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1.
J Nutr Sci Vitaminol (Tokyo) ; 68(5): 390-398, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36310073

RESUMEN

In Japan, fees for nutritional management (NM) was introduced in April 2009 to improve nutritional care for persons with disabilities residing in welfare facilities. The present study aimed to clarify (1) the nutritional status as well as eating-related functions and behaviors of such residents and (2) status of incorporating claim fees for NM and oral maintenance in facilities supporting persons with disabilities. This cross-sectional study approached 2,510 welfare facilities for persons with disabilities across Japan. Anonymous questionnaire surveys were conducted in August 2018. Among the 1,543 responses, 1,538 (61.3%) were valid for analysis. The median number of residents in a facility was 50. Among all residents (n=80,322), 16.9% were underweight (body mass index [BMI]<18.5) and 14.5% were obese (BMI≥25.0). Of the residents, 38.9% adjusted food form and 15.2% had eating behavior-related problems. In total, 723 (47.0%) and 54 (3.5%) facilities, claimed the fees for NM and oral maintenance, respectively. The main reasons for not implementing the claim fees for NM was the lack of time for nutritional care and management (NCM; 30.2%), absence of a registered dietitian (29.3%), and difficulty in assessing swallowing function (24.1%). Our results revealed that the implementation rates of claim fees for NM and oral maintenance were low despite most respondents having problems with the double burden of malnutrition and necessity of oral care, suggesting the importance of securing time for NCM, appointing registered dietitians, and evaluating swallowing function.


Asunto(s)
Personas con Discapacidad , Desnutrición , Humanos , Estado Nutricional , Estudios Transversales , Japón , Desnutrición/epidemiología , Desnutrición/prevención & control , Encuestas y Cuestionarios
2.
Int J Mol Sci ; 23(1)2021 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-35008728

RESUMEN

The prorenin/renin receptor ((P)RR) is a multifunctional protein that is widely distributed in various organs. Despite intensive research for more than 20 years, this receptor has not been fully characterized. In this study, we generated mice overexpressing the tubular epithelial (P)RR gene ((P)RR-TG mice) to test the previously reported functional role of (P)RR by Ramkumar et al. in 2015 using tubular specific (P)RR KO mice. (P)RR-TG mice were maintained and analyzed in individual metabolic cages and were administered angiotensin II blocker (ARB), direct renin inhibitor (DRI), and bafilomycin, that is, vacuolar ATPase (V-ATPase) antagonist. (P)RR-TG mice were hypertensive and had alkalized urine with lower osmolality and Na+ excretion. ARB and DRI, but not bafilomycin, concurrently decreased blood pressure. Bafilomycin acidized urine of (P)RR-TG mice, or equivalently this phenomenon restored the effect of overexpressed transgene, suggesting that (P)RR functioned as a V-ATPase in renal tubules. Afterall, (P)RR-TG mice were mated with alternative renin transgenic mice (ARen2-TG), which we identified as intracellular renin previously, to generate double transgenic mice (DT-TG). Lethal renal tubular damage was observed in DT-TG mice, suggesting that intracellular renin may be a ligand for (P)RR in tubules. In summary, (P)RR did not substantially affect the tissue renin-angiotensin system (RAS) in our model of tubular specific (P)RR gene over-expression, but alternative intracellular renin may be involved in (P)RR signaling in addition to conventional V-ATPase function. Further investigations are warranted.


Asunto(s)
Presión Sanguínea/fisiología , Espacio Intracelular/metabolismo , Túbulos Renales/patología , Túbulos Renales/fisiopatología , Receptores de Superficie Celular/metabolismo , Renina/metabolismo , Animales , Peso Corporal , Concentración de Iones de Hidrógeno , Ratones Transgénicos , Modelos Biológicos , Especificidad de Órganos , Concentración Osmolar , Fenotipo , Sodio/metabolismo , Sístole , Transgenes , Orina , Receptor de Prorenina
3.
Int J Mol Sci ; 21(11)2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32485919

RESUMEN

Ubiquitination is a representative, reversible biological process of the post-translational modification of various proteins with multiple catalytic reaction sequences, including ubiquitin itself, in addition to E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, E3 ubiquitin ligase, deubiquitinating enzymes, and proteasome degradation. The ubiquitin-proteasome system is known to play a pivotal role in various molecular life phenomena, including the cell cycle, protein quality, and cell surface expressions of ion-transporters. As such, the failure of this system can lead to cancer, neurodegenerative diseases, cardiovascular diseases, and hypertension. This review article discusses Nedd4-2/NEDD4L, an E3-ubiquitin ligase involved in salt-sensitive hypertension, drawing from detailed genetic dissection analysis and the development of genetically engineered mice model. Based on our analyses, targeting therapeutic regulations of ubiquitination in the fields of cardio-vascular medicine might be a promising strategy in future. Although the clinical applications of this strategy are limited, compared to those of kinase systems, many compounds with a high pharmacological activity were identified at the basic research level. Therefore, future development could be expected.


