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Biomedical subjects

Susan Miller

Publications and source records attributed to Susan Miller.

At least 19 recordsLinked to original sources

Micro-vessel density and the expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PdEGF) in classical Hodgkin lymphoma (HL).

There is little information to date regarding the role of angiogenesis in Hodgkin lymphoma (HL). The present study examines micro-vessel density and the expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial growth factor (PdEGF) in lymph node biopsies of patients with HL at presentation and relapse. Using immunohistochemistry, the degree of new blood vessel formation and the expression of VEGF and PdEGF was assessed in Hodgkin-rich tissue. The micro-vessel density (MVD) increased with disease progression in seven out of 11 cases. Expression of VEGF was observed in endothelial cells (EC) of some micro-vessels and also in follicular dendritic cells. The Hodgkin/Reed-Sternberg (H-RS) cells as well as the inflammatory lymphocytes were negative for VEGF. Cytoplasmic or cytoplasmic and nuclear expression of PdEGF by the H-RS cells was observed in five of the 11 presentation cases. The expression of PdEGF increased with disease progression in seven cases. In conclusion, Hodgkin tissue shows prominent vascularization. The increased MVD and PdEGF expression with disease progression merits further investigation.

Adolescent↗

Restrictive hemodynamics are present at the time of diagnosis of allograft coronary artery disease in children.

Clinical recognition of allograft coronary artery disease (ACAD) is challenging. We examined whether right heart hemodynamics can aid its diagnosis in pediatric recipients. We retrospective analyzed hemodynamic data of recipients with ACAD versus age and date-of-transplant matched controls. From 1982-2001, 18 cases fulfilled study entry criteria. Median age at transplant was 12 years for subjects and 8 years for controls. Median time to diagnosis of ACAD was 65 months (14.5-124 months) and 67 months (16-140 months) to arteriography for controls. The median right ventricular end-diastolic pressure (RVEDP) at diagnosis was 11.0 vs. 6.0 mmHg for controls (p = 0.003). Pulmonary capillary wedge pressure (PCWP) at diagnosis was 14.0 vs. 8.0 mmHg for controls (p = 0.001). When subdivided by severity of ACAD, the difference was greater in the moderate/severe group. Compared to the previous catheterization (median interval 10 months for subjects, 12.0 for controls ), there was an increase of 4.0 mmHg in RVEDP in ACAD subjects (n = 13, p = .003) versus 0 mmHg in controls (p = 0.042), and an increase in PCWP of 5.5 in subjects (p = .002) versus 0 mmHg in controls (p = 0.066). The presence of elevated filling pressures plus an interim increase should alert to the presence of ACAD and help guide further investigation.

Atrial Function, Right↗

The wildcat toolbox: a set of perl script utilities for use in peptide mass spectral database searching and proteomics experiments.

We describe in this communication a set of functional perl script utilities for use in peptide mass spectral database searching and proteomics experiments, known as the Wildcat Toolbox. These are all freely available for download from our laboratory Web site (http://proteomics.arizona.edu/toolbox.html) as a combined zip file, and can also be accessed via the Proteome Commons Web site (www.proteomecommons.org) in the tools section. We make them available to other potential users in the spirit of open source software development; we do not have the resources to provide any significant technical support for them, but we hope users will share both bugs and improvements with the community at large.

Algorithms↗

Verification of single-peptide protein identifications by the application of complementary database search algorithms.

Data produced from the MudPIT analysis of yeast (S. cerevisiae) and rice (O. sativa) were used to develop a technique to validate single-peptide protein identifications using complementary database search algorithms. This results in a considerable reduction of overall false-positive rates for protein identifications; the overall false discovery rates in yeast are reduced from near 25% to less than 1%, and the false discovery rate of yeast single-peptide protein identifications becomes negligible. This technique can be employed by laboratories utilizing a SEQUEST-based proteomic analysis platform, incorporating the XTandem algorithm as a complementary tool for verification of single-peptide protein identifications. We have achieved this using open-source software, including several data-manipulation software tools developed in our laboratory, which are freely available to download.

Algorithms↗

Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures.

