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Biomedical subjects

G Mazzucco

Publications and source records attributed to G Mazzucco.

At least 73 records · Page 4Linked to original sources

Mesangiolysis and endothelial lesions due to peroxidative damage in rabbits.

There is much evidence that oxygen free radicals (OFR) may be the final mediators of biochemical and molecular damage in many kidney diseases of different etiology (toxic, ischemic and immunologically mediated), involving mainly endothelium, basement membrane and tubular cells, but direct demonstration of a role in inducing mesangiolysis is lacking. An experimental model of renal damage caused by OFR was carried out in 6 rabbits using a mixture of xanthine-oxidase and xanthine, which produces a large amount of the radical superoxide anion. Both enzyme (0.0150 and 0.150 U/ml) and substrate (0.2 and 2 mM) were simultaneously infused in one kidney, while the controlateral kidneys perfused with buffer only were used as controls. Treated kidneys were compared to controls by light and electron microscopy. A further experiment was carried out in 4 other rabbits to evaluate the protection afforded by superoxide dismutase, the specific enzyme-scavenging superoxide anion. Microscopic studies showed dose-related ingravescent damage in the treated kidneys: capillary enlargement, subendothelial swelling, detachment of the endothelium from the basement membrane, mesangiolysis and microaneurysms. Control kidneys appeared to be normal. No significant differences were observed in the kidneys treated with addition of superoxide dismutase. These results are the first direct demonstration of a role of superoxide anion in the induction of mesangiolysis in rabbits. The lack of a protective effect by superoxide dismutase could mean that the superoxide anion triggers a chain of other OFR, further responsible for damage.

Animals↗

Gluten-induced experimental IgA glomerulopathy.

The effect of alimentary gluten and of its lectin-like fraction gliadin in inducing IgA mesangial deposits in BALB/c mice was investigated. In the pilot study G1 (4 mice), G2 (4 mice) and G3 (6 mice) received ovalbumin, human gamma-globulins, and crude gluten, respectively. The antigens, 1 mg/ml, were given in drinking water for 14 weeks. G4 (20 mice) were fed with standard mouse fodder. Gluten, as well as other alimentary antigens, induced IgA mesangial deposits with intense IgA staining in each animal, however a positive IgA staining was also observed in 10 of 20 adult controls. Antigliadin IgA antibodies were detected in renal tissue eluates from gluten-immunized mice but were found in eluates from control animals too. IgA deposits and antigliadin IgA in renal tissue were also observed in 3 of 7 adult mice (G7) fed for 30 weeks with standard fodder, then for 1 month with a protein-free diet supplemented with 20% amino acids. Conversely, there were no IgA mesangial deposits or IgA anti-gliadin antibodies in renal eluates of 1- or 2-week-old mice (G5 and G6). For the definitive protocol, 4-week-old BALB/c mice were selected and fed with basal glutenfree diet. G8 (14 mice) did not receive any alimentary immunogen in the drinking water, whereas G9 (15 mice) and G10 (15 mice) received ovalbumin and gliadin, respectively. G11 (15 mice) had standard gluten-containing diet. IgA deposits semiquantified by immunofluorescence scores were found to be significantly greater in G9 and G10 than in G8 (Student' t-test p1 less than 0.003, Mann-Whitney test p2 less than 0.001 and p1 less than 0.01, p2 less than 0.007, respectively), and in G11 than in G8 (p1 and p2 less than 0.05). The presence of positive IgA staining (greater than or equal to 2/6 scores) was significantly less frequent in G8 in comparison to G9 (chi-square test p3 less than 0.002), G10 (p3 less than 0.02) and G11 (p3 less than 0.04). Total serum IgA were significantly higher in orally immunized G9 and G10 than in G8 control mice (p1 less than 0.005, p2 less than 0.002). Anti-gliadin IgA in circulation as well as in renal deposit eluates were significantly increased in gluten-eating mice (G10 and G11) as compared with the gluten-free control group G8. These observations indicate that gliadin does induce IgA immune deposits in BALB/c mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pattern of double glomerulopathies: a clinicopathologic study of superimposed glomerulonephritis on diabetic glomerulosclerosis.

