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Biomedical subjects

C E Nelson

Publications and source records attributed to C E Nelson.

At least 37 records · Page 2Linked to original sources

Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.

Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LFS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.

Amino Acid Sequence↗

p53 functions as a cell cycle control protein in osteosarcomas.

Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfected cells to progress into S phase. This suggests that the role of the p53 gene as an antioncogene may be in controlling the cell cycle in a fashion analogous to the check-point control genes in Saccharomyces cerevisiae.

Amino Acid Sequence↗

Adult physical dysfunction content in professional curricula.

This study examined the content of occupational therapy professional curricula as it pertains to adult physical dysfunction and the opinions and perceptions of faculty responsible for this content area. Survey results from 28 of 66 academic institutions offering professional-level education were received and analyzed. A great diversity in content and emphasis was reflected in the areas of medical conditions, general approaches to evaluation and treatment, specific evaluations, and specific treatment techniques and modalities. Most of the respondents were pleased with students' performances in physical dysfunction Level II fieldwork, believed that course work was applicable to local clinical settings, and agreed that courses were constantly changing to reflect evolving occupational therapy theory. Approximately 30% of the respondents believed that they had inadequate time to prepare students for entry-level practice, and about half agreed that their department had the necessary equipment to teach evaluation and treatment content.

Adult↗

Effect of chemical treatment of poultry feed on survival of Salmonella.

After treatment with a chemical preservative [Myco Curb (Kemin Industries, Des Moines, IA) at .25, .5, .75, or 1.0%], sterilized commercial poultry feed was contaminated with either Salmonella typhimurium ATCC 6994 or with a strain isolated from commercial broiler carcasses. All treatments resulted in the elimination of detectable Salmonella from heavily contaminated feed within 72 h and from lightly contaminated feed within 24 h. Nonsterilized feed showed similar results. Commercial feed fed to broilers for 56 days and inoculated with Salmonella daily for Days 35 to 56 was treated with the chemical preservative at .5 and 1.0% for the last 7 days. Treatment resulted in a reduction of the number of fecal and intestinal samples positive for Salmonella, demonstrating elimination of Salmonella in the feed by use of the feed preservative.

Animal Feed↗

Ornithine decarboxylase activity and polyamine content in normal renal tissue and in renal carcinoma.

Ornithine decarboxylase (ODC) activity and contents of putrescine, spermidine and spermine were determined in cortical and medullary tissue and clear cell tumours in human kidneys. Medullary ODC activity was 75 +/- 9% (n = 6; p less than 0.05) of the respective cortical value. The ODC activity in renal tumours varied considerably but did not differ significantly from the respective cortical values. Similar concentrations of putrescine were found in cortex and medulla, but a 5-fold increase was found in the tumours (p less than 0.02). Significantly lower values (p less than 0.01) of spermidine and spermine were found in medulla when compared to cortex. No significant change was found for these amines in the carcinomas when compared with corresponding cortical tissue.

Adult↗

Automatic prediction of platelet utilization by time series analysis in a large tertiary care hospital.

The authors investigated the potential of various time series models to aid in the prediction of platelet utilization patterns at the authors' institution. During a seven-week feasibility study, prediction accuracy of time series models was slightly inferior to that of an experienced platelet transfusion coordinator. The models that adjusted for day-of-the-week variability were superior to simpler models in a prospective evaluation over a three-month period. Conversion to a time series model for platelet utilization prediction has resulted in significant savings in personnel costs for management of platelet concentrate inventory in the blood bank. Outdate rates have been lower than those achieved by the platelet transfusion coordinator, with no sacrifice in availability occurring during the evaluation period.

Blood Banks↗

Regulation of Proteinase Inhibitor Synthesis in Tomato Leaves : IN VITRO SYNTHESIS OF INHIBITORS I AND II WITH mRNA FROM EXCISED LEAVES INDUCED WITH PIIF (PROTEINASE INHIBITOR INDUCING FACTOR).

Messenger RNA was isolated from young excised tomato leaves, induced to accumulate proteinase Inhibitors I and II with the proteinase inhibitor inducing factor (PIIF), and translated in vitro in a rabbit reticulocyte lysate system. Translatable messenger RNAs specific for Inhibitors I and II were present in PIIF-induced leaves but were not present without PIIF induction. The nascent in vitro-synthesized inhibitors migrated with an apparent molecular weight 2,000 to 3,000 daltons larger than that of the two inhibitors isolated from leaves. The molecular weights of the preinhibitors were identical whether translated from mRNA from PIIF-induced leaves or translated from mRNA isolated from wounded leaves. Incubation of excised PIIF-induced plants in CO(2)-free air doubled the rate of in vivo synthesis of Inhibitor I over that in normal air (Ryan CA 1977 Biochem Biophys Res Commun 77: 1004-1008) but did not affect the rate of in vivo Inhibitor II accumulation. The rate of incorporation of (35)SO(4) (2-) into soluble proteins was 70% less when leaves were incubated in CO(2)-free air rather than normal air. Messenger RNA isolated from PIIF-induced plants incubated in the presence or absence of CO(2) was translated in vitro. The amount of in vitro-translatable mRNA present for each inhibitor (per microgram total mRNA) was the same in leaves incubated in either atmosphere. Therefore, the increased rate of synthesis and accumulation of Inhibitor I in a CO(2)-free atmosphere does not appear to result from an increased level of mRNA but appears to be controlled at a posttranscriptional level.