To glean biological differences and similarities of peripheral T-cell lymphoma-not otherwise specified [PTCL-NOS] to diffuse large B-cell lymphoma (DLBCL), a transcriptosome analysis was done on five PTCL-NOS and four DLBCL patients and validated by quantitative real-time reverse transcription-PCR on 10 selected genes. Normal peripheral blood T cells, peripheral blood B cells, and lymph node were used as controls. The resultant gene expression profile delineated distinct "tumor profile signatures" for PTCL-NOS and DLBCL. Several highly overexpressed genes in both PTCL-NOS and DLBCL involve the immune network, stroma, angiogenesis, and cell survival cascades that make important contributions to lymphomagenesis. Inflammatory chemokines and their receptors likely play a central role in these complex interrelated pathways: CCL2 and CXCR4 in PTCL-NOS and CCL5 and CCR1 in DLBCL. Highly overexpressed oncogenes unique to PTCL-NOS are SPI1, STK6, alpha-PDGFR, and SH2D1A, whereas in DLBCL they are PIM1, PIM2, LYN, BCL2A1, and RAB13. Oncogenes common to both lymphomas are MAFB, MET, NF-kappaB2, LCK, and LYN. Several tumor suppressors are also down-regulated (TPTE, MGC154, PTCH, ST5, and SUI1). This study illustrates the relevance of tumor-stroma immune trafficking and identified potential novel prognostic markers and targets for therapeutic intervention.

Base Sequence↗

Voice therapy for vocal fold paralysis.

There is no doubt that vocal fold paralysis is a debilitating condition affecting an individual's general health and quality of life. Optimal management of a patient with vocal fold dysfunction by an otolaryngologist, speech scientist, and speech language pathologist results in detailed objective videostroboscopic evaluation of glottal configuration during phonation, acoustic and aerodynamic measures, laryngeal EMG (if appropriate), and the patient's self-rating of vocal disability. Profound glottal incompetence is typically managed surgically with a few voice therapy sessions after surgery to ensure optimal vocal function. Patients with more adequate glottal closure are often seen for voice therapy and lost to follow-up when their voices improve enough to satisfy their vocal needs. It is essential that a complete battery of assessments, including perceptual, aerodynamic, acoustic, and stroboscopic measures, be obtained at periodic intervals in surgical and nonsurgical patients so as to evaluate vocal function over time. One of the few rigorous studies of perceptual, acoustic, aerodynamic, and videofiberscopic findings in patients after medialization with fat and thyroplasty assessed patients before surgery and at short (1-3 months),middle (4-6 months), and long (7-12 months) intervals after surgery. Improvement in most parameters at short- and long-term intervals was noted but not in the middle interval. The best results were obtained in women. Continued difficulty in increasing and maintaining subglottal pressure for high-intensity phonation was observed in both male and female patients. This fine study raises a number of questions as follows. What objective phonatory measures should be assessed before and after intervention and at what time intervals? Why were the women's results better than the men's results when no correlation of age, pulmonary function, or severity of preoperative voice and aerodynamic impairment was observed? Should voice therapy be initiated at the 4- to 6-month interval when voice quality diminished or within 1 to 2 months after surgery so that the decrement in vocal function might not occur? Why did vocal function ultimately improve after 7 to 12 months? Heuer et al and Colton and Casper found similar outcome satisfaction in patients electing surgery compared with those that were seen for voice therapy; however, the patients with lesser glottal incompetence in both studies opted for therapy. Can we better define vocal parameters that help to predict which patients may need surgery rather than therapy? Should all patients with high airflow measures but near-normal subglottal pressures and MPT greater than 10 seconds undergo 6 weeks of voice therapy rather than medical intervention? If all surgical patients were seen for 6 weeks of postoperative therapy, would voice satisfaction ratings increase to greater than 70%? Can we perceptively or objectively differentiate patients whose postoperative voices will be excellent from those whose voices will be merely adequate? These questions can only be answered by the development and implementation of a rigorous protocol studying women and men of varying ages with unilateral vocal fold paralysis choosing medialization surgery and electing voice therapy. Standardized assessments must include perceptual,aerodynamic, acoustic, stroboscopic, and patient satisfaction measures during soft- and loud-intensity tasks before and at periodic intervals after the two interventions.

Biomechanical Phenomena↗

Disruption of estrogen-regulated gene expression by dioxin: downregulation of a gene associated with the onset of non-insulin-dependent diabetes mellitus (type 2 diabetes).

