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Biomedical subjects

G Mazzucco

Publications and source records attributed to G Mazzucco.

At least 91 records · Page 5Linked to original sources

In vivo localization of C3 on the brush border of proximal tubules of kidneys from nephrotic patients.

Deposits of C3 but not of C1q and C4 were detected on the proximal tubules of kidneys from nephrotic patients with non-selective proteinuria. The incidence of tubular C3 deposits was significantly higher in patients with membranous glomerulonephritis, focal glomerulosclerosis, membrano-proliferative glomerulonephritis and non-selective proteinuria than in patients with minimal change disease, nephrotic syndrome and selective proteinuria or in patients with glomerular disease, but without nephrotic syndrome. The occurrence of tubular C3 deposits was positively correlated with the amount of urinary C3 excretion. In vitro studies showed that the human normal kidney as well as pathologic specimens negative for in vivo tubular C3 deposits were able to bind C3 on the brush border of proximal tubules when incubated with fresh heterologous serum. In contrast, in patients with non-selective proteinuria and in vivo tubular C3 deposits, the binding of heterologous C3 to the brush border of proximal tubules was markedly reduced. The positive correlation between the occurrence of tubular C3 deposits and the urinary complement excretion, together with the detection of the C3 breakdown products in the urines further supported the hypothesis that complement components, once filtrated through the glomerular barrier, might be activated by the brush border of the proximal tubule.

Adolescent↗

IgA1 and IgA2 immune complexes in primary IgA nephropathy and Henoch-Schönlein nephritis.

The distribution of IgA subclasses in IgA immune complexes (IgA IC) in sera of patients with primary IgA glomerulonephritis and Henoch-Schönlein purpura nephritis was analysed. High levels of IgA IC containing both IgA1 and IgA2 subclasses were present in correlation with the phases of clinical activity. In these nephropathies the finding of IgA subclass distribution in IgA IC similar to that found in secretions may add further support to the hypothesis that IgA IC are of mucosal origin, albeit a primary derangement of the humoral immune system in these patients cannot be disregarded.

Adolescent↗

Detection of monocytes and evaluation of their role in human glomerular pathology: the contribution of electron microscopy.

The potentialities of electron microscopy in detecting monocytes in human glomeruli are discussed and its reliability is compared with that of other techniques (such as enzyme histochemistry and immunohistochemistry) having the same purposes. The major advantages of electron microscopy are: the same material can be used for both monocyte detection and conventional diagnostic purposes; its high resolution power allows for information on the site of monocyte infiltration and clarification of some functions of the latter (such as the phagocytic activity on immune complexes or their participation to the basement membrane damage). Nevertheless, the suggested technique also has some disadvantages, in particular it permits to investigate only a small number of glomeruli and it creates difficulties in the identification of nonstimulated monocytes.

Glomerulonephritis↗

The brush border of proximal tubules of normal human kidney activates the alternative pathway of the complement system in vitro.

The aim of this investigation was to study complement fixation by normal human kidney tissue. C fixation was assessed on acetone-fixed sections of frozen human kidney. In addition, C consumption following incubation of normal fresh human serum with tubular or glomerular fractions of human kidney was measured. The results are consistent with the interpretation that the brush border of proximal tubules of human kidney activates the C system via the alternative pathway. It is suggested that this activation may occur in vivo in patients with a non-selective proteinuria.

Complement Activation↗

IgA1 and IgA2 in circulating immune complexes and in renal deposits of Berger's and Schönlein-Henoch glomerulonephritis.

IgA subclasses in circulating immune complexes (IgA1IC), serum immunoglobulins and mesangial deposits in Berger's and Schönlein-Henoch glomerulonephritis (GN) were studied. Both IgA1IC and IgA2IC were significantly higher in Berger's and Schönlein-Henoch GN than in healthy people. In phases of clinical activity both IgAIC subclasses further increased. The IgA1/IgA2 ratio was found not to differ from controls in either groups of patients. An increase in polymeric IgA was observed in Berger's and in Schönlein-Henoch GN. Both IgA subclasses were found in mesangial deposits.

Antigen-Antibody Complex↗

Severe glomerular mesangiolysis in a patient with rectal adenocarcinoma treated with cytotoxic drugs.

A 72 year old man with rectal adenocarcinoma developed chronic renal failure when treated by surgery and subsequent chemotherapy (5-fluorouracil, Mitomycin C and Cytosine arabinoside) and immunotherapy. Light microscopy provided evidence of severe glomerular changes with extensive mesangiolysis and vascular damage. Electron microscopy confirmed the mesangiolysis and showed nuclear changes in mesangial cells with nuclear pockets, chromatin loss and margination. There was further indirect evidence of endothelial cell damage. It is suggested that the glomerular changes should be attributed to a direct cytotoxic effect on the mesangial cells.

