Lieb-Schultz-Mattis Theorem in Higher Dimensions from Approximate Magnetic Translation Symmetry.

We prove the Lieb-Schultz-Mattis theorem on the energy spectrum of a general two- or three-dimensional quantum many-body system with the U(1) particle number conservation and translation symmetry. Especially, it is demonstrated that the theorem holds in a system with long-range interactions. To this end, we introduce approximate magnetic translation symmetry under the total magnetic flux Φ=2π instead of the exact translation symmetry, and explicitly construct low energy variational states. The energy spectrum at Φ=2π is shown to agree with that at Φ=0 in the thermodynamic limit, which concludes the Lieb-Schultz-Mattis theorem.

Botulinum toxin injection into the intrinsic laryngeal muscles to treat spasmodic dysphonia: A multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial.

BACKGROUND AND PURPOSE: Botulinum toxin (BT) injection into the laryngeal muscles has been a standard treatment for spasmodic dysphonia (SD). However, few high-quality clinical studies have appeared, and BT is used off-label in most countries. METHODS: We performed a multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial to obtain approval for BT (Botox) therapy in Japan. Twenty-four patients (22 with adductor SD and two with abductor SD) were enrolled. The primary end point was the change in the number of aberrant morae (phonemes) at 4 weeks after drug injection. The secondary end points included the change in the number of aberrant morae, GRBAS scale, Voice Handicap Index (VHI), and visual analog scale (VAS) over the entire study period. RESULTS: In the adductor SD group, the number of aberrant morae at 4 weeks after injection was reduced by 7.0 ± 2.30 (mean ± SE) in the BT group and 0.2 ± 0.46 in the placebo group (p = 0.0148). The improvement persisted for 12 weeks following BT injections. The strain element in GRBAS scale significantly reduced at 2 weeks after BT treatment. The VHI and VAS scores as subjective parameters also improved. In the abductor SD group, one patient responded to treatment. Adverse events included breathy hoarseness (77.3%) and aspiration when drinking (40.9%) but were mild and resolved in 4 weeks. CONCLUSIONS: Botulinum toxin injection was safe and efficacious for the treatment of SD. Based on these results, BT injection therapy was approved as an SD treatment in Japan.

Effect of Structural Differences in Collagen Sponge Scaffolds on Tracheal Epithelium Regeneration.

OBJECTIVE: We developed an in situ regeneration-inducible artificial trachea composed of a porcine collagen sponge and polypropylene framework and used it for tracheal reconstruction. In the present study, collagen sponges with different structures were prepared from various concentrations of collagen solutions, and their effect on the regeneration of tracheal epithelium was examined. METHODS: Collagen sponges were prepared from type I and III collagen solutions. The structures of the sponges were analyzed using scanning electron microscopy (SEM). Artificial tracheae, which were formed using the collagen sponges with different structures, were implanted into rabbits, and regeneration of the tracheal epithelium on the artificial tracheae was evaluated by SEM analysis and histological examination. RESULTS: The SEM analysis showed that collagen sponges prepared from 0.5% and 1.0% collagen solutions had a porous structure. However, the sponges prepared from a 1.5% collagen solution had a nonporous structure. After implantation of artificial tracheae prepared from 0.5% and 1.0% collagen solutions, their luminal surfaces were mostly covered with epithelium within 14 days. However, epithelial reorganization occurred later on artificial tracheae prepared from the 1.5% collagen solution. CONCLUSION: Collagen sponges with a porous structure are suitable for regeneration of the tracheal epithelium in our artificial trachea.

[Assessment of Cachexia in Head and Neck Cancer Patients Based on a Modified Glasgow Prognostic Score].

We retrospectively analyzed 54 patients who died of head and neck squamous cell caricinoma regarding the process and duration of cachexia using the modified Glasgow Prognostic Score (mGPS). The patients were classified as having cachexia when the serum albumin level was less than 3.5 mg/dL and the C-reactive protein (CRP) level was more than 0.5 mg/dL. The number of patients with cachexia was eight (8%) at the first visit and 50 (93%) at the time of death. In the 50 patients, the median and average time of having cachexia was 59 and 95 days, respectively. Thirty-two of the 50 patients (64%) died within three months after the presence of cachexia was confirmed. In this study, the time of having cachexia was so short, then the policy of care should be converted from aggressive into supportive in patients classified as having cachexia. mGPS would be an accurate assessment tool for cachexia and ascertain the end stage of head and neck cancer patients.

