Retroperitoneal Sarcoma Requiring Abdominal Aortic Replacement With Long-Term Survival: A Case Report.

Retroperitoneal sarcoma (RPS) is a rare disease. RPS invading the abdominal aorta is exceedingly rare and has a poor prognosis. There have been scattered cases of RPS treated with combined abdominal aortic replacement. However, the average survival time for these cases was only 8 months, with a 2-year survival rate of 21%, indicating a poor prognosis. In this case study, a 44-year-old man presented to our hospital complaining of abdominal pain. Multiple imaging findings suggested a retroperitoneal mass that was diagnosed as a malignant tumor. The patient underwent tumor resection with abdominal aortic replacement due to an RPS tumor invading the abdominal aorta. The histopathological grade was determined to be grade 3, the most malignant grade tumor, according to the Fédération Nationale des Centres de Lutte Contre le Cancer grading system. Postoperative chemotherapy with doxorubicin and ifosfamide was administered for five cycles. The patient has been alive for over 8 years after the operation without any recurrence. This case presents a long-term survival of RPS requiring abdominal aortic replacement.

[Successful Staged Repair of Double Rupture after Acute Myocardial Infarction:Report of a Case].

Double rupture is a very rare, and life-threatening complication after acute myocardial infection (AMI), which defined as the coexistence of any two of the three types of rupture include left ventricular free wall repture (LVFWR), ventricular septal perforation (VSP) and papillary muscule repture (PMR). We report here a case of successful staged repair of double rupture combined LVFWR and VSP. A 77-year-old woman with diagnosis of AMI in the anteroseptal area fell into cardiogenic shock suddenly just before starting coronary angiography. Echocardiography showed left ventricular free wall rupture, then an emergent operation was performed under intraaortic balloon pumping (IABP) and percutaneous cardiopulmonary support (PCPS) assistance using bovine pericardial patch and felt sandwich technique. Intraoperative transesophageal echocardiography revealed ventricular septal perforation on the apical anterior wall. Her hemodynamic condition was stable, therefore we selected a staged VSP repair to avoid surgery on freshly infarcted myocardium. Twenty-eight days after the initial operation, VSP repair was performed using the extended sandwich patch technique via right ventricle incision. Postoperative echocardiography revealed no residual shunt.

Membrane Sphingomyelin in Host Cells Is Essential for Nucleocapsid Penetration into the Cytoplasm after Hemifusion during Rubella Virus Entry.

The lipid composition of the host cell membrane is one of the key determinants of the entry of enveloped viruses into cells. To elucidate the detailed mechanisms behind the cell entry of rubella virus (RuV), one of the enveloped viruses, we searched for host factors involved in such entry by using CRISPR/Cas9 genome-wide knockout screening, and we found sphingomyelin synthase 1 (SMS1), encoded by the SGMS1 gene, as a candidate. RuV growth was strictly suppressed in SGMS1-knockout cells and was completely recovered by the overexpression of enzymatically active SMS1 and partially recovered by that of SMS2, another member of the SMS family, but not by that of enzymatically inactive SMS1. An entry assay using pseudotyped vesicular stomatitis virus possessing RuV envelope proteins revealed that sphingomyelin generated by SMSs is crucial for at least RuV entry. In SGMS1-knockout cells, lipid mixing between the RuV envelope membrane and the membrane of host cells occurred, but entry of the RuV genome from the viral particles into the cytoplasm was strongly inhibited. This indicates that sphingomyelin produced by SMSs is essential for the formation of membrane pores after hemifusion occurs during RuV entry. IMPORTANCE Infection with rubella virus during pregnancy causes congenital rubella syndrome in infants. Despite its importance in public health, the detailed mechanisms of rubella virus cell entry have only recently become somewhat clearer. The E1 protein of rubella virus is classified as a class II fusion protein based on its structural similarity, but it has the unique feature that its activity is dependent on calcium ion binding in the fusion loops. In this study, we found another unique feature, as cellular sphingomyelin plays a critical role in the penetration of the nucleocapsid into the cytoplasm after hemifusion by rubella virus. This provides important insight into the entry mechanism of rubella virus. This study also presents a model of hemifusion arrest during cell entry by an intact virus, providing a useful tool for analyzing membrane fusion, a biologically important phenomenon.

[Stanford Type A Acute Aortic Dissection after Coronary Artery Bypass Grafting using Automated Proximal Anastomotic Device].

