Publications by authors named "Akane Kondo"

19 Publications

  • Page 1 of 1

Expression of the core promoter factors TATA box binding protein and TATA box binding protein-related factor 2 in Drosophila germ cells and their distinct functions in germline development.

Dev Growth Differ 2020 Dec;62(9):540-553

Department of Biology, Faculty of Science and Engineering, Konan University, Kobe, Japan.

In Drosophila, the expression of germline genes is initiated in primordial germ cells (PGCs) and is known to be associated with germline establishment. However, the transcriptional regulation of germline genes remains elusive. Previously, we found that the BTB/POZ-Zn-finger protein, Mamo, is necessary for the expression of the germline gene, vasa, in PGCs. Moreover, truncated Mamo lacking the BTB/POZ domain (MamoAF) is a potent vasa activator. In this study, we investigated the genetic interaction between MamoAF and specific transcriptional regulators to gain insight into the transcriptional regulation of germline development. We identified a general transcription factor, TATA box binding protein (TBP)-associated factor 3 (TAF3/BIP2), and a member of the TBP-like proteins, TBP-related factor 2 (TRF2), as new genetic modifiers of MamoAF. In contrast to TRF2, TBP was found to show no genetic interaction with MamoAF, suggesting that Trf2 has a selective function. Therefore, we focused on Trf2 expression and investigated its function in germ cells. We found that Trf2 mRNA, rather than Tbp mRNA, was preferentially expressed in PGCs during embryogenesis. Depletion of TRF2 in PGCs resulted in decreased mRNA expression of vasa. RNA interference-mediated knockdown showed that, while Trf2 is required for maintenance of germ cells, Tbp is needed for their differentiation during oogenesis. Therefore, these results suggest that Trf2 and Tbp expression is differentially regulated in germ cells and that these factors have distinct functions in Drosophila germline development.
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http://dx.doi.org/10.1111/dgd.12701DOI Listing
December 2020

Efficient detection of copy-number variations using exome data: Batch- and sex-based analyses.

Hum Mutat 2021 Jan 11;42(1):50-65. Epub 2020 Nov 11.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Many algorithms to detect copy number variations (CNVs) using exome sequencing (ES) data have been reported and evaluated on their sensitivity and specificity, reproducibility, and precision. However, operational optimization of such algorithms for a better performance has not been fully addressed. ES of 1199 samples including 763 patients with different disease profiles was performed. ES data were analyzed to detect CNVs by both the eXome Hidden Markov Model (XHMM) and modified Nord's method. To efficiently detect rare CNVs, we aimed to decrease sequencing biases by analyzing, at the same time, the data of all unrelated samples sequenced in the same flow cell as a batch, and to eliminate sex effects of X-linked CNVs by analyzing female and male sequences separately. We also applied several filtering steps for more efficient CNV selection. The average number of CNVs detected in one sample was <5. This optimization together with targeted CNV analysis by Nord's method identified pathogenic/likely pathogenic CNVs in 34 patients (4.5%, 34/763). In particular, among 142 patients with epilepsy, the current protocol detected clinically relevant CNVs in 19 (13.4%) patients, whereas the previous protocol identified them in only 14 (9.9%) patients. Thus, this batch-based XHMM analysis efficiently selected rare pathogenic CNVs in genetic diseases.
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http://dx.doi.org/10.1002/humu.24129DOI Listing
January 2021

Update of the genotype and phenotype of KMT2D and KDM6A by genetic screening of 100 patients with clinically suspected Kabuki syndrome.

Am J Med Genet A 2020 10 17;182(10):2333-2344. Epub 2020 Aug 17.

Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.

Kabuki syndrome is characterized by a variable degree of intellectual disability, characteristic facial features, and complications in various organs. Many variants have been identified in two causative genes, that is, lysine methyltransferase 2D (KMT2D) and lysine demethylase 6A (KDM6A). In this study, we present the results of genetic screening of 100 patients with a suspected diagnosis of Kabuki syndrome in our center from July 2010 to June 2018. We identified 76 variants (43 novel) in KMT2D and 4 variants (3 novel) in KDM6A as pathogenic or likely pathogenic. Rare variants included a deep splicing variant (c.14000-8C>G) confirmed by RNA sequencing and an 18% mosaicism level for a KMT2D mutation. We also characterized a case with a blended phenotype consisting of Kabuki syndrome, osteogenesis imperfecta, and 16p13.11 microdeletion. We summarized the clinical phenotypes of 44 patients including a patient who developed cervical cancer of unknown origin at 16 years of age. This study presents important details of patients with Kabuki syndrome including rare clinical cases and expands our genetic understanding of this syndrome, which will help clinicians and researchers better manage and understand patients with Kabuki syndrome they may encounter.
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http://dx.doi.org/10.1002/ajmg.a.61793DOI Listing
October 2020

A truncated form of a transcription factor Mamo activates in embryos.

