ABSTRACT
BACKGROUND: The indications for fertility preservation (FP) have expanded. A few patients who underwent gonadotoxic treatment did not have the opportunity to receive FP, leading to concerns that these patients may develop premature ovarian insufficiency. However, the usefulness of FP in women with reduced ovarian reserve has also been questioned. Progestin-primed ovarian stimulation can improve the controlled ovarian stimulation (COS) protocol, but there is limited data on the efficacy of FP with progestin-primed ovarian stimulation. METHODS: We conducted a prospective study of 43 women with cancer or autoimmune diseases before and after gonadotoxic treatment at the reproductive unit of Keio University Hospital, counselled between 1 January 2018 and 31 December 2021. After counselling, informed consent was obtained for FP from 43 patients, with those who underwent gonadotoxic treatment of the primary disease being prioritised. Gonadotropin-releasing hormone analogue or progestin was used to suppress luteinising hormone in COS before or after gonadotoxic treatment. The number of cryopreserved mature oocytes was the primary outcome. RESULTS: Forty-three patients and 67 assisted reproductive technology cycles were included in the analysis. The median age at entry was 32 [inter quartile range (IQR), 29-37] years. All patients in the post-gonadotoxic treatment group had their oocytes frozen. Gonadotoxic treatment resulted in fewer oocytes [median 3 (IQR 1-4); pre-gonadotoxic treatment group: five patients, 13 cycles] vs. median 9 (IQR 5-14; pre-gonadotoxic treatment group: 38 patients, 54 cycles; P < 0.001). Although anti-Müllerian hormone levels were lower in the post-gonadotoxic treatment group (n = 5, 13 cycles, median 0.29 (IQR 0.15-1.04) pg/mL) than in the pre-gonadotoxic treatment group (n = 38, 54 cycles, median 1.89 (IQR 1.15-4.08) pg/mL) (P = 0.004), oocyte maturation rates were higher in the post-gonadotoxic treatment group [median 100 (IQR 77.5-100) %] than in the pre-gonadotoxic group [median 90.3 (IQR 75.0-100) %; P = 0.039]. Five patients in the pre-gonadotoxic treatment group had their cryopreserved embryos thawed, of which three had live births. CONCLUSIONS: Oocytes obtained for FP from women with cancer or autoimmune disease for FP are of satisfactory quality, regardless of whether they are obtained post-gonadotoxic treatment or COS protocols.
Subject(s)
Autoimmune Diseases , Fertility Preservation , Neoplasms , Pregnancy , Humans , Female , Fertility Preservation/methods , Prospective Studies , Progestins/therapeutic use , Cryopreservation/methods , Neoplasms/complications , Neoplasms/drug therapy , Oocyte Retrieval , Oocytes , Live Birth , Ovulation Induction/methods , Autoimmune Diseases/therapy , Retrospective StudiesABSTRACT
The purpose was to clarify the effects of Helicobacter pylori (H. pylori) eradication on the changes in serum lipid levels by comparing subjects with and without continuous H. pylori infection. The study subjects were 774 individuals (males 536, females 238, mean age 52.6 years) who visited between April 2013 and March 2016 for annual medical checkups. Serum total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), and triglyceride levels, and LDLC/HDLC ratio were compared between the subjects with and without H. pylori infection, as well as those with H. pylori eradication subjects. The HDLC level in the H. pylori-positive group was significantly lower as compared to the H. pylori-negative group. The serum level of HDLC in subjects with successful eradication of H. pylori tended to be higher, while the serum levels of total cholesterol, LDLC, and triglycerides tended to be lower in comparison to subjects with continuous H. pylori infection. In addition, the LDLC/HDLC ratio in the H. pylori-positive group was significantly higher than that in the H. pylori-negative group, and successful H. pylori eradication tended to reduce that ratio. In conclusion, successful eradication of H. pylori may have favorable effects on lipid metabolism.
