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1.
Opt Lett ; 45(6): 1515-1518, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32164005

RESUMO

The spectral resolution of broadband Fourier-transform coherent anti-Stokes Raman spectroscopy is limited by the maximum optical path length difference that can be scanned within a short time in an interferometer. However, alternatives to the Fourier transform exist which can bypass this limitation with certain assumptions. We apply one such approach to broadband coherent Raman spectroscopy using interferometers with a short delay line (low Fourier spectral resolution) and large delay line (high Fourier spectral resolution). With this method, we demonstrate that broadband coherent Raman spectroscopy of closely spaced vibrational bands is possible using a short delay line interferometer with comparable spectral resolution to the longer delay line instrument. We discuss how this approach may be particularly useful for more complex Raman spectra, such as those measured from biological samples.

2.
Muscle Nerve ; 58(6): 824-827, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30019482

RESUMO

INTRODUCTION: Needle electromyography (EMG) has been an important diagnostic tool, although discomfort may limit its use in some children. We investigated the diagnostic utility of the clustering index (CI) method, a quantitative analysis for surface EMG (SEMG), in children. METHODS: SEMG was recorded from the tibialis anterior muscle. Discriminant analysis between patients with neurogenic disorders and patients with myopathy was performed for whole epochs by using the CI and area values. RESULTS: Forty-five children (29 with myopathy, 16 with neurogenic disorders; age 9 ± 3.9 years) were enrolled. The mean discriminant function value of the neurogenic group was 0.58 ± 0.88 (-0.48-2.30), whereas that of the myopathic group was -0.55 ± 0.70 (-2.38-0.68). When the cutoff value was set at the limit of the other group, 17 of 29 children with myopathy and 7 of 16 children with neurogenic disorders were correctly classified. DISCUSSION: The CI method can be a useful noninvasive diagnostic tool in children with neuromuscular disorders. Muscle Nerve 58:824-827, 2018.


Assuntos
Eletromiografia/métodos , Potencial Evocado Motor/fisiologia , Músculo Esquelético/fisiopatologia , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/fisiopatologia , Adolescente , Criança , Pré-Escolar , Análise Discriminante , Feminino , Humanos , Lactente , Masculino
3.
Aesthetic Plast Surg ; 42(2): 442-446, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29101435

RESUMO

We describe a new wound management technique using a soft dressing material to stabilize the areola skin graft and protect the nipple after nipple-areola reconstruction at the final stage of breast reconstruction. We introduced a center-fenestrated multilayered hydrocellular polyurethane foam dressing material that provides adequate pressure and retains a moist environment for a smooth skin graft "take." Moreover, the reconstructed nipple can be monitored at any time through the fenestrated window for adequate blood circulation. Altogether, this simple and inexpensive wound dressing technique improves the clinical outcome. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Bandagens , Mamoplastia/métodos , Mamilos/cirurgia , Poliuretanos , Retalhos Cirúrgicos/transplante , Cicatrização/fisiologia , Adulto , Neoplasias da Mama/cirurgia , Estudos de Coortes , Estética , Feminino , Humanos , Japão , Mastectomia/métodos , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Estudos Retrospectivos
4.
Cureus ; 16(3): e56862, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38659568

