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Uracil derivatives having a vinyl group at the C-5 position and a sulfilimine moiety at the C-6 position were prepared and cyclized to 1,3,6-trisubstituted pyrrolo[2,3-d]pyrimidine-2,4-diones by sunlight photolysis in good yields.

The double processes of He in electron-impact ionization, single ionization with simultaneous excitation and double ionization, have been studied at large momentum transfer using an energy- and momentum-dispersive binary $(e,2e)$ spectrometer. The experiment has been performed at an impact energy of $2080\phantom{\rule{0.3em}{0ex}}\mathrm{eV}$ in the symmetric noncoplanar geometry. In this way we have achieved a large momentum transfer of $9\phantom{\rule{0.3em}{0ex}}\mathrm{a.u.}$, a value that has never been realized so far for the study on double ionization. The measured $(e,2e)$ and $(e,3\ensuremath{-}1e)$ cross sections for transitions to the $n=2$ excited state of ${\mathrm{He}}^{+}$ and to doubly ionized ${\mathrm{He}}^{2+}$ are presented as normalized intensities relative to that to the $n=1$ ground state of ${\mathrm{He}}^{+}$. The results are compared with first-order plane-wave impulse approximation (PWIA) calculations using various He ground-state wave functions. It is shown that shapes of the momentum-dependent $(e,2e)$ and $(e,3\ensuremath{-}1e)$ cross sections are well reproduced by the PWIA calculations only when highly correlated wave functions are employed. However, noticeable discrepancies between experiment and theory remain in magnitude for both the double processes, suggesting the importance of higher-order effects under the experimental conditions examined as well as of acquiring more complete knowledge of electron correlation in the target.

Background Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), whereas HTLV type 2 (HTLV-2), is not associated with ATL or any other leukemia. HTLV-1 encodes the transforming gene tax1, whose expression in an interleukin (IL)-2-dependent T-cell line (CTLL-2) induces IL-2-independent growth. Results In this study, we demonstrated that IL-2-independent growth induction by Tax1 was abrogated by mutations of the PDZ domain-binding motif (PBM) at the Tax1 C-terminus. HTLV-2 Tax2, which shares 75% amino acid identity with Tax1 but does not have a PBM, was not able to induce IL-2-independent growth of CTLL-2. Conclusion Our results suggest that Tax1, through interaction with PDZ domain protein(s) induces IL-2-independent growth, which may be a factor in multi-step leukemogenesis caused by HTLV-1.

We report the first experimental results showing transition-specific anisotropy of molecular frame (e, 2e) cross sections. Vector correlations between the two outgoing electrons and the fragment ion have been measured for specific ionization-excitation processes of H2. The results enable us to obtain molecular frame (e, 2e) cross sections for transitions to the 2ssigma(g) and 2psigma(u) excited states of H(2)(+), thereby making stereodynamics of the electron-molecule collisions directly visible.

Background Human T-cell leukemia virus type 1 (HTLV-1) is associated with the development of adult T-cell leukemia (ATL). HTLV-1 encoded Tax1 oncoprotein activates the transcription of genes involved in cell growth and anti-apoptosis through the NF-κB pathway, and is thought to play a critical role in the pathogenesis of ATL. While Tax1 expression is usually lost or minimal in ATL cells, these cells still show high constitutive NF-κB activity, indicating that genetic or epigenetic changes in ATL cells induce activation independent of Tax1. The aim of this study was to identify the molecules responsible for the constitutive activation of NF-κB in ATL cells using a retroviral functional cloning strategy. Results Using enhanced green fluorescent protein (EGFP) expression and blasticidin-resistance as selection markers, several retroviral cDNA clones exhibiting constitutive NF-κB activity in Rat-1 cells, including full-length CD30, were obtained from an ATL cell line. Exogenous stable expression of CD30 in Rat-1 cells constitutively activated NF-κB. Elevated expression of CD30 was identified in all ATL lines examined, and primary ATL cells from a small number of patients (8 out of 66 cases). Conclusion Elevated CD30 expression is considered one of the causes of constitutive NF-κB activation in ATL cells, and may be involved in ATL development.

We recently reported promoter polymorphisms in the IRF-1 gene, an interferon-inducible gene that plays an important role in host antiviral function. The promoter activity was shown to be different between different polymorphisms. In this study, we investigated the relationship between IRF-1 promoter polymorphisms and the response to interferon monotherapy for chronic hepatitis C. Eighteen patients with a low initial viral load or hepatitis C virus (HCV) genotype non-1b received 6-months course of interferon-β monotherapy. IRF-1 gene mutations and the treatment response were investigated. The IRF-1 promoter type possessing a higher promoter activity (−415C/−410A/−300A) was found in only three patients, all of which had a lower viral load than those with other promoter types and were able to obtain a sustained viral response. Flow cytometric analysis of peripheral blood mononuclear cells showed that the patients with a higher promoter activity of the IRF-1 had a significantly higher proportion of T helper 1-type CD4 + cells after interferon administration than those of other promoter types. These results suggest that IRF-1 promoter polymorphisms may contribute, at least partially, to host antiviral activity for chronic hepatitis C.

