Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009450 (infectious diseases)
 83,438 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mediterranean spotted fever, a tick-borne rickettsiosis caused by Rickettsia conorii, may lead to small-vessel or deep-vein thrombosis. In order to evaluate the role of endothelial cell alteration in this lesion, we infected human endothelial cells derived from umbilical veins with R. conorii. We report the induction of two previously unreported prothrombotic mechanisms in rickettsial disease: (i) a progressive decline in thrombomodulin antigen and (ii) early expression of tissue factor, and, as described for R. rickettsii infection, later release of von Willebrand factor from Weibel-Palade bodies. Thrombomodulin expression in infected endothelial cells, measured by the thrombin-dependent activation of protein C or flow cytometric analysis, decreased steadily between 4 and 24 h after inoculation with rickettsiae. R. conorii infection induced tissue factor expression, measured by clotting assay and flow cytometric analysis, which was detectable 2 h postinoculation, reached its maximum 4 h postinoculation, and progressively decreased thereafter. Infection resulted in a relatively late release of von Willebrand factor antigen into the culture medium. A double-label immunofluorescence assay for the simultaneous evaluation of von Willebrand factor and R. conorii showed that the depletion of cytoplasmic von Willebrand factor stored in Weibel-Palade bodies was due to a direct effect of the intracellular R. conorii. These disturbances of endothelial function observed with R. conorii-infected cells may provide a paradigm for the elucidation of thrombotic pathobiology with Mediterranean spotted fever.
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PMID:von Willebrand factor release and thrombomodulin and tissue factor expression in Rickettsia conorii-infected endothelial cells. 132 57

To investigate levels of coagulation inhibitors in sera from patients with Clostridium difficile-associated diarrhoea and colitis, commercially available antigen assays were used for immunochemical determination of antithrombin III, protein C and free protein S. Sera from patients with Clostridium difficile-associated diarrhoea and colitis showed significantly lowered levels of all measured inhibitors as compared to controls (Student's t test). Protein C (mean +/- SD): 0.70 +/- 0.30 vs. 1.28 +/- 0.23, t = 6.61, p less than 0.001; antithrombin: 0.70 +/- 0.21 vs. 0.90 +/- 0.17, t = 3.12, p less than 0.01; free protein S: 0.27 +/- 0.06 vs. 0.37 +/- 0.08, t = 3.7, p less than 0.001. Infection with C. difficile may lead to loss of coagulation inhibitors and constitutes a risk for thromboembolic complications.
Infection
PMID:Low levels of coagulation inhibitors in patients with Clostridium difficile infection. 153 51

Sepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 +/- 9.4 versus 1.6 +/- 1.5 ng/ml, p less than 0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 +/- 390 ng/ml versus 120 +/- 200 ng/ml, and 3.0 +/- 3.6 IU/ml versus 1.0 +/- 0.7 IU/ml, respectively, p less than 0.01). AT III was decreased in sepsis patients (58 +/- 28% in sepsis versus 79 +/- 26% in severe infectious disease, p less than 0.01) as was protein C (30 +/- 18% versus 58 +/- 27%, p less than 0.001). No significant difference was found for t-PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease.
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PMID:Fibrinolysis and coagulation in patients with infectious disease and sepsis. 190 55

Postoperative deep-vein thrombosis can lead to fatal pulmonary embolism on one side, and the development of a disabling postthrombotic syndrome, which can occur after some time. General thrombo-embolic prophylaxis can reduce the risk of postoperative thrombo-embolic complications. Predisposing factors include age, obesity, immobilization and recumbency. Cardiovascular diseases, malignant neoplasms, venous disorders, diseases associated with increased viscosity of blood, past deep-vein thrombosis and pulmonary embolisms, some infectious diseases with raised fibrinogen levels, and inherited or acquired clotting factor deficiency syndromes (antithrombin III, protein C, protein S) have an elevated risk of thrombosis. The surgery itself, when taking more than 20 minutes and performed under general anesthesia, is a major risk factor, as proven initiation of thrombosis is often on the operation table. Patients receiving regional or local anesthesia have a clearly reduced risk of thrombosis. After general surgery without thrombosis prophylaxis, a deep-vein thrombosis can be demonstrated by the fibrinogen uptake test in about 30% of all patients over the age of 40. After abdominal surgery an incidence of thrombosis of 14-33%, and after hip surgery an incidence of nearly 50%, have been established by means of the fibrinogen uptake test. However only 10% of these thromboses are expressed clinically. We therefore recommend Liquid Crystal Contact Thermography, which has a sensitivity of 94% and a specificity of over 80%, as a non-invasive, easily performed screening method in the diagnosis of deep-vein thrombosis. Apart from the physical methods, the use of heparin is also indicated in thrombo-embolic prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The thrombo-embolic risk in surgery. 193 69

