Proton-neutron interactions and the new atomic masses.

Double differences of masses can be used to isolate specific nucleonic interactions. With the new 2003 mass tabulation a significant increase in the number of empirical average proton-neutron interactions of the last nucleons can be extracted. It is shown that they exhibit dramatic and distinctive patterns, especially near doubly magic nuclei, that these patterns can be interpreted with a simple ansatz based on overlaps of proton and neutron orbits, and that the trends in p-n interactions across entire shells can be understood if they are correlated with the fractional shell filling. It is shown how these empirical interactions can be sensitive to changes in shell structure in exotic nuclei. Finally, these results are used to suggest criteria for future mass measurements with new exotic beam facilities.

Structural similarities between hematoidin crystals and asteroid bodies: evidence of lipid composition.

Hematoidin crystals (HC) are found in tissues where extravasated erythrocytes undergo degradation. Previous studies have determined that hematoidin is composed, in part, of a bilirubin-like pigment. In a previous study (Papadimitriou and Drachenberg, Ultrastruct. Pathol. 16, 413-421, 1992), we demonstrated that giant cell asteroid bodies (AB) are formed by membrane lipid bilayers. We evaluated three cases in which HC developed within splenic infarcts. The crystals were analyzed by light microscopy (LM), electron microscopy (EM), and X-ray microanalysis. A case of sarcoidosis with multiple epithelioid granulomas containing AB was studied for comparison. By LM the HC demonstrated intense, golden-color, fine threads, both intracellularly and extracellularly, in small and large clusters, and in radiating, star-shape patterns ranging in size from 2 to 200 microm. By EM the HC were composed of a core of empty clefts, consistent with dissolved lipids, suggestive of cholesterol crystals, and were surrounded by myelinoid membrane aggregates. The AB showed by LM significant morphological similarities with the intracellular HC. By EM, the AB were composed of a core of dense phospholipid bilayer tubes surrounded by a halo of myelinoid membranes. No accumulation of specific elements was found in either HC or AB by X-ray microanalysis. HC and AB show a similar star-shape morphology by both LM and EM. We postulate that this shape is due to the physicochemical properties of the accumulated lipids which originate from superfluous cell membranes created during cell fusion in the case of AB and after cellular (predominantly red cell) breakdown in the case of HC. The golden color of the HC likely results from adsorption of hydrophobic bilirubin-like pigments left over from erythrocyte breakdown into the accumulated lipids. Thus, this study shows two different (patho)physiological processes that lead to a markedly similar morphological end-product and provides further support to our proposed mechanism for AB formation.

Isolated visceral leishmaniasis presenting as an adrenal cystic mass.

A 69-year-old woman presented with a large left retroperitoneal suprarenal mass. Radical resection of the left kidney and the mass revealed a cystic adrenal tumor with a weight of 1500 g. Histologic examination showed that the cyst was composed mostly of partially organized clotted blood. The periphery of the mass consisted of a thin rim of cortical and medullary adrenal tissue with superimposed granulomatous chronic inflammation. The infectious nature of the process was manifested by the scattered intracellular and extracellular Leishmania amastigotes that were found throughout the lesion. The differential diagnosis of cystic adrenal masses and the unusual presentation of visceral leishmaniasis are discussed in this context.

"Thanatosomes": a unifying morphogenetic concept for tumor hyaline globules related to apoptosis.

Hyaline globules (HG) have been observed in a large variety of unrelated categories of tumors and benign tissues. Different explanations for their formation have been proposed, varying according to tumor type and anatomic location. We have studied 80 tumor cases containing HG, by light microscopy, electron microscopy, immunohistochemical stains for various plasma proteins, and in situ DNA-end labeling for apoptosis. On light microscopy, HG were invariably related to areas of increased apoptosis and often contained apoptotic nuclear fragments. The HG stained as expected, with variable intensity with acidic stains. Most cells containing HG stained with immunohistochemical stains for all plasma proteins examined (alpha-1-antitrypsin, ferritin, C3, kappa and lambda light chains, and IgG), indicating an increased plasma membrane permeability. A morphologic change associated with the increased permeability was cytoplasmic blebbing. In the HG themselves, immunohistochemical stains for the plasma proteins were either diffusely positive or stained only the periphery of the larger HG. Double stains for apoptosis and plasma proteins confirmed the increased plasma membrane permeability to proteins of apoptotic cells in general and cells containing HG in particular. Free hyaline globules were often linked to the extracellular matrix by fibrin fibrils. Ultrastructurally, the HG appeared as phagosomes/secondary lysosomes or areas of cytoplasmic condensation surrounded by rough endoplasmic reticulum whorls. These were always associated with intense cytoplasmic blebbing. We conclude that HG reflect stages of cell injury, which in most instances relate to apoptotic cell death. They are specifically associated with the cytoplasmic blebbing and condensation typically seen in this form of cell death. These phenomena are accompanied by plasma protein influx (insudated plasma) and formation of distinct intracellular "hyalinized" cellular fragments. With cell fragmentation, the HG become extracellular and are likely to be ultimately disposed of by a process of "remodeling" and incorporation into the extracellular matrix, followed by collagenization. The latter process partly occurs by the initial linking of all components (HG, collagen fibers, cellular fragments, etc.) by a network of fibrin. The process of formation of HG follows a stereotypical pathway independent of cell type. Because it results mostly from apoptotic cell death, it is more pronounced in rapidly growing tumors or posttreatment. We propose the term thanatosomes for the entire spectrum of HG to emphasize their relationship to cell death. HUM PATHOL 31:1455-1465.

Alexander disease: Alzheimer disease of the developing brain?

Alexander disease is a leukodystrophy-like neurodegenerative disease that typically presents in infancy or childhood. The disease is essentially a sporadic condition, and there is no known genetic predisposition or metabolic abnormality. The hallmark of the disease is the diffuse accumulation of Rosenthal fibers (RF) throughout the central nervous system. Although an etiological relationship of the RF to disease pathogenesis has been suspected since the initial description of Alexander disease, such a relationship has not been confirmed. We previously identified a number of oxidative post-translational modifications, including advanced glycation end products and lipid peroxidation adducts, in intimate association with the RF of Alexander disease. Such oxidative protein damage provides a mechanism, through protein crosslinking, for insolubility and accumulation of RF. Notably, these findings show a striking parallel with the biochemical features of age-related neurodegenerative diseases such as Alzheimer disease. Therefore, Alexander disease and Alzheimer disease likely share a common pathogenesis, namely oxidative injury as a potential primary process in the etiology and pathogenesis.