Lab animal welfare issue gathers momentum.
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Biomedical subjects
Publications and source records attributed to J L Fox.
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A powder dissolution method has been developed, and experiments with the hydroxyapatite suspensions confirm earlier conclusions based on dissolution from hydroxyapatite disks. Although a quantitative assessment of the properties of site 1 was not possible from the data obtained in the present study, a rather accurate and independent evaluation of the properties and the behavior of site 2 of the two-site model for hydroxyapatite dissolution was possible, and the results clearly validate the original two-site model. The present work together with the earlier disk studies show that dissolution from site 2 is well described by a first-order expression, rate = kc2 (Cs2-C), where kc2 is a first-order rate constant, Cs2 is the apparent solubility for site 2 (defined by an ion activity product, KHAP, of the form a10Ca2+PO43-a2OH-, and the solution conditions), and C is the microenvironmental solution concentration of hydroxyapatite. For four different precipitated hydroxyapatite preparations, a single KHAP value of 1 X 10(-128) +/- 1 was found to be consistent with experiments using solutions covering wide ranges of partial saturation and calcium-phosphate ratios. The hydroxyapatite powder and pellet methods (including the data evaluation procedures) now offer a powerful combination for investigating the complex kinetics associated with dental enamel dissolution in particular and enamel chemistry in general.
A method for quantitative determination of mineral density changes in dental enamel has been developed. It utilizes the quantitative microscopy capabilities of image analysis or photometer systems. Characteristic demineralization of bovine enamel in acetate buffers containing calcium and phosphate has been used to demonstrate the results. The method together with chemical kinetic data obtained from spectrophotometric and ion-selective electrode measurements of the bulk solution for calcium, phosphate, and fluoride permit important basic studies to be conducted on demineralization and remineralization of dental enamel.
The remineralization behavior of weak acid-treated bovine tooth enamel has been investigated using a recently developed quantitative microradiographic method. Acetate buffer solutions at pH 4.5 containing calcium, phosphate, and 10 ppm fluoride were used in this study. When the solution ion activity product ( KFAP = a10CA a6PO4 a2F ) was 1 X 10(-108), the remineralization of the demineralized region was relatively uniform and complete. On the other hand, when the KFAP was approximately less than or equal to 1 X 10(-112), remineralization of the outer 10-20 micron was incomplete. In addition, for the smaller KFAP solutions there was significant demineralization in the deeper recesses of the originally demineralized region. These results agree with a recent chemical kinetics study in which it was proposed that KFAP = 1 X 10(-112) demarcated the region of solution conditions in which remineralization only occurs from that in which simultaneous demineralization/remineralization takes place. A model consistent with all of the data is proposed.
The transport of hexylamine and octylamine through a silicone rubber membrane was studied as a function of buffer (phosphate) concentration and pH. The results were interpreted using a physical model which assumed a steady-state rate of transport and which accounted for the simultaneous diffusion and rapid equilibrium of all the aqueous species, the possible diffusion of both the amine and its protonated form through the membrane, and the effect of a stagnant aqueous diffusion layer on each side of the membrane. The following conclusions were reached: The thickness of the aqueous diffusion layer is approximately 100 micron, which is about the same as that previously measured for benzoic acid in this system. Transport of octylamine at pH greater than or equal to 10 is approximately 90% aqueous diffusion layer controlled, whereas hexylamine is approximately 50% aqueous diffusion layer controlled at high pH. The membrane permeability of octylamine is approximately 15-20 times that of hexylamine. This gives an incremental pi constant for the partition coefficient of approximately 0.61, as compared with the previously reported value of 0.56. At low pH (less than or equal to 5), the transport of the protonated species becomes important. The membrane permeabilities of these ammonium ions are about four or five orders of magnitude less than the membrane permeabilities of the corresponding amines. The membranes were examined at 30,000X with the scanning electron microscope, and no evidence of holes was found.
