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1.
Jpn J Radiol ; 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39340741

RESUMEN

PURPOSE: To evaluate the behavior of n-butyl cyanoacrylate-Lipiodol-iopamidol at a ratio of 2:3:1 (NLI231) with and without microcoils and/or flow control in embolization of medium-sized arteries in an in vitro vascular model. MATERIALS AND METHODS: A vessel model representing a common hepatic artery was prepared. Six scenarios were set for embolization, each ran three times: 1) NLI231 injected alone with flow control to 0 ml/min during and up to 5 min after embolization; 2) NLI231 injected into a mesh of microcoil of 5% density with the flow control; 3) NLI231 injected into a microcoil of 10% density with the flow control; 4) NLI231 injected alone without the flow control; 5) NLI231 injected into microcoil of 5% density without the flow control; 6) NLI231 injected into a microcoil of 10% density without the flow control. The microcoils were delivered to the embolization site, and NLI231 was injected. After 1 h of observation, distal filters were collected, and grades of migration (I = none, II = partial, III = almost all-all) were assessed for each scenario. RESULTS: Embolization was achieved in scenarios with NLI231 and microcoils regardless of flow control (p < 0.01). NLI231 did not migrate in scenarios with microcoils and flow control (p < 0.05). NLI231 with microcoils without flow control can embolize the vessel, but partial migration occurred, and the distal distance of the NLI231 complex from the embolization site was longer (p < 0.01). CONCLUSION: Combining sparse coiling with NLI231 may be feasible but is limited to use when flow control is available, or where distal embolization is permissible to some extent.

2.
Biology (Basel) ; 13(9)2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39336106

RESUMEN

Xerostomia induced by antidepressants such as imipramine has long been thought to be due to their anticholinergic effects. However, even antidepressants with low anticholinergic effects may have a high incidence of xerostomia. In salivary glands, norepinephrine activates alpha-adrenergic receptors in blood vessels and beta-adrenergic receptors in acinar cells, respectively, causing a decrease in the blood flow and an increase in the protein secretion, resulting in the secretion of viscous saliva with low water content and high protein content. A previous study demonstrated that perfusion of the submandibular glands of rats with serotonin significantly decreased saliva secretion. The results of the present study revealed the following: (1) that norepinephrine and serotonin, but not epinephrine nor dopamine, were detected in the interstitial fluids in rat submandibular glands; (2) that norepinephrine and serotonin concentrations in the dialysate was 4.3 ± 2.8 nM and 32.3 ± 19.6 nM at stable level, respectively; (3) that infusion with imipramine, a reuptake inhibitor of norepinephrine and serotonin, significantly and dose-dependently increased both norepinephrine and serotonin concentrations in the dialysate; and (4) that intraperitoneal administration of imipramine significantly increased both norepinephrine and serotonin concentrations in the dialysate. These results suggested that one of the mechanisms of xerostomia induced by reuptake inhibitors of norepinephrine and serotonin involves the activation of adrenergic and serotonin receptors in the salivary glands, respectively.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39230718

RESUMEN

BACKGROUND: Stem anteversion (SA) in total hip arthroplasty (THA) is crucial for postoperative outcomes, affecting dislocation risk and hip function. Accurate SA placement is challenged by intraoperative estimation methods, with discrepancies reported between predicted and true SA. This study investigates the effect of conventional methods and intraoperative fluoroscopic confirmation on SA accuracy in THA performed with a direct anterior approach using a traction table. METHODS: This involves 200 patients undergoing primary THA from August 2019 to January 2023, divided into a conventional group (n = 100) and a fluoroscopic group (n = 100). Postoperative SA measurements were conducted using computed tomography scans. Statistical analysis focused on comparing the SA angles and the prevalence of excessive SA (≥>35° and ≥>40°) between the groups. RESULTS: The fluoroscopic group showed a lower average SA angle (24.3° ± 8.3°) compared to the conventional group (30.0° ± 11.3°), with a statistically significant difference (p < 0.01). Excessive SA (≥>40°) was found in 17% of the conventional group, significantly reduced to 5% in the fluoroscopic group (p < 0.01). Similarly, SA exceeding 35° was present in 39% of the conventional group, compared to only 11% in the fluoroscopic group (p < 0.01), indicating a substantial reduction in excessive SA placements with fluoroscopic guidance. DISCUSSION: The study demonstrates that intraoperative fluoroscopic guidance significantly enhances the accuracy of SA placement in THA, reducing the variability and proportion of excessive SA. This suggests a critical reevaluation of conventional estimation methods in favor of fluoroscopic confirmation to improve surgical outcomes. CONCLUSION: Intraoperative fluoroscopic confirmation of knee external rotation angle markedly decreases the proportion of excessive SA and enhances the precision of stem placement in THA with a direct anterior approach. This technique represents a significant advancement in surgical practice, offering a simple and effective method to achieve optimal postoperative results.

