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D A Weber

Publications and source records attributed to D A Weber.

At least 37 records · Page 2Linked to original sources
PubMed1996

Quantitative 123I IMP and 99mTc HMPAO imaging in the dog following cocaine administration.

SPECT and associated imaging procedures were used in beagle dogs to (1) evaluate the uptake, distribution, and clearance properties of i.v.-injected 123I IMP (IMP) and 99mTc HMPAO (HMPAO) in the brain, lungs, liver, and kidneys; (2) quantify the acute effects (after 15 sec) of very low doses (0.5 or 1.0 mg/kg) cocaine on the kinetics and localization properties of IMP and HMPAO; and (3) evaluate comparative imaging properties of IMP and HMPAO for measuring regional cerebral blood flow (rCBF). Regional and global uptake and localization of IMP or HMPAO were evaluated in control studies using dynamic planar (0-30 min) and SPECT imaging (at 35 min). The regional distribution properties of IMP and HMPAO in the brain were estimated from regions of interest (ROIs) drawn around anatomic structures on MR slices and manually registered with corresponding SPECT slices. Cocaine significantly reduced the 30-min IMP uptake in the brain and lungs by approximately 15%, but only slightly changed HMPAO uptake in the brain and other organs. In the control studies, the respective uptakes of IMP in the brain and lungs were 9 and 39% greater (p < 0.01) than those of HMPAO. In control SPECT studies, the highest uptake of IMP was observed in the thalamus and progressively less activity was observed in the parietal lobe, frontal lobe, cerebellum, occipital lobe, and entire brain; activity in the olfactory bulb was lower than in all other regions. Cocaine reduced IMP uptake in the cerebellum (p < 0.01), occipital lobe (p < 0.01), and entire brain (p < 0.05). IMP uptake (cpm/pixel-mCi) in the different brain regions was 1.3 to 2.1 times greater than that of HMPAO (p < 0.001). HMPAO uptake was more homogeneous throughout the gray matter of the brain; no significant uptake differences were observed among flagged regions. Results indicate that single, acute doses of cocaine, 0.5 and 1.0 mg/kg, significantly altered the uptake and localization properties of IMP in the dog's brain, lungs, liver, and kidneys. Variations in regional uptake of IMP in the parietal, frontal, and occipital lobes, cerebellum, and thalamus were greater than with HMPAO.

Amphetamines↗
PubMed1996

Does detoxification reverse the acute lung injury of crack smokers?

The effect on chronic crack users of a 3 month detoxification programme on lung clearance of inhaled 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA) aerosol, spirometry and gas exchange was determined in a controlled in-patient clinical treatment setting. Imaging studies were carried out in eight chronic crack users (four crack-only and four crack plus tobacco) before and after the successful completion of the detoxification programme to measure the clearance of inhaled 99Tcm-DTPA from the lungs, an index of lung epithelial permeability. 99Tcm-DTPA lung clearance, expressed in terms of the biological half-time, T1/2, was determined from the slopes of the least-squares fit regression lines of the respective time-activity plots. The mean (+/- S.D.) global T1/2 values of the crack-only (75 +/- 39 min) and crack plus tobacco users (22 +/- 10 min) were significantly shorter (P < 0.02 and P < 0.001, respectively) than from the lungs of the non-smoking controls (124 +/- 29 min). This was consistent with increased lung epithelial permeability secondary to crack-related lung injury. The mean global T1/2 value of the crack plus tobacco users was significantly shorter (P < 0.05) than that of the crack-only users. After detoxification, the abnormally rapid lung clearance became normal in two of the four crack-only users studied, improved in a third and remained unchanged in the fourth, a subject whose T1/2 value was already normal initially. However, lung clearance improved in only one of the four crack plus tobacco users studied. Faster 99Tcm-DTPA clearance was the only impairment found in seven of the eight crack users, the eighth having restrictive lung disease. Crack-related lung injury, reflected by abnormally rapid 99Tcm-DTPA lung clearance, may be at least partially reversible after a 3 month period of abstinence from crack.

Adult↗
PubMed1996

Calibration of the delayed-gamma neutron activation facility.

