• Blood pressure impacts the renal T cell profile of male and female spontaneously hypertensive rats

      Tipton, Ashlee J.; Department of Physiology (2014-03)
      Of the 68 million Americans with hypertension, fewer than 46% have their blood pressure (BP) adequately controlled and women are more likely than men to have uncontrolled hypertension. This underscores the critical need for new treatment options; however, this is a challenge due to our lack of knowledge regarding the mechanism(s) driving essential hypertension. T cells have been implicated in hypertension in males. Prior to our work, the role of T cells in hypertensive females had been unexplored. We demonstrate that female spontaneously hypertensive rats (SHR) have a decrease in BP in response to an immunosuppressant, supporting an immune component to their hypertension. We further defined a sex difference in the renal T cell and cytokine profile in SHR. Female SHR have a more anti-inflammatory immune profile in their kidneys than males. To gain insight into the mechanisms mediating sex differences in the immune profile, male and female SHR were gonadectomized. Gonadectomy increased pro-inflammatory markers in both sexes and attenuated anti-inflammatory markers particularly in females. Therefore, while both male and female sex hormones promote an anti-inflammatory immune profile, female ii sex hormones contribute greater to their more anti-inflammatory profile, but do not explain the sex difference. To determine the impact of hypertension on the renal immune profile, experiments measured renal T cells and cytokines in hypertensive male and female SHR, normotensive Wistar Kyoto rats (WKY), and SHR treated with antihypertensive therapy. All T cells and cytokines measured were higher in SHR compared to the same sex WKY. Moreover, antihypertensive therapy decreased renal Tregs only in female SHR. These data suggest that increased BP in both sexes is associated with an increase in renal inflammation; however female SHR have a compensatory increase in renal Tregs in response to increases in BP. TGF-β is a key cytokine regulating Treg and Th17 differentiation and we found that female SHR express more TGF-β than males. Experiments assessed if female SHR possessed a sex hormone or BP-mediated increase in renal TGF- β corresponding with increases in Tregs. We determined that loss of female sex hormones and increased BP in female SHR increase renal TGF-β expression. We conclude that BP status drive sex differences in the renal T cell and cytokine profile of SHR.
    • Bone and soft tissue regenerative response following alveolar ridge augmentation using polysulfone implants with and without demineralized bone powder in macaca fascicularis

      Fouad, Salama S; Department of Oral Biology (1987-06)
      Successful augmentation of bone surfaces has great clinical application, particularly to the face and oral cavity regionso More than 24 mi 11 ion Americans are edentulous and must depend upon dentures to eat and to restore their norma 1 speech and appearance o Porous po lysul fane (PPSF) is frequently used to fill osseous voidso The purpose of this study was to· test tooth soft, ti.ssue and bone response to porous po lysul fane (PPSF), with and without demineralized bone powder (DBP) in Macaca fascicularise Six adult female monkeys, 12-15 year~ of ~ge, were used in this study. One animal was sacrificed and used as a bone donor and the other five were recipientso All mandibular molar teeth were extracted and masstve alveolectomies were performedo The wounds were left to heal for 5 to 8 1/2 months postoperativelyo At the time of implantation~ PPSF with DBP was inserted subperiosteally into the left mandibular edentulous areas while PPSF alone was inserted into the right sideso The. animals were sacrificed at 42, .60, or 90 days following implantationo Each mandible was cut- into 3mm thick coronal sections which were then examined and photographed with a dissecting microscopeo Some specimens were then decalcified, embedded in paraffin and sect i a ned and stained With. H & Eo Other specimens were processed undecalcified in glycol and methylmethacrylate for histomorphometric measurements and tetracycline labe1ling·., Also, some specimens were processed for scanning electron microscopyo No inflammation or untoward reaction of the 'implantation sites were noted at the time of sacrifice. Histologically, the 42 day specimens of the' DBP-PPSF side· (experimental side) revealed penetration of fibrous tissue rich in fibroblasts and vessels into the pores of PPSF comparirig to the PPSF side (control side)., The fibrous tissue also surrounded the implant., Some multinucleated giant cells and macrophages were present., At 60 days, the PPSF side showed more organized fibrous tissue and bone grew only for a. short distance into the polysulfone. In contrast, the PPSF-DBP side showed large amounts of .bone formation within the pores of the polysulfone and almost covered the implant., The newly formed bone contained osteocytes and was -surrounded by osteob 1 asts. At 90 days, the PPSF side showed more bone tormation on the lower half of the. implant" These res~lts suggested that PPSF is a suitable non-resorbable material that accommodates bone and soft tissue formation. A 1 so :p the use of DBP enhanced both rate and amount of the new bone., In· conclusion; PPSF with and without DBP is a suitable material that can be used successfully for alveolar ridge augmentation.
    • Bone regenerative response following bone augmentation using hydroxyapatite with and without growth factors

