Mean Platelet Volume Is Elevated in Patients with Psoriasis Vulgaris

Purpose

This retrospective study was done to investigate the mean platelet volume (MPV) level in patients with psoriasis vulgaris and its relationship with disease severity.

Materials and Methods

We undertook a cross-sectional study on 176 patients and 101 healthy controls to examine the association between MPV and psoriasis. Various clinical and laboratory parameters were analyzed and compared.

Results

Platelet distribution width and MPV were significantly higher in patients with psoriasis than controls. In addition, there was positive correlation between Psoriasis Area Severity Index (PASI) and MPV. When psoriasis patients were grouped into mild psoriasis (PASI<10) and moderate to severe psoriasis (PASI≥10), the MPV of the latter group was significantly elevated. Nevertheless, patients with higher MPV level (MPV≥10.4 fL) did not show higher PASI than lower MPV level (MPV<10.4 fL). MPV levels significantly decreased after improvements of psoriasis with various treatments. The variations of MPV and PASI also showed significant correlation.

Conclusion

We have shown that MPV is increased in psoriasis patients and correlates with disease severity. Therefore, MPV levels may be considered as a marker of disease severity of psoriasis.     

Differential Expression of Toll-Like Receptor Signaling Pathway Is Associated with Microscopic Polyangiitis in Peripheral Blood Neutrophils

Constitutive or excessive activation of Toll-like receptor (TLR) signaling pathway can disrupt the body’s immune tolerance to autoantigen, thus promoting the development of autoimmune disease. However, the expression profile of TLR signaling pathway in peripheral blood neutrophils in the pathogenesis of microscopic polyangiitis (MPA) remains unclear. Thus, improved understanding of the pathobiology of this disease may aid in the development of therapeutic targets for patients with MPA. In the present study, we assessed the expression of TLR signaling pathway-related genes in peripheral blood neutrophils in patients with MPA. PCR array analysis was performed on 20 patients with MPA and 12 healthy controls. Gene expression pro?le was performed using the human TLR for autoimmunity and inflammation PCR array of Genecopoeia, containing 84 genes related to TLR signaling pathway and six house-keeping genes. We then used quantitative real-time PCR to validate the array test. The array results identified 13 upregulated genes and 5 genes which were downregulated. The resulting qRT-PCR was consistent with the findings by PCR array. Our results suggest that peripheral blood neutrophils display changes in the expression of TLR signaling pathway-related genes associated with the pathogenesis of microscopic polyangiitis.     

Elevated Brachial-Ankle Pulse Wave Velocity Is Independently Associated with Microalbuminuria in a Rural Population

Microalbuminuria is a marker of generalized endothelial dysfunction resulting from arterial stiffness or insulin resistance, and brachial-ankle pulse wave velocity (baPWV) is a good measure of arterial stiffness. We aimed to investigate whether elevated baPWV is independently associated with microalbuminuria. This study included 1,648 individuals aged over 40 who participated in the baseline Multi-Rural Cohort Study conducted in Korean rural communities between 2005 and 2006. Participants were classified into less than 30 mg/g as normoalbuminuria or 30-300 mg/g as microalbuminuriausing urinary albumin creatinine ratio (UACR). The median and Q1-Q3 baPWV values were significantly higher in the microalbuminuric group both in men (1,538, 1,370-1,777 cm/s vs. 1,776, 1,552-2,027 cm/s, P < 0.001) and women (1,461, 1,271-1,687 cm/s vs. 1,645, 1,473-1,915 cm/s, P < 0.001). BaPWV was independently associated with microalbuminuria in both genders after adjusting for pulse rate; fasting blood glucose; triglyceride; homeostatic model assessment insulin resistance (HOMA_IR) and, history of hypertension and diabetes. Fasting blood sugar and HOMA_IR were judged as having nothing to do with multicolinearity (r = 0.532, P < 0.001). Elevated baPWV was independently associated with microalbuminuria regardless of insulin resistance among rural subjects over 40 yr.

Graphical Abstract

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Type D Personality Is Associated with Social Anxiety in the General Population

Background

Research on the emotional processes associated with Type D personality is important for its further conceptualization. We examined the associations of Type D personality with social and general anxiety symptoms in a large community sample.

