The level structures of the very neutron-rich nuclei 128Pd and 126Pd have been investigated for the first time. In the r-process waiting-point nucleus 128Pd, a new isomer with a half-life of 5.8(8) ...μs is proposed to have a spin and parity of 8(+) and is associated with a maximally aligned configuration arising from the g(9/2) proton subshell with seniority υ=2. For 126Pd, two new isomers have been identified with half-lives of 0.33(4) and 0.44(3) μs. The yrast 2(+) energy is much higher in 128Pd than in 126Pd, while the level sequence below the 8(+) isomer in 128Pd is similar to that in the N=82 isotone 130Cd. The electric quadrupole transition that depopulates the 8(+) isomer in 128Pd is more hindered than the corresponding transition in 130Cd, as expected in the seniority scheme for a semimagic, spherical nucleus. These experimental findings indicate that the shell closure at the neutron number N=82 is fairly robust in the neutron-rich Pd isotopes.
The acrosome plays an important role in fertilization. This study was designed to examine the role and behavior of a molecule,
equatorin (the antigenic molecule of the monoclonal antibody mMN9), ...localized at the equatorial segment of the acrosome. In
vitro fertilization (IVF) investigation was conducted to examine the role of this molecule, by assessing the effect of mMN9
in TYH medium (a modified Krebs Ringer bicarbonate solution) containing mMN9 at 0 (control), 25, 50, and 100 μg/ml. Under
these conditions, the IVF investigation was divided into two experiments: 1) the zona pellucida (zona)-intact experiment,
in which capacitated sperm inseminated cumulus- and zona-intact oocytes; and 2) the zona-free experiment, in which acrosome-reacted
sperm inseminated zona-free oocytes. It was found that mMN9 did not affect sperm motility, zona binding, or zona penetration,
but it significantly inhibited fertilization, reducing the rates of pronucleus and two-cell embryo formation in both the zona-intact
and zona-free oocyte experiments. In addition, when judged at 5 h after insemination in the zona-intact experiment, nearly
half of the unfertilized oocytes had accumulated sperm in the perivitelline space (perivitelline sperm), and concurrently
we confirmed by electron microscopy the presence of many unreleased cortical granules preserved beneath the oolemma, indicating
no occurrence of sperm-oocyte fusion. Confocal laser scanning light microscopy with indirect immunofluorescence demonstrated
that equatorin was localized at the equatorial segment in both capacitated and perivitelline sperm (acrosome-reacted sperm).
These results suggest that equatorin that is preserved at the equatorial segment is involved in the process of sperm-oocyte
fusion in mice.
Inducible costimulator (ICOS) and B7-related protein-1 (B7RP-1) constitute a receptor-ligand pair involved in T cell costimulation. In this study, the stimulatory effects of B7RP-1 on cellular and ...humoral immune responses were investigated giving mice a construct with the extracellular domain of murine B7RP-1 fused with human IgG1 Fc (B7RP-1-Fc). B7RP-1-Fc stimulated contact hypersensitivity (CH) given near either the time of sensitization or challenge with oxazolone. When given near challenge time, B7RP-1-Fc stimulated CH more than a construct containing the extracellular domain of murine B7.2 and Fc (B7.2-Fc). B7RP-1-Fc increased the number of cells in lymph nodes draining the skin sensitized with oxazolone, especially activated T cells. B7RP-1-Fc also increased the ability of the cells in these lymph nodes to induce CH when transfused into naive mice. B7RP-1-Fc stimulated the production of anti-keyhole limpet hemocyanin (KLH) Ab, increasing anti-KLH IgG, IgG2a, and IgE, whereas B7.2-Fc did not affect this production. B7RP-1-Fc also increased the number of cells in lymph nodes draining the skin immunized with KLH and their production of IFN-gamma, IL-4, and IL-10 in response to KLH. Finally, B7RP-1-Fc increased the presence of eosinophils in the bronchoalveolar lavage and lungs of mice sensitized and challenged with OVA so to mount an asthmatic reaction. B7RP-1-Fc stimulates both cellular and humoral immune responses in vivo by increasing number and function of T and B cells reacting to Ag exposure.
