RESUMEN
BACKGROUND: Heart failure (HF) patients with complex care needs often experience exacerbations during the transitional phase as care providers and settings change. Regional collaboration aims to ensure continuity of care; however, its impact on vulnerable patients certified as needing support or care under the Japanese long-term care insurance (LTCI) system remains unclear. METHODS AND RESULTS: We implemented a regional collaborative program for HF patients involving 3 pillars of transitional care with general practitioners and nursing care facilities: (1) standardized health monitoring using a patient diary and identification of exacerbation warning signs; (2) standardized information sharing among care providers; and (3) standardized HF management manuals. We evaluated outcomes within 1 year of discharge for patients hospitalized with HF and referred to other facilities for outpatient follow-up in 2017-2018 before program implementation (n=110) and in 2019-2020 after implementation (n=126). Patients with LTCI frequently received non-cardiologist follow up and care services and had a higher risk of all-cause mortality and HF readmission compared with those without LTCI (P<0.05). Program implementation was significantly associated with a greater reduction in HF readmissions among patients with LTCI compared with those without (P<0.05 for interaction), although mortality rates remained unchanged. CONCLUSIONS: A regional collaborative program significantly reduces HF readmissions in HF patients with LTCI who are at high risk of worsening HF.
RESUMEN
A unique design of our ultracompact microcavity wavelength conversion device exploits the simple principle that the wavelength conversion efficiency is proportional to the square of the electric field amplitude of enhanced pump light in the microcavity, and expands the range of suitable device materials to include crystals that do not exhibit birefringence or ferroelectricity. Here, as a first step toward practical applications of all-solid-state ultracompact deep-ultraviolet coherent light sources, we adopted a low-birefringence paraelectric SrB4O7 crystal with great potential for wavelength conversion and high transparency down to 130 nm as our device material, and demonstrated 234 nm deep-ultraviolet coherent light generation, whose wavelength band is expected to be used for on-demand disinfection tools that can irradiate the human body.
RESUMEN
The increased numbers of older and frail patients with heart failure (HF) means there is an urgent need to establish regional collaborative systems for medical and nursing care. However, expectations related to collaborative HF care among medical and care staff remain unclear. We conducted a questionnaire survey with staff in hospitals, clinics, and nursing care facilities (NCFs) who had experienced collaboration through the common HF collaborative pathway in the western region of Tottori Prefecture, Japan, from July 2019 to July 2020. We received 150 responses from hospitals and 41 responses from clinics and NCFs. Following introduction of the collaborative pathway, 57% of respondents from hospitals, 35% from clinics, and 71% from NCFs rated collaboration as improved. Staff from hospitals and clinics were most satisfied with improved education interventions following implementation of the collaborative pathway, and NCF staff were most satisfied with improved information sharing. Staff from hospitals and NCFs placed the highest importance on improving information sharing through collaboration, and clinic staff placed the highest importance on improving efficiency. The needs for collaborative HF care differ between hospitals, clinics, and NCFs. A collaboration program should be designed to meet the different needs of diverse staff in the community.
Asunto(s)
Insuficiencia Cardíaca , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Hospitales , Humanos , Japón , Encuestas y CuestionariosRESUMEN
Under 266-nm (deep ultraviolet, DUV) laser irradiation, an SrB4O7 (SBO) single crystal has been found to exhibit a surface laser-induced damage threshold (LIDT) of â¼ 16.4 J/cm2, which is higher than those of a synthetic silica glass (4.8 J/cm2) and a calcium fluoride (CaF2) crystal (11.4 J/cm2). By catalyst-referred etching (CARE), the LIDT of an SBO crystal can also be improved to around 24.1 J/cm2, which is 1.4 and 6.0 times higher compared to an unetched crystal and a silica glass, respectively. With high surface LIDTs, SBO single crystals can then be used as optical window materials for high-power DUV laser systems.
