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Biomedical subjects

P D Holt

Publications and source records attributed to P D Holt.

At least 19 recordsLinked to original sources
PubMed2000

Self-assembling amphiphilic siderophores from marine bacteria.

Most aerobic bacteria secrete siderophores to facilitate iron acquisition. Two families of siderophores were isolated from strains belonging to two different genera of marine bacteria. The aquachelins, from Halomonas aquamarina strain DS40M3, and the marinobactins, from Marinobacter sp. strains DS40M6 and DS40M8, each contain a unique peptidic head group that coordinates iron(III) and an appendage of one of a series of fatty acid moieties. These siderophores have low critical micelle concentrations (CMCs). In the absence of iron, the marinobactins are present as micelles at concentrations exceeding their CMC; upon addition of iron(III), the micelles undergo a spontaneous phase change to form vesicles. These observations suggest that unique iron acquisition mechanisms may have evolved in marine bacteria.

Amino Acids↗
PubMed1999

The track structures of ionizing particles and their application to radiation biophysics. I. A new analytical method for investigating two biophysical models.

A new approach to the interpretation of the effects of radiation on cells is described, in which sample particle tracks are constructed using a Monte Carlo computer program and the exposure of cellular targets to these tracks is simulated using a second program known as BIOPHYS. Data on the shapes and DNA contents of the cell nuclei are obtained from the literature. It is assumed that the sensitive material is DNA, and that the target is divided into cubes of approximately 2 nm (the diameter of the DNA helix) per side; the numbers of these cubes containing different numbers of ionizations are derived. Two different methods of analysing the output of BIOPHYS are described. In the first, it is assumed that lethality is caused by the occurrence of a number of ionizations equal to or greater than a certain threshold in one cube; in the second method, it is assumed that only two ionizations are required, in different parts of the cube, but that only some fraction of the cube is sensitive. These models have been applied to the interpretation of the variation of radiosensitivity with a linear energy transfer (LET) of spores of Bacillus subtilis exposed wet and dry, and good fits to the published experimental data were obtained using both models. Fits to experimental data for a range of other cell lines will be presented in a second paper.

Bacillus subtilis↗
PubMed1999

The track structures of ionizing particles and their application to radiation biophysics. II. Results for various organisms irradiated with protons, deuterons and alpha-particles.

Using knowledge of the track structure generated by ionizing particles together with details of the organisms being irradiated, the application of a new analytical method to two biophysical models to explain the inactivation of cells by radiation has been developed. It is shown that both models are equally successful in predicting experimental results and that good agreement is found with the data for single-strand phage, Bacillus subtilis spores, various strains of Escherichia coli, haploid and diploid yeast, and human diploid fibroblasts. The only significant discrepancy arose with T1-phage, for which a tentative explanation is offered. The differences in inherent radiosensitivity between organisms, after allowance is made for differences in target size, are attributed to differences in enzymatic repair systems and in the packing of the DNA.

Alpha Particles↗
PubMed1997

Consideration of tissue response in the application of the two-mutation model to radiation carcinogenesis.

The Moolgavkar-Venzon-Knudson (MVK) two-mutation model of carcinogenesis is an analytical model that predicts the variation of cancer yield-rate with time, and with dose of a carcinogen. The model is biologically based, and assumes that a specific mutation in a stem-cell will increase its rate of proliferation compared with that of unmutated cells, so that a clone of pre-malignant cells develops; a second specific mutation in any one of these will make it malignant, and a cancer will start to grow. The model has been used in recent years to analyse a number of sets of epidemiological data on carcinogenesis. The purpose of this paper is to point to a problem in the use of this model for radiation-induced carcinogenesis, namely that ionizing radiation causes reproductive death of stem cells, which leads to regenerative division and hence a change in the number of stem-cells at risk. The possible effects of such changes on the predictions of the model are discussed. At low dose-rates of continuous or chronic irradiation and at low doses of acute irradiation, it is expected that pre-malignant cells will be killed along with the unmutated cells, and that the regenerative division of the surviving pre-malignant cells will restore the numbers of both stem cells and pre-malignant cells to what they would have been in the absence of cell killing; hence, no net effect of the tissue regeneration is expected. At high dose-rates, the initial delay in regenerative division and subsequent faster proliferation are expected to lead to an initial reduction in tumour yield-rate with time (compared with that predicted by the MVK model) followed by a faster increase. For acute irradiation, in the particular case of beta-particle irradiation of the skin, at high doses where there are practically no surviving cells in the irradiated area, repopulation by unirradiated cells from the margin is predicted to lead to a decrease in tumour yield-rate with dose. The predictions have been compared with published data on the induction of osteosarcoma in mouse by repeated injection of 89Sr, the induction of skin tumours in rat by acute and chronic irradiation with electrons, and the induction of skin tumours in mouse by acute irradiation with beta-particles. At low doses and dose-rates the basic MVK model fitted the data well. At higher doses and dose-rates the expected effects of tissue regeneration were observed qualitatively, although there were some discrepancies in detail; these are discussed.

