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1.
Int J Urol ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38923021

RESUMO

OBJECTIVES: There is a lack of data on the number of surgeries required for endoscopic combined intrarenal surgery (ECIRS). Accordingly, we aimed to identify the learning curve for ECIRS performed by multiple surgeons. METHODS: We included 296 patients who underwent ECIRS at our university hospital between 2016 and 2021. A learning curve for percutaneous nephrolithotomy side was calculated considering urology-resident surgeons. The learning curve was retrospectively analyzed for surgical time, renal puncture time, stone-free rate, and complications and corrected for age, body mass index, stone size, computed tomography value, cumulative number of surgeries, and stone location. RESULTS: This study included cases performed by 32 surgeons, including 30 residents and 2 attending surgeons. The median number of surgeries performed by the residents and attending surgeons prior to this study was 4.5 and 90, respectively. The median number of surgical procedures performed during the training period was seven. The surgical time of the residents decreased as the number of cases increased, reaching a median surgical time of 111 min for the attending surgeons after 16.4 cases. Renal puncture time was achieved in 20.1 cases. Complications related to renal access were observed in 13.0% (34 patients), Clavien-Dindo grade II in 1.9% (5 patients), and grade III or higher in 0.8% (2 patients). Comparing the first to fifth cases with the 21st and subsequent cases, the complication rate improved from 35% to 13%. CONCLUSION: Our study demonstrated that ECIRS training provided 16-20 cases with a learning curve to achieve acceptable surgical outcomes.

2.
Int J Urol ; 29(9): 1054-1060, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35871263

RESUMO

OBJECTIVES: To evaluate the efficacy of ultrasound-assisted monitoring during shock wave lithotripsy for kidney and proximal ureteral calculi. METHODS: We retrospectively reviewed 535 patients who initially underwent shock wave lithotripsy for renal or proximal ureteral calculi between January 2012 and December 2021. The patients were divided into the X-ray group (n = 294) and ultrasound plus X-ray group (n = 241) based on the methods of targeting and monitoring calculi during shock wave lithotripsy. Because of differences in patient backgrounds, 1:1 propensity score-based matching was performed. The primary endpoint was the stone-free rate. RESULTS: In the final 1:1 matched cohort, 192 kidney stone cases and 162 proximal ureteral stone cases were analyzed. For patients with kidney calculi, the stone-free rate of the ultrasound plus X-ray group was significantly higher than that of the X-ray group (66.7% vs. 47.9%; P = 0.013). In the multivariate analysis, a large stone area (odds ratio 2.37), lower caliceal stones (odds ratio 3.37), and X-ray monitoring alone (odds ratio 0.49) were independently associated with shock wave lithotripsy failure. For patients with proximal ureteral stones, there was no significant difference in the stone-free rate between the ultrasound plus X-ray group and X-ray group (71.6% and 58.0%, respectively; P = 0.100). During the multivariate analysis, high computed tomography attenuation (odds ratio 2.31) and large stone area (odds ratio 2.18) were independent factors associated with residual stones after shock wave lithotripsy. CONCLUSIONS: Ultrasound-assisted monitoring may contribute to a higher stone-free rate for patients with kidney calculi, but not for those with proximal ureteral calculi.


Assuntos
Cálculos Renais , Litotripsia , Cálculos Ureterais , Humanos , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/terapia , Litotripsia/métodos , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Cálculos Ureterais/diagnóstico por imagem , Cálculos Ureterais/terapia
3.
Int J Urol ; 29(9): 977-982, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35384075

RESUMO

OBJECTIVES: In March 2019, cefazolin was unavailable owing to difficulty in procuring the active ingredient. Furthermore, the supply of alternative drugs, such as cefotiam and cefmetazole, was limited. In the Department of Nephro-Urology, fosfomycin-based drugs are used as substitutes for cefazolin, which is a perioperative prophylactic antibacterial drug. Herein, we investigated the effectiveness of fosfomycin sodium and cefotiam in preventing infection after endoscopic combined intrarenal surgery as a retrospective preliminary study. METHODS: A total of 200 patients who underwent endoscopic combined intrarenal surgery at our department between August 2017 and January 2021 were included. The patients were administered cefotiam (n = 95) or fosfomycin (n = 105) as perioperative antibacterial agents. There were no significant differences in the median age or surgery time between the cefotiam and fosfomycin groups. Propensity score matching was performed to match the preoperative urine bacterial counts of both groups. Sixty-eight patients were selected from each group. RESULTS: The median postoperative hospital stay duration was 4 days for the two groups. The median maximum postoperative temperatures were 37.5 and 37.4°C, respectively. There were no significant differences between the maximum postoperative temperatures in both groups. Furthermore, there were no differences between the groups regarding the white blood cell counts, C-reactive protein levels, and aspartate aminotransferase and alanine aminotransferase levels postoperatively, as well as in terms of postoperative fever requiring additional antibiotics. CONCLUSIONS: During a period of difficulty in acquiring cefazolin and cefotiam, the use of fosfomycin allowed us to continue with the procedure without increased clinical complications.


