Determination of dosimetric perturbations caused by aneurysm clip in stereotactic radiosurgery using gel phantoms and EBT-Gafchromic films.

Some radiotherapy patients are treated with titanium surgical aneurysm clips in the radiation field. This is of particular importance for stereotactic radiosurgery brain treatments, where the length of the blade of the clip may be comparable to the size of the radiation field. This study seeks to determine the extent of the dosimetric effects caused by surgical clips in stereotactic radiosurgery, using polyacrylamide gel phantoms and EBT type Gafchromic films. Using gel phantoms scanned with magnetic resonance imaging scanner, dose enhancement of around 20% was noted at distances less than 2 mm away from the clip surface. Gafchromic films showed about 6% variations in the dose up to few millimeters from the clip. These experimental results confirmed results predicted by Monte Carlo simulation techniques for higher density material surgical clips such as lead and platinum. Moreover, these experimental measurements clearly indicate dose reduction due to radiation attenuation behind the clip of about 4%.

High-resolution measurements of small field beams using polymer gels.

Small field sizes are increasingly becoming important in radiotherapy particularly since the introduction of intensity-modulated radiation therapy (IMRT) techniques. It is normally a challenging task to reliably measure the delivered dose and to determine its distribution in a medium for such small fields using conventional-type dosimeters such as gas ionisation chambers. Recently, attempts have been made to use films, but they are not tissue equivalent, they measure the dose only in two dimensions and they are not as responsive to radiations. In the present work, polyacrylamide gel (PAG) dosimeters are employed to measure the dose and its distribution in three dimensions for very small field sizes, such as those typically used in stereotactic radiosurgery. Field sizes of 6 x 6 and 18 x 18 mm in width are investigated. The results show an agreement with radiochromic film and ionisation diode measurements, with some variation in measured doses near the edge of the field, where the gel data decreases more rapidly than the other methods.

Identification and characterization of membrane estrogen receptor from MCF7 estrogen-target cells.

Estrogens control the proliferation of estrogen-target cells through a receptor mediated pathway. We have recently presented evidence that estradiol cancels the proliferative inhibition exerted by albumin on estrogen-target cells (indirect-negative hypothesis). We postulate that this mechanism requires the presence of a membrane estrogen receptor (mER)-membrane albumin receptor complex. Confirmation for mERalpha in MCF7 cells is now made using both the C542 monoclonal and ER-21 polyclonal antibodies (Ab)s specific for ERalpha. Western blot analysis of purified membrane proteins with ERalpha Abs revealed multiple high M(r) mERs (92 k, 110 k, and 130 k M(r)), as well as a 67 k M(r) mER; immunoreactive proteins were competed by inclusion of 500-fold molar excess C542 peptide. Ligand blot analysis of similar extracts with estradiol-peroxidase identified several potential mERs as well; two of these proteins were also recognized by C542 and ER-21 Abs (110 and 67 k M(r)). Fluorescence, confocal and electron microscopy of MCF7 cells fixed in 2.0% paraformaldehyde/0.1% glutaraldehyde identified specific mERalpha sites by immunocytochemistry. Specific binding of 3H-17beta-estradiol was reduced by a 200-fold molar excess of unlabeled 17beta-estradiol, but not by testosterone and progesterone. These results suggest that the ER on the plasma membrane of MCF7 cells is similar, but not identical to its intracellular counterpart. We propose that the observed mER actively participates in the estrogen-mediated proliferation of MCF7 cells.

Immunoaffinity isolation of native membrane glucocorticoid receptor from S-49++ lymphoma cells: biochemical characterization and interaction with Hsp 70 and Hsp 90.

The membrane glucocorticoid receptor (mGR), previously correlated with glucocorticoid-induced lymphocytolytic competency, was purified under nondenaturing conditions from mGR-enriched mouse S-49 T lymphoma cells. Proteins were immunoaffinity batch adsorbed to BUGR-2 monoclonal antibody-coupled protein A Sepharose 4B beads, and elution by epitope competition was compared with standard denaturation procedures. Elution with BUGR-2 epitope peptides released multiple mGRs (42-150 kDa) and heat shock proteins 70 and 90, suggesting that mGR interacts with these protein chaperones under physiological conditions. The mGR-heat shock protein 90 interaction was inhibited by 1 microM geldanamycin. Several other mGR binding partners were captured and most were dissociated from mGR by 0.6 M salt. Peptide maps of purified mGR displayed immunoreactive bands unique to mGR. Scatchard analysis estimated a k(d) value of 239 nM and a Bmax of 384 fmol/mg protein for mGR, compared to a k(d) of 19.5 nM and a Bmax of 90.3 fmol/mg protein for the intracellular GR (iGR). The rank order of affinities for mGR were RU-486 > dexamethasone > triamcinolone acetonide = aldosterone. Other steroids had no significant binding affinity. These results show that epitope-purified mGR on the plasma membrane of mouse lymphoma cells is similar but not identical to iGR.

Comparison of the morbidity of tetanus toxoid boosters with tetanus-diphtheria toxoid boosters.

A double-blind randomized trial was performed to compare the subjective morbidity of tetanus toxoid (T) with that of tetanus-diphtheria toxoid (Td). Symptoms occurred in 46 (48%) of 93 patients who received T, and in 75 of 100 patients who received Td (chi 2 = 12.3; P less than .001). The effectiveness of immunization is clear, but with shift from use of T to Td as recommended, adherence to immunization guidelines and taking of adequate immunization histories becomes even more important.