Clinicopathologic implications of TNFAIP3/A20 deletions in extranodal NK/T‐cell lymphoma

The A20/Tumor necrosis factor‐alpha‐induced protein 3 (A20/TNFAIP3) is a negative regulator of NF‐κB signaling. We analyzed the clinicopathologic implications of A20 deletions in extranodal NK/T‐cell lymphoma (NKTL). Fluorescence in situ hybridization analysis of the A20 gene was performed using archived formalin‐fixed tissues in 49 cases of NKTL. Among the 49 NKTL patients (median age, 48 y [10‐79]), stage I‐II (75% [36/48]) and upper aerodigestive tract (UAT)‐origin (84% [41/49]) were predominant. All A20 deletions were monoallelic and found in cases with UAT‐origin, accounting for 18% (9/49) of all NKTLs and 22% (9/41) of UAT‐origin. In univariate analysis, overall survival (OS) and progression‐free survival (PFS) were associated with stage, international prognostic index (IPI), B symptoms and number of extranodal sites, and OS with performance status and non‐UAT‐origin, but none with A20 deletion. In multivariate analysis, IPI predicted OS (P = .008 [HR = 23.4]) and PFS (P = .005 [HR = 34.0]). Risk was divided by B symptoms (P = .001 [OS]; P = .034 [PFS]) in low IPI subset (n = 36), and by A20 deletion (P = .029 [PFS]) in high IPI subset (n = 13). These results suggest a clinicopathologic implication of A20 in progression of NKTL.     

A Quantitative Study of Airway Changes on Micro-CT in a Mouse Asthma Model: Comparison With Histopathological Findings

Purpose

To evaluate airway changes in ovalbumin-induced asthmatic mice in terms of postmortem micro-CT images and pathological findings.

Methods

Asthma was induced in mice by intraperitoneal injection and nasal instillation of ovalbumin aluminium hydroxide into mice (experimental group, n=6), and another group of mice received intraperitoneal injection and nasal instillation of distilled phosphate-buffered saline (control group, n=6). Bronchial lumen area was measured in the main bronchial lumen of the distal third bronchial branch level (6 parts per each mouse) on axial scans of Micro-CT, using a Lucion''s smart pen (semi-automated) and a curve pen (manual). Bronchial wall thickness was obtained in 4 sections (2 levels on either side) after the third bronchial branch by measuring the diameter which was perpendicular to the longitudinal axis of the main bronchus on curved Multi-planar reconstruction (MPR) images. Histologic slides were obtained from the lesion that was matched with its CT images, and bronchial wall thicknesses were determined.

Results

The mean bronchial lumen area was 0.196±0.072 mm² in the experimental group and 0.243±0.116 mm² in the control group; the difference was significant. Bronchial wall thickness on micro-CT images (mean, 0.119±0.01 vs. 0.108±0.013 mm) and in pathological specimens (mean, 0.066±0.011 vs. 0.041±0.009 mm) were thicker in the experimental group than in the control group; bronchial wall thickness on micro-CT images correlated well with pathological thickness (for the experimental group, r=0.712; for the control group, r=0.46). The thick bronchial wall in the experimental group demonstrated submucosal hypertrophy along with goblet cell hyperplasia and smooth muscle hyperplasia.

Conclusions

The results of this study suggest that asthma may induce thickening of bronchial wall and narrowing of the lumen area on micro-CT images and that these results may significantly correlate with pathological findings.     

Evidence-Based,Pharmacological Treatment Guideline for Depression in Korea,Revised Edition

This paper aims to introduce, summarize, and emphasize the importance of the ''Evidence-Based, Pharmacological Treatment Guideline for Depression in Korea, Revised Edition''. The guideline broadly covers most aspects of the pharmacological treatment of patients in Korea diagnosed with moderate to severe major depression according to the DSM-IV TR. The guideline establishment process involved determining and answering a number of key questions, searching and selecting publications, evaluating recommendations, preparing guideline drafts, undergoing external expert reviews, and obtaining approval. A guideline adaptation process was conducted for the revised edition. The guideline strongly recommends pharmacological treatment considered appropriate to the current clinical situation in Korea, and should be considered helpful when selecting the appropriate pharmacological treatment of patients diagnosed with major depressive disorder. Therefore, the wide distribution of this guideline is recommended.     

