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Sepsis-induced cardiomyopathy (SICM) is one of the leading indicators for poor prognosis associated with sepsis. Despite its reversibility, prognosis varies widely among patients. Mitochondria play a key role in cellular energy production by generating adenosine triphosphate (ATP), which is vital for myocardial energy metabolism. Over recent years, mounting evidence suggests that severe sepsis not only triggers mitochondrial structural abnormalities such as apoptosis, incomplete autophagy, and mitophagy in cardiomyocytes but also compromises their function, leading to ATP depletion. This metabolic disruption is recognized as a significant contributor to SICM, yet effective treatment options remain elusive. Sepsis cannot be effectively treated with inotropic drugs in failing myocardium due to excessive inflammatory factors that blunt β-adrenergic receptors. This review will share the recent knowledge on myocardial cell death in sepsis and its molecular mechanisms, focusing on the role of mitochondria as an important metabolic regulator of SICM, and discuss the potential for developing therapies for sepsis-induced myocardial injury. [ABSTRACT FROM AUTHOR]

Three kinds of bis(aromatic fluoride) compounds, 3,5-bis(4-fluorobenzoyl)biphenyl (1), 3,5-bis(4-fluorobenzoyl)-1,1′:4′,1″-terphenyl (2), and 3,5-bis(4-fluorobenzoyl)-1,1′:4′,1″:4″,1′′′-quaterphenyl (3), were synthesized by cross-coupling of the corresponding triflates with phenylboronic acid. Linear poly(ether ketone)s (1x, 2x, and 3x) having phenyl, biphenyl, and terphenyl side groups, respectively, were prepared by the polycondensation of the bis(aromatic fluoride) compounds with bisphenol A (a) and 4,4′-dihydroxybiphenyl (b) in N-methyl-2-pyrrolidone. The obtained poly(ether ketone)s were characterized by X-ray diffraction, differential scanning calorimetry, and thermogravimetry. The structure–property relationships of these poly(ether ketone)s were examined and compared with those of poly(ether ketone)s (4x) having no side group, which were prepared from 3,5-bis(4-fluorobenzoyl)benzene (4). The properties of the poly(ether ketone)s, solubilities, and thermal properties were compared and discussed based on the length of the side groups. [ABSTRACT FROM AUTHOR]

In this study, we consider the Kondo temperature and differential conductance for an Aharonov-Bohm ring with an embedded quantum dot connected with noncollinear ferromagnetic leads. Starting from the tight-binding model, we propose an equivalent Anderson model, in which the density of states depends on the Aharonov-Bohm phase. By applying the poor man's scaling approach to the Hamiltonian, we derive the dependences of the Kondo temperature and differential conductance on the Aharonov-Bohm phase, spin polarization, angle of magnetic moment, and asymmetry parameters. We show conditions for the nonmonotonic behavior of the differential conductance in terms of the spin splitting and Aharonov-Bohm phase. In addition, by extending the model to the case of a finite ring size, we show that the Kondo temperature crucially depends on ring size, but the properties of the scaled temperature are similar to ones for the small ring-size limit. [ABSTRACT FROM AUTHOR]

Background: Dedifferentiated chondrosarcoma remains a significant therapeutic challenge. Studies performed to date have not identified efficacious chemotherapy regimens for this disease. Questions/purposes: We sought to (1) evaluate the disease-specific survival at 2 and 5 years of patients with dedifferentiated chondrosarcoma; (2) assess the prognostic variables (both patient- and treatment-related), including the use of chemotherapy with ifosfamide, that relate to survivorship; and (3) assess specific toxicities associated with ifosfamide use. Methods: Data from 41 patients with dedifferentiated chondrosarcoma diagnosed and treated at the University of Texas MD Anderson Cancer Center from 1986 to 2010 were analyzed for demographics, treatments, oncologic outcomes, and prognostic variables. There were 14 women and 27 men. The mean age at diagnosis was 58 years (range, 26-86 years). Seven patients presented with metastasis. Surgical resection alone was performed in 11 patients; resection and chemotherapy in 26 patients; resection and radiotherapy in two patients; and resection, chemotherapy, and radiotherapy in two patients. Ifosfamide-based regimens were used for 16 patients. In general, ifosfamide was used when the tumor was located in the trunk or if cisplatin was discontinued as a result of toxicity. Minimum followup was 8 months (median, 68 months; range, 8-281 months). Survival was estimated using Kaplan-Meier plots and analyzed by using the Cox proportional hazards model. Results: Disease-specific survival rates at 2 and 5 years were 33% and 15%, respectively. Multivariate analysis revealed that treatment without ifosfamide-based chemotherapy was the only independent negative prognostic factor for disease-specific survival (hazard ratio, 0.4; 95% confidence interval, 0.17-0.92; p = 0.03). Ifosfamide was discontinued in a patient as a result of renal dysfunction and was decreased in dose in another patient who developed encephalopathy. Conclusions: In this small retrospective study, it appeared that ifosfamide-based adjuvant chemotherapy combined with surgical resection offered a treatment advantage compared with patients who did not receive the drug in patients with dedifferentiated chondrosarcoma, although disease-specific survival for patients who have this rare tumor remains dismal. Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal chondrosarcoma (MSC) is a rare variant of chondrosarcoma. Because of the rarity of the disease, most studies only contain a small number of patients and thus the prognostic variables and role of adjuvant therapies remain controversial. Questions/purposes: We therefore asked (1) what the overall and disease-free survival were for patients with this diagnosis at 5 and 10 years; (2) whether there were significant prognostic factors associated with survival; and (3) whether use of adjuvant chemotherapy or radiotherapy was associated with survival in patients with MSC. Methods: We retrospectively reviewed the cases of MSC diagnosed from 1979 to 2010 at one referral center. Forty-three cases were identified. Thirty-seven cases were analyzed for demographics, treatments, and outcomes. Thirty patients with localized disease were analyzed for prognostic factors. The minimum followup was 1 month (mean, 6 years; range, 1 month to 17 years). There were 17 females and 20 males. The mean age at diagnosis was 33 years (range, 11-65 years). Nineteen cases were skeletal and 18 cases were extraskeletal. Seventy-six percent of the tumors were located in the trunk. Results: Five- and 10-year overall survival was 51% and 37%, respectively. Five- and 10-year disease-free survival was 23% and 5%, respectively. Age (< 30 years) and male sex were associated with poorer overall and disease-free survival in patients presenting with a localized tumor, respectively. Patients who did not receive radiotherapy were more likely to have a local recurrence. Adjuvant chemotherapy failed to show a significant association with overall, disease-free, metastasis-free, or local recurrence-free survival. Conclusions: The present study reinforced the role of adjuvant radiotherapy for local tumor control. Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Introduction: The differences in the d-dimer rise between women with singleton and multifetal pregnancies have not been studied extensively. Materials and Methods: d-Dimer levels were determined in 1089 blood specimens from 1089 women in various stages of pregnancy, including 977 and 112 women with singleton and multifetal pregnancies, respectively. None of the 1089 women developed hypertension or clinical venous thromboembolism during pregnancy or in the postpartum period. Results: The d-dimer levels were significantly and positively correlated with gestational week at examination in women with singleton or multifetal pregnancies. The d-dimer levels (μg/ml, mean±SD [number of specimens]) determined at the 1st trimester did not differ significantly (0.81±0.82 [102] for singleton vs. 1.20±0.77 [7] for multifetal), but those at the 2nd (1.61±1.45 [216] vs. 2.62±2.26 [59]) and 3rd (2.37±2.22 [659] vs. 4.02±2.14 [46]) trimesters were significantly higher in women with multifetal than singleton pregnancies. The 90th percentile value was 4.31μg/ml for 1089 specimens. A significantly greater number of women exceeded 4.31μg/ml during the 2nd (16.9% vs. 5.6%, P =0.0043) and 3rd (34.8% vs. 10.6%, P <0.0001) trimesters among those with multifetal than with singleton pregnancies. Conclusions: The degree of d-dimer rise in pregnancy was greater in women with multifetal than with singleton pregnancies. [ABSTRACT FROM AUTHOR]

