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1.
Pediatr Res ; 94(1): 304-312, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36624284

RESUMEN

BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality. We performed this study to test the hypothesis that left ventricular (LV) and right ventricular (RV) volumes assessed by three-dimensional echocardiography may be associated with mortality in CDH. METHODS: This study was a single-center retrospective cohort study involving 35 infants with CDH. RV and LV end-diastolic volume (RVEDV and LVEDV, respectively) were measured by three-dimensional echocardiography and were corrected by birth body weight (BBW) on day 1. RVEDV/BBW, LVEDV/BBW, and LVEDV/RVEDV were compared between CDH survivors and non-survivors. Receiver-operating characteristic curve analysis was performed to assess the predictive ability for mortality of the echocardiographic parameters. RESULTS: Comparing CDH non-survivors (n = 6) with survivors (n = 29), respectively, RVEDV/BBW was significantly larger (2.54 ± 0.33 vs 1.86 ± 0.35 ml/kg; P < 0.01), LVEDV/BBW was significantly smaller (0.86 ± 0.21 vs 1.22 ± 0.33 ml/kg; P < 0.001), and LVEDV/RVEDV was significantly lower (0.34 ± 0.06 vs 0.66 ± 0.18; P < 0.001). The area under the curve for LVEDV/RVEDV was the largest (0.98). CONCLUSIONS: Three-dimensional echocardiographic volume imbalance between the RV and LV was remarkable in CDH non-survivors. The LVEDV/RVEDV ratio may be associated with mortality in CDH. IMPACT: Mortality with congenital diaphragmatic hernia (CDH) is high, and evaluating left and right ventricular structures and functions may be helpful in assessing the prognosis. Three-dimensional (3D) echocardiography indicated that the left ventricular end-diastolic volume/right ventricular end-diastolic volume ratio within 24 h after birth was associated with mortality in CDH infants. The usefulness of this ratio should be validated in prospective multicenter studies involving larger numbers of patients.


Asunto(s)
Hernias Diafragmáticas Congénitas , Lactante , Recién Nacido , Humanos , Hernias Diafragmáticas Congénitas/complicaciones , Estudios Retrospectivos , Estudios Prospectivos , Ventrículos Cardíacos/diagnóstico por imagen , Ecocardiografía/métodos
2.
Gan To Kagaku Ryoho ; 50(13): 1968-1970, 2023 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-38303267

RESUMEN

74-year-old woman was diagnosed with locally advanced unresectable transverse colon cancer. She started CAPOX therapy as first-line therapy after ileostomy. After second course, MSI-high was detected, so nivolumab plus ipilimumab combination therapy was started as second-line therapy. After 4 courses of combination therapy, she was judged to be in partial response and surgery was performed. Histopathological diagnosis of the surgical specimen showed complete response, and she is still alive without recurrence 15 months after surgery.


Asunto(s)
Colon Transverso , Neoplasias del Colon , Femenino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/cirugía , Ipilimumab , Nivolumab/uso terapéutico , Anciano
3.
EMBO Rep ; 20(11): e47957, 2019 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-31524320

RESUMEN

In this study, we identified a previously uncharacterized skeletal satellite cell-secreted protein, R3h domain containing-like (R3hdml). Expression of R3hdml increases during skeletal muscle development and differentiation in mice. Body weight and skeletal muscle mass of R3hdml knockout (KO) mice are lower compared to control mice. Expression levels of cell cycle-related markers, phosphorylation of Akt, and expression of insulin-like growth factor within the skeletal muscle are reduced in R3hdml KO mice compared to control mice. Expression of R3hdml increases during muscle regeneration in response to cardiotoxin (CTX)-induced muscle injury. Recovery of handgrip strength after CTX injection was significantly impaired in R3hdml KO mice, which is rescued by R3hdml. Our results indicate that R3hdml is required for skeletal muscle development, regeneration, and, in particular, satellite cell proliferation and differentiation.


Asunto(s)
Diferenciación Celular/genética , Células Satélite del Músculo Esquelético/citología , Células Satélite del Músculo Esquelético/metabolismo , Secuencia de Aminoácidos , Animales , Biomarcadores , Proliferación Celular , Expresión Génica , Perfilación de la Expresión Génica , Ratones , Ratones Noqueados , Desarrollo de Músculos/genética , Fibras Musculares Esqueléticas/citología , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Proteína MioD/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Regeneración , Transducción de Señal
4.
PLoS Genet ; 13(12): e1007134, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29281635

