Direct renal pelvicocystostomy using tube cystoplasty in a cat with ureteral obstruction.

We describe a surgical technique to re-establish urine flow in a 3-year-old Scottish Fold cat. A ureteral stent and subcutaneous urinary bypass failed after their placement due to rapid mineralisation of the lumen. Direct pelvicocystostomy anastomosis using a modified tube cystoplasty technique was performed. A wide rectangular apex-based full-thickness flap was created from the ventral aspect of the urinary bladder, which was sutured longitudinally to form a large-diameter tube. The resulting tube-shaped portion of the bladder was then directly anastomosed to the renal pelvis. No major postoperative complications were observed and no further recurrence of obstruction of the upper urinary tract was noted during follow-up. The cat died at home 481 days postoperatively from an undetermined cause. A pelvicocystostomy technique can be considered as an alternative salvage surgical technique for obstructive ureteral disease in cats.

A new instrument for kinetics and branching ratio studies of gas phase collisional processes at very low temperatures.

A new instrument dedicated to the kinetic study of low-temperature gas phase neutral-neutral reactions, including clustering processes, is presented. It combines a supersonic flow reactor with vacuum ultra-violet synchrotron photoionization time-of-flight mass spectrometry. A photoion-photoelectron coincidence detection scheme has been adopted to optimize the particle counting efficiency. The characteristics of the instrument are detailed along with its capabilities illustrated through a few results obtained at low temperatures (<100 K) including a photoionization spectrum of n-butane, the detection of formic acid dimer formation, and the observation of diacetylene molecules formed by the reaction between the C2H radical and C2H2.

Electronic and spin structures of CaMn4Ox clusters in the S0 state of the oxygen evolving complex of photosystem II. Domain-based local pair natural orbital (DLPNO) coupled-cluster (CC) calculations using optimized geometries and natural orbitals (UNO) by hybrid density functional theory (HDFT) calculations.

Domain-based local pair natural orbital (DLPNO) coupled cluster single and double (CCSD) with triple perturbation (T) correction methods were performed to elucidate the relative stabilities of ten different intermediate structures of the CaMn4Ox cluster in the S0 state of the oxygen evolving complex (OEC) of photosystem II (PSII). Full geometry optimizations of all the S0 intermediates were performed by the UB3LYP-D3/Def2-TZVP methods, providing the assumed geometrical structures and starting natural orbitals (UNO) for DLPNO-CCSD(T)/Def2TZVP calculations. The effective exchange integrals (J) for the spin Hamiltonian models for the ten intermediates were obtained by the UB3LYP/Def2-TZVP calculations followed by the general spin projections. DLPNO-CCSD(T) calculations followed by the CBS extrapolation procedure elucidated that the (II, III, IV, IV) and (III, III, III, IV) valence states in the CaMn4O5 cluster of the OEC of the PS II were nearly degenerated in energy in the S0 state, indicating an important role of dynamical electron correlation effects for the valence and spin fluctuations in strongly correlated electron systems (SCESs) consisting of 3d transition metals.

The suppressive effect on CD4 T cell alloresponse against endothelial HLA-DR via PD-L1 induced by anti-A/B ligation.

While donor-specific human leukocyte antigen (HLA) antibodies are a frequent cause for chronic antibody-mediated rejection in organ transplantation, this is not the case for antibodies targeting blood group antigens, as ABO-incompatible (ABO-I) organ transplantation has been associated with a favorable graft outcome. Here, we explored the role of CD4 T cell-mediated alloresponses against endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A/B antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative response was enhanced in the presence of anti-HLA class I, but attenuated in the presence of anti-A/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) increased in response to anti-A/B ligation-mediated extracellular signal-regulated kinase (ERK) inactivation in endothelial cells that were detected even in the presence of interferon-γ stimulation. Anti-PD-1 antibody enhanced CD4 T cell proliferation, and blocked the suppressive effect of the anti-A/B antibodies. Educated CD25+ CD127- regulatory T cells (edu.Tregs ) were more effective at preventing CD4 T cell alloresponses to endothelial cells compared with naive Treg ; anti-A/B antibodies were not involved in the Treg -mediated events. Finally, amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical/compatible transplants. Taken together, our findings identified a possible factor that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.

