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1.
Rinsho Ketsueki ; 64(11): 1426-1430, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-38072429

RESUMO

A 43-year-old man presenting with oral bleeding was diagnosed with acute promyelocytic leukemia (APL). Induction chemotherapy consisting of all-trans retinoic acid and idarubicin was initiated, and disseminated intravascular coagulation (DIC) was treated with fresh frozen plasma and recombinant thrombomodulin infusions. The patient was free from neurological symptoms throughout the clinical course. However, cerebral hemorrhagic lesions were detected incidentally on magnetic resonance imaging performed to screen for leukemic central nervous system invasion at 2 weeks after treatment initiation. Imaging findings suggested subacute or later-phase cerebral hemorrhage. Platelet transfusions and other supportive care was provided. Serial imaging evaluations confirmed reduction of the hemorrhagic lesions. Hematological remission was achieved after induction chemotherapy, and no symptoms due to cerebral hemorrhage developed during the subsequent consolidation therapy. As patients with APL characteristically experience hemorrhagic events due to bleeding tendency caused by DIC, physicians should be aware of the possibility of asymptomatic cerebral hemorrhage in these patients.


Assuntos
Coagulação Intravascular Disseminada , Transtornos Hemorrágicos , Leucemia Promielocítica Aguda , Masculino , Humanos , Adulto , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/tratamento farmacológico , Coagulação Intravascular Disseminada/etiologia , Tretinoína/uso terapêutico , Hemorragia Cerebral/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
2.
Exp Hematol ; 116: 37-49, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36191884

RESUMO

We report the establishment of a novel activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) cell line, designated as TMD12, from a patient with highly refractory DLBCL. ABC-DLBCL is a subtype with a relatively unfavorable prognosis that was originally categorized using gene expression profiling according to its cell of origin. TMD12 cells were isolated from the pleural effusion of the patient at relapse and passaged continuously in vitro for >4 years. The cells displayed cluster of differentiation (CD)19, CD20, CD22, CD38, human leukocyte antigen-DR isotype, and κ positivity and CD5, CD10, CD23, and λ negativity, as detected using flow cytometric analysis. The chromosomal karyotypic analysis, including the spectral karyotyping method, confirmed t(1;19)(q21:q13.1), del(6q23), gain of chromosome 18, and other abnormalities. Mutation analyses, including whole-exome sequencing, revealed that TMD12 cells harbored mutations in MYD88 and CD79B, indicating an ABC subtype. TMD12 cells exhibited chronic active B-cell receptor signaling and constitutive activation of the nuclear factor κB pathway, which is typically associated with sensitivity to a specific Bruton tyrosine kinase inhibitor, ibrutinib. Intriguingly, TMD12 cells displayed moderate resistance to ibrutinib and lacked activation of Janus kinase/signal transducers and activators of transcription 3 signaling, another hallmark of this DLBCL subtype. Treatment with an inhibitor against tumor progression locus 2 (TPL2), a multifunctional intracellular kinase that is activated particularly downstream of Toll-like receptors or MYD88 and IκB kinase α/ß (IKKα/ß), suppressed the proliferation of TMD12 cells, implying the possible involvement of the TPL2-p105 pathway in the tumorigenesis of ABC-DLBCL. Because only a limited number of ABC-DLBCL cell lines are currently available, TMD12 cells might provide a useful tool in the search for novel druggable targets for this intractable lymphoma.


Assuntos
Linfoma Difuso de Grandes Células B , Fator 88 de Diferenciação Mieloide , Humanos , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Recidiva Local de Neoplasia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfócitos B/metabolismo , Linhagem Celular , Linhagem Celular Tumoral
3.
Rinsho Ketsueki ; 63(4): 260-264, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35491214

RESUMO

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolysis, thrombosis, and bone marrow failure. Infection, pregnancy, and surgical operation have the potential to evoke severe episodes of hemolysis and thrombosis. Therefore, the use of an antibody agent against complement component 5 (C5), eculizumab, one day before the operation is recommended. Ravulizumab is a newly approved long-acting antibody agent against C5. Thus, little is known about perioperative management with ravulizumab. We experienced a 43-year-old female patient who safely underwent laparoscopic cholecystectomy under ravulizumab treatment for PNH. Ravulizumab was administered one day before the operation. Laparoscopic cholecystectomy for cholelithiasis was performed under intravenous anesthesia, intermittent air compression of the lower extremities, and low pneumoperitoneum pressure. Additionally, heparin was administered, and the patient left the sickbed early without significant postoperative complications. Like eculizumab, complement inhibition by ravulizumab is also considered effective in the perioperative management of patients with PNH. However, close cooperation with surgeons and anesthesiologists and careful management based on clinical symptoms and laboratory data such as LDH, CH50, and D-dimer are essential.


