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Pathogenetic Implications (pathogenetic + implication)
Selected AbstractsDifferential expression of stromal cell,derived factor 1 and its receptor CXCR4 in the skin and endothelial cells of systemic sclerosis patients: Pathogenetic implicationsARTHRITIS & RHEUMATISM, Issue 9 2006Paola Cipriani Objective Systemic sclerosis (SSc) is characterized by early endothelial damage evolving to vascular desertification. Stromal cell,derived factor 1 (SDF-1) and its receptor CXCR4 regulate specific steps in new vessel formation. We undertook this study to determine whether an alteration of the SDF-1/CXCR4 axis might be involved in the pathogenetic mechanisms following ischemic damage during SSc. Methods We enrolled 36 SSc patients and 15 controls. Skin biopsy samples were obtained from each subject, and the expression of SDF-1 and CXCR4 was assessed by immunohistochemistry, reverse transcription,polymerase chain reaction (RT-PCR), and Western blot analyses. Furthermore, isolated microvascular endothelial cells (MVECs) from 4 patients with diffuse cutaneous SSc (dcSSc) and 3 controls were analyzed for SDF-1 and CXCR4 by confocal laser scanning microscopy, RT-PCR, and Western blotting. Results SDF-1 and CXCR4 were up-regulated in the skin of patients with early (edematous) SSc, both in the diffuse and limited cutaneous forms, and progressively decreased, with the lowest expression in the latest phases of both SSc subsets. MVECs from patients with dcSSc expressed significantly higher amounts of both isoforms of SDF-1 in the early stage of disease, with a progressive reduction of SDF-1 and CXCR4 in later stages. On the surface of cultured MVECs from patients with dcSSc, SDF-1 and CXCR4 colocalized in polarized areas, suggesting that they are activated in vivo and that they are under strict genetic control to retain capping function. Conclusion Due to its transient expression, SDF-1 could be considered a future therapeutic target to induce new vessel formation in SSc. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 3JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003F Terenghi Intravenous immunoglobulins (IVIg) are successfully used as immunomodulatory therapy in patients with multifocal motor neuropathy (MMN) but their mechanism of action remains unknown. An anti-idiotypic block of pathogenic autoantibodies has been often postulated even if other possible mechanisms, including a modulation of the release of various cytokines, have been proposed. To evaluate the expression of cytokines in patients with MMN and their possible modulation by IVIg, we determined circulating levels of TNF,, INF,, IL2, IL4, IL10, and IL12 by ELISA in serum samples of 17 patients with MMN and compared them with 12 patients with amyotrophic lateral sclerosis (ALS), 12 with multiple sclerosis (MS), 6 with chronic inflammatory demyelinating polyneuropathy (CIDP), 5 with myasthenia gravis (MG) and 12 healthy controls (NS). Comparable levels of INF,, IL2, IL4, IL10 and IL12 were detected in patients' sera and controls. Even if TNF, levels did not differ significantly among patients' groups, they were higher than in any healthy control (mean ± SD 1.2 ± 0.5 pg/ml, range 0.7,2.4 pg/ml), in 12 (70%) MMN patients (mean ± SD 3.6 ± 1.9 pg/ml; range 0.2,7.5 pg/ml), all ALS, 3 MS (25%), 2 CIDP (40%) and 2 MG (40%). We then measured the concentration of TNF, before and after IVIg therapy in 9 MMN and 2 ALS patients. In all but one MMN patients, circulating levels of TNF, slightly increased after treatment with IVIg (mean values 4.3 vs. 7.2 pg/ml) and decreased 3 weeks after therapy while in both ALS patients they decreased or remained unchanged. No detectable level of TNF, was found in IVIg preparation. This study shows that, similarly to what previously reported in other autoimmune neuropathy as GBS and CIDP, TNF, serum levels are slightly increased in MMN but, at odds with what reported in these disease, their concentration tend to increase parallel to clinical improvement after IVIg therapy. Further studies are necessary to clarify the pathogenetic implication of this finding and in particular whether a possible deviation from a presumably Th2 to a Th1 immune response may help explaining the effect of IVIg in MMN. [source] Diagnostic and pathogenetic implications of the