RESUMO
OBJECTIVES: We aimed to evaluate the feasibility and efficacy of surgical prostatectomy in renal transplant recipients (RTRs). METHODS: Between January 2008 and February 2017, we identified 13 RTRs who were diagnosed with localized prostate cancer and underwent radical prostatectomy. We reviewed all available clinicopathologic data for these 13 patients. RESULTS: The median patient age was 61 years and median serum prostate-specific antigen (PSA) was 8.79 ng/mL. The mean period between transplantation and diagnosis of prostate cancer was 136 months. The sources for the kidney transplants included 10 living and 3 deceased donors. Biopsies indicated that the Gleason scores were 7 in 10 patients and 8 to 10 in 3 patients. Meanwhile, the D'Amico risk classification indicated an intermediate risk in 9 patients and a high risk in 4 patients. Eight patients were at stage cT1 and 5 were at stage cT2. The surgical procedure was retropubic radical prostatectomy in one recipient, laparoscopic radical prostatectomy in 3 recipients, and robot-assisted radical prostatectomy in 9 RTRs. Intraoperative complications were not noted in any patient, although one patient demonstrated postoperative complications (Clavien grade ≥ 3). An indwelling urinary catheter was required in 3 patients for over 3 weeks due to delayed wound healing. Biochemical recurrence evaluated by PSA monitoring occurred in four patients. Postoperative graft function was stable in all but one patient who required resumption of dialysis before prostatectomy; however, all patients are alive at the time of publication with 12 patients showing well-functioning renal allografts. CONCLUSION: Prostatectomy may be a feasible and effective technique as an initial treatment for RTRs with localized prostate cancer.
Assuntos
Transplante de Rim , Prostatectomia/métodos , Neoplasias da Próstata/complicações , Neoplasias da Próstata/cirurgia , Transplantados , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: The skin of atopic dermatitis (AD) patients presents a significant dysbalance of the microbiome with a high colonization by Staphylococcus aureus (S. aureus), which positively correlates with the severity of the disease. OBJECTIVE: Understanding the role of epidermal dendritic cells (DC) as link between the innate and the adaptive immune systems in AD. METHODS: Comparative phenotypic and functional analysis of TLR2 on Langerhans cells (LC) and inflammatory dendritic epidermal cells (IDEC) in organotypic models as well as freshly isolated cells from healthy and AD skin. RESULTS: In situ analysis of freshly isolated LC and IDEC from AD skin revealed decreased TLR2 expression compared to LC from healthy skin. In contrast to IDEC, LC from AD skin failed to display any evidence for in situ activation. Exposure to TLR2 ligand Pam3Cys resulted in maturation and increased migratory activity of LC from normal skin. LC and IDEC from AD were unresponsive to TLR2 ligand in that they failed to mature and displayed a high spontaneous migratory activity. Keratinocytes from both healthy and AD skin expressed similar levels of TLR2. The production of IL-6 and IL-10 was impaired by Pam3Cys in supernatants from AD skin. IL-18 was significantly higher in supernatants from AD skin and not influenced by TLR2 ligation, when compared to healthy skin. CONCLUSION: Our results suggest that TLR2-mediated sensing of S. aureus-derived signals is strongly impaired in LC from AD skin. This phenomenon may partly contribute to the immune deviation in AD and the lack of S. aureus clearance.