RESUMEN
Background: With the aging of heart failure (HF) patients, collaboration between medical and nursing care facilities is essential for HF care. The aims of this study were: (1) to identify the factors that affect willingness of nursing care staffs to cooperate with HF care; (2) to test whether the internet video education is useful in improving their willingness to collaborate. Methods: A web-based questionnaire was e-mailed to 417 registered medical corporations that operated nursing care facilities in the prefecture where the authors work. Medical and care staff working at each facility were asked their willingness to cooperate with HF care and their problems about collaboration. Machine learning analysis was used to assess the factors associated with unwillingness to cooperate. After watching a 6-min YouTube video explaining HF and community collaboration, we reaffirmed their willingness to cooperate. Results: We received responses from 76 medical and care staff members. Before watching the video, 32.9% of participants stated that they were unwilling to cooperate with HF care. Machine learning analysis showed that job types, perceived problems of collaboration, and low opportunities to learn about HF were associated with unwillingness to cooperation. After watching the video, we observed an increase from 67.1% to 80.3% (p < 0.05) of participants willing to cooperate with HF care. Conclusions: Job types, perceived problems of collaboration, and low opportunities to learn about HF are associated with unwillingness of nursing care staff for HF care. Internet videos are potential learning tool that can easily promote community collaboration for HF.
RESUMEN
Background: Evidence on transitional care for heart failure (HF) in Japan is limited. MethodsâandâResults: We implemented a transitional HF management program in rural Japan in 2019. This involved collaboration with general practitioners or nursing care facilities and included symptom monitoring by medical/nursing staff using a handbook; standardized discharge care planning and information sharing on self-care and advance care planning using a collaborative sheet; and sharing expertise on HF management via manuals. We compared the outcomes within 1 year of discharge among patients hospitalized with HF in the 2 years before program implementation (2017-2018; historical control, n=198), in the first 2 years after program implementation (2019-2020; Intervention Phase 1, n=205), and in the second 2 years, following program revision and regional dissemination (2021-2022; Intervention Phase 2, n=195). HF readmission rates gradually decreased over Phases 1 and 2 (P<0.05). This association was consistent regardless of physician expertise, follow-up institution, or the use of nursing care services (P>0.1 for interaction). Mortality rates remained unchanged, but significantly more patients received end-of-life care at home in Phase 2 than before (P<0.05). Conclusions: The implementation of a transitional care program was associated with decreased HF readmissions and increased end-of-life care at home for HF patients in rural Japan.
RESUMEN
B-Myb is one member of the vertebrate Myb family of transcription factors and is ubiquitously expressed. B-Myb activates transcription of a group of genes required for the G2/M cell cycle transition by forming the dREAM/Myb-MuvB-like complex, which was originally identified in Drosophila. Mutants of zebrafish B-myb and Drosophila myb exhibit defects in cell cycle progression and genome instability. Although the genome instability caused by a loss of B-Myb has been speculated to be due to abnormal cell cycle progression, the precise mechanism remains unknown. Here, we have purified a B-Myb complex containing clathrin and filamin (Myb-Clafi complex). This complex is required for normal localization of clathrin at the mitotic spindle, which was previously reported to stabilize kinetochore fibres. The Myb-Clafi complex is not tightly associated with the mitotic spindles, suggesting that this complex ferries clathrin to the mitotic spindles. Thus, identification of the Myb-Clafi complex reveals a previously unrecognized function of B-Myb that may contribute to its role in chromosome stability, possibly, tumour suppression.
Asunto(s)
Clatrina/metabolismo , Proteínas Contráctiles/metabolismo , Proteínas de Microfilamentos/metabolismo , Proteínas Proto-Oncogénicas c-myb/metabolismo , Huso Acromático/metabolismo , Animales , Clatrina/aislamiento & purificación , Proteínas Contráctiles/aislamiento & purificación , Fibroblastos/metabolismo , Filaminas , Inestabilidad Genómica , Células HeLa , Humanos , Ratones , Proteínas de Microfilamentos/aislamiento & purificación , Mitosis , Complejos Multiproteicos/aislamiento & purificación , Complejos Multiproteicos/metabolismo , Proteínas Proto-Oncogénicas c-myb/aislamiento & purificaciónRESUMEN
BACKGROUND: The worldwide spread of coronavirus disease 2019 (COVID-19) is still not under control and vaccination in Japan started in February 2021, albeit later than in Europe and the USA. The COVID-19 vaccination frequently leads to minor adverse reactions, which may be more intense after the second dose. The number of case reports of myocarditis following COVID-19 vaccination have been recently increased. CASE SUMMARY: We report a case of a 26-year-old healthy man who presented to our hospital with chest pain on 24 May 2021, 4 days after his second COVID-19 vaccination. The electrocardiogram showed ST elevation with upward concavity in I, II, aVL, aVF, V4 to V6, and small Q wave in II, III, aVF. Laboratory studies revealed elevation of troponin I, creatine kinase, C-reactive protein, and negative viral serologies. Acute aortic dissection and pulmonary thromboembolism were ruled out by contrast-enhanced thoracoabdominal computed tomography. An urgent coronary angiogram was performed because an acute coronary syndrome was suspected, but no significant stenosis was found. Cardiac magnetic resonance imaging demonstrated oedema and late gadolinium enhancement of the left ventricle in a mid-myocardial and epicardial distribution. DISCUSSION: Although the temporal association does not prove causation, the very short span between the second vaccination and the onset of myocarditis suggests that this acute myocarditis seemed to be an adverse reaction to COVID-19 vaccine. To the best of our knowledge, this is the first published case of acute myocarditis following COVID-19 vaccine in Asia.