Assuntos
Fosfomicina , Antibacterianos/uso terapêutico , Cefazolina/uso terapêutico , Cefotiam , Fosfomicina/uso terapêutico , Humanos , Estudos Retrospectivos
4.
Brain ; 143(4): 1190-1205, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32201884

RESUMO

Recently, the genetic variability in lysosomal storage disorders has been implicated in the pathogenesis of Parkinson's disease. Here, we found that variants in prosaposin (PSAP), a rare causative gene of various types of lysosomal storage disorders, are linked to Parkinson's disease. Genetic mutation screening revealed three pathogenic mutations in the saposin D domain of PSAP from three families with autosomal dominant Parkinson's disease. Whole-exome sequencing revealed no other variants in previously identified Parkinson's disease-causing or lysosomal storage disorder-causing genes. A case-control association study found two variants in the intronic regions of the PSAP saposin D domain (rs4747203 and rs885828) in sporadic Parkinson's disease had significantly higher allele frequencies in a combined cohort of Japan and Taiwan. We found the abnormal accumulation of autophagic vacuoles, impaired autophagic flux, altered intracellular localization of prosaposin, and an aggregation of α-synuclein in patient-derived skin fibroblasts or induced pluripotent stem cell-derived dopaminergic neurons. In mice, a Psap saposin D mutation caused progressive motor decline and dopaminergic neurodegeneration. Our data provide novel genetic evidence for the involvement of the PSAP saposin D domain in Parkinson's disease.


Assuntos
Predisposição Genética para Doença/genética , Doença de Parkinson/genética , Saposinas/genética , Idoso , Animais , Estudos de Casos e Controles , Neurônios Dopaminérgicos/patologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Mutantes , Pessoa de Meia-Idade , Degeneração Neural/genética , Degeneração Neural/patologia , Doença de Parkinson/patologia
5.
Int J Urol ; 28(11): 1129-1135, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34342062

RESUMO

OBJECTIVES: To evaluate the safety and efficacy of the prone split-leg and the Galdakao-modified supine Valdivia positions during endoscopic combined intrarenal surgery. METHODS: A multi-institutional, retrospective cohort study was conducted between January 2014 and December 2018. The stone-free and complication rates were compared between the prone split-leg and the Galdakao-modified supine Valdivia positions. Anatomical variations were evaluated using contrast-enhanced computed tomography imaging. RESULTS: In total, 118 and 100 patients underwent endoscopic combined intrarenal surgery in the prone split-leg and Galdakao-modified supine Valdivia positions, respectively. Renal punctures in the prone split-leg position were predominantly executed through the lower calyces (78.0%), whereas those in the Galdakao-modified supine Valdivia position were primarily performed through the middle calyces (64.0%; P < 0.001). Surgical duration in the prone split-leg position was significantly shorter than that in the Galdakao-modified supine Valdivia position (106.5 vs 126.0 min; P = 0.0459). There were no significant differences in the stone-free rate between the two positions (78.8% vs 76.0%; P = 0.629). Incidences of urinary tract injury (P = 0.033) and febrile urinary tract infection (23.7% vs 10.0%; P = 0.011) in the prone split-leg position were significantly higher than that in the Galdakao-modified supine Valdivia position. The tilt of the major renal axis was significantly greater in the prone position than the corresponding values in the oblique position (19.4° vs 8.5°; P = 0.019). CONCLUSIONS: Anatomical variation might result in the differences of renal puncture calyx. Endoscopic combined intrarenal surgery in the Galdakao-modified supine Valdivia position may bring equal stone-free status, with a longer surgical time but fewer complications including febrile urinary tract infection and urinary tract injury than the prone split-leg position.


