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)

Natural or experimental feline immunodeficiency virus (FIV) infection in cats is often associated with hematologic abnormalities which are similar to those observed in human immunodeficiency virus (HIV) infected patients. To determine if cells in bone marrow are infected with FIV and whether severity of hematopoietic disorder is correlated with the level of viral infection, bone marrow tissues from ten experimentally and two naturally FIV infected cats were examined by in situ hybridization for presence of FIV RNA. Seven of the 12 FIV infected cats were also naturally or experimentally coinfected with feline leukemia virus (FeLV). FIV RNA was detected mainly in megakaryocytes and unidentified mononuclear cells in the bone marrow of cats that were sick and had marrow hypercellularity and immaturity. These included all cats in the acute phase of FIV infection and two of seven long term FIV infected cats. One long term FIV infected cat with lymphosarcoma was also positive for FIV RNA in bone marrow cells. The other four long term FIV infected cats were relatively healthy, with normal bone marrow morphology, and were negative for FIV infected cells. Bone marrow from three non-infected and two cats infected with FeLV alone were also negative for FIV RNA by in situ hybridization. We concluded that megakaryocytes and mononuclear cells were targets of the viral infection and that the presence of FIV RNA in cells of the bone marrow correlated with marrow hypercellularity and immaturity, and severity of illness.
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PMID:Detection of feline immunodeficiency virus infection in bone marrow of cats. 133 1

Alteration is a common pathological process inherent to kymatogenesis and responsible for congenital defects which are the basic nosological unit of early kymatogenesis. Intrauterine compensatory adaptation triggers proliferation of mesenchymal tissue or hyperplasia of parenchymal cellular elements with accelerated maturation. Blastomogenesis occurs in children primarily during kymatogenesis. This fact can explain rapid progression of malignant growth during the first five years of life, the tumors being of embryonic or visceral tissue. Circulatory disorders prevail in perinatal period. They are represented by such nosological units as intrauterine hemorrhages and pneumopathies and are related to tissue immaturity. Fetal inflammation can be attributed to productive and alterative components. It is prone to generalized infection typical for early months of life. Opportunistic and viral infection is a common pathology in early infancy being the main nosological unit in this period. Later on the infection becomes local. Chronicity of infection rests upon persistent tissue immaturity.
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PMID:[Nosology of the fetus and child as a problem of general pathology]. 317 12

Severe viral infection in newborns has been attributed to immaturity of the immune system including a defect in natural killer cytotoxicity (NKC) and decreased production of cytokines that are important for natural killer (NK) function. We investigated the induction of interferon (IFN)-gamma and activation of NK activity in adult and cord blood mononuclear cells (BMC) after IL-12 treatment. The levels of mRNA in these BMC were measured by Northern blot and reverse transcription-polymerase chain reactions using primers specific for IFN-gamma. The levels of IFN-gamma protein were measured by ELISA. In the absence of IL-12, only adult BMC spontaneously produced low levels of IFN-gamma. After IL-12 treatment, induction of IFN-gamma expression was detected as early as 4 h in both cord and adult BMC. Both cord and adult cells showed similar levels of IFN-gamma mRNA and protein expression in response to IL-12 at a concentration as low as 10 U/mL. In contrast, upon phorbol ester and ionomycin treatment, adult BMC produced more IFN-gamma mRNA than cord BMC. In a 51Cr release assay with human immunodeficiency-infected H9 cells as indicators, both cord and adult cells responded to IL-12 induction of NKC. Our findings demonstrate that cord BMC are capable of responding to IL-12 stimulation, competent in synthesizing IFN-gamma, and able to mount NKC. Thus, it appears that the deficiency in IFN-gamma production or NKC in cord cells is not due to an inherent defect in IL-12 response of the cord cells.
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PMID:Interleukin-12 induces interferon-gamma expression and natural killer cytotoxicity in cord blood mononuclear cells. 882 1

