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Biomedical subjects

M G Woldring

Publications and source records attributed to M G Woldring.

18 recordsLinked to original sources

Specificity of immunoassays. II. Heterogeneity of specificity of antibodies in antisera used for steroid immunoassay and the selective blocking of less specific antibodies, including a new method for the measurement of immunoassay specificity.

Practical aspects of the measurement of the specificity of immunoassay are reviewed. Antibody heterogeneity in an antiserum makes a pragmatic rather than a theoretical approach necessary. A new method for the measurement of immunoassay specificity is described. This method is based on the errors caused by the cross-reacting antigens and is directly relevant to the validity of results obtained by immunoassay methods. The effect of selectively blocking the least specific antibodies in antisera raised against steroid haptens is tested. The practical consequences of these considerations are tested using steroid radioimmunoassay and enzyme-immunoassay.

Androgens

Specificity of immunoassays. III. Use of two antisera of differing specificities to improve the specificity of steroid immunoassay.

The specificity of immunoassays can be improved by using a second antiserum to bind substances that cross-react. Both theory and practice show that the effectiveness of the procedure is dependent of the complex interplay of the concentrations of the two antibodies, the concentrations of the three antigens involved (the labelled tracer, the antigen whose concentration is to be measured and the substance that cross reacts) and the affinities of the antibodies for these antigens. Measured cross-reactions can frequently be reduced to zero in the most important concentration ranges thereby enabling one to perform assays upon unpurified materials which other wise would not be possible. Limitations of the method are discussed.

Androstenedione

Rapid decarboxylation of carbon-11 labelled DL-DOPA in the brain: a potential approach for external detection of nervous structures.

The cerebral distribution of the positron-emitting agent [1-11C]beta-(3,4-dihydroxyphenyl)-D,L-alpha-alanine ([11C]DOPA) was studied after intravenous injection in rats pretreated with the peripheral decarboxylase inhibitor, carbidopa. Within 15 min of injection the accumulation of carbon-11 was almost twice as high in cortical areas and cerebellum as in the striatum and the brain stem. After destruction of catecholamine-containing nerve endings with 6-hydroxydopamine, the level of carbon-11 in the striatum was higher than in rats not treated with this neurotoxin. Pretreatment of rats with haloperidol or L-DOPA did not change the distribution pattern of carbon-11. Without pretreatment with carbidopa a uniform distribution of the label in the brain was observed. We suggest that [11C]DOPA is a potentially useful agent for external detection with positron imaging systems in patients and large animals of brain regions rich in the enzyme dopa-decarboxylase. (EC 4.1.1.26).

Animals

Chemiluminescence-linked immunoassay.

Covalent complexes of a chemiluminescent compound (a luminol derivative), protein and a steroidal hapten have been used as a labelled antigen in a way analogous to the radioactive label in radioimmunoassay. The antibody-bound complex emits light when treated with hydrogen peroxide and copper acetate at high pH. The chemiluminescent complex bound to antibody can be displaced by free steroid to produce a standard curve in a way analogous to radioimmunoassay.

Animals

Analysis of extramedullary erythropoiesis in the spleen by a semiquantitative method using indium-111.

A semiquantitative method for evaluating the splenic uptake of 111In is described. With this method the uptake of indium in the spleen was significantly higher in seven patients with extramedullary erythropoiesis (EME) than in a control group of seven patients with comparable degrees of splenomegaly but without clinical and/or histological signs of EME. The discrimination between these groups could be further improved by also taking the degree of splenomegaly into account. It is concluded that the described technique is a valuable non-invasive aid for establishing the presence of EME in the spleen.

Adult

Clinical evaluation of radio-labelled bleomycin for tumor detection.

Investigations with bleomycin labelled with radionuclides other than 57Co in patients with cancer and in tumor-bearing animals are described. In patients 57Co-bleo appears to be a better tumor-seeking radiopharmaceutical than 111In-bleo, 99mTc-bleo or 197Hg-bleo. This can be explained by a higher stability in vivo and a better tumor-seeking property of 57Co-bleo and less disturbing activity in the cardiac pool and in bone and other normal tissues when assessing the scintigram. Results with 111In-bleo labelled in acidic solution are not essentially different from those with 111In-bleo labelled in neutral solution. Results of 197Hg-bleo are almost identical with those of 197HgCl2 regarding the tumor-seeking effect as well as the distribution in normal tissues and organs. Probably the complex of 197Hg to bleomycin is not stable in vivo. The superiority of 57Co-bleo over 99mTc-bleo, 197Hg-bleo and also over 67Cu-bleo is confirmed by experiments on tumor bearing animals. We may conclude that the indication for use of bleomycin as a tumor-seeking pharmaceutical labelled with 111In, 99mTc, 197Hg or 67Cu seems to be very limited.

