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1.
Diagnostics (Basel) ; 14(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38201411

RESUMO

Fetal hyperthyroidism can occur secondary to maternal autoimmune hyperthyroidism. The thyroid-stimulating hormone receptor antibody (TRAb) transferred from the mother to the fetus stimulates the fetal thyroid and causes fetal thyrotoxicosis. Fetuses with this condition are difficult to detect, especially after maternal Graves disease therapy. Here, we present two cases of fetal hyperthyroidism with maternal hypothyroidism and review the assessment and intrauterine therapy for fetal hyperthyroidism. Both women were referred at 22+ and 23+ weeks of gestation with abnormal ultrasound findings, including fetal heart enlargement, pericardial effusion, and fetal tachycardia. Both women had a history of Graves disease while in a state of hypothyroidism with a high titer of TRAb. A sonographic examination showed a diffusely enlarged fetal thyroid with abundant blood flow. Invasive prenatal testing revealed no significant chromosomal aberration. Low fetal serum TSH and high TRAb levels were detected in the cord blood. Fetal hyperthyroidism was considered, and maternal oral methimazole (MMI) was administered as intrauterine therapy, with the slowing of fetal tachycardia, a reduction in fetal heart enlargement, and thyroid hyperemia. During therapy, maternal thyroid function was monitored, and the dosage of maternal levothyroxine was adjusted accordingly. Both women delivered spontaneously at 36+ weeks of gestation, and neonatal hyperthyroidism was confirmed in both newborns. After methimazole and propranolol drug treatment with levothyroxine for 8 and 12 months, both babies became euthyroid with normal growth and development.

2.
Andrologia ; 54(2): e14316, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34791684

RESUMO

Y chromosome abnormalities are the leading cause of male infertility. The clinical detection of abnormalities is necessary for appropriate genetic counselling. This study describes the prevalence, distribution and characteristics of Y chromosome abnormalities, which should be considered in the clinical management of infertile males. A total of 121 patients with oligozoospermia, 120 with azoospermia and 88 normal individuals were recruited between June 2019 and July 2021. Y chromosome microdeletions were assessed using multiplex ligation-dependent probe amplification (MLPA). The abnormal Y chromosome prevalence was 30.70%, and it was most common in patients aged 26-40 years. The frequencies of azoospermia factor (AZF) deletion, duplication and deletions/duplications were 19.76%, 9.42% and 1.52% respectively. The most common abnormalities were AZFc deletion (19.80%), AZFc partial deletion (40.59%) and AZFc partial duplication (17.82%). Oligozoospermia was associated with an increased incidence of AZF deletion. In the subgroup analysis, patients <30 years old with azoospermia exhibited elevated follicle-stimulating hormone levels and oestradiol. Moreover, the incidence of AZF deletion was higher in those with azoospermia (OR: 2.12; 95% CI: 1.05-5.28; p = 0.023) or oligozoospermia (OR: 2.54; 95% CI: 1.13-5.79; p = 0.008) than in normal individuals for ages ≥30 years.


Assuntos
Azoospermia , Infertilidade Masculina , Oligospermia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual , Adulto , Azoospermia/diagnóstico , Azoospermia/epidemiologia , Azoospermia/genética , Deleção Cromossômica , Cromossomos Humanos Y/genética , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Masculino , Reação em Cadeia da Polimerase Multiplex , Oligospermia/diagnóstico , Oligospermia/genética , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética
3.
Clin Case Rep ; 9(10): e05001, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34721862

RESUMO

Pfeiffer syndrome (PS) is a rare autosomal dominant genetic disorder characterized by craniosynostosis, broad thumbs / toes. Here, we report a case of PS type 2 with increased nuchal translucency in early trimester.

4.
J Heart Lung Transplant ; 40(8): 856-859, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34059432

RESUMO

As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.


Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/cirurgia , COVID-19/complicações , COVID-19/cirurgia , Transplante de Rim , Transplante de Pulmão , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade
6.
Stem Cell Res ; 33: 233-246, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30458343

RESUMO

This study characterizes dynamic and apoptotic blebbing in human embryonic stem cells (hESC), identifies dynamic blebbing as a bottleneck to successful cell attachment during passaging, and demonstrates that dynamic blebbing can be rapidly stopped by plating cells on recombinant human laminin. In freshly plated hESC, dynamic and apoptotic blebbing differed in time of occurrence, bleb retraction rate, mitochondrial membrane potential, and caspase 3&7 activation. While dynamic blebbing can be controlled with drugs that inhibit myosin II, these methods have off-target effects and are not suitable for clinical applications. Recombinant human laminin-521 or addition of laminin-111 to Matrigel provided a safe method to drastically decrease dynamic blebbing and improve cell attachment with proteins normally found in the inner cell mass. Inhibition of focal adhesion kinase, which is activated by binding of integrins to laminin, prolonged dynamic blebbing and inhibited attachment. These data show that hESC bind rapidly to laminins through an integrin, which activates focal adhesion kinase that in turn downregulates dynamic blebbing. Laminins enabled hESC to rapidly attach during passaging, improved plating efficiency, enabled passaging of single pluripotent stem cells, and avoided use of inhibitors that have non-specific off-target effects. These data provide a strategy for improving hESC culture using biologically safe recombinant human proteins.


Assuntos
Células-Tronco Embrionárias Humanas/metabolismo , Integrinas/metabolismo , Laminina/metabolismo , Humanos , Transdução de Sinais
7.
Cell Physiol Biochem ; 37(1): 306-20, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26316078

RESUMO

BACKGROUND/AIMS: Nobiletin, a citrus flavonoid isolated from tangerines, alters ion transport functions in intestinal epithelia, and has antagonistic effects on eosinophilic airway inflammation of asthmatic rats. The present study examined the effects of nobiletin on basal short-circuit current (I(SC)) in a human bronchial epithelial cell line (16HBE14o-), and characterized the signal transduction pathways that allowed nobiletin to regulate electrolyte transport. METHODS: The I(SC) measurement technique was used for transepithelial electrical measurements. Intracellular calcium ([Ca(2+)]i) and cAMP were also quantified. RESULTS: Nobiletin stimulated a concentration-dependent increase in I(SC), which was due to Cl- secretion. The increase in I(SC) was inhibited by a cystic fibrosis transmembrane conductance regulator inhibitor (CFTR(inh)-172), but not by 4,4'-diisothiocyano-stilbene-2,2'-disulphonic acid (DIDS), Chromanol 293B, clotrimazole, or TRAM-34. Nobiletin-stimulated I(SC) was also sensitive to a protein kinase A (PKA) inhibitor, H89, and an adenylate cyclase inhibitor, MDL-12330A. Nobiletin could not stimulate any increase in I(SC) in a cystic fibrosis (CF) cell line, CFBE41o-, which lacked a functional CFTR. Nobiletin stimulated a real-time increase in cAMP, but not [Ca(2+)]i. CONCLUSION: Nobiletin stimulated transepithelial Cl- secretion across human bronchial epithelia. The mechanisms involved activation of adenylate cyclase- and cAMP/PKA-dependent pathways, leading to activation of apical CFTR Cl- channels.


Assuntos
Brônquios/efeitos dos fármacos , Cloretos/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Células Epiteliais/efeitos dos fármacos , Flavonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Brônquios/metabolismo , Cálcio/metabolismo , Linhagem Celular , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Células Epiteliais/metabolismo , Humanos , Iminas/farmacologia , Transporte de Íons/efeitos dos fármacos , Isoquinolinas/farmacologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Sulfonamidas/farmacologia
8.
Am J Emerg Med ; 32(3): 221-4, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24418441

