosis. Pathological lesions in the 65 patients with INS included minimal change NS (MCNS) in 31%, membranous glomerulonephritis (MGN) and focal segmental glomerulosclerosis (FSGS) in 18.5% each, and membranoproliferative GN (MPGN) in 12%. In 47 of the patients with INS, in whom no specific treatment had been given prior to renal biopsy, MCNS and MGN were observed with a similar frequency (26% and 23%, respectively), with FSGS and MPGN being found in 21% and 11%. These results indicate that the pathological lesions in adolescents with INS who undergo a renal biopsy more closely resemble those in adults, and are usually more severe than those in young children. However, it should be noted that our study was retrospective. Hence, there were probably some adolescents with INS who had a successful response to therapy and therefore did not have a renal biopsy performed.

Adolescent↗
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

Immunohistochemical and lectin dissection of the human nephron in health and disease.

Many renal diseases involving the tubular epithelium appear to preferentially affect certain nephron segments. While major portions of the nephron, such as proximal and distal convoluted tubules and collecting ducts, can be identified in the normal kidney, the distinction of diseased nephron segments can be difficult in tissue sections. Thus, to identify which nephron segments are involved in pathologic changes is usually impossible by routine histologic examination alone. Recently antibody and lectin probes that react with specific nephron segment-specific epitopes and carbohydrates, respectively, have become available. Some of these antibodies and lectins can be used on formalin-fixed, paraffin-embedded, archival tissues. Because renal tubules appear to retain their nephron segment-specific epitopes and glycoprotein moieties under most pathologic conditions, these nephron segment-specific tubular epithelial markers provide a method to study renal diseases involving the tubular system also in archival material. Such nephron segment-specific tubular epithelial markers are: the lectins, Tetragonolobus purpuras and Phaseolus vulgaris erythroagglutinin (proximal tubular markers); antibodies to low-molecular-weight cytokeratin (AE1/AE3); epithelial membrane antigen and the lectin Arachis hypogaea (distal nephron [distal convoluted tubule and collecting duct] markers); and antibodies to Tamm-Horsfall protein (labeling the thick ascending limb of Henle). We review the application of these and other renal tubular epithelial markers in the normal kidney and in various renal diseases including cystic disease of the kidney, interstitial nephritis, tubular atrophy, acute tubular necrosis, myeloma cast nephropathy, and renal tumors.

Humans↗
PubMed1993

Nonpapillary and papillary renal cell carcinoma: a cytogenetic and phenotypic study.

Cytogenetic and molecular genetic studies allow the common renal cell neoplasms to be separated into two main types: (1) Nonpapillary renal cell carcinomas (RCC) which have a loss of 3p13-pter sequences and (2) Papillary renal cell tumors having tri- or tetrasomies of chromosome 7 and trisomy 17. To investigate renal proximal (PT) and distal (DT) tubular epithelial phenotype expression in these genetically distinct neoplasms, a panel of antibodies and lectins selectively reactive with normal adult PT and DT was applied to 10 nonpapillary and seven papillary RCC. All tumors except one papillary RCC demonstrated characteristic karyotypes. Phenotype expression varied depending upon changes in the histopathologic patterns within a tumor. Among tumors composed of only one cell type, columnar, eosinophilic cells showed only PT staining and small, basophilic cells showed only DT staining. One tumor revealed a transition from small, basophilic cells to columnar, eosinophilic cells. The basophilic cells stained for DT markers and the eosinophilic cells for PT markers. One tumor consisted of nests of clear cells between indistinct papillary structures. The clear cells stained for both PT and DT markers. All 10 nonpapillary RCC demonstrated PT staining; nine exhibited DT markers. Staining was most intense in areas of tumor showing higher nuclear grades, tubuloglandular differentiation or in granular, eosinophilic cells and was absent or weak in solid groups of low nuclear grade clear cells. Papillary and nonpapillary RCC demonstrated lectin-binding or antigens associated with both PT and DT indicating a capacity for multipotential metanephric differentiation in each type of neoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Papillary↗
PubMed1992

Epstein-Barr virus infection-associated renal disease: diagnostic use of molecular hybridization technology in patients with negative serology.