Assuntos
Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Tolerância Imunológica , Células de Langerhans/imunologia , Células de Langerhans/metabolismo , Receptor 2 Toll-Like/metabolismo , Imunidade Adaptativa , Biomarcadores , Movimento Celular/imunologia , Citocinas/metabolismo , Dermatite Atópica/patologia , Feminino , Expressão Gênica , Humanos , Imunidade Inata , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunofenotipagem , Queratinócitos/metabolismo , Masculino , Ligação Proteica , Índice de Gravidade de Doença , Staphylococcus aureus/imunologia , Receptor 2 Toll-Like/genéticaAssuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Granuloma/induzido quimicamente , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Dermatopatias/induzido quimicamente , Neoplasias da Túnica Conjuntiva/patologia , Células Epitelioides/patologia , Feminino , Granuloma/patologia , Humanos , Melanoma/secundário , Pessoa de Meia-Idade , Dermatopatias/patologiaRESUMO
BACKGROUND: Short-chain fatty acids (SCFA) are microbial fermentation products absorbed by the colon. We recently reported that activation of the SCFA receptor termed free fatty acid receptor 3 (FFA3), expressed on cholinergic nerves, suppresses nicotinic acetylcholine receptor (nAChR)-mediated transepithelial anion secretion. This study aimed to clarify how activation of neurally expressed FFA3 affects colonic motor function. METHODS: FFA3-expressing myenteric neurons were identified by immunostaining; contractions of isolated circular muscle strips obtained from rat proximal colon were measured by isometric transducers. The effect of FFA3 agonists on defecation in vivo was examined in an exogenous serotonin-induced defecation model. KEY RESULTS: FFA3 immunoreactivity was located in nitrergic and cholinergic neurons in the myenteric plexus. In isolated circular muscle strips without mucosa and submucosa, the addition of nicotine (10 µM) or serotonin transiently relaxed the muscle through nitrergic neurons, whereas high concentrations of nicotine (100 µM) induced large-amplitude contractions that were mediated by cholinergic neurons. Pretreatment with FFA3 agonists inhibited nicotine- or serotonin-induced motility changes but had no effect on bethanechol-induced direct muscle contractions. The Gi/o inhibitor pertussis toxin reversed the inhibitory effect of an FFA3 agonist AR420626 on nicotine-evoked contractions, suggesting that FFA3 activation suppresses nAChR-mediated neural activity in myenteric neurons, consistent with an FFA3-mediated antisecretory effect. In conscious rats, exogenous serotonin increased the volume of fecal output, compared with the vehicle- or AR420626-treated groups. Pretreatment with AR420626 significantly suppressed serotonin-induced fecal output. CONCLUSION AND INFERENCES: FFA3 is a promising target for the treatment of neurogenic diarrheal disorders by suppressing nAChR-mediated neural pathways.
Assuntos
Colo/fisiologia , Motilidade Gastrointestinal , Neurônios/fisiologia , Receptores Acoplados a Proteínas G/fisiologia , Animais , Neurônios Colinérgicos/metabolismo , Colo/metabolismo , Defecação , Masculino , Contração Muscular , Plexo Mientérico/fisiologia , Neurônios/metabolismo , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Neurônios Nitrérgicos/metabolismo , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Serotonina/administração & dosagem , Antagonistas da Serotonina/administração & dosagemRESUMO
The risk of schizophrenia is increased in offspring whose mothers experience malnutrition during pregnancy. Polyunsaturated fatty acids (PUFAs) are dietary components that are crucial for the structural and functional integrity of neural cells, and PUFA deficiency has been shown to be a risk factor for schizophrenia. Here, we show that gestational and early postnatal dietary deprivation of two PUFAs-arachidonic acid (AA) and docosahexaenoic acid (DHA)-elicited schizophrenia-like phenotypes in mouse offspring at adulthood. In the PUFA-deprived mouse group, we observed lower motivation and higher sensitivity to a hallucinogenic drug resembling the prodromal symptoms in schizophrenia. Furthermore, a working-memory task-evoked hyper-neuronal activity in the medial prefrontal cortex was also observed, along with the downregulation of genes in the prefrontal cortex involved in oligodendrocyte integrity and the gamma-aminobutyric acid (GABA)-ergic system. Regulation of these genes was mediated by the nuclear receptor genes Rxr and Ppar, whose promoters were hyper-methylated by the deprivation of dietary AA and DHA. In addition, the RXR agonist bexarotene upregulated oligodendrocyte- and GABA-related gene expression and suppressed the sensitivity of mice to the hallucinogenic drug. Notably, the expression of these nuclear receptor genes were also downregulated in hair-follicle cells from schizophrenia patients. These results suggest that PUFA deficiency during the early neurodevelopmental period in mice could model the prodromal state of schizophrenia through changes in the epigenetic regulation of nuclear receptor genes.