Purpose

The aim of the current study was to disentangle the associations of Type D personality and its components with social anxiety and general anxiety in a large sample from the general population.

Methods

A random sample of 2,475 adults from the general population filled out questionnaires to assess Type D personality (DS-14), social anxiety (SIAS¹⁰, SPS¹¹, BFNE-II), and general anxiety (HADS-A, GAD-7).

Results

Type D individuals were characterized by increased levels of both social and general anxiety. The social inhibition (SI) component of Type D personality was most strongly associated with social interaction anxiety (r?=?.63), while negative affectivity (NA) was strongly associated with general anxiety (GAD-7: r?=?.70; HADS-A: r?=?.66). Within social anxiety, SI was more strongly associated with facets of social interaction anxiety than with social phobia. Multiple regression analysis showed that the synergistic interaction of NA and SI was a predictor of social anxiety (SIAS¹⁰: β?=?.32, p?<?.0005; SPS¹¹: β?=?.27, p?<?.0005; BFNE-II: β?=?.11, p?=?.007) independent of demographics and the scores on the individual Type D components. This interaction was not a significant predictor of general anxiety. Logistic regression using the dichotomous Type D classification demonstrated a 9.1-fold (95%CI, 7.0?11.8) increased odds of a score in the highest quartile of social interaction anxiety and a 7.6-fold (95%CI, 5.8–9.8) increased odds of high social phobia. Odds ratios for clinically relevant levels of general anxiety were 8.3 (95%CI, 5.5–12.5) for GAD-7 and 6.5 (95%CI, 3.4–12.6) for HADS-A.

Conclusion

In the general population, Type D individuals were characterized by both social and general anxiety. The SI component of Type D is strongly associated with social interaction anxiety and the synergistic interaction of NA and SI was associated with high social anxiety, above and beyond the main NA and SI effects.     

Elevated IL-6 in Midtrimester Amniotic Fluid Is Involved with the Onset of Preeclampsia

PROBLEM: The primary defect of placental development in preeclampsia is speculated to occur at midtrimester gestation. Abnormal feto-maternal immune reactions have been considered as factors in such defective placentation. METHOD OF STUDY: Midtrimester amniotic fluid specimens were retrospectively identified as coming from gestations that later had severe preeclampsia develop, gestations with normal outcomes, and gestations measured for cytokines tumor necrosis factor-α (TNF-α), interleukin (IL-1β, IL-6, and IL-8). The effect of each cytokine on thrombomodulin levels was tested in cultured trophoblast cells. RESULTS: Among the measured cytokines, IL-6 and IL-8 were significantly elevated in the midtrimester amniotic fluid of the future preeclamptic group. Trophoblasts stimulated with TNF-α plus IL-6 had significantly decreased levels of cellular thrombomodulin compared to those without cytokine addition. CONCLUSIONS: Elevated cytokines in midtrimester amniotic fluid suggest an abnormal fetomaternal immune response occurring before the clinical manifestation of preeclampsia. Cytokine-induced suppression of thrombomodulin in trophoblasts may be directly involved in the pathogenesis of preeclampsia.     

Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin

Neuroendocrine neoplasms (NENs) are derived from endocrine cells in various organs and share common morphological features. This study aimed to clarify whether NENs of different organs are comparable at the molecular pathologic level. We retrospectively collected 99 cases of NENs from gastro-entero-pancreatic, lung, and other organs and reclassified these according to identical criteria. Grade, site, and molecular expression profile including NE markers, Ki-67, p53, somatostatin receptor type 2A (SSTR2A), and phosphatase and tensin homolog (PTEN) were compared. PTEN immunoreactivity was also compared with genomic copy number by fluorescence in situ hybridization (FISH) and droplet digital polymerase chain reaction (ddPCR). No significant differences were observed in the immunoreactivities of NE markers, p53, SSTR2A, or PTEN expression in NENs between the different organ sites. PTEN and p53 functional inactivation along with the loss of membranous SSTR2A expression appeared to be commonly involved in high-grade NEN. FISH results were significantly correlated with the level of PTEN immunoreactivity and with the findings of ddPCR analyses. The demonstration that these tumors are comparable at the molecular level will likely contribute to the broadening of therapeutic options such as the use of somatostatin analogues and mTOR inhibitors against NENs regardless of the affected organ, whereas molecular characterization of tumor grade will be useful for determining treatment strategy.     

