Health-Related Quality of Life of Patients with Hidradenitis Suppurativa Measured with the 15D Instrument and Comparison with the General Population and Patients with Psoriasis.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease significantly impacting health-related quality of life (HRQoL). We measured the HRQoL of Finnish HS patients and compared it with that of the general population and psoriasis patients. METHODS: Twenty-six diagnosed HS patients completed the 15D HRQoL questionnaire (15D), the Dermatology Life Quality Index (DLQI), and the Beck Depression Inventory-21 (BDI-21). The correlation between the results of these instruments was analyzed and the 15D results were compared with an age-standardized general population and psoriasis patients. RESULTS: Compared with an age-standardized general population, HS patients scored statistically significantly worse on several 15D dimensions. A statistically significant difference compared to psoriasis patients was detected on the sexual activity dimension. Even though not statistically significant, the observed mean values of the remaining dimensions suggest that clinically important differences may exist. The 15D score negatively correlated with the DLQI score (r = -0.492; p = 0.011) and the BDI-21 score (r = -0.592; p = 0.001). CONCLUSIONS: HS is a serious condition, with an impact at least comparable to that of psoriasis. This study shows that the 15D is a feasible tool for examining HRQoL in HS patients.

Hypoxic preconditioning induces neuroprotective stanniocalcin-1 in brain via IL-6 signaling.

BACKGROUND AND PURPOSE: Exposure of animals for a few hours to moderate hypoxia confers relative protection against subsequent ischemic brain damage. This phenomenon, known as hypoxic preconditioning, depends on new RNA and protein synthesis, but its molecular mechanisms are poorly understood. Increased expression of IL-6 is evident, particularly in the lungs of animals subjected to hypoxic preconditioning. Stanniocalcin-1 (STC-1) is a 56-kDa homodimeric glycoprotein originally discovered in bony fish, where it regulates calcium/phosphate homeostasis and protects against toxic hypercalcemia. We originally reported expression of mammalian STC-1 in brain neurons and showed that STC-1 guards neurons against hypercalcemic and hypoxic damage. METHODS: We treated neural Paju cells with IL-6 and measured the induction of STC-1 mRNA. In addition, we quantified the effect of hypoxic preconditioning on Stc-1 mRNA levels in brains of wild-type and IL-6 deficient mice. Furthermore, we monitored the Stc-1 response in brains of wild-type and transgenic mice, overexpressing IL-6 in the astroglia, before and after induced brain injury. RESULTS: Hypoxic preconditioning induced an upregulated expression of Stc-1 in brains of wild-type but not of IL-6-deficient mice. Induced brain injury elicited a stronger STC-1 response in brains of transgenic mice, with targeted astroglial IL-6 expression, than in brains of wild-type mice. Moreover, IL-6 induced STC-1 expression via MAPK signaling in neural Paju cells. CONCLUSIONS: These findings indicate that IL-6-mediated expression of STC-1 is one molecular mechanism of hypoxic preconditioning-induced tolerance to brain ischemia.

The Burden of Hidradenitis Suppurativa in a Cohort of Patients in Southern Finland: A Pilot Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that impacts the quality of life. METHODS: We evaluated its burden in a cohort of 26 Finnish patients in a single-center cross-sectional study. Demographic data, disease history, clinical data, treatment patterns, and workability were collected. Patients responded to the Dermatology Life Quality Index (DLQI) and Beck Depression Inventory (BDI-21). RESULTS: Mean age of HS patients was 44.2 years and mean diagnostic delay was 13.7 years. Pain was rated the most bothersome symptom. Mean DLQI score was 8.31. Women consistently had higher scores than men for every item of the DLQI. Mean BDI-21 score was 10.69. Higher Hurley stage at visit (p = 0.001), female gender (p = 0.018), and higher BDI-21 score (p = 0.022) were variables that significantly affected the total DLQI score, whereas female gender (p = 0.004) was the only variable that significantly affected the total BDI-21 score using stepwise regression analysis. CONCLUSIONS: The burden of HS is for the first time reported in Finland. The diagnostic delay is longer than previously reported and the results suggest that women are impacted by the disease more than men.

