Biomedical subjects
Publications and source records attributed to S C Prasad.
Dosimetry of a new implant technique to treat brain tumors is presented. High grade gliomas or astrocytomas are surgically removed, and radioactive I-125 seeds are implanted on the surface of the cavity. A computational model is presented to determine the number of seeds and the activity of the seeds for a given dose and cavity size.
Ewing's sarcoma cell lines were compared to other cell lines for induction of DNA strand breaks by ionizing radiation and their ability to repair those breaks. The alkali-unwinding assay and alkaline sucrose gradient analysis were used for these studies. The alkali-unwinding assay revealed that the amount of DNA unwound per strand break in Ewing's sarcoma cells was less than for other cells and was not influenced by high-salt denaturation conditions. Ewing's sarcoma cells had similar induction and repair rates for strand breaks compared with other cell lines. The kinetics of unwinding suggests there are constraints to DNA unwinding in the chromatin of Ewing's sarcoma cells, possibly related to high levels of poly(ADP-ribose) polymerase in these cells.
A sensitive quantitation of DNA (0.2 to 10 ng) can be achieved using a 32P-labeled Alu probe to hybridize human DNA spotted onto nylon membrane. This allows the determination of radiation-induced single-strand breaks without the use of [3H]thymidine prelabeling of cells in culture. The sensitivity of this technique in HeLa cells is comparable to results obtained using the alkaline unwinding technique. The method is applicable to cells in both exponential and plateau phases of growth.
Application of a contact X ray therapy unit for endocavitary irradiation of selected rectal carcinomas is gaining acceptance as a treatment of choice. The patient is placed on a proctoscopic table in the surgical suite and the anus is anesthetized and dilated to allow insertion of a 3 cm diameter proctoscope designed to admit the X ray tube. The measured half-value layer for 50 kVp X rays filtered by 1.0 mm of aluminum was determined to be 0.65 mm of aluminium. The dose rate at the end of the 4.0 cm source-skin-distance (SSD) cone was measured to be on the order of 1000 rad/minute. Radiation surveys performed for several treatment geometries indicate that exposure rate levels in the environs immediately around the patient can be quite high. Radiation measurements were made for the following locations: where the radiotherapist stands holding the X ray tube; at the side of the patient where the technologist or any supporting personnel might stand; and at the patient's posterior surface in the direction where the anesthesiologist might stand. Radiation levels ranged from 0.001 to 1.0 roentgen (R) per hour and depend primarily on the depth and angle of the X ray tube inserted into the rectum.
Using thrombin and trypsin as probes, we determined: first, that low-density lipoprotein (LDL) receptor binding determinants switch from apolipoprotein (apo) E to apo-B within the very-low-density lipoprotein (VLDL) Sf 20-60 region of the metabolic cascade from VLDL1 (Sf 100-400) of hypertriglyceridemic (HTG) human subjects to LDL. Second, two different conformations of apo-E exist in HTG-VLDL Sf greater than 60, one accessible (greater than or equal to 1 mol/mol of particle) and one inaccessible (1-2 mol/mol) to both thrombin and the LDL receptor; normal VLDL (Sf greater than 60) have only the inaccessible conformation and therefore do not bind to the LDL receptor. Third, thrombin degrades apo-B into large fragments, three of which have electrophoretic mobilities similar to B-48, B-74, and B-26; this, however, has no effect on apo-B-mediated receptor binding. Fibroblast studies showed that thrombin could abolish receptor uptake of HTG-VLDL1 and HTG-VLDL2 (Sf 60-100), had little or no effect on HTG-VLDL3 (Sf 20-60), and no effect on uptake of intermediate-density lipoprotein (IDL) or LDL. Trypsin abolished the binding of HTG-VLDL1 and HTG-VLDL2, reduced that of HTG-VLDL3, but had little to no effect on IDL or LDL binding. Immunochemical techniques revealed that thrombin cleaved some apo-E into the E-22 and E-12 fragments; after trypsin treatment no apo-E was detected in any HTG-lipoprotein. Normal VLDL subclasses contained less apo-E than the corresponding HTG-VLDL subclasses and it was not cleaved by thrombin. Apo-B immunoreactivities of VLDL subclasses were not significantly changed after treatment with thrombin, although thrombin cleaved some of the B-100 of each VLDL subclass, and all apo-B in IDL and LDL, into 4-6 major large fragments. Trypsin converted all of the apo-B of each lipoprotein into smaller fragments (Mr less than 100,000). We conclude that apo-E of the thrombin-accessible conformation mediates uptake of HTG-VLDL1 and HTG-VLDL2 but that apo-B alone is sufficient to mediate receptor binding of IDL and LDL; the switch from apo-E to apo-B as the primary or sufficient binding determinant occurs within the VLDL3 (Sf 20-60) region of the metabolic cascade, where receptor binding first appears in VLDL subclasses from normal subjects.