Infection with Borrelia burgdorferi, the etiologic agent of Lyme disease, is associated with an early and dominant humoral response to the spirochete's 23-kDa outer surface protein C (OspC). We have cloned and expressed OspC as a fusion protein in Escherichia coli and have shown that patient serum samples react with it in an enzyme-linked immunosorbent assay (ELISA) (S. J. Padula, A. Sampieri, F. Dias, A. Szczepanski, and R. W. Ryan, Infect. Immun. 61:5097-5105, 1993). Now we have compared the detection of B. burgdorferi-specific immunoglobulin M antibodies in 74 individuals with culture-positive erythema migrans by a whole-cell ELISA, immunoblot, and the recombinant OspC (rOspC) ELISA. Seventy-six negative controls were also studied. With all of the tests, there was a statistically significant association between the duration of disease and the frequency of a positive result. With the rOspC ELISA, the predictive value of a positive test was 100% and the predictive value of a negative test was 74%. Similar results were obtained with the whole-cell ELISA and with the immunoblot using as the source of test antigen a strain of B. burgdorferi which expresses abundant levels of OspC. We conclude that the use of rOspC in an ELISA is a convenient, readily automated, and easily standardized test for the serodiagnosis of early Lyme disease.
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PMID:Use of recombinant OspC from Borrelia burgdorferi for serodiagnosis of early Lyme disease. 792 67

We observed 40 patients aged from 15 to 40 years who suffered either a transient ischemic attack or an arterial ischemic stroke. All patients were clinically and physically examined, i.e. chest-X rays, electrocardiograms, biological tests and C.T. scan or magnetic resonance imaging that confirmed the diagnosis of ischemic cerebral infarction. Most patients underwent echocardiography and angiography. The time span between the onset of the ischemic event and angiography was recorded. A few of them had CSF analysis and determinations of antithrombin III, protein C and protein S. The etiology was confirmed in 15 patients (5 cardioembolic diseases, 7 vasculopathies, 3 coagulopathies). Twenty three had well-known vascular risk factors, but also an increase in serum fibrinogen concentration, which might have been associated with specific predisposing factors: oral contraceptives, patent foramen ovale, migraine, craniocervical trauma, acute alcohol intoxication and infectious diseases. No cause was found in 2 patients. We suggest a practical approach and highlight the value of angiography when performed early in the course of the illness to enhance the percentage of positive diagnosis. About 45 p. 100 of the patients followed-up (mean duration: 3 years) were unable to resume normal professional activity.
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PMID:[Cerebral ischemic arterial accidents in young adults. 40 cases]. 802 69

The genetic diversity of dengue (DEN) virus was explored using two South American DEN-1 virus strains isolated from viremic human sera. DEN-1 virus strains BR/90 and FGA/89 were selected on the basis of their membrane fusion properties in mosquito cell cultures. Infection of mosquito cell lines with BR/90 virus strain induced a cytopathic effect characterized by syncytium formation whereas no cytopathic changes were observed with FGA/89. Cell-to-cell fusion experiments indicated that the fusogenic activity of FGA/89 required a lower pH than BR/90. Immunoreactivity analysis of the DEN-1 envelope (E) protein with monoclonal antibodies revealed a minor difference between the antigenic structures of FGA/89 and BR/90 virions. FGA/89 was less neurovirulent than BR/90 for newborn mouse. To determine the genetic origin of these modifications, the amino acid sequences of the structural proteins from these virus strains were compared. One amino acid difference was found within the carboxy-terminal domain of protein C. Five amino acid substitutions were found in the E proteins at positions 96, 180, 297, 379, and 473. Changes at positions 96, 297, and 379 map within two overlapping antigenic domains of protein E. These limited amino acid differences in the E protein could affect the biological properties and the antigenicity of the DEN virion.
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PMID:Differences between cell membrane fusion activities of two dengue type-1 isolates reflect modifications of viral structure. 835 94

Many tissues are found to contain populations of cells with an unusual dendritic shape, high levels of surface expression of MHC class II (Ia) gene products, and strong accessory function for the stimulation of specific clones of quiescent T lymphocytes. Dendritic cells (DC) represent major population of "professional" APC in various lymphoid and nonlymphoid tissues, distinct from cells of the monocyte/macrophage lineage. Among the best characterized nonlymphoid dendritic cells are epidermal Langerhans cells, but it has been shown that interstitium and epithelium of other organs also contain irregularly shaped, strongly MHC class II positive cells. In recent years, DC have been localized to alveolar septa in the lung, as well as within and just beneath airway epithelium, comprising a tightly meshed network that is reminiscent of epidermal Langerhans cells. In the gastrointestinal tract, conventional immunohistochemical analysis of mucosal class II MHC (Ia) staining reveals a morphologically heterogeneous pattern of staining in the lamina propria. DC that exhibit strong Ag-presenting activity in vitro have been extracted from enzymatic digests of colonic mucosa, but no previous reports of MHC class II-positive cells with pleiomorphic morphology have been recorded within the epithelium of the intestine. Employing a novel combination of nonconventional section planes, pre-embedding fixation, and immunohistochemical techniques, we now demonstrate Ia staining of cells with classical DC morphology within the epithelium of the intestine in normal specific pathogen-free rats. Our investigation suggests that cells with the morphologic and phenotypical characteristics of DC are present within the mucosal epithelium of the rat jejunum and colon, comprising a significant organized network. The number of DC within epithelium of the colon was 117 +/- 20 per 10-microns-thick cross-section. These findings have important theoretical implications for research on Ag processing and T cell activation in the context of allergic and infectious diseases in the gastrointestinal tract.
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PMID:Class II MHC antigen (Ia)-bearing dendritic cells in the epithelium of the rat intestine. 856 41

Immunomodulatory cytokines have been used with success as adjunctive therapy in genetic disorders such as chronic granulomatous disease and infectious diseases such as leishmaniasis and leprosy. As the first step toward developing novel methods to deliver immunomodulatory cytokines, we used retrovirus-mediated somatic gene transfer techniques to produce IFN-gamma from human peripheral blood CD34+ hemopoietic progenitor (PBHP) cells. After transduction, the PBHP cells were made to differentiate toward myelo-monocytic lineages. Only the PBHP-derived myelo-monocytic cells that were transduced with the IFN-gamma cDNA produced IFN-gamma(4 +/- 1.3 ng of IFN-gamma/10(6) PBHP cells.) Despite a reduction in the proliferation of IFN-gamma-transduced PBHP cells as well as a decrease in erythroid colony formation, there was an enhancement of monocyte differentiation and activation. Monocytes differentiated from the IFN-gamma-transduced PBHP cells demonstrated 1) up-regulation of MHC class I and II Ag expression, 2) increased Fc(gamma)RI expression, and 3) enhanced superoxide production in response to both opsonized zymosan (25-fold) and phorbol ester (3-fold). Furthermore, a functional response to a monocyte-specific chemokine, monocyte chemotactic protein-1 (mobilization of intracellular Ca2+) was seen only in the IFN-gamma-transduced cells. Thus, PBHP cells transduced with IFN-gamma cDNA produce not only biologically active IFN-gamma, but also enhanced monocyte differentiation, resulting in an activated state that includes unique functions, such as responsiveness to monocyte chemotactic protein-1. These transduced activated monocytes may be specifically suited to cellular therapy requiring homing to sites of inflammation where their anti- microbicidal, cytotoxic and APC functions play an important role in host defense against foreign pathogens.
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PMID:Autocrine activation of hemopoietic progenitor-derived myelo-monocytic cells by IFN-gamma gene transfer. 866 6

Dendritic cells (DC) are the most efficient APC for T cells. The clinical use of DC as vectors for anti-tumor and infectious disease immunotherapy has been limited by their trace levels and accessibility in normal tissue and terminal state of differentiation. In the present study, daily injection of human Flt3 ligand (Flt3L) into mice results in a dramatic numerical increase in cells co-expressing the characteristic DC markers-class II MHC, CD11c, DEC205, and CD86. In contrast, in mice treated with either GM-CSF, GM-CSF plus IL-4, c-kit ligand (c-kitL), or G-CSF, class II+ CD11c+ cells were not significantly increased. Five distinct DC subpopulations were identified in the spleen of Flt3L-treated mice using CD8 alpha and CD11b expression. These cells exhibited veiled and dendritic processes and were as efficient as rare, mature DC isolated from the spleens of untreated mice at presenting allo-Ag or soluble Ag to T cells, or in priming an Ag-specific T cell response in vivo. Dramatic numerical increases in DC were detected in the bone marrow, gastro-intestinal lymphoid tissue (GALT), liver, lymph nodes, lung, peripheral blood, peritoneal cavity, spleen, and thymus. These results suggest that Flt3L could be used to expand the numbers of functionally mature DC in vivo for use in clinical immunotherapy.
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PMID:Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. 892 Aug 82


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