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1.
J Nutr Health Aging ; 26(6): 590-597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35718868

RESUMO

OBJECTIVES: To investigate the predictive value of the BIA-derived phase angle with respect to the functional prognosis and baseline sarcopenia in patients undergoing post-stroke rehabilitation. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Overall, 577 Japanese patients admitted to a post-acute care hospital from 2016 to 2020 were recruited. MEASUREMENTS: Body composition analysis, which included BIA-derived phase angle and skeletal muscle mass, was performed using bioelectrical impedance analysis (BIA). Study outcomes included physical function assessed using the Functional Independence Measure (FIM-motor) and the level of dysphagia assessed using the Food Intake LEVEL Scale (FILS). Sarcopenia was defined as the loss of skeletal muscle mass and decreased muscle strength. Receiver operating characteristic curves were used to calculate the optimal cutoff value of BIA-derived phase angle to diagnose sarcopenia. Multivariate analyses were used to determine whether the BIA-derived phase angle at admission was associated with outcomes at discharge and baseline sarcopenia. RESULTS: After enrollment, 499 patients (mean age: 74.0 ± 13.1 years; 52.0% men) were examined. The median FIM-motor and FILS scores at admission were 47 (20-69) and 8 (7-10), respectively. Sarcopenia was observed in 43.2% of patients. After adjusting for potential confounders, BIA-derived phase angle was positively associated with FIM-motor scores at discharge (ß = 0.134, P < 0.001), FIM-motor score gain (ß = 2.504, P < 0.001), and FILS scores at discharge (ß = 0.120, P = 0.039). BIA-derived phase angle was negatively associated with the sarcopenia diagnosis at baseline (odds ratio = -0.409, P < 0.001); its cutoff value was 4.76° (sensitivity 0.800, specificity 0.790, P < 0.001) for sarcopenia diagnosis in men and 4.11° (sensitivity 0.735, specificity 0.829, P < 0.001) in women. CONCLUSION: BIA-derived phase angle was positively associated with the recovery of physical function and dysphagia level and negatively associated with baseline sarcopenia in patients undergoing post-stroke rehabilitation. The BIA-derived phase angle cutoff for sarcopenia diagnosis was 4.76° for men and 4.11° for women.


Assuntos
Transtornos de Deglutição , Sarcopenia , Reabilitação do Acidente Vascular Cerebral , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/reabilitação , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sarcopenia/diagnóstico
2.
Epidemiol Infect ; 143(5): 986-96, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25034254

RESUMO

SUMMARY The prevalence of Helicobacter pylori infection in Indonesia is controversial. We examined the H. pylori infection rate in 78 patients in a hospital in Surabaya using five different tests, including culture, histology, immunohistochemistry, rapid urease test, and urine antibody test. Furthermore, we analysed virulence factors in H. pylori strains from Indonesia. The H. pylori infection rate was only 11.5% in all patients studied, and 2.3% of Javanese patients and 18.0% of Chinese patients were infected (P = 0.01). Although severe gastritis was not observed, activity and inflammation were significantly higher in patients positive for H. pylori than in patients negative for H. pylori. Among genotypes identified from five isolated strains, cagA was found in four; two were vacA s1m1. All cagA-positive strains were oipA 'on' and iceA1 positive. We confirmed both a low H. pylori infection rate and a low prevalence of precancerous lesions in dyspeptic patients in a Surabaya hospital, which may contribute to the low incidence of gastric cancer in Indonesia.


Assuntos
Dispepsia/microbiologia , Gastrite/patologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/genética , Estômago/patologia , Adolescente , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/urina , Testes Respiratórios , Técnicas de Cultura , DNA Bacteriano/análise , Dispepsia/epidemiologia , Feminino , Gastrite/microbiologia , Genótipo , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/imunologia , Helicobacter pylori/isolamento & purificação , Humanos , Imuno-Histoquímica , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Estômago/microbiologia , Ureia/análise , Adulto Jovem
3.
J Chem Phys ; 139(14): 144705, 2013 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-24116639

