A case of aortic bicuspid valve with thrombus formation without severe stenosis and calcification

We encountered a patient with a history of juvenile cerebral infarction with an unknown cause in whom a mass adhering to the aortic valve (AV) surface was observed on echocardiography performed upon the development of heart failure. Mild AV stenosis (AS) with moderate regurgitation was noted, and valve repair was applied. It was found during surgery that the AV was a bicuspid valve (BAV) without calcification, and the mass was an organized thrombus. Thrombus formation on the AV with severe AS in BAV has been reported, but the organic lesion in the AV was mild in this patient.     

Unusual prolongation of radiation‐induced G2 arrest in tumor xenografts derived from HeLa cells

The effect of ionizing radiation on cell cycle kinetics in solid tumors remains largely unknown because of technical limitations and these tumors' complicated structures. In this study, we analyzed intratumoral cell cycle kinetics after X‐irradiation of tumor xenografts derived from HeLa cells expressing the fluorescent ubiquitination‐based cell cycle indicator (Fucci), a novel system to visualize cell cycle kinetics in vivo. Cell cycle kinetics after X‐irradiation was examined by using tumor sections and in vivo real‐time imaging system in tumor xenografts derived from HeLa cells expressing Fucci. We found that G2 arrest was remarkably prolonged, up to 5 days after 10‐Gy irradiation, in contrast to monolayer cultures where G2 arrest returned within 24 h. Cells isolated from tumors 5 days after irradiation exhibited a higher surviving fraction than those isolated immediately or one day after irradiation. In this study, we clearly demonstrated unusual post‐irradiation cell cycle kinetics in tumor xenografts derived from HeLa‐Fucci cells. Our findings imply that prolonged G2 arrest occurring in tumor microenvironments following irradiation may function as a radioresistance mechanism.     

A prospective multicenter phase II study of intrabone marrow transplantation of unwashed cord blood using reduced‐intensity conditioning

Cord blood transplantation (CBT) is associated with delayed hematopoietic recovery and graft failure. To overcome these problems, we conducted a prospective, multicenter phase II study of intrabone marrow transplantation in which patients received reduced‐intensity conditioning without anti‐thymocyte globulin (ATG). The primary endpoint was the probability of full donor engraftment. Forty patients with hematologic malignancies were enrolled. Cord blood (CB) cells were injected without washing into 4 iliac bone sites (2 at each hemipelvis), at which approximately 6 mL of CB was administered at one site with local anesthesia. Full donor engraftment rate was 86.8%. The cumulative incidence of neutrophil and platelet engraftment was 86.4% and 85.5%, respectively. The median time to neutrophil (>0.5 × 10⁹/L) and platelet (2.0 × 10⁹/L) recovery was 17.5 and 44 days, respectively. The probability of severe acute graft‐vs‐host disease (GVHD) was 47.5%. The cumulative incidence of extensive chronic GVHD was 3.0%. The probability of relapse and non‐relapse mortality was 30.4% and 28.0%, respectively. The survival rate at 3 years was 45.6%, although most patients were at an advanced stage. These results suggest that our intrabone marrow‐CBT procedure without using ATG improves hematopoietic recovery and decreases the incidence of chronic GVHD, but does not decrease the incidence of acute GVHD.     

The relationship between HAART use and sexual activity among HIV-positive women of reproductive age in Brazil, South Africa, and Uganda

The purpose of this study was to determine whether current HAART use is associated with recent sexual intercourse among HIV-infected women (18-49 years) from Brazil, South Africa and Uganda. We conducted an analysis of survey data from a cross-sectional study, which enrolled 179 HIV-infected women receiving regular care from the Mbarara Hospital HIV Clinic in Uganda (n=85); the Perinatal HIV Research Unit in Soweto, South Africa (n=50); and the IPEC-Fiocruz cohort in Rio de Janeiro, Brazil (n=44). The primary outcome was sexual intercourse in the previous month. Secondary outcomes were protected sex and contraceptive use. We found that overall, 46% reported recent sexual intercourse. After adjusting for covariates, recent sexual intercourse was not associated with HAART use (AOR: 0.76; 95%CI: 0.34-1.72); however, it was significantly associated with being currently married, wanting to have more children and having higher HAART optimism. Among women reporting recent sexual intercourse (n=83), HAART users were significantly more likely to practice protected sex (crude OR: 3.64; 95%CI: 1.41-9.38) and non-significantly more likely to use contraceptive methods (crude OR: 2.15; 95%CI: 0.77-5.99). In summary, self-reported recent sexual intercourse is not more likely among women on HAART. Moreover, sexually active HAART users may be more likely to practice protected sex and use contraceptives.     

