RESUMEN

AIM: Thrombocytopenia is widely recognized as a simple surrogate marker of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Thrombocytopenia of NAFLD has not been compared with that of hepatitis C virus-related chronic liver disease (CLD-C). Here, we examined whether there is any difference in the platelet counts between patients with NAFLD and CLD-C and investigated the underlying mechanisms. METHODS: A total of 760 biopsy-confirmed NAFLD and 1171 CLD-C patients were enrolled. After stratification according to the liver fibrosis stage, platelet counts between NAFLD and CLD-C patients were compared. The platelet count, spleen size, serum albumin level, serum thrombopoietin level, and immature platelet fraction (IPF) value were also compared after covariate adjustment using propensity score (PS) matching. RESULTS: The median platelet counts (×104 /µL) of NAFLD and CLD-C patients were 20.2 and 18.7 (p = 2.4 × 10-5 ) in F1; 20.0 and 14.5 (p = 2.1 × 10-12 ) in F2; 16.9 and 12.3 (p = 8.1 × 10-10 ) in F3; and 11.1 and 8.1 (p = 0.02) in F4, respectively. In the F3 group, NAFLD patients had a significantly higher platelet count and significantly smaller spleen volume than CLD-C patients. Although the serum thrombopoietin levels were comparable between NAFLD and CLD-C patients, the IPF value of NAFLD patients was significantly higher than that of CLD-C patients. CONCLUSIONS: NAFLD patients had a significantly higher platelet count than CLD-C patients following stratification according to the liver fibrosis stage. The milder hypersplenism and higher platelet production in NAFLD than CLD-C may have contributed to this difference.

RESUMEN

A 58-year-old woman presented to our hospital with complaints of dysphagia. Esophagogastroduodenoscopy showed an esophagogastric junction tumor with multiple duodenal intramural metastases, and computed tomography showed peritoneal metastasis. In the middle of her fourth cycle of chemotherapy, she displayed symptoms of a left-sided multi-cranial nerve palsy. She was diagnosed with Garcin syndrome caused by meningeal carcinomatosis from gastric cancer based on the results of gadolinium-enhanced brain magnetic resonance imaging and cytology of the cerebrospinal fluid. It is important not to overlook meningeal irritation symptoms or paralysis of cranial nerves and to consider the possibility of Garcin syndrome caused by meningeal carcinomatosis.

Asunto(s)

Enfermedades de los Nervios Craneales , Carcinomatosis Meníngea , Neoplasias Meníngeas , Neoplasias Gástricas , Femenino , Humanos , Imagen por Resonancia Magnética , Carcinomatosis Meníngea/complicaciones , Carcinomatosis Meníngea/diagnóstico , Persona de Mediana Edad , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/diagnóstico , Tomografía Computarizada por Rayos X

RESUMEN

AIM: To study the outcome of pregnancies with severely increased nuchal translucency (NT) thickness at the 11-13-week scan. METHODS: This study included 162 singleton pregnancies whose fetuses had increased NT thickness ≥ 5.5 mm between September 2013 and August 2018. The cases were divided into two groups: NT ≥ 6.5 mm (n = 112) (group A); and 6.5 mm > NT ≥ 5.5 mm (n = 50) (group B). Fetal (amniotic fluid) or placental (chorionic villous) chromosome analyses were conducted. Subsequent ultrasound findings, pregnancy outcome and structural defects in the neonates were recorded and analyzed. RESULTS: Abnormal karyotype was found in 71% (60/84) (group A) and 57% (21/37) (group B) of the cases respectively. In group A, 15 cases out of 24 with normal karyotype were born. Among these 15 cases, one case died soon after birth and 5 cases had associated abnormalities. In group B, 13 cases out of 18 with normal karyotype or negative noninvasive prenatal testing results and 1 case out of 2 cases with 47,XXY were born. All of them survived with no major anomaly. CONCLUSION: Incidence of chromosomal aberrations was high in the cases with severely increased NT thickness. But favorable outcome could be expected if the fetus had no chromosomal abnormality and no abnormal findings were found in second trimester ultrasound scan especially in a fetus with increased NT < 6.5 mm.

