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1.
Front Endocrinol (Lausanne) ; 14: 1238654, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795375

RESUMO

Background: Osteoporotic vertebral compression fractures commonly involve the superior vertebral body; however, their associated causes have not yet been clearly established. This study aimed to determine the trabecular structural differences between the superior and inferior regions of the vertebral body using cadaveric and clinical studies. Materials and methods: First, five vertebrae were collected from three human cadavers. The trabecular structures of the superior and inferior regions of each vertebral body were analyzed using micro-computed tomography (micro-CT), finite element analysis (FEA), and biomechanical test. Based on the results of the ex vivo study, we conducted a clinical study. Second, spine CT images were retrospectively collected. Bone volume and Hounsfield unit were analyzed for 192 vertebral bodies. Finally, after sample size calculation based on the pilot study, prospectively, 200 participants underwent dual-energy X-ray absorptiometry (DXA) of the lateral spine. The bone mineral densities (BMDs) of the superior and inferior regions of each lumbar vertebral body were measured. The paired t-test and Wilcoxon signed-rank test were used for the statistical analyses, and p-value < 0.05 was considered significant. Results: Cadaver studies revealed differences between the superior and inferior trabecular bone structures. The bone volume ratio, BMD, and various other trabecular parameters advocated for decreased strength of the superior region. Throughout the biomechanical study, the limitations of the compression force were 3.44 and 4.63 N/m2 for the superior and inferior regions, respectively. In the FEA study, the inferior region had a lower average displacement and higher von Mises stress than the superior region. In the clinical spine CT-based bone volume and BMD study, the bone volume was significantly higher in the inferior region than in the superior region. In the lateral spine DXA, the mean BMD of the superior region of vertebral bodies was significantly lower compared with that of the inferior region. Conclusion: The superior trabecular structure of the lumbar vertebral bodies possesses more biomechanical susceptibility compared with the inferior trabecular structure, confirming its dominant role in causing osteoporotic vertebral fractures. Physicians should also focus on the BMD values of the superior region of the vertebral body using lateral spine DXA to evaluate osteoporosis.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Corpo Vertebral , Microtomografia por Raio-X , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Estudos Retrospectivos , Fraturas por Compressão/complicações , Projetos Piloto , Vértebras Lombares/diagnóstico por imagem , Cadáver
2.
Front Med (Lausanne) ; 10: 1190021, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37593402

RESUMO

Background: Paraspinal muscle asymmetry is associated with low back pain (LBP) problems. This study aimed to analyze skeletal muscle areas around the lumbar vertebra and compare the ratio of anterior and posterior muscles between patients with lumbar herniated nucleus pulposus (HNP) and healthy individuals using abdominal pelvic computed tomography (APCT). Methods: After propensity score matching, 122 HNP patients and 122 non-HNP individuals were finally used for analyses. In APCT, axial cut images were collected at the level of the third lumbar vertebra lower end plate and only the muscle structure was obtained. After obtaining the muscular portion of their image, we measured the skeletal muscle area (SMA). Second, for analysis relation of sarcopenia and HNP, the status of low skeletal muscle mass was determined using a previously reported criteria based on APCT scans in the Republic of Korea. Results: From the analysis of the anterior-posterior muscles, the ratio of anterior SMA was statistically significantly larger in the HNP group than in the non-HNP group. Regarding the anatomical classification of trunk muscles, a statistically significant left-right imbalance to peripheral muscle in HNP men was observed. Regarding the status of low skeletal muscle mass, no statistical difference in prevalence between the two groups were observed. Moreover, no statistical difference in the prevalence of low skeletal muscle mass obesity was observed. Conclusion: The lumbar flexor muscle was larger in HNP than others, showing trunk muscle imbalance. However, low skeletal muscle mass is not associated with HNP.

