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Dividing orbital interactions into through-space (TS) and through-bond (TB) modes is valuable for understanding various molecular properties. In this paper, we elucidate how the quantum interference phenomenon known as σ interference in electron transport through σ systems arises from TS and TB interactions. We performed electron transport calculations using a combination of density functional theory and nonequilibrium Green's function methods, focusing on ethylenediamine, a classical molecule that effectively highlights the contrast between TS and TB interactions. Our results confirm that destructive σ interference occurs in the syn and gauche conformers of this molecule. To further investigate both TS and TB interactions, we employed two analytical methods: the fragment molecular orbital (FMO) method, which captures the effects of both TS and TB interactions, and the chemical graph theory method, which specializes in TB interactions. The FMO analysis demonstrated that TB interactions lead to the characteristic distribution and energy level alignment of the frontier orbitals. Additionally, it was clarified that a change in TS interaction, due to a variation in the dihedral angle of the molecule, alters the energy gap between these orbitals, resulting in the manifestation of σ interference in the syn and gauche conformers, but not in the trans conformer. The chemical graph theory analysis based on the ladder C model, aimed at exploring the topological origin of σ interference from the network of TB interactions, revealed that σ interference is caused by the cancellation between the walk associated with geminal interactions (σ-conjugation) and the one related to vicinal interaction (σ-hyperconjugation). Notably, it was found that the vicinal interaction, which changes sign with the dihedral angle, has a decisive influence on whether this cancellation occurs. These findings clarify that σ interference arises from the interplay between TS and TB interactions. This insight will be valuable for designing molecular systems that utilize σ interference.

The molecular mechanism of adhesion of two epoxy resins based on diglycidylether of bisphenol A (DGEBA) cured with 4,4'-diaminodiphenyl sulfone (DDS) and 4,4'-diaminodiphenylmethane (DDM) to the carbon fiber (CF) surface is investigated by employing density functional theory (DFT) calculations. The CF surface was modeled by the armchair-edge structure of graphite functionalized with carboxyl (COOH) groups. Two adhesion interfaces were constructed using the CF surface: one with the DGEBA-DDS molecule (CF/DGEBA-DDS interface) and the other with the DGEBA-DDM molecule (CF/DGEBA-DDM interface). The interfacial properties were analyzed by calculating the maximum adhesion stress ( S max ) at the interface. The adhesion stress-displacement curve revealed that S max is 1160.37 MPa, higher for the CF/DGEBA-DDS interface compared to the CF/DGEBA-DDM interface, which is 1060.48 MPa. The energy decomposition analysis showed a similar DFT contribution to adhesion stress for both interfaces, but the dispersion contribution is more significant at the CF/DGEBA-DDS interface. The crystal orbital Hamilton population (COHP) analysis revealed distinct interfacial interactions despite similar DFT contributions. Hydrogen bonding (H-bonding) between the functional groups at both interfaces including feeble OH-π interactions between the benzene rings of epoxy resins and COOH groups on the CF surface were observed. The orbital interaction energies calculated from integrated COHP, i.e., IpCOHP, revealed that the CF/DGEBA-DDS interface has six H-bonding interactions with large absolute IpCOHP values (>1 eV), whereas the CF/DGEBA-DDM interface has five. The interaction between the amine group of the DGEBA-DDM molecule and the CF surface has a large IpCOHP value among all interactions. The sulfone group being at the center of the DDS molecule and its strong surface interaction positioned the DGEBA-DDS molecule closer to the CF surface than the DGEBA-DDM molecule, enhancing dispersion interaction at the CF/DGEBA-DDS interface. Hence, the CF surface exhibits a stronger affinity toward the DGEBA-DDS molecule than the DGEBA-DDM molecule through dispersion interaction.

Here, we report that, in contrast to urea, thiourea functions as a "polar hydrophobic" hydrogen-bonding motif. Although thiourea is more acidic than urea, thiourea exchanges its N-H protons with water at a rate that is 160 times slower than that for urea at 70 °C. This suggests that thiourea is much less hydrated than urea in an aqueous environment. What led us to this interesting principle was the serendipitous finding that self-healable poly(ether thiourea) adhered strongly to wet glass surfaces. This discovery enabled us to develop an exceptionally durable all-underwater adhesive that can maintain large adhesive strength for over a year even in seawater, simply by mechanically mixing three water-insoluble liquid components on target surfaces. Because thiourea is hydrophobic, its hydrogen-bonding networks within the adhesive structure and at the adhesive-target interface are presumed to be dehydrated. For comparison, a reference adhesive using urea as a representative "polar hydrophilic" hydrogen-bonding motif was durable for less than 4 days in water. Highly durable all-underwater adhesives are needed in various fields of marine engineering and biomedical sciences, but their development has been a major challenge because a hydration layer that spontaneously forms in water always inhibits adhesion.