Assuntos
Cálculos Renais , Nefrostomia Percutânea , Endoscopia/efeitos adversos , Humanos , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Perna (Membro) , Posicionamento do Paciente , Estudos Retrospectivos
6.
J Appl Toxicol ; 40(12): 1614-1621, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32567707

RESUMO

Many chemical substances are detectable in house dust, and they are consequently taken into our bodies via the mouth and nose. Triphenyl phosphate (TPhP), a flame retardant that has an estrogen-like effect in vitro, is present in house dust at high concentrations. Estrogen exposure during development has significant influences on reproductive behavior in rodents, and its effects persist until maturity. In the present study, we investigated the effect of early life exposure to TPhP on the reproductive behavior of female rats. Oral treatment with TPhP (25 or 250 mg/kg), ethinyl estradiol (EE; 15 µg/kg) as a positive control, or sesame oil as a negative control, were given to female rats (from birth to 28 days of age). The 8-week-old rats were bilaterally ovariectomized. At 12-15 weeks of age, the rats were subjected to odor preference and sexual behavior tests. In the odor preference test, the oil group showed significantly higher preference for male odor than female odor, but the low-dose TPhP treatment group lost the preference for male odor, indicating a possible outcome of early life TPhP exposure on sexual recognition. In the sexual behavior test, both the EE and TPhP treatment groups displayed significantly less proceptive behavior. These results suggest that early life exposure to TPhP disturbs the normal sexual behavior of female rats.


Assuntos
Disruptores Endócrinos/toxicidade , Retardadores de Chama/toxicidade , Odorantes , Percepção Olfatória/efeitos dos fármacos , Organofosfatos/toxicidade , Comportamento Sexual Animal/efeitos dos fármacos , Olfato/efeitos dos fármacos , Fatores Etários , Animais , Etinilestradiol/toxicidade , Feminino , Masculino , Preferência de Acasalamento Animal/efeitos dos fármacos , Ratos Wistar , Fatores Sexuais
7.
J Appl Toxicol ; 38(5): 649-655, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29271492

RESUMO

Exposure to endocrine-disrupting chemicals may adversely affect animals, particularly during development. Tris(1,3-dichloroisopropyl) phosphate (TDCIPP) is an organophosphate with anti-androgen function in vitro that is present in indoor dust at relatively high concentrations. In male rats, androgens are necessary for the development of reproductive organs, as well as the endocrine and central nervous systems. However, we currently do not know the exact effects of TDCIPP exposure through suckling on subsequent reproductive behavior in males. Here, we show that TDCIPP exposure (25-250 mg kg-1 via oral administration over 28 consecutive days post-birth) suppressed male sexual behavior and reduced testes size. These changes were dose-dependent and appeared first in adults rather than in juveniles. These results demonstrate that TDCIPP exposure led to normal body growth and appearance in juveniles, but disrupted the endocrine system and physiology in adults. Therefore, assays should be performed using adult animals to ensure accuracy, and to confirm the influence of chemical substances given during early mammalian life.


Assuntos
Disruptores Endócrinos/toxicidade , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Wistar , Testosterona/sangue
8.
Proc Natl Acad Sci U S A ; 112(3): E311-20, 2015 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-25564662

RESUMO

Most mammals have two major olfactory subsystems: the main olfactory system (MOS) and vomeronasal system (VNS). It is now widely accepted that the range of pheromones that control social behaviors are processed by both the VNS and the MOS. However, the functional contributions of each subsystem in social behavior remain unclear. To genetically dissociate the MOS and VNS functions, we established two conditional knockout mouse lines that led to either loss-of-function in the entire MOS or in the dorsal MOS. Mice with whole-MOS loss-of-function displayed severe defects in active sniffing and poor survival through the neonatal period. In contrast, when loss-of-function was confined to the dorsal MOB, sniffing behavior, pheromone recognition, and VNS activity were maintained. However, defects in a wide spectrum of social behaviors were observed: attraction to female urine and the accompanying ultrasonic vocalizations, chemoinvestigatory preference, aggression, maternal behaviors, and risk-assessment behaviors in response to an alarm pheromone. Functional dissociation of pheromone detection and pheromonal induction of behaviors showed the anterior olfactory nucleus (AON)-regulated social behaviors downstream from the MOS. Lesion analysis and neural activation mapping showed pheromonal activation in multiple amygdaloid and hypothalamic nuclei, important regions for the expression of social behavior, was dependent on MOS and AON functions. Identification of the MOS-AON-mediated pheromone pathway may provide insights into pheromone signaling in animals that do not possess a functional VNS, including humans.


