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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To date, bone marrow transplantation affords the only successful means of achieving full immunologic reconstitution of patients with severe combined immunodeficiency disease (SCID). We have achieved immunologic reconstitution in 6 of 7 SCID patients using marrow transplants from compatible sib donors. One child died of Pneumocystis carinii pneumonia following early immunologic reconstitution. A second child died of sepsis without evidence of engraftment, despite 3 marrow grafts, and a third died unexpectedly from massive aspiration pneumonia following complete immunologic reconstititon. Thus, in 4 of 7 children with SCID full and long-lasting immunologic reconstitution has been achieved by transplantation of marrow from matched sib donors. From these initial efforts, much has been learned, and it is clear that several factors, some of which remain poorly understood, may influence the outcome of marrow grafting. However, despite the difficulties encountered, bone marrow transplantation continues to hold real promise for correction of this otherwise fatal disease.
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PMID:Compatible bone marrow transplantation and immunologic reconstitution of combined immunodeficiency disease. 23 81

The immunologic reconstitution of 7 patients with severe combined immunodeficiency disease was attempted with bone marrow transplantation from histoidentical donors. Four patients were successfully reconstituted and discharged from the hospital. Two patients died with sepsis. One patient died from a preexisting neurologic disease. All the patients who have been successfully reconstituted have had some degree of graft-vs-host disease. A dose of 50 x 10(6) nucleated bone marrow cells per kg seems necessary for successful engraftment. The use of density gradient separation had no advantage over whole, unfractionated bone marrow.
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PMID:Transplantation in severe combined immunodeficiency disease with hl-a identical bone marrow. 23 84

The hematologic and histologic features of two, nontwin, male siblings with severe combined immunodeficiency and variable granulocytopenia are compared to the four previously reported cases of reticular dysgenesis. These sibs died at 50 and 3 days of age, respectively, with Pseudomonas sepsis and congenital cytomegalovirus infection, respectively. A maternal uncle has selective IgA deficiency. Cord blood from the second sib contained a normal percentage of E-rosetting lymphocytes; however, these lymphocytes failed to respond to mitogenic stimulation in vitro. Erythrocyte and lymphocyte levels of adenosine deaminase were elevated in the father and the second sib. Serum immunoglobulin concentrations were low in both siblings.
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PMID:Severe combined immunodeficiency with leukopenia (reticular dysgenesis) in siblings: immunologic and histopathologic findings. 95 62

Isoimmunisation to platelet and lymphocyte antigens occurred during a woman's seven pregnancies and resulted in congenital thrombocytopenia and lymphocytopenia in the last two offspring. The youngest baby died aged 16 days of severe combined immunodeficiency (SCID) with maternal graft-versus-host disease. The other affected child, however, recovered fully from thrombocytopenia and lymphocytopenia after exchange transfusion for presumed sepsis. The clinical courses indicated that an isoimmune process had caused both the thrombocytopenia and the lymphocytopenia. In accord with this conclusion, maternal titres of IgG antibodies against paternal platelets fell continuously in serial blood samples taken after the last pregnancy. Cytotoxicity studies of the maternal serum towards lymphocytes from the other siblings and from unrelated donors showed that the paternal antigen involved was a non-HLA determinant. It is postulated that isoimmune lymphocytopenia with subsequent immunological suppression is a potential mechanism for SCID and intrauterine engraftment of maternal lymphocytes.
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PMID:Maternal isoimmunisation resulting in combined immunodeficiency and fatal graft-versus-host disease in an infant. 614 80

An analysis of a prospective study of viral infections in 12 patients with severe combined immunodeficiency is presented. Infections of viral etiology were common, with pulmonary and gastrointestinal infections being most frequent. Fourteen of 25 infections (56%) were nonsocomially acquired and 10 of 25 (40%) were community-acquired. The period of symptomatology and the duration of viral excretion were usually prolonged beyond those associated with disease in the general pediatric population. Pulmonary infections were associated with considerable morbidity and mortality. Gastrointestinal infections disrupted gastrointestinal function and possibly played a role in enteric Gram-negative bacillary sepsis. The inability of these patients to eradicate these viruses in the absence of immunologic reconstitution resulted in significant morbidity, often with a fatal outcome.
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PMID:Significance of viral infections in severe combined immunodeficiency disease. 686 84

