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Biomedical subjects

E Chang

Publications and source records attributed to E Chang.

At least 55 records · Page 3Linked to original sources

Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype.

Expression of the human telomerase catalytic component, hTERT, in normal human somatic cells can reconstitute telomerase activity and extend their replicative lifespan. We report here that at twice the normal number of population doublings, telomerase-expressing human skin fibroblasts (BJ-hTERT) and retinal pigment epithelial cells (RPE-hTERT) retain normal growth control in response to serum deprivation, high cell density, G1 or G2 phase blockers and spindle inhibitors. In addition, we observed no cell growth in soft agar and detected no tumour formation in vivo. Thus, we find that telomerase expression in normal cells does not appear to induce changes associated with a malignant phenotype.

Aspartic Acid↗

An evaluation of the nurse practitioner role in a major rural emergency department.

The purpose of this pilot study was to investigate whether nurse practitioners are able to provide a level of primary health service applicable to remote/isolated settings in wound management and treatment of blunt limb trauma. It was hypothesized that there would be no significant difference in the quality of care, or the level of client satisfaction, provided by the medical officers and the nurse practitioners in the study. Two groups participated in the study, nurse practitioners and medical officers. The study used a randomized trial design. Data were collected using quantitative and qualitative methods. Two hundred and thirty-two clients participated in the study. Of this number 63 were supervised cases in the pilot trial. In the randomized trial participants were distributed between nurse practitioners and medical officers (n = 169), of which 91 were randomized to medical officers and 78 to nurse practitioners. Telephone interviews were conducted to evaluate client satisfaction. The majority of study participants were surveyed for client satisfaction (n = 132). This represents approximately 78% of the randomized sample and multivariate analysis was carried out on the data. Study results indicate that there were no significant differences between the two groups in relation to client satisfaction. Very positive outcomes of treatment were consistent across groups in the study. The study also found that there was strong support for the role of the nurse practitioner in the rural emergency setting. Recommendations include further research to measure the efficacy of nurse practitioners utilizing the selected competencies in remote/isolated settings.

Adolescent↗

Direct binding and In vivo regulation of the fission yeast p21-activated kinase shk1 by the SH3 domain protein scd2.

The Ste20/p21-activated kinase homolog Shk1 is essential for viability and required for normal morphology, mating, and cell cycle control in the fission yeast Schizosaccharomyces pombe. Shk1 is regulated by the p21 G protein Cdc42, which has been shown to form a complex with the SH3 domain protein Scd2 (also called Ral3). In this study, we investigated whether Scd2 plays a role in regulating Shk1 function. We found that recombinant Scd2 and Shk1 interact directly in vitro and that they interact in vivo, as determined by the two-hybrid assay and genetic analyses in fission yeast. The second of two N-terminal SH3 domains of Scd2 is both necessary and sufficient for interaction with Shk1. While full-length Scd2 interacted with only the R1 N-terminal regulatory subdomain of Shk1, a C-terminal deletion mutant of Scd2 interacted with both the R1 and R3 subdomains of Shk1, suggesting that the non-SH3 C-terminal domain of Scd2 may be involved in defining specificity in SH3 binding domain recognition. Overexpression of Scd2 stimulated the autophosphorylation activity of wild-type Shk1 in fission yeast but, consistent with results of genetic analyses, did not stimulate the activity of a Shk1 protein lacking the R1 subdomain. Results of additional two-hybrid experiments suggest that Scd2 may stimulate Shk1 catalytic function, at least in part, by positively modulating protein-protein interaction between Cdc42 and Shk1. We propose that Scd2 functions as an organizing center, or scaffold, for the Cdc42 complex in fission yeast and that it acts in concert with Cdc42 to positively regulate Shk1 function.

Binding Sites↗

Membrane-limited expression and regulation of Na+-H+ exchanger isoforms by P2 receptors in the rat submandibular gland duct.

