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Biomedical subjects

C Mather

Publications and source records attributed to C Mather.

At least 19 recordsLinked to original sources

Transposition of the Drosophila element mariner into the chicken germ line.

The ability of the Drosophila transposable element mariner to transpose in the chicken was tested using a plasmid carrying an active mariner element injected into chick zygotes. Surviving embryos and chicks were analyzed for presence of mariner. Analysis of embryos that survived for at least 12 days of development indicated that mariner had transposed at high frequency into the chicken genome. Germline transmission of mariner from one of three surviving birds confirmed transposition. Analysis of the first-generation (G1) chicks showed that they each contained between one and three copies of mariner. Six different transposition events were represented in the G1 birds, and the transposition was catalyzed by expression of the mariner element's transposase gene. Transmission from G1 to G2 occurred at a 1:1 ratio. Mariner therefore has potential for development as a vector for transgenesis in avian species.

Animals

The palpation of pulses.

In 554 anaesthetised patients, the times taken to separately palpate and identify each of the carotid, radial, brachial and femoral pulses were recorded. The patients were divided into three groups based on the form of airway management chosen (tracheal tube, facemask or laryngeal mask airway). Our results demonstrate that in the operating theatre environment the identification of the radial pulse is the most rapid and reliable; by 5 s, 98% and by 10 s, more than 99% of radial pulses were identified. The carotid pulse was not so easily identified, requiring 10 s to enable an identification rate of greater than 95%. The presence of a laryngeal mask airway or a tracheal tube did not hinder the identification of carotid pulse.

Adolescent

Type 2 diabetes. Patient practices, and satisfaction with GP care.

OBJECTIVE: To document patients' practices and management of DM2, their satisfaction with diabetes care and their quality of life and functional status. DESIGN: Anonymous questionnaire completed by 467 patients recruited by 204 GPs in 124 practices in the Perth metropolitan area. RESULTS: Patients reported an adequate amount of monitoring for stable DM2. However, they lacked awareness of diabetes risk factors and complications from which they already suffered. Some 90% of patients reported a high level of satisfaction with GP care and only 2.4% of patients had more than a moderate degree of functional disability. CONCLUSION: Patients have a high level of satisfaction about the diabetes care received from their general practitioner. However, they lack awareness of their risk factors and complications of diabetes. A simple strategy is proposed to improve these deficits and to share the responsibility for diabetes care between patient and doctor.

Adult

Management of type 2 diabetes in Western Australian metropolitan general practice.

The purpose of this study was: (1) to record GP opinions, practices and outcomes for the care of Type 2 Diabetes Mellitus (DM2), (2) compare practice facilities and process of care with a criterion of recommended competent care and (3) determine if there were any differences between vocationally registered and non-vocationally registered GPs. A random sample of 204 metropolitan doctors from 124 practices was selected and an audit performed on 467 of their patient records. GPs pursued good blood sugar control and advocated lifestyle changes before hypoglycaemic drugs. Over 80% regard uncomplicated DM2 as a condition for general practice management. However, only 15% conducted an annual diabetes check, 9% had a diabetic register, 6% a diabetic recall system and 8% used a diabetic health care checklist for monitoring their patients. The most commonly recorded processes of medical audit in the previous 12 months were: blood pressure (94%), duration of diabetes (72%), blood glucose (70%), diet (66%), body weight (56%), HBA1c (52%) and ophthalmoscopy (50%). The least commonly recorded processes of care were body mass index (5%), inspection of the feet (18%), enquiries about vaginitis or impotence (23%). The amount of exercise, alcohol and tobacco was recorded in only 34% of records. Hypoglycaemic drugs were used appropriately but the most commonly used drugs for treating hypertension in DM2 patients were thiazide diuretics and beta-blockers. Vocationally registered (VR) doctors had better records, higher process of care scores and more were willing to participate in the study than non-vocationally registered (NVR) doctors. However, there was no difference in metabolic control between patients from either group. The use of a Diabetic Health Care Checklist would improve diabetes care especially in the search for early complications and in the recording of HBA1c and other metabolic parameters. The drugs commonly used to control hypertension can have adverse effects on glucose and lipid metabolism and should be replaced with glucose and lipid neutral drugs.

