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R D Neumann

Publications and source records attributed to R D Neumann.

At least 91 records · Page 5Linked to original sources
PubMed1988

Measurement of local Mr 97,000 and 250,000 protein antigen concentration in sections of human melanoma tumor using in vitro quantitative autoradiography.

An assay method that uses 125I-labeled monoclonal antibody (MoAb) and in vitro quantitative autoradiography was developed to determine the local concentration of tumor-associated antigens in tissue sections. Human melanoma biopsy specimens were evaluated for the expression of the Mr 97,000 and 250,000 protein antigens using MoAb-96.5 and MoAb-9.2.27, respectively. Tissue sections were incubated in solutions of increasing concentration of 125I-labeled MoAb with or without an excess of unlabeled antibody. Quantitative autoradiography was performed on the sections and compared with 125I standards to determine tumor-bound radioactivity and calculate bound pmol of MoAb per g of tumor. The total binding, nonsaturable binding, and specific binding of 125I-labeled MoAb to tumor were then computed. Specific binding of MoAbs to tumor tissue was saturable in all antigen-positive tumors. The maximal concentration of specific binding of antibody to tissue (Bmax) represented the tissue antigen concentration. Estimates of the Ka of antigen/antibody binding were also made. The reliability of the measurements was confirmed by testing sections from mixtures of antigen-positive and antigen-negative cells.

Antibodies, Monoclonal↗
PubMed1988

Intrapatient and interpatient comparison of tumor size and monoclonal antibody uptake in melanoma.

In two panels totaling 52 patients with melanoma who were imaged with In-111 labeled 96.5 or ZME-018 (ZME) monoclonal antibodies (MoAb), four patients demonstrated numerous metastases (greater than or equal to 20) in the subcutaneous tissues and peripheral lymph nodes. These constituted four intrapatient groups of tumors. These were selected for an intrapatient comparison of tumor size and uptake. Data on 16 additional patients imaged with 96.5 MoAb with fewer (less than or equal to 11) such tumor foci were pooled and used as an interpatient control group of tumors. Uptake was graded 0-5+ (liver = 4+). The data were similar in all five groups. All tumors with a diameter less than 0.7 cm were not detected. All large tumors were demonstrated, usually with high uptake. Small tumors (greater than or equal to 0.7 cm in diameter), however, showed variable uptake, from 0-4+. Thus, tumors within one patient were as variable in uptake as tumors between patients. Immunologic studies of melanoma tumor antigens have shown a similar variability. It is suggested that antigenic heterogeneity is responsible for the variable scintigraphic demonstration of such tumors.

Adult↗
PubMed1987

Quality control and the preparative purification of low antibody concentrations for radiolabelling using bifunctional chelates.

The conjugation of antibodies (Ab) with DTPA in the presence of contaminating low molecular weight proteins is inefficient. The selective precipitation of Ab with 18% Na2SO4 as a preparative purification method for small aliquots of low Ab concentrations is successful in eliminating all contaminants as monitored by high performance liquid chromatography at 214 nm and in allowing IgG recoveries greater than 94%. Subsequently, this allows efficient conjugation and radiolabelling of Ab.

Antibodies↗
PubMed1987

Scintigraphic detection of metastatic melanoma using indium 111/DTPA conjugated anti-gp240 antibody (ZME-018).

We evaluated the toxicity, pharmacokinetics, and localization of a monoclonal IgG2 alpha murine anti-human melanoma (gp240) antibody (ZME-018) that recognizes a tumor-associated cell surface glycoprotein of 240,000 molecular weight present in most melanomas. The antibody was conjugated with DTPA (diethylenetriamine pentaacetic acid) and labeled by chelation of 111In. One mg of antibody labeled with 5 mCi of 111In was infused, together with 0 to 40 mg of "cold" carrier ZME-018. The blood clearance, urinary excretion, and in vivo localization were determined in 26 patients. Scintigraphic images were obtained at 24 hours and 72 hours in all patients. Mild toxicity occurred in one patient. The half-time clearance of labeled monoclonal murine antibody (MoAb) from the blood increased from 16.1 hours at an antibody dose of 1 mg to 35.9 hours at 40 mg. Males showed faster clearance from the blood than did females or a single castrated male, perhaps due to selective concentration of antibody in the testes. Nonspecific uptake in liver, spleen, bone marrow, and intestine was seen in all patients. The percentage of known metastatic foci detected increased with the total dosage of antibody, from 23% at doses less than or equal to 5 mg, to 65%, 87% and 78% for 10, 20, and 40 mg, respectively. We conclude that at doses of greater than or equal to 10 mg, ZME-018 is a safe and potentially useful agent for the scintigraphic detection of metastatic malignant melanoma.

