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

Paneth cells, secretory epithelial cells of the small intestinal crypts, are proposed to contribute to local host defense. Both mouse and human Paneth cells express a collection of antimicrobial proteins, including members of a family of antimicrobial peptides named defensins. In this study, data from an anchored polymerase chain reaction (PCR) strategy suggest that only two defensin mRNA isoforms are expressed in the human small intestine, far fewer than the number expressed in the mouse. The two isoforms detected by this PCR approach were human defensin family members, HD-5 and HD-6. The gene encoding HD-6 was cloned and characterized. HD-6 has a genomic organization similar to HD-5, and the two genes have a striking pattern of sequence similarity localized chiefly in their proximal 5'-flanking regions. Analysis of human fetal RNA by reverse transcriptase-PCR detected enteric defensin HD-5 mRNA at 13.5 weeks of gestation in the small intestine and the colon, but by 17 weeks HD-5 was restricted to the small intestine. HD-6 mRNA was detectable at 13.5-17 weeks of gestation in the small intestine but not in the colon. This pattern of expression coincides with the previously described appearance of Paneth cells as determined by ultrastructural approaches. Northern analysis of total RNA from small intestine revealed quantifiable enteric defensin mRNA in five samples from 19 24 weeks of gestation at levels approximately 40-250-fold less than those observed in the adult, with HD-5 mRNA levels greater than those of HD-6 in all samples. In situ hybridization analysis localized expression of enteric defensin mRNA to Paneth cells at 24 weeks of gestation, as is seen in the newborn term infant and the adult. Consistent with earlier morphological studies, the ratio of Paneth cell number per crypt was reduced in samples at 24 weeks of gestation compared with the adult, and this lower cell number partially accounts for the lower defensin mRNA levels as determined by Northern analysis. Low levels of enteric defensin expression in the fetus may be characteristic of an immaturity of local defense, which is thought to predispose infants born prematurely to infection from intestinal microorganisms.
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PMID:Human enteric defensins. Gene structure and developmental expression. 862 37

Prostate secretory protein of 94 amino acids (PSP94) has shown the potential to be a diagnostic biomarker and a therapeutic agent for prostate cancer. Primates have been the main animal models for studying the biology of this molecule. We have cloned and analyzed the cDNA and promoter region of PSP94 from baboon (Papio anubis). Sequence divergence among baboon, monkey, pig, and human, in both the exons and 5'-flanking region indicates rapid evolution of the PSP94 gene. There are conserved steroid hormone response elements (SHRE) in the promoter region of all three primate species. Multiple, alternative transcripts starting near these SHREs and upstream to the TATA box were identified by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of 5'-cDNA ends (5' RACE) in primate prostatic tissues. This differential transcription initiation may be linked to androgen regulation of PSP94 gene expression. PSP94 transcripts were detected by RT-PCR in a wide variety of mucus-secreting tissues. However, the alternative transcripts were found only in the prostate. The distribution of the PSP94 protein in baboon secretory tissues was also examined by Western blot analysis using a polyclonal antibody against the human homolog. A positive immunoreactive band was detected, but it was weak, due probably to epitope divergence between the two species. In all young, healthy primate animals tested, the level of immunoreactive PSP94 in prostate tissues was lower than expected. In addition, RT-PCR combined with Southern blot analysis on prostate tissues in these animals failed to detect the PSP57 mRNA produced by alternative splicing of PSP94 primary transcript. These observations can be explained by the sexual immaturity and incomplete prostate development in these young primates. This explanation was supported by histological examination of their prostate during PSP94 immunohistochemistry.
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PMID:Molecular cloning and gene expression analysis of PSP94 (prostate secretory protein of 94 amino acids) in primates. 917 67

Subacute sclerosing panencephalitis(SSPE) is a progressive and fatal neurological illness without established treatment. As the precise mechanism how measles virus (MV) causes SSPE is still unknown, full clarification of pathogenesis and pathophysiology is essential to establish effective strategy to treat the illness. Viral, host and environmental factors are involved in the development of SSPE. As host factors, immaturity of immune system and central nervous system are well recognized. Recently, we demonstrated that functional polymorphisms of MxA, interleukin(IL)-4 and interferon regulatory factor-1 (IRF-1) genes are associated with the development of SSPE in Japanese. High-density oligonucleotide microarray and subsequent quantitative reverse transcriptase-polymerase chain reaction demonstrated that the mRNA levels of granulysin were decreased in SSPE patients and were increased in measles patients, suggesting that granulysin might play a role in the host defense against MV and possibly be involved in the pathogenesis or pathophysiology of SSPE. In a Turkish study, association between angiotensin converting enzyme (ACE) gene polymorphism and SSPE was shown.
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PMID:[Host genetic factors for the development of SSPE]. 1769 85

The non-nucleoside reverse transcriptase inhibitor efavirenz is part of the WHO guidelines for preferred first-line treatment of HIV-1-infected adults, pregnant and lactating women, and children. Efavirenz is well known to cause CNS toxicity. Although good data for CNS toxicity are available for adults, the opposite is true for children. Paediatric studies on this topic frequently suffer from small sample sizes or absence of thorough neuropsychiatric assessments. In this Personal View, we focus on two knowledge gaps of CNS toxicity of efavirenz in children. First, plasma concentrations of efavirenz are difficult to predict in children because of immaturity of and genetic variation in metabolic enzymes. Second, efavirenz exerts a lysergide (LSD)-like effect on brain serotonergic pathways and affects CNS metabolic pathways, including mitochondrial function. Whether these effects interfere with normal brain development is unknown. These uncertainties underline the imminent need for better monitoring of mental health and neurocognitive development in children given and exposed to efavirenz.
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PMID:Rethinking the risk-benefit ratio of efavirenz in HIV-infected children. 2759 55