Asunto(s)
Canales Epiteliales de Sodio/metabolismo , Hipertensión/metabolismo , Túbulos Renales Distales/metabolismo , Ubiquitina-Proteína Ligasas Nedd4/metabolismo , Aldosterona/metabolismo , Animales , Canales Epiteliales de Sodio/genética , Humanos , Ubiquitina-Proteína Ligasas Nedd4/genética , Cloruro de Sodio/metabolismo
4.
Vision Res ; 166: 52-59, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31855668

RESUMEN

Both luminance contrast and character size are critical factors affecting reading performance. Previous studies reported on the effect of luminance contrast on the reading-speed function, that is, the relationship between reading speed and character size. In particular, when contrast was reduced, the critical print size (CPS) was found to shift to a larger character size even though the maximum reading speed and function shape did not change [Japanese Journal of Ophthalmology 52(1) (2008) 44-47]. In the present study, the effect of luminance contrast on the reading function was quantitatively examined. Japanese phrases with a luminance contrast of 0.03-0.99 were prepared as stimuli. Observers with normal vision were asked to read aloud phrases with several character sizes. Then, the reading functions were obtained for each luminance contrast. CPS was found to increase as the luminance contrast decreased. The relationship between contrast and CPS was linear in log-log coordinates, that is, log-CPS increased as the log-contrast of the characters decreased. It was found that the contrast of the stimulus systematically affects the location of the reading function.


Asunto(s)
Sensibilidad de Contraste/fisiología , Luz , Lectura , Adulto , Pueblo Asiatico , Humanos , Lenguaje , Pruebas de Visión , Adulto Joven
5.
J Clin Med ; 8(9)2019 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-31443545

RESUMEN

BACKGROUND: Aspartate aminotransferase (AST) is pivotal in amino acid metabolism. However, the serum activity of AST, which leaks from multiple organs, including liver and skeletal muscle, is unknown in older underweight people, who are at high risk of skeletal muscle mass loss. Therefore, we measured the serum activities of AST and alanine aminotransferase (ALT), a liver-specific transaminase, in a large, community-based cross-sectional study. METHODS: Clinical parameters and lifestyles were characterized in 892,692 Japanese people with a wide range of body mass indexes (BMIs; 13-39.9 kg/m2), aged 40-74 years old, who were undergoing a medical checkup. A general linear model was used to calculate the estimated mean of serum AST (EM-AST) in each BMI category after adjustment for confounding factors, including past history of cardiovascular disease and waist circumference. RESULTS: Severe underweight (BMI 13-14.9 kg/m2) was present in 910 subjects (0.1%). Raw serum AST showed a J-shaped relationship with BMI, which was blunted in older subjects (60-74 years), and similar, but less curved relationships were identified for raw serum ALT and gamma-glutamyl transferase. These J-shaped relationships in serum AST were not altered when subjects were classified by sex, past history of cardiovascular and cerebrovascular diseases, and habitual exercise. EM-AST showed a U-shaped relationship, with a minimum at BMI 21-22.9 kg/m2, regardless of age and waist circumference. CONCLUSIONS: High serum AST but normal serum ALT is highly prevalent in older underweight people and might reflect skeletal muscle pathology.

