Arterial stiffness is increased in young women with endometriosis.

Endometriosis is a chronic gynaecological disorder that is accompanied by inflammation and oxidative stress. Atherosclerosis has a long subclinical progression in arteries of children and young adults decades before overt clinical manifestations of the disease. In this study, we determined arterial stiffness by measuring brachial-ankle pulse wave velocity (baPWV) in women with endometriosis to assess the presence of subclinical atherosclerosis. We also measured markers of inflammation and oxidative stress in women with endometriosis. baPWV in women with endometriosis aged over 30 years was significantly higher than that in women without endometriosis aged over 30 years (p < 0.05), but not in women aged less than 30. Serum high-sensitivity C-reactive protein level in women with endometriosis was significantly higher than that in controls (p < 0.05). Young women with endometriosis show significantly increased arterial stiffness, suggesting that women with endometriosis need to be cautious of the future onset of atherosclerosis.

Topological phase transitions driven by magnetic phase transitions in Fe(x)Bi2Te3 (0≤x≤0.1) single crystals.

We propose a phase diagram for Fe(x)Bi2Te3 (0≤x≤0.1) single crystals, which belong to a class of magnetically bulk-doped topological insulators. The evolution of magnetic correlations from ferromagnetic to antiferromagnetic gives rise to topological phase transitions, where the paramagnetic topological insulator of Bi2Te3 turns into a band insulator with ferromagnetic-cluster glassy behavior around x∼0.025, and it further evolves to a topological insulator with valence-bond glassy behavior, which spans over the region from x∼0.03 up to x∼0.1. This phase diagram is verified by measuring magnetization, magnetotransport, and angle-resolved photoemission spectra with theoretical discussions.

[Is emergency aortic root replacement combined with arch replacement safe?].

BACKGROUND: Aortic root replacement (ARR) combined with aortic arch replacement (AAR) is an invasive procedure even in elective cases. Nevertheless, such combined operations are often mandatory in acute type A aortic dissection. We examined whether emergency operation might have further incremental risks compared with elective surgery in this type of operations. METHODS: Forty-six cases of ARR combined with AAR were divided into 2 groups, the emergency (EM) group and the elective (EL) group. The EM group consisted of 10 cases of acute type A aortic dissection, whereas the EL group of 36:23 of chronic aortic dissection and 13 of true aneurysm. RESULTS: There were no statistical differences between the 2 groups in the durations of aortic crossclamp, selective cerebral perfusion and cardiopulmonary bypass. The incidences in the EM and EL groups were as follows:in-hospital death; 0 vs 3( 8%), respiratory failure; 4 (40%) vs 14 (39%), renal failure; 0 vs 6 (17%), IABP requirement; 1 (10%) vs 3 (8%), and cerebral infarction; 0 vs 1 (3%), respectively. CONCLUSION: Early surgical results of emergency ARR combined with AAR were almost equal to those in elective surgery.

Topologically-imposed vacancies and mobile solid 3He on carbon nanotube.

Low dimensional fermionic quantum systems are exceptionally interesting because they reveal distinctive physical phenomena, including among others, topologically protected excitations, edge states, frustration, and fractionalization. Our aim was to confine 3He on a suspended carbon nanotube to form 2-dimensional Fermi-system. Here we report our measurements of the mechanical resonance of the nanotube with adsorbed sub-monolayer down to 10 mK. At intermediate coverages we have observed the famous 1/3 commensurate solid. However, at larger monolayer densities we have observed a quantum phase transition from 1/3 solid to an unknown, soft, and mobile solid phase. We interpret this mobile solid phase as a bosonic commensurate crystal consisting of helium dimers with topologically-induced zero-point vacancies which are delocalized at low temperatures. We thus demonstrate that 3He on a nanotube merges both fermionic and bosonic phenomena, with a quantum phase transition between fermionic solid 1/3 phase and the observed bosonic dimer solid.

Beamlet deflection due to beamlet-beamlet interaction in a large-area multiaperture negative ion source for JT-60U.