4.
Brain Dev ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39242349

RESUMEN

BACKGROUND: Quantitative EEG is frequently used to monitor children affected by acute encephalopathy (AE), with the expectation of providing comprehensive insights into continuous EEG monitoring. However, the potential of quantitative EEG for estimating outcomes in this context remains unclear. We sought reliable prognostic markers within the color density spectral array (CDSA) of the continuous EEG for AE-affected children undergoing therapeutic hypothermia (TH). METHODS: This retrospective study analyzed CDSA data from eight scalp electrodes of 15 AE-affected children undergoing TH. Two CDSA features were investigated-high-frequency lines (HFLs) and periodic elevation in the low frequency band (PLFB)-along with the corresponding EEG characteristics. The inter-rater reliability for CDSA was assessed by four pediatric neurologists. Outcomes were grouped into either no/mild or severe decline in motor and cognitive functions, then compared with CDSA features. RESULTS: The median EEG recording time was 114 (81-151) h per child. While at least 41 % of HFLs corresponded to typical sleep spindles, 94 % of PLFB aligned with cyclic changes in the amplitude of delta/theta waves on the raw EEG. Inter-rater reliability was higher for HFLs than for PLFB (kappa values: 0.69 vs. 0.46). HFLs were significantly more prevalent in children with no/mild decline than in children with severe decline (p = 0.017), whereas PLFB did not differ significantly (p = 0.33). CONCLUSIONS: This study provides preliminary evidence that reduced HFLs on CDSA predict unfavorable outcomes in AE-affected children undergoing TH. This suggests that maintaining high-frequency waves is critical for optimal brain function.

5.
Clin Neuropharmacol ; 47(5): 163-167, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39171842

RESUMEN

OBJECTIVES: The authors have demonstrated that a plasma lamotrigine concentration of 12.7 µmol/L may be a threshold for a good therapeutic response to lamotrigine augmentation therapy in treatment-resistant depressed patients. Lamotrigine is a substrate of P-glycoprotein, breast cancer resistant protein and organic cation transporter 1, which are encoded by ABCB1 , ABCG2 , and SLC22A1 , respectively. There have been several polymorphisms that affect its function. The present study investigated the relationship between these polymorphisms and the steady-state plasma concentrations (Css) of lamotrigine in treatment-resistant depressed patients receiving lamotrigine as augmentation therapy. METHODS: One hundred twenty-nine treatment-resistant depressed patients were included in this study. Treatment resistance is defined as lack of therapeutic response to at least 3 psychotropics despite adequate doses and duration. Their diagnoses were as follows: major depressive disorder (n = 58), bipolar II disorder (n = 52), and bipolar I disorder (n = 19). Lamotrigine augmentation therapy for 8 weeks was conducted. The final lamotrigine doses were 75 mg/d for 39 patients with valproate and 100 mg/d for 90 without it. Blood was sampled at 8:00 am after the 8th week of treatment. Plasma lamotrigine levels were quantified by using LC/MS/MS. The polymorphisms of ABCB1 1236C>T, 2677G>T/A, 3435C>T, ABCG2 421C>A, and SLC22A1 1222G>A were detected by polymerase chain reaction analyses. RESULTS: No significant relationships were observed between these polymorphisms and the Css of lamotrigine in the patients with or without valproate. CONCLUSIONS: The present study suggests that these genetic polymorphisms do not play a role in controlling the Css of lamotrigine in treatment-resistant depressed patients treated with lamotrigine augmentation therapy.


