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1.
BMC Oral Health ; 24(1): 887, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39097715

RESUMO

BACKGROUND: A new diagnostic criterion for malnutrition, the Global Leadership Initiative on Malnutrition (GLIM) criteria, has been proposed. Despite a recognized link between malnutrition and oral health, further clarification is needed regarding this association when using the GLIM criteria. This study examined the association between malnutrition and oral health in community-dwelling older adults aged ≥ 85. METHODS: This study was conducted using data from the Tokyo Oldest Old Survey on Total Health study, and altogether 519 participants ≥ 85 years were enrolled. Malnutrition was assessed using the GLIM criteria. Oral health information, on the number of teeth, maximum occlusal force (MOF), saliva production, denture-related questions (dissatisfaction and frequency of use), dental visit history in the past year, whether participants enjoyed meals, and oral-related quality of life was assessed using the Geriatric Oral Health Assessment Index (GOHAI) were collected. MOF was assessed the average values of three measurements and lower tertile by sex as decline in MOF. For GOHAI, the score for each items (Q1-Q12) was also evaluated, and further, the decline in each item (score: 1-2 points on a 5-point scale) was assessed as a "problem with each items." Oral health factors differing between those with and without malnutrition were analyzed. For differing items, malnutrition risk was evaluated using Cox regression. RESULTS: Eighty-nine (17.1%) participants experienced malnutrition. Significant differences were observed in the decline in MOF, enjoyment of meals, individual scores for Q2, Q4, and Q6, and the problem with Q3, Q6, Q7, and Q11. Cox regression analysis showed that decline in MOF (odds ratio [OR]: 1.728, 95% confidence interval [CI]: 1.010-2.959), enjoyment of meals (OR: 0.502, 95% CI: 0.289-0.873), problem with Q3 (OR: 5.474, 95% CI: 1.301-23.028), Q6 (OR: 5.325, 95% CI: 1.026-27.636), and Q7 (OR: 2.867, 95% CI: 1.397-5.882) were associated with ORs of malnutrition. CONCLUSION: Decline in MOF, enjoyment of meals, swallowing problem (problem with Q3), limit contact due to oral condition (problem with Q6), and esthetics problem (problem with Q7) were associated with malnutrition as assessed using the GLIM criteria.


Assuntos
Vida Independente , Desnutrição , Saúde Bucal , Humanos , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Masculino , Qualidade de Vida , Avaliação Geriátrica , Força de Mordida
2.
J Physiol ; 599(19): 4497-4516, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34426971

RESUMO

Excitable cochlear hair cells convert the mechanical energy of sounds into the electrical signals necessary for neurotransmission. The key process is cellular depolarization via K+ entry from K+ -enriched endolymph through hair cells' mechanosensitive channels. Positive 80 mV potential in endolymph accelerates the K+ entry, thereby sensitizing hearing. This potential represents positive extracellular potential within the epithelial-like stria vascularis; the latter potential stems from K+ equilibrium potential (EK ) across the strial membrane. Extra- and intracellular [K+ ] determining EK are likely maintained by continuous unidirectional circulation of K+ through a putative K+ transport pathway containing hair cells and stria. Whether and how the non-excitable tissue stria vascularis responds to acoustic stimuli remains unclear. Therefore, we analysed a cochlear portion for the best frequency, 1 kHz, by theoretical and experimental approaches. We have previously developed a computational model that integrates ion channels and transporters in the stria and hair cells into a circuit and described a circulation current composed of K+ . Here, in this model, mimicking of hair cells' K+ flow induced by a 1 kHz sound modulated the circulation current and affected the strial ion transport mechanisms; the latter effect resulted in monotonically decreasing potential and increasing [K+ ] in the extracellular strial compartment. Similar results were obtained when the stria in acoustically stimulated animals was examined using microelectrodes detecting the potential and [K+ ]. Measured potential dynamics mirrored the EK change. Collectively, because stria vascularis is electrically coupled to hair cells by the circulation current in vivo too, the strial electrochemical properties respond to sounds. KEY POINTS: A highly positive potential of +80 mV in K+ -enriched endolymph in the mammalian cochlea accelerates sound-induced K+ entry into excitable sensory hair cells, a process that triggers hearing. This unique endolymphatic potential represents an EK -based battery for a non-excitable epithelial-like tissue, the stria vascularis. To examine whether and how the stria vascularis responds to sounds, we used our computational model, in which strial channels and transporters are serially connected to those hair cells in a closed-loop circuit, and found that mimicking hair cell excitation by acoustic stimuli resulted in increased extracellular [K+ ] and decreased the battery's potential within the stria. This observation was overall verified by electrophysiological experiments using live guinea pigs. The sensitivity of electrochemical properties of the stria to sounds indicates that this tissue is electrically coupled to hair cells by a radial ionic flow called a circulation current.


