Citations

Total joint arthroplasty (TJA) is implemented primarily for the relief of pain, and secondarily for achieving better function by increasing the joint’s strength and motion. In order to keep health costs low, it is desirable that the TJA achieves and maintains a long-term and secure fixation of the implanted components. Unfortunately, clinical follow-up shows that the prosthetic finger implant components have long-term complications including bone resorption, wear, loosening, and failure of the implant components. Although the mechanism of complications is not fully understood, it is well known that the wear and failure of prostheses are highly related to the mechanical forces or stresses of implant components. It is therefore desirable that reliable 3-D computational finite element analysis (FEA) models can be developed and used for the stress analysis of implants. In this study, the finger proximal interphalangeal (PIP) prosthetic components were analyzed using a nonlinear finite element method. Implant components under different joint flexion angles as well as different forces were studied. The stress distribution on the contact surface of the implant component was obtained. The developed FEA models can be used to examine the contact situations (contact stress, contact region, and stress distribution), which are critical to the wear and potential failure of the implant components. Based on FEA results, the design of the current finger PIP implants can be improved for optimum performance and a long-term fixation.

A new method for imaging and detecting modal shapes of vessels is introduced. Theory is developed that predicts the measured velocity is proportional to the value of the mode shape at the focal point of the ultrasound beam. Experimental a cylindrical gel phantom of large radius. This model simulates approximately a large artery and the surrounding body. The fundamental frequency was measured 83 Hz for the tube-phantom system. At this frequency the ultrasound transducer was scanned across the vessel plane with velocity measurement at one single point on the vessel and on the phantom by laser. The images obtained show clearly the interior tube and the modal shape of the tube.

Abstract The estrogen receptors (ER) α and β are important ligand-mediated transcription factors known to play significant biological roles in numerous tissues including bone. Despite the high homology shared by these receptors, recent studies have suggested that their function is largely unique. Although these receptors have been studied in detail for more than a decade, little data exist concerning the mechanisms by which these two proteins regulate distinct sets of genes. Using the TGFβ-inducible early gene-1 (TIEG) as a model, we demonstrate that TIEG is rapidly induced in response to estrogen in osteoblasts by ERβ, but not ERα. We have identified the regulatory elements utilized by ERβ and have demonstrated that ERβ recruits steroid receptor coactivator (SRC)1 and SRC2 to this regulatory region. Additionally, deletion of the ERβ-activation function 1 (AF1) domain drastically decreases the estrogen induction of TIEG. Through the use of chimeric receptors, we have demonstrated that the AF1 domain of ERβ is responsible for recruiting SRC1 and SRC2 and inducing the expression of TIEG in osteoblasts. Finally, SRC1, but not SRC2, is essential for TIEG induction by ERβ. Overall, these data demonstrate that the estrogen induction of TIEG is ERβ specific and that the AF1 domain of ERβ confers this specificity. Finally, a novel and important role for ERβ’s AF1 is implicated in the recruitment of specific coactivators, suggesting that the AF1 may play a significant role in conferring the differences in regulation of gene expression by these two receptors.

Vibro-acoustography is a new noncontact imaging method based on the radiation force of ultrasound. We extend this new technique for tissue characterization of arterial vessels by vibration techniques. In this paper a theoretical model for vibration analysis of arterial vessel with tissue is developed. Experimental studies were carried out on a silicone rubber tube embedded in a cylindrical gelatin phantom of larger radius, which simulates a large artery and the tissue body. The fundamental mode is well excited by the radiation force of ultrasound. The fundamental frequency was measured 81.8 Hz for a tube-phantom structure that is quite close to our theoretical prediction of 83.3 Hz.

Abstract Intrinsic or acquired chemoresistance to alkylating agents is a major cause of treatment failure in patients with malignant brain tumors. Alkylating agents, the mainstay of treatment for brain tumors, damage the DNA and induce apoptosis, but the cytotoxic activity of these agents is dependent on DNA repair pathways. For example, O6-methylguanine DNA adducts can cause double-strand breaks, but this is dependent on a functional mismatch repair pathway. Thus, tumor cell lines deficient in mismatch repair are resistant to alkylating agents. Perhaps the most important mechanism of resistance to alkylating agents is the DNA repair enzyme O6-methylguanine methyltransferase, which can eliminate the cytotoxic O6-methylguanine DNA adduct before it causes harm. Another mechanism of resistance to alkylating agents is the base excision repair (BER) pathway. Consequently, efforts are ongoing to develop effective inhibitors of BER. Poly(ADP-ribose)polymerase plays a pivotal role in BER and is an important therapeutic target. Developing effective strategies to overcome chemoresistance requires the identification of reliable preclinical models that recapitulate human disease and which can be used to facilitate drug development. This article describes the diverse mechanisms of chemoresistance operating in malignant glioma and efforts to develop reliable preclinical models and novel pharmacologic approaches to overcome resistance to alkylating agents.

ABSTRACT Zygomycete infections can be devastating in immunocompromised hosts. Difficulties in the histopathologic differentiation of this class from other filamentous fungi (e.g., Aspergillus spp., Fusarium spp.) may lead to delays in diagnosis and initiation of appropriate treatment, thereby significantly affecting patient outcome. A real-time PCR assay was developed to detect species of the zygomycete genera Absidia , Apophysomyces , Cunninghamella , Mucor , Rhizopus , and Saksenaea in culture and tissue samples. Primers and fluorescence resonance energy transfer hybridization probes were designed to detect a 167-bp conserved region of the multicopy zygomycete cytochrome b gene. A plasmid containing target sequence from Mucor racemosus was constructed as a positive control. The analytical sensitivity of the assay is 10 targets/μl, and a specificity panel consisting of other filamentous fungi, yeasts ( Candida spp.), and bacteria demonstrated no cross-reactivity in the assay. The clinical sensitivity and specificity of the assay from culture isolates were 100% (39/39) and 92% (59/64), respectively. Sensitivity and specificity determined using a limited number of fresh tissue specimens were both 100% (2/2). The sensitivity seen with formalin-fixed, paraffin-embedded tissues was 56% (35/62), and the specificity was 100% (19/19). The speed, sensitivity, and specificity of the PCR assay indicate that it is useful for the rapid and accurate detection of zygomycetes.