The JT-60U negative ion source has been designed to produce high current beams of 22 A through grids of 1080 apertures (five segments with nine rows of 24 apertures). One of the key issues is to steer such a high current beam through the multiaperture grids in order to focus the overall beam envelope because the beamlet-beamlet interaction may deflect the outer beamlets outward due to unbalanced space charge repulsion. To clarify the beam deflection in the JT-60U negative ion source, the beamlet trajectory in a multiaperture ion source was calculated by a three-dimensional simulation code. The measured angles of the outmost beamlets were in agreement with the calculated results where space charge of the beamlets was taken into account. It is noticed that the deflection of the outermost beamlet due to the beamlet-beamlet interaction is saturated at 5.2 mrad outward for beamlets more than ten.

Long pulse production of high current D(-) ion beams in the JT-60 negative ion source.

The first long pulse production of high power D(-) ion beams has been demonstrated in the JT-60 U negative ion sources, each of which was designed to produce 22 A, 500 keV D(-) ion beams. Voltage holding capability and the grid power loading were examined for long pulse production of high power D(-) ion beams. From the correlation between voltage holding and the light intensity of cathodoluminescence from the Fiber Reinforced Plastic insulators, the acceleration voltage for stable voltage holding capability was found to be less than 320-340 kV where the light was sufficiently suppressed. By tuning the extraction voltage, the grid power loadings in the ion sources were decreased to the allowable levels for long pulse injection without a significant reduction of the beam power. After tuning the acceleration and extraction voltages, D(-) ion beams of 12.5 and 9.8 A were produced at 340 keV with cesium seeding at a rate of approximately 14 microg/s into the ion sources. The pulse duration of these D(-) ion beams was extended step by step, and then was successfully extended up to 18 s without degradation of the negative ion production. The D(-) ion beams were neutralized to yield 3.6 MW D(0) beams by a gas cell, and then injected into the JT-60 U plasma. Further, a slight reduction of D(-) ion beam power allowed the longer injection duration of 21 s at a D(0) beam power of 3.2 MW. The success in the long pulse production of a high power D(-) ion beam shows that negative ion beams can be produced during a few tens of seconds without degradations of negative ion production and the voltage holding in a large Cs-seeded negative ion source.

The impact of earlier intervention by an antimicrobial stewardship team for specific antimicrobials in a single weekly intervention.

OBJECTIVE: The objective of this study was to evaluate the effects of earlier intervention by an antimicrobial stewardship team (AST) on antimicrobial use, antimicrobial resistance rates, and the clinical outcomes, without changing the weekly intervention schedule. METHODS: A retrospective study was conducted at Fukuoka University Hospital between April 2013 and March 2016. The effects were compared among three study periods (SP): SP1 (patients receiving anti-methicillin-resistant Staphylococcus aureus agents and carbapenems for ≥14 days), SP2 (patients receiving specific antimicrobials for ≥14 days), and SP3 (patients receiving specific antimicrobials regardless of the duration of treatment). RESULTS: The timing of AST intervention was shortened from an average of 15.5days after administration in SP1 to 4.2 days in SP3. The antimicrobial use density (AUD) of carbapenems and piperacillin-tazobactam decreased significantly (SP2 vs. SP3, p<0.05), and the costs of specific antimicrobials decreased (SP1, US$ 1080000; SP2, US$ 944000; SP3, US$ 763000). The rates of carbapenem resistance among Pseudomonas aeruginosa isolates showed a significant reduction from 16.2% in SP2 to 8.7% in SP3 (p<0.05). The mortality rate and length of stay did not change during the study period. CONCLUSIONS: Earlier intervention by an AST could contribute to the proper use of antimicrobials without adversely affecting patient outcomes.

Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma.

Epigenetic alterations like DNA methylation and the resulting inactivation of cancer-related genes often contribute to the development of various cancers. To identify the genes that are silenced by aberrant methylation in renal cell carcinoma (RCC), we subjected two RCC lines to methylated CpG island amplification/representational difference analysis. This identified 27 CpG islands. Combined bisulfite restriction analysis of these CpG islands in primary RCC cases revealed that four were methylated in a tumor-specific manner. One of these was identified as the human homeo-box gene B13 (HOXB13) gene, but the remaining three CpG islands were not associated with known genes. The methylation frequencies of HOXB13 in primary RCC samples and lines were 30 and 73%, respectively. The methylation status of HOXB13 correlated with the loss of its expression both in RCC lines and primary tumors, and methyltransferase inhibitor treatment induced the recovery of its expression. Exogenous expression of HOXB13 in RCC cells that lacked endogenous HOXB13 expression suppressed colony formation and induced apoptotic features. Furthermore, HOXB13 methylation correlated positively with tumor grade and microvessel invasion. These results suggest that HOXB13 is a novel candidate tumor suppressor gene in RCC and that its inactivation may play an important role in both RCC tumorigenesis and progression.

