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1.
PLoS One ; 15(3): e0229027, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32182240

RESUMEN

Human immunoglobulin G isotype 4 (IgG4) antibodies are suitable for use in either the antagonist or agonist format because their low effector functions prevent target cytotoxicity or unwanted cytokine secretion. However, while manufacturing therapeutic antibodies, they are exposed to low pH during purification, and IgG4 is more susceptible to low-pH-induced aggregation than IgG1. Therefore, we investigated the underlying mechanisms of IgG4 aggregation at low pH and engineered an IgG4 with enhanced stability. By swapping the constant regions of IgG1 and IgG4, we determined that the constant heavy chain (CH3) domain is critical for aggregate formation, but a core-hinge-stabilizing S228P mutation in IgG4 is insufficient for preventing aggregation. To identify the aggregation-prone amino acid, we substituted the CH3 domain of IgG4 with that of IgG1, changing IgG4 Arg409 to a Lys, thereby preventing the aggregation of the IgG4 variant as effectively as in IgG1. A stabilizing effect was also recorded with other variable-region variants. Analysis of thermal stability using differential scanning calorimetry revealed that the R409K substitution increased the Tm value of CH3, suggesting that the R409K mutation contributed to the structural strengthening of the CH3-CH3 interaction. The R409K mutation did not influence the binding to antigens/human Fcγ receptors; whereas, the concurrent S228P and R409K mutations in IgG4 suppressed Fab-arm exchange drastically and as effectively as in IgG1, in both in vitro and in vivo in mice models. Our findings suggest that the IgG4 R409K variant represents a potential therapeutic IgG for use in low-effector-activity format that exhibits increased stability.

2.
Injury ; 2020 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-32098675

RESUMEN

BACKGROUND: Bone distraction lengthening has been used for hand reconstruction. The healing process involved in this technique is affected by many factors. Here, the effectiveness and rates of healing of the phalanges and the metacarpals were evaluated in cases of traumatic finger amputation treated using an Ilizarov mini-fixator. METHODS: Fourteen phalanges and twelve metacarpals in 15 patients (13 males and 2 females) were treated with distraction lengthening using an Ilizarov mini-fixator between 2014 and 2017. All the digits had been subjected to traumatic amputation, and shortening of the remaining digit had occurred despite successful replantation in some cases. The healing indices of phalanges and metacarpals were analyzed. RESULTS: The mean patient age was 42.8 years. The mean lengthening of the phalanges was 13.3 mm, while that of the metacarpals was 26.5 mm. The mean consolidation times were 144.4 days for the phalanges and 154.1 days for the metacarpals. The mean healing indices of the phalanges and metacarpals were 114 days/cm and 60 days/cm, respectively. No bone grafts were needed in any of the patients. CONCLUSIONS: Distraction lengthening of the digits after traumatic amputation is an effective procedure for hand reconstructive surgery for either the phalanges or the metacarpals and is less invasive than other techniques. The rate of healing of the metacarpals is two times faster than that of the phalanges.

3.
Biochem Biophys Res Commun ; 524(2): 424-430, 2020 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-32007273

RESUMEN

LGP85/LIMP-2 is a type III transmembrane glycoprotein of lysosomes, which traverses the membrane twice with an N-terminal uncleaved signal sequence and C-terminal hydrophobic domain. In addition to functioning as a receptor for a lysosomal enzyme ß-glucocerebrosidase and for several enteroviruses, LGP85 plays a key role in the biogenesis and maintenance of endosomal/lysosomal compartments (ELCs). Our previous studies have demonstrated that overexpression of rat LGP85 into COS cells results in the enlarged ELCs, from where membrane trafficking is impaired. We show here that rat LGP85 is polyubiquitinated at the N-terminal short cytoplasmic domain that comprises of only three amino acid residues, alanine, arginine, and cysteine. Replacement of either arginine or cysteine with alanine within the N-terminal cytoplasmic domain did not influence the ubiquitination of LGP85, thereby indicating that ubiquitin (Ub) is conjugated to the α-NH2 group of the N-terminal alanine residue. Furthermore, we were able to define a domain necessary for ubiquitination in a region ranging from the amino acids 156 to 255 within the lumenal domain of LGP85. This is the first report showing that the integral lysosomal membrane protein LGP85 is ubiquitinated.

