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Biomedical subjects

A G Jones

Publications and source records attributed to A G Jones.

At least 37 records · Page 2Linked to original sources

Characterization of P-glycoprotein transport and inhibition in vivo.

The P-glycoprotein is an energy-dependent efflux pump capable of decreasing the intracellular concentration of a broad range of chemotherapeutic agents. [99mTc]Sestamibi, a P-glycoprotein transport substrate, is a sensitive probe of P-glycoprotein function both in vitro and in vivo. A human tumor model in nude mice was evaluated to determine whether [99mTc]Sestamibi could detect in vivo differences in P-glycoprotein expression and P-glycoprotein modulation by the reversal agent SDZ PSC 833. Differential [99mTc]Sestamibi accumulation based upon P-glycoprotein expression was demonstrated in xenografts in vivo. Dose-dependent inhibition of P-glycoprotein function was achieved with SDZ PSC 833. Administration of the reversal agent increased [99mTc]Sestamibi accumulation in the xenografts expressing P-glycoprotein. These observations show that [99mTc]Sestamibi as capable of detecting the modulation of P-glycoprotein in a solid tumor model by the reversal agent SDZ PSC 833.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The validity of two methods of mandibular superimposition: a comparison with tantalum implants.

The aim of this investigation was to examine and compare the validity of Björk's and Ricketts' methods for the superimposition of serial cephalometric radiographs of the mandible for the analysis of changes over the duration of routine orthodontic treatment in growing subjects (approximately 2 years). Pre- and posttreatment lateral cephalometric radiographs of 23 children, with tantalum markers implanted in the mandible, were studied. The differences in position of six dental and skeletal landmarks between superimposition on Björk's structures and on Ricketts' corpus axis were compared with those on the basis of the implants. A rotational effect was found for corpus axis resulting from differential movement of Xi point with growth, whereas Björk's method yielded results essentially similar to those of the implant-based superimposition. This resulted in statistically significant median differences between the two methods for all landmarks except pogonion and menton. The magnitude of the differences increased with distance from the central core of the mandible and were generally greater horizontally than vertically. Although most differences were less than 2 mm, approximately 10% of the subjects showed differences greater than 4 mm for molar and incisor landmarks. These findings suggest that, for growing subjects, Björk's method should be preferred Ricketts', which cannot be relied on to indicate the true (intramandibular) changes during orthodontic treatment in growing subjects.

Analysis of Variance↗

Uptake of cationic technetium complexes in cultured human carcinoma cells and human xenografts.

We evaluated lipophilicity, in vitro cell accumulation, and biodistribution of a series of 99mTc-ether isonitrile complexes to determine whether increased lipophilicity promotes extraction by tumor or enhances imaging properties of the radiopharmaceutical. Nine 99mTc-sestamibi analogs were synthesized and their lipophilicity was determined. Net cellular accumulation and membrane-potential-independent uptake were quantitatively compared in cultured human colon, breast, and lung carcinoma cells. The biodistribution of [99mTc-(2-methoxy-2-ethyl-isocyanopropane)6]+ (99mTc-MMBI) and [99mTc-(2-ethoxy-2-methyl-1-isocyanopropane)6]+ (99mTc-EIBI) was studied in nude mice using subcutaneous, subrenal capsule, and hepatic tumor xenografts. Accumulation of these compounds in colon cells correlated with increasing lipophilicity. Compared with 99mTc-sestamibi, 99mTc-EIBI exhibited (i) in colon cells both higher net accumulation and a higher specific/nonspecific uptake ratio; (ii) in all three cell lines higher membrane-potential-dependent accumulation; and (iii) in all subcutaneous tumor xenografts and in colon subrenal capsule and hepatic tumor xenografts higher tumor/background ratios.

Animals↗

Microsatellite evidence for monogamy and sex-biased recombination in the Western Australian seahorse Hippocampus angustus.

Four polymorphic microsatellite loci were used to assess biological parentage of 453 offspring from 15 pregnant males from a natural population of the Western Australian seahorse Hippocampus angustus. Microsatellite genotypes in the progeny arrays were consistent with a monogamous mating system in which both females and males had a single mate during a male brooding period. Multilocus genotypes implicated four females in the adult population sample as contributors of eggs to the broods of collected males, but there was no evidence for multiple mating by females. Based on genotypic data from the progeny arrays, two loci were linked tightly and the recombination rate appeared to be approximately 10-fold higher in females than in males. The utility of linked loci for parentage analyses is discussed.

Animals↗

A case of rapid deterioration: acute multiple sclerosis of the Marburg type.

Multiple sclerosis (MS) is a chronic, progressive, degenerative, autoimmune disease that usually follows a relapsing-remitting course. In most cases of MS, the clinical course is variable with the vast majority of patients having mild to moderate disabilities that develop over the course of years. A subset of acute forms of MS exist and may be relatively unknown to neuroscience nurses. The acute forms follow a virulent course and are associated with high morbidity and mortality. A case presentation of a patient with the Marburg variant of MS raises the neuroscience nurse's understanding of the challenges associated with caring for patients with this unusual form of MS.

