In vitro and in vivo reactivity to fungal cell wall agents in sarcoidosis.

Sarcoidosis is an inflammatory disease. Epidemiological and treatment studies suggest that fungi play a part in the pathogenesis. The aim of this work was to study the effect of fungal cell wall agents (FCWA) on the in vitro secretion of cytokines from peripheral blood monocytes from subjects with sarcoidosis and relate the results to fungal exposure at home and clinical findings. Subjects with sarcoidosis (n=22) and controls (n=20) participated. Peripheral blood mononuclear cells were stimulated with soluble or particulate ß-glucan (S-glucan, P-glucan), chitin or lipopolysaccharide (LPS), whereafter tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and IL-12 were measured. The severity of sarcoidosis was determined using a chest X-ray-based score. Serum cytokines (IL-2R, IL-6, IL-10 and IL-12) were determined. To measure domestic fungal exposure, air in the bedrooms was sampled on filters. N-acetylhexosaminidase (NAHA) on the filters was measured as a marker of fungal cell biomass. The induced secretion of cytokines was higher from peripheral blood mononuclear cells (PBMC) from subjects with sarcoidosis. P-glucan was more potent than S-glucan inducing a secretion. Chitin had a small effect. Among subjects with sarcoidosis there was a significant relation between the spontaneous PBMC production of IL-6, IL-10 and IL-12 and the NAHA levels at home. The P-glucan induced secretion of IL-12 was related to the duration of symptoms at the time of diagnosis. Their X-ray scores were related to an increased secretion of cytokines after stimulation with LPS or P-glucan. Subjects with sarcoidosis have a higher reactivity to FCWA in vitro and to home exposure. The influence of FCWA on inflammatory cells and their interference with the inflammatory defense mechanisms in terms of cytokine secretion could be important factors for the development of sarcoidosis.

Lack of association of immune-response-gene polymorphisms with susceptibility to sarcoidosis in Slovenian patients.

Sarcoidosis is a chronic inflammatory disease, characterized by granulomatous inflammation, prominently involving the respiratory system. The etiology of this disease has not yet been elucidated and the contribution of genetic is not yet completely understood. We searched for novel candidate genes, utilizing a system biology approach, based on data from published transcriptional, proteomic and linkage studies of sarcoidosis. The search revealed several new potential candidate genes involved in the pathogenesis of inflammatory lung diseases: 25-(OH)-vitamin D(3)-1alpha-hydroxylase (CYP27B1), endothelin-1 (EDN1) and glutathione S-transferase Pi (GSTP1). Variants of selected polymorphisms: -1260/ C>A in CYP27B1, Lys198Asn in EDN1, and Ile105Val in GSTP1, were examined to determine if they confer susceptibility to sarcoidosis, based on an analysis of 180 Slovenian patients in comparison with 283 healthy controls. Polymerase chain reactions using allele-specific oligonucleotides were performed. This disease was not significantly associated with genotypes CC at -1260/ C>A polymorphism in CYP27B1 (P = 0.68, odds ratio (OR) = 1.10, 95% confidence interval (CI) = 0.75-1.61), GG genotype at Lys198Asn polymorphism in EDN1 (P = 1.00, OR = 0.97, 95%CI = 0.65-1.44) and AA genotypes at Ile105Val polymorphism in GSTP1 (P = 0.53, OR = 0.87, 95%CI = 0.60-1.27). There was no association of polymorphisms in any of the genes with sarcoidosis.

Genetic variation in osteopontin gene is associated with susceptibility to sarcoidosis in Slovenian population.

Sarcoidosis is a systemic inflammatory disease characterised by appearance of granulomas. Precise etiology has not been elucidated. Osteopontin (Opn) is a Th1 cytokine whose levels have been found increased in granulomas and serum samples from patients with sarcoidosis. We investigated whether genetic variation in Osteopontin gene (OPN) gene contributes to susceptibility to sarcoidosis. Haplotype-block structure in the OPN gene region was investigated using data from HapMap project. Three representative SNPs have been selected from each block of SNPs in linkage disequilibrium (rs11730582-C/T, rs11728697-C/T and rs4754-C/T). Genotyping was performed using TaqMan SNP Genotyping Assays on a sample of 165 patients and 284 controls. Statistical analyses of association were performed using Chi-Square test and algorithms implemented in the haplo.stats and PHASE packages. Genotyping analysis revealed a significant difference in genotype frequencies at rs4754 polymorphism in groups of patients and controls under recessive genetic model (p=0.036, OR=1.99, 95%CI=1.04-3.82), CC homozygotes being significantly over-represented in the patients group. However these results failed to reach significance after correction for multiple testing (p=0.25). The frequencies of predicted haplotypes differed between patient and control groups, frequency of TTT haplotype was found to be significantly decreased in the group of patients with sarcoidosis (p=0.014, OR=0.40, 95%CI=0.20-0.79).Our results suggest that variation in the OPN gene might be significantly associated with sarcoidosis and that the TTT haplotype in OPN may act as a protective factor in sarcoidosis.

The effect of age on the grip force control in lateral grip.

In the paper we present the grip force tracking system for the evaluation of grip force control. We developed a grip measuring device which can be used for the computer assisted measurements of the grip force in real time. The device was used as an input to a force-tracking task where the subject applied the grip force according to the visual feedback from the computer screen. The performance of the task was evaluated by the tracking error between the target signal and the measured force. We assessed the grip force control in the groups of 10-year old children, 25- to 35-year old adults and 50- to 60-year old adults. The subjects performed a sinus tracking task which required periodic muscle activation to produce the desired output. The results of the average tracking errors show significant differences in grip force control among the three tested groups. The largest variability among subjects was observed in the group of children and older adults. No significant difference in force control was found between the dominant and non-dominant hand. The grip force tracking system presented is aimed to be used for the evaluation of grip force control in patients with different sensory-motor impairments.

The value of inspiratory-expiratory lateral decubitus views in the diagnosis of small pleural effusions.

AIM: To evaluate the usefulness of expiratory lateral decubitus views in the radiological diagnosis of small pleural effusions. MATERIALS AND METHODS: Patients referred for abdominal sonography for various reasons were examined for ultrasonographic features of pleural effusion. From November 1994 until May 1996, 36 patients were found to have pleural effusion not exceeding 15 mm in depth and were included in the study. Erect posteroanterior, lateral, and lateral decubitus (in inspiration and expiration) ragiographs were performed in all patients. RESULTS: The mean thickness of fluid was 4.3 mm on inspiratory lateral decubitus radiographs and 7.9 mm on expiratory lateral decubitus views (P < 0.005). In 31 of 36 patients (86%) there was a difference in the thickness of the fluid layer as measured in expiratory vs. inspiratory lateral decubitus radiographs. In 16% of patients, the fluid was not visible on inspiratory lateral decubitus projections. CONCLUSIONS: Expiratory lateral decubitus views may be useful for demonstrating small pleural effusions.