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61.
62.
Nympha B. D''Souza Abraham P. Bautista Charles H. Lang John J. Spitzer 《Alcoholism, clinical and experimental research》1992,16(1):64-67
Protein kinase (PK) C has been implicated in a number of cellular events, many of which are also known to be affected by ethanol (ETOH). ETOH intoxication is also known to impair immune function, thereby increasing the host's susceptibility to infection. The purpose of this study was to assess the effect of acute ETOH intoxication on PKC activity and its intracellular distribution in nonparenchymal liver cells following an E. coli lipopolysaccharide (LPS) challenge. The liver was chosen for the study because it is the primary site both for metabolism of ETOH and detoxification of gut derived bacterial products. Catheterized conscious rats were administered saline or ETOH (175 mg/100 g body weight as a bolus followed by a continuous, 7 hr infusion of 28 mg/100 body weight/hr). LPS was injected intravenously (100 micrograms/100 g body weight) 3 hr before the end of the saline or ETOH infusion. Kupffer and endothelial cells were isolated by collagenase-pronase digestion followed by centrifugal elutriation. PKC was assayed after extraction with digitonin containing buffer and partial purification on DE-52 cellulose minicolumns. LPS decreased PKC activity by 69% from control values. Although ETOH infusion alone did not affect PKC activity in Kupffer cells, it completely abrogated the LPS effect. A similar trend was observed for the endothelial cells. No significant differences were observed between groups with respect to the intracellular distribution of PKC. The down-regulation of PKC by LPS may represent a mechanism of functional adaptation of the immunocompetent cells to one of the cytokines, i.e., TNF, whose receptors are down regulated by activation of PKC.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
63.
Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. 总被引:23,自引:0,他引:23
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M Laruelle A Abi-Dargham C H van Dyck R Gil C D D''Souza J Erdos E McCance W Rosenblatt C Fingado S S Zoghbi R M Baldwin J P Seibyl J H Krystal D S Charney R B Innis 《Proceedings of the National Academy of Sciences of the United States of America》1996,93(17):9235-9240
The dopamine hypothesis of schizophrenia proposes that hyperactivity of dopaminergic transmission is associated with this illness, but direct observation of abnormalities of dopamine function in schizophrenia has remained elusive. We used a newly developed single photon emission computerized tomography method to measure amphetamine-induced dopamine release in the striatum of fifteen patients with schizophrenia and fifteen healthy controls. Amphetamine-induced dopamine release was estimated by the amphetamine-induced reduction in dopamine D2 receptor availability, measured as the binding potential of the specific D2 receptor radiotracer [123I] (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl]benzamide ([123I]IBZM). The amphetamine-induced decrease in [123I]IBZM binding potential was significantly greater in the schizophrenic group (-19.5 +/- 4.1%) compared with the control group (-7.6 +/- 2.1%). In the schizophrenic group, elevated amphetamine effect on [123I]IBZM binding potential was associated with emergence or worsening of positive psychotic symptoms. This result suggests that psychotic symptoms elicited in this experimental setting in schizophrenic patients are associated with exaggerated stimulation of dopaminergic transmission. Such an observation would be compatible with an abnormal responsiveness of dopaminergic neurons in schizophrenia. 相似文献
64.
