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1.
Nat Immunol ; 25(6): 1020-1032, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38831106

RESUMEN

The efficacy of T cell-based immunotherapies is limited by immunosuppressive pressures in the tumor microenvironment. Here we show a predominant role for the interaction between BTLA on effector T cells and HVEM (TNFRSF14) on immunosuppressive tumor microenvironment cells, namely regulatory T cells. High BTLA expression in chimeric antigen receptor (CAR) T cells correlated with poor clinical response to treatment. Therefore, we deleted BTLA in CAR T cells and show improved tumor control and persistence in models of lymphoma and solid malignancies. Mechanistically, BTLA inhibits CAR T cells via recruitment of tyrosine phosphatases SHP-1 and SHP-2, upon trans engagement with HVEM. BTLA knockout thus promotes CAR signaling and subsequently enhances effector function. Overall, these data indicate that the BTLA-HVEM axis is a crucial immune checkpoint in CAR T cell immunotherapy and warrants the use of strategies to overcome this barrier.


Asunto(s)
Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Receptores Inmunológicos , Miembro 14 de Receptores del Factor de Necrosis Tumoral , Microambiente Tumoral , Animales , Humanos , Inmunoterapia Adoptiva/métodos , Miembro 14 de Receptores del Factor de Necrosis Tumoral/metabolismo , Miembro 14 de Receptores del Factor de Necrosis Tumoral/inmunología , Miembro 14 de Receptores del Factor de Necrosis Tumoral/genética , Ratones , Microambiente Tumoral/inmunología , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Receptores Quiméricos de Antígenos/genética , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Linfocitos T Reguladores/inmunología , Transducción de Señal , Línea Celular Tumoral , Neoplasias/inmunología , Neoplasias/terapia , Ratones Noqueados
2.
Comput Biol Med ; 174: 108417, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38603900

RESUMEN

The antimicrobial susceptibility test (AST) plays a crucial role in selecting appropriate antibiotics for the treatment of bacterial infections in patients. The diffusion disk method is widely adopted AST method due to its simplicity, cost-effectiveness, and flexibility. It assesses antibiotic efficacy by measuring the size of the inhibition zone where bacterial growth is suppressed. Quantification of the zone diameter is typically achieved using tools such as rulers, calipers, or automated zone readers, as the inhibition zone is visually discernible. However, challenges arise due to inaccuracies stemming from human errors or image processing of intensity-based images. Here, we proposed a bacterial activity-based AST using laser speckle imaging (LSI) with multiple speckle illumination. LSI measures a speckle pattern produced by interferences of scattered light from the sample; therefore, LSI enables the detection of variation or movement within the sample such as bacterial activity. We found that LSI with multiple speckle illuminations provides consistent and uniform analysis of measured time-varying speckle images. Furthermore, our proposed method effectively identified the boundary of the inhibition zone using the k-means clustering algorithm, exploiting a result of speckle pattern analysis as features. Collectively, the proposed method offers a versatile analytical tool in the diffusion disk method.


Asunto(s)
Antibacterianos , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Rayos Láser
3.
Clin Psychopharmacol Neurosci ; 22(1): 87-94, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38247415

RESUMEN

Objective: : Diagnosis and assessment of depression rely on scoring systems based on questionnaires, either self-reported by patients or administered by clinicians, and observation of patient facial expressions during the interviews plays a crucial role in making impressions in clinical settings. Deep learning driven approaches can assist clinicians in the course of diagnosis of depression by recognizing subtle facial expressions and emotions in depression patients. Methods: : Seventeen simulated patients who acted as depressed patients participated in this study. A trained psychiatrist structurally interviewed each participant with moderate depression in accordance with a prepared scenario and without depressive features. Interviews were video-recorded, and a facial emotion recognition algorithm was used to classify emotions of each frame. Results: : Among seven emotions (anger, disgust, fear, happiness, neutral, sadness, and surprise), sadness was expressed in a higher proportion on average in the depression-simulated group compared to the normal group. Neutral and fear were expressed in higher proportions on average in the normal group compared to the normal group. The overall distribution of emotions between the two groups was significantly different (p < 0.001). Variance in emotion was significantly less in the depression-simulated group (p < 0.05). Conclusion: : This study suggests a novel and practical approach to understand the emotional expression of depression patients based on deep learning techniques. Further research would allow us to obtain more perspectives on the emotional profiles of clinical patients, potentially providing helpful insights in making diagnosis of depression patients.