A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) and ribavirin. HCV core Ag negativity could predict SVR on day 1 (sensitivity = 100%, specificity = 85.0%, accuracy = 86.4%), whereas RNA negativity could predict SVR on day 7 (sensitivity = 100%, specificity = 87.2%, accuracy = 88.6%). None of the patients who had detectable serum core Ag or RNA on day 14 achieved SVR (specificity = 100%). The predictive accuracy on day 14 was higher by RNA negativity (93.2%) than that by core Ag negativity (75.0%). The combined predictive criterion of both viral load decline during the first 24 h and basal viral load was also predictive for SVR; the sensitivities of Lumipulse-Ag and Amplicor-M were 45.5 and 47.6%, respectively, and the specificity was 100%. Amplicor-M had better predictive accuracy than Lumipulse-Ag in 2-week disappearance tests because it had better sensitivity. On the other hand, estimates of kinetic parameters were similar regardless of the detection method. Although the correlations between Lumipulse-Ag and Amplicor-M were good both before and 24 h after IFN administration, HCV core Ag seemed to be relatively lower 24 h after IFN administration than before administration. Lumipulse-Ag seems to be useful for detecting the HCV concentration during IFN therapy; however, we still need to understand the characteristics of the assay.

Theoretical fine spectroscopy has been performed for the valence ionization spectra of furan, pyrrole, and thiophene with the symmetry-adapted-cluster configuration-interaction general-R method. The present method described that the pi(1) state interacts with the pi(3) (-2)pi*, pi(2) (-2)pi*, and pi(2) (-1)pi(3) (-1)pi* shake-up states providing the split peaks and the outer-valence satellites, both of which are in agreement with the experiments. The intensity distributions were analyzed in detail for the inner-valence region. In particular, for furan, theoretical intensities were successfully compared with the intensity measured by the electron momentum spectroscopy. The interactions of the 3b(2) and 5a(1) states with the shake-up states were remarkable for furan and pyrrole, while the 4b(2) state of thiophene had relatively large intensity.

5 or 7-Trifluoromethyl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-2,4-diones 3, 5, 10, 13 and 4- or 6-trifluoromethylpyrazolo[3,4-b]pyridines 15, 16, 19, 21 were prepared from 6-aminouracils and 5-aminopyrazoles, respectively, in good yields by the use of building blocks such as 4,4,4-trifluoro-1-phenyl-1,3-butanedione, 1,1,1-trifluoro-4-phenyl-3-buten-2-one, 4-ethoxy-1,1,1-trifluoro-3-buten-2-one, and ethyl trifluoroacetoacetate.

The transintervertebral disc approach was proposed recently for percutaneous neurolytic celiac plexus block (NCPB). Its superior simplicity, reliability, as well as safety potentially overcome the technical hurdles of NCPB that may interfere with the practical use of this validated analgesic intervention for abdominal cancer pain. The present study was conducted to evaluate the effectiveness of the use of this approach in a resident education program for NCPB.The clinical results of NCPBs conducted from January 2001 to September 2002 were examined comparing that performed by institutional residents with that by specialized physicians authorized by the Japanese Society of Pain Clinicians. The transintervertebral disc approach was used in all cases. Each resident completed NCPB under close supervision of the specialists.Twenty-four patients received NCPB during the study period. Seven residents randomly completed 12 procedures and 4 specialists did others. The duration of fluoroscopy to complete the procedure was 256+/-109 sec in the resident group and 392+/-194 sec in the specialist group (ns). Significant pain reduction was obtained immediately after NCPB in all patients without any intergroup difference. No critical complication was observed in each group.The transintervertebral disc approach can be used effectively and safely in educational practice of NCPB for less-trained physicians.

58歳,女性.緩徐進行性の歩行障害.高度の変形性頸椎症と脊柱管狭窄,頸髄MRIでT2高信号変化より頸椎症性頸髄症を疑ったが,胸部X線で肺門部拡大あり.他のサルコイドーシス(サ症)の身体・血清学的所見は陰性.しかし縦隔内リンパ節生検でサ症を確認.診断治療を目的に副腎皮質ステロイドを投与し,神経・画像所見は寛解した.頸椎症性頸髄病変の存在例に一つでもサ症の所見が陽性時は,サ症の内科的治療を優先すべき点を強調した.