1. Cell-specific reverse transcriptase-polymerase chain reaction (RT-PCR), immunolocalization and microspectrofluorometry were used to identify and localize the Na+-H+ exchanger (NHE) isoforms expressed in the submandibular gland (SMG) acinar and duct cells and their regulation by basolateral and luminal P2 receptors in the duct. 2. The molecular and immunofluorescence analysis showed that SMG acinar and duct cells expressed NHE1 in the basolateral membrane (BLM). Duct cells also expressed NHE2 and NHE3 in the luminal membrane (LM). 3. Expression of NHE3 was unequivocally established by the absence of staining in SMG from NHE3 knockout mice. NHE3 was expressed in the LM and in subluminal regions of the duct. 4. Measurement of the inhibition of NHE activity by the amiloride analogue HOE 694 (HOE) suggested expression of NHE1-like activity in the BLM and NHE2-like activity in the LM of the SMG duct. Several acute and chronic treatments tested failed to activate NHE activity with low affinity for HOE as expected for NHE3. Hence, the physiological function and role of NHE3 in the SMG duct is not clear at present. 5. Activation of P2 receptors resulted in activation of an NHE-independent, luminal H+ transport pathway that markedly and rapidly acidified the cells. This pathway could be blocked by luminal but not basolateral Ba2+. 6. Stimulation of P2U receptors expressed in the BLM activated largely NHE1-like activity, and stimulation of P2Z receptors expressed in the LM activated largely NHE2-like activity. 7. The interrelation between basolateral and luminal NHE activities and their respective regulation by P2U and P2Z receptors can be used to co-ordinate membrane transport events in the LM and BLM during active Na+ reabsorption by the SMG duct.

Adenosine Triphosphate↗

Identification and cloning of a sequence homologue of dopamine beta-hydroxylase.

We have identified and cloned a cDNA encoding a new member of the monooxygenase family of enzymes. This novel enzyme, which we call MOX (monooxygenase X; unknown substrate) is a clear sequence homologue of the enzyme dopamine beta-hydroxylase (DBH). MOX maintains many of the structural features of DBH, as evidenced by the retention of most of the disulfide linkages and all of the peptidyl ligands to the active site copper atoms. Unlike DBH, MOX lacks a signal peptide sequence and therefore is unlikely to be a secreted molecule. The steady-state mRNA levels of MOX are highest in the kidney, lung, and adrenal gland, indicating that the tissue distribution of MOX is broader than that of DBH. Antisera raised to a fusion protein of MOX identifies a single band of the expected mobility by Western blot analysis. MOX mRNA levels are elevated in some fibroblast cell strains at replicative senescence, through this regulation is not apparent in all primary cell strains. The gene for MOX resides on the q arm of chromosome 6 and the corresponding mouse homolog has been identified.

Amino Acid Sequence↗

The reduction half cell in biomaterials corrosion: oxygen diffusion profiles near and cell response to polarized titanium surfaces.

Mechanically assisted corrosion processes can greatly increase the oxidation currents generated in passivating alloy systems like Co-Cr and titanium due to oxide film disruption. When oxide films are abraded, repassivation and ionic dissolution both occur at rates that are orders of magnitude higher than undisrupted surfaces. The excess electrons generated by these anodic processes must be consumed in corresponding reduction reactions that include the reduction of oxygen. If large enough, these reduction reactions may locally deplete the concentration of solution-dissolved oxygen and, in turn, affect cell behavior in the vicinity of the implant surface. To date, this hypothesis has not been tested. In the present study, a scanning electrochemical microscope was used to measure oxygen concentration profiles in vitro near a planar titanium electrode polarized to different voltages representative of those attainable by titanium undergoing mechanically assisted corrosion. The potentials investigated ranged from 0 mV to -1000 mV (AgCl). The oxygen concentration as a function of distance from the titanium surface was measured using a platinum-iridium microelectrode and an amperometric technique. Also, preliminary experiments were performed to assess the response of rat calvarial osteoblast-rich cells cultured for 2 h on titanium samples polarized to two different potentials (0 mV and -1000 mV versus AgCl). The results of this study indicate that oxygen concentrations near titanium surfaces are affected by sample potentials out to probe-sample distances as great as 500 microm. Within 2 microm of the surface, oxygen concentrations decreased by 15 to 25% for sample potentials between -100 and -500 mV. At potentials more negative than -600 mV, the oxygen concentration dropped rapidly to near zero by -900 mV. The cell experiments showed a statistically significant difference in the amount of cell spreading, as measured by projected cell area, between the two groups (p < 0.03), with the cells cultured at -1000 mV undergoing much less spreading. This implies that -1000 mV inhibits normal cell behavior at the titanium surface and that this is most likely due, at least in part, to a diminished oxygen supply.

