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1.
Reprod Med Biol ; 21(1): e12451, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386365

RESUMO

Purpose: Ovarian tissue cryopreservation and its auto-transplantation is promising technique in fertility preservation. Longevity of grafted tissue is limited though mechanism of follicle reduction is not fully understood. We evaluated histological alteration of vitrified-thawed ovarian tissue that grafted to nude mice. Materials and Methods: Human ovarian tissue was cryopreserved by vitrification. After thawing, they were grafted to mesentery of nude mice. Twelve weeks after transplantation, the implants were removed and histologically examined. The presence of follicles, the degree of fibrosis, and TUNEL staining in surrounding cortex were evaluated. The stromal expressions of alpha-smooth muscle actin (aSMA) were determined. Results: Normal ovarian cortex was decreased, and fibrotic area were significantly increased after grafting. The distributions of developmental stage of follicles shifted toward activation of follicular growth. Stromal TUNEL staining was increased in frozen/thawed tissue. The expression of aSMA were found in perifollicular stroma of growing follicles, which were decreased in grafted tissue associated with reduction of cortical stroma. Conclusions: Fibrosis, reduced cortical stroma, and activation of dormant follicles were concomitantly observed in grafted ovarian cortex, which may relate to limited longevity. Perifollicular aSMA expression can be regarded as a marker of the competence of cortical stroma that regulate follicular development.

2.
Reprod Med Biol ; 19(4): 425-431, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33071645

RESUMO

PURPOSE: Surgery for endometriomas may cause detrimental effects on ovarian reserve. We evaluated the safety of three-step laparoscopic surgery for endometriomas utilizing dienogest in terms of post-surgical ovarian reserve. METHODS: Twelve women received first look laparoscopy (FLL) with fenestration and drainage. Immediately after the surgery, they took oral dienogest 2 mg for three months; then, they received second look laparoscopy (SLL) with cystectomy. We compared serum AMH levels between women had three-step management with dienogest, and another twelve women had conventional one-step surgery without medications. In women had three-step procedures, the changes in concentration of proinflammatory cytokines and chemokines in peritoneal fluids were evaluated. RESULTS: Serum AMH levels were significantly decreased after three months of dienogest following FLL. AMH levels were also significantly decreased 3-6 months both after SLL and after one-step surgery; however, recovery of serum AMH levels at 9-12 months after surgery was evident in women had three-step surgery comparing to those of one-step surgery. Proinflammatory cytokines and chemokines in peritoneal fluids were downregulated at the time of SLL comparing to those of FLL. CONCLUSIONS: Three-step surgery with dienogest may be a beneficial approach to protect ovarian reserve. Dienogest may exert its effects in part by lowering proinflammatory cytokines and chemokines.

3.
Gynecol Endocrinol ; 34(5): 381-384, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29068264

RESUMO

17α-Hydroxylase deficiency is rare autosomal recessive disorder that manifested by hypertension, hypokalemia, delayed sexual development, primary amenorrhea and infertility. The information regarding infertility care and conception in women with this disorder are extremely limited. We report a 24-year-old Japanese woman with primary amenorrhea who was diagnosed as partial 17α-hydroxylase deficiency caused by homozygous 3 bp deletion in exon 1 of 17α-hydroxylase gene. In vitro fertilization with controlled ovarian stimulation was carried out and all viable embryo were frozen. During ovarian stimulation, serum progesterone levels were markedly elevated, and endometrial growth was impaired. Utilizing frozen-thaw embryo transfer under hormonal replacement (glucocorticoid, estradiol and progesterone), she had successfully given two consecutive live birth. Women with 17α-hydroxylase deficiency with residual ovarian reserve can afford reproductive success by appropriate diagnosis and treatment by assisted reproductive technology.


Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Transferência Embrionária , Fertilização in vitro , Terapia de Reposição Hormonal/métodos , Infertilidade Feminina/tratamento farmacológico , Resultado da Gravidez , Adulto , Estradiol/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Nascido Vivo , Gravidez , Progesterona/uso terapêutico , Resultado do Tratamento , Adulto Jovem
5.
J Hypertens ; 42(4): 694-700, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38088418

RESUMO

OBJECTIVE: This study aimed to identify the factors influencing home blood pressure measurement (HBPM) continuation in community-dwelling older adults. METHODS: A longitudinal analysis used the NOSE study intervention group datasets. The participants were encouraged HBPM with self-monitoring devices provided to them twice in the morning and twice in the evening. Every 7-day interval from the HBPM start date was defined as 1 week, and the number of HBPMs per week was counted. The first week in which the number of HBPMs was zero was defined as the week in which HBPM was discontinued. Participants who did not experienced discontinuation until the end of the observation period were considered complete survivors in the survival time analysis. RESULTS: Data from 437 participants were included in the analysis. Of these, 120 (27.5%) discontinued HBPM. In univariate analysis, factors significantly associated with HBPM discontinuation included exercise habits [hazard ratio per one unit 0.47; 95% confidence interval (CI) 0.31-0.69], social participation (hazard ratio 0.65; 95% CI 0.42-0.99), MoCA-J score (hazard ratio 0.94; 95% CI 0.90-0.98), and frailty (hazard ratio 5.20; 95% CI 2.87-9.43). In multivariate analysis, factors significantly associated with HBPM discontinuation included sex (hazard ratio 0.55; 95% CI 0.32-0.95; ref. = female individuals), smoking history (hazard ratio 1.69; 95% CI 1.02-2.80), exercise habits (hazard ratio 0.51; 95% CI 0.30-0.85), MoCA-J score (hazard ratio 0.93; 95% CI 0.88-0.98), and frailty (hazard ratio 3.31; 95% CI 1.50-7.29). CONCLUSION: Among community-dwelling older adults, female sex, smoking history, lack of exercise, cognitive decline, and frailty were identified as factors influencing HBPM discontinuation.


Assuntos
Fragilidade , Hipertensão , Humanos , Feminino , Idoso , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Fragilidade/complicações , Vida Independente
6.
Geriatr Gerontol Int ; 24 Suppl 1: 320-326, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38267253

RESUMO

AIM: To examine the actual conditions of older patients receiving home medical care after hospitalization over a period of 2 years in Japan. METHODS: The study population included 102 participants, aged ≥65 years, receiving home medical care, who consented to participate in the Osaka Home Care Registry (OHCARE) study in Japan over a period of 2 years. We investigated the actual conditions for returning home after hospitalization. RESULTS: The median age of the 102 participants was 84 years, and 61 (59.8%) were women. In the group that returned home, 42 (55.3%) of the respondents desired to recuperate in a familiar place, as in advanced care planning (ACP). During the 2-year follow-up period, the group that did not return home had significantly more deaths. A multivariate analysis showed the association in the presence of ACP (odds ratio: 4.72, 95% confidence interval: 1.60-13.86) and cardiac disease (odds ratio: 0.25, 95% confidence interval: 0.08-0.76). The lack of ACP in the medical records when the patient was admitted to the hospital may have prevented the return home. CONCLUSION: In older patients who had difficulty returning home after hospitalization, the lack of ACP in home medical care may have been an influencing factor. ACP could help continue with home medical care. Geriatr Gerontol Int 2024; 24: 320-326.