RESUMEN

Feeding, a vital behavior in animals, is modulated depending on internal and external factors. In the nematode Caenorhabditis elegans, the feeding organ called the pharynx ingests food by pumping driven by the pharyngeal muscles. Here we report that optical silencing of the body wall muscles, which drive the locomotory movement of worms, affects pumping. In worms expressing the Arch proton pump or the ACR2 anion channel in the body wall muscle cells, the pumping rate decreases after activation of Arch or ACR2 with light illumination, and recovers gradually after terminating illumination. Pumping was similarly inhibited by illumination in locomotion-defective mutants carrying Arch, suggesting that perturbation of locomotory movement is not critical for pumping inhibition. Analysis of mutants and cell ablation experiments showed that the signals mediating the pumping inhibition response triggered by activation of Arch with weak light are transferred mainly through two pathways: one involving gap junction-dependent mechanisms through pharyngeal I1 neurons, which mediate fast signals, and the other involving dense-core vesicle-dependent mechanisms, which mediate slow signals. Activation of Arch with strong light inhibited pumping strongly in a manner that does not rely on either gap junction-dependent or dense-core vesicle-dependent mechanisms. Our study revealed a new aspect of the neural and neuroendocrine controls of pumping initiated from the body wall muscles.


Asunto(s)
Optogenética/métodos , Músculos Faríngeos/metabolismo , Bombas de Protones/metabolismo , Animales , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/metabolismo , Ingestión de Alimentos/fisiología , Locomoción/fisiología , Neuronas Motoras/metabolismo , Músculo Esquelético/metabolismo , Faringe/metabolismo , Serotonina , Transducción de Señal/fisiología , Canales Aniónicos Dependientes del Voltaje/genética , Canales Aniónicos Dependientes del Voltaje/metabolismo
5.
Pediatr Int ; 61(5): 465-470, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30838731

RESUMEN

BACKGROUND: The main photochemical pathway in phototherapy for neonatal hyperbilirubinemia is the production and elimination (in bile or urine) of cyclobilirubin, which is a structural photoisomer of bilirubin, and which is most efficiently produced by green light. Green light-emitting diode (LED) phototherapy, however, has not been evaluated in the clinical setting because it is not recommended in American Academy of Pediatrics guidelines. We therefore compared the efficacy of green LED phototherapy and blue LED phototherapy in patients with neonatal hyperbilirubinemia. METHODS: In this prospective randomized controlled trial, neonates with hyperbilirubinemia were randomly allocated to a green LED or blue LED phototherapy group. Both groups underwent 24 h of phototherapy, and blood was sampled before and after 24 h of phototherapy. Total serum bilirubin (TSB) was measured using enzymatic methods and bilirubin photoisomers were measured on high-performance liquid chromatography. RESULTS: Thirty-four infants were randomized (green, n = 16; blue, n = 18). TSB decreased significantly from 15.3 ± 1.5 to 13.9 ± 1.5 mg/dL in the green LED group (P < 0.01) and from 16.2 ± 1.3 to 14.5 ± 1.7 mg/dL in the blue LED group (P < 0.01) after 24 h of phototherapy. No significant difference was found in TSB reduction after phototherapy between the groups. CONCLUSIONS: Both light sources produced a significant reduction in TSB, indicating clinical effectiveness.


Asunto(s)
Hiperbilirrubinemia Neonatal/terapia , Fototerapia/métodos , Bilirrubina/sangre , Color , Femenino , Humanos , Recién Nacido , Masculino , Estudios Prospectivos , Resultado del Tratamiento
6.
J Biol Chem ; 291(23): 12223-32, 2016 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-27129243

RESUMEN

Thermophilic rhodopsin (TR) is a photoreceptor protein with an extremely high thermal stability and the first characterized light-driven electrogenic proton pump derived from the extreme thermophile Thermus thermophilus JL-18. In this study, we confirmed its high thermal stability compared with other microbial rhodopsins and also report the potential availability of TR for optogenetics as a light-induced neural silencer. The x-ray crystal structure of TR revealed that its overall structure is quite similar to that of xanthorhodopsin, including the presence of a putative binding site for a carotenoid antenna; but several distinct structural characteristics of TR, including a decreased surface charge and a larger number of hydrophobic residues and aromatic-aromatic interactions, were also clarified. Based on the crystal structure, the structural changes of TR upon thermal stimulation were investigated by molecular dynamics simulations. The simulations revealed the presence of a thermally induced structural substate in which an increase of hydrophobic interactions in the extracellular domain, the movement of extracellular domains, the formation of a hydrogen bond, and the tilting of transmembrane helices were observed. From the computational and mutational analysis, we propose that an extracellular LPGG motif between helices F and G plays an important role in the thermal stability, acting as a "thermal sensor." These findings will be valuable for understanding retinal proteins with regard to high protein stability and high optogenetic performance.


