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1.
Int J Urol ; 31(7): 795-801, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38622823

RESUMO

OBJECTIVES: This study aimed to investigate perioperative complications and the details of postoperative ureteral stricture after ureteroscopy with laser lithotripsy (URS-L) for upper urinary tract stones in Japan. METHODS: Patient data on intra- and postoperative complications after ureteroscopy using URS-L were retrospectively collected from multiple centers in Japan between April 2017 and March 2020 with the cooperation of the Japanese Society of Endourology and Robotics. Data included the number of patients undergoing URS-L, number and type of intra- and postoperative complications, and detailed characteristics of postoperative ureteral stricture. RESULTS: In total, 14 125 patients underwent URS-L over 3 years at 82 institutions. Annual URS-L numbers gradually increased from 4419 in 2017, to 4760 in 2018, and 4946 in 2019. The total complication rate was 10.5%, which was divided into intra-operative complications in 1.40% and postoperative complications in 9.18%. The annual incidences of intra- and postoperative complications were not significantly different from year to year (p = 0.314 and p = 0.112). Ureteral perforation, ureteral avulsion, and the intra-operative conversion rate were 1.35%, 0.03%, and 0.02%, respectively. Fever >38°C, septic shock, blood transfusion, and postoperative mortality were 7.44%, 0.81%, 0.07%, and 0.04%, respectively. Ureteral stricture occurred in 0.8% of cases. The median length of stricture site was 10.0 mm and the success rate of stricture treatment was 54.6%. CONCLUSION: Although URS-L utilization has increased in Japan, the annual complication rate has remained steady. Although URS-L is a useful and less invasive procedure, devastating complications can still occur.


Assuntos
Litotripsia a Laser , Complicações Pós-Operatórias , Ureteroscopia , Humanos , Ureteroscopia/efeitos adversos , Japão/epidemiologia , Masculino , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade , Litotripsia a Laser/efeitos adversos , Litotripsia a Laser/métodos , Estudos Retrospectivos , Idoso , Adulto , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Cálculos Ureterais/cirurgia , Cálculos Ureterais/terapia , Obstrução Ureteral/etiologia , Obstrução Ureteral/epidemiologia , Constrição Patológica/etiologia , Constrição Patológica/epidemiologia , Incidência , Cálculos Renais/cirurgia , População do Leste Asiático
2.
Proc Natl Acad Sci U S A ; 116(32): 16080-16085, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31337675

RESUMO

Memory consolidation is augmented by repeated learning following rest intervals, which is known as the spacing effect. Although the spacing effect has been associated with cumulative cellular responses in the neurons engaged in memory, here, we report the neural circuit-based mechanism for generating the spacing effect in the memory-related mushroom body (MB) parallel circuits in Drosophila To investigate the neurons activated during the training, we monitored expression of phosphorylation of mitogen-activated protein kinase (MAPK), ERK [phosphorylation of extracellular signal-related kinase (pERK)]. In an olfactory spaced training paradigm, pERK expression in one of the parallel circuits, consisting of γm neurons, was progressively inhibited via dopamine. This inhibition resulted in reduced pERK expression in a postsynaptic GABAergic neuron that, in turn, led to an increase in pERK expression in a dopaminergic neuron specifically in the later session during spaced training, suggesting that disinhibition of the dopaminergic neuron occurs during spaced training. The dopaminergic neuron was significant for gene expression in the different MB parallel circuits consisting of α/ßs neurons for memory consolidation. Our results suggest that the spacing effect-generating neurons and the neurons engaged in memory reside in the distinct MB parallel circuits and that the spacing effect can be a consequence of evolved neural circuit architecture.


