Cell Type-Specific Relationships Among Immune Cells in Human Aortic Dissection Tissue.

BACKGROUND: Although recent studies have revealed the importance of inflammation in the pathogenesis of aortic dissection (AD), little is known about the relationships among inflammatory cells in human AD tissue. METHODS AND RESULTS: We assessed the relationships among various immune cell types, including neutrophils, macrophages (M1 and M2), B cells, and helper T cells (Th1, Th2, Th17, Treg and Tfh ) in human AD tissue. AD tissues displayed abundant infiltration of immune cells. Correlation analysis revealed two groups of highly correlated cell types: a group of neutrophils and M1 and M2 macrophages, and another group consisting of B cells and helper T cells. In one particular case of AD, we were able to analyze the correlations between neutrophils and M1 and M2 macrophages in the entry, border, and intact zones of the AD lesions. Neutrophils showed significant correlations with M1 and M2 macrophages in the border zones. The entry and border zones showed M1-dominant polarization, whereas the intact zone showed M2-dominant polarization. CONCLUSIONS: These findings indicate the existence of cell type-specific and site-specific interactions among immune cell types in human AD tissues.

Aortoesophageal fistula due to esophageal cancer: a case report of successful management.

BACKGROUND: Aortoesophageal fistula (AEF) is a rare but potentially life-threatening condition. The best treatment for the AEF due to esophageal carcinoma is still unresolved. Here, we report a rare case of AEF caused by esophageal cancer, that was successfully treated with emergency thoracic endovascular aortic repair (TEVAR), followed by esophagectomy and gastric tube reconstruction. CASE PRESENTATION: A 64-year-old man presented with loss of consciousness and hypotension during chemoradiotherapy for advanced esophageal cancer. Enhanced computed tomography showed extravasation from the descending aorta into the esophagus at the tumor site. We performed emergency TEVAR for the AEF, which stabilized the hemodynamics. We then performed thoracoscopic subtotal esophagectomy on day 4 after TEVAR to prevent graft infection, followed by gastric tube reconstruction on day 30 after TEVAR. At 9 months after the onset of AEF, the patient continues to receive outpatient chemotherapy and leads a normal daily life. CONCLUSION: TEVAR is a useful hemostatic procedure for AEF. If the patient is in good condition and can continue treatment for esophageal cancer, esophagectomy and reconstruction after TEVAR should be performed to prevent graft infection and maintain quality of life.

Synthetic Genes For Dynamic Regulation Of DNA-Based Receptors.

We present a strategy to control dynamically the loading and release of molecular ligands from synthetic nucleic acid receptors using in vitro transcription. We demonstrate this by engineering three model synthetic DNA-based receptors: a triplex-forming DNA complex, an ATP-binding aptamer, and a hairpin strand, whose ability to bind their specific ligands can be cotranscriptionally regulated (activated or inhibited) through specific RNA molecules produced by rationally designed synthetic genes. The kinetics of our DNA sensors and their genetically generated inputs can be captured using differential equation models, corroborating the predictability of the approach used. This approach shows that highly programmable nucleic acid receptors can be controlled with molecular instructions provided by dynamic transcriptional systems, illustrating their promise in the context of coupling DNA nanotechnology with biological signaling.

Effects of Pemafibrate on Reducing Oxidative Stress and Augmenting Angiogenesis in Ischemic Limb Tissue.

OBJECTIVE: Oxidative damage is observed in the ischemic limbs of patients with arteriosclerosis obliterans. We investigated whether pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, reduced oxidative stress in ischemic limbs and consequently rescued limb damage in model mice. MATERIALS AND METHODS: We surgically induced hind-limb ischemia in mice and orally administered pemafibrate solution (P-05 group, 0.5 mg/kg/day; P-10 group, 1.0 mg/kg/day) or control solution (control group). Seven days after the surgery, differences in reactive oxygen species (ROS) contents, antioxidative enzyme and transcription factor expression, blood flow, and capillary density in ischemic limbs were assessed. RESULTS: Tissue ROS levels were lower in the P-05 and P-10 groups compared with those in the control group. Although the tissue expression levels of nuclear factor-erythroid 2-related factor 2 increased in the P-10 group compared with that in the control group, no corresponding changes were observed in the tissue expression of four antioxidative enzymes. The limb salvage rates and capillary densities in ischemic limbs were higher in the P-05 and P-10 groups than that in the control group. CONCLUSION: Pemafibrate treatment reduced oxidative stress and augmented angiogenesis in ischemic limbs, contributing to prevention of limb damage in mice.

Large Thrombus Entrapped in a Patent Foramen Ovale during Inferior Vena Cava Filter Protection for Venous Thromboembolism.

