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Biomedical subjects

D King

Publications and source records attributed to D King.

At least 19 recordsLinked to original sources
PubMed1992

Antigen-specific activity of carcinoma-reactive BR64-doxorubicin conjugates evaluated in vitro and in human tumor xenograft models.

The anticarcinoma antibody BR64 was conjugated to a doxorubicin derivative, doxorubicin 13-[3-(2-pyridyldithio)propionyl]hydrazone, and the resulting conjugates (BR64-DOX) were evaluated for activity and immunological specificity in vitro and in human tumor xenograft models. The BR64-DOX immunoconjugates retained immunoreactivity and cytotoxicity and demonstrated antigen-specific cytotoxicity in vitro. The potency of BR64-DOX immunoconjugates in vitro was related to the drug:monoclonal antibody mole ratio of the conjugates. The antitumor activity of BR64-DOX conjugates was consistently superior to the maximal activity obtained with the parent drug, doxorubicin (DOX), in established human lung and human breast carcinoma xenograft models. The superior antitumor activity of BR64-DOX conjugates was reflected both in tumor growth inhibition and in regressions and cures of established tumors following the administration of tolerated doses of BR64-DOX. The antitumor activity of BR64-DOX conjugates was not the result of synergism between monoclonal antibody BR64 and DOX, because mixtures consisting of monoclonal antibody and optimized DOX were not more active than an equivalent dose of DOX administered alone. The antitumor activity of BR64-DOX conjugates was antigen specific; equivalent doses of nonbinding isotype-matched conjugates were not active against established tumor xenografts.

Adenocarcinoma↗
PubMed1992

The neuroretinal rim in descending optic atrophy.

We studied seven human eyes in which the changes of the neuroretinal rim areas following complete loss of all axons could be measured planimetrically. The mean diminution of the neuroretinal rim area was 40% (range from 26-72%). The optic nerve pathology causing the loss of axons was in the posterior portion of the nerve and the optic disc was therefore not directly disturbed by the injuries. It appears that less than half of the neuroretinal rim is occupied by nerve fibers.

Axons↗
PubMed1992

High-level expression of a recombinant antibody from myeloma cells using a glutamine synthetase gene as an amplifiable selectable marker.

We report a method for introducing a glutamine synthetase (GS) selectable marker into myeloma cells in which transfectants are selected by growth in a glutamine-free medium. Vector amplification can subsequently be selected using the specific inhibitor of GS, methionine sulphoximine (MSX). Using this system, DNA sequences encoding a chimeric B72.3 IgG4 antibody were expressed from hCMV-MIE promoters in NSO myeloma cells. A cell line was isolated after a single round of selection for vector amplification which contains approximately 4 copies of the vector, secretes 10-15 pg/cell/day cB72.3 antibody during exponential growth and can accumulate 560 mg/l antibody in a fed-batch air-lift fermentation system. Productivity is stable in the absence of MSX selection.

Animals↗
PubMed1992

Attitudes of elderly patients to medical students.

The attitudes of elderly patients towards clinical teaching of medical students was assessed by a structured interview carried out by a doctor unknown to the patient immediately prior to discharge. One hundred and thirty alert patients were approached on three acute geriatric medicine wards in the Royal Liverpool (Teaching) Hospital. A total of 106 (81.5%) patients were suitable for inclusion in the study (mean age, 80.2 years). Twenty-nine per cent did not know what a medical student was despite having been interviewed and examined by one. Fifty-nine per cent of patients had no prior knowledge that clinical teaching occurred. Fourteen patients (13 women, 1 man, P < 0.05) objected to being examined. Nineteen women patients were examined by a man student without a chaperone. Students usually (95%) asked permission to interview and examine the patients whereas doctors only asked patients in the context of bedside teaching (33%). Elderly patients were sympathetic towards ('They have to learn') and positive about ('It's good to have them') medical students. However, 29% of patients were not aware that a medical student was going to be a doctor despite being interviewed and examined. We suggest that the term should be used either with explanation or abandoned in favour of 'student doctor'. The level of awareness of clinical teaching was poor and examination of women patients without a chaperone caused distress and should be rectified.