Stanniocalcin in terminally differentiated mammalian cells.

Stanniocalcin (STC) is a glycoprotein hormone originally found in teleost fish, where it regulates the calcium/phosphate homeostasis, and protects the fish against toxic hypercalcemia. STC was considered an exclusive fish protein, until the cloning of cDNA for human (in 1995) and murine (in 1996) STC. We originally reported a high constitutive content of STC in mammalian brain neurons, and found that the expression of STC occurred concomitantly with terminal differentiation of neural cells. Since then, we have investigated the expression of STC in relation to terminal cell differentiation also in mammalian hematopoietic tissue, and fat tissues. In this review we summarize our findings on STC expression during postmitotic differentiation in three different cell systems; in neural cells, in megakaryocytes and in adipocytes. We also present findings, suggesting that STC plays a role for maintaining the integrity of terminally differentiated mammalian cells.

Differentiated Paju cells have increased resistance to toxic effects of potassium ionophores.

In this study we have investigated the impact of differentiation of neuronal cells on their sensitivity to microbial toxins. We used the human neural crest-derived tumor cell line Paju, which can be induced to differentiation in vitro by treatment with phorbol 12-myristate 13-acetate. Addition of the highly toxic potassium ionophores cereulide (4.5 and 9.0 ng/ml) or valinomycin (20 ng/ml), to cultures of undifferentiated Paju cells caused collapse of the mitochondrial membrane potential - measured with the fluorescent probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetrabenzimidazole carbocyanine iodide (JC-1) followed by detachment of the cells and their apoptotic death. After induced differentiation of the Paju cells, their mitochondria retained the membrane potential upon exposure to the toxins and the cells displayed increased resistance to apoptosis as compared with undifferentiated cells. This effect may be caused by an elevated expression of the anti-apoptotic protein Bcl-2 and of the neuroprotective factor, stanniocalcin, in differentiated cells.

Actin-depolymerizing factor homology domain: a conserved fold performing diverse roles in cytoskeletal dynamics.

Actin filaments form contractile and protrusive structures that play central roles in many processes such as cell migration, morphogenesis, endocytosis, and cytokinesis. During these processes, the dynamics of the actin filaments are precisely regulated by a large array of actin-binding proteins. The actin-depolymerizing factor homology (ADF-H) domain is a structurally conserved protein motif, which promotes cytoskeletal dynamics by interacting with monomeric and/or filamentous actin, and with the Arp2/3 complex. Despite their structural homology, the five classes of ADF-H domain proteins display distinct biochemical activities and cellular roles, only parts of which are currently understood. ADF/cofilin promotes disassembly of aged actin filaments, whereas twinfilin inhibits actin filament assembly via sequestering actin monomers and interacting with filament barbed ends. GMF does not interact with actin, but instead binds Arp2/3 complex and promotes dissociation of Arp2/3-mediated filament branches. Abp1 and drebrin are multidomain proteins that interact with actin filaments and regulate the activities of other proteins during various actin-dependent processes. The exact function of coactosin is currently incompletely understood. In this review article, we discuss the biochemical functions, cellular roles, and regulation of the five groups of ADF-H domain proteins.

Twinfilin-2a is dispensable for mouse development.

Twinfilins are evolutionarily conserved regulators of cytoskeletal dynamics. They inhibit actin polymerization by binding both actin monomers and filament barbed ends. Inactivation of the single twinfilin gene from budding yeast and fruit fly results in defects in endocytosis, cell migration, and organization of the cortical actin filament structures. Mammals express three twinfilin isoforms, of which twinfilin-1 and twinfilin-2a display largely overlapping expression patterns in non-muscle tissues of developing and adult mice. The expression of twinfilin-2b, which is generated through alternative promoter usage of the twinfilin-2 gene, is restricted to heart and skeletal muscles. However, the physiological functions of mammalian twinfilins have not been reported. As a first step towards understanding the function of twinfilin in vertebrates, we generated twinfilin-2a deficient mice by deleting exon 1 of the twinfilin-2 gene. Twinfilin-2a knockout mice developed normally to adulthood, were fertile, and did not display obvious morphological or behavioural abnormalities. Tissue anatomy and morphology in twinfilin-2a deficient mice was similar to that of wild-type littermates. These data suggest that twinfilin-2a plays a redundant role in cytoskeletal dynamics with the biochemically similar twinfilin-1, which is typically co-expressed in same tissues with twinfilin-2a.