Expression of Tn and sialyl-Tn antigens in the neoplastic transformation of uterine cervical epithelial cells.

The expression of simple mucin-type carbohydrate antigens, Tn and sialyl-Tn antigens, was evaluated by immunohistochemical staining with monoclonal antibodies in normal squamous epithelium, dysplasia, carcinoma in situ, and invasive squamous cell carcinoma of the uterine cervix. The expression of the Tn antigen detected by HB-Tn1 and B1.1 was found in 17 (20%) and 19 (23%) of the 83 invasive carcinomas, respectively, but was not found in the 36 normal squamous epithelia, 22 severe dysplasias, or 24 carcinomas in situ. The sialyl-Tn antigen was detected by HB-STn1 and TKH-2 in 14 (64%) and 11 (50%) of the 22 severe dysplasias, 13 (54%) and 10 (42%) of the 24 carcinomas in situ and 48 (58%) and 42 (51%) of the 83 invasive carcinomas, respectively, but was completely absent in 36 normal squamous epithelia. Coexpression of the sialyl-Tn antigen was observed in 89% of the cases expressing the Tn antigen. No significant difference was observed between the immunoreactivities of the antigens in the metastatic lymph nodes and primary tumors. No correlation was found between the expression of each antigen and clinical state, histologic type, depth of invasion, parametrial spread, lymphatic and vessel permeation, lymph node metastasis, or 5-year survival rate. The expression of Tn and sialyl-Tn demonstrates a specific change in the neoplastic progression from carcinoma in situ to invasive carcinoma and from normal to dysplasia, respectively, in squamous cell neoplastic lesions of the cervix. Tn and sialyl-Tn antigens may be useful markers for biologic investigation of neoplastic transformation in cervical squamous cell carcinoma.

von Hippel-Lindau protein promotes the assembly of actin and vinculin and inhibits cell motility.

Mutation of the von Hippel-Lindau (VHL) gene is responsible for familial and sporadic renal cell carcinomas as well as for cancers in many other organs. According to recent studies, the VHL protein (pVHL) is a multifunctional tumor suppressor protein associated with the inhibition of angiogenesis, cell cycle exit, fibronectin matrix assembly, and proteolysis. To examine whether pVHL affects other important cellular events such as morphogenesis, adhesion, cytoskeletal organization, or motility, we introduced the VHL gene into human kidney and lung cancer cells and compared its effects with those in parental cells. Compared with non-pVHL-expressing cells, the morphogenesis of pVHL-expressing cells was remarkably changed, with cells having many focal adhesions and stress fibers and a spreading morphology. The attachment ability of non-pVHL-expressing cells was significantly increased by expression of pVHL. Additional studies showed that vinculin was translocalized from the cytoplasm to the cell membrane by the pVHL expression, indicating induction of focal adhesion formation by pVHL. Furthermore, motility of the pVHL-expressing cells was significantly reduced compared with that of non-pVHL-expressing cells (P < 0.05). These results indicate that pVHL stabilized actin organization and inhibited cell motility through focal adhesion formation. Thus, pVHL plays a crucial role in cytoskeletal organization and motility and functions as a unique suppressor protein in malignant cells.

Establishment of the human BSMZ breast cancer cell line, which overexpresses the erbB-2 and c-myc genes.

A new cell line, designated BSMZ, was established from a malignant pleural effusion from a woman with breast cancer. This line has a doubling time of 27 h and has now been cultured for over 120 passages. The large, rounded BSMZ cells grow as both a monolayer and as aggregations in suspension. Intracytoplasmic lumen, a finding consistent with results from cells derived from mammary tissue, was detected on ultrastructural analysis. Injection of BSMZ cells into nude mice resulted in the growth of solid tumors 4 weeks after inoculation. The solid tumor was identical to the original BSMZ cells in microscopic and electron microscopic studies. These cells possess an average of 80 chromosomes. Expression of erbB-2 and c-myc genes was increased by 10-fold, while there was no detectable overexpression of the N-ras and c-myb genes. Southern analysis has revealed amplification of the erbB-2 and c-myc loci. The BSMZ cell line may therefore provide a useful model for the study of human breast cancer and overexpression of the erbB-2 gene.

beta-Microseminoprotein/prostatic secretory protein is a member of immunoglobulin binding factor family.