Acute Disease↗

A technetium-99m SPECT imaging agent which targets the dopamine transporter in primate brain.

The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for certain neurological diseases. In particular, the DAT is depleted in Parkinson's disease, and the extent of depletion correlates with the loss of dopamine. Herein we describe the design, synthesis, and biological evaluation of technepine, the first 99mTc-labeled SPECT imaging agent which targets the dopamine transporter in striatum. We have demonstrated that the DAT can accommodate a chelating unit attached to the 8-amine function of a tropane skeleton. Further, we have demonstrated for the first time that a molecule can be designed to carry the radionuclide 99mTc across the blood-brain barrier in sufficient quantity to obtain in vivo images of the striatum in monkeys. This advance will undoubtedly lead to the design of new receptor and transporter-mediated 99mTc agents which can label specific transporter and receptor targets in the central nervous system.

Animals↗

Comparison of uptake of 99mTc-alkylisonitriles in the rat 9L gliosarcoma tumor model.

The accumulation of three 99mTc(I) alkyl isonitriles was compared in vitro and in vivo using 9L gliosarcoma cells. In vitro, the uptake of 99mTc-EIBI and 99mTc-EPI was higher than that of 99mTc-MIBI. In vivo, however, there was no difference in the tumor concentration at 15 or 60 min postinjection and only a small difference at 24 h. The differences in uptake observed in vitro are apparently offset in vivo by differences in delivery of the tracers to the tumor.

Animals↗

Microsatellite analysis of maternity and the mating system in the Gulf pipefish Syngnathus scovelli, a species with male pregnancy and sex-role reversal.

Highly variable microsatellite loci were employed to study the mating system of the sexually dimorphic Gulf pipefish Syngnathus scovelli. In this species, like others in the family Syngnathidae, 'pregnant' males provide all parental care. Gulf pipefish were collected from one locale in the northern Gulf of Mexico, and internally carried broods of 40 pregnant males were analysed genetically. By comparing multilocus microsatellite fingerprints for the inferred mothers against expected genotypic distributions from the population sample, it was determined that: (i) only one male had received eggs from more than a single female; and (ii) on two separate occasions, two different males had received eggs from the same female. Given the high power to detect multiple matings by males, the first finding indicates that only rarely are individual males impregnated by multiple females during the course of a pregnancy. Conversely, given the lower power to detect multiple matings by females due to sampling constraints, the second finding suggests a high frequency of multiple successful matings by females. Thus, this population of Gulf pipefish displays a polyandrous genetic mating system. The relevance of these genetic findings is discussed with regard to the evolution of secondary sex traits in this species, and in other syngnathids.

Animals↗

Transmigration of permanent mandibular canines.

Transmigration is a rare occurrence relating to the movement of a mandibular canine across the mid-line of the mandible. Two cases are presented where patients referred for assessment of third molar problems subsequently revealed on radiological examination the asymptomatic phenomenon of transmigration. With dental panoramic radiography becoming more widespread among dental practitioners it is possible that more cases of transmigration will be observed.

Adult↗

A new approach to labeling cells with technetium-99m, Part II. Evaluation of radiolabeled human-lymphocyte immune functions.

Technetium-99m-modified polylysine (MPL) is a mild and efficient method for cell labeling that is easily applicable to human lymphocytes. 99mTc-MPL uptake is maximal in 40 min at room temperature. Cell labeling efficiency (from 60 to 80%) increases with rising concentrations of cells and labeling agent. In vitro stability of 99mTc-MPL on lymphocytes incubated in serum at 37 degrees C is high. Microautoradiography indicates that 99mTc-MPL is equally distributed within the cells. The radiolabeling procedure does not alter expression of surface receptors involved in T lymphocyte effector functions, adhesion function, cytolytic activity or proliferative response to IL-2.

Antibodies, Monoclonal↗

A new approach to labeling cells with technetium-99m, Part I. Preparation of modified polylysine and in vitro cell labeling.

A method for labeling cells with technetium-99m via hydrophilic, polycationic poly D-lysine modified by N-acetyl homocysteine has been developed. The modified polylysine (MPL) is labeled with 99mTc in > 95% yield and is stable for > 12 h. Maximum cell labeling is achieved by a 1-h incubation at room temperature with isolated leukocytes, granulocytes and peripheral blood mononuclear cells attaining 60-75% 99mTc incorporation, and red blood cells 35%. Ninety-two percent of the label is retained by leukocytes after a 1-h incubation at room temperature in 50% serum. The cell uptake of 99mTc-MPL is affected by the presence of negatively charged species in the medium; the inhibitory effects of 5% serum or serum albumin can be reversed by increasing the concentration of 99mTc-MPL, while those of heparin are not.