      Sohn, Jeong-Yeol; School of Graduate Studies (1997-09)
      The purpose of this study was to determine whether adding transforming growth factor-13 (TGF-13) which is known to promote osteogenesis or 15 amino acid polypeptide obtained from collagen type I (P-15) which is known to enhance DNA synthesis in cultured fibroblasts, would enhance the osseoint~gr.ation- of porous anorganic bovine bone block (HA-block) to mandibular bone surface. Total of 45 rabbits were divided into three equal groups. The buccal side of the mandible in ea.ch anesthetized animal was surgically exposed,. decorticated and 10 x 5 x 4 mm. HA (Group I), HA+ TGF-13 (Group II) or HA + P-15 (Group III) blocks. were affixed to .host bone using two, titanium screws. Animals were sacrificed, 1 wk, 4 wks and 8 wks after surgery. A core of the implant· and underlying host bone was used to determin.e osteocalcin using Western and Slot blot analyses before perfusing the animals with 4% forma}in. The contralateral sides were only decorticated and served as sham controls. The interface between the HAblock and the ho.st bone showed a signifi.cantly higher (P<0~05) number of mesenchymal cells in the HA + TGF--P. and HA + P-15 one week group when c.ompared. to HA-alone. This numb.er of mesenchymal ·cells declined significantly .by the 4th and 8th weeks. The proliferating cell nuclear antigen (PCNA) index using immunohistochemistry als.o showed a significant increase in the one week groups and· then also declined. Alkaline phosphatase, osteocalcin, bone volume, and new bone formation were all significantly increased by the 4th and 8th weeks and were significantly higher in the HA + TGF-13 and HA + P-15 at 4 wks after surgery. In addition, the macropores of the lower halves of all blocks were filled with new bo.ne. The den~ity of the newly formed bone was comparable to the control bone. These res.ults indicate that anorganic :bovine bQne blocks are osteoconductive and their pores permit growth of new bone. The adding of TGF-P or P-15 enhanced all parameters of osteogenesis at the mandibular bone surface.
    • Burnout and Job Satisfaction of Medical-Surgical Nurses

      Garbutt, Susan J.; School of Nursing (1981-12)
      Job satisfaction and burnout of medical-surgical nurses a n d t h e i r . r e 1 at i_ o n s h i p to . t h. e ~ ri u· r s .. e ' s o p t i. on t o w or k h e r I h i s s hi f t ·of choice was stud i e d . The Mas 1 a c h Burnout Inventory (Maslach and Jackson, 1981-), the Job Satisfaction-Instrument (Wall, ·1980; and Sorrow, 1980) and a Demographic Data Form were used to survey t~enty randomly selected registe~ed nurses f r o m e a c h . o f t h r e e s o u t h e a s t e r n h o s p l t a 1 s . ( t o t-a 1 N = 6 0 ) .. Result~ of this study indicated that as job satisfact}on increased, the intensity of burnout reported by medical-surgical nurses decreased. Frequency and intensity of burnout were positively correlated. Burnout occorred among n~rses who worked their choice of shift and among nurses who did not. However, nurses who worked their choice of shift reported a significantly lower intensity of burnout than nurses who did not work their choice of shift. This study prov.ides some interest-· ing data to be ~onside~ed by nurse administrators in working .with medical-sur9ical nurses. Replication and extension of this study is recommended.
    • The c-MYC oncogene deregulates global DNA methylation and hydroxymethylation to control genome-wide gene expression for tumor maintenance in leukemia/lymphoma

