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)

Neurological dysfunction has been shown to be associated with human immunodeficiency virus (HIV) infection. The incidence of these abnormalities is greater in HIV-infected children when compared with adults, and the patterns of neurological disease are also known to differ from those observed in the adult population. The reasons for these differences are unclear but are most likely related to the immaturity of the host's immune and central nervous systems at the time of infection. This is thought to be particularly true for infants infected with HIV prenatally. To examine these questions, the brains of fetal rhesus macaques that were infected with SIVmac251 at various time points in utero were examined. Direct fetal inoculations were performed on gestational day (GD) 65 (n = 8; early second trimester), GD 110 (n = 4; early third trimester) and GD 130 (n = 2; mid third trimester), with harvest of fetal tissues on GD 80, 100, 130, or 145. Eleven sham controls were included with harvest at correlative time points. Specimens were examined by routine histology, immunohistochemistry, and in situ hybridization to localize viral antigens and SIV nucleic acid. Histologically, scattered glial nodules, spongiosis, and mineralization were found in the basal ganglia and deep white matter in 4 of the 14 fetuses (3 inoculated on GD 65 and one on GD 110). These fetuses and those without histological lesions had viral nucleic acid and SIV antigen in the stroma of the choroid plexus, meninges, and external granular layer of the cerebellum and in columns of cells in the cortical plate. In contrast to juvenile and adult macaques, very few SIV-positive perivascular mononuclear cells were present. These findings suggest that SIV has a different distribution in the brain of fetal macaques after direct infection when compared with adult or juvenile animals. Furthermore, the results of these studies suggest that differences in neurological disease between pediatric and adult patients with acquired immune deficiency syndrome are most likely related to the time of infection.
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PMID:Localization of simian immunodeficiency virus nucleic acid and antigen in brains of fetal macaques inoculated in utero. 886 58

Measles is caused by infection with measles virus (MV), a negative strand RNA virus in the Morbillivirus genus of the Paramyxoviridae family. Measles is a highly infectious disease of humans spread by the respiratory route and characterized by fever and rash. Important complications include secondary infections associated with MV-induced immune suppression and the neurological disease post-infectious encephalomyelitis. The virus was first isolated in 1954 paving the way for development of the vaccines that have played an essential role in decreasing the worldwide morbidity and mortality due to measles. One of the first vaccines was a formalin-inactivated vaccine that provided only short-lived protection from infection and primed for a more severe disease, atypical measles. This vaccine was withdrawn. The other early vaccine was a live attenuated vaccine (LAV) developed by passage of the original isolate of Edmonston virus through cells in culture, primarily chicken cells. LAV was reactogenic and often given along with immune globulin. Further passage of the Edmonston virus resulted in further attenuation and the well-tolerated vaccines in common use today. LAV is generally given between 9 and 15 months of age. Seroconversion at 9 months is about 85% and at 12 months is about 95%. At younger ages seroconversion is hampered by the presence of maternal antibody and the immaturity of the immune system. The R0 (numbers of people in a susceptible population that will be infected by one person with the disease) for MV is 15-20 and interruption of endemic transmission of MV in a population requires that >95% of the population is immune. A second dose is necessary to achieve this level and can be given either as a part of a routine immunization program or through periodic mass vaccination campaigns. Research toward improved measles vaccines has focused on development of a vaccine that could be given before 6 months of age, needle-less delivery and heat stability. Several new recombinant vaccines expressing MV proteins have demonstrated induction of protective immunity in macaques and are in various stages of development.
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PMID:Measles vaccines. 1798 35

While studying the brain function of the human partial epilepsy gene, leucine-rich glioma-inactivated 1 (LGI1), a new mechanism of human epileptogenesis was revealed-persistent immaturity of glutamatergic circuitries. LGI1, a novel secreted protein, was found to be increased during the postnatal period; when glutamatergic synapses both downregulate their presynaptic vesicular release probability and reduce their postsynaptic NMDA-receptor subunit NR2B. During this same period, the dendritic arbor and spines are pruned and remodeled. Using bacterial artificial chromosome transgenic mouse techniques, excess wild-type LGI1 was shown to magnify these critical brain developmental events in the hippocampal dentate gyrus; while an epilepsy-associated, truncated, dominant-negative form of LGI1 blocked them. By contrast, the hippocampal dentate granule neuron GABAergic synapses and intrinsic excitability were unaltered. A role for LGI1 in downregulating glutamate synapse function was confirmed by germline gene deletion; this intervention also revealed a selective increase of glutamatergic synaptic transmission with unaltered GABAergic synapses and intrinsic excitability of hippocampal CA1 pyramidal neurons. Interestingly, the role of LGI1 in neurological disease was further expanded when a subset of patients with limbic encephalitis (an autoimmune disorder with memory loss in 100% and seizures in 80% of individuals) were discovered to carry autoantibodies to LGI1.
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PMID:Arrested glutamatergic synapse development in human partial epilepsy. 2115 44