ABSTRACT
AIM: This study aimed to examine female high school students' behavioral intention to prevent cervical cancer and related factors. METHODS: The participants were 2158 female high school students at 16 high schools in A prefecture in the Tohoku region in Japan. A self-administered questionnaire was carried out that was developed based on a conceptual framework comprising the Health Belief Model and Theory of Reasoned Action. RESULTS: The responses were obtained from 2072 students (96.0%). Of these, the answers of 2028 respondents were analyzed after excluding those participants who did not complete the behavioral intention item (effective response rate: 97.0%). A factor analysis and covariance structure analysis yielded a model with strong goodness-of-fit that explained the behavioral intentions based on an "Awareness of the importance and effectiveness of cervical cancer screening," "Obstacles to cervical cancer prevention behavior," "Subjective norms for adopting cervical cancer prevention behavior," and "The behavior of someone close that encourages cervical cancer prevention behavior." CONCLUSION: The statistical analysis yielded a model with strong goodness-of-fit that explained female high school students' behavioral intentions, which were related to four factors, including "the awareness of the importance and effectiveness of cervical cancer screening."
Subject(s)
Intention , Uterine Cervical Neoplasms/prevention & control , Adolescent , Factor Analysis, Statistical , Female , Humans , Japan , Risk Reduction Behavior , Students , Surveys and QuestionnairesABSTRACT
BACKGROUND: Previously we established an arthritis-prone FcγRIIB-deficient mouse strain (designated KO1). Anti-mouse CD11b mAb (5C6) has been reported to inhibit the recruitment of peripheral CD11b+ myelomonocytic cells from the blood to the inflammatory site. These cells include neutrophils and monocytes, both of which play important roles in the development of arthritis. Here we treated KO1 mice with 5C6 mAb in order to study its effect on arthritis development. METHODS: To evaluate the disease-preventive effect of 5C6, 4-month-old preclinical KO1 mice were divided into three groups: the first treated with 5C6 for 6 months, the second treated with normal rat IgG for 6 months, as a control, and the third left untreated. Arthritis severity and immunological abnormalities were compared among the groups, along with transcriptional levels of several important arthritis-related factors in ankle joints, spleen, and peripheral blood cells. RESULTS: The 5C6 treatment ameliorated arthritis in KO1 mice, showing decreases in inflammatory cell infiltration and osteoclast formation. Analysis of transcriptional levels in ankle joints revealed that compared with the two control groups, the 5C6-treated group showed downregulated expression of RANK, RANKL, MCP-1, RANTES, TNFα, and IL-6, and at the same time showed significantly up-regulated expression of the decoy receptor for RANKL, i.e. osteoprotegerin. In addition, the disease suppression was associated with the lower serum levels of autoantibodies, and the decreased frequencies of activated B cells and plasma cells. The expression levels of B cell activation/differentiation-related cytokines were suppressed in spleen and peripheral leukocytes of the 5C6-treated mice. Intriguingly, while untreated KO1 mice spontaneously developed marked monocytosis, the 5C6-treated mice showed the significantly down-regulated frequency of monocytes. CONCLUSIONS: The outcome of 5C6 treatment was complex, in which the 5C6-mediated disease-preventive effect is likely due on one hand to the decrease in the recruitment of inflammatory cells and osteoclast precursor monocytes from the periphery into the joints, and on the other hand to the suppression of B cell activation/maturation and of autoantibody production via the suppression of B cell stimulating cytokine production. The lower levels of these cytokines may be the secondary effect of the lower frequency of monocytes, since monocytes/macrophages are the major producers of these cytokines.