Assuntos
Potássio , Estria Vascular , Animais , Cóclea , Endolinfa , Cobaias , Células Ciliadas Auditivas
3.
Pflugers Arch ; 468(10): 1637-49, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27568193

RESUMO

The cochlea of the mammalian inner ear contains an endolymph that exhibits an endocochlear potential (EP) of +80 mV with a [K(+)] of 150 mM. This unusual extracellular solution is maintained by the cochlear lateral wall, a double-layered epithelial-like tissue. Acoustic stimuli allow endolymphatic K(+) to enter sensory hair cells and excite them. The positive EP accelerates this K(+) influx, thereby sensitizing hearing. K(+) exits from hair cells and circulates back to the lateral wall, which unidirectionally transports K(+) to the endolymph. In vivo electrophysiological assays demonstrated that the EP stems primarily from two K(+) diffusion potentials yielded by [K(+)] gradients between intracellular and extracellular compartments in the lateral wall. Such gradients seem to be controlled by ion channels and transporters expressed in particular membrane domains of the two layers. Analyses of human deafness genes and genetically modified mice suggested the contribution of these channels and transporters to EP and hearing. A computational model, which reconstitutes unidirectional K(+) transport by incorporating channels and transporters in the lateral wall and connects this transport to hair cell transcellular K(+) fluxes, simulates the circulation current flowing between the endolymph and the perilymph. In this model, modulation of the circulation current profile accounts for the processes leading to EP loss under pathological conditions. This article not only summarizes the unique physiological and molecular mechanisms underlying homeostasis of the EP and their pathological relevance but also describes the interplay between EP and circulation current.


Assuntos
Potenciais de Ação , Cóclea/fisiologia , Surdez/fisiopatologia , Líquido Extracelular/metabolismo , Animais , Cóclea/metabolismo , Surdez/metabolismo , Homeostase , Humanos , Potássio/metabolismo
4.
Pflugers Arch ; 468(9): 1609-19, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27344659

RESUMO

Eukaryotic cells exhibit negative resting membrane potential (RMP) owing to the high K(+) permeability of the plasma membrane and the asymmetric [K(+)] between the extracellular and intracellular compartments. However, cochlear fibrocytes, which comprise the basolateral surface of a multilayer epithelial-like tissue, exhibit a RMP of +5 to +12 mV in vivo. This positive RMP is critical for the formation of an endocochlear potential (EP) of +80 mV in a K(+)-rich extracellular fluid, endolymph. The epithelial-like tissue bathes fibrocytes in a regular extracellular fluid, perilymph, and apically faces the endolymph. The EP, which is essential for hearing, represents the potential difference across the tissue. Using in vivo electrophysiological approaches, we describe a potential mechanism underlying the unusual RMP of guinea pig fibrocytes. The RMP was +9.0 ± 3.7 mV when fibrocytes were exposed to an artificial control perilymph (n = 28 cochleae). Perilymphatic perfusion of a solution containing low [Na(+)] (1 mM) markedly hyperpolarized the RMP to -31.1 ± 11.2 mV (n = 10; p < 0.0001 versus the control, Tukey-Kramer test after one-way ANOVA). Accordingly, the EP decreased. Little change in RMP was observed when the cells were treated with a high [K(+)] of 30 mM (+10.4 ± 2.3 mV; n = 7; p = 0.942 versus the control). During the infusion of a low [Cl(-)] solution (2.4 mM), the RMP moderately hyperpolarized to -0.9 ± 3.4 mV (n = 5; p < 0.01 versus the control), although the membranes, if governed by Cl(-) permeability, should be depolarized. These observations imply that the fibrocyte membranes are more permeable to Na(+) than K(+) and Cl(-), and this unique profile and [Na(+)] gradient across the membranes contribute to the positive RMP.


