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Primary cilia on neural stem/progenitor cells (NSPCs) play an important role in determining cell fate, although the regulatory mechanisms involved in the ciliogenesis remain largely unknown. In this study, we analyzed the effect of the leukemia inhibitory factor (LIF) for the primary cilia in immortalized human NSPCs. LIF withdrawal elongated the primary cilia length, whereas the addition of LIF shortened it. Microarray gene expression analysis revealed that differentially expressed genes (DEGs) associated with LIF treatment were related with the multiple cytokine signaling pathways. Among the DEGs, C-C motif chemokine 2 (CCL2) had the highest ranking and its increase in the protein concentration in the NSPCs-conditioned medium after the LIF treatment was confirmed by ELISA. Interestingly, we found that CCL2 was a negative regulator of cilium length, and LIF-induced shortening of primary cilia was antagonized by CCL2-specific antibody, suggesting that LIF could influence cilia length via upregulating CCL2. The shortening effect of LIF and CCL2 on primary cilia was also observed in SH-SY5Y cells. The results of the study suggested that the LIF-CCL2 axis may well be a regulator of NSPCs and its primary cilia length, which could affect multiple cellular processes, including NSPC proliferation and differentiation.
Assuntos
Células-Tronco Neurais , Neuroblastoma , Humanos , Cílios/metabolismo , Transdução de Sinais , Fator Inibidor de Leucemia/genética , Fator Inibidor de Leucemia/metabolismo , Fator Inibidor de Leucemia/farmacologia , Células-Tronco Neurais/metabolismo , Diferenciação Celular/fisiologiaRESUMO
Intravascular large B-cell lymphoma can induce central nervous system manifestations, including strokes, due to small-vessel occlusion caused by lymphoma cells. However, involvement in large-sized vessels is rare. Here, we present an unusual autopsy case of an 88-year-old man showing a rapid transition from multiple strokes due to small vessel occlusion, typical of intravascular lymphoma, to progressive embolic strokes caused by the occlusion of major cerebral arteries. Magnetic resonance angiography demonstrated the major cerebral arteries associated with those multiple progressive strokes, including the right posterior cerebral artery, left anterior cerebral artery, and right middle cerebral artery, but the detectability was poor. A random skin biopsy at the abdomen confirmed the diagnosis of intravascular large B-cell lymphoma. The patient died 106 days after hospitalization despite intensive treatment. An autopsy revealed broad liquefactive necrosis in the area governed by the major cerebral arteries and multiple small infarctions caused by intravascular lymphoma cells in the small-sized vessels. In addition, the major cerebral arteries showed multiple thromboembolism with partial organization and clusters of intravascular lymphoma cells. Notably, those cells were shown aggregated and attached along the vascular wall of the basilar artery, which might have caused focal hypercoagulation in the near vessels. This aggregation might have disseminated widely in the other major cerebral arteries. Moreover, the cluster of intravascular lymphoma cells in the basilar artery was positive for tumor necrosis factor α, and similar histopathology findings were observed in the splenic veins. However, the pathogenesis of this rare phenomenon involving these cells remains unknown. From a clinical perspective, we should consider the possibility that intravascular lymphoma cells may provoke similar progressive embolic strokes.
Assuntos
AVC Embólico , Linfoma Difuso de Grandes Células B , Acidente Vascular Cerebral , Masculino , Humanos , Idoso de 80 Anos ou mais , Linfoma Difuso de Grandes Células B/complicações , Artérias Cerebrais/patologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , AutopsiaRESUMO
[Purpose] This study aimed to examine how supporting the knee from the front with a knee pad affected upper-limb dexterity while sitting. [Participants and Methods] A total of 14 healthy adult males were included in the study. As a measure of upper-limb dexterity, the number of pins was counted when the Purdue pegboard test was performed for 60 seconds. In addition, the ease of task performance was assessed using the visual analogue scale. There were two experimental conditions, with and without knee pad. The paired t-test was used to detect differences between the two conditions. A p-value of 0.05 was considered statistically significant. [Results] The Purdue pegboard test was 29.4 ± 2.5 and 27.9 ± 3.6 pins with and without knee pad, respectively. The VAS was 76.1 ± 10.3 and 62.9 ± 14.1 with and without knee pad, respectively. Both measured values were significantly higher with knee pad than without. [Conclusion] Supporting the knees from the front with knee pad improves upper-limb functionality while sitting, making it easier to perform seated tasks.