Subject(s)
Antibodies, Monoclonal/pharmacology , Arthritis, Rheumatoid/prevention & control , Autoantibodies/biosynthesis , CD11b Antigen/antagonists & inhibitors , Osteoclasts/drug effects , Receptors, IgG/deficiency , Animals , Ankle Joint/drug effects , Ankle Joint/metabolism , Antibodies, Monoclonal/immunology , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Autoantibodies/blood , Autoantibodies/immunology , CD11b Antigen/immunology , Cytokines/genetics , Cytokines/metabolism , Gene Expression/drug effects , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Knockout , Osteoclasts/metabolism , Receptors, IgG/genetics , Spleen/drug effects , Spleen/metabolismABSTRACT
Nihon Koshu Eisei Zasshi(JAPANESE JOURNAL OF PUBLIC HEALTH), Vol. 63 (2016) No. 11 p. 664-674: p668(Table 2).
ABSTRACT
A Wnt agonist, 2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl) pyrimidine, is a cell-permeable pyrimidine compound that has been shown to mimic the effect of Wnt. In this study, leukemic mouse cell lines, RAW 264.7 and J774.1, were incubated with the Wnt agonist. The Wnt agonist showed cell death in the concentration of 1-10 µM. The Wnt agonist did not show inhibition of GSK-3ß activity but induced ß-catenin accumulation in the nucleus. The Wnt agonist showed caspase-independent cell death, but no further involvement in cell death ER stress signaling. Here we discuss the possible mechanism of Wnt agonist-induced apoptotic cell death in RAW 264.7 cells.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Pyrimidines/pharmacology , Wnt Signaling Pathway/drug effects , Animals , Caspases/metabolism , Cell Death/drug effects , Cell Line, Tumor , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cell Survival/drug effects , Endoplasmic Reticulum Stress/drug effects , Mice , beta Catenin/metabolismABSTRACT
Objectives This study was conducted to develop a scale for measuring "attachment to the local community" for its use in health services. The scale is also intended to nurture new social relationships in late middle-aged individuals.Methods Thirty items were initially planned to be included in the scale to measure "attachment to the local community", according to a previous study that identified the concept. The study subjects were late middle-aged residents of City B in Prefecture A, located in Tokyo suburbs. From the basic resident register data, 1,000 individuals (local residents in the 50-69 year age group) were selected by a multi-stage random sampling technique, on the basis of their residential area, age, and sex (while maintaining the male to female ratio). An unsigned self-administered questionnaire was distributed to the subjects, and the responses were collected by postal mail. The collected data was analyzed using psychometric study of scale.Results Valid responses were obtained from 583 subjects, and the response rate was 58.3%. In an item analysis, none of the items were rejected. In a subsequent factor analysis, 7 items were eliminated. These items included 2 items with a factor loading of <0.40, 3 items loading on multiple factors and showing a factor loading of ≥0.40, and 2 items with a low factor correlation (0.04-0.16). These items included factors that related to only these 2 items. Consequently, 23 items in the following 4-factor structure were selected as the scale items: "Source of vitality to live life," "Intention to cherish ties with people," "Place where one can be oneself," and "Pride of being a resident." Cronbach's coefficient α for the entire scale of "attachment to the local community" was 0.95, demonstrating internal consistency. We then examined the correlation with an existing scale to measure social support; the results revealed a statistically significant correlation and confirmed criterion-related validity (P<0.001). In addition, the fit indices in a covariance structure analysis showed adequate values.Conclusions The developed scale was considered reliable and appropriate for measuring "attachment to the local community."
Subject(s)
Residence Characteristics , Age Factors , Aged , Female , Humans , Male , Middle Aged , Social Behavior , Surveys and QuestionnairesABSTRACT
IL-1ß is one of the inflammatory cytokines and is cleaved from pro-IL-1ß proteolytically by activated Caspase 1. For the activation of Caspase 1, inflammasome was formed by two signals, what is called, priming and triggering signals. In this study, it was found that mouse macrophage J774.1 cells, when treated by single large amount of lipopolysaccharide (LPS), produced a significant amount of IL-1ß. On the other hand, IL-1ß production was not detected when treated by a single, small amount of LPS. Then, focusing on endoplasmic reticulum (ER) stress response among stress responses induced by a large amount of LPS, when GSK2656157, a PERK inhibitor, was used for inhibition of ER stress, GSK2656157 reduced IL-1ß production dose-dependently. Next, when Thapsigargin, an ER stress reagent, was added with LPS, IL-1ß production increased more than by LPS alone. Thus, these results suggested that ER stress was involved in LPS-induced IL-1ß production. When the activation of Caspase 1 was examined by fluorescence activated cell sorter analysis, it was found that GSK2656157 inhibited LPS-induced Caspase 1 activation. Further, it was confirmed that GSK2656157 did not affect LPS-induced TNF-α production and activation of NF-κB and specifically inhibited the PERK/eIF-2α pathway. Therefore, it was found that GSK2656157 specifically inhibited ER stress induced by large amount of LPS and reduced LPS-induced IL-1ß production through inhibition of Caspase 1 activation.
