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N Quintana

Publications and source records attributed to N Quintana.

At least 19 recordsLinked to original sources
PubMed1998

Spontaneous cholangiofibrosis in Long-Evans Cinnamon rats: a rodent model for Wilson's disease.

The Long-Evans Cinnamon (LEC) rat is a rodent model of Wilson's disease characterized by ceruloplasmin deficiency, hepatic copper accumulation, and hepatocellular injury. So far, the LEC rat appears to be the only strain in which cholangiofibrosis develops spontaneously. The aim of the study reported here was to characterize the time course of development and investigate the structural and ultrastructural features of cholangiofibrosis and their possible relationship to hepatic copper and iron content. The livers of 54 rats (22 males), ages 5 to 113 weeks, were examined by light microscopy and graded for statistical analysis, with respect to extent of replacement of liver tissue by cholangiofibrosis. The study was complemented by electron microscopy, and by measurements of copper and iron contents by atomic absorption spectroscopy. Cholangiofibrosis was present in LEC rats by 20 weeks of age. The hyperplastic biliary epithelial cells varied markedly in size and shape, ranging from flat to cuboidal or elongated. Epithelial cells did not exhibit characteristics of intestinal cells. Some basement membranes had splits, duplications, or multiplications. Cytoplasmic organelles within hyperplastic biliary cells appeared unremarkable in contrast to the characteristic mitochondrial abnormalities present in neighboring hepatocytes. There was a positive correlation between histologic grades of cholangiofibrosis and ages of the animals (r = 0.68, P < 0.001), but no significant correlation between histologic grade and hepatic copper or iron content. We conclude that cholangiofibrosis is the predominant pathologic response to chronic liver injury induced by excess copper in LEC rats. The pathogenic role of copper in the development of cholangiofibrosis requires clearer definition.

Adenosine Triphosphatases↗
PubMed1995

An array of mitochondrial alterations in the hepatocytes of Long-Evans Cinnamon rats.

In an attempt to identify the cellular targets of copper toxicity, we studied the ultrastructure of hepatocytes in the livers of 23 Long-Evans Cinnamon (LEC) rats ranging in age from 10 to 89 weeks. The hepatic copper concentration ranged from 325 to 2,126 (mean, 930) micrograms/g dry weight. Thirteen rats displayed varying degrees of jaundice at the time of killing. Numerous nuclei were indented by cytoplasmic invaginations. Conspicuous abnormalities were displayed by mitochondria. These included marked pleomorphism; increased or diminished matrical density; rearrangement, elongation, dilatation, stacking, or disappearance of cristae; absence of matrical granules; presence of matrical inclusions of flocculent electron-dense deposits; and degenerative changes. The severity of the ultrastructural changes did not correlate with the hepatic copper concentration but did correlate with the degree of the icterus displayed by the rats. Certain mitochondrial changes resembled those encountered in the hepatocytes of patients with Wilson's disease, confirming that these organelles are important targets of copper toxicity.

Animals↗
PubMed1991

Light- and electron-microscopical study of a case of gold salt-induced hepatotoxicity.

A 56-yr-old woman with long-standing rheumatoid arthritis exhibited jaundice, pruritus and abdominal discomfort after 8 yr of periodic gold sodium thiomalate injections amounting to a cumulative dose in excess of 2.5 gm. Histopathological examination of the liver biopsy specimen showed submassive loss of parenchyma, collapse of reticulin and mixed cellular inflammatory infiltrates. Macrophages contained dark granules, which displayed the characteristics of aurosomes when examined by transmission electron microscopy and electron microprobe analysis. It is likely that hepatocellular injury occurred when the lysosomal storage capacity for gold was exceeded.

Arthritis, Rheumatoid↗
PubMed1988

Morphologic and chemical studies on a murine mutation (toxic milk mice) resulting in hepatic copper toxicosis.

The accumulation of excessive amounts of copper in the livers of toxic milk mice results in gross morphologic, histologic, and ultrastructural changes that are progressive with age even though the concentrations of copper tend to decrease in mice older than 6 months. Striking differences in morphologic integrity between regenerative nodules and the intervening parenchyma were observed. Profound changes in mitochondria, endoplasmic reticulum, and nuclei as well as accumulation of microvesicular lipid droplets were observed in injured hepatocytes. By contrast, the hepatocytes of regenerative nodules appeared well preserved. Comparisons with other inherited mammalian disorders associated with hepatic copper toxicosis indicate that copper causes species specific organelle injury.