Assuntos
Permeabilidade da Membrana Celular , Cóclea/metabolismo , Potenciais da Membrana , Potássio/metabolismo , Sódio/metabolismo , Animais , Cloretos/metabolismo , Cóclea/citologia , Cóclea/fisiologia , Endolinfa/metabolismo , Cobaias , Transporte de Íons , Masculino , Perilinfa/metabolismo
5.
Pflugers Arch ; 467(7): 1577-1589, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25143138

RESUMO

Unidirectional K(+) transport across the lateral cochlear wall contributes to the endocochlear potential (EP) of +80 mV in the endolymph, a property essential for hearing. The wall comprises two epithelial layers, the syncytium and the marginal cells. The basolateral surface of the former and the apical membranes of the latter face the perilymph and the endolymph, respectively. Intrastrial space (IS), an extracellular compartment between the two layers, exhibits low [K(+)] and a potential similar to the EP. This IS potential (ISP) dominates the EP and represents a K(+) diffusion potential elicited by a large K(+) gradient across the syncytial apical surface. The K(+) gradient depends on the unidirectional K(+) transport driven by Na(+),K(+)-ATPases on the basolateral surface of each layer and the concomitant Na(+),K(+),2Cl(-)-cotransporters (NKCCs) in the marginal cell layer. The NKCCs coexpressed with the Na(+),K(+)-ATPases in the syncytial layer also seem to participate in the K(+) transport. To test this hypothesis, we examined the electrochemical properties of the lateral wall with electrodes measuring [K(+)] and potential. Blocking NKCCs by perilymphatic perfusion of bumetanide suppressed the ISP. Unexpectedly and unlike the inhibition of the syncytial Na(+),K(+)-ATPases, the perfusion barely altered the electrochemical properties of the syncytium but markedly augmented [K(+)] of the IS. Consequently, the K(+) gradient decreased and the ISP declined. These observations resembled those when the marginal cells' Na(+),K(+)-ATPases or NKCCs were blocked with vascularly applied inhibitors. It is plausible that NKCCs in the marginal cells are affected by the perilymphatically perfused bumetanide, and these transporters, but not those in the syncytium, mediate the unidirectional K(+) transport.


Assuntos
Potássio/metabolismo , Simportadores de Cloreto de Sódio-Potássio/metabolismo , Ligamento Espiral da Cóclea/metabolismo , Animais , Cobaias , Transporte de Íons , Masculino , Potenciais da Membrana , ATPase Trocadora de Sódio-Potássio/metabolismo , Ligamento Espiral da Cóclea/citologia , Ligamento Espiral da Cóclea/fisiologia
6.
Eur J Neurosci ; 42(3): 1984-2002, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26060893

RESUMO

Stria vascularis of the mammalian cochlea transports K(+) to establish the electrochemical property in the endolymph crucial for hearing. This epithelial tissue also transports various small molecules. To clarify the profile of proteins participating in the transport system in the stria vascularis, membrane components purified from the stria of adult rats were analysed by liquid chromatography tandem mass spectrometry. Of the 3236 proteins detected in the analysis, 1807 were membrane proteins. Ingenuity Knowledge Base and literature data identified 513 proteins as being expressed on the 'plasma membrane', these included 25 ion channels and 79 transporters. Sixteen of the former and 62 of the latter had not yet been identified in the stria. Unexpectedly, many Cl(-) and Ca(2+) transport systems were found, suggesting that the dynamics of these ions play multiple roles. Several transporters for organic substances were also detected. Network analysis demonstrated that a few kinases, including protein kinase A, and Ca(2+) were key regulators for the strial transports. In the library of channels and transporters, 19 new candidates for uncloned deafness-related genes were identified. These resources provide a platform for understanding the molecular mechanisms underlying the epithelial transport essential for cochlear function and the pathophysiological processes involved in hearing disorders.