3.
Eur J Orthop Surg Traumatol ; 33(5): 1591-1598, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35763223

RESUMO

BACKGROUND: Various complications related to the prosthesis, such as implant loosening and stress shielding phenomenon, could develop after prosthetic replacement of the radial head. Stress shielding is known to occur around rigidly fixed implants. The purpose of this study was to evaluate the clinical influence and causative factors of the stress shielding phenomenon after radial head arthroplasty (RHA). METHODS: Clinical records and radiographs of 56 patients with unreconstructable radial head fractures who received radial head replacement between 2009 and 2019 were reviewed. Exclusion criteria were infection, loosening, and follow-up of less than 24 months. After exclusion, 35 patients were enrolled. Patients were divided into two groups: an anatomical press-fit group (Anatomical Radial Head System; Acumed, Hillsboro, OR, USA) and a round bipolar cemented group (RHS; Tornier, Montbonnot Saint-Martin, France). Stress shielding around the prosthesis was assessed in the serial radiological examination. Clinical results were assessed using Mayo elbow performance score (MEPS), Quick Disabilities of the Arm, Shoulder, and Hand (q-DASH) score, range of motion (flexion-extension arc and pronation-supination arc), and visual analog scale score (VAS). Correlations between stress shielding phenomenon and demographic data and functional results were analyzed. RESULTS: At an average follow-up of 43.06 (± 14.6) months, 14 (40%) out of 35 fixed stems demonstrated stress shielding. Our results showed that the rate of stress shielding was significantly higher in cases with a bilateral ligament injury and in the anatomical press-fit group (p = 0.028 and p = 0.0091, respectively). However, stress shielding around prostheses did not affect the clinical results (p > 0.05). CONCLUSION: The stress shielding phenomenon around radial head prosthesis may vary according to prosthetic design and severity of ligament injuries. Stress shielding does not affect the mid-term outcomes in the treatment of acute fractures of the radial head. LEVEL OF EVIDENCE III: Retrospective Cohort Comparison; Treatment Study.


Assuntos
Articulação do Cotovelo , Prótese de Cotovelo , Fraturas do Rádio , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/cirurgia , Fraturas do Rádio/cirurgia , Artroplastia , Amplitude de Movimento Articular
4.
Polymers (Basel) ; 14(24)2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36559754

RESUMO

The recycling of filaments used in three-dimensional (3D) printing systems not only mitigates the environmental issues associated with conventional 3D printing approaches but also simultaneously reduces manufacturing costs. This study investigates the effects of successive recycling of polylactic acid (PLA) filaments, which were used in the printing process, on the mechanical properties of recycled filaments and printed objects. The mechanical strengths of the printed PLA and the adhesion strengths between 3D-printed beads were evaluated via the tensile testing of the horizontally and vertically fabricated specimens. Gel permeation chromatography analysis revealed a reduction in the molecular weight of the polymer as a result of recycling, leading to a decrease in the mechanical strength of the 3D-printed product. Additionally, scanning electron microscopy images of the cutting plane showed that the fabricated beads were broken in the case of the horizontally fabricated specimen, whereas in the case of the vertically fabricated samples, the adhesion between the beads was weak. These findings indicate that the mechanical strength in the in-plane and out-of-plane directions must be improved by increasing the mechanical strength of the bead itself as well as the adhesion strength of the beads.

5.
Am J Sports Med ; 50(14): 3924-3933, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36300545

RESUMO

BACKGROUND: A retear after rotator cuff repair is a common problem; however, there is little information related to the prognosis after a retear. In addition, some patients with retears have satisfactory outcomes, which raises the question of whether a retear leads to a poor prognosis. PURPOSE: To identify radiological factors that influence the prognosis after a retear. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 51 patients with retears confirmed by magnetic resonance imaging at 1 year after arthroscopic rotator cuff repair with a minimum follow-up of 24 months were enrolled in this study. Patients were divided into 2 groups according to whether they achieved the minimal clinically important difference for clinical outcome measures. Range of motion and radiological variables, including preoperative and postoperative anteroposterior (AP) and mediolateral (ML) tear sizes, sagittal extent of the retear, acromiohumeral distance (AHD), and degree of fatty degeneration, were analyzed using magnetic resonance imaging. RESULTS: Overall, 36 patients were allocated to the good prognosis (GP) group and 15 to the poor prognosis (PP) group. The 2 groups had no significant differences in baseline demographics and preoperative radiological parameters. Postoperative range of motion was decreased in the PP group at the last follow-up. The AP and ML retear sizes decreased in both groups after arthroscopic rotator cuff repair, but the retear size was significantly larger in the PP group (both P < .05). The AHD increased in the GP group (P < .001) but decreased in the PP group (P = .230) postoperatively. Logistic regression analysis revealed that postoperative AHD (P = .003), fatty degeneration of the infraspinatus tendon (P = .001), posterior (P = .007) and anterior (P = .025) sagittal extent of the retear, and change in the AP tear size (P = .017) were related to poor outcomes after a retear. However, change in the ML tear size (P = .105) and middle sagittal extent of the retear (P = .878) were not related to a poor prognosis. Also, further analysis showed that posterior (P = .006) and anterior (P = .003) sagittal extent of the retear were related to rotator cable involvement. CONCLUSION: An increased AP retear size and decreased AHD were radiological parameters that were associated with poor clinical outcomes after a retear. In particular, patients who had posterior and anterior sagittal extent of the retear, possibly with rotator cable involvement and more severe fatty degeneration of the infraspinatus tendon, showed worse outcomes.


