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Biomedical subjects

J R Williams

Publications and source records attributed to J R Williams.

At least 109 records · Page 6Linked to original sources
PubMed1994

Effect of tumor irradiation on the uptake of lymphokine-activated killer cells in a murine tumor model.

Immunotherapy with lymphokine-activated killer (LAK) cells and interleukin 2 is one of the newer treatment modalities for cancer. This raises important questions concerning synergism or suppressive effects of other existing treatment modalities on adoptive immunotherapy with LAK cells. A tumor model with H4IIe hepatoma cells grown on each flank of ACI rats was developed to evaluate the effect of external beam irradiation of tumors on the subsequent concentration of LAK cells in these tumors. Tumors on one side were irradiated at 6, 12, or 16 Gy prior to injection of [3H]thymidine-labeled LAK cells. The effect of irradiation was measured as the ratio of 3H recovered in the unirradiated tumor compared to that in the irradiated tumor in the same animal as a function of dose and time after irradiation. This ratio was significantly greater than 1.0 for a radiation dose of 12 Gy (2.35 +/- 0.51) measured 2 days after irradiation, indicating a reduction in LAK cell numbers in the irradiated tumor. This reduction in LAK cell number persists up to at least 4 days following radiation exposure. A similar experiment using 125I-labeled interleukin 2 showed equal distribution in the irradiated and unirradiated tumors. Our data demonstrates that the concentration of LAK cells is markedly reduced by prior radiation, in contradistinction to increased uptake of immunoglobulins in irradiated tumors, as shown by others. If a similar reduction is observed for longer duration after radiation exposure, it might suggest a clinically important interaction between prior radiation exposure and adoptive immunotherapy.

Animals↗
PubMed1994

Use of bremsstrahlung radiation to monitor Y-90 tumor and whole body activities during experimental radioimmunotherapy in mice.

BACKGROUND: Large differences in uptake between tumors, even for the same size, frequently observed in clinical and experimental radioimmunotherapy (RAIT), make monitoring of uptake in individual tumors imperative in comparing protocols. 90Y, widely-used for RAIT, emits no gamma radiation and absorption of the beta particle in tissue makes its detection unsuitable for in vivo monitoring. We tested whether bremsstrahlung radiation, produced when betas are decelerated by nuclei, could be used to monitor tumor uptake. METHODS: Subcutaneous human LS174T colon carcinoma tumors were grown in the upper thigh of nude mice and labeled antibody injected intracardially. With the tumor placed in the 2 cm-diameter aperture in a lead collimator, photons with energies from 100 to 200 keV transmitted through plastic, which absorbed the beta particles, were counted to maximize shielding from the rest of the body. The contribution of the normal tissues was subtracted by counting the non-tumor-bearing leg in the same position. Excretion was calculated from whole body activity determined by removing the collimator, placing the mouse in a syringe surrounded by tissue-equivalent material 10 cm from the detector, and counting photons between 200 and 740 keV to minimize the effect of tissue attenuation. RESULTS: For tumors larger than 0.14 gm, a good correlation was obtained between the in vivo bremsstrahlung measurements and the measurements on excised tumors in a calibrated well counter. Similar excretion rates observed in all the animals suggested that the whole body counting was accurate. CONCLUSIONS: Bremstrahlung detection appears feasible and reliable for monitoring both tumor and whole body activities.

Animals↗
PubMed1994

A new method for determining dose rate distribution from radioimmuno-therapy using radiochromic media.

PURPOSE: To describe and evaluate a new, simple, inexpensive method for directly measuring the radiation dose and its spatial distribution generated from explanted tissues of animals previously injected with radiolabeled immunoconjugates or other agents. METHODS AND MATERIALS: This technique uses the newly developed radiochromic dye medium (Gafchromic) which responds reproducibly for therapeutic dose exposures, has high spatial resolution, does not require film processing, and is relatively insensitive to ambient light. We have evaluated the dose distribution from LS174T tumors and selected normal tissues in nude mice previously injected with 90Y labeled anti-carcinoembrionic antigen antibodies. Individual tissues from sacrificed animals are halved and the flat section of the tissue is placed onto the dosimetry media and then frozen. The dosimetry medium is exposed to beta and Bremsstrahlung radiation originating from the frozen tissues. The relative darkening of the dosimetry medium depends on the dose deposited in the film. The dosimetry medium is scanned with a commercial flatbed scanner and the image intensity is digitally stored and quantitatively analyzed. Isodose curves are generated and compared to the actual tissue outline. RESULTS: The absorbed dose distribution due to 90Y exposure show only slight gradients in the interior of the tissue, with a markedly decreasing dose near the edges of the tissue. In addition, the isodose curves follow the tissue outline except in regions having radii of curvature smaller than the range of the beta-particle (R90 = 5 mm). These results suggest that the shape of the tumor, and its curvature, are important in determining the minimum dose delivered to the tumor by radiation from 90Y monoclonal antibodies, and hence in evaluating the tumor response to the radiation. The dose and spatial dose distribution were calculated assuming that the total 90Y activity is distributed uniformly throughout a half ellipsoid. The calculated spatial dose distributions for the half ellipsoids were similar to those observed from the dosimetry media that had been exposed to radioactivity contained in the tumors. CONCLUSION: This method provides direct dose evaluation without elaborate summary calculations based on activity measurements from serial slices. The measured radiation dose actually indicates the dose rate at the time of animal sacrifice. Quantitative analysis of radiation emitted from the tissues is relatively fast, making it feasible to examine a number of tissues under a variety of conditions.