RESUMO

BACKGROUND: Ocular trauma is recognized as the leading cause of unilateral blindness. However, few studies to date have focused on the clinical features of hospital-based ocular emergencies. Effectiveness of trauma centers in treating ocular emergencies was compared with treatment in traditional community hospital emergency departments. Demographics, causes, and nature of ocular emergencies, as well as visual outcome in community hospitals emergency departments and trauma centers, were also examined. METHODS: Records of 1027 patients with ocular emergencies seen between July 2007 and November 2010 at 3 community hospitals emergency departments and 2 hospitals with level II trauma centers were retrospectively examined. Unpaired t test and Pearson χ(2) test were used to determine statistical significance. RESULTS: The incidence of patients requiring ophthalmic intervention was 77.2 per 100 000 in the community hospitals and 208.9 per 100 000 in the trauma centers. Rates of ocular emergencies were higher in middle-aged, white men. Orbital fractures were found in 86% of all orbital contusion cases in trauma centers, whereas 66.7% of patients with fall injuries and open globe diagnoses resulted in legal blindness. CONCLUSIONS: The middle-aged, white men are more vulnerable to ocular injuries caused mainly by motor vehicle accidents. The ability of trauma centers to provide comparable increases in vision outcomes, despite treating more severe ocular emergencies, demonstrates the effectiveness of trauma centers. Patients diagnosed as having orbital contusions or who have fall injuries deserve careful evaluation because they are more likely to have more severe sight-threatening injuries.


Assuntos
Cegueira/etiologia , Traumatismos Oculares , Hospitais Comunitários , Centros de Traumatologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Cegueira/epidemiologia , California/epidemiologia , Criança , Pré-Escolar , Emergências , Traumatismos Oculares/epidemiologia , Traumatismos Oculares/etiologia , Traumatismos Oculares/terapia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Resultado do Tratamento , Adulto Jovem
9.
Am J Gastroenterol ; 108(6): 942-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23629601

RESUMO

OBJECTIVES: The long-term outcomes of oral antiviral therapy without hepatitis B immune globulin (HBIG) in prevention of reinfection with hepatitis B after liver transplantation are not known. We aimed to determine the long-term outcomes from a large population of chronic hepatitis B (CHB) liver transplant recipients using oral antiviral therapy alone. METHODS: A total of 362 consecutive CHB patients transplanted from January 2003 to May 2011 were included. None of the patients received HBIG. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up. RESULTS: Of the 362 patients, 176 (49%), 142 (39%), and 44 (12%) were on lamivudine (LAM), entecavir (ETV), and combination therapy (predominantly LAM+adefovir), respectively, at the time of transplant. The median follow-up length was 53 months. The rate of hepatitis B surface antigen seronegativity and hepatitis B virus (HBV) DNA suppression to undetectable levels at 8 years was 88 and 98%, respectively. The virological relapse rates (>1 log increase IU/ml) at 1, 3, 5, and 8 years was 5, 10, 13 and 16%, respectively. The virological relapse rate at 3 years for LAM, ETV, and combination group was 17, 0, and 7%, respectively (P<0.001). Forty-two patients had virological relapse, of which 36 had YMDD mutation (31 in the LAM group and 5 in the combination group). The overall 8-year survival was 83%, with no difference between the three treatment groups (P=0.94). No mortality from HBV recurrence occurred in the 362 patients. CONCLUSIONS: Oral nucleoside/nucleotide analogs without HBIG are effective in preventing graft loss secondary to hepatitis B recurrence after liver transplantation. However, new agents with a high barrier to resistance should be used to minimize drug resistance and to prevent virological rebound.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/prevenção & controle , Lamivudina/uso terapêutico , Transplante de Fígado , Organofosfonatos/uso terapêutico , Adenina/uso terapêutico , Adulto , Idoso , DNA Viral/sangue , Quimioterapia Combinada , Feminino , Seguimentos , Guanina/uso terapêutico , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/genética , Hepatite B Crônica/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Modelos de Riscos Proporcionais , Prevenção Secundária , Taxa de Sobrevida , Carga Viral , Adulto Jovem
11.
Hepatology ; 56(4): 1557-66, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22544823

