Now showing items 26142-26161 of 39117

    • P-glycoprotein: Expression and function in normal circulating leukocytes

      Klimecki, Walter Thomas.; Dalton, William; Cress, Anne; Bowden, G. Tim; Dorr, Robert; Gandolfi, A. Jay (The University of Arizona., 1994)
      P-glycoprotein (P-gly) is a well characterized membrane protein, expressed in cancer cells, functioning as an efflux pump. This function confers drug-resistance. P-gly is also expressed in normal tissues such as the liver and kidney. In normal tissues P-gly has restricted expression. In the kidney P-gly is expressed in tubular brush border. This suggests a physiologic role for P-gly. A goal of this work was to determine whether P-gly, if present in leukocytes, followed the cell-type restriction seen in other P-gly positive normal tissues. Assays measuring P-gly included immunofluorescence, immunocytochemistry, and immunoblot analysis. Northern blot analysis and RT-PCR were used to measure mdr1 mRNA. P-gly function was assayed by measuring the verapamil-sensitive retention of rhodamine 123 (rh123). Immunofluorescent staining of leukocytes for lineage and P-gly revealed high levels of P-gly in CD56+ cells. CD8+ cells followed in staining, with CD4+ and CD19+ cells at intermediate levels, and CD14+ and CD15+ cells staining at background. RNA analysis by RT-PCR confirmed the immunofluorescence data, except for CD15+ cells, which demonstrated mdr1 mRNA similar to CD4+ cells. Function assays confirmed the immunofluorescence results, with efficient clearing of dye from CD56+ cells, followed by CD8+, CD4+, and CD19+ cells. CD14+ and CD15+ cells did not demonstrate P-gly function. Immunoblot analysis of membranes and immunocytochemical analysis of CD15+ cells demonstrated P-gly. The high level of functional P-gly observed in CD56+ cells prompted experiments to determine whether P-gly was involved in the CD56+ mediated cytolytic response. Using 4 inhibitors of P-gly mediated efflux, cyclosporine A, PSC 833, R-verapamil, and S-verapamil, NK cells were assayed for cytolytic function. Each compound demonstrated dose-response relationships in inhibiting NK-mediated cytolysis. Each compound also demonstrated a dose-response in inhibition of P-gly mediated efflux, although there was not an exact correlation between efflux inhibition and cytolysis inhibition. Nevertheless, the data in this study demonstrate a relatively high level of P-gly expression in CD56+ and CD8+ cells. In addition, the data support a role for P-gly in the cytolytic function of NK cells, although the point of P-gly involvement in the process of cytolysis remains to be defined.
    • The p53 homolog p63 modulates acute and chronic damage in irradiated salivary glands

      Limesand, Kirsten H; Mitchell, Geoffrey C; Limesand, Kirsten H; Burd, Randy; Gerner, Eugene; Briehl, Margaret; Martinez, Jesse (The University of Arizona., 2010)
      Head and neck cancer is diagnosed in more than 50,000 Americans each year, resulting in roughly 11,000 deaths. For this disease, a typical therapeutic regimen involves cisplatin, a radiosensitizer, given alongside targeted irradiation. While technological advances such as IMRT have been useful in sparing normal tissues from radiotherapy, the salivary glands occupy much of the head and neck and surround several lymph nodes, and thus, non-diseased salivary glands are often damaged. This causes reduced salivary output, damaged oral mucosa, dysphagia, malnutrition and tooth decay. Often, these side-effects are so severe that patients discontinue treatment, however, in many cases, salivary gland damage is permanent, and treatment options are palliative. Specifically, muscarinic-cholinergic agonists are used to enhance secretion from remaining salivary cells, although due to non-specific action, these drugs have a number of ill-effects. It is clear that therapies are needed to prevent radiation-induced salivary gland damage, as well as to restore glandular function in patients who are already suffering.Previous work from our group has shown that salivary gland dysfunction results from loss of acinar cells to radiation-induced apoptosis. Importantly, a single intravenous dose of IGF1 can prevent apoptosis and preserve salivary output when given immediately prior to irradiation. Because of its broad effects, however, IGF1 may never be a viable clinical option. Instead, our goal is to identify signaling events that mediate the radioprotective effects of IGF1 downstream of Akt. Because radiation-induced apoptosis in salivary glands is p53-dependent, we assessed the contributions of the p53 homologs p63 and p73 to the DNA damage response. Here, we show that IGF1 enhances cell cycle arrest following irradiation by reducing inhibitory binding of deltaNp63 to the p21 promoter. We hypothesize that IGF1-induced cell cycle arrest may allow time for DNA repair, thus preventing apoptosis and maintaining salivary function. In addition, we indicate chronic signaling events downstream of p63 that may contribute to permanent loss of salivary function by blocking differentiation of salivary progenitor cells. Together, these results indicate that p63 may be a valid therapeutic target for both prevention of damage and restoration of function in irradiated salivary glands.
    • The pachytene and somatic chromosome morphology of Cynodon dactylon (L.) Pers.