Assuntos
Estudos de Casos e Controles , Humanos , Prognóstico
6.
Knee Surg Sports Traumatol Arthrosc ; 30(11): 3851-3861, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35522311

RESUMO

PURPOSE: Patch augmentation for large and massive rotator cuff tears (LMRCTs) has been suggested as a repair strategy that can mechanically reinforce tendons and biologically enhance healing potential. The purpose of this study was to determine whether patients who underwent patch augmentation would have lower rates of retears and superior functional outcomes. METHODS: Patients who underwent arthroscopic rotator cuff repair (ARCR) with patch augmentation (group A) were matched by age, sex, degree of retraction, and supraspinatus muscle occupation ratio to those treated with ARCR without using a patch (group B) with a minimum follow-up of 24 months. The retear (Sugaya IV or V) rates were evaluated by magnetic resonance imaging at 3 and 12 months post-surgery. The Constant- Murley Score (CMS), Korean Shoulder Score (KSS), and University of California-Los Angeles Shoulder Rating Scale (UCLA) score were retrospectively analyzed. RESULTS: This study included 34 patients (group A, n = 17; group B, n = 17). The mean follow-up period was 46.5 ± 17.4 months. At postoperative 1-year follow-up, group B (6 patients, 35.3%) showed higher rates of retears than group A (1 patient, 5.9%), which was statistically significant (P = 0.034). However, the postoperative CMS, KSS, and UCLA scores did not differ between the two groups at 3 months, 12 months, and the final follow-up. Additionally, the clinical outcomes of patients with retear were not significantly different from those of the healed patients in both groups. CONCLUSION: The use of an allodermal patch for LMRCT is effective in preventing retears without complications. However, the clinical outcomes of ARCR using allodermal patch augmentation were not superior to those of only ARCR. LEVEL OF EVIDENCE: III.


Assuntos
Lesões do Manguito Rotador , Artroscopia , Humanos , Imageamento por Ressonância Magnética , Recidiva , Estudos Retrospectivos , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Resultado do Tratamento
7.
J Hand Surg Asian Pac Vol ; 27(2): 376-380, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35443882

RESUMO

Multiple dorsal fracture-dislocations of the carpometacarpal joints (CMCJ) occur from very high-energy trauma and are often associated with soft tissue injury or ischaemia. We report a 54-year-old male manual worker and a smoker who presented to the emergency room with history of compression of his right hand in a press machine. Radiographs showed dorsal fracture-dislocations of the scapho-trapezio-trapezoidal and third to fifth CMCJ's. Despite emergent Guyon canal and carpal tunnel release and closed reduction and pinning, skin pallor persisted in all digits. Brachial angiography revealed total occlusion of the radial and ulnar arteries and loss of the palmar arch at the level of the fracture. Heparin and Alprostadil were injected directly. On follow-up angiography three weeks later, the vessels were still occluded and collaterals provided digital circulation. Although digital sensations recovered, cold intolerance and stiffness resulted in a poor functional outcome. Level of Evidence: Level V (Therapeutic).


Assuntos
Articulações Carpometacarpais , Lesões por Esmagamento , Fratura-Luxação , Fraturas Ósseas , Fraturas Múltiplas , Traumatismos da Mão , Luxações Articulares , Articulações Carpometacarpais/diagnóstico por imagem , Articulações Carpometacarpais/lesões , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Ulnar/diagnóstico por imagem
8.
Front Med (Lausanne) ; 8: 790135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926531