Assuntos
Colecistectomia Laparoscópica , Hemoglobinúria Paroxística , Trombose , Adulto , Anticorpos Monoclonais Humanizados , Colecistectomia Laparoscópica/efeitos adversos , Feminino , Hemoglobinúria Paroxística/complicações , Hemoglobinúria Paroxística/tratamento farmacológico , Hemólise , Humanos , Gravidez , Trombose/etiologia
4.
Neuropsychopharmacol Rep ; 41(2): 179-184, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33606356

RESUMO

AIM: As an emergency measure during the coronavirus disease pandemic, the monitoring interval for clozapine use was temporarily extended beyond the regulatory requirement in Japan, which is the safest monitoring interval worldwide. In this study, we aimed to explore the effect of this measure on patients undergoing clozapine treatment. METHODS: This retrospective chart review study included patients with treatment-resistant schizophrenia (TRS) who were undergoing clozapine treatment at four psychiatric institutions in Japan. Demographic characteristics and clinical information of these patients were collected on April 27, 2020, when Japanese psychiatrists were virtually allowed to prescribe clozapine beyond the regulatory requirement. Furthermore, information of adverse events related to the emergency measure was collected and analyzed. RESULTS: Of the 41 patients with TRS included in this study, 19 patients underwent extended hematological monitoring during clozapine treatment. No psychiatric or hematological adverse events were observed in the patients during the extended monitoring interval. CONCLUSION: This study suggested that there were few adverse events of clozapine-treated patients related to emergency measures in Japan. However, hematological monitoring intervals during clozapine treatment have been emergently extended worldwide; hence, it is necessary to verify the results of these measures.


Assuntos
Agranulocitose/epidemiologia , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Esquizofrenia/tratamento farmacológico , Adulto , Agranulocitose/induzido quimicamente , COVID-19 , Monitoramento de Medicamentos/normas , Feminino , Humanos , Japão/epidemiologia , Masculino , Estudos Retrospectivos , SARS-CoV-2
5.
Environ Health Prev Med ; 21(6): 460-469, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27448295

RESUMO

OBJECTIVE: This study aimed to examine epidemiologically socio-environmental factors associated with diabetes mellitus among patients hospitalized with schizophrenia in Japan. METHODS: This was a cross-sectional study from a single psychiatric hospital. Study patients were adults aged ≥20 years who were hospitalized with schizophrenia one or more times between January 2013 and December 2014. From electronic medical records or health insurance claims, we extracted schizophrenia patients with an F2 code according to ICD-10, and assessed the association of various factors with diabetes mellitus among these patients in a multivariable analysis. RESULTS: During the 2-year period, there were 1899 patients hospitalized with a psychiatric disorder one or more times. Of them, a total of 770 adults with schizophrenia (285 men and 485 women) were eligible for our analysis. The standardized prevalence ratio of diabetes mellitus was 2.0 [95 % confidence interval (CI) 1.6-2.5] among men and 3.0 (95 % CI 2.5-3.6) among women in this hospital. There were no socio-environmental factors associated with diabetes mellitus among men. Among women, factors such as a 730-day hospitalization [adjusted odds ratio (OR) 3.82: 95 % confidence interval (CI) 1.52-9.64], and a medical protection/compulsory/discrimination hospitalization (adjusted OR 0.60, 95 % CI 0.36-0.99) were associated with diabetes mellitus. Compared with women living alone, those who were unmarried and lived together with someone had a significantly lower adjusted OR (0.41, 95 % CI 0.21-0.81). CONCLUSIONS: Socio-environmental factors such as length of hospitalization, type of hospitalization, and marital status and living arrangement were associated with diabetes mellitus among hospitalized women with schizophrenia.