Asunto(s)
Calor , Dominios Proteicos , Estructura Secundaria de Proteína , Rodopsinas Microbianas/química , Secuencia de Aminoácidos , Animales , Animales Modificados Genéticamente , Sitios de Unión/genética , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Cristalografía por Rayos X , Enlace de Hidrógeno , Simulación de Dinámica Molecular , Optogenética/métodos , Estabilidad Proteica , Bombas de Protones/química , Bombas de Protones/genética , Bombas de Protones/metabolismo , Rodopsinas Microbianas/genética , Rodopsinas Microbianas/metabolismo , Homología de Secuencia de Aminoácido , Thermus thermophilus/genética , Thermus thermophilus/metabolismo
7.
Psychogeriatrics ; 17(1): 52-60, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26786941

RESUMEN

BACKGROUND: Dementia care practitioner training is essential for professional caregivers to acquire medical knowledge and care skills for dementia patients. We investigated the significance of training in stress management by evaluating caregivers' job stress and coping style before and after they have completed training. METHODS: The subjects included 134 professional caregivers (41 men, 93 women) recruited from participants in training programmes held in Kanagawa Prefecture from August 2008 to March 2010. A survey using a brief job stress questionnaire and a coping scale was carried out before and after they completed their training. A t-test and multiple regression analysis were performed to evaluate the effects of the training. RESULT: After the training, the scores of modifiers on the job stress scale and of the coping scale increased, whereas the scores of stress reactions on the job stress scale decreased. However, there were no changes in participants' subjective cognition concerning their workplace environment. Furthermore, the change in stress reaction score tended to correlate with the change in consultation score in all participants and with the change in problem-solving and consultation in male participants. Among female participants, the change in stress reaction score tended to correlate with change in support from superiors and colleagues as modifiers. The factors that correlated to the change in stress reaction score differed between genders. CONCLUSION: The findings suggest that training caregivers improves their stress reaction and coping skills.


Asunto(s)
Adaptación Psicológica , Agotamiento Profesional/psicología , Cuidadores/educación , Cuidadores/psicología , Demencia/enfermería , Capacitación en Servicio/métodos , Estrés Psicológico , Adulto , Agotamiento Profesional/prevención & control , Demencia/psicología , Evaluación Educacional , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Evaluación de Programas y Proyectos de Salud , Escalas de Valoración Psiquiátrica , Encuestas y Cuestionarios
8.
Methods ; 68(3): 425-30, 2014 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-24593985

RESUMEN

Recent development of optogenetic techniques, which utilize light-driven ion channels or ion pumps for controlling the activity of excitable cells, has greatly facilitated the investigation of nervous systems in vivo. A new generation of optical silencers includes outward-directed proton pumps, such as Arch, which have several advantages over currently widely used halorhodopsin (NpHR). These advantages include the resistance to inactivation during prolonged illumination and the ability to generate a larger optical current from low intensity light. C. elegans, with its small transparent body and well-characterized neural circuits, is especially suitable for optogenetic analyses. In this article, we will outline the practical aspects of using of Arch and other proton pumps as optogenetic tools in C. elegans.


Asunto(s)
Caenorhabditis elegans/genética , Optogenética/métodos , Bombas de Protones/genética , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/efectos de la radiación , Luz , Sistema Nervioso/efectos de los fármacos , Sistema Nervioso/efectos de la radiación , Neuronas/efectos de los fármacos , Neuronas/efectos de la radiación , Bombas de Protones/efectos de los fármacos , Bombas de Protones/efectos de la radiación
9.
Hum Mol Genet ; 21(9): 2039-53, 2012 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-22286171

RESUMEN

Abnormalities in Z-disc proteins cause hypertrophic (HCM), dilated (DCM) and/or restrictive cardiomyopathy (RCM), but disease-causing mechanisms are not fully understood. Myopalladin (MYPN) is a Z-disc protein expressed in striated muscle and functions as a structural, signaling and gene expression regulating molecule in response to muscle stress. MYPN was genetically screened in 900 patients with HCM, DCM and RCM, and disease-causing mechanisms were investigated using comparative immunohistochemical analysis of the patient myocardium and neonatal rat cardiomyocytes expressing mutant MYPN. Cardiac-restricted transgenic (Tg) mice were generated and protein-protein interactions were evaluated. Two nonsense and 13 missense MYPN variants were identified in subjects with DCM, HCM and RCM with the average cardiomyopathy prevalence of 1.66%. Functional studies were performed on two variants (Q529X and Y20C) associated with variable clinical phenotypes. Humans carrying the Y20C-MYPN variant developed HCM or DCM, whereas Q529X-MYPN was found in familial RCM. Disturbed myofibrillogenesis with disruption of α-actinin2, desmin and cardiac ankyrin repeat protein (CARP) was evident in rat cardiomyocytes expressing MYPN(Q529X). Cardiac-restricted MYPN(Y20C) Tg mice developed HCM and disrupted intercalated discs, with disturbed expression of desmin, desmoplakin, connexin43 and vinculin being evident. Failed nuclear translocation and reduced binding of Y20C-MYPN to CARP were demonstrated using in vitro and in vivo systems. MYPN mutations cause various forms of cardiomyopathy via different protein-protein interactions. Q529X-MYPN causes RCM via disturbed myofibrillogenesis, whereas Y20C-MYPN perturbs MYPN nuclear shuttling and leads to abnormal assembly of terminal Z-disc within the cardiac transitional junction and intercalated disc.