Aged↗
PubMed1992

The law and medical fitness to drive--a study of doctors' knowledge.

We assessed doctors' knowledge on laws and recommendations regarding fitness to drive in certain medical conditions by a questionnaire survey. A total of 646 doctors consisting of 400 general practitioners and 246 hospital doctors of all grades were circulated with the questionnaire. The survey was anonymous so non-responders could not be re-circulated. The response rate was 26% general practitioners and 32% (hospital doctors). The results show the poor knowledge of doctors on several aspects of fitness to drive. It is necessary for all doctors to have a basic knowledge on the laws and recommendations on fitness to drive so that they can advise their patients correctly. Our survey clearly shows that doctors' knowledge is poor. Many drivers may therefore be placing themselves and others at risk. It is mandatory that this subject receives more attention in undergraduate and postgraduate education and that doctors should be regularly updated on new recommendations from the Driver and Vehicle Licensing Agency.

Automobile Driving↗
PubMed1992

Concentrations of vitamins A, C and E in elderly patients with Parkinson's disease.

Concentrations of the naturally occurring antioxidant vitamins A, C and E were measured in 27 patients with Parkinson's disease and 16 age-matched control subjects, from a similarly disabled patient group. There was no significant difference in the serum concentrations of vitamins A and E in the two groups. Vitamin C was significantly higher (P < 0.05) in the Parkinson's disease group, however, the mean leucocyte vitamin C concentration in the control group was low (101 nmol/10(8) WBCS) compared to established data in healthy young individuals (119-301 nmol/10(8) WBCS). There was no correlation between the severity or duration of Parkinson's disease and concentrations of vitamins A, C and E. There is therefore no evidence from this study that a deficiency of these antioxidants contributes to the onset or progress of Parkinson's disease.

Aged↗
PubMed1992

Viral inactivation in blood and red cell concentrates with benzoporphyrin derivative.

Using both the vesicular stomatitis virus (VSV) and feline leukemia virus (FeLV) as models we have shown that the photosensitizer benzoporphyrin derivative ring A (BPD), when activated with red light (600-700 nm), is effective in eliminating both free virus and virally infected cells from spiked blood products and whole blood drawn from viremic cats experimentally infected with FeLV, under conditions which appear to share red blood cells. The effect of photodynamic therapy on infected lymphocytes, as visualized by scanning electron microscopy, initially appeared as a limited area of tiny holes in the membrane. These holes were subsequently seen to increase in size until the membrane appeared completely decomposed. The red cell membranes however, seem to be undamaged by such photodynamic treatment.

Animals↗
PubMed1992

Doctors' knowledge of socio-legal aspects of patient care.

Doctors' knowledge of socio-legal aspects of patient care is poor. To quantify this a questionnaire on certain socio-legal topics was sent to 400 general practitioners and 250 hospital doctors. The responses were compared to a group of social workers. Both hospital doctors and general practitioners did badly on all topics considered. Social workers' knowledge was significantly better overall, (P < 0.01). Our results confirm the lack of knowledge amongst a broad spectrum of doctors. We suggest that this may be related to a lack of emphasis on these aspects in both undergraduate and postgraduate education.

Aged↗
PubMed1991

Pharmacokinetics and immune response of 131I-chimeric mouse/human B72.3 (human gamma 4) monoclonal antibody in humans.

Chimeric B72.3, composed of the V-regions of murine B72.3 and the constant regions of human immunoglobulin G4 heavy and kappa light chain, was administered as a 131I-labeled conjugate to 12 patients with metastatic colon cancer. Seven of these patients had an antibody response after initial infusion, and the immune response was primarily directed to the murine V-region, although a small proportion of the antibody response was directed to topographical epitopes requiring the presence of both murine V-region and human CH-1 and kappa constant regions (neo-epitopes). The pharmacokinetics included a plasma disappearance curve best fit by a two-compartmental model with an alpha t 1/2 of 18 +/- 7 h and a beta t 1/2 of 224 +/- 66 h. A second infusion of the same dose of 131I-chimeric B72.3 was administered to four of these patients 8 wk after the first infusion. Two patients who had a high antibody response to initial infusion had an anamnestic antibody response, and the infused ch-B72.3 rapidly disappeared from the circulation with associated immune complexes and free 131I in the plasma. One patient with no initial antibody response had no antibody response and identical pharmacokinetics on second infusion. One patient with a modest transient antibody response to initial infusion had no antibody response on second infusion and a modest shortening of plasma circulation. Thus, the human immunoglobulin G4 isotype chimeric B72.3 monoclonal antibody has a plasma half-life 6 to 8 times as long as murine B72.3 and retains considerable immunogenicity in some patients which can adversely affect repetitive infusions.