Assuntos
Comportamento Animal , Feromônios/fisiologia , Olfato/fisiologia , Comportamento Social , Animais , Aprendizagem da Esquiva , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL
9.
J Pept Sci ; 23(7-8): 610-617, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28370673

RESUMO

We recently identified a novel family of neutrophil-activating peptides including mitocryptide-1 and mitocryptide-2 (MCT-2) that are endogenously produced from various mitochondrial proteins. Among them, MCT-2 is an N-formylated pentadecapeptide derived from mitochondrial cytochrome b and is found to promote neutrophilic migration and phagocytosis efficiently. Signaling mechanisms of neutrophil activation by MCT-2 have been investigated at the cellular level, and MCT-2 has been demonstrated to be an endogenous specific ligand for formyl peptide receptor-2 (also referred to as formyl peptide receptor-like 1). It was also found that MCT-2 promoted neutrophilic functions via the activation of Gi2 proteins and phosphorylation of ERK1/2 consecutively. However, the physiological production, distribution, and functions of MCT-2 are not yet elucidated. Here, to investigate the roles of MCT-2 in vivo, we generated monoclonal antibodies (mAbs) against human MCT-2 (hMCT-2) that have two different characteristics. One mAb, NhM2A1, not only bound to the region of positions 10-15 of hMCT-2 but also recognized its C-terminal cleavage site that is presumably produced upon enzymatic hydrolysis of cytochrome b, indicating that NhM2A1 specifically interacts with hMCT-2 but not its parent protein. Moreover, we succeeded in acquiring a specific neutralizing mAb, NhM2A5, which blocks the bioactivities of hMCT-2. Specifically, NhM2A5 inhibited hMCT-2-induced ß-hexosaminidase release in neutrophilic/granulocytic differentiated HL-60 cells by binding to the region of positions 5-12 of hMCT-2. Functional analysis using obtained mAbs that specifically recognize hMCT-2 but not its parent protein, cytochrome b, and that neutralize bioactivities of hMCT-2 is expected to reveal the physiological roles of MCT-2, which are presently very difficult to investigate. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.


Assuntos
Anticorpos Monoclonais/imunologia , Proteínas Mitocondriais/imunologia , Animais , Citocromos b/metabolismo , Ensaio de Imunoadsorção Enzimática , Células HL-60 , Humanos , Camundongos , Proteínas Mitocondriais/metabolismo , Peptídeos/imunologia , Peptídeos/metabolismo , Suínos
10.
J Bacteriol ; 198(7): 1077-86, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26787768

RESUMO

UNLABELLED: The extremely halophilic archaeon Haloferax volcanii grows anaerobically by denitrification. A putative DNA-binding protein, NarO, is encoded upstream of the respiratory nitrate reductase gene of H. volcanii. Disruption of the narO gene resulted in a loss of denitrifying growth of H. volcanii, and the expression of the recombinant NarO recovered the denitrification capacity. A novel CXnCXCX7C motif showing no remarkable similarities with known sequences was conserved in the N terminus of the NarO homologous proteins found in the haloarchaea. Restoration of the denitrifying growth was not achieved by expression of any mutant NarO in which any one of the four conserved cysteines was individually replaced by serine. A promoter assay experiment indicated that the narO gene was usually transcribed, regardless of whether it was cultivated under aerobic or anaerobic conditions. Transcription of the genes encoding the denitrifying enzymes nitrate reductase and nitrite reductase was activated under anaerobic conditions. A putative cis element was identified in the promoter sequence of haloarchaeal denitrifying genes. These results demonstrated a significant effect of NarO, probably due to its oxygen-sensing function, on the transcriptional activation of haloarchaeal denitrifying genes. IMPORTANCE: H. volcanii is an extremely halophilic archaeon capable of anaerobic growth by denitrification. The regulatory mechanism of denitrification has been well understood in bacteria but remains unknown in archaea. In this work, we show that the helix-turn-helix (HTH)-type regulator NarO activates transcription of the denitrifying genes of H. volcanii under anaerobic conditions. A novel cysteine-rich motif, which is critical for transcriptional regulation, is present in NarO. A putative cis element was also identified in the promoter sequence of the haloarchaeal denitrifying genes.


Assuntos
Proteínas Arqueais/metabolismo , Regulação da Expressão Gênica em Archaea/fisiologia , Haloferax volcanii/fisiologia , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Anaerobiose , Proteínas Arqueais/genética , Desnitrificação/fisiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Dados de Sequência Molecular , Nitrato Redutase/genética , Nitrato Redutase/metabolismo , Plasmídeos , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Transcrição Gênica
11.
Biopolymers ; 106(4): 580-7, 2016 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-26600263