      Brilman, Leah Ann Moore (The University of Arizona., 1978)
    • A package efficient PC based AHPL to EDIF translator

      Hill, Fredrick J.; Lim, Yeow Lam, 1962- (The University of Arizona., 1990)
      Computed-Aided Design tools have assisted the digital designer at various levels of the design process. AHPL, A Hardware Programming Language, is a hardware description language which allows a digital system to be described at the register transfer level. AHPL circuit descriptions can be translated into logic gate networks using the HPCOM hardware compiler. The Electronic Design Interchange Format (EDIF) is a data exchange standard used to exchange data between CAD tools. By providing a translator to convert the logic gate networks from HPCOM into EDIF Netlist format, designs described in AHPL can be ported to other CAD tools. This thesis documents the development and implementation of a EDIF Netlist translator for the HPCOM generated logic network. The translator is designed to use every gate in a package and includes an option that converts logic gates to their NAND equivalents. Netlist outputs from the translator are simulated with the OrCAD Verification and Simulation Tools. These simulations are then compared with simulations from HPSIM to make sure the netlist output from the translator is indeed a gate level representation of the design as described by AHPL.

      Kratochwill, Thomas; Brown, Douglas Kirby (The University of Arizona., 1980)
      An instructional package is presented for training pre-intern psychologists in behavioral interviewing techniques. A specific interview format, the Problem Identification Interview, was combined with microsetting technology to provide an efficient method of training consultation verbal skills. The instructional package was evaluated with a multiple baseline across subjects design. Results of the study indicated that verbal skills specific to the interviewing format were acquired when the instructional package was used. The acquired skills were maintained across several experimental sessions and at a two month follow-up. A social validation questionnaire revealed that subjects of the study found the training to be preferable to traditional methods and relevant to future applied practice. The implications of this study for the training of psychologists and other professionals providing problem solving services were discussed.

      Bojorquez Romo, Antonio. (The University of Arizona., 1985)
    • Packrats, plants, and the Pleistocene in the lower Grand Canyon

      Phillips, Arthur Morton, 1947- (The University of Arizona., 1977)
    • Packstock hoofprint depth and soil strength relationships in wet meadow soils of Sequoia and Kings Canyon National Parks, California

      McClaran, Mitchel P.; Neuman, Michael John, 1964- (The University of Arizona., 1996)
      Penetrometer soil strength and the depth of packstock hoofprints were studied in two subalpine meadows in an attempt to develop a method for determining the seasonal readiness of wilderness meadows for packstock grazing at Sequoia & Kings Canyon National Parks, California. Soil and vegetation parameters (bulk density, water content, percent gravel, sand, silt, clay, and organic matter, above-ground biomass, and below-ground biomass in two diameter size classes) were also studied in order to understand their influence on soil strength and hoofprint depth. Of the four penetrometer tip sizes tested on a Lang penetrometer, a 9/16" diameter tip was found to be a good predictor of hoofprint depth. Both 9/16" soil strength and hoofprint depth were well predicted by soil water content and meadow vegetation type.
    • Pad-Wafer and Brush-Wafer Contact Characterization in Planarization and Post-Planarization Processes

      Philipossian, Ara; SUN, TING; Philipossian, Ara; Muscat, Anthony; Ogden, Kimberly; Lynch, David C. (The University of Arizona., 2009)
      This dissertation presents a series of studies relating to pad-wafer and brush-wafer contact characterization in planarization and post-planarization processes. These are also evaluated with the purposes of minimizing environmental impact and reducting cost of ownership.Firstly, a new method using spectral analysis based on real-time raw friction data is developed to quantify the total amount of mechanical interaction in the brush-fluid-wafer interface in terms of stick-slip phenomena in post-planarization scrubbing. This new method is remarkable from the standpoint of its potential to eliminate having to perform a multitude of experiments needed for constructing and interpreting Stribeck curves, and its application to processes where Stribeck curves fail to yield any useful data. Moreover, this method is applied to investigate the effect of brush roller design on scrubbing process and to analyze behaviors of eccentric brushes.In order to study pad-wafer contact in planarization processes, a mechanical characterization method (incremental loading test) is developed and applied to analyze different types of pads and pad surfaces subjected to various treatments. Along with optical interferometry and theoretical analysis, flow resistance due to pad land area topography can be estimated.The greatest contribution of this dissertation involves development of real pad-wafer contact area measurement technique using confocal microscopy. The real pad-wafer contact area is a difficult property to measure in planarization, yet it is a key feature to further understand the process. A custom-made sample holder with a sapphire window and a miniature load cell is used to collect confocal images at controlled values of down force.At last, the two newly developed techniques (incremental loading test and real pad-wafer contact area measurement using confocal microscopy) together with dual emission UV enhanced fluorescence imaging are utilized to investigate conditioning effects in planarization process.
    • Paean (Original composition)