Background. A large thrombus entrapped in the patent foramen ovale (PFO) is an extremely rare condition. Moreover, it is considered even rarer after temporary inferior vena cava filter (TIVCF) placement for the prevention of fatal pulmonary embolism due to venous thromboembolism (VTE). Case Report. A 58-year-old man presented with syncope following chest pain and dyspnea due to PE exacerbation during TIVCF protection, which then led to cardiogenic shock. Echocardiography revealed a large thrombus entrapped in the PFO, and computed tomography (CT) showed a bilateral pulmonary artery embolism. The patient was treated with open surgical embolectomy for a pulmonary artery thrombus and PFO thrombus with simultaneous closure of the PFO. The patient's postoperative course was uneventful. Results and Conclusion. Surgical embolectomy was useful with respect to the feasibility of resection of both intracardiac thrombus and pulmonary artery thrombus performed simultaneously, contributing to the prevention of systemic embolisms, and echocardiography plays an important role for early diagnosis.

Isolated External Iliac Artery Aneurysm with Fibromuscular Dysplasia.

Isolated aneurysms of the external iliac artery are rare in patients with fibromuscular dysplasia. In this study, we report the case of a 74-year-old man with advanced gastric cancer who was found to have a medium-sized aneurysm of the external iliac artery (35 mm) on preoperative computed tomography angiograms. The patient underwent laparoscopic gastrectomy followed by replacement of the external iliac artery 6 months later. Histological examination of biopsy specimens revealed fibromuscular dysplasia. The 6 month postoperative course was uneventful. Such a case of external iliac artery aneurysm caused by fibromuscular dysplasia is very rare, and open surgery is recommended for its removal.

Endovascular Aortic Repair for Heavily Calcified Abdominal Aortic Stenosis Using the Gore Viabahn Vbx Balloon-Expandable Covered Stent.

Open surgery for the treatment of focal infrarenal aortic stenosis in high-risk patients may result in complications and mortality. Endovascular aortic repair may be used to treat these lesions. Here, we present the case of a 78-year-old woman with severe, highly calcified stenosis of the infrarenal abdominal aorta, which was successfully treated with the GORE VIABAHN VBX (Gore Medical; Flagstaff, AZ) balloon-expandable covered stent. Long-term and randomized controlled studies comparing open surgery with EVAR are necessary to evaluate the usefulness of this novel device.

Data-driven and model-guided systematic framework for media development in CHO cell culture.

Proposed herein is a systematic media design framework that combines multivariate statistical approaches with in silico analysis of a genome-scale metabolic model of Chinese hamster ovary cell. The framework comprises sequential modules including cell culture and metabolite data collection, multivariate data analysis, in silico modeling and flux prediction, and knowledge-based identification of target media components. Two monoclonal antibody-producing cell lines under two different media conditions were used to demonstrate the applicability of the framework. First, the cell culture and metabolite profiles from all conditions were generated, and then statistically and mechanistically analyzed to explore combinatorial effects of cell line and media on intracellular metabolism. As a result, we found a metabolic bottleneck via a redox imbalance in the TCA cycle in the poorest growth condition, plausibly due to inefficient coenzyme q10-q10h2 recycling. Subsequent in silico simulation allowed us to suggest q10 supplementation to debottleneck the imbalance for the enhanced cellular energy state and TCA cycle activity. Finally, experimental validation was successfully conducted by adding q10 in the media, resulting in increased cell growth. Taken together, the proposed framework rationally identified target nutrients for cell line-specific media design and reformulation, which could greatly improve cell culture performance.

A miRNA-based diagnostic model predicts resectable lung cancer in humans with high accuracy.

Lung cancer, the leading cause of cancer death worldwide, is most frequently detected through imaging tests. In this study, we investigated serum microRNAs (miRNAs) as a possible early screening tool for resectable lung cancer. First, we used serum samples from participants with and without lung cancer to comprehensively create 2588 miRNAs profiles; next, we established a diagnostic model based on the combined expression levels of two miRNAs (miR-1268b and miR-6075) in the discovery set (208 lung cancer patients and 208 non-cancer participants). The model displayed a sensitivity of 99% and specificity of 99% in the validation set (1358 patients and 1970 non-cancer participants) and exhibited high sensitivity regardless of histological type and pathological TNM stage of the cancer. Moreover, the diagnostic index markedly decreased after lung cancer resection. Thus, the model we developed has the potential to markedly improve screening for resectable lung cancer.

Aortic Dissection Associated with Autosomal Dominant Polycystic Kidney Disease

A 78-year-old man who had been diagnosed with autosomal dominant polycystic kidney disease (ADPKD) and hypertension presented with chest pain. His family history was positive for ADPKD. Chest computed tomography (CT) revealed a type A aortic dissection with thrombotic occlusion of a false lumen and an ulcer-like projection in the ascending aorta, an aneurysm of the ascending aorta, and pericardial effusion. Abdominal CT showed multiple renal and hepatic cysts. At surgery, aortic dissection with thrombotic occlusion of the false lumen and an intimal tear in the distal ascending aorta were observed. Hemiarch replacement including the intimal tear was performed. The patient is doing well without requiring dialysis and without recurrence of aortic dissection or aneurysm under strict antihypertensive therapy 3 years after the operation. Pathological examination of aortic wall specimens revealed no degenerative abnormality. ADPKD should be kept in mind as one of the causative disorders of aortic dissection.