Among 1715 renal biopsies investigated by means of light microscopy, immunofluorescence, and/or electron microscopy, 20 cases of various glomerulopathies (GP) were found to be superimposed on diabetic glomerulosclerosis (DGS). The most frequently superimposed GPs were acute GN (nine cases) and cryoglobulinemic GN (six cases). Although the former association is known to occur, the latter has not so far been reported. In the other patients DGS was associated with crescentic GN (two cases), membranoproliferative GN, membranous GN, and IgA nephropathy (one case each). Morphologic clues allowing the identification of the superimposed GP and the diagnostic relevance of the available morphologic methods were stressed. In particular, light microscopy was sufficient to identify the superimposed crescentic GN, whereas immunofluorescence and/or electron microscopy were needed in the other cases in order to show the composition and the seat of the deposits, respectively. In addition, electron microscopy was useful in identifying some peculiar features such as humps, mesangial cell interposition, and organized deposits in cryoglobulinemic GN. The actual frequency of superimposed GPs is difficult to assess: either under or overestimation is possible. Pathologists must be aware that this miscalculation is not an episodic event and that the estimation must be carefully sought whenever clinical data are equivocal and not fully fitting with DGS alone. The duration of the diabetes seems to favor the superimposition of GN on DGS. In these patients the prognosis is poor, not only when it could be expected to be, as in the cases with superimposition of crescentic or membranoproliferative GN, but also when DGS is associated with acute GN, whose prognosis is generally favorable.

Adult↗

Leiomyoma and neurilemoma: report of two unusual non-epithelial tumours of the thyroid gland.

Two primary spindle cell tumours of the thyroid are described showing light microscopic features of leiomyoma and neurilemoma respectively. The origin from smooth muscle and nerve sheath was confirmed by both immunohistochemical reactions and ultrastructural findings. Review of the literature reveals only one case of leiomyoma and three cases of neurilemoma reported as developing within the thyroid gland. Our observations further support the view that leiomyoma and neurilemoma may occur at this unusual site and are recognizable entities.

Adult↗

Immune-mediated glomerulonephritis after exposure to paraquat.

Exposure to paraquat was followed 1 week later by mild respiratory distress in a previously healthy farmer who developed a mixed nephrotic/nephritic syndrome 3 months later. Percutaneous renal biopsy showed endo-extra-capillary proliferative glomerulonephritis associated with a linear pattern of IgG deposits along the glomerular capillary wall. This is the first case report of an association between exposure to a low dose of paraquat (as suggested by the mildness of the respiratory symptoms) and development of glomerulonephritis, possibly related to the occurrence of anti-glomerular basement membrane antibodies. The possibility is suggested that immune-mediated mechanisms of glomerular damage may be triggered by exposure to low-dose paraquat.

Adolescent↗

Ultrastructural glomerular findings in cryoglobulinemic glomerulonephritis.

Thirty-three renal biopsies of patients affected by cryoglobulinemic glomerulonephritis (CRYGN) were investigated by electron microscopy, paying particular attention to the nature of cells responsible of glomerular hypercellularity, the presence and site of electron-dense deposits and their ultrastructural characteristics. Personal as well as literature data suggest (a) diffuse glomerular hypercellularity found in most cases of CRYGN is mainly due to polymorphonuclear leukocytes and even more to monocyte exudation; (b) the interposition of the latter cell type in the glomerular capillary wall is the main responsible cause of the frequent occurrence of the membranoproliferative pattern in CRYGN, and (c) peculiar structures found in the electron dense deposits are characteristic of CRYGN and related to cryoglobulin composition. Electron microscopy therefore seems to be a valuable diagnostic procedure for this type of glomerulonephritis.

Cryoglobulinemia↗

Platelet cationic proteins are present in glomeruli of lupus nephritis patients.

Synthetic polycations have been shown to bind and neutralize glomerular polyanions (GPA), thereby increasing the permeability of the glomerular capillary wall (GCW). In the present study it is demonstrated that human platelet-derived cationic proteins (HuPlt CP), which are able to increase cutaneous vascular permeability, bind in vitro to the GCW following incubation of normal human kidney sections with purified HuPlt CP or with washed human platelets stimulated with thrombin, immune complexes (IC) and platelet-activating factor (PAF), or stimulated with a suspension of washed human platelets and polymorphonuclear leukocytes in the presence of phagocytable substrate. The antiserum used in immunofluorescence test to detect the binding of HuPlt CP was specific for two different molecular types of HuPlt CP, both with an isoelectric point (pI) of 10.5. Glomerular deposits of HuPlt CP were also detectable by immunofluorescence microscopy in renal glomeruli present in tissue obtained by biopsy from patients with systemic lupus erythematosus (SLE), a disease in which platelets have been implicated as mediator of glomerular injury. These data indicate that when activated platelets release HuPlt CP in vivo, these proteins bind to glomerular structures. The binding of HuPlt CP to GCW appears to be ionic in nature since heparin, a polyanion, prevents this binding in vitro. In addition, heparin, as well as a high molarity buffer, removed deposits of HuPlt CP bound in vitro to normal GCW or bound in vivo to glomeruli of patients with SLE. The binding of HuPlt CP to GCW is associated with loss of colloidal iron staining, a qualitative technique that demonstrates primarily epithelial cell surface anionic sialoglycoproteins. In experiments of in vitro binding of purified HuPlt CP to section of normal kidney treatment with heparin completely restores the normal pattern of colloidal iron staining suggesting ionic neutralization of GPA. In contrast, heparin is only partially effective in restoring colloidal iron staining in normal kidney sections treated with platelets directly stimulated with IC or PAF or in kidney sections of patients with SLE. These observations indicate that under these conditions the ionic interaction of HuPlt CP with GCW is only partially responsible for the loss of colloidal iron staining. The results of the present study suggest that biologically active polycationic mediators released from stimulated platelets localize in GCW and participate in the induction of glomerular injury.

