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Biomedical subjects

D Parker

Publications and source records attributed to D Parker.

At least 199 records · Page 11Linked to original sources

An evaluation of mucin-like carcinoma associated antigen (MCA) in breast cancer.

Serum levels of mucin-like carcinoma associated antigen (MCA) were measured in 80 healthy women, 109 patients with breast cancer at presentation and in samples taken from 45 patients with active metastatic breast cancer. The MCA levels in controls had an upper limit of normal of 19.6 U ml-1 in post-menopausal and 16.4 U ml-1 in premenopausal women. The levels at presentation in stages I and II and III were not significantly different from the post-menopausal controls. Longitudinal studies over 5-9 years in 20 patients with stage I and II disease who had remained tumour-free showed a narrow MCA range for each individual patient, but the mean and range of a single measurement in a further 63 of these patients were similar to those of the normal controls. Rising MCA levels occurred in 12/14 patients who developed metastases in 2-8 years after surgery, but local recurrence was not associated with a rise of MCA. Eighty per cent of patients with active metastatic disease had MCA levels greater than 15 U ml-1. MCA levels fell during clinical responses to therapy in metastatic cancer. In the context of follow-up serum MCA levels appear to be a sensitive indicator of metastatic disease; caution is required in the interpretation of isolated measurements.

Antigens, Neoplasm↗

The cloning and expression in Escherichia coli of sequences coding for p24, the core protein of human immunodeficiency virus, and the use of the recombinant protein in characterizing a panel of monoclonal antibodies against the viral p24 protein.

The sequences encoding the p24 core protein of human immunodeficiency virus type 1 were identified in a cDNA library made from infected CEM cells. The nucleotide sequence of the DNA coding for p24 was shown to be very similar but not identical to the sequences of lymphadenopathy virus and human T-cell leukaemia virus type IIIb. These sequences were expressed in Escherichia coli at the amino terminus of beta-galactosidase and used to screen a panel of monoclonal antibodies raised against virus-expressed p24. Regions containing the epitopes of five of the monoclonal antibodies were located using a series of amino- and carboxy-terminal deletion mutants of the recombinant p24 protein.

Blotting, Western↗

Hyperactivity in a group of children referred to a Scottish Child Guidance Service: a significant problem.

This study tested the hypothesis that if the same measure of hyperactivity was used a similar proportion of children in Britain referred for child guidance advice would be found to be hyperactive as in North America. Conners' Teacher Rating Scale for hyperactivity was completed for 89 of the first 100 primary school children referred in one school year to a schools' psychological service. The rating scale was also completed for a matched control group. A significant difference was found between the hyperactivity ratings of the two groups. Of the referred children 42.7 per cent were rated as hyperactive, similar to the reported incidence in North America.

Attention Deficit Disorder with Hyperactivity↗

Activation of the c-H-ras proto-oncogene by retrovirus insertion and chromosomal rearrangement in a Moloney leukemia virus-induced T-cell leukemia.

A rearrangement of the c-H-ras locus was detected in a T-cell line (DA-2) established from a Moloney leukemia virus-induced tumor. This rearrangement was associated with the high-level expression of H-ras RNA and the H-ras gene product, p21. DNA from DA-2 cells transformed fibroblasts in DNA transfection experiments, and the transformed fibroblasts contained the rearranged H-ras locus. The rearrangement involved one allele and was present in tissue from the primary tumor from which the cell line was isolated. Cloning and sequencing of the rearranged allele and comparison with the normal allele demonstrated that the rearrangement was complex and probably resulted from the integration of a retrovirus in the H-ras locus between a 5' noncoding exon and the first coding exon and a subsequent homologous recombination between this provirus and another newly acquired provirus also located on chromosome 7. These events resulted in the translocation of the coding exons of the H-ras locus away from the 5' noncoding exon region to a new genomic site on chromosome 7. Sequencing of the coding regions of the gene failed to detect mutations in the 12th, 13th, 59th, or 61st codons. The possible reasons for the complexity of the rearrangement and the significance of the activation of the H-ras locus to T-cell transformation are discussed.

Alleles↗

Effect of suckling and diurnal influences on the concentrations of taurine and other free amino acids in milk.

