Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The outcomes of 69 patients who received allogeneic bone marrow grafts for autosomal recessive osteopetrosis in the period between 1976 and 1994 were analyzed retrospectively. Four patients received bone marrow transplants (BMT) without prior myeloablative conditioning; transient osteoclast function was demonstrated in one of them. Sixty-five patients received myeloablative pretreatment. Recipients of a genotypically human leukocyte antigen (HLA)-identical BMT had an actuarial probability for 5-year survival, with osteoclast function, of 79%; recipients of a phenotypically HLA-identical bone marrow graft from a related or unrelated donor, or one HLA-mismatched graft from a related donor, had an actuarial probability for 5-year survival, with osteoclast function, of 38%; patients who received a graft from an HLA-haplotype mismatched related donor had a probability for 5-year survival of only 13%. The main problems in haplotype-nonidentical BMT were graft failure and BMT-related complications such as sepsis, bleeding, and interstitial pneumonia. Osteoclast function developed in all patients with full engraftment. Recovery of osteoclast function was associated with severe hypercalcemia in 24% of the patients with engraftment, especially those older than 2 years of age. At the time of BMT, severe visual impairment was present in 35% of the patients; of the 15 patients who had visual impairment at the time that a successful BMT was performed, two had improvement after BMT (13%). Within the total group, one patient had neurodegeneration. Engraftment of healthy donor cells had no influence on the progression of that abnormality and BMT thus had no beneficial effect on this phenotype of osteopetrosis. In general, however, early BMT remains the only curative treatment for autosomal recessive osteopetrosis.
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PMID:Bone marrow transplantation for autosomal recessive osteopetrosis. A report from the Working Party on Inborn Errors of the European Bone Marrow Transplantation Group. 799 61

We retrospectively analyzed the outcome of bone marrow transplantation (BMT) performed in 26 patients with Wiskott-Aldrich syndrome (WAS) in one center. Twenty-eight transplantation procedures were performed. Ten unselected patients received unmanipulated marrow from a donor with genetically identical human leukocyte antigen (HLA). Eight patients were cured and survive 1.5 to 16.5 years after BMT. One patient successfully received a T-cell-depleted marrow from a matched unrelated donor. Sixteen patients were selected to receive a related HLA partially incompatible BMT because of the occurrence of life-threatening complications from the WAS (i.e., refractory thrombocytopenia, autoimmunity including vasculitis and sepsis). All but one received T-cell-depleted marrow after a conditioning regimen of busulfan and cyclophosphamide. One patient had two BMTs. Engraftment occurred in 12 of 17 attempts. The addition of monoclonal antibodies to lymphocyte function-associated antigen-1 and CD2 molecules appeared to improve engraftment. Six patients were long-term survivors, whereas others died of viral infections (n = 7), among which Epstein-Barr virus-induced B-lymphocyte proliferative disorder was predominant. Delay in development of full T- and B-cell functions accounted for severe infectious complications. These results confirm the excellent outcome of HLA genetically identical BMT in WAS, whereas BMT from HLA partially incompatible donors should be strictly restricted to patients with severe complications of WAS.
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PMID:Bone marrow transplantation in 26 patients with Wiskott-Aldrich syndrome from a single center. 876 21

Acquired, idiosyncratic aplastic anaemia (AA) is a rare but potentially fatal haematological disorder. Severe AA constitutes an acute medical emergency, and supportive therapy is needed to prevent overwhelming sepsis or a life threatening haemorrhage. Specific therapy for the disease includes the choice between allogeneic stem cell transplantation (SCT) from an HLA-identical sibling or immunosuppressive therapy with anti-thymocyte globulin (ATG) and cyclosporin A (CSA). Long-term cure rates of 75-90% are now achieved following HLA (human leukocyte antigen) identical sibling bone marrow transplant. The use of donors other than HLA-id siblings for transplantation in AA remains experimental. Transplantation offers the patient a chance of cure, whilst treatment with immunosuppressive therapy carries a long-term risk of relapse and clonal transformation. The haemopoietic growth factors, apart from granulocyte colony stimulating factor (G-CSF), have been shown to be potentially toxic when given to patients with AA. A short course of G-CSF may be useful to help treat severe infection, but its longer-term use with ATG and CSA remains controversial. Results from immunosuppressive treatment continue to improve with time, as a result of the additional use of CSA with ATG, the use of repeat courses of ATG for non-responders and improvements in the supportive care of patients.
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PMID:Aplastic anaemia: management. 1098 51