      Muczynski, Robert; Rothacker, Kurt Van Meter, 1964- (The University of Arizona., 1988)
      This original composition is primarily in the key of C and is in a style of expanded tonality. Although the work loosely follows an established formal structure, the harmonic changes exist freely within this structure and occur more as modal changes rather than diatonic. The structure of the work is a loose sonata form including introduction, transitions and retransitions, and coda.
    • Pageantry in Arizona

      Clemans, Winifred Windus, 1894- (The University of Arizona., 1935)

      Moore, Ida M. (Ki); LATHROP, EMMA BRIDGET (The University of Arizona., 2016)
      The purpose of this honors thesis is to propose an evidence based best practice protocol for pain assessment and pain management in pediatric oncology patients. Pain is one of the most distressing aspects of treatment of cancer. Many pediatric oncology patients’ pain is undertreated or not treated as effectively as possible. The protocol presented was created to improve the quality of care and reduce the amount of pain experienced in this patient population. A literature review was performed on 11 studies retrieved from PubMed and CINHAL databases related to pain assessment, pharmacological pain management, and non-pharmacological alternative therapies for pain management. The evidence based recommendations for pain assessment were to use the Wong-Baker FACES® Pain Scale, FLACC scale, PQRST scale and Brief Pain survey depending on the age and developmental level of the patient. The pharmacological pain management was recommended for nurses to properly administer scheduled analgesia and administer pain medication per request. The recommended alternative therapies for pain management included are meditation, music therapy, massage therapy, and hypnosis. Evaluation of pain management will be performed by the patients and nurses’ assessment of the effectiveness of the pain management interventions.

      Porreca, Frank; Edelmayer, Rebecca M.; Vanderah, Todd W.; French, Edward D.; Ossipov, Michael H.; Sherman, Scott J. (The University of Arizona., 2009)
      Migraine patients often demonstrate cutaneous allodynia, defined as a hypersensitivity of the skin to touch or mechanical stimuli that is considered non-noxious under normal circumstances. The allodynia sometimes begins intracranially and spreads, via unknown mechanisms, to extracranial regions. The goal of the study was to develop and validate a model of cutaneous allodynia triggered by dural inflammation for pain associated with headaches, and to explore neuronal and glial mechanisms underlying generalized allodynia. Inflammatory mediators (IM) were applied to the dura of unanesthetized rats via previously implanted cannulas and sensory thresholds of the face and hindpaws were characterized. IM elicited robust and time-related facial and hindpaw allodynia which peaked after approximately three hours as well as FOS expression in the trigeminal nucleus caudalis (TNC), indicative of central sensitization. These effects were reminiscent of cutaneous allodynia seen in patients with migraine or other primary headache conditions, and were reversed by agents used clinically in the treatment of migraine including sumatriptan, naproxen, CGRP-antagonist, and morphine. Consistent with clinical observations, the allodynia was unaffected by an NK-1 antagonist. Having established facial and hindpaw allodynia as a useful animal surrogate of headache-associated allodynia, we next showed that blocking pain-facilitating processes from the rostral ventromedial medulla (RVM) interfered with its expression. Inactivation of the RVM with local anesthetic, destruction of putative pain-facilitation cells, and blockade of cholecystokinin receptors all prevented or significantly attenuated IM-induced allodynia. Electrophysiological studies confirmed activation of pain-facilitating "ON" cells and transient suppression of "OFF" cells in the RVM following IM. Additionally, microinjection of the RVM with a microglial inhibitor or sumatriptan also inhibited the expression of IM-induced cutaneous allodynia as well as microglial activation. Facial and hindpaw allodynia associated with dural stimulation is a useful surrogate of pain associated with primary headache including migraine and may be exploited mechanistically for the development of novel therapeutic strategies for headache pain. The data also demonstrate a requirement for activation of descending facilitation from the RVM, likely reliant on neuronal-glial interactions, for the expression of cranial and extracranial cutaneous allodynia. Consequently, the findings are consistent with a brainstem generator of allodynia associated with headache disorders.
    • Pain Facilitatory Cells in Rostral Ventromedial Medulla: Neurons Coexpressing Cholecystokinin-2 and Mu-Opioid Receptors

