Routine Referral by Urologists Increase Opportunities for Corneal Donation.

BACKGROUND: The levels of corneal donation are insufficient to meet the demand for corneal transplantation in Japan. To overcome this problem, we started to routinely mention the possibility of corneal donation to the families of patients who died in our hospital's Urology Department in February 2008. In this study, we evaluated the effectiveness of this approach. METHODS: We retrospectively reviewed the medical records of the patients who died in the Department of Urology, St. Marianna University School of Medicine Hospital, and analyzed the patients' characteristics and information about corneal donation. RESULTS: In total, 211 patients died in our department between February 2008 and March 2017, and 155 patients were medically suitable corneal donors. We mentioned the possibility of corneal donation to 129 (83.2%) families, and 29 (18.7%) families agreed. Three families subsequently withdrew their consent. Finally, 26 (16.8%) of the families that were approached about corneal donation by urologists agreed to donate their relatives' corneas. Another 2 families voluntarily offered to donate their relatives' corneas. Thus, 28 (18.1%) of 155 medically suitable donors donated their corneas for transplantation. Twenty-six (92.8%) donors were 60 years or older and all donors were affected with malignant genitourinary tumors. Fifty-four (96.4%) corneas were successfully transplanted into recipients. CONCLUSIONS: Even elderly patients who die of solid carcinoma can be an important source of corneal donors. In this study, we showed that routine referral by urologists increased corneal donation. If this approach were adopted by other departments, it might further increase the number of corneal donations.

A case of refractory lupus nephritis complicated by psoriasis vulgaris that was controlled with secukinumab.

It has been reported that T helper 17 cells are involved in the pathogenesis of systemic lupus erythematosus, but there is no report on interleukin-17-targeted therapy. We report a case of a 62-year-old female who presented with psoriasis vulgaris and refractory lupus nephritis. Because her conditions were resistant to conventional treatment, and flow cytometry confirmed the proliferation of activated T helper 17 cells in peripheral blood, and examination of a renal biopsy tissue sample confirmed infiltration of numerous interleukin-17-positive lymphocytes to the renal interstitium, administration of the anti-interleukin-17A antibody secukinumab was initiated. After starting secukinumab the clinical and biological features were improved.

Water scarcity hotspots travel downstream due to human interventions in the 20th and 21st century.

Water scarcity is rapidly increasing in many regions. In a novel, multi-model assessment, we examine how human interventions (HI: land use and land cover change, man-made reservoirs and human water use) affected monthly river water availability and water scarcity over the period 1971-2010. Here we show that HI drastically change the critical dimensions of water scarcity, aggravating water scarcity for 8.8% (7.4-16.5%) of the global population but alleviating it for another 8.3% (6.4-15.8%). Positive impacts of HI mostly occur upstream, whereas HI aggravate water scarcity downstream; HI cause water scarcity to travel downstream. Attribution of water scarcity changes to HI components is complex and varies among the hydrological models. Seasonal variation in impacts and dominant HI components is also substantial. A thorough consideration of the spatially and temporally varying interactions among HI components and of uncertainties is therefore crucial for the success of water scarcity adaptation by HI.

Photodynamic therapy mediates innate immune responses via fibroblast-macrophage interactions.

Antibacterial photodynamic therapy (PDT) has come to attract attention as an alternative therapy for drug-resistant bacteria. Recent reports revealed that antibacterial PDT induces innate immune response and stimulates abundant cytokine secretion as a part of inflammatory responses. However, the underlying mechanism how antibacterial PDT interacts with immune cells responsible for cytokine secretion has not been well outlined. In this study, we aimed to clarify the difference in gene expression and cytokine secretion between combined culture of fibroblasts and macrophages and their independent cultures. SCRC-1008, mouse fibroblast cell line and J774, mouse macrophage-like cell line were co-cultured and PDT treatments with different parameters were carried out. After various incubation periods (1-24 h), cells and culture medium were collected, and mRNA and protein levels for cytokines were measured using real-time PCR and ELISA, respectively. Our results showed that fibroblasts and macrophages interact with each other to mediate the immune response. We propose that fibroblasts initially respond to PDT by expressing Hspa1b, which regulates the NF-κB pathway via Tlr2 and Tlr4. Activation of the NF-κB pathway then results in an enhanced secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß) and neutrophil chemoattractant MIP-2 and KC from macrophages.