RESUMO

UNLABELLED: Liver transplantation (LT) is a cure for many liver diseases. Blood chimerism of donor origin can develop after LT, which raises the possibility of the existence of hematopoietic stem/progenitor cells (HSPCs) in the liver. We characterized the blood chimerism in a large cohort of 249 LT patients and analyzed putative HSPCs in adult human livers. The overall incidence of chimerism was 6.43%, of which 11.11% was among short-term (1 day to 6 months) and 3.77% was among long-term (6 months to 8 years) LT patients. Hematopoietic Lin(-) CD34(+) CD38(-) CD90(+) populations have been demonstrated to generate long-term lymphomyeloid grafts in transplantations. In human adult livers, we detected Lin(-) CD34(+) CD38(-) CD90(+) populations accounting for 0.03% ± 0.017% of the total single liver cells and for 0.05% ± 0.012% of CD45(+) liver cells. Both Lin(-) CD34(+) and Lin(-) CD45(+) liver cells, from extensively perfused human liver grafts, were capable of forming hematopoietic myeloid-lineage and erythroid-lineage methylcellulose colonies. More importantly, Lin(-) CD45(+) or CD45(+) liver cells could be engrafted into hematopoietic cells in an immunodeficient mouse model. These results are the first evidence of the presence of putative HSPC populations in the adult human liver, where the liver is a good ectopic niche. The discovery of the existence of HSPCs in the adult liver have implications for the understanding of extramarrow hematopoiesis, liver regeneration, mechanisms of tolerance in organ transplantation, and de novo cancer recurrence in LT patients. CONCLUSION: The human adult liver contains a small population of HSPCs. In LT patients, there are two types of chimerisms: transient chimerism, resulting from mature leucocytes, and long-term chimerism, derived from putative HSPCs in the liver graft.


Assuntos
Quimerismo , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Células-Tronco Hematopoéticas/imunologia , Transplante de Fígado/imunologia , Adulto , Idoso , Animais , Antígenos CD/imunologia , Estudos de Coortes , Modelos Animais de Doenças , Feminino , Hematopoese/imunologia , Hematopoese/fisiologia , Humanos , Transplante de Fígado/métodos , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Doadores de Tecidos , Transplante Heterólogo , Transplante Homólogo , Adulto Jovem
12.
Gastroenterology ; 141(4): 1212-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21762659

RESUMO

BACKGROUND & AIMS: We investigated the efficacy of entecavir, a cyclopentyl guanosine nucleoside analogue, as monoprophylaxis in patients with chronic hepatitis B who received a liver transplant. METHODS: We studied data from 80 consecutive patients who received a liver transplant (47 from living donors and 33 from deceased donors) for hepatitis B-related disease and entecavir monotherapy as prophylaxis. None of the patients received hepatitis B immunoglobulin. Indications for transplant included decompensation from cirrhosis (27.5%), acute-on-chronic hepatitis B (47.5%), and hepatocellular carcinoma (25%). The median follow-up time was 26 months (range, 5-40 months). Before transplant, 33 patients were not on antiviral therapy and 47 were on oral therapy (18 had received less than 3 months of treatment). RESULTS: At the time of transplant, the median log HBV DNA level was 3.5 copies/mL (range, 1.54-8.81); 21 patients (26%) had undetectable levels of HBV DNA. The cumulative rate of hepatitis B surface antigen (HBsAg) loss was 86% and 91% after 1 and 2 years, respectively. Ten patients had reappearance of HBsAg. Eighteen patients (22.5%) were HBsAg positive at the time of their last examination; 17 of these had undetectable levels of HBV DNA, and the remaining patient had a low level of HBV DNA (217 copies/mL). There was no evidence of mutations at sites that confer resistance to entecavir among patients who were HBsAg positive. CONCLUSIONS: Although only 26% of patients had complete viral suppression at the time of transplant, 91% lost HBsAg, with 98.8% achieving undetectable levels of HBV DNA. A hepatitis B immunoglobulin-free regimen of entecavir monotherapy is effective after liver transplantation for chronic hepatitis B.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/cirurgia , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/cirurgia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Adulto , Idoso , Antivirais/efeitos adversos , Biomarcadores/sangue , Carcinoma Hepatocelular/virologia , Distribuição de Qui-Quadrado , DNA Viral/sangue , Feminino , Guanina/efeitos adversos , Guanina/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hong Kong , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Viral , Adulto Jovem
13.
Liver Transpl ; 16(11): 1314-23, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21031547

