Raoul Fresco

Metastatic juxtaglomerular cell tumor in a 52-year-old man.

Juxtaglomerular cell tumor is a rare renal neoplasm arising from the juxtaglomerular apparatus. Approximately 70 cases have been reported in the English literature since it was first described by Robertson et al in 1967. This tumor has been considered benign and resection has so far been curative. In this paper, we report the first metastatic juxtaglomerular cell tumor. The 15-cm tumor occurred in the right kidney of a 46-year-old man. It invaded the renal vein, and was treated by radical nephrectomy in 1995. The diagnosis at that time was renal cell carcinoma. The patient was well for 6 years and then developed bilateral lung masses, which were resected. Microscopically, the tumors from the kidney and the lungs were similar, consisting of solid sheets of uniformly round-to-polygonal cells intermixed with abundant delicate vasculature. Both renal and pulmonary tumors were positive for vimentin, renin, and only focally to CD34. Electron microscopic studies performed on the paraffin-embedded renal tumor and formalin-fixed lung tumor revealed the typical rhomboid crystals of proto-renin. In consideration of the characteristic morphologic features, immunohistochemistry, and the presence of rhomboid crystals of proto-renin, the diagnosis was modified to malignant juxtaglomerular cell tumor.

Expanding the Pathologic Spectrum of Immunoglobulin Light Chain Proximal Tubulopathy

CONTEXT In plasma cell dyscrasias, involvement of the distal tubules is frequent and well characterized. In contrast, proximal tubules have only rarely been reported to show diagnostic pathology such as intracytoplasmic crystals. OBJECTIVE To look for additional morphologic features that might be helpful in the diagnosis of proximal tubulopathy associated with an underlying plasma cell dyscrasia. DESIGN We examined patients presenting with nonspecific renal symptoms who were found to have light chain restriction limited to proximal tubular epithelium by immunofluorescence. We correlated these results with light microscopy, electron microscopy, and the clinical findings. RESULTS By immunofluorescence, 5 patients had light chain restriction in proximal tubular epithelium. By light microscopy, only 1 patient had focal rhomboid crystals in the proximal tubular epithelium; all other biopsies failed to show any discernible pathology within the proximal tubules or elsewhere in the kidney. By electron microscopy, proximal tubules from 2 patients showed crystals with a latticelike structure, whereas the remaining 3 patients had only prominent phagolysosomes. However, by immunoelectron microscopy, the lysosomal content showed light chain restriction (in 2 cases studied). Post-kidney biopsy, all patients were diagnosed with multiple myeloma or plasma cell dyscrasia. One patient developed renal failure and had recurrence of crystals in the allograft. CONCLUSIONS Light chain proximal tubulopathy may be associated with the presence of crystals or with the presence of phagolysosomes with light chain restriction as the sole abnormality. Both kappa and lambda light chains may be involved. The prognosis is variable and the pathology may recur in transplants.

Tumor of the tongue containing heterotopic brain tissue

A polypoid tumor containing astrocytic glia and ependyma was excised from the base of the tongue of a 3-month-old infant. Neuroid elements were identified immunocytochemically and by means of electron microscopy. We attribute this rare anomaly to displacement of brain tissue in early embryogenesis before closure of the palate.

Heart transplantation in a patient with chloroquine-induced cardiomyopathy☆

We present the first report of a patient who underwent heart transplantation (HT) after endomyocardial biopsy (EMB) and revealed chloroquine-induced cardiomyopathy (CIC). This patient, who was treated with chloroquine for 6 years, developed a restrictive cardiomyopathy that progressed to congestive heart failure (CHF) resistant to medical management.

Failure to confirm the presence of a retrovirus in cultured lymphocytes from patients with Kawasaki syndrome.

ABSTRACT: We and others previously reported DNA polymerase activity in culture supernatants of peripheral blood mononuclear cells from patients with acute Kawasaki syndrome (KS). In the present study, we further characterized the previously detected polymerase activity and attempted to confirm its presence in cultured peripheral blood mononuclear cells from additional patients with KS. Characterization experiments indicated that the polymerase activity was typical of a DNA-dependent DNA polymerase rather than viral reverse transcriptase. Peripheral blood mononuclear cell cultures from 17 additional KS patients were negative for reverse transcriptase activity in three laboratories. Our findings do not provide support for a retroviral etiology of KS. Further studies should continue to focus on infectious agents in efforts to elucidate the etiology of KS.

The effect of maternal amino acid imbalance on fetal cerebral polyribosomes

Abstract Intravenous injection of an isotonic solution of L-phenylalanine or L-tryptophan to pregnant rats on the 20th day of gestation resulted in hyperaminoacidemia in the mother rats and increased concentration of the corresponding amino acid in the fetal cerebral cortices. Disaggregation of the polyribosomes from the fetal cerebral cortices was observed in the polyribosome profiles generated by ultracentrifugation in a linear sucrose gradient. Decreased capacity of in vitro protein synthesis was observed in a cell-free system using microsomal fractions from the phenylalanine or tryptophan-treated fetal cerebral cortices. These observations suggest that amino acid imbalance during pregnancy may be detrimental to fetal brain growth and development.