発端例は高校野球部生徒で左胸痛を主訴に受診した.血液検査,胸部単純X線,心電図,心エコー検査を行い,典型的ではなかったが,急性心膜炎疑いにて入院となった.その後同校野球部とサッカー部内で同様の症状を訴える生徒が多く出現し,流行性胸膜痛(Bornholm disease)の集団発生を考えた.経過により,コップやペットボトルの回し飲みによるエンテロウイルス属の経口感染を強く疑った.集団発生により流行性胸膜痛と診断できた興味深い症例であり,報告した.

N-(Uracil-6-yl)-S,S-diphenylsulfilimine (1) prepared from uracils reacted with aryldiazonium salts to give N-(5-arylazouracil-6-yl)-S,S-diphenylsulfilimines (2), β-azo-α,β-unsaturated sulfilimines, in good yields. The azosulfilimines (2) were converted on thermolysis into the corresponding 2H-1,2,3-triazolo[4,5-d]pyrimidine-5,7-diones (3) in good yields.

We developed a flowchart for the treatment of cancer-related hypercalcemia based on the review of previous reports. The treatment protocols were standardized in each group of four different ranges of serum calcium concentration (12, 12-14, 14-16,16 mg/dl). In each Ca range, specific treatment was adjusted according to the clinical evaluation of symptoms and progression of illness of the patients.

To provide additional pharmacokinetic evidence for the oral-to-parenteral relative potency ratio of 1:2 to 1:3 for chronic morphine use in a palliative care setting, we determined the plasma concentrations of morphine and its major metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), in hospitalized advanced cancer patients maintained on long-term oral or intravenous morphine. There were significant linear correlations between daily doses of morphine and plasma concentrations (molar base) of morphine, M3G and M6G for both routes of administration. The oral-to-intravenous relative ratios of the regression coefficients were 2.9 for morphine and 1.8 for morphine» / M6G. The morphine kinetic variables were not significantly influenced by any hepato-renal biochemical markers. These results support the commonly used oral-to-intravenous relative potency ratio of 1:2 to 1:3 in patients with cancer pain receiving chronic morphine treatment.

Bovine leukemia virus (BLV) is the etiologic agent of enzootic bovine leukosis (EBL). In a previous report, we found that in a sheep model, only CD5(-) B cells proliferated clonally, while CD5(+) B cells rapidly decreased when the disease progressed to the lymphoma stage. We demonstrate here that, although both CD5(+) and CD5(-) B cells, but not CD4(+) T, CD8(+) T and gammadeltaTCR(+)T cells, are protected from spontaneous ex vivo apoptosis in sheep infected with wild-type and a mutant BLV that encodes a mutant Tax D247G protein with elevated trans-activation activity, only CD5(-) B cells become the main target for ex vivo survival when the disease proceeds to the persistent lymphocytotic stage, which showed an increased expansion of the CD5(-) B cells. In addition, we identified, by four-color flow cytometric analysis, that in CD5(-) B cells, the apoptotic rates of cells that expressed wild-type and mutant BLV were greatly decreased compared with those of BLV-negative cells. There was only a slight reduction in the apoptotic rates in BLV-positive cells from CD5(+) B cells. In addition, supernatants from peripheral blood mononuclear cell (PBMC) cultures from wild-type- and mutant BLV-infected sheep mainly protected CD5(-) B cells from spontaneous apoptosis. Our results suggest that, although BLV can protect both CD5(+) and CD5(-) B cells from ex vivo apoptosis, the mechanisms accounting for the ex vivo survival between these two B-cell subsets differ. Therefore, it appears that the phenotypic changes in cells that express CD5 at the lymphoma stage could result from a difference in susceptibility to apoptosis in CD5(+) and CD5(-) B cells in BLV-infected sheep.

A 49-year-old man with syringomyelia and a Type I Arnold-Chiari malformation (Chiari-I) was diagnosed with growth hormone insensitivity syndrome (GHIS). He was short in stature, had high circulating levels of GH, and low circulating levels of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3). His GH responses to the administration of growth hormone-releasing hormone (GHRH) and L-DOPA were normal, but his levels of IGF-I and IGFBP-3 did not increase after the administration of exogenous GH. Direct genomic DNA sequencing revealed neither a mutation nor deletion in this patient's GH receptor (GHR) gene, though one polymorphism was detected, indicating that his GHR gene was normal. This is the first reported case of an association of GHIS with syringomyelia and Chiari-I malformation.