Asunto(s)

Medida de Translucencia Nucal , Ultrasonografía Prenatal , Aberraciones Cromosómicas , Femenino , Feto/diagnóstico por imagen , Humanos , Recién Nacido , Placenta , Embarazo , Primer Trimestre del Embarazo

RESUMEN

Since the introduction of direct-acting antiviral (DAA)-based combination therapies in September 2014 for patients with chronic hepatitis-C (CH-C), numerous patients have been diagnosed with hepatitis-C virus (HCV)-associated hepatocellular carcinomas (HCCs) during the screening performed prior to DAA therapy. The present study was conducted on the antiviral therapy for CH-C in two phases:i) the interferon (IFN) phase between January 2011 and August 2014 and ii) the DAA phase between September 2014 and September 2016. During the DAA phase, HCCs were detected in eight patients who were referred to our hospital for anti-HCV therapy. In contrast, HCCs were detected in only two patients during the IFN phase. The number of patients with newly detected HCC in the DAA phase (20.5%) who were referred for the anti-HCV therapy was significantly higher than that in the IFN phase (1.7%). Owing to the high efficacy and safety of the DAA therapy, the number of patients referred to our hospital for anti-HCV therapy increased from 40.5 persons/year in the IFN phase to 80.3 persons/year in the DAA phase. The average ages of patients in the DAA and IFN phases were 68 and 61 years, respectively. The increase in the number of patients with newly detected HCC referred for the anti-HCV therapy in the DAA phase could be attributed to the increase in the number of referred patients for anti-HCV therapy and the aging of these patients in the DAA phase. All the eight patients with newly detected HCC who were referred for anti-HCV therapy in the DAA phase received curative treatments. The median age, rate of liver cirrhosis, and median tumor size of the patients were 69 years, 13%, and 16mm. Therefore, the findings of this study indicate that DAA therapies not only eradicate HCV infection but also contribute to the early diagnosis of HCC by encouraging the HCV-infected patients to visit hospitals and by promoting active network between hepatologists and family physicians.

Asunto(s)

Antivirales/uso terapéutico , Carcinoma Hepatocelular/virología , Quimioterapia Combinada/métodos , Hepacivirus , Hepatitis C Crónica , Hepatitis C/tratamiento farmacológico , Neoplasias Hepáticas/virología , Anciano , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/terapia , Estudios Retrospectivos

RESUMEN

An 85-year-old woman underwent endoscopic retrograde cholangiopancreatography (ERCP) for obstructive jaundice. Selective bile duct cannulation was unsuccessful because of periampullary diverticula (PAD). A pancreatic spontaneous dislodgement stent (PSDS) (5F diameter, 3 cm, straight type) was inserted to prevent post-ERCP pancreatitis. Three days after ERCP, she complained of abdominal pain, and computed tomography revealed retroperitoneal perforation because of PSDS migration to the PAD. If the papillary orifice is observed at the diverticular rim or in the diverticula, a pigtailed PSDS on the duodenal side or flanged stent on the pancreatic ductal side should be inserted in order to prevent this rare adverse event.

Asunto(s)

Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Divertículo/cirugía , Ictericia Obstructiva/diagnóstico por imagen , Ictericia Obstructiva/cirugía , Peritoneo/lesiones , Peritoneo/cirugía , Stents/efectos adversos , Anciano de 80 o más Años , Femenino , Humanos , Peritoneo/diagnóstico por imagen , Resultado del Tratamiento