RESUMO

Introduction During total knee arthroplasty (TKA), also referred to as total knee replacement (TKR), patients may experience pain in the posterolateral knee. One possible cause is the impingement between the popliteus tendon and the femoral components. The purpose of this study was to analyze the posterolateral overhang of the femoral component using 3D template software. Methods Preoperative CT scan images of 50 knees (11 males and 39 females) with osteoarthritis of grade 2 or lower according to the Kellgren-Lawrence classification were analyzed. The mean age of the subjects was 73.8±7.6 years (range 52-84 years). The Athena (Soft Cube Co., Ltd., Osaka, Japan) knee 3D image-matching software was used for the analysis. The positions of the two femoral components (symmetrical and asymmetrical) were simulated. In the coronal plane, the component overhang was measured between the resected lateral part of the posterior femur and its corresponding component size, and the two designs were compared in three zones (proximal, central, and distal). Results In the simulated femoral component, the asymmetric design had a significantly lower component overhang than the symmetric design in the proximal zone of the lateral posterior condyle (0.2±1.9 mm vs. 3.5±1.6 mm, p<0.01). In the proximal zone, significant overhang (>3 mm) was observed in 30 knees (60.0%) with the symmetric design, but only three knees (6.0%) had asymmetric designs (p<0.01). Conclusions The posterolateral overhang of the lateral posterior condyle occurs when a symmetrical prosthesis is used. The use of an asymmetric implant with a small, rounded proximal portion of the lateral posterior condyle improves this overhang and is expected to decrease problems such as impingement of the popliteus tendon and improve patient satisfaction.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38317625

RESUMO

Medial collateral ligament (MCL) pie-crusting can balance the soft tissue during total knee arthroplasty but requires more studies with the finite element method (FEM). We have developed three models of MCL pie-crusting utilizing FEM, treating the MCL in the following ways: (1) as a singular elastic body with both ends attached to the bone (model A), (2) as 19 bundled elastic bodies, each attached to both ends of the bone (model B), and (3) as 19 bundled elastic bodies with an adhesive component in the gap, attached to both ends of the bone (model C). The pie-crusting model was created by adding a cut around the center of each model. The left side of the model was fixed and forces of 80 and 120 N in the positive direction of the x-axis were applied. Model A was extended by 0.0068 and 0.010 mm for approximately 10 punctures. Model B-2 was extended by 1.34 and 2.01 mm, approximately twice as much as model B-1. Model C was extended by 0.34 and 0.50 mm for every 10 punctures added. These findings clarify that the model composed of aggregates of fibers with adhesive parts (model C) is suitable for MCL pie-crusting analysis.

6.
Cureus ; 16(7): e64780, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39156378

RESUMO

Introduction Intraoperative and postoperative bleeding in total knee arthroplasty (TKA) affects postoperative outcomes. Although the hemostatic effect of a flowable gelatin hemostatic matrix (FGHM) is known across several surgical fields, its effectiveness on TKA remains controversial. This study aimed to compare the amount of bleeding across three groups treated with different doses of FGHM in TKA. Methods Overall, 122 knee joints of patients who underwent unilateral primary TKA were included and divided into three groups according to FGHM dose: absence of FGHM (control group, N=48), administration of 5 mL of FGHM (5 mL group, N=46), and administration of 8 mL of FGHM (8 mL group, N=38). Total hemoglobin (Hb) loss, drain output, hidden blood loss (HBL), calculated total blood loss (TBL) on the first postoperative day (POD1) and one week postoperatively (POD7), postoperative flexion angle at one week and discharge, and incidence of postoperative deep venous thrombosis (DVT) were assessed. Results At POD1, the mean total Hb losses were 6.3±3.1g (control group), 5.5±3.3g (5 mL group), and 5.3±2.5g (8 mL group), with no significant differences. At POD7, the mean Hb losses were 9.1±4.6g (control), 8.7±3.6g (5 mL), and 8.3±4.0g (8 mL), also with no significant differences. Mean drain outputs and HBLs showed no significant differences among groups. While there was a decreasing trend in TBL with higher FGHM doses, it was not statistically significant at either POD1 or POD7. There were no statistically significant differences in the mean postoperative flexion angle at POD7 or discharge among the groups (99.7±12.6°, 95.7±12.5°, 98.3±13.8° at POD7; 115.9±9.7°, 113.8±9.6°, 116.6±9.2° at discharge). Of these, only one patient in the 8 mL group developed proximal DVT. Conclusion Despite a trend towards decreased bleeding with FGHM, no significant differences were found among the three groups. However, the clinical utility of this hemostatic agent for reducing blood loss after primary TKA remains still unclear.

