Clinically uninvolved but not healthy-The skin of patients with atopic dermatitis is primed for itch and inflammation.

BACKGROUND: Atopic dermatitis (AD) is a highly prevalent inflammatory skin disorder characterized by episodic exacerbations and remissions. Why the clinically healthy skin of AD patients becomes rapidly inflamed and very pruritic is poorly understood. OBJECTIVE: To investigate cowhage- and histamine-induced itch and skin expression levels of their target receptors in lesional and non-lesional skin of AD, compared to the skin of patients with psoriasis, chronic spontaneous urticaria (CSU) and healthy subjects. METHODS: Patients with AD, psoriasis and chronic spontaneous urticaria (CSU) as well as healthy control subjects (HC) (n = 20 each) were assessed for differences in itch parameters, neurogenic flare reaction and local blood flow responses to skin provocations with cowhage and histamine. Skin biopsies from 10 AD, 10 psoriasis,11 CSU and 12 HC were obtained to assess expression of protease-activated receptors 2 and 4 (PAR-2, PAR-4), histamine H1 and H4 receptors (H1R, H4R), and mast cells. RESULTS: Provocation of non-lesional skin of AD patients with cowhage resulted in prolonged itch (p = 0.020), which was not observed in psoriasis and CSU. Significantly prolonged and more intense cowhage- and histamine-induced itch (for duration, peak and overall intensity) was also observed in lesional AD skin. Diminished neurogenic flare reaction and blood flow after histamine provocation were shown in AD and psoriasis patients. Non-lesional AD skin along with lesional AD and psoriasis skin showed an increased expression of PAR-2 and PAR-4, H1R and H4R. Mast cell number was higher in lesional AD and psoriasis skin (p = 0.006 and p = 0.006, respectively). CONCLUSION: The non-lesional skin of AD patients markedly differs from healthy skin in cowhage-induced itch responses and the expression of receptors for proteases and histamine. Proactive therapeutic interventions that downregulate these receptors may prevent episodic exacerbation in AD.

Expression of the JAK/STAT Signaling Pathway in Bullous Pemphigoid and Dermatitis Herpetiformis.

A family of eleven proteins comprises the Janus kinases (JAK) and signal transducers and activators of transcription (STAT) signaling pathway, which enables transduction of signal from cytokine receptor to the nucleus and activation of transcription of target genes. Irregular functioning of the cascade may contribute to pathogenesis of autoimmune diseases; however, there are no reports concerning autoimmune bullous diseases yet to be published. The aim of this study was to evaluate the expression of proteins constituting the JAK/STAT signaling pathway in skin lesions and perilesional area in dermatitis herpetiformis (DH) and bullous pemphigoid (BP), as well as in the control group. Skin biopsies were collected from 21 DH patients, from 20 BP patients, and from 10 healthy volunteers. The localization and expression of selected STAT and JAK proteins were examined by immunohistochemistry and immunoblotting. We found significantly higher expression of JAK/STAT proteins in skin lesions in patients with BP and DH, in comparison to perilesional skin and the control group, which may be related to proinflammatory cytokine network and induction of inflammatory infiltrate in tissues. Our findings suggest that differences in the JAK and STAT expression may be related to distinct cytokines activating them and mediating neutrophilic and/or eosinophilic infiltrate.

Corrigendum to "Expression and Clinical Significance of Cancer Stem Cell Markers CD24, CD44, and CD133 in Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis".

[This corrects the article DOI: 10.1155/2017/3276806.].

Expression and Clinical Significance of Cancer Stem Cell Markers CD24, CD44, and CD133 in Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis.

Cancer stem cells (CSC) play an important role in pancreatic carcinogenesis and prognosis. The study aimed at examining the expression of CD24, CD44, and CD133 in human PDAC and CP in order to evaluate its clinicopathological correlations and the clinical significance. Surgical specimens from 23 patients with PDAC and 15 patients with chronic pancreatitis after pancreatic resection were stained with CD24, CD44, and CD133 antibodies. The intensity of staining was scored from 0 (negative) to 3 (strongly positive). Results. Mean CD24 staining score in PDAC was 1.38 ± 0.76 and was significantly higher than that in CP: 0.70 ± 0.53 (p < 0.01); CD44 score in PDAC was 2.23 ± 0.42 and was significantly higher than that in CP: 1.87 ± 0.55 (p < 0.05); CD133 score 0.93 ± 0.58 was not different from CP: 0.71 ± 0.43 (p > 0.05). CD44 immunoreactivity was significantly higher (p < 0.05) in pT1 and pT2 patients together as regards pT3: 2.45 ± 0.37 versus 2.06 ± 0.38 as well as in N0 patients compared to N1 patients: 2.5 ± 0.38 versus 2.04 ± 0.34. Conclusions. CD24 and CD44 are upregulated in human pancreatic cancer compared to chronic pancreatitis. CD44 immunoreactivity decreases with the tumor advancement and may represent the negative PDAC prognostic factor. Each CSC marker was differently related to PDAC advancement. CD133 may lack clinical significance in PDAC.