4.
Biochem Biophys Res Commun ; 525(2): 348-353, 2020 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-32093886

RESUMEN

UDP-Glucuronosyltransferase (UGT, Ugt) is a major drug metabolizing enzyme family involved in the glucuronidation and subsequent elimination of drugs and small lipophilic molecules. UGT forms homo- and hetero-oligomers that enhance or suppress UGT activity. In our previous study, we characterized mouse Ugt1a1 and all the Ugt isoform belonging to the Ugt2b subfamily and revealed that mouse Ugt2b1 and Ugt1a1 cannot metabolize morphine. Mouse Ugt2b1 had been believed to function similarly to rat UGT2B1, which plays a major role in morphine glucuronidation in rat liver. Thus, in this study, we hypothesized that hetero-oligomerization with another Ugt isoform may affect Ugt2b1 catalytic ability. We co-expressed Ugt1a1 and Ugt2b1 in a baculovirus-insect cell system, and confirmed hetero-oligomer formation by co-immunoprecipitation. As reported previously, microsomes singly expressing Ugt1a1 or Ugt2b1 were inactive towards the glucuronidation of morphine. Interestingly, in contrast, morphine-3-glucuronide, a major metabolite of morphine was formed, when Ugt2b1 and Ugt1a1 were co-expressed. This effect of hetero-oligomerization of Ugt1a1 and Ugt2b1 was also observed for 17ß-estradiol glucuronidation. This is the first report demonstrating that UGT acquires a novel catalytic ability by forming oligomers. Protein-protein interaction of Ugts may contribute to robust detoxification of xenobiotics by altering the substrate diversity of the enzymes.

5.
Anticancer Res ; 40(1): 169-176, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892565

RESUMEN

BACKGROUND/AIM: Cancer stem cells (CSCs) are considered to be one of the causes of tumor recurrence after chemotherapy. The purpose of our study was to isolate CSCs from human colorectal cancer cell (CRC) lines. MATERIALS AND METHODS: Nine CRC lines were screened based on the expression level of potential CSC markers to identify putative CSCs. Tumor formation capacity in immunodeficient mice was compared with that of their counterparts. Stemness, differentiation potency and sensitivity to 5-fluorouracil (5-FU), in vitro, were also assessed. Microarray analysis was used to characterize the features of the putative CSCs. RESULTS: COLO 201 cells were separated into two populations based on CD44 expression. CD44 positive (CD44+) cells showed significantly higher tumor formation capacity than CD44- cells in immunodeficient mice. CD44+ cells also possessed stemness properties and lower sensitivity to 5-FU in vitro. Moreover, cancer stemness and chemoresistance-related genes were highly up-regulated in CD44+ cells. CONCLUSION: CD44+ COLO 201 cells possessed the features of CSCs; therefore, the present CSC model could serve as a valuable tool to accelerate CSC research.


Asunto(s)
Receptores de Hialuranos/metabolismo , Células Madre Neoplásicas/metabolismo , Animales , Biomarcadores , Biomarcadores de Tumor , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Modelos Animales de Enfermedad , Citometría de Flujo , Fluorouracilo/farmacología , Xenoinjertos , Humanos , Receptores de Hialuranos/genética , Ratones
6.
Br J Pharmacol ; 177(5): 1077-1089, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31660580