We performed radiofrequency ablation (RFA) therapy combined with intrahepatic arterial infusion chemotherapy for 7 patients with liver metastasis from colorectal cancer. Synchronous metastasis accounted for 5 cases and metachronous for 2 cases. Two cases were H1, 2 cases H2, and 3 cases H3. Following the resection of colorectal primary lesion, we performed RFA for liver metastasis, using a Cool-tip electrode purchased from Radionics (Burlington, MA, USA). The mean number of sessions per patient was 5.1 (1-10). Ablation time of each session was changed according to tumor size, as follows: less than 1 cm in diameter: 2 min, 2 cm: 5 min, 2.5 cm: 10 min. By using intra-operative catheterization, weekly intrahepatic arterial infusion chemotherapy was performed for liver metastasis. Excellent ablation was achieved in all cases by CT evaluation and no significant side-effect was observed. Average observation period was 15 months (maximal survival period was 31 months) and 6 patients are alive. RFA therapy combined with intrahepatic arterial infusion chemotherapy achieved excellent therapeutic effect, and maintained good quality of life in patients.

Purpose To evaluate the effects of total spinal block (TSB) on brain function, TSB-induced changes in cortical electrical activities were analyzed using power spectral analysis of an electroencephalogram (EEG). Methods Six patients suffering from chronic pain who were undergoing TSB therapy were studied. TSB was established with intrathecal 1% lidocaine (0.3 ml.kg(-1)) injected through the C1-2 lateral intervertebral space. Mechanical ventilation was continued via a laryngeal mask until the recovery of respiration. The EEG recording was started before TSB induction and continued until 10 min after extubation. The following processed EEG parameters were monitored: spectral edge frequency-90% (SEF90), spectral median frequency (SMF), and relative power in the frequency bands of delta, theta, alpha, beta, and the delta ratio [(alpha + beta)/delta]. Results TSB induced an unconscious state more than 40 min in all patients. During TSB, 12-13 Hz in SEF90 and 6-7 Hz in SMF were observed. These values are consistent with the previously reported prearousal threshold from general anesthesia. The other EEG descriptors did not change during the TSB-induced unconscious state. Conclusion The dissociation of cortical electrical activities and the clinical coma-like condition may be characteristic of the TSB-induced unconscious state.

Patients with intractable cancer pain often require non-pharmacological analgesic treatment that is accompanied by procedure-related pain. Previous works have shown that propofol infusion in adjunction to regional anesthesia provides appropriate sedation during such painful procedures. However, there are a few reports of its use to reduce procedure-related pain in terminal cancer patients. We report cases of propofol sedation during percutaneous vertebroplasty (PVP) in patients with metastatic vertebral compression fracture.Propofol was infused during PVP in eleven cancer patients after obtaining written informed consent. The infusion rate of propofol was adjusted using a target-controlled infusion pump to achieve appropriate sedation levels under monitoring bispectral index of the electroencepharogram. Hepatic and renal functions were evaluated using common serum markers, which were determined using standard hospital laboratory methods.The duration of the procedure was 65.5 +/- 5.5 (mean +/- SD) min. The required infusion rate was 8.66 +/- 1.50 mg.kg-1.hr-1. The interval from the termination of the infusion until emergence was 10.7 +/- 4.2 min. No life-threatening complications or significant changes in liver and renal functions were observed.Propofol can be used effectively and safely for sedation during PVP in terminal cancer patients.

In spite of several advantages, the need for postoperative ventilatory support limits the use of high-dose opioid anesthesia. We prospectively evaluated the effectiveness of naloxone infusion for the reversal of high-dose fentanyl anesthesia.Anesthesia was maintained with fentanyl in patients undergoing major abdominal surgery. After anesthesia, the trachea was extubated when intravenous naloxone, which was titrated in separate 50- micro g doses, established an acceptable level of consciousness and arterial blood gas (ABG) status under spontaneous respiration; this was followed by continuous infusion started at the rate of the sum of the bolus doses per hour. The naloxone infusion was terminated based on evaluation of the level of consciousness, ABG, and acute abstinence symptoms. Postoperative pain was evaluated using self-reported four-step categorical terms (none, mild, moderate, and severe). Plasma concentrations of fentanyl and naloxone were analyzed in 12 patients, using high-performance liquid chromatography.Fifty-seven out of 59 eligible patients were successfully extubated at 34 +/- 14 min after termination of fentanyl (total dose, 127 +/- 64 micro g.kg(-1); mean +/- SD) with naloxone (total bolus, 3.4 +/- 2.6 micro g.kg(-1)). All these patients recovered fully without ventilatory support under the naloxone infusion, which was terminated at 11 +/- 7 h. The reduction of the naloxone infusion rate effectively relieved the increased pain, and no supplemental analgesic was used in any patients during the naloxone infusion. Pharmacokinetic analysis did not indicate any correlations between plasma fentanyl and naloxone concentrations.The results suggest that naloxone infusion with individual dose titration facilitates the use of high-dose opioid anesthesia, maintaining the advantager of this anesthesia.