To determine the role of percutaneous vertebroplasty (PVP) in bone formation and the union of vertebral pseudarthrosis, we analyzed 14 patients with an average follow-up duration of 21 months. Evaluation methods included back pain (visual analog scale: VAS), wedge angle, dynamic mobility, radiographic remodeling including callus and spur formation, and union status. The Student's t test was used for statistical analysis and a probability of less than 0.05 was determined as a significant difference. Back pain improved in all 14 patients with a VAS score of 57.8 ± 23.5 mm (average ± standard deviation) preoperatively and 14.7 ± 16.4 mm at the final follow-up ( P < 0.001). The wedge angle decreased from 21.6° ± 8.3° (average ± standard deviation) preoperatively to 13.2° ± 6.9° at the final follow-up ( P < 0.001). Callus formation was seen in four patients. Bony spurs were seen in the affected vertebra in preoperative radiographs in all patients, and were further developed to a solidified form during follow up after PVP. Dynamic mobility of the affected vertebrae was 6.9 ± 2.9 mm preoperatively, which decreased to 1.1° ± 0.7° at the final follow-up ( P < 0.001). Notably, all patients showed the dynamic vertebral mobility of 2 mm or less. Nevertheless, only two patients exhibited the dynamic vertebral mobility of 0 mm at the final follow-up, which is referred to as bone union. These findings indicate that PVP serves as a mechanical stabilizer for vertebral pseudarthrosis, which leads to immediate pain relief and segmental bony responses. [ABSTRACT FROM AUTHOR]

The article presents a study on gene expression of dorsal root ganglion (DRG) neurons using a cDNA microarray in Sprague-Dawley rats with nerve root constriction. Distinct gene expression profiles were found using the cluster analysis method while upregulated gene categories were revealed through functional categorization. Other methods used include RNA preparation and labeling, hybridization to cDNA microarrays and data analysis, and real-time quantitative polymerase chain reaction (PCR).

Abstract: The first total synthesis of pelargonidin 3-O-6″-O-acetyl-β-d-glucopyranoside, an acylated anthocyanin of magenta-colored Verbena flowers, was successfully carried out. The key intermediate, protected kaemferol 3-O-glucoside, was constructed by the Baker–Venkataraman rearrangement from a glucosyloxyacetophenone followed by Zn–Hg reduction to the corresponding acylated anthocyanin. [Copyright &y& Elsevier]

Obstruction of the endograft limb by thrombosis has often been reported and may cause fatal complications such as leg necrosis or myonephropathic metabolic syndrome. The purpose of this study was to evaluate endograft antithrombogenicity by indium-111 platelet scintigraphy. Seventeen patients with abdominal aortic aneurysms were treated by endografting. Thirteen patients were treated with conventional open surgery using an artificial graft. The endograft was constructed from a self-expanding Z-shaped stent and woven polyester fabric, Autologous platelets labeled with indium-111 were injected at 2 weeks postoperatively. At 24 hours and 72 hours postinjection, the ratio of scintillation count of the endograft or graft to that of the native artery was calculated to assess platelet deposition. The normalization ratio was calculated as follows: (scintillation count per pixel of endograft or graft/circumference)/(scintillation count per pixel of the native femoral artery). Platelet factor 4 and beta-thromboglobulin were measured to evaluate the systemic platelets activity at 2 weeks postoperatively. There was no significant difference in platelet counts or labeling efficiency between the groups. The ratio was significantly higher in the endografting group than in the open surgery group at 72 hours postinjection (2.5 ±0.7 vs 3.9 ±1.1, P<.001). There was no significant difference in platelet factor 4 and beta-thromboglobulin between the groups. Although there was no difference in systemic platelet activity, endografting was associated with lower antithrombogenicity. It remains unclear whether lower antithrombogenicity causes thromboembolism as a complication of the procedure. The authors recommend the administration of antiplatelet drugs to prevent endograft obstruction in patients with very narrow iliac arteries. [ABSTRACT FROM AUTHOR]

Malignant fibrous histiocytoma (MFH) of the bone is a high-grade sarcoma characterized histologically by the composition of fibroblasts and pleomorphic cells with a prominent storiform pattern. Despite institution of multi-modality treatments, the prognosis for patients with this tumor remains unsatisfactory. In the present study, towards the goal of developing active immunotherapy for those affected, we established four cell lines from a 53-year-old woman who suffered from MFH of the humerus with lymph node metastases. MFH2003 and MFH2003-B7.1 were the primary lesion-derived cell line and its B7.1-transfectant, respectively. B2003-EBV and TIL2003 were a B cell line established from peripheral blood lymphocytes and a T cell line established from tumor-invaded lymph nodes, respectively. MFH2003 cells could be maintained over a period of 1 year in vitro, and could be xenotransplanted into nude mice. The phenotype of cells analyzed by immunostaining was similar to the original tumor. TIL2003 cells were all CD8+ and specifically recognized MFH2003 cells and MFH2003-B7.1 cells, but not B2003-EBV cells. An anti-HLA-class I monoclonal antibody completely blocked the anti-MFH2003 response of TILs2003. These findings indicate the existence of an anti-MFH specific immune response in the microenvironment of metastatic lymph nodes. The present autologous cell lines provide the basis for identification of novel tumor-associated antigens and may be helpful in the establishment of immunotherapy for patients with MFH of the bone. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [ABSTRACT FROM AUTHOR]

Abstract: An amide bond of a terpyridine-appended substrate, 6-(L-phenylalanylamino)-2,2′:6′,2″-terpyridine (2a), was cleaved to yield phenylalanine methyl ester quantitatively in the presence of catalytic amounts of Cu2+ not only in methanol but also in aqueous methanol at 30 °C. The reaction proceeds via formation of an N3O (three terpyridine nitrogens and one carbonyl oxygen) type 1:1 metal complex 2a-Cu2+. From spectral titration, the structure of the 2a-Cu2+ complex was confirmed to have three different protonation states, i.e., A (non-deprotonated amide with α-ammonium), D1 (deprotonated-amide with α-ammonium) and D2 (deprotonated-amide with α-amino) states. Among them, the complex in the D2 state was exclusively responsible for the observed mild, rapid and selective alcoholysis, showing the first-order rate constant of 6×10−3 s−1 or half-decay time of 2 min in methanol at 30 °C. Acidity of the amide proton was found to be higher than that of the ammonium proton in the complex, allowing formation of the highly reactive amide-deprotonated D2 state in methanol even without addition of external bases. Factors contributing to the high reactivity of the complex were discussed. [Copyright &y& Elsevier]