RESUMEN

BACKGROUND AND PURPOSE: Cytochrome P450 (CYP, P450) 3A4 is involved in the metabolism of 50% of drugs and its catalytic activity in vivo is not explained only by hepatic expression levels. We previously demonstrated that UDP-glucuronosyltransferase (UGT) 2B7 suppressed CYP3A4 activity through an interaction. In the present study, we target UGT1A9 as another candidate modulator of CYP3A4. EXPERIMENTAL APPROACH: We prepared co-expressed enzymes using the baculovirus-insect cell expression system and compared CYP3A4 activity in the presence and absence of UGT1A9. Wistar rats were treated with dexamethasone and liver microsomes were used to elucidate the role of CYP3A-UGT1A interactions. KEY RESULTS: UGT1A9 and UGT2B7 interacted with and suppressed CYP3A4. Kinetic analyses showed that both of the UGTs significantly reduced Vmax of CYP3A4 activity. In addition, C-terminal truncated mutants of UGT1A9 and UGT2B7 still retained the suppressive capacity. Dexamethasone treatment induced hepatic CYP3As and UGT1As at different magnitudes. Turnover of CYP3A was enhanced about twofold by this treatment. CONCLUSION AND IMPLICATIONS: The changes of kinetic parameters suggested that UGT1A9 suppressed CYP3A4 activity with almost the same mechanism as UGT2B7. The luminal domain of UGTs contains the suppressive interaction site(s), whereas the C-terminal domain may contribute to modulating suppression in a UGT isoform-specific manner. CYP3A-UGT1A interaction seemed to be disturbed by dexamethasone treatment and the suppression was partially cancelled. CYP3A4-UGT interactions would help to better understand the causes of inter/intra-individual differences in CYP3A4 activity.

7.
Zoological Lett ; 5: 30, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31548912

RESUMEN

Background: Teleost paired fins are composed of two endoskeletal domains, proximal and distal radials, and an exoskeletal domain, the fin ray. The zebrafish pectoral fin displays elaborately patterned radials along the anteroposterior (AP) axis. Radials are considered homologous to tetrapod limb skeletons, and their patterning mechanisms in embryonic development are similar to those of limb development. Nevertheless, the pattern along the AP axis in fin rays has not been well described in the zebrafish pectoral fin, although several recent reports have revealed that fin ray development shares some cellular and genetic properties with fin/limb endoskeleton development. Thus, fin ray morphogenesis may involve developmental mechanisms for AP patterning in the fin/limb endoskeleton, and may have a specific pattern along the AP axis. Results: We conducted detailed morphological observations on fin rays and their connection to distal radials by comparing intra- and inter-strain zebrafish specimens. Although the number of fin rays varied, pectoral fin rays could be categorized into three domains along the AP axis, according to the connection between the fin rays and distal radials; additionally, the number of fin rays varied in the posterior part of the three domains. This result was confirmed by observation of the morphogenesis process of fin rays and distal radials, which showed altered localization of distal radials in the middle domain. We also evaluated the expression pattern of lhx genes, which have AP patterning activity in limb development, in fin rays and during distal radial development and found these genes to be expressed during morphogenesis in both fin rays and distal radials. Conclusion: The fin ray and its connection to the endoskeleton are patterned along the AP axis, and the pattern along the AP axis in the fin ray and the radial connection is constructed by the developmental mechanism related to AP patterning in the limb/fin bud. Our results indicate the possibility that the developmental mechanisms of fin rays and their connection are comparable to those of the distal element of the limb skeleton.

8.
Sci Rep ; 9(1): 9621, 2019 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-31270353

RESUMEN

The impairment of learning and memory is a well-documented effect of both natural and synthetic cannabinoids. In the present study, we aimed to investigate the effect of acute administration of JWH-018, a synthetic cannabinoid, on the hippocampal metabolome to assess biochemical changes in vivo. JWH-018 elevated levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The increase of endocannabinoid levels in response to JWH-018 could be inhibited by co-administration of AM251, a CB1 receptor antagonist. Biochemical analyses revealed that this was the result of suppression of two hydrolases involved in endocannabinoid degradation (fatty acid amide hydrolase [FAAH] and monoacylglycerol lipase [MAGL]). Additionally, we showed that JWH-018 causes a reduction in the levels of brain-derived neurotrophic factor (BDNF), which is known to modulate synaptic plasticity and adaptive processes underlying learning and memory. The decrease of BDNF following JWH-018 treatment was also rescued by co-administration of AM251. As both endocannabinoids and BDNF have been shown to modulate learning and memory in the hippocampus, the alteration of their levels in response to JWH-018 may explain the contribution of synthetic cannabinoids to impairment of memory.

