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Biomedical subjects

A Goodwin

Publications and source records attributed to A Goodwin.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cloning and characterization of lung-endothelial cell adhesion molecule-1 suggest it is an endothelial chloride channel.

Lung-endothelial cell adhesion molecule-1 (Lu-ECAM-1) is an endothelial cell surface molecule that mediates adhesion of metastatic melanoma cells to lung endothelium. Here we analyze the organization of the Lu-ECAM-1 protein complex, report the sequence of Lu-ECAM-1 cDNAs, and reveal a novel function of the protein. Lu-ECAM-1 immunopurified from bovine aortic endothelial cells (BAEC) consists of tightly associated glycoproteins of 90, 38, and 32 kDa, with minor components of 130 and 120 kDa. We present evidence that all of these protein species are encoded by a single open reading frame whose initial translation product is proteolytically processed to yield the other products. Correct processing in vitro was demonstrated by transfection of the longest cDNA into human embryonic kidney 293 cells; immunoblot analysis showed that the approximately 120-kDa precursor gave rise to 90- and 38-kDa products. RNA blots of BAEC mRNA detected messages in agreement with the sizes of the cDNA clones in addition to several of high molecular weight. DNA blot analysis showed that Lu-ECAM-1 is conserved throughout its length in all mammals tested, usually as a single or low copy gene. In the bovine, Lu-ECAM-1 protein is 88% identical to a calcium-dependent chloride channel described recently in tracheal epithelium, Ca-CC. Probes for Lu-ECAM-1 mRNA and protein confirmed the presence of a homolog in this tissue. We show that messages for both proteins are present in lung while only Ca-CC is present in trachea and only Lu-ECAM-1 is present in BAEC. These results suggest that endothelial cells express a chloride channel that is related to, but distinct from, that expressed in tracheal epithelium. They further suggest that an adhesion molecule can also be a chloride channel.

Amino Acid Sequence↗
PubMed1997

Acute pulmonary oedema complicating laryngospasm.

Pulmonary oedema is an uncommon but important complication of laryngeal spasm which in turn occurs more commonly in ENT practice than in most other surgical specialties. A case is reported and the literature reviewed, with particular reference to the proposed pathophysiological mechanism of this phenomenon.

Acute Disease↗
PubMed1997

The influence of antagonist muscle control strategies on the isometric frequency response of the cat's ankle joint.

This study investigated the effect of various strategies to control the interaction between agonist and antagonist muscles on the frequency response of the isometric cat ankle joint actuated by the tibialis anterior (TA) and soleus (SOL) muscles. Some strategies were based on the physiologic need for increasing joint stability during forceful contractions; with these strategies, the proportional rate of physiologic antagonist activity was termed antagonist gain. Other strategies were based on the electrical stimulation literature, which advocates co-contraction at low force levels. The range of crossover of antagonist activity to the agonist's domain was termed overlap. Strategies consisting of 0%, 10%, and 20% antagonist gain were combined with 0%, 50%, and 100% overlap for a total of nine strategies. These were applied to the TA and SOL using sinusoidal input signals varying in frequency from 0.4 to 6 Hz. Gain and phase Bode plots were constructed through the use of the fast Fourier transforms (FFT's); and analysis of variance determined the significance of differences in gain and phase across frequencies. Best-fit models consisting of four poles and two zeroes were used to fit the experimental data and compared against an analytical model of muscles acting independently across the joint. Harmonic distortion was calculated to evaluate signal quality. It was found that changing the overlap and the antagonist gain produces significant changes in the dynamic response of the two-muscle joint system. The analytical approach to modeling such a system tends to consistently overestimate gain. It is suggested that signal quality is optimal when a moderate amount of antagonist gain (10%) is engaged, with overlap of 50% to smooth transitions between opposing movements. It is expected that this type of strategy will achieve optimum signal quality while preserving the long-term integrity of the joint.