RESUMO

Liver grafts from donors positive for antibody to hepatitis B core antigen (anti-HBc) may be used for transplantation in patients with hepatitis B virus (HBV)-related liver disease, and an occult HBV infection may develop from either source. Liver biopsy was performed for 31 patients who remained seronegative for hepatitis B surface antigen for a median of 44.5 months (range = 13.6-126.4 months) and received nucleoside analogue prophylaxis post-transplant. Nineteen of these recipients (61%) had received anti-HBc-positive grafts. Intrahepatic total HBV DNA and covalently closed circular DNA (cccDNA) levels were quantified, and the sequence was analyzed. Intrahepatic total HBV DNA and cccDNA were detectable in 26 (84%) and 16 (52%) of the 31 recipients, respectively, and they were more common when the donor was positive for anti-HBc (95% versus 67%, P = 0.038). The intrahepatic HBV DNA level correlated with the recipient pretransplant serum HBV DNA level (P = 0.06), and the intrahepatic HBV cccDNA level correlated with the donor intrahepatic HBV cccDNA level (P = 0.06). A phylogenetic analysis of the isolated HBV DNA sequence revealed HBV infections of both donor and recipient origins. In conclusion, an occult HBV infection after liver transplantation can originate from both the donor and recipient despite prolonged nucleoside analogue prophylaxis. The presence of intrahepatic HBV cccDNA is attributable more to the persistence of preexisting intrahepatic HBV cccDNA from a donor with previous exposure.


Assuntos
Hepatite B , Transplante de Fígado , Nucleosídeos , Doadores de Tecidos , Antivirais/farmacologia , Antivirais/uso terapêutico , DNA Viral/análise , Feminino , Hepatite B/imunologia , Hepatite B/prevenção & controle , Hepatite B/virologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Imunoglobulinas/farmacologia , Imunoglobulinas/uso terapêutico , Imuno-Histoquímica , Lamivudina/farmacologia , Lamivudina/uso terapêutico , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nucleosídeos/farmacologia , Nucleosídeos/uso terapêutico
14.
Liver Transpl ; 16(10): 1195-206, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20879018

RESUMO

Adult bone marrow-derived mesenchymal stem cells (MSCs) exist in all living species and are capable of differentiating into different types of specific cells. In this study, we demonstrate the therapeutic effectiveness of rat MSC transplantation in D-galactosamine (GalN)-induced acute liver injury and identified the novel pathways which are involved in hepatic differentiation of MSCs. In vivo, intraportal transplantation with 5 × 10(6) MSCs at 24 hours after GalN administration resulted in significant reduction in serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin compared to the control group. Engrafted MSCs actively proliferated, differentiated, and further enhanced hepatocyte proliferation activity. In vitro, coculture of MSCs with GalN-induced injured hepatocytes showed efficient differentiation and was evidenced by progressive increase in messenger RNA levels of hepatic markers, including albumin, α-fetoprotein, CCAAT-enhancer binding protein α, α-1-antitryspin, and hepatocyte nuclear factor-3ß. Immunofluorescent staining revealed that these cells were positive for albumin, α-fetoprotein, and cytokeratin 18, but not clusters of differentiation 34, cytokeratin 19, or OV6. During hepatic differentiation, signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling were constantly activated, and a gradual down-regulation of ß-catenin expression in messenger RNA and protein levels was detected. Hyper-interleukin-6 fusion protein but not interleukin-6 (IL-6) alone caused reduction in ß-catenin expression associated with the up-regulation of Wnt-5a in MSCs via activating the glycoprotein 130 (gp130)-mediated STAT3 signaling pathway, which indicates the operation of the trans-signaling mechanism. Activation of IL-6/gp130-mediated STAT3 signaling pathway in MSCs triggered wound healing, cell migration, and proliferation. In conclusion, transplantation of MSCs promotes cell proliferation and organ repair, and activation of IL-6/gp130-mediated STAT3 signaling pathway via soluble IL-6 receptor is crucial in hepatic differentiation of MSCs.