RESUMEN
A non-thermal atmospheric pressure plasma jet (APPJ) may stimulate cells and tissues or result in cell death depending on the intensity of plasma at the target; therefore, we herein investigated the effects of non-thermal plasma under non-contact conditions on the healing of full-thickness wounds in diabetic mice (DM+ group) and normal mice (DM- group). A hydrogen peroxide colorimetric method and high performance liquid chromatography showed that APPJ produced low amounts of reactive oxygen and nitrogen species. Ten-week-old male C57BL/6j mice with normal blood glucose levels (DM- group) and 10-week-old male C57BLKS/J Iar-+Leprdb/+Leprdb mice (DM+ group) received two full-thickness cutaneous wounds (4 mm in diameter) on both sides of the dorsum. Wounds were treated with or without the plasma jet or argon gas for 1 minute and were then covered with a hydrocolloid dressing (Hydrocolloid), according to which mice were divided into the following groups: DM+Plasma, DM+Argon, DM+Hydrocolloid, DM-Plasma, DM-Argon, and DM-Hydrocolloid. Exudate weights, wound areas, and wound area ratios were recorded every day. Hematoxylin and eosin staining was performed to assess re-epithelialization and α-SMA immunohistological staining to evaluate the formation of new blood vessels. Non-thermal plasma under non-contact conditions reduced the production of exudate. Exudate weights were smaller in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups. The wound area ratio was smaller for plasma-treated wounds, and was also smaller in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups on days 1-21 (p<0.01). Wound areas were smaller in the DM-Plasma group than in the DM-Argon group until day 14 and differences were significant on days 1-5 (p<0.01). The percentage of re-epithelialization was significantly higher in the DM+Plasma group than in the DM+Argon and DM+Hydrocolloid groups (p<0.01). The number of new blood vessels that had formed by day 7 was significantly higher in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups (p<0.05). These results indicate that treatment with the current non-thermal plasma APPJ device under non-contact conditions accelerated wound healing in diabetic mice.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Gases em Plasma , Animales , Argón , Glucemia , Coloides/farmacología , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/terapia , Eosina Amarillenta-(YS) , Hematoxilina , Peróxido de Hidrógeno , Masculino , Ratones , Ratones Endogámicos C57BL , Nitrógeno , Oxígeno , Gases em Plasma/farmacología , Gases em Plasma/uso terapéutico , Cicatrización de HeridasRESUMEN
We solubilised SWNTs of short length using a mechanochemical high-speed vibration milling (HSVM) through formation of complexes between the SWNTs and chelate complexes; the mixture formed a network structure on mica.
RESUMEN
This work focuses on design, construction, and optimization of configuration of a novel high voltage pulse power source for large-scale dielectric barrier discharge (DBD) generation. The pulses were generated by using the high-speed switching characteristic of an inexpensive device called silicon diodes for alternating current and the self-terminated characteristic of DBD. The operation started to be powered by a primary DC low voltage power supply flexibly equipped with a commercial DC power supply, or a battery, or DC output of an independent photovoltaic system without transformer employment. This flexible connection to different types of primary power supply could provide a promising solution for the application of DBD, especially in the area without power grid connection. The simple modular structure, non-control requirement, transformer elimination, and a minimum number of levels in voltage conversion could lead to a reduction in size, weight, simple maintenance, low cost of installation, and high scalability of a DBD generator. The performance of this pulse source has been validated by a load of resistor. A good agreement between theoretically estimated and experimentally measured responses has been achieved. The pulse source has also been successfully applied for an efficient DBD plasma generation.