9.
J Clin Orthop Trauma ; 10(3): 474-479, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31061572

RESUMEN

Objectives: To our knowledge, no cases have been reported so far regarding the treatment of proximal humerus fracture with intramedullary nail fixation via the Neviaser portal. This study aimed at evaluating the results of intramedullary nail fixation via the Neviaser portal for proximal humerus fracture. Methods: Four patients with 2-part proximal humerus fracture, who underwent the intramedullary nail fixation via the Neviaser portal, were included in this study. All the patients were females, and the mean age was 78.8 years. We evaluated their clinical and radiographic findings retrospectively. Results: The mean follow-up period was 12 months. All the patients achieved a bone-union without severe complications, such as deep wound infections or any neurological deficits. At the final follow-up, mean shoulder flexion, abduction, and external rotation were 123.5°, 118°, and 36°, respectively. Mean visual analog pain scale (VAS) score at the final follow-up was 21/100. Complications related to the implants were observed in two patients. In one patient, protrusion of the proximal tip of the nail occurred from the entry point, and this caused secondary subacromial impingement. In the other patient, insertion of the end-cap from the Neviaser portal was not possible, and this resulted in the failure of fixation postoperatively. Conclusion: The Neviaser portal may be suitable for the insertion of an intramedullary nail, because it facilitates to make an entry-point at the top of the humeral head. However, the problems related to the use of the present instruments still remain and need to be improved.

10.
Mol Pharmacol ; 95(5): 551-562, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30944207

RESUMEN

UDP-Glucuronosyltransferase (UGT) plays an important role in the metabolism of endogenous and exogenous compounds. UGT is a type I membrane protein, and has a dilysine motif (KKXX/KXKXX) in its C-terminal cytoplasmic domain. Although a dilysine motif is defined as an endoplasmic reticulum (ER) retrieval signal, it remains a matter of debate whether this motif functions in the ER localization of UGT. To address this issue, we generated systematic deletion mutants of UGT2B7, a major human isoform, and compared their subcellular localizations with that of an ER marker protein calnexin (CNX), using subcellular fractionation and immunofluorescent microscopy. We found that although the dilysine motif functioned as the ER retention signal in a chimera that replaced the cytoplasmic domain of CD4 with that of UGT2B7, UGT2B7 truncated mutants lacking this motif extensively colocalized with CNX, indicating dilysine motif-independent ER retention of UGT2B7. Moreover, deletion of the C-terminal transmembrane and cytoplasmic domains did not affect ER localization of UGT2B7, suggesting that the signal necessary for ER retention of UGT2B7 is present in its luminal domain. Serial deletions of the luminal domain, however, did not affect the ER retention of the mutants. Further, a cytoplasmic and transmembrane domain-deleted mutant of UGT2B7 was localized to the ER without being secreted. These results suggest that UGT2B7 could localize to the ER without any retention signal, and lead to the conclusion that the static localization of UGT results from lack of a signal for export from the ER.


Asunto(s)
Retículo Endoplásmico/metabolismo , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Eliminación de Secuencia/genética , Animales , Células COS , Calnexina/metabolismo , Línea Celular , Citoplasma/metabolismo , Dipéptidos/metabolismo , Humanos , Proteínas de la Membrana , Células Sf9
11.
PLoS One ; 14(3): e0212455, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30840664

RESUMEN

Glioblastoma is the leading malignant glioma with a poor prognosis. This study aimed to investigate the antitumor effects of natural killer cells in combination with temozolomide as the standard chemotherapeutic agent for glioblastoma. Using a simple, feeder-less, and chemically defined culture method, we expanded human peripheral blood mononuclear cells and assessed the receptor expression, natural killer cell activity, and regulatory T cell frequency in expanded cells. Next, using the standard human glioblastoma cell lines (temozolomide-sensitive U87MG, temozolomide-resistant T98G, and LN-18), we assessed the ligand expressions of receptors on natural killer cells. Furthermore, the antitumor effects of the combination of the expanded natural killer cells and temozolomide were assessed using growth inhibition assays, apoptosis detection assays, and senescence-associated ß-galactosidase activity assays in the glioblastoma cell lines. Novel culture systems were sufficient to attain highly purified (>98%), expanded (>440-fold) CD3-/CD56+ peripheral blood-derived natural killer cells. We designated the expanded population as genuine induced natural killer cells. Genuine induced natural killer cells exhibited a high natural killer activity and low regulatory T cell frequency compared with lymphokine-activated killer cells. Growth inhibition assays revealed that genuine induced natural killer cells inhibited the glioblastoma cell line growth but enhanced temozolomide-induced inhibition effects in U87MG. Apoptosis detection assays revealed that genuine induced natural killer cells induced apoptosis in the glioblastoma cell lines. Furthermore, senescence-associated ß-galactosidase activity assays revealed that temozolomide induced senescence in U87MG. Genuine induced natural killer cells induce apoptosis in temozolomide-sensitive and temozolomide-resistant glioblastoma cells and enhances temozolomide-induced antitumor effects in different mechanisms. Hence, the combination of genuine induced natural killer cells and temozolomide may prove to be a promising immunochemotherapeutic approach in patients with glioblastoma if the antitumor effects in vivo can be demonstrated.