Over the past three decades, there have been remarkable advances in the treatment of bone and soft tissue sarcomas. These include the introduction of adjuvant chemotherapy, establishment of guidelines for adequate surgical margins, and the development of post-excision reconstruction. There have also been advances in the field of immunotherapy against bone and soft tissue sarcomas, which, unfortunately, have received less attention. However, lack of progress in chemotherapybased treatments for bone and soft tissue sarcomas has reignited interest in immunotherapeutic approaches. Here we summarize current progress in the immunotherapy of bone and soft tissue sarcomas including the strategies utilized to identify tumor-associated antigens, and the design of clinical trials. [ABSTRACT FROM AUTHOR]

Background: Synovial sarcoma is a high-grade malignant tumor of soft tissue, characterized by the specific chromosomal translocation t(X;18), and its resultant SYT-SSX fusion gene. Despite intensive multimodality therapy, the majority of metastatic or relapsed diseases still remain incurable, thus suggesting a need for new therapeutic options. We previously demonstrated the antigenicity of SYT-SSX gene-derived peptides by in vitro analyses. The present study was designed to evaluate in vivo immunological property of a SYT-SSX junction peptide in selected patients with synovial sarcoma. Methods: A 9-mer peptide (SYT-SSX B: GYDQIMPKK) spanning the SYT-SSX fusion region was synthesized. Eligible patients were those (i) who have histologically and genetically confirmed, unresectable synovial sarcoma (SYT-SSX1 or SYT-SSX2 positive), (ii) HLA-A*2402 positive, (iii) between 20 and 70 years old, (iv) ECOG performance status between 0 and 3, and (v) who gave informed consent. Vaccinations with SYT-SSX B peptide (0.1 mg or 1.0 mg) were given subcutaneously six times at 14-day intervals. These patients were evaluated for DTH skin test, adverse events, tumor size, tetramer staining, and peptide-specific CTL induction. [ABSTRACT FROM AUTHOR]

We have previously reported that an osteosarcoma vaccine generated by ex vivo transfection of B7-1 cDNA induces protective as well as curative immunity against B7-1–negative parental osteosarcoma. Because establishment of human osteosarcoma cell lines, which is a prerequisite for ex vivo gene transfer, is rarely successful, we, in the present study, investigated the therapeutic efficacy of adenovirus-mediated in vivo B7-1 gene transfer to pre-established primary tumor as well as pulmonary metastasis of osteosarcoma. Adenovirus-mediated rat B7-1 gene transfer induced (a) expression of B7-1 molecules in osteosarcoma cells by both in vitro and in vivo infection procedures, (b) curative immunity against pre-established primary osteosarcoma and, subsequently, hosts gained protection against additional challenge of parental B7-1–negative osteosarcoma cells, (c) systemic immunity against pre-established pulmonary metastasis, and (d) activation of regional lymph node CD4+ T cells, expansion of dendritic cells and natural killer cells and the secretion of interferon-γ. These findings collectively support the therapeutic value of adenovirus-mediated in vivo gene transfer on osteosarcoma, which is of greater simplicity than cell-based B7-1 vaccine, and represent an attractive strategy for therapy of patients with metastatic osteosarcama who acquired resistance to current therapeutic protocols. Cancer Gene Therapy (2002) 9, 747–755 doi:10.1038/sj.cgt.7700491 [ABSTRACT FROM AUTHOR]

Reports on two cases of proximal radioulnar synostosis treated with a free vascularized fascio-fat graft. Post-traumatic case; Congenital disorder; Interference with supination and pronation of the forearm; Prevention of recurrent ankylosis.

A case of peroneal artery injury subsequently developed into a lesion resembling an extra-articular tenosynovial giant cell tumor, which is a type of pigmented villonodular synovitis (PVNS). This case supports the hypothesis that accident trauma, such as a vascular injury, can be the etiology of PVNS. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are sequence-specific inhibitors of post-transcriptional gene expression. However, the physiological functions of these non-coding RNAs in renal interstitial mesenchymal cells remain unclear. To conclusively evaluate the role of miRNAs, we generated conditional knockout (cKO) mice with platelet-derived growth factor receptor-β (PDGFR-β)-specific inactivation of the key miRNA pathway gene Dicer. The cKO mice were subjected to unilateral ureteral ligation, and renal interstitial fibrosis was quantitatively evaluated using real-time polymerase chain reaction and immunofluorescence staining. Compared with control mice, cKO mice had exacerbated interstitial fibrosis exhibited by immunofluorescence staining and mRNA expression of PDGFR-β. A microarray analysis showed decreased expressions of miR-9-5p, miR-344g-3p, and miR-7074-3p in cKO mice compared with those in control mice, suggesting an association with the increased expression of PDGFR-β. An analysis of the signaling pathways showed that the major transcriptional changes in cKO mice were related to smooth muscle cell differentiation, regulation of DNA metabolic processes and the actin cytoskeleton, positive regulation of fibroblast proliferation and Ras protein signal transduction, and focal adhesion-PI3K/Akt/mTOR signaling pathways. Depletion of Dicer in mesenchymal cells may downregulate the signaling pathway related to miR-9-5p, miR-344g-3p, and miR-7074-3p, which can lead to the progression of chronic kidney disease. These findings highlight the possibility for future diagnostic or therapeutic developments for renal fibrosis using miR-9-5p, miR-344g-3p, and miR-7074-3p. [ABSTRACT FROM AUTHOR]

We are concerned with an activator-inhibitor reaction-diffusion system with global coupling effect, which is proposed by Krischer and Mikhailov [Phys. Rev. Lett., 73 (1994), pp. 31653168]. By using the interface-dynamics approach, it is shown that when global coupling inhibition effect is stronger, radially symmetric localized equilibrium solutions are destabilized and there appear travelling wave solutions. When the global coupling effect is sufficiently strong, the collision between two travelling waves is discussed in one and two dimensions. [ABSTRACT FROM AUTHOR]

Background: The cardiac metabolic shift has been observed in failing heart for starvation of the energy. CPT1 is an enzyme which takes a fatty acid into mitochondria and dysfunction of CPT1 reduces myocardial mitochondria function and worsens heart failure.On the other hand, beta-3 adrenergic receptor (B3AR) which induces lipolysis expresses in failing heart. We considered whether β3AR regulation could influence CPT1 function in a septic heart. Methods and Results: We made a heart failure model by intraperitoneal injection of lipopolysaccharide (LPS) of 10 mg/kg into C57Bl/6 mice. We divided these subjects into 3 groups as 1mg/kg of the β3AR agonist CL316243 (CL), 1mg/kg of the β3AR selective antagonist SR59230A (SR) and 200μl of normal saline (NS). Kaplan-Meier analysis showed that 24 hour-survival rate was significantly improved in the SR. (the survival rate was 100% (SR), 60% (NS) and 20% (CL), n=10 of each). Echocardiography revealed decreased LVEF was observed at 6 hours after LPS and gradually restored within 24 hours. LVEF did not reduce in the SR (62.3±9.7%), whereas it got worse in the CL (32.5±6.4%) than that in the NS (47.1±6.2%). Myocardial ATP was preserved in the SR, while it was significantly decreased in the NS and the CL. Quantitative PCR analysis revealed that gene expressions associated with fatty acid oxidation (FAO) and mitochondrial function were improved in the SR; Cpt1 , an enzyme for free fatty acid intake to mitochondria to promote FAO, was upregulated in the SR. In addition, Pgc1α and Errα , which are transcriptional factors associated with mitochondrial biogenesis, were also improved in the SR. In contrast, those expressions were downregulated in the NS and the CL. Oil red o staining and electron microscopy of the septic heart showed that the deposition of lipid droplets which had not been utilized for energy in mitochondria was markedly increased in the CL, but significantly reduced in the SR. These results suggested the β3AR antagonist improved metabolic pathway of FAO and mitochondrial dysfunction. Conclusion: Blockade of the β3AR spared cardiac energy by ameliorating FAO and mitochondrial dysfunction through the improvement of CPT1 expression in a septic heart. The β3 AR is a novel metabolic target for endotoxin-induced heart failure. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We investigated the association between gestational diabetes mellitus (GDM) and perinatal outcomes stratified by pre‐pregnancy body mass index (BMI) and/or gestational weight gain (GWG). Materials and Methods: Data from the national birth cohort in the Japan Environment and Children's Study from 2011 to 2014 (n = 85,228) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The odds ratios (ORs) of perinatal outcomes were compared between women with and those without GDM. Results: The OR (95% confidence interval) of having a small for gestational age infant in the GDM group with a pre‐pregnancy BMI of ≥25.0 kg/m2 and insufficient GWG (<2.75 kg) was 1.78 (1.02–3.12). The OR of having a large for gestational age infant of the same BMI group with excessive GWG (>7.25 kg) was 2.04 (1.56–2.67). The OR of hypertensive disorders of pregnancy was higher in women with a BMI ≥18.5 kg/m2 in the GDM group than in the non‐GDM group. Conclusions: Large for gestational age and hypertensive disorders of pregnancy were associated with pre‐pregnancy BMI and GWG in either normal weight or overweight/obese women, and the relationship was strengthened when GDM was present. Women with GDM and a BMI of ≥25.0 kg/m2 are at risk of having small for gestational age and large for gestational age infants depending on GWG. [ABSTRACT FROM AUTHOR]

