Search PubMed⌕ Search

Biomedical subjects

I Sternlieb

Publications and source records attributed to I Sternlieb.

At least 73 records · Page 4Linked to original sources
PubMed1979

The role of radiocopper in the diagnosis of Wilson's disease.

In patients with normal serum concentrations of ceruloplasmin, measurement of the incorporation of radiocopper into this protein can aid in the clinically important differentiation of patients with hepatic illnesses that mimic Wilson's disease from patients with this disorder.

Adolescent↗
PubMed1977

The peroxisomes of human hepatocytes.

In an ultrastructural study of human liver biopsy specimens we found that peroxisomes are regularly present in normal human hepatocytes. Their relationships with the endoplasmic reticulum observed in other species and in other organs were also demonstrable in this material. Some normal peroxisomes were found to display marginal plates or peripheral crystalline inclusions which were present in pathologic specimens as well. In certain inherited metabolic disorders (Menkes' steely hair disease, analbuminemia) the volume of the individual peroxisomes appeared to be considerably reduced. But most pathologic processes affecting hepatocytes seem to produce any or several of the following: increased volume or numbers per cell, changes of shapes, alterations of the consistency of the matrix, appearance of dense numbers per cell, changes of shapes, alterations of the consistency of the matrix, appearance of dense inclusions, or clustering of peroxisomes in some portions of the cytoplasm. Some of these abnormalities are reversible based on observations in three patients with Wilson's disease treated with D-penicillamine. The mean +/- standard deviation of diameters of peroxisomes in four normal subjects was 0.618 +/- 0.143 mum. Significant reductions or increases in mean diameters of peroxisomes were noted in all but two of the 16 pathologic specimens. There were other morphologic abnormalities present in the remaining two specimens. We conclude that various pathologic processes involving the hepatocytic cytoplasm exert different effects on peroxisomes. Although no specific pattern of morphologic alteration emerged from this exploratory study, a possible involvement of peroxisomes ought to be considered whenever metabolic or pathologic processes affect the liver.

Biopsy↗
PubMed1977

Lipolysosomes in human liver: distribution in livers with fatty infiltration.

In this study we investigated whether lipolysosomes--lysosomes containing large lipid droplets--were present in livers of patients with various forms of hepatic injury. Organelles which displayed the same morphological characteristics and enzymatic activity as those originally described in the hamster and those found in the hepatocytes of patients with Wolman's or Wilson's disease were also found in hepatocytes of 13 of 14 randomly selected biopsy specimens from patients with minimal to severe fatty infiltration of the liver. The numbers and sizes of the lipolysosomes seemed to increase with the degree of fatty infiltration while their proportion in relation to the total number of lipid droplets remained below 5%. Based on these observations of a virtually constant association of lipolysosomes with excess lipid accumulation in liver cells we suggest that lysosomes probably play an important role in hepatic lipid metabolism and that various pathogenetic mechanisms may trigger their proliferation.

Adolescent↗
PubMed1976

Heavy metals and lysosomes.

