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Biomedical subjects

M Ford

Publications and source records attributed to M Ford.

At least 19 recordsLinked to original sources

Expression of the tumor-associated mucin MUC1 in an ovarian tumor cell line.

Epithelial sialomucins constitute a family of high-molecular-weight glycoproteins associated with epithelial cell surfaces. Aberrant expression of these molecules has been observed in certain types of human epithelial tumors. Members of the MUC1 family of mucins isolated from different tissue types have been shown to differ in biochemical properties and in immunological reactivity. The polymerase chain reaction (PCR) has been used in a study of the MUC1 mRNA expressed in ovarian tumor cells. The intron/exon structure of the ovarian mucin gene has been examined, the nucleotide sequence of regions of the cDNA 5' and 3' to a central highly repetitive region of the molecule determined and genomic clones for this mucin from the ovarian tumor cell line COLO316 have been isolated and analyzed. The results are compared with the nucleotide sequence data obtained by others for MUC1 cDNA in breast and pancreatic cell lines. With a single nucleotide exception, the splicing pattern and nucleotide sequence obtained from MUC1 mRNA in the ovarian cell line is the same as that of the mRNA found in breast and pancreatic cell lines. However, it appears that the use of alternate splice acceptors for intron I in the ovarian cell line studied here is independent of the specific sequence variation thought to determine splicing of MUC1 in breast tumor cells.

Base Sequence

Use of a combined right ventricular ejection fraction-oximetry catheter system for coronary bypass surgery.

OBJECTIVE: To evaluate the reproducibility and accuracy of a new pulmonary artery catheter system that provides both right ventricular ejection fraction and continuous venous oxygen saturation monitoring. DESIGN: Criterion standard study. SETTING: University medical center. PATIENTS: A consecutive sample of ten patients undergoing elective coronary artery bypass surgery provided informed consent for the study. Exclusion criteria included emergency surgery or clinically important preoperative tricuspid regurgitation as assessed by echocardiography. None of the patient sample was excluded. MEASUREMENTS: Catheter-derived mixed venous and arterial oximetry data were compared with simultaneous values obtained using conventional laboratory cooximetry methods. Measurements were performed before cardiopulmonary bypass and intermittently up to 48 hrs after cardiopulmonary bypass. The variability of cardiac output and computed right ventricular ejection fraction was also assessed concurrently with the oximetry analysis. RESULTS: A significant correlation was observed for mixed venous oxygen saturation between catheter-derived and laboratory cooximetry data (r2 = .81, p < .01). Similarly, arterial oxygen saturation values obtained from pulse oximetry and laboratory values were significantly related (r2 = .81, p < .01). The coefficient of variation for each set of five repeated measurements for cardiac output was 8%, and for computed right ventricular ejection fraction, it was 16%. CONCLUSIONS: The combined catheter system provides the means to monitor both mixed venous oxygen saturation and right ventricular ejection fraction. These data provide a reliable and detailed assessment of cardiopulmonary function that should prove beneficial in the critical care setting.

Aged

Screening for bacteriuria in urological patients using reagent strips.

A rapid and accurate ward-based method of diagnosing urinary infection would be of value in determining the prescription of antibiotics in pre-operative urological patients. This study describes the sensitivity and specificity of a screening technique based on commercially available reagent strips in the diagnosis of urinary infection. A total of 222 pre-operative samples and 83 post-operative samples was studied to compare the results of formal urine culture and reagent strips. Using a definition of a positive nitrite or a positive leucocyte esterase on the reagent strips as being suggestive of infection, it was found that the strips had a sensitivity of 91% and a specificity of 85% compared with formal culture in pre-operative samples. The results from post-operative samples were less satisfactory, the strips having a sensitivity of only 71% and specificity of 55%. The strips were insensitive but specific in the identification of pyuria in pre-operative specimens. These results suggest that reagent strips can be used as a ward-based method to identify men at risk of infection before urological procedures, and may allow selectivity in the use of peri-operative antibiotics.

Adolescent

Opioids and designer drugs.

Despite the increasing use of other illicit drugs, opioid abuse, overdose, and the ensuing medical complications continue to pose management challenges for the emergency physician. Heroin use is increasing as abusers of cocaine seek a drug to prolong cocaine's effects while blunting the postcocaine depression. Clandestine chemists have created newer, more powerful compounds--designer drugs--whose potencies are many-fold that of the presently available opioids. Aggressive airway support and use of naloxone enable the emergency physician to salvage many of these patients, leaving the many medical complications of parenteral and inhalational use as the greatest management challenge.

Ambulatory Care

Rapid conventional scheme for biochemical identification of antibiotic resistant enterobacteriaceae isolates from urine.

Six conventional biochemical tests were combined to produce an identification scheme. These tests included decarboxylation of lysine and ornithine, fermentation of glucose and cellobiose, indole production and urease production. Three hundred antibiotic resistant coliforms from urine specimens were tested by this scheme and also by the API 20E for comparison. Two hundred and seventy nine (93%) of organisms were correctly identified using the six tests, 17 (5.7%) were referred for further study, and four (1.3%) were misidentified. It is concluded that this combination of tests provides an inexpensive, accurate, and rapid tool for identification.

Bacteriological Techniques

Purification of bovine protoporphyrinogen oxidase: immunological cross-reactivity and structural relationship to ferrochelatase.

Protoporphyrinogen oxidase, the penultimate enzyme in the haem biosynthetic pathway has been purified to apparent homogeneity from bovine liver mitochondria, by a published method (Dailey, H.A. and Fleming, J.E., (1983)), with an additional ion-exchange chromatography step, using a Mono Q column on an FPLC-system. This gave a product with a 68% yield and 870-fold purification. Protoporphyrinogen oxidase (EC 1.3.3.4) has an apparent Mr of 57,000 and the Km for protoporphyrinogen IX was 16.6 microM. Activity of the isolated enzyme was increased by 66% in the presence of oleic acid, and evidence was obtained for a FAD prosthetic group. Ferrochelatase (EC 4.99.1.1) was purified and antibodies were raised in rabbits against ferrochelatase and protoporphyrinogen oxidase, respectively. Anti-protoporphyrinogen oxidase IgG showed marked cross-reactivity with ferrochelatase and anti-ferrochelatase IgG cross-reacted with protoporphyrinogen oxidase. In addition, radiolabelled peptides of both enzymes, generated by chymotrypsin, demonstrated common peptides when analysed by two-dimensional chromatography.

Animals

Structure of an inverted duplication formed as a first step in a gene amplification event: implications for a model of gene amplification.

Inverted duplications have been observed to be a common feature of gene amplification in mammalian cells and appear to be generated as a primary event in the amplification process (Ford et al., 1985; Ford and Fried, 1986). The structural features of the amplified inverted duplication, containing the polyoma virus oncogene middle T-antigen, were analysed in transformed 3B rat cells. No unusual sequences such as transposition elements were detected at the site of the inversion. The inversion was generated by a simple illegitimate recombination event in which only a single nucleotide directly at the point of the inversion cannot be accounted for from the sequence of the two parental strands. Possible structural (hairpin formation) and sequence (rich AT) features may have been involved in the illegitimate recombination event at the inversion join. In the cellular DNA near one of its joins with polyoma virus DNA an unusual sequence of 198 bp composed of 99 consecutive purine-pyrimidine pairs has been detected. A model for the generation of amplified DNA containing inverted duplications is proposed.

Animals

The dismantling of the mental hospital? Glenside Hospital surveys 1960-1985.

Results of the sixth quinquennial survey of the resident population of Glenside Hospital, Bristol, are reported. The total population continues to fall, but the rate of decline has slowed; the implications of this are discussed. Many patients live in an emotionally impoverished state, friendless and rarely leaving the hospital. Few in-patients are employed, even within the hospital. Considerable provision is made, however, for the employment of day-patients. To effectively resettle and support in the community those currently remaining in hospital will require increasingly extensive provision.

Adult

Large inverted duplications are associated with gene amplification.

Amplified DNA can be found in arrays of large repeated units, with each repeat unit containing a marker gene and surrounding DNA sequences. Amplified DNA sequences from established cell lines were assessed for the presence of repeat units in the form of inverted duplications. Inverted duplicated DNA was detected by virtue of its concentration-independent resistance to S1 hydrolysis after denaturation and rapid renaturation. Using this assay, inverted duplications were detected in amplified DNA (both DM and HSR configurations) containing the myc gene (16-50 copies/cell) in four human tumor cell lines and in amplified DNA containing the CAD gene (30-200 copies/cell) in three PALA-resistant BHK cell lines. The widespread association of inverted duplications with amplified DNA must bear on the amplification mechanism.

Animals

Ionizing radiation and DNA-chain elongation in ataxia telangiectasia lymphoblastoid cells.

DNA-chain elongation rates, determined by sedimentation analysis, were found to be similar in control and ataxia-telangiectasia lymphoblastoid cells. A gamma-radiation dose of 6 Gray, which had previously been shown to have a marked inhibitory effect on initiation of DNA replication, had no appreciable effect on elongation rates in either cell type. Elongation rates were also determined at 20 Gray of gamma-rays by pulsing cells with [3H]thymidine prior to irradiation to avoid anomalous sedimentation behaviour. At this radiation dose elongation was almost completely inhibited in control cells while little or no inhibition was observed in ataxia-telangiectasia cells. Deoxyribonucleoside triphosphate pool equilibration times were not altered at either dose.

Ataxia Telangiectasia

Treatment of angina pectoris with nifedipine and atenolol: efficacy and effect on cardiac function.

The antianginal effects of nifedipine 20 mg three times a day and atenolol 100 mg once a day singly and in combination were investigated in 16 patients with angina pectoris. The amount of work that could be done before angina and ST depression appeared was significantly increased by atenolol and the combination but not by nifedipine. At peak exercise the number of leads on a 16 point precordial electrocardiogram map that demonstrated greater than or equal to 1 mm ST segment depression was significantly reduced from a mean (SD) of 5.0 (0.4) on placebo to 3.7 (0.6), 2.8 (0.4), and 2.3 (0.7) on nifedipine, atenolol, and the combination respectively. Mean resting left ventricular ejection fraction, assessed by gated radionuclide ventriculography, did not change during any active treatment phase but increased significantly during exercise only on nifedipine and the combination. The nifedipine/atenolol combination was the most effective treatment, and the data suggest that nifedipine may be used to best advantage in combination with a beta blocker.

Angina Pectoris