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Biomedical subjects

D M Taylor

Publications and source records attributed to D M Taylor.

At least 163 records · Page 9Linked to original sources
PubMed1987

Autoclaved, formol-fixed scrapie mouse brain is suitable for histopathological examination, but may still be infective.

Autoclaving Creutzfeldt-Jakob disease (CJD)-infected brain after fixation has been proposed previously as a means of making it safe for handling in the laboratory, while preserving its microscopic integrity. However, the practice which was recommended (126 degrees C for 30 min) would be unlikely to achieve complete decontamination. Autoclaving scrapie mouse brain (an analogue for CJD) to the higher, recommended standard of 134-138 degrees C for 18 min was found to lead to some tissue damage but not sufficient to prevent meaningful qualitative and quantitative study of the histopathological lesions.

Animals↗
PubMed1987

TDPAC studies of the metal-binding sites in serum transferrin: comparison between 181Hf-labeled human- and rat-serum transferrin.

The binding of hafnium to human serum transferrin was studied using the time differential perturbed angular correlation (TDPAC-) technique. The samples were prepared in vitro by adding 181Hf-NTA solution to human serum. Two specific electric quadrupole interactions were observed, which correspond to two well-defined binding configurations. Their relative intensities depend on the pH, salt- and hafnium-concentrations, and on the incubation time. The present data may be compared with the results of a previous rat serum study, where the hafnium binding to transferrin behaved rather similarly. Small but significant differences, however, can be deduced from the TDPAC-parameters for these human and rat transferrin species. For either binding configuration, the electric field gradient (EFG) is slightly higher in the case of rat transferrin. The most characteristic difference, however, concerns the asymmetry parameter eta 2 of the second binding configuration, which is about 10% smaller for rat serum transferrin. The TDPAC-technique might be used as a sensitive and reliable analytical method to study the metal-binding sites of different transferrin species.

Animals↗
PubMed1987

131I labeled diphosphonates for the palliative treatment of bone metastases--IV. Syntheses of benzylidenediphosphonates and their organ distribution in rats.

Palliative treatment of bone pain induced by disseminated bone metastases can be performed with osteotropic, beta(-)-emitting radionuclides. Newly developed 131I labeled benzylidenediphosphonic acid (BDP) derivatives show osteotropic characteristics which suggest that they might possibly be useful radiopharmaceuticals for that purpose. Six BDP derivatives were synthesized with H, OH or NH2 in the 4- and alpha-position. Syntheses were performed by the formal addition of 2 mol of phosphorous acid in the presence of PBr3 to 1 mol of the respective benzonitrile. Transformation of the 4-methoxy and 4-nitro substituents, which were stable during the diphosphonate formation, to 4-HO and 4-NH2 was achieved by hydrolytic ether cleavage in boiling HBr and catalytic hydrogenation with Pd/C, respectively. Transformation of the alpha-amino to alpha-hydroxy group was achieved by the action of NaNO2 in HCl. 4-Hydroxybenzylidenediphosphonic acid (9) was formed unexpectedly during the reaction of 4-hydroxybenzoic acid with H3PO3/PBr3. The addition of 2 mol of phosphorous acid to the benzoic acid was accompanied by an additional reduction at the alpha-carbon. The new BDP derivatives were analyzed by HPLC, NMR and elemental analysis. After labeling with 131I the BDP derivatives were tested in female Sprague-Dawley rats to obtain organ uptake and kinetic data. The various substituents showed an influence on the bone affinity and the uptake in other organs. Among the BDP derivatives tested alpha-amino-(3-[131I]iodo-4-hydroxybenzylidene)diphosphonate (4a) showed the best biological characteristics.

Animals↗
PubMed1987

Identification of transferrin as the main binding site for protactinium in rat blood serum.

The distribution of 233Pa in rat serum at periods between 5 and 50 min after i.v. injection of a solution of protactinium chloride was studied by gel chromatography. Sequential analysis of sera on Sephacryl S-300 and DEAE-Sephadex showed that 233Pa was associated only with the transferrin fraction of the serum proteins. This finding was confirmed by iso-electric focusing electrophoresis. In the cytosol fractions prepared from the liver and kidneys of the 233Pa injected rats the nuclide was also shown to be protein bound.