There is good clinical and experimental evidence that oral tolerance exists in man and that the timing of antigen (food) administration is an important factor in the development of food allergic sensitisation and disease. Induction of tolerance is often seen as a T-helper 2-skewed response, which on one side may prevent harmful mucosal immune reactions, but on the other side may contribute to adverse responses in the susceptible individual. The primary mechanisms by which tolerance may be mediated include T-cell deletion, anergy, suppression 'ignorance' and apoptosis. Cell-mediated delayed hypersensitivity reactions (T-helper 1), which are implicated as a pathogenetic principle in the development of autoimmune and gastrointestinal inflammation are particularly well suppressed. Regulatory events during the induction of tolerance (or sensitisation) are not well characterised and remain at times controversial. The balance between tolerance (suppression) and sensitisation (priming) is dependent on several factors, such as: (a) genetic background; (b) nature of antigen and dose of antigen; (c) frequency of administration; (d) age (maturity v. immaturity) at first antigen exposure; (e) immunological status of the host (e.g. virus infection); dietary exposure of the mother; (g) antigen transmission via breast milk, and others. Overall, there is evidence in rodents that multiple low-dose feeds are more likely to induce regulatory cytokines (e.g. transforming growth factor-beta, interleukins 10 and 4) in part secreted by CD4+CD25+ T-regulatory cells. Despite the powerful suppressive effect of oral antigen exposure observed in experimental models, its application in clinical trials of autoimmune diseases has not yet yielded the expected beneficial results.
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PMID:Immunity induced after a feed of antigen during early life: oral tolerance v. sensitisation. 1206 95

In the central nervous system, the Japanese encephalitis virus can replicate only in neurons. The mechanism of the type of neurotropism was analyzed. The susceptibility to Japanese encephalitis virus infection in the rat brain was closely associated with neuronal immaturity. The initial specific binding of the virus to cells is one of the reasons for neurotropism of the Japanese encephalitis virus. The treatment of Japanese encephalitis virus infection with the neutralizing monoclonal antibody against the E protein did not inhibit the virus from binding to the cell surfaces, but strongly inhibited Japanese encephalitis virus-induced cell fusion and internalization of the virus into the host cells. One of the genome regions responsible for neuropathogenesis of the Japanese encephalitis virus was located on the E protein-coding region. The 138th amino acid of the E protein was important for neuropathogenesis expression of the Japanese encephalitis virus. The cell fusion activity of the E protein was closely correlated with neuropathogenesis of the virus.
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PMID:Neuropathogenesis of Japanese encephalitis virus. 1249 Nov 61

Haematopoietic stem cell transplantation is indicated in several haematologic and genetic diseases, the most notable being aplastic anemia and leukemias. Bone marrow has been the traditional source of these cells. Human umbilical cord blood (UCB) has recently become an alternative source of haematopoietic stem cells for transplants. The advantages of cord blood include noninvasive collection without risk to mother and neonate, low risk of viral infection, and immunologic immaturity of cord cells. Single umbilical cord blood donation is usually sufficient for transplantation to adult recipients. Additionally, banking of HLA-typed UCB appears valuable in patients lacking a family donor. This study has focused on basic "perinatological" parameters of umbilical cord blood: average volume of single donation UCB and initial storage conditions before isolation of haematopoietic stem cells. Additionally, the mean content of CD34+ haematopoietic stem cells in leukocyte, lymphocyte and mononuclear cell fractions was established. Correlations between levels of so-called pro-inflammatory cytokines (present in cord blood serum) and number, viability and clonogenicity of cord blood mononuclear cells were checked. UCB samples were obtained by "open" collection during vaginal deliveries and cesarean sections. The collected blood was stored in solutions of anticoagulants (ACD, CPDA-1, heparin) and culture media (PBS, Iscove medium, RPMI), during several time intervals (0-1 h, 1-6 h, 6-12 h, 12-24 h) and at two temperatures (+4 degrees C, ambient). UCB volumes, as well as MNC counts, correlated with delivery type, placental weight, neonatal body weight and duration of pregnancy. The concentration, viability and clonogenicity of MNCs were assessed after collection and storage. The subpopulation of CD34+ haematopoietic stem cells was isolated from MNCs using monoclonal antibodies and magnetic-based separation. The number, viability and clonogenicity of CD34+ cells were evaluated. Subsequently in some samples, the concentration of proinflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, IL-8, and TNF-alpha), number of mononuclear cells and in vitro clonogenicity of myeloid progenitors (CFU-GM) were determined. It was found that the collected blood volume depended on neonatal body weight (Fig. 1). Umbilical blood could be stored either at ambient temperature (Fig. 4) or +4 degrees C (recommended because of reduced risk of infection) for up to 24 hours in RPMI solution (Fig. 5) with heparin (Fig. 2, 3). CD34+ cell count correlated with mononuclear cell count only (Fig. 6). A negative correlation between the number of mononuclear cells and concentration of TNF-alpha was revealed (Fig. 7), as well as between the number of detectable CFU-GM and concentration of IL-1 beta (Fig. 8). In conclusion, UCB collection and short-term storage is a safe and simple method for graftable haematopoietic stem cell recovery. Save for IL-1 beta and TNF-alpha, cytokine levels did not correlate with the studied parameters of umbilical cord blood.
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PMID:[Improved method for delivery room collection and storage of human cord blood cells for grafting]. 1251 5

