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1.
Rheumatol Int ; 25(1): 28-32, 2005 Jan.
Article in English | MEDLINE | ID: mdl-13680143

ABSTRACT

We planned to investigate the expression of protein kinase C (PKC) isoforms in acinar epithelial cells of salivary glands in the non-obese diabetic (NOD) mouse to find out if they develop changes of the PKC system like those seen in the human counterpart, i.e. in Sjögren's syndrome. Parotid, submandibular, and sublingual glands from NOD and control BALB/c mice were stained with a panel of monoclonal antibodies directed against conventional (alpha, beta, and gamma), novel (delta, epsilon, and theta), and atypical (lambda and iota) PKC isoforms using the streptavidin/HRP method. Similarly to human labial salivary glands, acinar epithelial cells of the healthy control BALB/c mice contained two of the conventional PKC isoforms, alpha and beta. Acinar and ductal epithelial cells also contained the atypical PKC isoforms lambda and iota. PKC isoforms gamma, delta, epsilon, and theta were not found. NOD mice which displayed focal sialadenitis contained the same conventional and atypical PKC isoforms. The acinar cells in NOD mice, in contrast to the Sjögren's syndrome patients, did not lack PKC alpha or beta. On the contrary, PKC alpha and beta staining was stronger than in the control BALB/c mice. The present results demonstrate that both conventional and atypical PKC isoforms participate in the salivary epithelial cell biology and that there are mouse strain-associated and/or disease state-associated changes in their expression. The lack of PKC alpha and beta isoforms found in Sjögren's syndrome was not reproduced in NOD mice, which discloses one more difference between the human disease and its NOD mouse model.


Subject(s)
Diabetes Mellitus, Type 1/enzymology , Epithelial Cells/enzymology , Protein Kinase C/metabolism , Salivary Glands/enzymology , Sjogren's Syndrome/enzymology , Animals , Diabetes Mellitus, Type 1/pathology , Disease Models, Animal , Immunoenzyme Techniques , Isoenzymes/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred NOD , Signal Transduction , Sjogren's Syndrome/pathology
2.
Acta Ophthalmol Scand ; 82(5): 569-73, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15453855

ABSTRACT

PURPOSE: Non-obese diabetic (NOD) mice develop an autoimmune exocrinopathy characterized by hyposecretion of saliva and acinar cell atrophy. As the protein kinase C (PKC) system is involved in the signal transduction pathways associated with primary secretion and acinar cell differentiation and growth, the PKC profile was analysed in NOD mice. METHODS: Lacrimal glands from BALB/c, NOD, NOD scid and transgenic NOD x interferon-gamma (IFN-gamma) mice were analysed for their PKC profiles using antibodies against several conventional (alpha, beta, gamma), novel (delta, epsilon, theta) and atypical (iota, lambda) PKC isoforms using the Streptavidin/HRP (horseradish peroxidase) method. RESULTS: Acinar cells in BALB/c control mice expressed two conventional (alpha, beta) and two atypical (iota, lambda) PKC isoforms. In NOD and transgenic NOD x IFN-gamma mice the same isoforms were more strongly expressed. NOD scid mice lacked all other PKC isoforms except PKC lambda. CONCLUSIONS: Co-expression of several PKC isoforms in single cell type may be necessary for transcriptional activation and agonist-induced secretory responses. Hyposecretion in NOD mice was paradoxically associated with up-regulation of the PKC system. This may be associated with a deranged signal transduction per se rather than with the immune-inflammation, as the transgenic NOD x IFN-gamma mice showed similar PKC profiles. The NOD model does not reproduce lack/consumption of PKC II and PKC as in Sjögren's syndrome. This may be because the receptor autoantibodies in mice are directed against the adrenergic, not muscarinic, receptors. Lack and/or low level PKC expression in NOD scid mouse may explain the excessive acinar cell apoptosis in this model.


