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Biomedical subjects

D Acton

Publications and source records attributed to D Acton.

At least 19 recordsLinked to original sources
PubMed2004

A new method of arthroscopic reconstruction of the dislocated acromio-clavicular joint.

BACKGROUND: Symptomatic total acromio-clavicular joint dislocation (Rockwood et al. types III-VI) may be treated by surgical reconstruction. AIM: To describe an arthroscopically assisted technique to reconstruct anatomically the coraco-clavicular ligaments in acute or chronic (> 6 weeks) acromio-clavicular joint dislocation. METHODS: This new technique involves arthroscopic exposure of the coracoid process. Prior to introducing this technique, cadaveric studies were undertaken. RESULTS: Five patients underwent this procedure. All engaged in regular sports or manual-type work. All patients were discharged the same day with the shoulder immobilised for 4 weeks, with no heavy lifting for 3 months. All patients were pain-free at 6 weeks with full function and maximum Constant scores at 3 months. There have been no complications. CONCLUSIONS: A new, safe technique is described which provides a cosmetically acceptable, anatomically solid reconstruction of the coraco-clavicular ligaments.

Acromioclavicular Joint↗
PubMed2003

The effect of two nonresorbable suture types on the mechanical performance over a metal suture anchor eyelet.

An understanding of the mechanical properties of different suture materials is valuable when selecting the most appropriate suture and repair technique. Sutures should be strong, easy to handle and have high knot security. The introduction of suture anchors adds an additional variable regarding the effect of stress risers over the eyelet. Improving the mechanical properties of a suture may be a possible method to help avoid failure over stress risers such as the eyelet of suture anchor. This study examined the static and viscoelastic properties of a new polyethylene based non-resorbable suture (Fibrewire) over the eyelet of a standard anchor compared to braid polyester non-resorbable suture (Ethibond). Fibrewire had superior ultimate load properties compared to Ethibond (360.2 N+/-23.8 vs 191.9 N+/-17.3) as well as greater stiffness (61.3 N/mm+/-9.7 vs 8.1 N/mm+/-0.4) when tested in uniaxial tension through a metal anchor eyelet (Mitek) ( p<0.001). Fibrewire demonstrated greater stress relaxation than Ethibond ( p<0.05). Differences in the static and viscoelastic properties of suture may have implications in the post-operative period or during rehabilitation.

Equipment Failure Analysis↗
PubMed2003

Acute lateral dislocation of the patella: correlation of ultrasound scanning with operative findings.

Acute lateral dislocation of the patella has been associated with disruption of the medial restraints of the patella. Following non-operative management there is a re-dislocation rate of up to 44%. The purpose of this study was to test whether sonography is a reliable method of assessing the medial retinaculum after acute dislocation of the patella. Ten patients following acute patellar dislocation had an ultrasound scan (USS) performed by an experienced musculoskeletal radiologist. Each patient subsequently had an examination under anaesthetic, arthroscopy, and repair of the ruptured structures. The ultrasound reports were compared to the surgical findings to determine the accuracy of this investigation. USS located deficiencies in the ligamentous attachments to the medial border of the patella and the presence of avulsed bony fragments, all of which were confirmed at operation. The sonographic diagnosis of haematoma or torn fibres in the vastus medialis obliquus (VMO) corresponded with our operative findings. The most significant findings were the correlation of free fluid around the medial collateral ligament (MCL) with avulsion of the femoral attachment of the medial patellofemoral ligament (MPFL) and the presence of avulsed fragments of bone from the medial border of the patella.

Adolescent↗
PubMed2000

Should I scan or should I scope?

This paper proposes a clinical points-based method that can be used by less experienced orthopaedic surgeons who are faced with the dilemma 'Should I scan or should I scope?' By considering the history, the age of the patient and the clinical findings one can expect diagnostic performance equivalent to magnetic resonance imaging. The cost of MRI services must be considered when selecting patients for this investigation. We have suggested a threshold for requesting an MRI scan depending on the relative costs.

Journal Article↗
PubMed1999

DOCLINE update.

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Interlibrary Loans↗
PubMed1997

Bcl-2 reduces lymphomagenesis in deltaV-TCRbeta transgenic mice.