Infective Endocarditis Associated with Atopic Dermatitis.

We report a case of aortic valve infective endocarditis (IE) in a 24-year-old man with atopic dermatitis (AD). He had a history of balloon valvuloplasty for a stenotic bicuspid aortic valve, and had dental caries but no invasive dental procedure before the onset of IE. On admission, skin lesions of AD with itching and scratches were found on the neck, trunk, and extremities. Echocardiography showed a vegetation on the aortic valve with mild steno-regurgitation, but extension of IE to the annulus was not detected. Magnetic resonance imaging identified fresh cerebral infarction without neurological dysfunction, leading us to suspect an embolism. Blood cultures grew methicillin-sensitive Staphylococcus aureus. During emergency surgery, a vegetation attached to the conjoined cusp was observed, and the aortic valve was replaced with a mechanical valve. The patient recovered uneventfully without any complications such as recurrent IE or mediastinitis. We also review previously reported cases of IE associated with AD.

Coexistence of Right Ventricular Myxoma and Atrioventricular Septal Defect.

Although a small number of atrial myxomas are found in association with congenital cardiac defects, ventricular myxomas coexisting with congenital cardiac anomalies are extremely rare. We report a case of right ventricular (RV) myxoma coexistent with atrioventricular septal defect in an adolescent. Echocardiography showed an RV mass, a small ostium primum atrial septal defect, and a cleft of the left atrioventricular valve. Magnetic resonance imaging revealed a mass, suggesting a myxoma. The mass was excised simultaneously with repair of the anomalies and was histologically confirmed as a myxoma.

The Effect of Cisplatin on Blood Ammonia Elevation by Alanyl-Glutamine Supplementation.

BACKGROUND: Although there are many clinical studies in which the beneficial effect of glutamine formulation on mucositis induced by chemo/radiotherapy was evaluated, the results are sometimes conflicting with the report of clinical deterioration. Then, we hypothesized that chemotherapy may increase the incidence of hyperammonemia without comparable change of major parameters of hepatic/renal disorder. METHODS: To verify our hypothesis, we examined the increase in blood ammonia level with 1-h intravenous infusion of alanyl-glutamine on day 1-4 after cisplatin (CDDP) administration in rats and assessed the correlation with hepatic/renal parameters. RESULTS: Hepatic parameters (glutamate-oxaloacetic transaminase [GOT] and glutamic-pyruvic transaminase [GPT]) with CDDP did not change until day 3 and only GOT increased on day 4. Renal parameters (plasma creatinine, blood urea nitrogen) with CDDP continuously increased up to day 4. Alanyl-glutamine infusion significantly elevated blood ammonia level of CDDP rats with the peak on day 3, although the same dose did not change that of control rats. CONCLUSION: These results indicates that CDDP enhances the increase in blood ammonia level by glutamine supplementation without correlating with primary parameters for hepatic/renal dysfunction.

Usefulness of three-dimensional transesophageal echocardiography for diagnosis of hemolytic anemia due to inverted internal felt strip after surgery for aortic dissection.

Felt strips are widely used for reinforcement of the aortic stump in surgery for aortic dissection (AD). Postoperative hemolytic anemia (HA) due to an inverted internal felt strip at the aortic stump fixation for AD is extremely rare. A 70-year-old woman underwent ascending aorta replacement for acute type A AD, where both proximal and distal anastomotic sites were reinforced with Teflon felt strips. A week later, macroscopic hematuria and HA emerged. Three-dimensional transesophageal echocardiography (3D-TEE) demonstrated that the proximal inner felt strip turned up and protruded into the aortic inner lumen. At redo surgery, which was performed 2 weeks after the initial surgery, the findings of 3D-TEE were confirmed, and the inverted internal felt strip was replaced with a bovine pericardial strip. The findings of HA disappeared immediately after the second surgery. 3D-TEE is a very informative, valuable modality for accurate diagnosis that leads to a safe surgery.

A Case of Femoral Arterial Bleeding by an Unknown Origin Metastatic Groin Lymph Nodes Carcinoma.

We report a case of femoral arterial bleeding complicated with hemorrhagic shock caused by bacterial infection attributed to an inguinal lymph node metastasis of carcinoma of unknown primary. Because of severe preoperative condition, a venous patch plasty of ruptured artery, and omentopexy for the groin was performed as a less invasive surgery. But the recurrence of bleeding was occurred postoperatively. A staged operation, hemostasis with a venous patch plasty at a first stage, and an extra-anatomical bypass soon after improvement of shock condition in a second stage, can be one of surgical procedures to save the lives and salvage limbs.

