UMLS:C0029713 - FACTA Search

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Query: UMLS:C0029713 (immaturity)
4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute leukemia in the newborn child is a rare event. The clinical and biological characteristics differ from those normally encountered in the older child. Tumoral syndrome and extra-medullar locations are frequently described in the literature. Many authors have noted the difficulty of diagnosis due to the immaturity of the malignant proliferation. While it is generally agreed that therapeutic abstention is justified in the leukemoid reaction in Down's syndrome, the choice is debatable in the phenotypically intact newborn. For this reason, blastic karyotype analysis is essential and may provide guidelines when considering treatment. We report on a case history of acute monoblastic leukemia with translocation 9;11 that was diagnosed at birth in a normal newborn infant. The juxtaposition of c-ets 1 protooncogene and the beta-interferon gene has been associated with this kind of cytogenetic disease and probably constitutes a model for human leukemogenesis.
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PMID:[Acute congenital monoblastic leukemia and 9;11 translocation: a case]. 133 93

We have reviewed the results of treating over 100 HBV carriers with adenine arabinoside, adenine arabinoside monophosphate and lymphoblastoid interferon. In the homosexual group of carriers, adenine arabinoside and its monophosphate have no value. However in this group, lymphoblastoid interferon will produce a response in over 50% of cases. This lack of effectiveness of adenine arabinoside monophosphate in this group may stem from its immunosuppressant properties. In heterosexual carriers both adenine arabinoside monophosphate and lymphoblastoid interferons are effective in approximately 50% to 60% of cases. However, the response rate is different in the various racial groups. Northern European and Mediterranean people appear to respond whereas those from the Far East do not. This may reflect the fact that there are at least two mechanisms by which the chronic carrier state may arise. In 5% to 10% of adults, a relative deficiency of alpha interferon production exists, and this defect is found in the majority of HBV carriers in Western Europe. In these, interferon acts as a replacement therapy and excellent results may be obtained if the patient is treated early in the course of the disease. It would appear that as the duration of the infection increases, the virus may integrate into interferon-reactive consensus sites and prevent the cell from responding to interferon. In patients infected at birth, transplacental anti-HBc appears to modulate the immune response and, along with immaturity of the immune system at this age, results in failure to lyse infected cells. These patients do not benefit from interferon treatment: some form of immune manipulation is required.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A review of the efficacy of adenine arabinoside and lymphoblastoid interferon in the Royal Free Hospital studies of hepatitis B virus carrier treatment: identification of factors influencing response rates. 243 62

We have reviewed the results of treating over 100 HBV carriers with adenine arabinoside, adenine arabinoside monophosphate and lymphoblastoid interferon. In the homosexual group of carriers, adenine arabinoside and its monophosphate have no value. However, in this group, lymphoblastoid interferon will produce a response in over 50% of cases. The lack of effectiveness of adenine arabinoside monophosphate in this group may stem from its immunosuppressant properties. In heterosexual carriers both adenine arabinoside monophosphate and lymphoblastoid interferon are effective in approximately 50-60% of cases. However, the response rate is different in the various racial groups. Northern European and Mediterranean people appear to respond whereas those from the Far East do not. This may reflect the fact that there are at least 2 mechanisms by which the chronic carrier state may arise. In 5-10% of adults, a relative deficiency of alpha-interferon production exists and this defect is found in the majority of HBV carriers in Western Europe. In these, interferon acts as a replacement therapy and excellent results may be obtained if the patient is treated early in the course of the disease. It would appear that as the duration of the infection increases, the virus may integrate into interferon-reactive consensus sites and prevent the cell from responding to interferon. In patients infected at birth, transplacental anti-HBc appears to modulate the immune response and along with immaturity of the immune system at this age, results in failure to lyse infected cells. These patients do not benefit from interferon treatment: some form of immune manipulation is required.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of factors influencing response rate to antiviral therapy of chronic hepatitis B virus infection. A review of the efficacy of adenine arabinoside and lymphoblastoid interferon in the Royal Free Hospital studies. 243 75