Expression of an estrogen-regulated reporter gene, growth of MCF-7 cells in the presence of 17beta-estradiol (E2) or E2 plus TCDD, and DNA microarray plus real time quantitative PCR analyses of gene expression in MCF-7 cells were used to evaluate the effects of TCDD, a known E2 antagonist, on E2-regulated gene expression in human cells. TCDD added simultaneously with E2 exhibited significantly decreased E2-associated upregulation of reporter gene expression compared with cells treated with E2 alone, and decreased E2 enhancement of mitosis in MCF-7 cells. MCF-7 cells treated with E2 or E2 plus TCDD and DNA microarray-evaluated to determine patterns of gene expression, showed substantial differences in gene expression in TCDD-treated cells compared with E2-treated cells. Of the 2400 genes on the Perkin Elmer global array microchip utilized for this analysis, a minimum of 317 were significantly upregulated and 488 were significantly downregulated. Of these, the gene encoding insulin receptor substrate-1 (IRS-1), the protein product of which has been previously reported to be decreased, missing, altered, or defective in persons with type 2 diabetes mellitus, was evaluated by real time quantitative PCR to corroborate the array data. An evaluation of the potential consequences of TCDD-altered IRS-1 downregulation is presented.

Animals↗

Percutaneous translumbar spinal cord compression injury in dogs from an angioplasty balloon: MR and histopathologic changes with balloon sizes and compression times.

BACKGROUND AND PURPOSE: Our previous model of spinal cord injury (SCI) included six dogs undergoing 30-minute compression with a balloon in the subarachnoid space. We determined whether various balloon sizes and compression times creates a gradation of injuries. METHODS: In 17 dogs (including our original six), angioplasty balloons 2, 4, or 7 mm in diameter (2 cm long) were inflated at T6 for 30, 120, or 240 minutes. T1- and T2-weighted, gadolinium-enhanced, and short-tau inversion recovery (STIR) MR images were obtained at 1.5 T. Spinal canal occlusion (SCO) was measured as balloon area-spinal cord area. Hematoxylin-eosin and beta amyloid precursor protein staining were performed to demonstrate hemorrhage and axonal injury, respectively. Injuries were scored as mild, moderate, or severe. Trends were assessed with one-way analysis of variance. RESULTS: SCO was 12.5-20% for 2-mm balloons, 28-56% for 4 mm, and 62-82% for 7 mm. No abnormalities were seen with SCO <30%. T1- and T2-weighted images had the poorest diagnostic performance; STIR images were best for predicting hemorrhage and axonal injury. Hemorrhage was demonstrated more frequently than was axonal injury. SCO (P < .0001) and hemorrhage (P = .002) significantly increased with balloon size. Longer inflation times tended to increase injuries for a given size, but differences were not significant. CONCLUSION: Compression injuries depended on the level of SCO. The compression times tested had less effect than the degree of compression. The value of 1.5-T MR imaging varied with the sequence and improved with contrast enhancement. STIR images showed SCIs not otherwise detected.

Angioplasty, Balloon↗

Tacrolimus dosing in pediatric heart transplant patients is related to CYP3A5 and MDR1 gene polymorphisms.

Tacrolimus is a substrate for P-glycoprotein (P-gp) and cytochrome (CYP) P4503A. P-gp is encoded by the multiple drug resistance gene MDR1 and CYP3A is the major enzyme responsible for tacrolimus metabolism. Both MDR1 and CYP3A5 genes have multiple single nucleotide polymorphisms. The objective of this study was to evaluate whether the MDR1 exon21 and exon26 polymorphisms and the CYP3A5 polymorphism are associated with tacrolimus disposition in pediatric heart transplant patients. At 3, 6 and 12 months post transplantation, a significant difference in tacrolimus blood level per dose/kg/day was found between the CYP3A5 *1/*3 (CYP3A5 expressor) vs. *3/*3 (nonexpressor) genotypes with the *1/*3 patients requiring a larger tacrolimus dose to maintain the same blood concentration. There were no significant differences in tacrolimus blood level per dose/kg/day between MDR1 exon21 G2677T and exon 26 C3435T at 3 months, but both were found to have a significant association with tacrolimus blood level per dose/kg/day at 6 and 12 months. We conclude that specific genotypes of MDR1 and CYP3A5 in pediatric heart transplant patients require larger tacrolimus doses to maintain their tacrolimus blood concentration, and that this information could be used prospectively to manage patient's immunosuppressive therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Incidence of supraglottic activity in males and females: a preliminary report.