The pharmacological profile of N-(6-(2-(5-bromopyrimidine-2-yloxy)ethoxy)-5-(4-methylphenyl)pyrimidin-4-yl)-4-(2-hydroxy-1,1-dimethylethyl) benzensulfonamide sodium salt sesquihydrate (TA-0201), a new antagonist of endothelin receptors, was examined, using human recombinant and prostate endothelin receptors. In binding experiments with [125I]endothelin-1, TA-0201 showed extremely high affinity for recombinant endothelin ET(A) receptors (pK(i)=10.7), as compared with that for recombinant endothelin ET(B) receptors (pK(i)=7.8). Endothelin ET(A) and ET(B) receptors coexisted in human prostate with different proportions (endothelin ET(A) receptor: approximately 70%), which were distinguished by TA-0201 in the same manner as with recombinant receptors. Human prostate strips contracted in response to endothelin-1 and sorafotoxin S6c, but the maximum contraction induced by endothelin-1 was approximately three times greater than that induced by sarafotoxin S6c. The response to endothelin-1, but not to sarafotoxin S6c, was inhibited by TA-0201 and cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ123) (endothelin ET(A) receptor antagonist) but not by BQ788 (endothelin ET(B) receptor antagonist). These results suggest that TA-0201 is a highly selective endothelin ET(A) receptor antagonist and will be useful for understanding the physiological and pathological roles of the endothelin ET(A) receptor in human prostate and other tissues.

1,3-Dialkyl-6-chlorouracils were treated with S , S -diphenylsulfilimine to give N -(1,3-dialkyluracil-6-yl)- S , S -diphenylsulfilimines. The uracilylsulfilimines were nitrosated, acylated, or thiocarbamoylated to give N -(5-nitroso-, 5-acyl-, or 5-thiocarbamoyluracil-6-yl)sulfilimines, respectively. These conjugated sulfilimines were cyclized by thermolysis or photolysis to [1,2,5]oxadiazolo[3,4- d ], isoxazolo[3,4- d ], or isothiazolo[3,4- d ]pyrimidine derivatives.

Reactions of 1,2-dihydro-4H-3,1-benzothiazine-2,4-dithiones (trithioisatoic anhydrides) 3 with N-substi-tuted benzylamines 9 gave 1,2-dihydroquinazoline-4-thiones 10, o-thioureidodithiobenzoic acid 11, o-aminothiobenzamides 12, 2-amino-3,1-benzothiazine-4-thiones 13, or quinazoline-2,4-dithiones 14, depending on the kinds of amine and the reaction solvent. On the other hand, reaction of 3 with trialkyl phosphites afforded dialkyl (1,2-dihydro-2-thioxo-4H-3,1-benzothiazin-4-yl)phosphonates 18.

A laser diode (LD) with narrow beam divergence is attractive for a low cost subscriber light source module, since its high fiber-coupling efficiency enables lensless assembly. Integrating a beam-expander (BEX) with an LD is one of the most promising ways for decreasing beam divergence of an LD. In this paper, we explicitly analyzed the reflection in a horizontally tapered BEX integrated with a LD by the finite-difference time-domain (FD-TD) method using massively parallel processors to reduce computation time.

1,1-Dichloro-3-phenylsulfonyl-2-propanone was treated with arenediazonium chlorides to give 1-arylhydrazono-3,3-dichloro-1-phenylsulfonyl-2-propanones, which were cyclized to 1-aryl-5-chloro-3-(phenylsulfonyl)pyrazol-4-ols on treatmemt with base.

Accurate estimation of survival is important for effective palliative medicine of patients with cancer. In most clinical practice, however, the life expectancy has been predicted based on subjective evaluations. The purpose of this study was to find objective biological markers that can contribute to accurate prediction of survival in terminally ill cancer patients. Consecutive terminally ill cancer patients admitted to the Palliative Care Center in Tohoku University hospital from January to May 2001 were approached for this study. Forty-eight blood samples were obtained from 25 patients who provided a written informed consent. Common serum enzyme markers were determined using standard hospital laboratory methods. Cellular immunity status was evaluated by peripheral blood lymphocyte-subset analysis using flow cytometry. Mean patient survival was 33.5 +/- 21.6 (1-80) days. Multiple regression analysis revealed that lactate dehydrogenase (LDH) and the CD4+/CD8+ ratio were significantly associated with survival (r = 0.64, p0.0001). Further prospective studies are warranted to validate the usefulness of these determinants for accurate prediction of survival.