Prescribing direct oral anticoagulants (DOACs) with off-label dosage and administration is discouraged due to concerns about their effectiveness and safety. Consequently, our hospital pharmacist established a formulary with physicians for oral anticoagulants. Our study aimed to assess the adherence to this formulary by investigating the rate of appropriate DOAC prescribing. We included patients who were newly prescribed or continued on DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) at our hospital. We calculated the percentage of patients prescribed the correct dosage and administration according to the package insert and compared this across three time periods: pre-intervention (period A; April-September 2019), post-intervention phase 1 (period B; August 2021-January 2022), and post-intervention phase 2 (period C; November 2022-April 2023). We also examined the number of inquiries and consultation requests made by hospital pharmacists regarding DOAC dosage and administration. A total of 782 patients were surveyed (191 in period A, 263 in period B, and 328 in period C). The appropriate prescribing rates for DOACs were 79.1% in period A, 84.4% in period B, and 86.6% in period C. The proportion of cases where hospital pharmacists questioned or consulted doctors about DOAC dosage and administration was 3.7% in period A, 6.1% in period B, and 10.1% in period C. These findings indicate that active intervention by hospital pharmacists using the formulary regarding oral anticoagulant formularies may promote appropriate DOAC use.

The formation of Lewis pairs is an important chemical concept. Recently, the complexation of Lewis acidic tris(pentafluorophenyl)borane with Lewis basic moieties and subsequent reduction has emerged as a fascinating strategy for designing novel reactions and structures. The impact of the complexation and subsequent reduction of antiaromatic systems bearing Lewis base moieties has been investigated. We found how Lewis adduct formation stabilizes an antiaromatic system consisting of 9,10-dicyanoanthracene and tris(pentafluorophenyl)borane by using synthesis, X-ray crystallography, spectroscopic analysis, and quantum chemical calculations., (© 2023 Wiley-VCH GmbH.)

Face-to-face stacking of aromatic compounds leads to stacked antiaromaticity, while that of antiaromatic compounds leads to stacked aromaticity. This is a prediction with a long history; in the late 2000s, the prediction was confirmed by high-precision quantum chemical calculations, and finally, in 2016, a π-conjugated system with stacked aromaticity was synthesized. Several variations have since been reported, but essentially, they are all the same molecule. To realize stacked aromaticity in a completely new and different molecular system and to trigger an extension of the concept of stacked aromaticity, it is important to understand the origin of stacked aromaticity. The Hückel method, which has been successful in giving qualitatively correct results for π-conjugated systems despite its bold assumptions, is well suited for the analysis of stacked aromaticity. We use this method to model the face-to-face stacking systems of benzene and cyclobutadiene molecules and discuss their stacked antiaromaticity and stacked aromaticity on the basis of their π-electron energies. By further developing the discussion, we search for clues to realize stacked aromaticity in synthesizable molecular systems.

Background: In-hospital therapeutic drug monitoring (TDM) requires a suitable quantification method for target drugs from the viewpoint of precision, throughput, and testing costs. We previously developed a practical HPLC-UV platform for quantification of serum levels of various drugs. In this report, the platform was effectively applied to the quantification of patient serum levels of five different drugs by clinical professionals in our hospital during their daily work., Methods: The residual sera of patients receiving carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), vancomycin (VCM), or voriconazole (VRCZ) were used in the present clinical study. The quantification method for each drug consisted of rapid solid-phase extraction (SPE) of each drug in the patient serum, followed by optimized HPLC-UV analysis of the drug in the SPE eluate. Furthermore, patient serum levels of PHT, CBZ, and VCM were also measured by ligand-binding assay using a cobas ® analyzer in our hospital, and those of LTG and VRCZ were measured by HPLC-MS/MS at an outsourced provider. Passing-Bablok regression analysis and Bland-Altman analysis were employed to analyze the agreement of drug levels in patient sera, which was separately quantified using two different methods-our HPLC-UV platform and the cobas analyzer, or HPLC-UV and HPLC-MS/MS., Results: All analytical conditions of the present method using our HPLC-UV platform were well optimized for each target drug quantification in the patient's serum, and the quantification method for each drug was fully validated for accuracy, precision and reproducibility. Furthermore, Passing-Bablok regression analysis and Bland-Altman analysis revealed that patient serum levels of PHT, CBZ, and VCM quantified by our HPLC-UV platform were closely correlated with those quantified by the cobas ® analyzer, and the levels of LTG and VRCZ quantified by our HPLC-UV platform were also correlated with those quantified by HPLC-MS/MS., Conclusions: Our HPLC-UV platform can be performed without requiring special analytical techniques. This platform is expected to be used for the measurement of blood levels of multiple drugs for in-hospital routine TDM., (© 2023. The Author(s).)

This paper details the use of computational and informatics methods to design metal nanocluster catalysts for efficient ammonia synthesis. Three main problems are tackled: defining a measure of catalytic activity, choosing the best candidate from a large number of possibilities, and identifying the thermodynamically stable cluster catalyst structure. First-principles calculations, Bayesian optimization, and particle swarm optimization are used to obtain a Ti 8 nanocluster as a catalyst candidate. The N 2 adsorption structure on Ti 8 indicates substantial activation of the N 2 molecule, while the NH 3 adsorption structure suggests that NH 3 is likely to undergo easy desorption. The study also reveals several cluster catalyst candidates that break the general trade-off that surfaces that strongly adsorb reactants also strongly adsorb products., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Recent studies have theoretically and experimentally demonstrated that antiaromatic molecules with 4n π electrons exhibit stacked aromaticity according to π-π stacking when arranged in a face-to-face manner. However, the mechanism of its occurrence has not been clearly studied. In this study, we investigated the mechanism of stacked aromaticity using cyclobutadiene. When the antiaromatic molecules are stacked in a face-to-face manner, the orbital interactions between the degenerate singly occupied molecular orbitals (SOMOs) of the monomer unit cause a larger energy gap between the degenerate highest-occupied molecular orbitals (HOMOs) and the lowest-unoccupied molecular orbitals (LUMOs) of the dimer. However, the antiaromatic molecules are more stable in less symmetric conformations, mainly because of pseudo-Jahn-Teller distortions. In the case of cyclobutadiene, the two SOMOs of the monomer unit split into HOMO and LUMO because of the bond alternation. When the molecules are stacked in a face-to-face manner, the HOMO-LUMO gap of the dimer is smaller than that of the monomer due to the interactions between the HOMOs and LUMOs of the two monomer units. When the monomer units are within a specific distance of each other, the HOMO and LUMO of the dimer, which correspond to antibonding and bonding between the units, respectively, are interchanged. This alternation of molecular orbitals may result in an increase in the bond strength between the monomer units, exhibiting stacked aromaticity. We demonstrated that it is possible to control the distance exhibited by stacked aromaticity by engineering the HOMO-LUMO gap of the monomer units.