Assuntos
Ácido Araquidônico/deficiência , Disfunção Cognitiva , Ácidos Docosa-Hexaenoicos/deficiência , Epigênese Genética/genética , Desnutrição/complicações , Leite Humano/química , Córtex Pré-Frontal , Complicações na Gravidez/metabolismo , Efeitos Tardios da Exposição Pré-Natal , Receptores Citoplasmáticos e Nucleares/genética , Esquizofrenia , Animais , Animais Recém-Nascidos , Comportamento Animal , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Sintomas Prodrômicos , Esquizofrenia/etiologia , Esquizofrenia/genética , Esquizofrenia/fisiopatologiaRESUMO
A 26-year-old woman presented with recurrent attacks of widespread urticaria and systemic symptoms. The patient was a nurse, and the attacks occurred only in her workplace, without an apparent trigger. A patch test to cefotiam (CTM) induced an immediate skin reaction. ELISA detected the patient's serum IgE antibody binding to CTM conjugated with human serum albumin (CTM-HSA), and her basophils released histamine in response to CTM-HSA in a histamine release assay (HRA). Both reactions in ELISA and HRA were inhibited by pretreatment of the patient's serum or basophils with cefotiam. No crossreactivity in skin tests or in vitro assays was observed against other antibiotics, even those containing a beta-lactam ring and/or side chains similar to CTM. Certain antibiotics including CTM may cause extremely sensitive and specific contact urticaria syndrome, which is mediated by IgE and evoked even without apparent skin contact with the culprit drug and in the absence of any history of an allergic reaction against other antibiotics with similar structures.
Assuntos
Cefotiam/imunologia , Imunoglobulina E/imunologia , Doenças Profissionais/induzido quimicamente , Urticária/induzido quimicamente , Adulto , Cefotiam/efeitos adversos , Feminino , Humanos , Recursos Humanos de Enfermagem Hospitalar , Doenças Profissionais/imunologia , Urticária/imunologiaRESUMO
OBJECTIVE: The number of patients with foot gangrene caused by critical ischaemia and severe infection is increasing significantly in developed countries. The measurement of perilesional skin blood flow by skin perfusion pressure (SPP) is useful to select the appropriate treatment of gangrenous lesions, in that it is not affected by calcifications of blood vessels. However, the prognosis of a foot ulcer may also be affected by the level of blood sugar and infections. This study aimed to validate the use of SPP in cases of foot gangrene and ulcers in patients with and without diabetes mellitus (DM) and infection. METHOD: Clinical symptoms, ankle-brachial pressure index (ABPI) and SPP were assessed to evaluate the condition of each foot ulcer. Every foot ulcer was treated as independent, even if a participant had multiple ulcers. All ulcers for which we measured SPP were subject to the analysis. All ulcers were purely ischaemic in nature and were exclusively located on the foot or toes. RESULTS: Data were collected from 117 foot ulcers on 91 toes and feet from 65 patients. Almost all SPP values in healed cases were > 27 mmHg. There were three patients whose ulcers failed to heal by conservative treatments were complicated with severe infection. However, no effect of DM on the relationship between SPP values and prognosis was observed. Logistic regression analysis of all ulcers except for the 5 cases complicated with infection revealed that those with 30 mmHg or lower SPP values are likely to heal by conservative treatment with 23% or lower probability, whereas any ulcer with more than 50 mmHg SPP value and without severe infection may heal without the need for further operations with 80% or higher probability. CONCLUSION: The combination of SPP and careful evaluation of infection may be a good parameter to decide the appropriate treatment for ischaemic skin ulcers, regardless of the complication of DM.