Assuntos
Diabetes Mellitus/epidemiologia , Hospitalização/estatística & dados numéricos , Esquizofrenia/epidemiologia , Fatores Socioeconômicos , Adulto , Idoso , Estudos Transversais , Diabetes Mellitus/etiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Esquizofrenia/etiologia , Adulto Jovem
6.
J Plast Reconstr Aesthet Surg ; 65(2): 252-5, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21795130

RESUMO

BACKGROUND: Purpura fulminans (PF) is a rare syndrome of intravascular thrombosis and haemorrhagic infarction of the skin. The initial symptom of PF is peripheral purpura which progresses to necrosis very rapidly. The prognosis of PF is poor, and the mortality is reported to be around 40%. Even if the patient survives, the patient may require amputation or reconstruction for limbs and facial necrosis. CASE REPORT: A 48-year-old male suffered from PF following a left cerebellopontine angle tumour excision. His nose and upper lip fell into necrosis afterwards. We performed nose and upper lip reconstruction at 8 months after the onset. We used a forehead flap for the nasal reconstruction and a free forearm flap for the lining. His upper lip was reconstructed with bilateral nasolabial orbicularis oris myocutaneous flaps. RESULTS: The colour and texture match of the reconstructed nose and lip is good. He could open his mouth wide enough and close completely. CONCLUSIONS: Facial reconstruction after PF is very difficult, because the patient has extensive scarring around the defect and there is little intact facial tissue. However, we performed a facial reconstruction using local flaps as much as possible, and obtained good results.


Assuntos
Lábio/cirurgia , Músculo Esquelético/transplante , Nariz/cirurgia , Púrpura Fulminante/cirurgia , Rinoplastia/métodos , Transplante de Pele/métodos , Retalhos Cirúrgicos , Seguimentos , Antebraço/cirurgia , Testa/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade
7.
Pediatr Neurol ; 45(5): 344-6, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22000319

RESUMO

We describe an 8-year-old girl with the mildest form of acute necrotizing encephalopathy, associated with pandemic influenza A. She manifested a convulsion engendering deterioration of consciousness, although cranial computed tomography and magnetic resonance imaging within 4 hours after the convulsion revealed no abnormalities. Cranial magnetic resonance imaging 20 hours after the convulsion revealed lesions of the thalamus bilaterally, brainstem tegmentum, internal capsule, and white matter. She was diagnosed with acute necrotizing encephalopathy. Typically, the prognosis of acute necrotizing encephalopathy with a brainstem lesion is poor. Nevertheless, she recovered almost completely, after early intervention with pulsed methylprednisolone and high-dose γ-globulin therapy. She manifested a thermolabile phenotype of carnitine palmitoyltransferase II variants such as cystine-isoleucine-methionine phenotype type 9 (FVM-CIM; Phe352Cys-Val388Ile-Met647Met alleles), resulting in a predisposition to encephalopathy during influenza infection. This case is the first, to the best of our knowledge, of pandemic influenza A-associated acute necrotizing encephalopathy with a good outcome despite severe magnetic resonance imaging findings.


Assuntos
Vírus da Influenza A , Influenza Humana/diagnóstico , Leucoencefalite Hemorrágica Aguda/diagnóstico , Pandemias , Criança , Feminino , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Humana/complicações , Leucoencefalite Hemorrágica Aguda/etiologia
8.
J Plast Surg Hand Surg ; 45(2): 66-71, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21504275

RESUMO

We describe a new way to raise the V-Y advancement flap, which is useful for reconstruction of the lower lip. Various other methods have been reported in the past, but it has been necessary to choose the most suitable method for each particular case. A V-Y advancement flap from the submandibular region is one of the useful techniques to reconstruct the lower lip, and it is suitable for a wide horizontal defect. However, the conventional V-Y flap is insufficiently mobile and the reconstructed vermilion is thin because of the limitation of the pedicle. In such a case, the reconstructed lip may sag or cause an embarrassing defect. We developed a new way to raise the flap to obviate these problems. We use the V-Y advancement flap from the inferior margin of the defect in a conventional way after excision of the tumour, and use a mucosal flap to reconstruct the vermilion border. The skin side of the V-Y flap is undermined, and the orbicularis oris muscles are preserved on both sides as pedicles. The flap is then raised as a bipedicled musculocutaneous flap, which has adequate movement. After the flap has been sutured, the superior margin of the flap is de-epithelialised, and used to create the volume of the vermilion border. Functionally and cosmetically good results were achieved.