      Poole, Candace Jean; Biomedical Sciences (Augusta University, 2019-05)
      Aberrant DNA methylation is a characteristic feature of tumor cells. However, our knowledge of how DNA methylation patterns are established and maintained to contribute to tumorigenesis is limited. Inactivation of the c-MYC oncogene triggers tumor regression in T-cell acute lymphoblastic leukemia (T-ALL) resulting in dramatic changes to the chromatin landscape including DNA methylation. In this study, I investigated how MYC regulates DNA methylation and hydroxymethylation patterns to contribute to gene expression programs important for tumor maintenance in T-ALL and Burkitt lymphoma. I report that MYC maintains 5-methylcytosine (5mC) and 5-hydroxy-methylcytosine (5hmC) patterns by regulating the DNA methylation machinery, which is important for gene expression in T-ALL. DNA methyltransferases (DNMTs) initiate 5mC marks, while Ten-eleven translocation methylcytosine dioxygenases (TETs) oxidize 5mC to produce 5hmC as an intermediate modification, ultimately leading to active DNA de-methylation. I demonstrated that DNMT1 and DNMT3B are MYC target genes and that their expression is dependent on high MYC levels. Knockdown of DNMT3B in T-ALL reduced cell proliferation through cell cycle arrest and caused the reactivation of gene transcription through reversing promoter/CpG island methylation. Furthermore, I demonstrated that TET1 and TET2 expression is MYC-dependent, as high TET1 and low TET2 levels depend on oncogenic MYC. Knockdown of TET1 in T-ALL reduced cell proliferation through cell cycle arrest and caused genome-wide changes in 5mC and 5hmC corresponding to changes in gene programs important for ribosomal biosynthesis and protein synthesis. In contrast, ectopic expression of TET2 reduced tumor cell proliferation through apoptosis/necrosis and caused genome-wide changes in 5mC and 5hmC corresponding to changes in transcriptional regulatory gene programs. My finding that a coordinated interplay between components of the DNA methylation machinery is necessary for MYC-driven tumor maintenance highlights the potential of targeting specific DNMT or TET proteins for therapeutic strategies.
    • Calcyon, a novel partner of clathrin light chain, stimulatesclathrin-mediated endocytosis

      Xiao, Jiping; Xiao, Jiping; School of Graduate Studies (2006-12)
      In the central nervous system, clathrin-meriate,d endocytosis (CME) is crucial for ' I • efficient synaptic transmission as CME regulates both presynaptic release of neurotransmitter and postsynaptic responses to .transmitter. Clathrin-coated vesicle assembly and disassembly are regulated by som~ 30 adaptor and accessory proteins, most I of which interact with clathrin heavy chain. Calcy_on, which is a single transmembrane protein predominantly expressed in brain, is localized to vesicular compartments within pre and postsynaptic structures. Calcyon has been implicated as a candidate gene for schizophrenia, but the function of calcyon is not yet described. Using the calcyon cytosolic domain as bait, we isolated clathrin light chain (LC) in a yeast two-hybrid screen. The interaction domains were mapped to the heavy chain binding domain and Cterminal regions in LC. In calcyon, residues123 to 155 of calcyon mediated the interaction with LC. Addition of a purified fusion protein containing the calcyon C terminus stimulated clathrin self-assembly in vitro in a dose-dependent fashion. There was a high degree of overlap in the distribution of LC and-calcyon in neuronal processes and cell bodies. Co-immunoprecipitation studies further suggested an association of calcyon with adaptor proteins that play a role in clathrin coated vesicle formation at the plasma membrane, trans Golgi Network and endosomes. Compared to control, HEK293 cells overexpressing calcyon exhibited significantly enhanced transferring (Tfn) uptake but equivalent levels.ofTfn recycli1:1g. Copversely, transferrin uptake was largely abolished in neocortical neurons obta;ined from mice homozygous for a calcyon null allele, whereas recycling proceeded at wild type levels. Deletion of the calcyon gene in mice also inhibited agonist-sti~ulated endocytosis of the GluRl and GluR2 subunits of the ligand gated AMP A type glutamate receptor in primary neurons in cultures. Collectively, these data indicate a role for calcyon in clathrin-mediated endocytosis in brain.
    • Calpain-2 Activates Akt via the TGF~ 1-mTORC2 Pathway in Pulmonary Artery Smooth Muscle Cells