Assuntos
Diabetes Mellitus , Pé Diabético/fisiopatologia , Doenças Vasculares Periféricas/fisiopatologia , Pele/irrigação sanguínea , Cicatrização , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia , Índice Tornozelo-Braço , Pé Diabético/etiologia , Pé Diabético/cirurgia , Feminino , Pé/patologia , Úlcera do Pé/fisiopatologia , Úlcera do Pé/cirurgia , Gangrena , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/cirurgia , Pressão , Prognóstico , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Adulto JovemRESUMO
Autoantibodies to melanoma differentiation-associated protein 5 (MDA5) are associated with a subset of patients with dermatomyositis (DM) who have rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis. Intensive immunosuppressive therapy is initiated before irreversible lung damage can occur; however, there are few lines of evidence for the treatment of RP-ILD. Here, we report three cases of anti-MDA5 antibody-associated DM with RP-ILD in which the patients were treated with combined-modality therapy, including high-dose prednisolone, tacrolimus, intravenous cyclophosphamide and intravenous immunoglobulin (IVIG). In all three cases, serum ferritin levels, which are known to represent the disease activity of RP-ILD, were decreased after IVIG administration. IVIG might contribute to the control of the disease activity of anti-MDA5 antibody-positive DM. Moreover, palmar violaceous macules/papules around the interphalangeal joints, which was observed in all three cases in the incipient stage, might be a useful sign in suggesting a diagnosis of anti-MDA5 antibody-associated DM.
Assuntos
Dermatomiosite/prevenção & controle , Dermatoses da Mão/prevenção & controle , Imunoglobulinas Intravenosas/uso terapêutico , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/prevenção & controle , Idoso , Anti-Inflamatórios/administração & dosagem , Autoanticorpos/sangue , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Tacrolimo/administração & dosagem , Resultado do TratamentoRESUMO
Introduction: Although adjunctive aripiprazole improves hyperprolactinemia, sufficient evidence for its effects on sexual dysfunction has not been obtained. We assessed the usefulness of adjunctive aripiprazole for schizophrenia with sexual dysfunction. Methods: 22 Japanese schizophrenia patients with antipsychotic-induced hyperprolactinemia and sexual dysfunction were enrolled, and 19 of them completed the study. Aripiprazole was administrated in a flexible titration schedule to participants according to the judgment of each doctor, and patients were followed for 24 weeks. Serum prolactin, Clinical Global Impression Scales-Severity (CGI-S), and Nagoya Sexual Function Questionnaire (NSFQ) were measured at baseline and at 4, 8, 12, and 24 weeks. Results: Prolactin at week 4 and later was significantly lower than that at baseline. Compared to baseline, we observed a significant improvement in total sexual dysfunction as measured by NSFQ at week 8 and later. In males, erectile dysfunction was significantly reduced at week 24. In females, menstrual irregularity and galactorrhea were significantly reduced at week 24. CGI-S did not significantly change. Discussion: Although the small sample size is a limitation in this study, adjunctive aripiprazole may be useful treatment for sexual dysfunction including hyperprolactinemia in schizophrenia.
Assuntos
Aripiprazol/uso terapêutico , Esquizofrenia/complicações , Disfunções Sexuais Fisiológicas/complicações , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/complicações , Hiperprolactinemia/tratamento farmacológico , Masculino , Prolactina/sangue , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Disfunções Sexuais Fisiológicas/induzido quimicamenteRESUMO
Few biomarkers have been known that can easily measure clinical conditions in mental illnesses such as schizophrenia. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) is a new method that can measure ionized and low-molecular-weight metabolites. To explore global metabolomic alterations that characterize the onset of schizophrenia and identify biomarkers, we profiled the relative and absolute concentrations of the plasma metabolites from 30 patients with first-episode schizophrenia (FESZ, four drug-naïve samples), 38 healthy controls and 15 individuals with autism spectrum disorders using CE-TOFMS. Five metabolites had robust changes (increased creatine and decreased betaine, nonanoic acid, benzoic acid and perillic acid) in two independent sample sets. Altered levels of these metabolites are consistent with well-known hypotheses regarding abnormalities of the homocysteine metabolism, creatine kinase-emia and oxidative stress. Although it should be considered that most patients with FESZ received medication, these metabolites are candidate biomarkers to improve the determination of diagnosis, severity and clinical stages, especially for FESZ.