Adult↗

Steroid-sensitive nephrotic syndrome with mesangial IgA deposits: a separate entity? Observation of two cases.

In minimal-change steroid-sensitive nephrotic syndrome with selective proteinuria, mesangial IgA deposition at immunofluorescence is a very rare finding which has been previously considered a pure coincidence. Two patients, aged 6 and 14 years, respectively, with a steroid-sensitive but frequently relapsing nephrotic syndrome and highly selective proteinuria, exhibited minor glomerular alterations at light microscopy and an immunofluorescence deposition of predominant and diffuse mesangial IgA, confirmed by electron microscopy as dense deposits. The observed syndrome, that is surprisingly identical to sporadic literature reports, can be considered a separate entity or subgroup belonging either to IgA nephropathy or to lipoid nephrosis. In the latter case mesangial IgA could be the marker of an easy relapsing course.

Adolescent↗

Cell interposition in glomerular capillary walls in cryoglobulinemic glomerulonephritis (CRYGN). Ultrastructural investigation of 23 cases.

The present report describes ultrastructural findings on twenty-three cases of CRYGN showing membranoproliferative pattern under light microscopy. Attention was paid to the presence of double contoured peripheral basement membranes and to the characteristics of the interposed cells. The latter, according to the well known characteristics of membranoproliferative GN, are thought to be mesangial in nature. In fact, mesangial cells were found in 8 cases only, always associated with monocytes. Only monocytes were recorded in 12 cases, whereas in other 3 cases double contours were not connected to cell interposition. Despite similarities under light microscopy, CRYGN is therefore rather different from idiopathic membranoproliferative GN because of the prevalence of exudative changes, mainly due to monocyte infiltration, over proliferative lesions.

Cryoglobulinemia↗

Benign clear cell (sugar) tumor of the lung. A light microscopic, histochemical, and ultrastructural study with a review of the literature.

A case of a benign clear cell "sugar" tumor of the lung is reported. Light microscopy showed a uniform proliferation of clear cells filled with abundant glycogen. At the ultrastructural level, tumor cells were rich in free monogranular and rosette-forming glycogen, but no membrane-bound glycogen was demonstrated. Some cells showed plasma membrane interdigitations, microvilli, and macula occludens-type junctions. Many polymorphic secretory and sporadic haloed neurosecretory-like granules were observed, but argyrophil stains as well as a large set of immunohistochemical reactions specific for APUD derivation had negative results. A literature review of this puzzling entity with particular emphasis on the histogenetic hypotheses is presented, and a derivation from epithelial nonciliated bronchiolar (Clara) cells or epithelial serous cells is suggested.

Adult↗

Glomerular monocyte infiltration in human nephropathies: prevalence and correlation with clinical and morphological variables.

Glomerular monocyte infiltration was evaluated by histochemical means (nonspecific esterase) and/or electron microscopy in 305 renal biopsies belonging to a wide variety of human renal diseases. Significant monocyte infiltration was never observed in a first group of nepropathies (minimal change disease, nephrotic syndrome with IgM deposits, focal segmental glomerulosclerosis, membranous GN, Berger's GN, healed GN, dense deposit disease, chronic non specific GN, benign familial haematuria, Alport's disease, renal amyloidosis, arteriosclerotic kidney, light chain GN). Conversely, it was present at varying frequency in a second group of nephropathies including: acute GN (58.3%), persistent GN (10%), membranoproliferative GN (25.2%), eryoglobulinaemic GN (82.6%), lupus GN (36%), extracapillary proliferative GN (50%) and Schoenlein-Henoch GN (40%). The results indicate: 1) there is an evident association between monocyte infiltration and the subendothelial site of deposits; 2) the presence of monocytes is not affected by the size and extension of subendothelial deposits; 3) monocytes were more frequently observed when IgG, IgM and fibrinogen were present in the subendothelial deposits, Conversely, complement fractions do not seem to affect monocytic activity; 4) polymorphonuclear leukocyte exudation is less frequently found and mostly associated with monocyte infiltration; 5) in some GNs (persistent GN, cryoglobulinaemic GN and membranoproliferative GN), proteinuria was significantly higher in patients with than in those without monocyte infiltration, giving support to the hypothesis that in human beings as in experimental animals monocytes play a role in the pathogenesis of proteinuria.