Orbital angular momentum and spectral flow in two-dimensional chiral superfluids.

We study the orbital angular momentum (OAM) L_{z} in two-dimensional chiral (p_{x}+ip_{y})^{ν}-wave superfluids (SFs) of N fermions on a disk at zero temperature, in terms of spectral asymmetry and spectral flow. It is shown that L_{z}=νN/2 for any integer ν, in the Bose-Einstein condensation regime. In contrast, in the BCS limit, while the OAM is L_{z}=N/2 for the p+ip-wave SF, for chiral SFs with ν≥2, the OAM is remarkably suppressed as L_{z}=N×O(Δ_{0}/ϵ_{F})≪N, where Δ_{0} is the gap amplitude and ϵ_{F} is the Fermi energy. We demonstrate that the difference between the p+ip-wave SF and the other chiral SFs in the BCS regimes originates from the nature of edge modes and related depairing effects.

Effects of low temperature on ploidy levels in parthenogenetic and sexual forms of the weevil Scepticus insularis (Coleoptera: Curculionidae).

We examined whether the ploidy level of eggs from sexual and parthenogenetic females of the weevil Scepticus insularis changes when field-collected, egg-bearing females are exposed to low temperature, as suggested by a previous study. We observed no change in ploidy level in eggs laid by sexual females (n = 15) treated by low temperature (1.1-6.7°C). In contrast, eggs laid by parthenogenetic females were not stable in ploidy level, as 11 of 16 females tested laid both diploid and triploid eggs even before the low-temperature treatment. After the low-temperature treatment, the proportion of triploid eggs to total eggs increased in nine individuals and decreased in the rest, and the effect of the treatment on the overall change in frequency was significant. Our results thus show that exposure to cold does not induce a change in egg ploidy in the sexual form of S. insularis, although cold may affect ploidy levels in the eggs of parthenogens. Additionally, eggs laid by laboratory-reared, virgin sexual females (n = 13) did not hatch after the low-temperature treatment, indicating that the treatment did not induce parthenogenetic reproduction in normally sexually reproducing females of S. insularis. We also examined the effect of low temperature on the ploidy level of eggs from parthenogenetic females (n = 4) of another weevil species, Catapionus gracilicornis, and confirmed that the proportion of triploid eggs steeply decreased and that of diploid eggs increased after exposure to cold, being consistent with those of previous studies.

Fecundity of parthenogenetic and sexual forms of the flightless weevil Scepticus insularis (Coleoptera: Curculionidae) with and without effects from mating.

We measured the fecundity (number of eggs laid and number of eggs hatched) of the Parthenogenese and sexual forms of the weevil Scepticus insularis (Roelofs) with and without effects from mating, using one sexual and two parthenogenetic populations (one of the latter sympatric and the other allopatric with sexuals). When mated sexuals and unmated parthenogens were compared, the average number of eggs laid per female was largest for allopatric parthenogens (274 eggs), followed by sympatric parthenogens (223), and smallest for sexuals (169), with a significant difference only between allopatric parthenogens and sexuals (P < 0.05). The average number of eggs hatched per female was largest for allopatric parthenogens (136 hatchlings), followed by sexuals (119), and smallest for sympatric parthenogens (59), with a significant difference only between allopatric and sympatric parthenogens. In addition, mating significantly increased the reproductive output of sympatric parthenogens (59 vs. 188 hatchlings per female) by increasing egg productivity and hatching rate, but not that of allopatric parthenogens (136 vs. 133). The productivity of parthenogens of S. insularis is thus nearly equal to (in unmated sympatric parthenogens) or much higher (in other categories of parthenogens) than that of conspecific sexuals at the start of the larval stage, provided that the sex ratio of sexuals is 0.5 and all else being equal. Our results further showed that fecundity and other important aspects of the demography of parthenogenetic females may vary locally, or depending on whether they are sympatric or allopatric with sexuals.

Geographic distributions of sexual and parthenogenetic forms of the weevil Scepticus insularis (Coleoptera: Curculionidae) in Japan.