Asunto(s)
Cardiomiopatía Dilatada/genética , Cardiomiopatía Hipertrófica Familiar/genética , Proteínas Musculares/genética , Mutación , Animales , Animales Recién Nacidos , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/fisiopatología , Cardiomiopatía Hipertrófica Familiar/patología , Cardiomiopatía Hipertrófica Familiar/fisiopatología , Estudios de Casos y Controles , Codón sin Sentido , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Proteínas Musculares/fisiología , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/fisiología , Mutación Missense , Miocardio/patología , Miocitos Cardíacos/ultraestructura , Proteínas Nucleares/metabolismo , Linaje , Fenotipo , Unión Proteica , Ratas , Ratas Mutantes , Ratas Sprague-Dawley , Proteínas Represoras/metabolismo
10.
Int Immunol ; 25(1): 11-24, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22945875

RESUMEN

We have previously reported that the cytotoxic activity of murine CD8(+) CTLs specific for HIV-1 gp160 envelope protein was markedly inhibited in vitro by brief exposure to a free epitope peptide P18-I10 (aa: RGPGRAFVTI) using the epitope-specific CTL line (LINE-IIIB) or a clone (RT-1). We have also shown that recently stimulated P18-I10-specific murine CTLs rapidly fell into apoptosis in vitro after brief exposure to the free epitope peptide. In the present study, we examined whether similar inactivation or apoptosis of recently stimulated CTLs occurred in vivo by exposure to the free epitope peptide using TCR transgenic (Tg-RT-1) mice expressing TCRαß genes of CTL clone RT-1. When the Tg mice were inoculated with recombinant vaccinia virus expressing HIV-1-IIIB gp160 genes followed by injection of P18-I10 epitope peptide, apparent reduction in the number of CTLs determined by flow cytometry using H-2D(d)/P18-I10 pentamer was observed within a few hours after the injection. Most of the H-2D(d)/P18-I10 pentamer-stained cells were positive for Annexin V and apoptosis was confirmed by microscopic analyses. Moreover, when mice were pretreated with immunosuppressive agents, such as cyclosporin A and tacrolimus (FK506), induction of apoptosis by P18-I10 was significantly inhibited and CTL cytotoxicity was maintained. These results suggest that the rapid loss of virus-specific CD8(+) CTLs might occur in vivo through apoptosis in the early stages of viral infection when activated CTLs may encounter viral epitope(s) released from virus-infected cells attacked by CTLs and we can prevent the loss by pretreatment with immunosuppressive agents.


Asunto(s)
Apoptosis/efectos de los fármacos , Proteína gp120 de Envoltorio del VIH/inmunología , Proteínas gp160 de Envoltorio del VIH/inmunología , VIH-1/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Fragmentos de Péptidos/inmunología , Linfocitos T Citotóxicos/inmunología , Secuencia de Aminoácidos , Animales , Apoptosis/inmunología , Antígenos CD8/genética , Antígenos CD8/inmunología , Ciclosporina/administración & dosificación , Epítopos/genética , Epítopos/inmunología , Vectores Genéticos , Antígenos VIH/administración & dosificación , Antígenos VIH/inmunología , Proteína gp120 de Envoltorio del VIH/administración & dosificación , Proteínas gp160 de Envoltorio del VIH/administración & dosificación , Inmunosupresores/administración & dosificación , Ratones , Ratones Transgénicos , Datos de Secuencia Molecular , Fragmentos de Péptidos/administración & dosificación , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Linfocitos T Citotóxicos/virología , Tacrolimus/administración & dosificación , Virus Vaccinia/genética , Virus Vaccinia/inmunología
11.
Jpn J Antibiot ; 67(3): 175-91, 2014 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-25163251