Biopsy↗

Monocyte escape through a glomerular capillary basement membrane gap. An ultrastructural observation in a case of acute glomerulonephritis.

A focal discontinuity of glomerular basement membrane (GBM) with extravasation of a monocyte is described in a case of acute postinfectious glomerulonephritis in a 2-year-old girl. It is proposed that also monocytes could play a role in causing disruption of glomerular capillary wall. Moreover, this finding gives morphologic support to the hypothesis that monocyte-forming crescents reach the urinary space through GBM gaps.

Basement Membrane↗

Plasmapheresis in a patient with rapidly progressive idiopathic IgA nephropathy: removal of IgA-containing circulating immune complexes and clinical recovery.

Primary IgA nephropathy is generally considered a benign disease, but progression to renal failure is not uncommon and a rapidly progressive course is observed in some cases, especially when extensive epithelial crescents are present. Circulating IgA-containing immune complexes (IgAIC) seem to play the most important pathogenetical role, hence the authors adopted plasmapheretic treatment in association with immunosuppressive drugs for 1 patient affected by primary IgA nephritis, with florid crescents and progressive renal failure. IgAIC decreased significantly after each plasma exchange and finally returned to normal values; over the same period urinary protein loss and heavy microscopic hematuria gradually disappeared and renal function was completely recovered.

Antigen-Antibody Complex↗

Morphological parameters in lupus nephritis: their relevance for classification and relationship with clinical and histological findings and outcome.

One hundred and sixty-seven renal biopsies from 147 patients with lupus nephritis were studied retrospectively to assess the contribution to morphological classification by features assessed with immunofluorescence and electron microscopy, together with pathological indices obtained by scoring specific histologic changes. The prognostic relevance of the histologic scoring was also evaluated. The biopsies were assigned to the following classes: I, absence of glomerular lesions; II, mesangial proliferation; III, focal segmental proliferation; IVa, diffuse (more than 50 per cent of the glomeruli) but segmentally distributed proliferation; IVb, diffuse and generalised proliferation; IVc, extracapillary proliferation; Va, pure membranous changes; Vb, membranous changes with slight mesangial proliferation; VI, association of class V and class III or IV. The incidence and degree of some glomerular and non-glomerular 'active' and 'sclerotic' changes as assessed by light microscopy were evaluated in the different classes. Both the activity and sclerosis indices obtained by scoring these lesions were found to be significantly higher in classes with glomerular proliferative changes. Eighteen patients had a second biopsy and two of these had a third; more severe changes were observed in nine and improvement in four. In 146 biopsies light microscopy findings were compared with immunofluorescence patterns (negative, mesangial, mesangial and peripheral, peripheral, membranous). The mesangial pattern was mainly present in class II with a few examples in classes I and III; in the last two the mesangial-peripheral pattern was most common; the peripheral pattern was by far the most common in class IV (a, b and c) and frequent in class VI; a membranous pattern was the rule in class V and occasionally found in class VI. Immunoglobulins (Igs) and complement (C) fractions were simultaneously present in most cases, IgG, C3 and C1q being the commonest in all classes. Except for IgM and fibrinogen, the differences in distribution of Igs and C fractions among the various classes were statistically significant. The deposits most commonly found by electron microscopy in all biopsies were mesangial; subendothelial deposits were mainly found in classes with active glomerular changes, frequently associated with deposits at the other sites in the most severe cases. A highly significant correlation was found between the activity index and the sclerosis index and severity of the clinical picture at biopsy. An unfavourable progress was confined mainly to classes with extensive intracapillary proliferation and correlated significantly with the highest activity and sclerosis indices.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Essential mixed cryoglobulinemic glomerulonephritis associated with diabetic glomerulosclerosis. Light, immunofluorescence, and ultrastructural study of two cases.

The association of cryoglobulinemic glomerulonephritis with diabetic glomerulosclerosis is reported in two patients. Renal pathology was investigated by light and electron microscopy and by immunofluorescence on biopsy material from both patients and on autopsy material (obtained a few hours after death) from one patient. Glomerular involvement due to cryoglobulins preceded the development of diabetic glomerulosclerosis in one patient. This contrasts with what has been reported in the literature, where various types of glomerular lesions are reported to be superimposed on overt and often long-lasting diabetic glomerulopathy. Though the association may be coincidental, the immune complexes (cryoglobulins) may have accelerated the formation of the nodular hyaline diabetic lesions in the mesangium through a mesangiolytic process.

Cryoglobulinemia↗