Overexpression of the bcl-2 oncogene in the lymphoid compartment of transgenic mice prolongs the lifespan of lymphocytes and leads to a low incidence of lymphomas at later age. Transgenic mice carrying a mutated T-cell receptor lacking the variable domain (deltaV-TCRbeta) suffer from lymphocyte depletion and are highly predisposed to lymphoma development. We intercrossed Bcl-2-Ig and deltaV-TCRbeta transgenic mice to assess whether Bcl-2 could synergize with deltaV-TCRbeta in tumorigenesis as reported previously for other oncogenes. Surprisingly, bitransgenic deltaV-TCRbeta; bcl-2-Ig mice showed a reduction in the incidence of lymphomas. Analyses of prelymphomatous mice showed that Bcl-2 restored some of the phenotypic aberrations caused by the deltaV-TCRbeta transgene in the lymphoid compartment. The inhibitory activity of Bcl-2 on deltaVTCRbeta-induced lymphomagenesis was not observed when both transgenes were crossed into the RAG-1-/- background suggesting an important role for more mature lymphocytes in this phenomenon. These results show that, depending on the specific conditions, overexpression of Bcl-2 can both promote as well as impair lymphoma development.

Animals↗
PubMed1997

Overexpression of the FosB2 gene in thymocytes causes aberrant development of T cells and thymic epithelial cells.

We have examined the role of the AP-1 transcription factor on thymocyte maturation and thymus architecture by overexpressing FosB2 in transgenic mice. FosB2 is a naturally occurring splice variant of the FosB2 gene, encoding a truncated protein which lacks two domains necessary for transcriptional activation. The expression of FosB2 in the thymocytes severely affected their maturation and the structure of the whole thymus: the phenotype developed slowly during the first months of life, resulting in a progressive expansion of the medulla and concomitant reduction of the cortex. CD4+ thymocytes represented the major thymocyte population, whereas the CD4+ 8+ thymocytes were virtually absent. This phenotype appeared to be an intrinsic property of bone marrow derived cells, as it could be reproduced in bone marrow chimaeric mice. This pathology was very reminiscent to that observed in mice overexpressing c-Fos in thymic epithelium: also in that case the thymus underwent with age a progressive expansion of the epithelium and major changes in the ratio of thymocyte subsets, but the phenotype appeared to be an intrinsic property of the epithelial cells since it could not be reproduced by transgenic bone marrow transplantation. We speculate that both overexpression of FosB2 in thymocytes and overexpression of c-Fos in thymic epithelium results in aberrant signaling between thymocytes and stroma, that ultimately alters the thymic micromilieu, leading to this severe pathology.

Age Factors↗
PubMed1997

Activation of a novel proto-oncogene, Frat1, contributes to progression of mouse T-cell lymphomas.

Acceleration of lymphomagenesis in oncogene-bearing transgenic mice by slow-transforming retroviruses has proven a valuable tool in identifying cooperating oncogenes. We have modified this protocol to search for genes that can collaborate effectively with the transgene in later stages of tumor development. Propagation of tumors induced by Moloney murine leukemia virus (M-MuLV) in E mu-Pim1 or H2-K-myc transgenic mice by transplantation to syngeneic hosts permitted proviral tagging of 'progression' genes. Molecular cloning of common proviral insertion sites that were detected preferentially in transplanted tumors led to the identification of a novel gene, designated Frat1. The initial selection for integrations near Frat1 occurs in primary tumor cells that have already acquired proviruses in other common insertion sites, yielding primary lymphomas that contain only a minor fraction of tumor cells with an activated Frat1 allele. Transplantation of such primary lymphomas allows for a further expansion of tumor cell clones carrying a proviral insertion near Frat1, resulting in detectable Frat1 rearrangements in 17% of the transplanted E mu-Pim1 tumors and 30% of the transplanted H2-K-myc tumors, respectively. We have cloned and sequenced both the mouse Frat1 gene and its human counterpart. The proteins encoded by Frat1 and FRAT1 are highly homologous and their functions are thus far unknown. Tumor cell lines with high expression of Myc and Pim1 acquired an additional selective advantage in vivo upon infection with a Frat1-IRES-lacZ retrovirus, thus underscoring the role of Frat1 in tumor progression, and the ability of Frat1 to collaborate with Pim1 and Myc in lymphomagenesis.

Amino Acid Sequence↗
PubMed1997

Characterization of pal-1, a common proviral insertion site in murine leukemia virus-induced lymphomas of c-myc and Pim-1 transgenic mice.

Insertional mutagenesis with Moloney murine leukemia virus (MoMLV) in c-myc and Pim-1 transgenic mice permits the identification of oncogenes that collaborate with the transgenes in lymphomagenesis. The recently identified common insertion site pal-1, in MoMLV-induced lymphomas, is located in a region in which several independent integration clusters are found: eis-1, gfi-1, and evi-5. Proviral insertions of MoMLV in the different integration clusters upregulate the transcriptional activity of the Gfi-1 gene, which is located within the pal-1 locus. The eis-1/pal-1/gfi-1/evi-5 locus serves as a target for MoMLV proviral insertions in pre-B-cell lymphomas of Emu-myc transgenic mice (20%) and in T-cell lymphomas of H-2K-myc (75%) and Emu-pim-1 (93%) transgenic mice. Many tumors overexpress both Gfi-1 as well as Myc and Pim gene family members, indicating that Gfi-1 collaborates with Myc and Pim in lymphomagenesis. Proviral integrations in the previously identified insertion site bmi-1 are, however, mutually exclusive with integrations in the eis-1/pal-1/gfi-1/evi-5 locus. This finding suggests that Bmi-1 and Gfi-1 belong to the same complementation group in lymphoid transformation.