Assuntos
Músculos Faciais/transplante , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estética , Músculos Faciais/irrigação sanguínea , Feminino , Humanos , Neoplasias Labiais/patologia , Neoplasias Labiais/cirurgia , Masculino , Recuperação de Função Fisiológica , Medição de Risco , Técnicas de Sutura , Cicatrização/fisiologia
9.
Brain Dev ; 33(6): 530-3, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20926212

RESUMO

Congenital infection-like syndrome includes multiple disorders. Although novel syndromes have recently been described and their genetic defects identified, many cases remain unclassified. Here we report a patient with neuroradiologic findings of intracranial calcification and cerebellar hypoplasia, and clinical features of growth retardation, progressive pancytopenia, interstitial pneumonia, and immune abnormality. Our patient had a phenotypic overlap with Aicardi-Goutières syndrome and Hoyeraal-Hreidarsson syndrome, despite the absence of mutation in their responsible genes.


Assuntos
Calcinose , Córtex Cerebral/patologia , Infecções/genética , Doenças Autoimunes do Sistema Nervoso/genética , Doenças Autoimunes do Sistema Nervoso/patologia , Cerebelo/anormalidades , Disceratose Congênita/genética , Disceratose Congênita/patologia , Evolução Fatal , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/patologia , Humanos , Lactente , Infecções/fisiopatologia , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Masculino , Microcefalia/genética , Microcefalia/patologia , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/patologia , Síndrome
10.
Protein Expr Purif ; 71(1): 85-90, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20045733

RESUMO

Riboflavin-binding protein (RBP) is a glycophosphoprotein found in hen eggs. We previously identified the extraordinary characteristic of RBP in reducing bitterness. For a more detailed study on the mode of action and industrial application of this characteristic, we investigated the microbial production of recombinant RBP (rRBP). We constructed a chicken RBP gene expression vector by inserting the RBP cDNA in pNCMO2, the Escherichia coli-Brevibacillus choshinensis shuttle vector. B. choshinensis HPD31 transformants produced 0.8g/l of processed and unglycosylated RBP in a soluble form in the culture supernatant. However, the expressed RBP was partially dimerized and monomeric RBP was purified by two step anion-exchange and gel-filtration chromatographies. The purified rRBP elicited bitterness reduction against quinine and caffeine, although it largely lost its riboflavin-binding ability. These results indicated that glycosylation and riboflavin-binding ability are not essential for the bitterness reduction of RBP. In addition, we assessed the usefulness of the Brevibacillus system for the expression and secretion of RBP as a new type of bitterness inhibitor.


Assuntos
Bioquímica/métodos , Brevibacterium/metabolismo , Espaço Extracelular/metabolismo , Proteínas de Membrana Transportadoras/biossíntese , Proteínas de Membrana Transportadoras/farmacologia , Paladar/efeitos dos fármacos , Animais , Técnicas de Cultura de Células , Galinhas , Proteínas de Membrana Transportadoras/isolamento & purificação , Ligação Proteica , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Riboflavina/metabolismo , Fatores de Tempo
11.
Brain Dev ; 32(4): 285-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20005652

RESUMO

We report here an autopsy case of perinatal hypoxic brain damage showing hypoglossal hypoplasia and hyperplasia of the area postrema (AP) in the medulla oblongata. A 16-year-old girl who suffered from severe psychomotor developmental delay, epilepsy and tongue fasciculation, was shown by pathology to have a medullary change, as well as tongue atrophy and severe sclerotic changes in the cerebrum and cerebellum. Moderate to severe neuronal loss and gliosis were found in the brainstem. But neurons were preserved in the trigeminal nuclei, abducens nucleus and dorsal vagal nucleus. We performed a preliminary immunohistochemical analysis of sections of the medulla oblongata in our case, normal controls and disease controls with perinatal hypoxic ischemic encephalopathy (HIE). The normal and disease controls showed neither hypoglossal hypoplasia nor AP hyperplasia. The combination of hypoglossal hypoplasia and AP hyperplasia is unique and intriguing, and further analysis of the AP is required to understand developmental brain disorders.