RESUMEN

Sitafloxacin (STFX, Gracevit 50 mg, fine granules 10%), an oral quinolone antibacterial agent, was approved additionally for administration at a dose of 100 mg once a day in August 2011. A use-results survey on STFX 100 mg/day was performed from December 2011 to May 2013. In total, 1,186 case cards were collected from 226 medical institutions and 1,089 cases were subjected to a safety evaluation and 1,069 were subjected to an efficacy evaluation. The incidence of adverse drug reactions (ADRs) was 2.11% (23/1,089 cases) and no serious ADRs were observed. The major ADR was diarrhea at 1.10% (12/1,089 cases). Of these 12 cases, 10 cases developed symptoms within 4 days of treatment. All of them, except one case that could not be followed up, either recovered or improved. Nonsteroidal anti-inflammatory drugs of the phenyl acetate and propionate types, which require caution when coadministered with STFX, were used concomitantly by 17.6% (192/1,089 cases) of patients but no central nervous system ADRs were observed. The overall efficacy rate was 96.4% (1,030/1,069 cases) and by types of infections, it was 97.0% (387/399 cases) for respiratory tract infections, 96.7% (353/365 cases) for urinary tract infections, 94.7% (36/38 cases) for gynecological infections, 92.3% (132/143 cases) for otorhinolaryngological infections, 98.4% (122/124 cases) for dental and oral surgical infections. The efficacy rate in every category of site of infection exceeded 90%. The overall eradication rate was 94.4% (185/196 strains) including Gram-positive bacteria at 95.4% (62/65 strains), Gram-negative bacteria at 92.2% (94/102 strains), anaerobes at 100.0% (11/11 strains) and atypical bacteria at 100.0% (18/18 strains). In conclusion, this use-results survey confirmed that STFX 100 mg/day is an effective administration with no serious problems in its safety profile and efficacy rate of over 90% in every category of site of infection.


Asunto(s)
Antibacterianos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Fluoroquinolonas/administración & dosificación , Adolescente , Adulto , Anciano , Antibacterianos/efectos adversos , Esquema de Medicación , Femenino , Fluoroquinolonas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad
12.
Sci Rep ; 14(1): 11212, 2024 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755300

RESUMEN

The sei whale (Balaenoptera borealis) is an important species among baleen whales in the North Pacific and plays a significant role in the ecosystem. Despite the importance of this species, information regarding its migration patterns and breeding locations remains limited. To enhance the understanding of the phenology of North Pacific sei whales, we deployed satellite-monitored tags on these whales in the western and central North Pacific from 2017 to 2023. We fitted 55 sei whale tracks to a state-space model to describe the whales' seasonal movements at feeding grounds and their migratory behavior. The whales typically leave their feeding grounds between November and December, with migration pathways extending from off Japan to the west of the Hawaiian Islands. These southward transits converge in the waters of the Marshall Islands and north of Micronesia between 20° N and 7° N, which appear to be breeding grounds. After a brief stay at these breeding grounds, the whales migrate northward from January to February, reaching their feeding grounds around 30°N by March. To the best of our knowledge, this is the first study to present the phenology of feeding and breeding seasons and the migration pattern of North Pacific sei whales.


Asunto(s)
Migración Animal , Estaciones del Año , Animales , Migración Animal/fisiología , Océano Pacífico , Balaenoptera/fisiología , Ecosistema , Reproducción/fisiología , Cruzamiento , Ballenas/fisiología
13.
PLoS One ; 19(4): e0301588, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38662742

RESUMEN

This study investigated the close kinship structure of southern right whales on feeding grounds during austral summer seasons. The study was based on biopsy samples of 171 individual whales, which were genotyped with 14 microsatellite DNA loci. Kinship was investigated by using the LOD (Log Odds) score, a relatedness index for a pair of genotypes. Based on a cut-off point of LODPO > 6, which was chosen to balance false positives and negatives, a total of 28 dyads were inferred. Among these, 25 were classified as parent-offspring pairs. Additional genetic (mitochondrial DNA haplotypes) and biological (estimated body length, sex) data were used to provide additional information on the inferred close kin pairs. The elapsed time between sampling varied from 0 (close kin detected in the same austral summer season) to 17 years. All the kin pairs occurred within the Antarctic Indo sector (85°-135°E) and no pair occurred between whales within and outside of this sector. Six pairs were between individuals in high (Antarctic) and lower latitudes. Results of the present analysis on kinship are consistent with the views that whales in the Indo sector of the Antarctic are related with the breeding ground in Southwest Australia, and that whales from this population can occupy different feeding grounds. The present study has the potential to contribute to the conservation of the southern right whales through the monitoring of important population parameters such as population sizes and growth rate, in addition to assist the interpretation of stock structure derived from standard population genetic analyses.