Synthetic oligonucleotide probes were used to identify a cloned DNA fragment from the cyanobacterium Agmenellum quadruplicatum that contains the genes for the alpha and beta subunits of C-phycocyanin. The coding region for the alpha-subunit gene begins 108 base pairs downstream from the 3' end of the beta-subunit structural gene. The sequences of the coding regions for both genes have been determined as well as 379 base pairs of 5' flanking region, 204 base pairs of 3' flanking region, and the 108 base pairs between the two genes. The site of transcriptional initiation is located approximately equal to 325 base pairs upstream from the beta-subunit gene, and an open reading frame 114 base pairs long is found within this region. The significance of this additional open reading frame is not yet known. The derived amino acid sequences for both C-phycocyanin subunits were compared with other known C-phycocyanin sequences for homology. Homologies between the A. quadruplicatum alpha subunit and alpha subunits from other species were approximately equal to 70%, as were homologies between the A. quadruplicatum beta subunit and other beta subunits. Homologies between the various alpha and beta subunits were 21%-27%. Codon usage for both the C-phycocyanin alpha- and beta-subunit genes shows asymmetries for many amino acids that correspond closely to those seen in highly expressed Escherichia coli genes.
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T6-antigen-bearing Langerhans' cells were detected in a touch imprint of eosinophilic granuloma involving a thoracic vertebra of an 11-year-old boy. It is interesting to note that in this localized form of histiocytosis X, no T6-antigen-bearing Langerhans' cells were found in the peripheral blood. Immunofluorescence detection of T6 antigenicity has not been described in this disease and may serve as a rapid diagnostic test.
Preliminary studies showed that the vaginal membrane permeability coefficients for vidarabine (9-beta-D-arabinofuranosyladenine) varied widely within a group of mice of the same species and age. This finding prompted an investigation of the influence of the female mouse sexual cycle on the vidarabine permeability. By means of a vaginal smear technique, the sexual cycle, which was approximately 5 days in duration, was divided into five phases. The vaginal membrane permeability of vidarabine was determined during each phase. The results revealed that the permeability coefficients for vidarabine during the diestrus phase (3 X 10(-6)-4 X 10(-5) cm/sec) were 10-100 times higher than those obtained at the early estrus or estrus phases (1-3 X 10(-7) cm/sec). Further permeation studies on membranes at early estrus and estrus were performed by separating the cornified layer from the noncornified portion of the membrane. The low permeability coefficient of vidarabine across the cornified layer (4 X 10(-7) cm/sec) suggests that this layer may be the major diffusion barrier for vidarabine when the drug is topically applied. Collectively, the data also suggest that during estrus a three-layer diffusion model is appropriate, that during early diestrus a single-layer diffusion model may apply, and that during proestrus and postestrus the situations are intermediate and more complicated.
The effects of changing the ion activity product of the remineralization solution at pH 4.5 (pKFAP 108-118) on the remineralization behavior of demineralized bovine tooth enamel and hydroxyapatite pellets have been studied. Solutions containing calcium-4.5, phosphate, and fluoride in acetate buffers were used. The 45Ca/F molar ratios indicated the formation of fluoridated hydroxyapatite in the enamel or the pellet when the pKFAP values for remineralizing solutions were less than 112. When the pKFAP values were greater than 112, the 45Ca/F ratios were found to be much less than 5. Also, when the pKFAP values were large (greater than 112), the remineralization patterns based on the fluoride distribution in the tooth (or pellet) were found to be different than when the pKFAP values were small (less than 112). The hypothesis that a pKFAP value of 112 is the demarcation between remineralization only and simultaneous dissolution-remineralization has been proposed based on these results.
Analyses of bumetanide's dose-response relationship have been complicated by the hysteresis observed between the drug's urinary excretion rate and its sodium excretion. This apparent time lag reflects the disequilibrium between the urine concentration and effect compartment (biophase) which occurs during the early distribution phase. In the present article, an expanded pharmacodynamic model has been introduced in which the hypothetical effect compartment is linked, by a first-order process (Kue), to the urine compartment. Drug dissipation from the effect compartment occurs by means of the first-order rate constant, Keo. This representation accommodates bumetanide's luminal site of action in the kidney tubule as well as the drug's temporal component. Application of this model to the bumetanide-indomethacin interaction in dogs is examined.