Animals

Reevaluation of triethers as markers for triglycerides during gastric emptying.

The validity of using triethers as markers for triglycerides during gastric emptying was investigated. Rats were given a lipid mixture containing [75Se]triether plus [131I]triolein or [3H]triether plus [14C]triolein intragastrically. Similar studies were performed on humans using a homogenized test meal to which was added [75Se]triether plus corn oil. Analysis of gastric contents at various time intervals after administration of the test meal did not show evidence of separation of triglyceride and triether in the stomach. It is discussed that the disappointing results of other workers using [3H]triether may be due to an artifact associated with instability of the tritium-to-triether bond in the preparation used.

Animals

Estimation of fat absorption from single fecal specimens using 131I-triolein and 75Se-triether. A study in rats with and without induced steatorrhea.

The simultaneous use of 131I-triolein and 75Se-triether, a nonabsorbable marker, in a single oral dose to estimate fat absorption from incomplete fecal collections was tested in rats with and without induced steatorrhea. The results in normal rats showed that analysis of single stool samples allows a valid estimate of fat absorption as defined by the balance study based on the total fecal recovery of 131I. However, in the few normal rats with poor absorption, the absorption values from successively excreted stools showed a tendency to increase. Similar findings were obtained from biliary fistula rats with marked steatorrhea. No evidence of different intestinal transit rates of test fat and marker was observed in bile-diverted rats, thus suggesting that the observed inconsistency in fat absorption values from different stool specimens reflects intraprandial differences in the absorption of fat. Studies on rats subjected to intestinal ischemia do not support the suggestion of others that separation of fat and triether will occur if a mucosal defect is involved as the cause of fat malabsorption. It is concluded that this dual isotope technique may be of value in the clinical estimation of fat absorption, as it offers important technical advantages over conventional fat balance studies.

Animals

Cobalt-57-bleomycin scanning of hila and mediastinum in patients with bronchial carcinoma: a prospective study.

Because the results with cobalt-57-bleomycin (57Co-bleo) as a tumour-seeking agent in patients with pulmonary tumours were promising, a prospective study was carried out to test the sensitivity and selectivity of this technique for metastases in lung hila and mediastinum in a group of patients with bronchial cancer. The sensitivity of 57Co-bleo scintigraphy appeared to be higher than that of routine radiological investigations and mediastinoscopy. For this reason it is suggested that 57Co-bleo scintigraphy can be used as a method to select patients for mediastinoscopy.

Adult

Labelling of bleomycin with cobalt-57, indium-111, technetium-99m, mercury-197, lead-203, and copper-67.

The radiochemical purity of the cobalt-57 complex of bleomycin could be enhanced by adjusting the pH of the final product to a value between 5 and 6. This radiopharmaceutical appeared to have better tumor visualizing properties compared to the not neutralized preparation. The clinical use of the cobalt-57 bleomycin complex is however limited by the long physical half-life of the label, causing a risk of radioactive contamination. It appeared to be possible to label bleomycin with radioactive cations (111In3+, 99mTc4+, 197Hg2+ and 67Cu2+) having suitable gamma ray energies and short half-lifes. These bleomycin complexes showed a high radio-chemical purity judged by their behaviour on thin layer chromatography, paper chromatography, and electrophoresis, but their application as tumor visualizing radiopharmaceutical turned out to be disappointing compared with cobalt-57 bleomycin.

Bleomycin

Some experience with 57Co-labeled bleomycin as a tumor-seeking agent.

Bleomycin labeled with 57Co was used as a tumor-localizing agent in 132 patients. In patients with pulmonary tumors the primary localization concentrated radioactivity in 52 of the 54 appropriate cases; out of the 22 clinically known metastases, 19 were visible on the scan; 40 unknown metastases especially in hilus and mediastinum were found by the method and subsequently confirmed. In 22 patients with malignant lymphomas, 18 out of 22 known pathologic lymph glands above the diaphragm were visible on the scan; below the diaphragm the results of scanning in lymph glands and spleen were disappointing, probably because of the disturbing concentration of radioactivity in the kidneys, the bladder, the liver, and sometimes the gut. In 25 patients with various other tumors, 16 out of 22 known localizations above the diaphragm were visible; 2 were uncertain and 4 negative. Below the diaphragm the results were usually negative. In 24 patients with benign lesions, uptake of 57Co-bleomycin was visible on the scintigram in 4 patients with cavitating pulmonary tuberculosis, in 2 with pulmonary infections, in 1 with Caplan lesions of rheumatoid arthritis in the lung, and in 1 with sinusitis ethmoidalis. The significance of these results is discussed.

Bleomycin