6.
PLoS One ; 14(6): e0218096, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31206525

RESUMEN

The interaction between atherosclerosis and commensal microbes through leaky gut syndrome (LGS), which is characterized by impaired intestinal permeability and the introduction of undesired pathogens into the body, has not been fully elucidated. Our aim was to investigate the potential role of a ClC-2 chloride channel activator, lubiprostone, which is reported to have beneficial effects on LGS, in the development of atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. After a 15-week feeding period of a Western diet (WD), ApoE-/- mice were treated with a Western-type diet (WD) alone or WD with oral supplementation of lubiprostone for 10 weeks. This feeding protocol was followed by experimental evaluation of LGS and atherosclerotic lesions in the aorta. In mice with lubiprostone, in vivo translocation of orally administered 4-kDa FITC-dextran was significantly improved, and RNA expression of the epithelial tight junction proteins, Zo-1 and occludin, was significantly up-regulated in the ileum, compared to the WD alone group, suggesting a possible reversal of WD-induced intestinal barrier dysfunction. As a result, WD-induced exacerbation of atherosclerotic lesion formation was reduced by 69% in longitudinally opened aortas and 26% in aortic root regions. In addition, there was a significant decrease in circulating immunoglobulin level, followed by an attenuation of inflammatory responses in the perivascular adipose tissue, as evidenced by reduced expression of pro-inflammatory cytokines and chemokines. Lubiprostone attenuates atherosclerosis by ameliorating LGS-induced inflammation through the restoration of the intestinal barrier. These findings raise the possibility of targeting LGS for the treatment of atherosclerosis.


Asunto(s)
Apolipoproteínas E/deficiencia , Aterosclerosis/prevención & control , Íleon/efectos de los fármacos , Lubiprostona/farmacología , Permeabilidad/efectos de los fármacos , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Apolipoproteínas E/metabolismo , Aterosclerosis/metabolismo , Canales de Cloruro CLC-2 , Agonistas de los Canales de Cloruro/farmacología , Canales de Cloruro/metabolismo , Citocinas/metabolismo , Dieta Occidental/efectos adversos , Modelos Animales de Enfermedad , Íleon/metabolismo , Inmunoglobulinas/metabolismo , Inflamación/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Ratones , Ratones Endogámicos C57BL , Ocludina/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Proteína de la Zonula Occludens-1/metabolismo
7.
J Clin Med ; 8(3)2019 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-30893866

RESUMEN

BACKGROUND: It is unknown whether extremely high high-density lipoprotein cholesterol (HDL-C) has a protective effect against diabetes, which plays a key role in cardiovascular disease. METHODS: In a community-based cohort study of 387,642 subjects (40⁻68 years old) without diabetes, the incidence of diabetes 6 years later was determined according to baseline HDL-C (≤39, 40⁻49, 50⁻59, 60⁻69, 70⁻79, 80⁻89, 90⁻99, 100⁻109, or ≥110 mg/dL). RESULTS: At baseline, HDL-C ≥100 mg/dL was present in 12,908 subjects (3.3%), who had a better lipid profile and a high prevalence of heavy alcohol consumption and habitual exercise. The incidences of diabetes according to baseline HDL-C were 14.7, 11.2, 7.7, 5.3, 3.8, 2.8, 2.7, 2.5, and 3.5 per 1000 person-years, respectively. The adjusted relative risks (ARRs) for diabetes showed concave relationships with HDL-C, with minima at 80⁻89 mg/dL. The ARR (95% CI) of the lowest HDL-C category was 1.56 (1.40⁻1.74) and of the highest HDL-C category was 1.46 (1.18⁻1.81) (both p < 0.001), regardless of alcohol consumption. The latter ARR was higher in men (n = 219,047) (2.45 (1.70⁻3.53), p < 0.0001) after adjustment for baseline glycemic index. CONCLUSION: Both extremely high and low HDL-C represent risks for diabetes, which deserves further study.

8.
BMJ Open ; 9(2): e023323, 2019 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-30796118

RESUMEN

INTRODUCTION: The unmitigated incidence of cardiometabolic diseases, such as type 2 diabetes and metabolic syndrome, has gained attention in Japan. 'Big data' can be useful to clarify conflicting observations obtained from studies with small samples and about rare conditions that are often neglected. We epidemiologically address these issues using data from health check-ups conducted in Kanagawa Prefecture, the prefecture with the second largest population in Japan, in the Kanagawa Investigation of the Total Check-up Data from the National Database (KITCHEN). METHODS AND ANALYSIS: This research consists of a series of population-based cross-sectional studies repeated from 2008-2014 and 6-year cohort studies. Since 2017, we have reviewed the data of people living in Kanagawa Prefecture who underwent a health check-up mainly for general health and the prevention of metabolic syndrome. The sample size ranges from 1.2 million to 1.8 million people in the cross-sectional studies and from 370 000 to 590 000 people in the cohort studies. These are people aged 40-74 years, whose clinical parameters were measured and who responded individually to a questionnaire. We investigate potential associations and causalities of various aetiologies, including diabetes and metabolic syndrome, using clinical data and lifestyle information. With multidisciplinary analysis, including data-driven analysis, we expect to obtain a wide range of novel findings, to confirm indeterminate previous findings, especially in terms of cardiometabolic disease, and to provide new perspectives for human health promotion and disease prevention. ETHICS AND DISSEMINATION: Ethical approval was received from the Ethics Committee of Kanagawa University of Human Services (10-43). The protocol was approved in December 2016 by the Japanese Ministry of Health, Labour and Welfare (No. 121). The study results will be disseminated through open platforms including journal articles, relevant conferences and seminar presentations.


