Sheila Moriber Katz

Microscopic Nephrocalcinosis in Cystic Fibrosis

Airway, sweat-duct, and other epithelial cells in patients with cystic fibrosis display abnormal ion transport. To test whether the kidney, the organ most exquisitely adapted for ion transport, has a similar defect, we measured the levels of calcium excretion and searched for microscopic nephrocalcinosis in patients with cystic fibrosis. Thirty-eight specimens of kidney tissue were stained for calcium deposits, and 24-hour levels of urinary calcium excretion were measured in 14 patients and 15 control subjects. Microscopic nephrocalcinosis was observed in 35 of the 38 specimens (92 percent), and hypercalciuria (greater than 182 mg per gram of creatinine) in 5 of the 14 patients (36 percent). Notably, nephrocalcinosis was detected near the time of birth (in six patients under one year old, including two neonates and one stillborn infant), which supports the hypothesis that such renal calcium deposits reflect the genomic defect and are not due to longstanding pulmonary dysfunction, chronic infection, therapeutic agents, or disease progression. None of the patients with hypercalciuria or nephrocalcinosis had clinical evidence of renal dysfunction. The finding of microscopic nephrocalcinosis near the time of birth in patients with cystic fibrosis suggests a primary abnormality of calcium metabolism in the kidney. Studies of the pathophysiologic features of the kidney in cystic fibrosis may elucidate the molecular alterations observed in this disorder.

Pineoblastoma: an electron microscopic study.

The ultrastructure of a human pineoblastoma is described. Tumor cells formed nests, palisading rows and rosettes. Cells within nests were undifferentiated. Palisade and rosette forming cells had polarized cytoplasms and showed signs of differentiation and surface membrane specialization which included surface end‐bulb‐like protrusions of the cytoplasm, bulbous cilia with a 9 + 0 microtubular skeleton, and blunted microvilli. In the cytoplasm of tumor cells there were characteristic granular bodies, whorls of smooth endoplasmic reticulum and annulate lamellae. Some of these findings appear to be unique to pineal tumor and are reminiscent of photoreceptor cells in the pineal glands of lower vertebrates and human fetal pineal glands.

Reversible Nephrotic Range Proteinuria with Renal Artery Stenosis: A Clinical Example of Renin-Associated Proteinuria

Nephrotic range proteinuria occurred in a 60-year-old woman with renal artery stenosis and marked hyperreninemia. Treatment by nephrectomy produced resolution of both proteinuria and hypertension. The gradual resolution of the proteinuria postoperatively suggested the proteinuria, at least in part, came from the contralateral kidney. Foot process fusion in the nephrectomy specimen suggested it too was a source of proteinuria. A marked degree of hyperreninemia, as was present in this case, may be necessary before massive proteinuria occurs in renal artery stenosis.

Myelolipoma in a heterotopic adrenal gland. Light and electron microscopic findings

A symptomatic myelolipoma of the heterotopic adrenal gland was diagnosed as the cause of nephrotic syndrome and was surgically removed. Remission of the nephrotic syndrome promptly ensued. Ultrastructurally, the tumor consisted of well‐differentiated cells resembling adrenal cortical cells, bone marrow cells in various stages of differentiation, and lipid cells. Some cells that contained fat were of adrenal cortical origin, but the derivation of most lipid cells and of bone marrow elements could not be deduced from the present ultrastructural findings.

Cilia in the Human Kidney

Utilizing transmission electron microscopy we have found multiple cilia with a 9 + 2 microtubular pattern (the same type found in the bronchial tree) in the renal tubules of four adults with the nephrotic syndrome. Each patient had a different pathologic diagnosis: amyloidosis, lipoid nephrosis, membranoproliferative glomerulonephritis, and focal segmental glomerulosclerosis. Previously, multiple renal tubular cilia with 9 + 2 architecture had been reported in patients with Burnetts syndrome, systemic lupus erythematosus, and congenital nephrotic syndrome. Additionally, we found multiple cilia in the metanephric tubules of 4 of 4 human fetuses. Pathologists should be aware that cilia with various microtubular patterns occur in human adult kidneys.