Assuntos
Transtornos Globais do Desenvolvimento Infantil/metabolismo , Eletroforese Capilar/métodos , Espectrometria de Massas/métodos , Plasma/metabolismo , Esquizofrenia/metabolismo , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Transtornos Globais do Desenvolvimento Infantil/sangue , Feminino , Humanos , Masculino , Esquizofrenia/sangue , Adulto JovemRESUMO
Glutamate-induced excitotoxicity is thought to play an important role in several neurodegenerative diseases in the central nervous system (CNS). In this study, neuroprotection against glutamate-induced excitotoxicity was analyzed using acetylcholine (ACh), nicotine and the α7 specific nicotinic acetylcholine receptor (α7 nAChR) agonist, N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987), in cultured adult rat retinal neurons. Adult Long Evans rat retinas were dissociated and retinal ganglion cells (RGCs) were isolated from all other retinal tissue using a two-step panning technique. Once isolated, RGCs were cultured under various pharmacological conditions to demonstrate excitotoxicity and neuroprotection against excitotoxicity. After 3 days, RGCs were immunostained with antibodies against the glycoprotein, Thy 1.1, counted and cell survival was assessed relative to control untreated conditions. 500 µM glutamate induced excitotoxicity in large and small RGCs in an adult rat dissociated culture. After 3 days in culture with glutamate, the cell survival of large RGCs decreased by an average of 48.16% while the cell survival of small RGCs decreased by an average of 42.03%. Using specific glutamate receptor agonists and antagonists, we provide evidence that the excitotoxic response was mediated through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainic acid (KA) and N-methyl-d-aspartate (NMDA) glutamate receptors through an apoptotic mechanism. However, the excitotoxic effect of glutamate on all RGCs was eliminated if cells were cultured for an hour with 10 µM ACh, 100 µM nicotine or 100 nM of the α7 nAChR agonist, PNU-282987, before the glutamate insult. Inhibition studies using 10nM methyllycaconitine (MLA) or α-bungarotoxin (α-Bgt) supported the hypothesis that neuroprotection against glutamate-induced excitotoxicity on rat RGCs was mediated through α7 nAChRs. In immunocytochemical studies, double-labeled experiments using antibodies against Thy 1.1 and α7 nAChR subunits demonstrated that both large and small RGCs contained α7 nAChR subunits. The data presented in this study support the hypothesis that ACh and nicotinic acetylcholine receptor (nAChR) agonists provide neuroprotection against glutamate-induced excitotoxicity in adult rat RGCs through activation of α7 nAChR subunits. These studies lay the groundwork required for analyzing the effect of specific α7 nAChR agonists using in vivo models of excitotoxicity. Understanding the type of ACh receptors involved in neuroprotection in the rat retina could ultimately lead to therapeutic treatment for any CNS disease that involves excitotoxicity.