Assuntos
Área Postrema/patologia , Hiperplasia , Hipóxia Encefálica , Adolescente , Evolução Fatal , Feminino , Idade Gestacional , Humanos , Hiperplasia/etiologia , Hiperplasia/patologia , Hipóxia Encefálica/complicações , Hipóxia Encefálica/patologia , Recém-Nascido
12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 30(3): 284-9, 2008 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-18686606

RESUMO

OBJECTIVE: To transfect human alpha1, 2-fucosyltransferase (alpha1, 2-FT) gene to ovarian cancer cell line RMG-I and investigate the antigenic expression change of Lewis y and the other related oligosaccharides. METHODS: The expression vector pcDNA3.1(-)-HFUT-H was constructed by polymerase chain reaction (PCR) to clone human alpha1, 2-FT gene coding region. The alpha1, 2-FT gene stable high-expression cell line RMG-I-H was established by transfecting pcDNA3.1(-)-HFUT-H to ovarian cell line RMG-I. The change of alpha1, 2-FT activity in the cell line before and after the tranfection was confirmed by the determination of enzymatic activity. The changes of cell lipid and glucolipid, especially the change of type II oligosaccharide, in the cell line before and after the transfection was determined by Thin-Layer Chromatography (TLC) and TLC immunostaining method, respectively. RESULTS: The H-1 antigen and Lewis y antigen were obviously increased in the cell line RMG-1-H, especially the latter one, which was 20 times higher than before, and the type I saccharide chain Lewis b was decreased significantly. The main lipid components on the cell membrane, cholesterol and phosphatides, showed no change in the cell lines before and after the transfection, and the neutral glycolipid also showed no obvious change. CONCLUSIONS: The transfection of alpha1, 2-FT gene can increase the activity of alpha1, 2-FT in the cell line RMG-I and mainly increase the expression of Lewis y antigen simultaneously. The construction of RMG-I Lewis y high expression cell line provides a cell model for further study on the relationship between Lewis y antigen and biological behaviors in the ovarian cancer.


Assuntos
Fucosiltransferases/fisiologia , Antígenos do Grupo Sanguíneo de Lewis/metabolismo , Neoplasias Ovarianas/metabolismo , Transfecção/métodos , Linhagem Celular Tumoral , Cromatografia em Camada Fina , Feminino , Fucosiltransferases/genética , Humanos
13.
J Chromatogr B Analyt Technol Biomed Life Sci ; 852(1-2): 367-73, 2007 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-17383243

RESUMO

Changes in the molecular species of lipids associated with Pex2 gene-mutation were investigated to elucidate the pathogeneses of peroxisome biogenesis disorders. Although no differences were observed in the concentrations of cholesterol and phosphatidyl choline between mutated Z65 and control CHO-K1 cells, the amounts of cholesterol esters and glycolipids in Z65 cells were twice those in CHO-K1 cells, but phosphatidyl ethanolamine (PE), particularly 1-O-octadec-1'-enyl-2-oleoyl PE, was absent in Z65 cells by FABMS. Enhanced synthesis of glycolipids in Z65 cells was associated with an abundance of lignoceric acid-containing ones, suggesting a role of glycolipids in the retention of longer saturated fatty acids.


Assuntos
Glicolipídeos/metabolismo , Peroxissomos/fisiologia , Plasmalogênios/metabolismo , Espectrometria de Massas de Bombardeamento Rápido de Átomos/métodos , Animais , Células CHO , Cromatografia em Camada Fina , Cricetinae , Cricetulus , Glicolipídeos/classificação , Plasmalogênios/classificação
14.
Dermatology ; 212(4): 361-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16707886

RESUMO

BACKGROUND: Systemic corticosteroids are one of the most commonly used therapeutic modalities for patients with extensive alopecia areata (AA), although they entail several drawbacks. OBJECTIVE: To determine the best modality for systemic corticosteroid use in terms of their efficacy, relapse rate, and side effects. METHODS: Fifty-one patients with single or multiple AA (AA/multiplex) and 38 patients with alopecia totalis or AA universalis (AA totalis/universalis) were enrolled in this open study. They were randomly divided into three groups depending on the time of their initial visit. They were administered (1) oral dexamethasone (Dex) 0.5 mg/day for 6 months (Dex group), (2) intramuscular triamcinolone acetonide (imTA) 40 mg once a month for 6 months followed by 40 mg once every 1.5 months for 1 year (imTA group), and (3) pulse therapy (PT) using oral predonine 80 mg for 3 consecutive days once every 3 months (PT group). After the treatment, each treatment modality was evaluated by the response rate, relapse rate, and side effect profile. RESULTS: The response rate of AA/multiplex was significantly better in the imTA group than in the Dex group. The overall relapse rate and that of AA totalis/universalis were significantly better in the PT group than in the Dex group. Dysmenorrhea was the most common and problematic side effect. Impairment of the adrenocortical reserve was seen in 7% of the PT group and 23% of the imTA group, which was recovered without any further medical treatment. CONCLUSION: imTA or pulse therapy is effective for AA and has an acceptable level of side effects. The development of a new strategy to reduce the relapse rate is needed.


Assuntos
Alopecia em Áreas/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Prednisolona/uso terapêutico , Triancinolona Acetonida/uso terapêutico , Administração Oral , Adolescente , Adulto , Anti-Inflamatórios/efeitos adversos , Dexametasona/efeitos adversos , Quimioterapia Combinada , Feminino , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Humanos , Injeções Intramusculares , Japão , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Falha de Tratamento , Resultado do Tratamento , Triancinolona Acetonida/efeitos adversos
15.
No To Hattatsu ; 37(5): 407-12, 2005 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-16164247

RESUMO

Spinal muscular atrophy (SMA) is a common autosomal recessive disorder, caused by homozygous deletion of the survival motor neuron gene 1 (SMN1). SMN2, a gene highly homologous to SMN1, is considered to influence the severity of SMA. Patients with SMA have been classified into three types on the basis of age at onset and clinical severity. In the present study, we performed a quantitative analysis of SMN2 in 22 patients of SMA to further clarify the correlation between clinical severity and SMN2 gene dosage. We determined the SMN2 gene copy number based on real-time PCR. In 3 Type I patients with only one SMN2 copy, the clinical phenotype was the severest. The remaining 14 Type I patients had two or three copies of the SMN2 gene, and showed a variable clinical severity. A patient with 3 copies required artificial ventilation at 2 months old. Five Type II and Type III patients had at least 4 copies of the SMN2 gene. Although the SMN2 gene dosage correlates the clinical severity, the mechanism by which SMN2 shows compensation in some Type I patients remains to be determined.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Dosagem de Genes , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA/genética , Índice de Gravidade de Doença , Atrofias Musculares Espinais da Infância/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Reação em Cadeia da Polimerase/métodos , Proteínas do Complexo SMN , Proteína 1 de Sobrevivência do Neurônio Motor , Proteína 2 de Sobrevivência do Neurônio Motor
16.
Shi Yan Sheng Wu Xue Bao ; 38(6): 536-44, 2005 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-16416971

RESUMO

MFUT-II, a DNA fragment encoding murine alpha1,2-fucosyltransferase,was cloned by RT-PCR. The open-reading frame was ligated into mammalian expression vector pcDNA 3.1 (pcDNA3.1-MFUT-II) and was transiently transfected into COS-7 cells using a Cellphect Transfection kit. Moreover, the expression of the gene in murine tissues was analyzed with Northern hybridization showing a 3.5-Kb mRNA transcript product in several tissues. The existence of MFUT-II was detected by Southern blot. MFUT-II was found to be a new member of the murine alpha1,2-FT gene family. Its open reading frame encoded 347 amino acids with a predicted molecular mass of 39.21 kDa and exhibited sequence homology with murine H & Sec1 gene. MFUT-II also exhibited sequence homology with Human Se gene (79.0%), Rat FTB gene (89.0%) and Rabbit FT-III gene (77.0%), respectively. COS-7 cells transfected with pcDNA3.1-MFUT- II showed alpha 1,2-fucosyltransferase activity. Southern analysis revealed that MFUT-II was present in the mouse genome as a single-copy gene. In conclusion, MFUT-II was a murine Se gene.