This study investigated dose to bone tissue in electron beam therapy. Measurements were made using films and thermoluminescent dosimeters in a polystyrene phantom containing bone inhomogeneity for 15-MeV, 12-MeV, and 9-MeV electron beams. An increase in dose of approximately 18%, 12%, and 11%, for the three electron energies respectively, relative to the dose in polystyrene, was found for bone material having an electron density (relative to water) of 1.73. Measurements were also made using films for 15- and 9-MeV electrons in a phantom with a mandibular bone and teeth. A dose enhancement in bone of approximately 10% and 7%, respectively, for the two energies was found in the phantom where the electron density of bone was about 1.60. These results suggest that injury to bone is possible in those clinical situations where high doses of electrons are used for therapy.
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The dose to lung tissue in patients whose chest walls are irradiated with 6 and 9 MeV electron beams was estimated. Thermoluminescent dosimetry measurements in thoracic Section 18 of Rando phantom were compared with calculations by two different methods, the effective depth method and the average absorption equivalent thickness (AET) method. The calculations were based on a density of 0.45 (relative to water) for lung tissue in the Rando phantom which was determined from CT scan. The measurements agreed with calculations by the effective depth method within 7 per cent for 9 MeV electron beam at locations where lung tissue thickness was less than 4.5 cm. Larger discrepancy between measurement and calculations was found at greater depths. The effective depth method gave better agreement with measurements (within 14 per cent) compared with the average AET method. The effective depth method was used, to calculate the lung tissue dose at different depths beneath the chest wall. A lung density of 0.25 was assumed to conform to real irradiation situation. The calculations show that for a 9 MeV electron beam dose to lung at 5 cm depth beyond a 2 cm thick chest wall could be as high as 72 per cent of the dose at the maximum buildup depth. It is recommended that post-mastectomy patients with chest wall thickness less than 2 cm should be irradiated with an electron energy of less than 9 MeV or that the chest wall thickness be artificially increased with tissue equivalent bolus.
Pretreatment computed tomography (CT) scanning of the pelvis was performed in 100 consecutive patients with carcinoma of the prostate treated with external irradiation (82 patients) or interstitial I125 (18 patients). Treatment plan modifications prompted by CT scan findings were most frequent in patients with (clinical) involvement of the seminal vesicles in whom the conventional treatment planning often resulted in an underestimate of tumor volume. Seventeen of 32 (53%) such patients required an enlargement of treatment fields to adequately encompass the target volume. Using skeletal landmarks as reference, the dimensions of the prostate, seminal vesicles and the detectable tumor and their topographic relationships were systematically tabulated. These measurements provide a basis for the definition of the target volume in patients with carcinoma of the prostate in whom CT scans might not be available.
The contribution of computed tomography (CT) in radiotherapeutic treatment of lung cancer was evaluated. Radiation therapy ports prepared for 50 patients on the basis of routine diagnostic radiographs and without CT scan information were reviewed after CT scanning. Of 50 patients, 13 (26%) required alteration of treatment ports on the basis of the additional CT scan information. In 11 patients (22%) the changes resulted in an increase in field size to cover the tumor adequately, and in two patients (4%-) the field size was reduced to spare normal tissue. A three-phase study was completed to evaluate the impact of CT on quantitative parameters of two-dimensional treatment plans on 25 of the 50 patients. Treatment plans in the absence of CT scan and without lung transmission correction were compared with treatment plans where CT information was used and lung transmission corrections were performed. Numerical results for local efficiency and nonuniformity factor were compared for conventional, CT unoptimized, and CT optimized plans. Of the 25 patients, 14 (56%) had poorer local efficiency and 16 (64%) had nonuniformity factor exceeding 5% when treatment was planned without CT information. CT-optimized plans improved local efficiency in 16 (64%) of 25 patients and reduced nonuniformity to within 5% in 21 (84%). It is suggested that in the treatment planning of patients with lung cancer, CT scan information is essential for accurate determination of dose distribution and optimization of therapy.
Pixel-by-pixel correction for tissue inhomogeneities was performed with a CT-interfaced treatment planning system. The CT number for each pixel was converted to a physical density. Comparison of the resulting data with dose measurements in a RANDO phantom shows that pixel calculation overestimates dose by 5--7% at locations adjoining the lung, where loss of scatter is not taken into account by the algorithm. However, the new system does have some advantages over conventional treatment planning systems.
A method to study the loss of resolution of radiological images caused by patient motion is presented. Optical transfer functions (OTF) are computed for motion with uniform velocity and with simple harmonic oscillation. The line spread function (LSF) of a pattern of motion can be generated from the image of a long, narrow moving slit. Once the LSF is known the OTF of the motion can be obtained by Fourier transform.