Adult↗
PubMed1987

Arteriovenous fistula with false aneurysm of the inferior medial geniculate artery. A complication of total knee arthroplasty.

Two cases of traumatic arteriovenous fistula with false aneurysm of the inferior medial geniculate artery are reported as a complication of total knee arthroplasty. Both cases were diagnosed within the first two months following the knee surgery. Diagnosis in both cases was confirmed by arteriography. Surgical excision of this lesion with ligation of the inferior medial geniculate artery resolved both of these complications. Strict hemostasis in the region of the inferior medial geniculate artery following subperiosteal release of the medial ligaments in total knee arthroplasty should prevent this complication.

Aged↗
PubMed1986

The ultrapurification of indium-111 for radiotracer studies.

We have developed a procedure for the ultrapurification of 111In. A dried sample of 111InCl3 is dissolved in 1 ml of a freshly prepared KI solution of 4% in 4 N H2SO4. After 3 ml of anhydrous diethylether has been mixed well with the aqueous and centrifuged for 5 minutes at 2000 X g, the iodide salt of 111In is recovered with the organic solvent layer at approximately 92% of the original radioactivity. The organic phase is evaporated under a gentle stream of inert gas. After the sublimation of iodine, 111In is dissolved in a solvent of choice. The extraction is highly selective for In and separates it from, at least, Fe, Al, and Zn, principle associated cationic contaminants.

Cyclohexanones↗
PubMed1986

Preparation and immunoreactivity of high specific activity indium-111-DTPA labeled monoclonal antibody (MoAb) using ultrapure indium-111.

The preparation of high-specific activity 111In-DTPA-MoAb without increasing the number of DTPA molecules per Ab was investigated. Instant thin layer chromatography was used to assay the relationship between labeling efficiencies and specific activities. With ultrapurified 111In, the specific activity of the radiolabeled MoAb approached the expected theoretic maximum of 100 muCi/microgram. The bioactivity of such high-specific activity preparation showed no degradation as measured by in vitro cell binding assay.

Animals↗
PubMed1985

A modified procedure for rapid labelling of low concentrations of bioactive proteins with indium-111.

We describe the conjugation of DTPA to 100-500 micrograms of protein in concentrations of 0.6-1.0 mg/mL utilizing the mixed anhydride method. Free DTPA is removed by minicolumn gel filtration and centrifugation with minimal protein dilution. Radiolabelling at any selected pH can be achieved easily by diluting the protein in the desired buffer. The radiolabelling process can be monitored by instant thin layer chromatography. Any radiochemical impurity detected can be eliminated either by additional minicolumn filtration or further chelation with more conjugated protein. In citrate buffer at pH 6 with minicolumn gel chromatography we prepared 111In-DTPA-D3 (3.0 microCi/micrograms) monoclonal antibody and used it to image hepatocarcinoma in guinea pigs.

Animals↗
PubMed1983

Perfusion of nonventilated lung: failure of hypoxic vasoconstriction?

Alveolar hypoxia is a well established cause of regional vasoconstriction such that nonventilated segments are not perfused. The paradoxical situation of retained perfusion of nonventilated lung has seldom been discussed. Three clinical examples are illustrated. In each case coexistent chronic obstructive lung disease may have contributed to this unexpected finding by reducing pulmonary vascular capacity such that blood flow diversion from hypoxic segments was not possible.

Aged↗
PubMed1982

Ultrasonography and hepatobiliary scintigraphy in the assessment of biliary-enteric anastomoses.

Twenty-three patients with surgical diversion of the biliary tract were serially studied with ultrasonography and hepatobiliary scintigraphy using 99mTc-HIDA or 99mTc-disofenin. Refluxed biliary air resulted in nondiagnostic sonograms in 14% of cases. Persistent postoperative dilatation was present in five patients (22%). Scintigraphy allowed differentiation of biliary dilatation with obstruction from nonobstructed dilatation. By coordinating the noninvasive imaging results, those patients requiring study using direct injection of contrast material may be selected.