Surgical treatment strategy for hepatocellular carcinoma in patients with impaired liver function: hepatic resection or radiofrequency ablation?

Background

To compare the survival impacts of radiofrequency ablation (RFA) as an initial treatment for hepatocellular carcinoma (HCC) in patients with impaired liver functional reserve compared to those of hepatic resection (HR).

Chronic pulmonary thromboembolism pathologically showing homogeneous cellular alveolitis

A 60-year-old man was admitted to our hospital complaining of general malaise. Examination of arterial blood gases on room air revealed hypoxia. Pulmonary function test showed restrictive abnormality. Chest high-resolution CT showed diffuse mosaic attenuation without evident pulmonary artery abnormality on contrast chest CT. Based on these findings, interstitial pneumonia or chronic pulmonary thromboembolism was suspected. The findings of bronchoalveolar lavage revealed 4.4×10(5) cells/mL, including 89.6% macrophages, 9.4% lymphocytes, and 1.0% neutrophils. TBLB showed marked alveolitis. Moreover video-assisted thoracoscopic surgical biopsy was performed. Biopsies of the lung specimen showed focal infarct with surrounding mild mononuclear cell infiltrates (homogenous cellular alveolitis). (99m)Tc pulmonary perfusion and (81m)Kr ventilation scintigraphy showed V/Q mismatch. Furthermore, pulmonary angiography also revealed inadequate artery flow corresponding to the mismatch area of scintigraphy. Collagen vascular diseases and abnormality of coagulation factors were not detected. Multiple perfusion defects persisted for more than 6 months. Thus, finally the patient was diagnosed with chronic pulmonary thromboembolism, pathologically showing homogenous cellular alveolitis.     

Protective role of JAK/STAT signaling against renal fibrosis in mice with unilateral ureteral obstruction

Inflammation is involved in renal fibrosis, a final common pathway for kidney diseases. To clarify how JAK/STAT/SOCS system was involved in renal fibrosis, UUO was induced in BALB/c or SOCS3^+/− mice in the presence or absence of JAK inhibitor-incorporated nanoparticle (pyridine6–PGLA). UUO increased pSTAT3 and subsequently elevated SOCS3 levels in the obstructed kidneys. pSTAT3 levels were further increased in SOCS3^+/− mice. UUO-induced renal fibrosis was markedly suppressed in SOCS3^+/− mice, while it was aggravated by pre-treatment with pyridine6–PGLA. Although there were no differences in renal mRNA levels of TGF-β and collagens between wild and SOCS3^+/− mice, MMP-2 activity was enhanced in SOCS3^+/− UUO mice. Activated MMP-2 was completely suppressed by pyridine6–PGLA-pre-treatment. TNF-α one of JAK/STAT activators, increased pSTAT3 levels and subsequently induced MMP-2 activation in proximal tubular cells. These results suggest that JAK/STAT3 signaling may play a role in repair process of renal fibrosis in UUO partly via MMP-2 activation.     

Conserved epitopes dominate cross‐CD8+ T‐cell responses against influenza A H1N1 virus among Asian populations

Novel strains of influenza A viruses (IAVs) have emerged with high infectivity and/or pathogenicity in recent years, causing worldwide concern. T cells are correlated with protection in humans through cross‐reactive immunity against heterosubtypes of IAV. However, the different hierarchical roles of IAV‐derived epitopes with distinct levels of polymorphism in the cross‐reactive T‐cell responses against IAV remain elusive. In this study, immunodominant epitopes scattered throughout the entire proteome of 2009 pandemic influenza A H1N1 virus and seasonal IAVs were synthesized and divided into different pools depending on their conservation. The overall profile of the IAV‐specific CD8⁺ T‐cell immunity was detected by utilizing these peptide pools and also individual peptides. A dominant role of the conserved peptide‐specific T‐cell immunity was illuminated within the anti‐IAV responses, while the CD8⁺ T‐cell responses against the variable epitopes were lower than the conserved peptides. As previously demonstrated within a Caucasian population, we determined that GL9‐specific T cells, which also utilize Vβ 17 TCR (BV19), play a pivotal role in IAV‐specific T‐cell immunity within an HLA‐A2⁺ Asian population. Our study objectively reveals the different predominant roles of T‐cell epitopes among IAV‐specific cross‐reactive cellular immunity. This may guide the development of vaccines with cross‐T‐cell immunogenicity against heterosubtypes of IAV.