G Lesage SS Glaser S Gubba WE Robertson JL Phinizy J Lasater RE Rodgers G Alpini 《Gastroenterology》1996,111(6):1633-1644
BACKGROUND & AIMS: After partial hepatectomy, liver regeneration occurs with the return of hepatocyte mass to normal, Limited data exist regarding the renewal of the biliary tree after partial hepatectomy. This study tested the hypothesis that, after partial hepatectomy, the biliary tree regenerates by proliferation of the remaining cholangiocytes, leading to an increase in secretin-induced ductal bile secretion. METHODS: After 70% partial hepatectomy, cholangiocyte proliferation was assessed in situ by morphometric analysis and In vitro by measurement of 3H-thymidine incorporation. Ductal secretion was estimated by measurement of secretin receptor gene expression and adenosine 3',5'-cyclic monophosphate (cAMP) levels in vitro and by the effect of secretin on ductal bile secretion in vivo. RESULTS: DNA synthesis was undetectable in control cholangiocytes, increased and peaked at day 3 after partial hepatectomy, and returned to normal by day 28. Morphometric analysis showed regrowth of the biliary tree beginning at day 1 with restoration by day 10. The expression of secretin receptor gene and secretin-induced cAMP levels and secretin- induced bicarbonate-rich choleresis increased during the period of bile duct renewal. CONCLUSIONS: After partial hepatectomy, the increase in secretin-induced ductal bile secretion observed during bile duct renewal results from proliferation of remaining cholangiocytes. (Gastroenterology 1996 Dec;111(6):1633-44) 相似文献
65.
Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis 总被引:20,自引:0,他引:20
To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis. 相似文献
66.
The patterns of cell proliferation and cell migration were studied in three patients with the Sezary syndrome using autoradiographic techniques. Cell labeling patterns following pulse labeling with tritiated thymidine in vivo indicated that Sezary cells proliferate actively in skin and in lymph nodes but that few if any Sezary cells proliferate in the peripheral blood. In two of the patients serial samples were obtained. Label dilution patterns in skin and blood over time suggested that circulating Sezary cells originated in extracutaneous sites where cells were proliferating more rapidly than in the skin. Cells labeled in extracutaneous sites of proliferation appear rapidly in the blood, and their transit time through the peripheral blood compartment is short. Circulating Sezary cells may then be deposited in the skin where they resume proliferation at a low rate. Thus, while Sezary cells proliferate in both cutaneous and extracutaneous sites, proliferation appears to be more rapid in extracutaneous sites such as lymph nodes. This suggests that trials of systemic therapeutic approaches should be undertaken. 相似文献
67.
Engraftment of bone marrow cells into normal unprepared hosts: effects of 5-fluorouracil and cell cycle status 总被引:2,自引:7,他引:2
Bone marrow from animals treated with 5-fluorouracil (5FU) competes equally with normal marrow when assessed in vivo in an irradiated mouse, but shows markedly defective engraftment when transplanted into noncytoablated hosts. Using Southern Blot analysis and a Y-chromosome specific probe, we determined the level of engraftment of male donor cells in the bone marrow, spleen, and thymus of unprepared female hosts. We have confirmed the defective engraftment of marrow harvested 6 days after 5FU (FU-6) and transplanted into unprepared hosts and shown that this defect is transient; by 35 days after 5FU (FU-35), engraftment has returned to levels seen with normal marrow. FU-6 marrow represents an actively cycling population of stem cells, and we hypothesize that the cycle status of the stem cell may relate to its capacity to engraft in the nonirradiated host. Accordingly, we have evaluated the cycle status of engrafting normal and FU-6 marrow into normal hosts using an in vivo hydroxyurea technique. We have shown that those cells engrafting from normal marrow and over 70% of the cells engrafting from FU-6 marrow were quiescent, demonstrating no killing with hydroxyurea. We have also used fluorescent in situ hybridization (FISH) analysis with a Y-chromosome probe and demonstrated that normal and post-5FU engraftment patterns in peripheral blood were similar to those seen in bone marrow, spleen, and thymus. Altogether these data indicate that cells engrafting in normal, unprepared hosts are dormant, and the defect that occurs after 5FU is concomitant with the induction of these cells to transit the cell cycle. 相似文献
68.