Direct frequency comb measurement of OD + CO → DOCO kinetics.

The kinetics of the hydroxyl radical (OH) + carbon monoxide (CO) reaction, which is fundamental to both atmospheric and combustion chemistry, are complex because of the formation of the hydrocarboxyl radical (HOCO) intermediate. Despite extensive studies of this reaction, HOCO has not been observed under thermal reaction conditions. Exploiting the sensitive, broadband, and high-resolution capabilities of time-resolved cavity-enhanced direct frequency comb spectroscopy, we observed deuteroxyl radical (OD) + CO reaction kinetics and detected stabilized trans-DOCO, the deuterated analog of trans-HOCO. By simultaneously measuring the time-dependent concentrations of the trans-DOCO and OD species, we observed unambiguous low-pressure termolecular dependence of the reaction rate coefficients for N2 and CO bath gases. These results confirm the HOCO formation mechanism and quantify its yield.

Carnosol Is a Potent Lung Protective Agent: Experimental Study on Mice.

INTRODUCTION: Oxidative stress has been implicated in various disease states and ischemia/reperfusion injury is a direct consequence of oxidative stress in lung transplantation. Because the success rate of organ transplantation in which ischemia/reperfusion is inevitable is highly influenced by oxidative stress, development of strategies to control oxidative stress would be beneficial. Here we identified natural compounds to reduce oxidative stresses in isolated mouse lungs. METHODS: We screened compounds associated with antioxidative stress in 200 plant extracts by monitoring the activities of nuclear factor erythroid 2-related factor 2 (NRF2). Compounds found to ameliorate antioxidative stress were enriched and mice were administered the extract orally every day for 1 week. Then, the lungs were isolated and cultured in the culture medium at 37 °C. Lung damage was monitored by lactate dehydrogenase (LDH) released in the culture medium. Arterial (left ventricle) blood gas levels were also monitored after hilar clamping. RESULTS: We found that Callicarpa longissima extract was rich in NRF2 activators. The responsible compounds were carnosic acid and its oxidative product, carnosol. Carnosol induced heme-oxygenase 1 (HO-1) expression, which is downstream of NRF2, more efficiently than carnosic acid. CONCLUSIONS: Lungs from mice treated with C longissima extract were less damaged than those from control mice and accompanied by HO-1 induction. These results suggest that carnosol is a candidate compound to increase the success rate of lung transplantation.

Lung Transplantation for Lymphangioleiomyomatosis in a Single Japanese Institute, With a Focus on Late-onset Complications.

BACKGROUND: Although late-onset complications are important factors related to inadequate outcomes of lung transplantation (LTx), little is known about them. The results of LTx for lymphangioleiomyomatosis (LAM) patients, which is a large cohort of LTx recipients in Japan, especially with late-onset complications, are reported. METHODS: Thirteen consecutive LTx cases with LAM at our institute were evaluated, and those with late-onset complications were identified. RESULTS: The 5-year survival rate was 69.2%. There were 4 cases with late-onset complications. Case 1: A 35-year-old woman who underwent right single LTx and sustained uncontrollable massive chylous ascites. She underwent placement of a peritoneal-venous shunt, and the ascites was controlled. Unfortunately, she died of small cell cervical cancer (SCCC) 43 months after the LTx. Case 2: A 50-year-old woman who underwent left single LTx had pneumothorax of the native lung 16 months after the LTx. She underwent operative repair of the right lung with a polyglycolic acid (PGA) sheet. She had no recurrence of pneumothorax 1 year after the operation. Case 3: A 33-year-old woman, who underwent left single LTx, had recurrence of LAM in the transplanted lung 2 years after the LTx. She was started on sirolimus. Case 4: A 47-year-old woman, who underwent right single LTx, developed repeated high fevers. She developed an acute abdomen, and swollen subcutaneous lymph nodes were found. After lymph node biopsy, she was diagnosed as having post-transplant lymphoproliferative disorder, and she died 8 months after the LTx. CONCLUSION: It is hoped that these reports and the knowledge gained from them help improve the outcomes of LTx recipients.