RESUMEN

OBJECTIVE: To investigate the relationship between the severities of symptom dimensions in obsessive-compulsive disorder (OCD) and white matter alterations. METHODS: We applied tract-based spatial statistics for diffusion tensor imaging (DTI) acquired by 3T magnetic resonance imaging. First, we compared fractional anisotropy (FA) between 20 OCD patients and 30 healthy controls (HC). Then, applying whole brain analysis, we searched the brain regions showing correlations between the severities of symptom dimensions assessed by Obsessive-Compulsive Inventory-Revised and FA in all participants. Finally, we calculated the correlations between the six symptom dimensions and multiple DTI measures [FA, axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD)] in a region-of-interest (ROI) analysis and explored the differences between OCD patients and HC. RESULTS: There were no between-group differences in FA or brain region correlations between the severities of symptom dimensions and FA in any of the participants. ROI analysis revealed negative correlations between checking severity and left inferior frontal gyrus white matter and left middle temporal gyrus white matter and a positive correlation between ordering severity and right precuneus in FA in OCD compared with HC. We also found negative correlations between ordering severity and right precuneus in RD, between obsessing severities and right supramarginal gyrus in AD and MD, and between hoarding severity and right insular gyrus in AD. CONCLUSION: Our study supported the hypothesis that the severities of respective symptom dimensions are associated with different patterns of white matter alterations.

Asunto(s)

Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Trastorno Obsesivo Compulsivo/diagnóstico , Corteza Prefrontal/diagnóstico por imagen , Sustancia Blanca/patología , Adolescente , Adulto , Anisotropía , Encéfalo/patología , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/patología , Corteza Prefrontal/patología , Índice de Severidad de la Enfermedad , Adulto Joven

RESUMEN

AIM: The aims of this study were to determine whether the serum levels of precursor brain-derived neurotrophic factor (proBDNF), mature BDNF (mBDNF), and matrix metalloproteinase-9 (MMP-9) are altered in patients with eating disorders (ED), including anorexia nervosa (AN) and bulimia nervosa (BN), and to explore whether those levels are associated with decision-making abilities. METHODS: Nineteen women with AN, 28 women with BN, and 22 age-matched healthy control women (HC) were enrolled in the current study. All participants had their decision-making abilities assessed using the Iowa Gambling Task (IGT). Their eating-related pathophysiology and depressive/anxiety symptoms were also evaluated. RESULTS: The MMP-9 level in AN was significantly lower than that in either BN or HC, but the serum levels of proBDNF and mBDNF did not differ among the three groups. Investigation of the serum levels of proBDNF and MMP-9 in patients with ED and controls revealed a significant correlation between them. In the BN, there were positive correlations between mBDNF level and IGT performance and also between MMP-9 level and IGT performance, but these correlations did not occur in AN. The MMP-9 level was positively associated with the Symptom Scale, one of the subscales of the Bulimic Investigatory Test, Edinburgh, only in AN. CONCLUSION: These results suggest that the serum level of MMP-9 plays a role in the pathophysiology of AN, and both the serum levels of mBDNF and MMP-9 may be associated with decision-making abilities in patients with BN.

Asunto(s)

Toma de Decisiones/fisiología , Trastornos de Alimentación y de la Ingestión de Alimentos/sangre , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Metaloproteinasa 9 de la Matriz/sangre , Adolescente , Adulto , Factor Neurotrófico Derivado del Encéfalo/sangre , Femenino , Humanos , Pruebas Neuropsicológicas , Precursores de Proteínas/sangre , Adulto Joven

RESUMEN

Obsessive-compulsive disorder (OCD) is known as a clinically heterogeneous disorder characterized by symptom dimensions. Although substantial numbers of neuroimaging studies have demonstrated the presence of brain abnormalities in OCD, their results are controversial. The clinical heterogeneity of OCD could be one of the reasons for this. It has been hypothesized that certain brain regions contributed to the respective obsessive-compulsive dimensions. In this study, we investigated the relationship between symptom dimensions of OCD and brain morphology using voxel-based morphometry to discover the specific regions showing alterations in the respective dimensions of obsessive-compulsive symptoms. The severities of symptom dimensions in thirty-three patients with OCD were assessed using Obsessive-Compulsive Inventory-Revised (OCI-R). Along with numerous MRI studies pointing out brain abnormalities in autistic spectrum disorder (ASD) patients, a previous study reported a positive correlation between ASD traits and regional gray matter volume in the left dorsolateral prefrontal cortex and amygdala in OCD patients. We investigated the correlation between gray and white matter volumes at the whole brain level and each symptom dimension score, treating all remaining dimension scores, age, gender, and ASD traits as confounding covariates. Our results revealed a significant negative correlation between washing symptom dimension score and gray matter volume in the right thalamus and a significant negative correlation between hoarding symptom dimension score and white matter volume in the left angular gyrus. Although our result was preliminary, our findings indicated that there were specific brain regions in gray and white matter that contributed to symptom dimensions in OCD patients.

