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Biomedical subjects

G R Gallo

Publications and source records attributed to G R Gallo.

At least 55 records · Page 3Linked to original sources
PubMed1983

Experimental cholestasis promotes the deposition of glomerular IgA immune complexes.

Previous experimental and clinical studies support a role for the hepatobiliary system in the clearance of oligomeric IgA from serum, and alterations of this system have been associated with the deposition of IgA in the renal mesangium. The present studies in mice address the question of whether the mesangial deposition of IgA following cholestasis includes immune complexes. While bile duct ligation resulted in mesangial IgA deposition within several days in approximately 75% of animals, whether deliberately orally immunized, nonimmunized, or given injected immune complexes, mice that underwent sham operations had IgA deposits only if orally immunized. Moreover, mice that had been orally immunized or given injected immune complexes and whose bile ducts had been ligated contained deposits of specific IgA antibody and antigen. In the ligated mice some of the IgA was secretory IgA, as demonstrated by the presence of secretory component. Thus, bile duct ligation promotes the deposition of circulating IgA immune complexes, presumably by decreasing their clearance from serum, and gives rise to secretory IgA in the glomerular mesangium. The secretory immune system probably plays a role in the pathogenesis of idiopathic and cirrhosis-related human IgA nephropathy.

Animals↗
PubMed1983

Nephritogenicity and differential distribution of glomerular immune complexes related to immunogen charge.

Nephritogenicity and the differential distribution of glomerular deposits as a function of immunogen charge were examined in a murine model of chronic active serum sickness. A range of differentially charged immunogens was used, i.e., chemically modified highly cationic or anionic bovine gamma-globulin (BGG), native unmodified isoelectrically focused slightly cationic or anionic BGG, and heterogeneous native BGG. The amounts and distribution of immune complexes in glomeruli were compared by immunofluorescence and electron microscopy 3 to 10 weeks after the initiation of 15 intravenous injections of the five immunogens and 13 days after intraperitoneal continuous release of the native unmodified BGGs by osmotic pumps. The results demonstrate that the more cationic the immunogen, the more nephritogenic and the greater the tendency to form subepithelial deposits in the glomerular basement membrane. The observed differences in nephritogenicity and localization induced by focused unmodified cationic and anionic fractions of BGG particularly emphasize immunogen charge as a major factor influencing glomerular distribution of immune complexes in this model. The findings indicate that several degrees of nephritogenicity and the differential distribution of immune complexes can be related to immunogen charge and strongly suggest that charge interactions may be of fundamental importance in the pathogenesis of immune complex glomerulonephritis.

Animals↗
PubMed1982

Aggravation of experimental glomerulonephritis by superimposed clip hypertension.

To evaluate the possible enhancing effect of hypertension on the clinical and morphologic features of glomerulonephritis, two-kidney clip hypertension (CH) was superimposed on a mild form of nephrotoxic serum nephritis (NSN) in female Sprague-Dawley rats. The following parameters were assessed regularly over a 6-month period: blood pressure (BP), heart weight, proteinuria (UpV), and renal morphology. Blood pressure and heart weights were increased equally in clip hypertension and in nephrotoxic serum nephritis combined with clip hypertension. While only moderate proteinuria occurred in nephrotoxic serum nephritis (49 +/- 28 mg/24 hr) or clip hypertension (40 +/- 22 mg/24 hr) alone, the superimposition of clip hypertension on nephrotoxic serum nephritis resulted in heavy proteinuria (161 +/- 36 mg/24 hr) (P less than 0.001) after 5 months of hypertension. Glomerular histology in nephrotoxic serum nephritis showed infrequent focal and segmental proliferation and minimal sclerosis; vessels were normal. Clip hypertension was characterized by infrequent and mild vascular sclerosis and glomerular proliferation and sclerosis. Severe glomerular endo- and extracapillary proliferation and widespread glomerular and vascular sclerosis occurred in the majority of rats when nephrotoxic serum nephritis was combined with clip hypertension. The data demonstrate that clip hypertension enhances glomerular proliferation and sclerosis and results in the development of vascular sclerosis in experimental nephritis.

Animals↗
PubMed1982

Intrarenal vascular sclerosis in IgA nephropathy.

