Intraspecific divergence and convergence of floral tube length in specialized pollination interactions.

Floral tubes are often thought to be a consequence of adaptive specialization towards pollinator morphology. We explore floral tube length evolution within Tritoniopsis revoluta (Iridaceae), a species with considerable geographical tube length variation. We ask whether tube lengths of T. revoluta populations are associated with pollinator proboscis lengths, whether floral divergence occurs in the presence of different pollinators and whether floral convergence occurs between distantly related populations pollinated by the same pollinator. Finally, we ask whether tube length evolution is directional. Shifts between morphologically different pollinators were always associated with shifts in floral morphology, even when populations were very closely related. Distantly related populations had similar tube lengths when they were pollinated by the same pollinator. Shifts in tube length tended to be from short to long, although reversals were not infrequent. After correcting for the population-level phylogeny, there was a strong positive, linear relationship between floral tube length and pollinator proboscis length, suggesting that plants are functionally specialized on different pollinators at different sites. However, because tube length evolution in this system can be a bidirectional process, specialization to the local pollinator fauna is unlikely to result in evolutionary or ecological dead-ends such as canalization or range limitation.

Investigation of a MOSFET dosimetry system for midpoint dose verification in prostate 3D CRT/IMRT.

The suitability of MOSFETs (Metal Oxide Semiconductor Field Effect Transistors) for use in in-vivo dosimetry for IMRT prostate treatment and patient setup errors has been investigated in this work. MOSFETs were placed on entrance and exit surfaces of a number of different phantoms (with varying complexities from homogeneous to anthropomorphic). Dose measurements were then used to calculate a midpoint dose, which was compared with an IC placed at the isocentre. The agreements found between the calculated (MOSFETs) and the measured midpoint dose (IC) was: 0.7% for a prostate treatment verification and 3.5% for an IMRT treatment. MOSFETs placed on entry and exit surfaces can detect patient setup offsets of 2 cm, but do not have the sensitivity to confidently detect offsets of 1 cm or smaller.

[Surgery for congestive heart failure--the role of computed tomography in the pre- and postoperative diagnostic evaluation]. / Chirurgie der Herzinsuffizienz -- Stellenwert der Computertomographie in der prä- und postoperativen Diagnostik.

The treatment of advanced, drug resistant congestive heart failure gains in importance in the field of cardiac surgery. Cardiac imaging for preoperative assessment and follow-up focuses on the determination of ventricular volumes and function as well as on the detection of postoperative complications. Computed tomography (CT) is highly accurate irrespective of the individual patient's anatomic situation, has a low examiner dependence and short examination time, does not require an arterial vascular access and can be performed in patients with metal implants. CT is the modality of choice in the follow-up of heart transplants to detect extracardiac and cardiac complications including coronary calcifications as an early sign of transplant vasculopathy. In addition, CT visualizes the elements of mechanical assist devices and can identify their possible local cardiac and mediastinal complications. CT can detect fibrolipomatous involution of the mobilized muscle flap in dynamic cardiomyoplasty and can depict fibrous reactions along the epicardial mesh implant in passive cardiac containment. Further indications include assessment of typical local postoperative complications, such as intrathoracic infection and mediastinal bleeding, intracardiac thrombus formation or pericardial effusion. CT is routinely used for evaluating bypass patency but is limited in assessing associated valve defects since it does not visualize flow.

[Value of electron beam tomography (EBT)]. / Wertigkeit der Elektronenstrahl-Computertomographie (EBT) -- II. Nichtkardiale Anwendungen und Strahlenexposition.