RESUMEN
The effects of moricizine on Na+ channel currents (INa) were investigated in guinea-pig atrial myocytes and its effects on INa in ventricular myocytes and on cloned hH1 current were compared using the whole-cell, patch-clamp technique. Moricizine induced the tonic block of INa with the apparent dissociation constant (Kd,app) of 6.3 microM at -100 mV and 99.3 microM at -140 mV. Moricizine at 30 microM shifted the h infinity curve to the hyperpolarizing direction by 8.6 +/- 2.4 mV. Moricizine also produced the phasic block of INa, which was enhanced with the increase in the duration of train pulses, and was more prominent with a holding potential (HP) of -100 mV than with an HP of -140 mV. The onset block of INa induced by moricizine during depolarization to -20 mV was continuously increased with increasing the pulse duration, and was enhanced at the less negative HP. The slower component of recovery of the moricizine-induced INa block was relatively slow, with a time constant of 4.2 +/- 2.0 s at -100 mV and 3.0 +/- 1.2 s at -140 mV. Since moricizine induced the tonic block of ventricular INa with Kd,app of 3.1 +/- 0.8 microM at HP = -100 mV and 30.2 +/- 6.8 microM at HP = -140 mV, and cloned hH1 with Kd,app of 3.0 +/- 0.5 microM at HP = -100 mV and 22.0 +/- 3.2 microM at HP = -140 mV, respectively, either ventricular INa or cloned hH1 had significantly higher sensitivity to moricizine than atrial INa. The h infinity curve of ventricular INa was shifted by 10.5 +/- 3.5 mV by 3 microM moricizine and that of hH1 was shifted by 5.0 +/- 2.3 mV by 30 microM moricizine. From the modulated receptor theory, we have estimated the dissociation constants for the resting and inactivated state to be 99.3 and 1.2 microM in atrial myocytes, 30 and 0.17 microM in ventricular myocytes, and 22 and 0.2 microM in cloned hH1, respectively. We conclude that moricizine has a higher affinity for the inactivated Na+ channel than for the resting state channel in atrial myocytes, and moricizine showed the significant atrioventricular difference of moricizine block on INa. Moricizine would exert an antiarrhythmic action on atrial myocytes, as well as on ventricular myocytes, by blocking Na+ channels with a high affinity to the inactivated state and a slow dissociation kinetics.
Asunto(s)
Antiarrítmicos/farmacología , Moricizina/farmacología , Miocitos Cardíacos/efectos de los fármacos , Bloqueadores de los Canales de Sodio/farmacología , Canales de Sodio/efectos de los fármacos , Animales , Células Cultivadas , Cobayas , Atrios Cardíacos/citología , Ventrículos Cardíacos/citología , Cinética , Modelos Cardiovasculares , Miocitos Cardíacos/fisiología , Técnicas de Placa-Clamp , Canales de Sodio/fisiologíaRESUMEN
We herein report an outbreak of non-food-borne diarrhea which occurred in a nursing home due to enterotoxigenic Clostridium perfringens. The regional public health center in Gifu, Japan, recognized 7 patients with diarrhea in a nursing home, suspecting a food-borne illness. Bacteriological and epidemiological studies indicated that enterotoxigenic C. perfringens was the causative agent. However, suspected foods, the kitchen and the cooks carried no enteropathogenic bacteria, indicating that this outbreak was a non-food-borne diarrhea. The swab specimens obtained from the residential area of the nursing home were found to have enterotoxigenic C. perfringens. Isolates from the stool specimens of patients and environment were all serotype TW47, showing susceptibilities to ampicillin, levofloxacin, and clindamycin very similar to each other, and had banding patterns identical to each other by pulsed-field gel electrophoresis. These results strongly supported the existence of monoclonal spread of an enterotoxigenic C. perfringens among the environment of the nursing home and the residents. During 3 weeks 14 residents were involved in this outbreak. The extensive effort of keeping the residential area clean led to a prompt cease of this outbreak.
