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11.
James H. Resau Kosaku Sakamoto John R. Cottrell Eric A. Hudson Stephen J. Meltzer 《Cytotechnology》1991,7(3):137-149
Organ explant culture models offer several significant advantages for studies of patho-physiologic mechanisms like cell injury, secretion, differentiation and structure development. Organs or small explants/slices can be removed in vivo and maintained in vitro for extended periods of time if careful attention is paid to the media composition, substrate selection, and atmosphere. In the case of human tissues obtained from autopsy or surgery, additional attention must be paid to the postmortem interval, temperature, hydration, and cause of death. Explant organ culture has been effectively utilized to establish outgrowth cell cultures and characterize the histiotypic relationships between the various cell types within an organ or tissue.J. Resau is a visiting scientist at the NCI-LMO-DCE in Frederick, MD 21702, U.S.A.K. Sakamoto is a visiting scientist from the Department of Surgery, Gunma University School of Medicine, Maebashi, Japan 相似文献
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Structure of fragment E species from human cross-linked fibrin 总被引:6,自引:0,他引:6
Fragments E1, E2, and E3 are plasmic derivatives of fibrin encompassing the NH2-terminal region of the molecule. The first two species, but not the third, can bind to fragment DD, forming a (DD)E complex, and therefore probably contain binding sites involved in the polymerization of fibrin. For localization of these sites the structure of the fragments was determined by establishing the NH2- and COOH-terminal boundaries of the molecules and using the published amino acid sequence of fibrinogen. Fragment E1 encompasses Gly-alpha 17 to Lys-alpha 78, Gly-beta 15 to Lys-beta 122, and Tyr-gamma 1 to Lys-gamma 62, this representing the intact NH2-terminal region of fibrin. Fragment E2 is an asymmetric molecule which is lacking the sequence of Gly-beta 15 to Lys-beta 53 in one beta-chain remnant. This fragment E2 also lost Lys-beta 122 from the COOH terminal of the beta chain as compared with fragment E1. These cleavages did not affect the ability of fragment E2 to bind to fragment DD. Fragment E3 was heterogeneous, the main species encompassing Val-alpha 20 to Lys-alpha 78, Lys-beta 54 to Leu-beta 120, and Tyr-gamma 1 to Lys-gamma 53. Thus, the loss of the binding function involved in the formation of fibrin clot was associated with the removal of small fragments from all three polypeptide chains: alpha 17-19 (Gly-Pro-Arg), beta 15-53 from the remaining half of the molecule, beta 121 (Leu), and gamma 54-58 (Thr-Ser-Glu-Val-Lys). 相似文献
14.
M S Berry G A Cottrell 《Proceedings of the Royal Society of London. Series B, Containing papers of a Biological character. Royal Society (Great Britain)》1979,203(1153):427-444
A specified dopamine neuron in Planorbis corneus produces dopamine-mediated e.p.s.ps, i.p.s.ps or biphasic, depolarizing-hyperpolarizing p.s.ps in different follower neurons. The excitatory potentials were of three types. Some follower neurons exhibited slow e.p.s.ps (ca 1 s), and a long-lasting, slowly desensitizing, depolarizing response to iontophoresed dopamine. Others showed rapid (ca. 150 ms) e.p.s.ps, often of variable amplitude, and a rapid, quickly desensitizing, response to iontophoresed dopamine. The rapid e.p.s.ps were sometimes followed by the inhibitory response (biphasic potential). The e.p.s.ps were potentiated by hyperpolarization and reduced by depolarization, though they could not be inverted. The slow e.p.s.p. was shown to be associated with an increase in membrane conductance, but it has proved difficult to elucidate the ions involved. A third type of e.p.s.p. was produced by electrical transmission. The inhibitory potentials were generally reduced in amplitude by artificial hyperpolarization but could rarely be inverted. This is probably due in part to the presence of of electrotonic coupling between these follower neurons. The i.p.s.ps were associated with an increase in conductance which appeared small when measured in the cell body. However, the i.p.s.ps produced considerable shunting of electrotonic transmission between coupled followers indicating a large increase in conductance at the synapse. I.p.s.ps were unaffected by Cl-free solution but they were greatly reduced, though rarely inverted, by increasing the external K concentration. They were blocked by intracellular tetraethylammonium, or cooling. The effects on corresponding responses to iontophoresed dopamine were in each case the same as on the i.p.s.ps. It is concluded that the i.p.s.ps mediated by the dopamine neuron are produced by an increase in permeability to K+. On a few occasions i.p.s.ps mediated by the dopamine neuron were potentiated by hyperpolarization. This appeared to be caused by a sharp increase in membrane resistance with hyperpolarization of these particular neurons. However, mediation by a mechanism of conductance decrease could not be completely excluded. 相似文献
15.