There are only a few reports of renal disease associated with Epstein-Barr virus (EBV) infection. The diagnosis of EBV infection in these previously reported patients was based primarily on positive serology. Two patients with renal disease who, despite repeatedly negative serologies, were shown by molecular hybridization techniques--in situ hybridization (ISH) and polymerase chain reaction (PCR)--to have EBV infection are reported here. Site-specific molecular probes directed against specific, tandemly repeated EBV genomic regions were used. A synthetic 23-mer terminally biotin-labeled oligonucleotide probe selected from the EBV NotI region was used for ISH. For PCR, oligonucleotide primers were designed from sequences of the highly conserved, long internal direct repeat region of EBV to specifically amplify a 110-base-pair segment. The first patient, a 3-yr-old girl with a 1-yr history of fatigue, fever, splenomegaly, and lymphadenopathy developed hematuria. A renal biopsy revealed widespread glomerular mesangiolysis admixed with segmental mesangial sclerosis; no immune deposits were noted by electron microscopy or immunofluorescence. ISH on paraffin sections of the resected spleen and lymph nodes was positive for EBV. The second patient, a 28-yr-old male renal allograft recipient, received a double dose of OKT3. Seven weeks after transplantation, a renal biopsy revealed a lymphoproliferative disorder. Paraffin sections of the nephrectomy specimen were positive for EBV by both ISH and PCR. It was concluded that (1) EBV cannot be excluded on the basis of multiple negative serologies in some patients, and (2) ISH and PCR may lead to the detection of viral genomic information in renal and nonrenal tissues.

Adult↗
PubMed1992

Is cytomegalovirus associated with renal disease in AIDS patients?

Although it has been suggested that cytomegalovirus (CMV) infection of the kidney might facilitate the development of human immunodeficiency virus-associated nephropathy (HIVAN) or other morphologic renal changes in patients with AIDS, no systematic study has been performed on kidneys from AIDS patients. We examined 75 autopsy kidneys, two renal biopsy specimens, and a nephrectomy specimen from 78 HIV-infected patients (five with HIVAN) for the presence of CMV. Immunocytochemistry (ICC) utilizing a monoclonal antibody against the late antigen of CMV and in situ hybridization (ISH) with a biotinylated DNA probe for CMV sequences were used. The detection system for both ICC and ISH was streptavidin-conjugated alkaline phosphatase with Fast Red TR chromogen. CMV was detected in only 10 of the 78 kidneys examined (12.8%): eight by both methods, one by ISH only, and another by ICC only. All 10 positive kidneys were obtained from autopsies of patients with AIDS. The average number of positive cells (in approximately 15 x 10 mm sections) was 22 with ICC and 10 with ISH. Glomerular intracapillary cells (possibly endothelial cells) were the most commonly stained, followed by positive cells in the interstitium and peritubular capillaries. Relatively few tubular epithelial cells were stained. The majority of positive cells by either ICC or ISH did not show nuclear or cytoplasmic inclusions; however, only two of the 10 positive kidneys did not contain cells with typical Cowdry type-A intranuclear CMV inclusions. The most frequent pathologic finding in the kidneys positive for CMV by either ICC or ISH was acute tubular necrosis (in six of 10, 60%).(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Associated Nephropathy↗
PubMed1992

Conditions affecting the immunohistochemical detection of HIV in fixed and embedded renal and nonrenal tissues.

A number of studies have suggested that HIV infection can be detected in a variety of routinely fixed archival tissues using antibodies to various viral proteins. In order to study this immunocytochemical approach, paraffin sections were examined with a large panel of commercially available monoclonal antibodies against the various HIV proteins (5 antibodies to p24, 1 to p17, 1 to gp41, and 1 to gp120) using a streptavidin-biotin method. A polyclonal antibody against p24 was also tested. Formalin-fixed, paraffin-embedded HIV infected CEM E5 T cells were used as positive controls. Tissues from AIDS patients included 31 kidneys, 8 lymph nodes, 2 spleens and 3 brains. Non-AIDS tissues examined were 6 renal biopsies with focal segmental glomerulosclerosis, 5 with interstitial nephritis, 6 reactive lymph nodes, and a brain with encephalitis, all from patients not known to be at high risk for HIV infection. Additional negative controls included: 1) replacement of primary antibody with a hybridoma derived mouse monoclonal IgG1 standard, 2) omission of the primary antibody, and 3) sections of formalin-fixed paraffin-embedded CEM E5 T cells cultures not infected with HIV. Competition experiments with excess recombinant p24 protein were also performed. False positive staining with the IgG1 standard or with the antibodies to HIV proteins was frequently seen in tissues with pathologic findings (inflammation, hyalin degeneration), particularly following protein digestion. Protein digestion also had a major impact on specific staining. Digestion with proteinase K abolished specific staining for the core proteins of the virus (p17, p24) on the positive control sections.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Associated Nephropathy↗
PubMed1990

A clinicopathological study of 24 children with hemolytic uremic syndrome. A report of the Southwest Pediatric Nephrology Study Group.