SARCOIDOSIS OF TESTIS AND EPIDIDYMIS

Abstract A case of sarcoidosis involving the testes and epididymis is reported. The disease was bilateral, and evolved one year after discontinuation of corticoid therapy and was not accompanied by signs of systemic sarcoidosis.

Thymoma in a 12‐year‐old boy

A case of thymoma in a 12‐year‐old boy is presented. The patient had a history of thymic irradiation in infancy, and a family history of leukemia. The mass was readily resected and the patient is well 10 years later. The tumor contained an unusual admixture of normal thymic tissue with the neoplastic epithelial elements. This peculiar histologic pattern is discussed in relationship to the patients age and history.

Immune complex myositis associated with viral hepatitis

Sarcolemmal osmiophilic deposits were demonstrated by electron microscopy in the striated muscle of a patient who developed viral hepatitis associated myositis. HBsAg, IgG, and C3 were found in the same location, suggesting that the deposits represent immune complexes and the primary cause of myositis.

Gastrin induction of mRNA expression in rat colonic epithelium in vitro

A newly developed system of isolated rat colonic epithelial cells was utilized for a comprehensive study of protein synthesis influenced by gastrin. We found that synthetic human gastrin (0.01-100 nM) increased the incorporation of [35S]methionine into proteins within 2 hours. Peak incorporation was observed with 10 nM gastrin to more than two-fold above maintenance levels. Actinomycin-D (10 micrograms/ml) inhibited the stimulated increases in total protein synthesis indicating that the peptides trophic effect was mediated by the synthesis of new mRNA species. The effect of gastrin was comparably stronger than the one induced by the mitogen bombesin (1 nM). However, bombesin, a neuromodulator of gastrin release, did not produce an additive effect beyond that of gastrin on total protein synthesis. Gastrin stimulated the synthesis of many polypeptides resolved on two-dimensional polyacrylamide gel, an indicator of gastrins influence on the expression of various mRNA species. Some of these polypeptides may be used as markers in investigating colonic epithelial response to gastrin.

Glomerular endothelial endocytosis of subendothelial electron dense deposits

Abstract In 16 of 52 cases (32.5 per cent) of glomerulonephritis associated with glomerular subendothelial electron dense deposits, we detected endothelial endocytosis of osmiophilic material. Twelve patients had systemic lupus erythematosus, two had poststreptococcal glomerulonephritis, and two had idiopathic immune complex glomerulonephritis. The endocytosis was not observed in 13 patients suffering from membranoproliferative glomerulonephritis, in seven suffering from focal sclerosing glomerulonephritis, and in one suffering from hereditary nephritis. Therefore, the potential for endocytosis appeared to vary according to the illness. By light microscopy the 16 specimens exhibited features of acute proliferative glomerulonephritis. All the 14 with tissue sufficient for immunofluorescence study displayed deposition of immunoglobulins and complement along capillary loops and within the mesangium. By electron microscopy many of the subendothelial deposits were unassociated with endocytosis of osmiophilic matter, yet when endocytosis occurred, it was prominent. Hypertrophied endothelial cells occurred in zones of endocytosis. In nine of 16 cases small vacuoles within endothelial cells contained material of an electron density comparable to that of intramembranous and subendothelial deposits, but lyosomal degradation of the material was not noticed. There was frequent direct communication between osmiophilic material in capillary lumens, the subendothelial aspect of the glomerular basement membrane, and endothelial cytoplasmic processes. These communications suggested movement of osmiophilic material in some fashion. Neutrophils featuring vacuoles that contained osmiophilic material were only rarely observed, indicating that they may not assume a major role in degradation of deposits. Phagocytic activity of mesangial cells and nonresident monocytes was not studied. On the basis of our findings we propose that endothelial endocytosis of osmiophilic material might constitute a component of a transport mechanism or a digestive mechanism of glomerular immune deposits located in the subendothelial region.