Asunto(s)
Atención a la Salud/estadística & datos numéricos , Tamizaje Masivo/estadística & datos numéricos , Examen Físico/estadística & datos numéricos , Anciano , Estudios de Cohortes , Estudios Transversales , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/prevención & control , Femenino , Humanos , Japón , Masculino , Síndrome Metabólico/prevención & control , Persona de Mediana Edad , Encuestas y Cuestionarios
9.
Int J Mol Sci ; 18(6)2017 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-28604611

RESUMEN

The epithelial sodium channel (ENaC) plays critical roles in maintaining fluid and electrolyte homeostasis and is located in the aldosterone-sensitive distal nephron (ASDN). We previously found that Nedd4-2 C2 knockout (KO) mice showed salt-sensitive hypertension with paradoxically enhanced ENaC gene expression in ASDN under high oral salt intake. Eplerenone (EPL), a selective aldosterone blocker, is a promising therapeutic option for resistant or/and salt-sensitive hypertension. We examined the effect of EPL on Nedd4-2 C2 KO mice with respect to blood pressure, metabolic parameters, and molecular level changes in ASDN under high oral salt intake. We found that EPL failed to reduce blood pressure in KO mice with high oral salt intake and upregulated ENaC expression in ASDN. Thus, salt-sensitive hypertension in Nedd4-2 C2 KO was EPL-resistant. Gene expression analyses of laser-captured specimens in ASDN suggested the presence of non-aldosterone-dependent activation of ENaC transcription in ASDN of Nedd4-2 C2 KO mice, which was abolished by amiloride treatment. Our results from Nedd4-2 C2 KO mice suggest that enhanced ENaC gene expression is critically involved in salt-sensitive hypertension under certain conditions of specific enzyme isoforms for their ubiquitination.


Asunto(s)
Canales Epiteliales de Sodio/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Ubiquitina-Proteína Ligasas Nedd4/genética , Espironolactona/análogos & derivados , Animales , Presión Sanguínea/efectos de los fármacos , Canales Epiteliales de Sodio/genética , Eplerenona , Regulación de la Expresión Génica , Técnicas de Inactivación de Genes , Hipertensión/metabolismo , Masculino , Ratones , Ratones Noqueados , Cloruro de Sodio Dietético/farmacología , Espironolactona/farmacología
10.
Pathol Int ; 67(7): 331-341, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28590017

RESUMEN

Our group and others have previously reported that a fibrotic focus is a very useful histological factor for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 258 cases of invasive ductal carcinoma into those with and those without a fibrotic focus to investigate whether the presence of a fibrotic focus was significantly associated with the degree of tumor-associated macrophage (CD68, CD163 or CD204-positive) infiltration or whether the presence of tumor-associated macrophage infiltration heightened the malignant potential of invasive ductal carcinoma with a fibrotic focus. Multiple regression analyses demonstrated that a fibrotic focus was the only factor that was significantly associated with a high level of CD68-, CD163- or CD204-positive tumor-associated macrophage infiltration. The combined assessment of the presence or absence of a fibrotic focus and a high or a low level of CD204-positive tumor-associated macrophage infiltration clearly demonstrated that CD204-positive tumor-associated macrophage infiltration had a significant prognostic power only for patients with invasive ductal carcinoma with a fibrotic focus in multivariate analyses; CD204-positive tumor-associated macrophages might only exert a significant effect on tumor progression when a fibrotic focus is present within the invasive ductal carcinoma of the breast.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Fibrosis/patología , Macrófagos/patología , Adulto , Mama/metabolismo , Mama/patología , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/clasificación , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Femenino , Fibrosis/metabolismo , Humanos , Inmunohistoquímica , Macrófagos/metabolismo , Pronóstico , Receptores Depuradores de Clase A/metabolismo
11.
Trop Med Int Health ; 22(7): 784-796, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28510990

RESUMEN

Needs for surgical care are growing in low- and middle-income countries. Existing surgical care capacity indicators, focusing on the availability of equipment, personnel, and operation and anaesthetic skills, are not intended to evaluate perioperative nutrition management, which influences surgical outcomes. In this narrative review, we describe the prevalence of malnutrition and its clinical consequences among surgical patients in low- and middle-income countries, suggest potential measures to improve nutrition management and discuss the necessity of considering nutrition management as a component of surgical care capacity.