Adult

Transgenic birds by DNA microinjection.

We have developed a method for production of transgenic chickens by DNA microinjection of chick zygotes followed by ex vivo embryo culture. The fate of plasmid DNA microinjected into the germinal disc of zygotes was analyzed in embryos which survived for at least 12 days in culture. Approximately half of the embryos contained plasmid DNA, 6% at a level equivalent to one copy per cell in all tissues analyzed. Seven chicks, 5.5% of the total number of injected ova, survived to sexual maturity. One of these, a cockerel, transmitted the exogenous DNA to 3.4% of his offspring. These G1 birds have reached sexual maturity and have been bred to produce transgenic offspring, demonstrating that stable transmission of foreign DNA can be obtained by our method.

Animals

Isolation of a novel receptor tyrosine kinase cDNA expressed by developing erythroid progenitors.

Activation of distinct receptor tyrosine kinases (RTK), such as the products of the c-fms and c-kit proto-oncogenes, profoundly affects hematopoietic development. We have isolated a novel RTK cDNA, called met-related kinase (MRK), which is expressed on early erythroid progenitors. MRK is also expressed in many hematopoietic cell lines, and is not lineage restricted. Several regions within the catalytic domain of MRK have amino acid similarity to the c-met proto-oncogene and v-sea oncogene. Specific polyclonal anti-MRK antisera detects an 84-Kd polypeptide in COS cells transfected with an expression vector containing the MRK cDNA. Further studies of this novel RTK will provide potential insight into its role during hematopoiesis.

Amino Acid Sequence

'Smelly agents'.

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Anesthesia, Inhalation

Cell cycle-dependent initiation and lineage-dependent abrogation of GATA-1 expression in pure differentiating hematopoietic progenitors.

The programmed activation/repression of transcription factors in early hematopoietic differentiation has not yet been explored. The DNA-binding protein GATA-1 is required for normal erythroid development and regulates erythroid-expressed genes in maturing erythroblasts. We analyzed GATA-1 expression in early human adult hematopoiesis by using an in vitro system in which "pure" early hematopoietic progenitors are induced to gradual and synchronized differentiation selectively along the erythroid or granulocyte-macrophage pathway by differential treatment with hematopoietic growth factors. The GATA-1 gene, though virtually silent in quiescent progenitors, is activated after entrance into the cell cycle upon stimulation with hematopoietic growth factors. Subsequently, increasing expression along the erythroid pathway contrasts with an abrupt downregulation in the granulocyte-macrophage lineage. These results suggest a microenvironment-directed, two-step model for GATA-1 expression in differentiating hematopoietic progenitors that involves (i) cycle-dependent initiation and (ii) lineage-dependent maintenance or suppression. Hypothetically, on/off switches of lineage-restricted transactivators may underlie the binary fate decisions of hematopoietic progenitors.

Antigens, Surface

Somatic movement and oesophageal motility during isoflurane anaesthesia.

The quantal responses for somatic movement, and spontaneous and provoked lower oesophageal contractions (motility) were noted at the time of incision in 72 patients aged 40-65 yr, receiving varying concentrations of isoflurane. Probit analysis of the alveolar concentration of isoflurane required to prevent somatic movement revealed an MAC or EC50 (95% confidence limits) of 1.00 (0.82-1.17)% and EC95 of 2.16 (1.69-3.89)%. The EC50 of isoflurane to suppress spontaneous lower oesophageal contractions was 1.27 (1.12-1.43)%, and the EC95 2.13 (1.78-3.22)%. The EC50 for provoked lower oesophageal contractions was 1.31 (0.93-3.48)% and the EC95 was 6.18% (unable to compute confidence limits).

Adult

GATA-binding transcription factors in mast cells regulate the promoter of the mast cell carboxypeptidase A gene.

