Serological and genetic characterisation of a unique strain of adenovirus involved in an outbreak of epidemic keratoconjunctivitis

AIMS: To characterise a novel strain of adenovirus (Ad) type Ad8 (genome type Ad8I) involved in an epidemic keratoconjunctivitis (EKC) outbreak in Hiroshima city using serological testing and sequence analysis of the fibre and hexon gene. METHODS: A neutralisation test (NT) was performed in microtitre plates containing a confluent monolayer of A549 cells using 100 tissue culture infectious doses of virus and type specific antisera. The haemagglutination inhibition test was also carried out in microtitre plates with rat erythrocytes using four haemagglutination units of virus and twofold dilutions of serum. The fibre gene was sequenced by generating overlapping polymerase chain reaction products or by direct sequencing of genomic DNA. Primer selection was based on alignment of the fibre genes of human adenovirus serotypes Ad8, Ad19, Ad37, Ad9, and Ad15 available from Gene Bank. RESULTS: The virus strain was specifically neutralised by anti-Ad8 antibodies, although there was a major crossreaction with anti-Ad9 antibodies. Haemagglutination was equally inhibited by anti-Ad8 and anti-Ad9 antibodies. The predicted amino acid sequences of the hypervariable regions (HVRs) of the Ad8I hexon gene showed higher homology with Ad9 (83.3%) than with Ad8 (62.0%). However, the Ad8I fibre knob was more homologous to Ad8 (94.4%) than to Ad9 (91.6%). CONCLUSIONS: Ad8I is a unique strain of adenovirus because of its lower genomic homology with Ad8, major crossreactivity with Ad9 in NT, and mixed genetic organisation of HVRs of the hexon gene. These factors may have enabled the virus to circumvent acquired immunity, resulting in the outbreak.     

Mitigation of inflammation using the intravenous anesthetic dexmedetomidine in the mouse air pouch model

Dexmedetomidine, an α₂-adrenergic/imidazoline receptor agonist, is a widely used intravenous anesthetic. Its primary current usage is for sedation of patients in the intensive care unit. The mouse air pouch model is versatile in studying the anti-inflammatory effect of a drug on a local inflammation, which is induced by a variety of substances. In the present study, using the carrageenan-induced air pouch inflammation model, we tested whether dexmedetomidine mitigates inflammation occurring locally in the mouse air pouch. We found that dexmedetomidine dose-dependently inhibited the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the pouch and decreased the number of white blood cells (WBC) recruited into the pouch. Dexmedetomidine also dose-dependently inhibited the production of neutrophil chemokines, cxcl1 and cxcl2. Furthermore, the dexmedetomidine-induced decreased recruitment of WBC into the pouch was successfully reversed with intra-pouch administration of cxcl1/cxcl2, but not TNF-α or IL-6. Lastly, the inhibition of the production of the cytokines and chemokines with dexmedetomidine was reversed by the treatment of yohimbine, suggesting that dexmedetomidine’s anti-inflammatory effect is primarily via the stimulation of the α₂-adrenergic receptor. We conclude that dexmedetomidine has an anti-inflammatory property in the carrageenan-induced mouse air pouch inflammation model, and that the dexmedetomidine-induced inhibition of production of the neutrophil chemokines, cxcl1 and cxcl2, may be related, at least in part, to the inhibition of WBC intra-pouch recruitment.     

Soluble Fas and soluble Fas L levels in patients with acute pancreatitis

The FasL-Fas system is an apoptosis induction system and plays an important role in homeostasis and biophylaxis. The present study was conducted to investigate soluble Fas (sFas), soluble Fas ligand (sFasL), and tumor necrosis factor alpha (TNF-alpha) in patients with acute pancreatitis. As acute pancreatitis became severe, the levels of sFas in the serum increased significantly, while those of sFasL decreased significantly. A significant inverse correlation was observed between the serum levels of sFas and those of sFasL. Also, a significant positive correlation was observed between the levels of TNF-alpha and sFas. A greater increase in serum sFas and decrease in serum sFasL levels was observed in patients with complicating multiple organ dysfunction syndrome (MODS) than in those without it. The results of the study suggest that the pathological aggravation of acute pancreatitis could be related to changes in the Fas-FasL system.     