Animals↗
PubMed1994

Olfactory bulbectomy decreases social behavior in male prairie voles (M. ochrogaster).

Prairie voles (Microtus ochrogaster) are social rodents that show characteristics of monogamy including high levels of social behavior and male parental care. Behavioral studies of prairie voles have implicated chemosignals in the control of various components of social behavior and reproduction. In the present study, the role of the olfactory system in male behavior was examined following surgical removal of the olfactory bulbs. Decreases in measures of sexual, paternal, and other social behaviors were observed following bilateral olfactory bulbectomy, but not unilateral or sham bulbectomy. Some bilaterally bulbectomized males also showed a stereotypy, but this probably did not account for the changes in social behaviors.

Animals↗
PubMed1994

Breath ethane generation during clinical total body irradiation as a marker of oxygen-free-radical-mediated lipid peroxidation: a case study.

Total body irradiation (TBI) is used therapeutically for treatment of leukemias and other malignancies of the hemopoietic system. Ionizing radiation produces oxygen free radicals that contribute to cytotoxicity. Breath collected from one patient undergoing therapeutic TBI showed measurable changes in levels of ethane during treatment. Breath ethane is a marker of lipid peroxidation of n-3 fatty acids. The TBI treatment involved 4 days of irradiation. The largest changes in breath ethane occurred on Day 2. The increased levels of breath ethane on Day 2 were correlated to clinical manifestations of toxicity. The correlation of the onset of gastrointestinal side effects with higher levels of breath ethane suggests that breath ethane may be a clinically useful measure of the toxicity of various TBI fractionation treatment protocols currently in use at different medical centers. The levels of breath ethane on the other days of treatment were lower, suggesting that the oxidative-antioxidative balance of the patient may be important in protection against free radical mediated injury. These results for a single patient suggest that breath ethane may be a promising approach to elucidate the role of antioxidants in clinical TBI and should be extended for verification to a larger volunteer patient population.

Adult↗
PubMed1994

Oxytocin administered centrally facilitates formation of a partner preference in female prairie voles (Microtus ochrogaster).

Prairie voles (Microtus ochrogaster) are monogamous mammals that form male-female pair bonds. Partner preference formation, one component of the pair bond in prairie voles, occurs following male-female cohabitation and is facilitated by mating. The peptide hormone oxytocin is released during physical contact and particularly following vaginal stimulation. Oxytocin has been implicated in mother-infant bond formation. The present study tested the hypothesis that oxytocin participates in the partner preference component of pair bond formation in adult prairie voles. Ovariectomized female prairie voles were implanted with osmotic mini-pumps releasing oxytocin (1-100 ng/h) or artificial cerebrospinal fluid (CSF). Pumps were implanted intracerebroventricularly or subcutaneously and females then were housed for 6 h with a male partner, followed by a preference test in which females could elect to spend time with either the partner or an unfamiliar male. Females in groups that received centrally-administered oxytocin (10 or 100 ng/h), but not CSF, exhibited a significant preference for the partner present during infusion. The induction of a partner preference after oxytocin administration appeared specific for central oxytocin pathways as peripheral oxytocin administration was ineffective. Moreover, central administration of a selective oxytocin receptor antagonist inhibited the behavioral effect of exogenous oxytocin. These results suggest that oxytocin may be one factor contributing to the development of partner preferences in this monogamous rodent.

Amino Acid Sequence↗
PubMed1994

A portable dual energy x-ray absorptiometry technique for the measurement of bone mineral in preterm infants.

A dual energy x-ray absorptiometry technique has been developed for the measurement of bone mineral in preterm infants. Two films are taken of the infant's forearm using a standard mobile x-ray set on the ward at two x-ray energies. Included in the field of view is a double step wedge made of aluminum and Perspex. The images are digitized by viewing them on a light box with a TV camera. The bone mineral content in the forearm can then be mapped by the measurement of light intensity in matching pixels of the two films and comparison with the intensities in the step wedge. The bone mineral concentration in the radius, expressed as bone mineral per unit length (mg/mm), is calculated. The technique has been tested using phantoms of calcium hydroxylapatite set in a tissue equivalent material and in Perspex. It has been shown that the reproducibility of the technique is approximately 7% and that there is a systematic underestimate of bone mineral of about 17%. The technique has been shown to be linear up to a bone mineral concentration of 8 mg.mm-1. Longitudinal studies for 14 infants that show an initial 6-wk period of demineralization after birth with a subsequent mineralization phase are reported.

