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1.
Cell ; 178(5): 1159-1175.e17, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31442405

RESUMO

Expansion of CAG trinucleotide repeats in ATXN1 causes spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disease that impairs coordination and cognition. While ATXN1 is associated with increased Alzheimer's disease (AD) risk, CAG repeat number in AD patients is not changed. Here, we investigated the consequences of ataxin-1 loss of function and discovered that knockout of Atxn1 reduced CIC-ETV4/5-mediated inhibition of Bace1 transcription, leading to increased BACE1 levels and enhanced amyloidogenic cleavage of APP, selectively in AD-vulnerable brain regions. Elevated BACE1 expression exacerbated Aß deposition and gliosis in AD mouse models and impaired hippocampal neurogenesis and olfactory axonal targeting. In SCA1 mice, polyglutamine-expanded mutant ataxin-1 led to the increase of BACE1 post-transcriptionally, both in cerebrum and cerebellum, and caused axonal-targeting deficit and neurodegeneration in the hippocampal CA2 region. These findings suggest that loss of ataxin-1 elevates BACE1 expression and Aß pathology, rendering it a potential contributor to AD risk and pathogenesis.


Assuntos
Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Ataxina-1/metabolismo , Encéfalo/metabolismo , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Ataxina-1/deficiência , Ataxina-1/genética , Encéfalo/patologia , Região CA2 Hipocampal/metabolismo , Região CA2 Hipocampal/patologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Feminino , Frequência do Gene , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Neurogênese , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Repetições de Trinucleotídeos/genética , Regulação para Cima
2.
Eur Spine J ; 32(8): 2875-2881, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37029807

RESUMO

INTRODUCTION: Endoscopic techniques are becoming popular among spine surgeons because of their advantages. Though the advantages of endoscopic spine surgery are evident and patients can be discharged home within hours of surgery, readmissions can be sought for incomplete relief of leg pain, recurrent disc herniation, and recurrent leg pain. We aim to find out the factors related to the readmission of patients treated for lumbar pathologies. MATERIALS AND METHODS: This is a retrospective analysis of the data between the time duration of 2012 and 2022. Patients in the age group of 18-85 years, with lumbar disc herniation treated by transforaminal endoscopic lumbar procedures, were included. The patients who were readmitted within 90 days were included in the R Group and those who were not were included in the NR group. Univariable and multivariable logistic regression analyses were used to find the risk factors for 90-day readmission. RESULTS: There were a total of 1542 patients enrolled in this study. Sex, number of episodes before admission, hypertension, smoking, BMI, migration, disc height, disc height index, spondylolisthesis, instability, pelvic tilt (PT), and disc cross-sectional area (CSA) were found significant on univariable analysis. Age, spondylolisthesis, instability and muscle CSA were the only variables that were found to be statistically significant on multivariable analysis. CONCLUSIONS: This study shows that the elderly age group, presence of spondylolisthesis, segmental instability and decreased muscle cross-sectional area are independent risk factors for 90-day hospital readmissions. Patients having the above risk factors should be carefully counseled regarding the possibility of readmission in the future.


Assuntos
Discotomia , Deslocamento do Disco Intervertebral , Vértebras Lombares , Readmissão do Paciente , República da Coreia/epidemiologia , Fatores de Risco , Readmissão do Paciente/estatística & dados numéricos , Vértebras Lombares/cirurgia , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Endoscopia/estatística & dados numéricos , Discotomia/estatística & dados numéricos , Deslocamento do Disco Intervertebral/epidemiologia , Dor
3.
Eur Spine J ; 32(8): 2647-2661, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36973463