Subject(s)
Adenine/analogs & derivatives , Caspase 1/immunology , Indoles/pharmacology , Interleukin-1beta/immunology , Lipopolysaccharides/toxicity , Macrophages/immunology , eIF-2 Kinase/antagonists & inhibitors , Adenine/pharmacology , Animals , Cell Line , Enzyme Activation/drug effects , Enzyme Activation/immunology , MiceABSTRACT
NK cells resist engraftment of syngeneic and allogeneic bone marrow (BM) cells lacking major histocompatibility (MHC) class I molecules, suggesting a critical role for donor MHC class I molecules in preventing NK cell attack against donor hematopoietic stem and progenitor cells (HSPCs), and their derivatives. However, using high-resolution in vivo imaging, we demonstrated here that syngeneic MHC class I knockout (KO) donor HSPCs persist with the same survival frequencies as wild-type donor HSPCs. In contrast, syngeneic MHC class I KO differentiated hematopoietic cells and allogeneic MHC class I KO HSPCs were rejected in a manner that was significantly inhibited by NK cell depletion. In vivo time-lapse imaging demonstrated that mice receiving allogeneic MHC class I KO HSPCs showed a significant increase in NK cell motility and proliferation as well as frequencies of NK cell contact with and killing of HSPCs as compared to mice receiving wild-type HSPCs. The data indicate that donor MHC class I molecules are required to prevent NK cell-mediated rejection of syngeneic differentiated cells and allogeneic HSPCs, but not of syngeneic HSPCs.
Subject(s)
Gene Expression Regulation , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cells/metabolism , Histocompatibility Antigens Class I/metabolism , Killer Cells, Natural/immunology , Animals , Cell Differentiation , Gene Knockout Techniques , Graft Rejection/immunology , Graft Rejection/prevention & control , Hematopoietic Stem Cells/cytology , Histocompatibility Antigens Class I/genetics , Mice , Molecular Imaging , Transplantation, Homologous/adverse effects , Transplantation, Isogeneic/adverse effectsABSTRACT
Patients with chronic stroke often show increased flexor hypertonia in their affected upper limbs. Although an intervention strategy targeting the extensors of the affected upper limb might thus be expected to have benefits for functional recovery, conventional repetitive motor training has limited clinical utility. Recent studies have shown that repetitive transcranial magnetic stimulation could induce motor recovery. The present study tested whether 5 Hz repetitive transcranial magnetic stimulation of the upper-limb area of the primary motor cortex, combined with extensor motor training, had a greater effect on motor recovery than either intervention alone in stroke hemiparesis. Nine patients with chronic subcortical stroke and nine age-matched healthy subjects completed the crossover study. In separate sessions, we examined the single intervention effect of repetitive wrist and finger extension exercises aided by neuromuscular stimulation, the single intervention effect of 5 Hz repetitive transcranial magnetic stimulation and the combined effect of the two interventions. The motor functions were evaluated behaviourally in patients (Experiment 1) and electrophysiologically in healthy subjects (Experiment 2), both before and after the intervention. In addition, we tested the long-term effect by repeating the combined interventions 12 times in patients (Experiment 3). The motor functions were measured again 2 weeks after the end of the repetitive intervention period. In Experiment 1, the combined intervention, but neither of the single interventions, resulted in an improvement of extensor movement (P < 0.0001) and grip power (P < 0.05), along with a reduction of flexor hypertonia (P < 0.01), in their paretic upper limbs. In Experiment 2, only the combined intervention resulted in selective plastic changes of cortico-spinal excitability (P < 0.01), motor threshold (P < 0.001) and silent period (P < 0.01) for the extensors. In Experiment 3, we also confirmed long-term beneficial effects of the combined intervention in patients. These findings indicate that combining motor training with repetitive transcranial magnetic stimulation can facilitate use-dependent plasticity and achieve functional recovery of motor impairments that cannot be attained by either intervention alone. This method could be a powerful rehabilitative approach for patients with hemiparetic stroke.