Asunto(s)
Países en Desarrollo , Desnutrición/terapia , Apoyo Nutricional/métodos , Atención Perioperativa/métodos , Pobreza , Procedimientos Quirúrgicos Operativos , Humanos
12.
Int J Older People Nurs ; 12(3)2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28393489

RESUMEN

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are very common among older people, and previous studies showed that BPSD affects eating behaviour negatively, possibly resulting in undernutrition. In a previous study, we constructed a set of 11 items based on direct observations of older people with dementia during mealtime and named them 'SSADE: signs and symptoms accompanying dementia while eating'. AIMS: This study aimed to conduct a factor analysis to clarify the structure of the set of 11 SSADE items and to analyse the relationship of the SSADE with nutritional status. METHODS: We sampled 259 older people from 14 institutional facilities in Japan. To assess the status of the SSADE, we quantified each item according to its frequency and severity, using a 5-point scale. We also collected information regarding characteristics and nutritional status (body mass index [BMI], dietary intakes, body weight change, serum albumin level). We performed an exploratory factor analysis on the SSADE. In addition, associations between grouped factor scores and nutritional status were analysed. RESULTS: Exploratory factor analysis indicated four factors. 'Hypoactivity' including 'dietary agnosia' and 'drowsiness' correlated negatively with BMI and serum albumin levels. 'Hyperactivity' including 'agitation', 'delusion', 'wandering' and 'eating too rapidly' correlated negatively with BMI. 'Obsessiveness' including 'food refusal' and 'fad eating' correlated negatively with BMI, dietary intake and body weight change. 'Aberrant behaviours' including 'eating apraxia', 'pica' and 'stealing food' correlated positively with dietary intake. CONCLUSION: The identified factors of the SSADE were related to nutritional status, which may suggest acceptable factorial validity. IMPLICATIONS FOR PRACTICE: We expected the SSADE to contribute to the prevention and improvement of undernutrition, through the development of a concrete strategy for nutritional care planning by professional teams including dietitians in long-term care facilities.


Asunto(s)
Demencia/enfermería , Demencia/psicología , Conducta Alimentaria/psicología , Cuidados a Largo Plazo , Estado Nutricional , Anciano , Anciano de 80 o más Años , Análisis Factorial , Femenino , Humanos , Japón , Masculino
13.
Jpn J Clin Oncol ; 45(7): 642-9, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25989989

RESUMEN

OBJECTIVE: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a solvent-free paclitaxel coupled to human albumin without an associated increase in toxicity. The neoadjuvant study of primary breast cancer was planned to evaluate tumor response and safety of triweekly nanoparticle albumin-bound paclitaxel. METHODS: Patients with Stage II/III HER2-negative primary breast cancer received four courses of nanoparticle albumin-bound paclitaxel 260 mg/m(2) every 3 weeks (q3w), followed by four courses of epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) q3w. Tumor response after nanoparticle albumin-bound paclitaxel was histologically evaluated. In addition, the clinical response, breast-conserving rate and safety of this treatment were monitored. RESULTS: Among 53 patients who received nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide neoadjuvant chemotherapy, pathological complete response and near-pathological complete response were confirmed in 3 (5.7%) and 7 (13.2%) patients who had surgery, respectively. The overall objective response rate was 71.7% after completion of chemotherapy. Based on Positron Emission Tomography Response Criteria in Solid Tumors using (18)F-fluorodeoxyglucose, complete metabolic response and partial metabolic response after 2-3 courses of nanoparticle albumin-bound paclitaxel were 15.1 and 52.8%, respectively. The most common significant toxicities of q3w nanoparticle albumin-bound paclitaxel were Grade 3 muscle pain, neuropathy and febrile neutropenia, each in 1 (1.9%) patient. There were no incidences of anaphylaxis or Grade 4/5 adverse events. CONCLUSION: Neoadjuvant chemotherapy using q3w nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide was feasible in breast cancer patients with acceptable clinical response and drug tolerance, but conferred a low rate of pathological complete response. Monotherapy with q3w nanoparticle albumin-bound paclitaxel could be an appropriate substitute for solvent-based taxane in terms of therapeutic and safety management.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Terapia Neoadyuvante/métodos , Adulto , Anciano , Albúminas/administración & dosificación , Albúminas/efectos adversos , Biomarcadores de Tumor/análisis , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Docetaxel , Esquema de Medicación , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Femenino , Fluorodesoxiglucosa F18 , Humanos , Infusiones Intravenosas , Estimación de Kaplan-Meier , Persona de Mediana Edad , Nanopartículas , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Taxoides/administración & dosificación , Taxoides/efectos adversos , Resultado del Tratamiento
14.
Hum Pathol ; 46(6): 906-16, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25890786