RESUMO

OBJECTIVE: The study aims to assess the current development status of transforaminal full-endoscopic spine surgery (TFES) by exploring and analyzing the published literature to obtain an overview of this field and discover the evolution and emerging topics that are underrepresented. METHODS: Using Bibliometrix, CiteSpace, and VOSviewer, we analyzed the bibliometric data selected from the Web of Science Core Collection between January 2002 and November 2022. The descriptive and evaluative analyses of authors, institutes, countries, journals, keywords, and references are compiled. The quantity of research productivity was measured by the number of publications that were published. A quality indicator was thought to be the number of citations. In the bibliometric analysis of authors, areas, institutes, and references, we calculated and ranked the research impact by various metrics, such as the h-index and m-index. RESULTS: A total of 628 articles were identified in the field of TFES by the 18.73% annual growth rate of research on the subject from 2002 to 2022, constituting the documents are by 1961 authors affiliated with 661 institutions in 42 countries or regions and published in 117 journals. The USA (n = 0.20) has the highest international collaboration rate, South Korea has the highest H-index value (h = 33), and China is ranked as the most productive country (n = 348). Brown univ., Tongji univ., and Wooridul Spine represented the most productive institutes ranked by the number of publications. Wooridul Spine Hospital demonstrated the highest quality of paper publication. The Pain Physician had the highest h-index (n = 18), and the most cited journal with the earliest publication year in the area of FEDS is Spine (t = 1855). CONCLUSION: The bibliometric study showed a growing trend of research on transforaminal full-endoscopic spine surgery over the past 20 years. It has shown a significant increase in the number of authors, institutions, and international collaborating countries. South Korea, the United States, and China dominate the related areas. A growing body of evidence has revealed that TFES has leapfrogged from its infancy stage and gradually entered a mature development stage.


Assuntos
Bibliometria , Endoscopia , Humanos , China , República da Coreia , Coluna Vertebral/cirurgia
4.
Am J Hum Genet ; 98(6): 1243-1248, 2016 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-27236923

RESUMO

Spondyloepimetaphyseal dysplasias (SEMDs) comprise a heterogeneous group of autosomal-dominant and autosomal-recessive disorders. An apparent X-linked recessive (XLR) form of SEMD in a single Italian family was previously reported. We have been able to restudy this family together with a second family from Korea by segregating a severe SEMD in an X-linked pattern. Exome sequencing showed missense mutations in BGN c.439A>G (p.Lys147Glu) in the Korean family and c.776G>T (p.Gly259Val) in the Italian family; the c.439A>G (p.Lys147Glu) mutation was also identified in a further simplex SEMD case from India. Biglycan is an extracellular matrix proteoglycan that can bind transforming growth factor beta (TGF-ß) and thus regulate its free concentration. In 3-dimensional simulation, both altered residues localized to the concave arc of leucine-rich repeat domains of biglycan that interact with TGF-ß. The observation of recurrent BGN mutations in XLR SEMD individuals from different ethnic backgrounds allows us to define "XLR SEMD, BGN type" as a nosologic entity.


Assuntos
Biglicano/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação/genética , Osteocondrodisplasias/genética , Adulto , Idoso , Sequência de Aminoácidos , Biglicano/química , Biglicano/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Linhagem , Ligação Proteica , Conformação Proteica , Homologia de Sequência de Aminoácidos , Fator de Crescimento Transformador beta/química , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
5.
J Environ Manage ; 217: 373-380, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29625406

RESUMO

Ventilation air methane (VAM), which is the main source of greenhouse gas emissions from coal mines, has been a great challenge to deal with due to its huge flow rates and dilute methane levels (typically 0.3-1.0 vol%) with almost 100% humidity. As part of our continuous endeavor to further improve the methane adsorption capacity of carbon composites, this paper presents new carbon composites derived from macadamia nut shells (MNSs) and incorporated with carbon nanotubes (CNTs). These new carbon composites were fabricated in a honeycomb monolithic structure to tolerate dusty environment and to minimize pressure drop. This paper demonstrates the importance of biomass particle size distributions when formed in a composite and methane adsorption capacities at low pressures relevant to VAM levels. The selectivity of methane over nitrogen was about 10.4 at each relevant partial pressure, which was much greater than that (6.5) obtained conventionally (at very low pressures), suggesting that capturing methane in the presence of pre-adsorbed nitrogen would be a practical option. The equilibrium and dynamic performance of biomass-derived carbon composites were enhanced by 30 and 84%, respectively, compared to those of our previous carbon fiber composites. In addition, the presence of moisture in ventilation air resulted in a negligible effect on the dynamic VAM capture performance of the carbon composites, suggesting that our carbon composites have a great potential for site applications at coal mines because the cost and performance of solid adsorbents are critical factors to consider.