RESUMO

Recently, much attention has been paid to "nonclassical" bioactive peptides, which are fragmented peptides simultaneously produced during maturation and degradation of various functional proteins. We identified many fragmented peptides derived from various mitochondrial proteins including mitocryptide-1 and mitocryptide-2 that efficiently activate neutrophils. These endogenous, functionally active, fragmented peptides are referred to as "cryptides." Among them, mitocryptide-2 is an N-formylated cryptide cleaved from mitochondrial cytochrome b that is encoded in mitochondrial DNA (mtDNA). It is known that 13 proteins encoded in mtDNA are translated in mitochondria as N-formylated forms, suggesting the existence of endogenous N-formylated peptides other than mitocryptide-2. Here, we investigated the effects of N-formylated peptides presumably cleaved from mtDNA-encoded proteins other than cytochrome b on the functions of neutrophilic cells to elucidate possible regulation by endogenous N-formylated cryptides. Four N-formylated cryptides derived from cytochrome c oxidase subunit I and NADH dehydrogenase subunits 4, 5, and 6 among 12 peptides from mtDNA-encoded proteins efficiently induced not only migration but also ß-hexosaminidase release, which is an indicator of neutrophilic phagocytosis, in HL-60 cells differentiated into neutrophilic cells. These activities were comparable to or higher than those induced by mitocryptide-2. Although endogenous N-formylated peptides that are contained in mitochondrial damage-associated molecular patterns (DAMPs) have yet to be molecularly identified, they have been implicated in innate immunity. Thus, N-formylated cryptides including mitocryptide-2 are first-line candidates for the contents of mitochondrial DAMPs to promote innate immune responses. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 580-587, 2016.


Assuntos
Citocromos b/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Imunidade Inata , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Peptídeos/metabolismo , Animais , Citocromos b/genética , Citocromos b/imunologia , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/imunologia , Humanos , Mitocôndrias/genética , Mitocôndrias/imunologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/imunologia , Peptídeos/genética , Peptídeos/imunologia
12.
Nature ; 466(7302): 118-22, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20596023

RESUMO

Various social behaviours in mice are regulated by chemical signals called pheromones that act through the vomeronasal system. Exocrine gland-secreting peptide 1 (ESP1) is a 7-kDa peptide that is released into male tear fluids and stimulates vomeronasal sensory neurons in female mice. Here, we describe the molecular and neural mechanisms that are involved in the decoding of ESP1 signals in the vomeronasal system, which leads to behavioural output in female mice. ESP1 is recognized by a specific vomeronasal receptor, V2Rp5, and the ligand-receptor interaction results in sex-specific signal transmission to the amygdaloid and hypothalamic nuclei via the accessory olfactory bulb. Consequently, ESP1 enhances female sexual receptive behaviour upon male mounting (lordosis), allowing successful copulation. In V2Rp5-deficient mice, ESP1 induces neither neural activation nor sexual behaviour. These findings show that ESP1 is a crucial male pheromone that regulates female reproductive behaviour through a specific receptor in the mouse vomeronasal system.


Assuntos
Feromônios/metabolismo , Proteínas/metabolismo , Receptores Odorantes/metabolismo , Receptores de Feromônios/metabolismo , Comportamento Sexual Animal/fisiologia , Órgão Vomeronasal/metabolismo , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Feminino , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores Odorantes/deficiência , Receptores Odorantes/genética , Receptores de Feromônios/deficiência , Receptores de Feromônios/genética , Canais de Cátion TRPC/deficiência , Órgão Vomeronasal/citologia , Órgão Vomeronasal/inervação
13.
Biochem Biophys Res Commun ; 463(1-2): 54-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25986736

RESUMO

Mitocryptide-1 (MCT-1) is a novel neutrophil-activating peptide derived from mitochondrial cytochrome c oxidase subunit VIII, and its physiological role and involvement in various diseases have not yet been elucidated. Generating neutralizing antibodies against the function of MCT-1 is of particular importance for investigating its physiological and pathophysiological roles, because MCT-1 is a fragmented peptide of its mother protein and hence it is very difficult to manipulate its expression level genetically without affecting expression of the mother protein. Here, we report the successful generation of a neutralizing monoclonal antibody (MAb) against MCT-1. This MAb, designated NM1B1, which specifically bound to the region of positions 9-22 of MCT-1, showed concentration-dependent inhibition of MCT-1-induced migration and ß-hexosaminidase release in neutrophilic/granulocytic differentiated HL-60 cells. Thus, NM1B1, as a neutralizing MAb against MCT-1, could elucidate not just the physiological regulatory mechanisms of MCT-1 but also its pathophysiological involvement in various inflammatory diseases in vivo.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Complexo IV da Cadeia de Transporte de Elétrons/imunologia , Neutrófilos/imunologia , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Complexo IV da Cadeia de Transporte de Elétrons/química , Complexo IV da Cadeia de Transporte de Elétrons/genética , Epitopos/química , Epitopos/genética , Feminino , Células HL-60 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/imunologia
14.
J Hand Surg Am ; 39(8): 1553-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24996678