Human seminal plasma contains a factor that binds human IgG, designated as immunoglobulin binding factor (IgBF). Under reducing condition IgBF interacts with anti-Leu-11b, a murine monoclonal antibody raised against human FcgammaRIII/CD16. IgBF shows no binding activity under non-reducing condition. Three components having IgBF activity were separated by HPLC and their amino acid sequences determined. The main IgBF showed structural identity to beta-microseminoprotein (beta-MSP), prostatic secretory protein of 94 amino acids (PSP94) and beta-inhibin. The slight variation in the reported sequences of these proteins has been attributed to analytical error. In the present study the molecular masses of main IgBF and beta-MSP/PSP94 were found to be identical by mass spectrometry. In addition, a large component of IgBF and a shorter beta-MSP consisting of 93 amino acids were identified. The binding of beta-MSP for human IgG and anti-Leu-11b antibody is demonstrable only under reducing condition, determined by Western blot analysis. The present data clearly show that IgBF is a family composed of at least three isoforms. One of the members is beta-MSP/PSP94. This family should be designated as IgBF.

Autoantibody against testosterone in a woman with hypergonadotropic hypogonadism.

We demonstrate that antitestosterone autoantibody is produced in a 24-yr-old woman with hypergonadotropic hypogonadism. The serum testosterone level measured by RIA was extremely elevated (5.80 ng/mL); after elution, serum testosterone had returned to a normal female value (0.21 ng/mL). The clinical features were suggestive of no androgen activity. Primary follicles were present in the patent's ovary. After gonadotropin treatment, conception was achieved, and a normal female infant was delivered. A gel filtration study showed that the testosterone-binding activity was eluted at the position of 15,000-kDa Ig. Scatchard analysis revealed a low affinity antibody; the association constant was 0.034 x 10(3) mol-1, and the maximal binding capacity was 162 mumol/mL. An immunoprecipitation study the chain-specific antibodies showed that the antitestosterone autoantibody belonged to kappa-type IgG. This subject is the first reported case with an endocrine disorder who possessed autoantibodies against testosterone.

The complete nucleotide sequence of African horsesickness virus serotype 4 (vaccine strain) segment 4, which encodes the minor core protein VP4.

The complete sequence of RNA segment 4 of African horsesickness virus serotype 4 (AHSV-4) vaccine strain was determined from the full-length cDNA clone inserted into pBR322. The RNA is 1978 bp long (M(r) 1.27 x 10(6)) and contains an open reading frame encoding a protein of 642 amino acids (M(r) 75826) with a net charge of +10 at neutral pH. The 5' and 3' termini of AHSV-4 segment 4,5'GTTTAT... and ...CCTTAC3', were different from orbivirus characteristic terminal sequences, being 5'GTTAAA... and ...ACTTAC3'. A comparison of the sequence of AHSV-4 segment 4 with that of bluetongue virus (BTV) serotype 10 revealed 55.4% nucleotide similarity and 48.5% amino acid similarity. In addition, Northern blot hybridization showed that the full-length AHSV-4 segment 4 cDNA cross-hybridized well with the corresponding genes of serotype 1, 2, 3, 4 and 7 but slightly with serotype 5, 6 and 8 of attenuated AHSV.

High expression rate of Tn antigen in metastatic lesions of uterine cervical cancers.

The significance of altered expression of MN blood group antigens was examined by studies on the expressions of Thomsen-Friedenreich antigen (T antigen) and Tn antigen in primary and metastatic lesions of 29 human uterine cervical cancers. These antigens were measured by the avidin-biotin-peroxidase (ABC) method with peanut agglutinin (PNA) lectin for T antigen and Vicia villosa agglutinin (VVA) lectin for Tn antigen. Proportion of cancer cells expressing Tn antigen was higher in the metastatic lesions than in the primary tumors in 10 of the 29 cases, less in the metastasis than in the primary tumor in one case, and similar in the primary and metastatic lesions in the other 18 cases. Reaction for Tn antigen was positive in 24 (82.8%) of the 29 metastases, and in 17 (58.5%) of the 29 primary lesions. Thus, the rate of Tn antigen expression was significantly higher in the metastases than in the primary lesions (P < 0.05). On the other hand, there was no significant difference between the immunoreactivities of T antigen in metastases and primary tumors. These findings support our previous suggestion that expression of Tn antigen is closely related to the metastasis to regional lymph nodes and may reflect an important role of this carbohydrate in the process of metastasis of cervical cancer.