Tissue Cystathionine in Mice Treated with Cysteine and Homoserine

Extract: Mouse brain was demonstrated to concentrate DL-homoserine and L-cysteine from plasma. Simultaneous injection of 7.5 μmoles DL-homoserine and L-cysteine intraperitoneally to mice resulted in a marked increase of brain cystathionine at the end of 5 hr. The concentration of cystathionine in the experimental group (0.143 ± 0.022 μmole/g) was more than 6 times that of the control group (0.023 ± 0.011 μmole/g). By using unlabeled DL-homoserine and DL-cysteine-35S for injection, cystathionine in brain was found to be labeled, with a specific activity (67,800 dpm/μmole) approximately half that in the radioactive cysteine (115,000 dpm/μmole). These observations suggest that approximately half the cystathionine in brain has been derived from cysteine and, presumably, homoserine. The remaining half is presumed to have been derived from methionine.Chronic feeding of diets containing 5%, 2%, and 1% DL-homoserine and L-cysteine, 5% and 2% DL-homoserine, and 5%, 2%, and 1% L-cysteine to weanling mice resulted in a significant increase in cystathionine in brain compared with controls (0.148 ± 0.016, 0.049 ± 0.002, 0.044 ± 0.002, 0.040 ± 0.001, 0.043 ± 0.003, 0.069 ± 0.003, 0.036 ± 0.002, 0.034 ± 0.002, and 0.027 ± 0.003 μmole/g, respectively).After 34 weeks of dietary experiments, the animals fed with diets containing 5%, 2%, and 1% of both DL-homoserine and L-cysteine, 5% DL-homoserine, and 5% and 2% L-cysteine had significantly lower body weight than that of the controls (22.02 ± 0.290, 26.00 ± 0.460, 26.40 ± 0.462, 25.50 ± 0.504, 23.10 ± 0.388, 25.82 ± 0.512, and 28.53 ± 0.786 g, respectively). The lower weight gained in the experimental animals was correlated with less food intake.Autopsy on all the experimental animals and light microscopy of their brains, lungs, hearts, livers, spleens, suprarenals, kidneys, and intestines showed no pathology. However, electron microscopy of the livers of animals fed with diets containing 5% cysteine showed subcellular changes compatible with poor nutrition, possibly related to inadequate food intake.Animals on all the experimental diets remained fertile; they conceived and produced normal litters.Speculation: The observations reported in this paper demonstrated that cystathionine in brain was increased when mice were given cysteine and homoserine either by intraperitoneal loading or by chronic feeding. It is very probable that tissue cystathionine (particularly that of the brain) may be increased in patients with homocystinuria when adequate amounts of cysteine (or cystine) and homoserine are supplied in the diet. Excessive cysteine may produce unpalatability of the diet. However, this may be corrected by reducing the quantity of cysteine added, flavoring the diet, or by replacing the cysteine with cystine or calcium cystinate. Supplementation of cysteine (or cystine) and homoserine may be the only way to correct cystathionine deficiency in patients with pyridoxine-resistant homocystinuria.Our observations provide the biochemical basis for investigating the possible therapeutic value of supplementing the diet of homoeystinurie patients with cysteine (or cystine) and homoserine.

Successful revascularization of an occluded renal artery after prolonged anuria

Renal atherosclerosis and fibromuscular dysplasia are the most common causes of curable human renovascular hypertension and renal failure. Vascular reconstruction often preserves renal function, but renal failure is rarely reversed, especially after days of anuria. We report a case of a 23-year-old woman who as a child underwent a nephrectomy for congenital hydroureter and renal hypoplasia. She later experienced fibromuscular dysplasia of the remaining renal artery, which ultimately progressed to a complete occlusion and 31 days of total anuria. The patient was revascularized, and within 2 months renal function returned with a blood urea nitrogen and creatinine of 9.0 and 1.0 mg/dl, respectively. After a follow-up of 6 months the patients blood pressure remained 120/80 to 130/80 mm Hg without administration of hypertension medication. In this report we emphasize that under selected circumstances a kidney can survive prolonged ischemia and that delayed revascularization may reestablish renal function.

Systemic lupus erythematosus presenting with hyporeninemic hypoaldosteronism in a 10-year-old girl.

Hyperkalemia has been noted to occur spontaneously in patients with long-standing systemic lupus erythematosus who did not have advanced renal insufficiency. The patients previously described all had relatively normal renin-aldosterone systems, and the hyperkalemia was thus presumed to be secondary to a primary defect in renal tubular potassium secretion. We describe at 10-year-old girl with lupus nephritis, without significant renal insufficiency, who had hyperkalemia from hyporeninemic hypoaldosteronism postulated to be due to vasculitis involving the afferent/efferent arterioles and juxtaglomerular apparatus.

Definition of the pulmonary antibody response to ovalbumin following local challenge in systemically immunized rats.

Abstract The in vivo pulmonary immune response of rats to local stimulation with antigen was assessed by measuring antigen-specific antibody and antibody-secreting cells utilizing enzyme-immunoassay technology. Sprague-Dawley rats were immunized subcutaneously with ovalbumin (OA) emulsified in Freunds incomplete adjuvant, challenged with OA intratra-cheally on Day 19 and sacrificed 1, 2, 3, or 4 days later. Specific antibody-secreting cells in the lung-associated lymph nodes were enumerated with the ELISA-SPOT assay and antibody concentration in the pulmonary lavage fluids and sera was assessed with the ELISA. The greatest response for each parameter was on Day 2. Cellular infiltration of the lung was minimal. Cellular infiltrates consisted mainly of polymorphonuclear leukocytes and were most numerous in the lavage fluid on Days 1 and 2 and in the lung parenchyma on Day 2 after challenge. Local production versus serum transudation of antibody was evaluated by comparing the levels of OA-specific antibody to albumin in the lavage fluid and serum. The data showed that antibody in the lungs was primarily produced locally.