Hybridization of Bogoliubov Quasiparticles between Adjacent CuO_{2} Layers in the Triple-Layer Cuprate Bi_{2}Sr_{2}Ca_{2}Cu_{3}O_{10+δ} Studied by Angle-Resolved Photoemission Spectroscopy.

Hybridization of Bogoliubov quasiparticles (BQPs) between the CuO_{2} layers in the triple-layer cuprate high-temperature superconductor Bi_{2}Sr_{2}Cu_{2}Cu_{3}O_{10+δ} is studied by angle-resolved photoemission spectroscopy (ARPES). In the superconducting state, an anticrossing gap opens between the outer- and inner-BQP bands, which we attribute primarily to interlayer single-particle hopping with possible contributions from interlayer Cooper pairing. We find that the d-wave superconducting gap of both BQP bands smoothly develops with momentum without an abrupt jump in contrast to a previous ARPES study. Hybridization between the BQPs also gradually increases in going from the off nodal to the antinodal region, which is explained by the momentum dependence of the interlayer single-particle hopping. As possible mechanisms for the enhancement of the superconducting transition temperature, the hybridization between the BQPs as well as the combination of phonon modes of the triple CuO_{2} layers and spin fluctuations represented by a four-well model are discussed.

Socioecological differences in factors associated with inconsistent condom use with female sex workers and casual partners: an observational study of heterosexual men attending an anonymous HIV testing clinic in Singapore.

Sexual practices among heterosexual men may differ between female sex workers (FSWs) and casual partners. We surveyed 203 heterosexual men and investigated the attributes associated with inconsistent condom use among them. Lower educational attainment was positively associated with inconsistent condom use with FSWs (adjusted prevalence ratio (aPR) 2.63; P = 0.018) and casual partners (aPR 1.55; P = 0.022), whereas early age of sexual debut (aPR 3.00; P = 0.012) and alcohol use during sex (aPR 7.95; P < 0.001) were positively associated with inconsistent condom use with FSWs. Socioecological factors may explain such differences.

Composition of the microbiota in forestomach fluids and feces of Japanese Black calves with white scours.

The objective of this study was to characterize the composition of the forestomach and fecal microbiota in Japanese Black calves with white scours. Forestomach fluid, feces, and peripheral blood were collected from healthy calves ( = 5; age 10 ± 2 d) and scouring calves ( = 5; age 10 ± 1 d) on the day on which white scours occurred. The pH and concentrations of VFA, lactic acid, and ammonia nitrogen (NH-N) of the forestomach fluids were determined. Microbiota composition and gene copy numbers in the forestomach fluid and feces were analyzed by 454 pyrosequencing and quantitative real-time PCR (qPCR), respectively. The cytokine mRNA level in peripheral leukocytes was evaluated by qPCR. The pH of the forestomach fluid of the scouring calves tended to be higher than that of the healthy calves ( = 0.056). No significant difference was detected in the total VFA, lactic acid, or NH-N concentrations in the forestomach fluids of the 2 groups. Firmicutes, Bacteroidetes, and Proteobacteria were the predominant phyla in the forestomach fluid and feces. At the genus level, the relative abundance of in the forestomach fluid was significantly higher in the scouring calves ( < 0.05) and the relative abundance of in the feces was significantly higher than that in the forestomach in the healthy calves ( < 0.05). Furthermore, the bacterial diversity indices of feces were lower in the scouring calves. Quantitative PCR amplification using some of the primer pairs failed in the forestomach fluid and feces in both groups. These results suggested that fermentation in the forestomach may affect the occurrence of white scours, resulting in changes in the composition and diversity of the forestomach fluid and fecal microbiota in Japanese Black calves.

Enhanced superconducting gaps in the trilayer high-temperature Bi2Sr2Ca2Cu3O(10+δ) cuprate superconductor.

We report the first observation of the multilayer band splitting in the optimally doped trilayer cuprate Bi2Sr2Ca2Cu3O(10+δ) (Bi2223) by angle-resolved photoemission spectroscopy. The observed energy bands and Fermi surfaces are originated from the outer and inner CuO2 planes (OP and IP). The OP band is overdoped with a large d-wave gap around the node of Δ0∼43 meV while the IP is underdoped with an even large gap of Δ0∼60 meV. These energy gaps are much larger than those for the same doping level of the double-layer cuprates, which leads to the large Tc in Bi2223. We propose possible origins of the large superconducting gaps for the OP and IP: (1) minimal influence of out-of-plane disorder and a proximity effect and (2) interlayer tunneling of Cooper pairs between the OP and IP.