We described the interferon (IFN) regulatory factor-1 (IRF-1) promoter single nucleotide polymorphisms (SNPs), and the clinical and immunologic implications of these SNPs have been investigated. We successfully determined the mutation at -300 of the IRF-1 promoter by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and this mutation linked with other mutations in the promoter region. In our Japanese population, the frequency of the type -300*A/A was 11.9%, type A/G was 54.2%, and type G/G was 33.9%. We found no significant difference without IFN stimulation in the production levels of IFN-gamma and interleukin-10 (IL-10) from peripheral blood mononuclear cells (PBMC) between subjects with -300*A/A and those with other types. IFN-alpha stimulation, however, increased the levels of IFN-gamma significantly and decreased the IL-10 production level significantly only in the subject with -300*A/A type. Flow cytometric analysis showed that the Th1-type CD4(+) cell population was significantly increased by IFN-beta administration only in the patient with chronic hepatitis C with -300*A/A type. These results suggest that the IRF-1 promoter SNP types are positively involved in Th1-type response and, consequently, the -300*A/A type may be beneficial for viral elimination in chronic hepatitis C and IFN therapy.

Adiponectin, also referred to as AdipoQ or ACRP30, is a plasma protein produced and secreted exclusively from adipose tissue. The protein contains a collagen-like domain and a C1q-like globular domain. A protease-generated globular segment enhances fatty acid oxidation in muscles, thereby modulating lipid and glucose metabolism. Plasma adiponectin levels are inversely correlated with the severity of insulin resistance. A recent genome-wide scan study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Here, we screened Japanese patients with type 2 diabetes and age- and BMI-matched nondiabetic control subjects for mutations in adiponectin gene. We identified four missense mutations (R112C, I164T, R221S, and H241P) in the globular domain. Among these mutations, the frequency of I164T mutation was significantly higher in type 2 diabetic patients than in age- and BMI- matched control subjects (P0.01). Furthermore, plasma adiponectin concentrations of subjects carrying I164T mutation were lower than those of subjects without the mutation. All the subjects carrying I164T mutation showed some feature of metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and atherosclerosis. Our findings suggest that I164T mutation is associated with low plasma adiponectin concentration and type 2 diabetes.

6 10 mm, presence of a villous component and presence of high-grade dysplasia. In the presence of multiple polyps, only the size of the largest polyp was considered for the purpose of the analysis in this study. Seven staff physicians (T.N., M.T., H.K., Y.F., H.K., H.N. and S.T.) with extensive experience in endoscopy performed or supervised all the procedures. Ten trainees in their third, fourth or fifth year participated in a proportion of the procedures. The average number of colonoscopies staff physicians and trainees took part in was 2,528 8 1,409 and 115 8 38, respectively. According to previous reports, the minimum length of time during colonoscopic withdrawal was 6 min in both groups [1, 2] . Differences between groups were compared by Student’s t test for continuous variables and Fisher’s exact test or a 2 test for categorical variables. A total of 853 screening colonoscopy procedures that fulfilled the inclusion criteria for this study were recorded in the Tokyo Medical Center endoscopic database. Of the 853 procedures, 342 were conducted Dear Sir, Training of future endoscopists is essential for meeting the increasing demands for colonoscopy. It is still unknown whether the polyp detection rates might be compromised when trainees perform colonoscopy under the supervision of experienced examiners. We therefore attempted to assess whether there might be any differences in the polyp detection rates between procedures that are performed by experienced staff physicians alone (EP) and those that are performed with trainee participation (TP). Procedural data from all screening colonoscopies performed at the Tokyo Medical Center between January 1, 2006 and December 31, 2010 were reviewed. All patients had a positive result on the fecal occult blood test. The exclusion criteria included suboptimal bowel preparation and incomplete examination (inability to reach the cecum). Demographic information (age, gender) and the colonic lesion detection profile (size and number) were recorded. The polyps were classified as 1–9, 10–19 or 6 20 mm in size. Polyps that were 7 mm in diameter were measured by placing the open biopsy forceps, which have a span of 7 mm, against the lesion. Published online: September 7, 2011