Assessment of Hepatic Fibrosis Regression by Transient Elastography in Patients with Chronic Hepatitis B Treated with Oral Antiviral Agents

Transient elastography (TE) has been used as a non-invasive method for liver stiffness measurement (LSM) in patients with chronic liver disease. This study was performed to assess the change of LSM by TE and to assess its clinical usefulness during long-term oral antiviral therapy in patients with chronic hepatitis B (CHB). We retrospectively reviewed 83 CHB patients. The mean interval between two LSM was 411.5 ± 149.5 days. Initial and follow-up LSM was 16.15 ± 12.41 kPa and 11.26 ± 7.36 kPa, respectively (P < 0.001). The degree of regression of liver stiffness was -2.03 ± 0.36% per month. The fibrosis stage classified by LSM value improved in 37 (44.6%) patients during oral antiviral therapy. Of the 30 (36.1%) patients with LSM ≥ 14.1 kPa (cirrhosis) at 1st LSM, 12 (40%) proved to no longer have cirrhosis (≥ 1 decrease in fibrosis stage) at 2nd LSM. LSM significantly decreased in both baseline high (> upper limit of normal [ULN] × 2) and low (≤ ULN × 2) alanine aminotransferase groups during antiviral therapy (P < 0.001; P = 0.001, respectively). Long-term oral antiviral therapy resulted in the improvement of liver stiffness in a substantial portion of patients with CHB. TE may be used a useful clinical tool to assess disease progression in CHB patients.

Graphical Abstract

相似文献   

Colon Ischemia Associated with Buerger's Disease: Case Report and Review of the Literature

Buerger''s disease, or thromboangiitis obliterans, is a nonatherosclerotic inflammatory disease affecting the small- and medium-sized arteries and veins of the extremities (arms, hands, legs, and feet). It is most common in the Orient, Southeast Asia, India, and the Middle East, and usually affects men aged between 20 and 40 years, although it is becoming more common in women. It is well established that most such patients smoke heavily and experience an improvement in symptoms following smoking cessation. Mesenteric involvement in Buerger''s disease is extremely rare; however, we describe herein two cases of colon ischemia in patients who were previously diagnosed with lower-extremity Buerger''s disease. In one case, the patient developed colonic obstruction, and surgical resection was performed. Histopathologic findings were compatible with the chronic stage of Buerger''s disease. In the other case, angiography revealed abrupt occlusion of the inferior mesenteric artery with numerous collateral vessels, just like the corkscrew appearance found in the extremities. If patients with established Buerger''s disease of the extremities complain of gastrointestinal symptoms, early interventional diagnosis should be performed to prevent intestinal obstruction and gangrene.     

Clinical prognostic values of vascular endothelial growth factor, microvessel density,and p53 expression in esophageal carcinomas

Vascular endothelial growth factor (VEGF) is known to play a key role in tumor angiogenesis. The tumor-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on esophageal carcinoma and the correlation between VEGF and p53. Tissue samples were taken from 81 patients with esophageal carcinoma after surgery. VEGF and p53 expressions were examined by immunohistochemical staining. Microvessels in the tumor stained for CD34 antigen were also counted. VEGF and p53 expressions were observed in 51.3% (41/80) and 51.9% (41/79), respectively. The microvessel density was 70.9+/-6.7 (mean+/-SE) in VEGF-positive group and 68.7+/-5.1 in VEGF-negative group. However, no correlation was noted between VEGF and p53 expression. Whereas the tumor size, nodal status, depth of invasions, and tumor stage were associated with poor overall survival, VEGF expression or p53 expression was not. These results indicate that VEGF and p53 are highly expressed in esophageal carcinomas. Since the VEGF expression is not correlated with the p53 expression, microvessel density or clinicopathological findings, further studies with other angiogenic molecules are needed to determine the role in esophageal carcinomas.     