Animals↗
PubMed1995

Cat scratch disease: magnetic resonance imaging findings.

Cat scratch disease is an infectious lymphadenitis frequently occurring in children and adolescents. We present the magnetic resonance imaging findings of two patients with this disease. In both cases, lymphadenopathy was characterized by extensive stranding of the surrounding soft tissues, consistent with the inflammatory nature of this condition. Magnetic resonance imaging can be diagnostic and may obviate the need for invasive means of evaluation in patients suspected of having cat scratch disease.

Adult↗
PubMed1995

Strictures after gastric surgery: treatment with fluoroscopically guided balloon dilatation.

OBJECTIVE: Stricture formation resulting in impedance of gastric emptying is a relatively common complication after gastric surgery that involves anastomosis creation or pyloroplasty. Treatment of the stenosis with fluoroscopically guided balloon dilatation avoids further surgery. Accordingly, we report our experience with 32 dilating procedures in 24 consecutive patients who had the postoperative complication of obstruction at a surgically created gastric outlet. MATERIALS AND METHODS: Out of our series of approximately 650 fluoroscopically guided balloon dilatations, 32 procedures were performed on 24 patients with anastomotic strictures or pyloric narrowing after gastric surgery (vertical banded gastroplasty or gastric bypass surgery [n = 15], partial esophagectomy with esophagogastrostomy and pyloroplasty [n = 6], and partial gastrectomy with gastrojejunostomy [n = 3]). The group included 13 men and 11 women ranging from 32 to 79 years old (mean, 51 years). Diameters of the balloons chosen ranged from 10 to 20 mm, depending on the size of the surgically created anastomosis or pyloroplasty. Indications for balloon dilatation were clinical and radiographic evidence of gastric outlet obstruction. The procedures were done between 13 days and 10 years (mean, 14 months) after gastric surgery. The result of each procedure was assessed by evaluating clinical outcome (relief or recurrence of symptoms) during the follow-up period of 2 days to 36 months (mean, 8 months) after the procedure. RESULTS: In 17 of the 24 patients, the obstructive symptoms were treated successfully with a single dilatation procedure, and symptoms did not recur during follow-up ranging from 1 to 36 months (mean, 11 months). In the other seven patients, the procedure was considered unsuccessful because the patients experienced recurrent obstruction within 2 days to 13 weeks (mean, 3 weeks) after the initial procedure. In one of these, symptoms were relieved by a second procedure. Repeat dilatations in the other six patients were unsuccessful, and all six eventually required surgical revision for definitive treatment. No complicating perforations were noted as a result of dilatation. CONCLUSION: Our experience shows that fluoroscopically guided balloon dilatation is a simple and safe technique for treating obstructive symptoms caused by strictures occurring after gastric surgery. In the majority of patients, symptoms are relieved with a single balloon dilatation, eliminating the need for further surgery. However, patients whose obstructive symptoms recur after the initial balloon dilatation procedure are less likely to benefit from further dilatations and usually require surgery.

Adult↗
PubMed1994

Esophagoenteric anastomotic leaks: treatment with fluoroscopically guided balloon dilatation.

OBJECTIVE: Disruption of anastomosis soon after esophagectomy and esophagoenterostomy is a relatively common complication that leads to chronic enterocutaneous fistulous drainage through the surgical wound in the lower part of the neck or upper part of the chest. It is believed that narrowing of the anastomosis by postsurgical edema and granulation tissue forces the flow of swallowed saliva through the disrupted anastomosis and contributes to the maintenance of the leakage. We evaluated the role of fluoroscopically guided balloon dilatation for treatment of these esophagoenteric anastomotic leaks. MATERIALS AND METHODS: Sixteen consecutive patients with leaking esophagoenteric anastomoses in the neck or the upper part of the chest underwent fluoroscopically guided dilatations of the anastomosis 7-32 days (mean, 13 days) after surgery with 15- or 20-mm angioplasty balloons. Dilatation was done empirically, regardless of whether the anastomosis was visibly narrowed. Discharge of secretions through the surgical drains in the wounds was measured before and after the procedure to determine the response to treatment. RESULTS: In 10 patients whose anastomoses were leaking for an average of 6 days before the balloon dilatation, drainage ceased immediately after the procedure. In four patients with leakage averaging 13 days, response to dilatation was delayed; drainage continued briefly after the procedure but ceased after an average of 5 days. In one patient, drainage increased after dilatation but ceased after 4 days. In another patient, drainage continued for more than 2 weeks after the procedure, after which a second dilatation was performed without apparent success as drainage persisted for another 10 days. In no case was there evidence of further disruption of the anastomosis by the balloon dilatation. CONCLUSION: Fluoroscopically guided balloon dilatation appears to be an effective and safe technique for treatment of leaking esophagoenteric anastomoses. Early intervention seems to increase the effectiveness of the procedure.

