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T Cavallo

Publications and source records attributed to T Cavallo.

At least 73 records · Page 4Linked to original sources

Glomerulonephritis with coexistent immune deposits and antibasement membrane activity.

Six patients with coexistent antiglomerular basement membrane disease and granular immunoreactants in the glomerular basement membrane and mesangium are discussed. These six patients represent 35% of all patients with antiglomerular basement membrane nephritis examined over 10 years. All patients presented with acute, oliguric renal failure, and rapid deterioration in renal function. In all patients the pathogenetic role of the antiglomerular basement membrane antibody was confirmed by the demonstration of linear deposits of IgG along the glomerular basement membrane and antiglomerular basement membrane antibody activity in the serum or renal eluates, or both. Evidence for the existence of concurrent immune aggregates was obtained by immunofluorescence studies and electron microscopy. Radioimmunoassays, which were performed in two patients to detect circulating immune complexes, however, yielded negative results. The possible mechanisms concerned in the evolution of this condition and their potential implications are reviewed.

Adult↗

Immune complex disease complicating diabetic glomerulosclerosis.

We report immunopathologic findings observed in renal biopsies of 18 patients with diabetic glomerulosclerosis and associated glomerulonephritis. 10 patients had nodular and 8 patients diffuse diabetic glomerulosclerosis. Focal proliferative glomerulonephritis (4 patients), membranous glomerulonephritis (3 patients), postinfectious glomerulonephritis, Henoch-Schönlein nephritis, IgA nephropathy of Berger (1 patient each), and mesangiopathic glomerulonephritis (8 patients) were the superimposed conditions. In patients with diabetic renal disease, a rapid loss of renal function or an atypical urinalysis could be the expression of a superimposed immune complex disease. Because of functional and biochemical alterations, the glomeruli of diabetic patients may be more susceptible to immune-mediated injury.

Adult↗

Murine lupus nephritis: effects of cyclophosphamide on circulating and tissue bound immunoreactants.

We investigated the effects of cyclophosphamide (Cy) on immunoreactants of plasma and kidney of mice with lupus nephritis. Cy therapy decreased plasma concentrations of IgG, but not the concentrations of anti-DNA antibodies, C3, and C1q reactive materials; in glomeruli deposits of immunoreactants were mesangial in location and decreased overall. Although Cy arrested the nephritis of NZB/W mice, the anti-DNA activity in the renal eluates was very low and comparable in untreated and in treated mice. Immune complex systems other than, or in addition to, DNA-anti-DNA are likely to play a role in the pathogenesis and course of murine lupus nephritis.

Animals↗

Immunoreactants in murine lupus nephritis: effects of azathioprine.

We studied the effects of azathioprine on immunoreactants of plasma and kidney to determine factors that might be relevant to the arrest of nephritis in NZB/W mice. Before and after a course of azathioprine (or saline injections) for 12 weeks, we determined the plasma concentrations of IgG, complement (C3), antiDNA antibodies, and C1q-reactive materials; in the kidneys, we studied deposits of IgG, IgM, and C3 in glomeruli, and we determined the concentration of IgG and antiDNA activity of the eluted proteins. Azathioprine administered at the onset of nephritis preserved glomerular structure and function; the amount of tissue-bound immunoreactants was decreased overall, and immunoreactants were preferentially localized in mesangial areas. A decreased plasma concentration of IgG, but not the concentrations of antiDNA antibodies, C3 and C1q-reactive materials, was associated with the arrest of nephritis. The antiDNA activity in renal eluates was very low and was comparable in treated and untreated mice. Immune complex systems other than, or in addition to, DNA-antiDNA likely play a role in the pathogenesis of murine lupus nephritis.

Animals↗

Murine lupus nephritis. Effects of glucocorticoid on glomerular permeability.

We investigated the effects of methylprednisolone on the glomerular permeability of mice with lupus nephritis. At the onset of nephritis, the mice were divided into two groups: one group was injected with methylprednisolone and the other with saline; treatment continued for 12 weeks. We determined the protein concentration in specimens of urine collected every 2 weeks, and pre- and posttherapy urine samples were analyzed by electrophoresis. After 12 weeks, we injected anionic or cationized ferritin systemically into mice of each group and studied kidney samples by electron microscopy. At the onset of nephritis (5 months of age), proteinuria (5.2 mg/day) was selective and albumin was the predominant (87%) protein excreted. Electron-dense deposits were then confined to mesangial areas. In untreated mice, protein excretion values doubled at 5.5 months of age, tripled at 6 months of age, and increased 5-, 7-, 9-, and 11-fold at subsequent intervals of 2 weeks, to reach 55.0 mg/day at 8 months of age. Proteinuria was poorly selective, and protein excretion values correlated inversely with survival rate (35% at the end of study). The glomerular basement membranes were studded with electron-dense deposits and were depleted in anionic sites, as judged by decreased binding of cationized ferritin molecules. The anionic ferritin molecules permeated the basement membrane at the vicinity of electron-dense deposits and reached the urinary space through residual slit pores. In methylprednisolone-treated mice, by contrast, protein excretion values were low, proteinuria was selective, and remained virtually unchanged at 5.3 mg/day by 8 months of age. There were no deaths in this group. Most of the electron-dense deposits were present in mesangia. Anionic sites of the glomerular basement membranes were largely preserved and anionic ferritin molecules were mostly limited to the luminal aspect of the basement membrane. These studies suggest that methylprednisolone therapy preserved glomerular permeability characteristics by decreasing the localization of immunoreactants in glomeruli and by interfering with factors that favor the localization of immune complexes in the capillary wall.

