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Biomedical subjects

B Rutherford

Publications and source records attributed to B Rutherford.

18 recordsLinked to original sources
PubMed1998

Role of synthetic extracellular matrix in development of engineered dental pulp.

In cases of damaged oral tissues, traditional therapies, such as a root canal, replace the injured tissue with a synthetic material. However, while the materials currently used can offer structural replacement of the lost tissue, they are incapable of completely replacing the function of the original tissue, and often fail over time. This report describes a tissue engineering approach to dental pulp tissue replacement utilizing cultured cells seeded upon synthetic extracellular matrices. Human pulp fibroblasts were obtained and multiplied in culture. These cells were then seeded onto three different synthetic matrices: scaffolds fabricated from polyglycolic acid (PGA) fibers, a type I collagen hydrogel, and alginate in an effort to examine which matrix is most suitable for dental pulp tissue formation. In addition, methods previously developed for seeding and culturing pulp cells on PGA were optimized. Culturing cells on PGA resulted in a very high cell density tissue with significant collagen deposition. No cell proliferation was observed on alginate, and the growth of cells in collagen gels after 45 days was only moderate. These studies indicate dental pulp-like tissues can be engineered, and this may provide the first step to engineering a complete tooth.

Adult↗
PubMed1998

Prevention of cytokine accumulation in platelets obtained with the COBE spectra apheresis system.

BACKGROUND AND OBJECTIVES: Febrile nonhemolytic transfusion reactions frequently accompany platelet transfusions and may be due to accumulation of cytokines mediating inflammation during storage of platelet concentrates (PCs). We wished to determine whether PCs collected using the COBE(R) SpectraTM Apheresis System (Version 4) were sufficiently leukocyte reduced (LR) to limit cytokine accumulation during storage. MATERIALS AND METHODS: Cytokine accumulation - interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) - and release of platelet alpha-granule - P-selectin, transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor AB (PDGF-AB), von Willebrand factor (vWf) - or dense granule (serotonin) markers were investigated during a 7-day storage period comparing apheresis-collected, LR PCs (LR PCs) and random donor platelets prepared from whole blood (WB). RESULTS: Leukocyte counts were reduced 99.95% comparing LR PCs (5.7 x 10(5)/l) and WB PCs (1.09 x 10(9)/l). Little or no accumulation of leukocyte-derived cytokines was observed in LR PCs during storage in contrast to WB PCs. A reduction in the release of platelet alpha-granule proteins, such as P-selectin, TGF-beta1 and PDGF-AB, was observed on day 0 for LR PCs compared to WB PCs with little or no difference observed from day 3 to 7. Plasma vWf levels were higher in LR PCs compared to WB PCs on days 0-7. CONCLUSION: Leukocyte levels in PCs collected with the COBE Spectra Apheresis System are sufficiently low to limit cytokine production during 7 days of storage.

Blood Preservation↗
PubMed1996

Structure of recombinant rat UBF by electron image analysis and homology modelling.

We have studied the structure of recombinant rat UBF (rrUBF), an RNA polymerase I transcription factor, by electron microscopy and image analysis of single particles contrasted with methylamine tungstate. Recombinant rat UBF appeared to be a flat, U-shaped protein with a central region of low density. In the dominant projections, 2-fold mirror symmetry was seen, consistent with the dimerization properties of this molecule, and of dimensions in agreement with the length of DNA that rat UBF protects in footprinting studies. Electron microscopy of various rrUBF-DNA complexes confirmed that our recombinant protein was fully able to bind the 45S rDNA promoter, and that it caused substantial bends in the DNA. Upon extended incubation in a droplet covered by a lipid monolayer at the liquid-air interface, rrUBF formed long filamentous arrays with a railway track appearance. This structure was interpreted to consist of overlapping rrUBF dimers 3.5 nm apart, which value would represent the thickness of the protein. Our results show rrUBF to interact with and bend the promoter DNA into a roughly 10 nm diameter superhelix. Based on all these electron microscopical results, an atomic structure was predicted by homology modelling of the HMG fingers, and connected by energy minimized intervening segments.

Animals↗
PubMed1995

Transdentinal stimulation of reparative dentine formation by osteogenic protein-1 in monkeys.

Recombinant human osteogenic protein-1 (OP-1) when applied to freshly cut dentine stimulated significantly more reparative dentine than calcium hydroxide paste in permanent monkey teeth. The response to OP-1 was dependent upon the concentration applied to the tooth as a cavity liner as well as the thickness of the residual dentine. The response to calcium hydroxide was similarly dependent upon the thickness of the residual dentine. These data suggest that dental pulps contain cells, including perhaps mature odontoblasts, responsive to OP-1. Therefore OP-1 may be useful in the therapeutic induction of reparative dentine formation.