Assuntos
Carvão Mineral , Metano , Nanotubos de Carbono , Biomassa , Mineração , Ventilação
6.
Genet Med ; 18(6): 563-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26402641

RESUMO

PURPOSE: The purpose of this study was to evaluate the clinical utility of targeted exome sequencing (TES) as a molecular diagnostic tool for patients with skeletal dysplasia. METHODS: A total of 185 patients either diagnosed with or suspected to have skeletal dysplasia were recruited over a period of 3 years. TES was performed for 255 genes associated with the pathogenesis of skeletal dysplasia, and candidate variants were selected using a bioinformatics analysis. All candidate variants were confirmed by Sanger sequencing, correlation with the phenotype, and a cosegregation study in the family. RESULTS: TES detected "confirmed" or "highly likely" pathogenic sequence variants in 74% (71 of 96) of cases in the assured clinical diagnosis category and 20.3% (13 of 64 cases) of cases in the uncertain clinical diagnosis category. TES successfully detected pathogenic variants in all 25 cases of previously known genotypes. The data also suggested a copy-number variation that led to a molecular diagnosis. CONCLUSION: This study demonstrates the feasibility of TES for the molecular diagnosis of skeletal dysplasia. However, further confirmation is needed for a final molecular diagnosis, including Sanger sequencing of candidate variants with suspected, poorly captured exons.Genet Med 18 6, 563-569.


Assuntos
Sequenciamento do Exoma/métodos , Anormalidades Musculoesqueléticas/diagnóstico , Anormalidades Musculoesqueléticas/genética , Patologia Molecular , Variações do Número de Cópias de DNA/genética , Éxons/genética , Feminino , Humanos , Masculino , Anormalidades Musculoesqueléticas/fisiopatologia , Mutação , Linhagem , Fenótipo
7.
Eur Spine J ; 25(5): 1382-1388, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26818031

RESUMO

PURPOSE: A retrospective cross-sectional study was designed to explore the role of spinopelvic sagittal alignment in upper lumbar disc herniation (ULD) development. METHODS: A total of 207 consecutive patients who underwent surgery for single-level lumbar disc herniation [24 with ULD and 183 with lower lumbar disc herniation (LLD)] and 40 asymptomatic volunteers were enrolled. Full-length radiographs of the spine were taken to evaluate pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), thoracic kyphosis (TK), lumbar lordosis (LL), and sagittal vertical axis (SVA). The Roussouly classification was utilized to categorize all subjects according to their sagittal alignment. Spinopelvic parameters and Roussouly classification results were compared between groups. RESULTS: There were significant differences in PI, SS, PT, LL, and SVA between the ULD, LLD, and control groups. PI in the ULD (40.9°) was significantly lower than in the LLD and control groups (48.8° and 47.6°, respectively). LL was significantly lower in the ULD than in the LLD (-32.4° and -40°, respectively). There were significant differences between the three groups in Roussouly types. The LLD had a significantly higher proportion (62.6 %) of type 2 lordosis (flat back), and the ULD had a higher proportion (33.3 %) of type 1 lordosis than the other groups. CONCLUSIONS: This study demonstrated the importance of PI and lumbar curvature in the pathogenesis of ULD. The higher prevalence of short LL and long TK with low PI in the ULD group implies that an increased mechanical stress at this level may be one of the risk factors of ULD.


Assuntos
Deslocamento do Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Pelve/diagnóstico por imagem , Radiografia , Adulto , Feminino , Humanos , Lordose/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
8.
Korean J Physiol Pharmacol ; 20(1): 35-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26807021

RESUMO

To conduct a kinetic study of paraquat (PQ), we investigated 9 patients with acute PQ intoxication. All of them ingested more than 20 ml of undiluted PQ herbicide to commit suicide and arrived at our hospital early, not later than 7 h after PQ ingestion. The urine dithionite test for PQ in all of the nine patients was strongly positive at emergency room. Blood samples were obtained every 30 min for the first 2~3 h and then every 1 or 2 h, as long as the clinical progression was stable among the patients for 30 h after PQ ingestion. The area under the plasma concentration-time curve (AUCinf), which was extrapolated to infinity, was calculated using the trapezoidal rule. Toxicokinetic parameters, such as the terminal elimination half-life, apparent oral clearance, and apparent volume of distribution (Vd/F) were calculated. The maximum PQ concentration (Cmax) and the time to reach maximum PQ concentration (Tmax) were also obtained. Plasma PQ concentrations in nine patients were well described by a bi-exponential curve with a mean terminal elimination half-life of 13.1±6.8 h. Cmax and AUCinf were 20.8±25.7 mg/l and 172.5±160.3 h·mg/l, respectively. Apparent volume of distribution and apparent oral clearance were 50.9±61.3 l/kg and 173.4±111.2 l/h, respectively. There were a significant correlation (r =0.84; p<0.05) between the PQ amount ingested and Cmax. AUCinf also showed a significant correlation (r =0.83; p<0.05) with the PQ amount ingested. These correlations provide evidence that PQ has dose-linear toxicokinetic characteristics.