Assuntos
Surdez/fisiopatologia , Proteínas de Membrana Transportadoras/metabolismo , Estria Vascular/metabolismo , Animais , Bases de Dados Genéticas , Surdez/genética , Humanos , Masculino , Proteínas de Membrana Transportadoras/genética , Camundongos , Dados de Sequência Molecular , Proteômica , Ratos
7.
J Physiol ; 591(18): 4459-72, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23836687

RESUMO

The endocochlear potential (EP) of +80 mV in the scala media, which is indispensable for audition, is controlled by K+ transport across the lateral cochlear wall. This wall includes two epithelial barriers, the syncytium and the marginal cells. The former contains multiple cell types, such as fibrocytes, which are exposed to perilymph on their basolateral surfaces. The apical surfaces of the marginal cells face endolymph. Between the two barriers lies the intrastrial space (IS), an extracellular space with a low K+ concentration ([K+]) and a potential similar to the EP. This intrastrial potential (ISP) dominates the EP and represents the sum of the diffusion potential elicited by a large K+ gradient across the apical surface of the syncytium and the syncytium's potential, which is slightly positive relative to perilymph. Although a K+ transport system in fibrocytes seems to contribute to the EP, the mechanism remains uncertain. We examined the electrochemical properties of the lateral wall of guinea pigs with electrodes sensitive to potential and K+ while perfusing into the perilymph of the scala tympani blockers of Na+,K+-ATPase, the K+ pump thought to be essential to the system. Inhibiting Na+,K+-ATPase barely affected [K+] in the IS but greatly decreased [K+] within the syncytium, reducing the K+ gradient across its apical surface. The treatment hyperpolarized the syncytium only moderately. Consequently, both the ISP and the EP declined. Fibrocytes evidently use the Na+,K+-ATPase to achieve local K+ transport, maintaining the syncytium's high [K+] that is crucial for the K+ diffusion underlying the positive ISP.


Assuntos
Células Epiteliais/metabolismo , Potenciais da Membrana , Potássio/metabolismo , Rampa do Tímpano/metabolismo , Animais , Células Epiteliais/fisiologia , Células Gigantes/metabolismo , Células Gigantes/fisiologia , Cobaias , Transporte de Íons , Ouabaína/farmacologia , Perilinfa/metabolismo , Rampa do Tímpano/citologia , Rampa do Tímpano/fisiologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismo , Estrofantidina/farmacologia
8.
Fukuoka Igaku Zasshi ; 103(2): 43-8, 2012 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-22568127

RESUMO

We examined the cases that prescribed levofloxacin (LVFX) 500mg for middle ear diseases in our hospital. LVFX 500mg was prescribed in 18 cases (7 male, 11 female, 24-81 years old). LVFX was mainly used for the following clinical conditions, 1) otitis media with granulation proliferation: 3 cases, 2) infection to an artificial materials : 5 cases, 3) treatment for or prevention against the inflammation of the inner ear: 4 cases. Three of eighteen cases were ineffective by LVFX treatment. Bacteriological examination indicated LVFX-resistant MRSA or Pseudomonas aeruginosa were isolated in these three cases.


Assuntos
Antibacterianos/administração & dosagem , Otopatias/tratamento farmacológico , Orelha Média , Levofloxacino , Ofloxacino/administração & dosagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Otite Média/tratamento farmacológico
9.
Auris Nasus Larynx ; 49(3): 484-494, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34772563