Commun Biol 2019 20;2:422. Epub 2019 Nov 20.

1Department of Biology, Faculty of Science and Engineering, Konan University, Okamoto, Higashinada, Kobe, 658-8501 Japan.

Expression of the gene is associated with germline establishment. Therefore, identification of activator(s) should provide insights into germline development. However, the genes sufficient for activation remain unknown. Previously, we showed that the BTB/POZ-Zn-finger protein Mamo is necessary for expression in . Here, we show that the truncated Mamo lacking the BTB/POZ domain (MamoAF) is a potent activator. Overexpression of MamoAF was sufficient to induce expression in both primordial germ cells and brain. Indeed, Mamo mRNA encoding a truncated Mamo isoform, which is similar to MamoAF, was predominantly expressed in primordial germ cells. The results of our genetic and biochemical studies showed that MamoAF, together with CBP, epigenetically activates expression. Furthermore, MamoAF and the germline transcriptional activator OvoB exhibited synergy in activating transcription. We propose that a Mamo-mediated network of epigenetic and transcriptional regulators activates expression.
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http://dx.doi.org/10.1038/s42003-019-0663-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868150PMC
May 2020

Distribution of PAPP-A and total hCG between 11 and 13 weeks of gestation in Japanese pregnant women.

J Matern Fetal Neonatal Med 2020 Jun 28;33(12):2017-2022. Epub 2018 Nov 28.

Department of Obstetrics and Gynecology, Saitama Medical University Hospital, Saitama, Japan.

To establish the reference values for PAPP-A and total hCG between 11 and 13 weeks of gestation for the use of risk assessment of fetal aneuploidy in Japanese pregnant women. A multicenter prospective study was conducted. The subjects included only Japanese pregnant women with viable singleton who requested the first trimester combined (nuchal translucency and maternal serum marker) screening for fetal aneuploidy. Reference values of PAPP-A and total hCG in Japanese population were made and compared with them in Caucasian. Overall 1,751 Japanese pregnant women were analyzed. Median vales of maternal serum concentration in Japanese pregnant women from 11 + 0-13 + 6 weeks' gestation were ranged from 3.01 to 9.51 mIU/mL for PAPP-A and from 70.2 to 58.3 IU/mL for total-hCG, respectively. Regression curve of median maternal serum PAPP-A and total-hCG concentration against gestational days are significantly higher in Japanese comparing with Caucasian. At most distant values, Japanese serum concentration indicated 1.45 MoM for total-hCG and 1.70 MoM for PAPP-A based on Caucasian regression curves. A modification of the equations by specific reference values is necessary for Japanese pregnant women at the risk assessment of chromosomal abnormalities using the first trimester maternal serum marker.
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http://dx.doi.org/10.1080/14767058.2018.1536737DOI Listing
June 2020

Exome and copy number variation analyses of Mayer-Rokitansky-Küster- Hauser syndrome.

Hum Genome Var 2018 27;5:27. Epub 2018 Sep 27.

1Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa Japan.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital absence of the vagina and uterus. We conducted genome-wide SNP analyses and exome sequencing to detect the causes of MRKH syndrome. We identified de novo variants of , , and in three families and a variant of in a sporadic case. Here, we demonstrated the partial genetic makeup of Japanese MRKH syndrome.
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http://dx.doi.org/10.1038/s41439-018-0028-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160444PMC
September 2018

Laparoscopic Davydov Procedure for the Creation of a Neovagina in Patients with Mayer-Rokitansky-Kuster-Hauser Syndrome: Analysis of 7 Cases.

Tokai J Exp Clin Med 2016 Jun 20;41(2):81-7. Epub 2016 Jun 20.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Objective: Several surgical techniques have been described for creating a neovagina in patients with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, however as yet there is no standardized treatment. The aim of this report is to assess anatomic and functional outcomes after the laparoscopic Davydov procedure for the creation of a neovagina in patients with MRKH syndrome.

Methods: Seven patients with MRKH syndrome underwent the laparoscopic Davydov technique from January 2005 to August 2010. The anatomic and functional results were evaluated after 3, 6, 12, 24, 36, 48, and 60 months.

