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At least 559 records · Page 31Linked to original sources
PubMed2000

Gamma camera-mounted anatomical X-ray tomography: technology, system characteristics and first images.

Scintigraphic diagnosis, based on functional image interpretation, becomes more accurate and meaningful when supported by corresponding anatomical data. In order to produce anatomical images that are inherently registered with images of emission computerised tomography acquired with a gamma camera, an X-ray transmission system was mounted on the slip-ring gantry of a GEMS Millennium VG gamma camera. The X-ray imaging system is composed of an X-ray tube and a set of detectors located on opposite sides of the gantry rotor that moves around the patient along with the nuclear detectors. A cross-sectional anatomical transmission map is acquired as the system rotates around the patient in a manner similar to a third-generation computerised tomography (CT) system. Following transmission, single-photon emission tomography (SPET) or positron emission tomography (PET) coincidence detection images are acquired and the resultant emission images are thus inherently registered to the anatomical maps. Attenuation correction of the emission images is performed with the same anatomical maps to generate transmission maps. Phantom experiments of system performance and examples of first SPET and coincidence detection patient images are presented. Despite limitations of the system when compared with a state of the art CT scanner, the transmission anatomical maps allow for precise anatomical localisation and for attenuation correction of the emission images.

Adult↗
PubMed2004

The oligopeptide permease (Opp) of the plant pathogen Xanthomonas axonopodis pv. citri.

The oligopeptide permease (Opp), a protein-dependent ABC transporter, has been found in the genome of Xanthomonas axonopodis pv. citri ( Xac), but not in Xanthomonas campestris pv. campestris ( Xcc). Sequence analysis indicated that 4 opp genes ( oppA, oppB, oppC, oppD/F), located in a 33.8-kbp DNA fragment present only in the Xac genome, are arranged in an operon-like structure and share highest sequence similarities with Streptomyces roseofulvus orthologs. Nonetheless, analyses of the GC content, codon usage, and transposon positioning suggested that the Xac opp operon does not have an exogenous origin. The presence of a stop codon at one of the ATP-binding domains of OppD/F would render the uptake system nonfunctional, but detection of a single polycistronic mRNA and periplasmic OppA in actively growing bacteria suggests that the Opp permease is active and could contribute to the distinct nutritional requirements and host specificities of the two Xanthomonas species.

Bacterial Proteins↗
PubMed2006

Can 16-detector multislice CT exclude skeletal lesions during tumour staging? Implications for the cancer patient.

Current imaging guidelines recommend that many cancer patients undergo soft-tissue staging by computed tomography (CT) whilst the bones are imaged by skeletal scintigraphy (bone scan). New CT technology has now made it feasible, for the first time, to perform a detailed whole-body skeletal CT. This advancement could save patients from having to undergo duplicate investigations. Forty-three patients with known malignancy were investigated for bone metastasis using skeletal scintigraphy and 16-detector multislice CT. Both studies were performed within six weeks of each other. Whole-body images were taken 4 h after injection of 500 Mbq (99m)Tc-MDP using a gamma camera. CT was performed on a 16-detector multislice CT machine from the vertex to the knee. The examinations were reported independently and discordant results were compared at follow-up. Statistical equivalence between the two techniques was tested using the Newcombe-Wilson method within the pre-specified equivalence limits of +/-20%. Scintigraphy detected bone metastases in 14/43 and CT in 13/43 patients. There were seven discordances; four cases were positive on scintigraphy, but negative on CT; three cases were positive on CT and negative on scintigraphy. There was equivalence between scintigraphy and CT in detecting bone metastases within +/-19% equivalence limits. Patients who have undergone full whole-body staging on 16-detector CT may not need additional skeletal scintigraphy. This should shorten the cancer patient's diagnostic pathway.

Adult↗
PubMed2007

Circulation of a type 1 recombinant vaccine-derived poliovirus strain in a limited area in Romania.