Analysis of Variance↗
PubMed1997

Phenotypic and molecular characterization of three clinical isolates of Mycobacterium interjectum.

Introduction of molecular biology-based technology into an Australian mycobacterial reference laboratory has resulted in the identification of three isolates of Mycobacterium interjectum in the past 12 months. Conventional phenotypic methods failed to identify the species of these isolates, and high-performance liquid chromatography found that only one of the three isolates had a mycolic acid pattern similar to that of the type strain. In contrast, all three isolates were rapidly identified as M. interjectum by 16S rRNA gene sequence analysis. Two isolates were recovered from the lymph nodes of children with cervical lymphadenitis, confirming the pathogenicity of this organism. However, the third isolate was obtained from the sputum of an elderly male with chronic lung disease without evidence of clinical or radiological progression, suggesting that isolation of M. interjectum should not imply disease. With the increasing use of molecular biology-based technology in mycobacterial laboratories, M. interjectum may be recognized more frequently as a pathogen or commensal organism.

Aged↗
PubMed1996

Phosphorylation and activation of p42 and p44 mitogen-activated protein kinase are required for the P2 purinoceptor stimulation of endothelial prostacyclin production.

Extracellular ATP and ADP, released from platelets and other sites stimulate the endothelial production of prostacyclin (PGI2) by acting on G-protein-coupled P2Y2 and P2Y2 purinoceptors, contributing to the maintenance of a non-thrombogenic surface. The mechanism, widely described as being dependent on elevated cytosolic [Ca2+], also requires protein tyrosine phosphorylation. Here we show that activation of both these P2 receptor types leads to the tyrosine phosphorylation and activation of both the p42 and p44 forms of mitogen-activated protein kinase (MAPK). 2-Methylthio-ATP and UTP, selectively activating P2Y1 and P2Y2 purinoceptors respectively, and ATP, a non-selective agonist at these two receptors, stimulate the tyrosine phosphorylation of both p42mapk and p44mapk, as revealed by Western blots with an antiserum specific for the tyrosine-phosphorylated forms of the enzymes. By using separation on Resource Q columns, peptide kinase activity associated with the phosphorylated MAPK enzymes distributes into two peaks, one mainly p42mapk and one mainly p44mapk, both of which are stimulated by ATP with respect to kinase activity and phospho-MAPK immunoreactivity. Stimulation of P2Y1 or P2Y2 purinoceptors leads to a severalfold increase in PGI2 efflux; this was blocked in a dose-dependent manner by the selective MAPK kinase inhibitor PD98059. This drug also blocked the agonist-stimulated increase in phospho-MAPK immunoreactivity for both p42mapk and p44mapk but left the phospholipase C response to P2 agonists essentially unchanged. Olomoucine has been reported to inhibit p44mapk activity. Here we show that in the same concentration range olomoucine inhibits activity in both peaks from the Resource Q column and also the agonist stimulation of 6-keto-PGF1, but has no effect on agonist-stimulated phospho-MAPK immunoreactivity. These results provide direct evidence for the involvement of p42 and p44 MAPK in the PGI2 response of intact endothelial cells: we have shown that both the endothelial P2Y purinoceptors are linked to activation of MAPK, and that activation of this pathway is a requirement for the stimulation by ATP/ADP of endothelial PGI2 production.

Adenosine Triphosphate↗
PubMed1996

An economic evaluation of laparoscopic versus open inguinal hernia repair.

