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S M Bonsib

Publications and source records attributed to S M Bonsib.

At least 37 records · Page 2Linked to original sources

Radiation-induced changes in glomerular and tubular cell kinetics and morphology following irradiation of a single kidney in the pig.

PURPOSE: Radiation-induced changes in glomerular and tubular cell kinetics and morphology following irradiation of a single pig kidney were assessed. METHODS AND MATERIALS: The right kidney of 13 adult female Large White pigs was irradiated with a single dose of 9.8 Gy gamma rays. Animals were serially killed between 2 and 24 weeks postirradiation (PI); 1 h prior to postmortem each pig received 500 mg bromodeoxyuridine (BrdUrd). At postmortem, both kidneys were removed and tissue taken to prepare cell suspensions. The labeling index (LI) of these suspensions was measured using flow cytometry; in vivo BrdUrd incorporation in glomerular and tubular cells was determined immunohistochemically. The kidneys were also assessed histologically. RESULTS: Irradiation of the right kidney alone resulted in a significant increase in renal cell LI in both the irradiated and the contralateral unirradiated kidney within 2 weeks of irradiation; peak values of 1.57 +/- 0.32% and 1.04 +/- 0.13%, respectively, were seen 4 weeks PI, significantly greater (P < 0.001) than the preirradiation value of 0.18 +/- 0.01%. The LI values then declined with time, but remained greater than those seen prior to irradiation. A similar pattern of response was determined from counts of labeled glomerular and tubular cells identified immunohistochemically. The increase in labeled glomerular cells was seen 2 weeks PI, whereas that for the tubular cells did not occur until 4 weeks PI. The irradiated kidney exhibited diffuse, progressive glomerular alterations. In contrast, tubular damage was focal; the irradiated kidney also exhibited a prominent vasculopathy, involving arteriolar and peripheral interlobular artery thickening. The contralateral unirradiated kidney appeared unchanged. CONCLUSION: These findings confirm the hypothesis that the morphologic and kinetic responses observed after irradiation of a single kidney are similar to those observed after irradiation of both kidneys. Renal irradiation results in significant alterations in glomerular and tubular cell proliferation and morphology within 2-4 weeks of irradiation; glomerular changes appear predominant.

Animals↗

Radiation nephropathy: a review.

The marked radiosensitivity of renal tissue represents a limitation on the total radiotherapeutic dose that safely can be applied to treatment volumes that include the kidneys. Radiation nephropathy is characterized by a progressive reduction in renal hemodynamics associated with a severe anemia. The latter is often normochromic normocytic in character, but can progress to a microangiopathic hemolytic anemia. The pathogenic mechanisms responsible for the development of radiation nephropathy remain ill-defined. Experimental studies which allow serial determinations of functional, morphologic, and cell kinetic radiation-induced changes indicate that primarily glomerular but also tubular alterations occur in the primary stages of radiation nephropathy. Glomerular capillary endothelial cell loss is seen within several weeks of irradiation. Remaining endothelial cells exhibit increased permeability leading to a subendothelial transudate. Mesangiolysis also is observed. In contrast, podocytes appear to be relatively unaffected at this stage. The endothelial changes appear to resolve, but the mesangial lesions progress, with hypercellularity and/or hypertrophy, increased mesangial matrix, mesangial sclerosis, and ultimately, glomerulosclerosis. These mesangial changes are similar to those observed in other chronic glomerulopathies. Dietary protein restriction, corticosteroids, and ACE-inhibitors all can reduce the severity of experimental radiation nephropathy.

Animals↗

Necrotizing medullary lesions in patients with ANCA associated renal disease.

One hundred and five renal specimens from patients with antineutrophil cytoplasmic antibody and antiglomerular basement membrane antibody-associated diseases were reviewed for necrotizing lesions involving the renal medulla. Necrotizing medullary lesions were identified in eight of 56 cases in which medullary tissue was present. All eight were in patients with antineutrophil cytoplasmic antibody (ANCA) associated disease (seven, C-ANCA; one P-ANCA). Four types of medullary lesions were identified; necrotizing capillaritis (seven cases), necrotizing arteriolitis (two cases), pathergic granulomas (three cases) and papillary tip necrosis (one case). Both medullary arteriolitis and medullary peritubular capillaritis developed without corresponding cortical arteriolitis or cortical peritubular capillaritis. Although necrotizing glomerulonephritis was present in seven of eight patients, its activity did not parallel the severity of the medullary lesions. We conclude that several forms of necrotizing medullary vascular lesions may develop in ANCA-associated disease and that there is discordance between state of activity and types of vessel affected between cortical and medullary vascular compartments.

