Histologic, ultrastructural, and immunomicroscopic findings in 96 one hour human renal allograft biopsy specimens. Immunologic and clinical significance.

Predicting the outcome of human renal allografts based on studies of one hour biopsy specimens is still controversial. We have tried to correlate histologic, ultrastructural, and immunofluorescence findings in 96 one hour biopsy specimens with histocompatibility matching, the presence of preformed antibodies, allograft ischemia and preservation times, the donor's age, the original renal disease, and allograft source, function, and survival. Ultrastructurally, 22 allografts had fibrin deposits in glomerular loops. There was a significant correlation between this finding and poor allograft function (p < 0.01), cold ischemia time (p < 0.02), and cadaveric allograft source (p < 0.01). Sixteen allografts showed epithelial cell detachment from tubular basement membranes. This finding correlated with cadaveric allograft source (p < 0.01). Many other morphologic changes were evaluated by both light and electron microscopy, but they did not bear any significant relationship to any of the aforementioned clinical parameters. Of 30 biopsy specimens studied by direct immunofluorescence, 11 showed positive findings (immunoglobulins or C3) in either glomeruli, vessels, or both. There was no significant correlation between these findings and the clinical parameters.

Chronic hereditary nephritis. A clinicopathologic study of 23 new kindreds and review of the literature.

Thirty-three patients with chronic hereditary nephritis, obtained from 23 unrelated families, were evaluated with respect to clinicopathologic features. Renal tissue was examined by light microscopy in 25 cases, immunofluorescence in 19 cases, and electron microscopy in 16 cases. The light microscopic findings varied, and foam cells were present in only four cases. Immunofluorescence was negative in all but four cases, and in these the immunomicroscopic pattern was compatible with the findings of end stage glomeruli and hyaline arteriolar sclerosis. Although electron microscopy uniformly showed marked thinning or splitting of the glomerular basement membrane, parallel splitting of the glomerular basement membrane with interposition of electron dense granular particles was seen in only eight cases. Association of glomerular basement membrane splitting with granular particles was observed in four of six patients with IgA nephropathy, in two patients with benign familial hematuria, and in a normal kidney donor. Eleven patients, seven men and four women, had chronic renal failure requiring dialysis. Of five patients who received renal allografts, three are alive, with post-transplant survival ranging from 24 to 70 months. The other two died of septicemia.

Granular dense deposit disease.

During a retrospective study of dense deposit disease, we observed in three patients, unusual granular electron-dense deposits in the glomerular basement membrane in a laminar pattern. However, the distribution of these electron-dense deposits was similar to the distribution of the homogeneous, extremely electron-dense deposits of dense deposit disease. By light microscopy a membranoproliferative glomerulonephritis was demonstrated in two patients. The other patient had multiple myeloma with glomerulopathy and intratubular protein casts with histiocytic giant cell reaction. By immunofluorescence microscopy the presence of granular deposits in the glomerular basement membrane and mesangium was revealed in only one patient, with anti-human IgM and complement (C3). By electron microscopy was demonstrated the thickening of the glomerular basement membrane by densely packed small granular aggregates of varying sizes, ranging from 100 to 800 A in diameter. Similar electron-dense deposits in a laminar pattern were present in the Bowman's capsule and renal tubular basement membrane of two patients. The specific nature of these small electron-dense deposits is unknown.

Surface and transmission ultrastructural characteristics of desquamative interstitial pneumonitis.

A prospective study of eight patients with desquamative interstitial pneumonitis was performed, correlating surface ultrastructure as elucidated by scanning electron microscopy, transmission electron microscopy, viral cultures of fresh sterile lung tissue obtained at thoracotomy, and immunomicroscopy. The hypothesis that environmental pollutants may act as sensitizing agents to induce macrophage migration was pursued using high resolution elemental analysis to obtain a profile of the inorganic content of phagolysosomes in the free alveolar cell population. Four surface ultrastructural changes were observed: mild alveolar septal thickening, an apparent decrease in the number of pores of Kohn, alteration of the predominant alveolar lining population from membranous to granular pneumonocytes, and prominent intra-alveolar collections of cells with broad based ruffled projections and pseudopodia representing a macrophage population. Transmission electron microscopy corroborated these observations. Individual pneumonocyte degeneration manifested as cytoplasmic dissolution, mitochondrial swelling, chromatin disruption, and loss of lamellar bodies and endoplasmic reticulum was identified; occasionally degenerating granular pneumonocytes were displaced into the alveolar space by a supraseptal bulla containing fibrin and extracellular fluid. Viruses were not identified by ultrastructural or tissue culture techniques. High resolution elemental analysis of individual phagolysosome contents failed to reveal the presence of heavy metals or other inorganic compounds. Immune complexes were not identified by immunofluorescence microscopy. However, alveolar transeptal macrophage migration was observed by transmission electron microscopy. These observations suggest that desquamative interstitial pneumonitis represents a disease in which cellular, rather than humoral, immune processes predominate. Other nonspecific cellular immune responses under the influence of various lymphokines may be responsible for the observed morphologic alterations.

Vesicular myocardial change: an ultrastructural study of double membrane-bound vesicles in the human heart.

Vesicular myocardial change is a specific and common finding in the diseased hearts of humans and experimental animals. The small to large vesicles are generally bound by a double membrane. They are formed within myocardial cells and then possibly extruded into the extracellular space where they disintegrate or are phagocytosed by mononuclear cells. On the basis of our studies, most vesicles appear to be of mitochonrial origin. In humans, vesicular myocardial change appears to be most extreme in primary cardiomyopathy. It may also be present, but in lesser degree, in the apparently normal hearts of human adults. Vesicular myocardial change probably represents a specific mechanism by which myocardial cells eliminate damage mitochondria or other undesirable elements that build within them as a result of disease, aging, and perhaps normal physiological activity.