Prevention of Graft-versus-Host Disease by Adoptive T Regulatory Therapy Is Associated with Active Repression of Peripheral Blood Toll-Like Receptor 5 mRNA Expression

Acute graft-versus-host disease (GVHD) occurs in 40% to 60% of recipients of partially matched umbilical cord blood transplantation (UCBT). In a phase I study, adoptive transfer of expanded CD4⁺CD25⁺Foxp3⁺ natural regulatory T cells (nTregs) resulted in a reduced incidence of grade II-IV acute GVHD. To investigate potential mechanisms responsible for the reduced GVHD risk, we analyzed peripheral blood mononuclear cell mRNA expression of a tolerance gene set previously identified in operation- tolerant kidney transplant recipients, comparing healthy controls and patients who received nTregs and those who did not receive nTregs with and without experiencing GVHD. Samples from patients receiving nTregs regardless of GVHD status showed increased expression of Foxp3 expression, as well as B cell–related tolerance marker. This was correlated with early B cell recovery, predominately of naïve B cells, and nearly normal T cell reconstitution. CD8⁺ T cells showed reduced signs of activation (HLA-DR⁺ expression) compared with conventionally treated patients developing GVHD. In contrast, patients with GVHD had significantly increased TLR5 mRNA expression, whereas nTreg-treated patients without GVHD had reduced TLR5 mRNA expression. We identified Lin^-HLADR^-CD33⁺CD16⁺ cells and CD14⁺⁺CD16⁻ monocytes as the main TLR5 producers, especially in samples of conventionally treated patients developing GVHD. Taken together, these data reveal interesting similarities and differences between tolerant organ and nTreg-treated hematopoietic stem cell transplantation recipients.     

Hepatic Steatosis Is Associated with Elevated Serum Iron in Patients with Obesity and Improves after Laparoscopic Sleeve Gastrectomy

BackgroundIron is closely related to metabolism. However, the relationship between iron and hepatic steatosis has not been fully elucidated.ObjectiveWe aimed to investigate the triangular relationship between iron and hepatic steatosis and laparoscopic sleeve gastrectomy (LSG) in patients with obesity.MethodsA total of 297 patients with obesity and 43 healthy individuals with a normal BMI were enrolled. Eighty-two patients underwent LSG. Anthropometrics, glucose-lipid metabolic markers, and hepatic steatosis assessed by FibroScan (CAP value and E value) were measured at baseline, and again at follow-up time intervals of 6 months and 1 year after surgery.Results(1) Iron was significantly higher in patients with obesity or overweight than in the individuals with normal BMI (8.18 ± 1.47 vs. 7.46 ± 0.99 mmol/L, p = 0.002). Iron was also higher in subjects with high blood pressure, dyslipidemia, and hyperuricemia than non-corresponding disorders (all p < 0.05). Moreover, iron was significantly higher in the severe than mild or moderate non-alcoholic fatty liver disease (NAFLD) group (p = 0.046 and 0.018). (2) Iron was positively associated with body weight, BMI, waist-to-hip ratio, uric acid, liver enzymes, postprandial blood glucose, fasting insulin, HOMA-IR, triglycerides, free fatty acid, and hepatic steatosis (CAP value), and negatively associated with high-density lipoprotein cholesterol (all p < 0.05). Iron was also positively associated with the visceral adipose area in patients with obesity and negatively associated with the subcutaneous adipose area in patients with overweight (all p < 0.05). (3) Iron levels and CAP values were decreased gradually 6 months and 1 year after surgery (all p < 0.05).ConclusionsOverall, our results indicated that iron is associated with hepatic steatosis in obesity. The iron level was significantly higher in patients with severe NAFLD than with mild or moderate NAFLD. LSG may reduce iron levels while improving fat deposition in the liver.     