The delayed-gamma neutron activation facility at Brookhaven National Laboratory was originally calibrated using an anthropomorphic hollow phantom filled with solutions containing predetermined amounts of Ca. However, 99% of the total Ca in the human body is not homogeneously distributed but contained within the skeleton. Recently, an artificial skeleton was designed, constructed, and placed in a bottle phantom to better represent the Ca distribution in the human body. Neutron activation measurements of an anthropomorphic and a bottle (with no skeleton) phantom demonstrate that the difference in size and shape between the two phantoms changes the total body calcium results by less than 1%. To test the artificial skeleton, two small polyethylene jerry-can phantoms were made, one with a femur from a cadaver and one with an artificial bone in exactly the same geometry. The femur was ashed following the neutron activation measurements for chemical analysis of Ca. Results indicate that the artificial bone closely simulates the real bone in neutron activation analysis and provides accurate calibration for Ca measurements. Therefore, the calibration of the delayed-gamma neutron activation system is now based on the new bottle phantom containing an artificial skeleton. This change has improved the accuracy of measurement for total body calcium. Also, the simple geometry of this phantom and the artificial skeleton allows us to simulate the neutron activation process using a Monte Carlo code, which enables us to calibrate the system for human subjects larger and smaller than the phantoms used as standards.

Body Composition↗
PubMed1996

A revised dosimetric model of the adult head and brain.

UNLABELLED: During the last decade, several new radiopharmaceuticals have been introduced for brain imaging. The marked differences of these tracers in tissue specificity within the brain and their increasing use for diagnostic studies support the need for a more anthropomorphic model of the human brain and head. Brain and head models developed in the past have comprised only simplistic representations of this anatomic region. METHODS: A new brain model has been developed which includes eight subregions: the caudate nucleus, the cerebellum, the cerebral cortex, the lateral ventricles, the lentiform nucleus, the thalamus, the third ventricle and the white matter. This brain model has been included within a slightly modified version of the head model developed by Poston et al. in 1984. The head model, which includes both the thyroid and eyes, was modified in this work to include the cerebrospinal fluid within the cranial and spinal regions. RESULTS: Absorbed fractions of energy for photon and electron sources located in thirteen source regions within the new head model were calculated using the EGS4 Monte Carlo radiation transport code for radiations in the energy range 10 keV to 4 MeV. CONCLUSION: S-values were calculated for five radionuclides used in brain imaging (11C, 15O, 18F, 99(m)Tc and 123I) and for three radionuclides showing selective uptake in the thyroid (99(m)Tc, 123I, and 131I). S-values were calculated using 100 discrete energy points in the beta-emission spectrum of the different radionuclides.

Adult↗
PubMed1995

Requirement for peptide in alloreactive CD4+ T cell recognition of class II MHC molecules.

To examine the role of peptide in alloreactive class II MHC-restricted responses, we transfected I-A molecules into the Ag-processing defective mutant cell line, T2. Consistent with their defective Ag-processing phenotype, the T2 transfectants predominantly express SDS-unstable I-A molecules on their surface. These cells and phenotypically normal APCs were used to study primary and secondary alloreactive T cell responses in limiting dilution assays. The results demonstrate that the majority of CD4 T cells that participate in primary alloresponses and essentially all the CD4 T cells that participate in secondary alloresponses recognize I-A conformers that depend on the presence of peptide and do not recognize the SDS-unstable I-A expressed by T2 transfectants. To further investigate the requirement for peptide in these responses, we incubated the T2 transfectants with E alpha 52-68 peptide and generated SDS-stable I-A-peptide complexes on the cell surface. The I-Ab-E alpha peptide complexes expressed on T2 cells are stimulatory in secondary alloresponses if the T cells were exposed to the same I-A peptide complex during the priming step. These studies demonstrate that peptide-containing class II MHC is the relevant ligand for alloreactive T cells, and identify an alloreactive response to a peptide (E alpha 52-68) derived from a highly expressed cell surface "self" Ag, the I-E molecule.

Animals↗
PubMed1995

A role for microfilaments but not microtubules in processing soluble antigens.

Ag processing involves multiple intracellular membrane transport events required for delivery of Ag to degradative compartments in the endocytic pathway of antigen-presenting cells (APC) and transport of newly synthesized class II MHC proteins to compartments where peptide loading occurs. Movement and distribution of various subcellular vesicles have been shown to involve elements of the cytoskeletal network. We have examined the role of microtubules and microfilaments in Ag processing and presentation by B lymphoblastoid cells. Experiments with nocodazole or colchicine, drugs that disrupt the microtubule network, demonstrate that intact microtubules are not required for efficient processing of soluble Ag in these cells. Cytochalasins, which disrupt actin microfilaments, are observed to partially inhibit processing of soluble Ag. Inhibition is reversible and dependent on both the dose of drug and length of exposure. Control experiments demonstrate that the effect does not result from drug toxicity or decreased Ag uptake. Treatment of APC with cytochalasin B does not block delivery of internalized protein to dense lysosomes. However, the ability of the cells to catabolize internalized protein is partially inhibited. Our results suggest that microfilament-dependent, but not microtubule-dependent, vesicular transport may be required for efficient Ag processing in B lymphoblastoid cells.