BACKGROUND: The rapid and widespread introduction of minimal access surgery has major implications for the National Health Service. It cannot be assumed that replacing an open procedure with a minimal access alternative will be cost-effective. Laparoscopic inguinal hernia repair is a procedure for which the potential economic benefits are particularly unclear. It is currently being adopted in many centres, although limited evidence on its clinical and cost-effectiveness exists. METHODS: This economic comparison of laparoscopic versus open hernia repair was undertaken on data collected on 104 patients undergoing surgery on a day case basis, in the context of a randomized controlled trial. RESULTS: The mean total health service cost of laparoscopic repair was 1074 pounds versus 489 pounds for open repair [mean difference in total health service costs 583 pounds; 95 percent confidence interval (CI) 265 pounds-904 pounds]. This difference was largely accounted for by the difference in theatre costs. Laparoscopic repair remained significantly more expensive for most but not all of the scenarios explored in the sensitivity analysis. The direction of the cost-effectiveness ratio was not sensitive to assumptions about long-term recurrence. Neither was it sensitive to halving the operating time in the laparoscopic arm of the trial. When both operating time and the costs of consumables were reduced, laparoscopic repair remained more expensive, but results for this scenario did not achieve statistical significance on this sample size. CONCLUSIONS: Laparoscopic hernia repair appears an expensive option in most plausible situations. Furthermore, many uncertainties still exist about long-term outcome after the procedure and about the conditions necessary to maximize cost-effectiveness. Large-scale randomized studies to evaluate laparoscopic hernia repair are currently under way to address these issues. We suggest that further evidence is awaited before this technology is further diffused.

Adolescent↗
PubMed1996

Metabolic activities of metronidazole-sensitive and -resistant strains of Helicobacter pylori: repression of pyruvate oxidoreductase and expression of isocitrate lyase activity correlate with resistance.

In this study, we compared metronidazole (Mtz)-sensitive and -resistant strains of Helicobacter pylori for metabolic differences that might correlate with drug resistance. Included in this study was an isogenic Mtz(r) strain, HP1107, that was constructed by transforming genomic DNA from Mtz(r) strain HP439 into Mtz(s) strain HP500. Enzyme activities were also measured for Mtz(r) strains grown in the presence or absence of 18 micrograms of metronidazole per ml (ca. one-half of the MIC). These studies confirmed the presence of the Embden-Meyerhof-Parnas, Entner-Doudoroff, and pentose pathways. H. pylori strains expressed enzymatic activities indicative of a complete and active Krebs cycle. All strains expressed pyruvate oxidoreductase (POR) and alpha-ketoglutarate oxidoreductase (KOR) as measured with the redox-active dye benzyl viologen (30 to 96 nmol/min/mg of protein for POR and 30 nmol/min/mg of protein for KOR). When grown in the presence of Mtz at > or = 3.5 micrograms/ml, Mtz(r) strains expressed no detectable POR or KOR activity. The apparent repression of POR and KOR activities by Mtz affected bacterial growth as manifest by extended lag periods and growth yield reductions of > 30%. A dose-dependent relationship was demonstrated between the metronidazole concentration in the growth medium and the specific activity of POR measured in bacterial cell extracts. The observed repression was not due to inactivation of POR by Mtz. In addition to repression of POR and KOR activities, growth in the presence of Mtz also led to decreases in the activities of various Krebs cycle enzymes, including aconitase, isocitrate dehydrogenase and succinate dehydrogenase. All of the Mtz(r) strains examined expressed isocitrate lyase and malate synthase activities indicative of the glyoxylate bypass. No isocitrate lyase activity was detected in Mtz(s) strain HP500. Isocitrate lyase activity was expressed by HP500 following transformation to Mtz resistance (Mtz(r) strain HP1107) with DNA from an Mtz(r) strain. The results of this study suggest that Mtz resistance may be a recessive trait, possibly involving inactivation of a regulatory gene, that results in constitutive expression of isocitrate lyase. Repression of POR and KOR activities in response to low levels of Mtz may be a general response of H. pylori strains to Mtz, but only resistant strains manage to survive via activation of compensatory metabolic pathways.

Citric Acid Cycle↗
PubMed1995

Randomised controlled trial of laparoscopic versus open repair of inguinal hernia: early results.