Two cases of listeriosis in patients submitted to matched unrelated donor bone marrow transplantation are reported. The patients developed listerial septicemia and listerial septicemia with meningitis and encephalitis 39 and 29 days after transplantation, respectively. Including the present two cases, 19 Listeria monocytogenes infections in related and unrelated donor allogeneic bone marrow transplant recipients have been reported to date. Infection occurred earlier in unrelated donor transplant recipients. Listeriosis is a rare complication in allogeneic bone marrow transplant recipients; however, the widespread practice of performing transplants from a donor-alternative to a human leukocyte antigen-compatible sibling and, in this setting, the need for intensified immunosuppression may predict an increasing and earlier occurrence of listeriosis.
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PMID:Listeriosis in recipients of allogeneic bone marrow transplants from unrelated donors. 1105 7

Monocyte phenotype, their phagocytic capacity as well as the cytokine production from 10 patients with sepsis with low interleukin-6 (IL-6) serum concentrations (<1000 pg/mL) and 8 patients with sepsis with high IL-6 (> or = 1000 pg/mL) plasma concentrations were investigated within 24 hours of fulfilling the criteria for sepsis. Monocytes from patients with high IL-6 levels had higher levels of human leukocyte antigen (HLA)-DR, HLA-ABC, CD64, and CD71, and the production of tumor necrosis factor-alpha (TNF-alpha) and IL-8, as well as the capacity of monocytes to phagocytose, was significantly elevated. Of 8 patients with high levels of plasma IL-6, 4 patients died. In contrast, all 10 patients with low plasma IL-6 concentrations survived until day 28. Patients who died had constant high IL-6 concentrations during the first 3 days, whereas IL-6 levels in patients who survived decreased by 88%. Our data indicate that IL-6 levels are a better prognostic parameter in the early phase of sepsis than the monocyte HLA-DR expression.
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PMID:Relationship between interleukin-6 plasma concentration in patients with sepsis, monocyte phenotype, monocyte phagocytic properties, and cytokine production. 1109 99

Bacterial superantigens are believed to cause septic shock, although, because of the lack of superantigen-sensitive infection models, proof that superantigenicity underlies shock pathogenesis is lacking. This work demonstrates a clear superantigen effect in septic shock resulting from bacterial infection. Transgenic expression of human leukocyte antigen (HLA)-DQ, but not HLA-DR, specifically augments lymphocyte responses to streptococcal pyrogenic exotoxin A (SPEA). HLA-DQ transgenic mice had increased mortality after administration of SPEA or infection with Streptococcus pyogenes. Immune activation during infection was HLA-DQ transgene-dependent and was manifested by Vbeta-specific T cell repertoire changes and widespread lymphoblastic tissue infiltration. Unlike earlier models, which used toxin-induced shock, these T cell superantigen responses and lymphoblastoid changes were observed during invasive streptococcal sepsis. Lymphoid activation was undetectable in HLA-DQ mice infected with an isogenic SPEA(-) strain, which proves that a single superantigen can play a role in sepsis pathogenesis.
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PMID:Enhanced susceptibility to superantigen-associated streptococcal sepsis in human leukocyte antigen-DQ transgenic mice. 1142 13

Despite systematic antibiotic therapy, severe infections (septicemia, meningitis, or osteomyelitis) are a major cause of mortality and morbidity in children with sickle cell disease (SCD). In this study, we explored the possibility that polymorphism at the human leukocyte antigen (HLA) locus might constitute an immunogenetic modifying factor to the intrinsic susceptibility to infection in patients with SCD. A cohort of 80 SCD patients living in Paris, 43 with at least one major infectious complication and 37 without infections, were typed for HLA class II loci by polymerase chain reaction-sequence-specific primers (PCR-SSP). We found that significantly more patients without infections carry the HLA class II DRB1*15 specificity than did patients with infections (21.6% in the first group, versus 4.7% in the second group; chi(2) = 10.47, p(c) = 0.01), supporting a protective effect of this allele. Conversely, significantly more patients were found to carry the DQB1*03 specificity within the group of severe infections, supporting a negative effect (34.9% versus 12.2%, chi(2) = 9.41, p(c) = 0.01). These findings suggest a direct involvement of HLA polymorphism in the development of major infections in SCD. Together with previous data on polymorphism of the Fc receptor and of the mannose-binding lectin, they provide evidence for a polygenic immunomodulation of the constitutively increased infectious risk in SCD.
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PMID:Infectious complications in sickle cell disease are influenced by HLA class II alleles. 1187 37