Adenocarcinoma↗

The use of Mallory's phosphotungstic acid-hematoxilin (PTAH) stain in renal pathology.

High quality histology is needed in renal biopsy examination, especially when material for immunofluorescence and/or electron microscopy is not available. For these purposes Mallory PTAH stain was tried on 34 renal biopsies and the results were compared with the immunofluorescent and ultrastructural findings (used as a control of the reliability of the method). PTAH, besides showing extracellular structures, cytological details and rather subtle abnormalities, was able to detect the presence and the site of deposits. PTAH stains the material which appears as electron dense deposits in electron microscopy and as granular deposits in immunofluorescence, whereas it fails to stain linear deposits in immunofluorescence (which are not electron dense). Moreover, a good correspondence between PTAH and electron microscopic data was detected as far as the location of deposits is concerned.

Amyloidosis↗

Clinical significance of the detection of circulating immune complexes in lupus nephritis.

32 patients (22 biopsed) with lupus nephritis (LN) were observed for circulating immune complexes (IC). Solid phase C1q (SPC1q) and polyethylene glycol (PEG) precipitation tests were used. The patients were studied during the clinical follow-up in different phases of disease activity. Comparative studies between each histological class of LN and corresponding forms of idiopathic glomerulonephritis (IGN) were made: no significant differences were found between either mesangial LN and stalk mesangial IGN, or between focal proliferative LN an focal proliferative IGN. However, a significant difference was found for SPC1q data between diffuse proliferative LN and mesangiocapillary IGN, and between membranous LN and membranous IGN. LN, with an acute nephritic syndrome and hypocomplementemia, displayed SPC1q data significantly above the levels of IC found in IGN with similar clinical features. IC serum data would seem an important element for the diagnosis and the clinical management of patients affected by LN.

Adolescent↗

Circulating immune complexes containing IgA, IgG and IgM in patients with primary IgA nephropathy and with Henoch-Schoenlein nephritis. Correlation with clinical and histologic signs of activity.

A new conglutinin solid phase assay for the detection of immune complexes containing IgA (IgAIC) and other conglutinin tests for immune complexes containing IgG and IgM (IgGIC and IgMIC) were used in studies on 34 patients affected by Berger's GN (92 sera) and 12 affected by Henoch-Schoenlein GN (61 sera). Thirty-six patients were observed over follow-up periods of 2-43 months. Levels of IgAIC in both groups of patients were significantly higher than those in healthy people. The values obtained in patients with Henoch-Schoenlein GN were statistically higher than those obtained in patients with Berger's GN. Moreover, IgAIC were frequently found to be associated with IgGIC and/or IgMIC. In both groups of patients, the IgAIC levels were significantly correlated with the presence of signs of clinical and histological activity such as the magnitude of microscopic hematuria, a past history of macroscopic hematuria and the percentage of glomeruli with florid epithelial crescents.

Adolescent↗

Monocyte infiltration and glomerular hypercellularity in human acute and persistent glomerulonephritis. Light and electron microscopic, immunofluorescence, and histochemical investigation on twenty-eight cases.

Glomerular monocyte infiltration was searched for using staining for nonspecific esterase and/or electron microscopy in 28 patients with acute glomerulonephritis submitted to biopsy at different intervals from the beginning of the disease. Significant monocyte infiltration was detected in 12 cases displaying prominent intracapillary hypercellularity and granulocyte exudation. All cases but one were submitted to biopsy in the first 6 weeks of the disease. Negative cases, submitted to biopsy in the same period or in the later phases of the disease, displayed more or less evident mesangial hypercellularity as the prevailing feature. Most positive cases showed glomerular deposits of IgG. Phagocytosis of IgG by mononuclear cells was investigated in all cases positive for monocytes and in 10 negative ones, using an immunofluorescence technique on paraffin-embedded material. Only in the former group were a few or scanty IgG-phagocytosing monocytes detected in six cases. Our results only partially confirm the role of monocytes in causing glomerular hypercellularity in human acute glomerulonephritis. In fact, the relevance of this phenomenon appears much less important than in several well-known experimental models and in some cases of human chronic glomerulonephritis. Moreover, macrophage infiltration is present in cases with greater immunologic involvement and tends to decline with time. Therefore, it seems that, in human acute glomerulonephritis, glomerular hypercellularity results mainly from intrinsic cell proliferation.

Acute Disease↗

Glomerulonephritis with dense deposits: a variant of membranoproliferative glomerulonephritis or a separate morphological entity? Light, electron microscopic and immunohistochemical study of eleven cases.