      Abeyrathna, Prasanna; Deparment of Pharmacology and Toxicology (8/23/2016)
      Calpain is a family of calcium-dependent nonlysosomal neutral cysteine endopeptidases. Akt is a serine/threonine kinase that belongs to the AGC kinases and plays important roles in cell survival, growth, proliferation, angiogenesis, and cell metabolism. Both calpain and Akt are downstream signaling molecules of platelet-derived growth factor (PDGF) and mediate PDGF-induced collagen synthesis and proliferation of pulmonary artery smooth muscle cells (PASMCs) in pulmonary vascular remodeling. We found that inhibition of calpain-2 using the calpain inhibitor MDL28170 and calpain-2 siRNA attenuated Akt phosphorylation at serine-473 (S473) and threonine-308 (T308) as well as collagen synthesis and cell proliferation ofPASMCs induced by PDGF. Overexpression of calpain-2 in PASMCs induced dramatic increases in Akt phosphorylation at S4 73 and T308. Moreover, knockout of calpain attenuated Akt phosphorylation at S473 and T308 in smooth muscle of pulmonary arterioles of mice with chronic hypoxic pulmonary hypertension. The cell-permeable specific TGF~ receptor inhibitor SB431542 attenuated Akt phosphorylation at both S473 and T308 induced by PDGF and overexpressed calpain- 2 in PASMCs. Moreover, SB-431452 and knock down of ALK5 significantly reduced PDGF-induced collagen synthesis and cell proliferation of PASMCs. Nevertheless, neutralizing extracellular TGF~l using a cell-impermeable TGF~l neutralizing antibody did not affect PDGF-induced Akt phosphorylation at S473 and T308. Further, inhibition of mTORC2 by knocking down its component protein Rictor prevented Akt phosphorylation at S473 and T308 induced by PDGF and overexpressed calpain-2. These data provide the first evidence supporting that calpain-2 up-regulates PDGF-induced Akt phosphorylation via an intracrine TGF~ 1/mTORC2 mechanism.
    • CaMKIIβ association with F-actin in developing cortical neurons

      Lin, Yu-Chih; Department of Pharmacology and Toxicology (2008-08)
      Calcium/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase that is best known for its role in synaptic plasticity and memory. Although multiple roles of CaMKII have been identified in the hippocampus, its role in the developing cerebral cortex is less well understood. Immunostaining showed CaMKIIβ, but not CaMKIIα was expressed in embryonic day 18 (E18) cortical neurons at 4 days in vitro (DIV) and localized to a F-actin rich cytoskeletal structure we termed “microspike”. Further characterization of microspikes revealed that microspikes were composed of bundled actin, and were stable over time. Besides CaMKIIβ, several actin binding proteins, such as Arp3, cortactin and β1-integrin were also colocalized in microspikes. Fluorescence recovery after photobleaching (FRAP) analyses showed different dynamics of actin and CaMKIIβ in microspikes compared to dendrite spines. The colocalization of CaMKIIβ and F-actin in microspikes was dependent on the F-actin binding domain and the oligomerization domain. FRAP analyses confirmed the association of CaMKIIβ with F-actin in microspikes was via the F-actin binding domain. This association was altered by the co-expression of CaMKIIα. FRAP analyses with stabilized F-actin using jasplakinolide or cytochalasin-D further indicated CaMKIIβ, but not CaMKIIα, had a strong interaction with stable F-actin. Inhibiting calmodulin binding on CaMKII using a CaMKII inhibitor, KN93, dissociated CaMKIIβ from stable F-actin. Increasing CaMKIIβ activity with KCl or an active form of CaMKIIβ, CaMKIIβT287D, also dissociated CaMKIIβ from stable F-actin. A calmodulin binding mutant, CaMKIIβA303R, or a kinase dead mutant, CaMKIIβK43R, however, did not recover differently from wildtype CaMKIIβ. The differential binding of CaMKIIβ with F-actin shown in FRAP analyses correlated with CaMKIIβ enrichment in microspikes and the prominence of microspikes. While overexpressed CaMKIIβ increased the number of cells with microspikes, knockdown of CaMKIIβ with shRNA reduced it. Taken together, these data suggested that CaMKIIβ is associated with F-actin in cortical neurons, and this association is regulated by CaMKIIα and calcium signals contributing to the stability of microspikes.
    • CaMKIIβ association with F-actin in developing cortical neurons

