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Biomedical subjects

C A Mitchell

Publications and source records attributed to C A Mitchell.

At least 19 recordsLinked to original sources
PubMed1992

bFGF enhances the development of the collateral circulation after acute arterial occlusion.

An adequate collateral circulation is crucial to tissue survival subsequent to proximal major arterial occlusion. The precise mechanism of collateral blood vessel development and the biochemical mediators involved in this process are unknown. To evaluate the influence of a number of agents on the development of the collateral circulation, we developed a rat model of severe hind limb ischaemia. The recovery of blood flow after acute arterial occlusion was increased by exogenous basic fibroblast growth factor and heparin, and decreased by protamine. Erucamide (cis-13-docosenamide), an angiogenic lipid, had no effect on collateral blood flow. These results indicate that basic fibroblast growth factor and heparin are potential therapeutic agents in the treatment of peripheral vascular disease.

Animals↗
PubMed1992

Asthma morbidity in Australia: an epidemiological study.

OBJECTIVE: To examine the prevalence and management of asthma in adults and children in a population sample in eastern Australia. SETTING: A random sample of children from 33 primary schools in Sydney, Melbourne, Brisbane, and the Upper Hunter Valley (New South Wales), and their parents. DESIGN: A cross-sectional analytic survey of 8753 primary school children aged between 5 and 12 years, and their parents (n = 13,945 adults). Asthma prevalence and management practices were determined by parental responses to a questionnaire, and spirometry was performed in children with "probable asthma". RESULTS: Of 8753 children whose parents responded, the prevalence of current wheeze was 19.5% and diagnosed asthma was 17.1%. Of the children with "probable asthma", 30% had their lung function measured in the previous year, and 6% possessed both a peak flow meter and an action plan for their asthma. Undertreatment was likely, as preventive asthma medications (inhaled corticosteroids or sodium cromoglycate) were used regularly by only 25.5% of these children and by 44.3% of children who had asthma symptoms more than twice per week. Children with the diagnosis of asthma reported higher rates of preventive medication use and ventilatory function measurement than children with frequent symptoms without the diagnosis. In the 13,945 adults, the reported prevalence of asthma was 7%, of whom 39% were using preventive medications, 34% had their ventilatory function assessed in the previous year, and 7% had both a peak flow meter and an asthma action plan. CONCLUSIONS: The study illustrated the gap between the current level of asthma management in the community and the standards set by the Thoracic Society of Australia and New Zealand. Undertreatment and suboptimal management of asthma remain important problems in Australia.

Administration, Inhalation↗
PubMed1992

Nebuhaler versus wet aerosol for domiciliary bronchodilator therapy. A multi-centre clinical comparison.

OBJECTIVE: To compare the clinical effectiveness and patient acceptance of a large spacer device (Nebuhaler) for delivery of metered dose aerosol (MDI) terbutaline with nebulised wet aerosol terbutaline. DESIGN: Randomised open crossover study over two sequential four week treatment periods, following a two week run-in. SETTING: Multi-centre including five adult thoracic units and three paediatric centres throughout Australia. PATIENTS: Thirty-eight adults and 23 children with clinical asthma and reversible airflow obstruction (increase in forced expiratory volume in one second [FEV1] of greater than or equal to 15% in response to inhaled bronchodilator) entered the study proper. Six adults and one child withdrew. INTERVENTIONS: Terbutaline was administered four times daily via Nebuhaler/MDI or nebuliser. Clinical assessment with spirometry and peak flow readings was made after run-in and at the end of each treatment period. Patients recorded on diary cards daily peak expiratory flow rates and symptom scores and comparisons of these results for each treatment period were made. At the completion of the study patients answered a treatment preference questionnaire. RESULTS: No differences were found between the two treatment periods in diary card peak flow recordings and symptom score data, and in clinical assessment of spirometry and peak expiratory flow rates. There were also no differences between spirometry and peak flow values recorded at the clinic at randomisation and at the end of each treatment period, suggesting stable basal airflow obstruction over the period of the study. Thirty-two per cent of adults and 52% of children preferred the Nebuhaler/MDI combination, mainly because of convenience of use. Treatment preference was not related to any measured index of lung function. CONCLUSIONS: MDI terbutaline delivered via Nebuhaler provides clinical benefit similar to that of wet aerosol terbutaline in the long-term domiciliary management of patients with stable airflow obstruction.

