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Biomedical subjects

E J Hall

Publications and source records attributed to E J Hall.

At least 19 recordsLinked to original sources
PubMed1992

Taxol sensitizes human astrocytoma cells to radiation.

Taxol is a chemotherapeutic drug which acts by stabilizing microtubules, preventing normal mitosis and resulting in a block of the cell cycle at G2 and M. The drug is isolated from the yew, Taxus sp. L., and is currently being evaluated in a series of Phase II and Phase III clinical trials. Taxol blocks cells in the most radiosensitive phases of the cell cycle and thus could act as a cell cycle-specific radiosensitizer. We report the results of combined taxol-radiation exposures in the human Grade III astrocytoma cell line, G18. Taxol is a potent inhibitor of G18 cell division; a concentration of 10 nM is cytostatic for a cell population observed for at least two doubling times. Cell survival curves for G18 cells showed a significant concentration-dependent interaction between taxol and radiation. Treatment of G18 cells with a fixed taxol concentration and radiation dose showed the interaction to be dependent on the duration of taxol exposure and consequently the fraction of cells in the G2 or M phase of the cell cycle. The sensitizer enhancement ratio for 10 nM taxol at 10% survival is 1.8 and, for 1 nM taxol, it is 1.2. These results suggest that appropriate combinations of taxol have a more than additive interaction in human tissue culture and may have a role in clinical protocols.

Alkaloids↗
PubMed1992

Use of lithium for treatment of estrogen-induced bone marrow hypoplasia in a dog.

Marrow hypoplasia and consequent pancytopenia caused by simultaneous administration of estradiol cyclopentylpropionate and diethylstilbestrol were diagnosed in a 6-year-old Old English Sheep-dog. The dog was treated with lithium carbonate (11 mg/kg of body weight, PO, q 12 h) for 6 weeks. Despite the generally grave prognosis associated with estrogen toxicosis, lithium treatment was apparently successful in inducing regeneration of the bone marrow. Side effects of lithium treatment were not noticed.

Amoxicillin↗
PubMed1992

Boxer colitis.

Explore the source record for details and available documents.

Animals↗
PubMed1992

Immune responses to dietary antigens in gluten-sensitive enteropathy of Irish setters.

This study examined whether increased intestinal permeability in Irish setters with gluten-sensitive enteropathy was associated with altered immune responses to ingested antigens, and whether a humoral immune response to gluten is involved in the pathogenesis of the condition. Affected setters reared on a wheat-containing diet were compared with littermates reared on a cereal-free diet and age-matched control setters. Measurement of serum immunoglobulins revealed increased serum IgA concentrations in affected dogs. Antibody responses to a variety of dietary antigens were measured by ELISA. Antibody levels to ovalbumin, collagen I and II and soya were not significantly different from normal dogs. Anti-gliadin antibody concentrations were lower in affected dogs than controls, and correlated with immune complex formation as assessed by C1q binding. The study suggested a modified immune response in dogs with increased intestinal permeability, although there was no major systemic antibody response to dietary antigens.

Animals↗
PubMed1992

Oncogenic transforming potential of etanidazole.

The 2-nitroimidazole etanidazole is in Phase III randomized trials as an adjunct to radiotherapy in both the United States and Europe. Paradoxically, it is one of the more oncogenic radiosensitizers examined with the in vitro oncogenic transformation assay based on C3H 10T1/2 cells. To obtain an estimate of the possible number of second malignancies that might be induced in patients receiving the drug, the in vitro transformation assay was used to compare etanidazole with gamma-rays, for which cancer risk estimates are available from the Japanese survivors. For the clinical protocol used in RTw] studies, which results in a cumulative dose of 36 mM hr, the drug-induced cancer incidence was estimated to be 2.8 to 14%.

Animals↗
PubMed1992

Mechanism of oncogenicity for bioreductive drugs.

The oncogenic transforming potential of a series of bifunctional bioreductive drugs were examined under either aerated or hypoxic conditions to assess the contribution of side chains or nitroreduced products toward their carcinogenic mechanisms. Both the cytotoxicity and transforming effects of these drugs increased as a function of dose under hypoxia. In air and at doses that resulted in comparable cell killing, RSU-1069 and RB-88716 were substantially more oncogenic than RSU-1164 or SR-4233. In nitrogen, the oncogenicity of SR-4233 as a function of survival increased, whereas the transforming effect for the aziridine-containing drugs, RSU-1969 and RB-88716, decreased. These data suggest that, among the drugs examined, the transforming moiety in air is largely a function of the alkylating aziridine group. In hypoxia, the reduction of the nitro-moiety to the corresponding active metabolites may be responsible for much of the transformation observed.

Animals↗
PubMed1992

Taxol: a novel radiation sensitizer.

