Hanna Shiloh

Neuroblastomas contain iron-rich ferritin.

The ultrastructure of neuroblastoma was examined using unstained sections so that ferritin particles could be identified by the electron density of their iron cores. Ferritin and hemosiderin were found in ten of 11 neuroblastomas that were examined when the patients first presented. The study was therefore expanded to an additional group of children, including some diagnosed by noninvasive procedures and given chemotherapy before the excision of their tumors. In this second group 12 of 20 specimens contained ferritin and hemosiderin in variable amounts. In both groups there was a tendency for patients with advanced disease to have increased amounts of iron compounds in the tumor tissue (Stage III and particularly Stage IV). Most Stage IV patients also had elevated serum ferritin levels. However, based on the available heterogenous material, no absolute relationship could be established between age, disease stage, tumoral storage iron, and the level of serum ferritin. The presence of ferritin in neuroblastoma may be linked to the elevated serum ferritin levels and may be implicated in tumorigenesis.

Hepatomegaly Following Short-term High-dose Steroid Therapy

Summary Children treated with large doses of corticosteroids were found to develop hepatomegaly within a few days. No relationship could be established between the condition for which steroids were given and the liver enlargement. Liver biopsy was thought to be indicated, and thus was performed in three children because of diagnostic uncertainty. The light and electron microscopic examinations revealed normal liver architecture, without edema, sinusoid engorgement, or inflammatory changes. The hepatocytes were distended by increased amounts of glycogen. In a pattern reminiscent of some glycogen storage diseases, mitochondria and other cytosol components were displaced toward the cell membrane or around the nucleus, which occasionally contained glycogen. Moderate sinusoidal compression, interhepatocytic free glycogen particles, and mild increase in lipid droplets were also found. It is concluded that the hepatomegaly noted in patients given short-term, high-dosage steroid therapy is due to excessive glycogen accumulation within parenchymal cells. This finding is in accordance with observations in animals, as well as with biochemical studies demonstrating hepatocytic glycogen deposition after steroid therapy. Being benign and reversible, early hepatomegaly following administration of high-dose corticosteroids should not influence the initial therapeutic plan required by the basic disease.

Decreased expression of tissue inhibitor of matrix metalloproteinases in follicular fluid from women with polycystic ovaries compared with normally ovulating patients undergoing in vitro fertilization

OBJECTIVE To compare activity of matrix metalloproteinases (MMP) and expression of their tissue-specific inhibitor (TIMP) in the follicular fluid of normally ovulating women and women with the polycystic ovary syndrome (PCOS). DESIGN Prospective study. SETTING IVF unit and endocrine research unit. PATIENT(S) Fourteen patients undergoing IVF treatment (seven with normal ovulation and seven with PCOS). MAIN OUTCOME MEASURE(S) Activity of MMP-2 and MMP-9 and expression of MMP-1, TIMP-1, and TIMP-2 was measured in follicular fluid of the leading follicles by using gel zymography and immunoblot analysis. RESULT(S) The activity of MMP-2 and MMP-9 and expression of MMP-1 was similar in follicular fluid of normally ovulating patients and patients with PCOS. Significantly lower expression of TIMP-1 was found in follicular fluid of patients with PCOS women compared with normally ovulating patients. CONCLUSION(S) Because MMPs and TIMPs play a role in the physical and chemical structure of the follicular compartment, the decreased expression of TIMP in patients with PCOS may be part of a compensatory process to overcome the physical properties of the thick ovarian capsule.

Morphologic Observations in Iron Overload: An Update

With increasing progress in the biochemistry, immunology, biophysics and genetics of iron overload, an overview of the latest contributions of morphology seems appropriate. The presence of surplus iron in various tissues, as demonstrated by Perls’ stain, remains the major tool for the diagnosis of cytosiderosis of variable degree. However, since our previous review of experimental iron overload (Iancu and Shiloh, 1988), a number of important contributions were made in this field, with the help of light-and electron microscopy. Moreover, new methods of investigations were used to identify and quantitate the presence of iron-containing compounds.

Experimental iron overload: ultrastructural studies

Neither the role of iron nor the mechanism of cellular damage has been fully elucidated in primary (idiopathic, genetic) hemochromatosis (IHC), secondary, erythropoietic hemochromatosis (EHC), or transfusional hemochromatosis. Attempts to reproduce the features of human disease in experimental animals have been hitherto only partially successful, because laboratory animals seem to be quite resistant to iron overload, at least during the relatively short period of exposure to surplus iron. Although rather static in nature, electron microscopic studies have nonetheless contributed to the understanding of cytosiderosis. This overview summarizes the information gained from previous experiments and describes ultrastructural features of the newer models.

Intestinal Mucosa in Nephropathic Cystinosis

The major manifestations of nephropathic cystinosis are renal tubular acidosis, vitamin D-resistant rickets, and dwarfism. Cystine crystals are deposited in a variety of cells, mainly phagocytic, including macro-phages of the intestinal lamina propria. Previously, ultrastructural changes were suggested to occur in the absorptive epithelium as well, possibly as a result of local cystine toxicity. We report here on the light- and electron-microscopic findings in the jejunal mucosa of two patients, aged 4 and 9 years with nephropathic cystinosis. Cystine crystals were easily identified in semithin sections of plastic-embedded specimens as brick- and hexagon-shaped spaces in macrophages. Electron microscopy showed that all crystals were in single-membrane-limited bodies (lysosomes), within phagocytic cells, and exclusively located in the lamina propria. In contrast to previous findings, the absorptive epithelium showed no abnormalities. We conclude that the growth failure in cystinosis is not a consequence of morphological toxic alterations in the intestinal epithelium, but is related to the known metabolic abnormalities of this condition. The use of rectal suction biopsy as a means of diagnosing cystinosis is also suggested as an alternative to other diagnostic methods.