Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to clarify the clinical usefulness of the morphological classification of multiple myeloma (MM) originally proposed by Greipp, et al. and modified by us, Giemsa-stained MM cells in bone marrows obtained from 61 untreated patients were analyzed. According to the original classification, there was no significant difference in survival time between the patients with plasmablastic MM and those with other types. However, the mean survival time of each type of MM according to the modified classification was 2014 days in mature MM, 1564 days in intermediate MM, 967 days in immature MM, and 254 days in plasmablastic MM. The survival time of plasmablastic MM was significantly shorter than those of other types. DNA aneuploidy was observed more frequently in plasmablastic MM than in other types. Furthermore, PCNA- and Ki-67-positive rates were higher in plasmablastic MM than in other ones. Four of five patients with plasmablastic MM who were treated with VAD(vincristine, doxorubicin, dexamethasone) regimen showed no significant effect, and most patients with the type died of sepsis or renal failure. From these results, it was concluded that patients with plasmablastic MM have a poor prognosis. Moreover, our modified classification is recommended as a clinically useful approach for selecting treatment strategy and predicting an accurate prognosis.
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PMID:[Usefulness of the modified Greipp's morphological classification of multiple myeloma cells]. 899 Sep 39

Cytomegalovirus (CMV) titer in blood seems to be the principal determinant of clinical symptoms in immunosuppressed patients. We have developed an assay for quantitation of CMV DNA in serum. The assay requires the coamplification by polymerase chain reaction (PCR) of extracted serum DNA with 1000 molecules of mutated internal standard DNA, and then an ELISA detection system. We examined 133 paired buffy coats and sera from 15 patients with symptomatic infection. Sera were examined by quantitative PCR, and buffy coats were examined by qualitative PCR (with a detection threshold of approximately 40 copies per 150,000 cells). Serum viral titers peaked during the seventh week after transplant (median day 40, range 26-58) at about the time of symptom onset. Mean viral titer measured during the seventh week was 1.2 x 10(5) copies per milliliter of serum (standard error 6.5 x 10(4). Buffy-coat PCR results were generally concordant with results of serum PCR (overall concordance 103/133=77.4%). Serum CMV titer fell, as symptoms resolved with reduction of immunosuppression and specific antiviral therapy. High titers and poor response to antiviral therapy were observed in the context of excessive immunosuppression and bacterial sepsis. Measurement of serum CMV titer may be useful for the management of immunosuppressed transplant recipients, and provides a tool for the better understanding of factors that enhance or inhibit viral replication.
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PMID:Patterns of viremia in liver transplant recipients with symptomatic cytomegalovirus infection. 900 Jun 63

Tissue factor (TF) expression by peripheral blood monocytes during sepsis initiates intravascular thrombosis. Bacterial lipopolysaccharide (LPS) rapidly induces TF gene transcription in monocytes. The human TF promoter contains binding sites for the transcription factors AP-1, c-Rel/p65, Egr-1, and Sp1. NF-kappa B/Rel proteins have been shown to physically interact with both AP-1 and Sp1 proteins. In this study, we investigated the role of these transcription factors in uninduced and LPS-induced TF gene expression in human monocytic THP-1 cells. Deletional analysis indicated that five Sp1 sites mediated basal expression in uninduced cells. The two AP-1 sites bound c-Fos/c-Jun heterodimers in both unstimulated and LPS-stimulated cells. Maximal LPS induction of the TF promoter required the two AP-1 sites and the kappa B site within the LPS response element. Disruption of the conserved spacing between the proximal AP-1 site and the kappa B site abolished LPS induction. Replacement of the two AP-1 sites with intrinsically bent DNA partially restored LPS induction, suggesting an additional structural role for the AP-1 sites. Synergistic transactivation of the LPS response element in Drosophila Schneider cells by coexpression of c-Fos, c-Jun, c-Rel, and p65 or c-Jun and p65 required the transactivation domains of c-Jun and p65. These data indicated that c-Fos/c-Jun, c-Rel/p65, and Sp1 regulate TF gene expression in human monocytic cells.
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PMID:Regulation of the tissue factor gene in human monocytic cells. Role of AP-1, NF-kappa B/Rel, and Sp1 proteins in uninduced and lipopolysaccharide-induced expression. 908 93