Asunto(s)
Infecciones por Clostridium/transmisión , Clostridium perfringens/aislamiento & purificación , Enterotoxinas/biosíntesis , Anciano , Infecciones por Clostridium/epidemiología , Clostridium perfringens/metabolismo , Brotes de Enfermedades , Heces/microbiología , Hogares para Ancianos , Humanos , Japón/epidemiología , Casas de SaludRESUMEN
Tumor necrosis factor alpha (TNF-α) plays a role in apoptosis and proliferation in multiple types of cells, and defects in TNF-α-induced apoptosis are associated with various autoimmune diseases. Here, we show that TRIM27, a tripartite motif (TRIM) protein containing RING finger, B-box, and coiled-coil domains, positively regulates TNF-α-induced apoptosis. Trim27-deficient mice are resistant to TNF-α-d-galactosamine-induced hepatocyte apoptosis. Trim27-deficient mouse embryonic fibroblasts (MEFs) are also resistant to TNF-α-cycloheximide-induced apoptosis. TRIM27 forms a complex with and ubiquitinates the ubiquitin-specific protease USP7, which deubiquitinates receptor-interacting protein 1 (RIP1), resulting in the positive regulation of TNF-α-induced apoptosis. Our findings indicate that the ubiquitination-deubiquitination cascade mediated by the TRIM27-USP7 complex plays an important role in TNF-α-induced apoptosis.
Asunto(s)
Apoptosis , Proteínas de Unión al ADN/metabolismo , Proteínas Nucleares/metabolismo , Factor de Necrosis Tumoral alfa/fisiología , Proteasas Ubiquitina-Específicas/metabolismo , Ubiquitinación , Animales , Cicloheximida/farmacología , Fibroblastos/fisiología , Proteínas Activadoras de GTPasa/metabolismo , Células HEK293 , Células Hep G2 , Hepatocitos/fisiología , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/metabolismo , Poliubiquitina/metabolismo , Multimerización de Proteína , Inhibidores de la Síntesis de la Proteína/farmacología , Transporte de Proteínas , Ubiquitina-Proteína Ligasas , Peptidasa Específica de Ubiquitina 7Asunto(s)
Insuficiencia Cardíaca , Antagonistas Adrenérgicos beta/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Cuidados Paliativos al Final de la Vida , Humanos , Pronóstico , Remodelación VentricularRESUMEN
It is unknown whether salicylate enhances the action of antiarrhythmic agents on human Na+ channels with state dependency and tissue specificity. We therefore investigated effects of salicylate on quinidine-induced block of human cardiac and skeletal muscle Na+ channels. Human cardiac wild-type (hH1), LQT3-related mutant (ΔKPQ), and skeletal muscle (hSkM1) Na+ channel α subunits were expressed in COS7 cells. Effects of salicylate on quinidine-induced tonic and use-dependent block of Na+ channel currents were examined by the whole-cell patch-clamp technique. Salicylate enhanced the quinidine-induced tonic and use-dependent block of both hH1 and hSkM1 currents at a holding potential (HP) of -100 mV but not at -140 mV. Salicylate decreased the IC50 value for the quinidine-induced tonic block of hH1 at an HP of -100 mV, and produced a negative shift in the steady-state inactivation curve of hH1 in the presence of quinidine. According to the modulated receptor theory, it is probable that salicylate decreases the dissociation constant for quinidine binding to inactivated-state channels. Furthermore, salicylate significantly enhanced the quinidine-induced tonic and use-dependent block of the peak and steady-state ΔKPQ channel currents. The results suggest that salicylate enhances quinidine-induced block of Na+ channels via increasing the affinity of quinidine to inactivated state channels.
Asunto(s)
Quinidina/farmacología , Salicilatos/farmacología , Bloqueadores de los Canales de Sodio/farmacología , Canales de Sodio/genética , Canales de Sodio/metabolismo , Animales , Células COS , Chlorocebus aethiops , Corazón/efectos de los fármacos , Humanos , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/genética , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Mutación , Miocardio/metabolismo , Canal de Sodio Activado por Voltaje NAV1.5 , Unión Proteica , Quinidina/metabolismoRESUMEN
In this letter, we report that single-walled carbon nanotubes (SWNTs) can be dissolved in organic solvents through the formation of admixtures with barbituric acid.triaminopyrimidine (BA.TP) complexes using mechanochemical high-speed vibration milling (HSVM) and sonication methods. In contrast, neither BA nor TP alone were capable of solubilizing SWNTs. Moreover, the glutarimide (GI).TP complex was also found to be incapable of solubilizing SWNTs because the two carbonyl groups and one imino group of GI are located on only one side of the molecule such that the GI.TP complex cannot form the desired hydrogen-bonding network. These results strongly suggest that the formation of a hydrogen-bonding network makes possible the formation of multipoint interactions with the surfaces of the SWNTs.