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Tumor-associated macrophages (TAMs) and abnormalities in cancer cells affect cancer progression and response to therapy. TAMs are a major component of the tumor microenvironment (TME) in breast cancer, with their invasion affecting clinical outcomes. Programmed death-ligand 1 (PD-L1), a target of immune checkpoint inhibitors, acts as a suppressive signal for the surrounding immune system; however, its expression and effect on TAMs and the clinical outcome in breast cancer are unknown. In this study, we used high-throughput multiple immunohistochemistry to spatially and quantitatively analyze TAMs. We subjected 81 breast cancer specimens to immunostaining for CD68, CD163, PD-1, PD-L1, CD20, and pan-CK. In both stromal and intratumoral areas, the triple-negative subtype had significantly more CD68/CD163, CD68/PD-L1, and CD163/PD-L1 double-positive cells than the estrogen receptor (ER)/progesterone receptor (PR) subtype. Interestingly, a higher number of CD68+/PD-L1+/CK-/CD163- TAMs in the intratumoral area was correlated with a favorable recurrence rate (p = 0.048). These findings indicated that the specific subpopulation and localization of TAMs in the TME affect clinical outcomes in breast cancer.
Assuntos
Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Macrófagos Associados a Tumor , Humanos , Antígeno B7-H1/metabolismo , Macrófagos/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral , Macrófagos Associados a Tumor/citologia , Biomarcadores TumoraisRESUMO
We herein report a case of corticobasal syndrome (CBS) due to asymmetric degeneration of the motor cortex and substantia nigra with transactivation response DNA-binding protein of 43 kDa (TDP-43) proteinopathy, associated with Alzheimer's disease (AD) pathology. An 85-year-old man initially noticed that he had difficulty in walking and had trouble in moving his right hand and lower limb one year later. His gait disturbance was aggravated, and at the age of 87 years, his neurological examination revealed parkinsonism and positive frontal lobe signs. Brain magnetic resonance imaging (MRI) revealed atrophy of the left frontotemporal lobe and cerebral peduncle, and cerebral blood flow scintigraphy revealed hypoperfusion of the left frontotemporal lobe, leading to a possible diagnosis of CBS. At the age of 89 years, he was bedridden, and rarely spoke. He died of aspiration pneumonia five years after the onset of initial symptoms. At the autopsy, the brain weighed 1280 g and showed left-sided hemiatrophy of the cerebrum and cerebral peduncle. Neuropathological examination revealed AD pathology (Braak AT8 stage V, Braak stage C, CERAD B, Thal classification 5). Phosphorylated TDP-43 (p-TDP-43) immunohistochemistry revealed widespread deposits of dystrophic neurites (DNs), glial cytoplasmic inclusions (GCIs), and neuronal cytoplasmic inclusions (NCIs), which were most remarkable in layers II/III of the motor cortex and predominant on the left hemisphere of the frontal cortex, these neuropathology being consistent with frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) type A. Interestingly, neuronal loss in the substantia nigra was more severe on the left than the right side, with a few phosphorylated tau (p-tau) and p-TDP-43 deposits. It is highly likely that asymmetric TDP-43 pathology rather than symmetric tau pathology contributed to the laterality of degeneration of the cerebral cortex, substantia nigra, and pyramidal tract, which led us to suggest that TDP-43 proteinopathy might be a primary cause.