RESUMO

Background: This study aimed to determine whether the prevalence of acute vertebral osteoporotic compression fractures (VOCF) in the elderly population is related to the distribution of muscles and fat in the human body. Methods: Data of acute VOCF and non-VOCF patients presenting at our institution between January 2018 and May 2020 were analyzed. Patients aged 65 years and older, who underwent body composition test and dual-energy X-ray absorptiometry at the same time were enrolled. After applying exclusion criteria, patients were divided into four groups: normal, sarcopenia without obesity, obesity without sarcopenia, and sarcopenic obesity. Body mass index ≥25 kg/m2 was considered obesity, and sarcopenia was defined as skeletal muscle index lower than 7.0 kg/m2 in males and 5.4 kg/m2 in females. The VOCF rate was analyzed between the groups. Discussion: A total of 461 patients were included, of whom 103 were males. Among them, 163 (35.36%) had normal body composition, 151 (32.75%) had sarcopenia without obesity, 110 (23.86%) had obesity without sarcopenia, and 37 (8.03%) had sarcopenic obesity. The sarcopenic obesity group had the highest rate of acute VOCF (37.8%), which was statistically significant. Specifically, females with sarcopenic obesity and sarcopenia without obesity had significantly higher acute VOCF rates compared to those with normal body compositions. Multivariate analysis showed that sarcopenic obesity was significantly associated with acute VOCF rate overall, as well as in females. Conclusion: Sarcopenic obesity is strongly associated with acute VOCF, especially in females, and it could be an essential criterion for the prevention of acute VOCF.

9.
Biomolecules ; 11(8)2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34439850

RESUMO

Hydrogel is in the spotlight as a useful biomaterial in the field of drug delivery and tissue engineering due to its similar biological properties to a native extracellular matrix (ECM). Herein, we proposed a ternary hydrogel of gellan gum (GG), silk fibroin (SF), and chondroitin sulfate (CS) as a biomaterial for cartilage tissue engineering. The hydrogels were fabricated with a facile combination of the physical and chemical crosslinking method. The purpose of this study was to find the proper content of SF and GG for the ternary matrix and confirm the applicability of the hydrogel in vitro and in vivo. The chemical and mechanical properties were measured to confirm the suitability of the hydrogel for cartilage tissue engineering. The biocompatibility of the hydrogels was investigated by analyzing the cell morphology, adhesion, proliferation, migration, and growth of articular chondrocytes-laden hydrogels. The results showed that the higher proportion of GG enhanced the mechanical properties of the hydrogel but the groups with over 0.75% of GG exhibited gelling temperatures over 40 °C, which was a harsh condition for cell encapsulation. The 0.3% GG/3.7% SF/CS and 0.5% GG/3.5% SF/CS hydrogels were chosen for the in vitro study. The cells that were encapsulated in the hydrogels did not show any abnormalities and exhibited low cytotoxicity. The biochemical properties and gene expression of the encapsulated cells exhibited positive cell growth and expression of cartilage-specific ECM and genes in the 0.5% GG/3.5% SF/CS hydrogel. Overall, the study of the GG/SF/CS ternary hydrogel with an appropriate content showed that the combination of GG, SF, and CS can synergistically promote articular cartilage defect repair and has considerable potential for application as a biomaterial in cartilage tissue engineering.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Sulfatos de Condroitina , Fibroínas , Hidrogéis , Polissacarídeos Bacterianos , Engenharia Tecidual/métodos , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Células Cultivadas , Condrócitos , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacologia , Fibroínas/química , Fibroínas/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacologia , Coelhos , Alicerces Teciduais
10.
Arch Orthop Trauma Surg ; 141(10): 1711-1719, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33119801

RESUMO

INTRODUCTION: Distal radius fracture (DRF) is the most common upper extremity fracture. After the introduction of volar locking plate (VLP) fixation, treatment has shifted from conservative management to more operative management. The implant removal rate after VLP fixation in patients with DRF varies and the reasons for removal and associated patient characteristics have not been clearly defined. This study aimed to compare the characteristics of patients who underwent VLP with and without subsequent implant removal. Second, the rate of implant removal according to the implant position and type was investigated. Finally, we summarized clinical outcome with implant removal, the reasons for, and complications associated with implant removal. METHODS: In this retrospective study, patient data were collected between January 1, 2008, and December 31, 2017. The study population was divided into two groups based on subsequent implant removal. Data on patient characteristics, such as age, sex, comorbidities, side of the fractured arm, the AO Foundation and Orthopaedic Trauma Association classification of the DRF, plate position grade based on the Soong classification type, type of inserted plate, insurance coverage, and treatment costs were collected. Furthermore, we investigated the reason for implant removal, clinical outcomes, and post-removal complications. RESULTS: After applying the exclusion criteria, 806 patients with a total of 814 DRFs were included in the study. Among the 806 patients who underwent VLP fixation for DRF, 252 (31.3%) patients underwent implant removal. Among the patients undergoing implant removal, the mean age was 50.8 ± 14.0 years, 94 (37.3%) were male. The average time to implant removal from the fracture fixation was 12.1 ± 9.2 months (range 1-170 months). When comparing groups, patients who underwent implant removal were significantly younger and had fewer cases of diabetes, hypertension, and cancer history. According to the Soong plate position grade, the most common position was G1 in both groups. Although there was no significant difference (p = 0.075), more G2 cases were found in the removal group (15.0%) than in the retention group (10.2%). About 66.5% of the patients with implant removal had other health insurance as well as the national service, compared with 47% of the patients with implant retention. In total, 186 patients (73.8%) underwent implant removal despite being asymptomatic after the bony union. The patient satisfaction scores improved from 4.1 to 4.4 after implant removal, and 93% of the patients answered that they would choose implant removal again. Only 10% of the patients who underwent removal reported minor complications. No major complications were reported. CONCLUSION: Although the implant removal was conducted without clinical symptoms in the majority of patients, overall patients presented improved functional outcomes with implant removal. The evidence is inconclusive regarding its necessity, however, implant removal after VLP fixation for DRF is not a challenging procedure and is not associated with major complications. LEVEL OF EVIDENCE: Level IV.