Eleven cases of glomerulonephritis with dense deposits were selected on the basis of electron microscopic examination performed either on material treated according to conventional techniques (9 cases) or on previously paraffin-embedded material (2 cases). While uniform immunohistochemical patterns were observed, different features were shown by light microscopy: in only 3 cases were membranoproliferative or lobular patterns present, while in the others a varying degree of mesangial cell proliferation (moderate, mild or even very scanty with focal and segmental distribution) was detected. The generally accepted statement that glomerulonephritis with dense deposits represents a subgroup of membranoproliferative glomerulonephritis therefore seems questionable. In addition to several clinical and serological data, these morphological features give further support to the hypothesis that glomerulonephritis with dense deposits in all respects a peculiar and distinct form of glomerulonephritis.

Adolescent↗

Role of the T-cell system in glomerulonephritis induced in rats by human serum albumin (HSA). An immunological and morphological study.

The primary role of the T-cell system in immune-complex glomerulonephritis induced by intravenous weekly injections of human serum albumin (HSA) in rats has been demonstrated. The development of histological, ultrastructural and immunological glomerular alterations which are clearly recognizable in intact animals was prevented by neonatal thymectomy. In vitro tests of cellular immunity (LIF and PHA responsiveness) revealed a close relationship between the involvement of functioning T-cell subpopulations (at least T-helper) and the development of the classic glomerulonephritic pattern. In other words HSA antigen recognition by T lymphocytes, their cooperation with B lymphocytes, and the activation of the latter with related antibody response represent the immunological sequence which leads to the formation of the soluble circulating immune-complexes responsible for the glomerular injury. Our findings suggest that the same immunological sequence can represent the pathogenetic basis for many forms of glomerulonephritis in which T-dependent antigen stimulation is demonstrable. Our data are also discussed in the light of results obtained by others in immuneglomerulonephritis induced in nude athymic mice.

Animals↗

Colorectal polyposis with mixed juvenile and adenomatous patterns.

An unusual form of colorectal polyposis is described displaying juvenile, adenomatous and mixed patterns in a 17-year-old girl. Although juvenile polyposis is generally considered to be non-neoplastic in nature, in both the present and in other case reports histological findings support a neoplastic nature. Since an increase in the incidence of large bowel carcinomas has been found in subjects with a previous diagnosis of juvenile polyposis, these patients should be considered to be at risk, and submitted to follow up.

Adenoma↗

The presence and possible role of monocyte infiltration in human chronic proliferative glomerulonephritides. Light microscopic, immunofluorescence, and histochemical correlations.

Twenty-seven cases of chronic glomerulonephritis with proliferative pattern (11 cases of primary mixed IgG-IgM cryoglobulinemia, 8 cases of SLE, and 8 cases of primary membranoproliferative glomerulonephritis) were studied with particular attention to the glomerular monocyte infiltration. The latter, detected by means of nonspecific esterase technique, was compared with the presence of hyaline thrombi and intraluminal immunoglobulin lumps. Monocyte infiltration was heavy and almost constant in cryoglobulinemia, less important in SLE, and practically absent in membranoproliferative glomerulonephritis. By means of immunofluorescence technique on paraffin embedded material, monocytes are shown to contain IgG and IgM, suggesting a phagocytic activity on some types of immune complexes. Since monocytes are migrant cells, and therefore easily removable from the glomeruli by the bloodstream, it seems that they could be responsible for regression of glomerular hypercellularity as reported in some patients with cryoglobulinemia showing clinical improvement.

Chronic Disease↗

Glomerular findings in mixed IgG-IgM cryoglobulinemia. Light, electron microscopic, immunofluorescence and histochemical correlations.

A case of immune-complex glomerulonephritis with membrano-proliferative patterns in a patient with mixed IgG-IgM cryoglobulinemia has been investigated; particular attention has been payed to histological immunofluorescence, histochemical and electron microscopical findings in order to elucidate the nature of the intraluminal thrombi. The so called thrombi, strongly positive for IgG and IgM with the immunofluorescence, appeared to be clusters of mononuclear cells which, for their ultrastructural and histochemical (non-specific esterase activity) patterns have been considered as monocytes. They showed cytoplasmic vacuoles containing microtubular structures; the latter have been detected free in the capillary lumina and in the basement membranes as well. These structures have been considered as the ultrastructural counterpart of the IgG-IgM immune-complexes responsible of the nephropathy. Monocytes have been hypothesized to play a pathogenetical role, acting as cleaners of the cryoprecipitate from the capillary lumina.

Basement Membrane↗

[Glomerulonephritis and sarcoidosis: study of a case].

A case of rapidly progressing glomerulonephritis accompanied by sarcoidosis is presented. The immunological pathogenesis of the underlying disease was shown by the positivity of the reactions for anti-IgA and anti-betal C/beta 1 A globulins and the presence of thick deposits in the mesexential matrix and some parts of the thickened basal membrane. Since generalised sarcoidosis is regarded as the expression of an immunological reaction to an unknown, diffuse antigen, this type of glomerulonephritis may be associated with the particular immunopathological condition observed in sarcoidosis.

Adolescent↗