Hair shaft miRNA‐221 levels as a new tumor marker of malignant melanoma

miRNA‐221 (miR‐221) is known to be abnormally expressed in many human cancers. The serum levels of miR‐221 have been reported as a tumor marker for malignant melanoma (MM). We hypothesized that the hair shaft miR‐221 levels may be increased in patients with MM. We therefore assessed the possibility that hair shaft miR‐221 levels could be a marker for MM. The hair shaft miR‐221 levels were significantly higher in patients with MM than controls. The rates of increased hair shaft miR‐221 levels above the cut‐off value were comparable to those of serum 5‐S‐CD, which is a tumor marker commonly used for MM. Measurements of the hair shaft miR‐221 levels could have potential clinical value in the detection of MM. This is the first report investigating the hair shaft levels of an miRNA in patients with MM. Our investigations offer new insight into the relationship between miR‐221 and MM, and may provide a new, non‐invasive way to screen for melanoma.     

Three-dimensional angiography of arteries and veins around the stomach using multislice CT for preoperative simulation of laparoscopic gastric cancer surgery: trial of multiphase fusion method

Postcontrast CT scanning using multislice CT was performed for 20 patients with gastric cancer. Three-dimensional (3D) CT angiography of the arterial and venous phases was reconstructed using the volume-rendering technique and then fused. 3D-CT angiography showed the arteries and veins around the stomach, and multiphase fusion imaging was able to demonstrate clearly and three-dimensionally the gastric vascular anatomy. In conclusion, the multiphase fusion image was considered to be useful in the preoperative simulation of laparoscopic gastric cancer surgery.     

The adenosine A2A receptor is associated with methamphetamine dependence/psychosis in the Japanese population

Background

Suicide and major depressive disorders (MDD) are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene rs7305115 SNP may predispose to suicide attempts in MDD.

Methods

We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis.

Results

There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG) frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p < 0.001). The G-allele frequency was significantly higher in cases than control group (58.1% vs.45.6%, p < 0.001), but the A-allele carrier indicated a decreased trend in MDD with suicide behaviors than control group (41.9% vs.54.4%, p < 0.001). The multivariate logistic regression analysis indicated that TPH2 rs7305115 AA (OR 0.33, 95% CI 0.22-0.99), family history of suicide (OR 2.98, 95% CI 1.17-5.04), negative life events half year ago (OR 6.64, 95% CI 2.48-11.04) and hopelessness (OR 7.68, 95% CI 5.79-13.74) were significantly associated with the suicide behaviors in MDD patients.

Conclusions

The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.     

Synergistic effect of thyroid hormone and thyrotropin on iodothyronine 5'-deiodinase in FRTL-5 rat thyroid cells