Assuntos
Drosophila melanogaster/fisiologia , Consolidação da Memória/fisiologia , Corpos Pedunculados/fisiologia , Rede Nervosa/fisiologia , Animais , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Fosforilação , Transdução de Sinais , Sinapses/metabolismo
3.
Int J Urol ; 26(2): 217-222, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30461076

RESUMO

OBJECTIVES: To evaluate the detection rates of clinically significant prostate cancer classified according to the prostate imaging reporting and data system scoring system using magnetic resonance imaging/ultrasound rigid fusion targeted biopsy. METHODS: A total of 339 patients underwent transperineal magnetic resonance imaging/ultrasound rigid fusion targeted biopsy in our institution between January 2015 and July 2017. Patients with prostate imaging reporting and data system category 1 or 2 and those with a pre-biopsy prostate-specific antigen value of >30 ng/mL were excluded from this study. Finally, 310 patients were recruited. RESULTS: The detection rates of clinically significant prostate cancer with prostate imaging reporting and data system category 3, 4, and 5 were 1.0% (1/98), 35.1% (47/134) and 73.1% (57/78), respectively. The factors affecting the detection of clinically significant prostate cancer with prostate imaging reporting and data system categories 4 and 5 were: (i) prostate imaging reporting and data system category 5; (ii) prostate volume <40 cc; (iii) no previous biopsy; (iv) lesion located in the peripheral zone; and (v) prostate-specific antigen density >0.35 ng/mL/mL. CONCLUSIONS: The detection rate of clinically significant prostate cancer on magnetic resonance imaging/ultrasound rigid fusion targeted biopsy is very low in patients with prostate imaging reporting and data system category 3; therefore, patients with this classification should not undergo targeted biopsy. Prostate-specific antigen density, prostate volume, locations of suspected cancer and history of biopsy should be considered to predict the detection rate of clinically significant prostate cancer with prostate imaging reporting and data system categories 4 and 5.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética Intervencionista/métodos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico , Ultrassonografia de Intervenção/métodos , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre/métodos , Biópsia com Agulha de Grande Calibre/estatística & dados numéricos , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/estatística & dados numéricos , Japão , Imagem por Ressonância Magnética Intervencionista/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Ultrassonografia de Intervenção/estatística & dados numéricos
4.
BMC Urol ; 17(1): 117, 2017 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-29233150

RESUMO

BACKGROUND: This study compared the detection rates for clinically significant prostate cancer (CSPC) between magnetic resonance imaging and ultrasonography (MRI/US)-fusion-targeted biopsy (TB), systematic biopsy (SB) and combination of TB and SB. METHODS: This prospective study evaluated simultaneous TB and SB for consecutive patients with suspicious lesions that were detected using pre-biopsy multiparametric MRI. A commercially available real-time virtual sonography system was used to perform the MRI/US-fusion TB with the transperineal technique. The prostate imaging reporting and data system version 2 (PI-RADS v2) was assigned to categorize the suspicious lesions. RESULTS: A total of 177 patients were included in this study. The detection rate for CSPC was higher using SB, compared to TB (57.1% vs 48.0%, p = 0.0886). The detection rate for CSPC was higher using the combination of TB and SB, compared to only SB (63.3% vs 57.1%, p = 0.2324). Multivariate analysis revealed that PIRADS v2 category 4 and an age of <65 years were independent predictors for TB upgrading (vs. the SB result). CONCLUSIONS: PI-RADS v2 category 4 and an age of <65 years were predictive factors of upgrading the Gleason score by MRI/US-fusion TB. Thus, MRI/US-fusion TB may be appropriate for patients with those characteristics. TRIAL REGISTRATION: This study was retrospectively registered at the University Hospital Medical Information Network ( UMINID000025911 ) in Jan 30, 2017.


Assuntos
Imageamento por Ressonância Magnética/métodos , Períneo/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Ultrassonografia de Intervenção/métodos , Idoso , Idoso de 80 Anos ou mais , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Períneo/cirurgia , Estudos Prospectivos , Neoplasias da Próstata/cirurgia
5.
Psychiatry Clin Neurosci ; 71(10): 733-741, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28556440