Genome-wide association study identifies a potent locus associated with human opioid sensitivity.

Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. Although opioid sensitivity is well known to vary widely among individual subjects, several candidate genetic polymorphisms reported so far are not sufficient for fully understanding the wide range of interindividual differences in human opioid sensitivity. By conducting a multistage genome-wide association study (GWAS) in healthy subjects, we found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3-2q34 were strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery. The C allele of the best candidate single-nucleotide polymorphism (SNP), rs2952768, was associated with more analgesic requirements, and consistent results were obtained in patients who underwent abdominal surgery. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence' score on a personality questionnaire in healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated expression of a neighboring gene, CREB1. These results show that SNPs in this locus are the most potent genetic factors associated with human opioid sensitivity known to date, affecting both the efficacy of opioid analgesics and liability to severe substance dependence. Our findings provide valuable information for the personalized treatment of pain and drug dependence.

[Thoracic surgery for patients with bronchial asthma].

Thoracic surgery poses a risk for complications in the respiratory system. In particular, for patients with bronchial asthma, we need to care for perioperative complications because it is well known that these patients frequently have respiratory complications after surgery, and they may have bronchial spasms during surgery. If we can get good control of their bronchial asthma, we can usually perform surgery for these patients without limitations. For safe postoperative care, it is desirable that these patients have stable asthma conditions that are well-controlled before surgery, as thoracic surgery requires intrabronchial intubation for anesthesia and sometimes bronchial resection. These stimulations to the bronchus do not provide for good conditions because of the risk of bronchial spasm. Therefore, we should use the same agents that are used to control bronchial asthma if it is already well controlled. If it is not, we have to administer a ß2 stimulator, aminophylline, or steroidal agents for good control. Isoflurane or sevoflurane are effective for the safe control of anesthesia during surgery, and we should use a ß2 stimulator, with or without inhalation, or steroidal agents after surgery. It is important to understand that we can perform thoracic surgery for asthma patients if we can provide perioperative control of bronchial asthma, although these patients still have severe risks.

C-terminal mutation of RUNX1 attenuates the DNA-damage repair response in hematopoietic stem cells.

Loss-of-function mutations of RUNX1 have been found in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Although several reports have suggested roles for RUNX1 as a tumor suppressor, its precise function remains unknown. Because gene alterations of RUNX1 by themselves do not lead to the development of leukemia in mouse models, additional mutation(s) would be required for leukemia development. Here, we report that the C-terminal deletion mutant of RUNX1, RUNX1dC, attenuates DNA-damage repair responses in hematopoietic stem/progenitor cells. γH2AX foci, which indicate the presence of DNA double-strand breaks, were more abundantly accumulated in RUNX1dC-transduced lineage(-)Sca1(+)c-kit(+) (LSK) cells than in mock-transduced LSK cells both in a steady state and after γ-ray treatment. Expression profiling by real-time -PCR array revealed RUNX1dC represses the expression of Gadd45a, a sensor of DNA stress. Furthermore, bone marrow cells from MDS/AML patients harboring the RUNX1-C-terminal mutation showed significantly lower levels of GADD45A expression compared with those from MDS/AML patients with wild-type RUNX1. As for this mechanism, we found that RUNX1 directly regulates the transcription of GADD45A and that RUNX1 and p53 synergistically activate the GADD45A transcription. Together, these results suggest Gadd45a dysfunction due to RUNX1 mutations can cause additional mutation(s) required for multi-step leukemogenesis.

Isolation of a thermotolerant bacterium producing medium-chain-length polyhydroxyalkanoate.

AIMS: The aim of this study was to isolate a thermotolerant micro-organism that produces polyhydroxyalkanoates (PHAs) composed of medium-chain-length (mcl) HA units from a biodiesel fuel (BDF) by-product as a carbon source. METHODS AND RESULTS: We successfully isolated a thermotolerant micro-organism, strain SG4502, capable to accumulate mcl-PHA from a BDF by-product as a carbon source at a cultivation temperature of 45°C. The strain could also produce mcl-PHA from acetate, octanoate and dodecanoate as sole carbon sources at cultivation temperatures up to 55°C. Taxonomic studies and 16S rRNA gene sequence analysis revealed that strain SG4502 was phylogenetically affiliated with species of the genus Pseudomonas. This study is the first report of PHA synthesis by a thermotolerant Pseudomonas. CONCLUSIONS: A novel thermotolerant bacterium capable to accumulate mcl-PHA from a BDF by-product was successfully isolated. SIGNIFICANCE AND IMPACT OF THE STUDY: A major issue regarding industrial production of microbial PHAs is their much higher production cost compared with conventional petrochemical-based plastic materials. Especially significant are the cost of a fermentative substrate and the running cost to maintain a temperature suitable for microbial growth. Thus, strain SG4502, isolated in this study, which assimilates BDF by-product and produces PHA at high temperature, would be very useful for practical application in industry.