Objective To examine risk factors for Clostridium difficile infection (CDI) morbidity and mortality in Japan. Design Multimethod investigation including a case–control study and cohort study. Setting 47 participating facilities of the National Hospital Organization (NHO). Participants 1026 patients with CDI and 878 patients in the control group over the age of 18 years admitted to the subject NHO facilities from November 2010 to October 2011. Main outcome measures In a case–control study, we identify risk factors for CDI development. Next, in a cohort study, we identify risk factors for all-cause mortality within 30 days following CDI onset. Results A total of 1026 cases of CDI meeting the definitions of this investigation were identified, encompassing 878 patients at 42 of the 47 subject facilities. In the case–control study, we identified, compared with no antibiotics use, use of first-generation and second-generation cephem antibiotics (OR 1.44; 95% CI 1.10 to 1.87), use of third-generation and fourth-generation cephem antibiotics (OR 1.86; 95% CI 1.48 to 2.33) and use of carbapenem antibiotics (OR 1.87; 95% CI 1.44 to 2.42) the risk factors for CDI development. However, use of penicillin was not identified as a risk factor. In the cohort study, sufficient data for analysis was available for 924 CDI cases; 102 of them (11.0%) resulted in death within 30 days of CDI onset. Compared with no anti-CDI drug use, use of vancomycin was associated with reduced risk of mortality (OR 0.43; 95% CI 0.25 to 0.75) whereas metronidazole was not. Conclusions The findings mirror those of previous studies from Europe and North America, identifying the administration of broad-spectrum antibiotics as a risk factor for CDI development. The use of vancomycin is associated with a decreased risk of mortality.

We report a theoretical study on the valence-shell electronic excitations of N2O induced by electron impact. Momentum transfer–dependent generalized oscillator strengths (GOSs) or GOS profiles have been calculated for the low-lying electronic excitations using theoretical wave functions at the equation-of-motion coupled-cluster singles and doubles level. In the calculation, Herzberg–Teller vibronic effects are taken into account. The computed results are in overall agreement with experimental GOS profiles reported in the literature and reveal prominent roles of the bending vibration of N2O in the B1Δ and C1Π transitions.

We report the instrumental design and technical details of an (e, 2e) electron momentum spectroscopy (EMS) apparatus, which employs an ultrashort-pulsed incident electron beam with a repetition rate of 5 kHz and a pulse duration in the order of one picosecond. EMS data for the neutral Ar atom in the ground state measured by using the pulsed electron beam are presented to illustrate the potential abilities of the apparatus for ultrafast molecular dynamics. The results are discussed mainly in terms of signal intensity.

69 Background: Recently, abscopal effect, by which systemic anti-tumor effect by local radiation therapy (RT) was elicited, has been reported. This phenomenon was thought to be mediated by stress protein gp96, a key molecule in antigen-presenting. We tested the enhancement of dendritic cell (DC) therapy by various stress, such as radiation or modulated electro-hyperthermia (mEHT) in DC therapy for squamous cell carcinoma (SCC). Methods: Mouse SCC cells, SCCVII, were inoculated into the left femur (primary tumor) of C3H/He mice subcutaneously, and also similarly inoculated into non-treated chest subcutaneous tissue (secondary tumor). Only the primary tumor was exposed to 4 or 10 Gy of RT or 5-10 watts of mEHT. Then DCs was injected only into the primary tumor. Following that, tumor volumes of the primary and secondary tumor were measured. Next, the population of immune-related T-cells in tumor-draining lymph nodes (TDLN) and gp96 expression in the primary tumor were evaluated. Results: With intratumoral injection of DCs and RT, primary tumor growth was markedly suppressed. Furthermore, secondary tumor growth was also suppressed. On the other hand, the combination of DCs and mEHT could inhibit tumor growth at both the primary and the secondary tumor. As for the population of T-cells, the population of CD3+, CD 4+ and CD 8+T-cells in the TDLN was markedly elevated and that of FoxP3 was reduced my mEHT. Gp96 expression, a stress protein, was strongly enhanced after RT and mEHT. Conclusions: Stress, such as RT or hyperthermia can enhance the efficacy of DC therapy and can induce a strong antitumor effect by stimulating the expression of stress protein, gp96. These combination therapies can be a strong systemic immunotherapy for esophageal SCC.

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), and the viral oncoprotein Tax plays key roles in immortalization of human T-cells and leukemogenesis. Here, we identified the ubiquitin-specific protease 10 (USP10) as a Tax-interactor in T-cells. Upon an exposure to arsenic, an oxidative stress inducer, USP10 was recruited into stress granules (SGs), which are the anti-stress machinery. USP10-knockout indicated that USP10, through augmenting formation of SGs, reduced reactive oxygen species (ROS) production and inhibited ROS-dependent apoptosis. Tax mutants and USP10-knockdown indicated that Tax inhibits arsenic-induced SG formation, stimulates ROS production and augments ROS-dependent apoptosis, and they are all dependent on interactions of Tax with USP10. These findings suggest that USP10 is a host factor that controls stress-induced ROS production and apoptosis in HTLV-1-infected T-cells. A clinical trial showed that a combination therapy containing arsenic is effective against some forms of ATL. Thus, these findings may also be relevant to chemotherapy against ATL.