Results of surveillance bronchoscopy after cadaveric lung transplantation: a Japanese single-institution study.

BACKGROUND: The prevention and early detection of post-transplantation rejection and infection are key clinical points to achieve long-term survival after lung transplantation. Although surveillance bronchoscopy (SB) is performed in many transplantation centers, it is still controversial because of its undefined clinical significance and its possible complications. We evaluated the clinical utility of SB after cadaveric lung transplantation in Japan, where bilateral transplantation is officially limited to patients medically requiring bilateral grafts. PATIENTS AND METHODS: Twenty-eight patients who underwent cadaveric lung transplantation followed by SB were retrospectively analyzed with reference to the results of bronchoscopy. SB is routinely performed at 1, 2, 3, 6, and 12 months after lung transplantation and annually thereafter. Clinically indicated bronchoscopy (CIB) is considered in patients with suspected rejection or airway infection, and for follow-up examination after treatment for acute rejection. RESULTS: There were 206 bronchoscopies, including 189 SBs and 17 CIBs, performed in 28 patients who underwent cadaveric lung transplantation between 2000 and 2013 at Osaka University Hospital. Among SBs, 92 (49%) showed positive results of transbronchial lung biopsy (TBLB) or bronchoalveolar lavage (BAL), and intervention was applied following 34 SBs (18%). Among CIBs, 8 (47%) showed positive results of TBLB or BAL, with intervention performed in 3 patients (18%). A2-3 and B2R findings according to the revised International Society for Heart and Lung Transplantation (ISHLT) rejection score and airway infection/colonization were frequently observed within a year following lung transplantation. Cytomegalovirus infection was found in 7 SBs (6%) by TBLB only within 2 months after transplantation. Regarding complications, moderate bleeding occurred in 21 (11%), pneumothorax in 2 (1%), prolonged hypoxemia in 1 (0.5%), and pneumonia in 1 (0.5%) among the 189 SBs. CONCLUSION: SB frequently detects rejection and airway infection or colonization with minimum complications, especially within 12 months after cadaveric lung transplantation.

Comparative analysis of mRNA expression of surface antigens between histiocytic and nonhistiocytic sarcoma in dogs.

BACKGROUND: Definitive diagnosis of histiocytic sarcoma (HS) in dogs is relatively difficult by conventional histopathological examination because objective features of HS are not well defined. HYPOTHESIS: Quantitative analysis of mRNA expression of selected cellular surface antigens (SAs) specific to HS in dogs can facilitate objective and rapid diagnosis. ANIMALS: Dogs with HS (n = 30) and dogs without HS (n = 36), including those with other forms of lymphoma (n = 4), inflammatory diseases (n = 6), and other malignant neoplasias (n = 26). METHODS: Retrospective clinical observational study. Specimens were collected by excisional biopsy, needle core biopsy, or fine needle aspiration. To determine HS detection efficacy, mRNA expression levels of selected SAs specific to HS in dogs, including MHC class IIα, CD11b, CD11c, and CD86, were quantitatively analyzed using real-time quantitative polymerase chain reaction. RESULTS: Each SA mRNA expression level was significantly higher in HS dogs than in non-HS dogs (P = .0082). Cutoff values for discriminating between HS and non-HS dogs based on these expression levels were calculated on the basis of receiver-operating characteristic analysis. Accuracy of the cutoff values, including MHC class IIα, CD11b, CD11c, and CD86, was 87.9, 86.4, 86.4, and 84.8%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest that quantitative analysis of mRNA expression of the selected SAs could be an adjunctive diagnostic technique with high diagnostic accuracy for HS in dogs. Substantial investigation is required for exclusion of diseases with similar cell types of origin to lymphoma.