Gastrin has a role in gastrointestinal (GI) malignancy. This study provides pre-clinical evaluation of a novel, orally-active gastrin/cholecystokinin-2 receptor (CCK-2R) antagonist, Z-360.
(125)I ...gastrin-17 (G17) displacement and G17-stimulated calcium assays were used in classical CCK-2R-transfected cell lines. Akt phosphorylation was assessed by Western blotting. Z-360 efficacy in vivo was evaluated in three human xenograft models, and microvessel density and apoptosis in these models were investigated by immunohistochemistry.
Z-360 inhibited (125)I G17 binding to cells expressing CCK-2R, and G17-stimulated signalling. Reduced Akt phosphorylation in an oesophageal cell-line treated with Z-360 was reversed by co-treatment with G17. Z-360 increased survival in a gastric ascites model (p=0.011) and decreased tumour growth in a hepatic metastasis model (81%, p=0.02). In an orthotopic pancreatic model, Z-360 combined with gemcitabine decreased final tumour weight compared to single agents (84%, p=0.002) and there was increased apoptosis and decreased microvessel density in ex vivo tumour tissue.
These results show that the orally-active CCK-2R antagonist, Z-360 has high sub-nM affinity for classical CCK-2R, is well tolerated in vivo and exerts an anti-tumour effect.
IntroductionThe Japanese Red Cross Tokyo Blood Center collects approximately 600 000 blood donations every year. Since we experienced a fatal injury case related to vasovagal reaction (VVR) syncope ...in 2005, we conducted a cross-sectional study to elucidate factors contributing to VVR, the most frequent side effect, following whole blood and apheresis donations.MethodsComplications recorded at the collection sites after voluntary donations by Japanese Red Cross Tokyo Blood Center, in the 2006 and 2007 fiscal years, were analysed by univariate and multivariate logistic regression model. Of 1 119 716 blood donations over a full 2 years, complications were recorded for 13 320 donations (1.189%), among which VVR was the primary or secondary complication in 67%. Eligible 4303 VVR cases having sufficient information, and 40 256 control donors were prepared. Age, body mass index, predonation blood pressure, pulse, and biomarkers (eg, total protein, albumin, and haemoglobin) were compared between VVR group and control group.ResultsVVR group was significantly younger, lower body mass index, lower blood pressure, higher biomarkers' values (eg, total protein, albumin, and haemoglobin) than control group. (p<0.001) Furthermore, biomarkers' values and VVR incidences showed a dose-dependent manner. (Trend test p<0.01).ConclusionObviously, to prevent serious consequences, donors should be informed about importance of rest afterwards, and posture to take when symptoms occur. From our analysis, extra care should be considered including high biomarkers' concentrations (eg, total protein, albumin, and haemoglobin), which might reflect donor's dehydration state.
Abstract
Study question
What is status of use and live birth rates of cryopreservation oocyte for social reasons?
Summary answer
11.2% of the cryopreserved oocytes were warmed and transferred, and ...the oldest of the successful live birth was 39 years old.
What is known already
More people nowadays tend to delay marriage and childbearing due to the social circumstances. It is now gradually known that the pregnancy rate decreases with increasing age, since the donation of gametes from third parties is regulated by the Japanese society, oocyte cryopreservation for social reasons has been becoming common practice. However, not much is known about the subsequent pregnancy and childbirth. Therefore, we conducted a survey on the use and clinical outcomes of cryopreserved oocytes for social reasons in our clinic.
Study design, size, duration
This retrospective single-center study was conducted with a total of 285 women, 424 cycles from March 2014 to December 2019. A total of 2696 oocytes were cryopreserved by vitrification. Written informed consent was obtained from all women who participated in this study.
Participants/materials, setting, methods
Ovarian stimulation was performed mainly with GnRH antagonist protocol. An injection of 5000IU of HCG was administered when the diameter of dominant follicle reached 18mm. All oocytes were denuded enzymatically with 80 IU/ml hyaluronidase, followed by mechanical denudation. The oocytes were then evaluated at metaphase II by confirming the presence of the first polar body. Mature oocytes were cryopreserved by vitrification. The partner's sperm was injected into the vitrified-warmed oocytes.