In this analysis of 43 patients with IgA nephropathy, renal morphology was correlated with clinical data. Gross hematuria and mild proteinuria were typical among younger patients. Among older individuals the clinical spectrum was wider. A comparison with data previously obtained from the normal population indicated that disease-related glomerular sclerosis was present in 1/3 of initial biopsy specimens. The prevalent pattern of glomerular sclerosis was that of global tuft collapse, the type of sclerosis known to result from ischemia. Intrarenal vascular sclerosis was present in 1/3 of initial biopsies. Follow-up specimens from 6 patients showed progression of glomerular sclerosis, vascular sclerosis or both. Hypertension occurred in over 1/4 of patients. It is proposed that progressive renal damage in IgA nephropathy may not be solely immunologically mediated. Glomerular sclerosis may also be mediated by vascular sclerosis, or alterations in intrarenal hemodynamics in glomerulonephritis may have a direct damaging effect on both the glomerulus and the intrarenal vasculature.

Adolescent↗
PubMed1981

Nephrotoxicity of nitrosoureas.

Irreversible and progressive renal parenchymal damage and functional impairment occurred in the majority of patients receiving at least six courses (200 mg/m2 of BCNU and/or methyl CCNU at eight-week intervals) of nitrosoureas for therapy of malignant brain tumors. Seventeen of 18 patients who received at least six courses and all nine patients who received more than ten courses developed impaired renal function as judged by elevation of blood urea nitrogen and/or serum creatinine or decrease in filtration rate as determined by inulin clearance. Four patients have developed uremia. Renal tissue obtained from seven patients demonstrated tubular atrophy, interstitial fibrosis and glomerular sclerosis. This remarkably high incidence of renal damage occurred without a phase of acute renal failure and in the absence of significant urinary abnormalities, while producing an insidiously progressive interstitial renal lesion.

Adolescent↗
PubMed1981

Acquired cystic disease of kidney in chronic dialysis patients.

Eight cases of acquired cystic disease of the kidney (ACDK) associated with chronic renal failure and hemodialysis are described. No patient had a family history or clinical evidence of congenital adult polycystic kidney disease (CAPKD). Glomerulonephritis was the cause of renal failure in 6, and pyelonephritis in 2. Massive renal and perirenal hemorrhage necessitated 3 nephrectomies in 2 patients. Single kidney weights did not exceed 280 Gm., a major feature in the distinction of ACDK from CAPKD. Morphologically, in addition to the usual stigmata of end-stage kidneys, 40 to 80 per cent of the renal parenchyma was replaced by small cysts. Continuity of cysts with tubules was established by nephron dissection.

Female↗
PubMed1981

Charge of circulating immune complexes as a factor in glomerular basement membrane localization in mice.

The effect of the charge of circulating immune complexes on glomerular localization was studied in a model of passive serum sickness. Preformed immune complexes of heterogeneous or restricted charge, prepared in vitro from isoelectrically focused or chemically modified proteins, were injected intravenously into mice. The distribution of immune complexes in the kidney was compared by immunofluorescence and electron microscopy. Cationic but not anionic or electrophoretically heterogeneous immune complexes gave rise to diffuse localization in the glomerular basement membrane. The binding in subepithelial and subendothelial sites correlated with the known distribution of structural anionic sites. The observations suggest that electrostatic interactions between fixed anionic sites and immune complexes may be an important factor in glomerular trapping. Alternative mechanisms based on initial localization of excess free cationic antigen cannot be completely excluded and are also considered.

Animals↗
PubMed1980

Nodular glomerulopathy associated with nonamyloidotic kappa light chain deposits and excess immunoglobulin light chain synthesis.

A nodular glomerulopathy characterized by mesangial deposits of monoclonal kappa light chains was detected by immunofluorescence in a renal biopsy from a patient with proteinuria and hypertension. These nodules lacked the tinctorial and morphologic features of amyloid. Ultrastructurally, the nodules contained electron-dense granular deposits as well as fibrils in parallel arrangement. The fibrils measured 110-140 A in diameter. They were consistent in size with amyloid fibrils. However, they differed in lacking the randomly oriented network of typical amyloid fibrils and more closely resembled fibrils intrinsic to mesangial matrix. The patient had no bone marrow or X-ray evidence of myeloma and no evidence of free monoclonal light chains in serum or concentrated urines. Biosynthetic studies of the patient's bone marrow cells demonstrated unbalanced immunoglobulin synthesis with excess production of monoclonal kappa light chains. These observations suggest that the observed glomerulopathy results from direct deposition of monoclonal light chains. Deposits with kappa light chain determinants have been found in 7 other patients with similar nodular glomerulopathies, 4 of whom had diagnosed clinical myeloma. The lesion of nonamyloidotic nodular glomerulopathy previously described in 19 patients, nor examined by immunopathologic techniques or not shown to contain light chain determinants, may have a similar pathogenesis.

