Lung Adenocarcinoma With MUC4 Expression Is Associated With Smoking Status,HER2 Protein Expression,and Poor Prognosis: Clinicopathologic Analysis of 338 Cases

Background

MUC4 is a transmembrane glycoprotein that plays a role in the cell growth signaling pathway and has been studied in various organ malignancies. This study aimed to analyze MUC4 expression in resected lung adenocarcinomas (ADCs) to define the clinicopathologic characteristics of MUC4-positive cancers.

HOXB13:IL17BR and molecular grade index and risk of breast cancer death among patients with lymph node-negative invasive disease

Introduction

Studies have shown that a two-gene ratio (HOXB13:IL17BR) and a five-gene (BUB1B, CENPA, NEK2, RACGAP1, RRM2) molecular grade index (MGI) are predictive of clinical outcomes among early-stage breast cancer patients. In an independent population of lymph node-negative breast cancer patients from a community hospital setting, we evaluated the performance of two risk classifiers that have been derived from these gene signatures combined, MGI+HOXB13:IL17BR and the Breast Cancer Index (BCI).

Methods

A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 who did not receive adjuvant chemotherapy. For 191 cases (breast cancer deaths) and 417 matched controls, archived tumor tissues were available and analyzed for expression levels of the seven genes of interest and four normalization genes by RT-PCR. Logistic regression methods were used to estimate the relative risk (RR) and 10-year absolute risk of breast cancer death associated with prespecified risk categories for MGI+HOXB13:IL17BR and BCI.

Results

Both MGI+HOXB13:IL17BR and BCI classified over half of all ER-positive patients as low risk. The 10-year absolute risks of breast cancer death for ER-positive, tamoxifen-treated patients classified in the low-, intermediate-, and high-risk groups were 3.7% (95% confidence interval (CI) 1.9% to 5.4%), 5.9% (95% CI 3.0% to 8.6%), and 12.9% (95% CI 7.9% to 17.6%) by MGI+HOXB13:IL17BR and 3.5% (95% CI 1.9% to 5.1%), 7.0% (95% CI 3.8% to 10.1%), and 12.9% (95% CI 7.1% to 18.3%) by BCI. Those for ER-positive, tamoxifen-untreated patients were 5.7% (95% CI 4.0% to 7.4%), 13.8% (95% CI 8.4% to 18.9%), and 15.2% (95% CI 9.4% to 20.5%) by MGI+HOXB13:IL17BR and 5.1% (95% CI 3.6% to 6.6%), 18.6% (95% CI 10.8% to 25.7%), and 17.5% (95% CI 11.1% to 23.5%) by BCI. After adjusting for tumor size and grade, the RRs of breast cancer death comparing high- versus low-risk categories of both classifiers remained elevated but were attenuated for tamoxifen-treated and tamoxifen-untreated patients.

Conclusion

Among ER-positive, lymph node-negative patients not treated with adjuvant chemotherapy, MGI+HOXB13:IL17BR and BCI were associated with risk of breast cancer death. Both risk classifiers appeared to provide risk information beyond standard prognostic factors.     

Increased pain sensitivity of the upper extremities of TMD patients with myalgia to experimentally-evoked noxious stimulation: possibility of worsened endogenous opioid systems

The purpose of this study was to examine whether or not temporomandibular disorder (TMD) patients with chronic masticatory myalgia have increased pain sensitivity at remote sites outside of the head and neck region, and to evaluate whether the endogenous pain inhibitory systems triggered ischemic pain functions favorably in those patients. Twenty female TMD patients with chronic myalgia and 20 controls participated in this study. Ischemic pain was produced to activate endogenous opioids. The pain threshold time, pain tolerance time, pain intensity and pain unpleasantness were compared between the TMD patients and controls. The pressure pain thresholds in the hand were also compared before, between, and immediately after the ischemic pain. The TMD patients showed higher severe pain intensity and unpleasantness values and had lower pressure pain thresholds in the hand. Although both groups showed an increase in the pressure pain threshold, there was less of an increase in the pressure pain threshold in the TMD patients than in the controls. These findings indicate that TMD patients have increased pain sensitivity at remote sites, and also indicate additional evidence that the endogenous opioid systems may become impaired in TMD patients with chronic masticatory myalgia.     

Comparison of dynamic MRI at 3.0T and MDCT of pancreatobiliary disease: Evaluation with source,MPR, CPR,and MIP images for image quality and hepatic arterial and portal venous vessel conspicuity

Purpose

To compare contrast material‐enhanced three‐dimensional (3D) magnetic resonance imaging (MRI) at 3.0T and multidetector row computed tomography (MDCT) in the same patient with regard to image quality of pancreatobiliary disease and hepatic vascular conspicuity.

Materials and Methods

This study enrolled 32 patients with pancreatobiliary disease who underwent both gadolinium‐enhanced 3D dynamic MRI and multiphasic CT using 16‐MDCT. Data analysis of image quality was performed by two radiologists based on source images, multiplanar reconstruction (MPR), curved planar reconstruction (CPR), and maximum intensity projection (MIP) reconstruction. Determination of image quality was based on a 4‐point image quality rating scale.