Animals↗

Histamine-triggered localized vasculitis in patients with seropositive rheumatoid arthritis.

To gain some insight into the pathogenesis of vasculitis in rheumatoid arthritis, and to investigate its relation to circulating immunoreactants, we injected 50 microliters of histamine intradermally in four seropositive and four seronegative patients with rheumatoid arthritis. Skin biopsies obtained before histamine and at 4 hours after histamine were studied by immunofluorescence microscopy, and skin biopsies 24 hours after histamine were studied by light microscopy. At 4 hours after histamine, all seropositive patients demonstrated deposits of IgM and complement components in dermal vessels; by 24 hours, various degrees of leukocytoclastic vasculitis were noted. Circulating material reactive with Raji cells, C1q, or both, was present in 3/3 seropositive patients. In contrast, none of the seronegative patients exhibited vascular deposits of immunoreactants or vasculitis. The results indicate that patients with rheumatoid arthritis who are seropositive may have circulating complexes with appropriate characteristics to induce vasculitis and that vasoactive substances may be used to trigger their local deposition in vessels.

Adult↗

Altered glomerular permeability in the early phase of immune complex nephritis.

We investigated the pathogenesis of increased glomerular permeability in Balb/c mice after 5 weeks of administration of a polyclonal B cell activator (bacterial lipopolysaccharide). The glomerular transfer of anionic ferritin across the capillary walls and the urinary excretion of serum albumin served as probes of glomerular permeability; anionic groups of the glomerular basement membrane were assessed by the binding of cationized ferritin, and glomeruli were studied by light, immunofluorescence, and electron microscopy. The mice developed circulating immune complexes, proteinuria, and a proliferative glomerulonephritis, with mesangial and capillary loop deposits of immunoreactants. Increased transfer of anionic ferritin molecules occurred across capillary walls with and without demonstrable electron-dense deposits; detachments of visceral epithelium were not seen, and epithelial transport of anionic ferritin was negligible. Loss of anionic groups was extensive in glomerular capillary loops with and without associated electron-dense deposits. The findings indicate that an increase in glomerular permeability may precede the deposition of immunoreactants in the capillary wall; that filtration of macromolecules can occur across capillary walls with or without demonstrable immune deposits; and that loss of anionic groups of the glomerular basement membrane and enhanced filtration of macromolecules can occur in the absence of focal detachments of the visceral epithelium.

Animals↗

Murine lupus nephritis. Effects of glucocorticoid on circulating and tissue-bound immunoreactants.

We investigated the effects of methylprednisolone on immunoreactants of plasma and kidney to determine factors that might be relevant to the arrest of murine lupus nephritis. At the onset of nephritis, at about 5 months of age, the mice were divided in two groups and received either methylprednisolone or saline injections for 12 weeks. Before and after therapy (or saline injections), we determined the concentrations of plasma IgG, complement (C3), anti-DNA antibodies, Clq-reactive materials, creatinine, and urea nitrogen; in the kidneys, we assessed the relative distribution of IgG, IgM, and C3 in glomeruli, and we determined the concentration of IgG and anti-DNA activity of the eluted proteins. Our results indicated that methylprednisolone administered at the onset of nephritis preserved glomerular structure and function by decreasing the amount of tissue-bound immunoreactants and by inducing a preferential localization of immunoreactants in mesangia. Of the immunoreactants studied in plasma, a decreased concentration of IgG, but not the concentrations of anti-DNA antibodies, C3, and Clq-reactive materials, was associated with the arrest of nephritis. The anti-DNA activity in the renal eluates was very low and comparable in treated and untreated mice. Immune complex systems other than, or in addition to, DNA-anti-DNA likely play a role in the pathogenesis of murine lupus nephritis.

Animals↗

Murine lupus nephritis: effect of azathioprine on glomerular permeability and localization of immunoreactants.