4.
Mol Cancer ; 22(1): 200, 2023 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-38066564

RESUMEN

BACKGROUND: Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. METHODS: We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. RESULTS: Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. CONCLUSIONS: We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. TRIAL REGISTRATION: NCT05338931; Date: 2022-04-01.


Asunto(s)
Linfoma no Hodgkin , Receptores de Antígenos de Linfocitos T , Receptores Quiméricos de Antígenos , Humanos , Anticuerpos , Antígenos CD19 , Epítopos/metabolismo , Inmunoterapia Adoptiva/efectos adversos , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Receptores Quiméricos de Antígenos/metabolismo , Receptores de Antígenos de Linfocitos T/antagonistas & inhibidores
5.
Front Psychiatry ; 14: 1256571, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38239906

RESUMEN

Background: A psychiatric interview is one of the important procedures in diagnosing psychiatric disorders. Through this interview, psychiatrists listen to the patient's medical history and major complaints, check their emotional state, and obtain clues for clinical diagnosis. Although there have been attempts to diagnose a specific mental disorder from a short doctor-patient conversation, there has been no attempt to classify the patient's emotional state based on the text scripts from a formal interview of more than 30 min and use it to diagnose depression. This study aimed to utilize the existing machine learning algorithm in diagnosing depression using the transcripts of one-on-one interviews between psychiatrists and depressed patients. Methods: Seventy-seven clinical patients [with depression (n = 60); without depression (n = 17)] with a prior psychiatric diagnosis history participated in this study. The study was conducted with 24 male and 53 female subjects with the mean age of 33.8 (± 3.0). Psychiatrists conducted a conversational interview with each patient that lasted at least 30 min. All interviews with the subjects between August 2021 and November 2022 were recorded and transcribed into text scripts, and a text emotion recognition module was used to indicate the subject's representative emotions of each sentence. A machine learning algorithm discriminates patients with depression and those without depression based on text scripts. Results: A machine learning model classified text scripts from depressive patients with non-depressive ones with an acceptable accuracy rate (AUC of 0.85). The distribution of emotions (surprise, fear, anger, love, sadness, disgust, neutral, and happiness) was significantly different between patients with depression and those without depression (p < 0.001), and the most contributing emotion in classifying the two groups was disgust (p < 0.001). Conclusion: This is a qualitative and retrospective study to develop a tool to detect depression against patients without depression based on the text scripts of psychiatric interview, suggesting a novel and practical approach to understand the emotional characteristics of depression patients and to use them to detect the diagnosis of depression based on machine learning methods. This model could assist psychiatrists in clinical settings who conduct routine conversations with patients using text transcripts of the interviews.

6.
Front Chem ; 10: 873758, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35480392

RESUMEN

The chemical instability of perovskite oxides containing Sr is a critical issue for the long-term operation of solid oxide fuel cells. In this study, we demonstrate a remarkable improvement in the chemical and electrochemical stability of a heterostructured La0.6Sr0.4CoO3-δ (LSC)-Ce0.9Gd0.1O1.95 (GDC) electrode. Electrostatic spray deposition was employed to fabricate heterostructured nanoparticles in a single step with a coaxial nozzle supplying the LSC powders in the core nozzle and the GDC precursors in the shell nozzle. Moreover, the reducing fuel added to the GDC precursor solution induced the sol-gel combustion reaction in the droplet to form a uniform nanocrystalline GDC coating with high surface coverage. The high surface coverage of GDC on the LSC more significantly improved long-term stability compared with than of the bare LSC cathode at a constant current density of 1 A/cm2 at 600°C for 100 h.

