Complement c5a receptor facilitates cancer metastasis by altering T-cell responses in the metastatic niche.

The impact of complement on cancer metastasis has not been well studied. In this report, we demonstrate in a preclinical mouse model of breast cancer that the complement anaphylatoxin C5a receptor (C5aR) facilitates metastasis by suppressing effector CD8(+) and CD4(+) T-cell responses in the lungs. Mechanisms of this suppression involve recruitment of immature myeloid cells to the lungs and regulation of TGFβ and IL10 production in these cells.

Acute promyelocytic leukemia: four distinct patterns by flow cytometry immunophenotyping.

A total of 97 acute promyelocytic leukemia (APL) patients with adequate flow cytometry (FC) data, bone marrow aspirates and presence of t(15;17)/PML-RARA by cytogenetics and/or FISH studies were analyzed for immunophenotypic pattern. Leukemic cells had the following phenotype: CD11b-, CD11c-, CD13+, CD33+, CD45+, CD64+/-, CD117+, and HLA-DR-. A subset of cases showed also an expression of CD2, CD4, CD34, and CD56.

Immunophenotypic pattern of myeloid populations by flow cytometry analysis.

We present our experience with immunophenotypic characteristics of benign and malignant myeloid populations, with emphasis on differential diagnosis especially between eosinophils, dysplastic granulocytes, neoplastic promyelocytes, and monocytes. Eosinophils are characterized by bright CD45, high side scatter (SSC), very low forward scatter (FSC), positive CD11b, CD11c, CD13, CD15, and CD33. They are negative for CD10, CD14, CD16, CD56, CD64, and HLA-DR.

Nitric oxide affects IL-6 expression in human peripheral blood mononuclear cells involving cGMP-dependent modulation of NF-κB activity.

Interleukin 6 (IL-6) and nitric oxide (NO) are important mediators of the inflammatory response. We report that in human peripheral blood mononuclear cells (PBMCs), NO exerts a biphasic effect on the expression of IL-6. Using sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO) as NO-donating compounds, we observed that both mRNA and protein levels of IL-6 increased at lower (≤10μM) and decreased at higher (>100μM) concentrations of NO donors.

Different effects of soluble and particulate guanylyl cyclases on expression of inflammatory cytokines in rat peripheral blood mononuclear cells.

Inflammation involves the cooperation of various cells and biologically active molecules. An important intracellular messenger molecule participating in the regulation of the process is cyclic GMP (cGMP), which is synthesized by guanylyl cyclases (GCs). The GC family comprises cytosolic (soluble) and membrane-bound (particulate) enzymes.

Proline-rich polypeptide complex (PRP) regulates secretion of inflammatory mediators by its effect on NF-kappaB activity.

A proline-rich polypeptide complex (PRP) with immunoregulatory and procognitive activities shows beneficial effects in the Alzheimer's disease (AD). The mechanism of action of PRP is not yet fully clarified, we have shown that the PRP complex inhibits overproduction of reactive oxygen species, nitric oxide and proinflammatory cytokines induced by lipopolysaccharide (LPS). LPS stimulation exerts its inflammatory effects through the activation of the classical nuclear factor-kappaB (NF-kappaB) pathway.

Antibodies to 46-kDa retinal antigen in a patient with breast carcinoma and cancer-associated retinopathy.

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome usually associated with small-cell lung carcinoma and serum autoantibodies against recovering. We report the breast cancer woman with visual impairments and electrophysiological abnormalities characteristic of CAR. Her serum contained high-titer antibodies against alpha-enolase but not against other retinal proteins.

Cancer-associated retinopathy in patients with breast carcinoma.

Introduction: Cancer-associated retinopathy (CAR) is a paraneoplastic neurological syndrome resulting in progressive loss of vision and clinical signs of retinal degeneration. It is associated with various types of cancer and is also considered to be an autoimmune disorder that involves cross-reaction between autoantibodies and retinal proteins. The aim of this study was to establish whether immunoreactivity to retinal antigens (RAs) observed in patients with breast cancer is accompanied by any visual impairments.

Nuclear factor-kappaB activity in peripheral blood mononuclear cells in cachectic and non-cachectic patients with chronic heart failure.

Background: Inflammatory immune mechanisms are involved in the pathogenesis and progression of chronic heart failure (CHF), and also promote the development of generalised body wasting seen in this syndrome. We examined the activity of nuclear factor kappa-B (NF-kappaB), the major mediator of immune response, in peripheral blood mononuclear cells (PBMC) isolated from cachectic and non-cachectic patients with CHF.

Methods: Using electromobility shift assay, NF-kappaB activity was assessed in nuclear fractions of PBMC isolated from 43 patients with systolic CHF (88% men, age: 64 years [median], left ventricular ejection fraction [LVEF]: 30%, ischaemic CHF aetiology: 79%, NYHA class [I/II/III/IV]: 2/21/19/1, 10 patients with cardiac cachexia) and 12 healthy adult subjects.

Expression and activity of cGMP-dependent phosphodiesterases is up-regulated by lipopolysaccharide (LPS) in rat peritoneal macrophages.

It has been shown that cyclic GMP (cGMP) modulates the inflammatory responses of macrophages, but the underlying molecular mechanisms are still poorly understood. Looking for proteins potentially regulated by cGMP in rat peritoneal macrophages (PMs), in this study we analyzed expression and activity of cGMP-hydrolyzing and cGMP-regulated phosphodiesterases (PDEs). It was found that freshly isolated peritoneal exudate macrophages (PEMs) express enzymes belonging to families PDE1-3, PDE5, PDE10, and PDE11.

CD56-positive large B-cell lymphoma.