Geographic ranges of parthenogenetic animals often differ from those of their sexual conspecifics, providing valuable information about evolutionary histories. We studied the geographic distributions of sexual and parthenogenetic forms of the weevil Scepticus insularis (Roelofs) (Coleoptera, Curculionidae) on Honshu, Shikoku, and Kyushu Islands, Japan. We collected Scepticus insularis at 18 sites in the northern half of Honshu; sequenced 633 bp of the mitochondrial ND2 (NADH dehydrogenase subunit 2) gene for 102 Honshu beetles; and constructed a ML gene tree based on these sequences and sequences previously reported for 104 conspecific beetles from Hokkaido of known reproductive mode. The ND2 haplotypes fell into two distinct clades (I and II) separated by 9.5% nucleotide sequence divergence. The haplotypes from all parthenogenetic females on Hokkaido and those from all-female populations on Honshu invariably belonged to clade I, whereas sexual females on Hokkaido and some of the females in male/female populations on Honshu belonged to clade II. Haplotypes of males were in clade II, except for two Hokkaido males having a clade-I haplotype. Excluding these two enigmatic males, we treated individuals with clade-I haplotypes as parthenogenetic, and those with clade-II haplotypes as sexual. Parthenogenetic beetles were widespread throughout Hokkaido and central and northern Honshu, whereas sexuals were found only in three separate areas on Hokkaido and one on Honshu, often sympatrically with parthenogens. The distribution of S. insularis is congruent with the pattern termed geographic parthenogenesis.

[Endoscopic endonasal detection of cerebrospinal fluid leakage with topical fluorescein].

We evaluated the effectiveness of intraoperative topical application of fluorescein to detect the leakage point of cerebrospinal fluid(CSF)rhinorrhea. Three patients with CSF rhinorrhea were treated with an endoscopic endonasal technique. Ten percent fluorescein was topically used for intraoperative localization of the leak site. A change of the fluorescein color from brown to green due to dilation of CSF were recognized as evidence of CSF rhinorrhea. We repeated the procedure to detect any small defects. All CSF rhinorrheas were successfully repaired by this endoscopic endonasal approach. Topical application of fluorescein is simple and sensitive for identifying intraoperative CSF rhinorrhea.

Regeneration of tracheal epithelium using a collagen vitrigel-sponge scaffold containing basic fibroblast growth factor.

OBJECTIVES: Our group has had good results in tracheal mucosal regeneration using a collagen vitrigel-sponge scaffold in an animal model. In this study, the effectiveness of this scaffold with the application of basic fibroblast growth factor (b-FGF) was investigated. METHODS: A collagen vitrigel-sponge scaffold was fabricated with simultaneous addition of b-FGF. Three types of collagen vitrigel-sponge scaffolds were made: no b-FGF, 10 ng of b-FGF, and 100 ng of b-FGF. At 3, 5, 7, and 14 days after implantation in rats, the tracheas were removed and histologically evaluated. The regeneration of mucosal epithelium and the subepithelial layer was evaluated. RESULTS: Mucosal epithelium, including pseudostratified epithelium and ciliated cells, regenerated earlier in the scaffolds when b-FGF was applied than when b-FGF was not applied. Regeneration of the subepithelial layer, infiltration of inflammatory cells and fibroblasts, and angiogenesis were promoted earlier in the scaffolds with b-FGF application. CONCLUSIONS: Our technique for tracheal reconstruction using collagen vitrigel-sponge scaffolds with b-FGF application affords a feasible approach for accelerating the regeneration of the intraluminal surface and subepithelial layer of tracheal tissue.

Enhanced S100 calcium-binding protein P expression sensitizes human bladder cancer cells to cisplatin.