7.
Drugs R D ; 21(2): 157-168, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33721246

RESUMEN

BACKGROUND: Monoclonal antibodies (mAbs) have proved to be a valuable tool for the treatment of different cancer types. However, clinical use of an increasing number of mAbs, have also highlighted limitations with monotherapy for cancers, in particular for such with more complex mechanisms, requiring action on additional molecules or pathways, or for cancers quickly acquiring resistance following monotherapy. An example for the latter is the mAb trastuzumab, FDA approved for treatment of metastatic gastric carcinoma. To circumvent this, researchers have reported synergistic, anti-proliferative effects by combination targeting of HER2 and EGFR by trastuzumab and the EGFR-targeting mAb Cetuximab overcoming trastuzumab resistance. METHODS: Maintaining the proven functionality of trastuzumab, we have designed bi-specific antibody molecules, called AffiMabs, by fusing an EGFR-targeting Affibody molecule to trastuzumab's heavy or light chains. Having confirmed binding to EGFR and Her2 and cytotoxicity of our AffiMabs, we analyzed apoptosis rate, receptor surface levels, phosphorylation levels of receptors and associated signaling pathways as well as differentially expressed genes on transcriptome level with the aim to elucidate the mode of action of our AffiMabs. RESULTS: The AffiMabs are able to simultaneously bind HER2 and EGFR and show increased cytotoxic effect compared to the original trastuzumab therapeutic molecule and, more importantly, even to the combination of trastuzumab and EGFR-targeting Affibody molecule. Analyzing the mode of action, we could show that bi-specific AffiMabs lead to reduced surface receptor levels and a downregulation of cell cycle associated genes on transcriptome level. CONCLUSION: Our study shows that transcriptome analysis can be used to validate the choice of receptor targets and guide the design of novel multi-specific molecules. The inherent modularity of the AffiMab format renders it readily applicable to other receptor targets.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Neoplasias , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados/farmacología , Proliferación Celular , Humanos , Trastuzumab/farmacología
8.
Sci Rep ; 11(1): 7109, 2021 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-33782467

RESUMEN

The hydrogel of biomolecule-assisted metal/organic complex has the superior ability to form a uniform, continuous, and densely integrated structure, which is necessary for fine thin film fabrication. As a representative of nature-originated polymers with abundant reactive side chains, we select the gelatin molecule as an element for weaving the metal cations. Here, we demonstrate the interaction between the metal cation and gelatin molecules, and associate it with coating quality. We investigate the rheological property of gelatin solutions interacting with metal cation from the view of cross-linking and denaturing of gelatin molecules. Also, we quantitatively compare the corresponding interactions by monitoring the absorbance spectrum of the cation. The coated porous structure is systematically investigated from the infiltration of gelatin-mediated Gd0.2Ce0.8O2-δ (GDC) precursor into Sm0.5Sr0.5CoO3-δ (SSC) porous scaffold. By applying the actively interacting gelatin-GDC system, we achieve a thin film of GDC on SSC with excellent uniformity. Compare to the discrete coating from the typical infiltration process, the optimized thin film coated structure shows enhanced performance and stability.

9.
Anticancer Res ; 38(1): 287-293, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29277785

RESUMEN

BACKGROUND/AIM: To maximize success rate for development of HER2-targeted therapeutics, patient-derived xenograft (PDX) models reflecting HER2-positive gastric cancer (HER2+ GC) patients were established. MATERIALS AND METHODS: GC tissues obtained from surgery of GC patients were implanted into immune-deficient mice, and tumor tissue of HER2+ PDXs were verified of the patient-mimic HER2 expression by immunohistochemistry and explored for the feasibility by testing with Herceptin, the approved therapeutics and novel HER2 antibody therapeutics being developed. RESULTS: We obtained 5 cases of HER2+ GC PDX models reflecting patient's GC tumor, consisting of 2 cases of HER2 3+ and 2 cases of HER2 2+. Novel HER2 antibody displayed significantly improved anti-cancer efficacy in combination with Herceptin. CONCLUSION: The HER2+ GC PDX models were successfully established to be utilized for preclinical evaluation of HER2-targeting drugs and combined therapies for GC treatment, as an ideal platform of personalized tools for precision therapy.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Inmunológicos/uso terapéutico , Receptor ErbB-2/antagonistas & inhibidores , Neoplasias Gástricas/tratamiento farmacológico , Trastuzumab/uso terapéutico , Adenocarcinoma/patología , Anciano , Animales , Antineoplásicos Inmunológicos/farmacología , Femenino , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Medicina de Precisión , Receptor ErbB-2/inmunología , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/patología , Trastuzumab/farmacología , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Arch Craniofac Surg ; 17(1): 14-19, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28913246