CD56 (NCAM), a neural adhesion molecule, is normally expressed on natural killer cells and subsets of T cells and is commonly seen on hematolymphoid neoplasms such as plasma cell myeloma and acute myelogenous leukemia. It is uncommon in B-cell lymphoma. From 2001 to 2003 a cohort of 20 cases of CD56 B-cell lymphomas was identified by flow cytometry (<0.

Cyclic GMP-dependent protein kinase and soluble guanylyl cyclase disappear in elicited rat neutrophils.

The nitric oxide/soluble guanylyl cyclase/cGMP-dependent protein kinase (NO/sGC/PKG) cascade has been shown to affect important functions of circulating neutrophils. We demonstrate that neutrophils isolated from rats treated intraperitoneally with peptone protease cannot use this signaling pathway. Although PKG was detected at both the mRNA and protein levels in peripheral blood neutrophils (PBNs) of control rats, it was expressed neither in PBNs nor in peritoneal exudate neutrophils (PENs) of provoked rats.

Detection of serum antibodies to S-antigen by surface plasmon resonance (SPR).

Serum autoantibodies to visual arrestin, also termed S-antigen, have been shown to accompany several autoimmune-related diseases. However, they were also detected in sera of healthy individuals; there is lack of a sensitive and fast method for evaluation of putative differences between those two groups of antibodies. We show that, using biosensor technology based on surface plasmon resonance (SPR), it was possible to characterize real-time interactions of immune sera with immobilized arrestin.

[Role of arrestins in intracellular signaling].

Arrestins are cytosolic proteins involved in the termination of signaling by activated G protein-coupled receptors (GPCR). Four different arrestins are identified in mammals to date. Two of these are specific to retinal photoreceptor cells, while the other two (beta-arrestin 1 and 2) are ubiquitously expressed.

Coexpression of CD43 by benign B cells in the terminal ileum.

Expression of CD43 by B cells is often used as a diagnostic criterion in favor of a B-cell lymphoproliferative disorder, including small lymphocytic lymphoma/chronic lymphocytic leukemia, mantle cell lymphoma, Burkitt lymphoma, precursor B-lymphoblastic lymphoma, and a subset of marginal zone B-cell lymphomas. Benign B cells generally do not coexpress CD43. The authors analyzed 20 biopsies of the terminal ileum for nonneoplastic disease for expression of CD43 and compared them with other sites and with CD20, CD138, and CD3 reactivity.

Flow cytometry in the diagnosis of mediastinal tumors with emphasis on differentiating thymocytes from precursor T-lymphoblastic lymphoma/leukemia.

Flow cytometry (FC) has become the routine technique in the evaluation of hematopoietic neoplasms. Since the anterior mediastinum is a frequent site of involvement by both primary and secondary lymphoma/leukemia, flow cytometry plays an important role in the evaluation of mediastinal masses. The present study reviews 100 flow cytometry cases from patients presenting with mediastinal lesions.

Retinal antigens are recognized by antibodies present in sera of patients with multiple sclerosis.

Multiple sclerosis (MS) is frequently accompanied by visual symptoms including those related to retinal disorders. Since they may be a consequence of an autoimmune reaction, we examined whether sera of patients with diagnosed MS and changes in visual-evoked potentials contain antibodies against retinal antigens (retAgs). Immunoblot analysis revealed that MS sera recognized mainly a 46-kD antigen, a 41-kD antigen, retinal arrestin, to a smaller extent also 70-, 56-, 43-, and 36-kD proteins.

[cGMP-dependent protein kinases].

Cyclic GMP is common second messenger in a plethora of processes. Its major intracellular receptors are the cGMP-dependent protein kinases (PKGs). In this minireview we summarise the main results of studies on structure and physiological role of PKGs.

Metabolism of cyclic GMP in peritoneal macrophages of rat and guinea pig.

The aim of our studies was to establish which enzymes constitute the "cGMP pathway" in rat and guinea pig peritoneal macrophages (PM). We found that in guinea pig PM synthesis of the nucleotide was significantly enhanced in response to activators of soluble guanylyl cyclase (sGC) and it was only slightly stimulated by specific activators of particulate guanylyl cyclases (pGC). In contrast, rat PM responded strongly to atrial natriuretic peptide (ANP), the activator of pGC type A.

Down-regulation of pan-T-cell antigens, particularly CD7, in acute infectious mononucleosis.

Multiparameter flow cytometric analysis was performed on the peripheral blood samples from 25 patients with acute infectious mononucleosis. Phenotypic results were matched with those for patients without viral symptomatology. Samples from all patients with infectious mononucleosis exhibited an activated (HLA-DR+, CD38+) CD8+ cytotoxic-suppressor T-cell population with aberrant down-regulation of CD7, and samples from 2 (8%) of 25 patients also showed down-regulation of CD5.

Ca2+ differently affects hydrophobic properties of guanylyl cyclase-activating proteins (GCAPs) and recoverin.

Guanylyl cyclase-activating proteins (GCAPs) and recoverin are retina-specific Ca(2+)-binding proteins involved in phototransduction. We provide here evidence that in spite of structural similarities GCAPs and recoverin differently change their overall hydrophobic properties in response to Ca(2+). Using native bovine GCAP1, GCAP2 and recoverin we show that: i) the Ca(2+)-dependent binding of recoverin to Phenyl-Sepharose is distinct from such interactions of GCAPs; ii) fluorescence intensity of 1-anilinonaphthalene-8-sulfonate (ANS) is markedly higher at high [Ca(2+)](free) (10 microM) than at low [Ca(2+)](free) (10 nM) in the presence of recoverin, while an opposing effect is observed in the presence of GCAPs; iii) fluorescence resonance energy transfer from tryptophane residues to ANS is more efficient at high [Ca(2+)](free) in recoverin and at low [Ca(2+)](free) in GCAP2.