Asunto(s)

Encéfalo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/psicología , Adolescente , Adulto , Encéfalo/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/patología , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Adulto Joven

RESUMEN

OBJECTIVES: Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric disorders, with some speculating that a reason for difficulty in its treatment might be its coexistence with autism spectrum. We investigated the tendency for autistic spectrum disorders (ASD) in patients with OCD from a neuroimaging point of view using voxel-based morphometry. METHODS: We acquired T1-weighted images from 20 patients with OCD and 30 healthy controls and investigated the difference in regional volume between the groups as well as the correlation between Autism-Spectrum Quotient (AQ) scores and regional cerebral volumes of patients with OCD. RESULTS: Volumes in the bilateral middle frontal gyri were significantly decreased in patients with OCD compared to controls. Correlational analysis showed significant positive correlations between AQ scores and regional gray matter (GM) volumes in the left dorsolateral prefrontal cortex (DLPFC) and left amygdala. Furthermore, GM volumes of these regions were positively correlated with each other. CONCLUSIONS: The positive correlation of ASD traits in patients with OCD with regional GM volumes in the left DLPFC and amygdala could reflect the heterogeneity of patient symptoms. Our results suggest that differences in GM volume might allow classification of patients with OCD for appropriate therapy based on their particular traits.

Asunto(s)

Trastorno del Espectro Autista/patología , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Trastorno Obsesivo Compulsivo/patología , Adolescente , Adulto , Amígdala del Cerebelo/patología , Cuerpo Estriado/patología , Lóbulo Frontal/patología , Sustancia Gris/patología , Humanos , Persona de Mediana Edad , Tamaño de los Órganos , Corteza Prefrontal/patología , Adulto Joven

RESUMEN

BACKGROUND: Decision-making is reported to be impaired in anorexia nervosa (AN) and bulimia nervosa (BN), but the influence of mood status, pathophysiological eating, and weight concerns on the performance of decision-making ability between AN and BN is still unclear. The aims of this study were to investigate differential impairments in the decision-making process between AN, BN, and healthy controls (HC), and secondly, to explore the role of mood status, such as anxiety, depression, pathological eating, and weight concerns, in decision-making ability. METHODS: Patients suffering from AN (n = 22), BN (n = 36) and age-matched HC (n = 51) were assessed for their decision-making abilities using the Iowa Gambling Task (IGT). Self-reported questionnaires including the Eating Disorder Examination Questionnaire (EDE-Q), the Bulimia Investigatory Test, Edinburgh (BITE), the Eating Disorders Inventory, the Maudsley Obsessive-Compulsive Inventory measuring obsessive-compulsive traits, the Hospital Anxiety and Depression Scale, and the Toronto Alexithymia Scale were used to assess pathological eating concerns and attitude to feelings. RESULTS: Significant differences in IGT performance were observed between BN and HC. Significant negative correlation was found between IGT performance and the BITE symptom subscale in AN. In BN, there was a negative correlation between the EDE-Q weight concerns subscale and IGT performance. It was also found that increased anxiety, depression, and eating/weight concerns predicted poorer decision-making. CONCLUSION: Different patterns of association between pathological eating concerns/behaviors and performances in decision-making ability were found between AN, BN, and HC. Anxiety, depressive mood status, and eating/weight concerns were related to decision-making ability.