Adult↗
PubMed1980

Role of intrarenal vascular sclerosis in progression of poststreptococcal glomerulonephritis.

A comparison has been made of the percentage of sclerotic glomeruli found in normal subjects and in 31 patients 6 months to 15 years after an episode of acute poststreptococcal glomerulonephritis (PSGN). The findings establish that a greater than expected incidence of glomerular sclerosis occurs in the course of PSGN. The pattern of glomerular sclerosis frequently was that of contracted collapsed tufts, one known to result from ischemia. In the majority of specimens with significant glomerular sclerosis, there was co-existent vascular sclerosis (arterioles and/or prearterioles), and the incidence of both glomerular and vascular sclerosis increased with time from onset of PSGN. Intrarenal vascular sclerosis may thus be of major importance in the genesis and progression of glomerular sclerosis in PSGN.

Adolescent↗
PubMed1979

Human C4-binding protein. Association with immune complexes in vitro and in vivo.

C4-binding protein (bp), a glycoprotein with specific binding affinity for the activated form of C4 (C4b), has recently been isolated from human serum and partially characterized. This report demonstrates that C4-bp is incorporated into soluble immune complexes after complement activation in vitro. The reaction requires Ca++ ions and the presence of C4 in serum. Immunopathological studies of various forms of glomerulonephritis revealed intense C4-bp deposition in glomeruli from patients with immune-complex type of pathogenesis. C4-bp deposition was in close correlation with that of C4. These observations, together with the in vitro association of C4-bp to immune complexes, support the notion that the deposits in glomeruli represent the local accumulation of immune complexes.

Antigen-Antibody Complex↗
PubMed1977

Lupus nephritis. Clinical course as related to morphologic forms and their transitions.

An intensive study of the course of lupus nephritis has been undertaken in 88 patients in whom strict morphologic criteria were utilized in classification. All were treated with steroid, and 17 received cytotoxic drugs in addition. Focal proliferative lupus nephritis generally follows a benign course except in the occasional instances when transition to the diffuse proliferative or membranous forms occurs. Membranous lupus nephritis, when characterized by persistent nephrotic syndrome, leads slowly to renal failure, but this progression is aborted in the one-third in whom remission of the nephrotic syndrome can be achieved. A fatal outcome occurs within five years in the majority of those with diffuse proliferative lupus nephritis and the nephrotic syndrome, often in association with necrotizing renal vasculitis, severe hypertension and accelerated renal failure. A small number with the diffuse proliferative form have a remission and then show only mesangial abnormalities, usually, however, with the appearance of glomerular sclerosis. Progressive glomerular sclerosis is observed in some patients and may be a sequel of the remission of the diffuse or focal proliferative lesions, or it may represent still another form of lupus nephritis. Mesangial immune deposits with or without proliferation, at times in the absence of clinical renal disease, are observed early in the course of systemic lupus erythematosus (SLE) and may proceed to the diffuse proliferative or membranous forms. The present observations serve to emphasize the importance of strict morphologic classification in the comparison of different treatment regimens for lupus nephritis. In view of the grave prognosis of established diffuse proliferative lupus nephritis, which probably evolves from a mesangial involvement common to all patients with SLE from its onset, early therapy may be the key to the management of lupus nephritis.

Adolescent↗
PubMed1977

Experimental toxemia of pregnancy in the monkey, with a preliminary report on renin and aldosterone.

Experimental toxemia of pregnancy was induced in 8 pregnant monkeys (Macacamulatta) by reducing the abdomiinal aorta to one-third of its original diameter during the last month of gestation. It was characterized by hypertension and proteinuria. In the kidney, light and electron microscopy and immunofluorescence revealed findings similar to those in human toxemia. Focal necrosis in the liver and diffuse hemorrhagic infarctions in the placenta were also observed. Plasma renin activity and aldosterone levels, as determined in blood from the uterine vein, were elevated. None of these changes were found in 4 control animals.

Aldosterone↗