Assuntos
Acetilcolina/farmacologia , Fármacos Neuroprotetores/farmacologia , Receptores Nicotínicos/metabolismo , Retina/citologia , Células Ganglionares da Retina/metabolismo , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Animais , Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Células Cultivadas , Maleato de Dizocilpina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Ácido Glutâmico/toxicidade , Marcação In Situ das Extremidades Cortadas , Masculino , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Ratos , Ratos Long-Evans , Células Ganglionares da Retina/efeitos dos fármacos , Fatores de Tempo , Receptor Nicotínico de Acetilcolina alfa7RESUMO
BACKGROUND: Immunoglobulin (Ig) E plays an important role in the pathogenesis of allergic diseases such as atopic dermatitis and allergic asthma.We previously reported that a sulfate polysaccharide, fucoidan, suppressed IgE production by murine B cells in vitro. However, the mechanism by which fucoidan suppresses IgE production remains unclear. OBJECTIVE: We incorporated sulfate groups into cellulose and studied their biological characteristics in vitro to explore the possibility of converting biologically neutral polysaccharides to active reagents with antiallergic functions. MATERIAL AND METHODS: Cellulose was chemically processed using N,N-dimethylformamide (DMF) and DMF-sulfurtrioxide and recovered as cellulose sulfate with a molecular weight of around 10 kDa. We then studied the effect of cellulose sulfate on IgE production from B cells, IgE class-switching, and populations of IgE-secreting B cells prepared from murine spleen. We also investigated the effects of sulfated cellulose on the production of interleukin (IL) 4 and interferon (IFN) gamma and the expression of T-bet mRNA by splenic T cells. The cytotoxicity of cellulose sulfate was also examined. RESULTS: Cellulose sulfate suppressed IgE production in B cells stimulated with IL-4 and anti-CD40 antibody by inhibiting IgE class-switch recombination and decreasing the number of IgE-secreting B cells in vitro. Moreover, both cellulose sulfate and fucoidan suppressed IL-4 production and enhanced IFN-gamma production by murine T cells stimulated with anti-CD3 and anti-CD28 antibodies, despite the decrease in T-bet mRNA expression. CONCLUSIONS: Cellulose gains an antiallergic effect on B cells and T cells with the addition of sulfate groups.
Assuntos
Linfócitos B/efeitos dos fármacos , Celulose/análogos & derivados , Imunoglobulina E/biossíntese , Animais , Antialérgicos/imunologia , Antialérgicos/farmacologia , Anticorpos/imunologia , Linfócitos B/imunologia , Antígenos CD40/imunologia , Células Cultivadas , Celulose/imunologia , Celulose/farmacologia , Dimetilformamida , Formamidas/química , Imunoglobulina E/imunologia , Interferon gama/imunologia , Interleucina-4/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peso Molecular , Polissacarídeos/imunologia , Polissacarídeos/farmacologia , Baço/efeitos dos fármacos , Baço/imunologia , Proteínas com Domínio T/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
C1 inhibitor (C1-INH) deficiency [hereditary or acquired angio-oedema (HAE or AAE)] is characterized by recurring episodes of subcutaneous or submucosal oedema. Many different mutations in the C1-INH gene have been identified as a cause of HAE. We investigated the molecular basis of the disease in a Japanese woman with sporadic HAE. Direct sequencing of genomic DNA revealed no point mutation in the C1-INH gene. Quantitative real-time PCR showed that the copy number of the C1-INH gene in the patient was half that of a healthy control. Furthermore, we identified a 650-kbp deletion on the chromosome, which included the C1-INH gene. We evaluated the correlation between the patient's attacks and her coagulation activity. The levels of D-dimer were high during the angio-oedema attacks, and often exceeded the normal range even during remission, thus the level of D-dimer reflected the activity of HAE in this patient.
Assuntos
Angioedemas Hereditários/genética , Proteína Inibidora do Complemento C1/genética , Deleção de Sequência , Adulto , Angioedemas Hereditários/sangue , Povo Asiático , Éxons/genética , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Predisposição Genética para Doença , Humanos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Pre-mRNA of serotonin 2C receptor (HTR2C, 5-hydroxytryptamine (serotonin) receptor 2C) undergoes A-to-I type RNA editing, which is a post-transcriptional event leading to the change of genomically encoded information. RNA editing generates various HTR2C isoforms, each of which has distinctive receptor activity. Postmortem, animal, and pharmacological studies have suggested that the altered RNA editing of HTR2C is involved in the pathophysiology of mental disorders, although results remain inconsistent. Here we review the techniques used for estimation of RNA editing of HTR2C. Among the techniques reported so far, a high-throughput sequencing-based method would be the most powerful method of choice for the large-scale experiments. Several different methods that were previously developed, such as pyrosequencing and capillary electrophoresis, should be suitable for validation as well as for rapid screening or exploratory purposes.