RESUMEN

BACKGROUND: Most nasal bone fractures are corrected using non-invasive methods. Often, patients are dissatisfied with surgical outcomes following such closed approach. In this study, we compare surgical outcomes following blind closed reduction to that of ultrasound-guided reduction. METHODS: A single-institutional prospective study was performed for all nasal fracture patients (n=28) presenting between May 2013 and November 2013. Upon research consent, patients were randomly assigned to either the control group (n=14, blind reduction) or the experimental group (n=14, ultrasound-guided reduction). Surgical outcomes were evaluated using preoperative and 3-month postoperative X-ray images by two independent surgeons. Patient satisfaction was evaluated using a questionnaire survey. RESULTS: The experimental group consisted of 4 patients with Plane I fracture and 10 patients with Plane II fracture. The control group consisted of 3 patients with Plane I fracture and 11 patients with Plane II fracture. The mean surgical outcomes score and the mean patient dissatisfaction score were found not to differ between the experimental and the control group in Plane I fracture (p=0.755, 0.578, respectively). In a subgroup analysis consisting of Plane II fractures only, surgeons graded outcomes for ultrasound-guided reduction higher than that for the control group (p=0.007). Likewise, among the Plane II fracture patients, those who underwent ultrasound-guided reduction were less dissatisfied than those who underwent blind reduction (p=0.043). CONCLUSION: Our study result suggests that ultrasound-guided closed reduction is superior to blind closed reduction in those patients with Plane II nasal fractures.

12.
Arch Craniofac Surg ; 17(2): 86-89, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28913261

RESUMEN

Despite the fact that benign skin lesions can undergo malignant transformation, the necessity and timing of the surgical resection have yet to be established. In this study, we analyse three cases of benign-appearing skin lesions, which were found to be carcinomatous on histologic examination and review the literature regarding the importance of prophylactic removal of benign-appearing skin lesion. The first and second cases were female patients wishing for cosmetic surgery. The first patient had a benign-appearing lesion on dorsum nasi, and the second patient had an inconspicuous lesion right along the right nasolabial fold. The third patient was a middle-aged male with a pigmented lesion on the left cheek, who presented to the clinic only after having met the operating surgeon through an acquaintance outside the hospital setting. All of the lesions were suspected to be of benign nature and were excised for cosmesis only. However, histologic examination of these lesions showed that the first two tumors were basal cell carcinoma with the last tumor being squamouse cell carcinoma. Thus, it is considered that removal of benign like skin lesion will result in good prognosis of patients scheduled to undergo other surgery.

13.
Arch Craniofac Surg ; 17(2): 82-85, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28913260

RESUMEN

We report two cases of cleidocranial dysplasia, which was managed without significant craniofacial osteotomy. A mother and daughter, both of normal intelligence, presented with central forehead depression, mid-face hypoplasia, and blepharoptosis. The fact that they have an identically deformed face implied a genetic basis. In both patients, radiologic evaluation revealed the underdeveloped maxilla, persistent fontanelle opening, and cleidal aplasia. Clinical findings and radiologic studies were consistent with the diagnosis of cleidocranial dysplasia. Both patients underwent forehead plasty via bicoronal approach, augmentation rhinoplasty using tip plasty, and epicanthoplasty. In addition, the mother underwent malar augmentation using Medpor implantation and reduction genioplasty. The patients did not experience any postoperative complication and remained satisfied with the operation at 6-year follow-up.