OBJECTIVE: • To investigate the role of S100 calcium-binding protein P (S100P) in the gain of cis-diamminedichloroplatinum (II) (cisplatin) resistance in bladder cancer, having previously found, with cDNA microarrays using two pairs of parental (T24, KK47) and their cisplatin-resistant bladder cancer cell lines (T24/DDP10, KK47/DDP20), that S100P mRNA expression was significantly reduced in cisplatin-resistant cells. MATERIALS AND METHODS: • S100P mRNA and protein expression levels were investigated by northern and western blot analyses, respectively. • Intracellular S100P localization was examined by immunocytochemistry and immunohistochemistry. • S100P over-expression, obtained by transfection with S100P expression plasmid, was used to investigate whether or not S100P affected cellular resistance to cisplatin. RESULTS: • S100P mRNA showed increased expression by cisplatin stimulation in parental cell lines. • On the other hand, S100P mRNA and protein expression levels were markedly reduced in cisplatin-resistant cells. • The over-expression of S100P in resistant cells resulted in an increased sensitivity to cisplatin. CONCLUSIONS: • In bladder cancer cells, S100P was expressed and localized mainly in the nucleus. • S100P expression was also involved in cisplatin sensitivity. • S100P might thus represent a molecular marker predicting cisplatin sensitivity and a molecular therapeutic target for cisplatin-based chemotherapy.

Twist1 and Y-box-binding protein-1 promote malignant potential in bladder cancer cells.

OBJECTIVE: To investigate the roles of Twist1 and Y-box binding protein-1 (YB-1) and their potential as therapeutic targets in bladder cancer (BC), as both have been suggested to play important roles in tumour growth, invasion and drug resistance. MATERIALS AND METHODS: Bladder cancer cell lines (TCCsup, UMUC3, T24 and KK47 cells) were used. Twist1 and YB-1 expression levels were assessed by luciferase reporter assay, quantitative real-time polymerase chain reaction (PCR) and western blot analysis. Tumour growth and cell cycle were analysed by cell proliferation assay and flow cytometry, respectively. Invasive and motile abilities were investigated by scratch-wound test and migration assay, respectively. Cytotoxicity assay was performed to determine drug sensitivity. RESULTS: The findings showed that Twist1 regulated YB-1 expression in BC cells. Both Twist1 and YB-1 were involved in cell growth, invasion, motility and resistance to cisplatin and doxorubicin, but not to 5-fluorouracil (5-FU). CONCLUSION: The present study showed that Twist1 regulates YB-1 expression and that both Twist1 and YB-1 promote malignant potentials, including tumour growth, invasion and anti-cancer-drug resistance, indicating that both Twist1 and YB-1 are novel molecular targets in BC.

Phylogenetic relationships among bisexual and unisexual lineages of the weevil Scepticus insularis (Coleoptera: Curculionidae) on Hokkaido, Northern Japan.

We examined the geographic distributions and phylogenetic relationships of bisexual and unisexual (parthenogenetic) forms of the weevil Scepticus insularis on Hokkaido Island, northern Japan. Unisexual beetles were widespread throughout Hokkaido, whereas bisexuals were found only in three remote areas. Bisexuals (females and males) and unisexual females occurred sympatrically in two areas. We determined nucleotide sequences for part of the mitochondrial NADH dehydrogenase subunit 2 (ND2; 633 bp) gene for 104 individuals, and for part of the nuclear internal transcribed spacer region 2 (ITS2; 360 bp) for 91 individuals. In an ND2 gene tree, haplotypes of S. insularis fell into two distinct clades (A and B), which were genetically differentiated from one another by 9.1% nucleotide sequence divergence. Haplotypes of females identified as unisexual were all in clade A, whereas those of females identified as bisexual belonged to clade B. Haplotypes of males were in clade B, except for two males having a clade-A haplotype. Circumstantial evidence suggests that these two males were produced by unisexual females. The ND2 tree suggests that the current unisexual form of S. insularis on Hokkaido was of a single origin. In contrast, a gene tree for ITS2 haplotypes show no clear divergence between the two modes of reproduction, with two major haplotypes shared by unisexual females, bisexual females, and males. This incongruence between the nuclear and mitochondrial phylogenies may be attributable to occasional gene flow between the unisexual and bisexual lineages through males occasionally produced by unisexual females, but our results do not exclude the possibility that the two lineages share polymorphic ancestral ITS2 haplotypes.

Rare case of angiomyolipoma of the larynx.

We report a rare case of angiomyolipoma (AML) of the larynx. AML belongs to the family of perivascular epithelioid cell tumors (PEComas). We review the literature on PEComas and describe differences in immunohistochemical findings between renal AML and AML in the head and neck region.

