Health-related quality of life in patients with systemic lupus erythematosus: a Spanish study based on patient reports.

INTRODUCTION AND OBJECTIVES: Systemic lupus erythematosus (SLE) is a disease that significantly affects the quality of life and welfare of patients. SLE patients can be classified into multimorbidity levels using Clinical Risk Groups (CRGs) to help to incorporate predictive models of health needs. The goal of this study was to correlate CRGs with health-related quality of life (HR-QoL) and costs in SLE patients. METHODS: A questionnaire was administered to SLE patients in four hospital centers of the Valencian Community (Spain) between October 2015 and March 2016. The factors studied included HR-QoL (EQ-5D-5L and VAS), disease activity (SLAI/SELENA), damage (SLICC/ACR), and severity (IGK). RESULTS: The patients (N = 190, 92.06% female, age (mean ± SD) 47.23 ± 13.43 years) were sorted according to health status in nine CRGs. We found that most SLE patients (> 70%) were in CRGs 5 and 6. The main HR-QoL issues in these patients were related to mobility, ability to perform usual activities, and pain/discomfort. The scores (mean ± SD) for EQ-5D-5L and VAS were 0.74 ± 0.25 and 65.67 ± 23.52, respectively. We found that the age of the patients negatively affected their HR-QoL (r = - 0.266). SLE direct costs per patient increased with each CRG group, representing 71.92% of the total costs, while indirect costs were highly variable. The average cost per patient with SLE amounted to €8432.85 (year 2014). CONCLUSIONS: Patients' quality of life is related with age, disease activity, damage, and severity. Age was the parameter which most affects HR-QoL. Most costs of SLE are concentrated in two CRGs in which the HR-QoL deteriorates sharply.

Control of a family of phosphatase regulatory genes (phr) by the alternate sigma factor sigma-H of Bacillus subtilis.

A family of 11 phosphatases can help to modulate the activity of response regulator proteins in Bacillus subtilis. Downstream of seven of the rap (phosphatase) genes are phr genes, encoding secreted peptides that function as phosphatase regulators. By using fusions to lacZ and primer extension analysis, we found that six of the seven phr genes are controlled by the alternate sigma factor sigma-H. These results expand the potential of sigma-H to contribute to the output of several response regulators by controlling expression of inhibitors of phosphatases.

Cloning of DLM-1, a novel gene that is up-regulated in activated macrophages, using RNA differential display.

Tumors interact with their environment, reprogramming host cells to induce responses such as angiogenesis, inflammation, immunity and immune suppression. To understand these processes, it is important to identify and isolate new genes whose expression is induced in host tissues in response to tumors. Ascites tumors offer an attractive model for isolating such genes, because responding host peritoneal lining tissues can be cleanly separated from tumor cells growing in suspension within the peritoneal cavity. We here report the cloning by differential display of a novel gene, DLM-1, that is highly up-regulated in the peritoneal lining tissue of mice bearing MOT ascites tumors. Mouse peritoneal macrophages, stimulated by IFN-gamma or LPS, also expressed significant amounts of DLM-1. Up-regulation of DLM-1 became evident by 4h after stimulation with IFN-gamma and was not blocked by cycloheximide, suggesting the presence of IFN responding elements in its transcription regulation region. DLM-1 RNA was detected at significant levels in normal mouse lung, intestinal epithelium, liver and thymus by Northern blot analysis. In situ hybridization of MOT and HT-29 mouse subcutaneous transplanted solid tumors revealed strong DLM-1 expression in the host reactive stromal cells, but not the tumor cells. Sequence analysis of the full-length cDNA clone revealed that it encodes a protein of approx. M(r) 44330 with multiple potential protein kinase C and casein kinase II phosphorylation sites. Our data suggest that DLM-1 plays a role in such important processes as host response in neoplasia.

PDZK1, a novel PDZ domain-containing protein up-regulated in carcinomas and mapped to chromosome 1q21, interacts with cMOAT (MRP2), the multidrug resistance-associated protein.

