IgG4-related disease and the current status of diagnostic approaches

IgG4-related disease is a newly recognized systemic disease characterized by involving a wide range of organs. It includes the pancreas, biliary tree, salivary glands, periorbital tissues, upper aerodigestive tract, retroperitoneum, mediastinum, aorta, soft tissue, skin, central nervous system, breast, kidneys, prostate, lungs and lymph nodes. The elevated serum titer of immunoglobulin G4 (IgG4), which is the least common (3 % to 6 %) of the 4 subclasses of IgG, is a special marker for IgG4-related disease. However, its entity is still unknown. This article reviewed the literature to learn the IgG4-related diseases and their current status of diagnostic approaches

G-CSF mobilized PBMCs contribute to the liver function of cirrhotic rats

On the basis of the recently recognized potential of bone marrow stem cells to give rise to hepatocytes, we here investigated the role of G-CSF priming PBMCs played in the liver of cirrhotic rats. The animal model of liver cirrhosis was induced by injecting CCl4 in SD rats, and G-CSF was administered in hematopoietic stem cell mobilization doses. After the liver cirrhosis model was established, the female cirrhotic rats were divided into two groups. Group I only received G-CSF mobilization, group II received G-CSF mobilized PBMCs transplanted from the male cirrhotic rats. PKH26 staining and sex-determining region for the Y-chromosome gene were used to trace the transplanted cells. Liver function related factors were assayed under the animal automatic biochemistry analyzer, and the liver pathological changes were evaluated by HE staining. The comparative liver functions of the two groups were investigated by analysis of two sample t-tests. A P value of <0.05 was considered as significant in all analyses. Our results showed that the transplanted PBMCs could locate in the livers of the female rats. In addition, compared with the group I, rats in group II displayed significant liver improvement in serum ALB, ALT, AST and TBIL (p<0.05). However, the semi-quantitative classification of the liver pathological changes in both groups did not indicate a significant difference (p>0.05). The results indicated that mobilized PBMC transplant could contribute to liver function in cirrhotic livers, which might be an alternative therapy for liver cirrhosis

Expression of GCRG213p, LINE-1 endonuclease variant, significantly different in gastric complete and incomplete intestinal metaplasia.

BACKGROUND: Intestinal metaplasia (IM) of the gastric mucosa is classified as complete (Type I) and incomplete IM (Type II and III) subtypes, which showed significantly different risk for developing to gastric adenocarcinoma (GAC). GCRG213, a variant of L1-endonuclease (L1-EN), first identified in our lab, was upregulated in GAC tissue. However, the relationship between GCRG213 and IM subtypes is not clear. Our study explored the association of GCRG213 protein (GCRG213p) with IM subtypes. METHODS: Gastric cancer and/or para-tumor tissue samples were collected from 123 patients who underwent gastrectomy for intestinal type gastric adenocarcinoma. The subtypes of IM were characterized with Alcian blue-periodic acid-Schiff and High Iron Diamine-Alcian blue staining methods. Immunohistochemistry of GCRG213p was performed, and its expression in gastric adenocarcinoma and para-tumor tissue including dysplasia, IM, and normal mucosa were analyzed. RESULTS: GCRG213p was expressed in 48.94% IM, 57.14% dysplasia and 55.32% GAC, respectively. GCRG213p expression was higher in well and moderately differentiated adenocarcinoma (P = 0.037). In IM glands, GCRG213p expressed mainly in the cytoplasm of absorptive enterocytes with defined brush borders, but not in goblet cells. The expression of GCRG213p in type I IM (90.00%) was significantly higher than that in type II (36.36%) and type III (25.00%) (P \u3c 0.001). In normal gastric mucosa, GCRG213p was exclusively positive in the cytoplasm of gastric chief cells. CONCLUSIONS: The expression of GCRG213p in complete IM was significantly higher than in incomplete IM, which implies that GCRG213p may play a role on the developing of IM to adenocarcinoma. GCRG213p was exclusively expressed in chief cells, suggesting that it might be involved in cell differentiation from the chief cells to IM

Expression of a LINE-1 endonuclease variant in gastric cancer: its association with clinicopathological parameters

BACKGROUND: Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed not only in the germ lines but also in somatic tissues. It contributes to genetic instability, aging, and age-related diseases, such as cancer. Our previous study identified in human gastric adenocarcinoma an upregulated transcript GCRG213, which shared 88% homology with human L1 sequence and contained a putative conserved apurinic/apyrimidinic endonucleas1 domain. METHODS: Immunohistochemistry was carried out by using a monoclonal mouse anti-human GCRG213 protein (GCRG213p) antibody produced in our laboratory, on tissue microarray constructed with specimens from 175 gastric adenocarcinoma patients. The correlation between GCRG213p expression and patient clinicopathological parameters was evaluated. GCRG213p expression in gastric cancer cell lines were studied using Western blotting analysis. L1 promoter methylation status of gastric cancer cells was tested using methylation-specific PCR. BLASTP was used at the NCBI Blast server to identify GCRG213p sequence to any alignments in the Protein Data Bank databases. RESULTS: Most primary gastric cancer, lymph node metastases and gastric intestinal metaplasia glands showed positive GCRG213p immunoreactivity. High GCRG213p immunostaining score in the primary gastric cancer was positively correlated with tumor differentiation (well differentiated, p = 0.001), Lauren’s classification (intestinal type, p < 0.05) and a late age onset of gastric adenocarcinoma (≥65 yrs; p < 0.05). GCRG213p expression has no association with other clinicopathological parameters, including survival. Western blotting analysis of GCRG213p expression in gastric cancer cells indicated that GCRG213p level was higher in gastric cancer cell lines than in human normal gastric epithelium immortalized cell line GES-1. Partial methylation of L1 in gastric cancer cells was confirmed by methylation-specific PCR. BLASTP program analysis revealed that GCRG213p peptide shared 83.0% alignment with the C-terminal region of L1 endonuclease (L1-EN). GCRG213p sequence possesses the important residues that compose the conserved features of L1-EN. CONCLUSIONS: GCRG213p could be a variant of L1-EN, a functional member of L1-EN family. Overexpression of GCRG213p is common in both primary gastric cancer and lymph node metastasis. These findings provide evidence of somatic L1 expression in gastric cancer, and its potential consequences in the form of tumor

