Search PubMed⌕ Search

Biomedical subjects

R Myers

Publications and source records attributed to R Myers.

At least 91 records · Page 5Linked to original sources
PubMed1992

Quantitation of carbon-11-labeled raclopride in rat striatum using positron emission tomography.

Using conventional autoradiographic and tissue counting techniques, the experimental quantitation of in vivo kinetics of prospective or established radioligands for PET is animal and labour intensive. The present study tested the feasibility of using PET itself to quantitate the specific binding of [11C]raclopride to rat striatum and to study the effects of experimental manipulation of endogenous dopamine on binding parameters. Carbon-11-labeled raclopride was given i.v. to anaesthetised rats, positioned in a PET camera and dynamic emission scans acquired over 60 min. Time-activity curves were generated for selected regions of interest, representing striatum and cerebellum and the striatal data fitted to a compartmental model, using cerebellum as the input function, thus circumventing the need for individual metabolite-corrected plasma curves. In control rats, the binding potential (BP), defined as the ratio of the rate constants for transfer from "free to bound" and "bound to free" compartments, was of the order of 0.6. This was reduced threefold by predosing with nonradioactive raclopride. Increasing extracellular dopamine levels by predosing with d-amphetamine resulted in a significant decrease in BP whereas reducing extracellular dopamine by predosing with gamma-butyrolactone caused a significant increase. Thus, despite the limitation in spatial resolution of PET, specific binding of raclopride could be assessed from regional time-activity curves from individual rats. The system was sufficiently sensitive that changes in BP could be detected following modulation of endogenous dopamine levels, a finding of potential relevance to the interpretation of clinical PET data.

Animals↗
PubMed1992

The distribution of radioactivity in brains of rats given [N-methyl-11C]PK 11195 in vivo after induction of a cortical ischaemic lesion.

PK 11195 is a selective ligand for the peripheral-type benzodiazepine binding site (PTBBS). There are few such sites in normal brain but their number increases in association with tissue necrosis. The time-course of appearance of PTBBS around a focally induced ischaemic lesion in frontal cortex of rat brain was established by autoradiography using [N-methyl-3H]PK 11195. Using this information and the same experimental model of ischaemia, the distribution of radioactivity after injection of carbon-11 (t1/2 = 20.3 min, beta+ = 99.8%) labelled PK 11195 was studied. The purpose was to synthesize [N-methyl-11C]PK 11195 and to test its suitability as a tracer for depicting the presence of PTBBS in ischaemic lesions. The time-profiles of distribution of radioactivity in brain regions after intravenous injection of tracer and the ratio of radioactivity in lesioned compared with unlesioned cortex were determined. Data for the temporal (days after lesion induction) and for the regional retention of radioactivity were consistent with independent evidence (autoradiographic and immunohistochemical) for the occurrence of increased numbers of PTBBS, predominantly in association with macrophages, in areas undergoing necrosis.

Animals↗
PubMed1992

Quantification of in vivo binding of [3H]RX 821002 in rat brain: evaluation as a radioligand for central alpha 2-adrenoceptors.

On the basis of its established in vitro characteristics, [3H]RX 821002 was evaluated in rats as an in vivo radioligand for central alpha 2-adrenoceptors. Estimates for in vivo binding potential, obtained by compartmental analyses of time-radioactivity data, ranged between 1.9 for hypothalamus and 0.2 for cerebellum, with a regional distribution in brain which was similar to that observed in vitro. Selectivity and specificity of the signal were checked by predosing with either the alpha 2-antagonists, idazoxan or yohimbine, the alpha 2-agonist, clonidine, or the alpha 1-antagonist, prazosin. Pretreatment of the rats with the selective neurotoxin, DSP-4, had no significant effect on [3H]RX 821002 binding, suggesting that the majority of labelled sites were situated post-junctionally. The studies indicate that [3H]RX 821002 can be used experimentally as an in vivo marker for central alpha 2-adrenoceptors. The size and rate of expression of the specific signal encourage the development and assessment of [11C]RX 821002 for clinical PET studies.

Adrenergic alpha-Antagonists↗
PubMed1992

The Huntington's disease candidate region exhibits many different haplotypes.