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Trastorno Depresivo Resistente al Tratamiento , Lamotrigina , Proteínas de Neoplasias , Humanos , Lamotrigina/uso terapéutico , Lamotrigina/sangre , Femenino , Adulto , Persona de Mediana Edad , Masculino , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/sangre , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/genética , Trastorno Depresivo Resistente al Tratamiento/sangre , Triazinas/uso terapéutico , Triazinas/sangre , Triazinas/administración & dosificación , Transportador 1 de Catión Orgánico/genética , Quimioterapia Combinada , Polimorfismo Genético/genética , Polimorfismo de Nucleótido Simple , Ácido Valproico/uso terapéutico , Ácido Valproico/sangre , Antimaníacos/uso terapéutico
6.
Radiol Case Rep ; 19(10): 4260-4265, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39135676

RESUMEN

Primary racemose hemangioma of the bronchial artery (RHBA) is a rare congenital condition characterized by enlarged and convoluted bronchial arteries, often forming fistulas between the pulmonary artery or vein. Herein, we report a case of balloon-assisted embolization using N-butyl-2-cyanoacrylate (NBCA) performed for a primary RHBA in an asymptomatic 57-year-old woman. There were 2 tortuous and dilated branches of the right bronchial artery (RBA) (arising from the left subclavian artery and the descending thoracic aorta) which merged in the right pulmonary hilar region, forming multiple aneurysms that short-circuited the right pulmonary artery. Embolization was performed via the RBA arising from the subclavian artery using a triaxial system (a 5-Fr guiding catheter, a 2.7-Fr microballoon catheter, and a 1.9-Fr microcatheter). The guiding catheter was inserted into the peripheral side of the RBA using the microballoon catheter as an anchor; the balloon was slightly inflated and advanced further into the peripheral side using blood flow. The microcatheter was inserted as close to the aneurysms as possible and embolization was done using an NBCA-iodized oil mixture under blood flow control by the microballoon catheter. Bronchial artery embolization is the treatment of choice for primary RHBA because of the risk of rupture, and balloon-assisted techniques can help guide the catheter distally while also controlling blood flow.

7.
Intern Med ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198166

RESUMEN

A 58-year-old woman was admitted to our hospital with anasarca and generalized lymphadenopathy. Laboratory data showed serum Cr 1.48 mg/dL, CRP 2.38 mg/dL, PLT 102,000/µL, and anti-SS-A antibodies (SS-A-ab). A lymph node biopsy revealed a regressed germinal center and hypervascularization in the interfollicular area. The patient was diagnosed with TAFRO-like symptoms occurring with Sjögren's syndrome and HTLV-1 infection, and 80 mg of methylprednisolone and tocilizumab 8 mg/kg biweekly were initiated. Her body weight decreased from 59.4 to 41 kg, and pleural effusion disappeared 8 weeks later. This case suggests that TAFRO-like symptoms may occur in patients with Sjögren's syndrome with HTLV-1 infection.

8.
Mitochondrial DNA B Resour ; 9(8): 1015-1019, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119348

RESUMEN

Taraxacum albidum, a perennial herb of the Asteraceae family, exhibits both tetraploid and pentaploid in Japan. This study sequenced and characterized the complete chloroplast genome of T. albidum, revealing a 151,451 bp sequence with a typical quadripartite structure, comprising one large single-copy (LSC) region of 84,052 bp, one small single-copy (SSC) region of 18,541 bp, and two inverted repeat (IR) regions, IRa and IRb, each 24,429 bp in length. The chloroplast genome, excluding duplicates, contained 113 unique genes, including 79 protein-coding genes, 30 transfer RNA genes, and four ribosomal RNA genes. The GC content of this genome was 37.7%. Phylogenetic analysis revealed that T. albidum is most closely related to T. mongolicum, with the chloroplast genome sequences being nearly identical, differing by only one nucleotide. These findings suggest that the maternal lineage of T. albidum likely originates from T. mongolicum or its closely related species.

9.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38953720

RESUMEN

We describe a setup for time- and angle-resolved photoemission spectroscopy with wavelength-tunable excitation and an extreme ultraviolet probe. It is enabled by using the 10 kHz twin Ti:sapphire amplifiers seeded by the common Ti:sapphire oscillator. The typical probe energy is 21.7 eV, and the wavelength of the pump excitation is tuned between 2400 and 1200 nm by using the optical parametric amplifier. The spectral width of the extreme ultraviolet probe is 53 meV, and the time resolution is dependent on the wavelength for the pump, better than 60 fs for the pump energy >0.7 eV. This system enables the pump energy to be matched with a specific interband transition and to probe a wider energy-momentum space. We present the results for the prototypical materials of highly oriented pyrolytic graphite and Bi2Se3 to show the performance of our system.