Absorptiometry, Photon↗
PubMed1994

Comparison of spiral-acquisition computed tomography and conventional computed tomography in the assessment of pulmonary metastatic disease.

In a prospective study, spiral-acquisition computed tomography (SACT) of the thorax was evaluated in 104 patients with extrathoracic malignancy and suspected pulmonary metastases, and was directly compared with conventional computed tomography (CCT) in 23 patients. The following parameters were assessed: lesion detectability; the effect on lesion detectability of reconstruction of scans at 5 mm and 10 mm slice increments; breathing artefact and slice misregistration. The radiation dose of the two techniques was measured using thermoluminescent dosimeters placed within an anthropomorphic chest phantom, and the visibility of simulated metastases inserted into the phantom was also compared using CCT, standard SACT and SACT with pitch greater than 1.0. Where metastases were present, SACT scans showed significantly better lesion detectability than CCT scans (p < 0.001). Image reconstruction of SACT data at 5 mm increments conferred no significant advantage in lesion detectability over 10 mm increment reconstructions. Compared with CCT, SACT scans showed reduced breathing artefact, and a complete absence of slice misregistration (p < 0.01). Phantom measurements of radiation dose and resolution were similar for both techniques. Increasing the pitch of the spiral in SACT caused only a small decrease in phantom resolution, but with the advantage of a reduction in the radiation dose. Spiral-acquisition CT is superior to conventional CT for the assessment of pulmonary metastatic disease.

Adolescent↗
PubMed1994

An audit of the effect of a 24-hour emergency operating theatre in a district general hospital.

The recent introduction of a 24-hour emergency theatre for General Surgery provided an opportunity to audit its effect on emergency operating in a District General Hospital. Prior to its introduction much of the emergency operating was determined by theatre availability rather than clinical need. Half of the emergency operations were carried out between 10 pm and 8 am. This proportion was reduced to a third when a theatre was continually available. This had benefits for the patients in reducing their waiting time and also for the junior surgeons by increasing their sleep. A survey of the Region indicated that very few hospitals provided adequate emergency theatre facilities.

Emergencies↗
PubMed1993

Degradation fragments of L1 antigen enhance tyrosine hydroxylase-immunoreactive neurite outgrowth in mesencephalic cell culture.

The L1 antigen has been implicated in adhesion events controlling axonal elongation during formation of major fiber tracts, and promotes neurite outgrowth in culture. It is possible that injury of brain tissue causes neuronal surface molecules such as L1 antigen to be shed, and degradation fragments may therefore be present adjacent to the damage. These L1 fragments might then influence regeneration or injury-induced growth. We have evaluated neurite outgrowth from tyrosine hydroxylase-positive (TH +) E13 mesencephalic neurons grown in vitro on a substrate of mouse L1 antigen and on L1 degradation fragments separated by molecular weight. Mouse myelin-associated glycoprotein (MAG), laminin, poly-D-lysine, and fetal calf serum served as control substrates. L1 antibodies were added to one set of cultures (experimental), and compared to control cultures containing normal rabbit serum. After 3 days in vitro, the cultures were stained using an antibody against TH, and the length of the TH + neurites was measured by computer-assisted image analysis in a double-blind fashion. TH+ neurites were significantly longer when grown on L1 antigen, as well as on L1 degradation fragments, as compared to the control substrates. As compared to control normal rabbit serum, L1 antibodies eliminated the neurite-promoting effect of both the L1 substrate and the L1 degradation products. In addition, L1 substrates promoted clustering of TH + cells and the formation of loose bundles of TH + neurites. It is suggested that the L1 substrates influence TH-immunoreactive neurite outgrowth, at least partially, through indirect effects on glial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Factors modulating preferences of female house mice for males differing in t-complex genotype: role of t-complex genotype, genetic background, and estrous condition of females.

The present study investigates factors mediating odor and social preferences in female house mice (Muc domesticus) based on the t-complex genotype of males. Previous studies in this laboratory showed that females prefer the odors of wild-type (+/+) males over those that carry lethal genes (+/t). The purpose of this study was to determine the genetic, hormonal, and environmental factors that regulate these preferences. The variables examined include t-complex genotype, genetic background, estrous condition of test females (+/+ or +/t), and genotype of the test female's parents. Results indicate that female preferences for +/+ males are dependent upon the t-complex genotype and estrous condition of test females. Only +/t females in estrus showed preferences for +/+ males. Estrous cycle condition effects were seen in both wild (+/+w5) and inbred (129 +/tw5)females. Homozygous females (+/+) and diestrous females of both genotypes did not demonstrate preferences for either +/+ or +/t males.

Animals↗