Toll-Like Receptor 2 Arg677Trp Polymorphism Is Associated with Susceptibility to Tuberculosis in Tunisian Patients

Toll-like receptor 2 (TLR2) is critical in the immune response to mycobacteria. Herein, we report that the frequency of a human TLR2 Arg677Trp polymorphism (C2029T nucleotide substitution) in tuberculosis patients in Tunisia is significantly higher than in healthy controls (P < 0.0001). This finding suggests that this polymorphism could be a risk factor for tuberculosis.     

Low Serum Vitamin D Is Associated with Anti-Thyroid Peroxidase Antibody in Autoimmune Thyroiditis

Purpose

The association between autoimmune thyroid diseases (AITDs) and vitamin D deficiency is controversial. We aimed to evaluate the relationship between serum 25-hydroxy-vitamin D₃ [25(OH)D₃] and anti-thyroid antibody levels.

Materials and Methods

25(OH)D₃, anti-thyroid antibodies, and thyroid function measured in 304 patients who visited the endocrinology clinic were analyzed. The patients were subgrouped into the AITDs or non-AITDs category according to the presence or absence of anti-thyroid antibodies. The relationship between anti-thyroid peroxidase antibody (TPOAb) and 25(OH)D₃ was evaluated.

Results

The patients with elevated anti-thyroid antibodies had lower levels of serum 25(OH)D₃ than those who did not (12.6±5.5 ng/mL vs. 14.5±7.3 ng/mL, respectively, p<0.001). Importantly, after adjusting for age, sex, and body mass index, a negative correlation (r=-0.252, p<0.001) was recognized between 25(OH)D₃ and TPOAb levels in the AITDs group, but this correlation did not exist in the non-AITDs group (r=0.117, p=0.127). 25(OH)D₃ level was confirmed as an independent factor after adjusting for co-factors that may affect the presence of TPOAb in the AITDs group.

Conclusion

25(OH)D₃ level is an independent factor affecting the presence of TPOAb in AITDs. The causal effect of 25(OH)D₃ deficiency to AITDs is to be elucidated.     

S100A6 Overexpression Is Associated with Poor Prognosis and Is Epigenetically Up-Regulated in Gastric Cancer

S100A6 has been implicated in a variety of biological functions as well as tumorigenesis. In this study, we investigated the expression status of S100A6 in relation to the clinicopathological features and prognosis of patients with gastric cancer and further explored a possible association of its expression with epigenetic regulation. S100A6 expression was remarkably increased in 67.5% of gastric cancer tissues as compared with matched noncancerous tissues. Statistical analysis demonstrated a clear correlation between high S100A6 expression and various clinicopathological features, such as depth of wall invasion, positive lymph node involvement, liver metastasis, vascular invasion, and tumor-node metastasis stage (P < 0.05 in all cases), as well as revealed that S100A6 is an independent prognostic predictor (P = 0.026) significantly related to poor prognosis (P = 0.0004). Further exploration found an inverse relationship between S100A6 expression and the methylation status of the seventh and eighth CpG sites in the promoter/first exon and the second to fifth sites in the second exon/second intron. In addition, the level of histone H3 acetylation was found to be significantly higher in S100A6-expressing cancer cells. After 5-azacytidine or trichostatin A treatment, S100A6 expression was clearly increased in S100A6 low-expressing cells. In conclusion, our results suggested that S100A6 plays an important role in the progression of gastric cancer, affecting patient prognosis, and is up-regulated by epigenetic regulation.S100A6, also known as calcyclin, is a low-molecular-weight acidic protein containing 2 EF-hand calcium-binding motifs.^1,2 It was discovered on the basis of its cell cycle-dependent expression and is preferentially expressed in G₁ phase of the cell cycle after mitogenic stimuli.^3,4 S100A6 is a member of the S100 family, which are found localized to the cytoplasm and/or nucleus in a wide range of cell types.⁵ S100A6 may interact with binding or target proteins, thereby regulating dynamics of cytoskeleton constituents, cell growth and differentiation, and calcium homeostasis.^5,6,7,8,9,10Subsequent studies showed that S100A6 may also be involved in the regulation of cancer progression.¹¹ The deregulation of S100A6 expression during malignant transformation has thus far been described in human pancreatic cancer, malignant thyroid neoplasms, malignant melanoma, breast cancer, hepatocellular carcinoma, lung cancer, prostate cancer, and colorectal carcinoma.^{12,13,14,15,16,17,18,19,20,21} S100A6 overexpression has been reported to link with metastasis in colon cancer^14,15 and is a well-established marker of melanoma in which its level correlates with tumor invasiveness and poor prognosis. Although the high expression of S100A6 was reported in gastric cancer, its correlation with patient prognosis and clinicopathological features has not been fully investigated.²² Like other S100 proteins, S100A6 may promote cancer progression through specific roles in cell survival and apoptotic pathways,⁶ however the exact mechanism is unclear.In this study, we performed a detailed analysis of S100A6 expression in primary gastric cancer, matched metastatic lymph nodes, and liver metastatic nodules. Then we analyzed the relationship between S100A6 overexpression and clinicopathological features and patients prognosis. And to gain insight into the mechanism of the regulation of S100A6 expression in gastric cancer, we examined DNA methylation and histone modifications along the S100A6 gene, which may affect S100A6 expression in cancer cell lines by previous reports.^23,24     