RESUMO

The atomic and electronic structures of NiO(001)∕Au(001) interfaces were analyzed by high-resolution medium energy ion scattering (MEIS) and photoelectron spectroscopy using synchrotron-radiation-light. The MEIS analysis clearly showed that O atoms were located above Au atoms at the interface and the inter-planar distance of NiO(001)∕Au(001) was derived to be 2.30 ± 0.05 Å, which was consistent with the calculations based on the density functional theory (DFT). We measured the valence band spectra and found metallic features for the NiO thickness up to 3 monolayer (ML). Relevant to the metallic features, electron energy loss analysis revealed that the bandgap for NiO(001)∕Au(001) reduced with decreasing the NiO thickness from 10 down to 5 ML. We also observed Au 4f lines consisting of surface, bulk, and interface components and found a significant electronic charge transfer from Au(001) to NiO(001). The present DFT calculations demonstrated the presence of an image charge beneath Ni atoms at the interface just like alkali-halide∕metal interface, which may be a key issue to explain the core level shift and band structure.

4.
Diabetologia ; 56(5): 1088-97, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23412604

RESUMO

AIMS/HYPOTHESIS: The small G-protein ras-related C3 botulinum toxin substrate 1 (RAC1) plays various roles in mammalian cells, such as in the regulation of cytoskeletal organisation, cell adhesion, migration and morphological changes. The present study examines the effects of RAC1 ablation on pancreatic beta cell function. METHODS: Isolated islets from pancreatic beta cell-specific Rac1-knockout (betaRac1(-/-)) mice and RAC1 knockdown INS-1 insulinoma cells treated with small interfering RNA were used to investigate insulin secretion and cytoskeletal organisation in pancreatic beta cells. RESULTS: BetaRac1(-/-) mice showed decreased glucose-stimulated insulin secretion, while there were no apparent differences in islet morphology. Isolated islets from the mice had blunted insulin secretion in response to high glucose levels. In RAC1 knockdown INS-1 cells, insulin secretion was also decreased in response to high glucose levels, consistent with the phenotype of betaRac1(-/-) mice. Even under high glucose levels, RAC1 knockdown INS-1 cells remained intact with F-actin, which inhibits the recruitment of the insulin granules, resulting in an inhibition of insulin secretion. CONCLUSIONS/INTERPRETATION: In RAC1-deficient pancreatic beta cells, F-actin acts as a barrier for insulin granules and reduces glucose-stimulated insulin secretion.


Assuntos
Citoesqueleto de Actina/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Neuropeptídeos/metabolismo , Via Secretória , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Linhagem Celular , Hiperglicemia/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/citologia , Masculino , Camundongos , Camundongos Knockout , Neuropeptídeos/antagonistas & inibidores , Neuropeptídeos/genética , Pâncreas/citologia , Pâncreas/metabolismo , Perfusão , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Ratos , Técnicas de Cultura de Tecidos , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidores , Proteínas rac1 de Ligação ao GTP/genética
5.
J Chem Phys ; 136(12): 124303, 2012 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-22462853

RESUMO

This paper reveals the fact that the O adatoms (O(ad)) adsorbed on the 5-fold Ti rows of rutile TiO(2)(110) react with CO to form CO(2) at room temperature and the oxidation reaction is pronouncedly enhanced by Au nano-clusters deposited on the above O-rich TiO(2)(110) surfaces. The optimum activity is obtained for 2D clusters with a lateral size of ∼1.5 nm and two-atomic layer height corresponding to ∼50 Au atoms∕cluster. This strong activity emerging is attributed to an electronic charge transfer from Au clusters to O-rich TiO(2)(110) supports observed clearly by work function measurement, which results in an interface dipole. The interface dipoles lower the potential barrier for dissociative O(2) adsorption on the surface and also enhance the reaction of CO with the O(ad) atoms to form CO(2) owing to the electric field of the interface dipoles, which generate an attractive force upon polar CO molecules and thus prolong the duration time on the Au nano-clusters. This electric field is screened by the valence electrons of Au clusters except near the perimeter interfaces, thereby the activity is diminished for three-dimensional clusters with a larger size.