The "wait and see" approach in acute otitis media (AOM), consisting of postponing the antibiotic administration for a few days, has been advocated mainly to counteract the increased bacterial resistance in respiratory infections. This approach is not justified in children less than 2 years of age and this for several reasons. First, AOM is an acute inflammation of the middle ear caused in about 70% of cases by bacteria. Redness and bulging of the tympanic membrane are characteristic findings in bacterial AOM. Second, AOM is associated with long-term dysfunction of the inflamed eustachian tube (ET), particularly in children less than 2 years of age. In this age group, the small calibre of the ET together with its horizontal direction result in impaired clearance, ventilation and protection of the middle ear. Third, recent prospective studies have shown poor long-term prognosis of AOM in children below 2 years with at least 50% of recurrences and persisting otitis media with effusion (OME) in about 35% 6 months after AOM. Viruses elicit AOM in about 30% of children. A prolonged course of AOM has been observed when bacterial and viral infections are combined because viral infection is also associated with ET dysfunction in young children. Bacterial and viral testing of the nasopharyngeal aspirate is an excellent tool both for initial treatment and recurrence of AOM. Antibiotic treatment of AOM is mandatory in children less than 2 years of age to decrease inflammation in the middle ear but also of the ET particularly during the first episode. The best choice is amoxicillin because of its superior penetration in the middle ear. Streptococci pneumoniae with intermediary bacterial resistance to penicillin are particularly associated with recurrent AOM. Therefore the dosage of amoxicillin should be 90 mg/kg per day in three doses. In recurrent AOM with beta-lactamase-producing bacilli, amoxicillin should be associated with clavulanic acid at a dose of 6.4 mg/kg per day. The duration of the treatment is not established yet but 10 days is reasonable for a first episode of AOM. OME may be a precursor initiating AOM but also a complication thereof. OME needs a watchful waiting approach. When associated with deafness for 2-3 months in children over 2 years of age, an antibiotic should be given according to the results of the bacterial resistance in the nasopharyngeal aspirate. The high rate of complications of tympanostomy tube insertion outweighs the beneficial effect on hearing loss. The poor results of this procedure are due to the absence of effects on ET dysfunction. Pneumococcal vaccination has little beneficial effects on recurrent AOM and its use in infants needs further studies. Treatment with amoxicillin is indicated in all children younger than 2 years with a first episode of AOM presenting with redness and bulging of the tympanic membrane. Combined amoxicillin and clavulanic acid should be given in patients with beta-lactamase-producing bacteria. The duration of treatment is estimated to be at least 10 days depending on the findings by pneumo-otoscopy and tympanometry. Bacterial and viral testing of the nasopharyngeal aspirate is highly recommended particularly in children in day care centres as well as for regular follow-up. The high recurrence rate is due to the long-lasting dysfunction of the eustachian tube and the immune immaturity of children less than 2 years of age.
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PMID:What is new in otitis media? 1736 73