Electron beam tomography (EBT) has been scientifically evaluated to a much lesser degree for non-cardiac indications than for cardiac purposes. Therefore, four groups of investigators in Berlin (2), Mannheim and Munchen, which were supported by the Deutsche Forschungsgemeinschaft (DFG), included applications outside the heart in their evaluation of EBT technology. EBT has proven useful to look for pulmonary embolism and to assess other vessels (aorta, aortic branches, and intracranial arteries). Imaging of the lung parenchyma benefits from its intrinsic high contrast and from the fast data acquisition of EBT. Limited photon efficiency, higher radiation exposure, increased noise levels and other artifacts, however, markedly reduce the value of EBT for imaging of low contrast objects compared to conventional spiral CT and multislice CT (MSCT), compromising, in particular, the morphologic depiction of parenchymal abdominal organs and the brain. Consequently, scientific studies to further evaluate EBT for scanning of the brain and parenchymal abdominal organs were not pursued. Radiation exposure for non-cardiac EBT studies is up to three times higher than that for respective spiral CT studies, and in children EBT can only be advocated in select cases. Radiation exposure for the various prospectively triggered cardiac examination protocols of EBT is lower than that for conventional coronary angiography. Radiation exposure in cardiac multislice CT exceeds severalfold that of EBT, but the dose efficiency of EBT and MSCT are similar due to higher spatial resolution and less image noise of MSCT. In addition, modifications of MSCT (ECG pulsing) can further reduce radiation exposure to the level of EBT. Technical improvements of the EBT successor scanner "e-Speed" enable faster data acquisition at higher spatial resolution. Within comparative studies, the "e-Speed" will have to prove its value and competitiveness, particularly in comparison with multislice CT. After profound scientific assessment in a multicenter evaluation supported by the Deutsche Forschungsgemeinschaft (DFG) and regardless of the specific suitability of electron beam tomography for various cardiac and some non-cardiac indications, the investigators unanimously find the electron beam tomograph Evolution C150 XP not suitable as a whole body CT scanner.

[Diagnostic value of electron-beam computed tomography (EBT). I. Cardiac applications]. / Diagnostische Wertigkeit der Elektronenstrahl-Computertomographie (EBT). I. Kardiale Anwendungen.

Electron beam tomography (EBT) directly competes with other non-invasive imaging modalities, such as multislice computed tomography, magnetic resonance imaging, and echocardiography, in the diagnostic assessment of cardiac diseases. EBT is the gold standard for the detection and quantification of coronary calcium as a preclinical sign of coronary artery disease (CAD). Its standardized examination protocols and the broad experience with this method favor EBT. First results with multislice CT indicate that this new technology may be equivalent to EBT for coronary calcium studies. The principal value of CT-based coronary calcium measurements continues to be an issue of controversy amongst radiologists and cardiologists due to lack of prospective randomized trials. Coronary angiography with EBT is characterized by a high negative predictive value and, in addition, may be indicated in some patients with manifest CAD. It remains to be shown whether coronary angiography with multislice CT is reliable and accurate enough to be introduced into the routine work-up, to replace some of the many strictly diagnostic coronary catheterizations in Germany and elsewhere. Assessment of coronary stent patency with EBT is associated with several problems and in our opinion cannot be advocated as a routine procedure. EBT may be recommended for the evaluation of coronary bypasses to look for bypass occlusions and significant stenoses, which, however, can be equally well achieved with multislice CT. Quantification of myocardial perfusion with EBT could not replace MRI or other modalities in this field. EBT has proven to be accurate, reliable and in some instances equivalent to MRI, which is the gold standard for the quantitative and qualitative evaluation of cardiac function. Some disadvantages, not the least of which is the limited distribution of electron beam scanners, favor MRI for functional assessment of the heart.

Assessment of left ventricular volumes and function: intraindividual comparison of multi-slice spiral CT and electron beam CT in an animal model.

PURPOSE: To evaluate multi-slice spiral computed tomography (MSCT) for measurements of left ventricular volumes, ejection fraction (EF), and myocardial mass in comparison with electron beam CT (EBCT) as a reference method. MATERIAL AND METHODS: Six minipigs underwent both standardized contrast-enhanced MSCT (effective acquisition time per cardiac cycle 125.7+/-30.1 ms, reconstructed slice thickness 8 mm) and EBCT (acquisition time 50 ms, collimated slice thickness 8 mm). The contrast-to-noise ratio of the left ventricle was measured in each animal, and the contour sharpness of the myocardium was analyzed. Volumes (EDV, ESV, SV) ejection fraction (EF), and muscle mass were calculated by MSCT and by EBCT using the slice summation method. RESULTS: MSCT had a higher contrast-to-noise ratio and delineated the myocardial contours more sharply than EBCT. There was a close linear correlation between both modalities for all parameters (EDV: rP=0.88, ESV: rP=0.91, SV: rP=0.85, EF: rP=0.93; mass: rP=0.90; P<0.05 each). MSCT slightly overestimated ESV and slightly underestimated SV and EF compared with EBCT (P<0.05 each). CONCLUSIONS: Image quality in MSCT is superior to that of EBCT. Functional parameters correlate well between both modalities, but the accuracy of MSCT is limited by its lower temporal resolution.