RESUMO

PURPOSE: To report the effectiveness of single derotation osteotomy at the radial diaphysis for the treatment of congenital radioulnar (RU) synostosis. METHODS: Since 2000, we performed 35 radial diaphysis osteotomies on 17 boys and 9 girls younger than 9 years old (average, 5 y). The radius was cut at the midshaft and manually rotated to a neutral position. A long-arm cast was applied for 4 to 6 weeks. Complications of surgeries were recorded, and pre- and postoperative forearm position was measured. RESULTS: The average postoperative follow-up was 5 years. The patient age at the final follow-up ranged from 5 to 19 years. There were no major surgery-related complications. The average forearm position was improved from 72° pronation before surgery to neutral after surgery, except 2 forearms. Elbow flexion and extension showed no change. All parents noted that daily activities were improved after surgery, and they found the surgical scar in the midforearm acceptable. CONCLUSIONS: Single osteotomy at the radial diaphysis was effective for correcting pronation deformity in congenital RU synostosis in children younger than 9 years. Complications were few, and the correction was maintained through midterm follow-up. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Assuntos
Diáfises/cirurgia , Osteotomia/métodos , Rádio (Anatomia)/anormalidades , Sinostose/cirurgia , Ulna/anormalidades , Criança , Pré-Escolar , Diáfises/anormalidades , Feminino , Humanos , Lactente , Masculino , Rádio (Anatomia)/cirurgia , Ulna/cirurgia
15.
Autophagy ; 20(2): 349-364, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37733908

RESUMO

The VPS37A gene encodes a subunit of the endosomal sorting complex required for transport (ESCRT)-I complex that is frequently lost in a wide variety of human solid cancers. We have previously demonstrated the role of VPS37A in directing the ESCRT membrane scission machinery to seal the phagophore for autophagosome completion. Here, we report that VPS37A-deficient cells exhibit an accumulation of the apoptotic initiator CASP8 (caspase 8) on the phagophore and are primed to undergo rapid apoptosis through the intracellular death-inducing signaling complex (iDISC)-mediated CASP8 activation upon exposure to endoplasmic reticulum (ER) stress. Using CRISPR-Cas9 gene editing and comparative transcriptome analysis, we identified the ATF4-mediated stress response pathway as a crucial mediator to elicit iDISC-mediated apoptosis following the inhibition of autophagosome closure. Notably, ATF4-mediated iDISC activation occurred independently of the death receptor TNFRSF10B/DR5 upregulation but required the pro-apoptotic transcriptional factor DDIT3/CHOP to enhance the mitochondrial amplification pathway for full-activation of CASP8 in VPS37A-deficient cells stimulated with ER stress inducers. Our analysis also revealed the upregulation of NFKB/NF-kB signaling as a potential mechanism responsible for restraining iDISC activation and promoting cell survival upon VPS37A depletion. These findings have important implications for the future development of new strategies to treat human cancers, especially those with VPS37A loss.Abbreviations: ATG: autophagy related; BMS: BMS-345541; CASP: caspase; CHMP: charged multivesicular body protein; DKO: double knockout; Dox: doxycycline; ER: endoplasmic reticulum; ESCRT: endosomal sorting complex required for transport; gRNA: guide RNA; GSEA: gene set enrichment analysis; GSK157: GSK2656157; iDISC: intracellular death-inducing signaling complex; IKK: inhibitor of NFKB kinase; IPA: ingenuity pathway analysis; KO: knockout; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NFKB/NF-kB: nuclear factor kappa B; OZ: 5Z-7-oxozeaenol; RNA-seq: RNA sequencing; UPR: unfolded protein response; TFT: transcription factor target; THG: thapsigargin; TUN: tunicamycin; VPS: vacuolar protein sorting.