Assuntos
Serviços de Assistência Domiciliar , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Japão , Hospitalização , Hospitais
7.
J Ovarian Res ; 16(1): 52, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36922845

RESUMO

BACKGROUND: Androgen-producing granulosa cell tumor in adolescent girl is rare condition and clinical characteristics are not fully elucidated. CASE PRESENTATION: Seventeen years old girl complained of secondary amenorrhea was referred to our out-patient consultation. Markedly elevated serum testosterone, LH, and AMH levels were noted. Mild hirsutism and clitoromegaly were presented. Transabdominal ultrasonography and MRI revealed cystic mass occupied pelvic cavity probably originated from left ovary. Right ovary showed polycystic appearance. Laparoscopic left ovarian cystectomy was performed. After the surgery, her menstruation resumed along with normalized hormonal parameters, and clinical hyperandrogenism were improved. Since the scarcity of cellular lining of inner cyst wall, definitive pathological diagnosis was difficult. After the consultation with gynecological pathologist, the tumor was diagnosed as sex cord stromal tumor, highly suspicious for adult granulosa cell tumor. Residual left salpingo-oophorectomy was performed by additional laparoscopic surgery. Her serum testosterone and AMH levels were remained low with regular menstrual cycles and no evidence of recurrence. CONCLUSIONS: Androgen-producing cystic granulosa cell tumor is rare gynecological disorders, which need both gynecologic oncological and endocrinological approach. Its clinical manifestations may bring some clues to the pathogenesis of ovulatory dysfunctions, such as polycystic ovary syndrome.


Assuntos
Tumor de Células da Granulosa , Neoplasias Ovarianas , Síndrome do Ovário Policístico , Adolescente , Feminino , Humanos , Androgênios , Tumor de Células da Granulosa/diagnóstico , Tumor de Células da Granulosa/cirurgia , Tumor de Células da Granulosa/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/cirurgia , Síndrome do Ovário Policístico/complicações , Testosterona
8.
Immunology ; 132(2): 165-73, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20875078

RESUMO

Dendritic cells (DCs) are initiators of innate immunity and acquired immunity as cells linking these two bio-defence systems through the production of cytokines such as interferon-α (IFN-α) and interleukin-12 (IL-12). Nucleic acids such as DNA from damaged cells or pathogens are important activators not only for anti-microbial innate immune responses but also in the pathogenesis of IFN-related autoimmune diseases. Plasmacytoid DCs are regarded as the main effectors for the DNA-mediated innate immunity by possessing DNA-sensing toll-like receptor 9 (TLR9). We here found that double-stranded DNA (dsDNA) complexed with lipotransfectants triggered activation of human monocyte-derived DCs (moDCs), leading to the preferential production of IFN-α but not IL-12. This indicates that myeloid DCs also function as supportive effectors against the invasion of pathogenic microbes through the DNA-mediated activation in innate immunity. The dsDNA with lipotransfectants can be taken up by moDCs without co-localization of endosomal LAMP1 staining, and the dsDNA-mediated IFN-α production was not impaired by chloroquine. These findings indicate that moDC activation by dsDNA does not involve the endosomal TLR pathway. In contrast, single-stranded RNA (ssRNA) stimulated moDCs to secrete IL-12 but not IFN-α. This process was inhibited by chloroquine, suggesting an involvement of the TLR pathway in ssRNA-mediated moDC activation. As might be inferred from our findings, myeloid DCs may function as a traffic control between innate immunity via IFN-α production and acquired immunity via IL-12 production, depending on the type of nucleic acids. Our results provide a new insight into the biological action of myeloid DCs underlying the DNA-mediated activation of protective or pathogenic immunity.


Assuntos
DNA/imunologia , Células Dendríticas/imunologia , Interferon-alfa/metabolismo , Interleucina-12/metabolismo , Monócitos/imunologia , RNA/imunologia , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Humanos , Imunidade Inata , Interferon-alfa/imunologia , Interleucina-12/imunologia , Monócitos/citologia , Monócitos/metabolismo , Receptor Toll-Like 9/metabolismo
9.
Sci Rep ; 11(1): 2665, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514775

RESUMO

Many experiments have analyzed the effect of the space environment on various organisms. However, except for the group-rearing of mice in space, there has been little information on the behavior of organisms in response to gravity changes. In this study, we developed a simple Active Inactive Separation (AIS) method to extract activity and inactivity in videos obtained from the habitat cage unit of a space experiment. This method yields an activity ratio as a ratio of 'activity' within the whole. Adaptation to different gravitational conditions from 1g to hypergravity (HG) and from microgravity (MG) to artificial 1g (AG) was analyzed based on the amount of activity to calculate the activity ratio and the active interval. The result for the activity ratios for the ground control experiment using AIS were close to previous studies, so the effectiveness of this method was indicated. In the case of changes in gravity from 1g to HG, the ratio was low at the start of centrifugation, recovered sharply in the first week, and entered a stable period in another week. The trend in the AG and HG was the same; adapting to different gravity environments takes time.


Assuntos
Adaptação Fisiológica , Comportamento Animal , Hipergravidade , Ausência de Peso , Animais , Masculino , Camundongos
10.
Exp Anim ; 70(2): 236-244, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33487610

RESUMO

Clarification of the criteria for managing animal health is essential to increase the reliability of experiments and ensure transparency in animal welfare. For experiments performed in space, there is no consensus on how to care for animals owing to technical issues, launch mass limitation, and human resources. Some biological processes in mammals, such as musculoskeletal or immune processes, are altered in the space environment, and mice in space can be used to simulate morbid states, such as senescence acceleration. Thus, there is a need to establish a novel evaluation method and evaluation criteria to monitor animal health. Here, we report a novel method to evaluate the health of mice in space through a video downlink in a series of space experiments using the Multiple Artificial-gravity Research System (MARS). This method was found to be more useful in evaluating animal health in space than observations and body weight changes of the same live mice following their return to Earth. We also developed criteria to evaluate health status via a video downlink. These criteria, with "Fur condition" and "Respiratory" as key items, provided information on the daily changes in the health status of mice and helped to identify malfunctions at an early stage. Our method and criteria led to the success of our missions, and they will help establish appropriate rules for space experiments in the future.


Assuntos
Medicina Aeroespacial/métodos , Nível de Saúde , Camundongos , Voo Espacial , Animais , Reprodutibilidade dos Testes
11.
Clin Immunol ; 136(2): 205-16, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20471323

RESUMO

Although Bacillus Calmette-Guérin (BCG) has historically emerged as a potent adjuvant in cancer immunization through dendritic cell (DC) activation, the efficacy of its antitumor effect has been limited. Therefore, the strategy of adjuvant therapy using BCG needs to be improved by adding enhancers. Here we found that thymic stromal lymphopoietin (TSLP) acts as an enhancer for the BCG-mediated antitumor effect. While BCG-stimulated DCs induced CD8(+) T cell production of IFN-gamma without strong cell expansion, TSLP-stimulated DCs induced robust CD8(+) T cell expansion without high quantities of IFN-gamma production. Notably, DCs stimulated with both BCG and TSLP induced robust expansion of CD8(+) T cells that produced a large amount of IFN-gamma with a potent cytolytic activity related to granzyme B expression. Our data suggest that TSLP is a good adjuvant to enhance the BCG-mediated cytotoxic T cell effect through DC activation, and provide a functional basis for a novel strategy for antitumor immune-based therapy.


Assuntos
Adjuvantes Imunológicos/farmacologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Citocinas/farmacologia , Células Dendríticas/efeitos dos fármacos , Mycobacterium bovis/imunologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Adjuvantes Imunológicos/metabolismo , Adulto , Ligante de CD40/farmacologia , Linfócitos T CD8-Positivos/fisiologia , Citocinas/metabolismo , Células Dendríticas/fisiologia , Regulação da Expressão Gênica , Humanos , Neutrófilos/imunologia , Receptores de Citocinas/metabolismo , Receptores de Interleucina-7/metabolismo , Linfócitos T Citotóxicos/fisiologia , Linfopoietina do Estroma do Timo
12.
Mol Biol Cell ; 18(5): 1701-9, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17332504