Assuntos
Diferenciação Celular , Proliferação de Células , Doença Hepática Induzida por Substâncias e Drogas/cirurgia , Receptor gp130 de Citocina/metabolismo , Hepatócitos/transplante , Regeneração Hepática , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Quimiotaxia , Técnicas de Cocultura , Modelos Animais de Doenças , Feminino , Galactosamina , Regulação da Expressão Gênica , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Hepatócitos/metabolismo , Hepatócitos/patologia , Interleucina-6/metabolismo , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Comunicação Parácrina , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Fatores de Tempo
15.
Liver Transpl ; 15(3): 292-9, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19243002

RESUMO

Cellular immunity plays an important role in the long-term control of hepatitis B virus (HBV) infection. We studied the changes in HBV-specific CD4 T cell immunity after orthotopic liver transplantation (OLT) for chronic hepatitis B under antiviral prophylaxis. T cell proliferation and interferon-gamma production in response to in vitro challenge with HBV-encoded antigens were tested in 40 OLT recipients without HBV recurrence and in 12 OLT recipients with HBV recurrence more than 1 year after transplantation, and they were compared to 40 subjects with chronic HBV infection and to 23 subjects with self-limited HBV infection. The frequency and magnitude of the HBV-specific CD4 T cell response were significantly lower in 40 OLT recipients with HBV clearance, but the T cell reactivity to mitogen (phytohemagglutinin) and recall antigen (tetanus toxoid) was maintained. In the 12 OLT recipients with HBV recurrence, however, the HBV-specific T cell immunity was enhanced to a level comparable to that of patients with chronic hepatitis B, and the level was dependent on the serum viral load. In conclusion, HBV-specific CD4 T cell immunity is antigen-driven and evanesces with viral clearance, hence providing a favorable milieu for reactivation once prophylaxis is withdrawn. The cellular immunity in recipients with recurrence is not significantly different from that of individuals with chronic hepatitis B.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Imunidade Celular , Imunoglobulinas/uso terapêutico , Transplante de Fígado/imunologia , Adolescente , Adulto , Idoso , DNA Viral/sangue , Feminino , Antígenos de Superfície da Hepatite B/sangue , Humanos , Interferon gama/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Recidiva , Linfócitos T/imunologia , Resultado do Tratamento , Adulto Jovem
16.
Shock ; 27(3): 242-50, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17304104

RESUMO

Hypertonic saline (HS) treatment promotes interleukin (IL)-2 production and enhances T-cell activation by the release of cellular adenosine triphosphate (ATP) that activates P2 nucleotide receptors. Released ATP can be hydrolyzed to adenosine, which inhibits T-cell activation. We examined if adenosine affects the response of T cells to HS treatment, and found that the amount of ATP released from T cells is a function of the HS concentration and duration of HS exposure. Physiologically relevant HS concentrations (<40 mmol/L) induced rapid ATP release, with the highest ATP concentrations released within 1 min. The released ATP was converted to adenosine, which opposed the enhancing effects of HS on IL-2 production. We found that Jurkat and CD4+ primary human T cells express most abundantly the A2A and A2B adenosine receptor subtypes, which mediate the suppressive effects of adenosine, as the A2 receptor agonist CGS 21680 suppressed IL-2 production, whereas the A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl)xanthine augmented the enhancing effect of HS on T-cell function. Elimination of extracellular adenosine by adding exogenous adenosine deaminase also increased the enhancing effects of HS. These data suggest that the effect of HS treatment on T-cell function can be modulated with pharmacological agents that abolish the suppressive effects of adenosine formed from the ATP that is released in response to HS treatment.