Temporary regression of locally invasive polypoid rhinosinusitis in a dog after photodynamic therapy.

A 5-year-old male cross-breed dog with chronic rhinosinusitis was presented. Computed tomography (CT) revealed opacities consistent with soft tissue or fluid in the left nasal cavity and frontal sinus. A diagnosis of chronic rhinosinusitis with myxomatous polyps was based on the histology of biopsy samples, so prednisolone treatment was administered for 1 month. Although the clinical signs slightly improved, no changes were observed on the CT images. At 8 months after the initial presentation, the dog was treated with antivascular photodynamic therapy (PDT) using benzoporphyrin derivative monoacid ring A and, 11 days later, CT revealed remarkably decreased soft tissue opacity; the facial swelling and sneezing also resolved. Three additional sessions of PDT were performed at 114, 210, and 303 days after the first PDT because of recurrence of clinical signs. The disease was well controlled for approximately 10 months by antivascular PDT.

[General thoracic surgery for patients with coronary artery or aortic disease].

The incidence of thoracic surgery for patients with arteriosclerosis has increased with the aging of society. Pulmonary resection is generally indicated for patients with coronary artery or aortic disease, following careful preoperative evaluations of cardiopulmonary function and oncological resectability. When preoperative coronary revascularization is required, percutaneous coronary intervention with a bare metal stent might be effective, due to the intermission of antiplatelet therapy during surgery. Furthermore, a" non-dissecting" technique that preserves mediastinal adhesion and divides the lung parenchyma is an option for pulmonary resection in patients who previously underwent coronary arterial bypass grafting (CABG) using the ipsilateral internal thoracic artery. Perioperative analgesic management with epidural anesthesia is quite important to stabilize hemodynamics and avoid the use of nonsteroidal anti-inflammatory drugs, which may influence potential renal dysfunction. Postoperative arterial fibrillation, which reduces blood flow in the coronary artery with low cardiac output, can be predicted based on preoperative serum brain natriuretic peptide level, and prevented by prophylactic atrial natriuretic peptide infusion and immediately controlled with an ultrashort-acting beta-blocker. Thus, special attention is required for surgical interventions that include pulmonary resection in patients with coronary artery or aortic disease.

Peritoneovenous shunt for chylous ascites after lung transplantation for lymphangioleiomyomatosis.

A 37-year-old woman with lymphangioleiomyomatosis (LAM) who underwent right single-lung transplantation from a cadaveric donor developed persistent chylous ascites. Despite use of diuretics and sirolimus to reduce ascites-associated symptoms and to prevent gastroesophageal reflex triggered by increased abdominal pressure, the ascites were refractory, and periodic paracenteses were required. With placement of a peritoneovenous shunt (Denver shunt), the patient's abdominal circumference decreased, and her symptoms abated. Thus, placement of a peritoneovenous shunt can be an effective management strategy for refractory chylous ascites in patients with LAM, even after lung transplantation.

Immunology mini-review: the basics of T(H)17 and interleukin-6 in transplantation.