[Evaluation of passive cardiomyoplasty using left- and right-ventricular volume measurements by EBCT and MRI in patients with chronic congestive heart failure]. / Evaluierung der passiven Kardiomyoplastie mittels links- und rechtsventrikulärer EBCT- und MRT-Volumetrie bei Patienten mit chronischer Herzinsuffizienz.

PURPOSE: To evaluate the efficacy of passive cardiomyoplasty with the determination of biventricular volumes, global systolic function as well as left-ventricular muscle mass. MATERIALS AND METHODS: In 19 patients with congestive heart failure of idiopathic or ischemic origin, a polyester mesh-graft was implanted around both ventricles for stabilization and functional support. Before and three months after surgery, 15 patients underwent EBCT and 4 patients with impaired renal function underwent MRI, for the evaluation of the volume and ejection fraction of both ventricles. RESULTS: EBCT demonstrated a decrease from 385 to 310 ml in LV-EDV, from 312 to 242 ml in LV-ESV, from 209 to 160 ml in RV-EDV and from 149 to 87 ml in RV-ESV, and an increase from 20 to 26% in LV-EF and from 37 to 50% in RV-EF as well as a reduction of LV-MM from 300 to 274 g (p < 0.05 each). Similar results were obtained by MRI. CONCLUSION: Following passive cardiomyoplasty, EBCT and MRI revealed an improvement of the global systolic function as well as a reduction of biventricular volumes and left-ventricular muscle mass.

[Imaging of the coronary arteries by means of multislice helical CT: optimization of image quality with multisegmental reconstruction and variable gantry rotation time]. / Darstellung der Koronararterien mittels Mehrschicht-Spiral-CT: Optimierung der Bildqualität mittels Multisegment-Rekonstruktion und variabler Gantry-Rotationszeit.

PURPOSE: To evaluate the potential of multisegmental reconstruction and variable gantry rotation time for reducing motion-induced artifacts in coronary artery imaging by multislice helical CT. MATERIALS AND METHODS: The data sets of 20 patients (8 with HR < 60 bpm, 12 with HR > 60 bpm) were analyzed. The patients underwent multislice helical CT (Aquilion 8, Toshiba, Otawara, Japan) using the following parameters: 0.5 mm slice thickness, 250 mA, 120 kV, pitch of 0.25 and variable gantry rotation times of 400, 500, or 600 msec. Images were generated by halfscan and multisegmental reconstruction. In 9 coronary segments of each patient, the presence and severity of motion artifacts were assessed and graded on a scale between 5 (no artifacts) and 1 (heaviest artifacts). RESULTS: Diagnostically relevant motion artifacts were rare at low heart rates (< 60 bpm) for both types of image reconstruction (4 % of all segments). Higher heart rates (> 60 bpm) were associated with an increase in motion artifacts on halfscan reconstructions (33% of all segments, p < 0.05) but not on multisegmental reconstructions (4% of all segments). At low heart rates mean image quality did not differ between multisegmental and halfscan reconstruction (4.28 +/- 0.37 vs. 4.22 +/- 0.41; p > 0.05), whereas at higher heart rates image quality was better for multisegmental reconstruction than for halfscan reconstruction (4.23 +/- 0.47 vs. 3.11 +/- 0.63; p < 0.05). CONCLUSION: Multisegmental reconstruction with variable gantry rotation times suppresses motion artifacts and thus improves assessment of the coronary arteries in patients with higher heart rates.

[Incidence and distribution pattern of pulmonary saddle emboli: Diagnosis by electron beam tomography (EBT)]. / Häufigkeit und Verteilungsmuster pulmonalerSattelembolien: Diagnostik mittels Elektronenstrahl-Computertomographie (EBT).

PURPOSE: To determine the incidence of acute pulmonary emboli extending across the bifurcation of the main pulmonary artery, lobar arteries or segmental arteries (interpulmonary, interlobar or intersegmental saddle emboli, respectively). METHODS: 128 patients with clinically suspected acute pulmonary embolism underwent electron beam tomography (EBT). 140 scans were acquired in the continuous volume scanning mode (3 mm slice thickness). 100 ml of contrast material were intravenously administered. Studies were reviewed for the presence of acute pulmonary embolism and the number and location of interpulmonary, interlobar or intersegmental saddle emboli. Saddle emboli were defined as emboli extending across the bifurcation of a vessel into both branches by at least 5 mm each. RESULTS: 30 of 128 (23.4 %) patients (15 men; mean age 59 +/- 17 years) had acute pulmonary embolism. One or more saddle emboli were present in 20 of 30 patients (66.7 %), a total of 77 saddle emboli were detected ranging from 1 to 10 per patient. Distribution of the saddle emboli in the 20 patients was as follows: 5 interpulmonary, 28 interlobar and 44 intersegmental. CONCLUSIONS: Pulmonary saddle emboli are present in the majority of patients with acute pulmonary embolism. They are often multiple and may be found at different levels of the pulmonary arterial vasculature.