9.
Am J Med Genet A ; 167A(5): 1033-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25728306

RESUMO

Chromosomal translocation of 2q37.1 just distal to the NPPC gene coding for C-type natriuretic peptide (CNP) and subsequent overproduction of CNP have been reported to cause a skeletal overgrowth syndrome. Loeys-Dietz syndrome (LDS) is one of marfanoid overgrowth syndromes, of which subtype IV is caused by haploinsufficiency of transforming growth factor beta 2 (TGFB2). We report on a girl with clinical phenotypes of overgrowth syndrome, including long and slim body habitus, macrodactyly of the big toe, scoliosis, ankle valgus deformity, coxa valga, slipped capital femoral epiphysis, and aortic root dilatation. Karyotyping revealed a balanced chromosomal translocation between 1q41 and 2q37.1, and the breakpoints could be mapped by targeted resequencing analysis. On chromosome 2q37.1, the translocation took place 200,365 bp downstream of NPPC, and serum level of the amino terminal of CNP was elevated. The contralateral site of translocation on chromosome 1q41 disrupted TGFB2 gene, presumed to cause its haploinsufficiency. This case supports the concept that NPPC is overexpressed because of the loss of a specific negative regulatory control in the normal chromosomal location, and demonstrates the effectiveness of targeted resequencing in the mapping of breakpoints.


Assuntos
Síndrome de Loeys-Dietz/genética , Peptídeo Natriurético Tipo C/biossíntese , Translocação Genética/genética , Adolescente , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 2/genética , Feminino , Regulação da Expressão Gênica , Haploinsuficiência , Humanos , Cariotipagem , Síndrome de Loeys-Dietz/fisiopatologia , Peptídeo Natriurético Tipo C/sangue , Peptídeo Natriurético Tipo C/genética , Fenótipo , Fator de Crescimento Transformador beta2/genética
10.
Pediatr Nephrol ; 30(9): 1451-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25726036

RESUMO

BACKGROUND: Nephronophthisis 13 (NPHP 13) is associated with mutations in the WDR19 gene, which encodes for a protein in the intraflagellar transport complex. Herein, we describe six additional cases accompanied by Caroli syndrome or disease. METHODS: Targeted exome sequencing covering 96 ciliopathy-related genes was performed for 48 unrelated Korean patients with a clinical suspicion of NPHP. Mutations were confirmed by Sanger sequencing. We evaluated the expression of WDR19 in the biopsied kidney by immunohistochemistry in patients and controls. RESULTS: We detected three (3/48, 6.3 %) unrelated index cases with WDR19 mutations. One of the cases involved two siblings with the same mutation. Later, we detected an additional index case with a similar phenotype of kidney and liver involvement by Sanger sequencing of WDR19. The p.R1178Q mutation was common in all patients. All of the six affected patients from four families progressed to chronic kidney disease. Of note, all six patients had Caroli syndrome or disease. Immunohistochemistry for WDR19 showed localized expression along the luminal borders of the renal tubular epithelium in controls, whereas it showed diffuse cytoplasmic staining in the affected patients. CONCLUSIONS: Caroli disease is a major extra-renal phenotype associated with mutations in WDR19 in the Korean population. In this study, we visually validated the expression pattern of mutant WDR19 protein in the kidneys of NPHP 13 patients. More data are needed to identify the true frequency of p.R1178Q. Functional studies including transfection assay will provide solid grounds for the pathogenicity of each mutation.