Adolescent↗

Immunocytochemical analysis of band 3 protein in renal cell carcinoma, nephroblastoma, and oncocytoma.

Band 3 protein is an anion-exchange protein that in the human kidney is restricted to a subpopulation of collecting duct-intercalated cells; however, it is absent in the metanephric-derived cells of the nephron. We have studied band 3 protein expression in a series of 60 renal tumors that included 10 oncocytomas, 42 renal cell carcinomas, and eight nephroblastomas by using frozen tumors and a monoclonal antibody. We detected band 3 protein expression in nine of 10 oncocytomas but not in any renal cell carcinomas or nephroblastomas. This finding confirms that band 3 protein is a specific marker for oncocytoma and therefore may have a potential diagnostic application. It also supports the contention that renal cell carcinoma and oncocytoma are histogenically unrelated; the former is metanephric blastema derived and the latter is ampullary bud derived.

Adenoma, Oxyphilic↗

Coexistent anti-neutrophil cytoplasmic antibody and antiglomerular basement membrane antibody associated disease = report of six cases.

From a series of 95 patients biopsied for rapidly progressive glomerulonephritis, twelve patients were identified with anti-glomerular basement membrane-mediated renal disease who were also tested for antineutrophil cytoplasmic antibody (ANCA). Six patients had both anti-glomerular basement membrane and ANCA antibodies. Three of the latter six patients had significant extrarenal disease, including severe hemoptysis, while the remaining three patients had only renal disease. The three patients with extrarenal disease had either a myeloperoxidase-positive perinuclear-ANCA (two patients) or a proteinase-3-positive cytoplasmic-ANCA (one patient). Two patients with renal disease alone had a myeloperoxidase-negative and proteinase-3-negative perinuclear-ANCA, and one patient had a proteinase-positive cytoplasmic-ANCA. Renal biopsy in all six patients showed a severe necrotizing and crescentic glomerulonephritis involving 94 to 100% of glomeruli. Renal arteritis was also noted in one perinuclear-ANCA patient. Despite aggressive therapy with steroids, cyclophosphamide, and plasma exchange, two of the six double-antibody patients died and four are on dialysis. We conclude that ANCA is commonly present in anti-glomerular basement membrane-associated disease and believe that this observation may have implications in the serologic evaluation of ANCA- and anti-glomerular basement membrane-positive patients.

Adult↗

Occurrence of melanin in pheochromocytoma.

Melanin or a melanin-like pigment was observed in six of 19 pheochromocytomas. The intracellular pigment was Fontana-positive, bleach-labile dark brown to black material and distinct from coincidental hemosiderin and lipochrome. Ultrastructural components of the pigmented tumors include melanosomes and premelanosomes. Two patients with pigmented tumors had associated von Hippel-Lindau syndrome, and one had neurofibromatosis. The occurrence of melanin and melanosomes in pheochromocytoma has not been previously reported in the English literature. It is probably a reflection of the neural crest origin of this neoplasm.

Adrenal Gland Neoplasms↗

Renal artery stenosis modifies glomerular injury in antineutrophil cytoplasmic antibody-associated disease.

A 68-year-old man presented with renal failure, heart failure, gastrointestinal bleeding, and a pulmonary infiltrate. Serologic evaluation revealed a perinuclear antineutrophil cytoplasmic antibody (ANCA) at a titer of 1:1280, which on immunoblot and enzyme immunoassay showed antimyeloperoxidase specificity. Autopsy showed microscopic polyarteritis based on the presence of necrotizing alveolitis and crescentic glomerulonephritis. The extent and activity of the glomerular disease was modified by a right renal artery stenosis (RAS). Twenty percent of glomeruli on the right and 82% glomeruli on the left contained crescentic lesions. Furthermore, predominantly active lesions were associated with renal artery stenosis, while the contralateral kidney contained mostly organized crescents. This observation suggests that hemodynamic factors or its sequelae can influence the onset and severity of ANCA-associated disease.

Aged↗

Renal oncocytoma: diagnostic utility of cytokeratin-containing globular filamentous bodies.

Sixty-six renal cortical epithelial tumors were classified by light and electron microscopy into 18 oncocytomas and 48 renal carcinomas, and their pattern of cytokeratin and vimentin reactivity was evaluated by immunoperoxidase using paraffin-embedded tissue. We found by electron microscopy that most oncocytomas (11 of 15) contain globular filamentous bodies that consist of a complex of intermediate filaments and organelles. These structures were found to correlate on immunohistochemistry with a discrete punctate cytoplasmic pattern of cytokeratin reactivity, provided the antibody preparation contained specificity for cytokeratins 8 and 18. A similar punctate finding was not observed in four oncocytomas nor in the 48 renal carcinomas. Although 11 oncocytomas failed to express vimentin, seven tumors showed focal reactivity restricted to rare individual cells in areas of sclerosis (five tumors) or in cell clusters bordering central scars (two tumors). We conclude that many oncocytomas contain a potentially diagnostically useful punctate pattern of cytokeratin reactivity and that focal vimentin reactively may be observed in otherwise typical oncocytomas, restricted to tumor cells appearing to be undergoing atrophy.