[Left ventricular reduction surgery: pre- and postoperative evaluation by cine MRI]. / Linksventrikuläre Volumen-reduktion: Prä- und postoperative Evaluierung mit der Cine MRT.

AIM: To evaluate the role of cine magnetic resonance imaging (MRI) in the preoperative assessment and postoperative follow-up of patients undergoing left ventricular (LV) reduction surgery. PATIENTS AND METHODS: 6 patients with cardiomegaly were examined on a 1.5 T MR imager before and after LV reduction surgery. The heart was imaged along the short and long axes using a breath-hold ECG-triggered cine gradient-echo sequence for assessing ventricular and valvular morphology and function and performing volumetry (end-diastolic and end-systolic volumes, ejection fraction). RESULTS: Postoperatively, the mean ejection fraction increased from 21.7% to 33.4% and the end-diastolic and end-systolic left ventricular volumes decreased in all patients (304.0 and 252.5 ml before to 205.0 and 141.9 ml after surgery). Mean myocardial mass decreased slightly from 283.8 g to 242.7 g. Differences were significant for all parameters (p < 0.05). MRI allowed for the reliable assessment of post-operative valve morphology and yielded additional findings such as the presence of mitral valve insufficiency or ventricular thrombus. CONCLUSIONS: Cine MRI provides relevant information prior to left ventricular reduction surgery and reliably depicts functional and morphological changes in the early post-operative follow-up.

Phytochemical glyceollins, isolated from soy, mediate antihormonal effects through estrogen receptor alpha and beta.

The flavonoid family of phytochemicals, particularly those derived from soy, has received attention regarding their estrogenic activity as well as their effects on human health and disease. In addition to these flavonoids other phytochemicals, including phytostilbene, enterolactone, and lignans, possess endocrine activity. The types and amounts of these compounds in soy and other plants are controlled by both constitutive expression and stress-induced biosynthesis. The health benefits of soy-based foods may, therefore, be dependent upon the amounts of the various hormonally active phytochemicals within these foods. The aim was to identify unique soy phytochemicals that had not been previously assessed for estrogenic or antiestrogenic activity. Here we describe increased biosynthesis of the isoflavonoid phytoalexin compounds, glyceollins, in soy plants grown under stressed conditions. In contrast to the observed estrogenic effects of coumestrol, daidzein, and genistein, we observed a marked antiestrogenic effect of glyceollins on ER signaling, which correlated with a comparable suppression of 17 beta-estradiol-induced proliferation in MCF-7 cells. Further evaluation revealed greater antagonism toward ER alpha than ER beta in transiently transfected HEK 293 cells. Competition binding assays revealed a greater affinity of glyceollins for ER alpha vs. ER beta, which correlated to greater suppression of ER alpha signaling with higher concentrations of glyceollins. In conclusion, we describe the phytoalexin compounds known as glyceollins, which exhibit unique antagonistic effects on ER in both HEK 293 and MCF-7 cells. The glyceollins as well as other phytoalexin compounds may represent an important component of the health effects of soy-based foods.

Coronary artery bypass grafts: improved electron-beam tomography by prolonging breath holds with preoxygenation.

In 45 patients with coronary bypass grafts, the breath-hold interval with and that without preoxygenation was measured. Its effect on depiction of the distal graft anastomosis at electron-beam tomography was evaluated. Preoxygenation prolonged the breath-hold interval in most patients, thereby allowing greater anatomic coverage including more distal anastomoses. Preoxygenation may improve scanning of coronary bypass grafts and increase detectability of graft stenoses.

[Determination of left ventricular function parameters and myocardial mass: comparison of MRI and EBT]. / Bestimmung linksventrikulärer Funktionsparameter und der Myokardmasse: Vergleich von MRT und EBT.