      Lin, Yu-Chih; School of Graduate Studies (2008-08)
      Calcium/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase that is best known for its role in synaptic plasticity and memory .. Although multiple roles of CaMKII have been identified in the hippocampus, its role in the developing cerebral cortex is less well understood. Immunostaining showed Ca~KII~, but not CaMKIIa was expressed in embryonic day 18 (E 18) cortical neurons at 4 days in vitro (DIV) and localized to a F-actin rich cytoskeletal structure we termed "micro spike". Further characterization of micro spikes revealed that micro spikes were composed of bundled actin, and were stable over time. Besides CaMKII~, several actin binding proteins, such as Arp3, cortactiti"and ~1-integrin were also colocalized in microspikes. Fluorescence recovery after photo bleaching (FRAP) analyses showed different dynamics of actin and CaMKII~ in microspikes compared to dendrite spines. The colocalization of CaMKII~ and F-actin in microspikes was dependent on the F-actin binding domain and the oligomerization domain. FRAP analyses confirmed the association of CaMKIIP with F-actin in microspikes was via the F-actin binding domain. This association was altered by the co-expression of CaMKIIa. FRAP analyses with stabilized F-actin using jasplakinolide or cytochalasin-D further indicated CaMKIIP, but not CaMKIIa, had a strong interaction with stable F-actin. Inhibiting calmodulin binding on CaMKII using a CaMKII inhibitor, KN93, dissociated CaMKIIP from stable F-actin. Increasing CaMKIIP activity with KCl or an active form of CaMKIIP, CaMKIIPT287D, also dissociated CaMKIIP from stable F-actin. A calmodulin binding mutant, CaMKIIPA303R, or a kinase dead mutant, CaMKIIPK43R, however, did not recover differently from wildtype CaMKIIp. The differential binding of CaMKIIP with F-actin shown in FRAP analyses correlated with CaMKIIP enrichment in microspikes and the prominence of microspikes. While overexpressed CaMKIIP increased the number of cells with microspikes, knockdown of CaMKIIP with shRNA reduced it. Taken together, these data suggested that CaMKIIP is associated with F-actin in cortical neurons, and this association is regulated by CaMKIIa and calcium signals · contributing to the stability of micro spikes.
    • Cancer stressors and protective factors : predictors of stress experienced during treatment for childhood cancer

