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Biomedical subjects

T Wood

Publications and source records attributed to T Wood.

At least 37 records · Page 2Linked to original sources

Comparison of injuries in elite senior and junior Australian football.

Three thousand and thirty one AFL and 1034 injuries in the VSFL U/18 competition were recorded by club doctors over the 1992, 1993 and 1994 seasons. Hamstring strains had the highest incidence (86.4 per 10,000 player hours) and prevalence (30.2 hours missed per 1000 hours) of any injury in the AFL, but were significantly less common in the U/18 competition. Other injuries which were common in both competitions were ankle sprains, thigh haematomas, concussion, groin strains and head lacerations. Injury prevalence was higher overall in the AFL, with lower limb muscle strains (hamstring, calf, quadriceps) being significantly more prevalent than in the U/18 competition. Injuries which were significantly more prevalent in the U/18 competition included stress fractures and concussion. Subsequent to this study, coaches and medical staff in the U/18 competition were made aware of the high risk of stress fractures in young footballers with heavy training loads. The AFL injury survey is ongoing and in the process of being computerised; risk factors for specific injuries with high rates are being studied further.

Adolescent↗

Signal transduction in neuronal death.

Apoptosis in the nervous system is a necessary event during the development of the nervous system and is also present after genotoxic events, be they chronic as in aging or more acute after trauma and ischemia. Apoptotic events reflect an interplay between intrinsic signaling events that rely on cytokines, neurotransmitters, and growth factors and responses to extrinsic events that increase levels of radical oxygen species. Both intrinsically and extrinsically driven signal-transduction pathways act via transcription factors that regulate the coordinated timely expression of stress-response genes as part of a decision-making process that can commit cells to apoptosis or survival. Here we discuss the role of two transcription factors that participate in apoptosis in the nervous system: the activator protein AP-1 and nuclear factor kappaB.

Animals↗

Comparison of DNA sequences with protein sequences.

The FASTA package of sequence comparison programs has been expanded to include FASTX and FASTY, which compare a DNA sequence to a protein sequence database, translating the DNA sequence in three frames and aligning the translated DNA sequence to each sequence in the protein database, allowing gaps and frameshifts. Also new are TFASTX and TFASTY, which compare a protein sequence to a DNA sequence database, translating each sequence in the DNA database in six frames and scoring alignments with gaps and frameshifts. FASTX and TFASTX allow only frameshifts between codons, while FASTY and TFASTY allow substitutions or frameshifts within a codon. We examined the performance of FASTX and FASTY using different gap-opening, gap-extension, frameshift, and nucleotide substitution penalties. In general, FASTX and FASTY perform equivalently when query sequences contain 0-10% errors. We also evaluated the statistical estimates reported by FASTX and FASTY. These estimates are quite accurate, except when an out-of-frame translation produces a low-complexity protein sequence. We used FASTX to scan the Mycoplasma genitalium, Haemophilus influenzae, and Methanococcus jannaschii genomes for unidentified or misidentified protein-coding genes. We found at least 9 new protein-coding genes in the three genomes and at least 35 genes with potentially incorrect boundaries.

Amino Acid Sequence↗

A transcript map encompassing the multiple endocrine neoplasia type-1 (MEN1) locus on chromosome 11q13.

A transcription map of a 1200-kb region encompassing the MEN1 locus was constructed by direct cDNA selection and mapping ESTs. A total of 29 genes were mapped. Ten transcripts were identified by cDNA selection of a focused 300-kb genomic region telomeric to the MEN1 consensus region. Since many of the sequences cloned by cDNA selection also identified ESTs from the region, 19 additional RH-mapped ESTs were mapped to the entire contig region by PCR amplification of genomic clones. Nine known genes, 2 putative human homologues to mouse genes, and 18 novel transcripts map to the region. Transcripts that map to the MEN1 interval PYGM-D11S449 include SGC35223, IB1256, AA147620, ZFM1, FAU, and CAPN1. The latter 3 known genes have already been excluded as candidate MEN1 genes. The 2 putative human homologues of mouse genes Ltbp2 and Spa-1 may be candidate tumor suppressor genes, but they map telomeric to D11S449. Although both of these genes map outside the MEN1 consensus region they may play a role in sporadic endocrine tumors independent of the MEN1 gene or in other tumors, such as breast cancer, that have loss of heterozygosity within this region.