Asunto(s)
Apoptosis , Glioblastoma/inmunología , Inmunidad Celular/efectos de los fármacos , Células Asesinas Naturales/inmunología , Temozolomida/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Técnicas de Cocultivo , Glioblastoma/patología , Glioblastoma/terapia , Humanos , Células K562 , Células Asesinas Naturales/patología
12.
Photodiagnosis Photodyn Ther ; 25: 309-316, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30639584

RESUMEN

BACKGROUND: Recently, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX fluorescence was reported to be a useful tool during total surgical resection of high-grade gliomas. However, the labeling efficacy of protoporphyrin IX fluorescence is lower in metastatic brain tumors compared to that in high-grade gliomas, and the mechanism underlying protoporphyrin IX fluorescence in metastatic brain tumors remains unclear. Lung cancer, particularly non-small cell lung cancer (NSCLC), is the most common origin for metastatic brain tumor. Therefore, we investigated the mechanism of protoporphyrin IX fluorescence in NSCLC and associated metastatic brain tumors. METHODS: Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the protein and mRNA levels of five transporters and enzymes involved in the porphyrin biosynthesis pathway: peptide transporter 1 (PEPT1), hydroxymethylbilane synthase (HMBS), ferrochelatase (FECH), ATP-binding cassette 2 (ABCG2), and heme oxygenase 1 (HO-1). The correlation between protein, mRNA, and protoporphyrin IX levels in NSCLC cells were evaluated in vitro. Immunohistochemistry was used to determine proteins that played a key role in intraoperative protoporphyrin IX fluorescence in clinical samples from patients with NSCLC and pathologically confirmed metastatic brain tumors. RESULTS: A significant correlation between PEPT1 expression and protoporphyrin IX accumulation in vitro was identified by western blotting (P = 0.003) and qRT-PCR (P = 0.04). Immunohistochemistry results indicated that there was a significant difference in PEPT1 between the intraoperative protoporphyrin IX fluorescence-positive and protoporphyrin IX fluorescence-negative groups (P = 0.009). CONCLUSION: Expression of PEPT1 was found to be positively correlated with 5-ALA-induced protoporphyrin IX accumulation detected by photodynamic reaction in metastatic brain tumors originating from NSCLC.


Asunto(s)
Ácido Aminolevulínico/farmacología , Transportador de Péptidos 1/biosíntesis , Fotoquimioterapia/métodos , Protoporfirinas/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/biosíntesis , Western Blotting , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Ferroquelatasa/biosíntesis , Hemo-Oxigenasa 1/biosíntesis , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Metástasis de la Neoplasia , Reacción en Cadena en Tiempo Real de la Polimerasa , Espectrometría de Fluorescencia , Uroporfirinógenos/biosíntesis
13.
Anticancer Res ; 38(9): 5049-5056, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30194149