Actin Cytoskeleton↗
PubMed1995

Bone mineral and body fat measurements by two absorptiometry systems: comparisons with neutron activation analysis.

In 185 adults (68 white and 31 black males, 66 white and 20 black females), total body bone mineral density and content and body fat% were measured by two dual energy X-ray absorptiometry (DXA) systems--Norland XR-26, software version 2.4, and Lunar DPX, software versions 3.4 and 3.6. In a subgroup of 18 males (10 white, 8 black), body fat% and total body calcium were also measured by in vivo neutron activation analysis (IVNA). For total body calcium, the DPX 3.4 system gave the highest (1239 g), IVNA the lowest (1195 g), and the XR-26 (1226 g) was not significantly different from the DPX 3.6 results. For fat%, the XR-26 system gave the highest estimate (23.5%), whereas measurements by the DPX 3.4 and 3.6 systems (17.4 and 18.2%) were similar to the IVNA measurements (18.3%). BMD and BMC measurements by the two DXA systems were highly correlated but significantly different for the entire studied population except in the case of BMC in black males.

Absorptiometry, Photon↗
PubMed1995

DM enhances peptide binding to class II MHC by release of invariant chain-derived peptide.

Major histocompatibility complex (MHC) class II molecules bind antigenic peptides rapidly after biosynthesis in antigen-presenting cells (APCs). By contrast, the rate of peptide binding to purified class II molecules is remarkably slow. We find that purified HLA-DR molecules bind peptides rapidly in the presence but not the absence of HLA-DM, a recently identified heterodimer required for efficient antigen processing. The same effect is seen with immunoprecipitated DM, suggesting that DM interacts directly with DR. Class II-associated invariant chain peptides (CLIP) are selectively and rapidly released from DR during incubation with DM at pH 5. We conclude that DM is a cofactor that enhances peptide binding to DR molecules through a mechanism involving peptide exchange.

Amino Acid Sequence↗
PubMed1995

Positive selection in autoimmunity: abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis.

A novel 'multistep molecular mimicry' mechanism for induction of rheumatoid arthritis (RA) by bacterial antigens that activate T lymphocytes previously 'educated' by peptides derived from a class of human histocompatibility antigens is reported here. These antigens have the amino acid sequence QKRAA, which is also present on the Escherichia coli heat-shock protein dnaJ. Synovial fluid cells of early RA patients have strong immune responses to the bacterial antigen, but cells from normal subjects or controls with other autoimmune diseases do not. The activated T cells may cross-react with autologous dnaJ heat-shock proteins that are expressed at synovial sites of inflammation. Our findings may have direct relevance to new strategies for the immune therapy of RA.

Amino Acid Sequence↗
PubMed1995

Microbiological assessment of an improved stannous fluoride dentifrice.

Recently, a new stabilized stannous fluoride (SnF2) dentifrice (SSF) has been developed. The aim of the present work was to examine the antimicrobial activity of SnF2, and to assess the long-term microbial safety of this dentifrice in a series of in vitro and clinical evaluations. Results of in vitro time-kill experiments with representative oral bacteria demonstrated that SnF2 exerts broad antimicrobial activity against both Gram-positives and Gram-negatives and, in particular, has potent activity against Streptococcus mutans. Sixty-eight subjects participated in a nine-day plaque regrowth clinical study to assess the short-term antiplaque effect of SSF. The results revealed no significant differences from the negative control, suggesting that SnF2 does not detectably or directly alter plaque microbial viability or composition. Separately, evaluation of microbial safety in a subgroup of 120 subjects participating in a six-month clinical efficacy and safety trial found no significant ecological shifts between SSF and the negative (NaF dentifrice) control among 11 supragingival microbial populations examined. The potential for development of bacterial resistance to SnF2 was assessed under both in vitro and clinical conditions. In a rigorous assessment of the ability of bacterial populations to develop either phenotypic or genotypic resistance to SnF2, representative bacteria were exposed to continuous sub-lethal concentrations of SnF2 in a laboratory chemostat for at least 9 days. Results of time-kill experiments on exposed populations revealed no significant changes in susceptibility despite exposure of over 10(12) bacteria. Based on typical spontaneous mutation rates of 10(-6) to 10(-8), these results suggested that the potential for bacteria to develop resistance to SnF2 is low. Evaluation of susceptibility to SnF2 to over 800 bacterial isolates obtained over the course of the six-month clinical trial corroborate the in vitro findings, revealing no changes in susceptibility suggestive of development of resistance to SnF2 is a microbiologically safe agent for oral use and support separate clinical observations demonstrating the safety and efficacy of this stabilized SnF2 dentifrice.