Isolated Tricuspid Valve Endocarditis Caused by Infection of an Implanted Central Venous Access Port Device.

A 70-year-old man was referred to our hospital for an intermittent high fever attributed to subcutaneous pocket infection of an implanted central venous access port device caused by methicillin-resistant staphylococcus aureus and subsequent bloodstream infection. Echocardiography revealed a large vegetation on the posterior tricuspid leaflet, annular dilatation and moderate-to-severe tricuspid regurgitation. Valve surgery was performed for persistent infection despite 8 weeks of antibiotics therapy. At operation, vegetations and torn chordae tendineae were found on the posterior tricuspid leaflet. After total resection of the posterior tricuspid leaflet, bicuspidalization valvuloplasty with prosthetic ring annuloplasty was achieved without relapse of the infection or residual regurgitation.

[Glutamate as a potential protective drug in the gastrointestinal mucosa].

Monosodium glutamate (MSG) is known to provide the umami taste in the food. We have recently reported that glutamate has the potential to protect the small intestine against non-steroidal anti-inflammatory drugs (NSAIDs)-induced lesions in rats. In this paper, we examined this protective effect using sodium loxoprofen, one of the NSAIDs frequently used in Asian countries, to determine whether MSG accelerates the healing of loxoprofen-induced small intestinal lesions in rats. Loxoprofen at 60 mg/kg caused hemorrhagic lesions in the small intestine, mainly in the jejunum and ileum. These lesions spontaneously healed within 7 days, but this healing process was delayed by repeated administration of loxoprofen at low doses (10, 30 mg/kg) for 5 d after lesion induction. The healing-impairment action of loxoprofen was accompanied by the down-regulation of vascular endothelium-derived growth factor (VEGF) expression and an angiogenic response. The impaired healing caused by loxoprofen was significantly restored by co-treatment with a diet containing 5% MSG for 5 d, accompanied by the enhancement of VEGF expression and angiogenesis. We suggest that daily intake of MSG not only protects the small intestine against NSAIDs-induced damage but also exerts healing-promoting effects on these lesions.

A surgical case of papillary fibroelastoma originating from the left atrial ridge.

Papillary fibroelastomas are benign cardiac tumors with high embolic tendency, and usually originate from the cardiac valve. We report the case of a 49-year-old man who experienced sudden right hemiplegia and aphasia. Transesophageal echocardiography indicated a swinging tumor originating from the left atrial ridge between the orifice of the left atrial appendage and the anterolateral mitral annulus. Urgent tumor resection was performed to prevent further embolization. The histological findings of resected tumor were consistent with those of papillary fibroelastoma. To the best of our knowledge, all cases of papillary fibroelastomas that originate from the left atrial ridge are associated with cerebral vascular accidents. Therefore, prompt surgical resection is strongly recommended to prevent embolic events for those patients. .

Prophylactic effect of monosodium glutamate on NSAID-induced enteropathy in rats.

We reviewed the prophylactic effect of monosodium glutamate (MSG), a substance known as the "umami", on NSAID-induced small intestinal damage in rats. Loxoprofen, one of the NSAIDs frequently used in Asian countries, given orally at 60 mg/kg, caused hemorrhagic damage in the small intestine, mainly jejunum and ileum, concomitant with a down-regulation of Muc2 expression/ mucus secretion and an up-regulation of enterobacterial invasion and neutrophil migration as well as inducible nitric oxide synthase (iNOS) expression. The severity of these lesions was reduced by pretreatment with MSG (0.1~5%) given as a mixture of powder food (10 g/rat/day) for 5 days before administration of loxoprofen. The effect of MSG was accompanied by an up-regulation of Muc2 expression/ mucus secretion as well as a suppression of bacterial invasion, iNOS expression and myeloperoxidase activity. On the other hand, these lesions spontaneously healed within 7 days, but this process was hampered by loxoprofen at low doses (>10 mg/kg) given repeatedly for 5 days after ulceration. The healing-impairment effect of loxoprofen was accompanied by the down-regulation of vascular endothelium- derived growth factor (VEGF) expression and angiogenic response, and these responses were all antagonized by feeding diet containing 5% MSG for 5 days after ulceration. It is suggested that MSG exhibits a prophylactic effect against loxoprofen-induced small intestinal lesions, this effect is functionally associated with the up-regulation of Muc2 expression/mucus secretion, resulting in suppression of enterobacterial invasion and iNOS expression, the major pathogenic events in NSAID-induced enteropathy, and MSG also has the healing promoting effect on these lesions through enhancement of VEGF expression and angiogenesis.