Ethanolamine ammonia-lyase (EAL) catalyzes the adenosylcobalamin-dependent conversion of ethanolamine to acetaldehyde and ammonia. 1-OH of the substrate is hydrogen-bonded with Gluα287, Argα160, and Asnα193 and 2-NH2 with Gluα287, Glnα162, and Aspα362. The active site somewhat resembles that of diol dehydratase. All five residues were important for the high-affinity binding of the substrate and for catalysis. The -COO- group at residue α287 was absolutely required for activity and coenzyme Co-C bond cleavage, and there was a spatially optimal position for it, suggesting that Gluα287 contributes to Co-C bond homolysis, stabilizes the transition state for the migration of NH2 from C2 to C1 through partial deprotonation of spectator OH, and functions as a base in the elimination of ammonia. A positive charge and/or the hydrogen bond at position α160 and the hydrogen bonds at positions α162 and α193 with the substrate are important for catalysis and for preventing a radical intermediate from undergoing side reactions. Argα160 would stabilize the trigonal transition state in NH2 migration by electrostatic catalysis and hydrogen bonding with spectator OH, Asnα193 would contribute to maintaining the appropriate position and direction of the guanidinium group of Argα160, as well. Hydrogen bond acceptors were necessary at position α162, but hydrogen bond donors were rather harmful. Glnα162 might stabilize the trigonal transition state by accepting a hydrogen bond from migrating NH3+. The activity was very sensitive to the position of-COO- at α362. Aspα362 would assist Co-C bond homolysis indirecdy and stabilize the trigonal transition state by accepting a hydrogen bond from migrating NH3+ and electrostatic interaction. [ABSTRACT FROM AUTHOR]

Pyogenic spondylitis can be life-threatening for elderly patients. To discuss the characteristics of the disease in the elderly, medical records of 103 consecutive cases of pyogenic spondylitis were reviewed. Of these, 45 cases were 65 years of age or older, and these 45 cases were enrolled into further study. In this study, the proportion of elderly patients among the total number with pyogenic spondylitis was 43.7%, and this figure has increased with the passing of time as follows: 37.5% (1988-1993), 44.4% (1994-1999), and 55.5% (2000-2005). The microorganisms were isolated in 16 cases: Staphylococcus aureus in 13 cases (including methicillin-resistant Staphylococcus aureus in nine) and others in three. Twenty-five patients had associated diseases: diabetes in 18 patients and malignant tumors in seven. Thirty patients were treated conservatively, and 15 patients underwent surgery. Twenty-six patients had paralysis. All 15 patients treated surgically, and eight of the 11 patients treated conservatively showed improvement in paralysis. Bone union was achieved in all cases except one. Our results indicate that a good outcome can be expected from conservative treatment in elderly patients as well as the young. [ABSTRACT FROM AUTHOR]

Towards the goal of identifying tumor-rejection antigens on eradicated tumors in bone and soft tissue sarcomas, we evaluated the immune response against antigens presented by lost HLA class I molecules. Tumor specimens and peripheral blood samples were obtained from a 70-year-old woman with pleomorphic malignant fibrous histiocytoma. Over 1-year culture, a tumor cell line (MFH2004) was established. A B-cell line infected with Epstein-Barr virus (B2004-EBV) was developed from the blood samples. HLA genotypes of B2004-EBVcells were A*0206/2402, B*4006/4601, and C*0102/0801, whereas MFH2004 cells were defective for A*0206, B*4006, and C*0102. Loss of HLA-A2 expression was also proved immunohistochemically in the primary tumor tissues. Lost HLA-A2 in MFH2004 cells was retrieved by transfection of HLA-A*0206 cDNA to develop MFH2004-A2. Attempts to induce CTLs by mixed culture with autologous T cells and MFH2004 cells resulted in failure. In contrast, those with MFH2004-A2 induced CTL clones CTL2004-c6 and CTL2004-c17. These CTL clones specifically killed MFH2004-A2 but not MFH2004 or B2004-EBV in an HLA-A2-restricted manner. These findings suggest that CTL2004-c6 and CTL2004-c17 recognize autologous tumor-rejection antigens presented by HLA-A*0206, which may have been expressed by tumor cells that had been eradicated by the host's immunosurveillance system. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:271-278, 2008 [ABSTRACT FROM AUTHOR]

To stratify perioperative cardiac risk for endovascular surgery, pharmacologic stress single-photon emission computed tomography (SPECT) was performed in 206 patients. Of 8 patients who had cardiac events, 7 occurred in 67 patients with positive SPECT results, whereas only 1 occurred in 139 patients with negative SPECT results (7 of 67 vs 1 of 139, p &#60;0.002). Furthermore, a scintigraphic marker of a summed stress score ≥14 was the most important factor identifying patients who subsequently had cardiac events by multivariate analysis. [Copyright &y& Elsevier]

Aim: We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high‐risk pregnant women. Methods: Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age‐specific PPV and NPV were estimated. Results: Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78–99.96), 99.12% (95% CI: 96.83–99.76), and 100% (95% CI: 88.30–100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age‐specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. Conclusion: The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high‐risk pregnant women, and maternal age‐specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan. [ABSTRACT FROM AUTHOR]