Actinomyces↗
PubMed1994

Small animal imaging with pinhole single-photon emission computed tomography.

BACKGROUND: High resolution spatial details of the distribution of activity in three dimensions is required to evaluate the localization and dosimetric properties of radiolabelled monoclonal antibodies in tumors and normal tissues. Planar imaging of small animals with a resolution of 5-10 mm is usually the imaging modality of choice. The authors investigated high resolution single-photon emission computed tomographic (SPECT) imaging, based on a rotating pinhole scintillation camera. Although the sensitivity of the pinhole collimator is low, several radionuclides offer suitable decay properties to perform pinhole SPECT, especially in conjunction with high activity levels used in radioimmunotherapy. METHODS: Transverse, sagittal, and coronal sections were reconstructed using a three-dimensional cone-beam algorithm, which is a generalization of the two-dimensional fan-beam filtered backprojection algorithm. Before reconstruction, the pinhole projections were corrected for the decay of the radionuclide, geometric and intrinsic efficiency variations of the camera system, and center of rotation shift. RESULTS: The spatial resolution at 50 mm from the pinhole collimator with 3.3 mm aperture was 3.4 mm, and the sensitivity 7.2 c/s microCi for technetium-99m. With the 2 mm collimator the resolution was 2.2 mm, and the sensitivity was 2.6 c/s/microCi. To show the spatial resolution in vivo, a rat was injected with 185 MBq of technetium-99m-methylene diphosphonate or with 5 mCi technetium-99m-hexamethylpropylene amine oxime. The bone structures were well delineated in the methylene diphosphonate image, and in the hexamethylpropylene amine oxime image, the brain was nicely shown. For comparison a magnetic resonance image for the same section was done. CONCLUSIONS: High resolution SPECT imaging with the pinhole collimator provides mapping of the activity in three-dimensions, needed for more detailed biodistribution data and to perform more accurate dosimetry.

Algorithms↗
PubMed1994

Correlative image registration.

Image registration in nuclear medicine and radiology refers to the spatial matching or merging of two or more images from the same or different imaging modalities. The coordinates of the corresponding picture elements (pixels) from different images are transformed to align and equate their positions and spatial coordinates. Correlative image registration is a more restrictive term that applies to the matching of spatial coordinates of images coming from different imaging modalities. The registration of correlative images provides a useful approach to combine the best sensitivities and specificities of complementary procedures to detect, locate, monitor, and measure pathological and other physical changes. Here we review the registration of images from nuclear medicine (single-photon emission computed tomography, positron emission tomography and planar imaging) with those from other imaging modalities (magnetic resonance imaging, computed tomography, digital subtraction angiography and ultrasound) to closely correlate changes in metabolism, blood flow, receptor density, and other functional measurements with regional anatomy and morphological changes. The types of image registration applications, techniques, and terminology associated with image registration and examples of application are presented.

Angiography, Digital Subtraction↗
PubMed1994

Feasibility of dual radionuclide brain imaging with I-123 and Tc-99m.

A study was conducted to evaluate the feasibility of simultaneous dual radionuclide brain imaging with 123I and 99mTc using photopeak image subtraction techniques or offset photopeak image acquisition. The contribution of the photons from one radionuclide to a second radionuclide's photopeak energy window (crosstalk) was evaluated for SPECT and planar imaging of a brain phantom containing 123I and 99mTc for a range of activity levels and distribution properties approximating those in rCBF images of the adult human brain. Crosstalk was evaluated for 10% symmetrical energy windows centered on the 123I and 99mTc photopeaks and for 10% energy windows asymmetrically placed to the left and right of the center of the respective photopeaks. Major observations include: (1) in the centered photopeak windows, 99mTc crosstalk in the 123I window is 8.9% of the 99mTc seen in the 99mTc window and ranges from 37.5% to 75.0% of the 123I in the 123I window. 123I crosstalk is 37.8% of the 123I seen in the 123I window and ranges from 4.4% to 8.9% of the 99mTc seen in the 99mTc window; (2) the spatial distribution of a radionuclide's crosstalk photons differs from that observed in the radionuclide's photopeak window; (3) a 99mTc photopeak window offset to the left does not decrease 123I crosstalk, and the percentage of 99mTc scattered photons is significantly increased in the window.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pinhole SPECT: an approach to in vivo high resolution SPECT imaging in small laboratory animals.

