Alpha-crystallin B chains enhance cell migration in basal-like 2 triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) can be divided into six subtypes. Among these subtypes, the basal-like 2 (BL2) subtype shows the lowest five-year survival rate and highest risk of metastasis. Alpha-crystallin B chains (αB-crystallin), a small heat shock protein that is known to be involved in breast cancer metastasis, is highly expressed in the basal-like subtype but not in the other non-basal subtypes. Thus, we hypothesized that αB-crystallin may be an important factor involved in the worse prognosis of the BL2 subtype compared with those of the other TNBC subtypes. Here, we examined the role of αB-crystallin in cell motility in two TNBC cell lines: HCC1806 (BL2 subtype) and, as control, MDA-MB-436 (mesenchymal stem-like subtype). HCC1806 showed greater cell migration capacity and a higher expression level of the gene encoding αB-crystallin (CRYAB) than did MDA-MB-436. Short interfering RNA-mediated silencing of CRYAB expression significantly reduced the cell migration capacity of HCC1806 cells, whereas it had no effect in MDA-MB-436 cells, indicating that αB-crystallin is essential for the migration of HCC1806 cells. Thus, high αB-crystallin expression may be a contributing factor to the poor prognosis of BL2 TNBC.

Progesterone receptor membrane component 2 expression leads to erlotinib resistance in lung adenocarcinoma cells.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide a favorable treatment outcome in patients with EGFR mutation-positive non-small cell lung cancer. However, most of such patients become resistant to EGFR-TKIs within a year. Thus, clarifying the mechanism of acquired resistance to EGFR-TKIs has been a research focus. Here, we demonstrated that the expression of progesterone receptor membrane component 2 (PGRMC2) was upregulated in an erlotinib-resistant cell line, PC9/ER, compared with the parental PC9 lung cancer cells. Our previous study showed that PGRMC1 is responsible for acquired resistance to erlotinib; however, PGRMC2 has not been discussed yet. Thus, the aim of this study was to determine the role of PGRMC2 in acquired resistance to erlotinib. Transfection with PGRMC2 siRNA significantly enhanced the sensitivity to erlotinib in PC9/ER cells. Furthermore, knockdown of PGRMC2 reduced the expression of p21, which is known as cell-cycle inhibitor and antiproliferative effector. These results suggest that PGRMC2 partially contributes to erlotinib resistance in PC9/ER cells, and that investigation into the effect of PGRMC2 on apoptosis and the cell cycle are warranted.

Effect of load alterations on the effective regurgitant orifice area in chronic aortic regurgitation.

OBJECTIVE: To evaluate the load dependence of effective regurgitant orifice area (ROA) in an animal model of chronic aortic regurgitation. METHODS: Eight sheep were studied 10-20 weeks after the surgical creation of aortic regurgitation. After baseline studies, 500 ml of blood, angiotensin II, and nitroprusside were infused sequentially. Electromagnetic flow meters were used as reference standards to determine aortic regurgitation volume. The time-velocity integral was acquired using the continuous wave Doppler method. RESULTS: Baseline aortic regurgitant volume varied from 8 ml (regurgitant fraction 28%) to 29 ml (59%), with a mean (SD) value of 17 (8) ml; mean ROA was 0.15 (0.05) cm2. During angiotensin II infusion, aortic regurgitation volume (20 (8) ml) and mean diastolic aortoventricular pressure gradient (62 (18) mm Hg) increased by 26 (16)% and 48 (64)%, respectively (p < 0.01 for both). ROA did not change (0.16 (0.06) cm(2), p = 0.15). During nitroprusside infusion, aortic regurgitant volume (13 (7) ml, p = 0.05) and diastolic pressure gradient (25 (13) mm Hg, p < 0.05) decreased. ROA did not change (0.15 (0.05) cm2). When analysing 32 stages together, aortic regurgitant volume (r = 0.78, p < 0.01) and regurgitant fraction (r = 0.55, p < 0.01) correlated well with ROA. However, diastolic pressure gradient (r = 0.28) was not significantly correlated with ROA. CONCLUSIONS: In an animal model of chronic aortic regurgitation, ROA did not change with load alterations.