6.
J Chem Phys ; 136(12): 124707, 2012 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-22462888

RESUMO

The origin of the Ti 3d defect state seen in the band gap for reduced rutile TiO(2)(110) surfaces has been excitingly debated. The probable candidates are bridging O vacancies (V(O)) and Ti interstitials (Ti-int) condensed near the surfaces. The aim of this study is to give insights into the source of the gap state via photoelectron spectroscopy combined with ion scattering and elastic recoil detection analyses. We have made three important findings: (i) The intensity of the gap state observed is well correlated with the sheet resistance measured with a 4-point probe, inversely proportional to the density of Ti-int. (ii) Sputter∕annealing cycles in ultrahigh vacuum (UHV) lead to efficient V(O) creation and condensation of Ti-int near the surface, while only annealing below 870 K in UHV condenses subsurface Ti-int but does not create V(O) significantly. (iii) The electronic charge to heal a V(O) is almost twice that to create an O adatom adsorbed on the 5-fold Ti row. The results obtained here indicate that both the V(O) and Ti-interstitials condensed near the surface region contribute to the gap state and the contribution to the gap state from the Ti-int becomes comparable to that from V(O) for the substrates with low sheet resistance less than ∼200 Ω∕square.

7.
Osteoporos Int ; 23(2): 589-97, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21359670

RESUMO

SUMMARY: Subchondral trabecular bone structure was analyzed in knee osteoarthritis (OA) patients using 3-T MRI to investigate structural features of subchondral trabecular bone of knee OA. With OA progression, osteoporotic changes were observed in the lateral joint, showing a higher correlation than sclerotic changes in the medial joint. INTRODUCTION: To investigate structural features of subchondral trabecular bone of knee osteoarthritis (OA). METHODS: Sixty knees with KL grade 0-4 (all female) were examined. Fast imaging employing steady-state acquisition-cycled phases (FIESTA-c) and FatSat Spoiled gradient recalled acquisition in the steady state (SPGR) images were acquired by 3-T MRI. At four sites (the medial femur, medial tibia, lateral femur, and lateral tibia), subchondral trabecular bone structure was analyzed by FIESTA-c imaging, cartilage area was measured by SPGR imaging, and their correlation was analyzed. In addition, the subjects were classified into four groups from the cartilage area measured by SPGR imaging, and subchondral trabecular bone structure in each group was compared. RESULTS: As cartilage area decreased in the medial joint, bone volume fraction and trabecular thickness in the medial tibia increased, and bone volume fraction, trabecular thickness, number, and connectivity in the lateral femur and lateral tibia decreased (r ≥ 0.4 or ≤-0.4, p ≤ 0.001). Compared to medially, the changes laterally showed a higher correlation. When the medial-lateral ratio of trabecular thickness in the tibia was determined, it had the highest correlation coefficient (r=-0.7, p < 0.001). These changes were not significantly detected in the early stage. CONCLUSIONS: To more sensitively detect OA changes in subchondral trabecular bone structure, a focus on osteoporotic changes in the lateral joint and the medial-lateral ratio would be useful. Detectability of early OA remains unknown, but based on a strong correlation with the degree of OA progression, trabecular structural analysis of subchondral bone may be a useful parameter to evaluate OA severity and evaluate treatment.


Assuntos
Articulação do Joelho/patologia , Osteoartrite do Joelho/complicações , Osteoporose/etiologia , Idoso , Idoso de 80 Anos ou mais , Cartilagem Articular/patologia , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Osteoporose/diagnóstico , Tíbia/patologia
8.
Oncogene ; 30(6): 737-50, 2011 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-20890302

RESUMO

The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene had been isolated as an antagonist to RAS signaling; however, the mechanism of its action is not clear. In this study, the effect of loss of RECK function was assessed in various ways and cell systems. Successive cell cultivation of mouse embryonic fibroblasts (MEFs) according to 3T3 protocol revealed that the germline knockout of RECK confers accelerated cell proliferation and early escape from cellular senescence associated with downregulation of p19(Arf), Trp53 and p21(Cdkn1a). In contrast, short hairpin RNA-mediated depletion of RECK induced irreversible growth arrest along with several features of the Arf, Trp53 and Cdkn1a-dependent cellular senescence. Within 2 days of RECK depletion, we observed a transient increase in protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) phosphorylation associated with an upregulated expression of cyclin D1, p19(Arf), Trp53, p21(Cdkn1a) and Sprouty 2. On further cultivation, RAS, AKT and ERK activities were then downregulated to a level lower than control, indicating that RECK depletion leads to a negative feedback to RAS signaling and subsequent cellular senescence. In addition, we observed that epidermal growth factor receptor (EGFR) activity was transiently upregulated by RECK depletion in MEFs, and continuously downregulated by RECK overexpression in colon cancer cells. These findings indicate that RECK is a novel modulator of EGFR signaling.