UNLABELLED: The performance of pinhole SPECT and the application of this technology to investigate the localization properties of radiopharmaceuticals in vivo in small laboratory animals are presented. METHODS: System sensitivity and spatial resolution measurements of a rotating scintillation camera system are made for a low-energy pinhole collimator equipped with 1.0-, 2.0- and 3.3-mm aperture pinhole inserts. The spatial detail offered by pinhole SPECT for in vivo imaging was investigated in studies of the brain and heart in Fisher 344 rats by administering 201TICI, 99mTc-HMPAO, 99mTc-DTPA and 99mTc-MIBI. Image acquisition is performed using a rotating scintillation camera equipped with a pinhole collimator; projection data are acquired in conventional step-and-shoot mode as the camera is rotated 360 degrees around the subject. Pinhole SPECT images are reconstructed using a modified cone-beam algorithm developed from a two-dimensional fanbeam filtered backprojection algorithm. RESULTS: The reconstructed transaxial resolution of 2.8 mm FWHM and system sensitivity of 0.086 c/s/kBq with the 2.0-mm pinhole collimator aperture provide excellent spatial detail and adequate sensitivity for imaging the regional uptake of the radiopharmaceuticals in tumor, organs and other tissues in small laboratory animals. CONCLUSION: The resolution properties of pinhole SPECT are superior to those which have been achieved thus far with conventional SPECT or PET imaging technologies. Pinhole SPECT provides an important approach for investigating localization properties of radiopharmaceuticals in vivo.

Animals↗
PubMed1993

Biological homogeneity and precision of measurement: the boundary conditions for normal in body composition.

For compartments most urgently important to clinical medicine we have satisfactory levels of measurement precision, and the clinical considerations now are the availability of the methods, and the collection of data for normal subjects. Our colleagues in physics and imaging will improve measurement precisions, but the work most needed is to refine the biological side of the measurement equation. Large numbers of measurements, carefully done with carefully calibrated and unchanging systems, exist only for the special case of measuring body calcium in women, in the large cohort of approximately 2,500 women, studied by Aloia and Cohn with neutron activation, and for body potassium, in these women, and in the larger numbers of diverse age, sex, race, and size in the Rosetta study in our laboratory. Can we benefit from the "orthogonal measurements" and "orthogonal physiologic constraints" approaches, in which triangulation is used to combine measurements from several techniques to establish upper-lower bounds estimates by different techniques, with convergence on a "best fit" result? We have noted that the intrinsic homeostatic mechanisms of the body function with great precision to control body temperature, osmotic and ionic concentrations in the water phase, hypertrophy of muscle with exercise, and remodeling of bone by stress. We consider it unlikely that the control mechanisms are more loosely hinged for such secondary parameters as K/FFM and bone density.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1993

Calibration for measuring total body nitrogen with a newly upgraded prompt gamma neutron activation facility.

A description is given of the calibration and performance of the upgraded facility at Brookhaven National Laboratory (BNL) for measuring total body nitrogen using the technique of prompt gamma neutron activation analysis. With the improved calibration, total body nitrogen can be more accurately measured not only in normal subjects but also in obese and wasted patients. Body hydrogen is used as an internal standard. We examined the effect of a heavy-water premoderator on the uniformity of composite sensitivity, nitrogen and hydrogen measurement statistics, and dose to the subject. The calibration technique corrects the ratio of nitrogen-to-hydrogen counts measured from the subject for body size. Additionally, a correction for subcutaneous adipose tissue on the nitrogen-to-hydrogen count ratio is introduced. The newly upgraded BNL facility provides precision in counting statistics using a Remcal anthropomorphic phantom filled with a tissue-equivalent solution of 2.1% for a body dose of 0.35 mSv using a 2.5 cm D2O premoderator. The measurements were made at five 20 cm sections, counting for 200 s per section.

Calibration↗