OBJECTIVE: To establish the safety, short term outcome, and theatre costs of transabdominal laparoscopic repair of inguinal hernia performed as day surgery. DESIGN: Randomised controlled trial. The control operation was the two layer modified Maloney darn. SETTING: Teaching hospital and district general hospital. SUBJECTS: 125 men randomised to laparoscopic or open repair of inguinal hernia. OUTCOME MEASURES: Morbidity, postoperative pain and use of analgesics, quality of life, and theatre costs. Outcome was assessed by questionnaires administered to patients daily for 10 days and at six weeks postoperatively and by outpatient review at six weeks. Return to normal activity was assessed by questionnaire at three months. RESULTS: One vascular complication (2%) occurred in the group that had open repair. Seven complications (12%) including vessel injury and early recurrence arose in the group that had laparoscopic repair (difference in complication rate 10% (95% confidence interval 4% to 18%; P = 0.02). Pain scores and quality of life assessed by the short form 36 showed a significant benefit to the group that had laparoscopic repair in the early postoperative period. Return to normal activity was not significantly different between the two groups. Total theatre costs were higher in the group that had laparoscopic repair (mean cost for laparoscopic repair 850 pounds (622 pounds to 1078 pounds); mean cost for open repair 268 pounds (245 pounds to 292 pounds)). CONCLUSIONS: Because of the greater complication rate and higher theatre costs for laparoscopic repair and the patient outcome preferences expressed, the results of larger trials of clinical and cost effectiveness using recurrence as the primary outcome measure should be known before laparoscopic herniorrhaphy is widely adopted.

Adult↗
PubMed1995

NF-E2 and GATA binding motifs are required for the formation of DNase I hypersensitive site 4 of the human beta-globin locus control region.

The beta-like globin genes require the upstream locus control region (LCR) for proper expression. The active elements of the LCR coincide with strong erythroid-specific DNase I-hypersensitive sites (HSs). We have used 5' HS4 as a model to study the formation of these HSs. Previously, we identified a 101 bp element that is required for the formation of this HS. This element binds six proteins in vitro. We now report a mutational analysis of the HS4 HS-forming element (HSFE). This analysis indicates that binding sites for the hematopoietic transcription factors NF-E2 and GATA-1 are required for the formation of the characteristic chromatin structure of the HS following stable transfection into murine erythroleukemia cells. Similarly arranged NF-E2 and GATA binding sites are present in the other HSs of the human LCR, as well as in the homologous mouse and goat sequences and the chicken beta-globin enhancer. A combination of DNase I and micrococcal nuclease sensitivity assays indicates that the characteristic erythroid-specific hypersensitivity of HS4 to DNase I is the result of tissue-specific alterations in both nucleosome positioning and tertiary DNA structure.

Animals↗
PubMed1995

Treating childhood asthma with nebulised steroids.

Nebulised steroids are a very effective form of treatment. A very small dose of steroids is inhaled from a nebuliser in the form of a fine spray of minute droplets which allows the drug to be spread over a wide area of the lungs and rapidly absorbed. Nebulisers can be used from one month old upwards, e.g. in wheezy infants and toddlers. Very ill children too breathless to use other types of inhaler often benefit from a nebulised therapy. Nebulisers often improve compliance, particularly with toddlers. In many children, nebulised therapy maintains lung function as effectively as oral prednisolone, while minimising the risk of systemic side-effects and improving the patient's quality of life. Experienced primary health-care teams can start a child on nebulised therapy in the community, but it should ideally be initiated in conjunction with a local paediatrician skilled in asthma management. Well managed nebuliser therapy can help prevent hospital admissions.

Administration, Inhalation↗
PubMed1993

A rare complication of dental treatment: Streptococcus oralis meningitis.

A case of Streptococcus oralis meningitis is reported. This followed extraction of a normal tooth during routine orthodontic treatment. No focus of infection could be demonstrated, either local to or distant from the extraction site. Full recovery followed hospital admission and intravenous benzyl penicillin.

Child↗
PubMed1993

Sodium cromoglycate via inhaler and Autohaler.