HIV infection induces both immune deficiency and immune stimulation. Central to the pathology of HIV infection is reduction in the numbers and function of CD4 T cells. Impaired functions include decreased proliferation, IL-2 receptor expression and production of lymphokines (IL-2 and gamma interferon (IFN]. HIV infection stimulates B cells and CD8 T cells. This is seen relatively soon after HIV infection. Increased activation and immaturity are seen in both these cell groups. In vitro studies confirm HIV stimulation of these cells. Studies have been conducted on patients with AIDS and opportunistic infection (OI) or Kaposi's sarcoma (KS), with AIDS-related complex (ARC) or with persistent generalized lymphadenopathy (PGL), as well as on asymptomatic HIV-seropositive and -seronegative homosexually active men. The latter group has been followed at 6-month intervals for the past 2-3 years. Those who seroconverted (became HIV-infected) were studied to investigate early changes following HIV infection. To delineate the immunopathology of infection with HIV, serial testing of seropositive individuals was carried out to determine the rate of CD4-T-cell reduction. Lowered CD4-T-cell number and percentage and CD4/CD8 ratio correlate with the occurrence of AIDS and with survival after AIDS-KS diagnosis. Seropositive individuals, however, differed markedly in the rate of CD4-T-cell reduction; in some, no reduction in CD4 cells occurred over a two-year period of observation. We propose that, in individuals in which CD4 levels have reached a plateau, effective host resistance to further CD4 cytoreduction has occurred.
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PMID:Immune pathogenesis of AIDS and related syndromes. 295 95

We have studied NK activity against K562 cells of peripheral blood mononuclear cells (PBMC) from 83 patients affected with RA and searched for correlations with some clinical and laboratory parameters. In 65 patients T lymphocyte subsets were investigated by laser flow cytometry using monoclonal antibodies against OKT3, OKT4 and OKT8 antigens and in 25 patients also HNK-1+ cells were enumerated. NK activity in patients with RA resulted significantly decreased compared with controls (relative cytotoxic index = 0.68 +/- 0.74 versus 1.00 +/- 0.60, p less than 0.01). Decreased NK activity was not correlated with sex, age, duration of disease, ESR, haemoglobin, serum alpha-2-globulin, serum gamma-globulin, rheumatoid factor titre. The only clinical parameter correlated with decreased NK activity was the anatomical stage of the disease. NK activity depression resulted to be significantly correlated with OKT3+ cell percentage and at a lesser extent with OKT4+ and OKT8+ cell percentages. HNK-1+ cell percentage resulted only slightly reduced in patients with RA (13.1 +/- 8.7 versus 15.0 +/- 7.0) and there was only a modest correlation (p approximately equal to 0.10) between NK activity and HNK-1+ cell percentage. In order to elucidate the mechanisms of impaired NK activity in RA, experiments in vitro were carried out on PBMC of 23 patients to investigate the effects of the depletion of cells adherent to plastic, incubation with beta-interferon (1000 IU/ml) and incubation with indomethacin (10 -6M). Our data suggest that decreased NK activity in RA is mainly due to functional immaturity of NK cells and sometimes to inhibition by monocytes in some cases probably through prostaglandin release.
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PMID:Impaired natural killing activity in patients with rheumatoid arthritis. Clinical characteristics and a study of defective mechanisms. 348 36

The human newborn is particularly susceptible to infections in the neonatal period, due in part to the immaturity and naive state of the immune system. The role of interferon and natural killer cells in host defense in this age group is poorly defined. We have studied natural killer cells and the activation of the interferon system in cord blood. Most newborns (75%) had low natural killer cell activity, and this was unrelated to levels of the intracellular interferon-associated enzyme, 2'-5' oligoadenylate synthetase (2-5A synthetase). Newborn cells responded to interferon in vitro with an increase in natural killer activity, suggesting that this low natural killer cell activity is the result of fewer numbers of effector cells rather than a functional immaturity. Circulating serum interferon was detected in greater than 50% of maternal samples tested; however, this did not correlate with 2-5A synthetase levels in maternal or the corresponding cord blood mononuclear cells. Natural killer cell activity was low in the newborn in spite of activation of the interferon system in 39% of these individuals. This may be an important factor in susceptibility to infections in this period.
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PMID:The host defense system in the human newborn: the role of interferon and the natural killer cell. 608 99

In this paper we report that differentiation of the human promyelocytic leukemia cell line, HL60, along the myelocytic pathway, induced by retinoic acid (RA), or monocytic pathway, induced by phorbol-myristate acetate (PMA) and gamma interferon (IFN), was accompanied by a significant decline in 1,25-dihydroxycholecalciferol (1,25(OH)2D3) binding (control: 30.3 +/- 3.0 fM/10(6) cells; RA treated: 6.8 + 2.5 fM/10(6) cells; PMA treated: 12.3 +/- 6.7 fM/10(6) cells and IFN treated: 16.0 +/- 5.0 fM/10(6) cells). When differentiation and proliferation were uncoupled, by incubation with IFN or by inhibition of proliferation by cell density saturation, 1,25(OH)2D3 binding was better related to differentiation than to proliferation. Additionally we have compared 1,25(OH)2D3 binding levels in blasts from acute lymphocytic leukemia (ALL) patients (25.4 +/- 18.1 fM/10(6) cells) and normal, mature lymphocytes (10.6 +/- 2.1 fM/10(6) cells). Receptor binding was significantly higher (p < 0.05) in the immature blasts. Our data suggest that 1,25(OH)2D3 receptor levels could be considered a marker of functional immaturity, in these cells.
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PMID:Vitamin D3 binding activity during leukemic cell differentiation. 767 73

