G-protein beta3 subunit gene variant is unlikely to have a significant influence on serum uric acid level in Japanese workers

The C825T variant of the G-protein beta3 subunit (GNB3) gene has attracted renewed attention as a candidate gene for obesity, hypertension and hyperuricemia. The main role of G-protein is to translate signals from the cell surface into a cellular response. The 825T allele is associated with a splice variant of GNB3 protein and enhanced G-protein activation. We examined the relationship between this variant and the risk of hyperuricemia in Japanese workers. The study subjects were 1,452 men and 1,169 women selected from 3,834 men and 2,591 women in 1997. On the basis of common clinical criteria, hyperuricemia I was defined as serum uric acid >or= 7.0 mg/dl in men and 6.0 mg/dl in women or taking antihyperuricemic medication. The hyperuricemia I group consisted of 186 men and 20 women and its control of 1,266 men and 1,149 women. Hyperuricemia II was defined as serum uric acid > 5.7 mg/dl (median) in men and 3.9 mg/dl (median) in women or taking antihyperuricemic medication. The hyperuricemic II group consisted of 684 men and 570 women and its control of 768 men and 599 women. To replicate previous significant results in young Caucasian men, we selected these criteria because the authors of the study in young Caucasian men adopted the median in their subjects as a cut-off. The statistical power was estimated as 99% based on the significant results in Caucasians. Genotype and allele distributions in men and women with hyperuricemia I and II were not significantly different from those in the corresponding control groups. Logistic regression analysis on hyperuricemia I and II, and multiple regression on serum uric acid level demonstrated no significant effect of the C825T genotype. Despite the sufficient statistical power, this study could not demonstrate the significant influence of C825T on hyperuricemia or serum uric acid. The targeting of this polymorphism is unlikely to be beneficial in the prevention of hyperuricemia in the general Japanese population.     

Influenza A virus abrogates IFN-gamma response in respiratory epithelial cells by disruption of the Jak/Stat pathway

The innate immunity to viral infections induces a potent antiviral response mediated by interferons (IFN). Although IFN-gamma is detected during the acute stages of illness in the upper respiratory tract secretions and in the serum of influenza A virus-infected individuals, control of influenza A virus is not dependent upon IFN-gamma as evidenced by studies using anti-IFN-gamma Ab and IFN-gamma(-/-) mice. Thus, we hypothesized that IFN-gamma is not critical in host survival because influenza A virus has mechanisms to evade the antiviral activity of IFN-gamma. To test this, A549 cells, an epithelial cell line derived from lung adenocarcinoma, were infected with influenza virus strain A/Aichi/2/68 (H3N2) (Aichi) and/or stimulated with IFN-gamma to detect IFN-gamma-stimulated MHC class II expression. Influenza A virus infection inhibited IFN-gamma-induced up-regulation of HLA-DRalpha mRNA and the IFN-gamma induction of class II transactivator (CIITA), an obligate mediator of MHC class II expression. Nuclear translocation of Stat1alpha upon IFN-gamma stimulation was significantly inhibited in influenza A virus-infected cells and this was associated with a decrease in Tyr701 and Ser727 phosphorylation of Stat1alpha. Thus, influenza A virus subverts antiviral host defense mediated by IFN-gamma through effects on the intracellular signaling pathways.     

Multiple hepatocellular adenomas in a patient with glycogen storage disease type I: various enhancement patterns in MRI with Gd-EOB-DTPA

The patient is a 20-year-old man with glycogen storage disease type I (GSD-type I). In his teens, multiple focal hepatic masses were detected on abdominal ultrasonography (US), which were diagnosed as multiple hepatocellular adenomas from the imaging. During follow-up, these masses had shown intermittent growth in size. In the evaluation of Gd-EOB-DTPA (gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid) MR imaging, these masses showed various signal intensities from hypo- to hyperintense during the hepatocyte-specific phase. Intermittent growth and elevation of serum PIVKA-II levels indicate the potential for malignant transformation, so the patient underwent partial hepatectomy. The resected masses were all consistent with benign hepatocellular adenomas histopathologically.     

Decompressive craniectomy 116 h after malignant middle cerebral artery infarction

The optimal timing of decompressive craniectomy in pediatric patients after presentation with malignant middle cerebral artery infarction is unknown. We report herein the case of a previously healthy 6‐year‐old Japanese girl who had good outcome after emergency decompressive craniectomy 116 h after malignant middle cerebral artery infarction. This case suggests that the timing of decompressive craniectomy can be delayed until deterioration of neurological findings and, compared with adults, a more prolonged time course for surgical intervention might be acceptable.     