Animals↗
PubMed1986

Evidence that the heads of ADH-sensitive aggrephores are clathrin-coated vesicles: implications for aggrephore structure and function.

Antidiuretic hormone (ADH) induces the fusion of long tubular organelles (aggrephores) with the luminal membrane of the receptor cell, and the delivery of particle aggregates to the membrane. Water flow is believed to take place through the particles. Nothing is known about the origin of the particle aggregates, their incorporation into the aggrephores, or the possible relationship of the aggrephores to the vesicular traffic that takes place in the epithelial cell. In the present studies of the ADH-sensitive epithelial cells of the toad urinary bladder, we have found that the spherical heads of the aggrephores appear to be clathrin-coated vesicles. We propose that vesicles originating from sites such as the Golgi or the luminal membrane may be engaged in aggrephore assembly, the resupply of particle aggregates to the aggrephores, and/or the removal of aggregates, and that the aggrephores may be central points in the pattern of vesicular traffic in the cell.

Animals↗
PubMed1983

Immunocytochemical localization of gamma-glutamyltransferase in induced hyperplastic nodules of rat liver.

The immunocytochemical localization of gamma-glutamyltransferase [(5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2; gamma-GluTase] was demonstrated in hyperplastic liver induced by the carcinogen 2-acetylaminofluorene (2-AAF). The method used a specific antiserum and protein A-horseradish peroxidase and permitted visualization of antigenic sites at both the light and electron microscopic levels. Electron microscopy revealed deposits of 3,3'-diaminobenzidine (DAB) reaction product in the plasma membranes of (i) hyperplastic cells, (ii) bile canaliculi, (iii) endothelial cell membranes, and (iv) lymphocytes. The so-called ATPase activity was localized in the plasma membrane in bile canaliculi and in endothelial cells; the hyperplastic cells show marked variability in the levels of this activity.

2-Acetylaminofluorene↗
PubMed1983

Transepithelial endoplasmic reticulum in rat proximal convoluted tubule.

Inosine 5'-diphosphatase (IDPase) activity was demonstrated cytochemically in the endoplasmic reticulum of rat kidney proximal tubule cells in tissue fixed by perfusion with glutaraldehyde--formaldehyde. Incubation for IDPase activity at pH 7.2 was performed with and without 0.5 mM levamisole, a potent inhibitor of alkaline phosphatase (AlkPase) (M Borgers, J Histochem Cytochem 21:812, 1973). Levamisole treatment of sections eliminated all reaction product in the brush border, but did not affect the IDPase activity the endoplasmic reticulum (ER). The ER appears as a basilar-luminal-oriented transcellular structure, suggesting a possible cellular transport route. This study supports and extends earlier observations made by others that suggest a transport role for the ER in these cells. It also emphasizes the value of thick section cytochemistry.

Acid Anhydride Hydrolases↗
PubMed1982

Immunocytochemical localization of gamma-glutamyltransferase in rat kidney with protein A-horseradish peroxidase.

Immunocytochemistry with a specific antiserum and protein A-horseradish peroxidase permits visualization of the sites of gamma-glutamyltransferase [(5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2] at both the light- and the electron-microscope levels. As seen by light microscopy, the enzyme is localized only in the proximal convolutions of the renal tubules. Electron microscopy reveals dense deposits of 3,3'-diaminobenzidine reaction product embedded in the glycocalyx along the entire luminal surface of the microvilli and in the basolateral membranes.

Animals↗
PubMed1980

Endocytosis of asialoglycoprotein-enzyme conjugates by hepatocytes.

Desialylated glycoproteins were covalently linked to two cytochemically detectable enzymes, horseradish peroxidase or tyrosinase, and injected intravenously in amounts of approximately 0.5 per cent of total plasma glycoproteins into rats. Comparative studies of the rates of disappearance and distribution of free enzyme and conjugates established that recognition of the conjugates by the plasma membranes of hepatocytes was due to the exposure of the terminal galactose residue of the desialylated glycoproteins. At 1 minute after injection, reaction products of the enzyme markers were seen in coated pits and vesicles, elongated pinocytic channels and pleomorphic vesicles, at or close to the sinusoidal surface of hepatocytes. Vesicles containing reaction products were also observed along the lateral surfaces of hepatocytes. By 10 minutes, reaction products were seen in residual bodies near the biliary poles of hepatocytes. These studies confirm the existence of hepatocellular channels previously seen only with large excess of hemoglobin or following partial hepatectomy. They also indicate that the specific receptor for asialoglycoproteins is not restricted to the sinusoidal surfaces of hepatocytes and that transport to the catabolic sites proceeds via cytoplasmic channels and vesicles.