Assuntos
Doença de Caroli , Rim/patologia , Rim Policístico Autossômico Recessivo , Proteínas/genética , Adolescente , Doença de Caroli/diagnóstico , Doença de Caroli/genética , Criança , Proteínas do Citoesqueleto , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Mutação , Rim Policístico Autossômico Recessivo/diagnóstico , Rim Policístico Autossômico Recessivo/genética , Sequências Repetitivas de Aminoácidos/genética , República da Coreia , Adulto Jovem
11.
Pediatr Int ; 57(3): 431-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25443527

RESUMO

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in the Asian population. We studied a Korean pediatric cohort to delineate the clinical characteristics and genotypes. METHODS: A multicenter cohort of 51 Korean children with aHUS was screened for mutations using targeted exome sequencing covering 46 complement related genes. Anti-complement-factor-H autoantibody (anti-CFH) titers were measured. Multiplex ligation-dependent probe amplification assay was performed to detect deletions in the complement factor-H related protein genes (CFHR) in the patients as well as in 100 healthy Korean controls. We grouped the patients according to etiology and compared the clinical features using Mann-Whitney U-test and chi-squared test. RESULTS: Fifteen patients (group A, 29.7%) had anti-CFH, and mutations were detected in 11 (group B, 21.6%), including one with combined mutations. The remaining 25 (group C, 49.0%) were negative for both. The prevalence of anti-CFH was higher than the worldwide level. Group A had a higher onset age than group B, although the difference was not significant. Group B had the worst renal outcome. Gene frequencies of homozygous CFHR1 deletion were 73.3%, 2.7% and 1% in group A, group B + C and the control, respectively. CONCLUSIONS: The incidence of anti-CFH in the present Korean aHUS cohort was high. Clinical outcomes largely conformed to the previous reports. Although the sample size was limited, this cohort provides a reassessment of clinicogenetic features of aHUS in Korean children.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Autoanticorpos/imunologia , Fator H do Complemento/genética , Predisposição Genética para Doença , Mutação , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/imunologia , Criança , Pré-Escolar , Fator H do Complemento/metabolismo , Feminino , Frequência do Gene , Humanos , Incidência , Lactente , Masculino , Reação em Cadeia da Polimerase Multiplex , República da Coreia/epidemiologia
12.
J Biol Chem ; 288(9): 6295-305, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23303189

RESUMO

Regulation of intracellular pH is critical for the maintenance of cell homeostasis in response to stress. We used yeast two-hybrid screening to identify novel interacting partners of the pH-regulating transporter NBCe1-B. We identified Hsp70-like stress 70 protein chaperone (STCH) as interacting with NBCe1-B at the N-terminal (amino acids 96-440) region. Co-injection of STCH and NBCe1-B cRNA into Xenopus oocytes significantly increased surface expression of NBCe1-B and enhanced bicarbonate conductance compared with NBCe1-B cRNA alone. STCH siRNA decreased the rate of Na(+)-dependent pHi recovery from NH4(+) pulse-induced acidification in an HSG (human submandibular gland ductal) cell line. We observed that in addition to NBCe1-B, Na(+)/H(+) exchanger (NHE)-dependent pHi recovery was also impaired by STCH siRNA and further confirmed the interaction of STCH with NHE1 but not plasma membrane Ca(2+) ATPase. Both NBCe1-B and NHE1 interactions were dependent on a specific 45-amino acid region of STCH. In conclusion, we identify a novel role of STCH in the regulation of pHi through site-specific interactions with NBCe1-B and NHE1 and subsequent modulation of membrane transporter expression. We propose STCH may play a role in pHi regulation at times of cellular stress by enhancing the recovery from intracellular acidification.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Simportadores de Sódio-Bicarbonato/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Estresse Fisiológico/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Transporte de Cátions/genética , Linhagem Celular , Membrana Celular/genética , Membrana Celular/metabolismo , Proteínas de Choque Térmico HSP70/genética , Humanos , Concentração de Íons de Hidrogênio , Transporte de Íons/fisiologia , Ligação Proteica , Simportadores de Sódio-Bicarbonato/genética , Trocador 1 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/genética , Xenopus
13.
Environ Sci Technol ; 48(10): 6043-9, 2014 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-24787090