Assuntos
Senescência Celular/genética , Receptores ErbB/metabolismo , Proteínas Ligadas por GPI/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Neoplasias do Colo/genética , Ciclina D1/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Regulação para Baixo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibroblastos/metabolismo , Proteínas Ligadas por GPI/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Quinases Ativadas por p21/metabolismo
9.
Int J Oral Maxillofac Surg ; 36(1): 15-9, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17157477

RESUMO

Neoadjuvant chemotherapy (NAC) for oral squamous cell carcinoma has a positive impact on organ preservation and/or survival only in patients who achieve an excellent anti-tumour effect with this therapy. Predictive assay for NAC can play an important role in establishing tailor-made treatments for oral squamous cell carcinoma. In this retrospective study, the anti-tumour effects of cisplatin-based NAC in 70 patients with oral squamous cell carcinoma were reviewed in relation to biological markers of tumour cell proliferation activity: tumour grade, cellular DNA content, mitotic index, apoptotic index, ki-67 positive rate, and p53 and Bax expression. Tumour grade, Bax expression, apoptotic index and cellular DNA content were significantly correlated with the anti-tumour effects of NAC in univariate analysis. Tumour grade, Bax expression and apoptotic index were selected as independent predictive factors by means of multiple logistic analysis. Using the regression equation from these results, the prediction rate for anti-tumour effects was 70%. For patients in whom NAC is predicted to be ineffective, it may be necessary to choose another treatment option in order to improve their survival and quality of life.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose , Bleomicina/administração & dosagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Índice Mitótico , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Proteína X Associada a bcl-2/biossíntese
10.
Oncogene ; 25(49): 6457-66, 2006 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-16702953

RESUMO

The membrane-linked docking protein SNT-2/FRS2beta/FRS3 becomes tyrosine phosphorylated in response to fibroblast growth factors (FGFs) and neurotrophins and serves as a platform for recruitment of multiple signaling proteins, including Grb2 and Shp2, to FGF receptors or neurotrophin receptors. We previously reported that SNT-2 is not tyrosine phosphorylated significantly in response to epidermal growth factor (EGF) but that it inhibits ERK activation via EGF stimulation by forming a complex with ERK2. In the present report, we show that expression of SNT-2 suppressed EGF-induced cell transformation and proliferation, and expression level of SNT-2 is downregulated in cancer. The activities of the major signaling molecules in EGF receptor (EGFR) signal transduction pathways, including autophosphorylation of EGFR, were attenuated in cells expressing SNT-2 but not in cells expressing SNT-2 mutants lacking the ERK2-binding domain. Furthermore, SNT-2 constitutively bound to EGFR through the phosphotyrosine binding (PTB) domain both with and without EGF stimulation. Treatment of cells with MEK inhibitor U0126 partially restored the phosphorylation levels of MEK and EGFR in cells expressing SNT-2. On the basis of these findings, we propose a novel mechanism of negative control of EGFR tyrosine kinase activity with SNT-2 by recruiting ERK2, which is the site of negative-feedback loop from ERK, ultimately leading to inhibition of EGF-induced cell transformation and proliferation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Receptores ErbB/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Células Cultivadas , Regulação para Baixo/fisiologia , Fator de Crescimento Epidérmico/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteínas Mutantes/metabolismo , Células NIH 3T3 , Fosforilação , Ligação Proteica , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transdução de Sinais/fisiologia
11.
Biofactors ; 22(1-4): 165-7, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15630275

RESUMO

The effect of gamma-amino butyric acid (GABA)-enriched soybean on blood pressure was investigated in male spontaneously hypertensive rats. Ten-week-old rats were given diets containing graded levels of GABA-enriched soybean powder for 8 weeks. The systolic blood pressure in rats fed 0.15% GABA diet was significantly lower at 1st week and maintained lower values for 4 weeks as compared with 0% GABA controls. No effect on blood pressure was found in those of 0.03 and 0.3% GABA. The results suggest that there exist appropriate dietary GABA level to get the blood pressure lowering effect.


Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Glycine max , Hipertensão/tratamento farmacológico , Ácido gama-Aminobutírico/farmacologia , Animais , Dieta , Suplementos Nutricionais , Masculino , Ratos , Ratos Endogâmicos SHR , Sístole/efeitos dos fármacos
12.
Exp Clin Endocrinol Diabetes ; 110(7): 319-24, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12397529

RESUMO

To elucidate the association of lipoprotein(a) (Lp(a)) with diabetic retinopathy (DR), we studied the serum Lp(a) concentrations (n = 412), apolipoprotein(a) (apo(a)) phenotypes expressed by the number of kringle 4 (K4) repeats (n = 150), apo(a) gene genotypes (n = 161) of type 2 diabetes with or without DR. The 5'-untranslated region of apo(a) gene was classified into seven haplotypes (A to G) and 18 genotypes by PCR-RFLP at three distinct sites. The serum Lp(a) concentrations were significantly higher in diabetic patients than in normal controls. Furthermore, the patients with DR, especially proliferative retinopathy showed higher serum Lp(a) concentrations than those without DR. Although a negative correlation was found between the serum Lp(a) concentrations and the number of K4 repeats in total diabetic patients, no difference was seen in the distribution of the number of K4 repeats between those with and without DR. In the same apo(a) phenotypes, the patients with DR had higher Lp(a) concentrations than those without DR. Among the genotypes, type CC showed significantly higher serum Lp(a) concentrations than the other genotypes. However, there was no difference in the ratios of the type CC between the patients with and without DR. In conclusion, other factors than phenotypes and genotypes in the 5'-untranslated region of apo(a) may be responsible for the elevation of serum Lp(a) in diabetic patients with retinopathy.


Assuntos
Apolipoproteínas/sangue , Apolipoproteínas/genética , Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/genética , Lipoproteína(a)/sangue , Lipoproteína(a)/genética , Regiões 5' não Traduzidas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoproteína(a) , Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/sangue , Feminino , Genótipo , Heterozigoto , Homozigoto , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Kit de Reagentes para Diagnóstico , Valores de Referência
13.
Endocr Rev ; 22(6): 818-35, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11739335

RESUMO

Targeted gene mutations have established distinct, yet overlapping, developmental roles for receptors of the insulin/IGF family. IGF-I receptor mediates IGF-I and IGF-II action on prenatal growth and IGF-I action on postnatal growth. Insulin receptor mediates prenatal growth in response to IGF-II and postnatal metabolism in response to insulin. In rodents, unlike humans, insulin does not participate in embryonic growth until late gestation. The ability of the insulin receptor to act as a bona fide IGF-II-dependent growth promoter is underscored by its rescue of double knockout Igf1r/Igf2r mice. Thus, IGF-II is a true bifunctional ligand that is able to stimulate both insulin and IGF-I receptor signaling, although with different potencies. In contrast, the IGF-II/cation-independent mannose-6-phosphate receptor regulates IGF-II clearance. The growth retardation of mice lacking IGF-I and/or insulin receptors is due to reduced cell number, resulting from decreased proliferation. Evidence from genetically engineered mice does not support the view that insulin and IGF receptors promote cellular differentiation in vivo or that they are required for early embryonic development. The phenotypes of insulin receptor gene mutations in humans and in mice indicate important differences between the developmental roles of insulin and its receptor in the two species.


Assuntos
Insulina/fisiologia , Receptor IGF Tipo 1/fisiologia , Processamento Alternativo , Animais , Caenorhabditis elegans/genética , Drosophila melanogaster/genética , Transtornos do Crescimento/genética , Humanos , Insulina/genética , Fator de Crescimento Insulin-Like I/deficiência , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/fisiologia , Camundongos , Camundongos Knockout , Mutação , Receptor IGF Tipo 1/deficiência , Receptor IGF Tipo 1/genética , Receptor de Insulina/deficiência , Receptor de Insulina/genética , Receptor de Insulina/fisiologia , Transdução de Sinais
14.
J Neurochem ; 79(5): 959-69, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11739607