Adenoma↗

Immunocytochemical characterization of a monoclonal antibody directed against mitochondria reactive in paraffin-embedded sections.

The monoclonal antibody mES 13 was previously produced against bacterially expressed BALB ras p21 and was reported to have both membrane and cytoplasmic reactivity in formalin-fixed, paraffin-embedded tissue sections. In the current study, the cytoplasmic reactivity of mES 13 is investigated and demonstrated to be mitochondrial. Immunoelectron microscopic studies showed specific labeling of mitochondria without labeling of other organelles. In normal tissues, the antibody strongly labeled tissues known to have large amounts of mitochondria such as renal tubules, hepatocytes, and myocardium. The pattern of reactivity of tumors generally mimicked that of normal tissues, with carcinomas and melanomas usually showing stronger staining than sarcomas and lymphomas. Two granular cell tumors were negative. Among renal neoplasms, mES 13 strongly labeled renal oncocytomas and granular cell renal cell carcinomas and showed weaker staining of clear cell and chromophobe cell tumors. The mES 13 antibody should be useful in the characterization and diagnosis of tumors in which oncocytoma is in the differential diagnosis, especially when only paraffin-embedded tissue is available for study.

Adenoma↗

Relationship between renal histology and plasma antithrombin III activity in women with early onset preeclampsia.

Renal biopsy was performed in 12 women with the clinical diagnosis of severe, early-onset preeclampsia at the time of cesarean delivery for the express purpose of aiding future counseling on the risk of recurrence. The mean gestation at delivery was 30 +/- 3 weeks. The mean birthweight was 1090 +/- 505 gm. Four women (33%) were multiparous. Antithrombin III activity was determined immediately prior to delivery unrelated to clinical care and as part of other protocols. The biopsy was performed without difficulty in each, although the sample was inadequate in one patient. The clinical diagnosis of preeclampsia was confirmed in nine (82%). However, three of the nine had underlying renal disease, as did the two women without histologic evidence of preeclampsia (42% of the total). Correlations between laboratory parameters with the histopathologic diagnoses were sought. Neither uric acid, creatinine, blood urea nitrogen, platelet count, or 24-hour urinary protein measurements aided the differentiation of the various subgroups. Antithrombin III activity in women with biopsy-supported preeclampsia (77% +/- 12%) was significantly lower than that in women without histologic evidence of preeclampsia (116% +/- 8%). Antithrombin III activity correctly predicted biopsy findings in at least 9 of 11 (82%). These preliminary findings confirm the high frequency of underlying disease in women with early-onset preeclampsia. Although low antithrombin III activity does not differentiate between "pure" preeclampsia and superimposed disease, a normal antithrombin III activity is reassuring and more consistent with a nonpreeclamptic renal complication than with preeclampsia.

Adolescent↗

Chromophobe cell carcinoma: analysis of five cases.

Five cases of a recently characterized renal neoplasm, chromophobe cell carcinoma, encountered during an ultrastructural and DNA flow cytometric study of renal cortical neoplasms are described. These tumors usually are dark on gross examination and often are associated with focal hemorrhage or necrosis. Microscopically the tumor cell cytoplasm ranges from clear to eosinophilic, potentially eliciting a broad differential diagnosis encompassing renal cell carcinoma and oncocytoma. Ultrastructural studies disclosed the diagnostically required numerous complex cytoplasmic vesicles of unknown composition and origin, and DNA ploidy studies revealed an aneuploid cell population in three of five cases, which correlates with the malignant potential.

Adult↗

Renal biopsy frozen section: a fluorescent study of hematoxylin and eosin-stained sections.

When frozen sections of kidney are stained with hematoxylin and eosin (H&E) and viewed by standard fluorescence microscopy, crisp detail of nephron and vascular basement membranes is revealed. We studied by H&E fluorescence, control kidneys, and 85 renal biopsies which span a broad range of renal disease. We found that H&E fluorescence provides useful initial orientation by revealing the presence of cortex or medulla and number of glomeruli and vessels. It also reveals major structural alterations of nephron and vascular basement membranes (sclerosis, disruption, atrophy) and heavy deposition of abnormal material (fibrin, immune deposits, paraprotein). When coupled with direct immunofluorescence, a much greater understanding of the disease process is possible, prior to review of permanent sections.