RESUMO

OBJECTIVE: Concave deformities and gustatory sweating are the most common complications that cause substantial patient dissatisfaction after parotidectomy. Various surgical methods to prevent these complications have been described. However, effective techniques have not been established, especially in patients with medium- to large-sized parotidectomy defects. We evaluated the utility of infrahyoid myofascial flap reconstruction of parotidectomy defects for the prevention of these complications. METHODS: We conducted a retrospective case series study in patients with a benign or malignant parotid tumor measuring over 4 cm who underwent immediate pedicle infrahyoid myofascial flap reconstruction after total or subtotal parotidectomy or total resection of either the superficial or deep parotid gland at our hospital. Subjective analyses of facial symmetry, postoperative concave deformities of the anterior neck, gustatory sweating, voice disorders, odynophagia, neck scarring in the parotid and anterior neck areas, sensory disorders, pain, and neck stiffness were performed using patient interview data. Objective evaluations of facial symmetry were made by the first or second author. Both analyses were performed after a follow-up of more than six months. Additionally, patient demographic data, clinicopathological factors, parotidectomy and skin incision types, flap survival, and postoperative complications were evaluated. RESULTS: We included eight patients (male, n=5; mean age, 69.3 years [range, 37-93 years]). Procedures included total or subtotal parotidectomy (n=4), superficial lobe parotidectomy (n=2), and deep lobe parotidectomy with partial superficial lobe parotidectomy (n=2). Infrahyoid myofascial flaps reached the cranial tip of the parotid defect without tension, and their volume sufficiently filled the parotidectomy defect in all patients. There were no local signs of insufficient blood flow within the transferred flaps. Objective and subjective assessments were made after a mean duration of 1.2 years (range, 0.6-1.8). Postoperatively, no patient subjectively reported facial asymmetry. Objectively, facial symmetry was "good" in four patients and "fair" in four patients. No distinctly visible concave deformity in the parotid or anterior neck area occurred in any patient. Gustatory sweating occurred in one patient; this individual had the largest parotidectomy defect. Only one patient experienced donor site morbidity (mild anterior neck stiffness) related to infrahyoid myofascial flap elevation. CONCLUSION: Although complete prevention of gustatory sweating was unsuccessful, infrahyoid myofascial flap reconstruction of medium- to large-sized parotidectomy defects led to postoperative facial symmetry with minimal donor site morbidity.


Assuntos
Neoplasias Parotídeas , Sudorese Gustativa , Idoso , Humanos , Masculino , Glândula Parótida/cirurgia , Neoplasias Parotídeas/complicações , Neoplasias Parotídeas/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Retalhos Cirúrgicos , Sudorese Gustativa/prevenção & controle
10.
Clin Hemorheol Microcirc ; 82(1): 1-12, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35599472

RESUMO

BACKGROUND: Exercise-induced impairment of blood fluidity is considered to be associated with thrombosis development. However, the effects of L-arginine on blood fluidity after exercise remain unclear. OBJECTIVE: We investigated the mechanisms of impaired blood fluidity after high-intensity exercise, and examined whether L-arginine improves exercise-induced blood fluidity impairment in vitro. METHODS: Ten healthy male participants performed 15 minutes of ergometer exercise at 70% of their peak oxygen uptake levels. Blood samples were obtained before and after exercise. L-arginine and NG-monomethyl-L-arginine acetate (L-NMMA)-a nitric oxide (NO) synthase inhibitor-were added to the post-exercise blood samples. Using Kikuchi's microchannel method, we measured the blood passage time, percentage of obstructed microchannels, and the number of adherent white blood cells (WBCs) on the microchannel terrace. RESULTS: Exercise increased the hematocrit levels. The blood passage times, percentage of obstructed microchannels, and the number of adherent WBCs on the microchannel terrace increased after exercise; however, they decreased in a dose-dependent manner after the addition of L-arginine. L-NMMA inhibited the L-arginine-induced decrease in blood passage time. CONCLUSIONS: High-intensity exercise impairs blood fluidity by inducing hemoconcentration along with increasing platelet aggregation and WBC adhesion. The L-arginine-NO pathway improves blood fluidity impairment after high-intensity exercise in vitro.