RESUMEN

We previously reported that the number of mitotic and apoptotic figures in tumor cells in blood vessel tumor emboli had the greatest significant power for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. The purpose of the present study was to devise a grading system for blood vessel tumor emboli based on the mitotic and apoptotic figures of tumor cells in blood vessel tumor emboli, enabling accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 263 invasive ductal carcinomas into the following 3 grades according to the numbers of mitotic and apoptotic figures in tumor cells located in blood vessels within 1 high-power field: grade 0, no blood vessel invasion; grade 1, absence of mitotic figures and presence of any number of apoptotic figures, or 1 mitotic figure and 0 to 2 apoptotic figures; and grade 2, 1 mitotic figure and 3 or more apoptotic figures, or 2 or more mitotic figures and 1 or more apoptotic figures. Multivariate analyses with well-known prognostic factors demonstrated that grade 2 blood vessel tumor emboli significantly increased the hazard ratios for tumor recurrence independent of the nodal status, pathological TNM stage, hormone receptor status, or HER2 status. The presently reported grading system for blood vessel tumor emboli is the strongest histologic factor for accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast.


Asunto(s)
Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Neoplasias de Tejido Vascular/patología , Adulto , Mama/patología , Neoplasias de la Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias de Tejido Vascular/secundario , Células Neoplásicas Circulantes/patología , Pronóstico
15.
BMC Cancer ; 15: 253, 2015 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-25884795

RESUMEN

BACKGROUND: Advanced breast cancer patients have a higher risk of postoperative recurrence than early-stage breast cancer patients. Recurrence is believed to be caused by the increase in micrometases, which were not eradicated by preoperative or postoperative chemotherapy. Therefore, a new therapeutic strategy that can improve treatment efficacy is mandatory for advanced breast cancer. S-1 was shown to be effective and safe in Japanese metastatic breast cancer patients treated with previous chemotherapy, including anthracyclines. Thus, in this study, we evaluated S-1 as adjuvant chemotherapy in breast cancer patients after standard primary systemic chemotherapy. METHODS: The treatment consisted of 18 courses (a 2-week administration and a 1-week withdrawal; one year) administered at 80-120 mg/body/day. In cases judged to require postoperative radiotherapy, it was concurrently initiated on Day 1 of the study. If the estrogen receptor and/or human epidermal growth factor receptor 2 were positive, endocrine therapy and/or trastuzumab were permitted, concurrently. RESULTS: Of the 45 patients enrolled between September 2007 and September 2009 from 3 institutions, 43 patients were eligible. Thirty-two of the 43 (74.4%) patients received concurrent radiotherapy. Twenty-two of the 43 (51.2%) patients completed the scheduled courses of chemotherapy. The most common reasons for withdrawal of treatment were subjective symptoms, such as nausea, anorexia, or general fatigue during the first 9 courses of treatment in 9/43 (20.9%) patients, recurrence in 7/43 (16.3%) patients, and adverse events in 5/43 (11.6%) patients. The cumulative percentage of administration for 365 days was 66.4% (95% confidence interval: 50.8-79.1%). Although grade 3 neutropenia (9.3%), leukopenia (4.7%), and diarrhea (4.7%) were observed, they were manageable. No grade 4 adverse effects were observed. CONCLUSIONS: The percentage of Japanese breast cancer patients completing the 18-course treatment and the cumulative percentage of administration for 365 days using S-1 after standard primary systemic chemotherapy were similar with the results of another study of adjuvant chemotherapy for the Japanese gastric cancer patients with no severe adverse effects. A phase III trial investigating the usefulness of adjuvant S-1 is now ongoing in Japan, and it is expected that S-1 will have a significant survival benefit in breast cancer patients. UMIN000013469.


