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Biomedical subjects

C Smith

Publications and source records attributed to C Smith.

At least 271 records · Page 15Linked to original sources
PubMed1999

Inverse agonist properties of dopaminergic antagonists at the D(1A) dopamine receptor: uncoupling of the D(1A) dopamine receptor from G(s) protein.

The interaction of dopaminergic antagonists with the D(1A) dopamine receptor was assessed in PC2 cells that transiently express this receptor. The maximal binding and dissociation constants for the D(1A) dopamine receptor, using the ligand [(125)I]SCH23982 were 0.38 +/- 0.09 nM and 1 to 4 pmol/mg, respectively, when assessed 48 h after transfection with cDNA encoding the rat D(1A) receptor. Basal adenylyl cyclase activity increased 50 to 60% in membranes of transfected PC2 cells compared with control membranes. The dopaminergic antagonists clozapine, cis-flupenthixol, (+)-butaclamol, haloperidol, chlorpromazine, and fluphenazine inhibited constitutive adenylyl cyclase activity in membranes of cells expressing the D(1A) receptor. SCH23390, a selective D(1) dopamine receptor antagonist, and (-)-butaclamol did not alter basal cyclase activity, whereas dopamine increased enzyme activity in membranes expressing the D(1A) dopamine receptor. The coupling of D(1A) receptors with G(s) proteins was examined by immunoprecipitation of membrane G(salpha) followed by immunoblotting with a D(1A) dopamine receptor monoclonal antibody. Clozapine, cis-flupenthixol, (+)-butaclamol, haloperidol, and fluphenazine but not SCH23390 or (-)-butaclamol decreased D(1A) receptor-G(salpha) coupling by 70 to 80%, and SCH23390 was able to prevent the receptor-G(salpha) uncoupling induced by haloperidol or clozapine. These results indicate that some dopaminergic antagonists suppress basal signal transduction and behave as inverse agonists at the D(1A) dopamine receptor. This action of the dopamine receptor antagonists may contribute to their antidopaminergic properties that seem to underlie their clinical actions as antipsychotic drugs.

Adenylyl Cyclases↗
PubMed1999

Verrucous carcinoma of the female breast.

Verrucous carcinoma is a rare skin malignancy of squamous cell origin. It is characterised by negligible cellular atypia and a low mitotic rate. These are reflected in slow locally invasive behaviour and very infrequent metastatic spread. The tumour is also recognised in oral and anogenital sites. Cutaneous lesions present most commonly on the sole of the foot. We report a unique case occurring in the female breast.

Aged↗
PubMed1999

Treatment resistant small cell carcinoma of the cervix.

BACKGROUND: Small cell undifferentiated carcinoma of the cervix is an uncommon malignancy with a poor prognosis. Treatment of localized disease has an approximate 40% 5-year survival with multimodality therapies. CASE REPORT: We describe the case of a 24-year-old woman with small cell carcinoma of the cervix that recurred locally despite intensive chemotherapy and radiotherapy. Hysterectomy was performed and the patient is now 18 months disease free. Following treatment, the pathological appearance of the tumor had changed from a typical small cell neuroendocrine malignancy to a more intermediate neuroendocrine cell type. CONCLUSION: Small cell carcinoma of the cervix is a rare aggressive malignancy that may require cytostatic multimodality therapy including chemotherapy, radiotherapy and surgery, even in early stage disease.

Adult↗
PubMed1999

Ureterocele arising from a lower-pole moiety.

We report on an uncommon case of a ureterocele arising from the lower-pole ureter in a duplex system. To our knowledge, this represents the 3rd such case reported in the English literature. Ultrasonography and retrograde pyelogram established the diagnosis. The patient underwent left upper-pole nephroureterectomy with excision of the ureterocele and cross-trigonal ureteral reimplantation.

Child, Preschool↗
PubMed1999

Regulation of cell surface tissue transglutaminase: effects on matrix storage of latent transforming growth factor-beta binding protein-1.