Assuntos
Doença de Alzheimer/patologia , Córtex Motor/patologia , Substância Negra/patologia , Proteinopatias TDP-43/patologia , Idoso de 80 Anos ou mais , Atrofia/patologia , Autopsia , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Síndrome , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
[Purpose] This study aimed to investigate the effect of the combination of 15° tilt-in-space and recline angles on the fluctuation of shear forces exerted on the buttocks. [Participants and Methods] The participants were 11 healthy adult males. The parameters of the shear forces were the parallel and perpendicular forces exerted on the buttocks as measured by a force plate. The two conditions tested were T0R100-130 and T15R100-130. The tilt-in-space angles were set to 0° and 15° in the T0R100-130 and T15R100-130 conditions, respectively. The reclining angles were determined to be 100° to 130° in both conditions. [Results] Upon comparing the two conditions, the parallel and the perpendicular forces exerted on the buttocks in the T15R100-130 condition were significantly lower than those in the T0R100-130 condition in all positions of back support. Upon comparing the fluctuation values of the parallel and perpendicular forces, those applied in the T15R100-130 condition were significantly higher than those in the T0R100-130 condition. [Conclusion] These results suggest that the fluctuation of shear forces exerted on the buttocks could be decreased by using a combination of 15° tilt-in-space and reclining functions.
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A series of 8-methoxy or 8-methylquinolones bearing novel 3-aminooctahydrocyclopenta[c]pyrrole derivatives at the C-7 position was synthesized, and the pharmacological, physicochemical, and toxicological properties of the individual compounds were evaluated. Novel 8-methylquinolone 7, which includes a 3-amino-7-fluorooctahydrocyclopenta[c]pyrrole moiety at the C-7 position, showed potent antibacterial activity against both Gram-positive and negative pathogens. Compound 7 also demonstrated favorable pharmacokinetic and pharmacodynamic properties and an acceptably safe toxicological profile. Consequently, compound 7 was selected as a clinical candidate.
Assuntos
Antibacterianos/farmacologia , DNA Topoisomerases/metabolismo , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Quinolonas/farmacologia , Convulsões/tratamento farmacológico , Inibidores da Topoisomerase/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Células CHO , Cricetulus , Relação Dose-Resposta a Droga , Descoberta de Drogas , Canais de Potássio Éter-A-Go-Go/genética , Canais de Potássio Éter-A-Go-Go/metabolismo , Haplorrinos , Humanos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Quinolonas/síntese química , Quinolonas/química , Ratos , Estereoisomerismo , Relação Estrutura-Atividade , Distribuição Tecidual , Inibidores da Topoisomerase/síntese química , Inibidores da Topoisomerase/químicaRESUMO
Novel compounds based on 1a were synthesized with the focus of obtaining agonists acting upon peripheral BRS-3. To identify potent anti-obesity compounds without adverse effects on the central nervous system (CNS), a carboxylic acid moiety and a labile carboxylic ester with an antedrug functionality were introduced. Through the extensive synthetic exploration and the pharmacokinetic studies of intravenous administration in mice, the ester 2b was selected owing to its most suitable pharmacological profile. In the evaluation of food intake suppression in C57BL/6N mice, 2b showed significant in vivo efficacy and no clear adverse effects on blood pressure change in dogs administered the compound by intravenous infusion.
Assuntos
Acetatos/química , Fármacos Antiobesidade/síntese química , Compostos Heterocíclicos com 2 Anéis/química , Imidazóis/química , Receptores da Bombesina/agonistas , Acetatos/metabolismo , Acetatos/farmacologia , Animais , Fármacos Antiobesidade/metabolismo , Fármacos Antiobesidade/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Cães , Ingestão de Alimentos/efeitos dos fármacos , Meia-Vida , Frequência Cardíaca/efeitos dos fármacos , Compostos Heterocíclicos com 2 Anéis/metabolismo , Compostos Heterocíclicos com 2 Anéis/farmacologia , Humanos , Injeções Intravenosas , Camundongos , Camundongos Endogâmicos C57BL , Receptores da Bombesina/metabolismoRESUMO