Hypoxic preconditioning induces elevated expression of stanniocalcin-1 in the heart.

Animals exposed for a few hours to low oxygen content (8%) develop resistance against further ischemic myocardial damage. The molecular mechanism(s) behind this phenomenon, known as hypoxic preconditioning (HOPC), is still incompletely understood. Stanniocalcin-1 (STC-1) is an evolutionarily conserved glycoprotein originally discovered in fish, in which it regulates calcium/phosphate homeostasis and protects against toxic hypercalcemia. Our group originally reported expression of mammalian STC-1 in brain neurons and showed that STC-1 is a prosurvival factor that guards neurons against hypercalcemic and hypoxic damage. This study investigates the involvement of STC-1 in HOPC-induced cardioprotection. Wild-type mice and IL-6-deficient (Il-6(-/-)) mice were kept in hypoxic conditions (8% O(2)) for 6 h. Myocardial Stc-1 mRNA expression was quantified during hypoxia and after recovery. HOPC triggered a biphasic upregulation of Stc-1 expression in hearts of wild-type mice but not in those of Il-6(-/-) mice. Treatment of cardiomyocyte cells in culture with hypoxia or IL-6 elicited an Stc-1 response, and ectopically expressed STC-1 in HL-1 cells localized to the mitochondria. Our findings indicate that IL-6-induced expression of STC-1 is one molecular mechanism behind the ischemic tolerance generated by HOPC in the heart.

Upregulated expression of stanniocalcin-1 during adipogenesis.

Stanniocalcin-1 (STC-1) is a 56-kDa homodimeric protein originally discovered in bony fish, where it protects against toxic levels of environmental calcium by lowering the uptake of calcium via the gills and by increasing the reabsorption of phosphate in the kidney. Here we report expression of STC-1 in mammalian white and brown fat tissue. Coexpression of STC-1 and perilipin confirmed the presence of STC-1 in mature fat cells. Neoplastic adipocytes in well-differentiated liposarcomas also stained for STC-1, while the frequency of STC-1-positive cells was lower in high-grade liposarcomas. The kinetics of STC-1 expression during adipogenesis was investigated in 3T3-LI cells, which can be induced to adipocyte differentiation. Untreated 3T3-L1 cells displayed negligible amounts of STC-1, whereas 3T3-L1 cells, treated with an adipogenic cocktail, upregulated the expression of STC-1 concomitantly with acquisition of the adipocytic phenotype. We have previously reported a high expression of STC-1 in postmitotically differentiated neurons and megakaryocytes. We have also shown that expression of STC-1 confers increased resistance to hypoxic and oxidative stress in neurons. Given this, our findings suggest that STC-1, also in terminally differentiated adipocytes, may function as a "survival factor", which contributes to the maintenance of the integrity of mature adipose tissue.

Expression of stanniocalcin-1 in megakaryocytes and platelets.

Stanniocalcin-1 (STC) is a 56-kDa homodimeric glycoprotein hormone originally found in fish, in which it regulates calcium/phosphate homeostasis and protects against toxic hypercalcaemia. The recently characterized human STC is 80% similar to fish STC. We have earlier reported a high expression of STC in terminally differentiated human and rodent brain neurones, and found that STC contributes to the maintenance of their integrity. Here, we report that mature megakaryocytes and platelets display high STC content. K562 cells, induced to megakaryocytoid differentiation in vitro, acquired expression of STC, which was not seen in untreated K562 cells or cells induced to erythroid differentiation.