Supraglottic activity was rated from flexible endoscopic video recordings of subjects with normal laryngeal structure and function as they sustained vowels and repeated syllables and sentences. Judges rated these recordings for false vocal fold (FVF) adduction and anterior-to-posterior (A-P) compression at the initiation of the speech task, throughout the whole speech task (static supraglottic activity), and as brief individual adductions within a speech task (dynamic supraglottic activity). Significant differences in A-P (p < 0.0003) and FVF (p < 0.0000001) compression were found between tasks. Dynamic FVF activity was associated with glottal stops. Static A-P and FVF activities were present in males significantly more (p < 0.0001) than females. FVF activity associated with speech initiation was found in females significantly more (p = 0.0256) than males. Supraglottic activity plays a role in normal speech production, and should not necessarily be considered suggestive of a voice use pattern with excessive muscle tension.

Adult↗

Experimental third ventriculostomy performed using endovascular surgical techniques and their adaptation to percutaneous intradural neuronavigation: proof of concept cadaver study.

OBJECTIVE: Endoscopic third ventriculostomy has developed into a therapeutic alternative to shunting for the management of carefully selected patients with primarily noncommunicating hydrocephalus. This procedure, however, requires a general anesthetic and necessitates violation of the brain parenchyma and manipulation near vital neural structures to access the floor of the third ventricle. Using two cadavers and off-the-shelf angiographic catheters, we sought to determine whether it was possible to navigate a catheter, angioplasty balloon, and stent percutaneously through the subarachnoid space from the thecal sac into the third ventricle so as to perform a third ventriculostomy from below. METHODS: Using biplane angiography and off-the-shelf angiographic catheters along with angioplasty balloons and stents, we were able to pass a stent coaxially from the thecal sac to and across the floor of the third ventricle so as to achieve a third ventriculostomy from below. RESULTS: Coaxial catheter techniques allowed for the percutaneous insertion of a stent across the floor of the third ventricle. Ventriculostomy was confirmed by injecting contrast medium into the lateral ventricle and seeing it pass through the stent and into the chiasmatic cistern. CONCLUSION: We describe the performance of third ventriculostomies in two cadavers by use of the new concept of percutaneous intradural neuronavigation. This procedure may obviate the need for general anesthetic and minimize the potential for brain and vascular injury, especially if ultimately combined with magnetic resonance fluoroscopy.

Adult↗

Percutaneous translumbar spinal cord compression injury in a dog model that uses angioplasty balloons: MR imaging and histopathologic findings.

BACKGROUND AND PURPOSE: Previous animal models for spinal cord injury required laminectomy and exposure of the spinal cord to create direct trauma, compromising imaging by both surgical artifact and the nature of the production of the injury. Our purpose was to study a model that uses percutaneous intraspinal navigation with an angioplasty balloon, providing a controlled degree of spinal cord compression and allowing improved MR imaging of spinal cord injury. METHODS: Nine mongrel dogs were studied. MR images were obtained of six dogs after technique development in three dogs. Angioplasty balloons measuring 7 or 4 mm in diameter and 2 cm in length were placed in the midthoracic subarachnoid space. Imaging was performed by using a 1.5-T MR imaging unit before and after balloon inflation. The balloon was inflated within 5 seconds and deflated after 30 minutes. T1- and T2-weighted and contrast-enhanced images were acquired. Spinal cords were submitted for pathologic examination. RESULTS: All four animals with 7-mm balloons experienced hemorrhage, and three had axonal injury revealed by histopathologic examination. One of two animals with 4-mm balloons experienced no injury, and one had axonal injury without hemorrhage. Regional parenchymal enhancement was seen in two of the animals with 7-mm balloons. CONCLUSION: This percutaneous spinal cord injury model results in a graduating degree of injury. It differs from previous techniques by avoiding surgical exposure and the associated artifacts, yet it offers histopathologic findings similar to those of human spinal cord injury. The canine spinal cord is amenable to MR imaging with clinical imaging units. Further evaluations with various durations of compression and various balloon sizes are warranted.

Angioplasty, Balloon↗

Percutaneous intraspinal navigation: feasibility study of a new and minimally invasive approach to the spinal cord and brain in cadavers.

We describe a percutaneous approach for cerebral surgical access. After lumbar puncture, the spinal subarachnoid space was traversed by using standard angiographic guidewire techniques until the introducer catheters were in the intracranial space. Under fluoroscopic guidance, the intracranial subarachnoid space was navigated, and the ventricular system entered. Subarachnoid placement was confirmed with contrast-enhanced digital angiography. Placement anterior to the brain stem was confirmed in both cadavers during dissection, and spinal navigation without cord damage from the anterior or posterior approach was confirmed in one. Percutaneous intraspinal navigation is a new route of access for cerebrospinal surgery that has many potential applications.

Angiography↗