Asunto(s)
Repeticiones de Microsatélite , Ballenas , Animales , Ballenas/genética , Repeticiones de Microsatélite/genética , Femenino , ADN Mitocondrial/genética , Conducta Alimentaria , Haplotipos , Masculino , Regiones Antárticas , Genotipo , Estaciones del Año , Geografía
14.
Int J Rheum Dis ; 27(1): e14942, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37828793

RESUMEN

We describe the case of a 61-year-old woman with anti-signal recognition particle (SRP) antibody-positive immune-mediated necrotizing myopathy (IMNM) who exhibited biopsy-confirmed thrombotic microangiopathy (TMA). The patient developed proximal-dominant muscle weakness and was diagnosed with anti-SRP antibody-positive IMNM based on muscle biopsy results and serological examination. A high-dose corticosteroid prescription was initiated, followed by intravenous methylprednisolone and intravenous immunoglobulin therapy (IVIg). The patient showed IVIg-induced hemolytic anemia with preserved ADAMTS13 activity. Transient oral tacrolimus administration was initiated. Approximately 8 weeks after admission, the serum creatinine levels gradually increased. Renal histological examination revealed TMA, including ischemic changes in the renal tubules, stenosis, and occlusion of the interlobular arteries with fibrinoid necrosis of the afferent arteriolar walls. The arteriolar walls demonstrated an accumulation of C1q and C3c. Myofiber damage in patients with IMNM accounts for the activation of the classical pathway of the complement cascade in the sarcolemma due to antibody deposition. Additionally, a membrane attack complex is observed on capillaries in the muscle tissues of patients with anti-SRP antibody-positive IMNM. Although drug-induced pathomechanisms, such as IVIg and tacrolimus, can trigger the development of TMA, we suggest that the presence of serum anti-SRP antibodies would be implicated in complement-associated kidney vascular damage.


Asunto(s)
Enfermedades Autoinmunes , Miositis , Microangiopatías Trombóticas , Femenino , Humanos , Persona de Mediana Edad , Inmunoglobulinas Intravenosas/uso terapéutico , Músculo Esquelético/patología , Partícula de Reconocimiento de Señal , Tacrolimus , Autoanticuerpos , Miositis/inducido químicamente , Miositis/diagnóstico , Miositis/tratamiento farmacológico , Microangiopatías Trombóticas/inducido químicamente , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/tratamiento farmacológico
15.
Intern Med ; 63(4): 593-599, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-37407464

RESUMEN

The combination of systemic amyloid A (AA) amyloidosis and xanthogranulomatous pyelonephritis (XGP) resulting from a chronic urinary tract infection is extremely rare. We herein report a case of systemic AA amyloidosis secondary to XGP for which clinical remission developed after nephrectomy. To our knowledge, this is the first case report describing the clinical improvement of systemic AA amyloidosis secondary to XGP after nephrectomy in Japan. Clinicians should be aware of this uncommon combination and search for amyloid depositions in cases of XGP.


Asunto(s)
Amiloidosis , Pielonefritis Xantogranulomatosa , Infecciones Urinarias , Humanos , Pielonefritis Xantogranulomatosa/complicaciones , Pielonefritis Xantogranulomatosa/diagnóstico por imagen , Pielonefritis Xantogranulomatosa/cirugía , Amiloidosis/complicaciones , Amiloidosis/diagnóstico , Nefrectomía/efectos adversos , Infecciones Urinarias/complicaciones , Proteína Amiloide A Sérica
16.
J Am Nutr Assoc ; 42(3): 224-241, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35512781

RESUMEN

Prevalence of osteoarthritis (OA) is increasing alarmingly worldwide. Slowing down the progression of OA and diverse locomotive organ disorders is gaining interest in improving the quality of life (QOL) and extending healthy life-span. In a pilot study, intake of a small amount of undenatured type II collagen exhibited suppression of damage to the articular cartilage via oral immune tolerance. It also demonstrated improvement of knee and joint flexibility and mobility with continued intake of undenatured type II collagen (NEXT-II®) derived from chicken sternum cartilage. This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of 12 weeks of regular intake of NEXT-II® on joint and motor function in healthy Japanese male and female participants (aged 20 to <75 years).Sixty-four participants were randomized to receive either NEXT-II® (undenatured type II collagen 3.2 mg/d) or placebo over a period of 12 consecutive weeks. Efficacy on joint and motor functions were evaluated measuring knee passive range of motion as the primary outcome; the Japan Knee Osteoarthritis Measure (JKOM), Visual Analog Scale (VAS) for knee discomfort, and motor functions (10-meter walking and stair-climbing test) as the secondary outcomes; and Japan Low back pain Evaluation Questionnaire (JLEQ) and VAS for lower back discomfort as the exploratory outcomes.Fifty-eight participants (placebo = 28; NEXT-II® group = 30) completed the study. In the assessment of knee passive range of motion, significant improvements in "flexion" and "flexible angle (range)" were observed in the NEXT-II® group at 4, 8, and 12 weeks of treatment. NEXT-II® induced significant improvements in JKOM, VAS for knee and lower back discomfort, 10-meter walking test, stair-climbing test, and JLEQ.Results demonstrate that undenatured type II collagen is safe and efficacious in improving knee flexibility and mobility, reducing knee and lower back pain, and enhancing motor function.