      Marilyn, Hockenberry-Eaton; School of Nursing (1992-05)
      The purpose of this study was to evaluate cancer stressors · and protective factors as predictors of stress experienced during treatment for childhood cancer. The conceptual framework evolved from the stress and coping literature and childhood cancer research. A conveni~nce sample of 44 children between 6 1/2 and 13 .1/2 years of age receiving treatment for cancer were evaluated during two clinic visits. Protective factors included the child's self-perception, coping strategies, -perceived social support, and family environment. Cancer stressors included acute stressors represented by the type of treatment received during two clinic visits. Chronic stressors were evaluated by the child's perception of stressors related to the cancer experience. Responses to stressors were assessed by physiologic and psychologic indicators of stress. Physiologic measures included epinephrine, norepinephrine, and cortisol measures of urine and psychologic measures of state and t~ait anxiety. No significant differences were found in the physiologic or psychologic response to stressors in relation to the type of treatment received during either clinic visit. Epinephrine and norepinephrine were elevated for children during both clinic visits. Stepwise multiple regression analyses revealed that family expressiveness and the child's perceived global self-worth were the best predictors of epinephrine leve~s. Perceived social support from friends had the greatest effect on norepinephrine levels. Family activities and recreation and family intellectual cultural orientation were the best predictors of state anxiety The intensity of chronic cancer stressors, family activities and recreation, family intellectual cultural brientation, the child's perception of physical appearance, and the presence of family conflict had the greatest effect on trait anxiety. This study is the first to examine the child's perception of chronic cancer stressors and protective factors associated with treatment for cancer. The findings provide insight into the importance of the interactions among the nature of the stressor, perceptual meaning of the stressor, and physiologic and psychologic responses to stressors that may affect long-term adjustment to childhood cancer.
    • Cancer Stressors and Protective Factors: Predictors of Stress Experienced During Treatment for Childhood Cancer

      Hockenberry-Eaton, Marilyn; Department of Physiological and Technological Nursing (1992-05)
      The purpose of this study was to evaluate cancer stressors and protective factors as predictors of stress experienced during treatment for childhood cancer. The conceptual framework evolved from the stress and coping literature and childhood cancer research. A convenience sample of 44 children between 6 ½ and 13 ½ years of age receiving treatment for cancer were evaluated during two clinic visits. Protective factors included the child’s self-perception, coping strategies, perceived social support, and family environment. Cancer stressors include acute stressors represented by the type of treatment received during two clinical visits. Chronic stressors were evaluated by the child’s perception of stressors related to the cancer experience. Responses to stressors were assessed by physiologic and psychologic indicators of stress. Physiologic measures include epinephrine, norepinephrine, and cortisol measures of urine and psychologic measures of state and trait anxiety. No significant differences were found in the physiologic or psychologic response to stressors in relation to the type of treatment received during either clinic visit. Epinephrine and norepinephrine were elevated for children during both clinic visits. Stepwise multiple regression analyses revealed that family expressiveness and the child’s perceived global self-worth were the best predictors of epinephrine levels. Family activities and recreation and family intellectual cultural orientation were the best predictors of state anxiety. The intensity of chronic cancer stressors, family activities and recreation, family intellectual cultural orientation, the child’s perception of physical appearance, and presence of family conflict had the greatest effect of trait anxiety. This study is the first to examine the child’s perception of chronic cancer stressors and protective factors associated with treatment for cancer. The findings provide insight into the importance of the interactions among the nature of the stressor, perceptual meaning of the stressor, and physiologic and psychologic responses to stressors that may affect long-term adjustment to childhood cancer.
    • Canonical Wnt Signaling in Antigen Presenting Cells Regulates Microbiota-Induced Inflammation and Immune Cell Homeostasis in the Colon