Combined surgical and intraoperative endovascular approach for a giant internal carotid artery aneurysm in the high cervical region.

For the obliteration of a large aneurysm located at the cranial base or high cervical region, several therapeutic strategies including a parent vessel ligation, and endovascular occlusion have been reported, because it is difficult to access the aneurysm itself. We used a combined surgical and endovascular approach for the treatment of a large internal carotid artery aneurysm in the high cervical region. In the present case, we performed superficial temporal artery to middle cerebral artery bypass, then obliterated the aneurysm with distal coil embolization and proximal ligation in one session, using portable digital subtraction angiography. The combined endovascular and surgical approach involves less invasive surgery for complex cerebrovascular lesions.

Interaliasing distance of the flow convergence surface for determining mitral regurgitant volume: a validation study in a chronic animal model.

OBJECTIVES: We aimed to validate a new flow convergence (FC) method that eliminated the need to locate the regurgitant orifice and that could be performed semiautomatedly. BACKGROUND: Complex and time-consuming features of previously validated color Doppler methods for determining mitral regurgitant volume (MRV) have prevented their widespread clinical use. METHODS: Thirty-nine different hemodynamic conditions in 12 sheep with surgically created flail leaflets inducing chronic mitral regurgitation were studied with two-dimensional (2D) echocardiography. Color Doppler M-mode images along the centerline of the accelerating flow towards the mitral regurgitation orifice were obtained. The distance between the two first aliasing boundaries (interaliasing distance [IAD]) was measured and the FC radius was mathematically derived according to the continuity equation (R(calc) = IAD/(1 - radicalv(1)/v(2)), v(1) and v(2) being the aliasing velocities). The conventional 2D FC radius was also measured (R(meas)). Mitral regurgitant volume was then calculated according to the FC method using both R(calc) and R(meas). Aortic and mitral electromagnetic (EM) flow probes and meters were balanced against each other to determine the reference standard MRV. RESULTS: Mitral regurgitant volume calculated from R(calc) and R(meas) correlated well with EM-MRV (y = 0.83x + 5.17, r = 0.90 and y = 1.04x + 0.91, r = 0.91, respectively, p < 0.001 for both). However, both methods resulted in slight overestimation of EM-MRV (Delta was 3.3 +/- 2.1 ml for R(calc) and 1.3 +/- 2.3 ml for R(meas)). CONCLUSIONS: Good correlation was observed between MRV derived from R(calc) (IAD method) and EM-MRV, similar to that observed with R(meas) (conventional FC method) and EM-MRV. The R(calc) using the IAD method has an advantage over conventional R(meas) in that it does not require spatial localization of the regurgitant orifice and can be performed semiautomatedly.

Real-time three-dimensional color Doppler echocardiography for characterizing the spatial velocity distribution and quantifying the peak flow rate in the left ventricular outflow tract.

Quantification of flow with pulsed-wave Doppler assumes a "flat" velocity profile in the left ventricular outflow tract (LVOT), which observation refutes. Recent development of real-time, three-dimensional (3-D) color Doppler allows one to obtain an entire cross-sectional velocity distribution of the LVOT, which is not possible using conventional 2-D echo. In an animal experiment, the cross-sectional color Doppler images of the LVOT at peak systole were derived and digitally transferred to a computer to visualize and quantify spatial velocity distributions and peak flow rates. Markedly skewed profiles, with higher velocities toward the septum, were consistently observed. Reference peak flow rates by electromagnetic flow meter correlated well with 3-D peak flow rates (r = 0.94), but with an anticipated underestimation. Real-time 3-D color Doppler echocardiography was capable of determining cross-sectional velocity distributions and peak flow rates, demonstrating the utility of this new method for better understanding and quantifying blood flow phenomena.

Real-time three-dimensional echocardiographic study of left ventricular function after infarct exclusion surgery for ischemic cardiomyopathy.