Natural killer cell precursors in the CD44neg/dim T-cell receptor population of mouse bone marrow 总被引:1,自引:0,他引:1
Natural killer (NK) cells develop from the nonadherent cell component of NK long-term bone marrow (BM) cultures (NK-LTBMC). Because these nonadherent cells are depleted of mature NK cells and T cells, but appear to enriched for NK precursors, they were used as a starting population to begin to define the NK precursors that function in NK- LTBMC. As the stromal cell component of NK-LTBMC has been shown to support interleukin (IL)-2-induced, CD44 dependent, NK cell development from nonadherent NK precursors, NK-LTBMC stroma was used in a limiting dilution assay (LDA) to quantitate the precursors. NK-LTBMC in 96-well plates were irradiated (20 Gy) to kill hematopoietic cells (including the NK precursors), seeded with limiting dilutions of the cells to be quantitated, cultured with 500 U/mL IL-2 for 13 days and assayed for development of NK activity by adding 51Cr-labeled YAC-1 cells to the wells and evaluating the release of 51Cr after 4 hours. Flow cytometric analysis, sorting, and quantitation of the nonadherent cell component of NK-LTBMC showed that NK precursors were concentrated in the CD44neg/dim subset that comprised 10% of the "lymphoid" gated cells. When the CD44neg/dim subset was sorted from BM of mice treated with 5- fluorouracil (5-FU) day before (-1FUBM), there were about 30% T cells, but no NK-1.1+ cells. When the T cells were removed by sorting and the CD44neg/dim, alphabeta, gammadelta T-cell receptorneg (TCR-) subpopulation was seeded onto irradiated stroma with IL-2, they proliferated, developed NK activity, became NK-1.1+ and CD44bright and remained alphabeta, gammadelta TCR-. The frequency of NK precursors in this population as estimated from the LDA was about 1/500. 相似文献
69.
Human marrow erythropoiesis in culture. I. Characterization of methylcellulose colony assay 总被引:11,自引:0,他引:11
We examined the morphological and functional characteristics of human marrow erythrocytes cultured with a recently developed methylcellulose colony assay technique. Erythrocytic cells in various stages of development were observed, and a significant degree of maturational synchrony within individual colonies was noted. By light microscopy, colonies consisting of late normoblasts appeared compact, had an orange hue attributable to their hemoglobin, and demonstrated pseudoperoxidase activity, whereas colonies composed of early erythroblasts grew less compact or in clusters of smaller cell aggregates and showed no reddish tinge. Colonies possessing intermediate features were also observed. Maturational synchrony of individual colonies was confirmed using ransmission and scanning electron microscopy. The ultrastructure and cytochemistry of most immature cells were normal. The mature erythrocytes, however, were severely microcytic and hypochromic and contained one to several Heinz bodies. These defects in the cytoplasmic maturation of erythrocytes corresponded with impaired granulocytic maturation in culture, which we observed previously, and suggest environmental or nutritional defects in culture. Linearity of the method was confirmed using five normal bone marrows. Erythropoietin dose-responses observed in ten normal marrows were comparable to the previously reported results and revealed significant variation in individual plating efficiencies. 相似文献
70.
Oxidants released from inflammatory cells contribute to the pathogenesis of acute inflammatory edema in many models. Chemically produced oxidants can reversibly alter the barrier properties of cultured endothelial and epithelial monolayers. This report examines the effects of nonlytic doses of H2O2 on endothelial cell lipids. H2O2 oxidized omega-6 fatty acids in the endothelial cells and initiated hydrolysis of endothelial cell phospholipids. When endothelial cells were exposed to peroxidized linoleic acid, it caused lysis of the cells at doses 1,000-fold lower than effective doses of H2O2. The phospholipid hydrolysis was directed primarily at the inositol phospholipids and consisted of both A and C type phospholipase activity. The phospholipase A hydrolysis resulted in increases in endothelial cell free fatty acids and lysophosphatidylinositol. The phospholipase C hydrolysis resulted in increases in diglycerides, phosphatidic acid, and inositol polyphosphate levels. The phospholipase C hydrolysis of phosphatidylinositol is known to activate protein kinase C in most cells. Stimulation of protein kinase C with phorbol- 12,13-dibutyrate increased albumin flux across endothelial monolayers and altered endothelial cell shape, similar to effects of oxidants. These data are consistent with the hypothesis that oxidant-initiated hydrolysis of endothelial cell inositol phospholipids contributes to oxidant-mediated reversible changes in endothelial monolayer barrier function. 相似文献