After intensive immunisation campaigns with the oral polio vaccine (OPV) as part of the Global Polio Eradication Initiative, poliomyelitis due to wild viruses has disappeared from most parts of the world, including Europe. Here, we report the characterization of a serotype 1 vaccine-derived poliovirus (VDPV) isolated from one acute flaccid paralysis (AFP) case with tetraplegia and eight healthy contacts belonging to the same small socio-cultural group having a low vaccine coverage living in a small town in Romania. The genomes of the isolated strains appeared to be tripartite type 1/type 2/type 1 vaccine intertypic recombinant genomes derived from a common ancestor strain. The presence of 1.2% nucleotide substitutions in the VP1 capsid protein coding region of most of the strains indicated a circulation time of about 14 months. These VDPVs were thermoresistant and, in transgenic mice expressing the human poliovirus receptor, appeared to have lost the attenuated phenotype. These results suggest that small populations with low vaccine coverage living in globally well-vaccinated countries can be the origin of VDPV emergence and circulation. These results reaffirm the importance of active surveillance for acute flaccid paralysis and poliovirus in both polio-free and polio-endemic countries.

Animals↗
PubMed2006

Liver transplantation in the MELD era: a single-center experience.

Model for Endstage Liver Disease (MELD) score has been used to allocate organs since February 2002. This policy allocates organs to candidates with regard to severity of their underlying liver disease except in the case of hepatocellular carcinoma (HCC) patients. The purpose of this study was to determine the impact of MELD on waiting times, dropout rates, and transplantation rates in all patients awaiting liver transplantation at our center. The records of all patients listed for liver transplantation between May 28, 1999, and February 27, 2004, at the Mayo Clinic, Scottsdale, Arizona, were reviewed. Candidates were grouped by two time periods as pre-MELD or post-MELD based on date of MELD implementation (February 27, 2002). The incidence of deceased donor liver transplantation (DDLT), waiting time to DDLT, dropout rate from the waiting list because of clinical deterioration or death, and survival while waiting for or after DDLT were determined for each group. Three hundred fifty-one patients were listed for liver transplantation (195 pre-MELD, 156 post-MELD) during the study period. HCC patients had an improved rate of transplantation after MELD (pre-MELD, 1.39 persons per year; post-MELD, 3.48 persons per year). In all groups, with the exception of hepatitis C virus, the transplantation rates were the same for both categories. The hepatitis C virus group also had improved transplantation rates in the post-MELD period. HCC candidates under the new allocation policy have an increased incidence of DDLT in our institution. However, this has not disadvantaged patients with non-HCC diagnoses. Thus, the new MELD-based allocation policy has benefited all candidates by allowing more timely transplants.

Arizona↗
PubMed2006

Successful treatment with novel triple drug combination consisting of interferon-gamma, interferon alfacon-1, and ribavirin in a nonresponder HCV patient to pegylated interferon therapy.

Despite major advances in therapy of hepatitis C over the past decade, nearly half of the patients treated with the currently available regimens do not clear the virus. Therefore, there is a large unmet need for more effective therapy for patients who have failed pegylated interferon plus ribavirin therapy. We describe a case of a HCV genotype 1b patient who had failed previous combination therapies of interferon plus ribavirin and pegylated interferon plus ribavirin and was subsequently successfully treated with a novel triple drug combination consisting of interferon-gamma plus interferon alfacon plus ribavirin with the outcome of a sustained virologic response. This triple drug therapy combination could be an option for patients who have failed therapies with currently available pegylated interferons plus ribavirin. Prospective randomized studies are required to evaluate the effectiveness and tolerability of this regimen in this patient population.

Antiviral Agents↗
PubMed2005

Rational selection of structurally diverse natural product scaffolds with favorable ADME properties for drug discovery.

Natural product analogs are significant sources for therapeutic agents. To capitalize efficiently on the effective features of naturally occurring substances, a natural product-based library production platform has been devised at Aurigene for drug lead discovery. This approach combines the attractive biological and physicochemical properties of natural product scaffolds, provided by eons of natural selection, with the chemical diversity available from parallel synthetic methods. Virtual property analysis, using computational methods described here, guides the selection of a set of natural product scaffolds that are both structurally diverse and likely to have favorable pharmacokinetic properties. The experimental characterization of several in vitro ADME properties of twenty of these scaffolds, and of a small set of designed congeners based upon one scaffold, is also described. These data confirm that most of the scaffolds and the designed library members have properties favorable to their utilization for creating libraries of lead-like molecules.