BACKGROUND: Infarct exclusion (IE) surgery, a technique of left ventricular (LV) reconstruction for dyskinetic or akinetic LV segments in patients with ischemic cardiomyopathy, requires accurate volume quantification to determine the impact of surgery due to complicated geometric changes. METHODS AND RESULTS: Thirty patients who underwent IE (mean age 61+/-8 years, 73% men) had epicardial real-time 3-dimensional echocardiographic (RT3DE) studies performed before and after IE. RT3DE follow-up was performed transthoracically 42+/-67 days after surgery in 22 patients. Repeated measures ANOVA was used to compare the values before and after IE surgery and at follow-up. Significant decreases in LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were apparent immediately after IE and in follow-up (EDVI 99+/-40, 67+/-26, and 71+/-31 mL/m(2), respectively; ESVI 72+/-37, 40+/-21, and 42+/-22 mL/m(2), respectively; P:<0.05). LV ejection fraction increased significantly and remained higher (0.29+/-0.11, 0.43+/-0.13, and 0.42+/-0.09, respectively, P:<0.05). Forward stroke volume in 16 patients with preoperative mitral regurgitation significantly improved after IE and in follow-up (22+/-12, 53+/-24, and 58+/-21 mL, respectively, P:<0.005). New York Heart Association functional class at an average 285+/-144 days of clinical follow-up significantly improved from 3.0+/-0.8 to 1.8+/-0.8 (P:<0.0001). Smaller end-diastolic and end-systolic volumes measured with RT3DE immediately after IE were closely related to improvement in New York Heart Association functional class at clinical follow-up (Spearman's rho=0.58 and 0.60, respectively). CONCLUSIONS: RT3DE can be used to quantitatively assess changes in LV volume and function after complicated LV reconstruction. Decreased LV volume and increased ejection fraction imply a reduction in LV wall stress after IE surgery and are predictive of symptomatic improvement.

Validation of real-time three-dimensional echocardiography for quantifying left ventricular volumes in the presence of a left ventricular aneurysm: in vitro and in vivo studies.

OBJECTIVES: To validate the accuracy of real-time three-dimensional echocardiography (RT3DE) for quantifying aneurysmal left ventricular (LV) volumes. BACKGROUND: Conventional two-dimensional echocardiography (2DE) has limitations when applied for quantification of LV volumes in patients with LV aneurysms. METHODS: Seven aneurysmal balloons, 15 sheep (5 with chronic LV aneurysms and 10 without LV aneurysms) during 60 different hemodynamic conditions and 29 patients (13 with chronic LV aneurysms and 16 with normal LV) underwent RT3DE and 2DE. Electromagnetic flow meters and magnetic resonance imaging (MRI) served as reference standards in the animals and in the patients, respectively. Rotated apical six-plane method with multiplanar Simpson's rule and apical biplane Simpson's rule were used to determine LV volumes by RT3DE and 2DE, respectively. RESULTS: Both RT3DE and 2DE correlated well with actual volumes for aneurysmal balloons. However, a significantly smaller mean difference (MD) was found between RT3DE and actual volumes (-7 ml for RT3DE vs. 22 ml for 2DE, p = 0.0002). Excellent correlation and agreement between RT3DE and electromagnetic flow meters for LV stroke volumes for animals with aneurysms were observed, while 2DE showed lesser correlation and agreement (r = 0.97, MD = -1.0 ml vs. r = 0.76, MD = 4.4 ml). In patients with LV aneurysms, better correlation and agreement between RT3DE and MRI for LV volumes were obtained (r = 0.99, MD = -28 ml) than between 2DE and MRI (r = 0.91, MD = -49 ml). CONCLUSIONS: For geometrically asymmetric LVs associated with ventricular aneurysms, RT3DE can accurately quantify LV volumes.

Cosgrove-Edwards Annuloplasty System: midterm results.