Subject(s)
Arm/physiology , Movement/physiology , Neuronal Plasticity/physiology , Paresis/rehabilitation , Recovery of Function/physiology , Stroke Rehabilitation , Adult , Chronic Disease , Exercise Therapy/methods , Female , Humans , Male , Middle Aged , Paresis/etiology , Paresis/physiopathology , Stroke/complications , Stroke/physiopathology , Transcranial Magnetic Stimulation/methods , Upper Extremity/physiologyABSTRACT
How to treat CML patients who are resistant to inhibitors of BCR-ABL tyrosine kinase such as Imatinib is a very important and urgent issue in clinical hematology. Here, we report a case of Imatinib-treated CML in which intradermally administered WT1 peptide vaccine elicited WT1-specific immune responses and the resultant reduction in the persistent residual disease in co-administration of Imatinib. BCR-ABL mRNA levels were being maintained under the detection limit for 8 months since week 77 of vaccination. No adverse effects except local erythema at the injection sites were observed. The tetramer assay revealed that the decrease in BCR-ABL mRNA levels was associated with the increase in frequency of WT1-specific cytotoxic T lymphocytes, notably effector-memory type of that, in the patient's peripheral blood. The case presented here indicates that WT1 peptide vaccine may become a safe and cure-oriented therapy for CML patients who have residual disease regardless of the treatment with Imatinib.
Subject(s)
Cancer Vaccines/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , WT1 Proteins/immunology , Aged , Antineoplastic Agents/therapeutic use , Benzamides , Cancer Vaccines/chemistry , Cancer Vaccines/immunology , Combined Modality Therapy , Drug Resistance, Neoplasm , Female , Fusion Proteins, bcr-abl/antagonists & inhibitors , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology , Neoplasm, Residual , Piperazines/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrimidines/therapeutic use , RNA, Messenger , T-Lymphocytes, Cytotoxic/immunology , Vaccines, Subunit/immunology , Vaccines, Subunit/therapeutic use , WT1 Proteins/chemistryABSTRACT
PURPOSE: The present study aimed to clarify the relationship between health behavior and social support for the prevention of lifestyle-related diseases in the Tohoku region of Japan. METHODS: The subjects were 2,457 individuals aged > 40 years in 2005 who attended for physical checkup in "Town A" in Miyagi prefecture in the Tohoku region ofJapan. Data from 1,225 individuals who answered appropriately were analyzed. Questionnaire items comprised measures of health behavior and social support. Additionally, demographic characteristics, health status, medical history, family history of lifestyle-related diseases, and lifestyles of cohabiting family members were covered. Health behavior items included the Alameda seven health practices, while social support items included mental status, dietary habits, exercise, and available health support. Comparisons of health behavior scores with individual variables were analyzed using a t-test and one-way analysis of variance. Pearson's correlation coefficient and step-wise multiple regression by gender and age (40-64 years; 65 years or older) was employed for analysis of the factors concerning health behavior. RESULTS: Mental support was found to be related to health behavior in men aged 40-64 years after adjustment for diseases; however, no relationship between social support and health behavior was observed for men aged 65 years or older. Regardless of the diseases adjusted for, exercise support was related to health behavior in women aged 65 years or older. Among women aged 40-64 years, including those with diseases, support for dietary habits had a negative effect on health behavior while health information support had a positive effect. CONCLUSION: Mental support, exercise support, and health information support were found to have positive effects on health behavior, regardless of sex, age, and health status. The present findings indicate the importance of mental and exercise support for the prevention of lifestyle-related diseases, particularly in men aged 40-64 years, and in women aged 65 years or older.
