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Biomedical subjects

Alan Wilson

Publications and source records attributed to Alan Wilson.

12 recordsLinked to original sources
PubMed2007

The determination of muscle volume with a freehand 3D ultrasonography system.

Muscle morphology determines muscle function. An objective method to determine muscle volume in vivo will facilitate understanding of basic muscle function and will also provide a valuable tool for the clinician to assess the effectiveness of treatment. In this method-validation study, it is hypothesised that a freehand 3-D ultrasonography system provides a noninvasive method that allows the determination of muscle volume with high accuracy and precision. To test the hypotheses, repeated measurements were performed (1) on cadaver muscles in situ, (2) isolated muscles and (3) live animals. Volume measurements performed with 3-D ultrasonography were compared with measurements based on computed tomography and the water displacement method. The results of this study showed that 3-D ultrasound provided excellent precision and accuracy in the measurements on the isolated muscles and good precision in vivo. It is concluded that 3-D ultrasonography is an innovative technique that allows objective determination of muscle volume in vivo.

Animals↗
PubMed2006

Dopamine D2 and D3 receptors in human putamen, caudate nucleus, and globus pallidus.

Because radioactive raclopride and radioactive (+)-4-propyl-9-hydroxynaphthoxazine ((+)-PHNO) are used to image dopamine (DA) D2 and D3 receptors in the striatum and globus pallidus in humans, the present study examined the proportions of D2 and D3 receptors in postmortem tissues from these regions. Conflicting results were obtained when using a single concentration of remoxipride to occlude D2 receptors or using a single concentration of U99194A or FAUC 365 to occlude D3 receptors. However, using a range of concentrations of FAUC 365, a D3-selective antagonist, to inhibit the binding [(3)H]raclopride or [(3)H]-(+)-PHNO to D3 receptors at low concentrations (1-10 nM) and to inhibit ligand binding to D2 receptors at higher concentrations (100-2000 nM), it was possible to measure the proportion of D2 and D3 receptors in the tissues. This method revealed that these two radioligands detected only D2 receptors in the dorsal putamen and the dorsal caudate nucleus, but detected a mixed population of two-thirds D2 and one-third D3 DA receptors in the ventral putamen, the ventral caudate, and the globus pallidus. The present findings are in good agreement with the known gene expression data for D2 and D3 receptors in these human brain regions.

Animals↗
PubMed2006

P-wave amplitude and pulmonary artery pressure in scleroderma.

BACKGROUND AND PURPOSE: Scleroderma is an immune-mediated disease characterized by excess deposition of collagen leading to microvascular occlusion. Morbidity and mortality are often secondary to pulmonary hypertension from injury to pulmonary microvasculature and interstitial lung disease. This study correlated P-wave findings on the 12-lead electrocardiogram (ECG) with mean pulmonary artery pressure (mPAP) measured by right heart catheterization in patients with scleroderma. METHODS: A retrospective review of 12-lead ECGs in 23 patients referred to a rheumatology clinic with the diagnosis of scleroderma was performed. Right heart catheterization was performed within 1 month of the resting ECG. RESULTS: Linear regression related P-wave amplitude in lead II with mPAP (r = 0.52, P = .011) This model was 73% sensitive and 67% specific for the presence or absence of elevated mPAP. CONCLUSIONS: P-wave amplitude analysis on the ECG may be helpful in the assessment of pulmonary hypertension in patients with scleroderma.

Adult↗
PubMed2006

The tegument surface membranes of the human blood parasite Schistosoma mansoni: a proteomic analysis after differential extraction.

The blood fluke Schistosoma mansoni can live for years in the hepatic portal system of its human host and so must possess very effective mechanisms of immune evasion. The key to understanding how these operate lies in defining the molecular organisation of the exposed parasite surface. The adult worm is covered by a syncytial tegument, bounded externally by a plasma membrane and overlain by a laminate secretion, the membranocalyx. In order to determine the protein composition of this surface, the membranes were detached using a freeze/thaw technique and enriched by sucrose density gradient centrifugation. The resulting preparation was sequentially extracted with three reagents of increasing solubilising power. The extracts were separated by 2-DE and their protein constituents were identified by MS/MS, yielding predominantly cytosolic, cytoskeletal and membrane-associated proteins, respectively. After extraction, the final pellet containing membrane-spanning proteins was processed by liquid chromatographic techniques before MS. Transporters for sugars, amino acids, ions and other solutes were found together with membrane enzymes and proteins concerned with membrane structure. The proteins identified were categorised by their function and putative location on the basis of their homology with annotated proteins in other organisms.

