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)

The relationship between the endoplasmic reticulum (ER) and the sarcoplasmic reticulum (SR) of skeletal muscle cells has remained obscure. In this study, we found that ER- and SR-specific membrane proteins exhibited diverse solubility properties when extracted with mild detergents. Accordingly, the major SR-specific protein Ca(2+)-ATPase (SERCA) remained insoluble in Brij 58 and floated in sucrose gradients while typical ER proteins were partially or fully soluble. Sphingomyelinase treatment rendered SERCA soluble in Brij 58. Immunofluorescence staining for resident ER proteins revealed dispersed dots over I bands contrasting the continuous staining pattern of SERCA. Infection of isolated myofibers with enveloped viruses indicated that interfibrillar protein synthesis occurred. Furthermore, we found that GFP-tagged Dad1, able to incorporate into the oligosaccharyltransferase complex, showed the dot-like structures but the fusion protein was also present in membranes over the Z lines. This behaviour mimics that of cargo proteins that accumulated over the Z lines when blocked in the ER. Taken together, the results suggest that resident ER proteins comprised Brij 58-soluble microdomains within the insoluble SR membrane. After synthesis and folding in the ER-microdomains, cargo proteins and non-incorporated GFP-Dad1 diffused into the Z line-flanking compartment which likely represents the ER exit sites.
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PMID:Microdomains of endoplasmic reticulum within the sarcoplasmic reticulum of skeletal myofibers. 1799 28

Most type II restriction-modification (R-M) systems produce separate restriction endonuclease (REase) and methyltransferase (MTase) proteins. After R-M system genes enter a new cell, protective MTase must appear before REase to avoid host chromosome cleavage. The basis for this apparent temporal regulation is not well understood. PvuII and some other R-M systems appear to achieve this delay by cotranscribing the REase gene with the gene for an autogenous transcription activator/repressor (the 'C' protein C.PvuII). To test this model, bacteriophage M13 was used to introduce the PvuII genes into a bacterial population in a relatively synchronous manner. REase mRNA and activity appeared approximately 10 min after those of the MTase, but never rose if there was an inactivating pvuIIC mutation. Infection with recombinant M13pvuII phage had little effect on cell growth, relative to infection with parental M13. However, infection of cells pre-expressing C.PvuII led to cessation of growth. This study presents the first direct demonstration of delayed REase expression, relative to MTase, when type II R-M genes enter a new host cell. Surprisingly, though the C and REase genes are cotranscribed, the pvuIIC portion of the mRNA was more abundant than the pvuIIR portion after stable establishment of the R-M system.
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PMID:Real-time kinetics of restriction-modification gene expression after entry into a new host cell. 1833 33

Severe infectious diseases after liver transplant are associated with high risk of multiorgan failure and mortality. Septic shock is difficult to manage in this setting since it is often unresponsive to conventional aggressive therapy. Adjuvant therapies have been proposed in association with full combination treatment to sustain the failing organs and improve outcomes in severe sepsis. Recombinant human activated protein C drotrecogin alfa, Xigris) has been occasionally administered to treat posttransplant sepsis to modulate and downregulate the complex network of inflammatory and coagulopathic processes. Herein we have reported on a patient who was given drotrecogin alfa 15 days following liver transplant for acute septic shock originating from a nosocomially acquired pneumonia. Recombinant activated drotrecogin alfa, associated with conventional aggressive treatment, was efficacious to revert the life-threatening "slippery slope" of vasoplegia and uncontrolled diffuse inflammation.
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PMID:Activated recombinant protein C in septic shock early after liver transplantation: a case report. 1867 33

Of the 488 pediatric patients with thrombosis in a single center, 50 (10.2%) had nonstroke arterial thrombosis. Half of the nonstroke arterial thrombosis patients had a preceding arterial catheterization history. Infection was a common contributing underlying disorder among both catheterized and overall groups (28 and 42%, respectively). The third most common underlying risk factor for development of arterial thrombosis was associated cardiac disease, and 70% of these patients had congenital heart disease and 30% had dilated cardiomyopathy. The most common site of arterial thrombosis was the heart, and 22% of the patients developed arterial thrombosis following cardiac surgery for congenital heart diseases. The prothrombotic risk factors were also analyzed in the study group and factor V G1691A and PT G20210A heterozygous mutations were detected to be higher (16 and 4%, respectively) than those in healthy controls (7.4 and 2.3%, respectively). In addition to factor V G1691A and PT G20210A mutations, other prothrombotic risk factors including protein C and protein S deficiencies and elevated factor VIII levels were commonly associated with pediatric nonstroke arterial thrombosis cases in the present study. This finding indicates the importance of these factors in arterial thrombosis development, similar to venous thrombosis. Another striking factor of the study is the higher number of prothrombotic risk factors (more than three) in patients who had persistent thrombosis, indicating the need for more intensive treatment in these patients.
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PMID:Nonstroke arterial thrombosis in children: Hacettepe experience. 1868 35