Adult↗
PubMed1992

The v-sis oncogene product but not platelet-derived growth factor (PDGF) A homodimers activate PDGF alpha and beta receptors intracellularly and initiate cellular transformation.

The v-sis oncogene product p28v-sis and the platelet-derived growth factor (PDGF) B chain share 92% homology with each other and over 50% homology with the PDGF A chain. Exogenously added homodimers of PDGF A and PDGF B and of p28v-sis are potent mitogens but only PDGF B and p28v-sis induce transformation when endogenously expressed with a strong promoter. Because exogenous PDGF AA and PDGF BB both initiate a full mitogenic response, understanding the mechanisms underlying the difference in their transforming potential may clarify how growth factor genes act as oncogenes. In this work, we compared cells expressing high levels of PDGF A and v-sis. We observed that transformation by v-sis correlated directly with the rapid degradation (t1/2 approximately 20 min) of the alpha and beta PDGF receptors, with a failure of either the alpha or beta receptor to be fully processed and with the association of high levels of phosphatidylinositol (PI) 3-kinase with immunoprecipitates of the PDGF receptors. In contrast, in cells expressing essentially equal levels of PDGF A, transformation was not detected, alpha and beta PDGF receptor processing was normal, and association of PI 3-kinase with receptors in immunoprecipitates was not found above control values. The ability of v-sis to autoactivate PDGF receptors within processing compartments and to initiate activation of the PI 3-kinase signaling pathway coupled with the failure of PDGF A to activate its receptor intracellularly and to induce transformation when endogenously expressed at high levels suggests that the internal autoactivation of PDGF receptors may be essential for transformation by v-sis.

3T3 Cells↗
PubMed1992

Cellular differences in the regeneration of murine skeletal muscle: a quantitative histological study in SJL/J and BALB/c mice.

Skeletal muscle regeneration in SJL/J and BALB/c mice subjected to identical crush injuries is markedly different: in SJL/J mice myotubes almost completely replace damaged myofibres, whereas BALB/c mice develop fibrotic scar tissue and few myotubes. To determine the cellular changes which contribute to these differential responses to injury, samples of crushed tibialis anterior muscles taken from SJL/J and BALB/c mice between 1 and 10 days after injury were analysed by light and electron microscopy, and by autoradiography. Longitudinal muscle sections revealed about a 2-fold greater total mononuclear cell density in SJL/J than BALB/c mice at 2 to 3 days after injury. Electron micrographs identified a similar proportion of cell types at 3 days after injury. Autoradiographic studies showed that the proportions of replicating mononuclear cells in both strains were similar: therefore greater absolute numbers of cells (including muscle precursors and macrophages) were proliferating in SJL/J muscle. Removal of necrotic muscle debris in SJL/J mice was rapid and extensive, and by 6 to 8 days multinucleated myotubes occupied a large part of the lesion. By contrast, phagocytosis was less effective in BALB/c mice, myotube formation was minimal, and fibrotic tissue conspicuous. These data indicate that the increased mononuclear cell density, more efficient removal of necrotic muscle, together with a greater capacity for myotube formation in SJL/J mice, contribute to the more successful muscle regeneration seen after injury.

Animals↗
PubMed1992

Herbert screw: results of a single-centre trial.

We report the results of a single-centre trial of the Herbert screw in the treatment of acute fractures, fracture-dislocations and non-unions of the carpal scaphoid. In the trial, 22 patients were studied with a maximum follow-up of 2.5 years. Of the patients, 84 per cent had minimal or no pain, and 94 per cent were happy with their result or significantly improved. There was an average loss of 34 per cent of radial deviation of the wrist and of 10 per cent in cylinder grip strength. On radiographic examination, 86 per cent achieved satisfactory union. However, only 73 per cent of type D2 fractures united. Overall, the subjective and objective clinical results achieved were more satisfactory than the radiographic results would suggest.

Adult↗
PubMed1992

Investigation of pleural effusion: the role of bronchoscopy.

To assess the place of bronchoscopy in the investigation of pleural effusion, 245 patients presenting during a two year period were reviewed. Of the 46 patients who had bronchoscopy, a positive yield was obtained in 13, though in five of these a second pleural aspiration was also diagnostic. Bronchoscopy was more likely to be diagnostic in patients presenting with a cough (12/24) than in those with no cough (1/22) (p less than 0.001), and in those whose chest X-ray revealed significant radiological abnormalities such as hilar enlargement, lung mass or persisting consolidation (12/29), than in those without such changes (1/17) (p less than 0.01). Bronchoscopy has a limited role in the investigation of pleural effusion. The presence or absence of cough, and the appearance of the chest X-ray, are both important considerations when planning the investigation of an undiagnosed pleural effusion.