Monocytes from many critically ill patients show a low level of major histocompatibility complex type II (MHC II) expression. This phenomenon is believed to play a role in these patients' increased susceptibility to secondary infections. In the present study, we show that the level of monocyte human leukocyte antigen (HLA)-DR expression inversely correlates with the degree of severity of the sepsis syndrome. The defect of the monocyte HLA-DR expression resides in an intracellular sequestration of the MHC II molecules, a posttranslational effect. No significant decrease in the rate of transcription of HLA-DR, or its major transcriptional inducer, Class II transactivator, was noted. The levels of HLA-DR protein produced by monocytes from patients with septic shock were comparable to those from healthy volunteers. Plasma from patients with septic shock induced significant HLA-DR endocytosis resulting in decreased surface HLA-DR expression of normal donor monocytes. This effect was partially blocked by anti-interleukin (IL)-10 monoclonal antibody, but not by antagonists to transforming growth factor-beta1, prostaglandins, or beta-adrenergic agonists. Altogether, these data suggest that HLA-DR molecules are re-endocytosed and retained intracellularly in monocytes from patients with septic shock, and that this phenomenon is partially mediated by IL-10. IL-10 may represent a future target for immunomodulating patients with the sepsis syndrome or critically ill patients at risk of developing infections.
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PMID:Role of interleukin-10 in the intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock. 1245 Sep 29

Genetic epidemiologic studies suggest a strong genetic influence on the outcome from sepsis, and genetics may explain the wide variation in the individual response to infection that has long puzzled clinicians. Several candidate genes have been identified as important in the inflammatory response and investigated in case-controlled studies, including the tumor necrosis factor (TNF)-alpha and TNF-beta genes, positioned next to each other within the cluster of human leukocyte antigen class III genes on chromosome 6. Other candidate genes for sepsis and septic shock include the interleukin (IL)-1 receptor antagonist gene, the heat shock protein gene, the IL-6 gene, the IL-10 gene, the CD-14 gene, the Toll-like receptor (TLR)-4 gene, and the TLR-2 gene, to name a few. In this review, we summarize the evidence for a genetic susceptibility to development of sepsis and death from sepsis, discuss design of clinical genetics studies relevant to the study of complex disorders, consider the candidate genes likely to be involved in the pathogenesis of sepsis, and discuss the potential for targeted therapy of sepsis and septic shock based on genetic variability.
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PMID:Genetic polymorphisms in sepsis and septic shock: role in prognosis and potential for therapy. 1297 43

This study was performed to evaluate the impact of pro- and anti-inflammatory molecules and human leukocyte antigen DR (HLA-DR) expression as markers of immune status for the final outcome of septic patients. The study included 30 patients with severe sepsis due to community-acquired infections. Concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, IL-10, and transforming growth factor beta1 (TGF-beta1) in serum, as well as monocyte HLA-DR expression, were determined on admission and on days 3, 10, 13, and 17 during hospitalization. Of the 30 patients enrolled, 13 survived, while 17 died during their hospital stay. All patients had significantly lower HLA-DR expression and higher pro- and anti-inflammatory cytokine levels than healthy individuals. HLA-DR expression was significantly decreased in nonsurvivors at almost all time points. In nonsurvivors, higher levels in serum of TNF-alpha on days 13 and 17; IL-6 levels on day 3; and IL-10 on days 3, 10, and 13 were found. Baseline levels of TGF-beta1 were significantly higher in survivors. Independent risk factors of mortality were IL-10 levels on days 3 and 10, while monocyte HLA-DR expression on admission was a good predictor for survival. Several pro- and anti-inflammatory cytokines are oversynthesized during severe infections, especially in patients with a poor outcome. Monocyte HLA-DR expression is an early and constant predictive marker for survival in severe sepsis, while serum IL-10 levels on days 3 and 10 have negative prognostic value for the final outcome.
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PMID:Cytokine production and monocyte HLA-DR expression as predictors of outcome for patients with community-acquired severe infections. 1471 64


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