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Biomedical subjects

M Farrar

Publications and source records attributed to M Farrar.

9 recordsLinked to original sources
PubMed2004

Immunocytochemical analysis of AE1/AE3, CK 14, Ki-67 and p53 expression in benign, premalignant and malignant oral tissue to establish putative markers for progression of oral carcinoma.

Squamous cell carcinoma (SCC) is the most common form of oral malignancy and is often preceded by premalignant lesions, some of which are more likely to progress to carcinoma than others. In this study, a panel of monoclonal antibodies (AE1/AE3, cytokeratin [CK] 14, Ki-67 and p53) is applied to 10 cases of human oral tissue in each of six categories to establish staining patterns indicative of which lesions are more likely to progress to malignancy. The six tissue categories are normal tissue; abnormal benign lesions; mild, moderate and severe dysplasia; and SCC. A statistical analysis of Ki-67 and p53 immunoexpression is performed. The results showed that AE1/AE3 and CK 14 expression was reduced as a late event in oral carcinogenesis, particularly in poorly differentiated SCC. Expression of Ki-67 and p53 proved to be a weak but statistically significant predictor of malignant progression in oral tissue.

Antibodies, Monoclonal↗
PubMed2001

The Sheffield hybrid fixator--a clinical and biomechanical review.

The Sheffield hybrid fixator (SHF) was developed to complement and extend the use of current monolateral fixation systems. Unlike other hybrid designs, it relies on rings for the diaphyseal as well as the metaphyseal support. Since it is an all ring system it may be used to cross joints and perform progressive deformity and contracture correction. Unlike the Ilizarov system only one ring is required at each level and diaphyseal transfixation is avoided. Initial biomechanical testing has demonstrated similar mechanical characteristics to an all wire Ilizarov fixator, however, increased shear motion was noted due to the stiffness asymmetry between the segments controlled by wires and screws. The first 100 cases were reviewed with good patient compliance and satisfactory results. Minor component problems were identified and corrected during this period and no significant complications occurred. The device is recommended for a wide range of complex trauma and limb reconstruction uses.

Adult↗
PubMed1999

DNA bending and sequence-dependent backbone conformation NMR and computer experiments.

Although DNA bending plays a crucial role in several biological processes, very little is known experimentally about the relationship between sugar phosphate conformation and sequence directed bending. In this paper, we determine the coupling constants for a nonself-complementary 11-mer A-tract DNA duplex from 2D NMR experiments and along each chain of the duplex, we report the sugar pucker, torsional preferences and conformational averaging about the C3'-O3', C4'-C5' and C5'-O5' bonds for each nucleotide. The A-tract exists as an equilibrium blend of canonical B-form and noncanonical B-form in which the exocyclic C4'-C5' bond is in trans conformation as in the original Watson-Crick model [Crick, F.H.C. & Watson, J.D. (1954) Proc. Roy. Soc. (London), A223, 80-96]. The trans conformation at the C4'-C5' can increase the interphosphate distance and lead to local unwinding of the duplex and rolling of the base pair into the major groove. This will create a kink or hinge. At the 3'-end of the A-tract in the purine-thymine step, the duplex is compressed by the presence of a junction between A and B forms of DNA exclusively in one strand, with consequent reduction of the phosphate-phosphate distance. The coupling constant data seriously disagree with the A-tract DNA bending model of Crothers [Koo, H.-S., Wu, H.-M. & Crothers, D.M. (1986) Nature 320, 501-506], but is in agreement with the finding of Leroy et al. [Leroy, J.-L., Charretier, E., Kochoyan, M. & Gueron, M. (1988) Biochemistry 27, 8894-8898] that the structure that drives bending in the A-tract is locally different from B-DNA. Structural distortions are extremely localized with little or no propagation. It is likely that transcription factor proteins recognize these preexisting deformations in the free DNA itself and mold it into the matrix of the protein.

Computer Simulation↗
PubMed1996

Interleukin-2 receptor-specific fusion toxin inhibits barotrauma-induced arterial atherosclerosis.