BACKGROUND: Myasthenic symptoms can be present in patients with amyotrophic lateral sclerosis (ALS). These symptoms have been considered to be caused by the degeneration of distal motor neurons and the neuromuscular junction (NMJ). Recent studies suggested that antibody to low-density lipoprotein receptor-related protein 4 (LRP4) was a pathogenic agent of myasthenia gravis (MG), and it was also detected in ALS patients. CASE PRESENTATION: Patient 1: A 58-year-old Japanese man developed progressive weakness and subsequent myasthenic symptoms including oculomotor disturbance. Clinical examination and electrophysiological studies confirmed upper and lower motor neuron involvement and NMJ dysfunction, and anti-LRP4 antibody was detected in his serum. A series of immunotherapies, including steroid pulse therapy, intravenous immunoglobulin, and plasmapheresis, was performed, and the myasthenic symptoms partially improved. The titer of anti-LRP4 antibody subsequently decreased. However, the therapeutic effect was transient, and ALS symptoms progressed. His clinical findings fulfilled the criteria of probable ALS using the Awaji criteria. Patient 2: A 74-year-old Japanese man suffered from progressive weakness of all limbs and dropped head in the evening. He complained of diplopia with a lateral horizontal gaze. Probable ALS was diagnosed because of the upper and lower motor neuron signs, whereas anti-LRP4 antibody was detected. Several immunotherapies were administered, and the myasthenic symptoms partially responded to each therapy. However, the truncal muscle weakness progressed, and he died of respiratory failure. CONCLUSION: We report two anti-LRP4 antibody-seropositive ALS patients with myasthenia who were not typical of ALS patients, and showed partial responses to immunotherapies. The anti-LRP4 antibody-seropositive status may influence developing ALS and cause additional ALS symptoms.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Proteínas Relacionadas a Receptor de LDL/imunologia , Miastenia Gravis/complicações , Miastenia Gravis/imunologia , Idoso , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Exercise in the early stage after stroke onset has been shown to facilitate the recovery from physical dysfunction. However, the mechanism of recovery has not been clarified. In this study, the effect of exercise on spatial memory function recovery in the early stage was shown, and the mechanism of recovery was discussed using a rat model of brain embolism. METHODS: Intra-arterial microsphere (MS) injection induced small emboli in the rat brain. Treadmill exercise was started at 24 hours (early group) or 8 days (late group) after MS injection. The non-exercise (NE) and sham-operated groups were included as controls. Memory function was evaluated by the Morris water maze test, and hippocampal levels of brain-derived neurotrophic factor (BDNF) were measured by enzyme-linked immunosorbent assays. To further investigate the effect of BDNF on memory function, BDNF was continuously infused into the hippocampus via implantable osmotic pumps in the early or late stage after stroke. RESULTS: Memory function significantly improved only in the early group compared with the late and the NE groups, although hippocampal BDNF concentrations were temporarily elevated after exercise in both the early and the late groups. Rats infused with BDNF in the early stage exhibited significant memory function recovery; however, rats that received BDNF infusion in the late stage showed no improvement. CONCLUSION: Exercise elevates hippocampal BDNF levels in the early stage after cerebral embolism, and this event facilitates memory function recovery.
Assuntos
Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Terapia por Exercício , Hipocampo/metabolismo , Embolia Intracraniana/terapia , Transtornos da Memória/terapia , Memória , Acidente Vascular Cerebral/terapia , Animais , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/administração & dosagem , Caspase 3/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Infusões Parenterais , Embolia Intracraniana/metabolismo , Embolia Intracraniana/fisiopatologia , Embolia Intracraniana/psicologia , Masculino , Aprendizagem em Labirinto , Memória/efeitos dos fármacos , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Transtornos da Memória/psicologia , Ratos Sprague-Dawley , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Fatores de Tempo , Regulação para CimaRESUMO
Novel compounds based on the lead BRS-3 agonists from our HTS compounds 2a and 2b have been synthesized with the focus on obtaining peripheral BRS-3 agonists. To identify potent anti-obesity compounds without adverse effects on the central nerve system, a labile carboxylic ester with an antedrug functionality was introduced onto the terminal position. Through the extensive synthetic exploration and the pharmacokinetic studies of oral administration in mice, the phenol ester 17c was selected due to the most suitable pharmacological profile. In the evaluation of food intake suppression in B6 mice, 17c showed significant in vivo efficacy and no clear adverse effect on heart rate and blood pressure change in dog iv infusion. Our study paved the way for development of anti-diabetes and obesity drugs with a safer profile.