Results: The surgical procedure was performed with no major complications except in one case in which an intraoperative bladder injury occurred and was successfully corrected. The mean duration of surgery was 162.9 minutes (range, 120-230 min). Mean lengths/widths (cm) of the neovagina were 6.4/2.6, 6.5/2.5, 6.5/2.8, 6.4/2.8, 7.1/2.8, and 7.2/2.8 at 3, 6,12, 24, 36, 48, and 60 postoperative months, respectively.

Conclusion: The laparoscopic Davydov procedure seems to be a safe and effective surgical treatment for patients with MRKH syndrome if postoperative intermittent self dilation was done.
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June 2016

Does aberrant DNA methylation occur in human uterine leiomyomas? An attempt of genome-wide screening by MS-RDA.

Tokai J Exp Clin Med 2011 Sep 20;36(3):84-90. Epub 2011 Sep 20.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, and Department of clinical Genetics, Tokai University Hospital, Kanagawa, Japan.

Objective: Uterine leiomyoma are very common benign tumors in women of reproductive age. However, the molecular mechanisms of cause and development of these tumors are poorly understood. This study attempts to examine whether or not aberrant DNA methylation occurred in these tumors.

Methods: We carried out a genome-wide screen for aberrant DNA methylation, adopting methylation-sensitive-representational difference analysis (MS-RDA) using normal adjacent myometria as tester and myoma tissue driver.

Conclusion: A total of 192 clones identified by MS-RDA were sequenced, 27 DNA fragments derived from CpG islands (CGIs) were isolated, and seven of them were from CGI in the 5' regions of known genes, which include CHARC1, FAM44B, FLJ33655, HSUP, MLLT3, SLC16A1, and ZNF96. Then, methylation statuses of those CGIs were analyzed by methylation-specific polymerase chain reaction using 5 primary samples of human uterine leiomyoma. Aberrant DNA methylation did not observed in 7 genes in 5 human uterine leiomyoma eventually. This study is insufficient to identify aberrant DNA methylation occurring in the human uterine leiomyoma, a large population of primary samples and more attempts, such as the use of cell lines or primary monolayer cultures established from tissue samples, are warranted to clarify this issue.
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September 2011

Noninvasive measurement of fetal augmentation index by fetal aortic diameter pulse and flow velocity waveforms.

Acta Obstet Gynecol Scand 2011 Aug 14;90(8):839-45. Epub 2011 Jun 14.

Department of Medical Engineering, Tokyo City University, Tokai University School of Medicine, Japan.

Objective: To study fetal systemic arterial stiffness in normal fetuses and compromised fetuses who had umbilical placental insufficiency (UPI).

Design: Prospective study.

Setting: University departments.

Sample: A total of 118 normal fetuses (21-40 weeks) and 55 fetuses (UPI group) with evidence of potential compromise (high umbilical artery pulsatility index).

Methods: A new real-time noninvasive measurement system based on a combined Doppler ultrasound and echo-tracking system was used as a measure of aortic/systemic arterial stiffness. The augmentation index (AI) of the fetal thoracic descending aorta was measured by using simultaneous measurements of diameter pulse and flow velocity waveforms.

Main Outcome Measure: Augmentation index as a measure of stiffness.

Results: In normal fetuses, successful measurements for obtaining the AI were achieved in 103 of 118 fetuses. In the normal group, the AI, as well as placental resistance, decreased during the second trimester; in contrast, an increase in the AI was observed during the third trimester. Using the AI values from the normal group, the UPI group was divided into two subgroups: 29 fetuses with a normal AI and 26 fetuses with a high AI. The clinical outcome was significantly worse in the latter subgroup compared with the normal subgroup.

Conclusions: The increase of afterload caused by a high umbilical placental resistance was associated with a decrease of aortic distensibility in the compromised fetuses, suggesting an alteration of aortic wall structure.
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http://dx.doi.org/10.1111/j.1600-0412.2011.01173.xDOI Listing
August 2011

Gene expression of lymphocyte prolactin receptor was suppressed in lactating mothers.

Tokai J Exp Clin Med 2010 Jul 20;35(2):62-5. Epub 2010 Jul 20.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.