Interleukin 10 (IL-10) indirectly prevents antigen-specific T-cell activation, which is associated with downregulation of the antigen presentation and accessory cell functions of monocytes, macrophages, Langerhans cells and dendritic cells. In addition, IL-10 inhibits T-cell expansion by directly inhibiting IL-2 production by these cells. These properties of IL-10, together with its capacity to downregulate the production of proinflammatory cytokines and chemokines by activated monocytes, polymorphonuclear leucocytes and eosinophils, indicate that IL-10 is a potent immunosuppressant in vitro. IL-10 has similar activities in vivo. It inhibits lipopolysaccharide or staphylococcal enterotoxin B induced lethal shock in mice. In addition, IL-10 deficient mice develop chronic inflammatory bowel disease, which could be reduced, or prevented by IL-10 treatment. IL-10 also prevented the development of colitis in a SCID mouse model. Collectively, these data indicate that IL-10 has great potential therapeutical utility in the treatment of diseases, such as chronic inflammation, autoimmune diseases, transplant rejection, graft-versus-host disease and sepsis.
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PMID:Immunosuppressive and anti-inflammatory properties of interleukin 10. 854 Oct 28

The existence of interleukin-12-mediated innate immune responses to group B streptococci (GBS) was tested by examining T-lymphocyte-independent gamma interferon (IFN) production in cultured splenocytes from severe combined immunodeficiency mice. Splenocytes were cultured with killed or living GBS for 48 h, and then IFN was measured by enzyme-linked immunosorbent assay. Type III GBS as well as other extracellular bacterial agents of neonatal sepsis (staphylococci and enterococci) induced IFN production, which was enhanced by interleukin-2 and was inhibited by neutralizing antibodies to tumor necrosis factor alpha and to mouse interleukin-12. Interleukin-12 bioactivity was present in conditioned medium from GBS-treated adherent macrophages. Adherent peritoneal macrophages and bone marrow-derived natural killer cells from severe combined immunodeficiency mice cultured separately with GBS did not produce IFN, whereas cocultures did produce IFN. Functional macrophage activation was evident by nitric oxide production in GBS-treated splenocyte cultures. The results show that extracellular pathogens such as GBS, similarly to intracellular microbes, induce macrophage interleukin-12 and tumor necrosis factor alpha, which promote natural killer cell secretion of IFN, which then enhances innate phagocyte resistance mechanisms.
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PMID:Interleukin-12 and tumor necrosis factor alpha mediate innate production of gamma interferon by group B Streptococcus-treated splenocytes of severe combined immunodeficiency mice. 860 95

Adenoviral vectors may be useful tools to deliver a cytokine in vivo. A single intravenous injection of an adenovirus vector containing the human thrombopoietin (TPO) cDNA (AdRSVhuTPO) was able to induce a thrombocytosis for more than 6 weeks in SCID mice, associated with a megakaryocyte (MK) hyperplasia in different organs. A marrow and spleen fibrosis was observed at 6 weeks. In immunocompetent mice, a single AdRSVhuTPO injection led to a moderate and transient thrombocytosis without myelofibrosis. To evaluate the usefulness of TPO for the prevention of secondary side-effects during an aplastic period, mice were subjected to a myeloablative regimen 7 days after the intravenous AdRSVhuTPO injection. In this setting, TPO prevented mortality by accelerating hematological recovery. Survival was essentially related to an improvement in the leukopenia since all control mice died from septicemia. However, the effects of TPO may be potentiated by the release of inflammatory cytokines following the adenovirus infection; AdRSV beta galactosidase injected-mice had higher numbers of BFU-E and CFU-GM in the marrow than PBS-injected mice. Myelosuppression induced transient immunosuppression responsible for a sustained expression and elevation of platelet numbers for at least 5 months. These results further suggest that TPO may be an effective therapy in diminishing hematological complications related to myeloablative regimens, but emphasize that immunosuppression secondary to myelosuppression may lead to sustained expression associated with a risk of thrombosis and myelofibrosis when delivered by adenovirus vectors.
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PMID:Major effects of TPO delivered by a single injection of a recombinant adenovirus on prevention of septicemia and anemia associated with myelosuppression in mice: risk of sustained expression inducing myelofibrosis due to immunosuppression. 961 74

