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Identifiability: the first step in parameter estimation. 可辨识性:参数估计的第一步。
Federation proceedings Pub Date : 1987-06-01
J A Jacquez
{"title":"Identifiability: the first step in parameter estimation.","authors":"J A Jacquez","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The observations in an experiment define a set of observational parameters that are functions of the basic kinetic parameters of the model of the system. The problem of identifiability is concerned with whether the observational parameters uniquely specify the basic kinetic parameters. As such, it depends only on the functional relation between the two levels of parameters and not on errors of observation and the estimation procedure. It should be checked before doing the experiment. Given initial estimates of the basic kinetic parameters, identifiability can be checked, in a local sense, from data generated by simulating the experiment on the model.</p>","PeriodicalId":12183,"journal":{"name":"Federation proceedings","volume":"46 8","pages":"2477-80"},"PeriodicalIF":0.0,"publicationDate":"1987-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14718313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endothelial monolayer permeability to macromolecules. 内皮单层对大分子的渗透性。
Federation proceedings Pub Date : 1987-06-01
P J Del Vecchio, A Siflinger-Birnboim, J M Shepard, R Bizios, J A Cooper, A B Malik
{"title":"Endothelial monolayer permeability to macromolecules.","authors":"P J Del Vecchio,&nbsp;A Siflinger-Birnboim,&nbsp;J M Shepard,&nbsp;R Bizios,&nbsp;J A Cooper,&nbsp;A B Malik","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The barrier function of the endothelial monolayer has not been extensively investigated using the cultured endothelium. The in vitro approach may contribute to a more complete understanding of microvessel wall permeability. Our studies using an in vitro endothelial monolayer system have led us to the following conclusions: the endothelial monolayer is more permeable to small-molecular-weight substances than to large molecules; the permeability of albumin is different for endothelial cells derived from different vascular sites (higher for pulmonary venous than pulmonary arterial endothelium); basement membrane components may have a significant role in the permeability of albumin across the endothelium; control of endothelial monolayer permeability is determined not only by the characteristics of the macromolecule (i.e., size and charge) but also by the shape of the endothelial cells and the size of interendothelial space.</p>","PeriodicalId":12183,"journal":{"name":"Federation proceedings","volume":"46 8","pages":"2511-5"},"PeriodicalIF":0.0,"publicationDate":"1987-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14424725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunoassay of acetylcholinesterase. 乙酰胆碱酯酶免疫分析。
Federation proceedings Pub Date : 1987-06-01
S Brimijoin, Z R Rakonczay, P Hammond
{"title":"Immunoassay of acetylcholinesterase.","authors":"S Brimijoin,&nbsp;Z R Rakonczay,&nbsp;P Hammond","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>There is a twofold rationale for assaying acetylcholinesterase (AChE) (EC 3.1.1.7) immunologically, rather than by conventional activity-based methods: to measure the amount of enzyme protein in samples that may contain AChE of uncertain intrinsic activity; to bypass cumbersome procedures for determining the individual molecular forms of the enzyme. We have developed an immunodisplacement assay and a two-site immunoassay for AChE that are sensitive enough to measure the enzyme in samples of biological interest (assay thresholds of 10 and 0.1 ng, respectively). We have also used immunofluorescence with quantitative cell sorting as a means of analyzing AChE immunoreactivity in normal and abnormal human red blood cells. The introduction of form-specific immunoassays awaits the identification of suitably selective antibodies.</p>","PeriodicalId":12183,"journal":{"name":"Federation proceedings","volume":"46 8","pages":"2557-62"},"PeriodicalIF":0.0,"publicationDate":"1987-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14424729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drug-receptor relationships, selection of therapeutic goals, and adaptive control of pharmacokinetic systems. 药物受体关系,治疗目标的选择,以及药代动力学系统的适应性控制。
Federation proceedings Pub Date : 1987-06-01
R W Jelliffe
{"title":"Drug-receptor relationships, selection of therapeutic goals, and adaptive control of pharmacokinetic systems.","authors":"R W Jelliffe","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Drug-receptor relationships are governed by a host of environmental and physiological influences, which reduce the predictability of the therapeutic response to an administered dose of a drug. The management of patient therapy is aided by models that encompass the broadest aspects of the situation, from the probabilistic aspects of drug administration to the accuracy of the assay procedures for evaluating therapeutic efficacy.</p>","PeriodicalId":12183,"journal":{"name":"Federation proceedings","volume":"46 8","pages":"2494-501"},"PeriodicalIF":0.0,"publicationDate":"1987-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14425608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transendothelial transfer of macromolecules in vitro. 体外大分子的经内皮转移。