There are no reports on hip kinetics including contact forces and muscle activities during the golf swing after total hip arthroplasty (THA). The aim of this study was to identify the characteristics of three-dimensional dynamics during the golf swing. Ten unilateral primary THA patients participated in motion capture test of their driver golf swing. The driver swing produced approximately 20-30° of rotation in both lead and trail replaced hips. The mean hip contact forces (HCFs) of lead and trail replaced hips were 5.1 and 6.6 × body weight, respectively. Left and right THAs showed similar HCFs of lead and trail hips. More than 60% of the Percent maximum voluntary isometric contraction was found in bilateral iliopsoas muscles in all unilateral THA. Three factors [female sex, lower modified Harris Hip Score, and higher HCF of surgical side] were associated with the golf-related replacement hip pain. Golf is an admissible sport after THA because driver swings do not contribute excessive rotation or contact forces to hip prostheses. HCF could be reduced through swing adjustments, which may allow patients with golf-related replacement hip pain to develop a comfortable golf game free from pain., (© 2023. The Author(s).)

The adhesion mechanism of epoxy resin (ER) cured material consisting of diglycidyl ether of bisphenol A (DGEBA) and 4,4'-diaminodiphenyl sulfone (DDS) to pristine graphene and graphene oxide (GO) surfaces is investigated on the basis of first-principles density functional theory (DFT) with dispersion correction. Graphene is often used as a reinforcing filler incorporated into ER polymer matrices. The adhesion strength is significantly improved by using GO obtained by the oxidation of graphene. The interfacial interactions at the ER/graphene and ER/GO interfaces were analyzed to clarify the origin of this adhesion. The contribution of dispersion interaction to the adhesive stress at the two interfaces is almost identical. In contrast, the DFT energy contribution is found to be more significant at the ER/GO interface. Crystal orbital Hamiltonian population (COHP) analysis suggests the existence of hydrogen bonding (H-bonding) between the hydroxyl, epoxide, amine, and sulfonyl groups of the ER cured with DDS and the hydroxyl groups of the GO surface, in addition to the OH-π interaction between the benzene rings of ER and the hydroxyl groups of the GO surface. The H-bond has a large orbital interaction energy, which is found to contribute significantly to the adhesive strength at the ER/GO interface. The overall interaction at the ER/graphene is much weaker due to antibonding type interactions just below the Fermi level. This finding indicates that only dispersion interaction is significant when ER is adsorbed on the graphene surface.

To increase chemical reaction rates, general solutions include increasing the concentration/temperature and introducing catalysts. In this study, the rate constant of an electrophilic metal coordination reaction is accelerated 23-fold on the surface of layered aluminosilicate (LAS), where the reaction substrate (ligand molecule) induces dielectric polarization owing to the polar and anionic surface. According to the Arrhenius plot, the frequency factor (A) is increased by almost three orders of magnitude on the surface. This leads to the conclusion that the collision efficiency between the ligands and metal ions is enhanced on the surface due to the dielectric polarization. This is surprising because one side of the ligand is obscured by the surface, so the collision efficiency is expected to be decreased. This unique method to accelerate the chemical reaction is expected to expand the range of utilization of LASs, which are chemically inert, abundant, and environmentally friendly. The concept is also applicable to other metal oxides which have polar surfaces, which will be useful for various chemical reactions in the future., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Binary alloy catalysts have the potential to exhibit higher activity than monometallic catalysts in nitrogen activation reactions. However, owing to the multiple possible combinations of metal elements constituting binary alloys, an exhaustive search for the optimal combination is difficult. In this study, we searched for the optimal binary alloy catalyst for nitrogen activation reactions using a combination of Bayesian optimization and density functional theory calculations. The optimal alloy catalyst proposed by Bayesian optimization had a surface energy of ∼0.2 eV/Å 2 and resulted in a low reaction heat for the dissociation of the N≡N bond. We demonstrated that the search for such binary alloy catalysts using Bayesian optimization is more efficient than random search., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

In this study, we employ the Sachs graph theory to formulate the conduction properties of a single-molecular junction consisting of a molecule in which one carbon atom of an alternant hydrocarbon is replaced with a heteroatom. The derived formula includes odd and even powers of the adjacency matrix, unlike the graph of the parental structure. These powers correspond to odd- and even-length walks. Furthermore, because the heteroatom is represented as a self-loop of unit length in the graph, an odd number of passes of the self-loop will change the parity of the length of the walk. To confirm the aforementioned effects of heteroatoms on conduction in an actual sample, the conduction behavior of meta-connected molecular junctions consisting of a heterocyclic six-membered ring, whose conductive properties have already been experimentally determined, was analyzed based on the enumerated number of walks.