RESUMEN

BACKGROUND/AIM: Natural killer (NK) cells are considered potential antitumor effector cells. The aim of this study was to establish a novel type of a chimeric antigen receptor (CAR) NK cell line (CAR-KHYG-1) specific for epidermal growth factor receptor variant III (EGFRvIII)-expressing tumors and investigate the anti-tumor activity of EGFRvIII-specific-CAR-KHYG-1 (EvCAR-KHYG-1). MATERIALS AND METHODS: EvCAR-KHYG-1 was established by self-inactivated lentiviral-based transduction of the EvCAR gene and magnetic bead-based purification of EvCAR-expressing NK cells. The anti-tumor effects of EvCAR-KHYG-1 were evaluated using growth inhibition and apoptosis detection assays in glioblastoma (GBM) cell lines (EGFRvIII-expressing and non-expressing U87MG). RESULTS: The findings demonstrated that EvCAR-KHYG-1 inhibited GBM cell-growth via apoptosis in an EGFRvIII-expressing specific manner. CONCLUSION: This is the first study to establish a CAR NK cell line based on the human NK cell line KHYG-1. Therapy with EvCAR-KHYG-1 may be an effective treatment option for GBM patients.


Asunto(s)
Neoplasias Encefálicas/inmunología , Receptores ErbB/inmunología , Glioblastoma/inmunología , Células Asesinas Naturales/citología , Receptores de Antígenos de Linfocitos T/metabolismo , Neoplasias Encefálicas/terapia , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo , Vectores Genéticos/genética , Glioblastoma/terapia , Humanos , Células Asesinas Naturales/inmunología , Lentivirus/genética , Lentivirus/fisiología , Receptores de Antígenos de Linfocitos T/genética , Proteínas Recombinantes/metabolismo
14.
World Neurosurg ; 120: 54-58, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30172063

RESUMEN

BACKGROUND: Glioblastoma is the most common primary malignant tumor of the brain. Common radiologic findings using initial computed tomography (CT) reveal an intra-axial lesion with perifocal edema. Here, we present a rare case of diffuse subarachnoid hemorrhage (SAH) detected on an initial CT image in a patient without intracranial aneurysm in whom the final diagnosis was glioblastoma. CASE DESCRIPTION: We report the rare case of a 57-year-old man with glioblastoma in the right temporal lobe who presented with a sudden onset of disturbance of consciousness as an initial manifestation. Initial CT of the head revealed a diffuse SAH. Digital subtraction angiography revealed no cerebral aneurysm or dissection of intracranial arteries. The patient was treated for SAH of unknown etiology with conservative therapy, and a repeat digital subtraction angiography demonstrated no vascular disease. Eventually, he was discharged without any neurologic deficit. A follow-up CT of the brain revealed an intracerebral hemorrhage in the right temporal lobe, and magnetic resonance imaging revealed a ring enhancing lesion in the anterior section of right temporal lobe. The patient was transferred to our department, where he underwent surgical resection, and a pathologic diagnosis of glioblastoma was made. CONCLUSIONS: We present a rare case of glioblastoma mimicking SAH of unknown etiology and recommend including glioblastoma in the differential diagnosis of SAH of unknown etiology.


Asunto(s)
Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Glioblastoma/complicaciones , Glioblastoma/diagnóstico por imagen , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/etiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/cirugía , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Diagnóstico Diferencial , Glioblastoma/patología , Glioblastoma/terapia , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Subaracnoidea/patología , Hemorragia Subaracnoidea/terapia
15.
Hand (N Y) ; 12(5): NP95-NP98, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28719987

RESUMEN

BACKGROUND: Reconstruction of malunited diaphyseal fractures of the forearm is one of the most difficult treatments due to its complicated structure. Widespread usage of Digital Imaging and Communications in Medicine (DICOM) data of 3-dimensional (3D) computed tomography (CT) and 3D printing can make estimating the true plane of the deformity easy. METHODS: A 21-year-old man with limited supination due to left forearm nonunion deformity initially treated by locking plate fixation was referred to our hospital. We evaluated the deformity by superimposing the mirror image bone model of the contralateral normal bone onto a model of the affected bone and 3D real full-scale bone model. RESULTS: The patient underwent a manual corrective osteotomy according to our planning. He had satisfactory improvement of his symptoms with no complications. CONCLUSIONS: We postulated that our simple preoperative simulation and manual osteotomy with the aid of 3D CT reconstruction and 3D real full-scale bone model fit in the clinical practice as a recent trend.