Asunto(s)
Antraciclinas/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Ácido Oxónico/administración & dosificación , Tegafur/administración & dosificación , Adulto , Anciano , Neoplasias de la Mama/patología , Combinación de Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Ácido Oxónico/efectos adversos , Tegafur/efectos adversos
16.
J Vet Med Sci ; 77(7): 823-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25755021

RESUMEN

Vibrio vulnificus is the causative agent of primary septicemia, wound infection and gastroenteritis in immunocompromised people. In this study, signature-tagged mutagenesis (STM) was applied to identify the virulence genes of V. vulnificus. Using STM, 6,480 mutants in total were constructed and divided into 81 sets (INPUT pools); each mutant in a set was assigned a different tag. Each INPUT pool was intraperitoneally injected into iron-overloaded mice, and in vivo surviving mutants were collected from blood samples from the heart (OUTPUT pools). From the genomic DNA of mixed INPUT or OUTPUT pools, digoxigenin-labeled DNA probes against the tagged region were prepared and used for dot hybridization. Thirty tentatively attenuated mutants, which were hybridized clearly with INPUT probes but barely with OUTPUT probes, were negatively selected. Lethal doses of 11 of the 30 mutants were reduced to more than 1/100; of these, the lethal doses of 2 were reduced to as low as 1/100,000. Transposon-inserted genes in the 11 attenuated mutants were those for IMP dehydrogenase, UDP-N-acetylglucosamine-2-epimerase, aspartokinase, phosphoribosylformylglycinamidine cyclo-ligase, malate Na (+) symporter and hypothetical protein. When mice were immunized with an attenuated mutant strain into which IMP dehydrogenase had been inserted with a transposon, they were protected against V. vulnificus infection. In this study, we demonstrated that the STM method can be used to search for the virulence genes of V. vulnificus.


Asunto(s)
Vibrio vulnificus/genética , Factores de Virulencia/genética , Animales , Sondas de ADN , Femenino , Genes Bacterianos/genética , Ratones , Ratones Endogámicos ICR , Mutagénesis Insercional/métodos , Vibrio vulnificus/patogenicidad
17.
Geriatr Gerontol Int ; 14(3): 577-81, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24020472

RESUMEN

AIM: The present study was carried out to clarify tube feeding utilization and the prevalence of swallowing difficulty among residents in geriatric long-term settings, and to elucidate the implementation of swallowing assessment at four different types of facilities in Japan. METHODS: We mailed a questionnaire to a total of 4334 facilities. RESULTS: We received responses from 1137 (26.2%) facilities, including 440 (29.0%) from 1517 nursing homes, 275 (29.2%) from 941 long-term care facilities, 205 (18.1%) from 1134 sanatorium medical facilities and 217 (29.2%) from 742 rehabilitation hospitals. The number of tube-fed residents per 100 beds in each facility was 11.6 at the nursing homes, 7.4 at the long-term care facilities, 36.3 at the sanatorium medical facilities and 7.9 at the rehabilitation facilities. The number of residents per 100 beds with swallowing difficulty was 23.7 in the nursing homes, 15.6 in the long-term care facilities, 19.2 in the sanatorium medical facilities and 15.4 in the rehabilitation hospitals. The percentages of facilities that assessed swallowing difficulty were 31.8% of the nursing homes, 63.0% of the long-term care facilities, 77.9% of the sanatorium medical facilities and 91.7% of the rehabilitation hospitals. CONCLUSION: A large number of residents using a feeding tube and with difficult swallowing were observed in geriatric long-term settings without adequate evaluation of swallowing function.


Asunto(s)
Trastornos de Deglución/diagnóstico , Trastornos de Deglución/epidemiología , Nutrición Enteral/estadística & datos numéricos , Hospitales Especializados , Casas de Salud , Centros de Rehabilitación , Anciano , Anciano de 80 o más Años , Protocolos Clínicos , Deglución/fisiología , Técnicas de Diagnóstico del Sistema Digestivo/estadística & datos numéricos , Femenino , Encuestas de Atención de la Salud , Humanos , Japón/epidemiología , Cuidados a Largo Plazo , Masculino , Prevalencia
18.
Nihon Ronen Igakkai Zasshi ; 51(6): 547-53, 2014.
Artículo en Japonés | MEDLINE | ID: mdl-25749326