RESUMO

Transport of L-[3H]carnitine and acetyl-L-[3H]carnitine at the blood-brain barrier (BBB) was examined by using in vivo and in vitro models. In vivo brain uptake of acetyl-L-[3H]carnitine, determined by a rat brain perfusion technique, was decreased in the presence of unlabeled acetyl-L-carnitine and in the absence of sodium ions. Similar transport properties for L-[3H]carnitine and/or acetyl-L-[3H]carnitine were observed in primary cultured brain capillary endothelial cells (BCECs) of rat, mouse, human, porcine and bovine, and immortalized rat BCECs, RBEC1. Uptakes of L-[3H]carnitine and acetyl-L-[3H]carnitine by RBEC1 were sodium ion-dependent, saturable with K(m) values of 33.1 +/- 11.4 microM and 31.3 +/- 11.6 microM, respectively, and inhibited by carnitine analogs. These transport properties are consistent with those of carnitine transport by OCTN2. OCTN2 was confirmed to be expressed in rat and human BCECs by an RT-PCR method. Furthermore, the uptake of acetyl-L-[3H]carnitine by the BCECs of juvenile visceral steatosis (jvs) mouse, in which OCTN2 is functionally defective owing to a genetical missense mutation of one amino acid residue, was reduced. The brain distributions of L-[3H]carnitine and acetyl-L-[3H]carnitine in jvs mice were slightly lower than those of wild-type mice at 4 h after intravenous administration. These results suggest that OCTN2 is involved in transport of L-carnitine and acetyl-L-carnitine from the circulating blood to the brain across the BBB.


Assuntos
Acetilcarnitina/farmacocinética , Barreira Hematoencefálica/fisiologia , Química Encefálica/fisiologia , Encéfalo/metabolismo , Carnitina/farmacocinética , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Transporte de Cátions Orgânicos , Animais , Capilares/efeitos dos fármacos , Capilares/metabolismo , Células Cultivadas , Circulação Cerebrovascular/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C3H , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Membro 5 da Família 22 de Carreadores de Soluto , Distribuição Tecidual
15.
J Am Chem Soc ; 123(45): 11310-1, 2001 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-11697982
16.
Mol Cell Biol ; 21(16): 5624-30, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11463843

RESUMO

Receptors of the insulin/insulinlike growth factor (IGF) family have been implicated in the regulation of pancreatic beta-cell growth and insulin secretion. The insulin receptor-related receptor (IRR) is an orphan receptor of the insulin receptor gene (Ir) subfamily. It is expressed at considerably higher levels in beta cells than either insulin or IGF-1 receptors, and it has been shown to engage in heterodimer formation with insulin or IGF-1 receptors. To address whether IRR plays a physiologic role in beta-cell development and regulation of insulin secretion, we have characterized mice lacking IRR and generated a combined knockout of Ir and Irr. We report that islet morphology, beta-cell mass, and secretory function are not affected in IRR-deficient mice. Moreover, lack of IRR does not impair compensatory beta-cell hyperplasia in insulin-resistant Ir(+/-) mice, nor does it affect beta-cell development and function in Ir(-/-) mice. We conclude that glucose-stimulated insulin secretion and embryonic beta-cell development occur normally in mice lacking Irr.


Assuntos
Receptor de Insulina/fisiologia , Animais , Insulina/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Ilhotas Pancreáticas/embriologia , Ilhotas Pancreáticas/fisiologia , Camundongos , Camundongos Knockout , Receptor IGF Tipo 1/fisiologia
18.
Endocrinology ; 142(8): 3354-60, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11459778

RESUMO

We have previously shown that hepatocytes lacking insulin receptors (Ir-/-) fail to mediate metabolic responses, such as stimulation of glycogen synthesis, while retaining the ability to proliferate in response to IGFs. In this study we have asked whether overexpression of type I IGF receptors would rescue the metabolic response of Ir-/- hepatocytes. After IGF-I stimulation, insulin receptor substrate-1 and -2 phosphorylation and PI3K activity were restored to levels similar to or greater than those seen in wild-type cells. Rates of cell proliferation in response to IGF-I increased approximately 2-fold, whereas glycogen synthesis was restored to wild-type levels, but was comparatively smaller than that elicited by overexpression of insulin receptors. In summary, overexpression of IGF-I receptors in Ir-/- hepatocytes normalized insulin receptor substrate-2 phosphorylation and glycogen synthesis to wild-type levels, whereas it increased cell proliferation above wild-type levels. Moreover, stimulation of glycogen synthesis was submaximal compared with the effect of insulin receptor overexpression. We conclude that IGF-I receptors are more efficiently coupled to cell proliferation than insulin receptors, but are less potent than insulin receptors in stimulating glycogen synthesis. The data are consistent with the possibility that there exist intrinsic signaling differences between insulin and IGF-I receptors.