Psoriasis Associated with Opisthorchiasis under Conditions of Anthelmintic Therapy

Biopsy specimens from patients with psoriasis concomitant with chronic opisthorchiasis were examined. Severe clinical course of combined disease was associated with degenerative changes in epidermocytes, keratinization disorders, and diffuse inflammatory cell infiltration of the derma. Combined therapy including anthelmintic agents produced a positive effect: decreased the degree of acanthosis, increased intracellular regeneration of epidermocytes, and suppressed inflammatory reaction of the derma and hyperplasia of immunocompetent cells. These data attested to an important role of opisthorchiasis in the pathogenesis of psoriatic disease.     

Mutations in Toll-Like Receptor 3 Are Associated with Elevated Levels of Rotavirus-Specific IgG Antibodies in IgA-Deficient but Not IgA-Sufficient Individuals

Double-stranded RNA (dsRNA) triggers immune-mediated responses through toll-like receptor 3 (TLR3), which is involved in innate antiviral defense. Low expression of TLR3 was recently suggested to contribute to susceptibility to rotavirus infection. Thus, we investigated the role of two TLR3 polymorphisms (rs3775291 and rs5743305), both of which resulted in reduced protein function or expression, in healthy blood donors and IgA-deficient (IgAD) individuals. These polymorphisms were associated with elevated rotavirus-specific IgG titers in IgAD individuals but not in healthy individuals. Thus, we propose that TLR3 signaling does not contribute to the rotavirus-specific antibody response in IgA-sufficient individuals, whereas it is associated with elevated antibody titers in IgAD individuals.     

Down-Regulation of p27 Is Associated with Development of Colorectal Adenocarcinoma Metastases

The cyclin-dependent kinase inhibitor p27 is a negative regulator of the cell cycle and a potential tumor suppressor gene. Because we had previously demonstrated that loss of p27 protein is associated with aggressive behavior in colorectal adenocarcinomas, we used immunohistochemistry and in situ hybridization to evaluate the potential role of alterations in p27 expression in primary and metastatic colorectal adenocarcinomas. Parallel immunostaining was performed for Ki-67 and p53. We evaluated 13 cases of metachronous and 23 cases of synchronous primary and metastatic colorectal tumor pairs. In the synchronous subgroup (Stage IV tumors), 57% of the primary tumor and metastases pairs did not express p27 protein and the remainder were low expressors. In the metachronous subgroup, 54% of the primary tumors were low expressors and the remainder high expressors of p27 protein. There was a significant reduction in the expression of p27 in the metachronous metastases (mean positive cells: 14.5%) when compared to the corresponding primary tumors (mean positive cells: 41.8%), P = 0.0023. All the primary and metastatic tumors in the metachronous subgroup showed high levels of p27 mRNA expression. There was no association between loss of p27 and either Ki-67 count or p53 expression. Because p27 is known to be up-regulated when epithelial cells are grown in suspension, the down-regulation of p27 in circulating tumor cells may confer the ability to grow in an environment of altered extracellular matrix or intercellular adhesion properties, two situations which may facilitate metastases.