Blotting, Northern↗

Gastrin gene expression is required for the proliferation and tumorigenicity of human colon cancer cells.

The majority of human colon cancers express the gastrin gene, and a significant percentage bind gastrin-like peptides. However, it is not known if gastrin gene products are physiologically relevant to the growth and proliferation of human colon cancers. To investigate the functional role of gastrin gene expression, we examined the effect of gastrin antisense (AS) RNA expression on the growth and tumorigenicity of colon cancer cells. The full-length human gastrin cDNA was cloned in the AS direction in a retroviral vector under the transcriptional control of human cytomegalovirus promoter. Three representative human colon cancer cell lines that expressed negligible (Colo-205A) to significant (Colo-320 and HCT-116) levels of gastrin mRNA were transfected with either AS or control vectors and subjected to various growth studies in vitro and in vivo. The proliferative and tumorigenic potential of the AS clones from the gastrin-expressing cell lines was significantly suppressed compared to that of the control clones, whereas the growth of Colo-205A-AS cells (the negative control) was similar to that of the Colo-205A-C-cells, indicating the relative specificity of the antitumorigenic effects of AS gastrin RNA expression. We believe that this is the first evidence that supports a possible critical role of gastrin gene expression in the tumorigenicity of human colon cancers that express the gastrin gene. Because > 60-80% of human colon cancers express the gastrin gene, it can be expected that the growth of a significant percentage of these cancers may be critically dependent on the expression of gastrin gene products. Therapeutic measures, such as the AS strategy used in the present study, may therefore prove to be useful in treating human colon cancers in the future.

Animals↗

Randomised study of n of 1 trials versus standard practice.

OBJECTIVE: To compare outcomes between groups of patients with irreversible chronic airflow limitation given theophylline by n of 1 trials or standard practice. DESIGN: Randomised controlled study of n of 1 trials versus standard practice. SETTING: Tertiary care center outpatient department. SUBJECTS: 31 patients with irreversible chronic airflow limitation who were unsure that theophylline was helpful after an open trial. INTERVENTIONS: n Of 1 trials (single patient randomised multiple crossover comparisons of theophylline against placebo) followed published guidelines. For standard practice patients theophylline was stopped and resumed if their dyspnoea worsened; if their dyspnoea then improved theophylline was continued. For both groups a decision to continue or stop the drug was made within three months of randomisation. MAIN OUTCOME MEASURES: Exercise capacity as measured by six minute walking distance, quality of life as measured by the chronic respiratory disease questionnaire at baseline and six months after randomisation, and proportions of patients taking theophylline at six months. RESULTS: 26 patients completed follow up. 47% fewer n of 1 trial patients than standard practice patients were taking theophylline at six months (5/14 versus 10/12; 95% confidence interval of difference 14% to 80%) without differences in exercise capacity or quality of life. CONCLUSIONS: n Of 1 trials led to less theophylline use without adverse effects on exercise capacity or quality of life in patients with irreversible chronic airflow limitation. These data directly support the presence of a clinically important bias towards unnecessary treatment during open prescription of theophylline for irreversible chronic airflow limitation. Confirmation in a larger study and similar studies for other problems appropriate for n of 1 trials are needed before widespread use of n of 1 trials can be advocated in routine clinical practice.

Aged↗

Fracture management in general practice.

General practitioners are often confronted with patients who have sustained fractures. A clear understanding of the principles governing fracture management is essential particularly for those GPs who do not have easy access to orthopaedic surgeons. Inappropriately treated fractures can lead to chronic pain and deformity as well as the obvious medico-legal complications. If in doubt over the management of any fracture, obtain a second opinion. This article will aim to cover the important principles of fracture management, using a 'cook's tour' of the body to highlight these principles.