BACKGROUND: The Cosgrove-Edwards Annuloplasty System includes a universally flexible band that corrects mitral annular dilatation via measured plication of the posterior annulus. The purpose of this study was to evaluate midterm clinical and functional results in the first 197 patients receiving this flexible annuloplasty band at mitral valve repair. METHODS: From February 1993 to July 1994, 197 consecutive patients with mitral regurgitation had mitral valve repair using this system. Valve disease was degenerative in 73%, rheumatic in 15%, ischemic in 5%, infectious in 2.5%, and other in 4%. RESULTS: Immediately after repair, echocardiographic mitral regurgitation was none or trivial in 92%, 1+ in 5%, and 2+ in 3%. There were no hospital deaths. Late follow-up was available in 195 patients (99%), with 661 patient-years of follow-up available for analysis. Four-year actuarial survival was 93%, freedom from thromboembolism 94%, from endocarditis 98%, and from reoperation 95%. At a mean interval of 18 months, echocardiography in 157 patients demonstrated no or trace mitral regurgitation in 56%, 1+ in 24%, 2+ in 9%, 3+ in 6%, and 4+ in 3%. At a mean of 61 +/- 5 months, reconstruction of the mitral annulus from real-time three-dimensional echocardiographic images in 10 patients confirmed preserved nonplanar shape and sphincter mechanism of the mitral annulus. Annular orifice area decreased 28% +/- 11% during the cardiac cycle from a mean of 10.1 +/- 3.9 cm2 in diastole to 7.2 +/- 2.8 cm2 in systole. CONCLUSIONS: This annuloplasty system is effective for repair of mitral regurgitation secondary to all causes and preserves mitral annular flexibility and function at 5-year follow-up.

Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury.

Activating transcription factor 3 (ATF3), a member of ATF/CREB family of transcription factors, is induced in a variety of stressed tissue. ATF3 regulates transcription by binding to DNA sites as a homodimer or heterodimer with Jun proteins. The purpose of this study was to examine the expression and regulation of ATF3 after axonal injury in neurons in dorsal root ganglia (DRG) and spinal cord. In naive rats, ATF3 was not expressed in the DRG and spinal cord. Following the cut of peripheral nerve, ATF3 was immediately induced in virtually all DRG neurons and motoneurons that were axotomized, and the time course of induction was dependent on the distance between the injury site and the cell body. Double labeling using immunohistochemistry revealed that the population of DRG neurons expressing ATF3 included those expressing c-jun, and in motoneurons ATF3 and c-jun were concurrently expressed after axotomy. In contrast to c-jun, ATF3 was not induced transsynaptically in spinal dorsal horn neurons. We conclude that ATF3 is specifically induced in sensory and motoneurons in the spinal cord following nerve injury and should be regarded as an unique neuronal marker of nerve injury in the nervous system.

Impact of temporal resolution on flow quantification by real-time 3D color Doppler echocardiography: numerical modeling and animal validation study.

Real-time, 3D color Doppler echocardiography (RT3D) is capable of quantifying flow at the LV outflow tract (LVOT). However, previous works have found significant underestimation for flow rate estimation due to finite scanning time (ST) of the color Doppler. The authors have, therefore, developed a mathematical model to correct the impact of ST on flow quantification and validated it by an animal study. Scanning time to cover the entire cross-sectional image of the LVOT was calculated as 60 ms, and the underestimation due to temporal averaging effect was predicted as 18 +/- 7%. In the animal experiment, peak flow rates were obtained by spatially integrating the velocity data front the cross-sectional color images of the LVOT. By applying a correction factor, there was an excellent agreement between reference flow rate by an electromagnetic flow meter and RT3D (angstroms=-5.6 ml/s, r=0.93), which was significantly better than without correction (p<0.001). Real-time, color 3D echocardiography was capable of quantifying flow accurately by applying the mathematical correction.

New digital measurement methods for left ventricular volume using real-time three-dimensional echocardiography: comparison with electromagnetic flow method and magnetic resonance imaging.