Subject(s)
Chronic Disease/prevention & control , Health Behavior , Life Style , Social Support , Adult , Aged , Female , Humans , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
Transcriptional activation of metallothionein (MT) genes by heavy metals is a valuable system for understanding the functions of MT as well as the cellular response against heavy metals. Although it is now known that heavy metal signals culminating in MT induction converge upon a transcription factor MTF-1, the mechanism underlying the MTF-1 response to heavy metals has not been elucidated. To address this issue, we investigated various aspects of the in vivo response of MTF-1 against heavy metals. Chromatin immunoprecipitation assay showed that heavy metal-dependent DNA binding of MTF-1 is the critical step in vivo. MTF-1 is primarily localized in the nucleus so that heavy metal-dependent nuclear translocation demonstrated by other groups does not seem to be universal and hence may not be critical for activation of MTF-1. In the six Zn finger motifs, the hallmark of MTF-1, the third and the fourth fingers are essential for the nuclear localization of MTF-1. Furthermore, all fingers except the last are important for transcriptional activation function of MTF-1, suggesting their key role for MTF-1 function. Also, a cysteine cluster structure located in the C-terminal region of MTF-1 is critical for transactivating function of MTF-1. These results suggest a central role of the Zn-finger domain and intramolecular cooperation through a structural change of MTF-1 for its response to heavy metal challenge.
Subject(s)
DNA-Binding Proteins/physiology , Metallothionein/genetics , Metals, Heavy/toxicity , Transcription Factors/physiology , Transcriptional Activation , Animals , DNA/metabolism , Humans , Metallothionein/physiology , Protein Binding , Zinc Fingers , Transcription Factor MTF-1ABSTRACT
Biological activities of lipopolysaccharide (LPS) from Brucella melitensis 16M were characterized in comparison with LPS from Escherichia coli O55. LPS extracted from B. melitensis was smooth type by electrophoretic analysis with silver staining. The endotoxin-specific Limulus activity of B. melitensis LPS was lower than that of E. coli LPS. There was no significant production of tumor necrosis factor-alpha and nitric oxide in RAW 264.7 macrophage cells stimulated with B. melitensis LPS, although E. coli LPS definitely induced their production. On the other hand, B. melitensis LPS exhibited a higher anti-complement activity than E. coli LPS. B. melitensis LPS as well as E. coli LPS exhibited a strong adjuvant action on antibody response to bovine serum. The characteristic biological activities of B. melitensis are discussed.
Subject(s)
Brucella melitensis/pathogenicity , Lipopolysaccharides/toxicity , Animals , Cells, Cultured , Complement System Proteins/drug effects , Electrophoresis , Female , Male , Mice , Nitric Oxide/biosynthesis , Toll-Like Receptor 4/physiology , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
IL-5 preferentially activates B1 cells to produce natural antibodies cross-reactive to self antigens. To determine the role of IL-5 in antibody-mediated autoimmune disease, we generated systemic lupus erythematosus (SLE)-prone (NZB x NZW)F1 mice congenic for IL-5 transgene (TG-F1). The transgene unexpectedly reduced the incidence of lupus nephritis. Anti-DNA antibodies in sera and those produced by splenic B cells in vitro were markedly decreased in TG-F1 mice, while total polyclonal Ig levels were comparable to those in IL-5 transgene-negative (NZB x NZW)F1 (non-TG-F1) littermates. Flow cytometry-sorted splenic B1 cells showed a significant reduction of anti-DNA antibody synthesis in response to IL-5, while proliferative responses to IL-5 did not significantly differ between TG-F1 and non-TG-F1 mice. As TG-F1 mice aged, frequencies of peripheral B1 cells progressively increased, and the mice frequently developed B cell chronic lymphocytic leukemia (B-CLL). Our results suggest that dysregulated, continuous high expression of IL-5 in SLE-prone mice may directly or indirectly mediate a skewed signaling of proliferation/differentiation of self-antigen-activated B1 cells, leading to suppression of autoimmune disease, but instead to aberrant expansion of B1 cells, giving rise to B-CLL. Thus, this model may provide a clue to the pathogenesis of both SLE and B-CLL.