: PurposeTo report the effect of high-dose intravenous corticosteroid pulse therapy with and without orbital radiotherapy on Graves’ ophthalmopathy.: DesignNonrandomized clinical trial.: MethodsWe selected 39 Japanese patients (age range, 22–64 years; mean, 48 years; 31 women, 8 men) who had active Graves’ ophthalmopathy among 195 consecutive patients. In the first 20 patients, high-dose intravenous methylprednisolone pulse therapy (1 g per day for 3 successive days, repeated 3 times within 3 weeks) followed by 24-Gy orbital radiotherapy was performed. In the other 19 of the 39 patients, high-dose intravenous methylprednisolone pulse therapy without orbital radiotherapy was performed. Coronal computed tomography (CT) of the orbit and exophthalmometry were performed before the corticosteroid pulse therapy, and 1 and 6 months after the corticosteroid pulse therapy. The maximum coronal section area of the most hypertrophic rectus muscle in each eye was measured based on orbital CT imaging.: ResultsClinical findings at study entry were not significantly different between the two groups. No significant difference was found in the maximum coronal section area of the most hypertrophic rectus muscle and the results of exophthalmometry measurements in both groups before the therapy. Extraocular muscle hypertrophy was significantly reduced 1 month and 6 months after the therapy (P < .01) in both groups. However, no beneficial therapeutic effect on proptosis was observed in either group at 1 month and 6 months after the therapy. No significant difference in the therapeutic effect on extraocular muscle hypertrophy and proptosis was found between the two groups.: ConclusionsOrbital irradiation after corticosteroid pulse therapy had no beneficial therapeutic effects on rectus muscle hypertrophy or proptosis of active Graves’ ophthalmopathy during the 6-month follow-up period. [Copyright &y& Elsevier]

Although gestational hypertension (GH) is a well-known disorder, gestational proteinuria (GP) has been far less emphasized. According to international criteria, hypertensive disorders of pregnancy include GH but not GP. Previous studies have not revealed the predictors of progression from GP to preeclampsia or those of progression from GH to preeclampsia. We aimed to determine both sets of predictors. A retrospective cohort study was conducted with singleton pregnant women who delivered at 22 gestational weeks or later. Preeclampsia was divided into three types: new onset of hypertension/proteinuria at 20 gestational weeks or later and additional new onset of other symptoms at < 7 days or at ≥ 7 days later. Of 94 women with preeclampsia, 20 exhibited proteinuria before preeclampsia, 14 experienced hypertension before preeclampsia, and 60 exhibited simultaneous new onset of both hypertension and proteinuria before preeclampsia; the outcomes of all types were similar. Of 34 women with presumptive GP, 58.8% developed preeclampsia; this proportion was significantly higher than that of 89 women with presumptive GH who developed preeclampsia (15.7%). According to multivariate logistic regression models, earlier onset of hypertension/proteinuria (before or at 34.7/33.9 gestational weeks) was a predicator for progression from presumptive GH/GP to preeclampsia (odds ratios: 1.21/1.21, P value: 0.0044/0.0477, respectively). [ABSTRACT FROM AUTHOR]

Aim: To clarify whether maternal characteristics or laboratory parameters could help predict the onset of recurrent gestational diabetes mellitus (GDM). Methods: We enrolled 615 women with consecutive singleton deliveries at or after 28 GW from two perinatal medical centers between 2011 and 2019 and divided them into four groups according to whether they had GDM in the first and second pregnancies. The outcome of this study was to clarify the incidence and the predictors of recurrent GDM. Results: We found that among 72 women (11.7%) who had GDM during their first pregnancy, the rate of recurrent GDM was 47.2%. The 34 women (5.5%) with recurrent GDM gained significantly less weight in the first and second pregnancies and lost less weight between the first delivery and the second conception compared with those women without GDM in both pregnancies. Of women with GDM during the first pregnancy, 21 scored 2 or 3 (multiple) positive points on a 75‐g oral glucose tolerance test (OGTT) during their first pregnancies; the GDM recurrence rate among these women (66.7%) was significantly higher than that among the 51 women who scored 1 positive point (39.2%; p = 0.0411). During the first pregnancy, insulin administration therapy was significantly more frequent in women with recurrent GDM than in women without recurrent GDM (23.5% vs. 5.3%, p = 0.0396, respectively). Conclusion: A predictor of recurrent GDM onset was a score of 2 or 3 positive points on the OGTT during the first pregnancy. [ABSTRACT FROM AUTHOR]

Background: Currently, there is a disagreement between guidelines regarding platelet count cut-off values as a sign of maternal organ damage in pre-eclampsia; the American College of Obstetricians and Gynecologists guidelines state a cut-off value of < 100 × 109/L; however, the International Society for the Study of Hypertension in Pregnancy guidelines specify a cut-off of < 150 × 109/L. We evaluated the effect of mild thrombocytopenia: platelet count < 150 × 109/L and ≥ 100 × 109/L on clinical features of pre-eclampsia to examine whether mild thrombocytopenia reflects maternal organ damage in pre-eclampsia.Methods: A total of 264 women were enrolled in this study. Participants were divided into three groups based on platelet count levels at delivery: normal, ≥ 150 × 109/L; mild thrombocytopenia, < 150 × 109/L and ≥ 100 × 109/L; and severe thrombocytopenia, < 100 × 109/L. Risk of severe hypertension, utero-placental dysfunction, maternal organ damage, preterm delivery, and neonatal intensive care unit admission were analyzed based on platelet count levels. Estimated relative risk was calculated with a Poisson regression analysis with a robust error.Results: Platelet counts indicated normal levels in 189 patients, mild thrombocytopenia in 51 patients, and severe thrombocytopenia in 24 patients. The estimated relative risks of severe thrombocytopenia were 4.46 [95 % confidence interval, 2.59-7.68] for maternal organ damage except for thrombocytopenia, 1.61 [1.06-2.45] for preterm delivery < 34 gestational weeks, and 1.35 [1.06-1.73] for neonatal intensive care unit admission. On the other hand, the estimated relative risks of mild thrombocytopenia were 0.97 [0.41-2.26] for maternal organ damage except for thrombocytopenia, 0.91 [0.62-1.35] for preterm delivery < 34 gestational weeks, and 0.97 [0.76-1.24] for neonatal intensive care unit admission.Conclusions: Mild thrombocytopenia was not associated with severe features of pre-eclampsia and would not be suitable as a sign of maternal organ damage. [ABSTRACT FROM AUTHOR]

Background. Total anomalous pulmonary venous connection (TAPVC) is a critical congenital heart disease for which emergency surgery is required after birth. In cases of no intervention, TAPVC is associated with a high mortality rate in the first year of life. Although foetal echocardiographic techniques for diagnosing TAPVC have improved, TAPVC remains one of the most difficult congenital heart diseases to diagnose via foetal echocardiography. Here, we report a case of TAPVC with pulmonary venous obstruction (PVO), which was diagnosed via foetal echocardiography. Case Presentation. On foetal echocardiography at 32 weeks' gestation, a large atrial septal defect, enlarged superior vena cava, and continuous flow pattern in the vertical vein from the common chamber were observed in the foetus. Paediatric cardiologists and cardiac surgeons, neonatologists, and obstetricians planned to perform a caesarean section and emergency heart surgery. The male infant was born at 37 weeks' gestation via caesarean section, and postnatal echocardiography revealed PVO at the confluence of the superior vena cava and common chamber. Similarly, chest computed tomography confirmed the foetal diagnosis. The postnatal diagnoses were TAPVC type Ib, PVO, atrial septal defect, and patent ductus arteriosus. Surgical repair of the TAPVC was initiated within the first 3 hours of life. Screening brain echocardiography and head computed tomography revealed intracranial haemorrhage and hydrocephalus. Therefore, the patient underwent emergency bilateral external drainage on day 13. On day 48, a ventriculoperitoneal shunt was inserted owing to progressive brain ventricular dilatation. The patient was discharged home on postoperative day 68. Conclusions. Although the prognosis of TAPVC with PVO remains poor, continuous observation through foetal echocardiography and early interdepartmental collaboration can result in good outcomes. [ABSTRACT FROM AUTHOR]

