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Biomedical subjects

R Finn

Publications and source records attributed to R Finn.

At least 37 records · Page 2Linked to original sources

Technical challenges associated with the radiolabeling of monoclonal antibodies utilizing short-lived, positron emitting radionuclides.

Many factors, both physical and chemical, affect the radiolabeling of a chemical compound. These factors add a new dimension of complexity when the labeling of monoclonal antibodies is attempted with short-lived, positron emitting radionuclides. A lack of appreciation for the unique chemical separations associated with the radionuclide incorporated into the synthetic precursor can often lead to unexpected or non-reproducible results.

Antibodies, Monoclonal

Radioimmunodetection of neuroblastoma with iodine-131-3F8: correlation with biopsy, iodine-131-metaiodobenzylguanidine and standard diagnostic modalities.

Iodine-131-3F8, a murine IgG3 monoclonal antibody specific for ganglioside GD2 was evaluated by radioimmunoscintigraphy in 42 patients with neuroblastoma. Comparison was made with 131I-metaiodobenzylguanidine (MIBG), 99mTc-methylene diphosphonate (MDP) bone scans, as well as computed axial tomography (CT) or magnetic resonance imaging (MRI). Iodine-131-3F8 detected more abnormal sites (283) than [131I] MIBG (138) or 99mTc-MDP (69), especially in patients with extensive disease. In 20 patients with soft-tissue tumors demonstrated by CT/MRI, 131I-3F8 detected the disease in 18. Upon surgical resection, two tumors interpreted as negative with 131I-3F8 imaging revealed ganglioneuroma, one showing microscopic foci of neuroblastoma. In contrast, 131I-3F8 imaging identified tumors that were confirmed histologically as neuroblastomas. In 26 patients with evidence of marrow disease by antibody scans, 14/26 had confirmation by iliac crest marrow aspirate/biopsy examinations. We conclude that 131I-3F8 scintigraphy has clinical utility in the management of patients with neuroblastoma by improving the sensitivity of tumor detection.

3-Iodobenzylguanidine

Serum antibodies reactive with Saccharomyces cerevisiae in inflammatory bowel disease: is IgA antibody a marker for Crohn's disease?

Sera from patients with Crohn's disease (CD) and ulcerative colitis (UC) have been evaluated for antibodies reactive with Saccharomyces cerevisiae (anti-Sacc antibodies) using an enzyme-linked immunoassay (ELISA). IgG anti-Sacc antibodies were detected in 63% (25/40) of CD patients, compared with 15% (4/27) of UC patients (p less than 0.001) and 8% (5/60) healthy adult controls (p less than 0.001). Furthermore, the prevalence of detectable IgG anti-Sacc antibodies in adult patients with coeliac disease, dermatitis herpetiformis, irritable bowel syndrome or atopic eczema was not significantly different to controls. In comparison, the prevalence of detectable IgG anti-Escherichia coli antibodies was not significantly different between CD (75%) or UC (79%) patients. More particularly, elevated levels of serum IgA anti-Sacc antibodies were detected in 17/40 CD patients, but in none of the 27 UC patients. These data confirm that serum antibodies reactive with S. cerevisiae are strongly associated with CD and further show that serum IgA anti-Sacc antibodies may be specific for this disorder.

Adolescent

Positron emission tomographic imaging of cardiac sympathetic innervation and function.

Sites of uptake, storage, and metabolism of [18F]fluorodopamine and excretion of [18F]fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of [18F]-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of [18F]fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function.

Animals

Management of patients with renal failure complicated by cerebral oedema.

Dialysis disequilibrium due to cerebral oedema still causes a significant degree of both morbidity and mortality. We discuss the management of 5 such cases and demonstrate the improved stability during treatment with continuous veno-venous haemofiltration. This may be due to the improved osmotic stability during haemofiltration with a resultant decrease in the osmotic gradient across the blood-brain barrier.

Adult

Neuronal uptake and metabolism of 2- and 6-fluorodopamine: false neurotransmitters for positron emission tomographic imaging of sympathetically innervated tissues.

The neuronal uptake and metabolism of 2-fluorodopamine (2F-dopamine), 6-fluorodopamine (6F-dopamine) and tritium-labeled dopamine were compared in heart, submaxillary gland and spleen of rats to assess the utility of 18F-labeled 2F- or 6F-dopamine for positron emission tomographic imaging of sympathetically innervated tissues. Tritiated dopamine with and without 2F- or 6F-dopamine, or tritiated 2F-dopamine alone, were injected i.v. into rats that were or were not pretreated with desipramine to block catecholamine neuronal uptake or with reserpine to block vesicular translocation of catecholamines. Tissue and plasma samples were obtained at intervals up to 1 hr after injections. At 1 hr after injection of tritiated dopamine, tritium-labeled norepinephrine, dopamine, dihydroxyphenylacetic acid and dihydroxyphenylglucol accounted for less than 2% of the tritium in plasma but up to 92% of that in tissues; tritiated norepinephrine accounted for 70% or more of the tritium in tissues. In contrast, at 1 hr after injection of tritiated 2F-dopamine, tritiated 2F-norepinephrine accounted for 30 to 46% of the tritium in tissues. Desipramine and reserpine pretreatment blocked the tissue accumulation of tritiated and fluorinated dopamine as well as their dihydroxy-metabolites, indicating that accumulation of exogenous norepinephrine and dopamine analogs was within sympathetic storage vesicles. Relative to the doses of dopamine precursors, less 2F- and 6F-norepinephrine accumulated in tissues than tritiated norepinephrine, due largely to inefficient beta-hydroxylation of fluorinated dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Human serum antibodies reactive with dietary proteins. IgG subclass distribution.

The isotype distribution of human IgG antibodies reactive with common dietary proteins has been evaluated in sera from adult patients with the irritable bowel syndrome and with bronchial asthma using a solid-phase immunoassay (ELISA). In both these medical disorders, serum antibodies reactive with ovalbumin or gliadin were restricted predominantly to the IgG4 isotype; however, IgG antibodies reactive with bovine milk antigens, notably casein, were often restricted to both the IgG2 and IgG4 isotypes. A similar serum IgG antibody isotype distribution for these dietary protein antigens was also demonstrated in IgG antibody-positive healthy adults. These data amplify the view that production of antibodies of the IgG4 isotype may reflect a normal immune response to dietary protein antigens presented at mucosal surfaces.

Adult

Human serum antibodies reactive with dietary proteins. Antigenic specificity.

The antigenic specificity of human serum IgG antibodies reactive with common dietary proteins has been evaluated by competitive binding using a solid-phase immunoassay (ELISA). Antibodies reactive with bovine milk antigens were shown to be reactive predominantly with casein, rather than alpha-lactalbumin, beta-lactoglobulin, gamma-globulin or albumin. Furthermore, sera containing antibodies reactive with bovine casein, wheat gliadin and chicken ovalbumin showed competitive binding only by each respective dietary protein antigen. IgG4 antibodies specifically reactive with ovalbumin, gliadin or casein were also not cross-reactive in competitive binding studies. Furthermore, both IgG2 and IgG4 anti-milk antibodies showed significant inhibition only with bovine casein, and not with alpha-lactalbumin or beta-lactoglobulin. These data are relevant to concepts regarding the immunobiological role of antibodies of the IgG4 isotype.

Adult