Animals↗

Immunizing against depression and anxiety after spinal cord injury.

OBJECTIVE: To further report on the effectiveness of early psychological intervention in reducing anxiety and depressive mood in persons with spinal cord injury 2 years after injury. DESIGN: A nonrandomized, longitudinal, controlled trial. SETTING, OUTCOME MEASURES, AND INTERVENTION: Twenty-eight spinal cord injured persons participated in group cognitive behavior therapy during hospital rehabilitation. They were assessed for depressive mood and anxiety before, immediately after, and 12 and 24 months after treatment. The intervention group's responses on the measures were compared with a control group of 31 spinal cord injured persons who only received traditional rehabilitation services during their hospitalization. RESULTS: Subjects in the treatment group with high depression and anxiety scores before treatment were significantly less depressed and reduced their anxiety to a greater extent 2 years after the injury in comparison with similar persons in the control group. CONCLUSIONS: Group cognitive behavior therapy for spinal cord injured persons who are abnormally depressed and anxious appears to reduce depressive mood and anxiety in the short and long term.

Adult↗

Assessment of prostate cancer volume using endorectal coil magnetic resonance imaging: a new predictor of tumor response to neoadjuvant androgen suppression therapy.

OBJECTIVES: A clinical tool that can reliably assess prostate cancer response to androgen suppression is lacking. This pilot study was designed to identify the potential clinical factor(s) that correlate with tumor response after neoadjuvant therapy. METHODS: Twenty-one patients managed with definitive local therapy and neoadjuvant androgen suppression (median 3 months [range 2 to 7]) between 1995 and 1997 comprise the study population. Fisher's exact test was used to test the significance of the proportion of patients with a given clinical factor and the outcome of pathologic organ-confined disease. The clinical factors tested included preoperative prostate-specific antigen, biopsy Gleason score, clinical stage, months of total androgen suppression, the change in the endorectal magnetic resonance imaging (erMRI)-defined stage, the change in erMRI-defined tumor, and the change in the erMRI-defined prostate volume during neoadjuvant androgen suppression. RESULTS: All 21 patients had a decrease in the erMRI-determined prostate volume and prostate-specific antigen during androgen suppression, whereas only 10 of 21 (48%) had a reduction in the erMRI-determined tumor volume. There was a statistically significant increased proportion of patients with a decrease in the erMRI-determined tumor volume (P = 0.008) who had pathologic organ-confined disease. CONCLUSIONS: The results of this pilot study suggest that the changes in the erMRI-determined tumor volume occurring during androgen suppression may be predictive of the tumor response. Validation in a larger prospective study is currently underway.

Androgen Antagonists↗

Surface characteristics of Ti6Al4V alloy: effect of materials, passivation and autoclaving.

The properties of passivated films for Ti6Al4V alloy prepared by various methods (as-polished, brazed at 970 degrees C for 2 h and brazed at 970 degrees C for 8 h) were investigated. Four passivations (non-treated, nitric acid passivation, 400 degrees C-treated in air, and aged in boiling water), with or without autoclaving treatments, were adopted for evaluating the changes of surface properties, including chemical composition, chemical structure, and oxide thickness. From X-ray photoelectron spectroscopic (XPS) analyses, surface elements of copper and nickel in brazed samples were undetected for non-treated, acid-passivated and boiling water-aged specimens, while they were found in the 400 degrees C-treated specimen. The relative contents of Ti2++Ti3+ to Ti4+ were determined by passivation treatments, but were not related to the experimental materials and autoclaving treatment. Passivation and autoclaving decreased the Ti to Ti4+ ratio by virtue of an increase in oxide thickness. Of the four types of passivation treatment, the 400 degrees C thermal treatment exhibited the lowest content of suboxides and metallic elements and the thickest oxide by XPS analysis; however, this treatment may cause a desorption of the basic OH group in the hydration layer on the surface of titanium alloy.

Journal Article↗

A comparison of the corrosion behaviour and surface characteristics of vacuum-brazed and heat-treated Ti6Al4V alloy.