Adult↗
PubMed1994

Experimental calculations of droplet diffusion in a low-pressure cloud chamber.

A low-pressure cloud chamber was used for several years to display the tracks created by the passage of ionizing particles through vapors of interest. The spatial distributions of the ions that were formed were of special interest, but the accuracy with which these distributions could be determined was reduced by the presence of diffusion. This meant that the droplets, when photographed, had moved significantly away from the point of creation of the parent ion. In the present investigation photographs obtained by previous workers have been analyzed in an attempt to quantify the extent to which the droplets had diffused. The results suggest that the diffusion, when converted to standard density (1000 kg/m3), was independent of the pressure inside the cloud chamber and the mixture used. It could be represented by a one-dimensional root-mean-square diffusion distance whose value was calculated to be 2.42 +/- 0.04 nm. Values for the diffusion of thermalized electrons (< approximately 4 eV) before capture to form negative ions were also calculated. They appeared to lie in the range 3.5-5.0 nm, and were again independent of the pressure and nature of the mixture. The magnitude of the diffusion was large enough to mask any measurable prediffusion structure for a distance in the region of 10 nm radially around the track path of the alpha-particle and proton tracks analyzed.

Alpha Particles↗
PubMed1991

Brain anatomic effects of electroconvulsive therapy. A prospective magnetic resonance imaging study.

To determine prospectively whether electroconvulsive therapy (ECT) produces structural brain changes, 35 inpatients with depression underwent magnetic resonance imaging before and twice after (at 2 to 3 days and at 6 months) completion of a course of brief-pulse, bilateral ECT. The magnetic resonance images were analyzed blindly for evidence of changes in brain structure using two approaches: measurement of regional brain volumes and a pairwise global comparison. Structural brain abnormalities were present in many patients before ECT. The course of ECT produced no acute or delayed (6-month) change in brain structure as measured by alterations of the total volumes of the lateral ventricles, the third ventricle, the frontal lobes, the temporal lobes, or the amygdala-hippocampal complex. In five subjects, the pairwise global comparisons revealed an apparent increase in subcortical hyperintensity, most likely secondary to progression of ongoing cerebrovascular disease during follow-up. Our results confirm and extend previous imaging studies that also found no relationship between ECT and brain damage.

Amygdala↗
PubMed1988

The radiobiology of 24 keV neutrons. Measurement of the relative biological effect free-in-air, survival and cytogenetic analysis of the biological effect at various depths in a polyethylene phantom and modification of the depth-dose profile by boron 10 for V79 Chinese hamster and HeLa cells.

HeLa human carcinoma cells and V79 Chinese hamster fibroblasts have been irradiated in vitro with a beam of neutrons with a nearly pure 24 keV spectrum. The relative biological effectiveness (RBE) of the filtered neutron beam relative to 60Co gamma radiation was determined by irradiation of cell cultures "free-in-air". The values obtained for the RBE at 37% survival were 5.8 +/- 0.8, at a dose of 0.69 +/- 0.06 Gy for the HeLa cells and 3.14 +/- 1.1 at a dose of 1.09 +/- 0.091 Gy for the V79 cells. Cytogenetic analysis of the damage in irradiated V79 cells gave an RBE of 6.7 +/- 1.4. Irradiation in a polyethylene phantom markedly attenuated the beam's biological effect. For both cell lines 2 cm of polyethylene virtually eliminated cell killing. Addition of boron 10 to the medium led to increased cell killing and a value of 4 was obtained for the RBE of the 10B(n, alpha)7Li reaction in HeLa cells.

Animals↗
PubMed1988

Biophysical interpretation of the response of Chinese hamster cells to 24 keV neutrons.

The response of V79 Chinese hamster cells to a 24 keV neutron spectrum has been compared with data for the response of V79 cells to a range of higher neutron energies. The linear energy transfer (LET) distributions of the neutron spectra were calculated and the expected responses of the cells to the different spectra were calculated using published track-segment data on the response of V79 cells to charged particles with various LET values. The response of the cells to 24 keV neutrons was predicted satisfactorily by the LET distribution, in spite of the fact that the maximum range of the recoil protons is only 0.5 micron. The response was not correctly predicted by the microdosimetric parameter y*D evaluated in a 1 micron diameter sphere.

Animals↗
PubMed1987

A comparison of the radiation-induced mutation at the HGPRT locus in V79 and BHK cells.