Analysis of binding site for the novel small-molecule TLR4 signal transduction inhibitor TAK-242 and its therapeutic effect on mouse sepsis model.

BACKGROUND AND PURPOSE: TAK-242, a novel synthetic small-molecule, suppresses production of multiple cytokines by inhibiting Toll-like receptor (TLR) 4 signalling. In this study, we investigated the target molecule of TAK-242 and examined its therapeutic effect in a mouse sepsis model. EXPERIMENTAL APPROACH: Binding assay with [(3)H]-TAK-242 and nuclear factor-kappaB reporter assay were used to identify the target molecule and binding site of TAK-242. Bacillus calmette guerin (BCG)-primed mouse sepsis model using live Escherichia coli was used to estimate the efficacy of TAK-242 in sepsis. KEY RESULTS: TAK-242 strongly bound to TLR4, but binding to TLR2, 3, 5, 9, TLR-related adaptor molecules and MD-2 was either not observed or marginal. Mutational analysis using TLR4 mutants indicated that TAK-242 inhibits TLR4 signalling by binding to Cys747 in the intracellular domain of TLR4. TAK-242 inhibited MyD88-independent pathway as well as MyD88-dependent pathway and its inhibitory effect was largely unaffected by lipopolysaccharide (LPS) concentration and types of TLR4 ligands. TAK-242 had no effect on the LPS-induced conformational change of TLR4-MD-2 and TLR4 homodimerization. In mouse sepsis model, although TAK-242 alone did not affect bacterial counts in blood, if co-administered with ceftazidime it inhibited the increases in serum cytokine levels and improved survival of mice. CONCLUSIONS AND IMPLICATIONS: TAK-242 suppressed TLR4 signalling by binding directly to a specific amino acid Cys747 in the intracellular domain of TLR4. When co-administered with antibiotics, TAK-242 showed potent therapeutic effects in an E. coli-induced sepsis model using BCG-primed mice. Thus, TAK-242 may be a promising therapeutic agent for sepsis.

Efficacy of open patch-grafting under cardiopulmonary bypass for pulmonic stenosis in small dogs.

OBJECTIVE: To assess the efficacy of an open patch-graft technique under cardiopulmonary bypass (CPB) in small dogs. DESIGN AND METHODS: A retrospective analysis of 10 dogs with pulmonic stenosis. Records between 1992 and 2002 were reviewed. The effect of surgical correction was evaluated and perioperative parameters were compared between survivors and non-survivors. RESULTS: The postoperative pulmonary pressure gradient was reduced in all seven surviving patients. Mean +/- SE was 21.5 +/- 7.4 mmHg (range 3.0-54.2 mmHg) and 6/7 dogs were < 40 mmHg at 3 months postoperatively. Comparing the data between those patients that survived and those that did not, the preoperative pressure gradient (P = 0.04) and volume of the Glucose-Insulin-Kalium solution used (P = 0.001) were significantly higher in those that did not survive. CONCLUSION: Open patch-grafting can be performed in small-breed dogs and decreased the pulmonary pressure gradient in survivors at 3 months postoperatively. However, this technique is more invasive than balloon valvuloplasty and should be used cautiously in severely stenosed patients.

Inhibitory effects of small-molecule CCR5 antagonists on human immunodeficiency virus type 1 envelope-mediated membrane fusion and viral replication.