Immunocytochemical analyses of human plaques and experimental arterial lesions have implicated activated lymphocytes and monocytes in the pathogenesis of atherosclerosis, as demonstrated by the expression of interleukin-2 (IL-2) membrane receptors and major histocompatibility complex class II epitopes. The objective is to determine if targeting these cells with an IL-2 receptor-specific chimeric toxin, DAB486-IL-2, can inhibit experimental post-angioplasty vascular neointimal thickening. Twenty-two atherogenically modeled rabbits were treated in vivo with DAB486-IL-2 (0.1 mg/kg per day i.v.; n = 11) or placebo (n = 11) for 10 days following aortic balloon angioplasty (4 atm x 30 s each x 2 dilatations). In vitro 3H-leucine incorporation studies of mononuclear leukocyte and vascular smooth muscle cell protein synthesis inhibition by DAB486-IL-2 were also performed. Angioplasty sites were examined for evidence of hyperproliferative atherosclerotic narrowing by quantitative angiography and histomorphometry of neointimal cross-sectional area at baseline and 6 weeks after injury. In vitro Concanavalin-A stimulated rabbit mononuclear leukocyte protein synthesis was 50% inhibited by DAB486-IL-2 at a concentration (IC50) of 6 x 10(-11) M. Rabbit vascular smooth muscle cells were approximately 150-fold less sensitive to DAB486-IL-2 (IC50 = 10(-8) M). In vivo studies showed no change in angioplasty site angiographic minimum luminal diameter at 6 weeks in DAB486-IL-2 treated animals (from 2.96 +/- 0.52 to 2.96 +/- 0.48 mm; percent cross-sectional area reduction = 1 +/- 10%; P = N.S.). In control animals, luminal diameter decreased from 2.79 +/- 0.4 to 2.32 +/- 0.52 mm at 6 weeks, and percent cross-sectional area was reduced by 34 +/- 14% (P < 0.01 vs. placebo). Quantitative histomorphometric angioplasty segmental intimal cross-sectional area reduction of treated and placebo vessels also differed significantly (19 +/- 16% vs. 31 +/- 21%; P < 0.05). DAB486-IL-2 caused no adverse effects on animal survival, weight or hepatic transaminase levels. We conclude that post-angioplasty administration of the chimeric toxin DAB486-IL-2 inhibits angiographic narrowing and neointimal thickening in the atherogenic rabbit model. Although this IL-2 receptor-specific molecule was cytotoxic in vitro for activated mononuclear leukocytes and vascular smooth muscle cells, systemic toxicity did not occur in vivo at a dose comparable to that evaluated in clinical trials of this agent. Potential anti-proliferative effects of this chimeric toxin may be mediated by direct local inhibition of leukocyte-mediated inflammation, or through the indirect modification of vascular cell mitogenesis and cytokine release.

Angioplasty, Balloon↗
PubMed1990

Porcine heparin increases postoperative bleeding in cardiopulmonary bypass patients.

One hundred thirteen patients undergoing cardiopulmonary bypass were randomly assigned to receive either bovine or porcine heparin. Heparin was infused at 4.5 mg/kg during bypass and administered at the lesser of 70 units/kg or 5000 units/dose at 12-hour intervals postoperatively. Platelet counts decreased to 45% of preoperative levels during the first 3 days postoperatively (porcine, 44 +/- 13%, n = 50; bovine, 46 +/- 15%), but returned to preoperative levels by the seventh postoperative day. The average blood loss in the porcine heparin group significantly exceeded that of the bovine heparin group (porcine, 1350.7 +/- 727.8 ml; bovine, 1059.6 +/- 381.0 ml; p less than .01). Consequently, the platelet transfusion requirement was greater in the porcine heparin group (porcine, 1.7 +/- 3.9 units; bovine, 0.5 +/- 1.7 units; p less than .05); however, blood and blood component (with the exception of platelets) administration was not significantly different between the two groups. The four patients taking anticoagulants or antiinflammatory agents in the porcine group required a mean of 8.5 units of red blood cells (RBC) plus supplemental platelets. The seven such patients in the bovine group received a mean of 3.0 units of RBC and no platelets. Thus, the use of porcine heparin resulted in a generalized increase in postoperative bleeding with increased management problems in patients undergoing cardiopulmonary bypass.

Animals↗