RESUMEN

A total of 12 enterohemorrhagic Escherichia coli (EHEC) O157:H7 strains were isolated during a recent outbreak in a nursery school in Ehime Prefecture, Japan. These isolates were considered to be derived from a common strain when analyzed using an IS-printing method and pulsed-field gel electrophoresis. PCR analysis revealed that the isolates harbor stx1, stx2, eae, and hlyA. However, assessment of the production of the Stx proteins revealed that these isolates produced Stx1 but not Stx2. We determined their stx2 variants such as stx2c and found that the size of the PCR product was much larger than the expected size. Sequencing of the entire stx2 gene revealed that a 1310-bp fragment was inserted into the coding region of the Stx2A subunit and that the sequences of the insert were identical to those of IS1203v. According to the sequences around the insertion site, additional amino acid residues should be attached at the C-terminus of the A subunit, which may hamper the Stx2 complex formation. Finally, this study also suggested that such an insertion may lead to the misinterpretation of results when screening EHEC isolates for virulence genes by PCR.

Asunto(s)

Infecciones por Escherichia coli/microbiología , Escherichia coli O157/genética , Técnicas de Inactivación de Genes , Mutagénesis Insercional , Toxina Shiga II/genética , Preescolar , Elementos Transponibles de ADN , Brotes de Enfermedades , Electroforesis en Gel de Campo Pulsado , Infecciones por Escherichia coli/epidemiología , Escherichia coli O157/clasificación , Escherichia coli O157/aislamiento & purificación , Femenino , Humanos , Japón/epidemiología , Masculino , Tipificación Molecular , Análisis de Secuencia de ADN , Toxina Shiga II/metabolismo

RESUMEN

A 74-year-old man was referred to our hospital because of abdominal distension. Upper gastrointestinal endoscopy revealed advanced gastric cancer and early gastric cancer. HER2-positive and AFP-producing gastric cancer with peritonitis carcinomatosa showing no indication for operation was diagnosed by histopathological and radiological examinations. He was treated with trastuzumab, docetaxel, and S-1 combination chemotherapy. At the end of the second course of therapy, the primary lesion was remarkably decreased in size and was associated with a significant decrease in serum AFP level. No serious adverse events occurred except for grade 3-4 leukopenia and neutropenia. We carried out eight courses of chemotherapy. Trastuzumab, docetaxel, and S-1 combination chemotherapy promise to be one of the effective treatments for HER2-positive and AFP-producing gastric cancer that have no indication for radical cure excision.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Docetaxel , Combinación de Medicamentos , Humanos , Masculino , Ácido Oxónico/administración & dosificación , Receptor ErbB-2/análisis , Neoplasias Gástricas/química , Neoplasias Gástricas/metabolismo , Taxoides/administración & dosificación , Tegafur/administración & dosificación , Trastuzumab , alfa-Fetoproteínas/biosíntesis

RESUMEN

PROBLEM ß(2) glycoprotein1 (ß(2) GP1)-dependent antiphospholipid antibodies (aPL) increase the risk for recurrent pregnancy loss. We address whether anti-ß(2) GP1 antibodies can interact with phosphatidylserine (PS)-bearing CD1d on trophoblast cells and induce local inflammation. METHODS CD1d-bearing choriocarcinoma cells were used in flow cytometry and immunoprecipitation experiments. CD1d-mediated cytokine induction was assessed using antibody cross-linking. Cytokine production during co-culture of decidual lymphocytes with CD1d-bearing cells was also examined. RESULTS Trophoblast surface-expressed CD1d forms a complex with PS-bound ß(2) GP1. Anti-ß(2) GP1 mAb cross-linking causes IL12p70 release from CD1d-bearing cells. IL12p70 release from CD1d-bearing trophoblast cells was also induced during co-culture with human decidual lymphocytes. The addition of anti-ß2GP1 mAb to co-cultures resulted in a three-fold increase in IL12p70 secretion. IFNγ secretion from decidual lymphocytes was also induced during co-culture with anti-ß2GP1 mAbs. CONCLUSIONS ß(2) GP1-dependent IL12 release from CD1d-bearing trophoblast in the presence of aPL may link the antiphospholipid syndrome to pregnancy loss via an inflammatory mechanism.