Main results and the role of chance
The age groups in the first freezing cycle were 30-34 years (7.4%), 35-39 years (49.8%), 40-44 years (37.2%), and 45 years and older (5.6%), respectively. The mean number of OPU cycles was 1.1±0.4, 1.4±1.4, 1.5±1.1, and 1.7±1.7. The average number of retrieved oocytes was 9.5 ± 5.4, 7.3 ± 4.5, 5.6 ± 4.6, and 2.2 ± 2.2. The total number of cryopreserved oocytes was 10.4±5.9, 10.4±7.1, 8.8±6.8, and 3.3±3.4. Sixty-seven women had partners after oocyte cryopreservation, and 33 women (49.3%) had oocytes thawed. The mean age at oocytes freezing was 39.6±2.6 years, and the mean age at thawing was 42.2±2.5 years. The oocytes survival rates, fertilization rates, blastocyst rates and clinical pregnancy rates per embryo transferred of vitrified oocytes were 92.7% (328/354), 69.5% (228/328), 43.9% (87/198) and 31.1% (19/61), respectively. Of these, 15 women (45.5%) became pregnant with vitrified-warmed oocytes, and 10 (30.3%) had livebirth. 18 women did not become pregnant with vitrified-warmed oocytes. Subsequently, 3 of the 18 women then became pregnant in ART (5.6%), by IUI (5.6%), or spontaneously (5.6%), respectively.
Limitations, reasons for caution
Not applicable.
Wider implications of the findings
Of the 33 cases, 10 (30.3%) successfully gave birth, indicating the usefulness of oocyte cryopreservation for social reasons. However, considering that most of our patients were already around 40 years old, awareness of the benefits of oocytes cryopreservation at younger ages and education of reproductive health and rights is essential.
Trial registration number
none
MHC class II-expressing renal tubular epithelial cells (TEC) are able to present foreign peptide antigens to T cells. The costimulatory signals that are required for effective T cell activation upon ...antigen presentation by TEC have not been characterized. Various cultured TEC lines were examined for expression of the recently described costimulatory molecule B7RP-1 (B7h), a ligand of the T cell molecule inducible costimulator (ICOS), and expression was compared with that of B7.1, B7.2, and CD40. B7RP-1 and CD40 were abundantly expressed by cultured murine and human TEC, whereas B7.1 and B7.2 could not be detected. Stimulation with lipopolysaccharide or tumor necrosis factor-alpha did not induce B7.1 or B7.2 expression and did not alter B7RP-1 expression. Interestingly, interleukin-2 production by T cell hybridomas after antigen presentation by TEC was enhanced by blocking antibodies to B7RP-1 and ICOS. In contrast, blocking antibodies to B7RP-1 or ICOS exerted inhibitory effects on anti-CD3-activated murine splenocyte proliferation. Immunohistochemical staining of normal human kidneys demonstrated strong constitutive B7RP-1 expression in distal tubules, collecting ducts, and urothelium. In human kidneys with allograft rejection or interstitial nephritis, distinct B7RP-1 staining was also detected in proximal tubules, in areas of mononuclear infiltration. In conclusion, the B7RP-1/ICOS pathway negatively regulates T cell activation upon MHC class II-restricted antigen presentation by TEC. Because B7RP-1 is also expressed by tubules in vivo, it can be speculated that the B7RP-1/ICOS pathway could play an inhibitory role in TEC-mediated immune activation in the kidney.
Treatment of human U-937 myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with protein kinase C (PKC) βII-mediated activation of the stress-activated protein ...kinase (SAPK) pathway. The present studies demonstrate that the TPA response of U-937 cells includes the generation of reactive oxygen species (ROS). By contrast, the TPA-resistant U-937 cell variant (TUR), which is deficient in PKCβII expression, failed to respond to TPA with the induction of ROS. Moreover, we show that TPA-induced ROS production is restored in TUR cells stably transfected to express PKCβII. The results also demonstrate that TPA-induced ROS production is required for activation of the MEK kinase-1 (MEKK-1)→ SAPK pathway. In concert with this observation, treatment of U-937 with H2O2as a source of ROS is associated with activation of the MEKK-1→SAPK cascade. These findings indicate that PKCβII is required for TPA-induced ROS production and that the MEKK-1→SAPK pathway is activated by a ROS-mediated mechanism.
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