Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During fetal life, both Ig and TCR-gamma delta repertoires are enriched for a specific set of Ag receptors with limited diversity. In order to test the hypothesis that diversification of the human TCR-beta repertoire also follows a developmental program, we examined TCR-beta DJ and VDJ transcripts from fetal and adult thymi. A consistent bias for D beta 1.1 and J beta 1.1 was present in DJ transcripts amplified from 8-wk gestation thymi. Although it is possible to splice and translate D beta 1.1 in all three reading frames, 8-wk gestation fetal DJ transcripts were enriched for D beta 1.1 spliced to J beta 1.1 in reading frame one. Preference for D beta 1.1 reading frame one and for use of J beta 1.1 dwindled with increasing gestational age. Reading frame bias was not affected by the insertion of non-germ-line-encoded nucleotides (N regions) or by the site of gene splicing. In contrast, choice of reading frame and use of J beta 1.1 appeared random in VDJ transcripts from the same 8-wk gestation and adult thymic samples. Among the occasional VDJ transcripts that contained D beta 1.1-J beta 1.1 rearrangements, use of D beta reading frame one was rare. Up to 75% of DJ and VDJ transcripts at 8-wk gestation lacked N regions. Both the percentage of DJ and VDJ transcripts with N regions and the average number of inserted nucleotides per transcript increased with gestational age. Primarily as a result of enhanced N region addition, both the length and sequence diversity of the VDJ junctions increased markedly from 8-wk gestation to adult life with a concomitant increase in the potential size of the TCR-alpha beta repertoire. Terminal deoxynucleotidyl-transferase (TdT), the enzyme associated with N region addition, has not been detected in thymus before 19 wk of gestation. However, we were able to amplify TdT mRNA from all fetal thymi examined. This suggests that TdT may be expressed as early as 8 wk gestation, although at low levels. The early fetal thymus appears enriched for a population of thymocytes that produce minimal quantities of TdT, express a special set of TCR-beta DJ transcripts, and generate a TCR-beta repertoire with limited diversity. These findings support the hypothesis that limitations in the diversity of the TCR repertoire imposed at the time of gene rearrangement contribute to the immaturity of the fetal immune response.
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PMID:Developmental regulation of D beta reading frame and junctional diversity in T cell receptor-beta transcripts from human thymus. 131 Jul 10

Dopamine hydrochloride is widely used to increase blood pressure, cardiac output, urine output, and peripheral perfusion in neonates, infants, and older children with shock and cardiac failure. Its pharmacologic effects are dose dependent, and at low, intermediate, and high dosages include dilation of renal, mesenteric, and cerebral vasculature; inotropic response in the myocardium; and increases in peripheral and renal vascular resistance, respectively. The inotropic response is diminished in neonates compared with older children and adults due to maturational differences in norepinephrine stores. The clearance of dopamine varies widely in the pediatric population, depending on age. Its elimination half-life is approximately 2 minutes in full-term neonates and older children, and may be as long as 4-5 minutes in preterm infants. Due to immaturity of the autonomic nervous system, the drug may produce some adverse respiratory responses at high dose in neonates, the most common being tachycardia and cardiac arrhythmias. Dobutamine resembles dopamine chemically and is an analog of isoproterenol. It is relatively cardioselective at dosages used in clinical practice, with its main action being on beta 1-adrenergic receptors. Unlike dopamine, it does not have any effect on specific dopaminergic receptors. Dobutamine is used to increase cardiac output in infants and children with circulatory failure. Its elimination half-life is about 2 minutes in adults and older children. No information is available about its pharmacokinetics in neonates and infants. Adverse effects such as an increase in heart rate usually occur at high dosages.
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PMID:Dopamine and dobutamine in pediatric therapy. 268 52

Fibronectin and its integrin receptor alpha 5 beta 1 were studied by immunohistochemical methods in five normal canine mammary glands, four dysplastic glands and 18 mammary tumours. The aim of the study was to evaluate the possible changes in the alpha 5 beta 1 integrin receptor and its ligand fibronectin in relation to the metastatic capacity of canine mammary neoplasms. The immunostaining of alpha 5 beta 1 was very uniform in the hyperplastic glands but uneven in the mammary tumours. The expression of alpha 5 and beta 1 was diminished in metastatic tumours but there were some alpha 5-positive cells with pronounced features of malignancy and immaturity. Stromal fibronectin was increased in most cases and cytoplasmic staining of fibronectin was observed in epithelial and myoepithelial cells in mammary neoplasms but not in normal or dysplastic mammary tissue. There was no relationship between the content of alpha 5 beta 1 and the expression of fibronectin in canine mammary tumours.
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PMID:Expression of fibronectin and its integrin receptor alpha 5 beta 1 in canine mammary tumours. 787 Dec 57