Assuntos
Eletroforese Capilar/métodos , Técnicas Genéticas , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Edição de RNA , Receptor 5-HT2C de Serotonina/genética , Animais , Sequência de Bases , Humanos , Dados de Sequência Molecular , Receptor 5-HT2C de Serotonina/metabolismoRESUMO
Although endovascular surgery is now widely used to treat intracranial aneurysms, no comparative studies of clipping versus endovascular surgery to address distal ACA aneurysms at the same institution are available. We compared the results of these treatment modalities to address distal ACA aneurysms at our institution. We treated 68 patients with ruptured distal ACA aneurysms (endovascular surgery, n=13; clipping surgery, n=55). We performed a retrospective comparison of the treatment outcomes. To study the efficacy of endovascular surgery we classified all our cases into three types: type A were small-necked aneurysms, type B were wide-necked aneurysms on the parent artery, and type C were aneurysms in which the A3 portion of the ACA arose from the aneurysmal dome near the neck. Intraoperative hemorrhage occurred in 7.7% of aneurysms treated by endovascular surgery and in 34.5% treated by clipping surgery. In 7.7% of the endovascularly-treated aneurysms we noted coil migration during embolization surgery; venous infarction due to cortical vein injury occurred in 7.3% of clipped aneurysms. Of the endovascularly-treated aneurysms, 7.7% manifested post-embolization hemorrhage; 23.1% manifested coil compaction. In clipping surgery, postoperative rerupture occurred in 1.8% of the aneurysms; one patient presented with postoperative acute epidural hematoma. Clip dislocation was noted in 1.8% of aneurysms. Angiography was indicative of post-treatment vasospasm in 7.7% of aneurysms treated endovascularly and in 50.9% of the clipped aneurysms. The clinical outcome showed no significant difference between endovascular surgery and clipping surgery.
Assuntos
Aneurisma Roto/cirurgia , Aneurisma Roto/terapia , Embolização Terapêutica , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/diagnóstico por imagem , Angiografia Cerebral , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Instrumentos Cirúrgicos , Resultado do TratamentoRESUMO
MicroRNA (miRNA; miR) is a class of small regulatory RNA molecules, the aberrant expression of which can lead to the development of cancer. We recently reported that overexpression of miR-21 and/or miR-155 leads to activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway in malignant lymphomas expressing CD3(-)CD56(+) natural killer (NK) cell antigen. Through expression analysis, we show in this study that in both NK/T-cell lymphoma lines and samples of primary lymphoma, levels of miR-150 expression are significantly lower than in normal NK cells. To examine its role in lymphomagenesis, we transduced miR-150 into NK/T-cell lymphoma cells, which increased the incidence of apoptosis and reduced cell proliferation. Moreover, the miR-150 transductants appeared senescent and showed lower telomerase activity, resulting in shortened telomeric DNA. We also found that miR-150 directly downregulated expression of DKC1 and AKT2, reduced levels of phosphorylated AKT(ser473/4) and increased levels of tumor suppressors such as Bim and p53. Collectively, these results suggest that miR-150 functions as a tumor suppressor, and that its aberrant downregulation induces continuous activation of the PI3K-AKT pathway, leading to telomerase activation and immortalization of cancer cells. These findings provide new insight into the pathogenesis of malignant lymphoma.