Asunto(s)

Aborto Habitual/inmunología , Anticuerpos Antifosfolípidos/inmunología , Antígenos CD1d/inmunología , Síndrome Antifosfolípido/inmunología , Decidua/inmunología , Linfocitos/inmunología , Trofoblastos/inmunología , beta 2 Glicoproteína I/inmunología , Aborto Habitual/etiología , Aborto Habitual/patología , Anticuerpos Antifosfolípidos/efectos adversos , Anticuerpos Antifosfolípidos/metabolismo , Antígenos CD1d/genética , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/patología , Línea Celular Tumoral , Coriocarcinoma/inmunología , Coriocarcinoma/patología , Técnicas de Cocultivo , Reactivos de Enlaces Cruzados , Decidua/citología , Decidua/efectos de los fármacos , Femenino , Citometría de Flujo , Humanos , Inmunoprecipitación , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Interleucina-12/biosíntesis , Interleucina-12/inmunología , Linfocitos/citología , Linfocitos/efectos de los fármacos , Fosfatidilserinas/inmunología , Fosfatidilserinas/metabolismo , Embarazo , Trofoblastos/citología , Trofoblastos/efectos de los fármacos

RESUMEN

PROBLEM: Lysophosphatidic acid (LPA) is a bioactive lipid mediator and thought to play an important role in pregnancy. Plasma LPA is produced by autotaxin (ATX), and ATX activity in plasma increases during pregnancy paralleled with gestational weeks and decreases to near the non-pregnant level soon after delivery. However, the source of increased ATX during pregnancy is still uncertain. We hypothesized that the source of increased ATX might be placenta. METHOD OF STUDY: We investigated the protein and mRNA expression of ATX in human placenta using immunohistochemistry and RT-PCR, respectively. RESULTS: At all 3 gestational trimesters, immunohistochemical staining for placenta tissues revealed the most marked positive staining of ATX protein in trophoblasts. Real-time PCR revealed that mRNA amounts of ATX in placenta tissues paralleled with gestational weeks, i.e. ATX level in plasma. CONCLUSION: These findings suggest that trophoblasts might produce ATX and its bioactive resultant substance, LPA, paralleled with gestational weeks.

Asunto(s)

Lisofosfolípidos/biosíntesis , Complejos Multienzimáticos/biosíntesis , Fosfodiesterasa I/biosíntesis , Placenta/enzimología , Pirofosfatasas/biosíntesis , Femenino , Humanos , Lisofosfolípidos/sangre , Hidrolasas Diéster Fosfóricas , Placenta/citología , Embarazo , Trimestres del Embarazo/metabolismo , ARN Mensajero/biosíntesis , Trofoblastos/enzimología

RESUMEN

PROBLEM: Among class Ib human leukocyte antigen (HLA) molecules, HLA-E is known to be a major ligand of CD94/NKG2 receptor on natural killer (NK) cells, and to play a pivotal role in recognition of extravillous trophoblasts (EVTs) by maternal immune cells. However, it is scarcely known how HLA-E expression is regulated in EVTs. METHOD OF STUDY: In this study, we investigated whether progesterone, an essential hormone in maintaining pregnancy, regulated HLA-E expression in EVT-like cell line, JEG-3. HLA-E mRNA amount in cultured JEG-3 cells was assessed by real-time PCR and cell-surface HLA-E protein was analyzed by flowcytometry. RESULTS: Real-time PCR showed 3.5-fold increase 1 hour after the addition of 1000 ng/ml progesterone. This response was diminished by the addition of RU486, an antagonist for progesterone receptor. Flowcytometry indicated that 1000 ng/ml progesterone slightly enhanced HLA-E expression on the surface of JEG-3. CONCLUSION: These results suggest that progesterone up-regulates HLA-E expression in JEG-3 cells through the pathway mediated by progesterone receptor. Our findings might give a new insight into immunomodulatory function of progesterone at fetomaternal interface.

