Thuc Nguyen

Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis

Wiskott-Aldrich syndrome protein (WASp) is essential for optimal T cell activation. Patients with WAS exhibit both immunodeficiency and a marked susceptibility to systemic autoimmunity. We investigated whether alterations in Treg function might explain these paradoxical observations. While WASp-deficient (WASp(-/-)) mice exhibited normal thymic Treg generation, the competitive fitness of peripheral Tregs was severely compromised. The total percentage of forkhead box P3-positive (Foxp3(+)) Tregs among CD4(+) T cells was reduced, and WASp(-/-) Tregs were rapidly outcompeted by WASp(+) Tregs in vivo. These findings correlated with reduced expression of markers associated with self-antigen-driven peripheral Treg activation and homing to inflamed tissue. Consistent with these findings, WASp(-/-) Tregs showed a reduced ability to control aberrant T cell activation and autoimmune pathology in Foxp3(-/-)Scurfy (sf) mice. Finally, WASp(+) Tregs exhibited a marked selective advantage in vivo in a WAS patient with a spontaneous revertant mutation, indicating that altered Treg fitness likely explains the autoimmune features in human WAS.

Annular phased-array high-intensity focused ultrasound device for image-guided therapy of uterine fibroids

An ultrasound (US), image-guided high-intensity focused ultrasound (HIFU) device was developed for noninvasive ablation of uterine fibroids. The HIFU device was an annular phased array, with a focal depth range of 30-60 mm, a natural focus of 50 mm, and a resonant frequency of 3 MHz. The in-house control software was developed to operate the HIFU electronics drive system for inducing tissue coagulation at different distances from the array. A novel imaging algorithm was developed to minimize the HIFU-induced noise in the US images. The device was able to produce lesions in bovine serum albumin-embedded polyacrylamide gels and excised pig liver. The lesions could be seen on the US images as hyperechoic regions. Depths ranging from 30 to 60 mm were sonicated at acoustic intensities of 4100 and 6100 W/cm/sup 2/ for 15 s each, with the latter producing average lesion volumes at least 63% larger than the former. Tissue sonication patterns that began distal to the transducer produced longer lesions than those that began proximally. The variation in lesion dimensions indicates the possible development of HIFU protocols that increase HIFU throughput and shorten tumor treatment times.

Synthesis of Duplex DNA Containing a Spin Labeled Analog of 2′ Deoxycytidine

Abstract We report the chemical synthesis of phosphoramidite 8, containing a spin labeled analog of deoxycytidine, C∗, and its incorporation into synthetic DNA. The EPR characteristics of the resulting DNAs indicated that the motion of the spin label was well-correlated with the uniform modes of the macromolecule, but that correlation of the spin label with internal motion was less effective than that achieved using a spin labeled quinolone, Q.

Do initial radiographs agree with crash site mechanism of injury in pelvic ring disruptions? A pilot study.

Objective: Direction of injury force inferred from pelvic radiographs may be used in trauma care to predict associated injuries and guide intervention. Our objective was to compare injury direction determined from anteroposterior (AP) pelvic radiographs with injury forces determined from crash site investigation. Materials and Methods: We studied all 28 subjects from the Crash Injury Research Engineering Network (CIREN) database who met inclusion criteria of pelvic ring disruption, single-event crash, restrained front-seat occupant, diagnostic-quality pelvic radiography, and complete crash investigation data. Assessment of diagnostic quality of pelvic radiography was made by 2 radiologists who were blinded to all other subject information. Crash site investigation data included principal direction of force (PDOF), crash magnitude, and passenger compartment intrusion. An orthopedic trauma surgeon and a fellowship-trained emergency radiologist independently assessed the pelvic radiographs to determine the injury PDOF and the Young-Burgess and Tile fracture classifications, with disputes resolved by an additional emergency radiologist. Agreement between injury forces and pelvic radiographs was assessed using the kappa statistic. Results: The PDOF was anterior in 9 (32%) and lateral in 19 (68%) subjects. The readers agreed with the crash primary direction of force in 21 (75%) subjects (κ = 0.42). In subjects with lateral PDOF, agreement was 89% (17/19) compared to 44% for anterior PDOF (4/9). Interobserver agreement for the Young and Tile classification schemes was moderate (weighted kappa 0.44 and 0.54, respectively). Conclusion: Crash site investigation and pelvic radiography may provide conflicting information about primary direction of injuring forces. Presumed anterior impact based on PDOF is not in consistent agreement with the pattern of injury evident on the AP pelvic radiograph.

Transvaginal 3D Image‐Guided High Intensity Focused Ultrasound Array

The goal of this project is to develop a transvaginal image‐guided High Intensity Focused Ultrasound (HIFU) device using piezocomposite HIFU array technology, and commercially‐available ultrasound imaging. Potential applications include treatment of uterine fibroids and abnormal uterine bleeding. The HIFU transducer was an annular phased array, with a focal length range of 30–60 mm, an elliptically‐shaped aperture of 35×60 mm, and an operating frequency of 3 MHz. A pillow‐shaped bag with water circulation will be used for coupling the HIFU energy into the tissue. An intra‐cavity imaging probe (C9‐5, Philips) was integrated with the HIFU array such that the focal axis of the HIFU transducer was within the image plane. The entire device will be covered by a gel‐filled condom when inserted in the vaginal cavity. To control it, software packages were developed in the LabView programming environment. An imaging algorithm processed the ultrasound image to remove noise patterns due to the HIFU signal. The device...

Image‐guided high intensity focused ultrasound annular array for hemostasis and tumor treatment

To develop and characterize an ultrasound‐guided high intensity focused ultrasound (HIFU) array, an 11‐element annular phased array (aperture of 3.5×6.0 cm, focal depth of 3.0–6.0 cm, frequency of 3 MHz) was coupled to an imaging probe (C9‐5, Philips). LabView software was developed to control driving electronics and image guidance. Radiation force balance measurements, Schlieren imaging, and hydrophone field mapping were performed. Lesions were produced in gel phantoms, and ex vivo porcine liver and human cancerous uterus. The lesions were formed beginning at a focal depth of 6.0 cm and moving by 0.5 cm increments to 3.0 cm, and vice versa, with the overall treatment time of 2 min. The transducer had efficiency of 38%, with intensities of up to 6200 W/cm2 at the natural focus of 5 cm, in water. The 6 dB focal area varied from 0.4 mm2 (at 3 cm) to 1.5 mm2 (at 6 cm). The 3 to 6 cm tissue lesions were 2.7±0.5 cm in length, compared to 4.1±0.3 cm for the 6 to 3 cm lesions. The average lesion width was 1 cm. ...