The effects of T3 and T4 on the iodothyronine 5'-deiodinase (5'-D) activity in FRTL-5 rat thyroid cells were investigated. T3 and T4 stimulated the 5'-D activity in a dose-dependent manner. Kinetic studies showed that the stimulation of the 5'-D by T3 was associated with an increase in maximum velocity (Vmax) in [11.9 +/- 0.2 (mean +/- SE) and 25.4 +/- 0.9 pmol I-released/mg protein.min, respectively, in control and cultured with 10(-9) M T3 for four days] but without a change in apparent Michaelis-Menten constant (Km) (94.8 +/- 5.3 nM and 105.4 +/- 12.1 nM, respectively). Furthermore, cycloheximide (5 microM) completely abolished the stimulatory effect of T3 on the 5'-D activity. T3 and T4 also enhanced the 5'-D activity stimulated by TSH in a dose-dependent manner. Kinetic studies showed that the stimulatory effect of T3 on the 5'-D stimulated by TSH was again associated with an increase in Vmax (86.0 +/- 4.0 and 166.5 +/- 1.9 pmol I- released/mg protein.min, respectively, cultured with 0.3 U/liter TSH and cultured with TSH plus 10(-9) M T3 for four days) without a change in apparent Km (114.0 +/- 7.4 nM and 111.6 +/- 12.5 nM, respectively). Cycloheximide (5 microM) completely abolished the stimulatory effect of TSH plus T3 on the 5'-D activity. There were no significant differences observed between cells cultured with TSH and with TSH plus T3 in either the intra- or extracellular cAMP contents. Furthermore, T3 enhanced the 5'-D activity stimulated by (Bu)2 cAMP. These results strongly suggest that T3 or T4 was synergistic with TSH in stimulating the 5'-D activity in FRTL-5 cells, and that cAMP production would be an important component of the synergism.     

A case of cardiac herniation after extrapleural pneumonectomy for malignant thymoma

A 44-year-old man underwent radical thymectomy for malignant thymoma 5 years ago. He subsequently underwent right extrapleural pneumonectomy because a right pleural metastatic lesion had developed. The operation was completed uneventfully. Immediately after arrival at the intensive care unit, the patient appeared restless and in pain. His heart rate increased to 140 bpm and then abruptly decreased to 20–30 bpm concomitant with profound systolic hypotension of 30–40 mmHg. Chest X-ray showed that the heart was shifted into the right thorax. Emergent re-thoracotomy was performed and the heart was found to be malrotated and herniated from an upper defect of the pericardial patch in the right thoracic cavity. The heart was returned to the pericardium and the defect was covered with a pericardial patch. The blood pressure and heart rate became stable. He was transferred to the surgical ward from the intensive care unit on the first postoperative day. The rest of the course was uneventful and the patient was discharged on the seventh postoperative day. The incidence of cardiac herniation after extrapleural pneumonectomy following chemotherapy for malignant pleural mesothelioma has been reported to be around 3%. The risk of cardiac herniation should always be considered, especially after extrapleural pneumonectomy.     

Body diffusion-weighted MR imaging of uterine endometrial cancer: Is it helpful in the detection of cancer in nonenhanced MR imaging?

Objective

In this study, the authors discussed the feasibility and value of diffusion-weighted (DW) MR imaging in the detection of uterine endometrial cancer in addition to conventional nonenhanced MR images.

Methods and materials

DW images of endometrial cancer in 23 patients were examined by using a 1.5-T MR scanner. This study investigated whether or not DW images offer additional incremental value to conventional nonenhanced MR imaging in comparison with histopathological results. Moreover, the apparent diffusion coefficient (ADC) values were measured in the regions of interest within the endometrial cancer and compared with those of normal endometrium and myometrium in 31 volunteers, leiomyoma in 14 patients and adenomyosis in 10 patients. The Wilcoxon rank sum test was used, with a p < 0.05 considered statistically significant.

Results

In 19 of 23 patients, endometrial cancers were detected only on T2-weighted images. In the remaining 4 patients, of whom two had coexisting leiomyoma, no cancer was detected on T2-weighted images. This corresponds to an 83% detection sensitivity for the carcinomas. When DW images and fused DW images/T2-weighted images were used in addition to the T2-weighted images, cancers were identified in 3 of the remaining 4 patients in addition to the 19 patients (overall detection sensitivity of 96%). The mean ADC value of endometrial cancer (n = 22) was (0.97 ± 0.19) × 10⁻³ mm²/s, which was significantly lower than those of the normal endometrium, myometrium, leiomyoma and adenomyosis (p < 0.05).

Conclusion

DW imaging can be helpful in the detection of uterine endometrial cancer in nonenhanced MR imaging.