Effect of the synthetic immunomodulator, linomide, on experimental models of thyroiditis.
The drug Linomide is an immunomodulator showing marked down-regulation of several experimental autoimmune diseases. In this study, its effect on three different experimental models of thyroid disease and on spontaneous infiltration of salivary glands (sialoadenitis), was investigated. Although very effective at preventing thyroid infiltrates in mice immunized with mouse thyroglobulin and complete Freund's adjuvant and in spontaneous models of thyroiditis and sialoadenitis, it completely failed to modify experimental autoimmune thyroiditis (EAT) induced in mice immunized with mouse thyroglobulin and lipopolysaccharide. There was no significant shift in the observed isotypes of anti-mouse thyroglobulin antibodies and only anti-mouse thyroglobulin antibodies in the spontaneous model were completely down-modulated by the drug. One surprising fact to emerge was that Linomide-treated donor mice, although protected from thyroid lesions themselves, were still able to transfer EAT showing that they must have been effectively primed while being treated with Linomide. It is possible that the drug down modulated EAT by interfering with the trafficking of primed effector cells. (+info)
A case of coprophagia presenting with sialadenitis.
PRESENTATION: a 94-year-old woman with dementia was admitted to an acute geriatric ward with increasing confusion and falls. On two occasions she developed submandibular masses. Faeces were aspirated from her mouth and a diagnosis made of recurrent submandibular sialadenitis secondary to coprophagia. OUTCOME: the submandibular mass settled with antibiotics and oral care. Coprophagia was not observed on the ward, but faecal smearing was noted. With regular toileting, this behaviour ceased and sialadenitis did not recur. (+info)
The MR imaging assessment of submandibular gland sialoadenitis secondary to sialolithiasis: correlation with CT and histopathologic findings.
BACKGROUND AND PURPOSE: MR imaging has been proved to be effective in depicting wide variety of pathologic changes of the salivary gland. Therefore, we evaluated clinical usefulness of MR imaging for sialolithiasis. METHODS: Sixteen patients with sialolithiasis of the submandibular gland underwent MR imaging. MR images of the glands were obtained with a conventional (T1-weighted), fast spin-echo (fat-suppressed T2-weighted) and short inversion time-inversion recovery sequences. Contrast enhancement was not used. MR imaging features then were compared with clinical symptoms, histopathologic features of excised glands, and CT imaging features. RESULTS: Submandibular glands with sialolithiasis could be classified into three types on the basis of clinical symptoms and MR imaging features of the glands. Type I glands were positive for clinical symptoms and MR imaging abnormalities, and were characterised histopathologically by active inflammation (9 [56%] of 16). Type II glands were negative for clinical symptoms and positive for MR imaging abnormalities (4 [25%] of 16), and the glands were replaced by fat. Type III glands were negative for clinical symptoms and MR imaging abnormalities (3 [19%] of 16). CT features of these glands correlated well with those of MR imaging. CONCLUSION: These results suggest that MR imaging features may reflect chronic and acute obstruction, and a combination of CT and MR imaging may complement each other in examining glands with sialolithiasis. (+info)
Genetic basis of autoimmune sialadenitis in MRL/lpr lupus-prone mice: additive and hierarchical properties of polygenic inheritance.
OBJECTIVE: To clarify the mode of inheritance of autoimmune sialadenitis in MRL/MpJ-lpr/lpr (MRL/lpr) lupus-prone mice and identify the susceptibility loci. METHODS: MRL/lpr, C3H/HeJ-lpr/lpr (C3H/lpr), (MRL/lpr x C3H/lpr)F1 intercross, and MRL/lpr x (MRL/lpr x C3H/lpr)F1 backcross mice were prepared, and sialadenitis in individual mice was analyzed by histopathologic grading. The genomic DNA of the backcross mice was examined by simple sequence-length polymorphism analysis, and the highly associated polymorphic microsatellite markers with sialadenitis were determined as sialadenitis susceptibility loci. RESULTS: Four susceptible gene loci recessively associated with sialadenitis were mapped on chromosomes 10, 18, 4, and 1, respectively. These loci manifested additive and hierarchical properties in the development of sialadenitis. CONCLUSION: The results indicate that sialadenitis in MRL/lpr mice is under the control of polygenic inheritance, possibly involving allelic polymorphism. (+info)
In vivo evidence for the contribution of human histocompatibility leukocyte antigen (HLA)-DQ molecules to the development of diabetes.