Casts, Surgical↗

The bovine DNA polymerase beta promoter: cloning, characterization and comparison with the human core promoter.

The core promoter of the human DNA polymerase beta (beta Pol)-encoding gene (POL beta) is regulated through cis-elements for the ATF/CREB protein(s), and GC box-binding and initiation-site-binding proteins. The mechanism of promoter regulation has been studied using a nuclear extract transcription system from HeLa cells [Narayan et al., J. Biol. Chem. 269 (1994) 12755-12763]. To study the homologous promoter (ppol beta) in a bovine system, we cloned and characterized the 5'-flanking region of the bovine gene (pol beta). A 15.3-kb fragment of bovine genomic DNA containing the first two exons and 11 kb of 5'-flanking region was isolated from a testis library in bacteriophage lambda EMBL3. S1 nuclease mapping and primer extension analysis of the 5'-end of the pol beta mRNA identified the major transcription start point (tsp), which is located 142-bp 5' of the translational start codon. In transient expression assays using a bovine cell line, analysis of various 5'-deletion mutants demonstrated that a fragment of only 91-bp 5' of the tsp had promoter activity similar to that of a 1.37-kb fragment, so that cis-elements for basal transcription are located within this approx. 100-bp core promoter, as in the human promoter (pPOL beta). Comparison of the core promoters from the bovine and human genes revealed striking similarity, including an almost precise match of the tsp, the ATF/CREB-binding and Sp1-binding sites, and the spacing separating them.

Animals↗

Validation of a capillary electrophoresis method for the determination of potassium counter-ion levels in an acidic drug salt.

This paper describes the first report of the validation of a capillary electrophoresis method for the quantitative determination of potassium levels in the potassium salt of an acidic drug. Validation criteria include precision, linearity, robustness and repeatability. The use of an internal standard enabled precision values of < 1% RSD to be obtained for peak area ratios. Careful control of capillary conditioning and temperature enabled migration time precisions of < 0.5% RSD. Results obtained by this method were in agreement with those generated by ion exchange chromatography and the theoretical potassium content of samples tested. Features of the method, compared to alternative analytical techniques, include simplicity, speed and accuracy. The method is now in routine use within our laboratories.

Calibration↗

Antibody repertoire in the response to a protein antigen. Interrelated idiotypic families in the response to Ia.7.

Mouse alloantibodies to Ia.7 display a cross-reactive idiotype (CRI) recognized by xenogeneic anti-idiotypes. The CRI is expressed on serum Abs in all responding individuals and on all anti-Ia.7 mAbs, from mice of appropriate genetic types. In addition, both xenogeneic and allogeneic anti-idiotypes in this system have a striking ability to induce Ia.7-specific responses in mice never exposed to the Ag. Because of these unusual features, we have investigated the biologic and structural basis of the idiotypic sharing in this system. Ia.7-specific Ab populations induced by eight different Ab2 mAbs were analyzed for expression of each of the set of idiotopes. Two obvious explanations for the unusual properties of the system do not appear to be correct. 1) The induction of Ag-specific immunity was not caused by internal imagery; and 2) the Ab2s do not simply recognize the same idiotope, because they induce populations that were found to be distinct in idiotope expression. The biologic properties of the system are instead caused by a pattern of expression of idiotope sets on distinct but related Ab families, and a remarkable linkage of a series of different idiotopes to Ia.7-specific activity. Mouse anti-idiotypic responses failed to recognize the widely shared CRI site, even when sequential immunizations were performed. To examine the structural basis of Id sharing, light chains of three CRI+ mAbs were sequenced. They were found to be extremely homologous to each other and to the germ-line V kappa 21E gene, and they used either J1 or J2. A model containing families of distinct but related V regions is proposed for the anti-Ia.7 repertoire.

Animals↗

Molecular model of the specificity pocket of the hepatitis C virus protease: implications for substrate recognition.