Alkaloids↗
PubMed2003

Metabolic bone disease in patients with liver disease.

The coexistence of liver disease and osteopenic bone disease has been recognized for many years and is now the subject of increasing attention. Osteoporosis has been characterized well in patients with cholestatic liver disease, but new research suggests that osteopenia and osteoporosis may also be prevalent in patients with other chronic liver diseases. Although the precise mechanism of bone loss remains unclear, advances in treatment and prevention are bringing heightened awareness to this common problem.

Bone Diseases, Metabolic↗
PubMed1988

Cutaneous manifestations of candidiasis.

Candida is identified microscopically by the observation of hyphae, linear chains of asexually budding yeast. Since these structures do not grow extensively through the stratum corneum, cutaneous samples may require Gram stain for identification. Since Candida can colonize normal tissue and also be a culture contaminant, clinicians should consider predisposing factors and clinical presentation when making a diagnosis of candidiasis. Predisposing cutaneous factors for candidiasis include occlusion, maceration, and altered barrier function. The hallmarks of Candida infection are bright erythema, fragile papulopustules, and satellite lesions. Cutaneous and mucous membrane candidiasis may differ in appearance, and sexual transmission should be considered. Treatment usually involves a topical or oral anticandidal agent, such as an imidazole. Although implicated as a predisposing factor to candidiasis, mild topical steroids can be used as short-term adjuvant treatment of these infections; when used responsibly, steroids provide antiinflammatory effects that speed relief of patient discomfort.

Anti-Inflammatory Agents↗
PubMed1988

Tritium labeling of a powerful methylphosphonate inhibitor of cholinesterase: synthesis and biological applications.

7-(Methylethoxy phosphinyloxy)-1-methyl-quinolinium iodide (MEPQ), a powerful anti-cholinesterase methylphosphonate ester, was labeled with tritium (9 Ci/mmol) at the methylphosphonyl moiety (TCH2P(O)(OR)X) by an iodine-tritium replacement reaction. Kinetic measurements of the rate of inhibition of acetylcholinesterase (AChE) by [3H]MEPQ and its rate of hydrolysis in alkaline solution confirmed the identity of [3H]MEPQ with authentic MEPQ, which was prepared by the same reaction sequences. Gel-filtration experiments verified the radiospecificity of [3H]MEPQ. In vitro radiolabeling of both AChE and butyrylcholinesterase along with the whole-body autoradiography of [3H]MEPQ-treated mice suggests that [3H]MEPQ is a convenient marker for studying biological systems containing these esterases.

Acetylcholinesterase↗
PubMed1990

Biochemical and behavioral evidence for muscarinic autoreceptors in the CNS.

Muscarinic autoreceptors of the M2 subclass were examined in rat forebrain using a number of different methodologies, including receptor autoradiography and image analysis, regulation of acetylcholine release, phosphoinositide turnover, low-Km GTP hydrolysis, and behavioral analysis. The relatively minor population of M2 receptors in coronal sections was visualized by autoradiography and image analysis using [3H]quinuclidinyl benzilate in the presence of a concentration of pirenzepine that blocked most of M1 (and M4) receptors. The highest densities of M2 receptors in forebrain regions were found in the outer layers of the cortex, CA1 region of the hippocampus and striatum. The M2-, but not M1-selective antagonists were able to block the oxotremorine-induced attenuation of acetylcholine release in forebrain synaptosomes. Low concentrations of the M2-selective antagonist gallamine increased phosphoinositide turnover, which is thought to be an M1 postsynaptic response in the forebrain, in brain slices by a Ca2(+)-dependent mechanism. The M2-selective agonist oxotremorine produced a substantial stimulation of low-Km GTPase in cortical membranes, suggesting that M2 forebrain receptors are efficiently coupled to G-proteins in the cortex. Behavioral signs of cholinergic stimulation were observed after intracerebroventricular injections of M2-, but not M1-selective antagonists. It is suggested that a minor population of forebrain M2 receptors regulates acetylcholine release by a mechanism that includes coupling through G-proteins presynaptically at synapses for which the postsynaptic response involves phosphoinositide turnover. Selective blockade of these receptors produces both biochemical and behavioral signs of acetylcholine release.