Stanford type A acute aortic dissection after off-pump coronary artery bypass grafting( OPCAB) is a rare but potentially fatal complication. A 61-year-old man with subacute Stanford type B aortic dissection underwent a triple OPCAB using an automated proximal anastomotic device. On postoperative day 4, he had a sudden syncope. An enhanced computed tomography (CT) scan revealed Stanford type A acute aortic dissection. He underwent emergent total aortic arch replacement along with an open stent graft deployment. The entry of the dissection was located at the proximal anastomosis site of the vein graft. This case demonstrates that this device should be used carefully in patients with a history of Stanford type B aortic dissection.

[Stanford Type A Acute Aortic Dissection with Persistent Left Superior Vena Cava in a Turner Syndrome Patient:Report of a Case].

A 48-year-old woman who was diagnosed with Turner syndrome in her childhood presented with sudden onset of low back pain and respiratory discomfort. Contrast enhanced computed tomography scan revealed Stanford type A acute aortic dissection with persistent left superior vena cava (PLSVC). Emergency ascending aortic replacement was performed. After cardiopulmonary bypass was established through cannulating right femoral artery and right superior vena cava, inferior vena cava, another venous cannula was directly placed into the left superior vena cava. After core cooling, the right atrium was incised for retrograde cardioplegia. At a tympanic temperature of 25 ℃, circulatory arrest was started and retrograde cerebral perfusion was performed through right and left superior vena cava. Her postoperative course was uneventful.

[Non-anastomotic Pseudoaneurysm of a Prosthetic Graft with Sternal Erosion after Total Aortic Arch Replacement].

An 82-year-old man underwent total aortic arch replacement with a 24 mm Triplex four-branched graft for aortic arch aneurysm. After two years, he was diagnosed with pseudoaneurysms due to bleeding from a non-anastomotic site of the branch graft to the left common carotid artery and minor leakage from a distal anastomotic site of the main graft. A self-expandable Fluency covered stent and cTAG thoracic endograft were used for the aneurysm. After four years, he was referred to our hospital with a complaint of pulsatile swelling of the anterior chest wall. Contrast enhanced computed tomography (CT) revealed a pseudoaneurysm arising from a non-anastomotic site of the branch graft to the left common carotid artery, which extended into the anterior chest wall and the skin through the sternum. He underwent emergency endovascular repair using a Niti-S ComVi covered stent. The postoperative course was uneventful. Postoperative CT showed shrinkage of the pseudoaneurysm. The patient was discharged and required no reintervention during the follow-up.

Development of Genetic Diagnostic Methods for Detection for Novel Coronavirus 2019(nCoV-2019) in Japan.

During the emergence of novel coronavirus 2019 (nCoV) outbreak in Wuhan city, China at the end of 2019, there was movement of many airline travelers between Wuhan and Japan, suggesting that the Japanese population was at high risk of infection by the virus. Hence, we urgently developed diagnostic systems for detection of 2019 nCoV. Two nested RT-PCR and two real-time RT-PCR assays were adapted for use in Japan. As of February 8, 2020, these assays have successfully detected 25 positive cases of infection in Japan.

Endovascular Repair for Abdominal Aortic Rupture Caused by Periaortic Mantle Cell Lymphoma.

A 72-year-old man was referred to our hospital for the suspicion of ruptured abdominal aortic aneurysm. Before admission, he was suspected of having a malignant lymphoma and underwent excisional biopsy in his right groin. A contrast enhanced computed tomography scan revealed a massive retroperitoneal hematoma with an extravasation arising from the infrarenal abdominal aorta coexisting with an extensive retroperitoneal mass surrounding the aorta. An emergency endovascular aneurysm repair was performed and the postoperative course was uneventful. After the treatment, histological examination of the previous biopsy confirmed the diagnosis of mantle cell lymphoma.

Heat Shock Protein 90 Ensures the Integrity of Rubella Virus p150 Protein and Supports Viral Replication.