Assuntos
Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Azepinas/química , Azepinas/farmacologia , Receptores da Bombesina/agonistas , Animais , Fármacos Antiobesidade/síntese química , Fármacos Antiobesidade/farmacocinética , Azepinas/síntese química , Azepinas/farmacocinética , Cães , Avaliação de Medicamentos , Humanos , Camundongos , Modelos Moleculares , Conformação Molecular , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ratos , Relação Estrutura-AtividadeRESUMO
[Purpose] This study investigated the effect of hip position on muscle onset time during prone hip extension with knee flexion. [Subjects] The study included 21 healthy male volunteers. [Methods] Muscle onset times of the right gluteus maximus, right hamstrings, bilateral lumbar erector spinae, and bilateral lumbar multifidus were measured using surface electromyography during right hip extension with knee flexion in the prone position. Measurements were made with the hip in 3 positions: (1) neutral, (2) abduction, and (3) abduction and external rotation. [Results] Gluteus maximus onset relative to the hamstrings was significantly earlier with hip abduction and with hip abduction and external rotation compared with that with the hip in the neutral position. Gluteus maximus onset relative to the hamstrings was significantly earlier with hip abduction and external rotation compared with that with hip abduction. The bilateral multifidus and left lumbar erector spinae onset times relative to the hamstrings were significantly earlier with hip abduction and external rotation compared with those with hip abduction and with the hip in the neutral position. [Conclusion] Abduction and external rotation of the hip during prone hip extension with knee flexion is effective for advancing the onset times of the gluteus maximus, bilateral multifidus, and contralateral lumbar erector spinae.
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[Purpose] The purpose of this study was to investigate the effect of the timing of leg support elevation on the horizontal force acting on the buttocks in a reclining wheelchair. [Subjects and Methods] The participants were 17 healthy men. Two experimental conditions were tested: the leg-down and leg-up conditions. The back support was reclined at increasing angles, from the initial upright position (IUP), proceeding to the fully reclined position (FRP), and returned to the upright position (RUP). The posterior inclination phase was from IUP to FRP, and the returning inclination phase was from FRP to RUP. [Results] The horizontal force under the leg-up condition was significantly higher than that under the leg-down condition in all positions of back support. [Conclusion] The leg supports should be positioned downward before reclining the back support of a wheelchair.
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A PDE4B subtype selective inhibitor is expected to have a wider therapeutic window than non-selective PDE4 inhibitors. In this Letter, two series of 7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivatives and 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivatives were evaluated for their PDE4B subtype selectivity using human PDE4B2 and PDE4D2 full length enzymes. To improve their PDE4B selectivity over PDE4D, we optimized the substituents on the pyrimidine ring and the side chain phenyl ring, resulting in several derivatives with more than 100-fold selectivity for PDE4B. Consequently, we identified 2-(3-chloro-4-methoxy-phenyl)-5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivative 54 as a highly selective PDE4B inhibitor, which had potent hPDE4B inhibitory activity with an IC50 value of 3.0 nM and 433-fold PDE4B selectivity over PDE4D.
Assuntos
Óxidos S-Cíclicos/química , Óxidos S-Cíclicos/farmacologia , Fenilacetatos/química , Fenilacetatos/farmacologia , Inibidores da Fosfodiesterase 4/química , Inibidores da Fosfodiesterase 4/farmacologia , Sítios de Ligação , Óxidos S-Cíclicos/isolamento & purificação , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Estrutura Molecular , Fenilacetatos/isolamento & purificação , Inibidores da Fosfodiesterase 4/isolamento & purificaçãoRESUMO
The discovery and optimization of a novel series of BRS-3 agonists are described. We explored a potent BRS-3 agonist with low brain penetration to avoid an adverse effect derived from central nervous system exposure. Through the derivatization process, chiral diazepines 9f and 9g were identified as possessing low brain penetration as well as potent in vitro activity against human and mouse BRS-3s.
