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Biomedical subjects

A L Young

Publications and source records attributed to A L Young.

At least 37 records · Page 2Linked to original sources

Isolated pedunculated congenital corneal dermoid.

PURPOSE: To investigate a case of isolated pedunculated congenital corneal dermoid. METHODS: Case report. RESULTS: In a 14-day-old infant, the pedunculated portion of the dermoid was removed and confirmed by histopathologic examination. No surgical complication or recurrence was encountered, and the patient is waiting for a rotational autokeratoplasty. CONCLUSIONS: Prompt treatment of such an unusual tumor is important to allow for visual rehabilitation and development.

Corneal Diseases↗

The effect of unsaturated fatty acids on membrane composition and signal transduction in HT-29 human colon cancer cells.

The objective of the present study was to investigate the effect of membrane fatty acid (FA) composition on the activity of phospholipase C (PLC) in HT-29 human colon cancer cells. The membrane FA composition was altered by supplementing cultured cells with FAs of different composition. The FAs were stearic acid (18:0; SA), gamma linolenic acid (18:3 omega 6; gamma LnA); alpha linolenic acid (18:3 omega 3; alpha LnA;); eicosapentaenoic acid (20:5 omega 3; EPA) and docosahexaenoic acid (22:6 omega 3; DHA). The fatty acids were supplemented as a FA/BSA complex. Cells supplemented with SA served as the control. Tumor growth was followed by counting the number of cells in culture. The results indicate that polyunsaturated fatty acid (PUFA) supplementation had no consistent effect on tumor growth from 1 day to another throughout the 15 days of growth. The fatty acid composition of membranes indicates that cells incorporated and modified the supplemented fatty acids by desaturation, elongation and retroconversion. The unsaturation index (UI) of membranes of cells supplemented with EPA and DHA was higher than other groups. PLC activity; measured in the absence of GTP gamma(S) in the assay mixture; was not influenced by membrane FA modification. However, in the presence of GTP gamma(S) PLC of cells supplemented with 18:3(omega 6) was the lowest among the groups. It has been shown that 18:3(omega 6) accumulated the most in the phosphatidylethanolamine (PE) fraction. There was a negative correlation between the activity of PLC in the presence of G protein activation and PE 18:3 (omega 6) content without affecting UI. It was concluded that G protein may be sensitive to the level of 18:3(omega 6) content and not to the general fluidity of the membranes.

Animals↗

A government agency's responsibility to the consumer.

The U.S. Department of Agriculture's Office of Agricultural Biotechnology developed a proactive stance for informing consumers about biotechnology in 1987. Using a variety of information vehicles, the Office of Agricultural Biotechnology has developed a dialogue with various groups having different and sometimes very strident opinions about the use of genetic engineering in plants and animals. At the same time, the government agency has fulfilled its mandate to neither promote nor discourage the use of biotechnology methods in research, but rather to present the data and thus allow consumers to make an informed decision.

Agriculture↗

Biotechnology and potential nutritional implications for children.

The tools of biotechnology have enormous potential to develop new, safe, and nutritious foods and food products that could benefit the immediate and long-term nutritional and health needs of the pediatric population. This is especially true as more emphasis is placed on the prevention, rather than the treatment, of chronic degenerative and metabolic diseases. But the promise of biotechnology for nutritional and health benefits of children's diets must be accepted with cautious optimism. Many advances in food technology and nutritional composition of food animals and plants have already been made through biotechnology, but they represent only the beginning of the necessary research. These advances have been based on relatively little knowledge of basic human nutritional needs, particularly during the dynamic pediatric period of growth and development. More importantly, these advances have been predicated with no understanding of dietary nutrient interactions. Changing nutrient composition of foods through biotechnology may alter nutrient interactions, nutrient-gene interactions, nutrient bioavailability, nutrient potency, and nutrient metabolism. Biotechnology has the potential to produce changes in our foods and in our diet at a pace far greater than our ability to predict the significance of those changes on pediatric nutrition. The Human Genome Project, which relies on biotechnology, will revolutionize science and medicine. Pediatrics will be one of the first medical specialties to benefit from the outcome of this project as recombinant DNA manipulations will replace diet therapies for treating metabolic diseases. Somatic gene therapy eventually may be the ideal means for diagnosis, treatment, and cure of inherited diseases and metabolic disorders; however, many problems exist, especially in situations in which nutrients are involved in the complex regulation of gene expression. DNA and genes themselves do not determine the fate of an individual. The genetic material provides the potential for the individual, but this potential can be modified by environmental factors. The interaction of nutrients with genes is a major determinant in the final outcome of the individual. Biotechnology promises children a more productive and better quality of life, but achieving the full potential of this promise demands a continued diligent search for knowledge of nutrition and nutrient-gene interactions.

