Influence of various doses of aspirin (in vivo) on platelet arachidonic acid metabolism (ex vivo) and function

It has been reported that aortic homografts that have been cryopreserved before transplantation remain viable longer as an allograft than tissue stored at 4 degrees C in an antibiotic solution. In the present study, we tested the hypothesis that storage of cardiac valve tissue by cryopreservation or by antibiotic preservation may alter the metabolic status of the tissue. Initially, we collected aortic valves composed of cardiac tissue, aortic root, and valvular tissue from cadaver donors. These specimens were divided into three equal portions, and one portion was analyzed before storage while the other two parts were stored for 3 weeks at either 4 degrees C in an antibiotic solution or at -196 degrees C in liquid nitrogen. All specimens were examined with regard to the following parameters: tissue structure, tissue viability, cell proliferative capacity, metabolic function, and identification of cell-specific antigens. We found no significant alterations in the structure of any of the three tissue components after antibiotic preservation or cryopreservation; however, cell viability and cell number were decreased in all three groups. All tissue samples grew in culture before storage. When we compared activities of the following organellar marker enzymes--lysosomal acid lipase, plasma membrane 5' nucleotidase, mitochondrial cytochrome oxidase, and microsomal neutral alpha-glucosidase--we observed no major differences between tissues stored by either technique. In addition, we observed no loss of enzymic activity as a result of storage. Finally, when cell lines isolated from each tissue specimen were incubated with monoclonal antibodies against cell-specific antigens in an immunoperoxidase assay, all the cell cultures proved to be endothelial cells. These results suggest that although cardiac valve tissue stored by cryopreservation or by antibiotic preservation retained its normal structure and metabolic capabilities, both storage techniques produced significant decreases in cell numbers and viability. However, only endothelial cells from tissue stored by cryopreservation retained the capacity to proliferate in vitro. These findings have important implications for the function of aortic homografts transplanted after storage.     

Application of minimal spanning trees in glioma grading--a CLIPPER program for the calculation and construction of minimal spanning trees

We present a CLIPPER program for the calculation and graphical representation of minimal spanning trees (MST) which is available on request on diskette from the authors. The MST are a useful parameter for structural cluster detection. They can be applied to grading problems in tumour biology. We present and discuss the applicability of MST by an example from the field of astrocytoma grading.     

A recursion planning analysis of inductive completion

We use the AI proof planning techniques ofrecursion analysis andrippling as tools to analyze so-calledinductionless induction proof techniques. Recursion analysis chooses induction schemas and variables and rippling controls rewriting in explicit induction proofs. They provide a basis for explaining the success and failure of inductionless induction, both in deduction of critical pairs and in their simplification. Furthermore, these explicit induction techniques motivate and provide insight into advancements in inductive completion algorithms and suggest directions for further improvements. Our study includes an experimental comparison of Clam, an explicit induction theorem prover, with an implementation of Huet and Hullot's inductionless induction.     

Experimental diabetic renal growth: role of growth hormone and insulin-like growth factor-I

We have compared the kidneys of two inbred strains of rats (Lewis and Lewis-Dwarf) 7 days after the induction of diabetes mellitus with streptozotocin, in order to examine the influence of a selective growth hormone (GH) deficiency on diabetic renal growth and insulin-like growth factor-I (IGF-I) content of the kidneys. Insulin-like growth factor-I (IGF-I) content of the kidneys. Insulin-like growth factor-I was measured by radioimmunoassay and its distribution within the kidney by immunohistochemical staining. We detected a significant increase in both the wet weight (32.9 +/- 5.3%, P = 0.0085) and dry weight (16.3 +/- 6.3%, P = 0.046) of the kidneys of diabetic Lewis rats but dwarf rats, selectively deficient in GH, did not show a significant increase in either parameter. Extractable IGF-I increased within the kidneys of diabetic rats of both strains but to a lesser extent in the dwarf rats (+105 +/- 28% and +65 +/- 21% respectively, P < 0.01). In diabetic Lewis rats a positive correlation was noted between the severity of glycaemia and kidney IGF-I content (r = 0.604, P < 0.05) but no such correlation was noted in dwarf rats. Inulin-like growth factor-I immunostaining increased in diabetic rats of both strains, mainly within cells of the thick ascending limb of the loop of Henle including damaged and vacuolated cells. However, morphometric analysis of the staining showed that it was significantly less widespread in the diabetic dwarf rats (P = 0.026).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nonpeptide angiotensin II receptor antagonists. 1. Synthesis and in vitro structure-activity relationships of 4-[[[(1H-pyrrol-1-ylacetyl)amino]phenyl]methyl]imidazole derivatives as angiotensin II receptor antagonists

A novel series of non-biphenylyltetrazole angiotensin II receptor antagonists which contain a 1H-pyrrol-1-ylacetyl residue in place of the benzoyl residue in EXP 6803 have been developed. The receptor binding activity of several members of this new series was in the 10(-8) M range, which was better than that of EXP 6803. Introduction of a carboxylic acid moiety at the 2-position of the pyrrole ring enhanced the in vitro binding affinity at the receptor by 10-fold. Compounds containing an acetic acid (18) or a propionic acid residue (20) at the 5-position of the imidazole were more potent than the carboxylic acid analogue (24). The binding IC50 of the most potent compound 20 was 22 nM. Compounds 18, 20, and 24 in their best fit conformations were manually overlayed on that of the template conformation of EXP 6803 and EXP 8623, respectively. The synthesis and structure-activity relationship data are described.     

Regulation of monocyte chemoattractant protein-1 expression in adult human non-neoplastic astrocytes is sensitive to tumor necrosis factor (TNF) or antibody to the 55-kDa TNF receptor

A trifluoroacetamide analogue of siastatin B, (3S,4S,5R,6R)-6-(trifluoroacetamido)-4,5-dihydroxy-3-piperidine carboxylic acid has been chemically synthesized. This compound, as well as the previously synthesized analogue, (3R,4R,5R,6R)-6-(trifluoroacetamido)-3,4,5-trihydroxy-3-piperid inecarboxylic acid, showed marked inhibitory activity against beta-glucuronidase and significant inhibition of experimental pulmonary metastasis of the highly metastatic melanoma B16.     

UV-A-mediated activity of p-methoxymethylcinnamate

Methyl esters of hydroxycinnamic acids are photobiologically active. Cis(Z) and trans(E) p-methoxymethyl-cinnamate photosensitize Escherichia coli and Chinese hamster ovary cells. They also produce sister chromatid exchanges. Photosensitization is oxygen independent, and the cinnamates are not genetically active in the absence of light in the Ames Salmonella typhimurium test.