RESUMEN
Heat shock response is an adoptive response to proteotoxic stress, and a major heat shock transcription factor 1 (HSF1) has been believed to protect cells from cell death by inducing heat shock proteins (Hsps) that assist protein folding and prevent protein denaturation. However, it is revealed recently that HSF1 also promotes cell death of male germ cells. Here, we found a proapoptotic Tdag51 (T-cell death associated gene 51) gene as a direct target gene of HSF1. Heat shock and other stresses induced different levels of Hsps and Tdag51, which depend on cell types. Hsps bound directly to the N-terminal pleckstrin-homology like (PHL) domain of Tdag51, and suppressed death activity of the C-terminal proline/glutamine/histidine-rich domain. Tdag51, but not major Hsps, were induced in male germ cells exposed to high temperatures. Analysis of Tdag51-null testes showed that Tdag51 played substantial roles in promoting heat shock-induced cell death in vivo. These data suggest that cell fate on proteotoxic condition is determined at least by balance between Hsp and Tdag51 levels, which are differently regulated by HSF1.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Transducción de Señal , Espermatozoides/metabolismo , Testículo/metabolismo , Factores de Transcripción/metabolismo , Animales , Muerte Celular/genética , Proteínas de Unión al ADN/deficiencia , Células HeLa , Factores de Transcripción del Choque Térmico , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Calor , Humanos , Masculino , Ratones , Ratones Mutantes , Unión Proteica , Estructura Terciaria de Proteína/genética , Transducción de Señal/genética , Estrés Fisiológico/genética , Estrés Fisiológico/metabolismo , Factores de Transcripción/deficiencia , Factores de Transcripción/genéticaRESUMEN
Heat shock transcription factors (HSFs) play roles not only in heat shock response but also in development of the reproductive organs, brain, and lens. Here, we analyzed sensory organs and found abnormalities of the olfactory epithelium in adult HSF1-null mice, which is developmentally related to the lens. The olfactory epithelium was normal until postnatal 3 weeks but was not maintained later than 4 weeks in HSF1-null mice. The olfactory epithelium was atrophied with increased cell death of olfactory sensory neurons. Analysis of the epithelium revealed that induction of HSP expression and reduction of LIF expression are lacking in adult HSF1-null mice. We found that DNA binding activity of HSF1 is induced in the olfactory epithelium later than 4 weeks and that HSF1 binds directly to Lif gene and inhibits its expression. HSF4 has opposing effects on LIF expression and olfactory neurogenesis. These data indicate that HSF1 is required for the precise expression of Hsp and cytokine genes that is obligatory for maintenance of olfactory neurogenesis in adult mice and suggest that stress-related processes are involved in its maintenance.
Asunto(s)
Proteínas de Unión al ADN/fisiología , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica , Neuronas/metabolismo , Mucosa Olfatoria/metabolismo , Factores de Transcripción/fisiología , Animales , Secuencia de Bases , Sitios de Unión , Western Blotting , Bromodesoxiuridina/farmacología , Muerte Celular , Proliferación Celular , ADN/química , Proteínas de Unión al ADN/metabolismo , Factores de Transcripción del Choque Térmico , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Interleucina-6/metabolismo , Factor Inhibidor de Leucemia , Ratones , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Datos de Secuencia Molecular , Unión Proteica , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Olfato , Factores de Tiempo , Factores de Transcripción/metabolismoRESUMEN
Polyglutamine diseases are inherited neurodegenerative diseases characterized by misfolding and aggregation of proteins possessing expanded polyglutamine repeats. As overexpression of some heat shock protein (Hsp) suppresses polyglutamine aggregates and cell death, it is assumed that combined overexpression of Hsps will suppress that more effectively. Here, we examined the impact of active forms of heat shock transcription factor 1 (HSF1), which induces a set of Hsps, on polyglutamine inclusion formation and disease progression. We found that active HSF1 suppressed polyglutamine inclusion formation more significantly than any combination of Hsps in culture cells, possibly by regulating expression of unknown genes, as well as major Hsps. We crossed R6/2 Huntington disease mice with transgenic mice expressing an active HSF1 (HSF1Tg). Analysis of the skeletal muscle revealed that the polyglutamine inclusion formation and its weight loss were improved in R6/2/HSF1Tg mice. Unexpectedly, the life span of R6/2/HSF1Tg mice was significantly improved, although active HSF1 is not expressed in the brain. These results indicated that active HSF1 has a strong inhibitory effect on polyglutamine aggregate formation in vivo and in vitro.