This study reports the pattern of renal injury in 24 North American children with hemolytic uremic syndrome (HUS), and the extent of extrarenal involvement in 9 of these children examined at autopsy. Fifteen of the 24 children were studied during the first 16 days of hospitalization; their renal specimens demonstrated glomerular thrombotic microangiopathy (TMA) in 8 children, cortical necrosis in 1, and varying degrees of glomerular TMA and cortical necrosis in 6 children. Nine of the children were studied after 16 or more days of hospitalization; these patients had prominent renal arterial lesions. Of 9 children examined at autopsy, extrarenal microthrombi were identified in 8. In 4 children who died during the acute phase of the disease, hemorrhagic colonic necrosis (3 children) and pancreatic islet cell necrosis (2 children) were the principal extrarenal lesions encountered. Rare microthrombi were present in the brains of the 3 children who manifested seizures.

Aging↗
PubMed1990

Acquired immunodeficiency syndrome and the kidney.

Initial autopsy studies concerned primarily with the systemic manifestations of the acquired immunodeficiency syndrome (AIDS) did not indicate that significant renal problems were likely to occur in AIDS patients. However, several recent studies have suggested that important renal and electrolyte disorders develop frequently in at least some groups of AIDS patients. In this report, we review current information concerning such disorders and describe our study of the frequency and types of renal lesions in the first 50 AIDS patients undergoing autopsy at this institution. We conclude that a number of renal lesions and electrolyte abnormalities occur in AIDS patients, although the frequency and nature of these problems vary considerably from center to center. Studies from several centers, including our own, indicate that AIDS patients are particularly likely to develop tubulointerstitial lesions (such as nephrocalcinosis and interstitial nephritis) and electrolyte disorders. Additional studies from specific centers in New York City, Miami, Detroit, and Los Angeles indicate that AIDS patients can also develop glomerular lesions, including a variant of focal and segmental glomerulosclerosis (FSGS) associated with heavy proteinuria and rapidly progressive renal failure. Although FSGS is not commonly observed in all centers, AIDS patients with this lesion appear to have a distinctive combination of clinical and pathological features, suggesting that they have a specific "human immunodeficiency virus (HIV)-associated" nephropathy. Preliminary evidence suggests that this lesion may be related to direct renal HIV infection, although confirmation of this possibility is needed. The approach to the AIDS patient with renal disease should involve correction of reversible disorders and consideration of dialysis as necessary.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Mesangial immunoglobulin A deposits in minimal change nephrotic syndrome: a report of an older patient and review of the literature.

A 57-year-old patient with a history of monoclonal immunoglobulin A (IgA) gammopathy developed idiopathic nephrotic syndrome. Renal biopsy showed minimal glomerular changes with predominant glomerular mesangial IgA. The association of glomerular mesangial IgA with otherwise typical minimal change nephrotic syndrome has been noted before, and the literature concerning this combination of findings is reviewed. The patient herein described represents one of the two oldest patients yet reported with this syndrome and raises questions about the relationship between minimal change disease and IgA nephropathy. Severe proteinuria (and even the nephrotic syndrome) is not necessarily the harbinger of a poor prognosis in IgA nephropathy if the glomerular morphology is otherwise consistent with minimal change nephrotic syndrome. Such patients should be treated in a fashion similar to those with minimal change nephrotic syndrome. The significance of the IgA gammopathy in the pathogenesis of this case is unknown.

Fluorescent Antibody Technique↗
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

Acute tubulointerstitial nephritis in children: clinical, morphologic, and lectin studies. A report of the Southwest Pediatric Nephrology Study Group.

Clinical histories and renal biopsies were reviewed in 12 children with acute tubulointerstitial nephritis, which was drug related in eight, idiopathic in one, and multifactorial in three. Presentation with rashes and hypertension was most common in patients with drug-associated nephritis. Eosinophils, which were present in the majority of the renal biopsies, did not distinguish between drug-related and non-drug-related disease. The majority of the children had a good outcome irrespective of the insulting agent. Frequent tubular basement membrane breaks were identified in seven of the biopsies but were not associated with a poor outcome. Proximal tubule brush border thinning, demonstrated by periodic acid-Schiff and Tetragonolobus lotus staining, paralleled the severity of acute renal failure. Lectin and immunohistochemical techniques to identify proximal tubules (Tetragonolobus lotus), thick ascending limb of Henle (anti-Tamm-Horsfall protein antibodies), and collecting ducts (Arachis hypogaea) allowed better delineation of sites of inflammation and injury, showed collecting tubules to be involved in all cases, and demonstrated that small atrophic tubules were able to maintain the ability to stain with the appropriate lectin/antibody. It is proposed that studies using these techniques may better identify the nephron sites involved in a variety of renal diseases involving tubular segments.

Biopsy↗