Animals↗
PubMed2005

Regional distribution of serotonin transporter protein in postmortem human brain: is the cerebellum a SERT-free brain region?

INTRODUCTION: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a "SERT-free" reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. OBJECTIVE AND METHODS: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. RESULTS: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. CONCLUSION: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met.

Blotting, Western↗
PubMed2004

Electrocardiogram and clinical characteristics of patients referred for cardiac transplantation: implications for pacing in heart failure.

BACKGROUND: Permanent pacing for the treatment of heart failure (HF) has been the subject of intense research over the past decade. Those with conduction abnormalities may benefit most from pacing. The incidence of these conduction abnormalities in patients referred for cardiac transplantation and its relationship to outcome has not been well described. HYPOTHESIS: This study sought to determine the incidence of these abnormalities and to correlate these findings to outcome in this patient population. METHODS: A review of 100 patients referred for transplantation was performed. Data were analyzed in two groups: those with QRS duration < 120 ms and those with a QRS duration > 120 ms. Times to transplantation or death were analyzed in these two groups. RESULTS: Of these patients, 34% had QRS duration > or = 120 ms and survival was inversely associated with QRS duration. Of those with QRS duration < 120 ms, 24% (16) went on to cardiac transplantation or died. Of those with a QRS duration > or = 120 ms, 55% (17) went on to transplantation or died (p = 0.0134). CONCLUSIONS: This suggests that in addition to a multi-drug regimen for heart failure, 34% of patients referred for transplantation may benefit from additional therapy with biventricular pacing.

Cardiac Pacing, Artificial↗
PubMed2004

Immediate and 1-year survival of out-of-hospital cardiac arrest victims in southern New Jersey: 1995-2000.

Most studies report the out-of-hospital cardiac arrest (OHCA) survival to hospital discharge. One-year survival and neurological outcomes in southern New Jersey in 1996-2000 were analyzed using a retrospective data review. There were 1,597 cases of OHCA. Initial survival ranged between 15% in 2000 and 19% in 1997. Survival to hospital discharge, taken as a percent of the initial survivors, decreased from 44% in 1997 to 22% in 2000. In relation to all OHCA victims, survival to discharge decreased from 7.2% to 2.4%, respectively. On discharge from the hospital 19-50% of people had the diagnosis of anoxic brain damage. In ventricular fibrillation, survival to discharge was 41%, 46.7%, 40.7%, 37.5%, and 17.4%, respectively, from 1996 to 2000. The response time increased from 6.6 to 8.1 minutes. Correlation coefficient between in-hospital survival and response time was -0.73. The percent of people discharged with neurological damage increased from 38% to 50%. Initial survival was 29.2% in shockable and 7.5% in nonshockable rhythm (P < 0.001). Survival to discharge was 11.3% versus 1.6%, and survival to 1 year was 9.6% versus 0.7%, respectively (P < 0.001 for all). Overall, the neurologically favorable 1-year survival rate was 2.3% of all OHCA victims. One-year survival of OHCA victims without neurological deficits is low. In southern New Jersey the survival rate did not improve over the 5-year study. Not only initial (prehospital) mortality, but also "delayed" (in-hospital mortality) increases with increase of response time.

Brain Damage, Chronic↗
PubMed2003

[11C]-NS 4194 versus [11C]-DASB for PET imaging of serotonin transporters in living porcine brain.

