Aneuploid rescue precedes X-chromosome inactivation and increases the incidence of its skewness by reducing the size of the embryonic progenitor cell pool.

STUDY QUESTION: Do monosomy rescue (MR) and trisomy rescue (TR) in preimplantation human embryos affect other developmental processes, such as X-chromosome inactivation (XCI)? SUMMARY ANSWER: Aneuploid rescue precedes XCI and increases the incidence of XCI skewness by reducing the size of the embryonic progenitor cell pools. WHAT IS KNOWN ALREADY: More than half of preimplantation human embryos harbor aneuploid cells, some of which can be spontaneously corrected through MR or TR. XCI in females is an indispensable process, which is predicted to start at the early-blastocyst phase. STUDY DESIGN, SIZE, DURATION: We examined the frequency of XCI skewness in young females who carried full uniparental disomy (UPD) resulting from MR or TR/gamete complementation (GC). The results were statistically analyzed using a theoretical model in which XCI involves various numbers of embryonic progenitor cells. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 39 children and young adults ascertained by imprinting disorders. XCI ratios were determined by DNA methylation analysis of a polymorphic locus in the androgen receptor gene. We used Bayesian approach to assess the probability of the occurrence of extreme XCI skewness in the MR and TR/GC groups using a theoretical model of 1-12 cell pools. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 12 of 39 individuals (31%) showed skewed XCI. Extreme skewness was observed in 3 of 15 MR cases (20%) and 1 of 24 TR/GC cases (4.2%). Statistical analysis indicated that XCI in the MR group was likely to have occurred when the blastocyst contained three or four euploid embryonic progenitor cells. The estimated size of the embryonic progenitor cell pools was approximately one-third or one-fourth of the predicted size of normal embryos. The TR/GC group likely had a larger pool size at the onset of XCI, although the results remained inconclusive. LIMITATIONS, REASONS FOR CAUTION: This is an observational study and needs to be validated by experimental analyses. WIDER IMPLICATIONS OF THE FINDINGS: This study provides evidence that the onset of XCI is determined by an intrinsic clock, irrespectively of the number of embryonic progenitor cells. Our findings can also be applied to individuals without UPD or imprinting disorders. This study provides a clue to understand chromosomal and cellular dynamics in the first few days of human development, their effects on XCI skewing and the possible implications for the expression of X-linked diseases in females. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Grants-in-aid for Scientific Research on Innovative Areas (17H06428) and for Scientific Research (B) (17H03616) from Japan Society for the Promotion of Science (JSPS), and grants from Japan Agency for Medical Research and Development (AMED) (18ek0109266h0002 and 18ek0109278h0002), National Center for Child Health and Development and Takeda Science Foundation. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Significance of uterine corpus tumor invasion in early-stage cervical cancer.

OBJECTIVE: To examine characteristics and survival outcomes of women with surgically-treated cervical cancer exhibiting uterine corpus tumor invasion. METHODS: We utilized The Surveillance, Epidemiology, and End Results Program to identify cervical cancer patients who underwent hysterectomy between 1973 and 2003. Logistic regression models were used to identify risk factors for uterine corpus tumor invasion on multivariable analysis. Association of uterine corpus tumor invasion and cause-specific survival (CSS) from cervical cancer was examined with Cox proportional hazard regression models on multivariable analysis. RESULTS: We identified 837 (4.9%) cases of uterine corpus invasion and 16,237 (95.1%) cases of non-invasion. Median follow-up time was 14.0 years. There were 1642 deaths due to cervical cancer. Uterine corpus invasion was independently associated with older age, non-squamous histology, high-grade tumors, large tumor size, and nodal metastasis on multivariable analysis (all, P < 0.001). On univariable analysis, uterine corpus tumor invasion was significantly associated with decreased CSS compared to the non-invasion (5-year rates, 79.0% versus 94.5%, P < 0.001). After controlling for other significant prognostic factors, uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.45, 95% confidence interval 1.21-1.74). Among stage T1b cases (n = 6730), uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.95, 95%CI 1.47-2.60). Uterine corpus tumor invasion was significantly associated with decreased CSS in stage T1b1 disease (74.5% versus 90.7%, P < 0.001) and in stage T1b2 disease (67.0% versus 79.5%, P = 0.01). CONCLUSION: Uterine corpus tumor invasion is an independent prognostic factor for decreased survival of women with early-stage cervical cancer.