The functions of thyroid cells are regulated by a number of cytokines and growth factors in addition to TSH. Recent studies have revealed that several cytokines including interleukin (IL)-6 are involved in thyroid dysfunction. Oncostatin M (OSM) is a glycoprotein belonging to the same family of cytokines as IL-6, to which it is related by sequence and structural homology and the use of the signal-transducing receptor component gp130. We, therefore, studied the effect of OSM on iodide uptake and DNA synthesis by porcine thyroid cells in culture. OSM increased c-fos and c-jun mRNA levels but did not stimulate DNA synthesis. OSM inhibited iodide uptake stimulated by TSH; while IL-6 also inhibited iodide uptake, it was only about one-tenth as potent. IL-6 had about the same potency as OSM when it was added with soluble IL-6 receptor. OSM had no effect on cAMP production but inhibited iodide uptake stimulated by 8-bromo-cAMP and forskolin. These findings suggest that OSM exerts its inhibitory effects at the post-cAMP production step(s). OSM also inhibited thyroid peroxidase mRNA levels but had little effect on thyroglobulin mRNA levels. Investigations of the signal transduction system showed that gp130 and leukemia inhibitory factor (LIF) receptor beta subunit mRNA were detectable in porcine thyroid cells by reverse transcription (RT)-polymerase chain reaction (PCR). Together with the report that serum OSM and IL-6 concentrations are elevated to the same levels in patients with sepsis, these results suggest that OSM may contribute to the thyroid dysfunction in this condition.
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PMID:Oncostatin M: a new potent inhibitor of iodine metabolism inhibits thyroid peroxidase gene expression but not DNA synthesis in porcine thyroid cells in culture. 908 75

Group B streptococci (GBS) are a leading cause of neonatal sepsis and meningitis. Besides the type-specific capsule, which is considered to be a major virulence factor of the species, some proteins are believed also to be virulence determinants and have been found to elicit protective immunity. In the present work, the genes for two surface proteins, the alpha and beta antigens, were detected in hybridization tests with chromosomal DNA of clinical GBS isolates. Using as a probe a PCR-generated 1.5 kb part of the beta gene, hybridization was found for 4/19 type Ia, 8/11 type Ib, 5/6 type II but for 0/8 type III strains. Positive outcome of hybridization coincided with an ability of the strains to bind IgA. A 200 bp alpha gene probe hybridized with all tested strains of serotypes Ia, Ib or II but only with 4/17 type III strains. By Southern blot, it was found that the size of the EcoRI chromosomal gene fragments hybridizing with the alpha gene probe correlated with the genomic presence or absence of the beta gene, possibly reflecting evolutionary relationship between the two genes. This assumption was further supported by pulsed field gel hybridization analysis which, however, showed the chromosomal positions of these two genes not to be adjacent.
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PMID:Molecular analysis of clinical group B streptococcal strains by use of alpha and beta gene probes. 909 35

Two challenges (intraperitoneal lipopolysaccharide (LPS) administration and cecal ligation and puncture (CLP)) and two strains of mice (LPS-normoresponder (C3H/HeN) and LPS-hyporesponder (C3H/HeJ)) were used to investigate pathways of cell injury. After intraperitoneal administration of LPS, endotoxin was absorbed into the bloodstream (HeN, 10.4 +/- 9.4 x 10(4) EU/mL; HeJ, 14.7 +/- 6.0 x 10(4) EU/mL), but as expected, only C3H/HeN mice produced serum tumor necrosis factor (TNF) (HeN, 2.5 +/- 2.0 x 10(3)pg/mL; HeJ, 87.0 +/- 38.7 pg/mL). Gel electrophoretic analysis of DNA extracted from six organs demonstrated the apoptotic "ladder" only in the thymus and only in the HeN mice. When the mice were challenged with CLP, both HeN and HeJ produced a small amount of serum TNF (HeN, 5.8 +/- 3.5 x 10(2) pg/mL; HeJ, 2.2 +/- 2.5 x 10(2) pg/mL) and both strains had very mild endotoxemia (HeN, 23.4 +/- 3.8 EU/mL; HeJ, 27.9 +/- 10.1 EU/mL). The DNA fragmentation pattern characteristic of apoptosis was observed not only in thymus but also in spleen, lung, and Peyer's patch of gut of both strains. This organ-specific pattern was more pronounced in the thymus of HeN mice; otherwise, the organ-specific patterns were similar for HeN and HeJ mice challenged by CLP but absent in those same organs when those same mice were challenged with LPS. The data suggest the existence not only of an endotoxin-driven activation for thymic apoptosis, but also of an endotoxin-independent, TNF-independent pathway activating widespread apoptosis in the murine CLP model of sepsis.
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PMID:Cecal ligation and puncture (CLP) induces apoptosis in thymus, spleen, lung, and gut by an endotoxin and TNF-independent pathway. 911 Apr 9

1. Colchicine is a highly active alkaloid used in the treatment of gouty arthritis and pseudogout. In overdose colchicine inhibits cell division effecting organs with a high rate of cell turn-over, such as the gastrointestinal tract and bone marrow. Early fatality results from cardiovascular collapse and respiratory failure, however pancytopenia and overwhelming septicaemia can occur later. 2. We describe a case of suicidal ingestion of 25-30 mg of colchicine in a previously healthy 43-year-old woman. Initial symptoms were mainly gastrointestinal. By day 5 she had developed severe pancytopenia and early sepsis, which were successfully treated using granulocyte colony stimulating factor (G-CSF) 600 micrograms s.c. 3. In vitro G-CSF is produced by the haematopoietic system. However, G-CSF can now be produced by recombinant DNA cloning technology and thus is available clinically. 4. There is no recognised antidote for colchicine poisoning and treatment is symptomatic. Fab fragments may have a promising future in eliminating colchicine from the body, but are currently not clinically available. In those patients that survive the initial phase of poisoning, G-CSF offers an effective method of treating the pancytopenia and preventing overwhelming septicaemia. Daily monitoring of the patient's haematological status is strongly recommended.
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PMID:Granulocyte-colony stimulating factor in the treatment of colchicine poisoning. 915 49