Animals↗
PubMed1979

Retinal pigment epithelium. Interrelations of endoplasmic reticulum and melanolysosomes in the black mouse and its beige mutant.

By cytochemistry (acid phosphatase and tyrosinase activities) GERL, a specialized hydrolase-rich region of endoplasmic reticulum (ER), can be visualized in the cells of the mouse retinal pigment epithelium. Previously catalase cytochemistry permitted us to identify microperoxisomes, with numerous continuities to the ER. The present report reveals the extensive continuities of the ER to pigment granules in various stages of maturation. When the pigment granules, which we consider to be "melanolysosomes," first appear they consist of electron-opaque grains within dilated areas of the ER. As the dilations enlarge, fine fibrils appear in the ER cisternae. Thicker fibers develop from the fibrils; these fibers are generally obscured when melanin deposition occurs. At all stages, the melanolysosomes appear to be connected to the ER.

Acid Phosphatase↗
PubMed1978

Pyridoxal phosphatase: cytochemical localization in GERL and other organelles of rat neurons.

A phosphatase, hydrolyzing pyridoxal-5-phosphate (P5P), a physiologically active component of the vitamin B6 complex and an essential co-enzyme in the synthesis of neurotransmitters, has been localized cytochemically in the perikarya of neurons in the peripheral, autonomic and central nervous systems of the rat. Neurons in dorsal root ganglia, sympathetic ganglia and ventral horn of spinal cord were studied by light and electron microscopy, while Purkinje cells, neurons in the dentate nucleus of the cerebellum, thalamus, and hypothalamus were studied by light microscopy only. Optimal conditions for demonstrating this activity in aldehyde-fixed tissue were determined with dorsal root ganglia. At the optimal pH of 5.0, neurons in these ganglia and in all other neurons studied show pyridoxal-5-phosphatase (P5Pase) activity in GERL. Small neurons in dorsal root ganglia also display enzyme activity in the endoplasmic reticulum (ER); activities in GERL and ER are also appreciably high at neutral pH. Small and large neurons in these ganglia, and neurons of sympathetic ganglia, show variable P5Pase activity in the Golgi apparatus. These localizations differ from the usual sites of both acid phosphatase and alkaline phosphatase activities. The P5Pase activity, demonstrated cytochemically, is a new acid hydrolase activity in GERL.

Animals↗
PubMed1978

Studies on the secretory process in exocrine pancreas cells. II. C57 black and beige mice.

Published electron microscopic and cytochemical studies (thiamine pyrophosphatase and acid phosphatase) on exocrine pancreas cells of guinea pig, hamster, rat and rabbit have demonstrated that the nascent secretory granules, or condensing vacuoles, are part of GERL. The studies reported here show this to be true of the mouse pancreatic exocrine cells as well, thus permitting comparison of this cell type in the C57 black mouse and its "beige" mutant. This is of considerable interest because GERL is very much enlarged in these cells of the beige mouse. Most of GERL consists of wide dilated portions filled with electron-opaque materials that appear to be packaged into huge residual body-type lysosomes ("anomalous granules"). Acid phosphatase activity is demonstrable not only in these portions of GERL, but also in the condensing vacuoles as in pancreatic acinar cells in the black mouse where these dilated lysosome-producing regions are not present.

Animals↗
PubMed1977

Studies of the secretory process in the mammalian exocrine pancreas. I. The condensing vacuoles.

Phosphatase cytochemistry was used to distinguish between the Golgi apparatus and GERL (considered as a specialized region of endoplasmic reticulum [ER] at the inner [trans] aspect of the Golgi stack) in pancreatic exocrine cells of guinea pig, rat, rabbit, and hamster. The trans element of the Golgi stack exhibits thiamine pyrophosphatase (TPPase) but no acid phosphatase (AcPase) activity. In contrast, GERL shows AcPase but no TPPase activity. The nascent secretory granules, or condensing vacuoles, are expanded cisternal portions of GERL. Continuities of condensing vacuoles with rough ER are suggested, and it is proposed that some secretory components may have direct access to the condensing vacuoles from ER. Connections of Golgi apparatus with GERL were not seen.

Acid Phosphatase↗
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↗