The transcription factors GATA-1, GATA-2, and GATA-3 were found to be expressed in several mouse and rat mast cell lines that contain mast cell carboxypeptidase A (MC-CPA) and other proteases in their cytoplasmic granules. GATA-1 mRNA was not detected in P815 cells, an immature mouse mastocytoma-derived cell line that lacks electron-dense granules and has low levels of secretory granule proteases. Because the 5'-flanking regions of the mouse and human MC-CPA genes contained a conserved GATA-binding motif 51 base pairs upstream of their translation initiation sites, the ability of GATA-binding proteins to regulate the promoter activity of the MC-CPA gene was examined in rat basophilic leukemia cells, mouse P815 cells, and transfected mouse P815 cells that expressed GATA-1. In all three mast cell lines, the promoter activity of the MC-CPA gene depended on the GATA binding site. GATA-1, GATA-2, and GATA-3 are thus the first DNA-binding proteins identified in mast cells which regulate the promoter activity of a gene that encodes a secretory granule protease.

Animals

Activation of the erythropoietin receptor promoter by transcription factor GATA-1.

Erythropoietin, a glycoprotein produced by the kidneys in response to anemia and hypoxia, is a major growth factor for cells of the erythroid lineage. Erythropoietin interacts with high-affinity cell surface receptors (EpoR) present on developing progenitors and is required for their survival. Previously we characterized the gene for EpoR and demonstrated that its promoter acts in a cell-specific manner. Here we show that the hematopoietic-specific transcription factor GATA-1 is necessary, and indeed is sufficient as the sole cell-restricted regulator, for activation of the EpoR promoter in fibroblast transfection assays. Hence, GATA-1, which participates in transcriptional control of the majority of erythroid-expressed genes, also acts on the promoter of an essential lineage-restricted receptor (EpoR). This central contribution of GATA-1 to EpoR promoter function provides a mechanism whereby a cell-restricted regulator may ensure the viability and subsequent maturation of progenitor cells during hematopoietic differentiation.

3T3 Cells

Expression of GATA-binding proteins during embryonic development in Xenopus laevis.

Proteins that recognize the core sequence GATA are important regulators of hematopoietic-specific gene transcription. We have characterized cDNAs encoding the Xenopus laevis homologues of three related transcription factors, designated GATA-1, -2, and -3. Comparative sequence analysis reveals strong conservation of the zinc-finger DNA-binding domain among all vertebrate GATA-binding proteins. GATA-2 and GATA-3 polypeptides are homologous throughout their entire sequences, whereas GATA-1 sequence is conserved only in the region responsible for DNA binding. In Xenopus, RNAs encoding GATA-binding proteins are expressed in both larval and adult erythroid cells. GATA-1, -2, and -3 RNAs are first detectable in early gastrula (Nieuwkoop developmental stage 11). This is earlier than the appearance of the early larval alpha T1 globin RNA (stage 15), beta T1 globin RNA (stage 26), or blood island formation (stage 30). The expression of GATA-1, -2, and -3 in early development may signal an early commitment of mesoderm to form hematopoietic tissue.

Amino Acid Sequence

The efficacy of 0.75% bupivacaine with pH adjustment and hyaluronidase for peribulbar blockade: the incidence of prolonged ptosis.

A prospective, double masked, randomised study was performed to compare the speed of onset of peribulbar anaesthesia using pH adjusted 0.75% bupivacaine, with and without the addition of hyaluronidase. No significant difference in speed of onset occurred due to the addition of hyaluronidase. There were 7 cases of post operative ptosis in the study group, including 1 case of orbital apex syndrome and 2 cases of transient 3rd nerve palsy. This incidence of post operative ptosis using pH adjusted 0.75% bupivacaine was statistically significantly greater than in a matched control group who received a 50:50 mixture of 1% lignocaine and 0.5% bupivacaine with hyaluronidase (p < 0.05). The possible causes of this increased incidence of post operative ptosis are discussed.

Aged