Xerostomia Research Today is a free monthly online journal that collates and summarizes the latest research about Xerostomia, including details on dry mouth, treatment, causes, lack of saliva.

Severe alterations in expression and localisation of {alpha}6{beta}4 integrin in salivary gland acini from patients with Sjogren syndrome.

Velozo J, Aguilera S, Alliende C, Ewert P, Molina C, Pérez P, Leyton L, Quest A, Brito M, González S, Leyton C, Hermoso M, Romo R, González MJ

University of Chile, Santiago, Chile.

OBJECTIVES: In salivary glands from patients with Sjögren syndrome, overexpression of laminins 1 and 5 and disorganisation of the acinar basal lamina have been reported. Laminin 5 mediates association of the basal lamina with epithelial cells by forming adhesion complexes upon interaction with alpha6beta4 integrin. In the present work, mRNA and protein levels of alpha6beta4 integrin were determined and its localisation in salivary glands evaluated in patients with Sjögren syndrome. METHODS: Salivary glands of 12 patients with Sjögren syndrome and 8 controls were studied. The mRNA and protein levels of alpha6beta4 were determined by semiquantitative reverse transcriptase (RT)-PCR and western blot analysis, respectively. The subcellular localisation of alpha6beta4 and laminin were evaluated by confocal microscopy. RESULTS: In patients, no significant differences in alpha6 and beta4 mRNA levels were detected. However, beta4 integrin protein levels were significantly lower, whereas, changes in alpha6, were highly variable. In controls, alpha6beta4 was detected in the basolateral and basal surface of serous and mucous acini, respectively. In patients, alterations in alpha6beta4 distribution were particularly dramatic for acini with strong basal lamina disorganisation. alpha6beta4 was also detected in the cytoplasm and lateral plasma membrane in serous and mucous acini. CONCLUSION: Mild alterations in the basal lamina correlated with lateral redistribution of alpha6beta4 integrin and the formation of new cell-cell adhesions that help maintain acinar organisation and promote cell survival. Conversely, in cases with severe basal lamina alterations, lateral alpha6beta4 redistribution was no longer sufficient to maintain acinar cell survival. Thus, maintenance of equilibrium between cell-cell and cell-basal lamina attachment is required to sustain gland cell survival.

Published 13 May 2009 in Ann Rheum Dis, 68(6): 991-6.
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Articles on Xerostomia published 27 April 2009:

Anti-Ro/SSA autoantibody-mediated regulation of extracellular matrix fibulins in human epithelial cells of the salivary gland.   Scand J Rheumatol, 38(3): 198-206.

OBJECTIVES: The fibulins are a family of extracellular matrix (ECM) molecules that regulate the organ shape along with other growth factors and stromal cells and have recently been shown to be involved in a variety of cellular functions including proliferation, migration, differentiation, and survival. Important changes in acinar and ductal morphology and function, together with pronounced ECM remodelling, are detectable in the labial salivary glands (LSGs) of patients with Sjögren's syndrome ... [Abstract] [Full-text]

Heterogeneous nuclear ribonucleoprotein h1, a novel nuclear autoantigen.   Clin Chem, 55(5): 946-54.

BACKGROUND: Serum samples from patients with autoimmune connective tissue diseases that show a finely speckled antinuclear antibody (ANA) on indirect immune-fluorescence often have antibodies against unknown nuclear target antigens. To search for such autoantigens we applied a proteomic approach using sera from patients with a high ANA titer (>or=640) and finely speckled fluorescence but in whom no antibodies to extractable nuclear antigens (ENA) could be identified. METHODS: Using an ... [Abstract] [Full-text]

Articles on Xerostomia published 13 April 2009:

Intensity-modulated radiotherapy reduces radiation-induced morbidity and improves health-related quality of life: results of a nonrandomized prospective study using a standardized follow-up program.   Int J Radiat Oncol Biol Phys, 74(1): 1-8.