Acknowledgement of the breadth of T-cell pleiotropy has provoked increasing interest in the degree to which functional responsiveness is elicited by environmental cues versus differentiation. This is particularly relevant for young animals requiring rapid responses to acute environmental exposure. In young mice, gammadelta T cells are disproportionately important for immuno-protection. To examine the situation in humans, we compared populations and clones of T cells from term and preterm babies, and adults. By comparison with alphabeta T cells, neonate-derived gammadelta cells show stronger, pleiotropic functional responsiveness, and lack signatory deficits in IFN-gamma production. Emphasising the acquisition of functional competence in utero, IFN-gamma was produced by gammadelta cells sampled from premature births, and, although one month's post-partum environmental exposure invariably increased their TNF-alpha production, it had no consistent effect on IFN-gamma or IL-2. In sum, gammadelta cells seem well positioned at birth to contribute to immuno-protection and immuno-regulation, possibly compensating for selective immaturity in the alphabeta compartment. With regard to the susceptibilities of preterm babies to viral infection, gammadelta cells from preterm neonates were commonly impaired in Toll-like receptor-3 and -7 expression and compared with cells from term babies failed to optimise cytokine production in response to coincident TCR and TLR agonists.
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PMID:Neonates harbour highly active gammadelta T cells with selective impairments in preterm infants. 1954 11

In global terms, respiratory viral infection is a major cause of morbidity and mortality. Infancy, in particular, is a time of increased disease susceptibility and severity. Early-life viral infection causes acute illness and can be associated with the development of wheezing and asthma in later life. The most commonly detected viruses are respiratory syncytial virus (RSV), rhinovirus (RV), and influenza virus. In this review we explore the complete picture from epidemiology and virology to clinical impact and immunology. Three striking aspects emerge. The first is the degree of similarity: although the infecting viruses are all different, the clinical outcome, viral evasion strategies, immune response, and long-term sequelae share many common features. The second is the interplay between the infant immune system and viral infection: the immaturity of the infant immune system alters the outcome of viral infection, but at the same time, viral infection shapes the development of the infant immune system and its future responses. Finally, both the virus and the immune response contribute to damage to the lungs and subsequent disease, and therefore, any prevention or treatment needs to address both of these factors.
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PMID:Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. 2006 26

Alveolar macrophages (AMvarphis) secrete regulatory molecules that are believed to be critical in maintaining normal lung homeostasis. However, in response to activating signals, AMvarphis have been shown to become highly phagocytic cells capable of secreting significant levels of pro-inflammatory cytokines. There is evidence to suggest that susceptibility of Mvarphi subpopulations to viral infection, and their subsequent cytokine/chemokine response, is dependent on age of the host. In the present study, we compared bovine respiratory syncytial virus (BRSV) replication and induction of cytokine responses in neonatal ovine AMvarphis to those cells isolated from adult animals. While neonatal AMvarphis could be infected with BRSV, viral replication was limited as previously shown for AMvarphis from mature animals. Interestingly, following BRSV infection, peak mRNA levels of IL-1beta and IL-8 in neonatal AMvarphi were several fold higher than levels induced in adult AMvarphis. In addition, peak mRNA expression for the cytokines examined occurred at earlier time points in neonatal AMvarphis compared to adult AMvarphis. However, the data indicated that viral replication was not required for the induction of specific cytokines in either neonatal or adult AMvarphis. TLR3 and TLR4 agonists induced significantly higher levels of cytokine transcripts than BRSV in both neonatal and adult AMvarphis. It was recently proposed that immaturity of the neonatal immune system extends from production of pro-inflammatory cytokines to regulation of such responses. Differential regulation of cytokines in neonatal AMvarphis compared to adult AMvarphis in response to RSV could be a contributory factor to more severe clinical episodes seen in neonates.
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PMID:Differential expression of cytokine transcripts in neonatal and adult ovine alveolar macrophages in response to respiratory syncytial virus or toll-like receptor ligation. 2020 14


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