Although DQA1*0301/DQB1*0302 is the human histocompatibility leukocyte antigen (HLA) class II gene most commonly associated with human type 1 diabetes, direct in vivo experimental evidence for its diabetogenic role is lacking. Therefore, we generated C57BL/6 transgenic mice that bear this molecule and do not express mouse major histocompatibility complex (MHC) class II molecules (DQ8(+)/mII(-)). They did not develop insulitis or spontaneous diabetes. However, when DQ8(+)/mII(-) mice were bred with C57BL/6 mice expressing costimulatory molecule B7-1 on beta cells (which normally do not develop diabetes), 81% of the DQ8(+)/mII(-)/B7-1(+) mice developed spontaneous diabetes. The diabetes was accompanied by severe insulitis composed of both T cells (CD4(+) and CD8(+)) and B cells. T cells from the diabetic mice secreted large amounts of interferon gamma, but not interleukin 4, in response to DQ8(+) islets and the putative islet autoantigens, insulin and glutamic acid decarboxylase (GAD). Diabetes could also be adoptively transferred to irradiated nondiabetic DQ8(+)/mII(-)/B7-1(+) mice. In striking contrast, none of the transgenic mice in which the diabetes protective allele (DQA1*0103/DQB1*0601, DQ6 for short) was substituted for mouse MHC class II molecules but remained for the expression of B7-1 on pancreatic beta cells (DQ6(+)/mII(-)/B7-1(+)) developed diabetes. Only 7% of DQ(-)/mII(-)/B7-1(+) mice developed diabetes at an older age, and none of the DQ(-)/mII(+)/B7-1(+) mice or DQ8(+)/mII(+)/B7-1(+) mice developed diabetes. In conclusion, substitution of HLA-DQA1*0301/DQB1*0302, but not HLA-DQA1*0103/DQB1*0601, for murine MHC class II provokes autoimmune diabetes in non-diabetes-prone rat insulin promoter (RIP).B7-1 C57BL/6 mice. Our data provide direct in vivo evidence for the diabetogenic effect of this human MHC class II molecule and a unique "humanized" animal model of spontaneous diabetes. (+info)
Lower frequency of focal lip sialadenitis (focus score) in smoking patients. Can tobacco diminish the salivary gland involvement as judged by histological examination and anti-SSA/Ro and anti-SSB/La antibodies in Sjogren's syndrome?
OBJECTIVES: Prospectively collected computer database information was previously assessed on a cohort of 300 patients who fulfilled the Copenhagen classification criteria for primary Sjogren's syndrome. Analysis of the clinical data showed that patients who smoked had a decreased lower lip salivary gland focus score (p<0.05). The aim of this original report is to describe the tobacco habits in patients with primary Sjogren's syndrome or stomatitis sicca only and to determine if there is a correlation between smoking habits and focus score in lower lip biopsies as well as ciculating autoantibodies and IgG. METHODS: All living patients with primary Sjogren's syndrome or stomatitis sicca only, who were still in contact with the Sjogren's Syndrome Research Centre were asked to fill in a detailed questionnaire concerning present and past smoking habits, which was compared with smoking habits in a sex and age matched control group (n=3700) from the general population. In addition, the patients previous lower lip biopsies were blindly re-evaluated and divided by the presence of focus score (focus score = number of lymphocyte foci per 4 mm(2) glandular tissue) into those being normal (focus score 1). Furthermore the cohort was divided into three groups; 10-45, 46-60 and >/= 61 years of age. Finally the focus score was related to the smoking habits. Seroimmunological (ANA; anti-SSA/Ro antibodies; anti-SSB/La antibodies; IgM-RF and IgG) samples were analysed routinely. RESULTS: The questionnaire was answered by 98% (n=355) of the cohort and the percentage of current smokers, former smokers and historical non-smokers at the time of lower lip biopsy was not statistically different from that of the control group. Cigarette smoking at the time of lower lip biopsy is associated with lower risk of abnormal focus score (p<0.001; odds ratio 0.29, 95%CI 0.16 to 0.50). The odds ratio for having focal sialadenitis (focus score > 1) compared with having a non-focal sialadenitis or normal biopsy (focus score /= 61: odds ratio 0.36, 95%CI 0.10 to 1.43) although there was only statistical significance in the two younger age groups. Moreover, among current smokers at the time of the lower lip biopsy there was a decreasing odds ratio for an abnormal lip focus score with increasing number of cigarettes smoked per week (p trend 0.00). In the group of former smokers, which included patients that had stopped smoking up to 30 years ago, the results were in between those of the smokers and the historical non-smokers (odds ratio 0.57, 95%CI 0.34 to 0.97, compared with never smokers). Present or past smoking did not correlate with the function of the salivary glands as judged by unstimulated whole sialometry, stimulated whole sialometry or salivary gland scintigraphy. Among former smokers, the median time lapse between the first symptom of primary Sjogren's syndrome and the performance of the lower lip biopsy was approximately half as long as the median time lapse between smoking cessation and biopsy (8 versus 15 years). Hence, symptoms of Sjogren's syndrome are unlikely to have had a significant influence on smoking habits at the time of the biopsy. Among the seroimmunological results only anti-SSA/Ro and anti-SSB/La antibodies reached statistical significance in a manner similar to the way smoking influenced the focus score in lower lip biopsies. On the other hand the level of significance was consistently more pronounced for the influence of smoking on the focus score than for the influence on anti-SSA/Ro and anti-SSB/La autoantibodies. CONCLUSION: This is believed to be the first report showing that cigarette smoking is negatively associated with focal sialadenitis-focus score >1-in lower lip biopsy in patients with primary Sjogren's syndrome. Furthermore, tobacco seems to decrea (+info)
Primary structure of the sialodacryoadenitis virus genome: sequence of the structural-protein region and its application for differential diagnosis.