Assuntos
Arginina , Óxido Nítrico , Humanos , Masculino , ômega-N-Metilarginina/farmacologia , Arginina/farmacologia , Exercício Físico , Leucócitos , Agregação Plaquetária
11.
In Vivo ; 36(5): 2211-2217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36099114

RESUMO

BACKGROUND/AIM: Acid-electrolyzed functional water (FW) is an efficient bactericide and gargling with FW might be an effective method of oral care. We investigated the possible use of FW as a mouth wash by an in vitro study. MATERIALS AND METHODS: The bactericidal effect of FW against different species of bacteria (Staphylococcus aureus, Streptococcus pneumonia, Pseudomonas aeruginosa, and Candida albicans) was evaluated using the numbers of colony-forming units (CFU). The experiment was conducted using PBS, LISTERINE, and ConCool F (undiluted, and the optimal concentration indicated). To investigate the bactericidal mechanism of FW, the activity of superoxide dismutase (SOD), an indicator of oxidative action, was measured in S. aureus. FW was diluted with purified water to concentrations of 10, 30, 50, and 70%. The numbers of CFU were measured for each concentration. XTT assays were performed using HSC-3 and HeLa cells, to examine the viability of the cells following treatment with FW. The same experiment was conducted with PBS, LISTERINE, and undiluted ConCool F. RESULTS: No bacteria treated with FW formed colonies. SOD activity peaked at a 50% concentration of FW and was more than twice that of the control. A significant decrease in the number of CFU was observed following 50% treatment. Since the peaks of the SOD activity and the starting concentrations of the bactericidal effects coincided, the bactericidal effect of FW might be related to its oxidative effects. Bacteria treated with FW had the same survival rate as the other mouth washes. CONCLUSION: FW might be clinically applicable as a mouth wash.


Assuntos
Antissépticos Bucais , Água , Antibacterianos/farmacologia , Bactérias , Células HeLa , Humanos , Antissépticos Bucais/farmacologia , Staphylococcus aureus , Superóxido Dismutase/farmacologia , Água/farmacologia
12.
In Vivo ; 36(2): 979-984, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35241559

RESUMO

BACKGROUND/AIM: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5-fluorouracil plus cetuximab (EXTREME). PATIENTS AND METHODS: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. RESULTS: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. CONCLUSION: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.


Assuntos
Cisplatino , Neoplasias das Glândulas Salivares , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Cetuximab/efeitos adversos , Cisplatino/uso terapêutico , Fluoruracila , Humanos , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
13.
Anticancer Res ; 42(2): 981-989, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35093898

RESUMO

BACKGROUND/AIM: The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed. RESULTS: The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors. CONCLUSION: Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.


Assuntos
Carcinoma/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias das Glândulas Salivares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Carcinoma/metabolismo , Carcinoma/mortalidade , Carcinoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Análise de Sobrevida , Resultado do Tratamento
14.
J Neurosci Methods ; 351: 109074, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33450333

RESUMO

BACKGROUND: Essential tremor is the most prevalent movement disorder and is thought to be caused by abnormalities in the cerebellar system; however, its underlying neural mechanism is poorly understood. In this study, we found that mice lacking netrin-G2, a cell adhesion molecule which is expressed in neural circuits related to the cerebellar system, exhibited a microtremor resembling an essential tremor. However, it was difficult to quantify microtremors in netrin-G2 KO mice. NEW METHOD: We developed a new tremor detector which can quantify the intensity and frequency of a tremor. RESULTS: Using this system, we were able to characterize both the microtremors in netrin-G2 KO mice and low-dose harmaline-induced tremors which, to date, had been difficult to detect. Alcohol and anti-tremor drugs, which are effective in decreasing the symptoms of essential tremor in patients, were examined in netrin-G2 KO mice. We found that some drugs lowered the tremor frequency, but had little effect on tremor intensity. Forced swim as a stress stimulus in netrin-G2 KO mice dramatically enhanced tremor symptoms. COMPARISON WITH EXISTING METHODS: The detection performance even for tremors induced by low-dose harmaline was similar to that in previous studies or more sensitive than the others. CONCLUSIONS: Microtremors in netrin-G2 KO mice are reliably and quantitatively detected by our new tremor detection system. We found different effects of medicines and factors between human essential tremors and microtremors in netrin-G2 KO mice, suggesting that the causations, mechanisms, and symptoms of tremors vary and are heterogeneous, and the objective analyses are required.