We investigated the effect of azathioprine on glomerular permeability and deposition of immunoreactants in NZB/W mice. Glomerular permeability, assessed by proteins excreted in the urine and by a molecular probe of anionic sites of the basement membrane, underwent negligible changes, in comparison to pre-treatment findings, and deposits of immunoreactants were largely mesangial and were decreased overall. Therapy with azathioprine preserved glomerular structure and function by decreasing the amount of immunoreactants, by inducing a preferential mesangial localization of immunoreactants, and, possibly, by interfering with factors that favor the deposition of immunoreactants in the glomerular capillary wall.

Animals↗

Immune deposits and mesangial hypercellularity in minimal change nephrotic syndrome: clinical relevance.

Occasional patients with nephrotic syndrome and minimal histologic change demonstrate glomerular deposition of small amounts of immunoglobulin and complement. Some consider this a disease distinct from MCNS. To investigate the clinical importance of immune deposits and mesangial hypercellularity in the initial biopsy, the clinical records, follow-up data, and renal biopsies of 68 patients (ages 6 months to 16 years) with MCNS by light microscopy were reviewed. Among 68 patients followed a mean of 6.2 years, eight of 25 patients with immune deposits on initial renal biopsy were steroid nonresponsive. Only one of 43 patients without immune deposits was steroid nonresponsive (P = 0.00005). Of 44 patients with normal mesangial cellularity, 31 experienced fewer than three relapses a year, whereas of 15 patients with mesangial hypercellularity, only six experienced fewer than three relapses a year (P = 0.035). The data suggest that immune deposits and increased mesangial cellularity in children with NS and minimal light microscopic change may predict the clinical course.

Adolescent↗

Focal segmental glomerulosclerosis, crescent, and rapidly progressive renal failure.

The usual clinical course of focal segmental glomerulosclerosis is marked by progressive decrease in renal functional and sclerosis on biopsy over a period of months to years. We report a variant exemplified by 2 children who developed chronic renal failure within 12 weeks of the onset of nephrotic syndrome; repeat renal biopsies demonstrated extensive extracapillary glomerular proliferation and crescent formation. Both were males, less than 5 years of age, presenting with nephrotic syndrome resistant to steroid therapy and normal renal function. Renal biopsies done after 8 weeks of therapy, demonstrated findings compatible with focal segmental glomerulosclerosis. Within 12 weeks of onset of nephrotic syndrome, both patients experienced a decrease in renal function requiring dialysis. Repeat renal biopsies revealed extensive extracapillary glomerular proliferation with crescent formation. These patients represent a variant of focal segmental glomerulosclerosis characterized by rapid progression to renal failure with extensive extracapillary glomerular proliferation and crescent formation.

Biopsy↗

Cytomegalovirus: an ultrastructural study of the morphogenesis of nuclear inclusions in human cell culture.

We investigated the ultrastructural development and maturation of cytomegalovirus (CMV) nuclear inclusions (NIs) in human embryo thyroid cells at 1 to 144 h post-infection. At 5 h, most cells had rounded from an initial fibroblastic appearance and contained early NIs. At 24 h, early NIs were larger and better defined. At 48 h, although early NIs were still present, most cells had larger and presumably more mature NIs. These latter NIs consisted of several subunits, each made up of a fibrillar network enclosing an electron-lucent area which contained coarse and delicate granules. Also, at 48 h, virus particles were first seen in the nucleoplasm. At 72 h, in cells with more developed NIs, virus particles were closely associated with the fibrillar network. Between 96 and 144 h, the NIs reached maximum size and were made up of numerous subunits. The results indicate that two types of NIs coexist during CMV infection. The appearance of the early the late NIs coincides with the reported peaks of CMV DNA synthesis and thus may explain the biphasic pattern of DNA synthesis in CMV infection. Morphogenetic features of the NIs conform with the hypothesis that synthesis of CMV DNA may occur in the centre in each NI subunit and that the fibrillar network represents condensing capsid proteins.

Cells, Cultured↗

Immunopathologic study of minimal change glomerular disease with mesangial IgM deposits.

Renal biopsies from 21 patients with minimal change nephrotic syndrome and mesangial IgM deposits were investigated by means of fluorescence, light and electron microscopy; elution of tissue-bound antibody; and fixation of heterologous (guinea pig) complement. In 12 patients complement and IgM deposits were associated and, in 4 of these, electron dense deposits conforming to immune complexes were detected in mesangia. Antibody elution and heterologous complement fixation studies in tissues suggested that such immune reactants may represent interaction of complement-fixing antibody and antigen. Long-term follow-up studies are needed to determine the clinical relevance of IgM deposits in minimal change nephrotic syndrome.

Adolescent↗