An unusual case of IgA-dominant postinfectious glomerulonephritis: a case report and review of the literature.

We report a case of IgA-dominant postinfectious glomerulonephritis in a 49-year-old man presenting with acute kidney injury, nephrotic range proteinuria and hematuria. He suffered from ischemic heart disease, cardiac insufficiency, mitral regurgitation, tricuspid insufficiency, septal aneurysm and hypertension. Renal biopsy revealed segmental and focal endocapillary and mesangial hypercellularity, and thickening of the glomerular capillary wall. Immunofluorescence showed co-dominant strong coarse granular immunostaining of IgA, IgG and C3 mainly along the glomerular capillary wall. On electron microscopy some large subepithelial hump-shaped deposits were present. In summary, this case demonstrates the presence of a broad spectrum of glomerular histological findings in postinfectious glomerulonephritis.

Preserved global histone H4 acetylation linked to ETV6-RUNX1 fusion and PAX5 deletions is associated with favorable outcome in pediatric B-cell progenitor acute lymphoblastic leukemia.

Epigenetic dysregulation is a hallmark of cancer executed by a number of complex processes the most important of which converge on DNA methylation and histone protein modifications. Epigenetic marks are potentially reversible and thus promising drug targets. In the setting of acute lymphoblastic leukemia (ALL) they have been associated with clinicopathological features including risk of relapse or molecular subgroups of the disease. Here, using immunocytochemistry of bone marrow smears from diagnosis, we studied global histone H4 acetylation, whose loss was previously linked to treatment failure in adults with ALL, in pediatric patients. We demonstrate that preserved global histone H4 acetylation is significantly associated with favorable outcome (RFS, EFS, OS) in children with B cell progenitor (BCP) ALL, recapitulating the findings from adult populations. Further, for the first time we demonstrate differential histone H4 acetylation in molecular subclasses of BCP-ALL including cases with ETV6-RUNX1 fusion gene or PAX5 deletion or deletions in genes linked to B cell development. We conclude global histone H4 acetylation is a prognostic marker and a potential therapeutic target in ALL.

Mercury-induced nephrotic syndrome: a case report and review of the literature.

A 42-year-old man was admitted to the Nephrology Department because of nephrotic syndrome. Eight months prior to admission he attempted suicide by intravenous self-injection of 2.5 ml of elemental mercury. Renal biopsy was performed. Light microscopy findings showed normal glomeruli and injury of proximal tubular cells. Immunofluorescence was negative, and electron microscopy study revealed diffuse effacement of podocyte foot processes and vacuolization of podocyte cytoplasm. Minimal change disease was diagnosed. The patient was treated with 2,3-dimercaptopropane-1-sulfonate, for mercury detoxification, and steroids. In one-year follow-up the 24-h urine protein excretion decreased from 30 γ to 0.186 g, and the renal function remain normal. The presented case indicates that mercury intoxication should be mentioned as a cause of secondary minimal change disease.

Immunohistochemical analysis of mast cell infiltrates and microvessel density in oral squamous cell carcinoma.

The aim of the study was to evaluate mast cell concentration and microvessel density in perilesional and intralesional regions of oral squamous cell carcinoma (OSCC) and furthermore to assess the possible relationship between the above-mentioned parameters. Paraffin-embedded specimens from 47 cases of OSCC and 12 cases of normal mucosa were investigated immunohistochemically with anti-CD-31 antibody to stain microvessels and anti-tryptase antibody to visualize mast cells. The degree of vascularization and mast cell infiltration was measured with an image analysis system. The study revealed considerably increased microvessel density and mast cell abundance in intralesional and perilesional regions of OSCCs in comparison to normal mucosa. There was a significant positive correlation between microvessel density and mast cell concentration in both localizations of OSCCs (p < 0.02, p < 0.001, respectively), whereas a comparable correlation was not observed in normal mucosa. The obtained results suggest that mast cells play an important role in the regulation of angiogenesis in OSCC, although there are aspects of their activity of potential diagnostic and therapeutic significance which require further research.