[Purpose] To determine patient satisfaction after total hip arthroplasty in a Japanese cohort and to identify factors that significantly influence patient satisfaction. [Participants and Methods] This study included 285 patients who underwent primary total hip arthroplasty for osteoarthritis. Postoperative satisfaction, Oxford hip score, short form-12 mental component summary score, and University of California Los Angeles activity score were investigated. Muscle strength and daily step counts were determined using a hand-held dynamometer (μ-Tas F1) and activity monitor (ActivPAL) in 89 and 26 patients, respectively. Factors associated with postoperative satisfaction, Oxford hip score-activities of daily living, and University of California Los Angeles activity score were identified. The relationship between the Oxford hip score-activities of daily living and daily step counts was examined. [Results] Overall, 94.7% of the patients reported satisfaction with total hip arthroplasty. The Oxford hip score-activities of daily living and University of California Los Angeles activity score were significantly associated with patient satisfaction. Younger age and hip abductor strength were significantly associated with a higher Oxford hip score-activities of daily living and University of California Los Angeles activity score. The average daily step count was significantly correlated with the Oxford hip score-activities of daily living. [Conclusion] Self-reported physical activity levels significantly influenced patient satisfaction and were correlated with objective muscle strength and daily step count measurements. These findings can guide total hip arthroplasty patient counseling on the importance of muscle strength and activity levels., (2022©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Introduction: Measurement of blood Favipiravir (FPV) levels and accumulation of data in COVID-19 patients are critical for assessing FPV efficacy and safety. We performed a retrospective study based on measurements of blood levels of FPV and related factors in COVID-19 patients admitted to our hospital. Furthermore, we also investigated the association between blood FPV levels and uric acid level alterations before and after FPV administration., Methods: We enrolled 27 COVID-19 patients who had received FPV treatment at Hokushin General Hospital from April 1 to December 31, 2020. Age, gender, COVID-19 severity, presence of comorbidities, and laboratory data for each subject were investigated to identify factors that correlate with blood FPV levels. Uric acid levels were measured before and after FPV administration and a difference between the levels (i.e., a change of uric acid level) was evaluated., Results: When a significant univariate variable was input by the stepwise method and a combination of variables that maintained statistical superiority was searched, serum ferritin was the only factor that independently affected blood FPV level. Furthermore, in the high-FPV group (20 μg/mL or more), a significant increase in uric acid levels was observed after FPV administration. The increment value was significantly larger than that in the low-FPV group (less than 20 μg/mL)., Conclusions: Ferritin level was an important independent factor inversely affecting blood FPV level. Furthermore, a high blood FPV level induced the elevation of uric acid levels in COVID-19 treatment., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

An in-hospital rapid method for quantifying the serum level of favipiravir (FPV) in the pharmacological treatment of COVID-19 was developed by an appropriate combination of a solid-phase extraction treatment and a reversed-phase HPLC/UV detection system. The quantification method was well-validated and applied to measuring the serum FPV level in a clinical practice at a general hospital that accepts COVID-19 patients. Furthermore, an analysis of data from our preliminary interaction analysis revealed, for the first time, that FPV selectively forms complexes with ferric (Fe 3+ ) and cupric (Cu 2+ ) ions.

Photo-induced ring-opening reaction from flav-3-en-2-ol to 2-hydroxychalcone has been studied by time-resolved infrared (TR-IR) spectroscopy and quantum chemical calculations. A vibrational band due to the C═O stretching modes for intermediate species, enol forms of 2-hydroxychalcone in the electronic ground state, was observed at 1632 cm -1 in the TR-IR spectra after photoexcitation of flav-3-en-2-ol. We also found that the C═O stretching modes of the keto forms of 2-hydroxychalcone at 1664 cm -1 appeared immediately after photoexcitation and increased in intensity in synchronization with the depletion of the 1632 cm -1 band. Because the decay of the 1632 cm -1 band and the rise of the 1664 cm -1 band were fitted with bi-exponential model functions with common rate constants 0.5 and 11 μs -1 , we propose that two kinds of enol form, single bond cis - (s- cis -) and trans - (s- trans- ) enols, transformed into keto forms, cis -2-hydroxychalcone (Cc) and trans -2-hydroxychalcone (Ct), respectively. Quantum chemically calculated IR spectra of related species are consistent with the proposal. The observed temporal behavior of the TR-IR spectra indicates that there were reaction paths to the photogeneration of Cc and Ct within the time resolution of the TR-IR spectrometer (∼0.1 μs) in addition to the reaction paths via the enol forms of 2-hydroxychalcone.