Prolactin (PRL) receptor (PRL-R) was proven to be ubiquitously expressed by cells in the immune system, while the physiological role of PRL was established in milk production in mammary glands. We analyzed the mRNA content of PRL-R in human lymphocytes in normo- and hyperprolactinemic conditions to document the presence of functioning PRL-R of human lymphocytes. Blood samples were obtained prior to treatment, and with written informed consent, from outpatients with ovarian dysfunction and hyperprolactinemia (n = 8; 19 ~ 41 y/o), from breast-feeding mothers after normal delivery (n = 12; 27 ~ 36 y/o), and from healthy volunteers: men (n = 9; 33 ~ 40 y/o) and women (n = 9; 26 ~ 36 y/o). Subsequently, total RNA was prepared from the lymphocytes separated. The quantity of PRL-R mRNA was examined by reverse transcription and polymerase chain reaction and normalized with a simultaneously measured amount of b actin. The resultant mRNA level of PRL-R was analyzed for its correlation with serum concentration of PRL measured by immunoassay. PRL-R mRNA levels of lymphocytes were significantly suppressed in lactating mothers, while there was a statistically significant negative correlation between PRL-R mRNA and serum PRL levels. However, there was no significant difference of PRL-R mRNA in the pathological condition of outpatients with ovarian dysfunction and/or hyperprolactinemia. While a few investigators reported the extra-mammary regulation on PRL-R by PRL, our data suggest that the PRL-R levels of circulating lymphocytes could be down-regulated by the elevated serum levels of PRL and that pituitary PRL may participate in regulating the expression of PRL-R genes on cells of the human immune system, especially in physiological circumstances such as in the postpartum period.
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July 2010

Non-invasive assessment of arterial stiffness in appropriate-for-gestational age newborn infants.

Early Hum Dev 2008 Jun 21;84(6):403-8. Epub 2007 Dec 21.

Maternal & Perinatal Centore, Tokai University School of Medicine, Boseidai, Isehara-city, Kanagawa, 259-1193, Japan.

Background: Quantitative information about the elastic properties of the large arteries can be obtained by determination of the pressure and the pulsatile changes of arterial diameter.

Objective: To study the stiffness of major branches (common carotid artery; CCA, abdominal aorta; AA and femoral artery; FA) in newborn infants.

Study Design: The arterial stiffness index (SI) values were measured with a phase locked loop ultrasound technique to estimate the arterial systolic and diastolic diameters and their correlation with blood pressure.

Subjects: We studied 62 appropriate-for-gestational age infants (between 30 and 41 weeks of gestation at birth) including 33 preterm infants.

Results: The systolic and diastolic diameters of the CCA, AA and FA, as well as the SI, increased with the gestational age at birth. In the SI of the FA, there was considerable variation in the individual values for a given gestational age at birth. The gestational age associated increase in stiffness was statistically significant only in the CCA and the AA. Although the mechanical properties of the FA were significantly influenced by physical activities during the active waking and quiet sleeping states, the calculated SI values were less vulnerable to these activities in the central arteries.

Conclusion: These results indicate that the SI of the FA (peripheral muscular artery) is modified appreciably by vasoactive stimuli. The mechanical properties of the deeper elastic arteries in newborn infants provide sufficiently reliable information about changes caused by development.
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http://dx.doi.org/10.1016/j.earlhumdev.2007.10.009DOI Listing
June 2008

Usefulness of combined PET/CT for patient with epithelial ovarian cancer showing recurrence based on tumor marker CA125.

Tokai J Exp Clin Med 2007 Mar 20;32(1):23-7. Epub 2007 Mar 20.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.

We report the case of a 41-year-old patient with epithelial ovarian cancer of stage IIIc. One year and nine months after completion of chemotherapy performed after surgery, the level of the tumor marker CA125 began to increase gradually. Conventional computed tomography (CT) and magnetic resonance imaging (MRI) were performed, but the recurrence site could not be determined clearly. However, combined positron emission tomography/computed tomography (PET/CT) revealed a metastasis in the right external iliac lymph node. This allowed commencement of chemotherapy at an early recurrent stage and subsequently the level of CA125 showed a significant decrease.
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March 2007

IgG-antiphospholipid antibodies in follicular fluid of IVF-ET patients are related to low fertilization rate of their oocytes.

Am J Reprod Immunol 2006 May;55(5):341-8

Department of Obstetrics and Gynecology, Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan.

Problem: Patients undergoing in vitro fertilization and embryo transfer (IVF-ET) failures show an increased incidence of antiphospholipid antibodies (aPL) in their blood. The physiological manifestations of aPL in this patient group are nonetheless controversial. Pathological effects of aPL on embryos in vitro have been documented. We questioned whether aPL if found in follicular fluids (FFs) could result in embryonic damage.