Animals↗
PubMed1991

Pressurised aerosol inhalers: the cost of misuse.

Bronchodilator aerosols, if used correctly, have many advantages over other therapies in patients with chronic airflow limitation caused by asthma or chronic bronchitis. The use of pressurized aerosol inhalers was examined in a district general hospital: of 57 patients on these inhalers, 39 were unable to use the inhaler effectively, and 23 had never received any advice on inhaler technique. A single demonstration of correct technique decreased the failures to 21 patients and, after two demonstrations, to ten. The cost of the misused inhalers in this relatively small population was 450 pounds, and obviously this figure escalates when the prescription for these inhalers is repeated monthly. It is also increased when the total numbers of misused inhalers in the country are accounted for. The cost in terms of finance, in these days of medical audit and drug budgets, and, more importantly, in terms of patient health, is unacceptable and can be avoided by repeated tuition of technique.

Adult↗
PubMed1990

Direct sequencing of PCR-amplified junction fragments from tandemly repeated transgenes.

When microinjected foreign genes integrate into the genomes of mice, multiple copies are frequently found clustered together at one location. How they concatamerize--by the integration of large linearized concatamers that are formed by simple end-to-end linkage, by circularization of individual DNA fragments and recombination, or by some other means--is not understood. In the transgenic animals studied thus far by ourselves and others, integration frequency and transgene copy number do not seem to be significantly influenced by the complementarity of the ends of the DNA fragments that have been microinjected. We have utilized PCR amplification and DNA sequence analysis to study selected transgene junctions at the nucleotide level. In two transgenic mice carrying the synthetic RSVcat gene (injected with noncomplementary overhangs on the fragment ends), ends were 'nibbled' from 1 to 62 bases before being joined to an adjacent gene copy. Repeated dinucleotides, providing the most minimal of homologies, are present in half of the characterized junctions. Determination of the relative copy number of the junctions in each mouse supports the idea that transgene complexes can undergo additional rearrangements after the initial formation event.

Animals↗
PubMed1990

Establishment of immortalized primate epithelial cells with sub-genomic EBV DNA.

The genetic information in a sub-fragment of EBV DNA, designated p31 (containing less than a quarter of the viral genome and derived from a recombinant DNA cosmid library) allows epithelial cells from primary monkey and human kidney cultures to escape senescence under standard tissue culture conditions. A number of epithelial cell lines, designated M1/31, 483/31, 199/31 and HK/31, have been established and characterized following transfection of primary cells with p31 DNA. They share many properties, although morphologically they are not all identical. The cultures are immortalized but not fully transformed or tumorigenic. They appear to be phenotypically stable, although DNA hybridization studies indicate that genotypic alterations, including amplification, occur subsequent to transfection with p31 DNA and the establishment of a continuously proliferating epithelium. All cell lines consistently express high levels of cytokeratin 18 and varying amounts of cytokeratin 7, demonstrating their epithelial origin. From a single marmoset kidney (designated 199) a series of related immortalized cells, with subtle phenotypic differences, have been generated by p31 or sub-fragments of it. Although hallmarks of a "hit-and-run" mechanism are apparent in all of our studies, 2 different techniques (in situ hybridization or selection for cell survival in semi-solid media, followed by nucleic acid hybridization) show that, in late-passaged cultures, a small proportion of the cells still contain some viral DNA. The studies focus on genetic information within the BamHI A and I regions as being relevant to immortalization. The role of the EBV DNA fragment in the genesis of epithelial cell lines is considered.

Animals↗