Evaluation of floating impeller phenomena in a Gyro centrifugal pump.

The Gyro centrifugal pump developed as a totally implantable artificial heart was designed with a free impeller, in which the rotational shaft (male bearing) of the impeller was completely separated from the female bearing. For this type of pump, it is very important to keep the proper magnet balance (impeller-magnet and actuator-magnet) in order to prevent thrombus formation and/or bearing wear. When the magnet balance is not proper, the impeller is jerked down into the bottom bearing. On the other hand, if magnet balance is proper, the impeller lifted off the bottom of the pump housing within a certain range of pumping conditions. In this study, this floating phenomenon was investigated in detail. The floating phenomenon was proved by observation of the impeller behavior using a transparent acrylic pump. The impeller floating phenomenon was mapped on a pump performance curve. The impeller floating phenomenon is affected by the magnet-magnet coupling distance and rotational speed of the impeller. In order to keep the proper magnet balance and to maintain the impeller floating phenomenon at the driving condition of right and left pump, the magnet-magnet coupling distance was altered by a spacer which was installed between the pump and actuator. It became clear that the same pump could handle different conditions (right and left ventricular assist), by just changing the thickness of the spacer. When magnet balance is proper, the floating impeller phenomenon occurs automatically in response to the impeller rev. It is called "the dynamic RPM suspension".

Fine structural and immunohistochemical detection of collar enamel in the teeth of Polypterus senegalus, an actinopterygian fish.

This is the first detailed report about the collar enamel of the teeth of Polypterus senegalus. We have examined the fine structure of the collar enamel and enamel organ of Polypterus during amelogenesis by light and transmission electron microscopy. An immunohistochemical analysis with an antibody against bovine amelogenin, an antiserum against porcine amelogenin and region-specific antibodies or antiserum against the C-terminus, middle region and N-terminus of porcine amelogenin has also been performed to examine the collar enamel matrix present in these teeth. Their ameloblasts contain fully developed Golgi apparatus, rough endoplasmic reticulum and secretory granules. During collar enamel formation, an amorphous fine enamel matrix containing no collagen fibrils is found between the dentin and ameloblast layers. In non-demineralized sections, the collar enamel (500 nm to 1 µm thick) is distinguishable from dentin, because of its higher density and differences in the arrangement of its crystals. The fine structural features of collar enamel in Polypterus are similar to those of tooth enamel in Lepisosteus (gars), coelacanths, lungfish and amphibians. The enamel matrix shows intense immunoreactivity to the antibody and antiserum against mammalian amelogenins and to the middleregion- and C-terminal-specific anti-amelogenin antibodies. These findings suggest that the proteins in the enamel of Polypterus contain domains that closely resemble those of bovine and porcine amelogenins. The enamel matrix, which exhibits positive immunoreactivity to mammalian amelogenins, extends to the cap enameloid surface, implying that amelogenin-like proteins are secreted by ameloblasts as a thin matrix layer that covers the cap enameloid after enameloid maturation.

Modified thin abdominal wall flap (glove flap) for the treatment of acute burns to the hands and fingers.