The corrosion characteristics of the brazed Ti6Al4V specimens were analysed and compared with respect to the conventionally heat-treated specimens by an electrochemical corrosion test. The object of this research was to explore the potentiality of the brazed titanium for biomaterials. The characteristics of the 1300 degrees C heat-treated and the 970 degrees C brazed specimens, with passivation and sterilization treatment, were evaluated by measurement of corrosion potential, Ecorr, corrosion current densities, Icorr, polarization resistance of the reacted surface films, Rp, in a potentiodynamic test. The experimental results show that the corrosion rates of the heat-treated and the brazed samples are similar at Ecorr, and the value of Ecorr for the brazed sample is noble to the heat-treated samples. The passive current density of the brazed specimen is either lower or higher than the heat-treated specimen, depending on the polarization potential. By Auger electron spectroscopic and high-resolution X-ray photoelectron spectroscopic analysis on specimens from the potentiostatic test, the elements of copper and nickel in the brazing filler were not detected while less alumina was found in the reacted film of the brazed specimens when compared with the heat-treated specimens. The implication of the results is discussed.

Journal Article↗

Priority areas for clinical research in palliative care nursing.

This report highlights a number of current research issues and concerns in palliative care nursing. The aim of the study was to identify high clinical nursing research priorities in palliative care, drawing on the expertise of nine (n = 9) clinical nurse consultants currently working in this specialty. The Delphi method was used to collect and process data in the study. Thirteen high research priorities emerged which have relevance for nursing practice, patient and family care in the hospice and community care setting. In the context of this study, the concept of high priority relates to research participant consensus on the most pressing nursing research problems which require investigation to improve clinical practice. Study findings provide direction for clinical research and continuing education in palliative care which may benefit expert nurses and their patients.

Attitude of Health Personnel↗

Persistence of herpes simplex virus type 1 DNA in chronic conjunctival and eyelid lesions of mice.

Herpes simplex virus type 1 (HSV-1) causes chronic blepharitis and conjunctivitis as well as keratitis in humans. The pathogenesis of these inflammatory ocular and dermal lesions is not well understood. We have examined the persistence of HSV-1 DNA and its relationship to inflammatory lesions in the conjunctiva and eyelid skin of mice which were inoculated with HSV-1 by the corneal route. Viral DNA was detected by in situ PCR in the conjunctiva and eyelid tissue of infected mice at 5, 11, 23, and 37 days postinfection (p.i.). This DNA was localized in the epithelial cells of the conjunctiva and hair follicles and in the epidermal cells of the eyelid skin. Viral proteins were not detected in the conjunctiva or the eyelid skin after 5 days p.i., even though histopathological lesions were found at 23 and 37 days p.i. in both tissues. The DNA-containing cells were adjacent to sites of inflammation in the chronic lesions in both the conjunctiva and the eyelid skin. A similar temporal and spatial relationship between HSV-1 DNA and inflammatory lesions has been previously reported for the cornea. Our data suggest that the lesions in the cornea, conjunctiva, and eyelid skin progress similarly. Further studies are required to determine whether the long-term presence of HSV-1 is involved in the mechanism by which these chronic inflammatory lesions develop. The presence of HSV-1 DNA in these extraocular tissues for extended periods may constitute persistent viral infection of nonneuronal cells.

Animals↗

Comparison of progenitor cell content in sequential peripheral blood progenitor collections after mobilization with chemotherapy and granulocyte macrophage colony-stimulating factor.

Optimal timing of peripheral blood progenitor cell (PBPC) harvest to collect maximal stem cell numbers is unknown. We assessed the progenitor cell content in 128 PBPC harvests from 21 patients primed with chemotherapy and granulocyte macrophage-colony stimulating factor (GM-CSF) in relation to absolute neutrophil count (ANC) at collection time. Samples were obtained by leukapheresis during rebound from chemotherapy-induced neutropenia while receiving GM-CSF, and assayed by flow cytometry for CD34+ and by colony assays for CFU-GM and BFU-E. The CD34+ cell concentrations per sample tended to be greater at an ANC < 1,000 mm3 and decreased with rising ANC (p = 0.001). The CFU-GM and BFU-E concentrations per sample remained relatively constant with rising ANC (p = 0.72, p = 0.90, respectively). Total CD34+ cell number per harvest per kg slightly increased with ANC levels (p = 0.044) whereas the total CFU-GM and the total BFU-E per kilogram increased more modestly with rising ANC (p < 0.001, p < 0.001, respectively). We conclude that after priming with chemotherapy and GM-CSF, PBPC could be collected at different absolute neutrophil counts without greatly affecting total CD34+ cell numbers. The greater concentration of CD34+ progenitor cells at a lower ANC together with the CFU-GM and BFU-E peaking with higher ANC suggest a less mature progenitor cell population at lower ANC levels.