RESUMO

Treatment of ventilation air methane (VAM) with cost-effective technologies has been an ongoing challenge due to its high volumetric flow rate with low and variable methane concentrations. In this work, honeycomb monolithic carbon fiber composites were developed and employed to capture VAM with a large-scale test unit at various conditions such as VAM concentration, ventilation air (VA) flow rate, temperature, and purging fluids. Regardless of inlet VAM concentrations, methane was captured at almost 100%. To regenerate the composites, the initial vacuum swing followed by combined temperature and vacuum swing adsorption (TVSA) was applied. It was found that initial vacuum swing is a control step for the final methane concentration having 5 or 11 times the VAM enrichment by one-step adsorption, which is, to our knowledge, the best performance achieved in VAM enrichment technologies worldwide. Five-time enriched VAM can be utilized as a principle fuel for lean burn turbine. Also, it can be further enriched by second step adsorption to more than 25% which then can be used for commercially available gas engines. In this way, the final product can be out of the methane explosive range (5-15%).


Assuntos
Ar , Carbono/química , Metano/análise , Ventilação , Adsorção , Dióxido de Carbono/química , Fibra de Carbono , Nitrogênio/química , Porosidade , Reologia , Temperatura , Vácuo
14.
Asian Spine J ; 18(2): 265-273, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38650096

RESUMO

This retrospective case series of prospective data aims to describe the transaxillary approach for the treatment of upper thoracic spine pathology. Various surgical techniques and approaches have been reported across the literature to address upper thoracic spine pathology, including the cervicothoracic approach, anterior transsternal approach, posterolateral approach, supraclavicular approach, and lateral parascapular approaches. These techniques are invasive. A minimally invasive, less morbid, and direct access approach to the pathology of the upper thoracic spine has not been reported in the literature. Patients with pathology affecting the first thoracic vertebra up to the sixth thoracic vertebra were classified into the upper thoracic spine group. Patients with pathology below the sixth thoracic vertebra were excluded. Patients not having a minimum follow-up of 12 months were also excluded. The study analyzed 18 patients. The mean preoperative modified Japanese Orthopedic Association score was 7.2±1.44, which improved to 10.16±1.2 (p<0.05). The majority (14/18) of the patients had an excellent outcome. Three patients had good outcomes, and one patient had a fair outcome. Five cases of intraoperative dural leak were recorded, and one patient had postoperative neurological deficit. The transaxillary approach is a safe, viable, muscle-sparing, and minimally invasive approach for ventral pathologies of the upper thoracic spine.

15.
Int J Spine Surg ; 18(1): 73-80, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38320806

RESUMO

BACKGROUND: The treatment of Kummell disease remains controversial, with a wide variety of options proposed in the literature. This study aims to introduce a unique and minimally invasive approach for the treatment of Kummell disease and present the clinical results of this technique. METHODS: Twenty patients underwent surgery using the minimally invasive surgery transpedicular intrabody cage (MISTIC) technique from 2014 to 2016. Postoperatively, patients were seen at 3, 6, and 12 months after surgery. Visual analog scale and Oswestry Disability Index scores were collected, and patient outcomes were graded according to the modified MacNab's criteria. Radiological outcomes were assessed through measurements of the anterior vertebral height (AH), mean vertebral body height (BH), and segmental angle (SA) on standing lateral radiographs pre- and postoperatively. RESULTS: There was significant improvement in the SA, AH, and BH postoperatively. The SA improved from 15.2 ± 8.7° of kyphosis to 1.2 ± 5.2° (P < 0.01) in the immediate postoperative period. The AH increased from 13.3 ± 14.6 to 22.6 ± 12.2 mm (P < 0.01), and at the final follow-up, it was 21.9 ± 12.6 mm (P < 0.01). Similarly, the BH increased from 18.5 ± 6.8 to 25.6 ± 7.6 mm (P < 0.01) postsurgery, and at the final follow-up, it was 23.6 ± 4.4 mm (P < 0.01). CONCLUSIONS: The MISTIC technique offers significant correction of kyphosis and restoration of the vertebral anatomy following surgery. These results were maintained at 12 months postoperation, with a 100% union rate of the fractures. Additionally, patients experienced significant pain relief and improvement in their ODI scores that were maintained at 12 months.

