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Biomedical subjects

B J Allen

Publications and source records attributed to B J Allen.

At least 145 records · Page 8Linked to original sources
PubMedDate not supplied

In vitro and preclinical targeted alpha therapy for melanoma, breast, prostate and colorectal cancers.

Targeted alpha therapy (TAT) can inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotopes Tb-149 and Bi-213 were chelated to cancer specific monoclonal antibodies to form alpha-immunoconjugates (AIC) against melanoma, leukaemia, prostate and colorectal cancer, and to the plasminogen activator inhibitor type-2 (PAI2) to form alpha-PAI2 (API) against breast and prostate cancer. These conjugates were found to be highly stable, specific and cytotoxic in vitro. Melanoma and breast cancer tumour growth was observed in nude mouse models for untreated controls and non-specific AIC/API at 2 days post-subcutaneous inoculation of cancer cells. Complete inhibition of melanoma and breast cancer growth was found for local injections of AIC and API, respectively. Intra-lesional TAT of established melanoma showed that all melanomas regressed with 100 microCi injections of AIC. These results point to the potential application of local and systemic TAT in the management of metastatic cancer.

Alpha Particles↗
PubMedDate not supplied

Spatial patterns of child growth in Papua New Guinea and their relation to environment, diet, socio-economic status and subsistence activities.

Anthropometric data from the 1982/83 Papua New Guinea (PNG) National Nutrition Survey were analysed to identify geographical patterns of child growth and investigate their relation to a wide range of environmental, dietary and socio-economic variables. Standardized growth scores for length-for-age (LAZ), weight-for-age (WAZ) and weight-for-length (WLZ) were calculated based on an internal PNG growth reference. Hierarchical Bayesian spatial models based on conditional autoregressive (CAR) priors were subsequently used to model spatial patterns in scores and their relation to different sets of covariates. The geographical differences were bigger for linear growth than for increases in weight. Growth was most reduced in parts of Milne Bay Province, Madang Province, the Torricelli/Prinz Alexander Ranges, and in the area occupied by Angan people. Socio-economic status was the most important factor determining variation in growth within populations. Differences in diet and, to a lesser extent, the physical environment were the main determining factor of differences among populations. Covariate adjustment accounted for more spatially structured variation in LAZ and WAZ than in WLZ. All variables indicating higher socio-economic status were correlated with better growth, as was a high consumption of imported and local high quality foods such as cereals, legumes, tinned fish/meat or fresh fish. This indicates that nutritional interventions in PNG should aim at promoting the consumption of such high energy and high protein foods as well as strengthening the general economic base of rural populations.

Analysis of Variance↗
PubMedDate not supplied

Neutron capture therapy research in Australia.

Neutron capture therapy research in Australia has continued to grow since the first Australia-Japan workshop in April, 1986. The support base has broadened and the wide range of contributing laboratories includes universities, research institutes, and hospitals. Considerable progress has been made in boron chemistry--an accurate boron assay technique has been developed, boron analogues of chlorpromazine and thiouracil have been synthesised or nearly so, and decaborane conjugation with monoclonal antibodies has been achieved to the required loadings. In vitro cell survival experiments are proceeding in the Moata reactor using human melanoma and mouse cell lines incubated with enriched boronophenylalanine and boron tetraphenyl porphyrins. Electron microscopy examination of radiation damaged morphology shows considerable differences between cell lines. Progress with the nude mouse human melanoma model has been slow because of the lack of a reliable in vivo melanotic melanoma line, and the B16 mouse line is found to be more efficacious. Tailored beam calculations for the 10 MW HIFAR reactor indicate the difficulty of obtaining a suitable therapeutic beam because of the generated gamma dose in the beam filters. A new approach to NCT utilises the enormous cross section of 157Gd and the induced-Auger effect which has been shown to cause double strand breaks in circular DNA.

Animals↗
PubMedDate not supplied

Determination of the concentration of complex boronated compounds in biological tissues by inductively coupled plasma atomic emission spectrometry.

The application of inductively coupled plasma atomic emission spectrometry (ICP-AES) to the determination of the concentration of complex boron-containing compounds in biological tissue samples is described. Tissue digestion is achieved with perchloric acid and hydrogen peroxide in 1 hr at 75 degrees C. The ICP-AES method gave a linear response for elemental boron concentration in the range 0.05 to 100 ppm and does not require the reduction of the boron to a simple species, such as boric acid. Complete recovery of boron in complex boron cluster compounds was obtained. The procedure has been applied to the determination of the boron content in compounds synthesised for neutron capture therapy and is suitable for use in biodistribution studies of such compounds.

Animals↗
PubMedDate not supplied

Neutron irradiation of human melanoma cells.