7.
J Orthop Case Rep ; 14(9): 81-86, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39253648

RESUMO

Introduction: Open wedge distal tuberosity osteotomy (OWDTO) was the surgical treatment in which tibial tuberosity was attached proximal fragment to avoid an increase in patellofemoral joint pressure. The current paper reported a case of post-operative posterior aspect fracture of the tibia as a rare complication after OWDTO. Case Report: A 52-year-old Asian man had been performing OWDTO for medial knee osteoarthritis. The patient was injured by the tibial posterior aspect fracture due to minor trauma 2 months after surgery. Bone union was completed by transient unloading and ultrasound therapy, but the anteroposterior screw remained in the bone due to screw breakage during removal. Conclusion: Post-operative posterior aspect fracture of the tibia is a complication specific to OWDTO. It is difficult to detect the fracture on X-ray; therefore, the evaluation with computed tomography is recommended. It is possible that removal of the anteroposterior screw has become difficult in the event that this fracture occurs.

8.
Intern Med ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38403773

RESUMO

Post-transplant lymphoproliferative disorders (PTLDs) are lymphoproliferative diseases that occur after solid organ transplantation or hematopoietic stem cell transplantation (HSCT). The development of PTLD is often associated with reactivation of Epstein-Barr virus (EBV). A 26-year-old woman with a history of HSCT and total-body irradiation developed spinal cord hemorrhage from a radiation-induced cavernous hemangioma (RICH) shortly after the development of classical Hodgkin lymphoma PTLD with EBV reactivation. Although little is known about the factors leading to hemorrhagic events from spinal cord RICH, we suspect that EBV reactivation may have been a factor contributing to the hemorrhage in the present case.

9.
Muscle Nerve ; 48(2): 191-7, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23381934

RESUMO

INTRODUCTION: Contamination by far-field potentials (FFPs) may interfere with motor unit number estimation (MUNE) in the ulnar nerve. METHODS: Surface motor unit potentials (SMUPs) from 29 spinal and bulbar muscular atrophy (SBMA) patients and 27 control subjects were classified into SMUPs from the abductor digiti minimi muscle (ADM SMUPs) or non-ADM SMUPs, based on the waveform patterns from 3-channel recordings. RESULTS: The mean areas of the ADM SMUPs and non-ADM SMUPs in control subjects were 219.0 ± 131.3 and 63.7 ± 48.5 µVms, respectively. In SBMA patients they were 1988.9 ± 999.4 and 222.7 ± 125.7 µVms, respectively. The percentages of non-ADM SMUPs were 68 ± 22% in controls and 84 ± 15% in SBMA patients. CONCLUSIONS: Non-ADM SMUPs generated mainly by FFPs often had a negative onset in the routine lead and were indistinguishable from ADM SMUPs. More frequent exclusion of smaller non-ADM SMUPs in controls by size criteria would reduce the diagnostic yield of MUNE.


Assuntos
Potenciais de Ação/fisiologia , Mãos/inervação , Neurônios Motores/fisiologia , Músculo Esquelético/fisiologia , Nervo Ulnar/fisiologia , Adulto , Idoso , Estimulação Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Biomedicines ; 11(9)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37760932

RESUMO

Ubiquitin-like 3 (UBL3) is a membrane-anchored protein that plays a crucial role in sorting proteins into small extracellular vesicles. Aggregations of alpha-synuclein (α-syn) are associated with the pathology of neurodegenerative diseases such as Parkinson's disease. Recently, the interaction between UBL3 and α-syn was discovered, with potential implications in clearing excess α-syn from neurons and its role in disease spread. However, the regulator that can mediate the interaction between UBL3 and α-syn remains unclear. In this study, using the split gaussian luciferase complementation assay and RNA interference technology, we identified that QSOX2, HTATIP2, UBE3C, MGST3, NSF, HECTD1, SAE1, and ATG3 were involved in downregulating the interaction between UBL3 and α-syn. Notably, silencing MGST3 had the most significant impact. Immunocytochemistry staining confirmed the impact of MGST3 silencing on the co-localization of UBL3 and α-syn in cells. MGST3 is a part of the antioxidant system, and silencing MGST3 is believed to contribute to oxidative stress. We induced oxidative stress with hydrogen peroxide, observing its effect on the UBL3-α-syn interaction, and showing that 800 µM of H2O2 downregulated this interaction. In conclusion, silencing MGST3 downregulates the interaction between UBL3 and α-syn.