Subject(s)
Disease Models, Animal , Lacrimal Apparatus/enzymology , Lymphadenitis/enzymology , Lymphadenitis/etiology , Mice, Inbred NOD , Protein Kinase C/metabolism , Sjogren's Syndrome/complications , Animals , Immunohistochemistry , Isoenzymes/metabolism , Lymphadenitis/pathology , Mice , Mice, Inbred BALB C , Mice, SCID , Mice, Transgenic
3.
Ann Rheum Dis ; 62(10): 964-8, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12972475

ABSTRACT

OBJECTIVE: To characterise the psychological profiles of Sjögren's syndrome (SS) and patients with sicca symptoms but without SS; to find predictors for salivary gland function; to evaluate salivary scintigraphy as a method to differentiate between SS and patients with sicca symptoms but without SS. PATIENTS AND METHODS: Psychological tests (Medical Outcomes Study Short Form General Health Survey (SF-36), Jenkins Activity Survey, Toronto Alexithymia Scale, and Maastricht Questionnaire for vital exhaustion) were performed and assessment of the function of the salivary glands made in 26 patients with primary SS, 8 with secondary SS, and 9 with sicca symptoms but without SS. Data were analysed with BMDP new system version 1.0 statistical program. RESULTS: Psychological profiles were similar in all groups. Hb, RF, ANA, and SSA differentiated between the groups. Results of salivary scintigraphy were predicted to 51% by ANA, SSA, SSB, IgG, IgA, diagnosis, vitality, and role limitations due to emotional problems. No predictors were found for the resting salivary flow. Salivary scintigraphy was pathological in 21/26 (81%) and in 8/8 (100%) patients with secondary SS, but only in 2/9 (22%) patients with sicca symptoms without SS (p=0.002) (sensitivity 85.3%, specificity 77.8%). CONCLUSIONS: Patients with sicca symptoms but without SS have sickness behaviour similar to that of patients with SS. The results of salivary scintigraphy can be predicted by diagnosis and autoimmune findings; psychological characteristics added 20% to this predictive value. Distinction between SS and patients with sicca symptoms but without SS is difficult, but in addition to autoantibodies, salivary scintigraphy can be used for this purpose.


Subject(s)
Salivary Glands/diagnostic imaging , Sjogren's Syndrome/diagnostic imaging , Antibodies, Antinuclear/blood , Autoantibodies/blood , Biomarkers/analysis , Blood Sedimentation , C-Reactive Protein/analysis , Chi-Square Distribution , Diagnosis, Differential , Female , Hemoglobins/analysis , Humans , Immunoglobulins/blood , Male , Predictive Value of Tests , Psychological Tests , Radionuclide Imaging , Rheumatoid Factor/analysis , Sensitivity and Specificity , Sjogren's Syndrome/psychology , Statistics, Nonparametric
4.
Clin Exp Rheumatol ; 19(3): 313-6, 2001.
Article in English | MEDLINE | ID: mdl-11407086

ABSTRACT

OBJECTIVE: To assess the health status and fatigue in sicca patients with or without Sjögren's syndrome (SS) and to test whether the immune-inflammatory activity or the extent of the disease predict fatigue in SS. METHODS: The Medical Outcomes Study Short-Form General Health Survey (MOS SF-36) was used in 1 degree SS (n = 90), 2 degrees SS (n = 24), non-SS patients with sicca symptoms (n = 15) and healthy population controls (n = 126). Laboratory values and clinical findings were used to predict fatigue in SS. RESULTS: 74% of the SS and 80% of the non-SS sicca patients felt themselves tired. Vitality score values were 40.2 +/- 20.3 in 1 degree SS, 42.1 +/- 20.6 in 2 degrees SS and 29.0 +/- 15.8 in non-SS. The health profiles were similar in 1 degree and 2 degrees SS, worse (p < 0.001) than in normal controls, but in most aspects better than in non-SS sicca patients. In SS neither hemoglobin, ESR nor CRP predicted fatigue. Surprisingly, high serum IgG (p < 0.05), antinuclear antibodies (ANA) (p < 0.01) and SS-A antibodies (p < 0.05) values correlated positively with vitality. The number of disease manifestations correlated negatively with vitality (p < 0.004). The total number of disease manifestations, and ANA and/or SS-A autoantibodies were the best predictors of fatigue, but explained it only to 17-57%. CONCLUSION: Patients with fatigue and perceived ill health but without fibromyalgia had sicca symptoms and low basal tear and salivary secretion rates, indicating that cortical events can lead to a SS-like sicca syndrome. Even in SS fatigue is only in part explained by clinical disease manifestations and laboratory tests assessing inflammation and autoimmunity. Fatigue in both SS and non-SS sicca syndrome more likely correlates to other features, such as neuroendocrine aspects of the disease.


Subject(s)
Fatigue/diagnosis , Fatigue/immunology , Health Status , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/immunology , Adult , Aged , Antibodies, Antinuclear/blood , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/immunology , Female , Health Surveys , Humans , Immunoglobulin G/blood , Linear Models , Male , Middle Aged , Predictive Value of Tests
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