The immunoexpression of glomerular NF-κB in proteinuric patients with proliferative and non-proliferative glomerulopathies.

Recent studies suggest that NF-κB activation plays an essential role in the activation of mesangial cells and macrophages through the transcriptional induction of inflammatory mediators of glomerular inflammation and injury. The aim of the present study was to determine, using an image analysis system, glomerular immunoexpression of NF-κB (nuclear translocation of p65) in proteinuric patients with proliferative and non-proliferative glomerulopathies. Thirty-six proteinuric patients with idiopathic proliferative glomerulopathies (PG group) and 28 proteinuric participants with non-proliferative glomerulopathies (NPG group) were examined by percutaneous renal biopsy. As a control 12 biopsy specimens of the kidneys removed because of trauma were used. In the PG group the mean values of the glomerular immunoexpression of NF-κB were significantly increased as compared to both NPG patients and controls. In the PG but not in the MPG group glomerular immunoexpression of NF-κB was significantly positively correlated with the degree of proteinuria. Moreover, in the PG group glomerular immunoexpression of NF-κB was positively correlated with the mesangial cells, mesangial area and glomerular monocytes/macrophages. In conclusion, our results strongly suggest a role of NF-κB in glomerular injury in proteinuric patients with proliferative glomerulopathies.

Mast cells and eosinophils are involved in activation of ulcerative colitis.

PURPOSE: The intestinal mucosal immune cells such as the mast cells and eosinophils play an important role in the pathogenesis of ulcerative colitis (UC). The aim of present study was to compare the number of mast cells and eosinophils in patients with active and non-active ulcerative colitis. Another purpose was to found whether the number of eosinophils could correlate with number of mast cells in both tested groups. MATERIAL AND METHODS: The twenty-five of formalin-fixed, paraffin-embedded tissue specimens of active ulcerative colitis, the twenty of non-active ulcerative colitis and the ten of controls were retrieved from archival material. Tryptase and chymase immunopositive cells were detected using immunohistochemical method. Additionally, the number of mast cells and eosinophils were detected using the most common histochemical methods. RESULTS: The number of eosinophils and toluidine blue stained and tryptase immunopositive mast cells was significantly increased in active UC compared to non-active UC. In active stage of UC positive correlation between the number of mast cells stained with toluidine blue and the number of chymase and tryptase immunopositive mast cells were observed. Moreover, the number of eosinophils was significantly correlated with number of mast cells stained with toluidine blue and number of tryptase- and chymase immunopositive mast cells. In non-active stage of UC positive correlation was observed only between the number of mast cells stained with toluidine blue and chymase immunopositive cells and eosinophils. CONCLUSIONS: In conclusion, our findings confirmed that mast cells and eosinophils are functionally involved in the course of UC.

Renal immunoexpression of ghrelin is attenuated in human proliferative glomerulopathies

Background: Ghrelin is a novel 28 amino acid growth hormone-releasing peptide hormone that has been shown to inhibit cell proliferation and to decrease the production of proinflammatory cytokines by monocytes/macrophages. Moreover it decreases the release of endothelin-1 (ET-1), as well as mononuclear cell binding. Material and methods: Seventeen patients with proliferative glomerulopathies (PG)and 15 patients with non-proliferative glomerulopathies(NPG) were examined by percutaneous renal biopsy. As a control 11 biopsy specimens of the kidneys removed because of trauma were used. The immune expression of ghrelin and ET-1 was assessed semiquantitatively where as the interstitial monocytes/macrophages and interstitial area were evaluated quantitatively. Results: The mean value of the immune expression of ghrelin was significantly diminished in PG patients as compared to both NPG group and controls while the mean values of ET-1, interstitialCD68+ cells, as well as interstitial area were in PG group increased in comparison with controls and NPG patients, most of them significantly. In all groups there were significant negative correlations between immunostaining of ghrelin and ET-1, whereas negative correlation between immunostaining of ghrelin and CD68+ cells was significant only in PG group. Conclusions: We can confirm the presence of ghrelin in tubular epithelial cells in normal and diseasedhuman kidneys. Lack or low level of this protein in proliferative glomerulopathies may be, in part, responsible for interstitial accumulation of monocytes/macrophages in these cases (AU)