Subject(s)
B-Lymphocyte Subsets/immunology , B-Lymphocytes/immunology , Interleukin-5/genetics , Interleukin-5/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/etiology , Lupus Erythematosus, Systemic/immunology , Animals , Antibodies, Antinuclear/blood , Blotting, Southern , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Fluorescent Antibody Technique , Immunoglobulin G/blood , Immunoglobulin M/blood , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Lupus Nephritis/immunology , Mice , Mice, Transgenic , TransgenesABSTRACT
PROBLEM: This study was performed to investigate if patients' sera with anti-human sperm antibodies show inhibitory effects on in vitro fertilization (IVF) and embryo development in mice. METHOD OF STUDY: Patients' sera were collected from eight infertile women having sperm immobilizing antibodies and 17 infertile women without the antibodies. Male ICR mice and female F1 mice (BALB/c X C57BL/6J) were used. In mouse IVF, pre-incubated sperm were cultured in the medium containing patient's serum with or without sperm immobilizing antibodies, or bovine serum albumin (BSA) as a control. The fertilization rates and the incidences of blastocyst formation were compared. RESULTS: A mouse sperm immobilization test was established. Five (62.5%) of eight serum samples with sperm immobilizing antibodies and nine (52.9%) of 17 serum samples without the antibodies showed sperm immobilizing activities in mice. There was no significant difference between the two groups. Five sera with sperm immobilizing activities in human and mice, and five sera without sperm immobilizing activities in human or mice were used for the further experiments. The fertilization rates in BSA, patient's serum with sperm immobilizing antibodies, and that without the antibodies were 82.5% (746/904), 43.6% (508/1165), and 64.5% (669/1037), respectively. There were significant differences between the groups. The incidences of blastocyst formation were 59.9% (447/746), 31.7% (161/508), and 47.7% (319/669), respectively. There were also significant differences between the groups. CONCLUSIONS: Some of the patient's serum with and without sperm immobilizing antibodies could immobilize sperm with complement. However, as compared with control, sera with sperm immobilizing activities against human and mouse sperm significantly blocked IVF and inhibited embryo development in mice. Further studies are required to investigate the mechanisms of the blocking effects of antisperm antibodies on fertilization and embryo development using the mouse model.
Subject(s)
Antibodies/adverse effects , Infertility, Female/immunology , Spermatozoa/immunology , Animals , Blastocyst/immunology , Embryonic and Fetal Development , Female , Fertilization in Vitro , Humans , Infertility, Female/etiology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred ICRABSTRACT
The detailed mechanism of NO production in mouse vascular endothelial cells, END-D, was studied. The NO production in END-D cells was triggered by gamma interferon (IFN-gamma), but not LPS. However, LPS augmented the NO production in IFN-gamma-stimulated END-D cells. A high level of NO production was due to the expression of an inducible type of NO synthase (iNOS) in those cells. A significant amount of NO was detected 18 h after IFN-gamma stimulation, accompanied by the delayed iNOS expression. The JAK/STAT signal pathway mediated IFN-gamma-induced NO production, but did not participate in the LPS-induced augmentation. Further, no activation of nuclear factor (NF)-kappaB was involved in the NO production in END-D cells stimulated with either IFN-gamma and/or LPS. The mechanism of NO production in END-D cells was suggested to be different from that in mouse macrophages. The differential regulation of NO production in mouse vascular endothelial cells and macrophages is discussed.