16.
Biochim Biophys Acta ; 1822(2): 161-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22137887

RESUMO

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by lymphocyte infiltration into the salivary and lachrymal glands, leading to dry mouth and eyes. The presence of functional autoantibodies against muscarinic type 3 receptor (M3R) has been reported in pSS patients. However, the pathological role of anti-M3R autoantibodies in pSS salivary dysfunction remains controversial. METHODS: Purified IgGs were obtained from normal (control) and primary SS patients' sera (pSS IgG). Internalization of M3R and clathrin was analyzed by biochemical assay and immunofluorescence confocal microscopy using human submandibular gland (hSMG) cells. Cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) was measured by microspectrofluorimetry. RESULTS: Incubation of hSMG cells with pSS IgG (1mg/ml) significantly decreased M3R expression levels at the membrane. Carbachol-induced [Ca(2+)](i) transients (CICTs) in these cells were also inhibited by pSS IgG. In contrast to pSS IgG, control IgG had no effect on both the M3R expression level and CICTs. We found that binding of pSS IgG to M3R induces phosphorylation of the receptor, and that the pSS IgG-induced M3R internalization is prevented by the lysosomal inhibitor, chloroquine. In addition, pSS IgG decreased membrane clathrin expression, which was inhibited by atropine. Our immunofluorescence study further confirmed that pSS IgG induces a co-localization of M3R with clathrin and subsequent internalization of M3R. CONCLUSION: pSS IgG induces internalization of M3R partly through a clathrin-mediated pathway. The results suggest M3R internalization as a potential mechanism to explain the exocrinopathy seen in pSS patients.


Assuntos
Autoanticorpos/metabolismo , Imunoglobulina G/metabolismo , Receptor Muscarínico M3/metabolismo , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/metabolismo , Adulto , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Cálcio/metabolismo , Carbacol/farmacologia , Cloroquina/farmacologia , Clatrina/genética , Clatrina/metabolismo , Regulação para Baixo , Feminino , Imunofluorescência/métodos , Humanos , Imunoglobulina G/sangue , Microscopia Confocal/métodos , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Receptor Muscarínico M3/genética , Síndrome de Sjogren/sangue , Síndrome de Sjogren/genética , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/imunologia , Glândula Submandibular/metabolismo
17.
Biochem Biophys Res Commun ; 437(1): 18-22, 2013 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-23769829

RESUMO

Expression of inositol-1,4,5-trisphosphate (IP3) receptor-binding protein (IRBIT) has been reported in epithelial cells. However, its role in pHi regulation is not well understood. In this study, we investigated the role of IRBIT in pHi regulation, mediated by Na(+)/H(+) exchangers (NHEs), in salivary glands. We measured pHi recovery from cell acidification in BCECF-loaded salivary HSG cells. Western blot and co-immunoprecipitation (CO-IP) assays were also performed, showing that NHE1, 2 and 3 are expressed, and IRBIT binds to NHE3. HOE642, a specific NHE1 blocker, inhibited pHi recovery, but 40% pH(i) recovery was still observed even at the highest concentration of HOE642. Furthermore, pretreatment of the cells with siIRBIT significantly inhibited pHi recovery, indicating that NHE3 potentially plays a role in pHi recovery as well. The amount of membrane-localized NHE3 and its interaction with IRBIT are also significantly increased by cell acidification. In addition, we found that Ste20p-related proline alanine-rich kinase (SPAK) reverses the effect of IRBIT on membrane NHE3 translocation. Taken together, we conclude that IRBIT plays an important role in pHi regulation, mediated by NHE3, and further regulated by SPAK.


Assuntos
Espaço Intracelular/metabolismo , Lectinas Tipo C/metabolismo , Proteínas de Membrana/metabolismo , Glândulas Salivares/citologia , Trocadores de Sódio-Hidrogênio/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Linhagem Celular , Humanos , Concentração de Íons de Hidrogênio , Ligação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Transporte Proteico , Trocador 1 de Sódio-Hidrogênio , Trocador 3 de Sódio-Hidrogênio
18.
World Neurosurg ; 173: e408-e414, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36805502