Federation proceedings Pub Date : 1987-06-01
D M Shasby, R L Roberts
{"title":"Transendothelial transfer of macromolecules in vitro.","authors":"D M Shasby,&nbsp;R L Roberts","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The transendothelial transfer of macromolecules has been difficult to study because of the complexities of the in vivo models. We have developed a model of an endothelium cultured on a permeable support and used it to characterize the transendothelial transfer of albumin. Porcine pulmonary artery endothelial cells form a single layer of cells lining the gelatin-impregnated polycarbonate micropore filters, and the cells develop junctional structures similar to endothelial tight junctions observed in vivo. The monolayer resists the flow of electrical current, and the resistance is sensitive to extracellular calcium concentrations. Albumin transfer across the cultured monolayers was found to be asymmetric, and the rate of transfer from interstitium to lumen was greater than that from lumen to interstitium. The asymmetric transfer occurred against a concentration gradient and was abolished by treating the monolayer with NaCN. Increasing albumin concentrations increased the rate of interstitial to luminal transfer, and the process demonstrated saturation at an interstitial albumin concentration of 725 microM. These data point out the usefulness of the in vitro preparation to identify potentially important aspects of transendothelial transport that would be difficult to detect in vivo.</p>","PeriodicalId":12183,"journal":{"name":"Federation proceedings","volume":"46 8","pages":"2506-10"},"PeriodicalIF":0.0,"publicationDate":"1987-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14424724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunoquantitation of cytochrome b5 and methylcholanthrene-induced cytochromes P-450. 细胞色素b5和甲基胆碱诱导的细胞色素P-450的免疫定量。
Federation proceedings Pub Date : 1987-06-01
T K Shires, P A Krieter, L K Shawver, S L Seidel
{"title":"Immunoquantitation of cytochrome b5 and methylcholanthrene-induced cytochromes P-450.","authors":"T K Shires,&nbsp;P A Krieter,&nbsp;L K Shawver,&nbsp;S L Seidel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The enzyme-linked immunosorbent assay (ELISA) has been investigated for its ability to quantitate hydrophobic proteins like cytochromes b5 and P-450 at the subnanogram level. Issues encountered that have broad significance not only for ELISA, but for other qualitative and quantitative immunoassays as well, include the effects of detergent, the discriminatory capacity of ELISA, and the method for determining an assay's selectivity.</p>","PeriodicalId":12183,"journal":{"name":"Federation proceedings","volume":"46 8","pages":"2567-74"},"PeriodicalIF":0.0,"publicationDate":"1987-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13585880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Formation of a barrier by brain microvessel endothelial cells in culture. 脑微血管内皮细胞在培养中形成屏障。
Federation proceedings Pub Date : 1987-06-01
K Dorovini-Zis, P D Bowman, A L Betz, G W Goldstein
{"title":"Formation of a barrier by brain microvessel endothelial cells in culture.","authors":"K Dorovini-Zis,&nbsp;P D Bowman,&nbsp;A L Betz,&nbsp;G W Goldstein","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Endothelial cells (EC) isolated from bovine brain microvessels produce a continuous monolayer when grown in primary culture. The EC are joined together by tight junctions and contain few pinocytotic vesicles. Horseradish peroxidase (HRP) is unable to penetrate this in vitro barrier system. Exposure of the cells to 1.6 M arabinose produces a reversible separation of the tight junctions with penetration of HRP across the monolayer in a pattern similar to that observed in animals after infusion of hyperosmotic solutions into the carotid artery. The behavior of brain microvascular cells in culture suggest that they retain properties important to the formation of the blood-brain barrier.</p>","PeriodicalId":12183,"journal":{"name":"Federation proceedings","volume":"46 8","pages":"2521-2"},"PeriodicalIF":0.0,"publicationDate":"1987-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14424727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Leukocyte-derived metabolites of arachidonic acid in ischemia-induced myocardial injury. 花生四烯酸在缺血心肌损伤中的白细胞衍生代谢物。
Federation proceedings Pub Date : 1987-05-15
K M Mullane, J A Salmon, R Kraemer