An antigen abstract of Proleptus obtusus an intestinal nematode of the common dogfish has been shown to precipitate with a serum component of plaice. As the parasite has never been shown to infect plaice it is suggested that perhaps the serum component might be C–reactive protein (CRP). However, characterization of the component revealed that it was specific immunoglobulin analagous to antibody of the IgM class. It is suggested the helminth antigen involved is cross–reacting with a common antigen to which the plaice is normally exposed. 相似文献
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17.
Rebecca E. Williams Lisa Cottrell Matthew Jacobsen Lasantha R. Bandara Mike D. Kelly Sandy Kennedy 《Biomarkers》2013,18(6):472-490
N-Phenylanthranilic acid (NPAA) causes renal papillary necrosis (RPN) in the rat following repeated oral dosing. Non-invasive early detection of RPN is difficult, but a number of potential biomarkers have been investigated, including phospholipid and uronic acid excretion. This study used 1H-nuclear magnetic resonance (NMR) spectroscopic analysis of urine to investigate urinary metabolic perturbations occurring in the rat following exposure to NPAA. Male Alderley Park rats received NPAA (300, 500 or 700?mg?kg?1?day?1 orally) for 7?days, and urine was collected on days 7–8, 14–15, 21–22 and 28–29. In a separate study, urine was collected on days 1–2, 3–4, 5–6 and 7–8 from rats receiving 500?mg?kg?1?day?1. Samples were analysed by 1H NMR spectroscopy combined with multivariate data analysis and clinical chemistry. Histopathology and clinical chemistry analysis of terminal blood samples was carried out following termination on days 4, 6, 8 and 29 (4?week time course) and days 2, 4, 6 and 8 (8?day study). Urine analysis revealed a marked, though variable, excretion of β-hydroxybutyrate, acetoacetate and acetone (ketone bodies) seen on days 3–4, 5–6 and 7–8 of the study. It is postulated that the ketonuria might be secondary to an alteration in fatty acid metabolism due to inhibition of prostaglandin synthesis. In addition, an elevation in urinary ascorbate was observed during the first 8?days of the study. Ascorbate is considered to be a biomarker of hepatic response, probably reflecting an increased hepatic activity due to glucuronidation of NPAA. 相似文献
18.
Alana M. Rader Amy Cottrell Anna Kudla Tiffany Lum David Henderson Harshad Karandikar Susan G. Letcher 《Biotropica》2020,52(3):410-414
On 19 May 2018, a microburst caused 600 isolated forest gaps in a Costa Rican tropical forest. We surveyed fallen and standing trees within gaps to determine whether certain variables are associated with treefalls. Our results highlight considerations for future research to understand the impacts of microbursts in tropical forests. 相似文献
19.