11.
Cells ; 12(3)2023 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-36766735

RESUMO

Endocannabinoid 2-arachidonoylglycerol (2-AG) has been implicated in habituation to stress, and its augmentation reduces stress-induced anxiety-like behavior. Chronic restraint stress (CRS) changes the 2-AG levels in some gross brain areas, such as the forebrain. However, the detailed spatial distribution of 2-AG and its changes by CRS in stress processing-related anatomical structures such as the anterior cingulate cortex (ACC), caudate putamen (CP), nucleus accumbens (NAc), and piriform cortex (PIR) are still unclear. In this study, mice were restrained for 30 min in a 50 mL-centrifuge tube for eight consecutive days, followed by imaging of the coronal brain sections of control and stressed mice using desorption electrospray ionization mass spectrometry imaging (DESI-MSI). The results showed that from the forebrain to the cerebellum, 2-AG levels were highest in the hypothalamus and lowest in the hippocampal region. 2-AG levels were significantly (p < 0.05) upregulated and 2-AG precursors levels were significantly (p < 0.05) downregulated in the ACC, CP, NAc, and PIR of stressed mice compared with control mice. This study provided direct evidence of 2-AG expression and changes, suggesting that 2-AG levels are increased in the ACC CP, NAc, and PIR when individuals are under chronic stress.


Assuntos
Núcleo Accumbens , Córtex Piriforme , Camundongos , Animais , Núcleo Accumbens/metabolismo , Endocanabinoides/metabolismo , Giro do Cíngulo/metabolismo , Putamen
12.
Biomedicines ; 11(6)2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37371780

RESUMO

Ubiquitin-like 3 (UBL3) acts as a post-translational modification (PTM) factor and regulates protein sorting into small extracellular vesicles (sEVs). sEVs have been reported as vectors for the pathology propagation of neurodegenerative diseases, such as α-synucleinopathies. Alpha-synuclein (α-syn) has been widely studied for its involvement in α-synucleinopathies. However, it is still unknown whether UBL3 interacts with α-syn, and is influenced by drugs or compounds. In this study, we investigated the interaction between UBL3 and α-syn, and any ensuing possible functional and pathological implications. We found that UBL3 can interact with α-syn by the Gaussia princeps based split luciferase complementation assay in cells and immunoprecipitation, while cysteine residues at its C-terminal, which are considered important as PTM factors for UBL3, were not essential for the interaction. The interaction was upregulated by 1-methyl-4-phenylpyridinium exposure. In drug screen results, the interaction was significantly downregulated by the treatment of osimertinib. These results suggest that UBL3 interacts with α-syn in cells and is significantly downregulated by epidermal growth factor receptor (EGFR) pathway inhibitor osimertinib. Therefore, the UBL3 pathway may be a new therapeutic target for α-synucleinopathies in the future.