Assuntos
Tremor Essencial , Harmalina , Animais , Humanos , Camundongos , Camundongos Knockout , Netrinas , Tremor
15.
Cell Rep ; 37(6): 109966, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34758322

RESUMO

Sensory processing is essential for motor control. Climbing fibers from the inferior olive transmit sensory signals to Purkinje cells, but how the signals are represented in the cerebellar cortex remains elusive. To examine the olivocerebellar organization of the mouse brain, we perform quantitative Ca2+ imaging to measure complex spikes (CSs) evoked by climbing fiber inputs over the entire dorsal surface of the cerebellum simultaneously. The surface is divided into approximately 200 segments, each composed of ∼100 Purkinje cells that fire CSs synchronously. Our in vivo imaging reveals that, although stimulation of four limb muscles individually elicits similar global CS responses across nearly all segments, the timing and location of a stimulus are derived by Bayesian inference from coordinated activation and inactivation of multiple segments on a single trial basis. We propose that the cerebellum performs segment-based, distributed-population coding that represents the conditional probability of sensory events.


Assuntos
Potenciais de Ação , Cálcio/metabolismo , Cerebelo/fisiologia , Rede Nervosa/fisiologia , Núcleo Olivar/fisiologia , Células de Purkinje/fisiologia , Órgãos dos Sentidos/fisiologia , Animais , Teorema de Bayes , Cerebelo/citologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Rede Nervosa/citologia , Núcleo Olivar/citologia , Células de Purkinje/citologia , Órgãos dos Sentidos/citologia
16.
Eur J Orthod ; 32(2): 131-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20159792

RESUMO

It has previously been reported that low-energy laser irradiation stimulated the velocity of tooth movement via the receptor activator of nuclear factor kappa B (RANK)/RANK ligand and the macrophage colony-stimulating factor/its receptor (c-Fms) systems. Matrix metalloproteinase (MMP)-9, cathepsin K, and alpha(v) beta(3) [alpha(v)beta3] integrin are essential for osteoclastogenesis; therefore, the present study was designed to examine the effects of low-energy laser irradiation on the expression of MMP-9, cathepsin K, and alpha(v)beta3 integrin during experimental tooth movement. Fifty male, 6-week-old Wistar strain rats were used in the experiment. A total force of 10g was applied to the rat molars to induce tooth movement. A Ga-Al-As diode laser was used to irradiate the area around the moving tooth and, after 7 days, the amount of tooth movement was measured. To determine the amount of tooth movement, plaster models of the maxillae were made using a silicone impression material before (day 0) and after tooth movement (days 1, 2, 3, 4, and 7). The models were scanned using a contact-type three-dimensional (3-D) measurement apparatus. Immunohistochemical staining for MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 was performed. Intergroup comparisons of the average values were conducted with a Mann-Whitney U-test for tooth movement and the number of tartrate-resistant acid phosphatase (TRAP), MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3-positive cells. In the laser-irradiated group, the amount of tooth movement was significantly greater than that in the non-irradiated group at the end of the experiment (P < 0.05). Cells positively stained with TRAP, MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 were found to be significantly increased in the irradiated group on days 2-7 compared with those in the non-irradiated group (P < 0.05). These findings suggest that low-energy laser irradiation facilitates the velocity of tooth movement and MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 expression in rats.


Assuntos
Processo Alveolar/efeitos da radiação , Remodelação Óssea/efeitos da radiação , Lasers Semicondutores/uso terapêutico , Terapia com Luz de Baixa Intensidade , Técnicas de Movimentação Dentária , Processo Alveolar/metabolismo , Animais , Catepsina K/biossíntese , Análise do Estresse Dentário , Integrina alfaVbeta3/biossíntese , Masculino , Metaloproteinase 9 da Matriz/biossíntese , Osteoclastos/metabolismo , Osteoclastos/efeitos da radiação , Ratos , Ratos Wistar
17.
No To Hattatsu ; 41(6): 447-51, 2009 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-19928544

RESUMO

We report a 4-year-old boy with fulminating meningitis caused by Haemophilus influenzae (Hib). He suddenly developed fever, vomiting and then somnolence. As bacterial meningitis was suspected, treatment with antibiotics was started at 12 hours after the onset. However, there was a rapid progression of severe brain edema and brain hernia, leading to clinical brain death. His clinical course and neuroradiological findings mimicked those in patients with acute encephalopathy, with cytokine profiles in cerebrospinal fluid demonstrating a marked increase of inflammatory cytokines. From a review of the literature, fulminating Hib meningitis may be classified into two disease types: DIC plus multiple organ failure and acute brain swelling types. The present case belongs to the latter type, in which cytokine storm seems to play an important pathogenic role.