{"title":"Leukocyte-derived metabolites of arachidonic acid in ischemia-induced myocardial injury.","authors":"K M Mullane,&nbsp;J A Salmon,&nbsp;R Kraemer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Within minutes of occlusion of a major coronary artery the polymorphonuclear leukocytes (PMNs) are activated whereby they adhere to the vascular endothelium and migrate through the endothelial layer. Interactions with the endothelium can promote increased vascular resistance, diminished collateral flow, capillary blockade, and predisposition to vasospasm, as well as enhanced vascular permeability. On subsequent reperfusion entrapped leukocytes contribute to the no-reflow phenomenon, while more leukocytes gain access to the previously ischemic region. The leukocytes infiltrate the myocardium where they exacerbate the process of tissue injury and the development of arrhythmias. The release of leukocyte-derived mediators including arachidonic acid (AA) metabolites and oxygen-derived free radicals probably underlies these activities of the leukocytes. PMNs contain active lipoxygenase enzymes capable of metabolizing AA to products that are not normally found in the myocardium, and can dominate the metabolic profile of that tissue, leading to changes in myocardial integrity and function. Inhibitors of the lipoxygenase enzymes suppress the accumulation of leukocytes into the ischemic myocardium and reduce infarct size. However, because the drugs prevent cell invasion it cannot be inferred that a lipoxygenase metabolite per se is deleterious to the ischemic heart, inasmuch as any leukocyte-dependent mechanism of injury will be attenuated whether it is mediated by eicosanoids or by any other leukocyte-derived product. Additional studies with specific inhibitors/antagonists are required to determine the biochemical mechanisms underlying the different aspects of leukocyte-mediated myocardial injury.</p>","PeriodicalId":12183,"journal":{"name":"Federation proceedings","volume":"46 7","pages":"2422-33"},"PeriodicalIF":0.0,"publicationDate":"1987-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14238173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Consequences of activation and adenosine-mediated inhibition of granulocytes during myocardial ischemia. 心肌缺血时粒细胞活化和腺苷介导抑制的后果。
Federation proceedings Pub Date : 1987-05-15
R Engler
{"title":"Consequences of activation and adenosine-mediated inhibition of granulocytes during myocardial ischemia.","authors":"R Engler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>During acute myocardial ischemia, granulocytes accumulate and obstruct the microcirculation. Granulocytes remain plugged in individual myocardial capillaries on reperfusion and are the major cause of the no-reflow phenomenon. During 3 h of ischemia, the granulocyte content of myocardium measured by 111In labeling increases from 1.0 X 10(6) to 1.5 X 10(6) cells/g, and after 5 min of reperfusion increases to 2.4 X 10(6) cells/g. The effects of granulocytes during 1 h of acute ischemia were determined by comparing agranulocytic to whole blood perfusion. With whole blood collateral flow decreased, water content increased (edema), ventricular fibrillation was common, and 27% of capillaries had no-reflow, whereas in the absence of granulocytes, collateral flow increased, there was no edema, arrhythmias were rare, and the no-reflow phenomenon was completely prevented. It is unfortunate that the inflammatory signals triggered by ischemia remain active on acute reperfusion, limit tissue salvage, and perhaps cause reperfusion injury. Several activating stimuli for granulocytes are known, but what inhibits them? Adenosine is known to inhibit superoxide radical formation by granulocytes, and 5-amino-4-imidazole carboxamide-riboside (AICA-riboside) augments adenosine release from energy-deprived cells. In dogs subjected to 1 h of ischemia, AICA-riboside pretreatment augmented adenosine release by nearly 10-fold, which was accompanied by a significant increase in collateral blood flow and decreased arrhythmias. We propose a new hypothesis: adenosine acts as a natural antiinflammatory autacoid during transient injury linking the ability to catabolize ATP (an indicator of viability) to granulocyte inhibition, thus preventing premature activation of the inflammatory response to cell death. Granulocytes are active participants in acute myocardial ischemia and means to prevent their activation, remove them from the reperfusate, or inhibit them will be necessary for optimum reperfusion salvage.</p>","PeriodicalId":12183,"journal":{"name":"Federation proceedings","volume":"46 7","pages":"2407-12"},"PeriodicalIF":0.0,"publicationDate":"1987-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14691581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Conjugation-deconjugation reactions in drug metabolism and toxicity. 药物代谢和毒性中的偶联-解偶联反应。
Federation proceedings Pub Date : 1987-05-15
F C Kauffman
{"title":"Conjugation-deconjugation reactions in drug metabolism and toxicity.","authors":"F C Kauffman","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12183,"journal":{"name":"Federation proceedings","volume":"46 7","pages":"2434-45"},"PeriodicalIF":0.0,"publicationDate":"1987-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14675812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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