Method Of Study: Blood from 44 patients with three or more IVF-ET failures were tested by enzyme-linked immunosorbent assays (ELISA) for the presence of immunoglobulin (Ig)G, IgM and IgA aPL. Both the 29 aPL-positive and 15 aPL-negative patients gave permission for FF collection during their next IVF-ET attempt for additional aPL determinations.

Results: Patients with no aPL in their blood, had no aPL in their FFs. Patients with IgG and/or IgM aPL in their blood had IgG but not IgM in their respective FFs.

Conclusions: The presence of IgG aPL in FFs and increased infertility length were significantly related to lower fertilization rates, independently. Follicular fluid IgG aPL appears as a risk factor in association with successful IVF-ET outcomes.
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http://dx.doi.org/10.1111/j.1600-0897.2006.00374.xDOI Listing
May 2006

Pregnancy loss and endometriosis: pathogenic role of anti-laminin-1 autoantibodies.

Ann N Y Acad Sci 2005 Jun;1051:174-84

Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.

Laminin-1 is a major multifunctional glycoprotein that forms an integral part of the scaffolding network of basement membranes, and is the earliest synthesized component during embryogenesis. This protein (alpha1beta1gamma1) plays an important role in basement membrane assembly and epiblast differentiation during embryonic development. Anti-laminin-1 autoantibodies are known to cause infertility and recurrent spontaneous abortion in animals. Recently, we reported that the presence of IgG anti-laminin-1 antibodies (Abs) in the blood is significantly associated with recurrent first-trimester miscarriages and subsequent negative pregnancy outcomes. Interestingly, these antibodies are also strongly associated with infertility, especially infertility caused by endometriosis. Laminin-alpha1, laminin-beta1, and laminin-gamma1 mRNAs were also detected in 90% of endometriotic lesions, and all laminin-alpha1, laminin-beta1, and laminin-gamma1 chains were localized to the basement membranes of glandular epithelium in endometriotic peritoneal lesions. ELISA showed specific reactivity of the autoantibodies to a particular region of the laminin-1 molecule, that is, the alpha1 chain G domain. IgM monoclonal anti-laminin-1 Abs, which we recently established, also recognized the G domain and cross-reacted with human alpha1 chain located in the basement membrane of the glandular epithelium of human endometrium. We also established an animal model that produced high titers of anti-laminin-1 Abs after immunization with mouse laminin-1. Anti-laminin-1 Abs from the immunized mice caused a higher fetal resorption rate with lower embryonic and placental weights. Thus, anti-laminin-1 Abs may be important in the development of autoimmune-mediated reproductive failures, and the assessment of the such antibodies may provide a novel means for noninvasive diagnosis of endometriosis.
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http://dx.doi.org/10.1196/annals.1361.059DOI Listing
June 2005

Preconception peripheral natural killer cell activity as a predictor of pregnancy outcome in patients with unexplained infertility.

Am J Reprod Immunol 2005 Mar;53(3):126-31

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.

Problem: Preconception high peripheral natural killer (NK) cell activity in women with recurrent spontaneous abortion can predict subsequent miscarriages. We have examined prospectively, for the first time, the pregnancy rate in patients with unexplained infertility by measuring the peripheral NK activity.

Method Of Study: We tested the peripheral NK activity of 94 infertile women who despite treatment were unable to conceive for 6 or more months (mean; 2.4 years). Peripheral NK activity was measured by a chromium-51 release cytotoxicity assay. Women were followed for 2 years and assessed.

Results: In 77 patients who were followed for 2 years, 28 had conceived but 49 did not. The peripheral NK activity of the group that became pregnant (mean +/- S.D.; 34.5 +/- 13.8%) was significantly lower than that of non-conception group (42.3 +/- 13.3%, P = 0.017).

Conclusions: Our finding suggests that elevated peripheral NK activity in patients with unexplained infertility is a risk factor for attaining pregnancy success.
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http://dx.doi.org/10.1111/j.1600-0897.2005.00255.xDOI Listing
March 2005

Characterization of a murine anti-laminin-1 monoclonal antibody (AK8) produced by immunization with mouse-derived laminin-1.

Clin Dev Immunol 2005 Mar;12(1):67-73

Department of Obstetrics and Gynecology, Center for Specialized Clinical Science, Tokai University, School of Medicine, Ishehara, Japan.