Benzopyrans↗

Pulmonary-renal syndrome with "triad" involvement due to small vessel vasculitis.

We describe the clinical course and morphologic findings of a 22-year-old woman presenting with a systemic disease that included nasal ulceration, hemoptysis and rapidly progressive renal failure. Biopsies of nasal septum and lung revealed small vessel leukocytoclastic angiitis while renal biopsy showed a diffuse crescentic glomerulonephritis. Immunosuppressive therapy resulted in remission of clinical symptoms and resolution of glomerulonephritis as documented in a followup biopsy. Although her clinical presentation with triad organ involvement strongly suggested Wegener's granulomatosis, this case illustrates that other varieties of vasculitis may mimic Wegener's granulomatosis.

Adult↗

Clinical outcome of three discrete histologic patterns of injury in severe lupus glomerulonephritis.

There is a spectrum of glomerular pathology in patients with severe lupus glomerulonephritis (GN) that includes (1) severe segmental GN (SEG) with greater than or equal to 50% of glomeruli involved by active segmental inflammation, (2) diffuse GN, and (3) membranous GN with associated severe SEG or diffuse GN (MGN + PGN). The clinical and laboratory characteristics at entry and at follow-up of 85 patients in a prospective therapeutic trial of plasmapheresis were examined to determine if these morphologic variants had prognostic implications. Addition of plasmapheresis to the therapeutic regimen did not affect outcome, and the two treatment groups were analyzed together. Patients with the three patterns of lupus GN were similar demographically and clinically, and they had similar serum creatinines at entry (SEG, 1.87 +/- 0.28 mg/dL [mean +/- SE], v diffuse GN, 2.11 +/- 0.21, v MGN + PGN, 2.12 +/- 0.26; P = 0.75). Although significant differences were found in the initial serum C3 (SEG, 46 +/- 5 mg/dL, v diffuse GN, 34 +/- 3, v MGN + PGN, 45 +/- 3; P = 0.02) and urinary protein excretion (SEG, 3.6 +/- 0.6 g/24 h, v diffuse GN, 6.0 +/- 0.7, v MGN + PGN, 6.7 +/- 0.9; p = 0.03), none of the clinical or laboratory data predicted the morphologic pattern of the glomerular lesion. Adverse outcomes included defined clinical stop points, nonfatal renal failure, and death. One half of the patients with MGN + PGN (13/26) had an adverse outcome, compared with 5/24 patients with SEG and 11/35 patients with diffuse GN. This trend was supported by actuarial analysis of outcomes showing that patients with MGN + PGN had the lowest cumulative proportion without adverse outcome after 175 weeks of follow-up (MGN + PGN, 0.40, v SEG, 0.77, v diffuse GN, 0.64; P = 0.04). We concluded that (1) at presentation, the specific glomerular lesion in severe lupus GN cannot be predicted on clinical or serological criteria alone; (2) on the basis of morbidity and mortality, cases with all three morphologic variants should be classified as severe lupus GN; and (3) patients with MGN + PGN appear to experience more adverse outcomes than patients with SEG or diffuse GN.

Actuarial Analysis↗

Pulmonary-renal syndrome: clinical similarity amidst etiologic diversity.

The medical records and morphologic materials (59 biopsies, 7 autopsies) of 21 patients presenting with a pulmonary-renal syndrome (PRS) were reviewed. A variety of disorders (Goodpasture's syndrome, 3; vasculitis, 7; idiopathic crescentic glomerulonephritis, 7; spurious PRS, 4) may have PRS presentation. Seventeen patients had extrarenal vasculitis and/or crescentic glomerulonephritis and were treated with immunosuppression. Seven patients died, six from complications related to infections and cardiovascular disease but only one from his original disease. Four other patients ("spurious" PRS) who did not have crescents or extrarenal vasculitis did well with supportive therapy alone. We conclude that a pulmonary-renal syndrome is a common manifestation of diverse disorders which differ in their prognosis and therapy. Since clinical parameters alone are too insensitive to resolve the etiologic possibilities, multiple biopsies and serologies tests are required for a reliable diagnosis.

Adult↗

Renal sinus malignant lymphoma: a case report.

We report a case of renal sinus non-Hodgkin's lymphoma without contiguous adenopathy. Magnetic resonance and computed tomography images of this rare tumor were correlated with a pathologic specimen. On computed tomography the renal sinus lymphoma was evaluated as a well circumscribed, low-density mass owing to the mixture of the lymphomatous cells and fat tissues. Magnetic resonance showed the replacement of the renal sinus fat tissues with a spoke-like solid mass. The renal artery and vein were also evaluated thoroughly and were without tumor thrombosis.

Female↗