Antecedentes: La grelina es un péptido de reciente descubrimiento de 28 aminoácidos que libera la hormona del crecimiento y que se ha demostrado que inhibe la proliferación celular al igual que disminuye la producción de citoquinas proinflamatorias mediante monocitos/macrófagos. Además, reduce la liberación de endotelina-1 (ET-1), así como la unión de células mononucleares. Materiales y métodos: Se practicó biopsia renal percutánea a 17 pacientes con glomerulopatías proliferativas (GP) y a 15 pacientes con glomerulopatías no proliferativas (GNP). Como grupo de control se utilizaron 11 biopsias de riñones que habían sido extirpados por traumatismo. La inmunoexpresión de la grelina y la ET-1 se determinó semicuantitativamente mientras que se realizaba un análisis cuantitativo de la zona intersticial y de los monocitos/macrófagos intersticiales. Resultados: El valor medio de la inmuno expresión de la grelina se vio considerablemente disminuido en pacientes con GP, en comparación con el grupo de pacientes con GNP y de control, mientras que los valores medios de ET-1, células CD68+intersticiales, así como de la zona intersticial, se vieron incrementados en el grupo de pacientes con GP en comparación con el grupo de control y los pacientes con GNP, la mayoría de ellos de forma significativa. En todos los grupos se observaron correlaciones negativas importantes entre la expresión de grelina y de ET-1, mientras que la correlación negativa entre la expresión de grelina y de células CD68+ era relevante únicamente en el grupo de pacientes con PG. Conclusiones: Puede confirmarse la presencia de grelina en las células epiteliales tubulares en riñones humanos normales y enfermos. La falta o el reducido nivel de esta proteína en las glomerolopatías proliferativas pueden ser, en parte, la causa de la acumulación intersticial de monocitos/macrófagos en estos casos (AU)

Renal immunoexpression of ghrelin is attenuated in human proliferative glomerulopathies.

BACKGROUND: Ghrelin is a novel 28 amino acid growth hormone-releasing peptide hormone that has been shown to inhibit cell proliferation and to decrease the production of proinflammatory cytokines by monocytes/macrophages. Moreover it decreases the release of endothelin-1 (ET-1), as well as mononuclear cell binding. MATERIAL AND METHODS: Seventeen patients with proliferative glomerulopathies (PG) and 15 patients with non-proliferative glomerulopathies (NPG) were examined by percutaneous renal biopsy. As a control 11 biopsy specimens of the kidneys removed because of trauma were used. The immunoexpression of ghrelin and ET-1 was assessed semiquantitatively whereas the interstitial monocytes/macrophages and interstitial area were evaluated quantitatively. RESULTS: The mean value of the immunoexpression of ghrelin was significantly diminished in PG patients as compared to both NPG group and controls while the mean values of ET-1, interstitial CD68+ cells, as well as interstitial area were in PG group increased in comparison with controls and NPG patients, most of them significantly. In all groups there were significant negative correlations between immunostaining of ghrelin and ET-1, whereas negative correlation between immunostaining of ghrelin and CD68+ cells was significant only in PG group. CONCLUSIONS: We can confirm the presence of ghrelin in tubular epithelial cells in normal and diseased human kidneys. Lack or low level of this protein in proliferative glomerulopathies may be, in part, responsible for interstitial accumulation of monocytes/macrophages in these cases.

DNAzymes to mouse beta1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth.

Previously, we designed a DNAzyme (beta1DE) targeting the human beta1 integrin subunit, which efficiently digested the mRNA of the beta1 integrin subunit and downregulated beta1 integrin expression in endothelial cells. This DNAzyme blocked the adhesion of endothelial cells and abolished their ability to form microcapillary tubes in Matrigel. In our present study, we demonstrate that beta1DE effectively inhibited neovascularization in Matrigel plugs (BALB/c mice, n=20) and solid human carcinoma tumors developed in nude mice (BALB/cA nude (nu-/-)-B6.Cg-Foxn1(nu)) (n=30) using prostate carcinoma cells PC-3 (n=15) and colon adenocarcinoma cells CX1.1 (n=15). When injected intratumorally, it significantly reduced the tumor size and number of microvessels developed by both CX1.1 and PC-3 cells within the 3 weeks of experiment duration. Thus, DNAzymes targeting beta1 integrin genes can inhibit multiple key tumorigenic processes in vitro and in vivo and may serve as useful anti-cancer agents.