Long-term blockade of L/N-type Ca(2+) channels by cilnidipine ameliorates repolarization abnormality of the canine hypertrophied heart.

BACKGROUND AND PURPOSE: The heart of the canine model of chronic atrioventricular block is known to have a ventricular electrical remodelling, which mimics the pathophysiology of long QT syndrome. Using this model, we explored a new pharmacological therapeutic strategy for the prevention of cardiac sudden death. EXPERIMENTAL APPROACH: The L-type Ca(2+) channel blocker amlodipine (2.5 mg.day(-1)), L/N-type Ca(2+) channel blocker cilnidipine (5 mg.day(-1)), or the angiotensin II receptor blocker candesartan (12 mg.day(-1)) was administered orally to the dogs with chronic atrioventricular block for 4 weeks. Electropharmacological assessments with the monophasic action potential (MAP) recordings and blood sample analyses were performed before and 4 weeks after the start of drug administration. KEY RESULTS: Amlodipine and cilnidipine decreased the blood pressure, while candesartan hardly affected it. The QT interval, MAP duration and beat-to-beat variability of the ventricular repolarization period were shortened only in the cilnidipine group, but such effects were not observed in the amlodipine or candesartan group. Plasma concentrations of adrenaline, angiotensin II and aldosterone decreased in the cilnidipine group. In contrast, plasma concentrations of angiotensin II and aldosterone were elevated in the amlodipine group, whereas in the candesartan group an increase in plasma levels of angiotensin II and a decrease in noradrenaline and adrenaline concentrations were observed. CONCLUSIONS AND IMPLICATIONS: Long-term blockade of L/N-type Ca(2+) channels ameliorated the ventricular electrical remodelling in the hypertrophied heart which causes the prolongation of the QT interval. This could provide a novel therapeutic strategy for the treatment of cardiovascular diseases.

[Aortic dissection and annulo-aortic ectasia complicating systemic lupus erythematousus; report of a case].

A 31-year-old man with systemic lupus erythematosus had received long term steroid therapy. He had no compliant, but magnetic resonance imaging showed aortic dissection and annulo-aortic ectasia. Echocardiogram showed severe aortic regurgitation. Therefore aortic root replacement was performed. A histological study of the aortic wall demonstrated myxomatous degeneration in the media. He recovered uneventfully, except for receiving continious hemodia filtration during 4 days after the operation

[Infective endocarditis with the fistula from sinus Valsalva to right atrium and ventricle; report of a case].

A 77-year-old man complained general fatigue and fever. Preoperative echocardiography revealed vegetation of aortic valve, abnormal shunt flow from the sinus of Valsalva was detected in the right atrium and ventricle without perivalvular abscess cavity or aneurysm of the sinus of Valsalva. He diagnosed aortic valve endocarditis with aorto-right atrium and ventricle fistula. He received aortic valve replacement and patch closure at the sinus of Valsalva using the pericardium. Residural aortic-right atrium and ventricle shunt was not detected after the operation, the post operative course was uneventful without congestive heart failure nor signs of infection.

[Large coronary aneurysm after coronary intervention for acute myocardial infarction; report of a case].

A 59-year-old man was admitted to our hospital because of angina pectoris and a large right coronary aneurysm. Two years previously, he underwent percutaneous coronary balloon angioplasty for a stenotic lesion in right coronary artery (RCA) #3. Angiography and computed tomography showed a large right coronary aneurysm. On-pump coronary artery bypass grafting (CABG), ligation of RCA proximal and distal to the aneurysm, resection of the aneurysm was performed successfully. Postoperative course was uneventful with satisfactory angiographic results.

[Perforation due to new myocardial infarction long time; report of a case].