Asunto(s)
Colágeno Tipo II , Dolor de la Región Lumbar , Osteoartritis de la Rodilla , Femenino , Humanos , Masculino , Dolor de Espalda/tratamiento farmacológico , Colágeno Tipo II/uso terapéutico , Articulación de la Rodilla , Dolor de la Región Lumbar/tratamiento farmacológico , Osteoartritis de la Rodilla/tratamiento farmacológico , Proyectos Piloto , Calidad de Vida , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano
17.
Cell Immunol ; 280(2): 138-47, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23399840

RESUMEN

Although TGF-ß and IL-6 would turn CD8(+) T cells to differentiate into non-cytotoxic state, these treated cells were converted to cytolytic phenotypes after re-exposure to their antigenic epitope in vitro. Here, using spleen cells from TCR transgenic mice expressing TCRαß genes of clone RT1 recognizing an epitope peptide (P18-I10: RGPGRAFVTI) of HIV-1 gp160, we generated CD8(+) cytotoxic T lymphocytes (CTLs) activated by re-exposure to P18-I10 after primarily cultured with TGF-ß and IL-6 in vitro to examine their effector function. The CTLs, having strong cytotoxic activity in vitro, were not only resistant to Fas-FasL mediated apoptosis, but also insensitive to the suppression of their cytotoxicity by re-exposure to TGF-ß in vitro. Moreover, adoptive transfer experiments indicated that the CTLs are capable of eliminating recombinant vaccinia virus expressing HIV-1 gp160 in vivo. Taken together, our data suggest that TGF-ß and IL-6 may play pivotal roles in inducing apoptosis-resistant and TGF-ß-insensitive CTLs in vitro.


Asunto(s)
Apoptosis , Linfocitos T CD8-positivos/inmunología , Citotoxicidad Inmunológica , Proteínas gp160 de Envoltorio del VIH/inmunología , Factor de Crecimiento Transformador beta/farmacología , Animales , Linfocitos T CD8-positivos/efectos de los fármacos , Epítopos , Interleucina-6/farmacología , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Receptor fas/fisiología
18.
Jpn J Antibiot ; 65(6): 365-80, 2012 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-23593733

RESUMEN

Sitafloxacin (STFX, Gracevit 50mg, fine granules 10%), a new quinolone antibacterial agent, was approved in January 2008, and the use-results survey was carried out over the 2 years between December 2008 and November 2010. We studied the efficacy and safety of STFX in 1,452 patients with urinary tract infections (cystitis, pyelonephritis, urethritis). The total efficacy rate for urinary tract infections was 91.4% (1,235/1,351 patients). Efficacy rates, classified by the type of infection, were: uncomplicated cystitis 95.9% (466/486 patients), complicated cystitis 87.2% (511/586 patients), uncomplicated pyelonephritis 96.1% (49/51 patients), complicated pyelonephritis 93.5% (145/155 patients), and urethritis 87.7% (64/73 patients). Efficacy rates were 86.0% (49/57 patients) for non-responders to cephems and 77.4% (48/62 patients) for non-responders to quinolones. The eradication rate of indicated strains was 90.5% (545/602 strains). The eradication rates of major causative bacteria were; Escherichia coli 92.7% (294/317 isolates), Enterococcus faecalis 86.0% (43/50 isolates), Pseudomonas aeruginosa 66.7% (16/24 isolates), Klebsiella pneumoniae 95.2% (20/21 isolates), and Chlamydia trachomatis 88.9% (8/9 isolates). The incidence of adverse drug reactions (ADRs) was 2.71% (37/1,365 cases). Major ADRs were diarrhoea (0.88%, 12 cases) and hepatic function disorders (0.51%, 7 cases). A serious ADR (hepatic function abnormality) was observed in 1 case, and the hepatic function in this patient returned to normal after treatment with STFX was discontinued. In conclusion, these results suggest that STFX is a useful antibacterial agent with an efficacy rate of 91.4% against urinary tract infections, with a minimum efficacy rate of 87.2% (against complicated cystitis), and has no serious problems in its safety profile.