Chronic heart failure (CHF) is a critical disease in the aging population. Conventional therapy in hospitals cannot cure elderly patients with CHF at the end of life. Patients and their families experience anxiety and need comfortable care at home or in a nursing facility. To improve chronic cardiovascular disease management, we developed a simplified but integrated clinical pathway to facilitate medical and nursing care teamwork in the local community. Our institution is a central hospital in the North Shinshu district, which has an approximate population of 100000. We developed a pathway for both clinical program and information provision between our hospital and neighboring clinics. A hospital team evaluates and shares patient information with a homecare medical team every 6 months using the medical staff pathway. To maintain the efficacy and security of pharmacotherapy, a hospital clinical pharmacist reviews the prescriptions and prepares a drug profile book to share drug information between patients and all medical staff. These efforts have resulted in preventing adverse effects of drugs and reduced the cost of medications. Physical activity evaluation and nutrient guidance are also useful for patients to maintain their personal lifestyles. We initiated use of the pathway from 2009 and have followed up over 500 patients since then. We have also established a community partnership council to promote face-to-face communication among multiple categories of institutions and government agencies. Members of the council collaborate to help patients with cardiovascular disease to manage their own lives at home.

Aim: To clarify clinicopathological features of ductal carcinoma in situ (DCIS) visualized on [F-18] fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)., Methods: This study retrospectively reviewed 52 consecutive tumors in 50 patients with pathologically proven pure DCIS who underwent [F-18] FDG-PET/CT before surgery. [F-18] FDG-PET/CT was performed after biopsy in all patients. The mean interval from biopsy to [F-18] FDG-PET/CT was 29.2 d. [F-18] FDG uptake by visual analysis and maximum standardized uptake value (SUVmax) was compared with clinicopathological characteristics., Results: [F-18] FDG uptake was visualized in 28 lesions (53.8%) and the mean and standard deviation of SUVmax was 1.63 and 0.90. On univariate analysis, visual analysis and the SUVmax were associated with symptomatic presentation (P = 0.012 and 0.002, respectively), palpability (P = 0.030 and 0.024, respectively), use of core-needle biopsy (CNB) (P = 0.023 and 0.012, respectively), ultrasound-guided biopsy (P = 0.040 and 0.006, respectively), enhancing lesion ≥ 20 mm on magnetic resonance imaging (MRI) (P = 0.001 and 0.010, respectively), tumor size ≥ 20 mm on histopathology (P = 0.002 and 0.008, respectively). However, [F-18] FDG uptake parameters were not significantly associated with age, presence of calcification on mammography, mass formation on MRI, presence of comedo necrosis, hormone status (estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2), and nuclear grade. The factors significantly associated with visual analysis and SUVmax were symptomatic presentation (P = 0.019 and 0.001, respectively), use of CNB (P = 0.001 and 0.031, respectively), and enhancing lesion ≥ 20 mm on MRI (P = 0.001 and 0.049, respectively) on multivariate analysis., Conclusion: Although DCIS of breast is generally non-avid tumor, symptomatic and large tumors (≥ 20 mm) tend to be visualized on [F-18] FDG-PET/CT.

Cyclophosphamide and vincristine are known to be the chemotherapeutic agents most frequently associated with hyponatremia. Here, we report the case of a 69-year-old man with non-Hodgkin's lymphoma who developed severe hyponatremia during chemotherapy. The Japanese man was diagnosed with diffuse large B-cell lymphoma, and underwent chemotherapy treatment with THP-COP (cyclophosphamide, pirarubicin, vincristine, and prednisolone). In the first course of chemotherapy, he developed hyponatremia (nadir 109 mEq/L) and his urinary N-acetyl-β-D-glucosaminidase (NAG) level had increased. After the second courses of chemotherapy with rituximab, pirarubicin, and prednisolone, without cyclophosphamide and vincristine, he had developed light hyponatremia (nadir 130 mEq/L). However, after the third and fourth courses of chemotherapy with rituximab, pirarubicin, prednisolone, and cyclophosphamide, he had developed a medium level of hyponatremia (nadir 124-125 mEq/L) and his NAG level had increased further. The possible mechanism of this phenomenon is due to renal tubular damage by cyclophosphamide. We conclude that extra caution is necessary if a patient develops severe hyponatremia following chemotherapeutic treatment with cyclophosphamide and vincristine.

A 53-year-old woman ingested about 300 mL of 95% methanol. After immediate ethanol antagonist therapy and hemodialysis, she recovered completely. Few days later, the plasma concentration of methanol and formate was measured. A gas chromatography was used for the plasma methanol concentration measurement, and a colorimetric method was used for plasma formate concentration measurement (Formate Colorimetric Assay Kit; BioVision, California, USA). Patient's plasma methanol concentration before hemodialysis was 676.9 mg/dL and plasma formate concentration was 16.9 mg/dL. By removing blood methanol and formate using hemodialysis before formate accumulations in the body, the patient was discharged without any sequelae. We were able to obtain correlation between a gas chromatography and colorimetric method without gas chromatography-mass spectrometry, with good correlation coefficients. The sensitivity was sufficient for analyzing blood sample. Monitoring formate concentration is useful in determining the treatment and evaluating the prognosis of methanol poisoning. We suggest that this colorimetric method is useful in a facility with no access to a gas chromatography in order to measure a plasma formate concentration.

