Insulin-like growth factor-I and insulin-like growth factor binding proteins in the Zucker fatty rat: a case for differential tissue regulation.
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The spontaneous mammary tumors of the NMRI mouse are well developed microcystic adenocarcinomas. Serial isologous transplantation of the tumors results in nearly complete dedifferentiation to a solid tumor, in which only electron-microscopically rudimentary acinus-like microlumina can be observed. The adenocarcinomas produce A and B particles in abundance, with the A particles appearing intracellularly in the adluminal cytoplasmic regions of the epithelial cells in association with typical cellular structures and the B particles being restricted to closed extracellular compartments such as vacuoles or acini alone. The loss of alveolar organization in the solid tumors is followed by an almost complete reduction in mature B particles, while A particles are still regularly observed and appear to be less reduced in number. This suggests that the production of extracellular B particles is dependent upon the secretory activity of the tumor cells and that in nonsecreting cells it is predominantly a late step in virus release that is inhibited, not the synthesis of intracellular precursors.
Mice were intravenously injected with 125I-labelled native BSA and cationic mBSA. The amount of 125I-protein in the extra- and intravascular compartment was determined in normal joints and in joints in which the vascular permeability was increased by histamine. The extravasation of BSA and mBSA is different. More BSA compared with mBSA accumulated in normal joints and the extravasation of BSA increased almost 3 times shortly after histamine injection, whereas histamine hardly affected the extravasation of mBSA.
Cell kinetic studies on cultured human epidermal cells have indicated that cycling basal cells may be divided into at least two subpopulations that seem to differ with respect to the rate of DNA replication. The present study was undertaken in order to elucidate the biological significance of these subpopulations. The proliferation characteristics of cultured basal cells were changed by the addition of epidermal growth factor (EGF) and cholera toxin to the culture medium. It was shown that EGF and cholera toxin stimulated the growth of human epidermal cells in culture. Simultaneously, the terminal differentiation of the cells was inhibited resulting in a reduced multilayering and a reduced formation of the cornified envelope. However, only minor differences in the protein synthesis pattern were observed between cultures maintained in the presence or absence of the growth stimulators. The effect of EGF and cholera toxin on the basal cell subpopulations was investigated after 3H-thymidine labelling followed by cell sorting and autoradiography. In the presence of EGF and cholera toxin dramatic changes were induced in the labelling pattern of sorted S-phase cells indicating significant alterations in the balance between the subpopulations of cycling basal cells. Our results with these substances are in accord with the hypothesis that the observed cell kinetic subpopulations may be related to regeneration or early events in the differentiation process of the keratinocyte.
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We present the case of 38-year-old hypertensive patient with bilateral adrenal masses and with clinical and biochemical suspicion of pheochromocytoma. Magnetic resonance imaging at 1.5 T established correct diagnosis of coexisting adrenal pheochromocytoma and adenoma (nonhyperfunctioning). The case supports the usefulness of MRI for definitive evaluation of bilateral adrenal masses in patients with suspicion of pheochromocytoma.
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BACKGROUND: Diet restriction (DR) has been shown to extend the life spans of various laboratory animals, the mechanism may involve a decrease in oxidative stress. When determining if the total tissue defense has been altered, it is important to observe the overall direct antioxidant capacity, which consists of low molecular weight antioxidants (LMWA) and enzymes. AIM: To determine DR induced changes in total reducing power and overall direct antioxidant capacity of various mouse tissues. METHODS: Young female Sabra mice were fed a 60% food restricted diet for 40 days (DR group). Organs of the DR group and of ad libitum (AL) fed controls were then dissected and examined. A cyclic voltammetry method was used to quantify the total reducing power, which correlates with the overall LMWA activity. Specific LMWA were identified by HPLC-ECD. Superoxide dismutase activity and H2O2 degrading ability were measured in order to include the enzymatic antioxidant component. RESULTS: Short-term DR caused alterations in the total reducing power of various mouse tissues, indicating changes in the total scavenging ability of these tissues. Overall direct antioxidant capacity of heart, kidney and muscle was enhanced; liver and small intestine deteriorated; brain did not differ between DR and AL groups; lung and spleen exhibited a mixed response. CONCLUSIONS: We have shown for the first time that DR causes changes in the total reducing power of different mouse tissues, thus, affecting the overall direct antioxidant capacity. These findings support the suggestion that there may be a biological regulation of the antioxidant system.