Small heterodimer partner (SHP, NR0B2) is an atypical orphan nuclear receptor that inhibits transcriptional activation by several other nuclear receptors. We recently reported that mutations in the SHP gene are associated with insulin resistance. In the present study, we demonstrated that the SHP gene is expressed in adipose tissues. A reporter gene assay showed that a gene product of SHP increased the transcriptional activation of peroxisome proliferator-activated receptor (PPAR) gamma. SHP-mediated activation of PPARgamma was observed both in the presence and absence of the ligand of PPARgamma. Immunoprecipitation and glutathione S-transferase pull-down assay showed that SHP directly bound to PPARgamma and competed with nuclear receptor corepressor for binding to PPARgamma. Serial deletion studies indicated that the C terminus of SHP is important for PPARgamma activation. Mutant SHP proteins, which are found in naturally occurring mutation, showed less enhancing activity for PPARgamma than wild-type SHP. Our results suggest that SHP may act as an endogenous enhancer of PPARgamma.

Insulin resistance and its dreaded consequence, type 2 diabetes, are major causes of atherosclerosis. Adiponectin is an adipose-specific plasma protein that possesses anti-atherogenic properties, such as the suppression of adhesion molecule expression in vascular endothelial cells and cytokine production from macrophages. Plasma adiponectin concentrations are decreased in obese and type 2 diabetic subjects with insulin resistance. A regimen that normalizes or increases the plasma adiponectin might prevent atherosclerosis in patients with insulin resistance. In this study, we demonstrate the inducing effects of thiazolidinediones (TZDs), which are synthetic PPARγ ligands, on the expression and secretion of adiponectin in humans and rodents in vivo and in vitro. The administration of TZDs significantly increased the plasma adiponectin concentrations in insulin resistant humans and rodents without affecting their body weight. Adiponectin mRNA expression was normalized or increased by TZDs in the adipose tissues of obese mice. In cultured 3T3-L1 adipocytes, TZD derivatives enhanced the mRNA expression and secretion of adiponectin in a dose- and time-dependent manner. Furthermore, these effects were mediated through the activation of the promoter by the TZDs. On the other hand, TNF-α, which is produced more in an insulin-resistant condition, dose-dependently reduced the expression of adiponectin in adipocytes by suppressing its promoter activity. TZDs restored this inhibitory effect by TNF-α. TZDs might prevent atherosclerotic vascular disease in insulin-resistant patients by inducing the production of adiponectin through direct effect on its promoter and antagonizing the effect of TNF-α on the adiponectin promoter.

IMPLICATIONS We describe the successful management of thoracoscopic thoracic duct ligation in a 2.5-kg compromised infant by using selective lobar-bronchial blockade. The technique reduces the risk of intraprocedural physiologic impairment, allowing the benefits of otherwise minimally invasive thoracoscopic procedures, even when the conditions of children are severely compromised.

FOR pediatric video-assisted thoracic surgery, surgical access has been conventionally accomplished by the total collapse of the ipsilateral lung via blocking 1,2 or intubation 3,4 of the selected main bronchus. However, single-lung ventilation includes possible detrimental effects on the physiologic conditions in small children. 5 More selected exposure of the targeted intrathoracic space may decrease these risks. Recently, we reported a newly devised double-accessport endotracheal tube (DAPT) for pediatric one-lung anesthesia. 6 The tube provides independent access for ventilation and bronchial blocking using a balloon-tipped catheter so that fiberoptic adjustment of the balloon position is possible during sufficient ventilation. The current report describes the successful use of this device for selective lobar-bronchial blocking.

Investigation of functional groups, which give characteristic chemical properties to molecules, has been one of the most important theme in chemistry. Molecules having two equivalent functional groups have particularly attracted interests of many researchers. For the understanding of intramolecular interactions between the identical functional groups, Hoffmann et al. 1,2 have proposed the concept of through-space (TS) and through-bond (TB) interactions. TS interaction originates from the direct overlap between the semi-localized orbitals of the two functional groups, and places their symmetric linear combination (+) below the anti-symmetric one (-). In contrast, TB interaction, which occurs with participation of intervening bonds, may force the orbital ordering to be the reverse. These TS and TB interactions are usually competitive, and hence the orbital ordering depends on the molecule in question.