The investigational antineoplastic agent, taxol, a natural product from the yew, Taxus sp. L., is currently being evaluated in a series of Phase II clinical trials. To date, the drug has shown activity against ovarian cancer, lung cancer, and melanoma. Taxol is a potent microtubule stabilizing agent that selectively blocks cells in the G2 and M phases of the cell cycle and is cytotoxic in a time-concentration dependent manner. It is well known from radiobiological principles that G2 and M are the most radiosensitive phases of the cell cycle. On the rationale that taxol could function as a cell-cycle selective radiosensitizer, we examined the consequences of combined drug-radiation exposures on the human grade 3 astrocytoma cell line, G18. Survival curve analysis shows a dramatic interaction between taxol and ionizing radiation with the degree of enhanced cell killing dependent on taxol concentration and on the fraction of cells in the G2 or M phases of the cell cycle. The sensitizer enhancement ratio (SER) for 10 nM taxol at 10% survival is approximately 1.8. These results obtained with cycling aerated radioresistant brain tumor cells indicate that significant advantage may derive from appropriate time-concentration dependent interactions in combined modality protocols.

Alkaloids↗
PubMed1992

The 1991 George Edelstyn Memorial Lecture: needles, wires and chips--advances in brachytherapy.

The majority of quantitative data on the effects of dose-rate come from experiments with cultured cells in vitro. These data are reviewed, and it is concluded that results obtained from the in vitro experience may be carried over, in a quantitative manner, to guide clinical radiotherapeutic design. As an example, there are contradictory guidelines suggested to compensate for changes in dose-rate in interstitial wire-implant brachytherapy. The Paris group has suggested no dose correction is required for implant times from 3 to 8 days, while the Paterson/Ellis school suggests a significant correction. It is shown that, based on known radiobiological principles, this controversy can be resolved. These same radiobiological notions, as well as advances in computer technology, have led to the technique of pulsed brachytherapy, which allows the average dose-rate to be maintained at a constant rate, even when the wire activities have decayed.

Brachytherapy↗
PubMed1992

The development of cortico-motoneuronal projections investigated using magnetic brain stimulation in the infant macaque.

1. The effects of magnetic brain stimulation on electromyographic (EMG) activity recorded from arm and hand muscles have been investigated in five infant and six adult macaque monkeys under ketamine sedation. 2. In the adults, brief, short-latency EMG responses could be readily evoked with magnetic stimuli of 40-50% of the maximum stimulator output (1.5 T). 3. In a cross-sectional study of five infant macaques, it was difficult to evoke EMG responses in young infants (less than 5 months old). Clear short-latency responses were first evoked in an animal 5.75 months old. This change was accompanied by an increase in the probability of occurrence of the responses. 4. In a longitudinal study of two infant monkeys over a period ranging from 2.5 to 14.5 months of age we found that clear short-latency responses were first evoked at 4 and at 5.5 months, respectively. In both animals there was a steady fall in response threshold which reached the adult range at 6.5 and 8 months, respectively. EMG responses in animals older than 8 months were indistinguishable from those in adults. 5. In the longitudinal study we also noted that the latency of EMG responses to magnetic brain stimulation declined with age. Since there were no comparable changes in the peripheral conduction time in these animals, we attribute this result to a decrease in central conduction time. 6. Parallel behavioural observations of the natural behaviour of the same animals within a colony indicated that mature precision movements of the fingers were not used until 5-6 months of age. 7. In two adult monkeys, the latency of EMG responses evoked in the extensor digitorum and first dorsal interosseous muscles by direct stimulation of the corticospinal tract, via electrodes implanted in the medullary pyramids, was found to be 0.7-1.7 ms shorter than that of responses evoked by magnetic stimuli. It is argued that at least the earliest component of these latter responses is conducted over the cortico-motoneuronal pathway. 8. The mechanisms likely to contribute to the late appearance of EMG responses to brain stimulation are discussed. One of these is probably the establishment of mature cortico-motoneuronal connections, which are not present at birth.

Aging↗
PubMed1992

Dietary modulation of gluten sensitivity in a naturally occurring enteropathy of Irish setter dogs.

Gluten sensitivity in a naturally occurring enteropathy of Irish setter dogs, and the effects of excluding dietary cereal from birth on the subsequent response to gluten challenge were investigated. Peroral jejunal biopsy specimens were obtained at 1 year of age for morphometric and biochemical examinations, and intestinal permeability was assessed using 51Cr-ethylenediaminetetraacetic acid. Affected setters, reared on a normal wheat containing diet, exhibited partial villus atrophy, intraepithelial lymphocyte infiltration, reduced brush border alkaline phosphatase activity, and increased intestinal permeability. Gluten sensitivity was shown by introduction of a gluten free diet, which resulted in resolution of morphological and biochemical abnormalities and decreased intestinal permeability, and subsequent gluten challenge, which resulted in relapse. In contrast, littermates reared exclusively on a cereal free diet showed minimal changes when challenged with gluten, apart from intraepithelial lymphocyte infiltration. These findings document a gluten sensitive enteropathy in Irish setters and indicate that exclusion of dietary cereal from birth may modify subsequent expression of the disease.