      Lai, Josephine; Zhang, Wenjun; Lai, Josephine; French, Edward; Porreca, Frank; Rance, Naomi; Vanderah, Todd (The University of Arizona., 2005)
      This dissertation will examine the phenotype of pain facilitatory neurons in the rostral ventromedial medulla (RVM) and its role in neuropathic pain states. Activation of the descending facilitation pathways might be the result of plasticity in the RVM that is driven, at least in part, by the presence and activity of cholecystokinin type-2 receptors (CCK2R) mRNA expressing neurons. The expression of either opioid mu receptors (MOR) or CCK2R mRNA in the RVM was confirmed by in situ hybridization (ISH). Pretreatment with CCK8(s)-saporin resulted in a significant loss of CCK2R mRNA positive cells in the RVM, concomitant with a blockade of CCK8(s) induced hyperalgesia. The same treatment also significantly reduced the number of neurons labeled for MOR mRNA, hinting that MOR and CCK2R mRNA signals may be co-localized in some RVM cells. Consistent with these data, pretreatment with dermorphin-saporin significantly reduced the number of MOR mRNA labeled cells in the RVM, blocked RVM CCK8(s) induced hyperalgesia and reduced the number of CCK2R mRNA positive cells in the RVM. The co-localization was further confirmed by a dual label ISH approach using 35S-labeled CCK2R and Digoxigenin-labeled MOR riboprobes. Data showed that over 80% of labeled RVM neurons co-expressed both MOR and CCK2R mRNA, ~15% expressed only CCK2R mRNA, and very few cells expressed only MOR mRNA. The above findings may suggest that elimination of CCK2R mRNA expressing neurons result in removal of the driving force for descending facilitation from RVM, hereby block the development of neuropathic pain. Rats pretreated with CCK8(s)-saporin conjugates had a full reversal of thermal sensory threshold and partial reversal of tactile threshold starting at day 5 after SNL. The lesion effects of RVM CCK-SAP were evaluated by ISH. Comparing to saporin pretreated groups, CCK8(s)-saporin pretreatment significantly reduced the numbers of CCK2R mRNA labeled neurons within RVM. The data suggest that selective ablation of CCK2R mRNA expressing cells in RVM is sufficient to block the development of neuropathic pain, and thus confirm the hypothesis that CCK2R mRNA expressing cells may be an important player in descending facilitation from RVM as a mechanism of neuropathic pain.
    • Pain perception and joint mobility before and after total knee arthroplasty

      Ort, Suzanne Van; Arslanian, Christine Lucy (The University of Arizona., 1987)
      Joint mobility is dependent on comfort, thus pain is associated with mobility. This study examined the relationship between pain perception and joint mobility in arthritis patients before and after total knee arthroplasty. Pain perception was indicated by pain intensity, pain distress and pain expectation; joint mobility was represented by the degree of knee joint flexion. Visual analogue scales were used for pain intensity, pain distress and pain expectation; knee joint flexion as measured using a goniometer. Data were collected on 24 subjects preoperatively (T1), immediately postoperatively (T2) and forty-eight to seventy-two hours postoperatively (T3). Twenty-four subjects participated in the study. Significant paired t-test resulted for joint flexion at T1 and T3 and pain expectation at T2 and T3. Pearson product-moment correlation coefficients were significant for pain intensity and pain distress at all three times, pain intensity and joint flexion at T1 and pain intensity at T1 and at T2.
    • Pain-modulating effects of peripheral (CB2) cannabinoid receptors