Morphometric and immunohistochemical insight into focal segmental glomerulosclerosis in obese and non-obese patients

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Synaptopodin immunoexpression in steroidresponsive and steroid-resistant minimal change disease and focal segmental glomerulosclerosis

Antecedentes y objetivos: la sinaptopodina es una proteína de los podocitos y una parte del aparato contráctil basado en la actina de los procesos pediculados. Recientemente, se encontró que las proteínas expresadas por los podocitos son importantes para la integridad de la barrera de filtración glomerular. Los podocitos pueden verse dañadosen muchas formas de glomerulopatías, incluyendo la enfermedad de cambios mínimos (ECM) y la glomerulos-clerosis focal y segmentaria (GEFS). Este estudio se realizó para determinar si la inmunoexpresión de sinaptopodina en muestras de tejido renal difiere entre los pacientes con ECM respondedora a esteroides, ECM resistente a esteroides, y la GEFS. Métodos: la inmunoexpresión de sinaptopodina se evaluó mediante tinción de inmunoperoxidasa con un anticuerpo monoclonal anti-humano de ratón en 12 muestras de biopsia renal de pacientes con ECM respondedora a esteroides, 10 muestras renales de ECM resistente a esteroides, y en 14 muestras de biopsia renal de pacientes con GEFS. Se tomaron como controles 10 muestras tisulares de riñones extirpados por traumatismo. La expresión de sinaptopodina se cuantificó como el porcentaje de penacho glomerular mediante un sistema de análisi de la imagen computerizada.Resultados: en los contorles normales, la inmunoex-presión de sinaptopodina se vio en los podocitos a lo largo de la membrana basal glomerular en un patrón finalmente granular. No se observaron cambios en la inmunoexpresión de sinaptopodina en la ECM respondedora a esteroides frente a los controles. En pacientes con ECM resistente a esteroides y GEFS, se vio un patrón granular de inmunoexpresión de sinaptopodina. Las áreas de esclerosis en los pacientes con GEFS no mostraron expresión de sinaptopodina. El análisis estadístico mostró una inmunoexpresión de sinaptopodinasignificativamente disminuida en los glomerulos de pacientes con ECM resistente a esteroides y con GEFS en comparación con los grupos de ECM respondedora a esteroides y control. Además, en los tejidos renales de pacientes con GEFS, la inmunoexpresión de sinaptopodina estaba disminuida en comparación con las biopsias renales de pacientes con ECM resistente a esteroides. En conclusión, nuestros resultados sugieren que la distribución anormal y la expresión reducida de sinaptopodina podrían estar asociadas con una respuesta escasa al tratamiento con corticoides en la ECM y la GEFS (AU)

Background and objectives: Synaptopodin is protein of podocytes, and a part of the actin-based contractile apparatus of foot-processes. Recently, proteins expressed by the podocyte were found to be important for the integrity of the glomerular filtration barrier.Podocytes are injured in many forms of glomerulopathies, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). The study was undertaken to determinate if synaptopodin immunoexpression in renal tissue specimens differsbetween patients with steroid-responsive MCD, steroid-resistant MCD, and FSGS. Methods: Synaptopodin immunoexpression was evaluated by immunoperioxidase staining with a mouse anti-human monoclonal antibody in 12 renal biopsy specimens in patients with steroid-responsive MCD, 10 renal tissues in steroid-resistant MCD, and in 14 renal biopsy specimens in patients with FSGS. As a control 10 tissue specimens of the kidneys removed because of trauma were used. Synaptopodin expression was quantified as a percentage of glomerular tuft by computerized image analysis system. Results: In normal controls synaptopodin immunoexpression was seen in podocytes along theglomerular basement membrane in a finely linear pattern. No changes were found in synaptopodin immunoexpression in steroid-responsive MCD versus controls. In patientswith steroid-resistant MCD and FSGS a granular pattern of synaptopodin immunoexpression was seen. Areas of sclerosis in patients with FSGS did not demonstrate synaptopodin expression. Statistical analysis showed significantly diminished synaptopodin immunoexpresion in glomeruli in patients with steroid-resistant MCD and FSGS as compared with steroid-responsive MCD group and controls. Moreover, in renal tissues in patientswith FSGS the immunoexpression of synaptopodin was decreased in comparison with renal biopsies in patients with steroid-resistant MCD. In conclusions, our resultssuggest that abnormal distribution and reduced expression of synaptopodin may be associated with poor response to steroid therapy in MCD and FSGS (AU)

[Synaptopodin immunoexpression in steroid-responsive and steroid-resistant minimal change disease and focal segmental glomerulosclerosis].