Animals↗
PubMed1987

Influencing of ionizing radiation on herpes simplex virus and its genome.

The effects of cobalt-60 gamma-rays, 10 MeV electrons and 52 MeV deutrons on the survival of plaque-forming ability has been studied in various strains of herpes simplex virus (HSV). The results show that the D0 for the loss of plaque-forming ability in different HSV strains lies in the range 1-3 kGy. Irradiation of isolated HSV-1 DNA with cobalt-60 gamma-rays resulted in damage, as indicated by electrophoresis of purified viral DNA and by restriction endonuclease analysis, at doses of 1 kGy, with complete loss of structure at doses above 4 kGy. The infectivity of the irradiated naked DNA was lost at doses above 4 kGy, but after irradiation of the intact virus some plaque-forming ability was retained after doses of 10 or even 40 kGy. Thus the organization within the viral capsid may play a protective role by modifying the severity of the radiation damage, and preserving at least some degree of infectivity.

Cobalt Radioisotopes↗
PubMed1987

Differences in the uptake of transferrin bound 239Pu and 59Fe into multicellular spheroids of hepatocytes from adult male rats.

Hepatocytes were cultured as monolayers and multicellular spheroids, respectively. The uptake of both transferrin-bound metals, iron and plutonium, differed significantly between these two culture systems. The uptake into the multicellular spheroids for plutonium was about 30 times greater, and for iron about 4 times greater, than in monolayer-cultured hepatocytes, which is not a consequence of proliferation and/or de-differentiation of the hepatocytes in the multicellular spheroid culture system. A comparison of the iron and plutonium uptake showed that plutonium was delivered to the cells to an 8-fold greater extent than iron if the hepatocytes were cultured as spheroids. Additionally, the binding of plutonium was not inhibited by preincubation of the spheroids with the iron-transferrin complex. Therefore, we propose that there are two different binding sites for iron and plutonium on hepatocyte membranes.

Animals↗
PubMed1987

Influence of several chelating agents on the distribution and binding of cadmium in rats.

Male Sprague-Dawley rats were injected with 109CdCl2 (3 mumol Cd/kg) and killed between 1 h and 200 d afterwards. Metal concentration in the critical organs, i.e. liver and kidneys decreased very slowly. Within the cells Cd is found mainly in the cytosol and--at very early times--in the nuclei. Within the cytosol of the liver most of the metal is initially bound to proteins with high molecular weight but as early as 3 h after incorporation more than 90% is bound to metallothionein which is always the main binding site in the kidneys. Of the chelating agents tested only BAL and Puchel were able to reduce the body burden significantly. Both are lipophilic substances. Puchel cannot reduce the kidney Cd burden but removes Cd from the liver only while BAL is effective in both organs. Both chelating agents exert their effects at doses which are too near to the LD50 to be considered as safe enough for human use.

Acid Phosphatase↗
PubMed1987

The association between spontaneous pyelonephritis and maturity-onset diabetes mellitus in male MM mice.

Blood glucose and glucose tolerance tests demonstrated that many male MM mice are diabetic. Serial urine sampling showed that the diabetes occurred only in mature MM males and consisted of a single self-limiting episode. Histological examination of the pancreas, together with measurements of body weight, glycosylated haemoglobin and plasma insulin, revealed that the diabetes was of the maturity-onset insulin-resistant type. Bacteriological examination of the urine samples showed that urinary tract infection, a known feature of male MM mice, occurred in the diabetics but only after the onset of hyperglucosuria. It was concluded that the high urinary glucose levels of diabetic MM males are of prime importance in the aetiology of the renal infection which occurs rarely in non-diabetic MM males or in other strains in the colony. An infectious aetiology for the diabetes per se was excluded by the existence of diabetes in germfree MM males.