expression of hepatic transporters in focal lesions occurring in normal liverTHE JOURNAL OF PATHOLOGY, Issue 4 2005Sara Vander Borght Abstract Hepatocellular adenoma and focal nodular hyperplasia (FNH) are benign liver tumours. The differential diagnosis of these lesions and of well- to moderately differentiated hepatocellular carcinomas is often difficult but is very important in view of their different treatment. Although neither type of lesion is connected to the biliary tree, FNHs are cholestatic, whereas this is rarely the case for hepatocellular adenomas. This suggests that hepatocellular uptake and secretion of bile constituents is different in FNHs compared to adenomas. We therefore evaluated the expression and localization of hepatic transporters in hepatocellular adenomas, different types of FNH and well- to moderately differentiated hepatocellular carcinomas in non-cirrhotic liver and compared them with normal liver, using real-time RT-PCR and (semi-)quantitative immunohistochemistry. The parenchymal expression of the uptake transporter OATP2/8 (OATP1B1/3) was minimal or absent in adenoma, while there was strong and diffuse expression in FNH. We observed diffuse parenchymal expression of the basolateral export pump MRP3 in adenomas, while only reactive bile ductules and adjacent cholestatic hepatocytes were MRP3-positive in FNH. The MRP3/OATP2/8 expression pattern of atypical FNHs resembled that of adenomas, suggesting that both types of lesion are related. Most hepatocellular carcinomas showed decreased expression of one or more of the canalicular transporters (MDR1, MDR3, BSEP). The differences in transporter expression profile between FNHs and adenomas are most likely pathogenetically important and may explain why only FNHs are cholestatic. The finding that each type of focal lesion in non-cirrhotic liver has a specific transporter expression pattern may be useful in the establishment of a correct diagnosis by imaging or on needle biopsy. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] The absence of apoeccrine glands in the human axilla has disease pathogenetic implications, including axillary hyperhidrosisBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2007D.L. Bovell Summary Background, The existence of a third type of sweat gland in human axillary skin, the apoeccrine gland, with a capacity to produce much higher sweat output than the eccrine gland, was proposed from examination of microdissected glands. However, previous studies of axillary skin glands did not examine the entire individual glandular structure via serial sections and the markers used to identify the different glands gave conflicting results and, hence, the existence of the apoeccrine gland remains controversial. Objectives, To investigate human axillary sweat glands by serial section histology and immunofluorescence. Methods, Human axillary sweat glands were investigated by serial sectioning of paraffin wax-embedded skin samples taken by biopsy from four male and six female volunteers (age range 20,35 years). Sections were examined by light microscopy and immunofluorescence, using antibodies to antigens reported to be markers for discriminating between eccrine and apocrine gland cells: CD15, CD44, S100 and human milk fat globulin. Results, Light microscopy demonstrated that there were hair follicles and a mean ± SD of 76 ± 14 sweat glands cm,2. Eccrine and apocrine glands were found to be present; however, no glands resembling the apoeccrine glands were detected. Both types of sweat gland exhibited signs of being active, with segments of the secretory coils displaying flattened cells and dilated glandular lumina; however, this dilation did not extend to obvious changes in the width of the gland. None of the eccrine glands exhibited evidence of the presence of apocrine cells or vice versa. Immunofluorescence markers were found not to be specific and did not discriminate between the different types of glands or demonstrate the presence of apoeccrine glands. Conclusions, This is the first time that serial sections of axillary skin have been examined by histology and immunofluorescence. The markers reported to discriminate between apocrine and eccrine glands were found to be nonspecific. No evidence of apoeccrine glands was found either by histology or by immunofluorescence. [source] | ||||||||||