We established a human immunodeficiency virus type 1 (HIV-1) envelope (Env)-mediated membrane fusion assay and examined the small-molecule CCR5 antagonist TAK-779 and its derivatives for their inhibitory effects on HIV-1 Env-mediated membrane fusion and viral replication. The membrane fusion assay is based on HIV-1 long terminal repeat-directed beta-D-galactosidase reporter gene expression in CD4- and CCR5-expressed HeLa (MAGI-CCR5) cells after cocultivation with effector 293T cells expressing HIV-1 Env. Inhibition of HIV-1 replication was also determined in MAGI-CCR5 cells infected with the corresponding cell-free HIV-1. TAK-779 effectively suppressed R5 HIV-1 (strain JR-FL) Env-mediated membrane fusion as well as viral replication. Its 50% inhibitory concentrations (IC(50)s) for membrane fusion and viral replication were 0.87 +/- 0.11 and 1.4 +/- 0.1 nM, respectively. These values corresponded well to the IC(50) for (125)I-RANTES (regulated on activation, T cell expressed, and secreted) binding to CCR5 (1.4 nM). The inhibitory effects of 18 TAK-779 derivatives on membrane fusion differed from one compound to another. However, there was a close correlation among their inhibitory effects on membrane fusion, viral replication, and RANTES binding. The correlation coefficient between their IC(50)s for membrane fusion and viral replication was 0.881. Furthermore, since this assay depends on Env expressed in the effector cells, it is also applicable to the evaluation of CXCR4 antagonists. These results indicate that the HIV-1 Env-mediated membrane fusion assay is a useful tool for the evaluation of entry inhibitors.

Experimental study of materials for patch graft on right ventricular outflow tract under extracorporeal circulation in dogs--comparison between Denacol EX-313-treated bovine jugular vein graft and expanded polytetrafluoroethylene (EPTFE) graft.

A comparison between a bovine jugular vein treated with a hydrophilic polyepoxy compound cross-linker (Denacol), and expanded polytetrafluoroethylene (EPTFE), an artificial material, as a patch graft for the reconstruction of the right ventricular outflow tract under extracorporeal circulation in dogs, as if they had pulmonic stenosis, was made. Hemodynamic and histological examinations were conducted two weeks after the transplantation. Hemodynamic problems were not observed in either the Denacol or EPTFE groups. Macroscopically, organization of new tissue on the graft surface was more marked in the EPTFE group than in the Denacol group, and newly-formed tissue was seen surrounding the border of the graft and burying it in the EPTFE group. In the Denacol group, microscopic findings revealed the presence of inflammatory cells and fibroblasts, and an invasion of the graft by collagen fibers and elastic fibers. In the EPTFE group, there was minimal cellular infiltration of the graft and a thick layer consisting of collagen fibers and fibroblasts was observed around the graft. These results indicated that two weeks after transplantation the graft was better assimilated and organized with blood vasculature in the patch graft in the Denacol group than in the EPTFE group.

ATP suppresses the K(+) current responses to FSH and adenosine in the follicular cells of Xenopus oocyte.

The application of either follicle-stimulating hormone (FSH) or adenosine (Ade) induces a K(+)-current response in the follicular cells surrounding a Xenopus oocyte under a voltage clamp. These K(+)-current responses are reported to be produced by an increase in intracellular cAMP. A previous application of ATP to the same cells markedly depressed the K(+)-current responses to FSH and Ade. Furthermore, a 2 min application of phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C (PKC), significantly depressed the K(+)-current responses to FSH and Ade, but it had no significant effect on the Cl(-)-current response to ATP. An application of either ATP or PDBu also depressed the K(+)-current response induced by intracellularly applied cAMP. In contrast to the effect of PDBu, the application of 1-octanol, an inhibitor of gap junction channel, significantly depressed both the Ade- and ATP-induced responses, indicating that the acting site of 1-octanol is different from that of PKC. The results suggest that the depressing effect of ATP on the FSH- and Ade-induced K(+)-current responses might be mediated by PKC activation and that the site of PKC action might be downstream of the cAMP production involved in the K(+) channel opening.

Physiological and pharmacological characteristics of quisqualic acid-induced K(+)-current response in the ganglion cells of Aplysia.

The extracellular application of either quisqualic acid (QA) or Phe-Met-Arg-Phe-NH2 (FMRFamide) induces an outward current in identified neurons of Aplysia ganglion under voltage clamp. The time course of the QA-induced response is significantly slower than that induced by FMRFamide. The reversal potential for both responses was -92 mV and was shifted 17 mV in a positive direction for a twofold increase in the extracellular K(+) concentration. The QA-induced response was markedly depressed in the presence of Ba(2+), a blocker of inward rectifier K(+)-channel, whereas TEA, a Ca(2+)-activated K(+)-channel (BK(Ca)) blocker, or 4-AP, a transient K(+) (A)-channel blocker, had no effect on the response. The QA-induced K(+)-current was significantly suppressed by CNQX and GYKI52466, antagonists of non-NMDA receptors. However, the application of either kainate or AMPA, agonists for non-NMDA receptors, produced no type of response in the same neurons. The QA-induced K(+)-current response was not depressed at all by an intracellular injection of either guanosine 5'-O-(2-thiodiphosphate) (GDP-betaS) or guanosine 5'-O-(3-thiotriphosphate) (GTP-gammaS), but the FMRFamide-induced response was markedly blocked by both GDP-betaS and GTP-gammaS in the same cell. Furthermore, the QA- and FMRFamide-induced K(+)-current responses were both decreased markedly when the temperature was lowered to 15 degrees C, from 23 degrees C. These results suggested that the QA-induced K(+)-current response is produced by an activation of a novel type of QA-receptor and that this response is not produced by an activation of the G protein.

