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Biomedical subjects

D C Young

Publications and source records attributed to D C Young.

At least 109 records · Page 6Linked to original sources

Radical neck dissection: is it enough?

This series of 307 patients who underwent radical neck dissection showed an overall recurrence rate of 19 percent. Clinical staging of disease was an accurate predictor of both recurrence and survival. Extranodal disease dramatically increased recurrence and decreased survival. Although our recurrence rate after radical neck dissection was lower than that previously reported for surgery alone, it was still significantly higher than that after adjuvant radiotherapy. We conclude that histologically proved neck disease should be treated by radical neck dissection, followed by adjuvant radiotherapy to decrease recurrence and, it is hoped, improve survival.

Aged↗

Control of bacterial alkaline phosphatase synthesis and variation in an Escherichia coli K-12 phoR mutant by adenyl cyclase, the cyclic AMP receptor protein, and the phoM operon.

Mutant phoR cells show a clonal variation phenotype with respect to bacterial alkaline phosphatase (BAP) synthesis. BAP clonal variation is characterized by an alternation between a Bap+ and Bap- phenotype. The switching is regulated by the phoM operon and the presence of glucose; the pho-510 mutant form of the phoM operon abolishes both BAP clonal variation and the effect of glucose (B.L. Wanner, J. Bacteriol. 169:900-903, 1987). In this paper we show that a mutation of the adenyl cyclase (cya) and the cyclic AMP receptor protein (crp) gene also abolish BAP clonal variation; either simultaneously reduces the amount of BAP made in phoR mutants. Also, the pho-510 mutation is epistatic; it increases BAP synthesis in delta cya phoR and delta crp phoR mutants. These data are consistent with the wild-type phoM operon having a negative, as well as a positive, regulatory role in gene expression. Furthermore, the data suggest that adenyl cyclase and Crp indirectly regulate BAP synthesis in a phoR mutant via an interaction with the phoM operon or its gene products. However, phoM operon expression was unaffected when tested with phoM operon lacZ transcriptional fusions. In addition, the switching Bap phenotype was not associated with an alternation in phoM operon expression.

Adenylyl Cyclases↗

Field experience trials comparing narasin and monensin.

Narasin is effective against all species of chicken coccidia when tested in battery cage and floor pen studies. To confirm the efficacy of narasin under practical broiler production conditions, the drug was fed at concentrations of 60 ppm or 80 ppm to broiler chickens being raised by six different commercial broiler producers in five different geographic areas. Monensin was fed in each trial at a concentration of 100 ppm or 121 ppm as a reference control. The usual management practices of each of the integrated broiler companies were followed throughout the respective trials. Nine trials were conducted and approximately 100,000 broilers were tested for each treatment. No adverse reactions attributable to treatments were observed in any of the trials, and performance results obtained with narasin-medicated birds were generally comparable with those obtained with monensin-medicated birds in the same trial. These findings support the conclusion that narasin at final feed concentrations in the range of 60 to 80 ppm can be safely and effectively used as an anticoccidial agent in commercial broiler production facilities.

Animals↗

In vitro expression of colony-stimulating factor genes by human acute myeloblastic leukemia cells.

Cells from most cases of acute myeloblastic leukemia (AML) proliferate in vitro in response to one or more colony-stimulating factor (CSF). Previous studies have suggested that some AML cells can produce their own CSFs, but the frequency of this phenomenon is unclear. In this study, Northern blot hybridization was used to detect mRNA transcripts for granulocyte-monocyte CSF (GM-CSF), granulocyte-CSF (G-CSF), and macrophage-CSF (M-CSF) in 22 randomly selected cases of AML. Ten cases expressed one CSF transcript (generally M-CSF), one case expressed two CSF transcripts, and six cases expressed all three. The expression of CSF transcripts did not significantly correlate with the French-American-British classification, with the possible exception that four of the five cases expressing all three CSF mRNAs were FAB M1. Six cases had autonomous growth of clonogenic cells in agar, and all six cases expressed one or more type of CSF transcript. None of the five evaluated cases lacking all three CSF transcripts had autonomous growth. However, there were many cases in which CSF transcripts were present and no autonomous growth was observed. In response to exogenously added human recombinant CSFs, 11 of 18 cases proliferated in response to GM-CSF, 8 of 18 cases in response to G-CSF, and 0 of 10 cases in response to M-CSF. Response to a CSF was not significantly correlated with the presence or absence of CSF transcripts, particularly for M-CSF. These results show that CSF transcripts are frequently detected in AML, although with a substantial degree of heterogeneity. It is possible that CSF production contributes to unregulated growth in some cases of AML.