Sialodacryoadenitis virus (SDAV) is a coronavirus that is commonly found in laboratory rats and that causes sialodacryoadenitis and respiratory illness. We cloned and sequenced the 3' terminal 9.8 kb of the genomic RNA and analyzed the structure of the viral genome. As with mouse hepatitis coronaviruses (MHVs), the SDAV genome was able to code for a spike protein, a small membrane protein, a membrane-associated protein, and a nucleocapsid protein. In addition, the hemagglutinin-esterase gene capable of encoding a protein of 439 amino acids (aa) was identified. The putative functional site for acetylesterase activity was present in the HE protein as Phe-Gly-Asp-Ser (FGDS), suggesting that the SDAV HE protein might have retained the esterase activity. Immediately upstream of the HE gene and downstream of the polymerase 1b gene, the NS2 nonstructural-protein gene was identified with a coding capacity of 274 aa. A motif of UCUAAAC was identified as a potential transcription signal for subgenomic mRNA synthesis. Large insertions of 172, 127, and 44 aa were detected in the N-terminal half of the predicted S protein of SDAV when its sequence was compared to the sequences of MHV 2, MHV JHM, and MHV A59, respectively. The sequence information on the SDAV S-protein gene was applied to a differential diagnostic PCR to detect and distinguish the rat coronavirus from mouse coronaviruses. This is the first report on the comprehensive genetic information of any rat coronavirus. (+info)
"Lymphoid" chemokine messenger RNA expression by epithelial cells in the chronic inflammatory lesion of the salivary glands of Sjogren's syndrome patients: possible participation in lymphoid structure formation.
OBJECTIVE: Many studies have shown that the microanatomic organization of infiltrating leukocytes in the salivary gland lesions of patients with Sjogren's syndrome (SS) resembles the structure of lymphoid organs. A newly defined set of chemokines referred to as "lymphoid," which orchestrate leukocyte microenvironmental homing and contribute to the formation of lymphoid structures, provides directional clues. The aim of this study was to investigate the possible existence of "lymphoid" chemokines in the chronic inflammatory lesions of SS patients and thus validate their potential involvement in the disease process. METHODS: Twelve patients with primary SS, 3 patients with secondary SS, 4 patients with other autoimmune disorders, and 4 control individuals were the subjects of this study. Reverse transcriptase-polymerase chain reaction analysis was performed in order to examine the messenger RNA (mRNA) expression of "lymphoid" chemokines. Furthermore, in situ hybridization studies revealed chemokine mRNA localization. Immunohistochemistry was also applied in order to identify the cell types that expressed the chemokine mRNA. RESULTS: STCP-1/monocyte-derived chemokine and TARC mRNA were expressed in the majority of patients with primary and secondary SS, in 2 of 4 patients with other autoimmune disorders, and in 2 of 4 controls. BCA-1, ELC, and PARC mRNA were only detected in patients with primary and secondary SS. SLC mRNA was also detected in 1 non-SS patient. The main cellular sources of chemokine mRNA were ductal epithelial cells and infiltrating mononuclear leukocytes. CONCLUSION: The expression pattern of "lymphoid" chemokine mRNA points further to the role of epithelial cells in the pathogenesis of SS and offers new insight into the potential mechanisms that could be involved in leukocyte attraction and in the in situ formation of secondary lymphoid tissue structures. (+info)