A study on the functions of ubiquitin metabolic system related gene FBG2 in gastric cancer cell line

<p>Abstract</p> <p>Background</p> <p>FBG2 (F-BOX6) gene is an important member in ubiquitin metabolic system F-BOX family, and forms E3 complex with the other members in the family. But its role in gastric cancer is still not clear. In the present study, we intended to investigate the influence of FBG2 on the growth, proliferation, apoptosis, invasion and cell cycle of the gastric cancer line MKN45 and gastric cell line HFE145.</p> <p>Methods</p> <p>As a critical component of ubiquitin-protein ligase complex, FBG2 cDNA was subcloned into a constitutive vector PCDNA3.1 followed by transfection in MKN45 and HFE145 by using liposome. Then stable transfectants were selected and appraised. The apoptosis and cell cycles of these clones were analyzed by using flow cytometry. The growth and proliferation were analyzed by cell growth curves and colony-forming assay respectively. The invasion of these clones was tested by using cancer cell migration assay. The FBG2 stable expression clones(MKN-FBG2 and HFE-FBG2) and their control groups were detected and compared respectively.</p> <p>Results</p> <p>MKN-FBG2 grew faster than MKN45 and MKN-PC(MKN45 transfected with PCDNA3.1 vector). HFE-FBG2 grew faster than HFE145 and HFE-PC(HFE145 transfected with PCDNA3.1 vector). The cell counts of MKN-FBG2 in the forth, fifth, sixth and seventh days were significantly more than those of others (P < 0.05). Cell cycle analysis showed that MKN-FBG2 and HFE-FBG2 proliferated faster, proportions of cells in G2-M and S were different significantly with control groups (P < 0.05). Results of colony-forming assay showed that the colony formation rates of MKN-FBG2 and HFE-FBG2 were higher than those of control groups (P < 0.05). The results of cell migration assay were all negative.</p> <p>Conclusion</p> <p>FBG2 can promote the growth and proliferation of gastric cancer cells and normal gastric cells. It can help tumor cell maintain malignant phenotype too. But it can have a negative influence on the apoptosis or the ability of invasion of gastric cancer cells.</p

Cognitive Function Recovery Pattern in Adult Patients With Severe Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Longitudinal Study

Objective: To observe the dynamic characteristics of cognitive function following early application of immunotherapy in adult patients with severe anti N-methyl D-aspartate receptor (anti-NMDAR) encephalitis.Methods: Serial neuropsychological assessments were performed at three sequential time points in five adult patients with severe anti-NMDAR encephalitis following early-initiated immunotherapy. The three sequential points were 1–2, 6, and 11–12 months after treatment. Five normal subjects without psychological or neurological diseases were assessed as a control group.Results: Following early-initiated immunotherapy, all five patients demonstrated a gradual improvement of overall cognitive function over the 1-year follow-up period. All patients had suffered from a comprehensive cognitive function disorder from the early stages of the illness. Six months after the immunotherapy, the treatment group showed no significant differences in verbal episodic memory function compared with the control group. One year after the immunotherapy, non-verbal episodic memory function in the treatment group had normalized. The results of other tests related to frontoparietal cognitive function revealed damage of varying degrees during these three phases.Conclusion: The results of this sequential observation study indicated a three-phase recovery pattern of cognitive function in adult patients with severe anti-NMDAR encephalitis following early initiated immunotherapy. These findings extend current understanding of the recovery mechanisms of cognitive function impairment in this disease

Blood Pressure Characteristics in Moderate to Severe Renal Insufficiency

Background/Aims: Ambulatory blood pressure monitoring (ABPM) in chronic kidney disease (CKD) patients has been extensively studied, but few investigations have attempted to relate ABPM with CKD stages. The objectives of this article were to compare ABPM parameters for the diagnosis and treatment determination of CKD with daytime clinic blood pressure (BP) measurements. We also investigated BP and renal injury in combined hypertension and CKD. We supposed ABPM was important in combined hypertension and CKD. Methods: We compared ABPM in hypertension patients, including 152 patients with combined hypertension and CKD. Patients with combined hypertension and CKD were grouped according to severity into stages 1 through 3 (Stage 1-3) and stages 4 and 5 (Stage 4-5). Results: In the Stage 4-5 group, systolic BP (SBP) (daytime, nighttime and 24 h mean), diastolic BP (DBP), pulse pressure and SBP standard deviations (SD) (daytime and 24 h) were higher. SBP and DBP loads were significantly higher in the Stage 4-5 group. The nighttime load was higher than the daytime load. Mean arterial pressure (MAP) was higher and heart rates (HR) were faster in the Stage 4-5 group. Conclusions: BP load should be a component employed in ABPM to determine cardiovascular risk stratification. MAP and HR might be associated with risk to develop end-stage renal disease