Biotechnology↗

Peptides with sequences similar to glycine, arginine-rich motifs in proteins interacting with RNA are efficiently recognized by methyltransferase(s) modifying arginine in numerous proteins.

Several proteins that interact with RNA, e.g. the heterogenous ribonucleoprotein particle A and B proteins, fibrillarin and nucleolin, contain the modified amino acid NG,NG-dimethylarginine. Here, we report that two synthetic peptides, Ac-GGRGGFGGRGGFGGRGGFG-NH2 (R3) and GGFGGRGGFG-NH2 (R1), which are based on methylated sequences in fibrillarin and nucleolin, inhibit the methylation of a large majority of the methyl-accepting proteins observed in extracts of adenosine dialdehyde-treated PC12 cells. Concomitantly, the peptides themselves become methylated, suggesting that they compete for the same enzyme that carries out the bulk of N-methylation in PC12 cells. R3 potently inhibits formation of NG,NG-dimethylarginine in PC12 substrates, with a lesser effect on NG-monomethylarginine and NG,N'G-dimethylarginine. Bovine brain contains an activity that methylates PC12 methyl acceptors. After partial purification, the bovine methyltransferase efficiently modifies R3 and R1, yielding half-maximal rates of methylation at approximately 0.2 and approximately 2 microM peptide, respectively. A search of the GenPept database for the FGGRGGF motif revealed 13 candidate methyl acceptors containing arginine and at most two similar substitutions or one mismatch. Of these, 10 are known or presumed to interact with RNA. These findings are consistent with the hypothesis that a majority of proteins containing NG,NG-dimethylarginine interact with RNA.

Amino Acid Sequence↗

Effect of activin A on globin gene expression in purified human erythroid progenitors.

The regulatory control of human erythropoiesis through a purified protein, activin A, was examined. Previous studies using mixed populations of bone marrow cells suggested that activin A has an indirect effect on cellular proliferation and DNA synthesis of erythroid progenitors through the mediation of accessory cells. In present studies, the cultures of purified erythroid progenitors were used to examine the effect of activin A on globin gene expression. Human erythroid burst-forming units (BFU-E) were partially purified from peripheral blood, and after 8 days of culture the cells generated consisted mainly of erythroid colony-forming units (CFU-E). It was found that the subsequent 7-day cultures of these purified progenitors yielded similar numbers and size distributions of erythroid colonies, regardless of the presence of activin A in the cultures. In addition, these erythroid progenitor cells were responsive, in terms of stimulation of DNA synthesis, to the addition of erythropoietin, but not to treatment by activin A. Therefore, once the erythroid progenitors are depleted of accessory cells, activin A has little effect on both the proliferation and the DNA synthesis of these progenitors. However, when these purified erythroid progenitors were cultured in the presence of activin A, the levels of all alpha, beta, and epsilon globin transcripts and hemoglobins were significantly increased. In addition, disuccinimidyl suberate was found to chemically cross-link 125I-activin A to cell surface binding proteins (45 to 54 Kd) in both purified erythroid progenitors and K562 cells. The labeling of these binding proteins was specifically inhibited by the presence of unlabeled activin A, but not transforming growth factor-beta. These results suggest that, in addition to its indirect effect on DNA synthesis and cellular proliferation of erythroid progenitors, activin A directly affects the levels of globin mRNAs and hemoglobins in developing human erythroid cells through its specific surface binding receptor(s).

Activins↗

Regulation of globin gene expression in human K562 cells by recombinant activin A.