[A case of renal cell carcinoma producing alpha-fetoprotein].

Renal cell carcinoma (RCC) producing alpha-fetoprotein (AFP) is a rare condition with only 11 cases reported in Japan to our knowledge. A 69-year-old man was admitted to our hospital for further examination of an incidental right renal tumor. Laboratory tests showed markedly increased serum level of AFP whereas both HBs antigen and anti-HCV antibody were negative. Computed tomography and magnetic resonance imaging imagings showed a right renal tumor but no tumor in liver, testis or lymph node. We performed right radical nephrectomy. Serum level of AFP declined within the normal range 7 weeks after nephrectomy according to its half-life curve. The tumor specimen was composed mainly of granular cells. Immunohistochemical examination of the tumor cells proved the presence of AFP in the cytoplasm. The possibility of AFP as a tumor marker of renal cell carcinoma in this case was presented.

Real-time observation of a single DNA digestion by lambda exonuclease under a fluorescence microscope field.

A fluorescence microscopy technique has been developed to visualize the behavior of individual DNA and protein molecules. Real-time direct observation of a single DNA molecule can be used to investigate the dynamics of DNA-protein interactions, such as the DNA digestion reaction by lambda exonuclease. In conventional methods it is impossible to analyze the dynamics of an individual lambda exonuclease molecule on a DNA because they can only observe the average behavior of a number of exonuclease molecules. Observation of a single molecule, on the other hand, can reveal processivity and binding rate of an individual exonuclease molecule. To evaluate the dynamics of lambda exonuclease, a stained lambda DNA molecule with one biotinylated terminal was fixed on an avidin-coated coverslip and straightened using a d.c. electric field. Microscopic observation of digestion of a straightened DNA molecule by lambda exonuclease revealed that the DNA digestion rate was approximately 1000 bases/s and also demonstrated high processivity.

Strain variation in renal carcinogenesis by N-ethyl-N-hydroxyethylnitrosamine in F1 (Wistar-Fischer) rats.

The present study was conducted to compare the incidences of renal tumors in Wistar (W), Fischer (F) and F1 rats (WF: female Wistar rats x male Fischer rats; FW: female Fischer rats x male Wistar rats) induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN). Levels of 8-OHdG in renal DNA were also investigated in Wistar and Fischer rats. After 2000 ppm of EHEN was administered orally for 2 weeks, the animals were fed basal diet until week 32. Wistar males and females demonstrated significantly higher sensitivity regarding induction of renal lesions, while both WF and FW rats had similar incidences, generally intermediate between those for the two parent strains. The formation of 8-OHdG was maximal 60-180 min after an intraperitoneal dose of 750 mg/kg to Wistar and Fischer rats, which correlates with the increase tending to the incidence of renal tumors in male and female Wistar and Fischer rats. The results suggest that EHEN induction of renal tumors is related to oxygen radical damage and that the genes in the Wistar strain responsible for the sensitivity are not inherited in a sex-dependent fashion, despite the male being more susceptible.

Hypertrophic cardiomyopathy in two kittens.

Two 2-month-old kittens presented with a loud cardiac murmur. One cat showed severe signs of heart failure such as respiratory effort and exercise intolerance. Echocardiography revealed left ventricular concentric hypertrophy and severe left ventricular outflow obstruction. They died at 5 and 12 months of age, respectively. Necropsy and histopathology confirmed hypertrophic cardiomyopathy.

Overexpression of p53 protein and MDM2 in papillary carcinomas of the thyroid: Correlations with clinicopathologic features.