The biological characteristics and in vitro radiosensitivity of melanoma cells to thermal neutrons were investigated as a guide to the effectiveness of boron neutron capture therapy. Plateau phase cultures of three human malignant melanoma-established cell lines were examined for cell density at confluence, doubling time, cell cycle parameters, chromosome constitution, and melanin content. Cell survival dose-response curves, for cells preincubated in the presence or absence of p-boronophenylalanine. HCl (10B1-BPA), were measured over the dose range 0.6-8.0 Gy (N + gamma). The neutron fluence rate was 2.6 x 10(9) n/cm2/s and the total dose rate 3.7 Gy/h (31% gamma). Considerable differences were observed in the morphology and cellular properties of the cell lines. Two cell lines (96E and 96L) were amelanotic, and one was melanotic (418). An enhanced killing for neutron irradiation was found only for the melanotic cells after 20 h preincubation with 10 micrograms/ml 10B1-BPA. In view of the doubling times of the cell lines of about 23 h (96E and 96L) or of 36 h (418), it seems likely that an increased boron uptake, and hence increased radiosensitivity, might result if the preincubation period with 10B1-BPA is extended to several hours longer than the respective cell cycle times.

Boron Compounds↗
PubMedDate not supplied

Induction of DNA double-strand breaks by 157Gd neutron capture.

The rationale of boron (10B) neutron capture therapy (BNCT) is based on the high thermal neutron capture cross section of 10B and the limited maximum range (about one cell diameter) of the high LET fission products of the boron neutron capture (NC) reaction. The resulting radiochemical damage is confined to the cell containing the BNC reaction. Although other nuclides have higher thermal neutron capture cross sections than 10B, NC by such nuclides results in the emission of highly penetrating gamma rays. However, gadolinium-157 (157Gd) n-gamma reaction is also accompanied by some internal conversion and, by implication, Auger electron emission. Irradiation of Gd3+-DNA complexes with thermal neutrons results in the induction of DNA double-strand (ds) breaks, but the effect is largely abrogated in the presence of EDTA. Thus, by analogy with the effects of decay of Auger electron-emitting isotopes such as 125I, the Gd NC event must take place in the close proximity of DNA in order to induce a DNA ds break. It is proposed that 157Gd-DNA ligands therefore have potential in NCT. The thermal neutron capture cross section of 157Gd, a nonradioactive isotope, is more than 50 times that of 10B.

DNA↗
PubMedDate not supplied

Morphological changes in human melanoma cells following irradiation with thermal neutrons.

Morphological changes in two human melanoma cell lines, MM96 and MM418, following irradiation with thermal neutrons, were studied using light and electron microscopy. The results show that the response of human malignant melanoma cells to neutron irradiation is both cell line dependent and dose dependent, and that in any given cell line, some cells are more resistant to irradiation than others, thus demonstrating heterogeneity in respect to radiosensitivity. Cells repopulating MM96 flasks after irradiation were morphologically similar to the cells of origin whereas in MM418 flasks cells differentiated into five morphologically distinct subgroups and showed increased melanization. The results also show that radiation causes distinctive morphological patterns of damage although ultrastructural changes unique to the high LET particles released from boron 10 neutron capture are yet to be identified.

Boron Compounds↗
PubMedDate not supplied

Magnesium-potassium interactions in cardiac arrhythmia. Examples of ionic medicine.

Ionic biology involving Ca2+, Na+, K+ and Mg2+ across the cell membrane and in the development of the action potential is reviewed with reference to cardiac arrhythmia. K+ and Mg2+ deficiency which frequently occur together lead to abnormal ionic transfer of Na+, K+ and Ca2+ with development of automaticity, triggered impulses and reentrant tachycardia. Tachycardia occurring in acute myocardial ischemia, congestive heart failure, hypertensives on diuretics and digitalis toxicity is examined according to the concept of ionic imbalance. A protocol for prevention and treatment of cardiac tachyarrhythmia is proposed with this concept in mind.

Action Potentials↗
PubMedDate not supplied

ECMO assisted angioplasty for cardiomyopathy patients with unstable angina.

Patients who are otherwise unsuitable candidates for coronary bypass surgery or standard coronary angioplasty (PTCA) may be successfully treated with PTCA during ECMO. Five patients (3 men, 2 women), with a mean age of 57 years, are reported on here. They were not considered good candidates for standard therapy because of poor left ventricular function (mean EF, 24; range, 16 to 28%). Patients were supported by percutaneous femoral bypass using a BARD CPS machine, and underwent successful PTCA of either two vessels (three patients) or three vessels (two patients); in addition, one patient had dilatation of a stenotic aortic valve. Patients were supported with ECMO for 26 to 140 (mean 104) minutes, and required transfusion with 0 to 4 (mean 2) units of blood during or after the procedure. Complications included groin hematoma in two patients. All were discharged within 4 days of the procedure. Follow-up of the patients has been completed (4-7 mo) with no further hospitalizations for unstable angina. All patients remain in NYHA Class II or III. These data suggest that ECMO-assisted angioplasty is a safe and effective method of palliation of unstable angina associated with cardiomyopathy.

Adult↗