PURPOSE: Comparative volumetric assessment of the left ventricle by magnetic resonance imaging (MRI) and electron beam tomography (EBT) in patients with ischemic and dilated cardiac disease. METHODS: Thirty-two patients underwent cine MRI and EBT in the multislice mode. All studies were triggered to the ECG. Left ventricular ejection fraction (EF), end-diastolic (EDV) and end-systolic volume (ESV), and myocardial mass (MM) were determined by 3D-volumetry by MRI and EBT and results were compared. RESULTS: The correlation between MRI and EBT for EF, EDV, ESV, and MM were r = 0.86, r = 0.95, r = 0.95, and r = 0.93, respectively. CONCLUSIONS: There is an excellent correlation between MRI and EBT in determining left-ventricular parameters. Both methods are suitable for volumetric assessment of the left ventricle.

Rapid screening of environmental chemicals for estrogen receptor binding capacity.

Over the last few years, an increased awareness of endocrine disrupting chemicals (EDCs) and their potential to affect wildlife and humans has produced a demand for practical screening methods to identify endocrine activity in a wide range of environmental and industrial chemicals. While it is clear that in vivo methods will be required to identify adverse effects produced by these chemicals, in vitro assays can define particular mechanisms of action and have the potential to be employed as rapid and low-cost screens for use in large scale EDC screening programs. Traditional estrogen receptor (ER) binding assays are useful for characterizing a chemical's potential to be an estrogen-acting EDC, but they involve displacement of a radioactive ligand from crude receptor preparations at low temperatures. The usefulness of these assays for realistically determining the ER binding interactions of weakly estrogenic environmental and industrial compounds that have low aqueous solubility is unclear. In this report, we present a novel fluorescence polarization (FP) method that measures the capacity of a competitor chemical to displace a high affinity fluorescent ligand from purified, recombinant human ER-[alpha] at room temperature. The ER-[alpha] binding interactions generated for 15 natural and synthetic compounds were found to be similar to those determined with traditional receptor binding assays. We also discuss the potential to employ this FP technology to binding studies involving ER-ss and other receptors. Thus, the assay introduced in this study is a nonradioactive receptor binding method that shows promise as a high throughput screening method for large-scale testing of environmental and industrial chemicals for ER binding interactions.

Induction of the estrogen specific mitogenic response of MCF-7 cells by selected analogues of estradiol-17 beta: a 3D QSAR study.

Analogues of estradiol-17 beta (E2) have been evaluated for estrogen receptor (ER) binding affinity and mitogenic potential in the human breast cancer cell line MCF-7. These 42 compounds represent subtle modifications of the natural estrogen structure through the placement of hydroxyl, amino, nitro, or iodo groups around the ring system in addition to, or as replacement of, the 3- and 17 beta-hydroxyls of E2. The mitogenic activity of the analogues was found to be related to ER binding only to a limited extent. In order to elucidate structural features that are uniquely responsible for receptor binding affinity or mitogen potential of estrogens, the three-dimensional quantitative structure-activity (QSAR) method Comparative Molecular Field Analysis (CoMFA) was employed. Separate CoMFA models for receptor binding and cell growth stimulation were optimized through the use of various alignment rules and region step size. Whereas the CoMFA contour plots did outline the shared structural requirements for the two measured biological properties, specific topological features in this set of estrogens were delineated that distinguish mitogenic potential from ER binding ability. In particular, steric interference zones which affected growth extend in a band from above the A-ring to position 4 and below, whereas the ER binding steric interference zones are limited to isolated polyhedra in the 1, 2 and 4 positions and the alpha face of the B-ring. In addition, electronegative features located around the A-, B-, or C-rings contribute to receptor affinity. However, growth is dependent only on electronegative and electropositive properties near the 3-position. In a final QSAR model for the mitogenic response, the value of ER binding was included along with structural features as a descriptor in CoMFA. The resulting 3D-QSAR has the most predictive potential of the models in this study and can be considered a prototype model for the general evaluation of a steroidal estrogen's growth stimulating ability in MCF-7 cells. For example, the location of D-ring contours illustrate the model's preference for 17 beta-hydroxy steroids over the less mitogenic 17 alpha- and 16 alpha-hydroxy compounds. In addition, the enhanced mitogenic effect of steric bulk in the 11 alpha-position is also evident. The QSAR studies in this report illustrate the fact that while ER binding may be a required factor of the estrogen dependent growth response in MCF-7 cells, particular structural characteristics, in addition to those responsible for tight receptor binding, must be present to induce an optimal mitogenic response. Therefore, this report demonstrates that the CoMFA QSAR method can be utilized to characterize structural features of test compounds that account for different types of estrogenic responses.