RESUMO

AIM: Although the association between maternal depression and bonding failure during pregnancy and after delivery has been investigated, the causal relationships remain unclear. METHODS: A total of 751 women (mean [SD] age, 32.1 [4.4] years) completed the Mother-Infant Bonding Questionnaire and the Edinburgh Postnatal Depression Scale during early pregnancy before week 25 (T1), during late pregnancy around week 36 (T2), and at 5 days after delivery (T3). We created a structural regression model to clarify the relationships between depressive mood and bonding failure during pregnancy and at 5 days after delivery. The model was tested with structural equation modeling. RESULTS: Our non-recursive model fit the data well, and we found that: (i) during T2, bonding failure predicted depressive mood (P < 0.01, r = 0.23); (ii) at T3, bonding failure predicted depressive mood (P < 0.05, r = 0.31); (iii) during T1, depressive mood was correlated with bonding failure (P < 0.01, r = 0.45); (iv) depressive mood during T1 predicted depressive mood during T2 (P < 0.01, r = 0.58); (v) depressive mood during T2 predicted depressive mood at T3 (P < 0.01, r = 0.45); (vi) bonding failure during T1 predicted bonding failure during T2 (P < 0.01, r = 0.84); and (vii) bonding failure during T2 predicted bonding failure at T3 (P < 0.01, r = 0.44). The determinant coefficients of depressive mood and bonding failure at T3 were 0.41 and 0.28, respectively. CONCLUSION: Our large-scale cohort study indicates that bonding failure predicts depressive mood during pregnancy and 5 days after delivery. These findings suggest that protection and support for pregnant women with depressive mood and bonding failure may prevent both issues during pregnancy and the early stage after delivery.


Assuntos
Depressão/psicologia , Relações Mãe-Filho/psicologia , Apego ao Objeto , Adulto , Feminino , Humanos , Gravidez , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Adulto Jovem
6.
J Neurosci ; 35(14): 5557-65, 2015 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-25855172

RESUMO

Long-term memory (LTM) formation requires de novo gene expression in neurons, and subsequent structural and functional modification of synapses. However, the importance of gene expression in glia during this process has not been well studied. In this report, we characterize a cell adhesion molecule, Klingon (Klg), which is required for LTM formation in Drosophila. We found that Klg localizes to the juncture between neurons and glia, and expression in both cell types is required for LTM. We further found that expression of a glial gene, repo, is reduced in klg mutants and knockdown lines. repo expression is required for LTM, and expression increases upon LTM induction. In addition, increasing repo expression in glia is sufficient to restore LTM in klg knockdown lines. These data indicate that neuronal activity enhances Klg-mediated neuron-glia interactions, causing an increase in glial expression of repo. Repo is a homeodomain transcription factor, suggesting that further downstream glial gene expression is also required for LTM.


Assuntos
Condicionamento Clássico/fisiologia , Proteínas de Drosophila/metabolismo , Regulação da Expressão Gênica/fisiologia , Proteínas de Homeodomínio/metabolismo , Memória de Longo Prazo/fisiologia , Neuroglia/metabolismo , Animais , Moléculas de Adesão Celular/genética , Células Cultivadas , Sistema Nervoso Central/citologia , Condicionamento Clássico/efeitos dos fármacos , Cicloeximida/farmacologia , Drosophila , Proteínas de Drosophila/genética , Proteínas do Olho/genética , Feminino , Antagonistas de Hormônios/farmacologia , Masculino , Memória de Longo Prazo/efeitos dos fármacos , Camundongos Transgênicos , Mifepristona/farmacologia , Mutação/genética , Neuroglia/efeitos dos fármacos , Neurônios/metabolismo , Inibidores da Síntese de Proteínas/farmacologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA/fisiologia
8.
Lab Invest ; 96(2): 230-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26595172

RESUMO

Nuclear hormone receptor liver X receptor-alpha (LXRα) has a vital role in cholesterol homeostasis and is reported to have a role in adipose function and obesity although this is controversial. Conversely, mesenchymal stem cells (MSCs) are suggested to be a major source of adipocyte generation. Accordingly, we examined the role of LXRα in adipogenesis of MSCs. Adult murine MSCs (mMSCs) were isolated from wild-type (WT) and LXR-null mice. Using WT mMSCs, we further generated cell lines stably overexpressing GFP-LXRα (mMSC/LXRα/GFP) or GFP alone (mMSC/GFP) by retroviral infection. Confluent mMSCs were differentiated into adipocytes by the established protocol. Compared with MSCs isolated from WT mice, MSCs from LXR-null mice showed significantly increased adipogenesis, as determined by lipid droplet accumulation and adipogenesis-related gene expression. Moreover, mMSCs stably overexpressing GFP-LXRα (mMSC/LXRα/GFP) exhibited significantly decreased adipogenesis compared with mMSCs overexpressing GFP alone (mMSC/GFP). Since Wnt/beta-catenin signaling is reported to inhibit adipogenesis, we further examined it. The LXR-null group showed significantly decreased Wnt expression accompanied by a decrease of cellular beta-catenin (vs WT). The mMSC/LXRα/GFP group exhibited significantly increased Wnt expression accompanied by an increase of cellular beta-catenin (vs mMSC/GFP). These data demonstrate that LXRα has an inhibitory effect on adipogenic differentiation in mMSCs with Wnt/beta-catenin signaling. These results provide important insights into the pathophysiology of obesity and obesity-related consequences such as metabolic syndrome and may identify potential therapeutic targets.


Assuntos
Adipócitos/metabolismo , Adipogenia/fisiologia , Diferenciação Celular/fisiologia , Receptores Nucleares Órfãos/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Células Cultivadas , Humanos , Receptores X do Fígado , Células-Tronco Mesenquimais/citologia , Camundongos , Receptores Nucleares Órfãos/genética , Via de Sinalização Wnt/fisiologia
9.
BMC Psychiatry ; 16: 212, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27389341

RESUMO

BACKGROUND: The Mother-Infant Bonding Questionnaire (MIBQ) has been widely used to assess maternal emotional involvement with infants. Although the reliability and validity of the MIBQ in the postpartum period has been confirmed, it remains unclear whether the MIBQ is appropriate to assess maternal bonding in both pregnancy and the postpartum period over time. Our study were aimed to 1) examine the reliability and validity of the MIBQ for clinical use among pregnant and postpartum women; and 2) examine the factor structure of the items, create subscales, and confirm the stability of the MIBQ in the pregnancy and postpartum periods. METHODS: Participants (n = 751, mean age 32.1 ± 4.4 years) completed the MIBQ and the Edinburgh Postnatal Depression Scale (EPDS) in early pregnancy (before week 25), in late pregnancy (around week 36), 5 days after delivery, and 1 month after delivery. We randomly divided participants into two sample sets. We conducted an exploratory factor analysis of the nine MIBQ items using data from one group of mothers (Group 1; n = 376) in all four periods. The factor structure derived from the exploratory factor analysis was confirmed by a confirmatory factor analysis in the second group (Group 2; n = 375) of mothers in all four periods. RESULTS: Exploratory factor analysis yielded two factors: Lack of Affection (LA) and Anger and Rejection (AR). Confirmatory factor analysis demonstrated that LA and AR factors existed for the MIBQ in all periods. Cronbach's alpha coefficients were 0.879 and 0.584, respectively. The scores for LA and AR were significantly correlated over the four time periods. Mothers with higher AR scores on the MIBQ at any of the four periods had higher scores on the EPDS. CONCLUSIONS: The MIBQ has two subscales regardless of the timing of the assessment. The MIBQ is appropriate for pregnant as well as postpartum women to assess maternal bonding toward the fetus and infant.


Assuntos
Mães/psicologia , Apego ao Objeto , Período Pós-Parto/psicologia , Gestantes/psicologia , Adulto , Afeto , Ira , Análise Fatorial , Feminino , Humanos , Lactente , Japão , Gravidez , Reprodutibilidade dos Testes , Inquéritos e Questionários
10.
Clin Nephrol ; 83(6): 345-50, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26009019

RESUMO

BACKGROUND: Several catheter placement procedures have been described for initiation of peritoneal dialysis, including percutaneous insertion, open surgery, and laparoscopic surgery. However, the optimal approach to catheter placement for peritoneal dialysis remains controversial, because each procedure has specific advantages and disadvantages. PATIENTS AND METHODS: From June 2010 to October 2014, we performed a nephroscope-assisted "pulling-thread" technique for placement of peritoneal dialysis catheters in 46 patients with end-stage renal disease at our medical center. We retrospectively reviewed the operation-related data, early catheter-related complications during the first month after placement, and longterm technical catheter survival. RESULTS: Catheters in all 46 patients were placed precisely in a single step during surgery. The mean operative time was 63.0±18.2 minutes, and no intra-operative complications occurred in any patient. Early catheter-related complications included only exit-site infection (n=2; 4.3%) and catheter obstruction (n=2; 4.3%). There was a mean follow-up period of 18.3±12.7 months. The probability of catheter survival at 1 year was 97.1% and at 2 years was 80.1%. CONCLUSION: Our technique has the advantages of simplicity, safety, minimal equipment, low early catheter- related complication rate, and favorable long-term catheter outcome, making it ideal for patients with end-stage renal disease.


Assuntos
Cateterismo/métodos , Cateteres de Demora , Falência Renal Crônica/terapia , Diálise Peritoneal/instrumentação , Adulto , Idoso , Cateterismo/efeitos adversos , Endoscópios , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Proc Natl Acad Sci U S A ; 109(27): 10885-90, 2012 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-22711815

RESUMO

Cold-inducible RNA-binding protein (Cirp) was the first cold-shock protein identified in mammals. It is structurally quite different from bacterial cold-shock proteins and is induced in response to mild, but not severe, hypothermia. To clarify the physiological function of Cirp in vivo, we produced cirp-knockout mice. They showed neither gross abnormality nor defect in fertility, but the number of undifferentiated spermatogonia was significantly reduced and the recovery of spermatogenesis was delayed after treatment with a cytotoxic agent, busulfan. Cirp accelerated cell-cycle progression from G0 to G1 as well as from G1 to S phase in cultured mouse embryonic fibroblasts. Cirp directly bound to dual-specificity tyrosine-phosphorylation-regulated kinase 1B (Dyrk1b, also called Mirk) and inhibited its binding to p27, resulting in decreased phosphorylation and destabilization of p27. Cirp did not affect binding of Dyrk1b to cyclin D1 but inhibited phosphorylation of cyclin D1 by Dyrk1b, resulting in cyclin D1 stabilization. In the spermatogonial cell line GC-1spg, suppression of Cirp expression increased the protein level of p27, decreased that of cyclin D1, and decreased the growth rate, which depended on Dyrk1b. Consistent changes in the protein levels of p27 and cyclin D1 as well as the percentage of cells in G0 phase were observed in undifferentiated spermatogonia of cirp-knockout mice. In undifferentiated spermatogonia of wild-type mice, Cirp and Dyrk1b colocalized in the nucleus. Thus, our study demonstrates that Cirp functions to fine-tune the proliferation of undifferentiated spermatogonia by interacting with Dyrk1b.


Assuntos
Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas de Ligação a RNA/metabolismo , Espermatogônias/citologia , Espermatogônias/fisiologia , Animais , Ciclo Celular/fisiologia , Diferenciação Celular/fisiologia , Proliferação de Células , Células Cultivadas , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação para Baixo/fisiologia , Fibroblastos/citologia , Fibroblastos/fisiologia , Fase G1/fisiologia , Masculino , Camundongos , Camundongos Knockout , Fosforilação/fisiologia , Proteínas de Ligação a RNA/genética , Fase de Repouso do Ciclo Celular/fisiologia , Quinases Dyrk
12.
Psychiatry Clin Neurosci ; 68(8): 631-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24521214

RESUMO

AIM: Postnatal depression has demonstrated long-term consequences on child cognitive and emotional development; however, the link between maternal and child pathology has not been clearly identified. We conducted a prospective study using self-rating questionnaires to clarify the association between bonding disorder and maternal mood during pregnancy and after childbirth. METHODS: A total of 389 women participated in this study and completed questionnaires. Participants were asked to complete the Edinburgh Postnatal Depression Scale (EPDS) and the Mother-to-Infant Bonding Scale four times during pregnancy and the postpartum period. RESULTS: We found statistically significant weak to moderate correlations (r = 0.14-0.39) between the EPDS and Mother-to-Infant Bonding Scale scores at each testing period. Women who experienced low mood tended to have stronger bonding disorder. Furthermore, the effectiveness of attachment between the mother and child was closely related to the mood of the mother as measured by the EPDS. CONCLUSION: We observed different patterns of bonding and maternal mood. Distinct subtypes regarding maternal mood and formation of mother-to-infant attachment suggests that analysis of bonding disorder should be performed considering the course of maternal depressive symptoms.


Assuntos
Depressão Pós-Parto/psicologia , Depressão/psicologia , Relações Mãe-Filho/psicologia , Apego ao Objeto , Complicações na Gravidez/psicologia , Adulto , Feminino , Humanos , Gravidez , Estudos Prospectivos , Autorrelato , Adulto Jovem
13.
BMC Med ; 11: 182, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23945290

RESUMO

BACKGROUND: Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic myelopathy characterized by motor dysfunction of the lower extremities and urinary disturbance. Immunomodulatory treatments are the main strategy for HAM/TSP, but several issues are associated with long-term treatment. We conducted a clinical trial with prosultiamine (which has apoptotic activity against HTLV-I-infected cells) as a novel therapy in HAM/TSP patients. METHODS: We enrolled 24 HAM/TSP patients in this open-label clinical trial. Prosultiamine (300 mg, orally) was administered once daily for 12 weeks. We monitored changes in the motor function of the lower extremities and urinary function as well as copy numbers of the HTLV-I provirus in peripheral blood mononuclear cells (PBMCs). RESULTS: Improvement in the motor function of the lower extremities based on a reduction in spasticity (for example, decrease in time required for walking and descending a flight of stairs) was observed. In an urodynamic study (UDS), bladder capacity and detrusor pressure and then maximum flow rate increased significantly. Detrusor overactivity and detrusor-sphincter dyssynergia improved in 68.8% and 45.5% of patients observed at pretreatment, respectively. Improvement in UDS corresponded with improvements in the score of nocturia-quality of life questionnaire. HTLV-I proviral copy numbers in PBMCs decreased significantly (approximately 15.4%) compared with pretreatment levels. CONCLUSIONS: These data suggest that prosultiamine can safely improve motor dysfunction of the lower extremities and urinary disturbance as well as reduce HTLV-I provirus levels in peripheral blood. It therefore has potential as a new therapeutic tool for HAM/TSP patients. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) number, UMIN000005969. Please see related commentary: http://www.biomedcentral.com/1741-7015/11/183.


Assuntos
Infecções por HTLV-I/tratamento farmacológico , Tiamina/análogos & derivados , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Infecções por HTLV-I/patologia , Humanos , Perna (Membro)/fisiologia , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Atividade Motora , Provírus/isolamento & purificação , Tiamina/uso terapêutico , Resultado do Tratamento , Micção/fisiologia , Carga Viral , Adulto Jovem
14.
Cancer Cell ; 8(1): 75-87, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16023600

RESUMO

Gankyrin is an ankyrin repeat oncoprotein commonly overexpressed in hepatocellular carcinomas. Gankyrin interacts with the S6 proteasomal ATPase and accelerates the degradation of the tumor suppressor Rb. We show here that gankyrin has an antiapoptotic activity in cells exposed to DNA damaging agents. Downregulation of gankyrin induces apoptosis in cells with wild-type p53. In vitro and in vivo experiments revealed that gankyrin binds to Mdm2, facilitating p53-Mdm2 binding, and increases ubiquitylation and degradation of p53. Gankyrin also enhances Mdm2 autoubiquitylation in the absence of p53. Downregulation of gankyrin reduced amounts of Mdm2 and p53 associated with the 26S proteasome. Thus, gankyrin is a cofactor that increases the activities of Mdm2 on p53 and probably targets polyubiquitylated p53 into the 26S proteasome.


Assuntos
Regulação da Expressão Gênica , Proteínas Nucleares/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteína do Retinoblastoma/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Anquirinas/metabolismo , Apoptose , Células Cultivadas , Humanos , Imunoprecipitação , Camundongos , Dados de Sequência Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Inibidores de Proteassoma , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-mdm2 , RNA Interferente Pequeno/farmacologia , Proteína do Retinoblastoma/genética , Proteína Supressora de Tumor p53/genética , Dedos de Zinco
15.
Hinyokika Kiyo ; 59(9): 573-7, 2013 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-24113755

RESUMO

A 60-year-old woman received a right radical nephrectomy for a right renal cell carcinoma (8.5×5.4 cm), cT2N0M0, in August 2000. The histopathological findings revealed a clear cell carcinoma, pT2, grade 1, INFα, v (-). She was started on interferon α (sumiferon : 300 IU) because of an adrenal metastasis from the renal cell carcinoma in August 2008. However, the tumor gradually enlarged and there was a potential to infiltrate the pancreatic body-tail. Therefore, we began the administration of sunitinib for pre-surgical therapy in June 2010, because she had a good performance status, no metastasis to other organs except for the left adrenal gland, and the passage of eight years from the time of resection of the primary origin tumor. She had a good response to therapy, which shrank the tumor by 40% (partial response). Therefore we performed a left adrenalectomy in June 2011. The histopathological findings revealed a metastatic renal cell carcinoma. We stopped the administration of after the operation sunitinib after the operation. She has since preserved her quality of life without any recurrence for 19 months.


Assuntos
Neoplasias das Glândulas Suprarrenais/secundário , Neoplasias das Glândulas Suprarrenais/terapia , Adrenalectomia , Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/terapia , Quimioterapia Adjuvante , Indóis/administração & dosagem , Neoplasias Renais/patologia , Cuidados Pré-Operatórios , Pirróis/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Sunitinibe , Resultado do Tratamento
16.
IJU Case Rep ; 6(6): 329-333, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37928277

RESUMO

Introduction: Disseminated carcinomatosis of the bone marrow in prostate cancer is rare and has a poor prognosis. Although strong evidence suggests that novel hormonal agents improve the prognosis of metastatic prostate cancer, their effectiveness in cases of disseminated carcinomatosis of the bone marrow remains unclear. Case presentation: We encountered two cases of prostate cancer with disseminated carcinomatosis of the bone marrow at the time of initial diagnosis. One patient was treated with enzalutamide, abiraterone, docetaxel, cabazitaxel, denosumab, and radium-223 and died 38 months after the initial diagnosis. The other patient was treated with apalutamide and denosumab, and had progression-free survival for 17 months after the initial diagnosis. Conclusion: These results suggest that novel hormonal agents may improve the prognosis of prostate cancer even in patients with disseminated carcinomatosis of the bone marrow.

17.
J Neurol Neurosurg Psychiatry ; 83(9): 935-40, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22764264

RESUMO

OBJECTIVE: We developed an assay that detects autoantibodies against the main immunogenic region (MIR) located at the extracellular end of the nicotinic acetylcholine receptor (AChR) α subunit, and investigated its clinical relevance in myasthenia gravis (MG). METHODS: In this retrospective cohort study, we measured MIR antibody (Ab) titres in sera obtained before treatment and analysed their associations with clinical parameters in 102 MG patients from two neurological centres. MIR Ab titres were determined using a modified competition immunoprecipitation assay in the presence or absence of monoclonal antibody 35. RESULTS: 11 of 23 (47.8%) ocular type and 66 of 72 (91.7%) generalised type MG patients were positive for the presence of MIR Abs, defined as a titre >16.8% (3 SDs above the mean for 70 healthy controls). A significantly higher MIR Ab titre (p<0.001) was shown in generalised type (47.9±19.2%) rather than in ocular type MG patients (16.4±8.4%). Bivariate regression analysis using both titre levels of MIR Ab and routine AChR binding Ab as variables revealed MIR Abs to be an exclusive indicator positively associated with disease severity (Myasthenia Gravis Foundation of America classification, p<0.0001; Quantitative MG score, p=0.008), the presence of bulbar symptoms (p<0.0001) and thymoma (p=0.016), and negatively associated with ocular MG (p<0.0001). CONCLUSIONS: MIR Ab titre levels show much better correlations with factors related to disease severity compared with AChR binding Ab titres. The MIR Ab assay may be useful for predicting MG symptom severity, especially for discriminating between ocular and generalised types of MG.


Assuntos
Autoanticorpos/sangue , Miastenia Gravis/imunologia , Receptores Nicotínicos/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Miastenia Gravis/diagnóstico , Ratos , Ratos Endogâmicos Lew , Receptores Nicotínicos/efeitos dos fármacos , Estudos Retrospectivos , Índice de Gravidade de Doença
18.
Hinyokika Kiyo ; 57(11): 633-7, 2011 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-22166828

RESUMO

An 85-year-old man had planned a laparoscopic right nephrouretectomy for a right lower ureteral cancer, pT1, G3. Two months prior to the surgery, he was re-examined because of continuing macrohematuria. He had a 50 mm tumor in his urinary bladder and tumors from the right upper to lower urinary tract by computed tomographic (CT) examination and cystoscopy. He did not have any metastasis. We diagnosed a cT3N0M0 for the right ureteral cancer and a cT3N0M0 for the bladder cancer. A right nephrouretectomy and cystectomy were then performed. The histopathologic examination revealed an urothelial carcinoma with a choriocarcinoma.


Assuntos
Coriocarcinoma/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Ureterais/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso de 80 Anos ou mais , Coriocarcinoma/cirurgia , Cistectomia , Humanos , Masculino , Nefrectomia , Neoplasias Ureterais/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Urotélio
19.
Fukuoka Igaku Zasshi ; 102(4): 130-3, 2011 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-21706892

RESUMO

This study examined patients with Kanemi Yusho. The patients' height, weight, and bone mineral density were measured. The density of the distal end of the radius was measured using dual energy X-ray absorptiometry and the calcaneum was measured with ultrasound. We also measured urine levels of cross-linked N-telopeptides of type I collagen, serum tartrate-resistant acid phosphatase 5b, serum bone-specific alkaline phosphatase, serum Ca, serum P and blood PCB level. The patient group that took PCBs when they were 0 to 18 years old (such patients were 42 to 60 years old at the time of the study) showed no correlation between the bone density of the radius and calcaneum in spite of treatment received when they were over 18 years of age (> 60 years of age at the time of the study). The bone mineral density in Kanemi Yusho was not different from the control group. The levels of only serum bone-specific alkaline phosphatase were correlated with the bone mineral density of the radius and calcaneum in patients treated when they were over 18 years of age (currently over 60 years old). PCBs might have had an effect on bone density and bone metabolism.


Assuntos
Densidade Óssea , Oryza/intoxicação , Óleos de Plantas/intoxicação , Bifenilos Policlorados/intoxicação , Absorciometria de Fóton , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Contaminação de Alimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade
20.
Rheumatol Int ; 30(7): 987-9, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19543730

RESUMO

Macrophagic myofascitis (MMF) is an unusual inflammatory myopathy characterized by muscle infiltration by macrophages and lymphocytes. Here, we describe a case of MMF which is associated with rheumatoid arthritis. A 53-year-old Japanese rheumatoid arthritis (RA) patient presented with focal tenderness of lower extremities. Magnetic resonance imaging showed evidence of myofascitis involving fascias of anterior tibialis muscle. Muscle biopsy showed a unique pathological pattern of MMF. MMF is known to be associated with vaccination containing aluminum. However, our case was not related to aluminum containing vaccinations and etiologies are unknown. The possible link needs to be discussed.


Assuntos
Artrite Reumatoide/complicações , Macrófagos/patologia , Síndromes da Dor Miofascial/imunologia , Síndromes da Dor Miofascial/patologia , Miosite/imunologia , Miosite/patologia , Biópsia , Fáscia/imunologia , Fáscia/patologia , Fáscia/fisiopatologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Imunossupressores/uso terapêutico , Perna (Membro)/patologia , Perna (Membro)/fisiopatologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Músculo Esquelético/imunologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Síndromes da Dor Miofascial/fisiopatologia , Miosite/fisiopatologia , Prednisolona/uso terapêutico , Tacrolimo/uso terapêutico , Resultado do Tratamento
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