Altered expression of Lewis antigen on tissue and erythrocytes in gastric cancer patients

To elucidate the clinical significance of phenotypic alterations of Lewis antigen in gastric cancer patients, we investigated Lewis antigens by analyzing the genotypes of the Le and Se genes and by comparing the results obtained with the phenotypic expression of Lewis antigen in gastric cancer tissue and blood cells. One hundred and twenty gastric cancer patients were examined and compared with respect to Lewis blood phenotype and genotype. The expression of Le(a), Le(b), sialylated Le(a), and sialylated Le(x) antigens was immunohistochemically examined in uninvolved gastric mucosa, intestinal metaplasia, and cancerous tissue. We also analyzed the significance of Lewis antigen expression by analyzing patient survival. The frequencies of the Lewis phenotypes of RBCs corresponding to Le(a+b-), Le(a-b+), and Le(a-b-) were 16%, 58%, and 26%, respectively. The Le and le allele gene frequencies calculated from genotyping in gastric cancer patients were 0.623 and 0.377, respectively. The frequency for Le(a-b-) of the RBC phenotype had a tendency to be higher in cancer patients than in normal healthy Koreans. However, no difference in the Lewis gene frequency was found between these gastric cancer patients and healthy persons. The phenotype of Le(a-b+) was most prevalent in uninvolved gastric mucosal tissue, whereas the most prevalent form in tumor tissue was Le(a-b-). Sialyl-Le(a) and sialyl-Le(x) antigens were hardly detectable in uninvolved gastric mucosa, whereas the two antigens were expressed highly in intestinal metaplastic mucosa and tumor cells. In conclusion, the loss of Lewis antigen expression in tissue and on RBCs in gastric cancer patients is not a result of genetic influences, but rather a result of sialylation in tissue. We also confirm that poor prognosis is associated with dimeric sialyl-Le(x) and vascular spread.     

Overlapping gene mutations of hepatitis B virus in a chronic hepatitis B patient with hepatitis B surface antigen loss during lamivudine therapy

Disappearance of hepatitis B surface antigens (HBsAg) in chronic hepatitis B usually indicates clearance of hepatitis B virus (HBV) infection. However, false HBsAg negativity with mutations in pre-S2 and 'a' determinant has been reported. It is also known that YMDD mutations decrease the production of HBV and escape detection of serum HBsAg. Here, we report overlapping gene mutations in a patient with HBsAg loss during the lamivudine therapy. After 36 months of lamivudine therapy in a 44-yrold Korean chronic hepatitis B patient, serum HBsAg turned negative while HBV DNA remained positive by a DNA probe method. Nucleotide sequence of serum HBV DNA was compared with the HBV genotype C subtype adr registered in NCBI AF 286594. Deletion of nucleotides 23 to 55 (amino acids 12 to 22) was identified in the pre-S2 region. Sequencing of the 'a' determinant revealed amino acid substitutions as I126S, T131N, M133T, and S136Y. Methionine of rtM204 in the P gene was substituted for isoleucine indicating YIDD mutation (rtM204I). We identified a HBV mutant composed of pre-S2 deletions and 'a' determinant substitutions with YMDD mutation. Our result suggests that false HBsAg negativity can be induced by combination of overlapping gene mutations during the lamivudine therapy.     

No evidence for interaction between 5-HT2A receptor and serotonin transporter genes in schizophrenia

This study was to aim at investigating the potential interaction for the serotonin receptor gene (5-HTR) 2A and serotonin transporter gene (5-HTTLPR) polymorphisms in the development of schizophrenia, as well as the interaction of the two polymorphisms in relation with symptomatology, family history, age of onset and antipsychotic response. Genomic DNA analysis with polymerase chain reaction (PCR) was used for the genotyping. One hundred and eleven (111) patients with schizophrenia and 172 normal controls participated in the study. We did not find any association between the individual polymorphism and schizophrenia. The significant interaction effect between 5-HTTLPR and 5-HTR2A polymorphisms on the development of schizophrenia as well as on the antipsychotics response, family history, symptomatology and age at onset, was not found. However, subject with 5-HTR2A*TT genotype were found to have lower age of onset, compared to their counterparts (p=0.01). These results suggest that the interaction between 5-HTTLPR and 5-HTR2A polymorphisms may not contribute to susceptibility to schizophrenia as well as some clinical factors such as antipsychotic response, at least in the Korean population.