Asunto(s)
Diáfisis/cirugía , Fracturas Mal Unidas/cirugía , Imagenología Tridimensional , Osteotomía/métodos , Impresión Tridimensional , Fracturas del Radio/cirugía , Placas Óseas , Diáfisis/anomalías , Diáfisis/diagnóstico por imagen , Diáfisis/lesiones , Fijación Interna de Fracturas/métodos , Fracturas Mal Unidas/diagnóstico por imagen , Humanos , Masculino , Modelos Anatómicos , Radio (Anatomía)/anomalías , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/cirugía , Fracturas del Radio/diagnóstico por imagen , Supinación , Tomografía Computarizada por Rayos X , Adulto Joven
16.
J Wrist Surg ; 6(2): 163-169, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28428920

RESUMEN

Background The low-profile dorsal locking plating (DLP) technique is useful for treating dorsally comminuted intra-articular distal radius fractures; however, due to the complications associated with DLP, the technique is not widely used. Methods A retrospective review of 24 consecutive cases treated with DLP were done. Results All cases were classified into two types by surgical strategy according to the fracture pattern. In type 1, there is a volar fracture line distal to the watershed line in the dorsally displaced fragment, and this type is treated by H-framed DLP. In type 2, the displaced dorsal die-punch fragment is associated with a minimally displaced styloid shearing fracture or a transverse volar fracture line. We found that the die-punch fragment was reduced by the buttress effect of small l-shaped DLP after stabilization of the styloid shearing for the volar segment by cannulated screws from radial styloid processes. At 6 months after surgery, outcomes were good or excellent based on the modified Mayo wrist scores with no serious complications except one case. The mean range of motion of each type was as follows: the palmar flexion was 50, 65 degrees, dorsiflexion was 70, 75 degrees, supination was 85, 85 degrees, and pronation was 80, 80 degrees; in type 1 and 2, respectively. Conclusion DLP is a useful technique for the treatment of selected cases of dorsally displaced, comminuted intra-articular fractures of the distal radius with careful soft tissue coverage.

17.
J Orthop Sci ; 22(3): 447-452, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28325701

RESUMEN

PURPOSE: Early diagnosis of attritional wear of the flexor pollicis longus (FPL) tendon is essential in preventing subsequent tendon rupture. There are currently few objective methods of assessing FPL attrition. We hypothesized that color Doppler imaging could visibly detect FPL tendon attrition, and analyzed our results. METHODS: We evaluated ultrasound imaging of the contact between the FPL tendon and a volar locking plate using the real-time B-mode and Doppler waveforms of the FPL tendon using the continuous Doppler wave mode in 40 patients who underwent fixation of the distal volar locking plate for distal radius fracture. Twenty out of 40 patients underwent plate removal surgery after ultrasound evaluation. We also assessed the relationship between the Doppler waveforms and attrition of the FPL tendon in these 20 patients. RESULTS: Based on the ultrasound findings (n = 40), we divided Doppler waveforms of the FPL tendon into three categories: type 1, spindle wave; type 2, spindle wave with spike; and type 3, spike wave. There were 23, 11, and six patients with type 1, 2, and 3 waveforms in the affected hand, respectively. There were 37 patients with type 1, three with type 2, and no patient with type 3 waveforms in the contralateral wrist. Of the 20 patients who underwent plate removal, five had type 3 waveforms. We found tendon fraying or partial tears in three of these five patients. In addition, all five patients showed changes to type 1 or 2 waveforms after plate removal. None of the other 15 patients with type 1 or 2 waveforms had any tendon injuries during plate removal. CONCLUSIONS: Spike Doppler waveform can indicate abnormal findings, and may be a useful method to predict tendon attrition, because of its visibility. DIAGNOSTIC STUDY: Level III evidence.