Asunto(s)

Regulación de la Expresión Génica , Antígenos HLA/genética , Antígenos de Histocompatibilidad Clase I/genética , Progesterona/fisiología , Receptores de Progesterona/fisiología , Trofoblastos/metabolismo , Línea Celular Tumoral , Coriocarcinoma , Expresión Génica/efectos de los fármacos , Humanos , Mifepristona/farmacología , Progesterona/farmacología , ARN Mensajero/metabolismo , Receptores de Progesterona/efectos de los fármacos , Trofoblastos/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Antígenos HLA-E

RESUMEN

Mucosal epithelia of the human lower reproductive tract (vagina, cervix, and penile urethra) are exposed to sexually transmitted microbes, including Chlamydia trachomatis. The in vivo susceptibility of each tissue type to infection with C. trachomatis is quite distinct. CD1d is expressed on the surface of antigen-presenting cells, including mucosal epithelial cells, and interacts specifically with invariant NKT cells. Invariant NKT cells play a role in both innate and adaptive immune responses to microbes. Here we assessed CD1d expression in normal reproductive tissues by using immunohistochemistry. Immortalized epithelial cell lines from the human lower reproductive tract (vagina, endocervix, and penile urethra) were examined for CD1d expression and for ligand-induced cytokine production induced by CD1d cross-linking. CD1d expression in normal tissue was strong in the vagina but weak in the endocervix and penile urethra. Gamma interferon exposure induced CD1d transcription in all of the cell types studied, with the strongest induction in vaginal cells. Flow cytometry revealed cell surface expression of CD1d in vaginal and penile urethral epithelial cells but not in endocervical cells. Ligation of surface-expressed CD1d by monoclonal antibody cross-linking promoted interleukin-12 (IL-12) and IL-15, but not IL-10, production in vaginal and penile urethral cells. No induction was demonstrated in endocervical cells. CD1d-mediated cytokine production in penile urethral cells was abrogated by C. trachomatis infection. Basal deficiency in CD1d-mediated immune responsiveness may result in susceptibility to sexually transmitted agents. Decreased CD1d-mediated signaling may help C. trachomatis evade detection by innate immune cells.

Asunto(s)

Antígenos CD1/metabolismo , Chlamydia trachomatis/patogenicidad , Citocinas/biosíntesis , Células Epiteliales/inmunología , Genitales/inmunología , Membrana Mucosa/inmunología , Antígenos CD1d , Cuello del Útero/citología , Cuello del Útero/inmunología , Cuello del Útero/microbiología , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Femenino , Genitales/citología , Genitales/microbiología , Humanos , Ligandos , Masculino , Membrana Mucosa/citología , Membrana Mucosa/microbiología , Especificidad de Órganos , Pene/citología , Pene/inmunología , Pene/microbiología , Vagina/citología , Vagina/inmunología , Vagina/microbiología

RESUMEN

CD1d is a specific ligand for the invariant Valpha24Vbeta11-natural killer T (iNKT) cells that play an important role in placental development during early human pregnancy. The localization and regulation of placental CD1d expression remain unclear. Immunohistochemistry of human early gestational placentas revealed CD1d was present in villous and extravillous trophoblast (EVT) but not in syncytiotrophoblast or decidual cells. CD1d immunoreactivity in EVT cells decreased with EVT differentiation. Flow cytometry of primary cultured human trophoblast cells confirmed cell-surface expression of CD1d decreased with time in culture. These changes in CD1d expression occur at the level of transcription. TGF-beta1 secreted from the cultured EVT cells accumulated with time in culture and directly suppressed CD1d expression, as evidenced by monoclonal antibody neutralization of TGF-beta1 effects. Thus, trophoblast differentiation is characterized by TGF-beta1-mediated decreases in trophoblast cell CD1d expression. This effect may support appropriate activation of decidual iNKT cells at the maternal-fetal interface.