Animals↗
PubMed1987

The subcellular distribution of 238Pu and 239Pu in primary cultures of rat hepatocytes.

The subcellular distribution of 238Pu and 239Pu after incubation of primary cultures of rat hepatocytes with the citrate complex of these metals was studied, and the results were compared with data from in vivo experiments. As in vivo, the lysosomes are the principal organelles in which 238Pu and 239Pu are accumulated. In contrast to in vivo studies, 239Pu is also detectable on the pericellular membranes and in the cell nuclei, where it is predominantly bound to a high-molecular-weight component. The percentage of the total cellular 239Pu which can be recovered in the cell nuclei increased with incubation time from 10% at 1 h to nearly 30% at 5 h. Plutonium-238, an isotope with 270-fold higher specific activity than 239Pu, showed no association with the nuclei. The membrane-bound fraction of 239Pu, as determined using the exogenous chelator diethylenetriaminepentaacetic acid decreased from 30% at shorter incubation times to 15% at longer incubation periods. After incubation with 238Pu the membrane fraction and the cytosolic fraction contained higher concentrations of the radionuclide than after incubation with 239Pu.

Animals↗
PubMed1986

Potassium-induced epileptiform activity in area CA3 varies markedly along the septotemporal axis of the rat hippocampus.

Hippocampal slices are generally treated as equivalent regardless of their site of origin along the septotemporal axis. In this study, spontaneous epileptiform bursting was induced in area CA3 of rat hippocampal slices by bathing them in 7 mM potassium. The frequency of spontaneous bursting was measured in all viable slices from 12 hippocampi. Burst frequency was found to vary markedly and in a consistent fashion with site of slice origin along the septotemporal axis. Burst frequency was maximal in slices from near the temporal end and declined progressively toward the septal end. This finding was independent of slicing angle. These results demonstrate that site of slice origin along the septotemporal axis is an important confounding variable in in vitro studies of hippocampal neuronal activity. Furthermore, they support the notion that the temporal portion of the hippocampus may be more prone to seizure activity than the septal hippocampus, possibly because of factors intrinsic to the hippocampus.

Action Potentials↗
PubMed1986

In vivo and in vitro studies of hafnium-binding to rat serum transferrin.

The binding of hafnium to rat serum transferrin was studied using the time differential perturbed angular correlation (TDPAC) technique. Hafnium is interesting as a toxic metal binding to transferrin because it behaves metabolically similarly to plutonium. The isotope 181Hf offers favorable access to the TDPAC-method. Samples were prepared in vivo by intravenous injection of Hf-NTA, Hf-citrate, and Hf-oxalate solutions, respectively, into Sprague-Dawley rats and in vitro by adding Hf-NTA solution to fresh rat serum. In both cases two specific electric quadrupole interactions were observed, which correspond to two well-defined binding configurations. They may be attributed to the N-terminal and the C-terminal binding site in the transferrin molecule. The 181Hf-distribution between these two binding states depends on pH, salt and hafnium concentrations, temperature, and incubation time. With a fast TDPAC-setup of four BaF2-detectors a time resolution of about 600 ps could be achieved. The specific binding configurations of 181Hf and the comparatively slow relaxation times lead to spectra of considerable accuracy.

Animals↗
PubMed1986

The binding of plutonium to transferrin in the presence of tri-n-butyl phosphate or nitrate and its release by diethylenetriaminepenta-acetate and the tetrameric catechoylamide ligand LICAMC(C).

The binding of plutonium to human apo-transferrin and to rat serum was investigated following delivery of the metal to the protein either as the plutonium-tri-n-butyl phosphate (Pu-TBP) complex in n-dodecane or as plutonium nitrate. Chromatographic behaviour, the failure to bind to iron-saturated transferrin and the release of plutonium by the chelating agents CaNa3DTPA and 3,4,3-LICAM(C) suggest that the transferrin complexes formed from the two plutonium compounds are similar. The tetracatechoylamide ligand LICAM(C) was found to be about 500 times more effective than DTPA, on a molar basis, for the release of plutonium from transferrin in rat serum.

Animals↗