Analysis of Variance↗
PubMed1995

Electron spectroscopic imaging of encapsidated DNA in vaccinia virus.

We have used electron spectroscopic imaging to locate the phosphorus in vaccinia DNA in situ in unstained, ultrathin sections of virions. The phosphorus of the DNA backbone appeared to form a halo on the core periphery surrounding a phosphorus-impoverished central element. These results constrain models for how DNA could be packaged into mature vaccinia particles.

DNA, Viral↗
PubMed1995

A new biological approach to vital pulp therapy.

Molecular biology is providing opportunities to develop new strategies or agents for the treatment of a wide variety of diseases. The availability of large amounts of highly purified proteins produced by recombinant DNA techniques is an obvious example. Recent evidence has implicated proteins belonging to the bone morphogenetic protein (BMP) subgroup of the transforming growth factor beta supergene family in tooth formation and dentinogenesis. It has long been known that bone and dentin contain bone morphogenetic protein activity. Recently, recombinant human BMP-2, -4, and -7 (also known as OP-1), have been shown to induce reparative dentin formation in experimental models of large direct pulp exposures in permanent teeth. The manner in which these agents act appears unique. New reparative dentin replaces the stimulating agents applied directly to the partially amputated pulp. Hence, the new tissue forms contiguous with, largely superficial to, and not at the expense of the remaining vital pulp tissue. This suggests a therapeutic approach permitting the induction of a predetermined and controlled amount of reparative dentin. Additionally, OP-1 has been associated with the formation of reparative dentin after application to a freshly cut but intact layer of dentin. These findings may provide future clinicians with additional options for the treatment of substantially damaged or diseased vital teeth.

Animals↗
PubMed1990

PTCA of the left coronary artery when the right coronary artery is chronically occluded.

Angioplasty of the left coronary artery was undertaken in 65 patients with a chronic total occlusion of the right coronary artery (CLOSED RCA) and in 105 patients with no significant disease in the right coronary artery (OPEN RCA). No patient had attempted dilatation of the right coronary artery. CLOSED RCA versus OPEN RCA patients differed with respect to presence of poor left ventricular (LV) function (12% versus 4%, p = 0.07), number of stenoses per patient (2.2 versus 1.8, p less than 0.05), and stenoses in both left anterior descending and left circumflex artery (39% versus 23%, p less than 0.05). Procedural complications were low for both CLOSED RCA (one death) and OPEN RCA (one emergency bypass surgery) patients. At late follow-up (mean = 17 months), there was no difference in survival between CLOSED RCA and OPEN RCA patients (95% versus 93%, p = NS). Late cardiac events (death, bypass surgery, or myocardial infarction) occurred in 26% of CLOSED RCA patients and in 16% of OPEN RCA patients (p = ns). The absence of angina at follow-up was more frequent in OPEN RCA compared with CLOSED RCA patients (84% versus 61%, p less than 0.01). Angioplasty of the left coronary artery can be performed in CLOSED RCA patients without excessive procedural risk; however, at follow-up continued anginal symptoms are common.

Angioplasty, Balloon, Coronary↗
PubMed1984

C3-mediated release of prostaglandin from human monocytes. Behaviour in short-term culture.

C3b and C3bi, cleavage products of the third component of human complement (C3), stimulate purified human monocytes to release immunoreactive prostaglandin (PG) and thromboxane B2 (TxB2) in vitro. The stimulant must be present in culture for more than 4 hr to achieve maximal PG release during a 24 hr culture period. Preculturing monocytes for 24 hr or more greatly diminishes the capacity of such cells to be stimulated to release PG or TxB2. This diminished capacity is not simply due to loss of complement receptors by a large percentage of cultured cells, since the percentage of C3b receptor-bearing cells is similar at the inception (85%) and after 120 hr of culture (84%). The addition of arachidonic acid (AA) at a concentration of 2.5 micrograms/ml at the beginning of the culture period enhances the PG release induced by C3b or C3bi. However, addition of the same concentration of AA to precultured cells fails to restore the ability of these cells to respond to C3b, C3bi, or AA. The diminished release of PG and TxB2 into the culture medium is not accompanied by an increase in release of PGF2 alpha or other eicosanoids, as determined by thin layer chromatography. Cells that were cultured in the presence of C3b for 24 hr will, however, respond to the addition of AA during the second 24 hr of culture by releasing PG and TxB2. Thus, engagement of C3 receptors by soluble ligands influences the expression of the PG-secretory phenotype by cultured human monocytes.

Arachidonic Acids↗
PubMed1983

Surgical treatment of papillary muscle rupture.