Assuntos
Genes Supressores de Tumor , Linfoma de Células T/genética , MicroRNAs/fisiologia , Apoptose , Proteínas de Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células , Senescência Celular , Humanos , Linfoma de Células T/patologia , Linfoma de Células T/prevenção & controle , MicroRNAs/análise , Proteínas Nucleares/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/genética , TelômeroRESUMO
We present optical conductivity studies of the type-I clathrate Ba8Ga16Sn30, using a terahertz time-domain spectrometer (0.3-3.0 THz). The lowest-lying spectral peak at 0.72 THz due to the Ba(2) ion's off-center vibration in the oversized cage shows a drastic and anomalous temperature dependence. Below about 100 K, the single broad peak splits into two subpeaks, and with further lowering of the temperature, the spectral shape of this so-called rattling phonon shows non-Boltzmann broadening to the point that the linewidth becomes comparable to the peak frequency. Whereas the initial splitting can be understood by assuming a multiwell anharmonic potential, the strong linewidth broadening toward low temperature cannot, since the Boltzmann factor generally sharpens the low-temperature spectra. The observed behavior suggests strong interaction between the local anharmonic phonons and other excitations.
RESUMO
Bipolar disorder (BD) is a severe mental disorder characterized by recurrent episodes of mania and depression. Serotonin transporter (HTT) is a target of antidepressants and is one of the strongest candidate molecules of mood disorder, however, genetic study showed equivocal results. Here, we performed promoter-wide DNA methylation analysis of lymphoblastoid cell lines (LCLs) derived from two pairs of monozygotic twins discordant for BD. To rule out the possible discordance of copy number variation (CNV) between twins, we performed CNV analysis and found the copy number profiles were nearly identical between the twin pairs except for immunoglobulin-related regions. Among the three genes we obtained as candidate regions showing distinct difference of DNA methylation between one of the two pairs, hypermethylation of SLC6A4, encoding HTT, in the bipolar twin was only confirmed by bisulfite sequencing. Then, promoter hypermethylation of SLC6A4 in LCLs of BD patients was confirmed in a case-control analysis. DNA methylation of SLC6A4 was significantly correlated with its mRNA expression level in individuals with the S/S genotype of HTTLPR, and mRNA expression level was lower in BD patients carrying the S/S genotype. Finally, DNA methylation of the same site was also higher in the postmortem brains of BD patients. This is the first study to report the role of epigenetic modification of SLC6A4 in BD using an unbiased approach, which provides an insight for its pathophysiology.
Assuntos
Transtorno Bipolar/genética , Metilação de DNA/genética , Doenças em Gêmeos , Epigenômica/métodos , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Transtorno Bipolar/metabolismo , Estudos de Casos e Controles , Linhagem Celular Transformada , Epigenômica/instrumentação , Feminino , Predisposição Genética para Doença , Humanos , Ativação Linfocitária/genética , Masculino , Pessoa de Meia-Idade , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Gêmeos MonozigóticosRESUMO
BACKGROUND: The evaluation of disease severity and activity of chronic urticaria (CU) is essential for the adequate treatment of patients. However, there is no reliable biomarker for such evaluations. Recently, markers of blood coagulation and fibrinolysis have been revealed to be elevated in severe cases of CU. In this article, we studied the coagulation/fibrinolysis and inflammation markers and their relationship to disease activity in patients with CU. METHODS: Plasma fibrin degradation products (FDP), d-dimer and serum C-reactive protein (CRP) were measured with the assessment of disease severity and skin reaction to autologous serum in 82 patients with CU and 37 patients with acute urticaria, idiopathic angioedema (AE) or inducible types of urticaria (IU). RESULTS: The levels of FDP in patients with CU were significantly higher than those in patients with IU, but no other differences in FDP, d-dimer and CRP were observed among patients with different types of urticaria. These markers of patients with CU were well correlated with each other and significantly associated with disease severity of CU, but not with skin reactions to autologous serum. In 37 patients with CU, levels of all these parameters reduced as their disease condition improved, while they increased when the disease became aggravated. Regarding FDP, this relationship was observed even if FDP concentrations were within normal range throughout the study. CONCLUSIONS: The measurement of plasma FDP, d-dimer and serum CRP may be useful for the assessment of disease activity of CU.