Acetylcholine↗
PubMed1985

A novel immunoassay with direct relevance to protection against organophosphate poisoning.

Antiparaoxon immune sera were employed in a new immunoassay based on competition between acetylcholinesterase and antibodies for the binding of paraoxon. Unlike radioimmunoassay, the new assay described herein can be extended to predict the feasibility of antibodies to confer in vivo protection of acetylcholinesterase against organophosphate poisoning. The toxicity of paraoxon was reduced in mice which were preinjected with the immune sera.

Acetylcholinesterase↗
PubMed1994

RT-PCR cloning of Rab3 isoforms expressed in peritoneal mast cells.

Rab proteins are ras-like low molecular mass GTP-binding proteins, which are postulated to act as specific regulators of membrane trafficking in exocytosis and endocytosis. We have previously shown that synthetic peptides, corresponding to the effector domain of Rab3 proteins, stimulate a complete exocytotic response in mast cells. We have used a PCR-cloning strategy to investigate the presence of mRNA encoding Rab3 in mast cells. RNA based PCR was then performed on mast cell RNA using degenerate oligonucleotide primers based on two conserved sequences among Rab3 proteins. However, no PCR products were obtained, even for proteins known to be expressed in high copy numbers in mast cells (beta-actin and Fc receptor). We have found that the problem resides in the presence of mast cell secretory granule derived heparin, that copurifies with the RNA; heparin has been shown to inhibit the activity of reverse transcriptase and Taq polymerase in PCR. After treating the RNA (obtained from about 500 mast cells) with heparinase, several PCR products of varying size were obtained using primers specific for Rab3 proteins. These products were cloned and sequenced. We have found clones containing sequences that had a 100% homology at the deduced amino acid level to a portion of Rab3B and Rab3D (amino acids 16 to 83).

Amino Acid Sequence↗
PubMed1994

Screening for hemochromatosis: a cost-effectiveness study based on 12,258 patients.

BACKGROUND/AIMS: Current emphasis in hemochromatosis has focused on early detection and treatment to prevent permanent liver damage and hepatocellular carcinoma. Thus far, only normal population and high-risk groups have been screened but not patients seeking medical care. METHODS: Serum iron levels were determined in consecutive fasting blood samples collected in the morning from 12,258 Mayo Clinic patients. RESULTS: One hundred twenty-seven patients had an initial serum iron concentration > or = 180 micrograms/dL. Eight patients (age, 38-71 years; 7 men and 1 woman) had transferrin saturation > or = 62% (range, 84-99) and serum ferritin value > or = 400 micrograms/L (range, 457-4004) with no other explanation for the abnormal iron test results. Three patients (2 male and 1 female) had markedly elevated hepatic iron concentration (range, 11,080-29,719 micrograms/g dry wt) and hepatic iron index (range, 2.9-8.4) indicative of homozygous hemochromatosis. One patient who refused liver biopsy had 7 g of iron removed by phlebotomy and is likely homozygous. Two patients had hepatic iron indices < 1.5 and are probably heterozygous. The genetic status of 1 patient is indeterminate, and 1 patient with normal hepatic iron concentration and hepatic iron index had chronic active hepatitis. None had cirrhosis, diabetes, or cardiomyopathy. No patients with hemochromatosis would have been detected without this study. CONCLUSIONS: The yield in this study, 0.33 cases of 1000 screened, is approximately one tenth of the predicted homozygote frequency by recent estimates. Even at this yield, screening appears cost-effective.

Adolescent↗