One hundred and eighty-one children with asthma were entered into a randomized, controlled, crossover study comparing sodium cromoglycate via a metered dose inhaler (MDI) and a breath-actuated inhaler (Autohaler). There were no significant differences in pulmonary function tests (FEV1, FVC, PFER), symptom scores and bronchodilator use between the two devices. However both patients' and clinicians' opinions of sodium cromoglycate effectiveness were significantly better (P < 0.01) for the Autohaler. Autohaler was also thought to be easier to use (P < 0.001) and better for co-ordination of actuation with inhalation (P < 0.001). The Autohaler is as efficacious as the metered dose inhaler used by good co-ordinators. It seems to be the significantly better device with respect to ease of use, actuation and co-ordination which may aid compliance.

Adolescent↗
PubMed1987

Dietary composition and renal function in healthy subjects.

Increments in dietary protein intake can increase glomerular filtration rate (GFR) in humans, and the glomerular hyperfiltration induced by high protein intake has been incriminated in the progression of glomerulosclerosis related to age and a number of renal diseases. GFR (as 51Cr-EDTA clearance) was measured in 18 vegans, 16 lactovegetarians and 18 omnivorous control subjects, matched for age. Omnivores ate significantly more total protein and protein of animal origin than the other two groups. Vegetable protein comprised 100% of the vegans' daily protein intake and 64% of the lactovegetarians', both significantly higher than the omnivores' (32%). Vegans and lactovegetarians also ate more carbohydrate and fibre than omnivores, although fat intake was similar. Mean GFR was significantly lower in the vegans than in the omnivores (100 +/- 13 vs. 113 +/- 16 ml/min/1.73 m2; p less than 0.04) and was intermediate in the lactovegetarians (105 +/- 16 ml/min/1.73 m2). Omnivores had significantly higher mean urinary albumin excretion rate (p less than 0.05) than vegans, and higher mean diastolic blood pressure than both vegans and lactovegetarians (p less than 0.01). The vegan diet is associated with glomerular and systemic haemodynamic changes which may be beneficial in the prevention of glomerular sclerotic changes in health and disease.

Albuminuria↗
PubMed1985

Classification of severe school attendance problems.

Sixty-four children taken to court for failure to attend school were reliably classified into 4 groups, according to whether they exhibited the features of 'school refusal' and/or 'truancy'. About a fifth of them were found to exhibit 'school refusal'; a third showed 'truancy'; less than a sixth exhibited both 'school refusal' and 'truancy' combined; and over a third had the characteristics of neither condition. Differences between these categories were found in manifestations of psychiatric disturbance and in responsiveness to a court adjournment procedure.

Absenteeism↗
PubMed1984

Intravenous anaesthesia in the upper limb: a review of 225 cases.

The technique of intravenous regional anaesthesia for the upper limb is described and its use in 225 patients is reported. The method can be used for elective or emergency surgery on the hand or upper limb and has been found to be safe, simple and effective.

Anesthesia, Conduction↗
PubMed1983

Transcutaneous recording of single neuron activity in the cerebral cortex of the monkey.

A new method is described for recording responses of single neurons in the monkey's cerebral cortex by passing a microelectrode directly through the overlying skin and dura. Previous to this recording a window had been cut in the calvarium, and the bone deficit repaired using a full-thickness skin graft. Stable unitary recordings have been made over a period of one year following craniotomy, the only skull attachment being a small stainless steel peg, on which the microdrive was mounted when required.

Animals↗
PubMed1982

Touching textured surfaces: cells in somatosensory cortex respond both to finger movement and to surface features.

Single neurons in Brodmann's areas 3b and 1 of the macaque postcentral gyrus discharge when the monkey rubs the contralateral finger pads across a textured surface. Both the finger movement and the spatial pattern of the surface determine this discharge in each cell. The spatial features of the surface are represented unambiguously only in the responses of populations of these neurons, and not in the responses of the constitutent cells.

Animals↗