Asunto(s)

Antígenos CD1/metabolismo , Diferenciación Celular , Vellosidades Coriónicas/inmunología , Embarazo/inmunología , Trofoblastos/citología , Trofoblastos/inmunología , Antígenos CD1/análisis , Antígenos CD1/genética , Antígenos CD1d , Células Cultivadas , Vellosidades Coriónicas/química , Decidua/inmunología , Regulación hacia Abajo , Femenino , Regulación de la Expresión Génica , Humanos , Células Asesinas Naturales/inmunología , Activación de Linfocitos , Transcripción Genética , Factor de Crecimiento Transformador beta1/metabolismo , Trofoblastos/química

RESUMEN

PROBLEM: To get insight into the basis for the empirical usage of herbal medicines, such as Tokishakuyaku-san (Toki) and Sairei-to (Sai) in the treatment of recurrent abortion and intrauterine growth restriction, we examined whether these medicines modulate the production of granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine working as an important mediator for intercellular communication in the embryonic development, in decidual stromal cells (DSCs). METHOD OF STUDY: Human DSCs were cultured with either Toki or Sai at several different concentrations. The effect on cell proliferation was assessed by WST-8 assay. GM-CSF released into culture medium was analyzed using enzyme-linked immunosorbent assay, and semi-quantitative polymerase chain reaction was carried out to see GM-CSF mRNA expression in DSCs. RESULTS: Sai inhibited the proliferation of cultured DSCs, while no interference was observed in the presence of Toki. Both Toki and Sai enhanced the release of GM-CSF into culture medium. The amount of GM-CSF mRNA in cultured DSCs was as well increased by either Toki or Sai. CONCLUSION: Considering the significance of GM-CSF in embryonic development, clinical benefit of these herbal medicines in the treatment of recurrent abortion might be based on the shown pharmacological reaction related to GM-CSF.

Asunto(s)

Aborto Habitual/prevención & control , Decidua/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos de los fármacos , Células del Estroma/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Decidua/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/biosíntesis , Humanos , Embarazo , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células del Estroma/metabolismo

RESUMEN

PROBLEM: Human leukocyte antigen (HLA)-F together with other class 1b HLAs may play a pivotal role in immunological interaction at feto-maternal interface. However, it is not elucidated whether HLA-F is expressed on cell surface of extra-villous trophoblasts (EVTs). METHOD OF STUDY: The localization of HLA-F in placenta of each trimester was investigated by immunohistochemistry. The expression modality of HLA-F molecule was compared with that of HLA-G in cultured EVTs using flowcytometry. RESULTS AND CONCLUSION: In immunohistochemical study, remarkable staining for HLA-F was confirmed in EVTs throughout gestation. HLA-F expression was restricted to be intracellular in cultured EVTs. HLA-F expression was increased with time in culture, which was accompanied by the increase of cell surface HLA-G. Consequently, HLA-F lacking in cell surface expression on EVTs may not contribute to the direct cell-to-cell immune reaction but might work supportively modifying the function of HLA-G.

Asunto(s)

Antígenos HLA/análisis , Antígenos de Histocompatibilidad Clase I/análisis , Trofoblastos/inmunología , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Membrana Celular/inmunología , Femenino , Citometría de Flujo , Antígenos HLA/metabolismo , Antígenos HLA-G , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Embarazo , Trofoblastos/citología , Trofoblastos/metabolismo

RESUMEN

The catalytic and folding properties of "DSL ribozyme" were investigated. This artificial ligase ribozyme was constructed by installing a catalytic unit to a designed self-folding RNA. The self-folding RNA was composed of three helices connected via two tertiary interactions that served as scaffolding in the molecular design. The present analysis revealed that the tertiary interaction between the GAAA loop and its specific receptor plays a crucial role in the folding of the active structure and the precise positioning of the catalytic site. On the basis of the analyses, the ribozyme was redesigned and converted to two advanced forms--a smaller derivative with appreciable catalytic activity and a derivative with RNA polymerase-like activity. The study demonstrates that redesign of an artificial ribozyme is effective and efficient if its structural elements are finely resolved. This kind of molecular transformation should serve as a prototypic model for understanding the molecular organization and evolution of naturally occurring ribozymes.

Asunto(s)

Ligasas/química , ARN Catalítico/química , Dominio Catalítico , Evolución Molecular , Ligasas/genética , Mutación , Conformación de Ácido Nucleico , ARN Catalítico/genética