This study sought to analyze the outcome of patients with post-treatment locally recurrent uterine carcinoma treated with Au-198 seed permanent interstitial re-irradiation (Au-198 IRI). A retrospective review of the data of 15 patients with post-treatment locally recurrent uterine carcinoma treated with Au-198 IRI between 1991 and 2009 was performed to evaluate the disease response, local control, overall survival and complication rates. All the patients had received definitive radiation therapy or surgery as the initial treatment. None were judged as being suitable candidates for surgical treatment, and were referred for Au-198 IRI. Au-198 IRI was performed for the vaginal wall in 8 patients, vaginal stump in 4 patients, vulva in 2 patients, and cervix in 1 patient. The median tumor volume was 1.3 cm(3)(range, 0.4-6.9), the median treated volume was 6.3 cm(3)(range, 1.8-11), and the median prescribed dose was 76 Gy (range, 68-90). At a median follow-up duration of 19 months (range, 4.3-146.9), 13 of 15 patients (87%) showed complete responses after Au-198 IRI, although 10 of these 13 patients (77%) developed repeat central recurrence again between 2.5 and 49.7 months after the Au-198 IRI (median, 12.5 months). The overall 2-year local control rate and 2-year overall survival rate in the 15 patients were 33% and 64%, respectively. Two (13%) of the 15 patients experienced late complications that were more severe than Grade III. As a result, Au-198 IRI is considered to be one of the salvage treatment modalities with tolerable complications for inoperable centrally recurrent uterine carcinoma.

Ferrocene-based ligands 1,1'-di(pyrazinyl)ferrocene (L1) and 1,1'-di(2-pyrimidinyl)ferrocene (L2) were synthesized and copper and silver complexes were obtained from L1. Coordination polymers [{Cu(2)(PhCOO)(4)}(L1)](n) (1), [{Cu(2)(C(5)H(11)COO)(4)}(L1)](n) (2), and [{Cu(2)(OAc)(4)}(L1)](n).0.5n[Cu(2)(OAc)(4)(H(2)O)(2)].1.5nCH(3)CN (3) resulted from the reaction with the corresponding copper carboxylates. In all three complexes, L1 links the dinuclear copper carboxylate units to form one-dimensional step-like chains. In 2, these chains are further linked by [Cu(2)(OAc)(4)(H(2)O)(2)] dinuclear units via hydrogen bonding to form sheet structures. The reaction of L1 with copper(I) iodide resulted in a multinuclear complex [(CuI)(4)(L1)(2)].(L1) (4), which contains a [(CuI)(4)(L1)(2)] diferrocene unit with a step-like (CuI)(4) core. Reactions of L1 with silver(I) salts resulted in silver-bridged diferrocenes [Ag(2)(L1)(2)]X(2) (X = ClO(4) (5a, b), NO(3) (6a-c) and PF(6) (7)), some of which incorporate aromatic solvents into their crystal lattices. The intramolecular Ag...Ag separations in these metallamacrocycles (3.211-3.430 A) depended upon the counter-anions and on the coordination mode of the silver ions. In all of these coordination complexes, L1adopts a synperiplanar eclipsed conformation and acts as a bidentate ligand, with only the 5-nitrogen of each pyrazine ring involved in coordination.

In 3T3-L1 preadipocytes, hormonal induction causes adipose conversion and facilitates the expression of insulin-sensitive glucose transporter, GLUT4. Evidence has accumulated that, in 3T3-L1 preadipocytes, the formation of GLUT4 storage vesicle and its translocation to plasma membrane precede both lipid accumulation and expression of GLUT4 and C/EBPalpha, a key transcription factor for adipose differentiation. On the other hand, 3T3-C2 fibroblastic cells, a subline of 3T3-L1, follow adipogenic process till mitotic clonal expansion stage (2 days after hormonal induction), but do not proceed to terminal differentiation stage (8 days after the induction), resulting in a lack of adipose conversion and GLUT4 expression. Here we show that, when myc-tagged GLUT4 was retrovirally expressed in 3T3-C2 cells, insulin-stimulated GLUT4 translocation did occur on day 2 after the induction. On day 8 after the induction, however, neither GLUT4 translocation nor the expression of C/EBPalpha was observed. We also created 3T3-C2 cells stably expressing both myc-tagged GLUT4 and C/EBPalpha, demonstrating that co-expressed cells showed insulin-stimulated GLUT4 translocation on day 8 after the induction, as well as adipose conversion coupling with PPARgamma expression. Our results provide evidence that C/EBPalpha has the potential to maintain the ability of insulin-stimulated GLUT4 translocation in C/EBPalpha-deficient 3T3-C2 fibroblastic cells.

A commonly occurring nucleotide polymorphism of the insulin-receptor substrate 2 (IRS-2) gene at amino acid 1057 from Glycine to Asparaginic acid (G1057D) was recently shown to be a determinant of insulin sensitivity in both glucose-tolerant individuals and those with type 2 diabetes. With respect to the latter, the IRS-2 D1057 allele increase the risk of insulin resistance among obese individuals. After we reconstructed haplotypes from the G1057D variant and the -769C/T replacement that was newly identified, we investigated the possibility that the IRS-2 gene affects insulin sensitivity in Japanese glucose-tolerant subjects (n = 260) and type 2 diabetic patients (n = 123). We did not find that the D1057 allele and haplotype pairs were associated with the risk of diabetes. However, type 2 diabetic patients, particularly obese patients, carrying the D1057 allele and the CA haplotype were associated with insulin resistance. Furthermore, we suggested that the TG and CG haplotypes might have a protective role against insulin resistance. This observation raises the possibility that both the IRS-2 D1057 allele and the CA haplotype are useful genetic markers for identifying obese individuals who are particularly susceptible to insulin resistance.