Bronchoscopy↗
PubMed1992

Corticosteroids in acute severe asthma: effectiveness of low doses.

BACKGROUND: Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known. METHODS: The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intravenous aminophylline and nebulised salbutamol four hourly. Patients were given low, medium, or high doses of intravenous hydrocortisone and then 20, 40, or 60 mg/day respectively of oral prednisone with a reducing regimen over the following 12 days. Beclomethasone dipropionate, 400 micrograms twice daily by metered dose inhaler, was also started. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and visual analogue dyspnoea scores (VAS) were recorded daily in hospital and PEF and VAS twice daily after discharge for a total of 12 days. RESULTS: The 66 subjects (40 female) who completed the study had a mean (SD) age of 31(14) years. On presentation mean (SD) FEV1% predicted in the low (n = 22), medium (n = 20), and high dose (n = 24) groups was 17(13), 19(12), and 19(11) and after emergency bronchodilator treatment 32(20), 30(12), and 36(13). After 24 hours of treatment the respective post-bronchodilator FEV1% predicted values were 62(22), 62(23), and 65(28) compared with 71(24), 69(22), and 71(24) after 48 hours. No significant difference between the groups was detected. PEF and VAS improved with treatment over the 12 days but was not influenced by steroid dose. CONCLUSIONS: Hydrocortisone 50 mg intravenously four times a day for two days followed by low dose oral prednisone is as effective in resolving acute severe asthma as 200 or 500 mg of hydrocortisone followed by higher doses of prednisone.

Acute Disease↗
PubMed1992

A semi-empirical model for prediction of how post-retained crowns will fail under compressive loading.

The aim of this in vitro study was to determine the relative contributions to retention of the different components of the post-retained crown and the mode of failure when the crown was loaded at 50 degrees to the vertical (i.e., in an apical direction). Failure was initiated in all the specimens as a rotation of the crown about a point on the labial surface of the root at the crown-root interface with pull-out of the post. A semi-empirical model was developed to explain this mode of failure. From experimental results, it was noted that the retention provided by the post was the most significant factor in the equation. However, large variation in the maximum forces recorded from pull-out tests on 40 posts suggested that the glass-ionomer cement was acting in the manner of a brittle composite material whose failure may be attributed to defects in the structure causing stress concentrations. The probability of survival at each ultimate strength recorded experimentally was plotted for comparison with the curve generated by the derived Weibull function. Close agreement was noted. Thus, for any given force applied compressively at 50 degrees to the vertical to a post-retained crown of known dimensions, it is possible, by use of the described equation, to calculate the force, P, applied to the post. This value of P may then be inserted into the Weibull equation to give the probability of the crown failing under that applied force.

Animals↗
PubMed1991

Cloning and expression of human 75-kDa inositol polyphosphate-5-phosphatase.

Inositol polyphosphate-5-phosphatase (5-phosphatase) hydrolyzes inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate and thereby functions as a signal terminating enzyme in cellular calcium ion mobilization. A cDNA encoding human platelet 5-phosphatase has been isolated by screening for beta-galactosidase fusion proteins that bind to inositol 1,3,4,5-tetrakisphosphate. The sensitivity of the screening procedure was enhanced 50- to 100-fold by amplification of "sublibraries" prior to carrying out binding assays. The sequences derived from the "expression clone" were used to screen human erythroleukemia cell line and human megakaryocytic cell line cDNA libraries. We obtained two additional clones which together consist of 2381 base pairs. The amino-terminal amino acid sequence from the 75-kDa 5-phosphatase purified from platelets is identical to amino acids 38-56 predicted from the cDNA. This suggests that the platelet 5-phosphatase is formed by proteolytic processing of a larger precursor. The cDNA predicts that the mature enzyme contains 635 amino acids (Mr 72, 891). Antibodies directed against recombinant TrpE fusion proteins of either an amino-terminal region or a carboxyl-terminal region immunoprecipitate the enzyme activity from a preparation of the 75-kDa form of platelet 5-phosphatase (Type II) but do not precipitate the distinct 47-kDa 5-phosphatase (Type I) also found in platelets. In addition, the recombinant protein expressed in Cos-7 cells has the same 5-phosphatase activity as the platelet 5-phosphatase.