RESUMO

OBJECTIVE: High-grade migrated lumbar disc herniation (LDH) such as up-migrated and down-migrated discs are challenging pathologies to treat. High-grade migrated discs are usually sequestered and situated adjacent to the medial pedicle wall. This can be easily addressed if the pedicle is used as an access route. The authors present a retrospective case series of high-grade migrated LDH treated using a full endoscopic transforaminal approach. MATERIALS AND METHODS: This is a retrospective case series. The clinical outcomes in the patients were evaluated according to improvement in the symptoms as suggested by improvement in Visual Analog Score (VAS) and Oswestry Disability Index (ODI) scores in the immediate postoperative period and at the final follow-up. The radiological outcomes were evaluated using postoperative magnetic resonance imaging and computed tomography scans. After the data were collected and tabulated, descriptive statistics were used for continuous variables. The t test was used to determine the significance of changes in the VAS and ODI scores. Statistical significance was set at P < 0.05. RESULTS: Five patients underwent discectomy using the transpedicular technique, and the mean preoperative VAS scores for the back and leg were 7.2 ± 0.83 and 8.4 ± 0.54, respectively. The mean VAS scores at the final follow-up for the back was 0.2 ± 0.4 and 0 for the leg (P < 0.05). The mean preoperative ODI score was 72 ± 8.3, which improved to 6 ± 4.69 at the final follow-up (P < 0.05). All patients had a hospital stay of 1 day. CONCLUSIONS: The full endoscopic transpedicular approach is a good option for treating highly migrated LDH. Surgical planning, including pedicle morphometry and the angle of the approach, should be undertaken preoperatively for the best results.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Seguimentos , Resultado do Tratamento , Discotomia Percutânea/métodos , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Endoscopia/métodos
19.
Clin Case Rep ; 11(12): e8246, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38111513

RESUMO

Key clinical message: Spinal cord herniation is an uncommon diagnosis. There should be a high index of suspicion to diagnose spinal cord herniation when a patient presents with incomplete neurological deficits. Surgical repair of the hernia can have postoperative complications with new neurological deficits and they should be considered during the treatment. Abstract: A 37-year-old male presented with insidious onset upper back pain and altered sensations of pain and temperature over the right half of the body below the nipple for 2 months. MRI of the thoracic spine showed an anterolateral defect (left) at the level of T2-T3 vertebra. The defect was covered by a dural graft and the wound was closed with a drain On the 3rd postoperative day, neurological weakness progressed to paraplegia. Patient was treated by exploration and decompression of the hematoma. The deficits were completely recovered at one-month follow-up. Patients with spinal cord herniation and neurologic deficits when treated timely have good outcomes.

20.
PLoS One ; 18(4): e0283924, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37018239

RESUMO

Lumbar spinal stenosis is a common spinal degenerative condition. Minimally invasive interlaminar full-endoscopic decompressive laminectomy provides greater patient satisfaction and faster recovery than open decompressive laminectomy. The aim of our randomized controlled trial will be to compare the safety and efficacy of interlaminar full-endoscopic laminectomy and open decompressive laminectomy. Our trial will include 120 participants (60 per group) who will undergo surgical treatment for lumbar spinal stenosis. The primary outcome will be the Oswestry Disability Index measured at 12 months postoperatively. Secondary patient-reported outcomes will include back and radicular leg pain measured via a visual analog scale; the Oswestry Disability Index; the Euro-QOL-5 Dimensions score measured at 2 weeks and at 3, 6, and 12 months postoperatively; and patient satisfaction. The functional measures will include time to return to daily activities postoperatively and walking distance/time. The surgical outcomes will include postoperative drainage, operation time, duration of hospital stay, postoperative creatine kinase (an indicator of muscle injury) level, and postoperative surgical scarring. Magnetic resonance and computed tomography images and simple radiographs will be obtained for all patients. The safety outcomes will include surgery-related complications and adverse effects. All evaluations will be performed by a single assessor at each participating hospital who will be blinded to group allocation. The evaluations will be conducted preoperatively and at 2 weeks and 3, 6, and 12 months postoperatively. The randomized, multicenter design of the trial, blinding, and justification of the sample size will reduce the risk of bias in our trial. The results of the trial will provide data regarding the use of interlaminar full-endoscopic laminectomy as an alternative to open decompressive laminectomy that results in similar surgical findings with less invasiveness. Trial registration: This trial is registered at cris.nih.go.kr. (KCT0006198; protocol version 1; 27 May 2021).


Assuntos
Laminectomia , Estenose Espinal , Humanos , Laminectomia/métodos , Descompressão Cirúrgica/métodos , Estenose Espinal/cirurgia , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Vértebras Lombares/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
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