Assuntos
Fraturas do Rádio , Adulto , Placas Ósseas , Fixação Interna de Fraturas , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas do Rádio/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
11.
J Trace Elem Med Biol ; 61: 126534, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32361684

RESUMO

PURPOSE: Osteoporosis has a high worldwide prevalence and detrimental consequences (e.g., increased fracture risk). The amount of bone mineral in bone tissue (i.e., bone mineral density [BMD]) is most widely used indicator of osteoporosis in clinical medicine. Selenium is an essential micronutrient for animals and humans. It is a cofactor for antioxidant enzyme reduction (e.g., glutathione peroxidase). It also enhances immune surveillance and modulates cell proliferation. Study findings on the associations between BMD and selenium levels are inadequate and contradictory. The purpose of this study was to examine the associations between hair selenium levels and lumbar spine and femur BMD values. METHODS: Using a cross-sectional study design, we assessed the associations between hair selenium levels and BMD values in 1,167 Korean adults who underwent a health check-up. Each subject was assigned to one of two groups based on BMD (normal group [T-score ≥ -1.0] or low BMD group [T-score < -1.0]). The associations between hair selenium levels and the risk for low BMD were estimated using multivariate logistic regression models. RESULTS: Study participants with lower hair selenium levels were older and had higher phosphorous, alkaline phosphatase, and osteocalcin levels. They also had lower BMDs, corrected serum calcium levels, uric acid levels, and creatinine clearance. Participants with low BMDs had significantly lower hair selenium levels (P < 0.001). After adjusting for osteoporosis-related risk factors, the risk of a low BMD was significantly greater for the lower hair selenium quartile groups (P = 0.045). CONCLUSION: In conclusion, this study found that lower hair selenium levels were associated with low BMD values, independent of the other osteoporosis risk factors examined. Further prospective studies are warranted to determine the role of selenium in the development of osteoporosis.

12.
Materials (Basel) ; 12(16)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416249

RESUMO

This research objective was to determine the significant parameters for effective plasma assisted machining (PAM) of Ti-6Al-4V and to derive optimal processing conditions. PAM parameters such as feed rate, spindle speed, and depth of cut have significant effects on its machining characteristic. In this study, the design of experiments (DOE) was used to select optimal machining conditions for PAM. The signal-to-noise (S/N) ratio was analyzed using the Taguchi method and the contributions of the factors were determined using analysis of variance (ANOVA). Finally, the optimal PAM machining conditions were selected using response optimization. In addition, the energy efficiency of conventional machining (CM) and the PAM were compared. The energy efficiency was analyzed by specific cutting energy. The cutting force and surface roughness of PAM decreased by 60.2% and 70.5%, respectively, in optimal PAM machining conditions.

13.
Chemistry ; 24(13): 3263-3270, 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29389044

RESUMO

Nickel cobalt sulfide nanoparticles embedded in holey defect graphene hydrogel (HGH) that exhibit highly porous structures and uniform nickel cobalt sulfide nanoparticle sizes are successfully prepared by a facile solvothermal-hydrothermal method. As an electrode material for supercapacitors, the as-prepared NiCo2 S4 @HGH shows ultra-high specific capacitances of 1000 F g-1 and 800 F g-1 at 0.5 and 6 A g-1 , respectively, owing to the outstanding electrical conductivity of HGH and high specific capacitance of NiCo2 S4 . After 2100 charge/discharge cycles at a current density of 6 A g-1 , 96.6 % of the specific capacitance was retained, signifying the superb durability of NiCo2 S4 @HGH. Moreover, remarkable specific capacitance (312.6 F g-1 ) and capacity retention (87 % after 5000 cycles) at 6 A g-1 were displayed by the symmetric solid-state supercapacitor fabricated by using NiCo2 S4 @HGH electrodes. These auspicious supercapacitor performances demonstrate that the as-developed solvothermal-hydrothermal approach can be widely used to prepare graphene-coupled binary metal sulfides for high-performance supercapacitor applications.