Two viral nonstructural proteins, p150 and p90, are expressed in rubella virus (RUBV)-infected cells and mediate viral genome replication, presumably using various host machineries. Molecular chaperones are critical host factors for the maintenance of cellular proteostasis, and certain viral proteins use this chaperone system. The RUBV p150 and p90 proteins are generated from a precursor polyprotein, p200, via processing by the protease activity of its p150 region. This processing is essential for RUBV genome replication. Here we show that heat shock protein 90 (HSP90), a molecular chaperone, is an important host factor for RUBV genome replication. The treatment of RUBV-infected cells with the HSP90 inhibitors 17-allylamino-17-desmethoxygeldanamycin (17-AAG) and ganetespib suppressed RUBV genome replication. HSP90α physically interacted with p150, but not p90. Further analyses into the mechanism of action of the HSP90 inhibitors revealed that HSP90 activity contributes to p150 functional integrity and promotes p200 processing. Collectively, our data demonstrate that RUBV p150 is a client of the HSP90 molecular chaperone and that HSP90 functions as a key host factor for RUBV replication.IMPORTANCE Accumulating evidence indicates that RNA viruses use numerous host factors during replication of their genomes. However, the host factors involved in rubella virus (RUBV) genome replication are largely unknown. In this study, we demonstrate that the HSP90 molecular chaperone is needed for the efficient replication of the RUBV genome. Further, we reveal that HSP90 interacts with RUBV nonstructural protein p150 and its precursor polyprotein, p200. HSP90 contributes to the stability of p150 and the processing of p200 via its protease domain in the p150 region. We conclude that the cellular molecular chaperone HSP90 is a key host factor for functional maturation of nonstructural proteins for RUBV genome replication. These findings provide novel insight into this host-virus interaction.

Both Sphingomyelin and Cholesterol in the Host Cell Membrane Are Essential for Rubella Virus Entry.

Rubella virus (RuV) causes a systemic infection, and transplacental fetal infection causes congenital rubella syndrome. In this study, we showed that treatment of cells with sphingomyelinase inhibited RuV infection. Assays using inhibitors of serine palmitoyl transferase and ceramide transport protein demonstrated the contribution of sphingomyelin (SM) to RuV infection. Compelling evidence for direct binding of RuV to lipid membranes at neutral pH was obtained using liposome coflotation assays. The absence of either SM or cholesterol (Chol) abrogated the RuV-liposome interaction. SM and Chol (SM/Chol) were also critical for RuV binding to erythrocytes and lymphoid cells. Removal of Ca2+ from the assay buffer or mutation of RuV envelope E1 protein Ca2+-binding sites abrogated RuV binding to liposomes, erythrocytes, and lymphoid cells. However, RuV bound to various nonlymphoid adherent cell lines independently of extracellular Ca2+ or SM/Chol. Even in these adherent cell lines, both the E1 protein Ca2+-binding sites and cellular SM/Chol were essential for the early stage of RuV infection, possibly affecting envelope-membrane fusion in acidic compartments. Myelin oligodendrocyte glycoprotein (MOG) has recently been identified as a cellular receptor for RuV. However, RuV bound to MOG-negative cells in a Ca2+-independent manner. Collectively, our data demonstrate that RuV has two distinct binding mechanisms: one is Ca2+ dependent and the other is Ca2+ independent. Ca2+-dependent binding observed in lymphoid cells occurs by the direct interaction between E1 protein fusion loops and SM/Chol-enriched membranes. Clarification of the mechanism of Ca2+-independent RuV binding is an important next step in understanding the pathology of RuV infection.IMPORTANCE Rubella has a significant impact on public health as infection during early pregnancy can result in babies being born with congenital rubella syndrome. Even though effective rubella vaccines are available, rubella outbreaks still occur in many countries. We studied the entry mechanism of rubella virus (RuV) and found that RuV binds directly to the host plasma membrane in the presence of Ca2+ at neutral pH. This Ca2+-dependent binding is specifically directed to membranes enriched in sphingomyelin and cholesterol and is critical for RuV infection. Importantly, RuV also binds to many cell lines in a Ca2+-independent manner. An unidentified RuV receptor(s) is involved in this Ca2+-independent binding. We believe that the data presented here may aid the development of the first anti-RuV drug.

Analysis of VSV pseudotype virus infection mediated by rubella virus envelope proteins.

Rubella virus (RV) generally causes a systemic infection in humans. Viral cell tropism is a key determinant of viral pathogenesis, but the tropism of RV is currently poorly understood. We analyzed various human cell lines and determined that RV only establishes an infection efficiently in particular non-immune cell lines. To establish an infection the host cells must be susceptible and permissible. To assess the susceptibility of individual cell lines, we generated a pseudotype vesicular stomatitis virus bearing RV envelope proteins (VSV-RV/CE2E1). VSV-RV/CE2E1 entered cells in an RV envelope protein-dependent manner, and thus the infection was neutralized completely by an RV-specific antibody. The infection was Ca2+-dependent and inhibited by endosomal acidification inhibitors, further confirming the dependency on RV envelope proteins for the VSV-RV/CE2E1 infection. Human non-immune cell lines were mostly susceptible to VSV-RV/CE2E1, while immune cell lines were much less susceptible than non-immune cell lines. However, susceptibility of immune cells to VSV-RV/CE2E1 was increased upon stimulation of these cells. Our data therefore suggest that immune cells are generally less susceptible to RV infection than non-immune cells, but the susceptibility of immune cells is enhanced upon stimulation.