Ionizing radiation (IR) is an important component in the therapy of localized prostate cancer. Identification of protein alterations during IR-induced apoptosis prostate cancer cells is an important step toward understanding the new metabolic status of the dying cell. In the present study, we report changes in protein profile that define the execution phase of the apoptotic response in the in vitro model of tumorigenic radiation-transformed SV40-immortalized human prostate epithelial cells (267B1-XR), induced to undergo programmed cell death by IR. We employed an approach that involves use of analytical two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) coupled with Western blotting with specific antisera. Our results point out that apoptotic cells experience significant reduction in the levels of the intermediate filament proteins, keratins-18, 19, vimentin and the associated 14-3-3 adapter proteins. At the same time, molecular chaperones such as glucose-regulated protein 94, calreticulin, calnexin, and protein disulfide isomerase exhibit marked accumulation in these dying cells. The present data indicate that apoptosis-associated processes in prostate epithelial cells include solubilization of the rigid intermediate filament network by specific proteolysis as well as increased levels of endoplasmic reticulum (ER) proteins with chaperone functions.
Carcinogenic progression in most epithelial systems is a multistep process and presents as numerous (un)stable intermediate stages prior to the development of a fully malignant phenotype. Recently, we reported the neoplastic transformation of an SV40 immortalized, neonatal human prostate epithelial cell line (267B1) by multiple exposures to X-rays [1, 2]. The parental 267B1 cells acquired anchorage-independence and exhibited morphological transformation following exposure to two consecutive doses of 2 Gy. Exposure of either the parental 267B1 cells or the anchorage-independent derivatives (F3-SAC) to a total dose of 30 Gy of X-rays yielded tumorigenic transformants (267B1-XR and 267B1-SXR, respectively). All of these radiation-treated derivatives (F3-SAC, 267B1-XR, and 267B1-SXR) were characterized by reduced cell size and poorly organized actin stress fibers [2, 3]. The present study examines the protein expression changes associated with cytoskeletal alterations during the different steps of neoplastic progression induced by X-rays in the in vitro human prostate cell system. This analysis was achieved by using the high resolving power of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) in the 267B1, F3-SAC, 267B1-XR, and 267B1-SXR cells. We report changes in the expression of gelsolin in the partially transformed, anchorage-independent, nontumorigenic (F3-SAC) cells and a progressive loss of expression of tropomyosin isoforms (TM-1 and TM-3), and myosin light chain-2 (MLC-2) in the tumorigenic (267B1-XR; 267B1-SXR) cells, respectively. In contrast, our results demonstrate that the levels of the small GTP-binding protein Rho-A, an active participant in the actin stress fiber organization, are not altered during neoplastic progression of these 267B1 cells. Thus the changes in synthesis of gelsolin, tropomyosins, and MLC-2 provide a rationale for the alterations in the actin stress fiber formation and reduction in cell size during the exposure of prostate epithelial cells to multiple doses of X-rays.
The radiant intensity along the anode-cathode dimension of a line-focus x-ray focal spot tends to peak at the center and decrease gradually to zero at the edges. In recognition of this varying intensity, the ICRU has recommended that the anode-cathode dimension of the focal spot be reported as 0.7 times the dimension measured with a pinhole camera. In this paper more objective correction factors are developed. These correction factors are based upon comparison of calculated MTFs of focal spots with Gaussian and cosine intensity distributions with the MTF for focal spots with a uniform intensity distribution.
Corrections for nonuniform x-ray intensity distributions have been computed for the dimension perpendicular to the anode-cathode axis of x-ray-tube focal spots. These correction factors were developed from comparison of OTFs for focal spots with uniform intensity distributions to those for focal spots with symmetric double-peaked intensity distributions.
A relation is developed between tolerance dose and field size from an analysis of available clinical data on skin-tolerance doses for various treatment field sizes in radiotherapy. It is shown that plots of log-dose against log-field-size for various fractionation schedules give isoeffect lines all having approximately the same slope. This suggests a power law relation between tolerance dose and field size. A generalized form of NSD equation, incorporating the field-size dependence of tolerance dose, is shown to follow naturally when this new relation is combined with Ellis' NSD relation. Certain discrepancies between the sets of data used in the present analysis are pointed out and it is suggested that more data are needed before the generalized NSD relation can be applied under varying conditions of dose, time, fractionation, and field size.
In computed tomography the finite width of the collimator aperture implies that the image is reconstructed from scans having finite strip width. This blurs the image and limits scanner resolution. Bracewell has discussed the nature of the blurring produced and suggested a method to partially restore the image under the assumption that the x-ray focal spot has a uniform intensity distribution. However, pinhole radiographs of x-ray focal spots reveal intensity distribution in the scanning plane which peaks at the edges of the focal spot with a reduced intensity in the center. A model is presented which simulates this intensity distribution as the sum of two point sources of x rays separated by a uniform line source. This results in a point absorber response function which is a superposition of two rectangular distributions and the one discussed by Bracewell. The corresponding tranfer function is derived which shows that the intensity distribution of the focal spot influences the high spatial frequency components of the reconstructed image more than the low frequency components.