Regenerative potential of basic fibroblast growth factor contained in biodegradable gelatin hydrogel microspheres applied following vocal fold injury: Early effect on tissue repair in a rabbit model.

INTRODUCTION: Postoperative dysphonia is mostly caused by vocal fold scarring, and careful management of vocal fold surgery has been reported to reduce the risk of scar formation. However, depending on the vocal fold injury, treatment of postoperative dysphonia can be challenging. OBJECTIVE: The goal of the current study was to develop a novel prophylactic regenerative approach for the treatment of injured vocal folds after surgery, using biodegradable gelatin hydrogel microspheres as a drug delivery system for basic fibroblast growth factor. METHODS: Videoendoscopic laryngeal surgery was performed to create vocal fold injury in 14 rabbits. Immediately following this procedure, biodegradable gelatin hydrogel microspheres with basic fibroblast growth factor were injected in the vocal fold. Two weeks after injection, larynges were excised for evaluation of vocal fold histology and mucosal movement. RESULTS: The presence of poor vibratory function was confirmed in the injured vocal folds. Histology and digital image analysis demonstrated that the injured vocal folds injected with gelatin hydrogel microspheres with basic fibroblast growth factor showed less scar formation, compared to the injured vocal folds injected with gelatin hydrogel microspheres only, or those without any injection. CONCLUSION: A prophylactic injection of basic fibroblast growth factor -containing biodegradable gelatin hydrogel microspheres demonstrates a regenerative potential for injured vocal folds in a rabbit model.

Foxo3a expression and acetylation regulate cancer cell growth and sensitivity to cisplatin.

Many advanced cancers receive cisplatin-based chemotherapy. However, cisplatin resistance is a major obstacle for cancer chemotherapy. Foxo3a is a member of the Foxo transcription factor family, which modulates the expression of genes involved in DNA damage repair, apoptosis, and other cellular processes. In this study, we found that cisplatin-resistant cells were more sensitive to the anticancer agent mithramycin than their parental cells, and had a decreased level of Foxo3a expression. Foxo3a knockdown increased cell proliferation and resistance to cisplatin. On the other hand, mithramycin stimulated Foxo3a expression through reactive oxygen species production and sensitized cells to cisplatin, which was abolished by Foxo3a knockdown, while the acetylation status of Foxo3a was decreased in response to cisplatin treatment and was lower in cisplatin-resistant cells. Knockdown of Foxo3a-associated acetyltransferase p300 promoted cancer-cell growth and cisplatin resistance. In addition, non-acetylation-mimicking Foxo3a overexpression decreased cancer cell growth and sensitized cells to cisplatin less than wild-type Foxo3a overexpression. The current work may contribute to the evaluation of the therapeutic potential of inducing the Foxo3a pathway and acetylating the Foxo3a transcription factor, and lead to the reevaluation of cancer treatments based on mithramycin.

P300/CBP-associated factor regulates Y-box binding protein-1 expression and promotes cancer cell growth, cancer invasion and drug resistance.

Twist1 has been proposed to have oncogenic properties. Although Twist1 was reported to interact with p300/CBP-associated factor (PCAF) and to inhibit the functions of PCAF, it remains unclear how PCAF affects the functions of Twist1, cell growth, invasive ability, and cellular sensitivity to anticancer agents. We found that PCAF, Twist1, and Y-box binding protein-1 (YB-1) expressions were elevated in cisplatin- and doxorubicin-resistant cancer cells. Luciferase reporter assays revealed that PCAF manipulation modulated YB-1 transcription in a Twist1-dependent manner. In addition, PCAF regulated the Twist1 intracellular localization and the Twist1 transcriptional activity through its acetylation function to the Twist1. Suppression of PCAF expression reduced YB-1 expression in human urothelial cancer KK47 cells. As a result, the cell growth and invasive ability of KK47 cells was retarded by PCAF knockdown, and PCAF knockdown rendered KK47 cells sensitive to cisplatin and doxorubicin, but not to 5-fluorouracil. The present data suggest that Twist1 and YB-1 as well as PCAF may be promising molecular therapeutic targets.

Tip60 promotes prostate cancer cell proliferation by translocation of androgen receptor into the nucleus.