Alkaline Phosphatase↗
PubMed1992

Biological intercomparisons of neutron beams used for radiotherapy generated by p(+)-->Be in hospital-based cyclotrons.

The new generation of hospital-based neutron therapy facilities involve cyclotrons using protons on beryllium. The spectrum of neutrons produced includes a large and variable proportion of low-energy neutrons that are poorly penetrating but biologically effective. Cells cultured in vitro were used to compare the three US facilities at Seattle, M.D. Anderson and UCLA, together with the UK facility at Clatterbridge. Cyclotrons were compared within a given experiment on the same day using cells from a common suspension. Among the three US facilities, the relative potency factor at a depth of 25 mm differs by about 11%, with Seattle the least and UCLA the most biologically effective. Clatterbridge was compared directly with M.D. Anderson and found to be less effective by about 5%; it has a slightly lower biological effectiveness than any of the US facilities. There is evidence for an increased biological effectiveness in the build-up region, which reduces the effective skin sparing potential. There is not much difference in build-up between the three US facilities. Using the proton-on-beryllium neutron production process results in a wide spectrum of neutrons with a large but variable low-energy component. The biological effectiveness of the beam depends on target design and thickness as well as the design of the collimating system. Consequently the biological effectiveness of neutron beams generated by this process must be assessed on an individual basis. It cannot be assumed that because cyclotrons have similar accelerating energies that the relative biological effectiveness will be the same.

Animals↗
PubMed1992

The dose-rate effect in interstitial brachytherapy: a controversy resolved.

Low-dose-rate interstitial implants generally involve a range of dose rates varying from about 0.3 to 1.5 Gy/h. It has been a matter of some debate as to whether such a variation in dose rate has any impact on clinical results, i.e. whether implant treatment time needs to be taken into account when prescribing the treatment dose. In particular, Paterson and Ellis both published data based on clinical experience suggesting that the prescribed dose should vary with overall treatment time, whereas the Paris school suggested that isoeffect dose should not be varied for treatment times between 3 and 8 days. Experimental radiobiological data obtained in vitro and in vivo imply a significant change in biological effectiveness over this range of dose rates with a greater variation for normal-tissue late effects than for tumour control. We show, based on radiological considerations and model calculations, that the disagreement between the two schools in their recommendations for generating isoeffect doses for different treatment times was a result of two factors. First, the Paterson recommendation was unequivocally based on matching limiting late effects, whereas the Paris system recommendations were based on an analysis of a combination of late and early effects. Second, the Paterson recommendations were based on a dosimetry system in which the dose rate does not change greatly with tumour volume, whereas the Paris recommendations were based on a dosimetric system in which dose rate is correlated with tumour volume, which in turn is correlated with changes in both tumour control and, especially, necrosis.

Animals↗
PubMed1992

Small intestinal bacterial overgrowth and enhanced intestinal permeability in healthy beagles.

The small intestine of healthy adult Beagles was examined to determine whether subclinical abnormalities might exist that would be relevant to the use of Beagles in pharmacologic studies. Duodenal juice was obtained for qualitative and quantitative bacteriologic examinations; jejunal mucosa was taken for morphologic and biochemical investigation, and intestinal permeability was assessed by quantification of 24-hour urinary excretion of 51Cr-labeled EDTA after its oral administration. Comparisons were made with findings in healthy adult dogs of other breeds that served as controls. Small intestinal bacterial overgrowth was found in 14 of the 21 Beagles examined, and represented a mixed flora that included obligate anaerobic bacteria in 8 dogs and exclusively aerobic bacteria in 6 dogs. Intestinal permeability (percentage urinary recovery of 51Cr-labeled EDTA; mean +/- SEM) was considerably higher (P < 0.01) in Beagles with anaerobic overgrowth (37.6 +/- 3.2%) or aerobic overgrowth (30.5 +/- 4.8%), compared with Beagles with no overgrowth (17.3 +/- 1.6%) and with controls (11.1 +/- 1.0%). In Beagles, significant (r = 0.54, P = 0.03) correlation was observed between 24-hour urinary recovery of 51Cr-labeled EDTA and bacterial numbers in duodenal juice. Morphologic changes in jejunal mucosa were minimal, and specific activities of brush border enzymes were not significantly decreased, apart from aminopeptidase N, but activities of lysosomal and endoplasmic reticular marker enzymes were higher in the 3 groups of Beagles with anaerobic, aerobic, or no overgrowth, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