Assuntos
Trifosfato de Adenosina/metabolismo , Adenosina/metabolismo , Estresse Fisiológico/patologia , Linfócitos T/metabolismo , Adenosina Desaminase/metabolismo , Separação Celular , Humanos , Hidrólise , Interleucina-2/metabolismo , Células Jurkat , Leucócitos Mononucleares/metabolismo , Modelos Biológicos , Receptores Purinérgicos P1/metabolismo , Cloreto de Sódio/farmacologia , Fatores de Tempo
17.
Liver Transpl ; 13(1): 71-9, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17031830

RESUMO

Both animal and human studies have demonstrated the adoptive transfer of immunity against hepatitis B virus (HBV) through liver transplantation that may be attributed to the presence of HBV-specific immunocompetent cells of donor origin in liver grafts. In this study, we characterized the resident lymphocytes in 41 human liver grafts by immunohistochemical staining and flow cytometry and directly identified the intragraft HBV-specific lymphocytes in relation to the donor's and subsequent recipient's immunity using enzyme-linked immunospot assay. A significant number of HBV-specific T and B cells were detectable in 59.4% (19/32) and 28.1% (9/32), respectively, of liver grafts from HBV-immune donors. The presence of various HBV-specific lymphocytes was closely associated with each other and with a higher serum titer of antibody against hepatitis B surface antigen (anti-HBs) in donors (P < 0.05). After liver transplantation, 17 of 35 (48.6%) patients with chronic HBV infection showed a spontaneous anti-HBs production, which was significantly associated with a higher number of donor-derived T lymphocytes specific for hepatitis B surface antigen (P = 0.043). In conclusion, the presence of considerable numbers of donor-derived HBV-specific immunocompetent cells in grafts may account for the adoptive transfer of HBV immunity through liver transplantation.


Assuntos
Vírus da Hepatite B/metabolismo , Hepatite B/imunologia , Hepatite B/virologia , Transplante de Fígado/métodos , Fígado/virologia , Linfócitos/virologia , Adulto , Idoso , Linfócitos B/imunologia , Biópsia , Feminino , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Humanos , Imuno-Histoquímica , Interferon gama/metabolismo , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia
18.
Clin Cancer Res ; 12(17): 5248-52, 2006 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-16951245

RESUMO

PURPOSE: Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously showed that aberrant mRNA splicing of the liver intestine-cadherin gene CDH17 in liver tissues was triggered by the specific constellation of two CDH17 single nucleotide polymorphisms (651T and IVS6+35G). CDH17 aberrant splicing was highly associated with tumor dissemination and shorter survival of HCC patients. Consequently, it is highly relevant to assess whether the presence of these single nucleotide polymorphisms in the general population represents a risk to the development of HCC. EXPERIMENTAL DESIGN: We conducted a case-control study including 164 HCC and 99 cirrhosis patients and 293 healthy controls. Genotyping was done by PCR and direct sequencing. Odds ratio (OR) and chi2 analysis were used to analyze genotypes and haplotypes. RESULTS: Genotypes 651TT [OR, 2.62; 95% confidence interval (95% CI), 1.34-5.03] and IVS6+35 GG (OR, 1.95; 95% CI, 1.04-3.62) were highly associated with HCC disease. The 651T (C>T) and IVS6+35G (A>G) alleles were also overrepresented in HCC patients and, in particular, the T-G haplotype was the most prevalent in HCC patients when compared with healthy controls (OR, 1.57; 95% CI, 1.167-2.109; P=0.004), which was in agreement with the aberrant splicing observed in tumor tissues. There was no significant difference in genotype and allele frequencies between cirrhosis patients and controls. CONCLUSION: The functional T-G haplotype of CDH17 (651 C>T and IVS6+35A>G) is a genetic susceptibility factor for the development of HCC in a Chinese population.