BACKGROUND: Burns to the dorsum of the fingers and hands require debridement and immediate coverage by skin flap at the earliest opportunity. In such situations, the conventional abdominal wall flap is still commonly used as it is a convenient and safe technique, but the foremost problem with this flap is that it is thick and therefore cosmetically unacceptable; it is also functionally not very suitable as the bulkiness of the digits prevents full range of motion. We have developed a modified thin abdominal flap (glove flap) which attains good results. METHODS: Incisions are made in the skin of the abdominal wall only where the hand is to be inserted and where each of the finger tips will be pulled through. The flap is undermined just under the skin to the depth that preserves the subcutaneous vascular networks to create a thin flap. The interdigital area of the flaps should not be undermined so as to create a glove-type pocket. The hand is then inserted in this subcutaneous pocket. After insertion of the injured hand for 10 to 14 days, the flap is resected and attached to the hand. RESULTS: Seven hands of 5 patients were treated by this technique and all the flaps survived safely. The function of the hands and fingers, including range of motion (ROM) in each joint, was successfully salvaged. The reconstructed hands and fingers were aesthetically pleasing. CONCLUSIONS: Although the abdominal wall flap is not a new technique, our modifications to this flap make it possible to acquire functionally and aesthetically better results. Although many excellent techniques such as perforator flaps have been reported recently, we conclude that the abdominal wall flap is still a very useful technique because it can be performed easily, safely and within a short time.

Participation of glutathione in the elimination of Porphyromonas gingivalis in vivo.

INTRODUCTION: Glutathione is involved in immune responses such as cell proliferation and bactericidal activity. The aim of this study was to see whether glutathione influences the intraperitoneal elimination of Porphyromonas gingivalis in Fusobacterium nucleatum-immunized mice. METHODS: Mice were immunized with P. gingivalis or F. nucleatum, and then P. gingivalis was inoculated into the peritoneal cavity of the mice. After various lengths of time, the numbers of bacteria were determined by a colony-forming assay and by polymerase chain reaction. The effect of glutathione on the elimination of P. gingivalis was explored by changing the intracellular glutathione level. Furthermore, we examined the effects of glutathione on the peritoneal levels of interferon-gamma, a macrophage activator, and of nitrite, a derivative of nitric oxide that acts as an antimicrobial agent when produced by macrophages and neutrophils. RESULTS: Inoculated P. gingivalis was eliminated more rapidly from F. nucleatum-immunized mice than from P. gingivalis-immunized mice. Interferon-gamma levels in peritoneal lavage fluid and glutathione levels in peritoneal exudate cells were higher in F. nucleatum-immunized mice than in P. gingivalis-immunized mice. When P. gingivalis-immunized mice were given glutathione monoethylester (a derivative of glutathione that is converted to glutathione intracellularly through hydrolysis) into the peritoneal cavity, the elimination of P. gingivalis was accelerated. On the other hand, when F. nucleatum-immunized mice were given L-buthionine-[S,R]-sulfoximine (an inhibitor of glutathione synthesis) into the peritoneal cavity, the elimination of P. gingivalis was suppressed. CONCLUSION: In F. nucleatum-immunized mice, glutathione may have a key role in the defense against P. gingivalis infections.

Effect of iguratimod and other anti-rheumatic drugs on adenocarcinoma colon 26-induced cachexia in mice.

OBJECTIVE: To examine the effect of iguratimod (T-614) and other anti-rheumatic drugs on a mouse model of adenocarcinoma-induced cachexia. METHODS: Cachexia was induced in BALB/c mice by s.c. inoculation of colon 26/clone 20 cells (day 0). The drugs were administered p.o. daily from day 0 for 15 days for prophylactic experiments and from day 7 for 8 days for therapeutic experiments. Serum biochemical parameters and wasting of adipose tissue and muscle were evaluated as the nutritional condition in tumor-bearing mice at day 14. Interleukin-6 (IL-6) levels in serum and tumor tissue of those mice were also quantified. RESULTS: Administration of T-614 did not inhibit the tumor growth, but it resulted in attenuation of cachexia symptoms, such as the reduction in epididymal fat and gastrocnemius muscle, and the decrease of serum albumin. Furthermore, T-614 decreased the serum levels of IL-6, and reduced its gene expression in the tumor tissues. Exogenously administered IL-6 nullified the suppressive effect of T-614. Prednisolone prevented the weight loss and the wasting without inhibiting tumor growth. Methotrexate and indomethacin did not exert any preferable effects in a therapeutic dosing schedule. CONCLUSIONS: Our results demonstrate that T-614 exerts an anticachectic effect in tumor-bearing mice through the inhibition of IL-6 gene expression.