Effect of L-fucose and D-glucose concentration on L-fucoprotein metabolism in human Hep G2 cells and changes in fucosyltransferase and alpha-L-fucosidase activity in liver of diabetic rats.

L-Fucose is a monosaccharide that is present at low concentrations in serum and is a normal constituent of glycoproteins. In some pathological conditions, such as cancer, rheumatoid arthritis, and diabetes, there is an abnormal fucosylation of acute phase serum proteins. Because most serum proteins are produced in the liver, we have examined L-fucose accumulation, metabolism, and secretion of L-fucose-containing proteins in human Hep G2 liver cells. Accumulation of L-fucose by Hep G2 cells approached 3.5 nmol/mg protein after a 48 h incubation. This accumulation appears similar to accumulation in other cells, which we have shown occurs via a specific transport protein. Exogenous L-fucose was incorporated into protein in both O- and N-linked glycosidic linkages. After a 48 h incubation, 61% of the accumulated L-fucose was incorporated into protein and secreted into the medium, whereas 39% of the L-fucose remaining in the cells was incorporated into integral membrane proteins. Utilizing reverse-phase high-performance liquid chromatographic separation of L-[5,6-(3)H]fucose-containing proteins and detection by scintillation counting, we determined that two major fucoproteins and numerous minor fucoproteins were produced and secreted by normal Hep G2 cells. This elution profile was unchanged when glucose-conditioned cells were examined. By size-separating secreted proteins by nondenaturing HPLC we determined that the size of the two major fucoproteins were approximately 60 and approximately 100 kDa. In these studies we also examined the effect of diabetes on hepatic fucosyltransferase and serum alpha-L-fucosidase activity and found that the activity of these enzymes is increased by 40 and 100%, respectively in diabetic rats.

Supplemental myo-inositol prevents L-fucose-induced diabetic neuropathy.

Nerve myo-inositol depletion, which has been implicated in the pathogenesis of acute experimental diabetic neuropathy, can be reproduced in normal rats by feeding diets enriched in L-fucose, a competitive inhibitor of sodium-dependent myo-inositol transport. Previously, we reported that L-fucose feeding for 6 weeks reproduces the effect of experimental diabetes on nerve Na+-K+-ATPase activity and conduction velocity, which can be prevented by simultaneous dietary myo-inositol supplementation. To further validate this model of myo-inositol depletion, we examined the effects of long-term (24-week) L-fucose feeding and dietary myo-inositol supplementation on nerve Na+-K+-ATPase, nerve conduction velocity, and myelinated nerve fiber pathology. After 24 weeks of L-fucose enriched (10 or 20%) diets, nerve myo-inositol levels and Na+-K+-ATPase activity decreased significantly (P < 0.05) and were associated with a 25-30% reduction in nerve conduction velocity, all of which were completely prevented by 1% dietary myo-inositol. Twenty percent L-fucose diet resulted in significant axonal atrophy, paranodal swelling (P < 0.001), and paranodal demyelination (P < 0.005), without increasing Wallerian degeneration or nerve fiber loss, a pattern qualitatively similar to that seen in early murine diabetic neuropathy. Dietary myo-inositol supplementation prevented these structural changes and increased nodal remyelination, supporting a role of myo-inositol depletion in the genesis of early diabetic neuropathy. The L-fucose model system may therefore serve as an experimental tool to elucidate the pathophysiological role of isolated myo-inositol depletion and its consequences in the multifactorial pathogenesis of diabetic neuropathy.

Ligand-based identification of environmental estrogens.

Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) paradigm, was used to examine the estrogen receptor (ER) binding affinities of a series of structurally diverse natural, synthetic, and environmental chemicals of interest. The CoMFA/3D-QSAR model is statistically robust and internally consistent, and successfully illustrates that the overall steric and electrostatic properties of structurally diverse ligands for the estrogen receptor are both necessary and sufficient to describe the binding affinity. The ability of the model to accurately predict the ER binding affinity of an external test set of molecules suggests that structure-based 3D-QSAR models may be used to supplement the process of endocrine disruptor identification through prioritization of novel compounds for bioassay. The general application of this 3D-QSAR model within a toxicological framework is, at present, limited only by the quantity and quality of biological data for relevant biomarkers of toxicity and hormonal responsiveness.