Adult↗

The effectiveness of group psychological intervention in enhancing perceptions of control following spinal cord injury.

OBJECTIVE: This research investigated the effects of a structured psychological intervention, delivered during hospital rehabilitation, on the perceptions of control in people with spinal cord injury (SCI). METHOD: A longitudinal study was designed to assess perceptions of control (using an objective measure of locus of control) in SCI persons who participated in specialised group cognitive-behavioural therapy (CBT) during hospital rehabilitation. The treatment SCI group's responses on locus of control were compared with a control group of SCI persons who only received traditional rehabilitation services during their hospitalisation. RESULTS AND CONCLUSIONS: Mean locus of control scores were not high (i.e. external) for both groups and there were no overall group differences on locus of control responses across time in comparison to the control group. However, subjects in both groups who initially perceived life as externally controlled were extracted to form subgroups. The members of the subgroup who received CBT were significantly more likely to feel in control of themselves 2 years post injury compared to similar persons in the control group. Furthermore, an external locus of control was significantly but mildly associated with depressive mood 2 years after the injury. This research suggests that the provision of a structured psychological program in the rehabilitation stage will be beneficial for many SCI persons who feel that they have little control over their lives.

Adolescent↗

Myxoid leiomyosarcoma of the uterus: a case report and review of the literature.

A case report of myxoid leiomyosarcoma of the uterus in a 54-year-old woman is presented as a rare variant of uterine sarcoma. Only 14 cases have been described in the literature. These tumors have a striking myxoid appearance and exhibit highly malignant behavior despite their low mitotic index. Although it is difficult to establish the nature of the neoplastic cells in the myxoid areas, both light microscopical and immunohistochemical characteristics showed features of smooth muscle cells in some of the cellular areas. Our patient had a tumor which arose in association with hyalinized benign leiomyomatous lesion. Like other reported cases of myxoid leiomyosarcoma, the tumor behaved aggressively.

Female↗

[Myasthenia gravis in Santo Tomás Hospital 1990-1997].

Myasthenia Gravis is an infrequent disease. Diagnosis and treatment must be done early to avoid high morbidity that can compromise patients lives. Nine cases were identified during the eight year 1990-1997 at the Santo Tomas Hospital of Panama city but one had to be excluded because he refused treatment. Most of the patients (7/8) had symptoms for more than 3 months. The diagnosis of Myasthenia Gravis requires a high index of suspicion and the clinical impressión must be confirmed by various diagnostic studies that include the edrophonium test, the repetitive stimulation test, the therapeutic test with pyridostigmine, the determination of acetylcholine anti-receptor antibodies and a CT Scan of the thorax. Medical treatment consists mainly of anticholinesterase agents and surgical treatment consists of thymectomy by means of an extended transternal ablation. Operative results were excellent, seven out of eight improved.

Adolescent↗

BK virus as a potential co-factor in human cancer.

BK virus (BKV) is a member of the polyomavirus family that persistently infects 75-80% of the human population. BKV encodes a large T antigen which is responsible for the transforming functions of the virus. Recent studies have shown an association of BKV DNA with a variety of human tumours including pancreatic islet, brain, urinary tract and Kaposi's sarcoma. Despite the detection of BKV DNA in several human tumours, there is no clear evidence for a causative role in tumour formation. We have sought to characterize the interactions of BKV TAg with cellular tumour suppressor proteins including p53, pRb, p107, and p130 in an attempt to further understand the molecular mechanisms of transformation by BKV. We have shown that BKV TAg can bind to and functionally inhibit p53 and the p53-mediated response to DNA damage. Additionally, we have shown that low levels of BKV TAg are sufficient to induce free E2F and a serum-independent phenotype despite the absence of detectable interactions with pRb family members. Taken together, these results suggest that BKV TAg can both inhibit the cellular response to DNA damage and induce proliferation, allowing for potential accumulation of mutations in cellular growth control genes. These results suggest a possible role for BKV TAg in cellular transformation and tumour formation in the human host.

Antigens, Polyomavirus Transforming↗