Posttransplant lymphoproliferative disorder (PTLD) is associated with Epstein-Barr virus (EBV), and may clinically resemble acute allograft rejection. Three methods to show EBV in tissue were evaluated in 15 liver allograft biopsies from 12 patients including four with PTLD: (1) semiquantitative polymerase chain reaction (PCR) for EBV DNA; (2) in situ hybridization for EBV RNA (EBER); and (3) immunoperoxidase for EBV latent membrane protein (LMP). Index cases had a PCR dot blot result of "positive" or "weak positive." Findings were correlated with histology, clinical data, therapy, and outcome. All four PTLD patients had a clinical diagnosis of acute rejection. All four showed EBV: PCR 4, EBER 4, LMP 3, Liver function tests were elevated in three, but EBV viral capsid antigen (VCA) IgM was not increased in three, but EBV viral capsid antigen (VCA) IgM was not increased in three. Immunosuppression was withdrawn and all four patients underwent a second transplantation. One died 4 days posttransplant with disseminated PTLD, two died of sepsis at 1.5 and 14 months, and one is well at 3 years without PTLD. Eleven biopsies without PTLD showed: acute rejection 7, acute rejection and hepatitis 1, hepatitis B 1, and non-inflammatory changes 2. In this group, EBV results included: PCR weak positive in 10 and 1+ in one, EBER negative in ten and rare positive cells in one, LMP negative in 11. Liver function tests were elevated in 10, whereas VCA IgM was not increased in three and increased in one. Patients with acute rejection were treated with increased immunosuppression: none developed PTLD, with follow-up of at least 6 months in nine cases. Two patients died within 4 months of biopsy. One patient with PTLD in tonsils had a liver biopsy showing both acute rejection and EBV (PCR 1+, rare EBER + small cells). Histological studies combined with special EBV detection methods, can be useful to evaluate atypical lymphoid infiltrates in liver allograft biopsies and confirmation of a diagnosis of PTLD. All three methods are useful; EBER and PCR are the most sensitive. EBER and LMP can use paraffin sections.
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PMID:Posttransplant lymphoproliferative disorder in liver allograft biopsies: a comparison of three methods for the demonstration of Epstein-Barr virus. 915

Neonatal infections range from early-onset vertically acquired infections to nosocomial bacterial sepsis, and they account for significant morbidity and mortality globally. The recent emergence of perinatally acquired HIV-1 infection has also placed an enormous burden on existing meager health resources in developing countries. The risk of early-onset group B streptococci sepsis may be related to heavy genital tract colonization at term. Perinatally acquired HIV-1 infection also occurs at birth, with higher rates of infection after vaginal delivery. Detection of circulation HIV-1 viral DNA by polymerase chain reaction offers an extremely sensitive screening method in the neonatal period. In contrast, rapid confirmation of bacterial sepsis in the newborn still poses considerable problems. A review of data on antimicrobial prophylaxis of preterm premature rupture of membranes does reveal improved neonatal outcome. However, the rapid and widespread emergence of multidrug resistance among bacterial pathogens dictates the need for judicious use of antibiotics, as well as close attention to preventive strategies.
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PMID:Neonatal infections. 920 40

Transcription factors are DNA-binding proteins that regulate gene expression. Nuclear factor-kappa B (NF-kappa B) is a critical transcription factor for maximal expression of many cytokines that are involved in the pathogenesis of inflammatory diseases, such as adult respiratory distress syndrome (ARDS) and sepsis syndrome. Activation and regulation of NF-kappa B are tightly controlled by a group of inhibitory proteins (I kappa B) that sequester NF-kappa B in the cytoplasm of immune/inflammatory effector cells. NF-kappa B activation involves signaled phosphorylation, ubiquitination, and proteolysis of I kappa B. Liberated NF-kappa B migrates to the nucleus, where it binds to specific promoter sites and activates gene transcription. The activation of NF-kappa B initiates both extracellular and intracellular regulatory events that result in autoregulation of the inflammatory cascade through modulation of NF-kappa B activation. Recently, activation of NF-kappa B has been linked to ARDS and has been shown to be a critical proximal step in the initiation of neutrophilic inflammation in animal models. Activation of NF-kappa B can be inhibited in vivo by treatment with antioxidants, corticosteroids, and the induction of endotoxin tolerance. Identification of more specific and efficacious inhibitors of NF-kappa B activation might prove beneficial for the treatment of cytokine-mediated inflammatory diseases.
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PMID:The role of nuclear factor-kappa B in cytokine gene regulation. 922 3


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