Analysis of 78 Huntington's disease (HD) chromosomes with multi-allele markers revealed 26 different haplotypes, suggesting a variety of independent HD mutations. The most frequent haplotype, accounting for about one third of disease chromosomes, suggests that the disease gene is between D4S182 and D4S180. However, the paucity of an expected class of chromosomes that can be related to this major haplotype by assuming single crossovers may reflect the operation of other mechanisms in creating haplotype diversity. Some of these mechanisms sustain alternative scenarios that do not require a multiple mutational origin for HD and/or its positioning between D4S182 and D4S180.

Alleles↗
PubMed1992

Laser resection of granulation tissue secondary to transtracheal oxygen catheter.

Oxygen therapy through a transtracheal catheter has been used increasingly for the long-term delivery of continuous oxygen. Compared to nasal cannula it results in significant reduction in oxygen flow requirements. This form of therapy has gained patient acceptance because of several advantages including improved convenience, aesthetics, compliance, and mobility. Reported complications generally have been minor, including subcutaneous emphysema, cough, "mucous ball" formation and mild hemoptysis. In this report, we describe a case of granulation tissue formation at the transtracheal catheter puncture site which was treated with Nd:YAG laser bronchoscopy to reestablish patency of the upper airway. No recurrence was noted after two years of follow-up.

Bronchoscopy↗
PubMed1991

[3H]PK 11195 and the localisation of secondary thalamic lesions following focal ischaemia in rat motor cortex.

The peripheral-type benzodiazepine binding site (PTBBS) ligand, PK 11195, is known to be a marker of damage in the central nervous system, the binding being predominantly to macrophages. Using photochemically induced focal cortical ischaemia as a lesion model in the rat, we have investigated the detection of secondary lesions using [3H]PK 11195 and ex vivo autoradiography. Secondary lesions in the thalamus became apparent during the second week post-lesioning, at a time when [3H]PK 11195 binding around the primary lesion was beginning to subside. Using Brain Browser software, the identity of the labelled thalamic nucleus was confirmed, objectively, as the ventrolateral nucleus, known to have reciprocal connections with the lesioned cortical area. As with the primary lesion, high densities of PTBBS correlated with infiltration of macrophages. Three-dimensional reconstruction of [3H]PK 11195 autoradiograph images showed binding along white matter tracts between the primary and secondary lesions. We conclude that radiolabelled PK 11195 given in vivo can be used in the visualisation of secondary lesions and their associated degenerating tracts.

Animals↗
PubMed1991

Citalopram: labelling with carbon-11 and evaluation in rat as a potential radioligand for in vivo PET studies of 5-HT re-uptake sites.

In vivo autoradiography of [N-methyl-3H]citalopram in rat brain shows a differential regional localization which correlates with the localization of 5-HT re-uptake binding sites defined in vitro. A comparison of the biodistribution of [N-methyl-3H]citalopram over 2 h after i.v. injection in (1) control rats (2) rats pre-dosed with either citalopram or paroxetine and (3) rats chemically-lesioned with p-chloroamphetamine provides an estimate of specific binding relative to total binding in vivo. The ratio of binding in certain regions (e.g. cingulate) to binding in a reference tissue (e.g. cerebellum) at 30-120 min post injection is c. 1.4. In view of these results a method was developed for labelling citalopram with carbon-11 (t1/2 = 20.3 min, beta + = 99.8%) to provide a potential radioligand for studies using positron emission tomography. Thus, reaction of nca [11C]iodomethane, prepared from cyclotron-produced [11C]carbon dioxide, with norcitalopram in ethanol containing 2,2,6,6-tetramethyl-piperidine for 5 min at 95 degrees C gives crude [N-methyl-11C]citalopram in 60% radiochemical yield, decay-corrected. HPLC on silica gel provides radiochemically and chemically pure [N-methyl-11C]citalopram, as assessed by TLC, HPLC and MS. This product (isolated radiochemical yield, 49%) is easily formulated for i.v. injection. Up to 2 GBq of formulated product with a specific activity of c. 15 GBq/mumol have been prepared within 40 min from the end of radionuclide production. The described radiosynthesis has also been applied to give the single biologically active (+)-enantiomer of [N-methyl-11C]citalopram rather than the racemate. This product gives enhanced specific signal in the rat following i.v. injection, the ratio of uptake in regions of interest relative to cerebellum approaching 2 at 90 min.

Animals↗
PubMed1991

Macrophage and astrocyte populations in relation to [3H]PK 11195 binding in rat cerebral cortex following a local ischaemic lesion.