Evidence has accumulated that some of the angiotensin II AT1 receptor antagonists have insulin-sensitizing property. We thus examined the effect of telmisartan on insulin action using 3T3-L1 adipocytes. With standard differentiation inducers, a higher dose of telmisartan effectively facilitated differentiation of 3T3-L1 preadipocytes. Treatment of both differentiating adipocytes and fully differentiated adipocytes with telmisartan caused a dose-dependent increase in mRNA levels for PPARgamma target genes such as aP2 and adiponectin. By contrast, telmisartan attenuated 11beta-hydroxysteroid dehydrogenase type 1 mRNA level in differentiated adipocytes. Of note, we demonstrated for the first time that telmisartan augmented GLUT4 protein expression and 2-deoxy glucose uptake both in basal and insulin-stimulated state of adipocytes, which may contribute, at least partly, to its insulin-sensitizing ability.

Purpose: Prostate-specific membrane antigen (PSMA), which is a transmembrane glycoprotein predominantly expressed in prostate cancer, is an attractive target for tumor-specific immunotherapy. To identify human leukocyte antigen (HLA)-A24-restricted epitope peptides from PSMA for further application of the dendritic cell (DC)-based immunotherapy targeting prostate cancer, we have screened several PSMA-encoded HLA-A24-binding peptides for their capabilities to elicit specific antitumor CTL response in vitro., Experimental Design: The amino acid sequence of PSMA was screened for peptides consisting of 9 or 10 amino acids, which possess the known HLA-A24-binding motif. Nine candidate peptides were screened for binding to HLA-A24 molecules. Then, each of these nine peptides was studied to determine whether CTL responses could be induced by primary in vitro immunization of CD8(+) T cells using peptide-pulsed autologous DCs derived from peripheral blood mononuclear cells of HLA-A24(+) healthy donor as antigen-presenting cells. The antigen specificity of the CTL lines was confirmed using several tumor cell lines as target cells, which were genetically modified to express both HLA-A24 and PSMA., Results: Two peptides, LYSDPADYF and NYARTEDFF, were demonstrated to elicit CTL lines that lyse peptide-pulsed, HLA-A24(+) B-lymphoblastoid cells. Each of the CTL lines recognized their specific PSMA-expressing target cells in a HLA-A24-restricted manner. The capability to release IFN-gamma by the CTL lines was specifically inhibited by anti-MHC class I and anti-CD8 monoclonal antibodies but not by anti-MHC class II and anti-CD4 monoclonal antibodies., Conclusion: Two novel HLA-A24-restricted PSMA-derived epitopes were identified in this study. These epitopes can be used to further evaluate the clinical utility of DC-based immunotherapeutic strategies for treatment of hormone-refractory prostate cancers.

The Amplicor Mycobacteria, a PCR-based assay, is a rapid test for the detection of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare in clinical samples. To estimate the reliability and reproducibility of the method, a cooperative blind study was conducted among 9 laboratories. Materials used for testing consisted of 105 sputum and 30 water samples containing known numbers of M. bovis BCG, M. avium, M. intracellulare, and samples without bacteria. Only 2 out of the 9 laboratories correctly identified the presence or absence of mycobacterial DNA in all 135 samples. In sputum samples, 6 out of the 9 laboratories detected mycobacterial DNA in all positive samples, and 4 out of the 9 laboratories correctly reported the absence of DNA in the negative samples, indicating the need for good laboratory practice and development of reference reagents to monitor the performance of the whole study, including pretreatment of clinical samples. The main problem was lack of specificity rather than lack of sensitivity. From about half of the laboratories, false-positive results were reported, however, the ratio was below 6%; 1% (1/106 sputum samples) in 3 laboratories, 1.9% (2/105) in 2 laboratories, and 5.7% (6/105) in one laboratory, respectively. These results indicate that the Amplicor Mycobacteria is quite useful for a rapid diagnosis of tuberculosis.

The Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD) is a rapid test for the detection of Mycobacterium tuberculosis, utilizing the rRNA amplification method. For assessing the reliability and reproducibility of the method, a co-operative blind study was conducted among 6 laboratories. Materials for test were sputum and water samples containing known numbers of Mycobacterium bovis BCG or Mycobacterium avium, and samples without bacteria. From three of 6 laboratories, false-positive results were reported for bacteria negative samples, however, the ratio was below 10%; 8.3% (3/36 samples), 5.6% (2/36), and 2.8% (1/36), respectively. It indicates the indispensability of negative controls for sample pretreatment and RNA extraction stages in the routine MTD test. In every laboratory, all the samples with 10(2) BCG in water and 10(4) BCG in sputum were found to be MTD positive. For the sputum samples with 10(2) BCG, positive results with the ratio above 80% were reported from 4 laboratories. These results indicate that the MTD test based on rRNA amplification method is quite useful for the rapid diagnosis of M. tuberculosis infection.

Variation in the nucleotide sequence of the HPV 16 E7 gene in preinvasive cervical intraepitherial neoplasia (CIN) and invasive cervical carcinoma specimens was analyzed. Direct DNA sequencing of PCR-amplified products with primers different from those used for PCR with 5'-end labeling generated distinct sequence ladders with a low background, even in specimens containing relatively low copy numbers of HPV. Of 14 cervical neoplasias, 11 cases showed sequence diversity from prototype HPV16, and a total of 22 nucleotide exchanges were detected. Nine of these led to single amino acid exchanges: [Thr5] to [Lys5] in one case and [Asn29] to [Ser29] in eight cases. The [Ser29] E7 was distributed uniformly among invasive carcinomas and precancerous legions, and was also found in a normal cervix. The [Lys5] E7 and [Ser29] E7 had transforming potential similar to the prototype E7 assessed by cooperation with the activated ras gene in rat embryo fibroblasts.