Amino Acid Sequence↗
PubMed1991

Growth and protein production kinetics of a murine myeloma cell line transfected with the human growth hormone gene.

A model mammalian cell system for the production of recombinant proteins was investigated. Murine myeloma cells which had lost the ability to produce both heavy and light chain immunoglobulin molecules were transfected with a vector containing the immunoglobulin heavy chain promoter and enhancer elements linked to the human growth hormone gene. The growth kinetics of G32, a clonal isolate, were found to be similar to both the parent myeloma and hybridomas. However, production of hGH by G32 was growth associated, rather than as a secondary metabolite as is the case for hybridomas. In addition, G32 produced hGH at molar levels greater than most hybridomas.

Animals↗
PubMed1991

Respiratory symptoms in Queensland schoolchildren: an association between month of birth and respiratory illness.

We have examined the relationship between month of birth and episodes of wheezing, productive cough, eczema and hayfever, and also standardized maximum mid-expiratory flow (FEF25-75) in a representative sample of 4549 Australian primary schoolchildren (mean age 10.1 years). Children experiencing frequent wheezing (one or more episodes per month) were more likely to be born in spring and summer (odds ratio = 1.6, 95% confidence interval = 1.1-2.4), but this was not seen for less severe disease. No effect of season or birth month was seen for the other illnesses examined or for lung function.

Australia↗
PubMed1990

Pathway for the formation of D-3 phosphate containing inositol phospholipids in intact human platelets.

We have identified the structure of phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) in human platelets. These lipids accounted for less than 2% of the total 32P incorporated into inositol phospholipids in the platelets. All three lipids were labeled in unstimulated platelets, but incorporation of 32P changed rapidly by 15 s after thrombin stimulation, suggesting that they are important in platelet activation. Specific inositol polyphosphate phosphatases were used to both identify the lipid structures and to determine the route of synthesis of these lipids. During 32P labeling and after thrombin stimulation of human platelets, as much as 60% of the total radioactivity present in PtdIns(3,4)P2 was found in the D-4 phosphate and only 35% in the D-3 phosphate indicating that PtdIns(3)P is the precursor of PtdIns(3,4)P2. In addition, the D-5 and D-4 phosphates of PtdIns(3,4,5)P3 each contained 35-40% of the total radioactivity in the molecule compared with only 18-28% in the D-3 position, suggesting that PtdIns(3,4)P2 and not PtdIns(4,5)P2 is the major precursor of this lipid. These results define the predominant pathway for synthesis of these lipids in platelets as PtdIns----PtdIns(3)P----PtdIns(3,4)P2----PtdIns(3,4,5)P3.

Blood Platelets↗
PubMed1990

Dental abnormalities associated with familial expansile osteolysis: a clinical and radiographic study.

Familial expansile osteolysis is a rare and possibly unique form of hereditary bone dysplasia with dental manifestations that has affected 42 members of a Northern Ireland family for five generations. Twenty-seven family members, aged 3 to 60 years, were examined clinically and radiographically, and it was found that cervical and/or apical root resorption is an early manifestation of the dysplasia. Of the 20 family members with skeletal manifestations of familial expansile osteolysis, 16 showed root resorption. Root resorption may therefore be a good prognosticator for later bone involvement.

Adolescent↗
PubMed1990

The process of new plasmalemma formation in focally injured skeletal muscle fibers.

The major ultrastructural events in murine skeletal muscle fibers were examined 3 to 24 hr after segmental injury induced by painting with aldehyde fixative. At 3 hr the viable stump of injured myofibers was separated from the necrotic segment by a zone of supercontracted myofibrils. No demarcating membrane was evident at this time, although occasionally collapsed segments of plasmalemma partially covered the viable stump. By 12 hr after injury myonuclei near the viable stump were centrally placed and numerous whorls of membrane material appeared in the vicinity of the Golgi apparatus. At this stage a convoluted, tortuous membrane exhibiting extensive interdigitations has sealed the structurally normal part of the injured fiber. The myoplasm immediately within this demarcating membrane possessed few myofilaments but numerous vesicles and tubules, several of which were continuous with the demarcating membrane; most degraded sarcoplasmic organelles remained external to the demarcating membrane and leukocytes were observed internalizing the debris. It appears that after segmental injury to skeletal muscle fibers, active production of new sarcoplasmic membranes occurs, which contributes to the formation of the part of the plasmalemma that demarcates the viable portion of the muscle fiber from the injured area.

Animals↗