The outcomes of organ transplantation are determined by graft rejection, the mechanisms of which are some of the most important areas of study in the transplantation field. The main cause of rejection is the immunologic response of the recipient toward the transplanted organ. The immunologic responses are regulated by T-cell subsets, especially helper T-cells, which have been characterized as T(H)1 or T(H)2 cells according to their profiles of cytokines production. A unique subset of recently identified lymphocytes, the regulatory T cells (T(reg)s), seem to play a role in tolerance. The recently identified T(H)17 cells are a subset of effector-helper lymphocytes that specifically secrete interleukin (IL) 17. Interestingly, T(H)17 and T(reg) both develop from naïve T cells on stimulation by transforming growth factor ß. The difference is only the existence of IL-6, a proinflammatory cytokine. T(H)17 clears pathogens that are not adequately handled by T(H)1 and T(H)2 elements, as well as contributing to autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory diseases. Autoimmune diseases are caused by reactions to self-antigens. T(H)17 (or IL-17) and IL-6 are also thought to be involved in rejection after organ transplantation. We examined the contributions of T(H)17 and IL-6 in bronchiolitis obliterans (BO), the histologic finding in chronic rejection of lung transplantations. Earlier studies have reported that T(H)17 and IL-6 contribute not only to chronic rejection of lung transplantations, but also to the rejection of other solid organs, e.g., heart, liver, and kidney. In addition, prospective avenues of research on T(H)17 and IL-6 in transplantation have emerged from the perspectives of recent studies.

Diminished regulatory T cells in cutaneous lesions of thymoma-associated multi-organ autoimmunity: a newly described paraneoplastic autoimmune disorder with fatal clinical course.

Thymoma-associated multi-organ autoimmunity is a rare, autoimmune disease that causes colitis, liver dysfunction and cutaneous graft-versus-host (GVH)-like skin damage. This paraneoplastic autoimmune disorder may be due to inadequate T cell selection in the tumour environment of the thymus. Although sporadic case reports have revealed its clinical features, little is known about its pathological mechanism. By comparing the skin-infiltrating T cell subsets with those of GVH disease (GVHD) and other inflammatory skin diseases, we sought to elucidate the pathological mechanism of thymoma-associated multi-organ autoimmunity. Histopathological and immunohistochemical analysis of skin biopsies was performed for three patients with thymoma-associated multi-organ autoimmunity. Histopathological findings of thymoma-associated multi-organ autoimmunity were indistinguishable from those of patients with acute GVHD, although the aetiologies of these diseases are completely different. The frequency of regulatory T cells (T(regs)) is reduced in cutaneous lesions and CD8+ cytotoxic T lymphocytes that massively infiltrate into the epidermis of patients with thymoma-associated multi-organ autoimmunity. Additionally, the ratio of T helper type 17 (Th17) cells to CD4+ cells in patients with thymoma-associated multi-organ autoimmunity and acute GVHD was higher than that in healthy controls, but similar to that in psoriasis vulgaris patients. Similarity of the skin-infiltrating T cell subsets with those of acute GVHD suggested that skin damage in patients with thymoma-associated multi-organ autoimmunity might be induced by self-reactive cytotoxic T lymphocytes under the diminished suppressive capacity of T(regs).

Conjoined twins pregnancies: experience with 36 cases from a single center.

OBJECTIVE: To review a single center's experience in the management of twin pregnancies with conjoined fetuses. METHODS: Retrospective study describing prenatal findings, delivery details, surgical treatment and perinatal outcome. RESULTS: The study included 36 twin pregnancies with conjoined twins seen over a period of 12 years in a single tertiary hospital: 69.4% were thoracopagus, 13.9% parapagus, 8.3% omphaloischiopagus 5.6% omphalopagus and 2.8% cephalopagus. Cardiac defects were present in 91.6% of twin pairs and associated malformations were present in 61.8% of the cases: limb abnormalities in 36.1%, abdominal wall defects in 25.0%, cleft lip and/or palate in 13.9% and congenital diaphragmatic hernia in 5.5%. Surgical separation was considered not feasible and prognosis lethal in 30 (83.3%) cases. Termination of pregnancy was performed in 12 pregnancies of poor prognosis. Cesarean section was performed in all remaining cases. Five sets of twins underwent surgical separation and six children survived. Overall survival in our series was 8.3% and, among the livebirths, 13.6%. CONCLUSION: Conjoined twin pregnancies should be referred to tertiary centers for detailed fetal anomaly and echocardiographic assessment to evaluate prognosis and determine the possibility of postnatal surgical separation.