Assuntos
Haemophilus influenzae , Meningite por Haemophilus/diagnóstico , Edema Encefálico/etiologia , Pré-Escolar , Citocinas/análise , Progressão da Doença , Humanos , Masculino
18.
Neurosci Res ; 61(1): 49-55, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18314210

RESUMO

We carried out voltage-sensitive dye imaging of the guinea pig auditory cortex to determine whether the ongoing and spontaneous activities of the cortex exhibit spatial coherence reflecting the tonotopic organization of the cortex. We used independent component analysis and a signal-plus-noise model to extract ongoing activities from the observed signals including physiological noise and stimulus-evoked activities. We analyzed the cross-correlations of background activities between all pairs of recording channels and found that ongoing and spontaneous activities in the auditory cortex exhibited anisotropic spatial coherence extending along the isofrequency bands.


Assuntos
Córtex Auditivo/fisiologia , Estimulação Acústica , Animais , Anisotropia , Mapeamento Encefálico , Corantes , Cobaias , Processamento de Imagem Assistida por Computador , Masculino , Análise de Componente Principal , Tomografia de Coerência Óptica
19.
J Biomed Opt ; 13(5): 054008, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19021388

RESUMO

Optical topography (OT) signals measured during an experiment that used activation tasks for certain brain functions contain neuronal-activation induced blood oxygenation changes and also physiological changes. We used independent component analysis to separate the signals and extracted components related to brain activation without using any hemodynamic models. The analysis procedure had three stages: first, OT signals were separated into independent components (ICs) by using a time-delayed decorrelation algorithm; second, task-related ICs (TR-ICs) were selected from the separated ICs based on their mean intertrial cross-correlations; and third, the TR-ICs were categorized by k-means clustering into TR activation-related ICs (TR-AICs) and TR noise ICs (TR-NICs). We applied this analysis procedure to the OT signals obtained from experiments using one-handed finger-tapping tasks. In the averaged waveform of the TR-AICs, a small overshoot can be seen for a few seconds after the onset of each task and a few seconds after it ends, and the averaged waveforms of the TR-NICs have an N-shaped pattern.


Assuntos
Algoritmos , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Potenciais Evocados/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Reconhecimento Automatizado de Padrão/métodos , Análise e Desempenho de Tarefas , Feminino , Humanos , Masculino , Análise de Componente Principal
20.
Cell Rep ; 22(11): 2873-2885, 2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29539417

RESUMO

Multisensory integration (MSI) is a fundamental emergent property of the mammalian brain. During MSI, perceptual information encoded in patterned activity is processed in multimodal association cortex. The systems-level neuronal dynamics that coordinate MSI, however, are unknown. Here, we demonstrate intrinsic hub-like network activity in the association cortex that regulates MSI. We engineered calcium reporter mouse lines based on the fluorescence resonance energy transfer sensor yellow cameleon (YC2.60) expressed in excitatory or inhibitory neurons. In medial and parietal association cortex, we observed spontaneous slow waves that self-organized into hubs defined by long-range excitatory and local inhibitory circuits. Unlike directional source/sink-like flows in sensory areas, medial/parietal excitatory and inhibitory hubs had net-zero balanced inputs. Remarkably, multisensory stimulation triggered rapid phase-locking mainly of excitatory hub activity persisting for seconds after the stimulus offset. Therefore, association cortex tends to form balanced excitatory networks that configure slow-wave phase-locking for MSI. VIDEO ABSTRACT.


Assuntos
Córtex Cerebral/fisiologia , Neurônios/fisiologia , Animais , Córtex Cerebral/citologia , Camundongos
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