A 65-year-old man was admitted to the hospital because of effort chest pain, 8 years after he received coronary artery bypass grafting [CABG: left internal thoracic artery (LITA) to left anterior descending artery (LAD), saphenous vein graft (SVG) to first diagonal branch (D1) and SVG to postero-lateral branch (PL)]. Emergent coronary angiography revealed right coronary artery occlusion with well patent bypass grafts. Percutaneus coronary intervention (PCI) was performed successfully, but 9 hours later, ventricular septal perforation (VSP) was occurred. Swan-Ganz catheter revealed that pulmonary to systemic blood flow ratio (Qp/Qs) was 2.6. In spite of intensive medical care, his hemodynamics was gradually exacerbated. Subsequent intracavitary repair with equine pericardial patch, sutured using interrupted mattress sutures with felt pledgets, was performed. He had an uneventful recovery thereafter, extubated and weaned from an intra-aortic balloon pumping at the 1st day. He was discharged from hospital on the 27th postoperative day.

[Endovascular stent-grafting for mycotic thoracic aortic aneurysm].

We report 3 cases of endovascular stent-grafting (ESG) for mycotic thoracic aortic aneurysm. The case 1 was a rupture of pseudoaneurysm of the descending aorta caused by mediastinitis due to perforation of esophageal ulcer. The patient underwent emergent ESG for temporary control of the rupture. He underwent esophagus reconstruction 5 month after ESG. The case 2 was admitted due to inflammatory reaction. She was diagnosed with mycotic descending aortic aneurysm and underwent elective ESG because of her old age. Her postoperative course was uneventful and no infection recurred. The case 3 underwent ESG for a ruptured mycotic descending aortic aneurysm. But 113 days after ESG, he underwent ESG again for a ruptured endoleak of the stentgraft. His blood culture demonstrated methillin-resistant Staphylococcus aureus (MRSA). He died of rupture to bronchus and esophagus at 18th day after ESG. We believe that ESG is useful in high risk patients for temporary management of the rupture.

False-positive positron emission tomography appearance with 18F-fluorodeoxyglucose after definitive radiotherapy for cancer of the mobile tongue.

(18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is an effective tool for evaluating the results of radiotherapy. However, some false-positive appearances caused by physiological or pathological accumulation are reported. We report on three patients who showed a high accumulation of FDG in the lingual muscles but had no recurrent tumour after definitive radiotherapy for the mobile tongue. All patients had squamous cell carcinoma of the tongue and received interstitial radiotherapy with small sources. High uptake was seen in the lingual muscles without recurrence or inflammation, based on physical and MR examinations. This false-positive appearance is thought to relate to ill-balanced high activity of the lingual muscles after definitive radiotherapy.

Thoracic chordoma: review and role of FDG-PET.

Chordoma is an uncommon primary bone tumor and the thoracic spine is the least common of all sites for a chordoma. It may recur despite slow-growing nature. Precise literature review will be performed and possible use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) for detection of both primary and recurrent diagnosis will be discussed. This article presents the case of a 73-year-old male patient who complained of back pain. Magnetic resonance (MR) imaging, computed tomography (CT) and FDG-PET demonstrated thoracic lesion and biopsy revealed chordoma. The patient was operated on and histological findings showed the tumor was chondroid chordoma. He suffered recurrence after 7 months by FDG-PET. He received 6,000 rads radiation therapy and is neurological free but, suffered backache 15 months after initial diagnosis. Only 12 cases including this case were reported precisely and this is the first report of FDG-PET for both initial and recurrent diagnosis of chordoma.

[Successful consecutive seven time's surgical repair of Marfan syndrome].

We report a patient with Marfan syndrome who received successful 7 consecutive operations during 11 years. She underwent descending aortic replacement for chronic type B dissection at the age of 24. Mitral valve replacement (MVR) was performed for mitral regurgitation (MR) at the age of 30, and abdominal aortic replacement was done for persistent dissection at the age of 31, aortic root and arch replacement was done at the age of 34. The 9 months later, she received re-MVR for dysfunction of bioprosthesis and tricuspid valve anuloplasty (TAP) for tricuspid regurgitation (TR). But severe paravalvuler leakage of mitral valve necessitated direct closure of detachment. Thoracoabdominal replacement was performed for rupture of persistent dissection at the age of 35. She was discharged on the 54th day after the 7th surgery.