RESUMO

The tumor suppressor p53 is a key transcriptional factor regulating the induction of cellular senescence by oncogenic signals. The activity of p53 is regulated by recruitment into promyelocytic leukemia (PML)-nuclear bodies (NBs) as well as by stabilization through posttranslational modifications such as phosphorylation and acetylation. Here we found that MORC3 (microrchidia3)-ATPase activated p53 and induced cellular senescence in normal human and mouse fibroblasts but not p53-/- fibroblasts. Conversely, genotoxic stress-induced phosphorylation and stabilization of p53 but barely increased its transcriptional activity in Morc3-/- fibroblasts. MORC3 localized on PML-NBs in presence of PML and mediated recruitment of p53 and CREB-binding protein (CBP) into PML-NBs. In contrast, expression of ATPase activity-deficient mutant MORC3-E35A or siRNA repression of MORC3 impaired the localization of p53 and Sp100 but not CBP on PML-NBs. These results suggest that MORC3 regulates p53 activity and localization into PML-NBs. We identified a new molecular mechanism that regulates the activity of nuclear proteins by localization to a nuclear subdomain.


Assuntos
Proteínas Nucleares/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Antígenos Nucleares/metabolismo , Autoantígenos/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , Senescência Celular , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Doxorrubicina/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Genes p53 , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transfecção , Proteína Supressora de Tumor p53/deficiência , Proteína Supressora de Tumor p53/genética
13.
Front Surg ; 7: 600202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33263001

RESUMO

Background: As its name indicates, anti-Müllerian hormone (AMH) is primarily found as an inhibitor of the Müllerian duct in male fetus. On the other hand, AMH may act as a mediator of Müllerian duct-derived female tissue, such as endometrium in normal and pathological conditions. However, the role of AMH in the functional regulations of endometriosis is not well understood. It can be hypothesized that AMH in peritoneal fluids may affect the activity of peritoneal endometriosis. In this study, we investigated the levels of AMH in peritoneal fluids (PF) in women with and without endometriosis. Methods: PF were collected during laparoscopy from 90 women diagnosed as having advanced endometriosis (rASRM stage III, n = 30; stage IV, n = 60), and 32 women without endometriosis were served as control. Paired serum samples were also collected before the surgery. AMH in PF and serum were measured by ELISA. Individual clinical information was collected. AMH levels were compared according to the presence of endometriosis. The expression of AMHR2 in peritoneal endometriotic lesions obtained during laparoscopy was examined by immunohistochemistry. Results: AMH levels in PF were positively and significantly correlated with serum AMH levels in both women with and without endometriosis (R 2 = 0.17, P < 0.0001; R 2 = 0.30, P = 0.001, respectively). Serum AMH levels were inversely and significantly correlated with age in women with endometriosis (R 2 = 0.092, P = 0.004) and in control women without statistical significance (R 2 = 0.078, P = 0.12). AMH levels in PF were also inversely but not significantly correlated with age in women with and without endometriosis (R 2 = 0.029, P = 0.11 and R 2 = 0.027, P = 0.37, respectively). Mean age and serum AMH levels were not significantly different between two groups. On the other hand, AMH levels in PF were significantly lower in women with endometriosis compared to those of control women [2.15 ± 2.13 (mean ± SD) vs. 4.40 ± 4.77 ng/mL, P = 0.0001]. AMHR2 are localized at glandular epithelium and stromal cells in the ectopic endometrium of peritoneal endometriosis. Conclusions: Women with endometriosis may present lower PF AMH levels even if they retain serum levels similar to women without disease. As peritoneal endometriosis expresses a specific receptor for AMH, lower AMH levels in PF of women with advanced endometriosis may be involved in the pathophysiology of peritoneal endometriosis.

14.
J Appl Toxicol ; 29(4): 356-63, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19224547

RESUMO

To evaluate new drugs' potential for hepatosteatosis, we developed a cell-based assay using a fluorescent fatty acid analog: BODIPY558/568 C12. Rat primary hepatocytes were exposed to positive reference compounds [cyclosporine A (CsA), clofibrate (CFR), tetracycline (TC), valproic acid (VPA), carbon tetrachloride (CCl4), tamoxifen (TMX)] in the presence of BODIPY558/568 C12. The formation of fluorscecent particles or lipid droplets in the cytoplasm was confirmed by confocal laser scanning microscopy and electron microscopy respectively. The accumulation of BODIPY558/568 C12 was measured by fluorometry and high content imaging method. All positive reference compounds increased fluorescent particles in number and fluorescence intensity. High content imaging was more sensitive and selective method than fluorometry to detect fluorescent particles. Gene expression analysis of the hepatocytes showed two patterns: genes related to lipid metabolism/synthesis were down-regulated by oxidative stress inducing compounds: CsA, TC and TMX, and up-regulated by peroxisome proliferator-activated receptor-alpha agonists: CFR and VPA. From these findings, we concluded that the cell-based assay developed in this study is an appropriate method to predict drugs' potential for hepatosteatosis, and gene expression analysis is useful to profile the mechanism of the hepatosteatosis.


Assuntos
Compostos de Boro/toxicidade , Fígado Gorduroso/induzido quimicamente , Corantes Fluorescentes , Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Lipídeos/toxicidade , Animais , Células Cultivadas , Fígado Gorduroso/patologia , Corantes Fluorescentes/química , Fluorometria , Processamento de Imagem Assistida por Computador , Lipídeos/química , Masculino , Microscopia Confocal , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley
15.
Cancers (Basel) ; 11(2)2019 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-30813491

RESUMO

Neoantigens derived from tumor-specific genetic mutations might be suitable targets for cancer immunotherapy because of their high immunogenicity. In the current study, we evaluated the immunogenicity of 10 driver mutations that are frequently expressed in various cancers using peripheral blood mononuclear cells from healthy donors (n = 25). Of the 10 synthetic peptides (27-mer) derived from these mutations, the six peptides from KRAS-G12D, KRAS-G12R, KRAS-G13D, NRAS-Q61R, PIK3CA-H1047R, and C-Kit-D816V induced T cell responses, suggesting that frequent driver mutations are not always less immunogenic. In particular, immune responses to PIK3CA-H1047R, C-Kit-D816V, KRAS-G13D, and NRAS-Q61R were observed in more than 10% of the donors. All six peptides induced human leukocyte antigen (HLA) class II-restricted CD4⁺ T cell responses; notably, PIK3CA-H1047R contained at least two different CD4⁺ T cell epitopes restricted to different HLA class II alleles. In addition, PIK3CA-H1047R and C-Kit-D816V induced antigen-specific CD8⁺ T cells as well, indicating that they might contain both HLA class I- and class II-restricted epitopes. Since the identified neoantigens might be shared by patients with various types of cancers and are not easily lost due to immune escape, they have the potential to be promising off-the-shelf cancer immunotherapy targets in patients with the corresponding mutations.

16.
Clin Chim Acta ; 495: 545-551, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158356

RESUMO

BACKGROUND: Autoimmune reactions and subsequent inflammation may underlie spermatogenic dysfunction and endometriosis-related infertility. The aim of this study is to identify disease-specific antigens in immune complexes (ICs) in seminal plasma (SP) and in follicular fluid (FF). METHODS: Immune complexome analysis, in which nano-liquid chromatography-tandem mass spectrometry is employed to comprehensively identify antigens incorporated into ICs in biological fluids, was performed for specimens collected from infertile couples undergoing assisted reproduction. Forty-two male patients consisting of subjects with oligozoospermia (n = 6), asthenozoospermia (n = 8), and normal semen analysis (n = 28). Fifty-eight female patients consisting of subjects with ovarian endometriosis (n = 10) and control women without disease (n = 48). RESULTS: Four disease-specific antigens were identified in subjects with oligozoospermia, while five disease-specific antigens were detected in subjects with asthenozoospermia, some of which are involved in sprematogenesis. Eight antigens were detected only in subjects with endometriosis. CONCLUSION: Functional characteristics of disease-specific antigens were found to correspond to the pathogenesis of male and female infertility. The formation of ICs may contribute to spermatogenic dysfunction and endometriosis-related infertility via loss of function of the related proteins. Immune complexome analysis is expected to be a valuable tool for the investigation of novel diagnostic methods and treatment strategies for infertility.


Assuntos
Antígenos/imunologia , Líquido Folicular/imunologia , Infertilidade Feminina/imunologia , Infertilidade Masculina/imunologia , Sêmen/imunologia , Adulto , Feminino , Humanos , Masculino
17.
J Nutr Sci Vitaminol (Tokyo) ; 54(5): 409-15, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19001774

RESUMO

Segment membranes from 4 citrus species selected from 4 sections were treated with water to obtain polysaccharides containing pectin. The extracts, which inhibited pancreatic lipase activity in a concentration-dependent manner, were divided into high molecular weight fractions [molecular weight (M.W.) >300,000], which inhibited the activity strongly, and low molecular weight fractions (M.W. <300,000), which did not show such strong inhibition. The high molecular weight fractions were composed mainly of a characteristic sugar of pectin, namely, galacturonic acid. A galacturonic acid-rich fraction purified by anion exchange chromatography from a water extract also strongly inhibited the activity. The inhibitory activity of the high molecular weight fraction was much stronger than that of commercial citrus pectin. The results suggest that pectin from segment membranes of citrus fruits might be useful as a functional food, especially as a fat-reducing material.


Assuntos
Carboidratos/farmacologia , Citrus , Ácidos Hexurônicos/farmacologia , Monoacilglicerol Lipases/metabolismo , Pectinas/química , Extratos Vegetais/farmacologia , Animais , Carboidratos/isolamento & purificação , Citrus/química , Frutas , Ácidos Hexurônicos/isolamento & purificação , Membranas , Peso Molecular , Monoacilglicerol Lipases/antagonistas & inibidores , Pâncreas/enzimologia , Estruturas Vegetais , Suínos
18.
Mol Ther Methods Clin Dev ; 10: 327-340, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30191159

RESUMO

No treatment is available to address the neurological need and reversibility of MPS II. We developed a scAAV9-hIDS vector to deliver the human iduronate-2-sulfatase gene and test it in mouse model. We treated MPS II mice at different disease stages with an intravenous injection of scAAV9-mCMV-hIDS at different doses. The treatments led to rapid and persistent restoration of IDS activity and the reduction of glycosaminoglycans (GAG) throughout the CNS and somatic tissues in all cohorts. Importantly, the vector treatment at up to age 6 months improved behavior performance in the Morris water maze and normalized the survival. Notably, vector treatment at age 9 months also resulted in persistent rIDS expression and GAG clearance in MPS II mice, and the majority of these animals survived within the normal range of lifespan. Notably, the vector delivery did not result in any observable adverse events or detectable systemic toxicity in any treated animal groups. We believe that we have developed a safe and effective gene therapy for treating MPS II, which led to recent IND approval for a phase 1/2 clinical trial in MPS II patients, further supporting the extended potential of the demonstrated systemic rAAV9 gene delivery platform for broad disease targets.

19.
Int J Rheum Dis ; 21(6): 1287-1292, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29879312

RESUMO

OBJECTIVE: To determine the effect of leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a) on ovarian function preservation in systemic lupus erythematosus (SLE) patients treated with cyclophosphamide (CYC) in clinical practice. METHODS: We enrolled 30 premenopausal female SLE patients who fulfilled the 1997 American College of Rheumatology revised criteria and were treated with intravenous CYC (IVCY) in 2008-2017. We used Kaplan-Meier survival estimates to compare the GnRH-a-treated patients and those not treated with GnRH-a as controls. We performed Cox regression analyses to identify factors associated with premature ovarian failure (POF), incidences of cardiovascular events, strokes and osteoporosis after IVCY therapy. RESULTS: After a mean follow-up of 41 months, POF developed in one of the 16 GnRH-a-treated patients (6%) versus seven of the 14 controls (50%). Significantly improved cumulative ovarian protection over time was observed in the GnRH-a-treated group (P = 0.030). The hazard model analysis showed that treatment with GnRH-a during IVCY therapy is an independent factor associated with POF after IVCY therapy (adjusted hazards ratio = 0.12, 95% CI 0.01-0.67, P = 0.013) but not incidences of cardiovascular events, strokes or osteoporosis. CONCLUSION: The combined use of GnRH-a with IVCY therapy was associated with a significant reduction of POF among premenopausal women with SLE, suggesting that the addition of GnRH-a can be a strategy to prevent POF among premenopausal women with SLE after IVCY therapy.


Assuntos
Ciclofosfamida/efeitos adversos , Fármacos para a Fertilidade Feminina/uso terapêutico , Preservação da Fertilidade/métodos , Imunossupressores/efeitos adversos , Infertilidade Feminina/prevenção & controle , Leuprolida/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ovário/efeitos dos fármacos , Insuficiência Ovariana Primária/prevenção & controle , Administração Intravenosa , Adulto , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Ciclofosfamida/administração & dosagem , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Preservação da Fertilidade/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Incidência , Infertilidade Feminina/induzido quimicamente , Infertilidade Feminina/epidemiologia , Infertilidade Feminina/fisiopatologia , Estimativa de Kaplan-Meier , Leuprolida/efeitos adversos , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Análise Multivariada , Osteoporose/epidemiologia , Ovário/fisiopatologia , Pré-Menopausa , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/epidemiologia , Insuficiência Ovariana Primária/fisiopatologia , Modelos de Riscos Proporcionais , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Intern Med ; 56(16): 2089-2095, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28781325

RESUMO

Objective To analyze the clinical characteristics and endoscopic features of patients with lanthanum deposition in the stomach. Patients We retrospectively reviewed seven patients with lanthanum deposition in the stomach who were diagnosed at Okayama Saiseikai General Hospital. We investigated the patient sex, age at diagnosis, medical and medication histories, gastrointestinal symptoms, complications, presence or absence of gastric atrophy, and outcome. We also investigated any changes in the endoscopic features if previous endoscopic images were available. Results Seven patients (six males and one female) had lanthanum deposition. The median age was 65 years (range, 50-79 years). All patients had been undergoing dialysis (continuous ambulatory peritoneal dialysis in one patient, hemodialysis in six patients). The dialysis period ranged from 16 to 73 months (median, 52 months). The patients had all been taking lanthanum carbonate for a period ranging from 5 to 45 months (median, 27 months). Gastric atrophy was noted in 6 patients (85.7%). One patient had difficulty swallowing, and 1 other patient had appetite loss. The other 5 patients were asymptomatic. Endoscopic features included annular whitish mucosa (n = 4), diffuse whitish mucosa (n = 3), and whitish spots (n = 2). Five patients underwent multiple esophagogastroduodenoscopy. The endoscopic features were unchanged in 2 patients, whereas the whitish mucosa became apparent and spread during the course in 3 patients. Conclusion We identified 7 patients with lanthanum deposition in the stomach. All patients showed whitish lesions macroscopically. Although the pathogenicity of gastric lanthanum deposition is uncertain, lanthanum-related lesions in the stomach progressed during continuous lanthanum phosphate intake in several patients.


Assuntos
Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Lantânio/uso terapêutico , Diálise Renal/efeitos adversos , Estômago/química , Idoso , Feminino , Humanos , Hiperfosfatemia/diagnóstico por imagem , Hiperfosfatemia/patologia , Japão , Lantânio/análise , Masculino , Pessoa de Meia-Idade , Fosfatos/análise , Estudos Retrospectivos
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