Journal Article↗

In vitro synthesis of pre-proteins of vacuolar compartmented proteinase inhibitors that accumulate in leaves of wounded tomato plants.

Two proteinase inhibitor proteins that are compartmented in leaf vacuoles (lysosomes) were synthesized in vitro. mRNA was isolated from 17-day-old expanding tomato leaves by extraction with chaotropic buffers followed by chromatography on oligo(dT)-cellulose and was translated with a rabbit reticulocyte lysate system. Preparations of mRNA from leaves of both wounded plants and unwounded plants directed the incorporation of equivalent amounts of label into trichloroacetic acid-precipitable proteins. Only mRNA from leaves of wounded plants directed label into proteins that could be immunoprecipitated with rabbit IgG specific for either inhibitor I or inhibitor II. These results indicate that the wound-induced accumulation of proteinase inhibitors I and II in leaf vacuoles is a result of the presence of translatable mRNA species not present in leaves of unwounded plants. Gel electrophoresis of the immunoprecipitates in NaDodSO(4)/urea/polyacrylamide gels revealed that inhibitors I and II were translated in vitro as precursors about 2000 daltons larger than the inhibitors found in leaves. The presence of the additional polypeptide sequences in the newly synthesized inhibitors indicates that the inhibitors are processed either during or after synthesis, and the presequences may be signal peptides that are part of the process of inhibitor transport into the vacuolar compartments of tomato leaf cells.

Journal Article↗

N-acetyltransferase phenotype and risk in urinary bladder cancer: approaches in molecular epidemiology. Preliminary results in Sweden and Denmark.

A variable but often significant proportion of urinary bladder cancer in urban areas can be attributed to occupational and cultural (cigarette smoking) situations associated with exposures to various arylamines. The variable N-acetylation of carcinogenic arylamines by human hepatic enzyme systems, the known genetic regulation and polymorphic distribution of this enzyme activity in humans, and the known enhanced susceptibility of individuals with the genetically-distinct "slow acetylator" phenotype to various arylamine toxicities, has prompted examination of possible correlations between N-acetyltransferase phenotype and urinary bladder cancer risk in rural and urban populations. In this context, N-acetylation is viewed as a component of detoxication pathways with respect to arylamine bladder carcinogenesis. In preliminary utilizations of this approach, a population of urban urinary bladder cancer patients from Copenhagen, Denmark displayed a 13% excess (p = 0.065) of individuals with the slow acetylator phenotype (46/71 = 64.8%) when compared to a Danish control population (38/74 = 51.4%). These data are consistent with the possibility that arylamines may play an etiological role in bladder cancer in this locale and that slow acetylator individuals may be at higher relative risk (1.74) than rapid acetylator individuals. As 95% of patients reported histories of smoking, it was not possible to isolate and examine smoking factors. In contrast, a population of rural urinary bladder cancer patients from Lund, Sweden, where bladder cancer incidence (20/100,000) (1971) is lower than in Copenhagen (43.8/100,000) (1968-72), no difference in slow acetylator distribution was observed between bladder cancer (80/115 = 69.6%) and Swedish control (79/118 = 66.9%) populations, indicating a relative lack of involvement of arylamines in the etiology of rural bladder cancer. Populations of "spontaneous" bladder cancer patients would be expected to contain variable portions of disease related to arylamine exposure and would be less likely to display a detectable correlation than would an industrial population with documentable arylamine exposure. Consequently, confirmation of this hypothesis is being pursued by examination of industrial populations in an effort to obtain an empirical estimate of relative risk for slow and rapid acetylator phenotypes. These studies involve exposure-matched workmen both with and without bladder cancer.

Acetyltransferases↗

Characterization of different regions of the normal human urinary bladder by means of scanning electron microscopy.

A study of the normal human urinary bladder and the proximal urethra was performed using scanning electron microscopy (SEM). Biopsies were evaluated from 27 male patients with benign prostatic hyperplasia, without history or sign of urinary tract malignancy and with cystoscopically normal mucosal finding. The specimens were obtained from the dome, the side-walls and the trigone of the bladder. The characteristic surface architecture of the transitional epithelium was observed in different anatomical regions of the human urinary bladder.

Aged↗

Surface characteristics of malignant human urinary bladder epithelium studied with scanning electron microscopy.

Biopsies were obtained from 28 male and seven female patients with cystoscopically and histologically confirmed urinary bladder carcionoma. Tissue specimens for light microscopy and scanning electron microscopy (SEM) were obtained from the tumours as well as from cystoscopically tumour-free mucosa of the dome, the lateral walls and the trigone of the urinary bladder and also from the proximal urethra. Certain surface structural changes, which seem to represent malignancy, present in different regions of the urinary bladder were detected by SEM, although not visible by light microscopy.

Aged↗

Collection and evaluation of normal exfoliated urinary bladder cells in man using scanning electron microscopy.

Normal exfoliated urinary bladder cells were collected from midstream urine samples from 21 male patients. Procedures for urine filtration using Millipore filters of Nucleopore filters, cell fixation and preparation for scanning electron microscopy investigation were developed. Correlations were made between the surface morphology of exfoliated cells and that of biopsies from different anatomical regions of the urinary bladder. Scanning electron microsocopy (SEM) of exfoliated normal urinary bladder cells proved to be a more sensitive method for discovering cellular surface details than light microscopy. This information forms the basis for further SEM studies of cell surface alterations due to urothelial diseases.

Cell Membrane↗