Results

The overall image quality of the MRI axial images was superior to that of the axial MDCT images. The MRI protocol yielded an average score of 3.8 points versus 3.5 for the CT imaging. No significant difference was found between 3.0T MRI and MDCT images in MPR or CPR image quality. Image quality for visualization of the distal intrahepatic segmental arteries was significantly improved using MDCT imaging. No significant difference was found between the MDCT and 3.0T MR in portal vein branch image quality.

Conclusion

High‐resolution dynamic contrast‐enhanced MR imaging at 3.0T is a comprehensive technique which provides high image quality in pancreatobiliary disease. J. Magn. Reson. Imaging 2009;29:846–852. © 2009 Wiley‐Liss, Inc.     

Genetic variation in hormone metabolizing genes and risk of testicular germ cell tumors

Testicular germ cell tumors (TGCT) that arise in young men are composed of two histologic types, seminomas and nonseminomas. Risk patterns for the two types appear to be similar and may be related to either endogenous or exogenous hormonal exposures in utero. Why similar risk patterns would result in different histologic types is unclear, but could be related to varying genetic susceptibility profiles. Genetic variation in hormone metabolizing genes could potentially modify hormonal exposures, and thereby affect which histologic type a man develops. To examine this hypothesis, 33 single nucleotide polymorphisms (SNPs) in four hormone metabolism candidate genes (CYP1A1, CYP17A1, HSD17B1, HSD17B4) and the androgen receptor gene (AR) were genotyped. Associations with TGCT were evaluated among 577 TGCT cases (254 seminoma, 323 nonseminoma) and 707 controls from the US Servicemen’s Testicular Tumor Environmental and Endocrine Determinants (STEED) study. There were no significant associations with TGCT overall based on a test using an additive model. However, compared to homozygotes of the most common allele, two nonredundant SNPs in CYP1A1 were inversely associated with nonseminoma: CYP1A1 promoter SNP rs4886605 OR = 0.75 (95% CI = 0.54–1.04) among the heterozygotes and OR = 0.37, 95% CI = 0.12–1.11 among the homozygotes with a p-value for trend = 0.02; rs2606345 intron 1 SNP, OR = 0.69 (95% CI = 0.51–0.93) among heterozygotes and OR = 0.70 (95% CI = 0.42–1.17) among homozygotes, with a p-value for trend = 0.02. Caution in interpretation is warranted until findings are replicated in other studies; however, the results suggest that genetic variation in CYP1A1 may be associated with nonseminoma. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Variants in inflammation genes and the risk of biliary tract cancers and stones: a population-based study in China

To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary tract cancer has been increasing in recent decades. The study included 411 cases with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct, and 47 ampulla of Vater), 895 with biliary stones, and 786 controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer. Of the 62 SNPs examined, 14 were related to the risk of biliary cancer and stones. Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer. Of the 10 genes with multiple SNPs from which we inferred haplotypes, only one IL8RB haplotype, consisting of 3 SNPs (rs2230054, rs1126579, and rs1126580), was associated with the risk of bile duct cancer (P = 0.003) and biliary stones (P = 0.02), relative to the most frequent haplotype. In summary, common variants in genes that influence inflammatory responses may predispose to gallstones and biliary tract cancer, suggesting the need for future studies into the immunologic and inflammatory pathways that contribute to biliary diseases, including cancer.     

Epidemiological survey of allergic diseases in first-year junior high school students in Wakayama Prefecture in 2003

Allergic diseases have been increasing in prevalence in developed countries, including Japan. The aim of the present report was to determine the prevalence of allergies in Wakayama prefecture using an epidemiological study. In total, 759 first-year students attending junior high school in Hidaka country, Wakayama prefecture, were surveyed. The results for 699 cases were then analyzed. A questionnaire regarding allergic diseases, specific IgE measurements performed using a MAST26 system (Hitachi Co., Ltd.), and total serum IgE levels measured using RIST (Pharmacia Co., Ltd.) were performed. The prevalence (present + past) of various allergic diseases was 37.9%. The prevalence of rhinitis, including pollinosis, was 31.0%, while that of atopic dermatitis was 26.2% and bronchial asthma was 11.3%. The positive rates for specific IgE antibodies against Japanese cedar pollen was 48.6%. The positive rate for Dermatophagoides farinae, timothy and housedust II were 44.2%, 29.6%, and 28.9%, respectively. Statistically significant differences were recognized between the students with allergic rhinitis, atopic dermatitis, allergic conjunctivitis or bronchial asthma and positive results for D. farinae, housedust II, cedar pollen, Penicillium, Cladosporium, or Aspergillus-specific antibodies. Regarding family history (two generations), a statistical significant difference between family history and positivity for specific IgE antibodies like D. farinae, housedust II, ragweed, cedar pollen or Cladosporium was observed. The total IgE titer was correlated with the number of positive allergen items. The increasing prevalence of various allergic diseases in developed countries remains a mystery, but the hygienehypothesis has attracted some attention. The findings of this epidemiologic study will contribute to basic data on the increasing prevalence of various allergic diseases.     