In vitro, the novel diazabicyclononane NS 4194 has several thousand-fold selectivity for blocking the transport into rat brain synaptosomes of [(3)H]-serotonin in comparison to [(3)H]-dopamine or [(3)H]-noradrenaline. We have prepared [(11)C]-NS 4194 in order to test its properties for PET imaging of brain serotonin transporters in comparison with the well-documented tracer [(11)C]-DASB. Both compounds had rapid clearance from blood to brain of living pigs. The apparent equilibrium distribution volumes in cerebellum were 35 ml g(-1) for [(11)C]-NS 4194 and 11 ml g(-1) for [(11)C]-DASB. Pretreatment of pigs with citalopram did not reduce the uptake of either tracer in cerebellum, validating the use of that tissue as a nonbinding reference tissue for kinetic analysis of specific binding. The binding potential (pB) calculated for [(11)C]-NS 4194 using arterial input models was close to 0.5 in the telencephalon, and was 60% displaced by citalopram. However, the reference tissue method of Lammertsma was unsuited to calculate pB for this tracer, apparently due to its excessive nonspecific binding. In contrast to the relatively homogeneous binding of [(11)C]-NS 4194, the pB of [(11)C]-DASB ranged from 0.6 in frontal cortex to 2 in the mesencephalon when calculated by the method of Lammertsma. Parametric maps of the pB of [(11)C]-DASB showed a pattern consistent with the known distribution of serotonin transporters in pig brain in vitro, and there was a uniform displacement of 80% of the specific binding after citalopram treatment in vivo. In conclusion, [(11)C]-DASB is in several respects superior to [(11)C]-NS 4194 for the detection of serotonin uptake sites by PET.

Animals↗
PubMed2003

Structure-activity relationship of imidazo[1,2-a]pyridines as ligands for detecting beta-amyloid plaques in the brain.

A series of novel beta-amyloid (A beta) aggregate-specific ligands, 2-(4'-dimethylaminophenyl)-6-iodoimidazo[1,2-a]pyridine, 16(IMPY), and its related derivatives were prepared. An in vitro binding study with preformed A beta aggregates showed that 16(IMPY) and its bromo derivative competed with binding of 2-(4'-dimethylaminophenyl)-6-iodobenzothiazole, [125I]7(TZDM), a known ligand for A beta aggregates, with high binding affinities (K(i) = 15 and 10 nM, respectively). In vitro autoradiography of brain sections of a transgenic mouse (Tg2576) with [125I]16(IMPY) displayed high selective binding to amyloid-like structures, comparable to that observed by staining with thioflavin-S visualized under fluorescence. In vivo biodistribution after an intravenous injection of [125I]16(IMPY) in normal mice showed a high initial brain uptake and fast washout, indicating a low background activity associated with this iodinated ligand. Taken together, the data suggests that [123I]16(IMPY) may be useful for imaging A beta aggregates in patients with Alzheimer's disease.

Alzheimer Disease↗
PubMed2003

11C-labeled stilbene derivatives as Abeta-aggregate-specific PET imaging agents for Alzheimer's disease.

A series of stilbene derivatives as potential diagnostic imaging agents targeting amyloid plaques in Alzheimer's disease (AD) were synthesized and evaluated. The syntheses of the stilbenes were successfully achieved by a simple Wadsworth-Emmons reaction between diethyl (4-nitrobenzyl)phosphonate and 4-methoxybenzaldehyde. 4-N,N-dimethylamino-4'-methyoxy and the corresponding 4-N-monomethylamino-, 4'-hydroxy stilbenes showed good binding affinities towards Abeta aggregates in vitro (K(i) < 10 nM). The (11)C labeled 4-N-methylamino-4'-hydroxystilbene, [(11)C]4, was prepared by (11)C methylation of 4-amino-4'-hydroxystilbene. The [(11)C]4 displayed a moderate lipophilicity (log P = 2.36), and showed a very good brain penetration and washout from normal rat brain after an iv injection. In vitro autoradiography of transgenic AD mouse brain sections showed a high specific labeling of beta-amyloid plaques, whereas the control sections showed no binding. Taken together the data suggest that a relatively simple stilbene derivative, [(11)C]4, N-[(11)C]methylamino-4'-hydroxystilbene, may be useful as a positron emission tomography (PET) imaging agent for mapping Abeta plaques in the brain of patients with Alzheimer's disease.

Alzheimer Disease↗