13.
J Biol Chem ; 286(34): 29594-600, 2011 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-21757738

RESUMO

Expansion of polyglutamine (pQ) chain by expanded CAG repeat causes dominantly inherited neurodegeneration such as Huntington disease, dentatorubral-pallidoluysian atrophy (DRPLA), and numbers of other spinocerebellar ataxias. Expanded pQ disrupts the stability of the pQ-harboring protein and increases its susceptibility to aggregation. Aggregated pQ protein is recognized by the ubiquitin proteasome system, and the enzyme ubiquitin ligase covalently attaches ubiquitin, which serves as a degradation signal by the proteasome. However, accumulation of the aggregated proteins in the diseased brain suggests insufficient degradation machinery. Ubiquitin has several functionally related proteins that are similarly attached to target proteins through its C terminus glycine residue. They are called ubiquitin-like molecules, and some of them are similarly related to the protein degradation pathway. One of the ubiquitin-like molecules, FAT10, is known to accelerate protein degradation through a ubiquitin-independent manner, but its role in pQ aggregate degradation is completely unknown. Thus we investigated its role in a Huntington disease cellular model and found that FAT10 molecules were covalently attached to huntingtin through their C terminus glycine. FAT10 binds preferably to huntingtin with a short pQ chain and completely aggregated huntingtin was FAT10-negative. In addition, ataxin-1,3 and DRPLA proteins were both positive for FAT10, and aggregation enhancement was observed upon FAT10 knockdown. These findings were similar to those for huntingtin. Our new finding will provide a new role for FAT10 in the pathogenesis of polyglutamine diseases.


Assuntos
Doença de Huntington/metabolismo , Modelos Biológicos , Epilepsias Mioclônicas Progressivas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Peptídeos/metabolismo , Ubiquitinas/metabolismo , Ataxina-1 , Ataxina-3 , Ataxinas , Células HEK293 , Humanos , Doença de Huntington/genética , Epilepsias Mioclônicas Progressivas/genética , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Peptídeos/genética , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Solubilidade , Expansão das Repetições de Trinucleotídeos/genética , Ubiquitinas/genética
14.
JBJS Case Connect ; 12(3)2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35962731

RESUMO

CASE: A 21-year-old man presented with knee pain secondary to tibial plateau malunion and an osteochondral defect 1 year after open reduction and initial fixation. Two-stage reconstruction with transplantation of a bulk heat-treated osteochondral allograft and an autologous chondrocyte implantation was performed. CONCLUSION: This technique may be a good choice for large defects in the articular cartilage in cases of tibial plateau malunion. It may be a viable alternative for defect reconstruction, resulting in favorable early clinical, functional, and radiological outcomes.


Assuntos
Cartilagem Articular , Condrócitos , Adulto , Aloenxertos , Cartilagem Articular/cirurgia , Condrócitos/transplante , Temperatura Alta , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Masculino , Adulto Jovem
15.
Sci Rep ; 12(1): 12104, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35840805

RESUMO

Photoisomerization of lipids has been well studied. As for the eyes, photoisomerization from 11-cis isomer to all-trans-retinal is well-known as the first step of the visual transduction in the photoreceptors. In addition to that, there would be other ocular lipids that undergo photoisomerization, which may be involved in ocular health and function. To explore any photoisomerizable lipids in the eyes, the nonirradiated and sunlight-irradiated eyeball extracts were subjected to liquid chromatography-mass spectrometry analysis, followed by the identification of the decreased lipid species in the irradiated extracts. Surprisingly, more than nine hundred lipid species were decreased in the irradiated extracts. Three lipid species, coenzyme Q10 (CoQ10), triglyceride(58:4), and coenzyme Q9, were decreased both significantly (p < 0.05) and by more than two-fold, where CoQ10 showed the most significant decrease. Later, photoisomerization was identified as the prominent cause underlying the decrease of CoQ10. Interestingly, CoQ10 in the sunlight-irradiated fresh eyeballs was also isomerized. Both the visible light and ultraviolet radiation were capable of producing CoQ10 isomer, while the latter showed rapid action. This study is believed to enhance our understanding of the biochemistry and photodamage of the eye and can potentially contribute to the advancement of opto-lipidomics.