We have built a model of the specificity pocket of the protease of hepatitis C virus on the basis of the known structures of trypsin-like serine proteases and of the conservation pattern of the protease sequences among various hepatitis C strains. The model allowed us to predict that the substrate of this protease should have a cysteine residue in position P1. This hypothesis was subsequently proved by N-terminal sequencing of two products of the protease. The success of this "blind" test increases our confidence in the overall correctness of our proposed alignment of the enzyme sequence with those of other proteases of known structure and constitutes a first step in the construction of a complete model of the viral protease domain.

Amino Acid Sequence↗

Cyclopsychotride A, a biologically active, 31-residue cyclic peptide isolated from Psychotria longipes.

A preliminary characterization is provided of a naturally occurring cyclic peptide with interesting and potent biological activity. A 31-residue cyclic peptide, designated cyclopsychotride A [1], was obtained from the organic extract of the tropical plant, Psychotria longipes. Compound 1 inhibited [125I] neurotensin (NT) binding to HT-29 cell membranes (IC50 3 microM) and also stimulated increased levels of cytosolic Ca2+ in two unrelated cell lines that do not express NT receptors. The peptide was found to dose-dependently increase intracellular Ca2+ at concentrations ranging from 3 to 30 microM, and this response was not blocked by a known NT antagonist. Cyclopsychotride A [1] possesses three disulfide linkages and is thought to be the largest cyclic peptide isolated from a natural source. Both 1H-nmr and cd spectroscopy showed 1 to be highly structured.

Amino Acid Sequence↗

Nonrecurrent primary basal cell carcinoma of the lower extremity with late metastasis.

BACKGROUND: Metastatic basal cell carcinoma (MBCC) is rare, with most cases of head and neck origin and from large multi-recurrent tumors. MBCC is very rare from lower extremities and even more rare from primary tumors that were small and treated without local recurrence. OBJECTIVE: This paper presents a case of MBCC in a 78-year-old woman who had previously undergone resection without local recurrence of a small lower extremity basal cell carcinoma. CONCLUSION: MBCC can present atypically with site of origin on lower extremities, initial tumor size small, and nonrecurrence of the primary tumor site. The clinician should be aware of this as well as understand that prompt and aggressive surgical therapy to localized metastases may extend survival.

Aged↗

Reaping maximum benefits from minimally invasive surgery.

A study conducted by Deloitte & Touche examined the use of minimally invasive surgery (MIS)--specifically laparoscopic cholecystectomy, laparoscopically assisted vaginal hysterectomy laparoscopic inguinal hernia repair and thoracoscopic wedge resection--at nine U.S. hospitals. From a total hospital cost perspective, two procedures studied reduce hospital costs, one is a breakeven and one increases hospital costs. In addition, with MIS there is a major shift in resource consumption from nursing care units to the operating room. Best practices, defined as most efficient staffing levels, operative times, lengths of hospital stay and other treatment characteristics practiced at the study hospitals, were also identified. Hospitals can maximize their return on MIS by providing ample training to surgical and processing staff, standardizing on equipment, wisely choosing when to use custom kits, block scheduling for MIS and incorporating MIS into the hospital's strategic plan.

Ancillary Services, Hospital↗

Identification of the major cytochrome P450s of subfamily 2C that are expressed in brain of female rats and in olfactory lobes of ethanol treated male rats.

The reverse transcriptase (RT)/polymerase chain reaction (PCR) methodology was used with a set of primers that corresponds to two conserved regions of the cytochrome P450s of subfamily 2C, in order to identify the members of this group of enzymes that are expressed at the RNA level in rat brain. Seven RT/PCR clones were sequenced from female brain, and four were found to code for P450 2C7 while three for P450 2C12. Using the same methodology nine RT/PCR clones were sequenced from olfactory lobes of ethanol treated male rats and three were found to code for P450 2C6, one for P450 2C11, three for P450 2C12 and two for P450 2C23. Neither ethanol administration nor hypophysectomy or growth hormone treatment had significant effects on the expression levels of these cytochromes in the brain.

Animals↗