Between 1971 and 1979, 16 patients underwent mitral valve replacement for papillary muscle rupture after infarction. Nine of these patients were operated on within 3 days of papillary muscle rupture. Eight patients had low cardiac output syndrome prior to operation. Six patients had concomitant coronary artery bypass, and 1 patient had resection of an associated left ventricular aneurysm. There were 3 operative deaths (19% mortality). Surviving patients have been followed for a total of 49 patient-years. There have been 2 late deaths, each a result of coronary artery disease. Six of the 11 surviving patients are asymptomatic; the others are in New York Heart Association Functional Class II or III. The actuarial 5-year survival was 75%. These data support the concept that an aggressive attitude should be taken toward early diagnosis and surgical treatment of postinfarction papillary muscle rupture.

Aged↗
PubMed1983

Monocyte-mediated bone resorption involves release of nondialyzable substances in addition to prostaglandin.

Human monocytes were stimulated by lectins to release prostaglandin and other factor(s) that induce bone resorption in vitro. High concentrations of indomethacin failed to inhibit production by stimulated monocytes of most of the bone-resorbing activity. This activity was retained in culture supernatants after extensive dialysis. These data demonstrate that monocytes are capable of the simultaneous production of prostaglandins and nondialyzable bone-resorbing factor(s). This (these) factor(s) may mediate localized bone resorption associated with certain chronic inflammatory diseases.

Bone Resorption↗
PubMed1983

C3 cleavage products stimulate release of prostaglandins by human mononuclear phagocytes in vitro.

Human monocytes cultured for up to 48 hr in serum-free, chemically defined culture media released low levels of prostaglandin. C3b, C3bi, and C3c stimulated an indomethacin-sensitive, dose-responsive increase in the amount of monocyte prostaglandin released by 18 hr after treatment. Native C3 and C3d, which do not bind to monocyte receptors, failed to stimulate increased prostaglandin release. Lymphocytes, treated and untreated, produced 10(-2) to 10(-3) as much prostaglandin as the monocytes. These data support the concept that monocytes are a significant source of leukocyte prostaglandin. They also introduce an important new biologic function for the C3 fragments C3b, C3bi, and C3c.

Cells, Cultured↗
PubMed1982

Activated human mononuclear phagocytes release a substance(s) that induces replication of quiescent human fibroblasts.

Human mononuclear phagocytes (HMP) treated in vitro with N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) released a soluble substance(s) that induced in vitro replication of subconfluent, quiescent, serum-free human fibroblasts. The response was enhanced if nonmitogenic plasma-derived serum (PDS) was added to the HMP-conditioned media after harvest. The capacity of serum-free, quiescent fibroblasts to respond to the HMP-released substance(s) diminished with time in culture. The diminished proliferative response was reversed by adding PDS to the MDP-HMP-conditioned media. Similar results were obtained in parallel experiments using platelet-derived growth factor (PDGF). These data suggest that the HMP-associated growth-promoting substances may, like PDGF, act co-ordinately with substances in PDS to stimulate the proliferation of cells in vitro.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1977

Polymer sorption of nitroglycerin and stability of molded nitroglycerin tablets in unit-dose packaging.

The sorption of nitroglycerin by thermoplastic polymers and the stability of molded nitroglycerin tablets in strip packaging were studied. The polymers investigated varied greatly in their affinity for nitroglycerin, the order of decreasing affinity being: vinyls greater than low density polyethylene greater than ionomers greater than high density polyethylene. With the proper choice of packaging, molded nitroglycerin tablets stabilized with povidone maintained acceptable potency for up to 2 years at 26 degrees when strip packaged in unit doses. Chemical decomposition (hydrolysis) of nitroglycerin also was investigated. Povidone accelerated the decomposition of nitroglycerin; at high temperature, decomposition was a significant factor in tablet stability for tablets containing povidone.

Adsorption↗
PubMedDate not supplied

Engineering dental pulp-like tissue in vitro.

Injury or infection of adult dental pulp often necessitates root canal therapy. This terminates dentin formation and subsequent tooth maturation. In addition, the synthetic materials currently utilized to replace lost tooth structure are not capable of completely replacing the function of the lost tissue, and often fail over time. This report describes a technique to engineer new pulp-like tissues utilizing cultured cells and synthetic extracellular matrices. Fibroblasts were obtained from human adult dental pulps and multiplied in culture. These cells were subsequently seeded onto synthetic matrices fabricated from fibers (approximately 15 microns in diameter) of polyglycolic acid (PGA). The pulp-derived fibroblasts adhered to the fibers, proliferated, and formed a new tissue over 60 days in culture with a cellularity similar to that of native pulp. These tissues may find application in the regeneration of oral tissues and may provide novel systems in which to study the biocompatibility of materials and chemicals used in dentistry.

Adult↗