Using a cytochemical approach, we examined the role of tissue transglutaminase (tTgase, Type II) in the incorporation of latent TGF-beta binding protein-1 (LTBP-1) in the extracellular matrix of Swiss 3T3 fibroblasts in which tTgase expression can be modulated through a tetracycline-controlled promoter. Increased tTgase expression led to an increased rate of LTBP-1 deposition in the matrix, which was accompanied by an increased pool of deoxycholate-insoluble fibronectin. Matrix deposition of LTBP-1 could also be reduced by the competitive amine substrate putrescine. Immunolocalization at the fluorescence and electron microscopic level showed that extracellular tTgase is located at the basal and apical surfaces of cells and at cell-cell contacts, and that LTBP-1 is co-distributed with cell surface tTgase, suggesting an early contribution of tTgase to the binding of LTBP-1 to matrix proteins. LTPB-1 was also found to co-localize with both intracellular and extracellular fibronectin, and increased immunoreactivity for LTBP-1 and fibronectin was found in large molecular weight polymers in the deoxycholate-insoluble matrix of fibroblasts overexpressing tTgase. We conclude that regulation of tTgase expression is important for controlling matrix storage of latent TGF-beta1 complexes and that fibronectin may be one extracellular component to which LTBP-1 is crosslinked when LTBP-1 and tTgase interact at the cell surface. (J Histochem Cytochem 47:1417-1432, 1999)

3T3 Cells↗
PubMed1999

Homogeneous Cell- and Bead-Based Assays for High Throughput Screening Using Fluorometric Microvolume Assay Technology.

High throughput drug screening has become a critical component of the drug discovery process. The screening of libraries containing hundreds of thousands of compounds has resulted in a requirement for assays and instrumentation that are amenable to nonradioactive formats and that can be miniaturized. Homogeneous assays that minimize upstream automation of the individual assays are also preferable. Fluorometric microvolume assay technology (FMAT) is a fluorescence-based platform for the development of nonradioactive cell- and bead-based assays for HTS. This technology is plate format-independent, and while it was designed specifically for homogeneous ligand binding and immunological assays, it is amenable to any assay utilizing a fluorescent cell or bead. The instrument fits on a standard laboratory bench and consists of a laser scanner that generates a 1 mm(2) digitized image of a 100-µmm deep section of the bottom of a microwell plate. The instrument is directly compatible with a Zymark Twistertrade mark (Zymark Corp., Hopkinton, MA) for robotic loading of the scanner and unattended operation in HTS mode. Fluorescent cells or beads at the bottom of the well are detected as localized areas of concentrated fluorescence using data processing. Unbound flurophore comprising the background signal is ignored, allowing for the development of a wide variety of homogeneous assays. The use of FMAT for peptide ligand binding assays, immunofluorescence, apoptosis and cytotoxicity, and bead-based immunocapture assays is described here, along with a general overview of the instrument and software.

Journal Article↗
PubMed1999

Dose independent pharmacokinetics of caffeine after intravenous administration under a chronic food-limited regimen.

Several studies have shown that caffeine follows non-linear pharmacokinetics in both rats and humans. Recent data have demonstrated that caffeine may following linear pharmacokinetics when administered orally and intraperitoneally to food-limited rats. In this study the pharmacokinetics of caffeine was analyzed following intravenous (i.v.) administration to rats under a food-limited regimen. Four rats were administered four doses of caffeine and a standard dose of the caffeine metabolites, paraxanthine, theobromine, and theophylline. Caffeine pharmacokinetic parameters were dose independent following intravenous doses ranging from 1 to 20 mg/kg. Furthermore, the caffeine area under the curve (AUC) increased linearly as a function of dose. The mean fraction of caffeine converted to paraxanthine, theobromine, and theophylline was 16%, 16%, and 7%, respectively. The linear pharmacokinetics demonstrated in the present study may be attributed to the induction of hepatic metabolism under a chronic food-limited regimen.

Animals↗
PubMed1999

Syme amputation for the treatment of fibular deficiency. An evaluation of long-term physical and psychological functional status.