14.
PLoS One ; 10(7): e0134600, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26225765

RESUMEN

Anti-HER2 murine monoclonal antibody 1E11 has strong and synergistic anti-tumor activity in HER2-overexpressing gastric cancer cells when used in combination with trastuzumab. We presently optimized this antibody for human therapeutics. First, the complementarity determining regions (CDRs) of the murine antibody were grafted onto human germline immunoglobulin variable genes. No difference in affinity and biological activity was observed between chimeric 1E11 (ch1E11) and humanized 1E11 (hz1E11). Next, affinity maturation of hz1E11 was performed by the randomization of CDR-L3 and H3 residues followed by stringent biopanning selection. Milder selection pressure favored the selection of more diverse clones, whereas higher selection stringency resulted in the convergence of the panning output to a smaller number of clones with improved affinity. Clone 1A12 had four amino acid substitutions in CDR-L3, and showed a 10-fold increase in affinity compared to the parental clone and increased potency in an in vitro anti-proliferative activity assay with HER2-overepxressing gastric cancer cells. Clone 1A12 inhibited tumor growth of NCI-N87 xenograft model with similar efficacy to trastuzumab alone, and the combination treatment of 1A12 and trastuzumab completely removed the established tumors. These results suggest that humanized and affinity matured monoclonal antibody 1A12 is a highly optimized molecule for future therapeutic development against HER2-positive tumors.


Asunto(s)
Anticuerpos Monoclonales Humanizados/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Afinidad de Anticuerpos , Regiones Determinantes de Complementariedad/inmunología , Genes erbB-2 , Neoplasias Gástricas/terapia , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales Humanizados/química , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Desnudos , Datos de Secuencia Molecular , Homología de Secuencia de Aminoácido , Neoplasias Gástricas/genética
15.
Arch Plast Surg ; 42(2): 143-9, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25798384

RESUMEN

BACKGROUND: Adipose tissue damage of cryopreserved fat after autologous fat transfer is inevitable in several processes of re-transplantation. This study aims to compare and analyze the survivability of adipocytes after thawing fat cryopreserved at -20℃ by using thawing methods used in clinics. METHODS: The survival rates of adipocytes in the following thawing groups were measured: natural thawing at 25℃ for 15 minutes; natural thawing at 25℃ for 5 minutes, followed by rapid thawing at 37℃ in a water bath for 5 minutes; and rapid thawing at 37℃ for 10 minutes in a water bath. The survival rates of adipocytes were assessed by measuring the volume of the fat layer in the top layers separated after centrifugation, counting the number of live adipocytes after staining with trypan blue, and measuring the activity of mitochondria in the adipocytes. RESULTS: In the group with rapid thawing for 10 minutes in a water bath, it was observed that the cell count of live adipocytes and the activity of the adipocyte mitochondria were significantly higher than in the other two groups (P<0.05). The volume of the fat layer separated by centrifugation was also measured to be higher, which was, however, not statistically significant. CONCLUSIONS: It was shown that the survival rate of adipocytes was higher when the frozen fat tissue was thawed rapidly at 37℃. It can thus be concluded that if fats thawed with this method are re-transplanted, the survival rate of cryopreserved fats in transplantation will be improved, and thus, the effect of autologous fat transfer will increase.