Assuntos
Hepatócitos/citologia , Hepatócitos/metabolismo , Mitose/fisiologia , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/deficiência , Animais , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Divisão Celular/fisiologia , Transformação Celular Viral , Células Cultivadas , Quinase 3 da Glicogênio Sintase , Hepatócitos/virologia , Proteínas Substratos do Receptor de Insulina , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Camundongos Knockout/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas/metabolismo , Fosforilação , Receptor de Insulina/genética , Vírus 40 dos Símios/fisiologia , Somatomedinas/fisiologia
19.
Kurume Med J ; 48(1): 43-7, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11402619

RESUMO

Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors. This study aimed at clarifying the clinical significance of the changes in the serum VEGF (S-VEGF) concentrations in patients with lung cancer during anticancer chemotherapy. Subjects comprised 29 patients with lung cancer (13 adenocarcinomas, 7 squamous cell carcinomas, and 9 small cell carcinomas) who were treated with cisplatin-based chemotherapy. S-VEGF was measured by ELISA. We compared the S-VEGF concentrations between the responders and nonresponders to anticancer chemotherapy. S-VEGF concentrations before treatment of the chemotherapy (pretreatment S-VEGF concentrations) were correlated with the number of WBC, neutrophil count, monocyte count and platelet count but not the lymphocyte count. The mean pretreatment S-VEGF concentrations in responders and those in nonresponders were not significantly different, 509.7 pg/ml in the former and 382.8 pg/ml in the latter, respectively., The S-VEGF concentrations in the responders decreased to a mean of 356.0 pg/ml and 304.1 pg/ml during and at the end of therapy, respectively while those in the nonresponders increased to a mean of 474.2 pg/ml and 598.4 pg/ml during and at the end of therapy. The S-VEGF concentration changes in the responders were significantly different from those in the nonresponders (p = .006). The S-VEGF concentration may relate to tumor burden, however it may not be a good marker for tumor burden, because it can be influenced by various factors such as neutrophil which increases during infection. A decrease in S-VEGF concentrations may improve neoangiogenesis and the immune response, and may correlate with improvements in the quality of life and survival of patients.


Assuntos
Fatores de Crescimento Endotelial/sangue , Neoplasias Pulmonares/tratamento farmacológico , Linfocinas/sangue , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
20.
Dig Surg ; 18(2): 111-7, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11351155

RESUMO

BACKGROUND/AIMS: D2 gastrectomy has been regarded as an inconvenient procedure with high morbidity and no survival benefit in the West. Recent western studies, however, especially from specialist centers, have shown a survival benefit and the safety of D2 gastrectomy. The aim of this study is to clarify the safety of D2 gastrectomy (defined by the Japanese Research Society for the Study of Gastric Cancer), even if carried out by a junior surgeon, and to show that it is not a particularly difficult or special procedure. METHODS: Patients who underwent a typical distal gastrectomy (DG) with D2 resection (n = 344) and total gastrectomy (TG) with D2 resection (n = 111) were analyzed. The subjects were divided into 3 groups according to the postgraduate year of the operator (group I = the surgeon's postgraduate experience was less than 5 years; group II = surgeons with more than 5 years and less than 10 years postgraduate experience; group III = surgeons with more than 10 years postgraduate experience). The rate of postoperative complications and the 5-year survival rate were compared among the 3 groups. RESULTS: The overall operative mortality rate, hospital death rate and the overall rate of postoperative complications were 1.2, 2.0 and 10.2% in DG patients, and 14.4, 0 and 1.8% in TG patients, respectively. There was no significant difference in the operative blood loss, the rate of operative mortality, hospital death rate and postoperative complications among the 3 groups. There was no significant difference in the 5-year survival rate among the 3 groups in each stage. CONCLUSION: The postoperative mortality rate, morbidity rate and 5-year survival rate after a typical D2 gastrectomy were independent of the experience of the operator. It is considered to be a safe and useful procedure in view of the rate of postoperative complications and the long-term survival rate, even if performed by a junior trainee under the supervision of experienced surgeons in a nonspecialized hospital.


Assuntos
Competência Clínica/normas , Gastrectomia/efeitos adversos , Gastrectomia/normas , Cirurgia Geral/educação , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/normas , Corpo Clínico Hospitalar/educação , Segurança , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Perda Sanguínea Cirúrgica , Feminino , Gastrectomia/métodos , Gastrectomia/mortalidade , Mortalidade Hospitalar , Hospitais Municipais , Humanos , Japão/epidemiologia , Excisão de Linfonodo/mortalidade , Masculino , Pessoa de Meia-Idade , Morbidade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do Tratamento
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