Amino Acid Sequence↗
PubMed1996

Peripheral neuropathy in mice transgenic for a human MDR3 P-glycoprotein mini-gene.

We have generated mice transgenic for a human MDR3 mini-gene, under control of a hamster vimentin promoter. Expression of the MDR3 transgene was found in mesenchymal tissues, peripheral nerves, and the eye lens. These MDR3 transgenic mice have a slowed motor nerve conduction and dysmyelination of their peripheral nerves. An extensive dysmyelination in some transgenic strains results in a severe peripheral neuropathy with paresis of the hind legs. How expression of the MDR3 transgene causes these abnormalities is unknown. The MDR3 gene encodes a large glycosylated plasma membrane protein with multiple transmembrane spanning domains, which are involved in the translocation of the phospholipid phosphatidylcholine through the hepatocyte canalicular membrane. The ability of the MDR3 P-glycoprotein to alter phsopholipid distribution in the plasma membrane of Schwann cells may cause the damage. It is also possible, however, that the presence of a large glycoprotein in the cell membrane may be sufficient to severely disturb myelination of peripheral nerves.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

BCL-2 expression and mitochondrial activity in leukemic cells with different sensitivity to glucocorticoid-induced apoptosis.

The present study investigates the relationship between mitochondrial activity and the expression of the BCL-2 gene in a panel of six human and murine leukemia/lymphoma cell lines. The cell lines all contained normal glucocorticoid receptors but differed widely in sensitivity to dexamethasone, ranging from very sensitive S49 lymphoma to completely resistant HL-60 acute leukemia cells. In this panel, 10- to 15-fold differences in basal adenosine triphosphate (ATP) content and adenosine diphosphate (ADP)/ATP ratio were correlated with up to fivefold differences in bcl-2 protein (in human cells) and approximately 25-fold difference in bcl-2 mRNA content (all cell lines). Moreover, ATP content and BCL-2 gene expression were inversely correlated with glucocorticoid sensitivity and cell cycle length. In resistant cell lines, sensitivity to dexamethasone was restored by the mitochondrial inhibitors rotenone and meta-iodobenzylguanidine. This sensitization was not accompanied by detectable reductions in bcl-2 mRNA or protein content, suggesting that the inhibitors were capable of overriding BCL-2-mediated inhibition of apoptosis. Increased mitochondrial activity and (overexpressed) BCL-2 appeared closely related properties of glucocorticoid-resistant cells, sharing common cellular targets in hormone-induced apoptosis.

Adenosine Diphosphate↗
PubMed1993

Pim-1 levels determine the size of early B lymphoid compartments in bone marrow.

The mouse proto-oncogene Pim-1, which encodes two cytoplasmic serine-threonine-specific protein kinases, is frequently activated by proviral insertion in murine leukemia virus-induced hematopoietic tumors. Transgenic mice overexpressing Pim-1 show a low incidence of spontaneous T cell lymphomas, whereas null mutant mice lack an obvious phenotype. We have analyzed the early B lymphoid compartment from both null mutant and E mu-Pim-1 transgenic mice. The level of Pim-1 expression appears to be a determining factor in the ability of these cells to respond to the growth factors interleukin 7 (IL-7) and SF (steel factor). The impaired response in null mutant mice could be rescued by introduction of a functional Pim-1 transgene. Moreover, overexpression of Pim-1 facilitates the derivation of primitive lymphoid cell lines that are dependent on combined stimulation with IL-7 and SF or insulin-like growth factor 1. These results for the first time identify the involvement of Pim-1 in a normal cellular function, as an important regulator of early B lymphopoiesis in mice.

Animals↗
PubMed1990

Functional analysis of the fsoC gene product of the F7(1) (fso) fimbrial gene cluster.

Contrary to what would be expected from data in the literature, mutations in the fsoC gene of the F7(1) (fso) P-fimbrial gene cluster do not completely block fimbrial biogenesis. fsoC mutants still express small amounts of fimbriae of normal length, which carry the non-adhesive minor subunit protein, FsoE, but lack the adhesin, FsoG. The FsoC protein operates at the same stage in fimbrial biogenesis as the FsoF and FsoG proteins. The data suggest that FsoC, FsoF and FsoG interact to form an initiation complex for fimbrial biogenesis.

Antigens, Bacterial↗