Assuntos
Caderinas/genética , Carcinoma Hepatocelular/genética , Predisposição Genética para Doença , Neoplasias Hepáticas/genética , Alelos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Haplótipos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
19.
Am J Transplant ; 5(8): 1893-900, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15996236

RESUMO

Hepatitis B virus (HBV) genotype influences chronic hepatitis B disease profile but its relevance in liver transplantation (LTx) is not known. HBV genotype was identified by direct sequencing from pre-transplant sera of 119 patients who underwent LTx using lamivudine prophylaxis (genotype A,1; B,43; C,74; D,1). The baseline characteristics and outcome of 43 genotype B and 74 genotype C patients were compared. Genotype B patients had significantly more pre-transplant acute flare, worse liver functions and higher model for end-stage liver disease score. Fewer genotype B patients had HBeAg (13% vs. 32%; p=0.017), but HBV DNA seropositivity (by bDNA assay) was comparable (26% vs. 23%; p=0.727). The 3-year graft survival was 83% for genotype B and 89% for genotype C (p=0.2). The rate of HBsAg clearance or seroreversion was the same. The cumulative rate of viral breakthrough due to lamivudine-resistant mutants at 3 years was 4% for genotype B and 21% for genotype C (p=0.017). Liver biopsy after viral breakthrough showed recurrent hepatitis B in 7 of 10 genotype C patients, including 2 with fibrosing cholestatic hepatitis, and no histologic recurrence in 2 genotype B patients. In conclusion, HBV genotypes B and C are associated with different patterns of end-stage liver diseases that required transplantation, and genotype C may carry a greater risk and severity of recurrence due to lamivudine-resistant mutants.


Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/cirurgia , Lamivudina/administração & dosagem , Transplante de Fígado , Adolescente , Adulto , Idoso , Farmacorresistência Viral , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/metabolismo , Hepatite C/genética , Hepatite C/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Inibidores da Transcriptase Reversa/administração & dosagem , Prevenção Secundária , Resultado do Tratamento
20.
J Immunol ; 173(4): 2507-15, 2004 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-15294966

RESUMO

This study aims to investigate the potential role of vascular endothelial growth factor (VEGF) and VEGF-R2 (fetal liver kinase (Flk)-1) in mediating macrophage activities in small-for-size liver transplantation. A rat orthotopic liver transplantation model was performed using either whole, 50, or 30% liver grafts (both 50 and 30% were regarded as small-for-size) in syngeneic or allogeneic combinations, respectively. Firstly, the mRNA and protein levels of VEGF and Flk-1 in liver grafts were detected by RT-PCR and Western blot, and the number of Flk-1(+) macrophages (labeled by ED1) was determined by flow cytometry. It was found that the small-for-size isografts and allografts presented higher levels of VEGF and Flk-1 expression than the whole isograft and allograft. In addition, a higher number of Flk-1(+)ED1(+) cells were detected in the small-for-size isografts and allografts than the whole isograft and allograft. Secondly, our study revealed that macrophage cell lines did not initially express detectable Flk-1, but could be induced by VEGF, and the inducible expression of Flk-1 in macrophages was related to their migration and proliferation activities. Finally, our study demonstrated that the induction of Flk-1 expression on macrophages by VEGF was associated with the expression of NF-kappaB and heat shock protein 90. In conclusion, the present study showed that the up-regulated expression of VEGF and its interaction with Flk-1 in small-for-size liver grafts might facilitate the activities of macrophages.


Assuntos
Transplante de Fígado/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Animais , Western Blotting , Divisão Celular/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Proteínas de Choque Térmico HSP90/imunologia , Proteínas de Choque Térmico HSP90/metabolismo , Masculino , NF-kappa B/imunologia , NF-kappa B/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante Homólogo , Transplante Isogênico , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/imunologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/imunologia
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