Aim: In Hokkaido, Japan, the number of people suffering from coronavirus disease 2019 (COVID‐19) is rapidly increased, and by the end of February 2020, there were already 70 confirmed cases of the disease. We investigated the safety of urgently initiated maternal telemedicine in preventing the spread of the coronavirus infection. Methods: This retrospective, single‐institution study examined maternal telemedicine at the department of obstetrics of the Hokkaido University Hospital from March 4 to April 2, 2020. The physicians remotely examined the pregnant women from their homes using a visual communication system which kept communication confidential, performed prenatal checkup and administered medical care according to their various blood pressures, weights and cardiotocograms. Results: Forty‐four pregnant women received a total of 67 telemedicine interventions. Thirty‐two pregnant women (73%) had complications, and 22 were primiparas (50%). Telemedicine interventions were provided 19 times at less than 26 weeks of gestation, 43 times between 26 and 36 weeks of gestation and 5 times after 37 weeks of gestation. There was one case with an abnormality diagnosed during the remote prenatal checkups, and the patient was hospitalized on the same day. However, there were no abnormal findings observed in mothers and children during the other 66 remote prenatal checkups and medical care. Conclusion: Maternal telemedicine can be safely conducted in pregnant women who are at risk of having an underlying disorder or fetal abnormality 1 month following the start of the attempt. It should be considered as a form of maternal medical care to prevent the spread of COVID‐19. [ABSTRACT FROM AUTHOR]

Pregnant women with diabetes mellitus (DM) are at high risk for hypertensive disorder of pregnancy (HDP). Women with poor control DM sometimes have heavy-for-dates infants. However, women with HDP sometimes have light-for-dates infants. We aim to clarify the relationship between glycemic control and fetal growth in women with DM and/or subsequent HDP. Of 7893 women gave singleton birth at or after 22 gestational weeks, we enrolled 154 women with type 1 DM (T1DM) or type 2 DM (T2DM) whose infants did not have fetal abnormalities. Among women with T1DM or T2DM, characteristics of the three groups (with HDP, without HDP, and with chronic hypertension [CH]) were compared. No women with T1DM had CH, but 19 (17.4%) of 109 with T2DM did. HDP incidence was similar between women with T1DM (22.2%) and T2DM without CH (16.7%). Among women with T1DM, the incidences of fetal growth restriction (FGR) with and without HDP were similar. However, among women with T2DM without CH, this incidence was significantly higher among those with HDP (33.3%) than among those without HDP (5.3%), was significantly more common with HbA1c levels at first trimester ≥ 7.2% (33.3%) than with those < 7.2% (5.6%), and significantly more numerous without pre-pregnancy therapies for DM (23.3%) than with them (3.3%). Among women with T2DM and HDP, those with FGR had smaller placenta SDs and higher insulin dosages at delivery than those without light-for-dates. In multivariate analysis, the presence of diabetic nephropathy was a predictor of T1DM and HDP (P = 0.0105), whereas HbA1c levels ≥ 7.2% before pregnancy was a predictor of T2DM and HDP (P = 0.0009). Insulin dosage ≥ 50U/day at delivery (P = 0.0297) and the presence of HDP (P = 0.0116) independently predicted T2DM, HDP, and FGR development. Insufficient pre-pregnancy treatment of DM increased the risk of HDP. [ABSTRACT FROM AUTHOR]

Objective: To examine whether laboratory parameters can predict the onset of recurrent hypertensive disorders of pregnancy (HDP).Methods: A retrospective study of 257 women with consecutive deliveries at a hospital in Sapporo, Japan, between 2009 and 2017. Women were divided into four groups according to whether or not they had HDP in the first and second peripartum periods (HDP-HPD, HDP-Non, Non-HDP, Non-Non). HDP was defined as gestational hypertension and/or proteinuria. Laboratory parameters measured on the day of or 1 day before delivery were compared between peripartum-1 and peripartum-2.Results: Frequency of HDP in peripartum-2 was higher among the 24 (9.3%) women with HPD in peripartum-1 (6/24, 25.0%) than among the 233 (90.7%) women without (3/233, 1.3%) (P<0.001). In peripartum-1, women with HDP had lower median antithrombin activity than those without (74% vs 89%, P=0.021). Antithrombin activity in peripartum-1 was also lower in the HDP-HDP (67%) than in the HDP-Non (79%) group (P=0.021). Antithrombin activities of 77% or less at the first delivery predicted HDP in peripartum-1 (P<0.001) and 70% or less predicted HDP in peripartum-2 (P=0.018).Conclusion: Women with HDP in peripartum-1 had a higher incidence of HDP recurrence. Low antithrombin before a first delivery might predict recurrent HDP in a second pregnancy. [ABSTRACT FROM AUTHOR]

Aim: This study was performed to evaluate maternal changes in laboratory characteristics after fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS).Methods: A retrospective review was conducted among 30 women with monochorionic diamniotic twin pregnancy with TTTS who underwent FLP at 16-26 weeks of gestation. Maternal laboratory parameters were measured before and after FLP.Results: The pre-FLP mean hemoglobin level (10.0 g/dL), hematocrit level (30.0%), platelet count (229 × 109/mL), fibrinogen level (461 mg/dL), and antithrombin activity (96.8%) decreased after FLP (8.5 g/dL, 25.5%, 204 × 109/mL, 403 mg/dL, and 83.6%, respectively) and returned to normal spontaneously within 2 weeks (9.6 g/dL, 29.4%, 293 × 109/mL, 460 mg/dL, and 102.4%, respectively). The D-dimer level before FLP (2.41 μg/mL) increased after FLP (4.28 μg/mL), and the elevated level was maintained for 2 weeks (3.24 μg/mL). The symptomatic venous thromboembolism (VTE) was not detected after FLP in any of the 30 patients. However, one woman had pulmonary embolism after subsequent cesarean section.Conclusion: Changes in maternal anemia and coagulation/fibrinolysis after FLP for TTTS returned to normal spontaneously within 2 weeks. Maternal elevation of D-dimer level after FLP might be a warning indicator of VTE. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to examine how the number of patients diagnosed with pre‐eclampsia increased according to the Japanese classification of hypertensive disorders of pregnancy (HDP) that was revised in 2018. The effect of new classification on perinatal outcomes was also analyzed. Methods: We enrolled 181 women with HDP who delivered at Hokkaido University Hospital between February 2011 and December 2017. All women were reclassified on the basis of the new classification, in which proteinuria was not required to diagnose pre‐eclampsia in patients with maternal organ damage. The number and reasons of reclassification and the admission rate to the neonatal intensive care unit (NICU) and gestational age (GA) at the onset of HDP and at delivery were analyzed. Results: In this cohort, 17 (9.4%) of 181 women with HDP were reclassified. Low platelet count (41.2%) and uteroplacental dysfunction (41.2%) were the two main causes for reclassification. GA at the onset of HDP (33.6 [29.9–36.1] weeks vs 37.4 [35.7–38.4] weeks; P < 0.001) and at delivery (35.9 [32.4–37.3] weeks vs 38.1 [37.3–39.6] weeks; P < 0.001) were significantly earlier in women with reclassification than women without reclassification. The NICU admission rate was higher in women with reclassification than women without reclassification (70.6% vs 20.4%; P < 0.001). Conclusion: Almost 10% of pregnant women were newly diagnosed with pre‐eclampsia as per the new Japanese classification of HDP. Women with reclassification as pre‐eclampsia had a greater risk of preterm delivery and NICU admission than those who were not reclassified. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to underscore problems associated with the dipstick test and determination of protein concentration alone in spot-urine ( P-test) compared with spot-urine protein-to-creatinine ratio ( P/ Cr test) and to determine whether urine collection for 24-h test was complete. Material and Methods Dipstick and P/ Cr tests were performed simultaneously in 357 random spot-urine specimens from 145 pregnant women, including 35 with pre-eclampsia. Positive results were defined as ≥1+ on dipstick test, protein concentration ≥30 mg/dL on P-test, and P/ Cr ratio ≥ 0.27 (mg/mg) on P/ Cr test. Sixty-four 24-h urine tests (quantification of protein in urine collected during 24 h) were performed in 27 of the 145 women. We assumed that P/ Cr ratio ≥ 0.27 predicted significant proteinuria (urinary protein ≥ 0.3 g/day). The 24-h urine collection was considered incomplete when urinary creatinine excretion was <11.0 mg/kg/day or >25.0 mg/kg/day. Results Forty-four percent (69/156) of specimens with a positive test result on dipstick test contained protein < 30 mg/dL. Dipstick test was positive for 25.7% (69/269) of specimens with protein < 30 mg/dL and for 28.8% (79/274) of specimens with P/ Cr ratio < 0.27. P-test results were positive for 7.3% (20/274) and negative for 18.1% (15/83) of specimens with P/ Cr ratio < 0.27 and ≥0.27, respectively. Incomplete 24-h urine collection occurred in 15.6% (10/64) of 24-h urine tests. Daily urinary creatinine excretion was 702-1397 mg, while creatinine concentration varied from 16 mg/dL to 475 mg/dL in spot-urine specimens. Conclusion Dipstick test and P-test were likely to over- and underestimate risks of significant proteinuria, respectively. The 24-h urine collection was often incomplete. [ABSTRACT FROM AUTHOR]