Assuntos
Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Regulação Enzimológica da Expressão Gênica , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Southern Blotting , Células COS , Chlorocebus aethiops , Clonagem Molecular , Fucosiltransferases/química , Humanos , Camundongos , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Coelhos , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-318820

RESUMO

<p><b>OBJECTIVE</b>To compare the substrate specificity of three murine GDP fucose: beta-galactoside alpha1,2-fucosyltransferases (alpha1,2-FT).</p><p><b>METHODS</b>Three members of MFUT- I, -II and -III, coding for a alpha1,2-FT, a GDP-fucose, were cloned from a cDNA of murine small intestine by reverse transcription-polymerase chain reaction. The coding regions were ligated into mammalian expression vector pcDNA 3.1 (pcDNA3.1-MFUT-I, pcDNA3.1-MFUT- II , and pcDNA3.1-MFUT- III) and were transiently transfected into COS-7 cells using a cellphect transfection kit. Then the cells were analyzed for expression and function of alpha1,2-FT and the substrate specificity of three alpha1,2-FT was compared.</p><p><b>RESULTS</b>MFUT- I, -II, and -III exhibited sequence homology with human H (77%), Se (79%), and Sec1 (75%) genes, respectively. COS-7 cells transfected with pcDNA3.1-MFUT- I and pcDNA3.1-MFUT- II showed alpha1,2-FT activity, but no activity was detected in COS-7 cells transfected with pcDNA3.1- MFUT-III. MFUT- II showed alpha1,2-FT activity with both asialo-monosialoteterahexosyl ganglioside (GA1) and monosialoteterahexosyl ganglioside (GM1) as substrates to produce fucosyl GA1(FGA1) and fucosyl GM1(FGM1), respectively, but MFUT- I only showed alpha1,2-FT activity with GA1. The relative activity of MFUT- II with GA1 was 80-90-folds higher compared with MFUT- I, and the relative activity of MFUT- II with GA1 was 10-20-folds higher than that of GM1. The fucosyltransferase encoded by the MFUT- II gene showed the enzyme activity not only responsible for the synthesis of type 4-H antigens FGA1 and FGM1, but also responsible for the synthesis of type 1-H and 2-H antigens with lactotetraosylceramide and neolactotetraosylceramide as substrates.</p><p><b>CONCLUSION</b>MFUT- II is the main alpha1,2-FT in mouse and MFUT- II can product type 4-H antigen FGA1 and FGM1, but MFUT- I only synthesizes FGA1. MFUT-III has no alpha1,2-FT activity.</p>


Assuntos
Animais , Camundongos , Antígenos de Bactérias , Células COS , Chlorocebus aethiops , Clonagem Molecular , Fucosiltransferases , Química , Genética , Metabolismo , Gangliosídeos , Metabolismo , Especificidade por Substrato , Transfecção
18.
Lipids ; 39(1): 43-50, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15055234

RESUMO

We investigated lipid composition and FA metabolism in Chinese hamster ovary CHO-K1) cells and Pex5-mutated CHO-K1 (ZP102) cells to clarify the biochemical bases of peroxisome biogenesis disorders (PBD). ZP102 cells have defective peroxisomes and exhibit impairments of peroxisomal beta-oxidation of FA and plasmalogen biosynthesis. In addition, we identified FA metabolic alterations in the synthesis of several classes of lipids in ZP102 cells. The concentration of FFA in ZP102 cells was twice that in CHO-K1 cells, but methyl esters and TAG were decreased in ZP102 cells in comparison with control cells. Also, ceramide monohexoside (CMH) concentration with ZP102 cells was significantly increased compared with the control cells. The FA molecular species, particularly the saturated to unsaturated ratios, of individual lipids also differed between the two cell types. The rate of incorporation of [14C]-labeled saturated acids into sphingomyelin (SM) and CMH in ZP102 cells was higher than that in CHO-K1 cells. Lignoceric acid incorporated into cells was predominantly utilized for the synthesis of SM at 24 h after removal of [14C]lignoceric acid from the culture medium. ZP102 cells showed higher fluorescence anisotropy of 1,3,5-diphenylhexatriene, corresponding to lower membrane mobility than in CHO-K1 cells. In particular, alteration of lipid metabolism by a Pex5 mutation enhanced metabolism of saturated FA and sphingolipids. This may be related to the reduced membrane fluidity of ZP102 cells, which has been implicated in the dysfunction of membrane-linked processes in PBD.


Assuntos
Ácidos Graxos/metabolismo , Fluidez de Membrana , Peroxissomos/genética , Animais , Células CHO , Isótopos de Carbono , Cricetinae , Cricetulus , Metabolismo dos Lipídeos , Mutação , Peroxissomos/metabolismo
19.
Gynecol Oncol ; 87(3): 295-302, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12468328

RESUMO

OBJECTIVE: The objective of this study was to determine whether sonographically depicted ovarian tumor growth is fractal, and the mean fractal dimension differs according to stages of the disease and histologic types. METHODS: The fractal dimensions of outlines of sonographically depicted solid components in 160 ovarian tumors were measured using a box-counting method. RESULTS: The mean fractal dimensions of the surface of intracystic solid components in serous, mucinous, endometrioid, and clear cell adenocarcinoma were 1.259, 1.243, 1.238, and 1.182, respectively. These values were significantly greater than the topological dimension of a line (=1). The value was significantly higher in stage I or II (1.381) than stage III or IV (1.205) in serous carcinoma (P = 0.02), but not significantly different in clear cell carcinoma (1.187 and 1.172, respectively). In stage I or II, the value of serous carcinoma (1.381) was significantly higher than that of clear cell carcinoma (1.187) (P = 0.03). The value of mucinous cystadenoma of low malignant potential was 1.337, which was also significantly greater than 1. The mean fractal dimensions of outlines of solid tumors in cases with dysgerminoma and thecoma-fibroma were 1.036 and 1.023, respectively. These values were not significantly different from 1. CONCLUSION: This study shows that the surface of solid components in cystic epithelial ovarian cancers has a fractal structure, and the mean fractal dimension may differ according to stages of the disease and histologic types. Fractal geometry, a vocabulary of irregular shapes, can be useful for describing the pathological architecture of ovarian tumors and for yielding insights into the mechanisms of tumor growth.


Assuntos
Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Divisão Celular/fisiologia , Cistadenocarcinoma Mucinoso/diagnóstico por imagem , Cistadenocarcinoma Mucinoso/patologia , Disgerminoma/diagnóstico por imagem , Disgerminoma/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumor da Célula Tecal/diagnóstico por imagem , Tumor da Célula Tecal/patologia , Ultrassonografia
20.
Transplantation ; 74(4): 543-50, 2002 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-12352917

RESUMO

BACKGROUND: Infection is a serious complication after liver transplantation. Immunization is one means of controlling infections. The objective of this study was to investigate the efficacy and safety of simultaneous administration of several vaccines before transplantation and the efficacy and safety of administration under immunosuppressive conditions after transplantation. METHODS: Fifty-eight patients who underwent living-related liver transplantation between April 1994 and March 2000 were included in this study. Simultaneous administration of a maximum of six vaccines was performed in a short period of time before transplantation. We also readministered vaccines to 15 patients with waning antibody titers after transplantation from June 1999. We investigated whether patients could seroconvert for measles, rubella, mumps, and varicella after immunization and how long antibody titers could be retained by measuring them several times throughout the period before and after transplantation. We also examined side effects caused by immunization. RESULTS: The rates of seroconversion against measles, rubella, mumps, and varicella after the pretransplantation vaccination were 82%, 100%, 90%, and 95%, respectively. The rates of reseroconversion against measles, rubella, mumps, and varicella after the posttransplantation revaccination were 85%, 100%, 100%, and 71%, respectively. Although antibody titers against these viruses generally waned with time, no patient exhibited any serious illness or side effects. CONCLUSION: Although 12 of 58 patients (21%) had an infection, pretransplantation immunization was effective to prevent serious illness, especially for the 6 months after transplantation. Posttransplantation live-vaccine administration under immunosuppressive conditions is effective and safe.


Assuntos
Imunização , Transplante de Fígado , Adolescente , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia
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