Dane D. Jensen Cody B. Godfrey Christian Niklas Meritxell Canals Martina Kocan Daniel P. Poole Jane E. Murphy Farzad Alemi Graeme S. Cottrell Christoph Korbmacher Nevin A. Lambert Nigel W. Bunnett Carlos U. Corvera 《The Journal of biological chemistry》2013,288(32):22942-22960
TGR5 is a G protein-coupled receptor that mediates bile acid (BA) effects on energy balance, inflammation, digestion, and sensation. The mechanisms and spatiotemporal control of TGR5 signaling are poorly understood. We investigated TGR5 signaling and trafficking in transfected HEK293 cells and colonocytes (NCM460) that endogenously express TGR5. BAs (deoxycholic acid (DCA), taurolithocholic acid) and the selective agonists oleanolic acid and 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide stimulated cAMP formation but did not induce TGR5 endocytosis or recruitment of β-arrestins, as assessed by confocal microscopy. DCA, taurolithocholic acid, and oleanolic acid did not stimulate TGR5 association with β-arrestin 1/2 or G protein-coupled receptor kinase (GRK) 2/5/6, as determined by bioluminescence resonance energy transfer. 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide stimulated a low level of TGR5 interaction with β-arrestin 2 and GRK2. DCA induced cAMP formation at the plasma membrane and cytosol, as determined using exchange factor directly regulated by cAMP (Epac2)-based reporters, but cAMP signals did not desensitize. AG1478, an inhibitor of epidermal growth factor receptor tyrosine kinase, the metalloprotease inhibitor batimastat, and methyl-β-cyclodextrin and filipin, which block lipid raft formation, prevented DCA stimulation of ERK1/2. Bioluminescence resonance energy transfer analysis revealed TGR5 and EGFR interactions that were blocked by disruption of lipid rafts. DCA stimulated TGR5 redistribution to plasma membrane microdomains, as localized by immunogold electron microscopy. Thus, TGR5 does not interact with β-arrestins, desensitize, or traffic to endosomes. TGR5 signals from plasma membrane rafts that facilitate EGFR interaction and transactivation. An understanding of the spatiotemporal control of TGR5 signaling provides insights into the actions of BAs and therapeutic TGR5 agonists/antagonists. 相似文献
20.
Munter T Cottrell L Ghai R Golding BT Watson WP 《Chemico-biological interactions》2007,166(1-3):323-331
Chloroprene (2-chloro-1,3-butadiene, 1) is oxidised by cytochrome P450 enzymes in mammalian liver microsomes to several metabolites, some of which are reactive towards DNA and are mutagenic. Much less of the metabolite (1-chloroethenyl)oxirane (2a/2b) was formed by human liver microsomes compared with microsomes from Sprague-Dawley rats and B6C3F1 mice. Epoxide (2a/2b) was a substrate for mammalian microsomal epoxide hydrolases, which showed preferential hydrolysis of the (S)-enantiomer (2b). The metabolite 2-chloro-2-ethenyloxirane (3a/3b) was rapidly hydrolysed to 1-hydroxybut-3-en-2-one (4) and in competing processes rearranged to 1-chlorobut-3-en-2-one (5) and 2-chlorobut-3-en-1-al (6). The latter compound isomerised to (Z)-2-chlorobut-2-en-1-al (7). In microsomal preparations from human, rat and mouse liver, compounds 4, 5 and 7 were conjugated by glutathione both in the absence and presence of glutathione transferases. There was no evidence for the formation of a chloroprene diepoxide metabolite in any of the microsomal systems. The major adducts from the reaction of (1-chloroethenyl)oxirane (2a/2b) with calf thymus DNA were identified as N7-(3-chloro-2-hydroxy-3-buten-1-yl)-guanine (20) and N3-(3-chloro-2-hydroxy-3-buten-1-yl)-2'-deoxyuridine (23), with the latter being derived by alkylation at N-3 of 2'-deoxycytidine, followed by deamination. Adducts in DNA were identified by comparison with those derived from individual deoxyribonucleosides. The metabolite (Z)-2-chlorobut-2-en-1-al (7) formed principally two adducts with 2'-deoxyadenosine which were identified as a pair of diastereoisomers of 3-(2'-deoxy-beta-d-ribofuranosyl)-7-(1-hydroxyethyl)-3H-imidazo[2,1-i]purine (25). The chlorine atom of chloroprene thus leads to different intoxication and detoxication profiles compared with those for butadiene and isoprene. The results infer that in vivo oxidations of chloroprene catalysed by cytochrome P450 are more important in rodents, whereas hydrolytic processes catalysed by epoxide hydrolases are more pronounced in humans. The reactivity of chloroprene metabolites towards DNA is important for the toxicology of chloroprene, especially when detoxication is incomplete. 相似文献