AIM: The aim of this study was to investigate the feasibility and accuracy of using symmetrically rotated apical long axis planes for the determination of left ventricular (LV) volumes with real-time three-dimensional echocardiography (3DE). METHODS AND RESULTS: Real-time 3DE was performed in six sheep during 24 haemodynamic conditions with electromagnetic flow measurements (EM), and in 29 patients with magnetic resonance imaging measurements (MRI). LV volumes were calculated by Simpson's rule with five 3DE methods (i.e. apical biplane, four-plane, six-plane, nine-plane (in which the angle between each long axis plane was 90 degrees, 45 degrees, 30 degrees or 20 degrees, respectively) and standard short axis views (SAX)). Real-time 3DE correlated well with EM for LV stroke volumes in animals (r=0.68-0.95) and with MRI for absolute volumes in patients (r-values=0.93-0.98). However, agreement between MRI and apical nine-plane, six-plane, and SAX methods in patients was better than those with apical four-plane and bi-plane methods (mean difference = -15, -18, -13, vs. -31 and -48 ml for end-diastolic volume, respectively, P<0.05). CONCLUSION: Apically rotated measurement methods of real-time 3DE correlated well with reference standards for calculating LV volumes. Balancing accuracy and required time for these LV volume measurements, the apical six-plane method is recommended for clinical use.

Excitability of spinal cord and gracile nucleus neurons in rats with chronically injured sciatic nerve examined by c-fos expression.

Low-threshold sensory pathways have been suggested to have an important role in the formation and maintenance of sensory abnormalities which are observed after peripheral nerve injury. Fos-like immunoreactive (Fos-LI) neurons are expressed in spinal cord laminae III-IV and the gracile nucleus by electrically stimulating the injured nerves at Abeta strength after sciatic nerve transection in rats. This suggests that the excitability of these neurons is increased by nerve injury. In this study, we investigated which receptors are involved in the regulation of the increased excitability in spinal and gracile nucleus neurons. The sciatic nerve of Sprague-Dawley rats (150 g) was transected 7 days before the experiment day. The rats were administered morphine, muscimol, baclofen, MK-801, CNQX, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) or clonidine i.p., and then electrically stimulated at 0.1 mA to the proximal region to the nerve injury site under urethane anesthesia. Two hours after the stimulation, Fos-LI expression was increased in the spinal cord dorsal horn and the gracile nucleus in control rats. Baclofen inhibited the Fos-LI expression both in the spinal cord and the gracile nucleus. Morphine inhibited only the Fos-LI expression in the posterior cutaneous (PC) nerve territory of laminae I-II, but not in the sciatic nerve (SC) territory, laminae III-IV nor the gracile nucleus. MK-801 had an inhibitory but complicated effect in laminae I-II and the gracile nucleus. The other drugs were not effective on Fos-LI expression. It is suggested that the GABA(B) receptor has a pivotal role in the regulation of Fos-LI expression after electrical stimulation to the injured low-threshold sensory fibers, and other receptors have little effect on the Fos-LI expression.

Validation of the accuracy of both right and left ventricular outflow volume determinations and semiautomated calculation of shunt volumes through atrial septal defects by digital color Doppler flow mapping in a chronic animal model.

OBJECTIVES: The aim of the present study was to quantitate shunt flow volumes through atrial septal defects (ASDs) in a chronic animal model with surgically created ASDs using a new semiautomated color Doppler flow calculation method (ACM). BACKGROUND: Because pulsed Doppler is cumbersome and often inappropriate for color flow computation, new methods such as ACM are of interest. METHODS: In this study, 13 to 25 weeks after ASDs were surgically created in eight sheep, a total of 24 hemodynamic states were studied at a separate open chest experimental session. Electromagnetic (EM) flow probes and meters were used to provide reference flow volumes as the pulmonary and aortic flow volumes (Qp and Qs) and shunt flow volumes (Qp minus Qs). Epicardial echocardiographic studies were performed to image the left and right ventricular outflow tract (LVOT and RVOT) forward flow signals. The ACM method digitally integrated spatial and temporal color flow velocity data to provide stroke volumes. RESULTS Left ventricular outflow tract and RVOT flow volumes obtained by the ACM method agreed well with those obtained by the EM method (r = 0.96, mean difference = 0.78 +/- 1.7 ml for LVOT and r = 0.97, mean difference = -0.35 +/- 3.6 ml for RVOT). As a result, shunt flow volumes and Qp/Qs by the ACM method agreed well with those obtained by the EM method (r = 0.96, mean difference = -1.1 +/- 3.6 ml/beat for shunt volumes and r = 0.95, mean difference = -0.11 +/- 0.22 for Qp/Qs). CONCLUSIONS: This animal study, using strictly quantified shunt flow volumes, demonstrated that the ACM method can provide Qp/Qs and shunt measurements semiautomatically and noninvasively.

