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Human thrombin and FXa mediate porcine endothelial cell activation; modulation by expression of TFPI-CD4 and hirudin-CD4 fusion proteins

Aside from their critical role in thrombosis, activated coagulation factors also have inflammatory properties and these may be important during delayed xenograft rejection (DXR). This study assessed whether porcine EC could be activated by factor Xa (FXa) and thrombin (FIIa) and whether expression of tissue factor pathway inhibitor (TFPI)-CD4 and hirudin-CD4 fusion proteins could prevent such acti

Long-term persistence of a discotheque-associated invasive Neisseria meningitidis group C strain as proven by pulsed-field gel electrophoresis and porA gene sequencing

A duster of a Neisseria meningitidis serogroup C strain causing invasive disease was investigated. Five out of seven cases were associated with a particular discotheque. The strains were indistinguishable, as revealed by pulsed-field gel electrophoresis and sequencing of variable regions of the porA gene, but caused strikingly different clinical presentations during 5 months.

Regulated inhibition of coagulation by porcine endothelial cells expressing P-selectin-tagged hirudin and tissue factor pathway inhibitor fusion proteins

Background. Thrombotic vascular occlusion resulting in infarction occurs during hyperacute rejection of allografts transplanted into sensitized patients and remains a major problem in experimental xenotransplantation. A similar process is also found in disorders of diverse etiology including atherosclerosis, vasculitis, and disseminated intravascular coagulation. Methods. We have previously constr

Cisplatin at clinically relevant concentrations enhances interleukin-2 synthesis by human primary blood lymphocytes

Cytotoxic drugs influence the expression of certain genes in cancer cells. Cisplatin has recently been shown to modulate interleukin (IL)-1 and tumor necrosis factor (TNF)-α production in macrophages. In this study, we wanted to investigate whether cisplatin interferes with the IL-2, IL-2 receptor (IL-2R), interferon (IFN)-γ, and TNF-α expression in phytohemagglutin-stimulated human peripheral blo

Inhibition of tissue factor-dependent and -independent coagulation by cell surface expression of novel anticoagulant fusion proteins

Background. Thrombotic vascular occlusion occurs in disorders of diverse etiology, including atherosclerosis, vasculitis, and disseminated intravascular coagulation. The same process results in hyperacute rejection of renal allografts transplanted into sensitized patients and remains a major problem in experimental xenotransplantation. Methods. We have previously described the design and expressio

Long-term survival and complete cures of B16 melanoma-carrying animals after therapy with tumor-targeted IL-2 and sea

The bacterial superantigen (SAg) staphylococcal enterotoxin A (SEA) is a potent inducer of CTL activity and cytokine production in vivo. To engineer SAg for cancer immunotherapy, we genetically fused SEA to a Fab fragment of the C215 tumor-reactive antibody. Strong reduction of lung metastasis was seen in mice carrying established lung metastases of the poorly immunogenic B16-C215 melanoma after F

Expression of hirudin fusion proteins in mammalian cells : A strategy for prevention of intravascular thrombosis

Background - Intravascular thrombosis occurs in disorders of diverse pathogeneses, including allograft and xenograft rejection. In this in vitro study, we describe an approach for tethering the specific thrombin inhibitor hirudin to plasma membranes as part of a genetic strategy for regulating intravascular coagulation. Methods and Results - An HLA class I leader sequence was fused with hirudin li

Endothelial cells expressing an inflammatory phenotype are lysed by superantigen-targeted cytotoxic T cells

The objective of this study was to investigate whether the superantigen staphylococcal enterotoxin A (SEA), which binds to HLA class II and T-cell receptor Vβ chains, can direct cytotoxic T cells to lyse cytokine-stimulated endothelial cells (EC). In addition, we wanted to determine whether SEA- primed cytotoxic T cells could be targeted to EC surface molecules as a means of a novel cancer immunot

Perforin and IFN-γ are involved in the antitumor effects of antibody- targeted superantigens

The bacterial superantigen staphylococcal enterotoxin A (SEA) is a potent inducer of cytokine production and cytotoxic T cell responses. To target a T cell attack against tumor cells we have genetically engineered a fusion protein of SEA and the Fab part of the tumor-reactive mAb C215. Injection of this Fab-SEA fusion protein to mice carrying lung metastases of the poorly immunogenic B16 melanoma

Ciprofloxacin induces an immunomodulatory stress response in human T lymphocytes

Exposure of cells to adverse environmental conditions invokes a genetically programmed series of events resulting in the induction of specific genes. The fluoroquinolone antibiotic ciprofloxacin has recently been reported to upregulate interleukin-2 (IL-2) gene induction. In the present investigation, the effect of ciprofloxacin at supratherapeutic concentrations on immediate-early (

The Laminin Interactome : A Multifactorial Laminin-Binding Strategy by Nontypeable Haemophilus influenzae for Effective Adherence and Colonization

Laminin is a well-defined component of the airway basement membrane (BM). Efficient binding of laminin via multiple interactions is important for nontypeable Haemophilusinfluenzae (NTHi) colonization in the airway mucosa. Here we identified elongation factor thermo-unstable (EF-Tu), L-lactate dehydrogenase (LDH), Protein D and peptidoglycan-associated lipoprotein P6 as novel laminin-binding protei

Honeybee-specific lactic acid bacterial supplements have no effect on American foulbrood infected honeybee colonies

Paenibacillus larvae, causative agent of American Foulbrood (AFB), is the primary bacterial pathogen affecting honeybees and beekeeping. The main methods for controlling AFB are incineration of diseased colonies or prophylactic antibiotic treatment (e.g. tylosin), neither of which is fully satisfactory. The search for superior means for controlling AFB has led to an increased interest in the natur

Effect of Brief Admission to Hospital by Self-referral for Individuals Who Self-harm and Are at Risk of Suicide. A Randomized Clinical Trial

Importance To our knowledge, there is no consensus regarding when individuals who repeatedly self-harm and are at risk of suicide should be hospitalized. To evaluate a new alternative, we examined the effects of brief admission (BA) to hospital by self-referral.Objectives To determine the effects of BA on inpatient service use and on secondary outcomes of daily life functioning, nonsuicidal self-i

The Common Ownership Boom - Or: How I Learned to Start Worrying and Love Antitrust

Is common ownership the Doomsday Machine for the operation of free markets, competition and capitalism as we know it? An observer of cutting-edge law and economics literature may indeed tend to believe that we are approaching a point of ultimate antitrust apocalypse. This article tries to unfold the ongoing antitrust-focused debate by exploring a series of questions: i) who is a common owner; ii)