A method for detecting rash and fever illness-associated viruses using multiplex reverse transcription polymerase chain reaction.

In this study, a new multiplex RT-PCR method for detecting various viral genes in patients with rash and fever illnesses (RFIs) was constructed. New primer sets were designed for detection of herpes simplex viruses 1 and 2 (HSV1 and 2), and Epstein-Barr virus (EBV). The newly designed and previously reported primer sets were used to detect 13 types of RFI-associated viruses by multiplex RT-PCR assay systems. Moreover, to eliminate non-specific PCR products, a double-stranded specific DNase was used to digest double-stranded DNA derived from the templates in clinical specimens. RFI-associated viruses were detected in 77.0% of the patients (97/126 cases) by the presented method, multiple viruses being identified in 27.8% of the described cases (35/126 cases). Detected viruses and clinical diagnoses were compatible in 32.5% of the patients (41/126 cases). Sensitivity limits for these viruses were estimated to be 101 -103 copies/assay. Furthermore, non-specific PCR products were eliminated by a double-stranded specific DNase with no influence on sensitivity. These results suggest that this method can detect various RFI-associated viruses in clinical specimens with high sensitivity and specificity.

Bioprosthetic mitral valve dysfunction due to native valve preserving procedure.

Mitral valve replacement with preservation of the mitral leaflets and subvalvular apparatus is considered to maintain left ventricular geometry and function and reduce the risk of myocardial rupture. However, the routine use of this technique may lead to early complications such as left ventricular outflow tract obstruction and even mitral inflow obstruction, requiring reoperation. We describe a rare case of bioprosthetic mitral valve dysfunction caused by a native valve preserving procedure.

[Postoperative Superior Mesenteric Artery and Cerebral Infarction Possibly due to the Thrombus at the Left Superior Pulmonary Vein Stump].

Pulmonary vein stump thrombus (PVST) was thought to be a rare complication after lung resection. Several cases of embolism due to PVST were reported previously. However, in recent paper, PVST was reported to be found in 13.5% of patients after left upper lobectomy ( LUL). We experienced a case of PVST that induced acute embolism of the superior mesenteric artery at 2 weeks after LUL. After discontinuation of anticoagulation therapy, development of PVST was confirmed by computed tomography scan at 12 months after LUL resulting in cerebral infarction.

[Reconstruction of the superior vena cava for invasive thymoma under monitoring of regional cerebral saturation of oxygen].

A 63-year-old man was referred to our department for surgical resection of invasive thymoma (type B3)after 2 courses of chemo-therapy resulted in stable disease. Resection of the tumor was done through a median sternotomy under monitoring of regional cerebral saturation of oxygen (rSo2) using near-infrared spectroscopy (NIRS). The tumor invaded to the right upper lobe (S3), the right phrenic nerve, the superior vena cava (SVC), and the bilateral brachiocephalic vein (BCV). Although bilateral clamping of the BCVs induced significant decrease in rSo2, unilateral clamping of the BCV did not. Therefore, reconstruction of the SVC by sequential reconstruction of BCVs was carried out, and the tumor was successfully and safely excised with the SVC and a part of the right upper lobe.

Hemothorax with a high carbohydrate antigen 19-9 level caused by a bronchogenic cyst.

A 58-year-old man presented with right-sided chest pain. Radiography and computed tomography showed a pleural effusion in the right chest and a mass in the right hilum. Thoracentesis showed a hemothorax. The carbohydrate antigen (CA) 19-9 level in the pleural effusion was very high, requiring differentiation from malignancy. Positron emission tomography showed no significant fluorodeoxy glucose (FDG) accumulation. Magnetic resonance imaging revealed a cystic lesion. The tumor was resected for both a diagnosis and treatment. A pathological examination demonstrated a bronchogenic cyst. An immunohistochemical study suggested that the cyst was the source of the hemothorax and the high CA19-9 level.

[A case of mucinous adenocarcinoma of the sigmoid colon with disseminated carcinomatosis of the bone marrow successfully treated with FOLFOX4/bevacizumab].