Asunto(s)
Antibacterianos/uso terapéutico , Fluoroquinolonas/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Adulto , Anciano , Femenino , Fluoroquinolonas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Infecciones Urinarias/microbiología
19.
Medicine (Baltimore) ; 101(44): e31641, 2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36343083

RESUMEN

Development of delirium during hospitalization impairs the activities of daily living in elderly hospitalized patients. In clinical practice, early mobilization from bed is recommended to reduce delirium incidence and hospitalization stay. However, the effects of early mobilization on elderly inpatients with delirium have not been established yet. The aim of this study was to investigate the association between early mobilization and the duration of delirium in elderly inpatients with delirium. This retrospective cohort pilot study examined 45 participants (23 males, 22 females; mean age: 84.5 ±â€…6.6 years), who developed delirium during hospitalization. Of the participants, 28 were surgically treated and 17 were non-surgically treated. We classified early or delayed mobilization based on the median number of days until the start of mobilization and compared after propensity score matching to adjust for baseline characteristics. Additionally, we examined the correlation between the number of days until the start of mobilization and the duration of delirium. The duration of delirium was significantly shorter in the early mobilization group, particularly in terms of sitting on the bed and wheelchair use than that in the delayed mobilization group {median: 4.0 [interquartile range (IQR): 2.0-6.0] vs 8.0 [IQR: 7.0-14.5] days, P = .013; median: 3.0 [IQR: 2.0-5.5] vs 11.0 [IQR: 7.5-14.5] days, P = .004, respectively}. Moreover, the duration of delirium significantly positively moderate correlated with the time until the start of sitting on the bed and wheelchair use (Spearman r = 0.527; P = .012, Spearman r = 0.630; P = .002, respectively). The results of this study suggest that early mobilization from sitting on the bed or wheelchair use after hospitalization or surgery may shorten the duration of delirium. Because the sample size of this pilot study is small, careful interpretation is needed, and further research is warranted.


Asunto(s)
Delirio , Masculino , Femenino , Humanos , Anciano , Anciano de 80 o más Años , Delirio/etiología , Delirio/epidemiología , Proyectos Piloto , Ambulación Precoz/efectos adversos , Estudios Retrospectivos , Actividades Cotidianas , Hospitalización
20.
J Cardiothorac Surg ; 17(1): 182, 2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-35974374

RESUMEN

BACKGROUND: The past half century has seen the near eradication of transfusion-associated hazards. Intraoperative cell salvage while widely used still poses significant risks and hazards due to human error. We report on a case in which blood collected from a patient with lung cancer was mistakenly administered to a patient undergoing cardiac surgery who should have received his own collected blood. The initial investigation found that the cause of the patient harm was violations of procedures by hospital personnel. A detailed investigation revealed that not only violations were the cause, but also that the underlying causes included haphazard organizational policies, poor communication, workload and staffing deficiencies, human factors and cultural challenges. CASE PRESENTATION: On August 14, 2019, a 72-year-old male was admitted to our hospital for angina pectoris and multivessel coronary artery disease. Cardiac surgery was performed using an autologous salvage blood collection system, and there were no major problems other than the prolonged operation time. During the night after the surgery, when the patient's blood pressure dropped, a nurse retrieved a blood bag from the ICU refrigerator that had been collected during the surgery and administered it at the physician's direction, but at this time neither the physician nor the nurse performed the required checking procedures. The blood administered was another patient's blood taken from another surgery the day before; an ABO mismatch transfusion occurred and the patient was diagnosed with DIC. The patient was discharged 65 days later after numerous interventions to support the patient. An accident investigation committee was convened to analyze the root causes and develop countermeasures to prevent a recurrence. CONCLUSION: This adverse event occurred because the protocol for intraoperative blood salvage management was not clearly defined, and the procedure was different from the standard transfusion practices. We developed a new workflow based on a human factors grounded, systems-wide improvement strategy in which intraoperative blood collection would be administered before the patient leaves the operating room to completely prevent recurrence, instead of simply requiring front-line staff to do a double-check. Implementing strong systems processes can reduce the risk of errors, improve the reliability of the work processes and reduce the likelihood of patient harm occurring in the future.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Recuperación de Sangre Operatoria , Anciano , Transfusión Sanguínea , Transfusión de Sangre Autóloga/efectos adversos , Transfusión de Sangre Autóloga/métodos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/métodos , Humanos , Masculino , Recuperación de Sangre Operatoria/métodos , Reproducibilidad de los Resultados
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