Discordant expression of c-Ret and glial cell line-derived neurotrophic factor receptor alpha-1 mRNAs in response to motor nerve injury in neonate rats.

Adult motoneurons can survive following axotomy, whereas neonate motoneurons result in cell death. Following hypoglossal nerve axotomy in neonate rat, Glial cell line-Derived Neurotrophic Factor (GDNF) receptor alpha-1 (GFRalpha-1) mRNA expression was dramatically suppressed in the injured motoneurons, while a slight increase of c-Ret mRNA expression was observed. In adult, both GFRalpha-1 and c-Ret mRNAs increased substantially after axotomy. The present result suggests that the difference of motoneuron fate after axotomy may be partly due to the coordinate or discordant responses of GFRalpha-1 and c-Ret expression to nerve injury.

[Effects of imaging parameters on automated cardiac flow measurement using color Doppler echocardiography].

The color Doppler echocardiographic technique has been developed for automated cardiac flow measurement (ACM). This study evaluated the effect of imaging parameters on stroke volume measurement. Cardiac output derived from the ACM method was compared with that obtained from pulsed wave Doppler in 36 patients (26 men and 10 women, mean age 54 +/- 8 years) in whom clear two-dimensional and color Doppler images of the left ventricular outflow tract were obtained. The effects of frame rate, color gain and moving target indicator (MTI) filter on cardiac output were evaluated in 13 patients (8 men and 5 women, mean age 49 +/- 6 years). Using ACM at a frame rate of 30 Hz, optimal color gain setting and high-frequency MTI filter (cutoff frequency: 915 Hz), there was an excellent correlation in cardiac output between the ACM and pulsed wave Doppler methods (stroke volume: r = 0.91, SEE = 0.32 l/min). Using ACM at a frame rate of 30, 22 and 15 Hz, the differences in stroke volume were 4.4%, 5.2% and 8.6%, respectively. When color gain was reduced, left ventricular stroke volume reduction was 12.1% (-2 dB), 18.9% (-4 dB). In contrast, there was no significant change in stroke volume measurement when color gain was increased. There was a significant decrease in stroke volume using the low-frequency MTI filter [cutoff frequency: 467 Hz (-35.6%)] and medium-frequency MTI filter [cutoff frequency: 703 Hz (-13.4%)]. Color Doppler imaging parameters are extremely important for automated assessment of cardiac output.

Quantification of aortic regurgitant volume by a newly developed automated cardiac flow measurement method: an in vitro study.

BACKGROUND: Quantifying regurgitant volumes is important for treatment of patients with valvular aortic regurgitation. Simple, reliable methods to quantify aortic regurgitation have been sought both in the catheterization laboratory and the echocardiography laboratory. OBJECTIVES: The aim of our study was to investigate the applicability of a new automated cardiac flow measurement method with color Doppler velocity data for quantifying retrograde flow volumes of aortic regurgitation in an ascending aorta model. METHODS AND RESULTS: A 2-chamber pulsatile flow system with a modeled ascending aorta and a regurgitant aortic valve orifice was developed. The model could generate "aortic regurgitation-like" waveforms through the use of an electrically controlled valve. The regurgitant flows through the orifice (8.5 to 28.1 mL/beat) were measured by an ultrasound flowmeter; they were also calculated in the ascending aorta 1.0 cm above the orifice by the automated cardiac flow measurement method, which integrated spatially distributed digital flow velocity data through "diastole." Calculated regurgitant volumes measured with the low color Doppler filter (5.4 cm/s) agreed well with those measured with the flowmeter (r=.99, P < .001, mean difference=2.2+/-3.7 mL). However, the regurgitant volume was underestimated when 2 higher filter settings were used (9.6 and 10.9 cm/s). Although there was no significant difference in mean volume, higher frame rate (19 frames/s) provided more reproducible results with smaller standard deviation as compared with lower frame rate (7 frames/s). CONCLUSIONS: This new automated cardiac flow measurement method appears to be promising for semiautomatic quantification of aortic regurgitant volume. Appropriate choice of filter setting and high frame rate assists reliable data acquisition.