Assuntos
Luz Solar , Raios Ultravioleta , Cromatografia Líquida , Lipídeos , Ubiquinona/análogos & derivados
16.
Muscle Nerve ; 44(4): 539-46, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21826683

RESUMO

INTRODUCTION: A reliable electrophysiological marker for clinical trials is increasingly needed in spinal and bulbar muscular atrophy (SBMA). We previously developed a quantitative analysis method for surface electromyography (SEMG), the clustering index (CI) method. Our purpose was to test the utility of the CI method for evaluating lower motor neuron involvement in SBMA patients. METHODS: Subjects included 29 SBMA patients and 27 healthy controls. The recording electrode was placed over the abductor digiti minimi (ADM) muscle with a proximal reference. The Z-score, based on the CI method, was compared with compound muscle action potential (CMAP) amplitude and motor unit number estimation (MUNE), with regard to sensitivity. RESULTS: The Z-scores of the CI method, CMAP amplitude, and MUNE were abnormal in 100%, 72%, and 93% of the patients, respectively. Interrater reliability of the CI method was sufficiently high. CONCLUSION: The CI method is promising as a non-invasive electrophysiological marker in SBMA.


Assuntos
Neurônios Motores/fisiologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular Espinal/patologia , Potenciais de Ação/fisiologia , Adulto , Idoso , Análise por Conglomerados , Eletromiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/fisiopatologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
J Chem Phys ; 134(2): 024525, 2011 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-21241138

RESUMO

Halogenated volatile anesthetics are frequently used for inhaled anesthesia in clinical practice. No appropriate biological method has been available for visualizing their localization in action. Therefore, despite their frequent use, the mechanism of action of these drugs has not been fully investigated. We measured coherent anti-Stokes Raman scattering (CARS) spectra of sevoflurane and isoflurane, two of the most representative volatile anesthetics, and determined the low-frequency vibrational modes without nonresonant background disturbance. Molecular dynamics calculations predict that these modes are associated with multiple halogen atoms. Because halogen atoms rarely appear in biological compounds, the entire spectral landscape of these modes is expected to be a good marker for investigating the spatial localization of these drugs within the intracellular environment. Using live squid giant axons, we could detect the unique CARS spectra of sevoflurane for the first time in a biological setting.


Assuntos
Isoflurano/química , Éteres Metílicos/química , Simulação de Dinâmica Molecular , Teoria Quântica , Sevoflurano , Análise Espectral Raman , Vibração
18.
J Mol Neurosci ; 71(9): 1796-1801, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33433851

RESUMO

The phenotypes of patients with disease-associated variants in DNMT1 have been classified into two syndromes: hereditary sensory and autonomic neuropathy type 1E (HSAN1E, MIM614116, https://www.omim.org/ ) and autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN, MIM604121). The amino acid codon 511 is a hotspot, and p.Y511C is the most frequently observed disease-associated variant among those in HSAN1E patients, whereas there have been only a few reports on patients with p.Y511H. In this study, we report on the cases of a kindred carrying the DNMT1 variant NM_001130823.2:c.1531 T > C (p.Y511H) presenting with the ADCA-DN phenotype. The review of the literature further revealed that later ages at onset and the presence of cerebellar ataxia are the main characteristics of patients carrying the DNMT1 p.Y511H as compared with those carrying DNMT1 p.Y511C. Although HSAN1E and ADCA-DN are proposed to be called DNMT1-complex disorders owing to their overlapping symptoms, this finding suggests a distinct genotype-phenotype correlation regarding the DNMT1 p.Y511H and p.Y511C variants.


Assuntos
Ataxia Cerebelar/genética , DNA (Citosina-5-)-Metiltransferase 1/genética , Fenótipo , Idoso , Ataxia Cerebelar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem
19.
J Neurosci ; 29(41): 13042-52, 2009 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-19828817