      Swafford, Daniel Joseph; Department of Biochemistry and Molecular Biology / Cancer Center (8/3/2018)
      Aberrant Wnt/β-catenin-signaling occurs in several inflammatory diseases including inflammatory bowel disease (IBD) and IBD-associated colon carcinogenesis. However, its role in shaping mucosal immune responses to commensals in the gut remains unknown. Here, we investigated the importance of canonical Wnt signaling in CD11c+ antigen presenting cells (APCs) in controlling intestinal inflammation. Using a mouse model of ulcerative colitis, we demonstrated that canonical Wnt-signaling in intestinal CD11c+ antigen presenting cells (APCs) controls intestinal inflammation by imparting an anti-inflammatory phenotype. Genetic deletion of Wnt co-receptors, low-density lipoprotein receptor-related protein 5 and 6 (LRP5/6) in CD11c+ APCs in mice (LRP5/6ΔCD11c mice) resulted in enhanced intestinal inflammation with increased histopathological severity of colonic tissue. This was due to microbiota-dependent increased production of pro-inflammatory cytokines and decreased expression of immune regulatory factors such as IL-10, retinoic acid (RA), and IDO. In addition, loss of LRP5/6-mediated signaling in CD11c+ APCs resulted in altered microflora and T cell homeostasis, which led to a loss of systemic tolerance to oral antigen. Furthermore, our study demonstrates that conditional activation of β-catenin in CD11c+ APCs in LRP5/6ΔCD11c mice resulted in reduced acute intestinal inflammation with decreased histopathological severity of colonic tissue. Loss of canonical Wnt signaling in CD11c+ APCs also results in an increase in colonic polyp formation and exacerbation of chronic inflammation/injury. This was also heavily dependent on the presence and composition of the gut microbiota, as fecal transfers from LRP5/6ΔCD11c mice to floxed control (LRP5/6FL/FL) mice that were administered an antibiotic cocktail produces a polyp load and weight loss similar to that of LRP5/6ΔCD11c mice without treatment. Additionally, our study demonstrates that conditional activation of β-catenin in CD11c+ APCs in LRP5/6ΔCD11c mice reduces severity of inflammation-associated colon carcinogenesis in these mice. Furthermore, we show that treatment of LRP5/6ΔCD11c mice with either RA or IL-10 reduces severity of inflammation-associated colon carcinogenesis. Mechanistically, RA and IL-10 may independently reduce key inflammatory factors at the acute phase of colitis. These results ultimately reveal a mechanism by which intestinal APCs control intestinal inflammation and immune homeostasis via the canonical Wnt signaling pathway, which may serve as a promising target for chronic inflammatory disorders.
    • Cardiovascular and behavioral changes associated with morphine abstinence in the physically dependent rat: a neuropharmacological study of both the spinal and supraspinal components of withdrawal

      Marshall, Dennis C; Department of Pharmacology and Toxicology (1984-10)
      ·.Physical depende.nce upon narcotics is, revealed in a characterfstic withdrawal syndrome of autonomic and behavioral changes evoked· by the administration of a narcotic antagonist. Although these changes have bee~ described, the mechanisms and locations within the central nervous system responsible for these effects are· unknown. My research was designed to develop an .objective animal model of dependency which could be used to identify mechanisms associated with narco.tic wi t.hdrawal. Cardiovascular and behavioral responses were ~valuat·ed following naloxone administration to·. freely moving rats made. physically dependent by a chronic intra-ar~ terial infusion of.morphine over 5 days. Naloxone evoked an elevation in mean arterial pressure (M·:AP) which· increased in a dose. and time dependent manner over the infusion schedule·whereas traditional behavioral signs of withdrawal were variable. Cardiovascular and behavioral signs of withdra~al also were e.lici ted by regional naloxone injection into various areas of the central nervo.us system including the spinal cord. Intrathecally administered, anticholinergic agents reduced the naloxone-induced increase in MAP along with some behavioral si.gns of wi thdr·awal. Spinal-t.ransected ( V.l), I dependent rats generated a profound hypertensive response to naloxone which was abolished·. by ganglionic or ct-adrenergic. blockade, spinal pithing or surgical dorsal root section. .Anticholinergic agents, intrathecally administered to spin~l-transected rats, resulted in an augmented hypertensive r~sponse to naloxone. These results indicate that 1) the naloxone-induced increase (MAP) in morphine dependent rats can serve as an objective and more sensitive measure of the degree of physical dependence than behavioral responses of withdrawal, 2) the spinal cord is capable of initiating cardiovascular and behavioral signs of withdrawal which can be modified by intrathecal administration of anticholinergic agents, 3) independent of supraspinal influences the spinal cord itself can generate a profound_ increase in mean arterial pressure which requires afferent information for its expression and, 4) at least two opposing cholinergic mechanisms which regulate cardiovascular activity exist with~n the spinal cord; one which is descending and facilitatory and another which is intrinsic and inhibitory.
    • Care-Cure Oreintations of Nurses Working in Critical Care and General Medical-Surgical Units