We have previously demonstrated that a high proportion of RAG-2 SCID knockout mice, which lack T and B cells, develop orofacial abscesses and disseminated infections following pulpal infection, whereas immunocompetent control mice do not. In the present study, we sought to identify the components of the adaptive immune response which contribute to protection against disseminating anaerobic infections and sepsis. For this purpose, various genetically engineered immunodeficient mice were employed, including RAG-2 SCID, Igh-6 (B-cell deficient), Tcrb Tcrd (T-cell deficient) and Hc(0) (C5 deficient). For abscess induction, the mandibular first molars were subjected to pulp exposure on day 0. Teeth were infected with a mixture of four anaerobic pathogens, including Prevotella intermedia, Streptococcus intermedius, Fusobacterium nucleatum, and Peptostreptococcus micros, and teeth were sealed to prevent communication with the oral cavity. The findings demonstrate that both RAG-2 SCID and B-cell-deficient mice, but not T-cell- or C5-deficient mice, have increased susceptibility to the development of disseminating anaerobic infections. Abscess-susceptible RAG-2 SCID and B-cell-deficient mice also showed a significant loss of body weight, splenomegaly, and absent antibacterial antibody production. Furthermore, dissemination was significantly reduced, from 74 to 25%, in susceptible RAG-2 mice by passively transferred antibody, predominantly immunoglobulin G2b (IgG2b) and IgM, against the infecting bacterial innoculum. Fractionated IgG-enriched preparations were more efficient in transferring protection than IgM preparations. We conclude that an antibody-mediated mechanism(s), most likely bacterial opsonization, is of importance in localizing anaerobic root canal infections and in preventing their systemic spread.
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PMID:B-Cell deficiency predisposes mice to disseminating anaerobic infections: protection by passive antibody transfer. 1099 65

Sepsis is a major mortality concern with burned patients, who have an increased susceptibility to infectious complications. PBMC from 41 of 45 severely burned patients (91%) failed to produce macrophage inflammatory protein 1alpha (MIP-1alpha) in cultures, while 2355-6900 pg/ml MIP-1alpha were produced by healthy donor PBMC, stimulation with anti-human CD3 mAb. Healthy chimeras (SCID mice inoculated with healthy donor PBMC) treated with anti-human MIP-1alpha mAb and patient chimeras (SCID mice reconstituted with burned patient PBMC) were susceptible (0% survival) to infectious complications induced by well-controlled cecal ligation and puncture. In contrast, patient chimeras treated with human recombinant MIP-1alpha and healthy chimeras were resistant ( approximately 77-81% survival). Similarly, after anti-mouse CD3 mAb stimulation, splenic mononuclear cells from burned mice (6 h to 3 days after thermal injury) did not produce significant amounts of MIP-1alpha in their culture fluids. Normal mice treated with anti-murine MIP-1alpha mAb and burned mice were susceptible to cecal ligation- and puncture-induced infectious complications, while burned mice treated with murine recombinant MIP-1alpha and normal mice were resistant. Burned patients seemed to be more susceptible to infectious complications when the production of MIP-1alpha was impaired.
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PMID:An increase in the susceptibility of burned patients to infectious complications due to impaired production of macrophage inflammatory protein 1 alpha. 1237 Mar 81


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