10.
Pediatr Neurol ; 155: 126-132, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38636169

RESUMEN

BACKGROUND: Various factors contribute to the development of infection-related acute encephalopathy (AE) in children, such as infectious agents and chronic underlying disorders. We studied underlying disorders in children with AE to identify predisposing factors of AE. METHODS: We investigated underlying disorders or past histories in patients with two types of AE from the database in the Tokai area of Japan between 2009 and 2022: 204 patients with AE with reduced subcortical diffusion (AED) and 137 with clinically mild encephalopathy with a reversible splenial lesion (MERS). We compared them with 89 patients with acute disseminated encephalomyelitis (ADEM) to clarify the specific disorders in the two AE types. RESULTS: The prevalence of underlying disorders in AED (34%, 70 patients) was significantly higher than that in ADEM (12%, 11 patients) (P < 0.01). The prevalence of underlying disorders in MERS was 23% (32 patients). The underlying disorders included seizure disorders, premature birth, genetic/congenital disorders, and endocrine/renal diseases. In patients with seizure disorders in AED, five patients (18%) had Dravet syndrome and four (15%) had West syndrome, whereas none with MERS had these syndromes. Twenty-five (12%) of 204 patients with AED, three (2%) with MERS, and one (1%) with ADEM were preterm or low birth weight. CONCLUSIONS: The high prevalence of seizure disorders suggests that seizure susceptibility is an important predisposing factor in AED. Premature birth also has an impact on the development of AED. Caution is required regarding the development of AE in patients with chronic seizure disorders or premature birth.


Asunto(s)
Encefalopatías , Humanos , Masculino , Femenino , Preescolar , Lactante , Niño , Encefalopatías/epidemiología , Encefalopatías/etiología , Encefalopatías/complicaciones , Adolescente , Japón/epidemiología , Prevalencia , Recién Nacido , Encefalomielitis Aguda Diseminada/epidemiología , Encefalomielitis Aguda Diseminada/etiología , Encefalomielitis Aguda Diseminada/complicaciones
11.
Neuroendocrinology ; 114(7): 658-669, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38643753

RESUMEN

INTRODUCTION: Axons of magnocellular neurosecretory cells project from the hypothalamus to the posterior lobe (PL) of the pituitary. In the PL, a wide perivascular space exists between the outer basement membrane (BM), where nerve axons terminate, and the inner BM lining the fenestrated capillaries. Hypothalamic axon terminals and outer BMs in the PL form neurovascular junctions. We previously had found that collagen XIII is strongly localized in the outer BMs. In this study, we investigated the role of collagen XIII in the PL of rat pituitaries. METHODS: We first studied the expression of Col13a1, the gene encoding the α1 chains of collagen XIII, in rat pituitaries via quantitative real-time polymerase chain reaction and in situ hybridization. We observed the distribution of COL13A1 in the rat pituitary using immunohistochemistry and immunoelectron microscopy. We examined the expression of Col13a1 and the distribution of COL13A1 during the development of the pituitary. In addition, we examined the effects of water deprivation and arginine vasopressin (AVP) signaling on the expression of Col13a1 in the PL. RESULTS: Col13a1 was expressed in NG2-positive pericytes, and COL13A1 signals were localized in the outer BM of the PL. The expression of Col13a1 was increased by water deprivation and was regulated via the AVP/AVPR1A/Gαq/11 cascade in pericytes of the PL. CONCLUSION: These results suggest that pericytes surrounding fenestrated capillaries in the PL secrete COL13A1 and are involved in the construction of neurovascular junctions. COL13A1 is localized in the outer BM surrounding capillaries in the PL and may be involved in the connection between capillaries and axon terminals.