Nanoblock coupling effect in iodine intercalated [Bi(0.82)CaO(2)](2)[CoO(2)](1.69) layered cobaltite.

We report on the structural, microstructural, and electronic properties of iodine intercalated [Bi0.82CaO2]2[CoO2]1.69 misfit cobaltite. We first prove through a detailed and careful structural study that the block layer structure can be modified in the desired way. Iodine enters the material between the [BiO] double layers, and the c-cell parameter of the pristine compound is elongated by 3.6 Angstrom. On the basis of this result, we point out the coupling between the block-layer structure and the transport properties. Additionally, we provide in-depth commentary and discussion of some extra results, clarifying some doping effects in the quasi-2D studied phase. Finally, we also propose some expressions that might be useful to material scientists for the tuning of the properties of such compounds.

Malignant mixed müllerian tumor of primary mesenteric origin.

Malignant mixed müllerian tumor (MMMT) is a rare tumor. A literature search revealed very few reports on MMMT, especially those arising in the peritoneum. We recently encountered an MMMT of primary mesenteric origin associated with left fallopian tube cancer. There have been no previous reports about its occurrence in the mesentery. When cases of peritoneal MMMT were reviewed, the disease was found to be associated with synchronous or metachronous gynecologic tumors of müllerian duct origin (ie, ovarian tumors, primary serous carcinoma of the peritoneum, fallopian tube cancer, endometrial cancer, and adenocarcinoma of the cervix) in 12 out of 32 patients (37.5%). Peritoneal MMMT are frequently associated with gynecologic tumors.

A pilot study of weekly docetaxel therapy for recurrent ovarian cancer, tubal cancer, and primary peritoneal cancer.

We investigated the efficacy and toxicity of salvage chemotherapy with weekly docetaxel for recurrent ovarian cancer, tubal cancer, and primary peritoneal cancer after treatment with regimens containing platinum or paclitaxel. The 15 subjects were managed as outpatients and received at least two courses of docetaxel therapy (35 mg/m2 on days 1, 8 and 15). Antitumour activity was assessed radiologically and from the CA-125 level. Among five patients with measurable lesions, one showed partial remission and three showed stable disease. Based on CA-125 levels, there were three partial remissions and five patients with stable disease (progression-free survival was 7.5 months and 7.6 months, respectively). During 61 courses, the severe toxicities were grade 3 leukopaenia/neutropaenia (6.7%) or grade 2 oedema and pleural effusion (13.3%). Weekly docetaxel may be useful salvage chemotherapy for recurrent ovarian cancer, tubal cancer, and peritoneal cancer, especially as tumour dormancy therapy.

Dome-shaped magnetic phase diagram of thermoelectric layered cobaltites.

Using muon spin spectroscopy we have found that, for both NaxCoO(2) (0.6

Effective weekly docetaxel for recurrent ovarian cancer: A case report.

We experienced a case of recurrent ovarian cancer that responded to weekly docetaxel. The patient had stage IIIC ovarian cancer (poorly differentiated serous adenocarcinoma). After initial remission was achieved by chemotherapy with paclitaxel and carboplatin plus cytoreductive surgery, the disease recurred and irinotecan therapy achieved temporary remission. During maintenance therapy with oral etoposide, the disease recurred again. We then tried five courses of weekly docetaxel therapy and it successfully controlled the disease. The progression-free survival time on weekly docetaxel treatment is now 7 months and the toxicity was extremely low. This patient demonstrates the effectiveness of weekly docetaxel as salvage chemotherapy for recurrent ovarian cancer.