Cell Division↗

Interferon-gamma induces expression of the interleukin 2 receptor gene in human monocytes.

Interferon-gamma induces surface expression of interleukin 2 (IL2) receptors on human monocytes and the monocytic cell line U937. Freshly prepared peripheral blood monocytes and U937 cells were found to lack detectable IL 2 mRNA, but exposure of these cells to interferon-gamma induced IL 2 receptor message at 6 h of culture. At least two IL 2 receptor transcripts were detected (3.5 and 1.5 kb) in both monocytes and U937 cells, similar in size to IL 2 receptor transcripts in activated T cells. These results show that interferon-gamma induces expression of the monocyte IL 2 receptor gene.

Cell Line↗

Preterm birth at 23 to 26 weeks' gestation: is active obstetric management justified?

To determine if active perinatal management was justified in preterm deliveries at less than or equal to 26 weeks' gestation, the outcome (survival and short- and long-term morbidity) of 43 infants (group I) born between 23 and 26 weeks' gestation was compared with that of 17 infants (group II) born at 27 weeks' gestation. Of the 12 surviving infants in group I (survival 28%), 11 were ventilated (median = 50 days), eight had moderate to severe bronchopulmonary dysplasia, and four had mild retrolental fibroplasia. At follow-up, two infants had physical disabilities with moderate to severe functional impairment, one had a minor disability, and nine had normal neurodevelopment. In contrast, of the 13 surviving infants in group II (survival 76%), nine were ventilated (median = 8 days), six had moderate to severe bronchopulmonary dysplasia, and six had mild RLF. At follow-up, one infant had a physical disability with moderate to severe functional impairment, four had minor disabilities, and eight had normal development. Perinatal factors that positively influenced survival in the two groups combined included active perinatal management, antenatal steroids, female sex, and absence of clinical chorioamnionitis and asphyxia. Although group I infants had a significantly higher mortality rate (p less than 0.05) and required a longer duration of ventilation (p less than 0.05), no differences in the incidence of postnatal complications or long-term morbidity at 2 to 4 years of age were evident between the two groups.

Child Development↗

Characterization of product RNAs synthesized in vitro by poliovirus RNA polymerase purified by chromatography on hydroxylapatite or poly(U) Sepharose.

The size of the product RNA synthesized by the poliovirus RNA polymerase and host factor was significantly affected by the type of column chromatography used to purify the polymerase. Dimer length product RNA was synthesized by the polymerase purified by chromatography on hydroxylapatite. This contrasted with the monomer length product RNA synthesized by the polymerase purified by chromatography on poly(U) Sepharose. The poly(U) Sepharose-purified polymerase was shown to contain oligo(U) that functioned as a primer. The addition of host factor to reactions containing the poly(U) Sepharose-purified polymerase significantly increased the synthesis of monomer length product RNA, in agreement with previous studies. This product RNA, however, did not immunoprecipitate with anti-VPg antibody and thus was not linked to VPg or a VPg-related protein. Thus, it was concluded that the synthesis of monomer length product RNA by the poly(U) Sepharose-purified polymerase and host factor was caused by oligo(U) priming rather than VPg priming.

Chromatography↗

Repeated sequence elements in the high molecular weight basic nuclear proteins from the winter flounder.