Expression of p53 protein and MDM2 was evaluated in paraffin-embedded tissue from 78 patients with papillary carcinomas of the thyroid (PCT), in order to elucidate the relationship between them and their correlations with some clinicopathologic features implicated in tumor progression. These proteins were expressed in nuclei of tumor cells, but not in non-tumor cells. Staining was defined as positive when 10% or more of tumor cells expressed these proteins. The number of cases positive for p53 protein was 21/78 (27%), and that positive for MDM2 was 26/78 (33%). Co-overexpression of p53 protein and MDM2 was observed in 12/78 cases (15%). A significant positive relationship was found between them (P < 0.01); p53-positive cases tended to be also positive for MDM2 and vice versa. Statistical analysis revealed that overexpression of p53 protein significantly correlated with large tumor size (P = 0.0271) and the presence of capsular invasion (P = 0.04). There were significant positive correlations between tumor size and intrathyroidal invasion and between tumor size and capsular invasion in PCT, suggesting that p53 protein overexpression is associated only with tumor progression (tumor size). However, we could not find any significant correlations between MDM2 expression and clinicopathologic features. Our findings suggest that overexpression of p53 protein and MDM2 in papillary carcinoma of the thyroid is associated with the progression of the tumors, and that p53 may be a marker of the progression of PCT.

Treated natural history of superficial bladder cancer.

BACKGROUND: The present study was conducted to examine the natural history of superficial bladder cancer. METHODS: One hundred and forty-four patients with superficial bladder cancer who had been treated with transurethral resection of bladder tumor (TURBt) alone were analyzed. RESULTS: The non-recurrence rate was 64.8% at 36 months and 61.2% at 60 months after TURBt. When the non-recurrence rate after TURBt was analyzed by background variables, the rate differed significantly between the solitary tumor group and the multiple tumor group. The tumor recurrence hazard curves for the entire population had one high peak before 500 days and another slight peak around 1500 days after TURBt. CONCLUSIONS: These results will provide basic information useful when evaluating new regimens of intravesical instillation therapy for prophylaxis of superficial bladder cancer after our complete TURBt in the Nara Uro-Oncology Research Group.

The R-type pyocin of Pseudomonas aeruginosa is related to P2 phage, and the F-type is related to lambda phage.

Pseudomonas aeruginosa produces three types of bacteriocins: R-, F- and S-type pyocins. The S-type pyocin is a colicin-like protein, whereas the R-type pyocin resembles a contractile but non-flexible tail structure of bacteriophage, and the F-type a flexible but non-contractile one. As genetically related phages exist for each type, these pyocins have been thought to be variations of defective phage. In the present study, the nucleotide sequence of R2 pyocin genes, along with those for F2 pyocin, which are located downstream of the R2 gene cluster on the chromosome of P. aeruginosa PAO1, was analysed in order to elucidate the relationship between the pyocins and bacteriophages. The results clearly demonstrated that the R-type pyocin is derived from a common ancestral origin with P2 phage and the F-type from lambda phage. This notion was supported by identification of a lysis gene cassette similar to those for bacteriophages. The gene organization of the R2 and F2 pyocin gene cluster, however, suggested that both pyocins are not simple defective phages, but are phage tails that have been evolutionarily specialized as bacteriocins. A systematic polymerase chain reaction (PCR) analysis of P. aeruginosa strains that produce various subtypes of R and F pyocins revealed that the genes for every subtype are located between trpE and trpG in the same or very similar gene organization as for R2 and F2 pyocins, but with alterations in genes that determine the receptor specificity.

[The problem of a long-term follow up in patients with renal cell carcinoma].

PURPOSE: We investigated on a problem of long-term follow up in patients with renal cell carcinoma. PATIENTS AND METHODS: A total of 287 patients with renal cell carcinoma treated in Nara Medical University and affiliated facilities from January 1980 to December 1990 were examined. And we investigated the trend of explanation to patients including 287 patients from 1991 to 1995. RESULTS: Up to December 1995, there are 76 patients (26.5%) unable to be followed and 211 patients able to be followed. The former group patients were less declared cancer rather than the latter group patients. Of 76, 22 patients (28.9%) might misunderstand completely recovering from the cancer disease. For the recent 5 years, those patients who were declared cancer increased, and those patients who were explained benign disease decreased. CONCLUSION: These results suggested that declaration of cancer is important for patients with renal cell carcinoma to be followed for a long-term.