Evaluation of floating impeller phenomena in a gyro centrifugal pump.

The Gyro centrifugal pump, developed as a totally implantable artificial heart, was designed with a free impeller in which the rotational shaft (male bearing) of the impeller was completely separated from the female bearing. For this type of pump, it is very important to keep the proper magnet balance (impeller-magnet and actuator-magnet balance) to prevent thrombus formation or bearing wear. When the magnet balance is not proper, the impeller is jerked down into the bottom bearing. On the other hand, if magnet balance is proper, the impeller is lifted off the bottom of the pump housing within a certain range of pumping conditions. In this study, this floating phenomenon was investigated in detail. The floating phenomenon was proven by observation of the impeller behavior by means of a transparent acrylic pump. The impeller floating phenomenon was mapped on a pump performance curve. The impeller floating phenomenon is affected by the magnet-magnet coupling distance and the rotational speed of the impeller. To keep the proper magnet balance and to maintain the impeller floating phenomenon at the driving conditions of right and left pumps, the magnet-magnet coupling distance was altered by a spacer that was installed between the pump and actuator. It became clear that the same pump could handle different conditions (right and left ventricular assist) by changing the thickness of the spacer. When magnet balance is proper, the floating impeller phenomenon occurs automatically in response to the impeller revolution. This is called "the dynamic revolutions per minute suspension."

Preoperative diagnosis of fallopian tube cancer by imaging.

Primary cancer of the fallopian tube (FTC) is among the most unusual gynecologic malignancies and rarely is diagnosed correctly before surgery. The imaging results of eight patients with FTC and four with benign tubal disease were analyzed. FTCs were small cystic or solid masses that typically were shaped like a sausage, a snail, or a gourd, regardless of clinical stage.

Operating point control system for a continuous flow artificial heart: in vitro study.

We proposed and developed a practical and effective servo control system for rotary blood pumps. A rotary blood pump for assisting the failing natural heart should be operated only in physiologically acceptable conditions. The operation of a rotary blood pump is based on the rotational speed of the impeller and pressure head. If the pump flow and the pressure head are set within an acceptable range, the driving condition is deemed normal condition, and this control system maintains the preset operating point by applying proportional and detective control (PD control). If the pump flow or pressure head is outside the acceptable range, the driving condition is determined to be abnormal condition, and this system operates the pump in a recovery fashion. If the driving condition is kept under abnormal conditions of sudden decrease of the flow, the condition is termed a suction condition. The controller releases the pump from the suction condition and later returns it to the normal condition. In this study, we evaluated these servo control modes of the centrifugal pump and confirmed whether the performance of this proposed operating point control system was practical.

Effects of SRT and DO on N2O reductase activity in an anoxic-oxic activated sludge system.

Nitrous oxide (N2O) is emitted from wastewater treatment processes, and is known to be a green house gas contributing to global warming. It is thus important to develop technology that can suppress N2O emission. The effects of sludge retention time (SRT) and dissolved oxygen (DO) on N2O emission in an anoxic-oxic activated sludge system were estimated. Moreover, the microbial community structure in the sludge, which plays an important role in N2O suppression, was clarified based on nitrous oxide reductase (nosZ) gene analysis by molecular biological techniques. The results showed that under low SRT conditions, nitrification efficiency was reduced and the N2O emission rate in the oxic reactors was increased. It was also observed that N2O emission was enhanced under low DO conditions, where the available oxygen is insufficient for nitrification. Moreover, molecular analysis revealed that the clones identified in this study were closely related to Ralstonia eutropha and Paracoccus denitrificans. The fact that the identified sequences are not closely related to known culturable denitrifier nosZ sequences indicates a substantial in situ diversity of denitrifiers contributing to N2O suppression, which are not reflected in the cultivatable fraction of the population. The further application of these new molecular techniques should serve to enhance our knowledge of the microbial community of denitrifying bacteria contributing to N2O suppression in wastewater treatment systems.