Abstract: Background: Complete automation of high-performance liquid chromatography (HPLC) for determination of hemoglobin F (%Hb F) and hemoglobin A1c (%Hb A1c) levels has made this procedure available in many clinical laboratories. However, the physiological changes in %Hb F during pregnancy and the effects of physiological and supraphysiological levels of %Hb A1c on measurement of %Hb F have not been studied extensively. Methods: Simultaneous determination of %Hb F and %Hb A1c was conducted in 490 blood samples obtained before (n =21), during the 1st (n =150), 2nd (n =116), and 3rd (n =192) trimesters of pregnancy, and postpartum (n =11) from 357 women, including 60 women with hyperglycemia but unaffected by clinical fetomaternal hemorrhage, by HPLC. Results: Mean (SD) Hb F levels were 0.71% (0.25%) before pregnancy. The value of 0.82% (0.47%) during the 1st trimester decreased significantly to 0.66% (0.35%) during the 2nd trimester and to 0.58% (0.38%) during the 3rd trimester. The level was 0.62% (0.31%) approximately one year after delivery. Thus, %Hb F was highest during the 1st trimester of pregnancy. The effects of varied %Hb A1c levels on %Hb F measurements were clinically negligible. Conclusions: The data presented in this work may be used as reference intervals of %Hb F determined with HPLC during pregnancy. [Copyright &y& Elsevier]

Abstract: Objective: The circumflex iliac nodes distal to the external iliac nodes (CINDEINs) are included in the regional lymph nodes that are commonly dissected during systematic lymphadenectomy for ovarian cancer. Because in recent years CINDEIN dissection has been reported as a significant risk factor for postoperative lower limb lymphedema, we investigated the validity of omitting the CINDEIN dissection by evaluating the distribution pattern of positive lymph nodes in ovarian cancer, in order to improve postoperative quality of life (QOL). Methods: We performed a retrospective chart review of 142 patients with ovarian cancer who had undergone systematic lymphadenectomy between 1995 and 2010. We assessed the distribution pattern of lymph node metastasis and the presence of CINDEIN metastasis according to the pT classification (pT1, pT2, and pT3). Results: Of the 142 patients, 71, 21, and 50 were classified into pT1, pT2, and pT3, respectively. The lymph nodes most frequently involved were the para-aortic lymph nodes superior to the mesenteric artery (14%), followed by the obturator nodes (11%), the internal iliac nodes (9.4%), and the common iliac nodes (7.4%). Although the frequency of CINDEIN metastasis was 5.3% (6 of 114 cases with CINDEIN dissection), no metastasis to the CINDEINs was observed in pT1 patients. Conclusions: It may be acceptable to omit CINDEIN dissection during surgery for pT1 ovarian cancer in view of postoperative QOL. [Copyright &y& Elsevier]

Obstructive sleep apnea (OSA) is not only a cause of hypertension; it also possibly affects the pathogenesis and progression of aortic disease because an inspiratory effort-induced increase in negative intrathoracic pressure generates mechanical stress on the aortic wall. The objective of the present study was to examine the incidence by location of OSA as a complication in patients with aortic aneurysm and patients with aortic dissection (AD). An overnight sleep study was conducted in the following study groups: the aortic disease group ( n = 95) consisting of patients with thoracic aortic aneurysm (TAA, n = 32), patients with abdominal aortic aneurysm (AAA, n = 36), and patients with AD ( n = 27); and a control group ( n = 32), consisting of patients with coronary risk factors who were matched with the aortic disease group for age, gender, and body mass index (BMI). The 3% oxygen desaturation index (ODI) was significantly higher in all the TAA, AAA, and AD groups ( P = 0.045, P = 0.003, and P = 0.005, respectively) than in the control group. The incidence of moderate to severe OSA [apnea hypopnea index (AHI) ≥15 events/h] was significantly higher in the first three groups ( P = 0.026, P = 0.001, P = 0.003, respectively) than in the control group, while no significant difference was found between the TAA group and the AAA group with respect to these variables. Furthermore, no significant differences were found between the thoracic AD subgroup and the abdominal AD subgroup with respect to AHI and 3% ODI, as well as with respect to the incidences of moderate to severe OSA. Patients with TAA, patients with AAA, and patients with AD showed high incidences of moderate to severe OSA. Although this result suggests that OSA may be one of risks for aortic disease, unelucidated mechanism(s) other than negative intrathoracic pressure may be involved in the pathogenesis of aortic disease. [ABSTRACT FROM AUTHOR]

Purpose: To minimize surgical invasiveness for extensive aortic aneurysms and expand the indications for thoracic endovascular aortic repair (TEVAR), we evaluated outcomes of hybrid procedures combining conventional surgical aortic repair and TEVAR for thoracic aortic aneurysms. Methods: The following hybrid procedures were performed: second-stage TEVAR after total aortic arch replacement using the elephant trunk as the landing zone in 17 patients; and for multiple aortic aneurysms, vascular graft replacement and TEVAR in 13 patients, vascular graft replacement and TEVAR with bypass in 2 patients, and TEVAR with bypass in 23 patients. Results: There were three (5.3%) hospital deaths, from serious complications including stroke, paraplegia, paraparesis, and aspiration pneumonia; and eight late deaths. There was only one aneurysm-related death, of a patient who underwent emergency surgery for an esophageal fistula resulting from enlargement of a residual false lumen of a thoracoabdominal aorta after second-stage TEVAR. Conclusion: Hybrid procedures minimize surgical invasiveness in thoracic aortic aneurysm repair, but further evaluation of a larger number of patients is necessary. [ABSTRACT FROM AUTHOR]