Evaluation of a simple loop-mediated isothermal amplification test kit for the diagnosis of tuberculosis.

OBJECTIVE: A new loop-mediated isothermal amplification (LAMP) test kit, including a simple DNA extraction device for the detection of Mycobacterium tuberculosis complex, was developed for commercial use and evaluated for its usefulness in diagnosing tuberculosis (TB). DESIGN: The LAMP test was performed using untreated and N-acetyl-L-cysteine (NALC) NaOH-treated sputum specimen. The efficiency of the kit was compared with other conventional laboratory examinations, including other nucleic acid amplification (NAA) tests. RESULTS: The sensitivity of LAMP using raw sputum (direct LAMP) in smear- and culture-positive specimens was 98.2% (95%CI 94.9-99.4), while the sensitivity in smear-negative, culture-positive specimens was 55.6% (95%CI 43.4-68.0). The diagnostic sensitivity of direct LAMP for the diagnosis of individuals with TB was 88.2% (95%CI 81.4-92.7). The sensitivity values of direct LAMP were slightly, but not statistically significantly lower than those of Cobas Amplicor MTB and TRC Rapid MTB, while the sensitivity of the LAMP test using NALC-NaOH treated sputum was significantly lower than other NAA tests (P < 0.05) for smear-negative, culture-positive specimens. The new commercial version of the LAMP kit was easy to handle and yielded results within 1 h of receiving sputum specimens. CONCLUSIONS: This test is considered a promising diagnostic tool for TB, even for peripheral laboratories with limited equipment, such as those in developing countries.

Less maintenance immunosuppression in lung transplantation following hematopoietic stem cell transplantation from the same living donor.

Living-donor lobar lung transplantation (LDLLT) is one of the final options for saving patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). We retrospectively investigated 19 patients who had undergone LDLLT after HSCT in Japan. Eight patients underwent LDLLT after HSCT in which one of the donors was the same living donor as in HSCT (SD group), while 11 received LDLLT from relatives who were not the HSCT donors (non-SD group). In the SD group, three patients underwent single LDLLT. The 5-year survival rate was 100% and 58% in the SD and non-SD groups, respectively. In the SD group, postoperative immunosuppression was significantly lower than in the non-SD group. Two patients died of infection and one died of post-transplant lymphoproliferative disease (PTLD) in the non-SD group, while only one patient died of PTLD 7 years after LDLLT in the SD group. Hematologic malignancy relapsed in two patients in the non-SD group. For the three single LDLLTs in the SD group, immunosuppression was carefully tapered. In our study, LDLLT involving the same donor as for HSCT appeared to have advantages related to lower immunosuppression compared to LDLLT from relatives who were not the HSCT donors.

MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways.

The tyrosine kinase c-Src is upregulated in various human cancers, but the molecular mechanisms underlying c-Src-mediated tumor growth remain unclear. Here we examined the involvement of microRNAs in the c-Src-mediated tumor growth. Microarray profiling revealed that c-Src activation downregulates a limited set of microRNAs, including miR-99a, which targets oncogenic mammalian target of rapamycin (mTOR) and fibroblast growth factor receptor 3 (FGFR3). Re-expression of miR-99a suppressed tumor growth of c-Src-transformed cells, and this effect was restored by the overexpression of mTOR. The downregulation of miR-99a was also observed in epidermal growth factor- and Ras-transformed cells, and it was suppressed by inhibiting the mitogen-activated protein kinase (MAPK) pathway. Furthermore, miR-99a downregulation is associated with mTOR/FGFR3 upregulation in various human lung cancer cells/tissues. The tumorigenicity of these cells was suppressed by the introduction of miR-99a. These findings suggest that the miR-99a-mTOR/FGFR3 pathway is crucial for controlling tumor growth in a wide range of human cancers that harbor upregulation of the Src-related oncogenic pathways.