BACKGROUND AND OBJECTIVES: Synaptopodin is protein of podocytes, and a part of the actin-based contractile apparatus of foot-processes. Recently, proteins expressed by the podocyte were found to be important for the integrity of the glomerular filtration barrier. Podocytes are injured in many forms of glomerulopathies, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). The study was undertaken to determinate if synaptopodin immunoexpression in renal tissue specimens differs between patients with steroid-responsive MCD, steroid-resistant MCD, and FSGS. METHODS: Synaptopodin immunoexpression was evaluated by immunoperioxidase staining with a mouse anti-human monoclonal antibody in 12 renal biopsy specimens in patients with steroid-responsive MCD, 10 renal tissues in steroid-resistant MCD, and in 14 renal biopsy specimens in patients with FSGS. As a control 10 tissue specimens of the kidneys removed because of trauma were used. Synaptopodin expression was quantified as a percentage of glomerular tuft by computerized image analysis system. RESULTS: In normal controls synaptopodin immunoexpression was seen in podocytes along the glomerular basement membrane in a finely linear pattern. No changes were found in synaptopodin immunoexpression in steroid-responsive MCD versus controls. In patients with steroid-resistant MCD and FSGS a granular pattern of synaptopodin immunoexpression was seen. Areas of sclerosis in patients with FSGS did not demonstrate synaptopodin expression. Statistical analysis showed significantly diminished synaptopodin immunoexpresion in glomeruli in patients with steroid-resistant MCD and FSGS as compared with steroid-responsive MCD group and controls. Moreover, in renal tissues in patients with FSGS the immunoexpression of synaptopodin was decreased in comparison with renal biopsies in patients with steroid-resistant MCD. IN CONCLUSIONS: our results suggest that abnormal distribution and reduced expression of synaptopodin may be associated with poor response to steroid therapy in MCD and FSGS.

Association of stem cell factor expression in nasal polyp epithelial cells with aspirin sensitivity and asthma.

Mast cells constitute a significant proportion of cells infiltrating nasal polyp tissue, and epithelial cells may release stem cell factor (SCF), a cytokine with chemotactic and survival activity for mast cells. We aimed to assess the expression of SCF in human nasal polyp epithelial cells (NPECs) as related to patients' clinical phenotypes. Nasal polyp tissues were obtained from 29 patients [including nine with aspirin (ASA)-hypersensitivity and 12 with bronchial asthma] undergoing polypectomy for nasal obstruction. Epithelial cells were obtained following 6-week culture of nasal polyps explants. The SCF released into the culture supernatant was assessed by enzyme-linked immunosorbent assay (ELISA) and total SCF mRNA in the polyp tissue was determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). For the whole group of patients, the number of polypectomies correlated with expression of SCF mRNA (r = 0.62; P < 0.005), SCF protein in the NPECs supernatants (r = 0.39; P < 0.05) and with density of mast cells in epithelial layer (r = 0.37; P < 0.05) and stromal layer (r = 0.5; P < 0.01) of nasal polyps. The SCF/beta-actin mRNA ratios were significantly higher in ASA-hypersensitive (AH) asthmatics (median 0.97, range: 0.8-1.5) when compared with ASA-tolerant (AT) patients (median 0.5, range: 0.1-0.7; P < 0.001). The SCF protein concentration in NPEC supernatants was also significantly higher in AH asthmatics (median 1.10 pg/microg DNA, range: 0.4-1.9) when compared with AT patients (median 0.1 pg/microg DNA, range: 0.02-1.2; P < 0.001). In the subpopulation of ASA-sensitive asthmatics the number of polypectomies correlated also with the density of mast cells and eosinophils in the polyp tissue.