BACKGROUND: Syme amputation is an accepted treatment for fibular deficiency. With improvement in limb-lengthening procedures, there has been renewed interest in limb salvage for these patients. The purpose of the present study was to evaluate the physical and psychological results in ten young adults who had had a Syme amputation for the treatment of fibular deficiency when they were children. METHODS: The evaluation consisted of physical examination, prosthetic assessment, psychological testing, and physical performance testing of knee extension and flexion with use of a Cybex-II dynamometer. RESULTS: Five patients reported no difficulty with the involved limb since the Syme amputation, four had had minor secondary procedures (three medial distal femoral or proximal tibial hemiepiphyseodeses, one reconstruction with an autologous patellar ligament graft, one revision of the stump, and one tibial osteotomy) on the affected extremity, and one had mild instability of the knee that had been treated nonoperatively. All ten patients had an appropriate, functional Syme prosthesis, and none reported difficulty with walking or running. On psychological testing, this group generally did not differ from the norm with regard to occupational satisfaction, personal growth, relationships with family members and peers, and recreational behavior. The patients' overall assessment of self-reported quality of life and self-esteem was similar to that of normative adult samples. In general, these patients were leading active, productive lives and had always done so. CONCLUSIONS: On the basis of the results of this study, we concluded that young adults who have had a Syme amputation apparently are not limited in their ability to pursue and achieve personal goals. In order to justify recommending limb salvage rather than early Syme amputation for the treatment of fibular deficiency, the results of multistaged lengthening and reconstruction would have to match the functional, psychological, and cost-effective results for the patients whom we studied, who had had a Syme amputation.

Adolescent↗
PubMed1999

Post transplant CD8+ gammadelta T-cell lymphoma associated with human herpes virus-6 infection.

Gammadelta T-cell lymphoma is a rare T-cell lymphoproliferative disorder that has been reported in both immunocompetent and immunocompromised persons. This report describes a forty eight year old patient who developed gammadelta T-cell lymphoma four years after undergoing living-related kidney transplantation. The lymphoma expressed CD2, CD3, CD7, CD8 and CD56, and the gammadelta T-cell receptor and did not express CD5, CD4 and the alphabeta T-cell receptor. In addition, HHV-6 was cultured from the patient's bone marrow, marking the first time that this virus has been associated with gammadelta T-cell lymphoma. Since all patients with gammadelta T-cell lymphoma described to date have responded poorly to standard combination chemotherapies, the patient was treated with the purine analogue 2-chlorodeoxyadenosine. While he responded transiently to treatment, long term remission was not achieved indicating that additional therapeutic approches still need to be developed, for the management of this disorder.

Antigens, CD↗
PubMed1999

Beyond correspondence, video conferencing, and voice mail: Internet-based master's degree courses in nursing.

The changing health care system and increasing demands for primary care providers have prompted an increase in nurse practitioner programs in the United States. Nurses in rural areas that are underserved by primary care practitioners often are faced with time and distance barriers to returning to school for advanced education. This article describes Internet-based courses as a unique distance learning platform for preparing primary care nurse practitioners at the University of Kansas (KU) School of Nursing. Discussion includes course development process, matching methods to course content, and other information on promoting interaction between students and faculty.

Curriculum↗
PubMed1999

Interventions in a heart transplant recipient with a histrionic personality disorder.

Organ transplantation is a psychosocially demanding process. Patients must undergo a comprehensive evaluation to await a donor organ that may never become available. After transplantation, recipients must deal with the acceptance of a new organ and comply with a medical regimen that includes numerous medications, follow-up exams, and procedures. Emotional well-being is monitored throughout the transplant process. However, despite the best of efforts and thorough pretransplant bio-psycho-social evaluations, it is possible for patients to have significant psychopathology that remains undetected. Following the stress of transplantation, such patients may present with exacerbation of symptomatology, which has the potential to negatively affect compliance and long-term outcome.