Alternative expression of Shc family members in nerve-injured motoneurons.

Expression of Shc family protein (Shc/ShcA, SCK/ShcB and N-Shc/ShcC) and Grb2 mRNAs in the hypoglossal motoneurons after axotomy was examined by in situ hybridization. In normal hypoglossal motor neurons, N-Shc mRNA was expressed predominantly, whereas the Shc mRNA level is very low. Rat hypoglossal nerve injury reversed the expressions of these two molecules in hypoglossal motoneurons. Shc mRNA expression was up-regulated markedly whereas N-Shc was down-regulated after nerve injury. Expression levels of SCK, another Shc family member, and Grb2 were unaffected by nerve injury. These results suggest that, whereas the N-Shc-mediated pathway dominates under normal conditions, an alternative Shc-mediated pathway is utilized in the event of nerve injury. By changing the expression of the Shc family members, the signaling pathway can be altered and various responses induced for nerve regeneration.

Calculation of aortic regurgitant volume by a new digital Doppler color flow mapping method: an animal study with quantified chronic aortic regurgitation.

OBJECTIVES: The aim of the present study was to quantitate aortic regurgitant volume and regurgitant fraction in a chronic animal model with surgically created aortic regurgitation using a new semiautomated color Doppler flow calculation method. BACKGROUND: The conventional noninvasive methods for evaluating the severity of aortic regurgitation have not been accepted widely nor compared with truly quantitative reference standards. METHODS: Eight to 20 weeks after aortic regurgitation was surgically induced in six sheep, a total of 22 hemodynamic states were studied. Electromagnetic flow probes and meters provided reference flow data. Epicardial color Doppler echocardiographic studies were performed to image left ventricular outflow tract forward and aortic regurgitant blood flows. The new method digitally integrated spatial and temporal color flow velocity data for left ventricular outflow tract forward flow and ascending aortic regurgitant flow. The pulsed Doppler method using the velocity-time integral was also used to obtain regurgitant volumes and regurgitant fractions. RESULTS: Regurgitant volumes and regurgitant fractions by the new method agreed well with those obtained electromagnetically, whereas the pulsed Doppler method overestimated these reference data (mean [+/-SD] difference 0.23 +/- 2.9 ml vs. 11 +/- 5.8 ml, p < 0.0001 for regurgitant volume; mean difference 1.2 +/- 7.6% vs. 19 +/- 13%, p < 0.0001 for regurgitant fraction). CONCLUSIONS: This animal study, using strictly quantified aortic regurgitant volumes, demonstrated that the digital color Doppler method provides accurate aortic regurgitant volumes and regurgitant fractions without cumbersome measurements.

Quantitative measurement of volume flow rate (cardiac output) by the multibeam Doppler method.

A new method has been developed for measuring the volume flow rate of blood flowing through large vessels or outflow tracts of the heart. In this article we describe the principle of a method that can reduce the dependence of the Doppler angle of flow measurement by setting the sample points along a line to which every ultrasound beam is perpendicular. To evaluate the accuracy of this method, flow phantom experiments were made for both steady and pulsatile flows. The volume flow rate measured by this method agrees well with that observed by an ultrasound flowmeter (r = 0.99) when the vessel diameter is large (25 mm). However, this method overestimates by 40% when the vessel diameter is small (8 mm). To make this method applicable to small vessels, an improvement in the lateral resolution of Doppler measurement is necessary. It has been concluded that this method can be used to measure the cardiac output or volume flow rates in large vessels.