A 68-year-old man complaining of back pain was given the diagnosis of mucinous adenocarcinoma of the sigmoid colon with disseminated carcinomatosis of bone marrow and disseminated intravascular coagulation(DIC). We started chemotherapy using FOLFOX4. After we confirmed that DIC had improved following 2 courses of FOLFOX4, bevacizumab was added to FOLFOX4. Laboratory studies revealed a serum CEA level of 11, 432 ng/mL, which improved to 245 ng/mL after a total of 9 courses of chemotherapy. Chemotherapy is continuing as scheduled at 6 months from the onset of this disease.

Japanese encephalitis virus core protein inhibits stress granule formation through an interaction with Caprin-1 and facilitates viral propagation.

Stress granules (SGs) are cytoplasmic foci composed of stalled translation preinitiation complexes induced by environmental stress stimuli, including viral infection. Since viral propagation completely depends on the host translational machinery, many viruses have evolved to circumvent the induction of SGs or co-opt SG components. In this study, we found that expression of Japanese encephalitis virus (JEV) core protein inhibits SG formation. Caprin-1 was identified as a binding partner of the core protein by an affinity capture mass spectrometry analysis. Alanine scanning mutagenesis revealed that Lys(97) and Arg(98) in the α-helix of the JEV core protein play a crucial role in the interaction with Caprin-1. In cells infected with a mutant JEV in which Lys(97) and Arg(98) were replaced with alanines in the core protein, the inhibition of SG formation was abrogated, and viral propagation was impaired. Furthermore, the mutant JEV exhibited attenuated virulence in mice. These results suggest that the JEV core protein circumvents translational shutoff by inhibiting SG formation through an interaction with Caprin-1 and facilitates viral propagation in vitro and in vivo.

Stromal p16 expression differentiates endometrial polyp from endometrial hyperplasia.

Endometrial polyps are very common benign endometrial lesions, but their pathogenesis is poorly understood, except for a few studies indicating the possibility of benign stromal neoplasm. Although the histopathological diagnosis of endometrial polyp on a surgical specimen is straightforward, it is often difficult to differentiate endometrial polyp from endometrial hyperplasia on a biopsy or curettage specimen. Presently, there is no immunohistochemical marker helpful in this differential diagnosis. In this study, we examined p16 expression in 35 endometrial polyps and 33 cases of endometrial hyperplasia that included 16 simple hyperplasias, 14 complex atypical hyperplasias, and 3 complex hyperplasias without atypia. Stromal p16 expression differed significantly between the two groups; it was seen in 31 (89 %) endometrial polyps, but in only 1 (3 %) endometrial hyperplasia. The percentage of p16-positive stromal cells ranged from 10 to 90 % (mean, 47 %) and the positive cells tended to be distributed around glands. Six cases of endometrial hyperplasia within an endometrial polyp were also examined and all cases showed stromal p16 expression. There was no difference in glandular p16 expression between endometrial polyps 33 (94 %) and hyperplasia 27 (82 %). The p16-immunoreactivity was mostly confined to metaplastic epithelial cells in both groups. Stromal p16 expression might be a peculiar characteristic of endometrial polyp and constitute a useful marker for the diagnosis, especially in fragmented specimens from biopsy or curettage. Stromal p16 expression might be a reflection of p16-induced cellular senescence, which has been documented in several benign mesenchymal neoplasms.

Proteomic analysis of hepatitis C virus (HCV) core protein transfection and host regulator PA28γ knockout in HCV pathogenesis: a network-based study.

Hepatitis C virus (HCV) causes chronic liver disease worldwide. HCV Core protein (Core) forms the viral capsid and is crucial for HCV pathogenesis and HCV-induced hepatocellular carcinoma, through its interaction with the host factor proteasome activator PA28γ. Here, using BD-PowerBlot high-throughput Western array, we attempt to further investigate HCV pathogenesis by comparing the protein levels in liver samples from Core-transgenic mice with or without the knockout of PA28γ expression (abbreviated PA28γ(-/-)CoreTG and CoreTG, respectively) against the wild-type (WT). The differentially expressed proteins integrated into the human interactome were shown to participate in compact and well-connected cellular networks. Functional analysis of the interaction networks using a newly developed data warehouse system highlighted cellular pathways associated with vesicular transport, immune system, cellular adhesion, and cell growth and death among others that were prominently influenced by Core and PA28γ in HCV infection. Follow-up assays with in vitro HCV cell culture systems validated VTI1A, a vesicular transport associated factor, which was upregulated in CoreTG but not in PA28γ(-/-)CoreTG, as a novel regulator of HCV release but not replication. Our analysis provided novel insights into the Core-PA28γ interplay in HCV pathogenesis and identified potential targets for better anti-HCV therapy and potentially novel biomarkers of HCV infection.