Adaptation, Psychological↗
PubMed1999

Multidisciplinary team dynamics in the production of problem-based-learning cases in issues related to older adults.

Two important goals in allied health education are to prepare future allied health professionals to function as members of interdisciplinary teams and to increase their awareness of issues related to the growing older adult population. The responsibility for achieving these goals rests on the faculty and administrators of allied health education programs, who may not themselves be proficient in either of these domains. A multidisciplinary team of health educators and administrators was brought together to produce six problem-based learning (PBL) cases related to older adults. Members of the team represented a variety of disciplines in health care, diverse philosophies of educational development, a variety of roles in allied health education, and differing levels of knowledge of issues related to older adults--parameters similar to those found in the members of an interdisciplinary healthcare team. The methods by which this multidisciplinary group functioned and the dynamics in attaining the goals of the project are presented.

Aged↗
PubMed1999

Pneumocystis carinii pneumonia in HIV infected patients from South Africa.

OBJECTIVE: To compare the spectrum of pulmonary disease in human immunodeficiency virus positive patients of African and European origin, with particular reference to Pneumocystis carinii pneumonia. DESIGN: Descriptive study with retrospective record review. SETTING: Tertiary care, university teaching hospitals in Johannesburg, South Africa. SUBJECTS: Sixty seven HIV-infected patients and 36 HIV-negative renal transplant patients (who served as controls) whose sputa were negative for tuberculosis and Pneumocystis carinii, and who had fibreoptic bronchoscopic evaluation for pulmonary disease between January 1985 and August 1992. MEASUREMENTS: Histological and cytological evaluation of pulmonary diseases. RESULTS: In the HIV infected group Pneumocystis carinii pneumonia was the most frequent disease in patients of both African and European origin but occurred less commonly in Africans than in Europeans (27.3% and 58.8%, respectively; p = 0.01). There was no statistically significant difference between patients of African and European origin in the frequency of any other diagnosis. In the renal transplant group the most frequent diagnosis was non-specific interstitial pneumonitis (Africans 33.3%, Europeans 37.0%), followed by Pneumocystis carinii pneumonia (Africans 22.2%, European 14.8%). There was no difference between HIV-infected and renal transplant patients in the frequency of any diagnosis. CONCLUSION: Pneumocystis carinii pneumonia should be considered in the diagnosis of HIV-infected African patients with pulmonary disease whose sputum smears for tuberculosis are negative.

AIDS-Related Opportunistic Infections↗
PubMed1999

Screening of high-risk infants using distortion product otoacoustic emissions.

Otoacoustic emissions have been used as an objective and noninvasive test of cochlear function. Due to its ease of use, accuracy, and test-retest reliability, otoacoustic emissions testing is considered an excellent tool for evaluating difficult-to-test patients. This project involved screening infants at high risk of congenital hearing loss. These infants were selected from the Special Infant Clinic at Queen's University, Kingston, Ontario. The first part of this project was to establish a distortion product otoacoustic emissions (DPOAEs) "norm" as the reference for this group of patients. A prospective study was then conducted to compare DPOAE and auditory brainstem response (ABR) as screening tools for this group of patients. Auditory brainstem response has been the gold standard for evaluating the hearing status of these infants. We will also present our experience in testing over 50 patients at high risk of congenital hearing loss using DPOAEs.

Audiometry, Evoked Response↗
PubMed1999

African Americans and the medical establishment.

The African American community's response to the AIDS epidemic has reflected the profound mistrust of the medical establishment which many African Americans feel. Among African Americans, the belief that the epidemic originated in a genocidal plot is widespread. It is thought that organized medicine has been significantly involved in this plot. If we look at African Americans' historical relationship to the medical establishment from the era of slavery to the recent past, the suspicious attitudes which make such beliefs possible can be seen as an intelligible response to a new disease which disproportionately affects African Americans. Successful medical and public health responses to the epidemic have depended and will continue to depend upon overcoming the historical legacy of suspicion and gaining the trust of the community.

Acquired Immunodeficiency Syndrome↗