Asunto(s)
Diagnóstico Precoz , Fijación Interna de Fracturas/métodos , Placa Palmar/cirugía , Fracturas del Radio/diagnóstico , Traumatismos de los Tendones/cirugía , Tendones/diagnóstico por imagen , Ultrasonografía Doppler/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Placas Óseas , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Placa Palmar/diagnóstico por imagen , Periodo Posoperatorio , Fracturas del Radio/complicaciones , Fracturas del Radio/cirugía , Rotura , Traumatismos de los Tendones/diagnóstico , Traumatismos de los Tendones/etiología , Tendones/fisiopatología , Tendones/cirugía , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
18.
World Neurosurg ; 97: 759.e9-759.e12, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27742503

RESUMEN

BACKGROUND: A spontaneous fusiform aneurysm in the middle cerebral artery (MCA) can present with both ischemic and hemorrhagic symptoms, but this aneurysm's clinical course and prognosis are unclear because of its rarity. CASE DESCRIPTION: An asymptomatic fusiform-shaped aneurysm was found in a branch of the right middle cerebral artery (MCA) incidentally during a medical check-up in a 51-year-old woman with no medical history. This aneurysm was followed by annual magnetic resonance imaging with no medical treatment. A distal side of the branch of the MCA harboring the fusiform aneurysm gradually narrowed, and finally occluded 6 years after initial detection. The stump of the branch transformed into an aneurysmal dilatation, which grew for 2 years. To prevent future subarachnoid hemorrhage, surgical intervention was performed. An aneurysmal dilation with a thin wall was found to originate between an intact branch and a funicular occluded branch, which was obliterated with clip application. At 3-year follow-up, no regrowth or de novo aneurysm could be seen. CONCLUSION: This is the first case report in which serial images demonstrate the stepwise occlusion of an artery with fusiform change and the evolution of a stump aneurysm in the MCA over an extended period.


Asunto(s)
Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/cirugía , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Angiografía por Resonancia Magnética , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Humanos , Hallazgos Incidentales , Estudios Longitudinales , Persona de Mediana Edad , Resultado del Tratamiento
19.
J Neurooncol ; 129(2): 231-41, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27393349

RESUMEN

Nitrogen-containing bisphosphonates (N-BPs), which prevent bone resorption, exert direct and γδT cell (GDT)-mediated antitumor effects against several tumor cell types, including glioblastoma (GBM). However, limited information is available regarding the antitumor effects of N-BPs in GBM. Specifically, the antitumor effects of minodronate (MDA), a third-generation N-BP, in GBM are yet unclear. This study aimed to investigate the antitumor effects of MDA in GBM in vitro and in vivo. We performed growth inhibition and apoptosis detection assays using the GBM cell lines U87MG and U138MG. Apoptosis inhibition assays were also conducted. In vivo xenograft assays were performed in highly immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Sug)/Jic mice subcutaneously implanted with U87MG and U138MG cells. Growth inhibition and apoptosis detection assays demonstrated that MDA inhibited GBM cell growth via apoptosis, which was markedly enhanced by ex vivo expanded GDT. A pan-caspase inhibitor, z-VAD-fmk, inhibited MDA-induced U138MG apoptosis and MDA/GDT-induced U87MG and U138MG apoptosis. But z-VAD-fmk increased MDA-induced U87MG apoptosis. MDA/GDT-mediated apoptosis was blocked by the anti-T cell receptor (TCR) Vγ9, mevalonate pathway inhibitor, granzyme B inhibitor, and antitumor necrosis factor (TNF)-α. In vivo xenograft assays showed that combined intraperitoneal administration of MDA/GDT induced antitumor effects on unestablished U87MG-derived subcutaneous tumors. MDA exerted direct and GDT-mediated anti-GBM apoptotic effects in a caspase-dependent manner. GDT recognized MDA-exposed GBM cells via TCRVγ9 and induced apoptosis via granzyme B and TNF-α release. Because MDA elicited anti-GBM effects in synergy with GDT in vivo, a combination of MDA and ex vivo-generated GDT could be an effective treatment in patients with GBM.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/terapia , Difosfonatos/uso terapéutico , Glioblastoma/terapia , Imidazoles/uso terapéutico , Linfocitos Intraepiteliales/fisiología , Linfocitos Intraepiteliales/trasplante , Clorometilcetonas de Aminoácidos/farmacología , Animales , Anexina A5/metabolismo , Apoptosis/efectos de los fármacos , Inhibidores de Caspasas/farmacología , Recuento de Células , Línea Celular Tumoral , Proliferación Celular , Difosfonatos/farmacología , Femenino , Humanos , Masculino , Ratones Endogámicos NOD , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
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