Asunto(s)
Colágeno Tipo XIII , Animales , Ratas , Masculino , Colágeno Tipo XIII/metabolismo , Sistemas Neurosecretores/metabolismo , Arginina Vasopresina/metabolismo , Ratas Wistar , Neurohipófisis/metabolismo , Hipófisis/metabolismo , Pericitos/metabolismo , Membrana Basal/metabolismo
12.
Biol Open ; 13(4)2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38533608

RESUMEN

Circadian rhythms are indispensable intrinsic programs that regulate the daily rhythmicity of physiological processes, such as feeding and sleep. The cricket has been employed as a model organism for understanding the neural mechanisms underlying circadian rhythms in insects. However, previous studies measuring rhythm-controlled behaviours only analysed locomotive activity using seesaw-type and infrared sensor-based actometers. Meanwhile, advances in deep learning techniques have made it possible to analyse animal behaviour and posture using software that is devoid of human bias and does not require physical tagging of individual animals. Here, we present a system that can simultaneously quantify multiple behaviours in individual crickets - such as locomotor activity, feeding, and sleep-like states - in the long-term, using DeepLabCut, a supervised machine learning-based software for body keypoints labelling. Our system successfully labelled the six body parts of a single cricket with a high level of confidence and produced reliable data showing the diurnal rhythms of multiple behaviours. Our system also enabled the estimation of sleep-like states by focusing on posture, instead of immobility time, which is a conventional parameter. We anticipate that this system will provide an opportunity for simultaneous and automatic prediction of cricket behaviour and posture, facilitating the study of circadian rhythms.


Asunto(s)
Conducta Animal , Ritmo Circadiano , Gryllidae , Postura , Animales , Postura/fisiología , Gryllidae/fisiología , Sueño/fisiología , Programas Informáticos , Locomoción
13.
Epilepsia ; 65(5): 1304-1313, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38469885

RESUMEN

OBJECTIVE: Individuals with Dravet syndrome (DS) exhibit progressive gait disturbance. No quantitative studies have been conducted to evaluate the effectiveness of medication for gait disturbance. Therefore, the aim of this study was to evaluate the effectiveness of levodopa for pathological gait in people with DS using three-dimensional gait analysis (3DGA). METHODS: Nine individuals with DS, ages 6-20 years, participated in a crossover study of levodopa and were randomly assigned to the levodopa precedence or no levodopa precedence group. Levodopa/carbidopa hydrate was prescribed at a dose of 5 mg/kg/day (body weight <60 kg) or 300 mg/day (body weight ≥60 kg). The medication was taken for 4-6 weeks (4-week washout period). 3DGA was performed three times before the study, with and without levodopa. A mixed-effects model was used to evaluate the effectiveness of levodopa. The primary outcome was the change in the Gait Deviation Index (GDI). In addition, spatiotemporal gait parameters, 6-minute walking distance (6MD), and balance were evaluated. The correlation between the effectiveness of levodopa and age or gait performance before starting levodopa was analyzed. RESULTS: Levodopa improved the GDI by 4.2 points, (p = .029), 6MD by 52 m (p = .002), and balance test result by 4.1 mm (p = .011) in participants with DS. No severe adverse events were observed, with the exception of one participant, who exhibited fever and consequently stopped taking levodopa. Levodopa was more effective in younger participants with a higher baseline gait performance. SIGNIFICANCE: Our randomized crossover trial showed that levodopa has the potential to improve gait disturbance in people with DS.


Asunto(s)
Estudios Cruzados , Epilepsias Mioclónicas , Trastornos Neurológicos de la Marcha , Levodopa , Humanos , Levodopa/uso terapéutico , Masculino , Femenino , Adolescente , Adulto Joven , Niño , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/etiología , Epilepsias Mioclónicas/tratamiento farmacológico , Análisis de la Marcha , Resultado del Tratamiento , Carbidopa/uso terapéutico , Marcha/efectos de los fármacos , Combinación de Medicamentos
14.
Respir Investig ; 62(3): 442-448, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38522360

RESUMEN

BACKGROUND: Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients' quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted. METHODS: Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered. RESULTS: A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor. CONCLUSIONS: We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.