Factors affecting the taurine and free amino acid content of human milk from a single donor have been examined. Taurine concentration was highest during the transition from colostrum to milk, attaining 400 microM. Concentrations fell thereafter, reaching 150 microM at 115 d post partum. Other free amino acids showed an opposite developmental pattern. Samples collected immediately after infant feeding were systematically lower in taurine than those collected immediately before feeding, but the differences were relatively small. Concentrations of other amino acids were unaffected by suckling on day 4. On day 6, however, decreases ranged from 16 per cent for glutamate to 46 per cent for threonine. Samples collected every 2 h over a 72-h period on days 113 to 115 post partum showed no diurnal variation in taurine content, neither did samples collected over a 24-h period on days 4, 6, 11, and 12. Serine and glycine showed a similar lack of periodicity. Aspartate, alanine, glutamine, threonine and glutamate levels, on the other hand, were lowest in the early morning, and highest in the early afternoon. High to low ratios ranged from 1.7 for glutamate to 4.1 for aspartate. Sample collection for taurine, serine and glycine analysis can probably be made without concern as to time of day or relationship to infant feeding. For the other amino acids, however, these factors need to be considered.

Adult↗

Use of narcotic antagonists to modify stereotypic self-licking, self-chewing, and scratching behavior in dogs.

We evaluated 2 narcotic antagonists, naltrexone and nalmefene, for treatment of refractory self-licking, self-chewing, and scratching behavior in dogs. Eleven dogs with various irritative or pruritic disorders were medicated with naltrexone (1 mg/kg of body weight, sc) or nalmefene (1 to 4 mg/kg, sc), after a period of control observation during which the dogs had not been medicated. The time for which the dogs were involved in self-licking, self-chewing, or scratching was determined retrospectively by analysis of videotapes. The rates of involvement in either activity before and after treatment were calculated and compared statistically. Treatment with a narcotic antagonist significantly reduced the time spent self-licking, self-chewing, or scratching in 7 of 11 dogs, was partially effective in 3 dogs, and was ineffective in one dog. Dogs with acral lick dermatitis responded most to treatment.

Animals↗

Structure and expression of the guinea-pig alpha-lactalbumin gene.

The entire guinea-pig alpha-lactalbumin gene was isolated from a genomic DNA library constructed in the bacteriophage lambda L47. The complete nucleotide sequence of the gene and its immediate 5' and 3' flanking sequences were determined and compared with those of the human and rat alpha-lactalbumin genes. This demonstrates that the size, organization and sequence of the exons is highly conserved between species, and reveals the presence of the highly conserved potential regulatory 'milk box' consensus sequence [RGAAGRAAA(N)TGGACAGAAATCAA(CG)TTTCTA] between positions -140 and -110 relative to the transcriptional start point. A guinea-pig LINE repeat sequence was also present in the 5' flanking region between positions -520 and -1195. Transfection of the alpha-lactalbumin gene cloned in a bovine papilloma virus vector into the mouse C127 and human MCF-7 mammary tumour cell-lines gave rise to stable but seemingly constitutive expression of alpha-lactalbumin. Expression was from the correct transcriptional start point, resulting in the accumulation of correctly processed mRNA and the secretion of alpha-lactalbumin into the culture medium.

Animals↗

Human recombinant insulin-like growth factor I. I. Development of a serum-free medium for clonal density assay of growth factors using BALB/c 3T3 mouse embryo fibroblasts.

A serum-free clonal density growth assay was developed for the quantification of the biological activity of human recombinant insulin-like growth factor I (IGF-I). The assay measures IGF-I stimulated growth of Balb/c 3T3 cells cultured over 4 d on poly-D-lysine-coated plastic surfaces in a serum-free medium formulation composed of a 1:1 (vol/vol) mixture of Ham's F12 and Dulbecco's modified Eagle's media, supplemented with 3.0 ng/ml bovine basic fibroblast growth factor (bFGF), 10 micrograms/ml human transferrin, 100 micrograms/ml ovalbumin, and 1.0 microM dexamethasone. Low-temperature trypsinization of serum-supplemented stock cultures combined with the use of poly-D-lysine-coated plates made it unnecessary to use serum or fibronectin to promote cell attachment and survival. Serum-free growth conditions were optimized with respect to the concentrations of the supplements. Addition of IGF-I resulted in 3.5-fold more cells than control cultures without IGF-I after 4 d. Deletion of BFGF resulted in no IGF-I stimulation of growth. The concentrations of various preparations of IGF-I required to achieve one-half maximal stimulation of cell number (ED50) ranged between 1.25 and 4.7 ng/ml. In parallel assays, IGF-I was 6.6 times more potent than human recombinant insulin-like growth factor II and 32 times more potent than insulin. When cells were seeded into medium containing IGF-I, transferrin, ovalbumin, and dexamethasone but no bFGF, growth was minimal. Dose-response addition of bFGF showed an ED50 of 0.9 ng/ml. The methods reported are useful to monitor the biological potency of recombinant and natural-source growth factors as well as providing a new means of studying the multiple growth factor requirements of Balb/c 3T3 cells in culture.

Animals↗

Human recombinant insulin-like growth factor I. II. Binding characterization and radioreceptor assay development using Balb/c 3T3 mouse embryo fibroblasts.

The binding of human recombinant insulin-like growth factor I (IGF-I) to BALB/c 3T3 mouse embryo fibroblasts has been characterized, resulting in the development of a radioreceptor assay. Binding of radioiodinated IGF-I (125I-IGF-I) to washed monolayers of BALB/c 3T3 cells was specific, time dependent, and stable, being maximal after a 10-h incubation at 15 degrees C with no loss of bound ligand or cells through 25 h. Scatchard analysis identified a class of high affinity binding sites with Kd = 59.6 pM and an estimated 1.57 X 10(5) receptors/cell. Half-maximal displacement of bound 125I-IGF-I occurred with 15 to 20 ng/ml unlabeled IGF-I competitor. Insulin-like growth factor II and insulin were far less effective competitors, providing half-maximal displacement at concentrations of 130 to 170 ng/ml and 2 to 3 micrograms/ml, respectively. Epidermal growth factor, transforming growth factor type alpha, and acidic and basic fibroblast growth factors did not compete for 125I-IGF-I binding at 1 microgram/ml. Cells fixed with glutaraldehyde before ligand binding did remain attached to culture dishes more tightly; however such pretreatment destroyed approximately 70% of ligand binding. Crosslinking data indicated that 125I-IGF-I binds specifically to a 330-kDalton receptor as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. This receptor dissociated into 130-kDalton subunits when analyzed in the presence of dithiothreitol.

Animals↗

Forensic dental training in Australia.

To facilitate in the identification of victims of a major disaster a trained dental manpower reserve is required. In the state of New South Wales, Australia, an annual three-day training course has been designed to familiarize dentists from both the public and private sectors with identification techniques. The course is aimed to preserve the flexibility of personnel so that they can be utilized in a variety of roles rather than rigidly structuring the make up of a team. It is envisaged though, that in a mass disaster situation teams would be specialized into dental autopsy, antemortem or comparison roles.

Disaster Planning↗

Improved sensitivity in bone scintigraphy using quantitative spinal profile analysis.

Full-length skeletal scintiscans were acquired onto a data processor in a series of 256 X 256 matrices. A series of interactive computer programs enables the operator to select profiles down the spine and to standardize them by interpolation to a standard length and by normalization to a given count level. The counts within any section of a profile can then be calculated and the profile examined for any significant deviation from a reference 'normal' curve. In a study of 68 patients, 66% of the spinal profiles were judged abnormal, compared with 26% of scans assessed by visual inspection alone. Of 14 patients with positive profiles and negative or equivocal visually assessed scans, 11 had developed metastases within 14 months of the scan. All five patients with positive profile and raised alkaline phosphatase have died of metastatic disease. The technique appears to increase the sensitivity of bone scintigraphy.

Bone Neoplasms↗

A comparison of the random-zero and standard mercury sphygmomanometers.

Both the standard mercury sphygmomanometer and the random-zero sphygmomanometer have been used in epidemiological studies and clinical trials. Problems arise in comparing studies since, in addition to other methodological differences, the readings obtained with the random-zero sphygmomanometer have been found to be lower than those obtained with the standard mercury sphygmomanometer. In the present study, blood pressures were measured in 66 subjects to examine the comparability of findings with the two instruments. Trained observers measured blood pressures simultaneously using a double-headed stethoscope and one cuff connected to the two sphygmomanometers. Use of instrument was randomly assigned for each blood pressure measurement; each observer was unaware of the other's blood pressure reading. Readings were lower with the random-zero sphygmomanometer; mean difference ranged from 2.5 to 3.3 mm Hg for systolic pressure and 1.9 to 2.7 mm Hg for diastolic pressure. Digit distributions recorded by the two observers for the standard mercury sphygmomanometer and the random-zero sphygmomanometer were not significantly different for either systolic or diastolic blood pressure. Intraindividual variation was greater with the random-zero sphygmomanometer than with the standard mercury sphygmomanometer. These data do not indicate that one instrument is clearly superior to the other, although in studies where the observer seeks to reduce the bias of multiple readings per person, the random-zero sphygmomanometer may be the more appropriate instrument. Critical to the use of either instrument are careful training, standardization, certification, and periodic recertification of observers.

Adult↗