Neuron-selective gene transfer is an attractive therapeutic strategy for neurological disorders. Selective gene transfer requires high efficiency as well as tissue specificity of the target molecule employed. Selection of an optimal target molecule is critical. Here, we contrived the hybridoma library screening to identify optimal target molecules for neuron selective gene transfer using fiber mutant adenoviruses as targeting tools. We generated genetically modified adenoviruses incorporating Z33, an IgG Fc-binding motif from Staphylococcus protein A, at the fiber (Adv-FZ33 and Adv-FdZ). The Z33 vectors were capable of infecting cells through use of linked antibodies against surface antigen molecules.In this report, we established hybridoma clone 6E3 and mouse monoclonal antibody (mAb6E3) by this screening technique and identified the target antigen as Na,K-ATPase β1. Flow cytometry, chemiluminescent β-Gal reporter gene assays and immunocytochemistry using mAb6E3 and fiber mutant adenovirus documented efficient gene transfer into PC12 cells. This showed Na,K-ATPase β1 functions as the effective receptor for gene transfer into neurons. Immunohistochemistry images of rat spinal cord tissue showed that Na,K-ATPase β1 was expressed in neurons but not in oligodendrocytes or astrocytes. Experiments to transduce genes into neuron-glia cocultures using mAb6E3 and fiber mutant adenovirus resulted in neuron-selective gene transfer. These data indicate that Na,K-ATPase β1 is a good candidate molecule for neuron-selective gene transfer. Gene transfer via Na,K-ATPase β1 may be a useful strategy for treating neurological disorders, especially local disorders.Molecular Therapy (2006) 13, S346–S346; doi: 10.1016/j.ymthe.2006.08.986 [ABSTRACT FROM AUTHOR]

The methods of homologous high-level expression and simple large-scale purification for coenzyme B12-dependent ethanolamine ammonia-lyase of Escherichia coli were developed. The eutB and eutC genes in the eut operon encoded the large and small subunits of the enzyme, respectively. The enzyme existed as the heterododecamer α6β6. Upon active-site titration with adeninylpentylcobalamin, a strong competitive inhibitor for coenzyme B12, the binding of 1 mol of the inhibitor per mol of the αβ unit caused complete inhibition of enzyme, in consistent with its subunit structure. EPR spectra indicated the formation of substrate-derived radicals during catalysis and the binding of cobalamin in the base-on mode, i.e. with 5,6-dimethylbenzimidazole coordinating to the cobalt atom. The purified wild-type enzyme underwent aggregation and inactivation at high concentrations. Limited proteolysis with trypsin indicated that the N-terminal region is not essential for catalysis. His-tagged truncated enzymes were similar to the wild-type enzyme in catalytic properties, but more resistant to p-chloromercuribenzoate than the wild-type enzyme. A truncated enzyme was highly soluble even in the absence of detergent and resistant to aggregation and oxidative inactivation at high concentrations, indicating that a short N-terminal sequence is sufficient to change the solubility and stability of the enzyme. [ABSTRACT FROM PUBLISHER]

We herein present a 60 years old woman with Takayasu arteritis and an extensive thoracic aortic aneurysm who initially underwent a total aortic arch replacement. Then, in the second stage, thoracic endovascular aortic repair was performed using the elephant trunk graft as the proximal landing zone at four weeks after aortic arch repair. The postoperative course was relatively uncomplicated, but a type II endoleak was noted. Currently, about 5 years postoperatively, the slight type II endoleak from intercostal artery persists, but aneurism dilatation has not been noted, so the patient is being followed up. [ABSTRACT FROM AUTHOR]

A Neurometer device is an electrical nerve stimulator used to determine the current perception threshold (CPT) evoked by stimulating A-beta fibers at 2,000 Hz, A-delta fibers at 250 Hz and C fibers at 5 Hz. CPT evaluation is used for analyzing peripheral nerve dysfunction. In this study, the sensory disturbance of the lower-extremity was quantitatively analyzed using CPT testing before and after lumbar discectomy. In 33 patients (L4/5: 16 and L5/S: 17), as subjective evaluations, tactile sensation and leg pain were assessed before and 2 weeks after surgery. In the subjectively improved group ( n = 22), significant decreases in CPT at 2,000 and 250 Hz were noted postoperatively, whereas in the unchanged group ( n = 11), no significant changes in CPT at any frequencies was noted. The leg pain improved in all patients. Likewise, CPT at 5 Hz, which stimulated C fiber, decreased significantly for both improved and unchanged groups. CPT measured by a Neurometer is very useful in assessing lower-extremity sensory functions before and after surgery for lumbar disc herniation. [ABSTRACT FROM AUTHOR]

As a tetrameric major histocompatibility complex (MHC) class I-peptide complex (tetramer) is capable of detecting antigen-specific cytotoxic T lymphocyte (CTL) by flow cytometry, significant information about the generation of in vivo immunity can be obtained. It is, however, difficult to make a soluble wild type of MHC class I heavy chain by the prokaryotic expression system. Therefore, we developed a new method for making soluble mutant HLA-A&ast;2402 heavy chain. In this method, signal sequences were deleted, and the codon was changed to silent mutated nucleotide sequences that bacteria could use as preferable codon. When purified mutant HLA-A&ast;2402 molecules were examined for the protein generation by SDS-polyacrylamide gel electrophoresis (PAGE) and western blotting using anti-HLA class I monoclonal antibody (mAb) as compared with wild type, a large amount of mutant heavy chain could be detected. In contrast, the expression of wild-type stable HLA-A&ast;2402 heavy chain molecule was not detected in this system. Consequently, by using mutant HLA-A&ast;2402/peptide tetramers, CTL precursors (CTLp) that specifically recognize antigenic peptide derived from the X;18 chromosomal translocations of synovial sarcoma were detected in patients'' PBL. [Copyright &y& Elsevier]

We report here that the Id2 (inhibitor of DNA binding 2) gene is a novel target of transcriptional activation by EWS–FLI1 and EWS–ERG, two fusion proteins that characterize Ewing family tumors (EFTs). To identify downstream targets of these EWS–ETS fusion proteins, we introduced EWS–ETS fusion constructs into a human fibrosarcoma cell line by retroviral transduction. cDNA microarray analysis revealed that Id2 expression was up-regulated by introducing the EWS–ETS fusion gene but not by the normal full-length ETS gene. An Id2 promoter-luciferase reporter assay showed that transactivation by EWS–ETS involves the minimal Id2 promoter and may function in cooperation with c-Myc within the full-length regulatory region. A chromatin immunoprecipitation assay revealed direct interaction between the Id2 promoter and EWS-FLI1 fusion protein in vivo. Significantly higher expression of Id2 and c-Myc was observed in all of the six EFT cell lines examined compared to six other sarcoma cell lines. Moreover, high levels of Id2 expression were also observed in five of the six primary tumors examined. Id2 is generally thought to affect the balance between cell differentiation and proliferation in development and is highly expressed in several cancer types. Considering these previous studies, our data suggest that the oncogenic effect of EWS–ETS may be mediated in part by up-regulating Id2 expression.Oncogene (2002) 21, 8302–8309. doi:10.1038/sj.onc.1206025 [ABSTRACT FROM AUTHOR]