Much can be gained by reassessing the processes which determine the ability of lysosomes to take up or exclude, sequester and mobilize heavy metals. To achieve a better understanding of these events, the chemical forms, intracellular pathways and modes of delivery of metals to lysosomes, as well as the specific physiologic ligands and molecular targets susceptible to metal toxicity have to be identified. None of these can be derived from measurements of metal contents of whole lysosomal fractions because the metal's "effective concentration" at a specific target site may be affected by the binding properties of the lysosomal ligand as well as by those of cation carrier proteins present in the cytosol (e.g., metallothionein), and by interactions with and competitions by other cellular organelles. Therefore, the possibility of such events diminishing or enhancing a metal's direct effect observable in in vitro systems has to be considered before extrapolating to the in vivo situation. Another pitfall to be wary of is the equation of an organelle's relative affinity for a metal in vitro with its susceptibility to the metal's toxic effects. This is evident, albeit at a tissue level rather than at that of organelles, from the discordance between the low affinity of nervous tissue for lead and this metal's pronounced encephalopathic effect. The answers to some of the questions raised in this review may possibly lead to pharmacologic applications, particularly to the development of effective agents for the removal from or the inactivation of toxic metals deposited in lysosomes. At present, considerable uncertainty exists regarding the possible interaction of therapeutic chelating agents with lysosomes in vivo. We do not know, for example, whether the contrasts between the remarkable effectiveness of penicillamine in mobilizing copper from tissues and the limited effectiveness of desferioxamine in removing excess iron stores can be accounted for by differences in accessibility of these two chelators to lysosomes. Or, alternatively, can these differences in effectiveness be related to different ligands or macromolecules interacting with each metal? At least part of the lysosomal iron is bound to ferritin molecules which may not be susceptible to the action of chelating agents after incorporation. Such speculation is not without foundation since ferritin molecules are heterogeneous. However, whether this heterogeneity, which is reflected in different organ-specific patterns of distribution (Powell et al. 1973), is the result of differing affinities of the isoferritins for specific subcellular organelles has not been established. It is conceivable that ferritin molecules present in the cytoplasm may be subtly different from those taken up by lysosomes, implying that the latter are endowed with capabilities for selection of specific macromolecules...

Animals↗
PubMed1976

R-bodies of human rectal epithelial cells.

Distinctive globular bodies, ranging in diameter from 0.2mu to 1.5mu, were encountered in the cytoplasm of epithelial cells of human rectal mucosa. These profiles, surrounded by a unit membrane, contained a uniform population of electron-dense rods 50 nm wide and 100 to 250 nm long. Although neither the origin nor the relationships of these rod-containing bodies (R-bodies) to other cytoplasmic organelles could be established, morphologic and cytochemical studies demonstrated clear differences from multivesicular bodies.

Epithelial Cells↗
PubMed1976

Effects of anticopper therapy on hepatocellular mitochondria in patients with Wilson's disease: an ultrastructural and stereological study.

Liver biopsy specimens from 7 patients with Wilson's disease (hepatolenticular degeneration), obtained before and after 3 to 5 years of D-penicillamine therapy, were studied by electron microscopy and stereology. The characteristic mitochondrial abnormalities encountered in the hepatocytes of untreated patients were less pronounced or disappeared after treatment in 5 of the 7 patients. Simultaneously, relative mitochondrial volume, surface density of the external mitochondrial membranes, and the number of these profiles per unit area increased, whereas abnormal elevations SGOT and SGPT returned to normal levels.

Adolescent↗
PubMed1975

D-penicillamine induced Goodpasture's syndrome in Wilson's disease.

Fatal pulmonary hemorrhages and rapidly progressive glomerulonephritis occurred in three patients with Wilson's disease (hepatolenticular degeneration) who had been treated with penicillamine for 2 to 31/2 years. Light microscopic studies of the kidneys showed severe glomerulonephritis with crescent formation, and the lungs showed intraalveolar hemorrhages. Although the clinical and pathologic abnormalities were those of Goodpasture's syndrome, immunofluorescence microscopic studies in the one case tested showed an interrupted, rather than linear, fluorescence pattern.

Adult↗
PubMed1975

Lipolysosomes in human hepatocytes. Ultrastructural and cytochemical studies of patients with Wilson's disease.

Lipid droplets surrounded by a peripheral membrane closely apposed to an electron-dense layer and containing acid phosphatase activity, similar to the lipolysosomes in hamsters described by Nehemiah and Novikoff (J. Cell Biol. 59: 246a, 1973; Exp. Mol. Pathol. 21:398, 1974), were found in the hepatocytes of patients with Wilson's disease. These organelles account for 1 to 2 per cent of the observed lipid droplets at the stage of the disease when excess fat is present. The occurrence of lipolysosomes in a condition not known to be associated with an acid lipase deficiency suggests that lipolysosomes may represent a nonspecific, alternate route for the mobilization of excess lipid from hepatocytes.

Acid Phosphatase↗