Subject(s)
Endothelium, Vascular/metabolism , Macrophages/metabolism , Nitric Oxide/metabolism , Animals , Cell Line , DNA-Binding Proteins/metabolism , Dose-Response Relationship, Drug , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Escherichia coli/immunology , Interferon-gamma/pharmacology , Janus Kinase 1 , Lipopolysaccharides/pharmacology , Macrophages/cytology , Macrophages/drug effects , Mice , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II , Protein-Tyrosine Kinases/metabolism , STAT2 Transcription Factor , Signal Transduction , Trans-Activators/metabolismABSTRACT
The 2:1 charge-transfer (CT) salts (1(2).FeBr(4) and 1(2).GaBr(4)) of ethylenedithiotetrathiafulvalenoquinone-1,3-dithiolemethide (1) with FeBr(4)(-) and GaBr(4)(-) counteranions were obtained as needle crystals, whose structures are almost the same as each other. The 1 molecules form a one dimensionally stacked column with alternation of their molecular axis direction, while the counteranions are aligned in parallel with the 1-stacked columns with the direction of their distorted-tetrahedral geometry maintained. The room-temperature electrical conductivities measured on the single crystals of 1(2).FeBr(4) and 1(2).GaBr(4) were 4.6 and 2.1 S cm(-1), respectively. From the temperature dependences of their electrical conductivities in both cases the electrical conducting properties were metallic between ca. 170 and 300 K, but below ca. 170 K converted to be semiconducting and continued till 5 K, although the activation energies are very small (4-10 meV). For 1(2).FeBr(4) very weak and antiferromagnetic interaction occurred between the d spins of FeBr(4)(-) ions in the temperature range of ca. 1-300 K. However, below ca. 15 K the ferromagnetic interaction was reversely preferential possibly by participation of the pi spin of 1.
ABSTRACT
The dicyanomethylene group and not the quinone oxygen atoms is the site of the first one-electron reduction for the dicyanohetereotriquinone methide 1, although the dicyanomethylene group is substituted at a cyclopentadienyl-like five-membered ring! Compound 1 is amphoteric and undergoes a five-stage sequence of one-electron redox reactions.
ABSTRACT
Novel heteroquaterphenoquinones, 5,5'-bis(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1-ylidene)-5,5'-dihydro-2,2'-bithienyl (3) and its 2,2'-biselenienyl (4), 2,2'-bifuryl (5), and 2,2'-bi-N-methylpyrrolyl (6) analogues, were synthesized by a stepwise cross-coupling reaction or by a more convenient one-pot oxidative homocoupling reaction of heterocycle-substituted phenols. Despite a highly conjugation-extended system, the quinones 3-6 are very stable in the solid state and in solution in common organic solvents. These quinones undergo a reversible one-stage, two-electron reduction up to dianions and a two-stage, one-electron oxidation reaction up to dications. The E(1)(red) of these quinones increases with the increase in the aromaticity of the incorporated heterocycles. The E(1)(ox) of these quinones appears to be specified by the ionization potential of the incorporated heterocycles. Thus, the N-methylquinone 6 exhibiting the lowest E(1)(ox) value exhibits the smallest E(1)(sum) among the quinones 3-6. The quinone 5 was revealed to exist in an unusual O-cis conformation in the solid state by X-ray crystallography, whereas the quinone 3 exists in an S-trans conformation in the solid state. The cis and trans isomers are interconvertible in solution in 3-5, whereas only N-trans isomer was detected for 6 in (1)H NMR spectroscopy. The quinones 3-6 exhibit a very intense absorption maximum in the near-infrared region of 662-827 nm. Of these, the maximum absorption wave length of 6 shifts to a more bathochromic region by 149-165 nm than those of 3-5. The quinones 3-6 can be used as dyestuffs in various fields for laser-driven high-density optical storage media.