      Malan, T. Philip, Jr.; Ibrahim, Mohab Mohamed (The University of Arizona., 2004)
      Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive evidence implicates the CB1, receptor in the production of antinociception, inflammatory hyperalgesia, and peripheral nerve injury-induced sensory hypersensitivity. In previous work included in my masters thesis, our laboratory has demonstrated the capacity of CB2 receptors located outside the central nervous system (CNS) to inhibit acute nociception and inflammatory hyperalgesia. In this thesis, I use AM1241, a CB2 receptor-selective agonist to test the hypothesis that CB2 receptor activation reverses the tactile and thermal hypersensitivity characteristic of neuropathic pain in L5/L6 spinal nerve ligation model. The CB2 receptor-mediated nature of these effects was demonstrated using receptor-selective antagonists, as well as mice deficient in the genes coding for CB1 or CB2 receptors. Experiments using site-specific injections suggest AM1241 acts peripherally at the site of nerve injury and the site of application of the sensory stimulus. The peripheral nature of the effects of AM1241 is consistent with the peripheral distribution of CB 2 receptors. Given the peripheral actions of AM1241, I hypothesized and demonstrated that topical application of AM1241 modulates pain responses. Additionally, I began to examine the mechanisms by which CB2 receptor activation modulates pain responses. The effects of AM1241 were reversed by the opioid receptor antagonist, naloxone and by a sequestering antiserum to beta-endorphin. In addition, the effects of AM1241 were not observed in beta-opioid receptor knockout mice. These results suggest that the endogenous opioid peptide, mu-endorphin plays an essential role in CB2 receptor mediated pain inhibition. Further, AM1241 stimulated release of beta-endorphin from rat skin tissue and cultured human keratinocytes. The stimulation of beta-endorphin release by AM1241 was inhibited by the CB2 receptor-selective antagonist, AM630, and was not observed in skin from CB2 receptor knockout mice, demonstrating that it is mediated by CB2 receptor. These results suggest that CB2 receptor activation produces antinociception by stimulating the release of beta-endorphin from local cells and that beta-endorphin released acts at beta-opioid receptors to inhibit the responsiveness of primary afferent neurons.
    • Painful Paradoxes: Unresolved Cultural Tensions and the Response to Human Suffering in The Rape of Lucretia

      Baliani, Patrick; Lovett, Amber Carol (The University of Arizona., 2013)
      Myths are cultural repositories that reveal a society’s most intimate values, as well as its flaws. The rape of Lucretia is the myth of the founding of the Roman Republic, which is inspired by the rape of the Roman wife Lucretia by the Etruscan Prince Sextus Tarquinius, and her subsequent suicide. This myth has been revisited and reinterpreted many times since its creation, partly because it continues to present a paradox that defies interpretation: "If [Lucretia] is adulterous, why praise her? If chaste, why slay her?" (St. Augustine 29). The various reinterpretations of the myth made changes, whether subtle or dramatic, that sought to translate the story, rendering it understandable to a Christian audience. Each reinterpretation of the myth has also tried to either reconcile or emphasize this paradox, reflecting both the author’s interpretation and the contemporaneous cultural values, but most importantly hinting at the problematic response to personal suffering by individuals and societies.
    • Painleve Analysis, Lie Symmetries and Integrability of Nonlinear Ordinary Differential Equations

      Lu, Yixia; Ercolani, Nicholas M.; Ercolani, Nicholas M.; Flaschka, Hermann; Tabor, Michael (The University of Arizona., 2005)
      The Painleve analysis plays an important role in investigating local structure of the solutions of differential equations, while Lie symmetries provide powerful tools in global solvability of equations. In this research, the method of Painleve analysis is applied to discrete nonlinear Schrodinger equations and to a family of second order nonlinear ordinary differential equations. Lie symmetries are studied together with the Painleve property for second order nonlinear ordinary differential equations.In the study of the local singularity of discrete nonlinear Schrodinger equations, the Painleve method shows the existence of solution blow up at finite time. It also determines the rate of blow-up. For second order nonlinear ordinary differential equations, the Painleve test is introduced and demonstrated in detail using several examples. These examples are used throughout the research. The Painleve property is shown to be significant for the integrability of a differential equation.After introducing one-parameter groups, a family of differential equations is determined for discussing solvability and for drawing more meaningful conclusions. This is the most general family of differential equations invariant under a given one-parameter group. The first part of this research is the classification of the integrals in the general solutions of differential equations obtained by quadratures. The second part is the application of Riemann surfaces and algebraic curves in the projective complex space to the integrands. The theories of Riemann surfaces and algebraic curves lead us to an effective way to understand the nature of the integral defined on a curve. Our theoretical work then concentrates on the blowing-up of algebraic curves at singular points. The calculation of the genus, which essentially determines the shape of a curve, becomes possible after a sequence of blowing-ups.The research shows that when combining both the Painleve property and Lie symmetries possessed by the differential equations studied in the thesis, the general solutions can be represented by either elementary functions or elliptic integrals.

      Bhappu, Anita D.; STITT, AUBRY ALEXANDRA (The University of Arizona., 2016)
      This reflection serves as a complement to my experiential honors thesis project, which involved an exploration and execution of a fundraising business. During my two-semester honors thesis project, I composed a value proposition, obtained consumer insights, generated sample inventory for trial sales and consumer testing, and ultimately launched a small fundraising business through an Etsy shop and direct selling of my custom-made products.