Mutation response at the HGPRT locus has been compared in two differing cell lines: V79/4, an aneuploid Chinese-hamster fibroblast line with a complement of 20 chromosomes, and BHK21-C13, a diploid Syrian-hamster fibroblast line with a complement of 44 chromosomes. The data presented show that BHK is slightly more radiosensitive than V79/4; however, the toxicity curves and expression times are similar for both cell lines. If radiosensitivity is taken into account, a common line can be drawn for radiation mutagenesis. We conclude from the data that radiation-induced mutagenesis is broadly equivalent in the two cell lines examined, and is not dependent on the chromosome complement.

Animals↗
PubMed1987

The production of chromosome aberration in Chinese hamster fibroblasts exposed to 24 keV neutrons.

A filtered reactor beam, consisting mainly of 24 keV neutrons, was used to study the induction of chromosome aberrations in the V79/4(AH1) Chinese hamster cell line. The yields of both dicentrics and acentrics were linear with dose and the value of relative biological effectiveness (RBE) for dicentrics at low doses was 6.5 +/- 1.4. This value was similar to that found previously for a neutron spectrum with mean energy 2.1 MeV, and suggests that the RBE of neutrons does not increase to very high values in the energy region below 100 keV. This result does not support the suggestions of Davy (1969) and Key (1971) that the neutron RBE rises to very high values in the intermediate energy range.

Animals↗
PubMed1986

A critical comparison of the micronucleus yield from high and low LET irradiation of plateau-phase cell populations.

Experimental data are presented which cast doubt on the usefulness of micronucleus assays as a quantitative measure of radiation damage. Synchronised (G1) Syrian hamster fibroblasts (BHK21 C13) were exposed to doses of gamma- or neutron radiation which yielded equivalent survival response. The cultures were examined at intervals during a 120-h post-irradiation incubation, for the appearance of micronuclei. Dose-response curves for the micronucleus yield constructed at a single sample time of 30 h were compared with those for the peak yield, irrespective of sampling time at each dose. When the total production of acentric fragments was compared with the peak yield of micronuclei no clear correlation could be seen. Qualitative hypotheses have been suggested to account for the various features of the data. The production and expression of micronuclei has been found to be a very complicated relationship and is a warning against too simplistic an interpretation of micronuclei data.

Animals↗
PubMed1986

Inactivation of Chinese hamster V79/4(AH1) and HeLa cells by 24 keV neutrons.

Cell survival studies have been carried out with a filtered neutron beam providing a nearly pure, high intensity source of 24 keV neutrons. These suggest that 24 keV neutrons behave as high LET radiation. The RBE at 37 per cent survival was approximately 2.2 for V79 Chinese hamster cells while HeLa cells gave a value of 2.9.

Animals↗
PubMed1985

Induction of chromosome aberrations and cell killing in Syrian hamster fibroblasts by gamma-rays, X-rays and fast neutrons.

Chromosome aberrations were scored in BHK21 C13 Syrian hamster fibroblasts, exposed to 60Co gamma-rays, 250 kV X-rays, 15 MeV neutrons or neutrons of mean energy 2.1 MeV produced from the 9Be(d,n)10B reaction. The cells were irradiated in stationary phase, where they are concentrated in the G1 phase of the cell cycle. Within experimental uncertainty there was no detectable difference between the responses to 60Co gamma-rays and to 250kV X-rays. The r.b.e. for the production of dicentrics, based on the 'one-hit' component of response, was (5 +/- 2) for the 15 MeV neutrons and (12 +/- 5) for the 2.1 MeV neutrons. For each radiation, a graph of the proportion of cells without a dicentric, centric ring or acentric fragment corresponded closely to the survival curve for stationary-phase cells obtained in the same experiment.

Animals↗
PubMed1983

Complement-activating rheumatoid-factor-containing complexes in patients with rheumatoid vasculitis.

The role of complement and rheumatoid factor in immune complexes was examined in patients with a variety of rheumatic diseases. This was done by assessing the amount of rheumatoid factor (RF) bound from sera by F(ab)2 anti-C3 attached to a solid matrix. High levels of RF bound to C3 were detected in patients with rheumatoid arthritis complicated by vasculitis but rarely and in lower levels in patients with synovitis, ankylosing spondylitis, and systemic lupus erythematosus. The activity was bound to anti-C3 through anti-C3 antibodies because little was bound by normal F(ab)2 and was evidently complexed in the sera before in-vitro testing, since it was precipitated by 2 . 5% polyethylene glycol and sedimented with high molecular weight material on sucrose density gradient ultracentrifugation. It is considered that RF-containing complexes are present in vasculitic sera and have the potential to bind complement in vivo.

Antigen-Antibody Complex↗