Recent studies indicate that a purified protein, activin A, belongs to the transforming growth factor beta (TGF-beta) superfamily. Similar to TGF-beta, activin A can have different biologic activities, depending on the target tissues. We used recombinant activin A to demonstrate a possible regulatory role of this protein in modulating human erythroid differentiation in the human erythroid cell line, K562. Using genomic probes containing the second exon of alpha, beta, gamma, and epsilon globins, relative abundance of various types of globin transcripts in untreated and activin-treated K562 cells was examined with S1 nuclease analysis. Despite considerable homology amongst various globin sequences, these globin probes were highly specific for their unique mRNA species in the analyses. It was shown that the abundance of specific globin probe fragments for gamma and epsilon globins (209 nucleotides) as well as alpha (180 nucleotides), which were protected from S1 digestion, increased many fold in K562 cells treated with activin A. In contrast, there were no specific transcripts of beta globin detected in either the control or activin-treated cells. The increases in the level of fetal and embryonic beta-like and alpha globin transcripts also confirmed earlier studies of Northern and slot-blot analyses using globin cDNA as probes. In addition, nuclear run-off transcription assay using isolated nuclei indicated that most of the increase in the globin transcripts after activin treatment could be attributed to the stimulation of transcription rate for globin genes. Transient transfection assays also provide evidence that activin A significantly stimulated transcriptional activity of an epsilon globin promoter in K562, but not in the nonerythroid Chinese hamster ovary cells. Therefore, it was concluded that activin A exerts its effects on globin gene expression at the level of transcription in erythroid cells.

Activins↗

A White House perspective on risk assessment and risk communication.

The fear of malign influences in our environment is so widespread today that the general public believes that it is those factors they cannot control that will bring about their early demise. Our goals in government must be to effectively communicate information on environmental risks, and to develop a disciplined way of approaching environmental assessment and regulation so as to reduce those risks.

Animals↗

Plaque formation with influenza viruses in dog kidney cells.

Infectious influenza and parainfluenza viruses were produced as plaql passages of egg-grown viruses in MDCK monolayers. Virus titres of 10(6) to 10(11) p.f.u./ml were obtained for several A and B strains of influenza and parainfluenza viruses.

Animals↗

Two forms of 4-aminobutyrate transaminase in guinea pig brain.

4-Aminobutyrate transaminase (GABA-T, 4-aminobutyrate alpha-oxoglutrate aminotransferase, EC 2.6.1.19) is an enzyme that inactivates the inhibitory neurotransmitter, GABA, but its pharmacological function is uncertain. Two forms of guiena pig brain GABA-T were isolated by DEAE-cellulose chromatography and designated as GABA-T-I and II, corresponding to an anionic and a cationic form. The enzymes were inhibited by high concentrations of a cationic form. The enzymes were inhibited by high concentrations of alpha-oxoglutrate (alpha-KG). Kinetic consists for GABA, when determined at pH 7.9 adn 1 mmol/l alpha-KG, were 0.74 mmol/l. GABA-T activity was inhibited by chloride and other anions. Kinetic analysis revealed chloride ion as a conpetitive inhibitor against GABA, but the Ki values differed among GABA-T-I and II (Ki equals 120 and 60 mmol/l, respectively). Similar degrees of difference were observed with acetate and lactate ion. These results suggest that GABA-T-II may regulate the GABA level in the inhibitory neurons and may play a similar functional role as that exhibited by monoamine oxidase in other synapses.

4-Aminobutyrate Transaminase↗

Methyl ester of N-formylmethionyl-leucyl-phenylalanine: chemotactic responses of human blood monocytes and inhibition of gold compounds.

N-formylmethionyl-leucyl-phenylalanine, a potent hemotactic peptide for human polymorphonuclear leukocytes, is less chemotactic for human blood monocytes. Esterification of the N-formylated tripeptide enhances its chemotactic activity for monocytes by more than 4 logs, whereas a decrease by 3 logs is observed for polymorphonuclear leukocytes. These results indicate the participation of the C-terminal carboxyl group in chemotaxis of different cell types. We have also observed the selective inhibition of chemotactic responsiveness of human blood monocytes by a clinically useful antirheumatic drug, sodium aurothiomalate. Since this is the first in vitro cell migration model of inflammation in which gold compounds have demonstrated activity in micromolar concentrations, it suggests a site of action for this antirheumatic drug.

Chemotaxis, Leukocyte↗