PK 11195 is a selective and specific ligand for the peripheral-type benzodiazepine binding site. Its potential for in vivo visualisation of lesioned human brain using positron emission tomography (PET) is currently being assessed. The present study examines the relationship between the temporal development of a local ischaemic lesion with its associated cell populations and the binding of [3H]PK 11195 in rat brain. Unilateral cortical infarcts were induced using the photosensitive dye Rose Bengal. At time intervals from 1 to 7 days after lesioning, the localisation of [3H]PK 11195 binding was determined using in vivo and in vitro autoradiography. Sections adjacent to those used for autoradiography were processed for immunohistochemistry using glial fibrillary acidic protein for astrocytes and ED-1 for macrophages. The results show that the binding of [3H]PK 11195 correlates in both time and spatial localisation with the appearance of macrophages around the lesion. Reactive astrocytes, although present, occupy a separate region in the tissue surrounding the lesion and lie outside the region defined by the [3H]PK 11195 binding. We conclude that the [3H]PK 11195 signal associated with this ischaemic lesion originates primarily from binding to macrophages and that [11C]PK 11195 could be used for imaging acute inflammatory response in human brain using PET.

Animals↗
PubMed1991

Large-scale preparation of a highly purified solvent-detergent treated factor VIII concentrate.

Large-scale adaptation of a recently reported glycine precipitation method for the production of factor VIII (FVIII) concentrate is described. Scaling up of the method required some modification including the addition of aluminum hydroxide to the glycine buffer to reduce the level of contaminating proteins in the final preparation and the use of centrifugation to replace filtration by glass beads. Furthermore, the resultant product was virus inactivated by incorporation of the organic solvent and detergent technique. At industrial level, the modified method gave a good recovery of FVIII activity (230 IU/l plasma) with high purity (4 IU/mg protein). The final product, after virus inactivation and lyophilization, yielded 185 IU of FVIII activity per liter of starting plasma and was considered to be suitable for clinical evaluation.

Detergents↗
PubMed1990

The reduction of radiation damage to the spinal cord by post-irradiation administration of vasoactive drugs.

Radiation induced white matter necrosis in the rat spinal cord is preceded by changes in permeability of the blood brain-barrier, reduced blood flow, and infarction so that the necrosis is an ischemic necrosis. Attempts have been made to modify this developing pathology by the administration of drugs post-irradiation but just prior to the changes in vascular permeability. Verapamyl, a calcium channel blocker, had no effect on the development of ataxia. Dipyridamole, a drug which increases blood flow and reduces thrombosis, delayed and reduced the onset of ataxia. A low iron diet and desferrioxamine which reduces reperfusion injury also delayed and reduced ataxia. These results support the thesis that vascular changes are an important pathway in the development of radiation necrosis and that reperfusion injury is an important factor in the development and exacerbation of radiation damage to the spinal cord.

Animals↗
PubMed1990

The radiosynthesis of [18F]PK 14105 as an alternative radioligand for peripheral type benzodiazepine binding sites.

A method has been developed for labelling PK 14105 [N-methyl-N-(1-methyl-propyl)-1(2-fluoro-5-nitrophenyl)isoquinoline-3- carboxamide], a ligand that has high affinity and selectivity for peripheral type benzodiazepine binding sites (PBBS), with NCA fluorine-18 (t1/2 = 109.8 min, beta + = 96.9%). The method involves treating the 2-chloro-analogue with cyclotron-produced NCA [18F]fluoride in dimethyl sulphoxide, with rubidium carbonate as base, at 140 degrees C for 20 min. Purification is achieved by separation on a reverse phase Sep-Pak followed by PHLC on a silica gel column, to give chemically and radiochemically pure product with a specific activity of ca 7.4 GBq/mumol (200 mCi/mumol), decay-corrected to the end of radionuclide production (EOB). The radiosynthesis requires 210 min. giving a radiochemical yield of 10-20%, decay-corrected to EOB. [18F]PK 14105 was found to bind avidly to sites associated with kainic acid-induced unilateral lesions of rat striata. Such binding was blocked by pre-dosing the rat with PK 11195, so providing evidence for specific binding to PBBS. These results suggest that [18F]PK 14105 has potential for studying phenomena associated with PBBS in man by PET.

Animals↗