In maturing sperm of the winter flounder, histones are not replaced by protamines but instead joined by a group of high molecular weight basic nuclear proteins. Despite their large size and number of components, these proteins were reduced to a relatively simple set of peptides by a "limit" digestion with endoprotease Lys-C. Nine of these peptides, that together account for half of the mass of the digest, were purified by two rounds of chromatography on a C18 reverse-phase high pressure liquid chromatographic column and analysed by sequential Edman degradation. Their sequences can be divided into two homology groups. Seven of the peptides contain all or part of a dodecapeptide consensus sequence, NH2-Ser-Pro-Met-Arg-Ser-Arg-Ser-Pro-Ser-Arg-Ser-Lys-COOH, which appears to be tandemly repeated. This dodecapeptide contains a previously recognized consensus phosphorylation sequence, NH2-Arg-Ser-Arg-Ser-Pro-COOH, in which both serines are phosphorylated during the early stages of spermiogenesis. The other homology group has the sequence NH2-Arg-Arg-Val-X-X-Pro-Lys-COOH, where X-X is either Gln-Thr or Pro-Ser. The dodecapeptide and heptapeptide sequences form at least 35 and 11%, respectively, of the high molecular weight basic nuclear proteins and are, therefore, repeated many times over in these proteins. A search for identical or homologous sequences within the Protein Sequence Database indicated that they are unique. The closest matches were to protamines and some viral DNA-binding proteins.

Amino Acid Sequence↗

Constitutive expression of the granulocyte-macrophage colony-stimulating factor gene in acute myeloblastic leukemia.

Expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene was studied by Northern blot analysis in normal human hematopoietic cells and a series of leukemias. GM-CSF messenger (m)RNA was detected in activated T cells, but not in normal bone marrow cells, monocytes, or nonactivated T cells. In contrast, leukemic cells from 11 of 22 cases of acute myeloblastic leukemia expressed GM-CSF transcripts. Biologically active CSF was detected in supernatant conditioned by 6 of these 11 leukemias. Expression of the GM-CSF gene was not detected in "common" (pre-B cell) acute lymphoblastic leukemia (11 cases tested) or chronic myeloid leukemia (4 cases tested). These results show that the GM-CSF gene is constitutively expressed in a subset of patients with AML, and further suggest that expression of this gene could contribute to the abnormal growth properties characteristic of AML.

Antigen-Antibody Reactions↗

Expression of the M-CSF (CSF-1) gene by human monocytes.

Monocyte colony-stimulating factor (M-CSF, CSF-1) is a macrophage lineage-specific growth factor. Northern blot analysis using a human M-CSF cDNA probe and a specific bioassay for human M-CSF were used to investigate the cellular sources of M-CSF. Expression of the M-CSF gene was induced in blood mononuclear cells stimulated by phorbol myristate acetate (PMA) or gamma-interferon. When mononuclear cells were fractionated into highly purified populations of T cells and monocytes, M-CSF transcripts were detected predominantly in monocytes. Further, monocytes stimulated with PMA released an M-CSF-like activity. These results demonstrate that M-CSF can be produced by activated cells of the macrophage lineage.

Cells, Cultured↗

Fetal biophysical profile and perinatal death.

Antepartum assessment of 5034 high-risk pregnancies to predict perinatal death included five biophysical variables (nonstress test, fetal breathing movements, fetal movements, fetal tone, and amniotic fluid volume) which combined to form a biophysical profile score. We assessed 4148 fetuses within seven days of delivery. The ability of each variable to predict perinatal death was expressed as the likelihood ratio, which incorporates sensitivity and specificity into one number. The predictive ability was most accurate with fetal movement (likelihood ratio 48.1) and the combined biophysical profile score (likelihood ratio 51.0). The biophysical profile score was more likely to predict perinatal death due to asphyxia (seven of eight) than lethal anomaly (six of 19). The overall perinatal mortality was 7.6 per 1000 total births. The perinatal mortality rate was 1.0 for a normal biophysical profile score, 31.3 for an equivocal score, and 200.0 for an abnormal score. The false-negative rate for the biophysical profile score was 0.7 per 1000.

Amniotic Fluid↗

The effects of GM-CSF and G-CSF in promoting growth of clonogenic cells in acute myeloblastic leukemia.

A small subset of leukemic cells from most patients with acute myeloblastic leukemia (AML) have properties of stem cells and can be assayed by colony formation in agar or methylcellulose. Colony formation generally requires the addition of exogenous growth factors, but the exact factors required are incompletely defined. The AML colony-promoting activities of two recombinant human colony-stimulating factors (GM-CSF and G-CSF) were investigated by using blasts from 48 patients with AML. In nine cases, no colonies formed with either CSF. In seven cases colonies formed only in response to G-CSF and in 11 cases only in response to GM-CSF. In 21 cases colonies formed in response to either GM-CSF or G-CSF, and in 12 of these cases there was an additive effect between the two CSFs in determining maximum colony size. For cases responding to both GM- and G-CSF, the total number of colonies formed in response to the combination of both CSFs was almost always less than additive compared with the number of colonies formed in response to the individual CSFs. Further, the AML-CFU responding to either GM-CSF or G-CSF could not be distinguished by surface markers or by the cytochemical staining pattern of the colonies. These results suggest that there is considerable overlap between the GM-CSF- and G-CSF-responsive AML-CFU subpopulations in most cases. For five of seven cases, the combination of GM-CSF and G-CSF could replace a leukocyte feeder layer in providing maximum growth stimulation. These results indicate that GM-CSF and G-CSF are active growth factors for AML cells and are frequently additive in promoting maximum colony size.

Adult↗

Secretion of interleukin-1 by acute myeloblastic leukemia cells in vitro induces endothelial cells to secrete colony stimulating factors.

The interaction of acute myeloblastic leukemia (AML) cells with stromal cells was investigated by adding AML-conditioned media to cultures of human endothelial cells. This conditioned media contained factors that induced expression of both the granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte CSF (G-CSF) genes and release of colony stimulating activity from endothelial cells. The conditioned media contained interleukin-1 (IL-1) bioactivity and the endothelial cell stimulatory activity was partially neutralized by anti-IL-1 antiserum. Constitutive expression of the IL-1-beta gene was detected in ten of 17 AML cases analyzed. These results suggest that the unregulated secretion of IL-1 by AML cells can induce stromal cells in vitro to overproduce CSFs. This could contribute to the unrestricted growth of AML cells.

Acute Disease↗

Single-centre randomised trial of ritodrine hydrochloride for preterm labour.

106 women between 24 and 33 weeks' gestation and in preterm labour, rigidly defined to include cervical dilatation plus regular uterine contractions, were randomly allocated to receive either intravenous ritodrine hydrochloride or no tocolytic treatment. Ritodrine treatment significantly delayed delivery for 24 hours or less but did not significantly modify the ultimate perinatal consequences of preterm labour.

Adult↗

Amniotic fluid phosphatidylglycerol and phosphatidylcholine phosphorus as predictors of fetal lung maturity.

The contents of phosphatidylglycerol and phosphatidylcholine phosphorus in amniotic fluid (10,000 X g pellets) were studied as predictors of fetal lung maturity. The presence of phosphatidylglycerol predicted the absence of neonatal respiratory distress syndrome with 99% probability. When phosphatidylglycerol was absent, phosphatidylcholine phosphorus was a reliable predictor if measured 3 to 7 days before delivery. The probability that respiratory distress syndrome would not occur was 94% when phosphatidylcholine phosphorus was greater than 6. When measurement was performed within 2 days of delivery, the probability that respiratory distress syndrome would not occur fell to 69%. As measured in amniotic fluid, phosphatidylglycerol and phosphatidylcholine phosphorus are reliable antenatal predictors of fetal pulmonary maturity and, therefore, are useful in the management of a number of obstetric conditions.

Amniocentesis↗

Anti-VPg antibody precipitation of product RNA synthesized in vitro by the poliovirus polymerase and host factor is mediated by VPg on the poliovirion RNA template.

Antibody to the poliovirus genome-linked protein, VPg, specifically immunoprecipitated the product RNA synthesized in vitro by the poliovirus RNA polymerase and HeLa cell host factor when VPg-linked poliovirion RNA was used as a template. The largest product RNA that was immunoprecipitated was twice the size of the template RNA. The complete denaturation of the product RNA with CH3HgOH had no effect on the immunoprecipitation reaction. In contrast, CH3HgOH denaturation prevented the immunoprecipitation of the oligo(U)-primed product RNA. Immunoprecipitation of the product RNA synthesized in the host-factor-dependent reaction was prevented if VPg was removed from the template RNA by pretreatment with proteinase K or if an RNA template without VPg was used in the reaction. The results support our previous evidence that a covalent linkage exists between the labeled negative-strand product RNA and the VPg-linked template RNA and suggest that the purified polymerase and host factor initiated RNA synthesis in vitro in the absence of VPg or a VPg-precursor protein.

Antibodies, Viral↗