Asunto(s)
Asma Variante con Tos , Reflujo Gastroesofágico , Humanos , Tos Crónica , Japón/epidemiología , Prevalencia , Calidad de Vida , Tos/epidemiología , Tos/etiología , Tos/diagnóstico , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/epidemiología , Enfermedad Crónica
15.
Med Devices (Auckl) ; 17: 89-95, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38404633

RESUMEN

Background: Multiple needle punctures during central venous line insertion can lead to serious complications. Needle deterioration owing to repeated punctures may be a major cause. We hypothesized that there is an optimal bevel angle for a back-cut point needle that is resistant to deterioration. In this study, we examined the effect of bevel angle differences in a back-cut point needle on needle tip deterioration caused by multiple punctures. Methods: The resin target was punctured perpendicularly using back-cut point needles with three bevel angles (15°, 17°, and 19°; n=8 for each angle) at a speed of 200 mm/min. The same needle was used for ten consecutive punctures at different locations on the target. The force applied to the needle was recorded as puncture force. The puncture force waveform is bimodal. The second peak values, which formed the maximum values of puncture force, were the focus of the main analysis. We considered a 5% elevation from the first to the 10th puncture force as needle deterioration, and the average slope value of the regression line between the puncture number and puncture force was used. When the upper limit of the 95% confidence interval (CI) of the slope value was less than 0.008889, the needle was considered to be resistant to deterioration. Results: The slopes of the second peak values during 10 consecutive punctures for each bevel angle (15°, 17°, 19°) were 0.003011 ± 0.01085 [-0.006056, 0.012077], 0.006116±0.007431 [-0.000096, 0.012328], and 0.001515 ± 0.005783 [-0.003320, 0.006349], respectively (mean ± standard deviation [95% CI]). Only the 19° angle needle had a smaller upper limit of the 95% CI for a slope value of 0.008889. Conclusion: The 19° bevel angle back-cut point needle was more resistant to deterioration than the 15° and 17° angle needles were.

16.
Bioorg Med Chem ; 99: 117603, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38246115

RESUMEN

NHE5, an isoform of the Na+/H+ exchanger (NHE) protein, is an ion-transporting membrane protein that regulates intracellular pH and is highly expressed in colorectal adenocarcinoma. Therefore, we hypothesized that NHE5 inhibitors can be used as anticancer drugs. However, because NHE1 is ubiquitously expressed in all cells, it is extremely important to demonstrate its selective inhibitory activity against NHE5. We used amiloride, an NHE non-selective inhibitor, as a lead compound and created UTX-143, which has NHE5-selective inhibitory activity, using a structure-activity relationship approach. UTX-143 showed selective cytotoxic effects on cancer cells and reduced the migratory and invasive abilities of cancer cells. These results suggest a new concept wherein drugs exhibit cancer-specific cytotoxic effects through selective inhibition of NHE5 and the possibility of UTX-143 as a lead NHE5-selective inhibitor.


Asunto(s)
Amilorida , Sodio , Amilorida/farmacología , Sodio/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , Proteínas de la Membrana/metabolismo , Hidrógeno , Concentración de Iones de Hidrógeno
17.
Genes Cells ; 29(1): 39-51, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37963657

RESUMEN

The c-Jun N-terminal kinase-associated leucine zipper protein (JLP), a scaffold protein of mitogen-activated protein kinase signaling pathways, is a multifunctional protein involved in a variety of cellular processes. It has been reported that JLP is overexpressed in various types of cancer and is expected to be a potential therapeutic target. However, whether and how JLP overexpression affects non-transformed cells remain unknown. Here, we aimed to investigate the effect of JLP overexpression on chromosomal stability in human non-transformed cells and the mechanisms involved. We found that aneuploidy was induced in JLP-overexpressed cells. Moreover, we established JLP-inducible cell lines and observed an increased frequency of chromosome missegregation, reduced time from nuclear envelope breakdown to anaphase onset, and decreased levels of the spindle assembly checkpoint (SAC) components at the prometaphase kinetochore in cells overexpressing the wild-type JLP. In contrast, we observed that a point mutant JLP lacking the ability to interact with dynein light intermediate chain 1 (DLIC1) failed to induce chromosomal instability. Our results suggest that overexpression of the wild-type JLP facilitates premature SAC silencing through interaction with DLIC1, leading to aneuploidy. This study provides a novel insight into the mechanism through which JLP overexpression is associated with cancer development and progression.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Neoplasias , Humanos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Leucina Zippers , Dineínas/genética , Dineínas/metabolismo , Neoplasias/metabolismo , Inestabilidad Cromosómica , Aneuploidia , Mitosis
18.
Jpn J Radiol ; 42(2): 182-189, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37874526