The past decades have been marked by spectacular progress towards understanding how dendritic cells (DCs) interact with T cells to elicit protective immune responses to fight infectious diseases and cancer. DCs that are lying at the interface between innate and adaptive immunity, are educated in peripheral tissues prior to their journey to the secondary lymphoid organs (SLO) whereby they dictate different classes of T cell responses. Uncontrolled or unwanted inflammatory responses are the price to pay to eliminate pathogens. However, if not self-limited, they may induce collateral damages that result in chronic inflammation often associated with autoimmune disorders. CD47 and its two ligands, i.e. thrombospondin 1 (TSP-1) and SIRP-alpha, were identified as a previously unappreciated inhibitory axis of DC and T cell functions. TSP-1 is predominantly a negative regulator of DC and T cell function while basal SIRP-alpha ligation on APC by CD47 enforces tolerance. Yet, CD47/SIRP-alpha interaction positively controls DC and innate cell transendothelial migration. Due to the promiscuity of the protein interactions for CD47 and its ligands, it is quite interesting to note that deletion of the CD47 gene in mice largely agrees with the in vitro data with human cells. In fact, the well-conserved tissue distribution of CD47 and SIRP-alpha across species may facilitate the transition from bench to bedside. We thus propose CD47/TSP-1/SIRP-alpha axis as an important sensor to maintain homeostasis and regulate innate and adaptive immune responses.
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PMID:CD47 in the immune response: role of thrombospondin and SIRP-alpha reverse signaling. 1885 18

Infection of immature dendritic cells (DCs) by virus stimulates their maturation into APC. Infected DCs can also expose uninfected DCs to a panoply of cytokines/chemokines via paracrine signaling. Mathematical modeling suggests that a high rate of paracrine signaling is likely to occur among DCs located in three-dimensional space. Relatively little is known about how secreted factors modify the early response to virus infection. We used a transwell experimental system that allows passage of secreted factors, but not direct contact, between virus-infected DCs and uninfected DCs to investigate paracrine signaling responses. Paracrine signaling from infected DCs induced an antiviral-primed DC state distinct from that of mature virus-infected DCs that we refer to as antiviral-activated DCs (AVDCs). AVDCs had increased surface MHC class II and CD86 levels, but in contrast to virus-infected DCs, their MHC class I levels were unchanged. Imaging flow cytometry showed that AVDCs had an increased rate of phagocytosis compared with naive DCs. Experiments with IFN-beta cytokine indicated that it may be responsible for CD86, but not MHC class II regulation in AVDCs. Both IFN-inducible and IFN-independent genes are up-regulated in AVDCs. Notably, AVDCs are relatively resistant to virus infection in comparison to naive DCs and achieve accelerated and augmented levels of costimulatory molecule expression with virus infection. AVDCs show a distinct antiviral-primed state of DC maturation mediated by DC paracrine signaling. Although further in vivo study is needed, the characteristics of the AVDC suggest that it is well suited to play a role in the early innate-adaptive transition of the immune system.
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PMID:Antiviral-activated dendritic cells: a paracrine-induced response state. 1898 Nov 6

To study the prevalence of oral lesions in HIV infected patients and its relationship with CD4+ cell count in Georgia 732 HIV positive adult patients who were admitted to the Infectious Diseases, AIDS and Clinical Immunology Research Center (IDACIRC) since January, 2006 till October, 2008 were evaluated. Each patient underwent full clinical and standard laboratory examination. CD4+ cell count was determined by the Becton-Dickinson FACSCalibur flow cytometer (MultiTEST CD3 FITC/CD8 PE/CD45 PerCP/CD4 APC Reagent). Socio-demographic data was obtained using a standard questionnaire at the epidemiology department of IDACIRC. Oral manifestations were diagnosed according to EEC clearinghouse classification (1993). Oral lesions were revealed in 546 patients (75%). 186 patients (25%) did not exhibit any oral complications. The prevalence of two or more simultaneously exhibited types of lesions was as follows: three types of lesions were detected in 45 patients (6%) and two types of lesions were detected in 245 patients (33%). The investigation revealed oral candidiasis constituted the most common form of oral lesions, representing a 64% (467 patients), followed by HIV associated periodontal diseases in 216 patients (30%), recurrent aphthous like ulcerations in 118 patients (16%), oral hairy leukoplakia in 58 patients (8%), orolabial herpes simplex infection in 50 patients (7%), human papillomavirus (wart like lesions) in 37 patients (5%) and Kaposi's sarcoma in 3 patients (0.4%). Most of oral lesions cases were found in patients with low CD4+ cell count. Results of this study provide evidence that mucous membrane disorders with HIV infection might serve as an indicator for advanced HIV infection, immunosuppression and decreased CD4 cell counts. The physicians who are taking care of HIV patients have to be familiar with HIV-associated mucocutaneous diseases, their diagnoses, and management.
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PMID:Oral lesions in HIV-positive patients in Georgia. 1912 19

The rational design of new vaccines engineered to target key components of the host immune response is crucial to aid control of important infectious diseases such as tuberculosis. In this report, we determined whether modifying the function of pulmonary APC could improve protection against infection with Mycobacterium tuberculosis. Targeted delivery to the lung of the cytokine GM-CSF, expressed by the Mycobacterium bovis BCG vaccine strain, increased pulmonary DC numbers and secretion of the immunoregulatory cytokine IL-12, compared with parental BCG immunization. This impact on APC number by BCG:GM-CSF resulted in accelerated priming of antigen-specific CD4+ T cells in the mediastinal lymph nodes and increased migration of activated CD4+ T cells into the lung. i.n. administration of BCG:GM-CSF resulted in significantly increased protection against M. tuberculosis infection compared with mice vaccinated with BCG alone. BCG:GM-CSF exhibited an improved safety profile, as immunodeficient RAG1-/- mice vaccinated i.n. with BCG:GM-CSF survived significantly longer than control BCG-vaccinated mice. These data demonstrate that manipulating immune cells in the lung by BCG-based delivery of GM-CSF can assist the development of protective mucosal immunity against pulmonary bacterial infection.
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PMID:Modulation of pulmonary DC function by vaccine-encoded GM-CSF enhances protective immunity against Mycobacterium tuberculosis infection. 1983 Jul 35

Most novel vaccines against infectious diseases are based on recombinant Ag; however, only few studies have compared Ag-specific immune responses induced by natural infection with that induced by the same Ag in a recombinant form. Here, we studied the epitope recognition pattern of the tuberculosis vaccine Ag, TB10.4, in a recombinant form, or when expressed by the pathogen Mycobacterium tuberculosis (M.tb), or by the current anti-tuberculosis vaccine, Mycobacterium bovis BCG. We showed that BCG and M.tb induced a similar CD4+ T-cell specific TB10.4 epitope-pattern, which differed completely from that induced by recombinant TB10.4. This difference was not due to post-translational modifications of TB10.4 or because TB10.4 is secreted from BCG and M.tb as a complex with Rv0287. In addition, BCG and TB10.4/CAF01 were both taken up by DC and macrophages in vivo, and in vitro uptake experiments revealed that both TB10.4 and BCG were transported to Lamp+-compartments. BCG and TB10.4 however, were directed to different types of Lamp+-compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely different recognition of the same protein.
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PMID:Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis. 2018 78

Malnutrition induces a decrease in immunity that affects the ability of the organism to deal with an infectious challenge. The clotting system is considered a branch of immunity and its activation is important in the pathogenesis of an infectious disease. This work was conducted to determine coagulation modifications in malnourished hosts before and during infection. Weaned mice were malnourished via a protein-free diet. Well-nourished control mice (WNC) consumed a balanced conventional diet. Malnourished mice (MN) and WNC were challenged intranasally with Streptococcus pneumoniae. Blood, bronchoalveolar lavages (BAL), and lung samples were taken at different times post infection. The results were that MN showed altered hemostatic tests and fibrin(ogen) deposits in the lung. Thus, an increase in thrombin-antithrombin complexes (TATc) in plasma and BAL was observed. In the MN group, infection induced a rise in TATc in plasma and BAL and increased plasma fibrinogen and fibrin(ogen) deposits in the lung. A decrease in activated protein C and antithrombin in BAL and an early decrease followed by an increase in plasma Factor VIII were also observed. Thus, malnourishment induced a procoagulant state increased by infection. This is the first work that presents results of an exhaustive study of coagulation in malnourished hosts before and during an infection.
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PMID:Coagulation activation in an experimental pneumonia model in malnourished mice. 2118 76


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