RESUMEN

AIM: This study aimed to identify factors associated with malnutrition in community-dwelling disabled elderly. METHODS: A cross-sectional study of baseline data for 1,142 community-dwelling elderly (81.2±8.7 years) from of the KANAGAWA-AICHI Disabled Elderly Cohort (KAIDEC) study was conducted. The data included the participants' demographic characteristics, nutritional status (Mini Nutritional Assessment short-form: MNA-SF), dysphagia status (Dysphagia Severity scale: DSS), comorbidity, basic activities of daily living (bADL), hospitalization with in the past three months and care level according to the Long-Term Care Insurance program. The participants were considered to be in malnutrition or at risk of malnutrition if their MNA-SF score was 0-7 or 8-11, respectively. The chi square test, analysis of variance, Jonckheere-Terpstra trend test and logistic regression analysis were used for the statistical analysis. RESULTS: A total of 16.7% of the participants were classified as having malnutrition. In addition, a higher prevalence of malnutrition was associated with a higher care level in the long-term care insurance program, and malnutrition was associated with a lower bADL score, the presence of dysphagia and dementia and hospitalization with in the past three months. CONCLUSIONS: The present study demonstrated that malnutrition in community-dwelling disabled elderly is associated with a lower bADL score, the presence of dysphagia and dementia and hospitalization with in the past three months.


Asunto(s)
Desnutrición/diagnóstico , Evaluación Nutricional , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Personas con Discapacidad , Femenino , Evaluación Geriátrica , Humanos , Vida Independiente , Masculino
19.
Gan To Kagaku Ryoho ; 40(2): 225-7, 2013 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-23411960

RESUMEN

We report a case of a trastuzumab-resistant human epidermal growth factor receptor-2(HER2)-positive breast cancer patient with extensive liver metastases and associated impaired liver function, who showed an excellent response to the combination of trastuzumab and capecitabine. The patient was a 59-year-old postmenopausal woman with multiple liver metastases at first examination. She first received anthracycline-based chemotherapy, and after progression was followed up with a combination of trastuzumab and paclitaxel. Despite an initial response to this treatment, liver metastases rapidly progressed. Although palliative treatment was considered because of her impaired liver function, she received capecitabine while continuing trastuzumab. This combination therapy showed an excellent response, and a good quality of life(QOL)was maintained for a long time without any severe adverse events. The continuation of trastuzumab is considered effective after having progressed by trastuzumab including pretreatment, and we consider it worth while to give a combination of trastuzumab and capecitabine to patients with extensive liver metastases and associated impaired liver function, because of the treatment's synergistic effect and low risk of causing severe adverse events.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Receptor ErbB-2/análisis , Trastuzumab
20.
Nihon Eiseigaku Zasshi ; 68(1): 11-21, 2013.
Artículo en Japonés | MEDLINE | ID: mdl-23358372

RESUMEN

OBJECTIVE: The purpose of this study was to examine the effectiveness of the Functional Improvement Program of the Musculoskeletal System among users of Preventive Care Service under Long-Term Care Insurance. METHODS: A total of 3,073 subjects were analyzed. We used the prediction formula to estimate the predicted value of the Kihon Checklist after one year, and calculated the measured value minus the predicted value. The subjects were divided into two groups according to the measured value minus predicted value tertiles: the lowest and middle tertile (good-to-fair measured value) and the highest tertile (poor measured value). We used a multiple logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of the good-to-fair measured values of the Kihon Checklist after one year, according to the Functional Improvement Program of the Musculoskeletal System. RESULTS: In potentially dependent elderly, the multivariate adjusted ORs (95% CI) of the good-to-fair measured values were 2.4 (1.3-4.4) for those who attended the program eight times or more in a month (vs those who attended it three times or less in a month), 1.3 (1.0-1.8) for those who engaged in strength training using machines (vs those who did not train), and 1.4 (1.0-1.9) for those who engaged in endurance training. CONCLUSIONS: In this study, among potentially dependent elderly, those who attended the program eight times or more in a month and those who engaged in strength training using machines or endurance training showed a significant improvement of their functional capacity.


Asunto(s)
Actividades Cotidianas , Seguro de Cuidados a Largo Plazo , Sistema Musculoesquelético , Servicios Preventivos de Salud , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Seguro de Cuidados a Largo Plazo/economía , Japón , Masculino , Persona de Mediana Edad , Sistema Musculoesquelético/fisiopatología , Valor Predictivo de las Pruebas
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