Adult↗

The re-establishment of molar occlusion following orthognathic surgery.

The effect on distal molar occlusion following mandibular orthognathic surgery is highlighted. Two cases are presented in which at the completion of orthodontic/surgical treatment a stable molar occlusion was re-established by adjunctive restorative treatment. The clinical problem highlighted, illustrates the importance of restorative support for patients with residual post-orthodontic and post-surgical occlusal problems.

Crowns↗

Anaesthesia in the elderly. Special considerations.

The physiological effects of aging may alter the pharmacokinetics and pharmacodynamics of many anaesthetic drugs. Premedicants should be avoided in the very old, and intravenous induction agents given in reduced dosage. The new inhalational agents, desflurane and sevoflurane, may be useful in this patient group; sevoflurane can also be administered to induce anaesthesia. However, both these agents can have adverse cardiovascular effects at high concentrations. The nondepolarising neuromuscular blocking drug, atracurium, is useful in the elderly because it does not undergo organ disposition. It may, however, cause histamine release, with resultant hypotension and tachycardia. It is as yet uncertain whether the isomer of atracurium, cisatracurium, will have any advantages in this age group, but it appears to be free from histamine-releasing effects. If residual neuromuscular block is antagonised in the elderly, then the dosage of anticholinesterase should be titrated using neuromuscular monitoring, as these agents can have adverse effects in this age group. Postoperative analgesia requires careful control in the elderly. Several methods of administration exist for relieving pain in this age group, but each has disadvantages. Anaesthesia in the elderly therefore requires skill and judgement based on these physiological and pharmacological considerations.

Aged↗

Generation of hydroxyl radicals by nucleohistone-bound metal-adriamycin complexes.

A recently developed method has been utilized to demonstrate the generation of hydroxyl radicals (HO.) in the immediate proximity of DNA by copper(II)/iron(III)-adriamycin in the presence of ascorbate and hydrogen peroxide. SECCA, a succinylated derivative of coumarin, generates the fluorescent 7-hydroxy-SECCA following reaction with HO.. SECCA was coupled to polylysine or to histone H1 and then complexed to DNA. When HO. was generated in the proximity of DNA by polylysine-coupled iodine-125, which emits short range Auger electrons, 7-hydroxy-SECCA was produced. DMSO was only moderately efficient in reducing the fluorescence induction, demonstrating the "local" generation of HO. in this system. Copper(II)/iron(III)-adriamycin in the presence of ascorbate and hydrogen peroxide generated the fluorescent 7-hydroxy-SECCA both when SECCA was free in solution and when SECCA was DNA-conjugated. With SECCA free in solution, the fluorescence induction was almost eliminated in the presence of HO. scavengers (ethanol, tert-butanol or DMSO) and the relative efficiency of the scavengers in reducing the fluorescence followed their rate constant with HO.. Furthermore, SECCA incubated with a single oxygen-generating compound demonstrated no fluorescence induction. When SECCA was positioned in close proximity to DNA as a SECCA-histone-H1-DNA complex, the relative efficiency of the scavengers in reducing the fluorescence still followed their rate constant with HO.; overall however the scavengers were much less effective in reducing the fluorescence, due presumably to the formation of HO. radical in the immediate vicinity of DNA. These data suggest that copper(II)/iron(III)-adriamycin produces HO. in the presence of ascorbate and hydrogen peroxide whether unbound or bound to DNA and suggest that in the latter case scavengers would not prevent HO. from attacking chromatin. In addition, the ability of DMSO to trap HO. was shown to decrease as the conformation of the H1-DNA complex becomes more compact indicating the strong dependence of the trapping ability on chromatin conformation.

Chemical Phenomena↗

Are anterior occlusal radiographs indicated to supplement panoramic radiography during an orthodontic assessment?

Five hundred pairs of dental panoramic tomographs (DPT) and maxillary anterior occlusal radiographs (AO) from patients referred to the orthodontic department of a dental teaching hospital were examined to assess the diagnostic yield from a panoramic radiograph of the premaxillary region alone and then assess the additional yield when this view was supplemented by a maxillary anterior occlusal radiograph. Of the 500 DPTs assessed, 208 (42%) lacked clarity of the premaxillary region when the labial segments were used to locate the patient in the DPT machine. An association was found between patients who had abnormal incisor relationships and poor clarity in the premaxillary region of the DPT. Overall 165 (33%) of the supplementary AO views were used to support or refute findings identified on the DPT. It was concluded that in patients referred for an orthodontic assessment, supplementary radiography of the premaxilla may be justified in the following situations: 1. unsatisfactory image quality which may frequently be the case where there are abnormal incisor relationships, 2. localisation of tooth position by vertical parallax and 3. where a reasonable expectation that pathology exists on clinical grounds.

Humans↗