PURPOSE: The purpose of this study was to compare intensity-modulated radiation therapy (IMRT) and three-dimensional conventional radiotherapy (3D-CRT) with regard to patient-rated xerostomia, Radiation Therapy Oncology Group (RTOG) acute and late xerostomia and health-related quality of life (HRQoL) among patients with head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: Included were 241 patients with HNSCC treated with bilateral irradiation +/- chemotherapy. Since 2000, all ... [Abstract] [Full-text]

Articles on Xerostomia published 16 March 2009:

Complement inhibitor C4b-binding protein in primary Sjögren's syndrome and its association with other disease markers.   Scand J Immunol, 69(4): 374-80.

A subgroup of patients suffering from primary Sjögren's syndrome (pSS) display unexplained low levels of complement components C3 and/or C4 which is associated with increased risk of non-Hodgkin's lymphoma. C4b-binding protein (C4BP) is a major fluid-phase complement inhibitor which can influence C4 and C3 levels. Therefore we analysed C4BP levels in the sera of patients with pSS to better understand the disturbances in complement in pSS. Associations with other disease markers were also ... [Abstract] [Full-text]

Articles on Xerostomia published 2 March 2009:

Analysis of salivary flow and dose-volume modeling of complication incidence in patients with head-and-neck cancer receiving intensity-modulated radiotherapy.   Int J Radiat Oncol Biol Phys, 73(4): 1252-9.

PURPOSE: To investigate dose-volume effects of salivary flow and the functional recovery over time, using salivary function data and different models of normal tissue complication probability (NTCP). METHODS AND MATERIALS: A total of 59 patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT) were analyzed in the present study. The toxicity was evaluated using the Radiation Therapy Oncology Group (RTOG) scale and salivary flows, both unstimulated (USF) and ... [Abstract] [Full-text]

Articles on Xerostomia published 24 February 2009:

Autoimmune autonomic ganglionopathy with Sjögren's syndrome: significance of ganglionic acetylcholine receptor antibody and therapeutic approach.   Auton Neurosci, 146(1): 33-5.

Autoimmune autonomic ganglionopathy (AAG) is a disorder defined by antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia. We report two patients with chronically progressing dysautonomia with Sjögren's syndrome (SS). The first case showed elevated titer of ganglionic acetylcholine receptor (AChR) antibody and improved with oral intake of prednisolone. In contrast, the second case showed no elevation of ganglionic AChR antibody titer and had poor response to ... [Abstract] [Full-text]

Articles on Xerostomia published 20 February 2009:

Sjögren's syndrome of the parotid gland: value of diffusion-weighted echo-planar MRI for diagnosis at an early stage based on MR sialography grading in comparison with healthy volunteers.   Rofo, 181(3): 242-8.

PURPOSE: To investigate the value of diffusion-weighted echo-planar imaging (DW-EPI) for quantifying functional changes of the parotid gland in Sjögren's disease and to evaluate whether ADC mapping allows for early diagnosis based on MR sialography grading. MATERIALS AND METHODS: Using a DW-EPI sequence at 1.5 T (b-factors: 0, 500 and 1000 sec/mm (2)), the parotid glands of 52 healthy volunteers and 13 patients with histologically verified affection of Sjögren's disease were examined. All ... [Abstract] [Full-text]

Articles on Xerostomia published 13 February 2009:

Increased frequency of CD16+ monocytes and the presence of activated dendritic cells in salivary glands in primary Sjögren syndrome.   Ann Rheum Dis, 68(3): 420-6.

OBJECTIVES: In the salivary glands of patients with primary Sjögren Syndrome (pSjS) an accumulation of dendritic cells (DCs) is seen, which is thought to play a role in stimulating local inflammation. Aberrancies in subsets of monocytes, generally considered the blood precursors for DCs, may play a role in this accumulation of DCs. This study is aimed at determining the level of mature CD14lowCD16+ monocytes in pSjS and their contribution to the accumulation of DCs in pSjS. METHODS: Levels of ... [Abstract] [Full-text]

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