Inmunoexpresión de la perforiza y la granzima b en los linfocitos del infiltrado del rechazo agudo en el riñón humano trasplantado / Immunoexpression of perforin and granzyme B on infiltrating lymphocytes in human renal acute allograft rejection

La destrucción del injerto renal se puede efectuar mediante el contacto directo célula-célula entre el linfocito T activado y una célula diana, que va a dar lugar a una liberación de moléculas citotóxicas. La perforina y la granzima B se pueden utilizar como marcadores de activación de las células citotóxicas en el tejido trasplantado. El objetivo de este estudio fue determinar la inmunoexpresión de la perforina y la granzima B por parte de los linfocitos que infiltran el tejido renal durante el rechazo agudo, y valorar la existencia de algún tipo de correlación entre el fenotipo de los linfocitos infiltrantes y las células que expresan gránulos citotóxicos, asi como con la severidad del daño del injerto definido por los criterios Banff 97. La tinción de la immunoperoxidasa se hizo con anticuerpos monoclonales anti- perforina, -granzima B, -CD3 and -CD8 en biopsias de 21 enfermos con rechazo agudo: Banff 97 IA (n = 11) y Banff 97 IB (n = 10). Como control se usaron 11 biopsias de enfermos trasplantados sin signos de rechazo.Todas las biopsias con rechazo agudo contenían un gran número de células CD3 + T (Banff IA: 437,4 ñ 154,4 y Banff IB: 825 ñ 339,9 vs 123,4 ñ 52,5 en controles) y linfocitos CD8+T (Banff 97 IA: 177,6 ñ 89,2 y Banff IB: 293,2 ñ 112,4 vs 64,2 ñ 37,1 en controles). La tinción para granzima B y perforina fue negativa en los controles. La positividad para la perforina fue similar en los rechazos agudos Banff IA y Banff IB (1,5 ñ 0,6 vs 1,8 ñ 0,8, respectivamente). El recuento de células granzima B+ fue significativamente superior en el grupo con rechazo agudo Banff IB (128,3 ñ 74,3) que en los Banff IA (48,2 ñ 18,3). Además, en los rechazos agudos Banff IB, El número de células granzima B+ y perforina + se correlacionó con el número de células CD8 + T. En conclusión, nuestros resultados sugieren que en el rechazo tubulointersticial agudo, los linfocitos T citotóxicos juegan un papel fundamental. Se sugiere que la fuerte positividad para la ganzima B en las células que infiltran el tejido renal es un marcador de severidad del daño causado al injerto (AU)

Immunoexpression of perforin and granzyme B on infiltrating lymphocytes in human renal acute allograft rejection.

Graft destruction can be effected by direct cell-to-cell contact between activated effector T cell and a target graft resulting in delivery of cytotoxic molecules. Perforin and granzyme B can be used as activation markers for cytotoxic cells in allograft tissue. The aim of the study was to determine the immunoexpression of perforin and granzyme B by immune cells infiltrating renal tissue during acute allograft rejection and to evaluate any correlation between the phenotype of infiltrating lymphocytes and cells expressing cytotoxic granules as well as the severity of graft damage as defined by Banff 97 criteria. Immunoperoxidase staining was carried out using monoclonal antibodies anti-perforin, -granzyme B, -CD3 and -CD8 on renal allograft biopsy specimens from twenty one patients with acute renal transplant rejection: Banff 97 IA (n = 11) and Banff 97 IB (n = 10). As a control 11 biopsy specimens of renal transplant patient without any signs of rejection were used. All allograft biopsy specimens with acute renal transplant rejection contained a high number of CD3+ T cells (Banff IA: 437.4 +/- 154.4 and Banff IB: 825 +/- 339.9 vs 123.4 +/- 52.5 in controls) and CD8+ T lymphocytes (Banff 97 IA: 177.6 +/- 89.2 and Banff IB: 293.2 +/- 112.4 vs 64.2 +/- 37.1 in controls). Immunostaining for granzyme B and perforin was negative in controls. The immunopositivity for perforin was similar in Banff IA and Banff IB acute allograft rejection (1.5 +/- 0.6 vs 1.8 +/- 0.8, respectively). Granzyme B+ cell count was significantly higher in severe rejection group Banff IB (128.3 +/- 74.3) than in Banff IA group (48.2 +/- 18.3). Moreover, in acute allograft rejection Banff IB the number of granzyme B+ cells and perforin+ cells was correlated with the number of CD8+ T cells. In conclusion, our results suggest that in acute tubulointerstitial allograft rejection activated cytotoxic T lymphocytes play a major role. The strong immunopositivity for granzyme B on infiltrating cells in renal transplant tissue is suggested as a marker of severity of graft damage.