14.
J Biol Chem ; 291(5): 2319-30, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26627827

RESUMO

Epiregulin (EPR) is a ligand of the epidermal growth factor (EGF) family that upon binding to its epidermal growth factor receptor (EGFR) stimulates proliferative signaling, especially in colon cancer cells. Here, we describe the three-dimensional structure of the EPR antibody (the 9E5(Fab) fragment) in the presence and absence of EPR. Among the six complementarity-determining regions (CDRs), CDR1-3 in the light chain and CDR2 in the heavy chain predominantly recognize EPR. In particular, CDR3 in the heavy chain dramatically moves with cis-trans isomerization of Pro(103). A molecular dynamics simulation and mutational analyses revealed that Arg(40) in EPR is a key residue for the specific binding of 9E5 IgG. From isothermal titration calorimetry analysis, the dissociation constant was determined to be 6.5 nm. Surface plasmon resonance analysis revealed that the dissociation rate of 9E5 IgG is extremely slow. The superimposed structure of 9E5(Fab)·EPR on the known complex structure of EGF·EGFR showed that the 9E5(Fab) paratope overlaps with Domains I and III on the EGFR, which reveals that the 9E5(Fab)·EPR complex could not bind to the EGFR. The 9E5 antibody will also be useful in medicine as a neutralizing antibody specific for colon cancer.


Assuntos
Anticorpos Monoclonais Humanizados/química , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Epirregulina/química , Animais , Anticorpos Monoclonais Humanizados/imunologia , Calorimetria , Análise Mutacional de DNA , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Imunoglobulina G/química , Camundongos , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Mutação , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Ressonância de Plasmônio de Superfície
15.
Biochem Biophys Res Commun ; 441(4): 1011-7, 2013 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-24239549

RESUMO

Growth factors are implicated in several processes essential for cancer progression. Specifically, epidermal growth factor (EGF) family members, including epiregulin (EREG), are important prognostic factors in many epithelial cancers, and treatments targeting these molecules have recently become available. Here, we constructed and expressed humanized anti-EREG antibodies by variable domain resurfacing based on the three-dimensional (3D) structure of the Fv fragment. However, the initial humanized antibody (HM0) had significantly decreased antigen-binding affinity. Molecular modeling results suggested that framework region (FR) residues latently important to antigen binding included residue 49 of the light chain variable region (VL). Back mutation of the VL49 residue (tyrosine to histidine) generated the humanized version HM1, which completely restored the binding affinity of its murine counterpart. Importantly, only one mutation in the framework may be necessary to recover the binding capability of a humanized antibody. Our data support that HM1 exerts potent antibody-dependent cellular cytotoxicity (ADCC). Hence, this antibody may have potential for further development as a candidate therapeutic agent and research tool.


Assuntos
Anticorpos Monoclonais Humanizados/biossíntese , Fator de Crescimento Epidérmico/imunologia , Sequência de Aminoácidos , Anticorpos Monoclonais Humanizados/química , Anticorpos Monoclonais Humanizados/imunologia , Fator de Crescimento Epidérmico/antagonistas & inibidores , Epirregulina , Células HCT116 , Humanos , Região Variável de Imunoglobulina/biossíntese , Região Variável de Imunoglobulina/química , Região Variável de Imunoglobulina/imunologia , Células Jurkat , Luciferases/biossíntese , Modelos Moleculares , Dados de Sequência Molecular , Fatores de Transcrição NFATC/metabolismo , Engenharia de Proteínas , Receptores de IgG/biossíntese
16.
Appl Opt ; 45(34): 8659-73, 2006 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17119563

RESUMO

A catadioptric wide-angle lens having a rectilinear projection scheme has been developed with a view to possible applications in the security-surveillance area. The lens has been designed for a miniature camera with a video graphics array-grade 1/3 in. color CCD sensor. The field of view of the lens is over 151 degrees , and still distortion is under 1%. Furthermore, the modulation transfer function is better than 0.3 at 70 line pairs/mm over the whole active area of the image sensor.

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