16.
Mol Oncol ; 9(2): 398-408, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25306393

RESUMEN

The synergistic interaction of two antibodies targeting the same protein could be developed as an effective anti-cancer therapy. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast and gastric cancer patients, and HER2-targeted antibody therapy using trastuzumab is effective in many of these patients. Nonetheless, improving therapeutic efficacy and patient survival is important, particularly in patients with HER2-positive gastric cancer. Here, we describe the development of 1E11, a HER2-targeted humanized monoclonal antibody showing increased efficacy in a highly synergistic manner in combination with trastuzumab in the HER2-overexpressing gastric cancer cell lines NCI-N87 and OE-19. The two antibodies bind to sub-domain IV of the receptor, but have non-overlapping epitopes, allowing them to simultaneously bind HER2. Treatment with 1E11 alone induced apoptosis in HER2-positive cancer cells, and this effect was enhanced by combination treatment with trastuzumab. Combination treatment with 1E11 and trastuzumab reduced the levels of total HER2 protein and those of aberrant HER2 signaling molecules including phosphorylated HER3 and EGFR. The synergistic antitumor activity of 1E11 in combination with trastuzumab indicates that it could be a novel potent therapeutic antibody for the treatment of HER2-overexpressing gastric cancers.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Antineoplásicos/farmacología , Anticuerpos Neutralizantes/farmacología , Antineoplásicos/farmacología , Receptor ErbB-2/antagonistas & inhibidores , Neoplasias Gástricas/tratamiento farmacológico , Línea Celular Tumoral , Sinergismo Farmacológico , Humanos , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Trastuzumab
17.
Arch Plast Surg ; 41(4): 325-9, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25075352

RESUMEN

BACKGROUND: Liposuction is a procedure to reduce the volume of subcutaneous fat by physical force. Intracellular storage fat is composed of triglyceride, whereas circulating fat particles exist as cholesterol or triglycerol bound to carrier proteins. It is unavoidable that the storage form of fat particles enters the circulation system after these particles are physiologically destroyed. To date, however, no studies have clarified the fatal characteristics of fat embolism that occurs after the subclinical phase of free fat particles. METHODS: A mixture of human lipoaspirate and normal saline (1:100, 0.2 mL) was injected into the external jugular vein of rats, weighing 200 g on average. Biopsy specimens of the lung and kidney were examined at 12-hour intervals until postoperative 72 hours. The deposit location and transport of the injected free fat particles were confirmed histologically by an Oil Red O stain. RESULTS: Inconsistent with previous reports, free fat particles were transported from the intravascular space to the parenchyma. At 24 hours after infusion, free fat particles deposited in the vascular lumen were confirmed on the Oil Red O stain. At 72 hours after infusion, free fat particles were accumulated compactly within the parenchymal space near the perivascular area. CONCLUSIONS: Many surgeons are aware of the fatal results and undiscovered pathophysiologic mechanisms of free fat particles. Our results indicate that free fat particles, the storage form of fat that has been degraded through a physiological process, might be removed through a direct transport mechanism and phagocytotic uptake.

18.
Arch Craniofac Surg ; 15(3): 117-120, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28913203

RESUMEN

BACKGROUND: Lipomas can be categorized into deep and superficial lipomas according to anatomical depth. Many cases of forehead lipomas are reported to be deep to the muscle layer. We analyze ultrasound in delineating depth of forehead lipomas. METHODS: A retrospective review was performed for all patients who underwent excision of forehead lipomas between January 2008 and March 2013 and for whom preoperative ultrasound study was available. Sensitivity and specificity of ultrasound imaging was evalauted against depth finding at the time of surgical excision. RESULTS: The review identified 42 patients who met the inclusion criteria. Preoperative ultrasound reading was 18 as deep lipomas and 24 as superficial. However, intraoperative finding revealed 2 of the 18 deep lipomas to be superficial and 13 of the 24 superficial lipomas to be deep lipomas. Overall, ultrasonography turned out to be 69% (29/42) accurate in correctly delineating superficial versus deep lipomas. CONCLUSION: Lipomas of the forehead tend to be located in deeper tissue plane compared to lipomas found elsewhere in the body. Preoperative ultrasonography of lipomas can be helpful, but was not accurate in identifying the depth of forehead lipomas in our patient population. Even if a forehead lipoma is found to be superficial on ultrasound, operative planning should include the possibility of deep lipomas.