RESUMO

Amyloid beta protein (Abeta), a pathogenic molecule associated with Alzheimer's disease, is produced by gamma-secretase, which cleaves the beta-carboxyl terminal fragment (betaCTF) of beta-amyloid precursor protein in the middle of its transmembrane domain. How the cleavage proceeds within the membrane has long been enigmatic. We hypothesized previously that betaCTF is cleaved first at the membrane-cytoplasm boundary, producing two long Abetas, Abeta(48) and Abeta(49), which are processed further by releasing three residues at each step to produce Abeta(42) and Abeta(40), respectively. To test this hypothesis, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to quantify the specific tripeptides that are postulated to be released. Using CHAPSO (3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxyl-1-propanesulfonate)-reconstituted gamma-secretase system, we confirmed that Abeta(49) is converted to Abeta(43/40) by successively releasing two or three tripeptides and that Abeta(48) is converted to Abeta(42/38) by successively releasing two tripeptides or these plus an additional tetrapeptide. Most unexpectedly, LC-MS/MS quantification revealed an induction period, 3-4 min, in the generation of peptides. When extrapolated, each time line for each tripeptide appears to intercept the same point on the x-axis. According to numerical simulation based on the successive reaction kinetics, the induction period exists. These results strongly suggest that Abeta is generated through the stepwise processing of betaCTF by gamma-secretase.


Assuntos
Secretases da Proteína Precursora do Amiloide/fisiologia , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Fragmentos de Peptídeos/metabolismo , Precursor de Proteína beta-Amiloide/química , Análise de Variância , Animais , Células CHO/ultraestrutura , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Ácidos Cólicos/farmacologia , Cromatografia Líquida/métodos , Cricetinae , Cricetulus , Detergentes/farmacologia , Imunoprecipitação/métodos , Modelos Biológicos , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Fragmentos de Peptídeos/análise , Estrutura Terciária de Proteína/fisiologia , Especificidade por Substrato , Espectrometria de Massas em Tandem/métodos , Fatores de Tempo
20.
Invest Ophthalmol Vis Sci ; 61(11): 27, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32931575

RESUMO

Purpose: To report the ocular characteristics of neuronal intranuclear inclusion disease (NIID)-related retinopathy with expansion of the CGG repeats in the NOTCH2NLC gene. Methods: Seven patients from six families (aged 66-81 years) diagnosed with adult-onset NIID were studied. Ophthalmologic examinations, including the best-corrected visual acuity (BCVA), Goldmann perimetry, fundus photography, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT), and full-field electroretinography (ERGs), were performed. The expansion of the CGG repeats in the NOTCH2NLC gene was determined. Results: All patients had an expansion of the CGG repeats (length approximately from 330-520 bp) in the NOTCH2NLC gene. The most common symptoms of the five symptomatic cases were reduced BCVA and night blindness. The other two cases did not have any ocular symptoms. The decimal BCVA varied from 0.15 to 1.2. Goldmann perimetry was constricted in all four cases tested; physiological blind spot was enlarged in two of the cases. The FAF images showed an absence of autofluorescence (AF) around the optic disc in all cases and also showed mild hypo-AF or extinguished AF in the midperiphery. In all cases, the OCT images showed an absence of the ellipsoid zone of the photoreceptors in the peripapillary region, and hyperreflective dots were also present between the retinal ganglion cell layer and outer nuclear layer. The macular region was involved in the late stage of the retinopathy. The full-field ERGs showed rod-cone dysfunction. Conclusions: Patients with adult-onset NIID with CGG repeats expansions in the NOTCH2NLC gene had similar ophthalmologic features, including rod-cone dysfunction with progressive retinal degeneration in the peripapillary and midperipheral regions. The primary site is most likely the photoreceptors. Because the ocular symptoms are often overlooked due to dementia and occasionally precede the onset of dementia, detailed ophthalmological examinations are important for the early diagnosis of NIID-related retinopathy.


Assuntos
Regulação da Expressão Gênica , Doenças Neurodegenerativas/complicações , Receptor Notch2/genética , Retina/metabolismo , Doenças Retinianas/genética , Idoso , Idoso de 80 Anos ou mais , Eletrorretinografia , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Corpos de Inclusão Intranuclear/genética , Masculino , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/genética , RNA/genética , Receptor Notch2/biossíntese , Retina/patologia , Doenças Retinianas/etiologia , Doenças Retinianas/metabolismo , Estudos Retrospectivos , Tomografia de Coerência Óptica
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