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Biomedical subjects

W L Dunn

Publications and source records attributed to W L Dunn.

81 records · Page 5Linked to original sources

A new histochemical method for the selective periodate oxidation of total tissue sialic acids.

Evaluation of the intensity of the periodic acid-Schiff (PAS) staining produced following oxidation for 1 h at 4 degrees C with 0.4 mM periodic acid in approximately 1 M hydrochloric acid indicated that this reagent completely oxidized all available sialic acid residues of either the sialo- or sialosulphoglycoproteins of human and rat colon or the sialoglycoproteins of rat sublingual gland. These conditions produced no visible Schiff staining of either neutral macromolecules or vicinal diols located on hexose, 6-deoxyhexose or N-acetylhexosamine residues ('neutral sugars') of sialo- and sialosulphoglycoproteins. Furthermore, there was no extraction of epithelial glycoproteins or de-O-acylation of side chain substituted sialic acid residues. These data demonstrate that 0.4 mM periodic acid in approximately 1 M hydrochloric acid can be used as a specific reagent for the selective visualization of sialic acids in the PAS procedure. Studies of the mechanism of the oxidation of neutral sugars with 0.4 mM periodic acid in approximately 1 M hydrochloric acid indicated that their lack of PAS reactivity was not due to the production of Schiff unreactive hemiacetals or hemialdals. It is suggested that the selectivity of 0.4 mM periodic acid in approximately 1 M hydrochloric acid is a result of an increase in the rate of the oxidation of the sialic acid residues together with a decrease in the rate of oxidation of neutral sugars.

Animals↗

Histochemical studies of epithelial cell glycoproteins in normal rat colon.

Two general classes of glycoproteins have been identified in the colonic epithelial cells of the Sprague Dawley rat. Glycoproteins belonging to the first of these classes contain sialic acids both with and without side chain o-acyl substituents, abundant o-sulphate ester and 'neutral sugars' (hexose, 6-deoxyhexose or N-acetyl hexosamine residues) with oxidisable vicinal diols and are located in the goblet cells of the descending colon and in goblet cells populating the upper halves of the crypts of the ascending colon. In the descending colon, the sulphosialoglycoproteins in the goblet cells in the base of the crypts contain sialic acids without side chain o-acyl substituents. It appears that as these cells migrate up the crypts, there is o-acylation of the side chains of the sialic acids of the glycoproteins and an increase in the quantity of 'neutral sugars' without a corresponding increase in sialic acid. Glycoproteins with similar properties to those of the goblet cells of the upper halves of the crypts of the descending colon, but containing less sulphate, are found in the goblet cells of the upper half of the crypts of the ascending colon. The second general class of glycoproteins contain sialic acids all, or almost all of which, are substituted at position C8 and only relatively small quantities of sulphate. They are located in the mucous cells of the descending colon, the deep crypt secretory cells of the ascending colon and the columnar absorptive cell brush border.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Monte Carlo analysis of multi-layer targets for production of 15O.

A Monte Carlo simulation code was written to analyze multi-layer targets for production of 15O. The code models beam-particle transport through the target and production and transport of generated radionuclides; it can be used to assess the effects on radionuclide production of several beam and target design variables. A pathlength correction feature is included that relaxes restrictions inherent in previous ion transport codes and a variance reduction procedure is implemented that significantly improves code efficiency.

Monte Carlo Method↗

Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.

UNLABELLED: Radiation dosimetry studies were performed in patients with non-Hodgkin's lymphoma (NHL) treated with 90Y Zevalin (90yttrium ibritumomab tiuxetan, IDEC-Y2B8) on a Phase III open-label prospectively randomized multicenter trial. The trial was designed to evaluate the efficacy and safety of 90Y Zevalin radioimmunotherapy compared to rituximab (Rituxan, MabThera) immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed NHL. An important secondary objective was to determine if radiation dosimetry prior to 90Y Zevalin administration is required for safe treatment in this patient population. METHODS: Patients randomized into the Zevalin arm were given a tracer dose of 5 mCi (185 MBq) (111)In Zevalin (111indium ibritumomab tiuxetan) on Day 0, evaluated with dosimetry, and then administered a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve Zevalin biodistribution. Following administration of (111)In Zevalin, serial anterior and posterior whole-body scans were acquired and blood samples were obtained. Residence times for 90Y were estimated for major organs, and the MIRDOSE3 computer software program was used to calculate organ-specific and total body radiation absorbed dose. Patients randomized into the rituximab arm received a standard course of rituximab immunotherapy (375 mg/m(2) weekly x 4). RESULTS: In a prospectively defined 90 patient interim analysis, the overall response rate was 80% for Zevalin vs. 44% for rituximab. For all patients with Zevalin dosimetry data (N=72), radiation absorbed doses were estimated to be below the protocol-defined upper limits of 300 cGy to red marrow and 2000 cGy to normal organs. The median estimated radiation absorbed doses were 71 cGy to red marrow (range: 18-221 cGy), 216 cGy to lungs (94-457 cGy), 532 cGy to liver (range: 234-1856 cGy), 848 cGy to spleen (range: 76-1902 cGy), 15 cGy to kidneys (0.27-76 cGy) and 1484 cGy to tumor (range: 61-24274 cGy). Toxicity was primarily hematologic, transient, and reversible. The severity of hematologic nadir did not correlate with estimates of effective half-life (half-life) or residence time of 90Y in blood, or radiation absorbed dose to the red marrow or total body. CONCLUSION: 90Y Zevalin administered to NHL patients at non-myeloablative maximum tolerated doses delivers acceptable radiation absorbed doses to uninvolved organs. Lack of correlation between dosimetric or pharmacokinetic parameters and the severity of hematologic nadir suggest that hematologic toxicity is more dependent on bone marrow reserve in this heavily pre-treated population. Based on these findings, it is safe to administer 90Y Zevalin in this defined patient population without pre-treatment (111)In-based radiation dosimetry.

Antibodies, Monoclonal↗

Distortion introduced in radionuclide camera views by multiformat imagers.

The degree of spatial distortion of radionuclide camera images introduced by the multiformat imager is compared in six different cameras. The instruments tested were the Ohio Nuclear 110 and 410S, Searle Pho Gamma LFOV, and the General Electric 400T. We found image nonlinearity variations of 4 to 25%; this illustrates the need for industrial standards applied to imager spatial distortion performance.

Photography↗

A Monte Carlo model for absorbed dose calculations in computed tomography.

A Monte Carlo program has been devised that estimates the total absorbed energy and mean dose in defined regions within phantoms exposed to rotating x-ray sources. The calculations deal with fanlike beams of rectangular cross section projected onto elliptic cylindrical phantoms, which may be inhomogeneous. The effects of coherent scattering, which may be significant in a narrow-beam geometry, can be studied. The code can score the exit flux, allowing study of the relationship between dose and image quality. The model is described, the code is verified, and typical results are presented.

Models, Theoretical↗