      Fisher, Barbara; Department of Nursing (1980-11)
      The purpose of this study was to examine .the attitudes of hurses working in crtttca1 care and medical-surgical units toward patient care and cure. A total populatinn·and random sample of 167 subjects (77 nurses working tn critical· care untts, 3 males and 74 females and 90 nurses working on medical-surgi'cal units,. 3 males and 87, ·females) was selected from three participating acute care tertiary general hospitals in urban Georgia. Data wer~collected using a self-administered valid and reliable reseatch instrument consisting of Linn's (1974) C~re-Cure Scale as modified by - . . _the· investigator, and a -demographtc data questionhaire -also de~el_oped by the investigator. The primary finding of the study indicated that for the population studied medical-surgical nurses were more care oriented than were critical care nurses. Critical care and generai iried·ica·'i-surgi'cal nur-scis dif·t-ercd s·ignificantiy (iJ< 0.01) ii1 or·ientation toward patient care and cure.
    • Caring for Their Mothers: The Experiences, Self-Care Practices, and Cultural Influences of African American Women Caregivers

      Chappell, Harriet E. H.; Department of Physiological and Technological Nursing (2007-07)
      The growth of minority older populations has created an increased need for African American family caregivers. African American women are at increased risk when the demands of caregiving are added to their existing health disparities. The purpose of this study was to understand the caregiving experiences of African American women, their ability to provide selfcare, and the influences of the African American culture on caregiving. Qualitative description was used to study 12 African American women caring for their mothers. Themes extrapolated from the data were commitment to care, self-care by the daughter caregivers, and the difficult times. An integrated pattern was also identified: Influences of African American Culture on caregiving. African American daughter caregivers have a profound commitment to provide the care needed by their mothers. The daughter caregivers’ self-care was balanced within and impacted by the demands and stresses of caregiving. The African American culture embodied expectations for daughter caregivers to provide care but also facilitated sources of support and strength.
    • Caring for their mothers: the experiences, self-care practices, and cultural influences of african american women caregivers

      Chappell, Harriet Elizabeth Haynie; School of Graduate Studies (2007-07)
      The growth of minority older populations has created an increased need for African American family caregivers. African American women are at increased risk when the demands of caregiving are added to their existing health disparities. The purpose of this study was to understand the caregiving experiences of African American women, their ability to provide selfcare, and the influences of the African American culture on caregiving. Qualitative description was used to study 12 African American women caring for their mothers. Themes extrapolated from the data were commitment to care, self-care by the daughter caregivers, and the difficult times. An integrated pattern ·was also identified: Influences of African American Culture on caregiving. African American daughter caregivers have a profound commitment to provide the care needed by their mothers. The daughter caregivers' self-care was balanced within and impacted by the demands and stresses of caregiving. The African American culture embodied expectations for daughter caregivers to provide care but also facilitated sourc,es of support and strength.
    • Catching the Asthma: Family Caring For School-Aged Asthmatic Children

      Horner, Sharon D; Catching the Asthma: Family Caring for School-Aged Asthmatic Children (1992-04)
    • Catching the Asthma: Family Caring for School-aged Asthmatic Children

      Horner, Sharon D; Department of Physiological and Technological Nursing (1992-04)
      The purpose of this study was to explore the process of family caring in families that had a school-aged child with asthma. One focus of this study was to explore the impact of chronicity on the family, specifically looking beyond illness-management issues. Another focus of this study was to uncover the evolution of family caring within the context of school-aged developmental changes. Grounded theory was the research methodology used to discover the strategies, goals, and dimensions of family caring. The research questions used to begin this exploration were: "What is (are) the experience(s) of family caring?" "How does chronicity impact family caring?" These questions presented a number of avenues for exploration. The impact of chronicity on family caring has not previously been explored in depth. Management of the needs of the family member who has a chronic illness (care-taking) has been studied extensively. Various studies have identified the problems families experience related to care-taking tasks, meeting family members' needs, financial burden, stress, role overload, as well as other dynamics of family functioning. None of these studies have explored the emotive and commitment dimensions of caring (caring for and caring about). An exploration of illness-management in day-to-day living was certainly included in the interviewing process; however, this study extended the exploration of chronicity into all aspects of family life to uncover the dimensions of family caring. Specifically, "How do family members care for and care about each other, while taking care of self and others?"