The effect of protease inhibitors, leupeptin and pepstatin A, on the metabolism of acetylated low density lipoprotein (acetyl-LDL) was investigated in cultured rat peritoneal macrophages and compared with that of chloroquine. While both leupeptin and pepstatin inhibited the proteolytic degradation of 125I-acetyl-LDL, a combination of both showed an additive effect. Similar to chloroquine, both protease inhibitors diminished [3H] oleate incorporation into cellular cholesteryl[3H] oleate and increased cholesterol content of macrophages. These results suggest that both thiol protease and cathepsin D participate in the physiological degradation of apolipoprotein in macrophages. The inhibition of apolipoprotein degradation seemed to have an effect on cholesterol metabolism in macrophages cultured with acetyl-LDL.

Objective: We have assessed the mechanisms which maintain euthyroidism in acromegalic patients despite the suppression of thyrotrophin (TSH) secretion., Materials: Fourteen untreated patients with acromegaly were analysed. Ten patients were also studied after pituitary surgery., Methods: Thyroid hormones, growth hormone (GH), insulin-like growth factor-I (IGF-I) and thyroidal uptake of radioactive iodine, thyrotrophin releasing hormone (TRH) test and basal metabolic rate (BMR) were measured before and after pituitary surgery., Results: Nine patients had palpable goitres. The TSH response to TRH stimulation was suppressed in eight patients, who maintained normal serum levels of total T3, T4 and free T4. The patients with normal TSH response had lower levels of free and total T4 than controls. The response of TSH to TRH correlated inversely with the serum level of total and free T4, and also with the plasma level of IGF-I (r = -0.74, P less than 0.05, n = 9). After pituitary surgery, the serum levels of total and free T4 were elevated for at least up to 6 months, with a decrease in the T3/T4 ratio and the BMR., Conclusion: GH may have a direct stimulatory action on the thyroid secretion of T4 possibly via increased IGF-I, despite suppressed TSH secretion. The post-operative elevation of serum T4 suggests the persistent secretion of T4 from the thyroid gland, in spite of instantaneous normalization of the accelerated conversion of T4 to T3, even after reduction of excess GH secretion.

Recovery of thyroid function in patients with both thyroid and renal dysfunction was studied. Among 245 patients with primary hypothyroidism (serum TSH greater than 10 mU/l), 36 had mild to severe renal dysfunction (serum urea nitrogen greater than 7.1 mmol/l and creatinine greater than 106 mumol/l). Of these 36 patients, recovery of the thyroid function after iodine restriction was observed in 30 (83%), in whom an elevated serum non-hormonal iodine level (median 236, range 67-15,591 micrograms/l, N = 19) and a high thyroidal radioactive iodine uptake (51.5 +/- 29.3% at 24 h, N = 26) were observed. The perchlorate discharge test was positive in 7 of 13 patients examined, suggesting an iodide organification defect rather than an atrophic or destructive change in the thyroid. Antithyroid antibodies were negative in 22 patients (73%) and an almost normal thyroid gland or colloid goitre was confirmed histologically in 8 of them. After a 13.2 mg potassium iodide loading test, 24 h urinary excretion of iodine was about 60% in normal controls, but only 10% in a different group of six euthyroid patients with renal dysfunction. These findings suggest that impaired renal handling of iodine rather than autoimmune mechanism may have a significant role in the pathogenesis of reversible hypothyroidism found in patients with renal dysfunction, probably through a prolonged Wolff-Chaikoff effect.

The Inhibitory effect of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), a hydrohobic carboxyl modifying reagent, on the N,N'-dicyclohexylcarbodiimide (DCCD)-sensitive Na+/H(+)-antiporter in Archaebacterial H. halobium, was studied. The inhibition time course suggests that a single carboxyl residue is modified by EEDQ. The profile of pH dependence of EEDQ effect and the competitive binding of [14C]-DCCD and EEDQ indicate that EEDQ does not compete with DCCD for the same site but modifies one of the two functional H+ binding sites previously reported [Murakami and Konishi (1989) Arch. Biochem. Biophys. 271, 515-523].

Purified C. perfringens type A enterotoxin fed orally in an amount of 5 mg caused both vomiting and diarrhea in the monkey only when the gastric juice had been neutralized. Exposure of enterotoxin to pH 4.0 or below rapidly destroyed the activity. All three monkeys receiving sodium bicarbonate and 2.4 X 10(10) viable cells grown in DS medium developed diarrhea, and only one of them vomited once. The diarrhea lasted for 13, 18 and 19 hr. The symptoms were similar to those reported in human cases of C. perfringens food poisoning. These results have verified the general notion that C. perfringens food poisoning should be categorized as a true "intravital intoxication". The reversed passive hemagglutination test detected enterotoxin directly in most fecal samples. This method may be applicable for diagnosis of human cases of C. perfringens food poisoning. Neither enterotoxin nor anti-enterotoxin was detected in serum samples taken from any monkey up to 21 days after the challenge. We are tempted to conclude, therefore, that no significant amount of C. perfringens enterotoxin is absorbed from the intestine.