Assuntos
Azepinas/síntese química , Barreira Hematoencefálica , Receptores da Bombesina/agonistas , Animais , Azepinas/metabolismo , Azepinas/farmacologia , Encéfalo/efeitos dos fármacos , Células Cultivadas , Humanos , Camundongos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
[Purpose] The purpose of this study was to investigate the influence of the rotational axis position of a reclining wheelchair's back support on fluctuations in the shear force applied to the buttocks while the back support is reclined. [Subjects] The subjects were 12 healthy adult men. [Methods] The shear force applied to the buttocks was measured using a force plate. This study used two different experimental conditions. The rotational axis of the back support was positioned at the joint between the seat and the back support for the rear-axis condition, and was moved 13â cm forward for the front-axis condition. [Results] With the back support fully reclined, the shear forces were 11.2 ± 0.8%BW and 14.1 ± 2.5%BW under the rear-axis and front-axis conditions, respectively. When returned to an upright position, the shear forces were 17.1 ± 3.1%BW and 13.8 ± 1.7%BW under the rear-axis and front-axis conditions, respectively. Significant differences appeared between the two experimental conditions (p < 0.01). [Conclusion] These results suggest that the shear force value could be changed by altering the position of the back support's rotational axis during reclining.
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[Purpose] This study investigated the selective activation of the gluteus maximus during a prone hip extension with knee flexion exercise, with the hip joint in different positions. [Subjects] The subjects were 21 healthy, male volunteers. [Methods] Activities of the right gluteus maximus, right hamstrings, bilateral lumbar erector spinae, and bilateral lumbar multifidus were measured using surface electromyography during a prone hip extension with knee flexion exercise. Measurements were made with the hip joint in each of 3 positions: (1) a neutral hip joint position, (2) an abduction hip joint position, and (3) an abduction with external rotation hip joint position. [Results] Gluteus maximus activity was significantly higher when the hip was in the abduction with external rotation hip joint position than when it was in the neutral hip joint and abduction hip joint positions. Gluteus maximus activity was also significantly higher in the abduction hip joint position than in the neutral hip joint position. Hamstring activity was significantly lower when the hip was in the abduction with external rotation hip joint position than when it was in the neutral hip joint and abduction hip joint positions. [Conclusion] Abduction and external rotation of the hip during prone hip extension with knee flexion exercise selectively activates the gluteus maximus.
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An 82-year-old woman developed a droopy right eyelid with ipsilateral hemiparesis. Her ocular symptom was caused by weakness of the right frontalis, which is usually seen in patients with peripheral facial nerve palsy. However, head MRI showed acute cerebral infarction of the left lenticulostriate artery, and electroneurography did not detect damage to the right facial nerve. To explain the pathophysiology in this patient, asymmetrical bilateral cortex innervation to the right upper face was hypothesized. This case suggested that patients with some hemispheric strokes could develop upper facial weakness mimicking facial nerve palsy, and clinicians should pay attention to this potential pitfall in the differential diagnosis of facial nerve palsy.
Assuntos
Paralisia Facial , Imageamento por Ressonância Magnética , Humanos , Feminino , Idoso de 80 Anos ou mais , Paralisia Facial/etiologia , Paralisia Facial/diagnóstico , Diagnóstico Diferencial , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/complicações , Infarto Cerebral/etiologia , Doença Cerebrovascular dos Gânglios da Base/diagnóstico por imagem , Doença Cerebrovascular dos Gânglios da Base/complicações , Doença Cerebrovascular dos Gânglios da Base/etiologiaRESUMO
A 75-year-old man developed sudden-onset tetraparesis preceded by chest pain. MRI of the cervical spine on the day of onset showed no abnormalities. Although his motor symptoms improved gradually, the weakness of the muscles innervated by the C5 nerve root persisted. Sensory and autonomic deficits were detected on an additional neurological examination, and follow-up MRI eight days after onset revealed spinal cord infarction at the right anterior horn at C3-C4. This case suggests that motor symptoms mimicking a radiculopathy could be present during the course of spinal cord infarction.
Assuntos
Traumatismos da Medula Espinal , Isquemia do Cordão Espinal , Masculino , Humanos , Idoso , Quadriplegia , Imageamento por Ressonância Magnética , Isquemia do Cordão Espinal/diagnóstico por imagem , Isquemia do Cordão Espinal/etiologia , Vértebras Cervicais/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Infarto/diagnóstico por imagem , Infarto/etiologiaRESUMO
Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively. We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163+PD-L1+ macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68+, CD163+, and CK+ cells with PD-L1+ phenotypes had higher B7-H3 expression compared to PD-L1- cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies.