Clearance and micropuncture study of renal function in mercuric chloride treated rats.
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Biomedical subjects
Publications and source records attributed to R Anderson.
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BACKGROUND: Many gene therapy applications require the co-ordinated delivery of more than one reading frame. We wished to systematically compare IRES in the context of a retroviral vector to determine which was the most effective for protein production and viral titre. To do this we monitored expression of IL-12, as co-ordinated expression of both p35 and p40 subunits is required for production of the active heterodimer. METHODS: Retroviral vectors were constructed to express human IL-12 in which an IRES initiates translation of the p40 subunit, with the IRES optimally aligned to the initiation codon of p40. Vectors containing an IRES from either polio virus (PV), encephalomyocarditis virus (EMCV), foot and mouth disease virus (FMDV) or murine leukaemia virus (MLV) were compared with a vector expressing IL-12 as a single protein (Flexi-12; in which the two IL-12 subunits are linked by a peptide). RESULTS: All vectors produced high titre virus and directed synthesis of IL-12 in target cells. The bicistronic vectors containing the IRES from EMCV and PV were the most effective in infected 3T3 cells, producing up to 40 ng IL-12/10(6) cells/48 h, similar to the 50 ng IL-12/10(6) cells/48 h obtained with Flexi-12. The IRES from PV was the most efficient in human melanoma cells. CONCLUSIONS: Bicistronic retroviral vectors have been constructed that effectively transduce target cells and produce high levels of protein. Target cell specificity of IRES function was observed. The combination of Flexi-12 and the IRES from PV will be useful in the generation of vectors expressing IL-12 with a second protein such as IL-2 for transduction of melanoma cells.
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A prospective and randomized clinical trial of an inception cohort of diabetic kidney recipients to test the hypothesis that maximized metabolic control of diabetes prevents or delays diabetic nephropathy in the renal allografts was initiated approximately three years ago. Notwithstanding the fact that all our diabetic patients were on prednisone and therefore metabolically unstable, we achieved and maintained a clear difference between the standard control (group A) and the maximized control patients (group B). At 13 months of study, the mean fasting blood glucose mg% (A: 242 +/- 22, B: 130 +/- 9, p less than 0.001), nonfasting blood glucose (A: 276 +/- 40, B: 135 +/- 10, p less than 0.001), 24 hour urine glucose (A: 85 +/- 16, B: 5 +/- 1, p less than 0.001), and glycosylated hemoglobin % (A: 13 +/- 0.9, B: 10 +/- 0.8, p less than 0.01) were all clearly and statistically significantly higher for the group A patients. These results show the feasibility of such a trial using the tools available today to treat diabetes.
Although iris melanomas have an excellent prognosis when diagnosed and treated early, they should not be considered benign lesions. The authors report the orbital recurrence of a melanoma in a patient whose eye had been enucleated 30 years earlier because of an iris melanoma. The clinical, epidemiological and pathological characteristics of iris melanomas are summarized and compared to those of other uveal melanomas. The similarities suggest that iris melanomas are not by nature more benign than other uveal melanomas and that their better prognosis is due to the earlier detection allowed by their more obvious location.
This study examined outcome data from two nurse-midwifery operated home birth services in Texas. All clients who planned a home birth within the two services during 1987 comprised the population. Analyses revealed that women choosing home birth with these nurse-midwives were more frequently married, usually white, and more educated when compared with the overall U.S. childbearing population. Analgesia, episiotomy, and cesarean delivery were all found at lower rates than is reported when birth occurs in a hospital setting; complications occurred less frequently or at similar rates to those reported in the home birth literature and national statistics. Research, educational, and clinical implications of the study are discussed.
This paper describes efforts by the National Centers of Excellence in Women's Health to develop a woman-specific primary care satisfaction instrument suitable for quality improvement and research.
Because of improved life expectancy for people with HIV infection, today's clinician needs to understand and manage chronic symptoms that limit function and quality of life. The authors describe two collaborative HIV symptom-management studies conducted by the Division of Intramural Research of the National Institute of Nursing Research. Studies such as these are necessary to provide nurses and other healthcare personnel with the knowledge essential for appropriate, comprehensive, and quality patient care.
Clinically stable HIV-infected men (N = 106) receiving investigational antiretrovirals were recruited. Subjects were divided into three HIV disease severity groups by CD4+ cell count. Standard measures of body composition were assessed, as well as serum measures of visceral protein stores and kilocalorie intake. Group 1 subjects (CD4+ T cells < 200) had significantly lower measures of body fat as compared with Group 2 (CD4 between 200 and 600) and Group 3 (CD4 > 600) despite adequate kilocalorie intake. Group 2 and Group 3 were not significantly different from each other. Our entire cohort had significantly lower muscle mass compared to norms. Our data demonstrate that people with advanced HIV disease have reduced muscle and fat.
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