RESUMEN

PURPOSE: To investigate the dose stability of craniospinal irradiation based on irradiation method of proton beam therapy (PBT). METHODS AND MATERIALS: Twenty-four pediatric and young adult brain tumor patients (age: 1-24 years) were examined. Treatment method was passive-scattered PBT (PSPT) in 8 patients and intensity-modulated PBT (IMPT) in 16 patients. The whole vertebral body (WVB) technique was used in 13 patients whose ages were younger than 10, and vertebral body sparing (VBS) technique was used for the remaining 11 patients aged 10 and above. Dose stability of planning target volume (PTV) against set-up error was investigated. RESULTS: The minimum dose (Dmin) of IMPT was higher than that of PSPT (p = 0.01). Inhomogeneity index (INH) of IMPT was lower than that of PSPT (p = 0.004). When the irradiation field of the cervical spinal cord level (C level) was shifted, the maximum dose (Dmax) was lower in IMPT, and mean dose (Dmean) was higher than PSPT as movement became greater to the cranial-caudal direction (p = 0.000-0.043). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000-0.034). When the irradiation field of the lumber spinal cord level (L level) was shifted, Dmax was lower in IMPT as movement became greater to the cranial direction (p = 0.000-0.028). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000-0.022). CONCLUSIONS: The PTV doses of IMPT and PSPT are robust and stable in both anterior-posterior and lateral directions at both C level and L level, but IMPT is more robust and stable than PSPT for cranial-caudal movements. TRIAL REGISTRY: Clinical Trial Registration number: No. 04-03.


Asunto(s)
Neoplasias Encefálicas , Irradiación Craneoespinal , Terapia de Protones , Radioterapia de Intensidad Modulada , Adolescente , Adulto , Niño , Preescolar , Humanos , Lactante , Adulto Joven , Neoplasias Encefálicas/radioterapia , Irradiación Craneoespinal/métodos , Órganos en Riesgo/efectos de la radiación , Terapia de Protones/métodos , Protones , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos
19.
Cell Chem Biol ; 31(4): 792-804.e7, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-37924814

RESUMEN

Master transcription factors such as TP63 establish super-enhancers (SEs) to drive core transcriptional networks in cancer cells, yet the spatiotemporal regulation of SEs within the nucleus remains unknown. The nuclear pore complex (NPC) may tether SEs to the nuclear pore where RNA export rates are maximal. Here, we report that NUP153, a component of the NPC, anchors SEs to the NPC and enhances TP63 expression by maximizing mRNA export. This anchoring is mediated through protein-protein interaction between the intrinsically disordered regions (IDRs) of NUP153 and the coactivator BRD4. Silencing of NUP153 excludes SEs from the nuclear periphery, decreases TP63 expression, impairs cellular growth, and induces epidermal differentiation of squamous cell carcinoma. Overall, this work reveals the critical roles of NUP153 IDRs in the regulation of SE localization, thus providing insights into a new layer of gene regulation at the epigenomic and spatial level.

20.
Plant Physiol Biochem ; 206: 108297, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38154295

RESUMEN

The introduction of exogenous particles into plants has promising applications in agriculture and biotechnology. Nanoparticles can be transported into plants through foliar application or root uptake. However, both methods have limitations in terms of the size of the particles (<40 nm) that can be transported due to the barriers of the cell wall and cuticle. In the present study, we proposed a novel method to deliver particles of up to 110 nm into plants by cutting the stem of tomato seedlings. We demonstrated for the first time, using water-insoluble silica colloids, that not only nanoparticles but also submicron particles can be transported toward the leaves when the plant stem is used as the entry point of particles. Thirty-five-day-old tomato seedlings were used as the target plants. When the cut stem seedlings were immersed in the colloidal particle suspension for up to 24 h, significant particle accumulation was observed in the nodes and leaves. The relatively low particle concentrations (10 mg/L) allowed effective transport throughout the plants. Silica particles with average diameters of 10 nm and 110 nm were both well transported and moved through the stem. Even after the particles entered the plant, adventitious roots were formed, resulting in the formation of whole plants with roots, stems, and leaves. This method can be applied not only to tomatoes but also to other food crops for various applications in plant biotechnology.


Asunto(s)
Solanum lycopersicum , Plantones , Agua , Tallos de la Planta , Dióxido de Silicio , Raíces de Plantas
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