Assuntos
NF-kappa B , Neoplasias , Humanos , Caspase 8/genética , NF-kappa B/metabolismo , Autofagia , RNA Guia de Sistemas CRISPR-Cas , Apoptose/genética , Estresse do Retículo Endoplasmático , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo
16.
BJUI Compass ; 4(2): 173-180, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36816147

RESUMO

Objectives: The objective of this work is to investigate the impact of the pelvicalyceal anatomical system (PCS) on calyceal stone formation and surgical outcomes of endoscopic combined intrarenal surgery (ECIRS) for renal and/or proximal ureteral stones with a diameter >15 mm. Patients and methods: PCS was classified as Type I (single pelvis) or Type II (divided pelvis) according to the simple anatomical Takazawa classification. Using prospectively collected data from January 2016 to April 2020, 219 patients were retrospectively reviewed. After excluding patients who underwent a staged procedure, had hydronephrosis greater than grade 2, prior nephrostomy tubes, and failed to access the renal collecting system, 115 patients (Type I: 81, Type II: 34) were included, and the distribution of calyceal stones and surgical outcomes in ECIRS were compared between Types I and II PCS. Results: The median number of renal stone calyces in the Type II group was significantly more than that in the Type I group (p = 0.016). In particular, the Type II group possessed more upper stone calyces. Multivariate logistic regression analysis revealed that Type II PCS was associated with an increased odds ratio (OR) for the presence of upper stone calyces (OR: 2.93, p = 0.018). The stone-free (SF) status at 1 month after surgery, confirmed by abdominal plain radiography, was significantly higher in the Type I group compared with that in Type II (67.9% vs. 39.4%, respectively; p = 0.006). The requirement for additional surgical interventions was significantly higher in the Type II group compared with that in Type I (35.4% vs. 7.4%, respectively; p < 0.001). Multivariate analysis revealed that the number of stone calyces (OR: 4.26; p = 0.001) and Type II PCS (OR: 3.43; p = 0.009) were independent predictors of residual stones after ECIRS. Conclusion: We first revealed that the anatomic properties of PCS play a role in both upper calyceal stone formation and in the success of the ECIRS procedure. Because the SF rate in Type II PCS was significantly lower than that in Type I PCS, additional percutaneous nephrolithotomy tracts might be required, even for ECIRS.

17.
Urol J ; 20(2): 109-115, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36127829

RESUMO

PURPOSE: This study aimed to analyze a feasible and suitable surgical precautionary preparatory technique. The techniques of double-gloving with hygienic hand wash (DH) and single-gloving with surgical hand wash (SS) were compared for their ability to prevent postoperative infection in robotic and laparoscopic minimally invasive surgeries. MATERIALS AND METHODS: A prospective, non-randomized, multicenter study was conducted between January 2016 and June 2020. We divided the robotic and laparoscopic cases into two groups: DH and SS. Data on infectious outcomes were collected. Propensity score matching was performed to control for operative characteristics between the two groups. The primary endpoint was the presence of fever and surgical site infections (SSIs) indicating postoperative infection. RESULTS: Among four medical centers, seven surgeons were allocated to either the DH or the SS group. A total of 221 and 251 patients underwent DH and SS, respectively. Propensity score matching, which included 171 cases from each group, showed that the incidence of fever during hospitalization was significantly lower in the DH group than that in the SS group (11.7% vs. 23.4%, p=0.007). Multivariable analysis revealed that DH was associated with a reduced odds ratio for developing postoperative fever during hospitalization (risk ratio: 0.49, p=0.043). No differences were found in SSI before and after hospitalization between the two groups. CONCLUSION: DH resulted in less postoperative fever and had a comparable effect in preventing SSIs. This procedure could be an alternative to the SS protocol in some minimally invasive surgeries.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Prospectivos , Infecção da Ferida Cirúrgica , Laparoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Retrospectivos
18.
J Pediatr Orthop ; 32(7): 724-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22955537

RESUMO

BACKGROUND: The purpose of this study is to report the natural history of pediatric trigger thumb with locked interphalangeal joint, the efficacy of a splint for this condition, and the outcome of late surgery. METHODS: Medical records of 64 patients were retrospectively reviewed. Patients were treated with a coil splint when parents and patients accepted; otherwise, regular observation was conducted. Splint application and/or observation were terminated either when the patient gained full range of active motion without snapping, or underwent surgical intervention. RESULTS: In splint group, 92% of the patients experienced complete symptom relief in 22 months, whereas 60% resolved completely in 59 months in observation group. The differences were statistically significant. One thumb in a patient with bilateral involvement remained locked while the other completely resolved. The rest of the patients also showed improved symptom from locking to snapping. Four patients with residual snapping underwent surgery at the age of 8 years and above without any deformity and complication. CONCLUSIONS: Splint was efficient in shortening the time for symptom relief; however, the natural history revealed the self-limiting nature of this condition. Late surgery was safe and effective for residual snapping and can be presented as one treatment option to the patients and families, combined with conservative treatment. LEVEL OF EVIDENCE: Level III--retrospective comparative study.


Assuntos
Articulações dos Dedos/patologia , Contenções , Dedo em Gatilho/terapia , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Amplitude de Movimento Articular , Estudos Retrospectivos , Polegar , Fatores de Tempo , Resultado do Tratamento , Dedo em Gatilho/patologia , Dedo em Gatilho/cirurgia
19.
J Hand Surg Am ; 36(3): 432-8, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21333463

RESUMO

PURPOSE: Osteochondromas in pediatric digits occasionally require surgical treatment due to restricted finger motion and/or angulatory deformity. However, the patients are growing children, and the indication for surgical treatment is controversial. We reviewed our cases in order to clarify characteristics of tumors and to report surgical outcomes. METHODS: We performed surgeries on 17 osteochondromas in the digits of 16 patients. The average age at surgery was 3.6 years. Ten of 16 patients had solitary osteochondroma, and 6 patients had been diagnosed with multiple osteochondromatosis. We classified osteochondroma into 3 types, according to their locations. Type A is located at the nonepiphyseal metaphysis of the bone (9 lesions), type B in the metaphysis on the epiphyseal plate side (5 lesions), and type C in the diaphysis (3 lesions). Surgery was indicated for either or both restricted motion and angulatory deformity. Simple excision of the tumor was performed in 14 lesions, wedge osteotomy in 2 fingers, and osteotomy with excision of tumor in 1 finger. The average follow-up period was 49 months (range, 14-155 mo). RESULTS: Surgical outcomes in types B and C were all good, the deformities were well corrected, and range of motion was improved. On the other hand, in type A, 2 cases still had more than 30° of restricted motion at the final follow-up, and another 2 cases showed more than 10° of angulatory deformity. CONCLUSIONS: For type A, early surgical treatment is recommended to prevent the progress of the finger deformity and to improve motion. When the tumors are oriented more laterally and include less than a third of the joint surface, we recommend sufficient tumor excision, which can include part of the articular surface.


Assuntos
Neoplasias Ósseas/cirurgia , Falanges dos Dedos da Mão , Osteocondroma/cirurgia , Fatores Etários , Neoplasias Ósseas/complicações , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Osteocondroma/complicações , Osteocondroma/patologia , Osteotomia , Estudos Retrospectivos , Resultado do Tratamento
20.
J Neuroendocrinol ; 33(12): e13057, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34748241

RESUMO

Vasopressin-synthesizing neurons are located in several brain regions, including the hypothalamic paraventricular nucleus (PVN), supraoptic nucleus (SON) and suprachiasmatic nucleus (SCN). Vasopressin has been shown to have various functions in the brain, including social recognition memory, stress responses, emotional behaviors and circadian rhythms. The precise physiological functions of vasopressin-synthesizing neurons in specific brain regions remain to be clarified. Conditional ablation of local vasopressin-synthesizing neurons may be a useful tool for investigation of the functions of vasopressin neurons in the regions. In the present study, we characterized a transgenic rat line that expresses a mutated human diphtheria toxin receptor under control of the vasopressin gene promoter. Under a condition of salt loading, which activates the vasopressin gene in the hypothalamic PVN and SON, transgenic rats were i.c.v. injected with diphtheria toxin. Intracerebroventricular administration of diphtheria toxin after salt loading depleted vasopressin-immunoreactive cells in the hypothalamic PVN and SON, but not in the SCN. The number of oxytocin-immunoreactive cells in the hypothalamus was not significantly changed. The rats that received i.c.v. diphtheria toxin after salt loading showed polydipsia and polyuria, which were rescued by peripheral administration of 1-deamino-8-d-arginine vasopressin via an osmotic mini-pump. Intrahypothalamic administration of diphtheria toxin in transgenic rats under a normal hydration condition reduced the number of vasopressin-immunoreactive neurons, but not the number of oxytocin-immunoreactive neurons. The transgenic rat model can be used for selective ablation of vasopressin-synthesizing neurons and may be useful for clarifying roles of vasopressin neurons at least in the hypothalamic PVN and SON in the rat.


Assuntos
Técnicas de Transferência de Genes , Genes Transgênicos Suicidas , Neurônios/metabolismo , Vasopressinas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Toxina Diftérica/farmacologia , Deleção de Genes , Genes Transgênicos Suicidas/efeitos dos fármacos , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/genética , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos , Ratos Endogâmicos Lew , Ratos Transgênicos , Núcleo Supraóptico/efeitos dos fármacos , Núcleo Supraóptico/metabolismo , Vasopressinas/genética
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