Interstitial deletion of chromosome 16q: 16q22 is critical for 16q- syndrome.

Partial deletion of 16q is rare; to our knowledge only 12 cases have been published. Fryns et al. [Hum Genet 38:343-346, 1977] described the first of these cases and proposed a new clinical entity. Our patient was a girl and had many minor anomalies of the kind often observed in 16q- syndrome. Severe failure to thrive due to emesis and diarrhea were also observed. High resolution banding methods showed that the chromosome constitution of the patient was 46,XX,del(16)(q22.1q22.3). This suggests that 16q22 is critical for the syndrome.

Case of ovarian dysgenesis and dilated cardiomyopathy supports existence of Malouf syndrome.

We describe an 18-year-old girl with ovarian dysgenesis, dilated cardiomyopathy, mild mental retardation, broad nasal base, blepharoptosis, and minor skeletal abnormalities. This unusual association of manifestations was first reported by Malouf et al. [1985]. Our patient, although a sporadic case, supports the existence of Malouf syndrome.

Inhibitory effects of tunicamycin on the mixed lymphocyte reaction and mitogen-induced lymphocyte blastogenesis.

The role of asparagine(Asn)-linked saccharides on the surface of lymphocytes in cellular interactions was examined by performing studies on the effects of tunicamycin (TM), which inhibits the glycosylation of proteins N-glycosylated at asparagine residues, on the mixed lymphocyte reaction (MLR) and mitogen-induced lymphocyte blastogenesis of human lymphocytes by measuring 3H-thymidine (TdR) incorporation. Responses were expressed as percentages of that of the control (MLR without TM). The lymphocyte blastogenesis in the one- and two-way MLR were, respectively, 43.1% and 48.0% of the control at 0.1 microgram/ml of TM, and 5.5% and 7.2% at 1 microgram/ml of TM. The inhibitory effect of TM on the one-way MLR was shown using TM-pretreated stimulator cells, TM-pretreated responder cells or both. TM blocked lymphocyte blastogenesis in the secondary as well as in the primary MLR. The inhibitory effect of TM on the two-way MLR was observed when TM was added on day 0 to day 2, but not on day 4 of incubation. TM blocked mitogen-induced lymphocyte blastogenesis by phytohemagglutinin, concanavalin A or by pokeweed mitogen. As TM had no cytotoxic effect on cultured cells, these inhibitory effects of TM were thought to be due to the loss of Asn-linked saccharides from glycoprotein of the surface of lymphocytes. These findings indicated that Asn-linked saccharides of glycoprotein on the surface of lymphocytes were important in cellular interactions that are necessary for the cellular immune response.

Fluorescence in situ hybridization to assess transitional changes of aneuploidy for chromosomes 7, 8, 10, 12, 16, X and Y in metastatic prostate cancer following anti-androgen therapy.

There have been few detailed studies conducted on the cell population in relation to cytogenetic changes between the pre- and post-treatment periods in patients with prostate cancer. We investigated numerical chromosome changes associated with anti-androgen therapy, using fluorescence in situ hybridization (FISH). FISH using chromosome-specific centromeric probes was used to assess transitional changes in the frequency of aneuploidy for chromosomes 7, 8, 10, 12, 16, X, and Y in prostate cancer during the pre- and post-treatment periods. Gains of chromosomes 7, 8 and 12 were notable in the pre-treatment samples (8 out of 9 cases in chromosome 7; 8 out of 9 cases in chromosome 8; 7 out of 9 cases in chromosome 12), while a notable reduction in the number of cells with extra copies of these chromosomes was observed in post-treatment specimens. Other chromosomes did not show noticeable change in their FISH signals at each phase of clinical treatment in all 9 cases. Changes in cell number with high ploidies of chromosome 7, 8 and 12 reflect the clinical effects of anti-androgen therapy at the early phase, which might explain the androgen dependency of metastatic prostate cancer cells.