Formation of advanced glycation end‐product‐modified superoxide dismutase‐1 (SOD1) is one of the mechanisms responsible for inclusions common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutation,and transgenic mice expressing human SOD1 gene mutation

Neuronal Lewy body‐like hyaline inclusions (LBHI) and astrocytic hyaline inclusions (Ast‐HI) are morphological hallmarks of certain familial amyotrophic lateral sclerosis (FALS) patients with superoxide dismutase‐1 (SOD1) gene mutations, and transgenic mice expressing the human SOD1 gene mutation. The ultrastructure of inclusions in both diseases is identical: the essential common constituents are granule‐coated fibrils approximately 15– 25 nm in diameter and granular materials. Detailed immunohistochemical analyses have shown that the essential common protein of the inclusions in both diseases is an SOD1 protein. This finding, together with the immunoelectron microscopy finding that the abnormal granule‐coated fibrils comprising the inclusions are positive for SOD1, indicates that these granule‐coated fibrils containing SOD1 are important evidence for mutant SOD1‐linked disease in human and mouse. For im‐munoelectron microscopy, the granule‐coated fibrils are modified by advanced glycation endproducts (AGE) such as N^?‐carboxymethyl lysine, pyrraline and pentosidine (Maillard reaction). Based on the fact that AGE themselves are insoluble molecules with direct cytotoxic effects, the granule‐coated fibrils and granular materials are not digested by the lysosomal and ubiquitin systems. The neurons and astrocytes of the normal individuals and non‐transgenic mice show no significant immunoreactivity for AGE. Considered with the mutant‐SOD1 aggregation toxicity, a portion of the SOD1 comprising both types of the inclusion is modified by the AGE, and the formation of the AGE‐modified SOD1 (probably AGE‐modified mutant SOD1) is one of the mechanisms responsible for the aggregation (i.e. granule‐coated fibril formation).     

Detection of New H5N1 High Pathogenicity Avian Influenza Viruses in Winter 2021–2022 in the Far East,Which Are Genetically Close to Those in Europe

Many high pathogenicity avian influenza (HPAI) cases in wild birds due to H5N1 HPAI virus (HPAIV) infection were reported in northern Japan in the winter of 2021–2022. To investigate the epidemiology of HPAIVs brought to Japan from surrounding areas, a genetic analysis of H5 HPAIVs isolated in northern Japan was performed, and the pathogenicity of the HPAIV in chickens was assessed by experimental infection. Based on the genetic analysis of the hemagglutinin gene, pathogenic viruses detected in northern Japan as well as one in Sakhalin, the eastern part of Russia, were classified into the same subgroup as viruses prevalent in Europe in the same season but distinct from those circulating in Asia in winter 2020–2021. High identities of all eight segment sequences of A/crow/Hokkaido/0103B065/2022 (H5N1) (Crow/Hok), the representative isolates in northern Japan in 2022, to European isolates in the same season could also certify the unlikeliness of causing gene reassortment between H5 HPAIVs and viruses locally circulating in Asia. According to intranasal challenge results in six-week-old chickens, 50% of the chicken-lethal dose of Crow/Hok was calculated as 10^4.5 times of the 50% egg-infectious dose. These results demonstrated that the currently prevalent H5 HPAIVs could spread widely from certain origins throughout the Eurasian continent, including Europe and the Far East, and implied a possibility that contagious viruses are gathered in lakes in the northern territory via bird migration. Active monitoring of wild birds at the global level is essential to estimate the geographical source and spread dynamics of HPAIVs.     

Potential inhibitory effects of low-dose thoron inhalation and ascorbic acid administration on alcohol-induced hepatopathy in mice

Although thoron inhalation exerts antioxidative effects in several organs, there are no reports on whether it inhibits oxidative stress-induced damage. In this study, we examined the combined effects of thoron inhalation and ascorbic acid (AA) administration on alcohol-induced liver damage. Mice were subjected to thoron inhalation at 500 or 2000 Bq/m³ and were administered 50% ethanol (alcohol) and 300 mg/kg AA. Results showed that although alcohol administration increased the levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the serum, the combination of thoron inhalation (500 Bq/m³) and AA administration 24 h after alcohol administration effectively inhibited alcohol-induced liver damage. The combination of thoron inhalation (500 Bq/m³) and AA administration 24 h after alcohol administration increased catalase (CAT) activity. Alcohol administration significantly decreased glutathione (GSH) levels in the liver. The GSH content in the liver after 2000 Bq/m³ thoron inhalation was lower than that after 500 Bq/m³ thoron inhalation. These findings suggest that the combination of thoron inhalation at 500 Bq/m³ and AA administration has positive effects on the recovery from alcohol-induced liver damage. The results also suggested that thoron inhalation at 500 Bq/m³ was more effective than that at 2000 Bq/m³, possibly because of the decrease in GSH content in the liver. In conclusion, the combination of thoron inhalation at 500 Bq/m³ and AA administration promoted an early recovery from alcohol-induced liver damage.