Laminin-1 is a structural glycoprotein that forms an integral part of the scaffolding of basement membranes, and plays an important role during embryonic development. We have recently demonstrated a significant association between anti-laminin1 antibodies (Abs) and reproductive failure, such as recurrent spontaneous abortions and infertility-associated endometriosis in both human and mouse studies. In the present study, we established an IgM (micro, kappa) monoclonal anti-laminin-1 Ab (AK8) by immunizing mice with mouse Engelbreth-Holm-Swarm sarcoma (EHS)-derived laminin-1. The AK8 monoclonal antibody (mAb) reacted with particular peptide sequences from the globular G domain of mouse laminin-alpha1 chain of using ELISA and Western blot techniques. The peptide tertiary structure of the epitope recognized by AK8 mAb was predicted using eight synthesized domain peptide sequences and three consensus sequences obtained by phage displayed random peptide library. Basement membranes of endometrium of pregnant mice and humans were immunostained with AK8 mAb. Thus, AK8 mAb recognized a common structure present in the G domain of the laminin-alpha1 chain in both mice and humans. The passive immunization of mice with AK8 mAb may represent a suitable animal model for anti-laminin-1 Ab-mediated reproductive failure.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270721PMC
http://dx.doi.org/10.1080/17402520400014168DOI Listing
March 2005

Anti-laminin-1 autoantibodies, pregnancy loss and endometriosis.

Clin Dev Immunol 2004 Sep-Dec;11(3-4):261-6

Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.

Laminin-1 is a major component and multifunctional glycoprotein of basement membranes that consists of three different subunits, alpha1, beta1 and gamma11 chains. It is the earliest synthesized network-forming protein during embryogenesis and plays an important role in embryonic development, embryonic implantation and placentation. We have recently shown that IgG anti-laminin-1 antibodies were significantly associated with recurrent first-trimester miscarriages and with subsequent pregnancy outcome. Interestingly, these antibodies were also observed in patients with endometriosis-associated infertility but not in patients with other causes of infertility, including tubal factors, hormonal and uterine abnormalities. Laminin-alpha1, -beta1 and -gamma1 mRNAs have been detected in 90% of endometriotic lesions and all laminin-alpha1, -beta1 and -gamma1 chains were localized in the basement membranes of glandular epithelium in endometriotic peritoneal lesions. Western blot analysis showed that anti-laminin-1 antibodies from those patients reacted with all laminin-1's chains. ELISA also confirmed that one of the target epitopes for these antibodies was located in a particular region of the laminin-1 molecule, i.e. the carboxyl-terminal globular G domain of alpha1 chain. IgM monoclonal anti-laminin-1 autoantibody, that we recently established, also recognized the G domain. Anti-laminin-1 antibodies from mice immunized with "mouse" laminin-1, caused a higher fetal resorption rate with lower embryonic and placental weights. Thus, anti-laminin-1 antibodies may be important in development of autoimmune-mediated reproductive failures and the assessment of the antibodies may provide a novel non-invasive diagnosis of endometriosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2486330PMC
http://dx.doi.org/10.1080/17402520400001678DOI Listing
January 2005

Increased depression and anxiety in infertile Japanese women resulting from lack of husband's support and feelings of stress.

Gen Hosp Psychiatry 2004 Sep-Oct;26(5):398-404

Department of Obstetrics and Gynecology, Center for Specialized Clinical Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.

We report that infertile women in Japan as well as in the Western world have high levels of emotional distress, anxiety, and depression. The reasons for anxiety and depression in infertile women are easy to presume but remain unclear. We conducted the present study to assess the relationship between the anxiety and depression of infertile Japanese women and their thought processes and emotional well-being with regard to their infertility. A cross-sectional questionnaire was administered to 101 infertile Japanese women who visited the infertility clinic at Tokai University. Inventories included the Hospital Anxiety and Depression Scale (HADS) and our original infertility questionnaire, which is composed of 22 questions to assess attitudes and emotional status in facing the stigma of infertility. After factor analysis, comparison between the HADS and the infertility questionnaire was made with simultaneous multiple regression analyses. Anxiety and depression in childless Japanese women were significantly associated with lack of husband's support and feeling stress. Our findings should prove useful in designing and implementing psychological support programs for infertile Japanese women. Psychological interventions to relieve or diminish these conditions might have significant therapeutic benefits for women attending infertility clinics in Japan.
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http://dx.doi.org/10.1016/j.genhosppsych.2004.05.002DOI Listing
February 2005