BACKGROUND: There are currently few effective therapies for castration-resistant prostate cancer (CRPCa). CRPC which is resistant to castration is thought to result from increased activation of the androgen/androgen receptor (AR) signaling pathway, which may be augmented by AR coactivators. METHODS: Luciferase reporter assay, Western blotting, quantitative real-time polymerase chain reaction, fluorescence microscopy, cell proliferation assay, and flow cytometry for cell-cycle analysis were used to resolve a role of Tip60 regulating AR in PCa cells. RESULTS: Tip60 regulated transcriptions of AR target genes androgen independently. Tip60 knockdown induced translocation of AR into the cytoplasm. Acetylation-mimicking mutations in the nuclear localization signal sequence caused AR protein to mainly localize in the nucleus despite androgen starvation, whereas non-acetylation-mimicking mutations caused AR to mainly localize in the cytoplasm despite androgen stimulation. Tip60 overexpression in castration-resistant LNCaP derivative CxR cells resulted in increases in the acetylated form of AR and AR localization in the nucleus even without androgen. Consequently, Tip60 silencing suppressed the growth of AR-expressing PCa cells by inducing cell-cycle arrest at the G1 phase, similar to inhibition of androgen/AR signaling. Furthermore, Tip60 knockdown suppressed the cell growth of CxR cells. CONCLUSIONS: Tip60 is involved in the proliferation of PCa cells as an AR coactivator. Modulation of Tip60 expression or function may be a useful strategy for developing novel therapeutics for PCa, even CRPC, which remain dependent on AR signaling, by overexpressing AR and its coactivators.

Transurethral endoscopic treatment of patients with upper tract urothelial carcinomas using neodymium-YAG and/or holmium-YAG laser ablation.

OBJECTIVE: To report our experience of treating patients with original and recurrent upper tract urothelial carcinomas (UC) using endoscopic lasers, with holmium-YAG and/or neodymium-YAG laser ablation, and for whom tumour stage and grade were obtained by endoscopic biopsy. PATIENTS AND METHODS: From March 2003 to March 2007, 15 patients with upper tract UC were treated with endoscopic laser ablation as the primary management. Patients were followed up by intravenous urography, computed tomography, urine cytology and/or ureteroscopic surveillance at 3- to 12-month intervals. The median (range) follow-up was 25.5 (13-51) months. RESULTS: Of the 15 patients, five had an upper tract recurrence during the follow-up. Three of these were treated with total nephroureterectomy and two had a progression in tumour stage or grade. Three patients had residual tumours; they were treated with repeated endoscopic laser treatments and had no recurrence over a median (range) of 24 (13-26) months. The renal preservation rate was 12/15 and the local recurrence rate was six/15 after the initial endoscopy. The median operative duration and tumour size were 60 min and 10 mm, respectively. CONCLUSION: Patients with low-grade and -stage disease and normal contralateral kidneys also benefit from this approach, if there is an adequate endoscopic biopsy. As the operative duration tended to be associated with the maximum tumour size, this treatment is potentially available for a maximum tumour size of <4 cm; if the tumour is <4 cm surgery will require <120 min.

Activator protein 2 alpha (AP2alpha) suppresses 42 kDa C/CAAT enhancer binding protein alpha (p42(C/EBPalpha)) in head and neck squamous cell carcinoma.

The tumor suppressor C/CAAT enhancer binding protein alpha (C/EBPalpha) is a transcription factor involved in cell cycle control and cellular differentiation. A recent study showed that C/EBPalpha is frequently downregulated in head and neck squamous cell carcinoma (HNSCC) by DNA methylation in an upstream regulatory region. Here, we investigated how DNA methylation in the upstream regulatory region disrupts the transcriptional regulation of C/EBPalpha in HNSCC. The results reveal that aberrant methylation correlates with methyl binding domain protein binding and repressive histone modifications. This methylated region contains previously uninvestigated AP2alpha binding sites. AP2alpha suppresses C/EBPalpha promoter activity and protein expression. Interestingly, silencing AP2alpha by shRNA increases the antiproliferative isoform of C/EBPalpha (p42(C/EBPalpha)). Furthermore, growth analysis revealed that these 2 isoforms yield very different proliferative properties in HNSCC.