Nephronophthisis is a common genetic cause of end-stage renal disease in childhood. Recently, Invs was identified as the gene mutated in the infantile form of nephronophthisis. Humans with nephronophthisis develop a large number of extrarenal manifestations, including situs variations, anomalies of the hepatobiliary system, retinal degeneration and cerebellar ataxia. Mice homozygous for a mutation in the Invs gene (inv mouse) die during the first week after birth as a result of renal and liver failure. Although organ anomalies have been characterized in human nephronophthisis and the inv mouse, little is known about the tissue expression of the Invs gene product, inversin. We have used laser confocal microscopy of paraffin-embedded murine tissue sections to provide the first detailed characterization of the distribution of inversin in various organs. Our results show that inversin is localized to distal tubules in the kidney, hepatic bile ducts, acinar and ductal pancreatic cells, epithelial intestinal cells, splenic germinal centres, bronchiolar epithelial cells, dendrites of cerebellar Purkinje cells, retinal neural cells and spermatocytes and spermatids in the testis. The localization of inversin in distal tubules in the kidney and in extrarenal tissues suggests that the expression of this protein has an important function in a variety of organs. Further studies are required to understand the way in which mutations in the Invs gene lead to the multi-organ pathology of inv mouse and human nephronophthisis.
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The expression of Annexins V and VIII by human lung, liver, kidney, skin, heart, uterus, spleen and skeletal muscle was investigated by ELISA. All investigated tissues contained Annexin V. Its level varied with the tissue from around 5 microgram (skin) to approximately 120 micrograms (spleen) per g of wet tissue. Contradistinctionally Annexin VIII expression was less ubiquitous and less abundant. Only lung, skin, liver, and kidney expressed Annexin VIII. Its levels were approximately 100-fold less then the Annexin V levels. Immunohistochemical analysis of lung sections revealed Annexin VIII presence exclusively in the endothelia. Annexin V and VIII levels of cultured human umbilical vein endothelial cells, human arterial smooth muscle cells, human lung fibroblasts and HeLa cells were measured by ELISA. All cell types expressed Annexin V whereas only HeLa cells had detectable levels of Annexin VIII. The results indicate a tissue specific expression of Annexin VIII by lung endothelium, suggesting a highly specialised function.
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The concentration of ouabain binding sites (OBS), a measure of the abundance of sodium/potassium-dependent ATPase (Na/K-ATPase), was measured in cerebral cortex (CC), cerebellum (CBL), brown adipose tissue (BAT), and heart of neonatal rats with congenital hypothyroidism. In euthyroid rats, the concentration of OBS was 50- to 100-fold greater in the nervous tissue than in the nonnervous tissue. Congenital hypothyroidism resulted in a significant reduction in the number of OBS in all four tissues. Although in absolute terms (pmol/mg protein) the reduction was greater in the nervous tissues, in relative terms it was much greater in the nonnervous tissues. The restoration of OBS concentration was much more sensitive to T4 in CC, CBL, and BAT than in heart. In contrast, the response of OBS concentration to T3 in hypothyroid rats was greater in the heart, followed by the BAT and CBL, being minimal in CC. The sensitivity to T4 replacement correlated with the degree of the stimulation of the type II 5'deiodinase (5'D-II) by hypothyroidism, whereas the response to exogenous T3 correlated with the fraction of the tissue T3 that derives from plasma T3 and inversely with the plasma T3 concentration required to saturate 50% of the nuclear receptors as reported in previous studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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