Adult↗
PubMed1980

Current status of ventilation-perfusion imaging.

The major clinical use of ventilation-perfusion (V/Q) scintigraphy is for the diagnosis of pulmonary embolism (PE). Accurate diagnosis of PE is essential since effective treatment is available but involves some risk to the patient. The scintigraphic characteristics of PE are segmental perfusion defects in lung that is normally ventilated and normal on the radiograph. The inherent shortcoming of perfusion scintigraphy is its lack of specificity. Combining a ventilation study with perfusion imaging improves the diagnostic specificity of lung scintigraphy. Xenon-133 is currently the most commonly used radionuclide for routine ventilation studies; a long washout technique is more sensitive than single-breath imaging when this radionuclide is used. We obtain preperfusion xenon-133 ventilation studies with a 4-min rebreathing equilibrium phase and a long 5-min washout phase to obtain maximum information. It is imperative that V/Q studies be interpreted with a current high quality chest radiograph. Interpretation of V/Q studies for PE is perhaps best done by assigning a probability diagnosis, since rarely is absolute specificity possible. This article details the criteria we use for these probability determinations.

Adult↗
PubMed1976

Adenocarcinoma in biliary papillomatosis.

A patient with multicentric biliary papillomatosis associated with invasive adenocarcinoma of the bile duct is reported. This case documents the progression to malignancy of a lesion generally thought to be benign. It serves to alert clinicians to a rare but important cause of recurrent biliary obstruction. The literature on this entity is reviewed.

Adenocarcinoma↗
PubMedDate not supplied

Quantitation of triple-helix formation using a photo-cross-linkable aryl azide/biotin/oligonucleotide conjugate.

DNA triple-helix formation has potential applications in gene mapping and as the basis of "antigene" pharmaceuticals; however, the methods for quantitation of triple-helix formation are limited, especially for purine(purine-pyrimidine)-based triplexes. We present a novel method for detection and quantitation of triple-helix formation by triple-helix-forming oligonucleotides. The oligonucleotide is conjugated to a photoactivatable cross-linker, sulfosuccinimidyl 3-[[2-[6-(biotinamido)-2-(p-azidobenzamido)hexanamido] ethyl]dithio] propionate. After incubation with the target DNA, exposure to light labels the target with biotin. The labeled target can be quantified by a chemiluminescent assay. A 26-mer oligonucleotide previously reported to form a purine(purine-pyrimidine) triplex with the upstream region of the c-myc gene was studied and found to bind to its target with Kd of approximately 100 nM at 37 degrees C, 10 mM MgCl2, pH 7.5, consistent with previous reports. This new technique can be used under a variety of conditions and in kinetic experiments and may be extendible to use in living cells.

Azides↗
PubMedDate not supplied

Dosimetry and risk from low- versus high-LET radiation of Auger events and the role of nuclide carriers.

PURPOSE: To analyse the lethality to mammalian cells of (125)I-decays in DNA, in antipyrine in the whole cell and in oligodeoxynucleotides in the nucleus outside DNA as a function of Auger event-site and number. MATERIALS AND METHODS: Auger events cause both low- and high-linear energy transfer energy depositions including charge neutralization at the daughter nuclide. Microdosimetry allows the expression of absorbed dose to a defined micromass and the number of such events at given sites. Published data were used to relate micromass dose and event number to the dose to reduce survival to 37% of the initial survival (D37). RESULTS: The D37 of (125)I-decays in DNA was 0.1 Gy in terms of absorbed dose to the cell nucleus and about 30 in terms of average decays per nucleus or whole cell. The D37 of (125)I-decays in antipyrine was 1.5 Gy for absorbed dose to the cell nucleus, about 250 in terms of average decays per nucleus and about 2 x 10(3) for average decays per whole cell. (125)I-decays in oligodeoxynucleotides were much less toxic than (125)I-decays in antipyrine by a factor of about 25 in terms of average absorbed dose to the cell nucleus, by a factor or about 40 in terms of average decays per cell nucleus and by a factor of six in terms of average decays per whole cell. CONCLUSION: The unexpected low toxicity of (125)I-decays in nuclear oligodeoxynucleotides outside the DNA in comparison with (125)I-decays in antipyrine in the nucleus or the whole cell demands further attention on the role of oligodeoxynucleotides in altering cellular radiation sensitivity.

Animals↗