Impact of knowledge-based iterative model reconstruction on myocardial late iodine enhancement in computed tomography and comparison with cardiac magnetic resonance

We evaluated the image quality and diagnostic performance of late iodine enhancement computed tomography (LIE-CT) with knowledge-based iterative model reconstruction (IMR) for the detection of myocardial infarction (MI) in comparison with late gadolinium enhancement magnetic resonance imaging (LGE-MRI). The study investigated 35 patients who underwent a comprehensive cardiac CT protocol and LGE-MRI for the assessment of coronary artery disease. The CT protocol consisted of stress dynamic myocardial CT perfusion, coronary CT angiography (CTA) and LIE-CT using 256-slice CT. LIE-CT scans were acquired 5 min after CTA without additional contrast medium and reconstructed with filtered back projection (FBP), a hybrid iterative reconstruction (HIR), and IMR. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were assessed. Sensitivity and specificity of LIE-CT for detecting MI were assessed according to the 16-segment model. Image quality scores, and diagnostic performance were compared among LIE-CT with FBP, HIR and IMR. Among the 35 patients, 139 of 560 segments showed MI in LGE-MRI. On LIE-CT with FBP, HIR, and IMR, the median SNRs were 2.1, 2.9, and 6.1; and the median CNRs were 1.7, 2.2, and 4.7, respectively. Sensitivity and specificity were 56 and 93% for FBP, 62 and 91% for HIR, and 80 and 91% for IMR. LIE-CT with IMR showed the highest image quality and sensitivity (p?<?0.05). The use of IMR enables significant improvement of image quality and diagnostic performance of LIE-CT for detecting MI in comparison with FBP and HIR.     

Transarterial Infusion of Cisplatin and Doxorubicin in Bladder Cancer: Original Article

Forty-five patients (median age 63 years) with muscle invasive bladder cancer were treated with transcatheter intraarterial infusion (TAI) of cisplatin (CDDP) and doxorubicin. They received a total of 114 courses (median 3 courses per patient) of TAI. Complete response was obtained in 20 patients (44%), partial response in 17 (38%), stable disease in 6(13%), and progression of disease in 2 patients (5%). The overall response rate was 82% at a median follow-up of 36 months. The actuarial survival of the patient population was 72% at 5 years; 36 patients were alive and 9 had died of cancer progression. The treatment was generally extremely well tolerated without major complications. The current study also revealed the fact that papillary carcinomas were more sensitive to this therapy than were non-papillary tumors. Overall, response rate and local control were significantly higher in low-grade than in high-grade tumors. The observed high complete response and good survival rate suggest that intraarterial CDDP and doxorubicin might be highly effective for localized invasive bladder cancer.     

Trastuzumab-mediated antibody-dependent cellular cytotoxicity against esophageal squamous cell carcinoma.

PURPOSE: In the present study, we investigated the degree of protein expression and gene amplification of HER-2 in esophageal squamous cell carcinoma (SCC) cell lines and freshly isolated tumors, and trastuzumab-mediated biological activity, in particular antibody-dependent cellular cytotoxicity (ADCC) against HER-2-expressing esophageal SCC cell lines. EXPERIMENTAL DESIGN: Ten different SCC cell lines with various levels of HER-2 status evaluated by flow cytometry, immunocytochemistry (HercepTest), and fluorescence in situ hybridization were evaluated for ADCC, growth inhibitory, or apoptosis-inducing activities mediated by trastuzumab. RESULTS: Trastuzumab induced ADCC against HER-2-expressing esophageal SCC and the activities reflected the degree of HER-2 expression analyzed by flow cytometric analysis, but not by HercepTest nor fluorescence in situ hybridization analysis. Furthermore, trastuzumab-mediated ADCC against transforming growth factor-beta-producing SCC was enhanced by the treatment with SB-431542, which is a selective inhibitor of the phosphorylation induced by transforming growth factor-beta. There were very marginal effects of anti-proliferative or apoptosis-inducing activities mediated by trastuzumab for HER-2-expressing esophageal SCC. CONCLUSION: HER-2-expressing esophageal SCC cells could be killed by trastuzumab-mediated ADCC and the activity reflected the degree of HER-2 expression detected by flow cytometry.