19.
Clin Orthop Surg ; 3(3): 202-10, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21909467

RESUMEN

BACKGROUND: Some dysplastic hips with favorable radiographic parameters fail to develop normally, suggesting that we should consider cartilaginous or soft tissue structures for further information regarding the condition of the hip. The purpose of this study was to provide a clear definition of concentric reduction in developmental dysplasia of the hip (DDH) based on magnetic resonance imaging (MRI), and to determine how radiographic and MR-based parameters could be used together to treat dysplastic hips. METHODS: We studied range of motion (ROM)-MRI of 25 patients with unilateral hip dysplasia (mean age at the time of MR imaging, 44.1 months). Each ROM-MRI consisted of a set of bilateral hip scans in the following positions: neutral; abduction; abduction- internal rotation; abduction-internal rotation-flexion; and adduction. Before MR scanning, the 25 patients received the following primary treatments: closed reduction (n = 15; at a mean age of 14.5 months); and open reduction (n = 10; at a mean age of 10.0 months). The following new parameters appear to be useful in treating DDH: 1) the labral angle, the angle the labrum makes with the acetabulum; 2) the uncorrected labral deformity (ULD), the "residual deformity" (deflection of the labrum) when the affected labrum is freed from pressure in abduction; and 3) the zone of compressive force (ZCF), the region of the acetabulum through which the body weight acts on the femoral head. RESULTS: A concentrically-reduced hip is one in which the labrum points downward in the neutral position, at the same angle as that of the normal side; and in which the ZCF is zone 3, the inner acetabular zone as defined herein. The ULD and the ZCF may be determined precisely as we have done, or the physician may simply observe the changes in the orientation of the labrum and compare the changes qualitatively to the unaffected side, and likewise for the medial joint space. CONCLUSIONS: Detailed analysis of the labrum as permitted by ROM-MRI, together with acetabular index and other parameters measured from radiographs, provides important information for physicians treating childhood hip dysplasia.


Asunto(s)
Luxación Congénita de la Cadera/diagnóstico , Imagen por Resonancia Magnética , Preescolar , Femenino , Luxación Congénita de la Cadera/diagnóstico por imagen , Luxación Congénita de la Cadera/fisiopatología , Luxación Congénita de la Cadera/cirugía , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/patología , Articulación de la Cadera/fisiopatología , Humanos , Lactante , Masculino , Radiografía , Rango del Movimiento Articular
20.
Clin Orthop Surg ; 3(2): 114-20, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21629471

RESUMEN

BACKGROUND: The results after acetabular fracture are primarily related to the quality of the articular reduction. We evaluated the results of internal fixation of posterior wall fractures with using three-step reconstruction. METHODS: Thirty-three patients (mean age at the time of injury, 47.9 years; 28 males and 5 females) were followed for a minimum of 2 years after surgery. The three-step reconstruction included 1) preservation of soft tissues and reduction of the marginally impacted osteochondral (articular) fragments using screws, 2) filling the impacted cancellous void with a bone graft, and 3) reinforcement with buttress-plating. Clinical evaluation was done according to the criteria of D'aubigne and Postel, while the radiological criteria were those of Matta. The associated injuries and complications were evaluated. RESULTS: The clinical results were excellent in 15 (45.5%) patients and they were good in 5 (15.2%), (i.e., satisfactory in 60.7%), while the radiologic results were excellent in 10 (30.3%) and good in 14 (42.4%) (satisfactory in 72.7%). Heterotopic ossification was common, but this did not require excision, even without prophylactic treatment with indomethacin. Deep infection was the worst complication and this was accompanied by a poor outcome. CONCLUSIONS: This study confirms that three-step reconstruction facilitates accurate and firm reduction of displaced posterior wall fractures of the acetabulum. Therefore, we anticipate less long-term arthrosis in the patients treated this way.


Asunto(s)
Acetábulo/lesiones , Acetábulo/cirugía , Fijación Intramedular de Fracturas/métodos , Fracturas Óseas/cirugía , Acetábulo/diagnóstico por imagen , Adulto , Anciano , Placas Óseas , Tornillos Óseos , Trasplante Óseo , Femenino , Fracturas Óseas/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Osificación Heterotópica , Radiografía , Infección de la Herida Quirúrgica , Resultado del Tratamiento , Adulto Joven
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