We recently reported the isolation and partial characterization of two novel proteins, MAP17 and PDZK1. Using in situ hybridization, we demonstrated that MAP17 and PDZK1 mRNAs are markedly up-regulated in human carcinomas. PDZK1, originally isolated as a protein interacting with MAP17, contains four PDZ protein-interaction domains and could potentially interact with as many as four target proteins. In this paper, we confirm the overexpression of PDZK1 in human carcinomas using a specific antibody and demonstrate the localization of the PDZK1 gene to human chromosome 1q21, a region frequently altered in neoplastic conditions. Using the yeast two-hybrid system, we have also determined that PDZK1 interacts with the carboxy-terminal portion of cMOAT (MRP2), the canalicular multispecific organic anion transporter associated with multidrug resistance. This is of particular interest because proteins containing PDZ domains are involved in the clustering and signaling pathways of membrane-associated proteins, including ion channels. Therefore, the protein cluster formed by the association of cMOAT, PDZK1, and MAP17 could play an important role in the cellular mechanisms associated with multidrug resistance, and PDZK1 may represent a new target in cancer cells resistant to chemotherapeutic agents.

Interaction between RGS7 and polycystin.

Regulators of G protein signaling (RGS) proteins accelerate the intrinsic GTPase activity of certain Galpha subunits and thereby modulate a number of G protein-dependent signaling cascades. Currently, little is known about the regulation of RGS proteins themselves. We identified a short-lived RGS protein, RGS7, that is rapidly degraded through the proteasome pathway. The degradation of RGS7 is inhibited by interaction with a C-terminal domain of polycystin, the protein encoded by PKD1, a gene involved in autosomal-dominant polycystic kidney disease. Furthermore, membranous expression of C-terminal polycystin relocalized RGS7. Our results indicate that rapid degradation and interaction with integral membrane proteins are potential means of regulating RGS proteins.

Differential expression of frpHE: a novel human stromal protein of the secreted frizzled gene family, during the endometrial cycle and malignancy.

By using the differential display technique to identify genes that are differentially expressed in human endometrial carcinoma compared with normal endometrium, we have cloned frpHE, a novel member of the secreted frizzled gene family. By in situ hybridization, we have determined that frpHE is expressed by mesenchymal cells but not by epithelial cells. The expression of frpHE is modulated during the endometrial cycle: it is expressed in the stroma of proliferative endometrium and not significantly detectable in secretory or menstrual endometrium, suggesting that frpHE is under hormonal regulation. In addition, the expression of frpHE mRNA is markedly up-regulated in the stroma of endometrial hyperplasia and carcinoma and in the stroma of in situ and infiltrating breast carcinomas. Injection of frpHE mRNA in Xenopus embryos inhibited the Wnt-8 mediated dorsal axis duplication. These results indicate that frpHE functions as a regulator of the Wnt-frizzled signaling pathway and is involved in endometrial physiology and carcinogenesis.

Identification and partial characterization of PDZK1: a novel protein containing PDZ interaction domains.

We recently reported the isolation and partial characterization of a novel membrane-associated protein designated MAP17. In normal tissues, MAP17 was expressed only in the apical brush border of proximal tubular epithelial cells of the human adult kidney. However, MAP17 was diffusely expressed in most carcinomas originating in the kidney, colon, lung, and breast. Transfection of MAP17 into the HT29 carcinoma cell line markedly decreased cell proliferation in vitro and tumor growth in vivo, suggesting that MAP17 plays a role, either direct or indirect, in the control of cell proliferation. In an attempt to elucidate the function of MAP17, we screened a human kidney cDNA library for interacting proteins using the yeast two-hybrid system and isolated a novel protein containing PDZ protein interaction domains, which we have named PDZK1. PDZK1 is a 519-amino acid protein with a molecular weight of 63 kd; it is expressed in the kidney, pancreas, liver, gastrointestinal tract, and adrenal cortex. In situ hybridization experiments showed that the expression of PDZK1 was limited to epithelial cells. In the kidney, it colocalized with MAP17 in the brush border of proximal tubular epithelial cells. In addition, PDZK1 was overexpressed in selected tumors of epithelial origin. Although the function of PDZK1 has yet to be determined, proteins containing PDZ domains have been shown to play important roles as diverse as cell-cell interaction, cell differentiation, growth control, ion channels organization, and signal transduction. This is of particular interest because MAP17 is localized in areas either of cell-cell contact or where ion channels are localized, for example in the kidney. PDZK1 may represent the link between the cell membrane-where it interacts with MAP17-and other cytoplasmic proteins involved in biologic functions such as cell proliferation, differentiation, and ion transport.