Interleukin-12 (IL-12) is a critical cytokine regulating natural killer (NK) and T-cell function. We hypothesized that the impaired ability of cord blood (CB) to produce normal adult levels of IL-12 in response to stimulation may contribute to the immaturity of CB immunity. Furthermore, exogenous IL-12 may compensate for the immaturity in CB cellular immunity and have the potential for immunotherapy post cord blood transplantation. We compared the expression and production of IL-12 from activated cord versus adult mononuclear cells (MNC), regulatory mechanisms associated with IL-12 expression in CB MNC, and the effects of IL-12 on induction of CB interferon (IFN)-gamma production, NK, and lymphokine-activated killer (LAK) cytotoxicity. Northern analysis and enzyme-linked immunosorbent assay were performed in lipopolysaccharide (LPS)-stimulated CB and adult peripheral blood (APB) MNC. IL-12 mRNA expression was induced within 6 hours with LPS (10 micrograms/ml) and reached peak levels at 12 hours in both CB and APB MNC. However, IL-12 mRNA expression and protein accumulation in CB MNC were 35.8% +/- 4.84% (12 hours, n = 11, P < .05), and 17.6% +/- 1.7% (24, 72, 96 hours, n = 9, P < .05) respectively, when compared with APB MNC. Nuclear run-on assays showed no differences between CB and APB MNC in both the basal levels of transcription and the degree of transcriptional activation. However, the half-life of IL-12 p40 mRNA was approximately threefold lower in activated CB MNC than in activated APB MNC (CB: 114 +/- 3.0 minutes v APB: 353 +/- 7.8 minutes, n = 3, P < .05). Exogenous IL-12 (10 U/mL) induced a significant increase of IFN-gamma from both CB and APB MNC (24 hours, 72 hours, P < .05, n = 3). The stimulated CB IFN-gamma level reached comparable levels produced by unstimulated APB. IL-12 treatment also significantly enhanced CB NK cytotoxicity against K562 and NB-100 cell lines to the comparable levels of APB (P < .05, n = 4). CB MNC was more responsive to IL-12 stimulation with respect to IFN-gamma production, NK, and LAK cytotoxicity when compared with APB. The present study suggests that IL-12 mRNA and protein expression is decreased in activated CB. This discrepancy in IL-12 production is secondary, at least in part, to the altered posttranscriptional regulation. The impaired, ability of CB MNC to produce IL-12 in response to stimulation may contribute to the decrease in IFN-gamma production and NK cytotoxicity. However, IL-12 enhanced IFN-gamma and NK activity in CB MNC up to the comparable levels of APB MNC. These findings suggest that reduced expression and production of IL-12 from activated CB may contribute to the immaturity in CB cellular immunity and contribute, in part, to decreased graft-versus-host disease following CB stem cell transplantation.
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PMID:Decreased interleukin-12 (IL-12) from activated cord versus adult peripheral blood mononuclear cells and upregulation of interferon-gamma, natural killer, and lymphokine-activated killer activity by IL-12 in cord blood mononuclear cells. 870 53

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

The newborn immune system differs quantitatively and functionally from that of adults. Development of the immune system has important implications for childhood diseases. The immaturity of the immune system in the first years of life may contribute to failure of tolerance induction and in the development of allergic disease. T cell function is diminished, especially the capacity to produce cytokines; production of interferon (IFN)-gamma, and IL-4 is strongly reduced. IFN-gamma has been found to be even lower in cord blood of newborns with a family history of atopy. Differences in other cell types (natural killer cells, antigen-presenting cells, and B cells) could also play a role in the development of allergic disease. Current data suggest that irregularities in IgE synthesis, helper T cell subsets (Th1, Th2, CD45RA, and CD45RO), cytokines (IL-4, IFN-gamma), and possibly other cell types may play a role in the development of allergy in childhood. Moreover, the role of cell surface molecules, like co-stimulatory molecules (CD28, CD40L), activation markers (CD25), and adhesion molecules (LFA-1/ICAM-1, VLA-4/ VCAM-1) is also discussed. These variables are modulated by genetic (relevant loci are identified on chromosome 5q, 11q, and 14) and environmental forces (allergen exposure, viral infections, and smoke). The low sensitivity of current predictive factors for the development of allergic diseases, such as cord blood IgE levels, improves in combination with family history and by measurement of in vitro responses of lymphocytes and skin reactivity to allergens. New therapeutic approaches are being considered on the basis of our current understanding of the immunopathology of allergic disease, for instance cytokine therapy and vaccination with tolerizing doses of allergen or peptides.
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PMID:Development of immune functions related to allergic mechanisms in young children. 886 70

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