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L A Warren

Publications and source records attributed to L A Warren.

12 recordsLinked to original sources
PubMed2001

New methods for the assessment of in vitro and in vivo stress cracking in biomedical polyurethanes.

This article describes a new test method for the assessment of the severity of environmental stress cracking of biomedical polyurethanes in a manner that minimizes the degree of subjectivity involved. The effect of applied strain and acetone pre-treatment on degradation of Pellethane 2363 80A and Pellethane 2363 55D polyurethanes under in vitro and in vivo conditions is studied. The results are presented using a magnification-weighted image rating system that allows the semi-quantitative rating of degradation based on distribution and severity of surface damage. Devices for applying controlled strain to both flat sheet and tubing samples are described. The new rating system consistently discriminated between the effects of acetone pre-treatments, strain and exposure times in both in vitro and in vivo experiments. As expected, P80A underwent considerable stress cracking compared with P55D. P80A produced similar stress crack ratings in both in vivo and in vitro experiments, however P55D performed worse under in vitro conditions compared with in vivo. This result indicated that care must be taken when interpreting in vitro results in the absence of in vivo data.

Biocompatible Materials↗
PubMed2000

Polydimethylsiloxane/polyether-mixed macrodiol-based polyurethane elastomers: biostability.

A series of four thermoplastic polyurethane elastomers were synthesized with varying proportions of poly(hexamethylene oxide) (PHMO) and poly(dimethylsiloxane) (PDMS) macrodiols. The macrodiol ratios (by weight) employed were (% PDMS:% PHMO) 100:0, 80:20, 50:50 and 20:80. The weight fraction of macrodiol in each polymer was fixed at 60%. The mixed macrodiols were reacted with 4,4'-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BDO) chain extender. The biostability of these polymers was assessed by strained subcutaneous implantation in sheep for three months followed by microscopic examination. Pellethane 2363-80A and 2363-55D were employed as control materials. The mechanical properties of the polymers were tested and discussed along with the biostability results. The results showed that soft, flexible PDMS-based polyurethanes with very promising biostability can be successfully produced using the mixed macrodiol approach. The formulation with 80% PDMS macrodiol produced the best result in terms of a combination of flexibility, strength and biostability.

Biocompatible Materials↗
PubMed1989

Identification of the 1.4 kb and 4.0 kb messages for the lipoprotein associated coagulation inhibitor and expression of the encoded protein.

Lipoprotein-Associated Coagulation Inhibitor (LACI) is a factor Xa dependent inhibitor of the factor VII(a)/Tissue Factor catalytic complex. Deduced from partial cDNA sequence, LACI's amino acid sequence has recently been reported. Northern blot analysis showed LACI cDNA hybridizes to RNAs of 1.4 and 4.0 kb in size. To complete the characterization of the LACI message(s), overlapping LACI cDNAs were isolated from a human endothelial cell library. Sequence analysis revealed the clones' inserts span 4023 bases of sequence, consisting of 381 bases of 5' untranslated sequence, an open reading frame of 912 bases, 2682 bases of 3' untranslated sequence and 48 bases of poly(A) sequence. In addition, a short 1.4 kb insert which encodes for LACI was found to contain 49 bases of 3' untranslated sequence and a 3' poly(A) tail. The 1.4 kb of sequence is contained in the 4.0 kb sequence, except for 14 bases of 5' sequence, suggesting that the LACI messages arise by the use of alternative termination and polyadenylation signals during processing. Northern blot analysis of RNA isolated from cells treated with actinomycin D showed both RNA species appear to be relatively stable. Using a bovine papilloma virus vector, LACI cDNA was transfected into mouse C127 fibroblasts. The recombinant LACI is recognized by polyclonal anti-LACI IgG, binds to factor Xa and inhibits VII(a)/Tissue Factor activity in a similar fashion as LACI purified from HepG2 cell conditioned media.

Amino Acid Sequence↗
PubMed1989

Functional significance of the Kunitz-type inhibitory domains of lipoprotein-associated coagulation inhibitor.

Blood coagulation can be initiated when factor VII or VIIa, a plasma protease, binds to its essential cofactor, tissue factor (TF), and proteolytically activates factors IX and X, triggering a cascade of events which eventually leads to the formation of thrombin and a fibrin clot. Plasma contains a lipoprotein-associated coagulation inhibitor (LACI) which inhibits activated factor X (Xa) directly and, in a Xa-dependent way, inhibits VII(a)/TF activity, presumably by forming a quaternary Xa/LACI/VII(a)/TF complex. Sequence analysis of complementary DNA clones has shown that LACI contains three tandemly repeated Kunitz-type serine protease inhibitory domains. To investigate the relationship between these Kunitz structures and LACI function, we have used site-directed mutagenesis to produce altered forms of LACI in which the residue at the active-site cleft of each Kunitz domain has been individually changed. The second Kunitz domain is required for efficient binding and inhibition of Xa, and both Kunitz domains 1 and 2 are required for the inhibition of VIIa/TF activity; but alteration of the active-site residue of the third Kunitz domain has no significant effect on either function. We propose that in the putative inhibitory complex, Kunitz domain 1 is bound to the active site of VII(a)/TF and that Kunitz domain 2 is bound to Xa's active site.

Humans↗
PubMed1988

Basic anatomy of the human eye for artists.

When illustrating an eye, it is important for the artist to know the anatomy of its constituent layers, the dimensions of the major ocular structures, and visual characteristics of various tissues in order to produce an accurate representation. In this article, the normal eyeball will be described layer by layer, from the outer sclera to the structures inside with an emphasis on the concerns of the artist when rendering eyes.

Eye↗
PubMed1988

The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action.

Blood coagulation is initiated when plasma factor VII(a) binds to its essential cofactor tissue factor (TF) and proteolytically activates factors X and IX. Progressive inhibition of TF activity occurs upon its addition to plasma. This process is reversible and requires the presence of VII(a), catalytically active Xa, Ca2+, and another component that appears to be associated with the lipoproteins in plasma, a lipoprotein-associated coagulation inhibitor (LACI). A protein, LACI(HG2), possessing the same inhibitory properties as LACI, has recently been isolated from the conditioned media of cultured human liver cells (HepG2). Rabbit antisera raised against a synthetic peptide based on the N-terminal sequence of LACI(HG2) and purified IgG from a rabbit immunized with intact LACI(HG2) inhibit the LACI activity in human serum. In a reaction mixture containing VIIa, Xa, Ca2+, and purified LACI(HG2), the apparent half-life (t1/2) for TF activity was 20 seconds. The presence of heparin accelerated the initial rate of inhibition threefold. Antithrombin III alpha alone had no effect, but antithrombin III alpha with heparin abrogated the TF inhibition. LACI(HG2) also inhibited Xa with an apparent t1/2 of 50 seconds. Heparin enhanced the rate of Xa inhibition 2.5-fold, whereas phospholipids and Ca2+ slowed the reaction 2.5-fold. Xa inhibition was demonstrable with both chromogenic substrate (S-2222) and bioassays, but no complex between Xa and LACI(HG2) could be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Nondenaturing PAGE, however, showed that LACI(HG2) bound to Xa but not to X or Xa inactivated by diisopropyl fluorophosphate. Thus, LACI(HG2) appears to bind to Xa at or near its active site. Bovine factor Xa lacking its gamma-carboxyglutamic acid-containing domain, BXa(-GD), through treatment with alpha-chymotrypsin, was used to further investigate the Xa requirement for VIIa/TF inhibition by LACI(HG2). LACI(HG2) bound to BXa(-GD) and inhibited its catalytic activity against a small molecular substrate (Spectrozyme Xa), though at a rate approximately sevenfold slower than native BXa. Preincubation of LACI(HG2) with saturating concentrations of BXa(-GD) markedly retarded the subsequent inhibition of BXa. The VII(a)/TF complex was not inhibited by LACI(HG2) in the presence of BXa(-GD), and further, preincubation of LACI(HG2) with BXa(-GD) slowed the inhibition of VIIa/TF after the addition of native Xa. The results are consistent with the hypothesis that inhibition of VII(a)/TF involves the formation of a VIIa-TF-XA-LACI complex that requires the GD of XA.(ABSTRACT TRUNCATED AT 400 WORDS)

Anticoagulants↗
PubMed1982

A model for evaluation of postural hypotension induced by drugs in conscious restrained normotensive rats.

A rat model was developed for use in evaluating postural hypotensive activity of a compound. Conscious normotensive rats were restrained on a tilt board with special restrainers to avoid blocking limb circulation. Dose response curves were explored to delineate the potential postural hypotensive activity of a compound. In response to a 2-min 90 degree head-up tilt, only a negligible changes in blood pressure was observed in the control state. The conscious rat was therefore able instantaneously to compensate for postural change. This ability, however, was blocked by guanethidine. The compound induced a dose-related hypotension and a further, dose-dependent drop in blood pressure on tilt. Hydralazine, on the other hand, induced only dose-dependent hypotension, but no change in blood pressure response from control tilts. Since these findings appear to be in accord with human clinical data, this rat model may be suitable for use in evaluating potential postural hypotensive activity of compounds.

Anesthetics↗
PubMed1980

The importance of catecholamine uptake inhibition in the reversal of guanethidine blockade of adrenergic neurons.

Adrenergic neuron blockade was induced by guanethidine in the pithed rat preparation. The pressor response to spinal electric stimulation was inhibited. The guanethidine blockade was reversed or prevented not only by tricyclic antidepressants but also by tripelennamine (an H1 antihistamine), tranylcypromine (a monoamine oxidase inhibitor) and viloxazine (a new antidepressant structurally unrelated to tricyclic antidepressants). Since these compounds all share neuronal uptake inhibitory activity, it seems that this property per se is sufficient to reverse/prevent the adrenergic neuron blockade induced by guanethdine.

Animals↗