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1.
Endocr J ; 70(9): 933-939, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37380447

RESUMO

Although rare, endogenous hypercortisolemia, including Cushing's disease (CD), is known to cause bowel perforation and to mask typical symptoms of bowel perforation, leading to delayed diagnosis. Additionally, elderly patients with CD are considered to be at a higher risk for bowel perforation because intestinal tissue fragility tends to increase in the elderly. Herein, we describe a rare case in which a young adult patient with CD was diagnosed with bowel perforation associated with CD following severe abdominal pain. A 24-year-old Japanese man was admitted to the hospital for the evaluation of ACTH-dependent Cushing's syndrome. He suddenly complained of severe abdominal pain on the 8th day of hospitalization. Computed tomography revealed free air around the sigmoid colon. The patient was diagnosed with bowel perforation, underwent emergency surgery, and was saved. He was subsequently diagnosed with CD, and the pituitary adenoma was resected transsphenoidally. To date, eight cases of bowel perforation due to CD had been reported, with a median age of 61 years at the time of bowel perforation. Hypokalemia was detected in half of the patients, and all had a history of diverticular disease. Nevertheless, not many patients complained of peritoneal irritation. In conclusion, this is the youngest reported case with bowel perforation due to CD and the first report of bowel perforation in a patient without a history of diverticular disease. Bowel perforation may occur in patients with CD, irrespective of age and the presence of hypokalemia, diverticular disease, or peritoneal irritation.


Assuntos
Síndrome de Cushing , Doenças Diverticulares , Hipopotassemia , Perfuração Intestinal , Hipersecreção Hipofisária de ACTH , Humanos , Masculino , Adulto Jovem , Dor Abdominal/complicações , Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico , Doenças Diverticulares/complicações , Hipopotassemia/complicações , Inflamação , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/diagnóstico
2.
BMC Endocr Disord ; 22(1): 300, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36461073

RESUMO

BACKGROUND: 17α-hydroxylase deficiency (17OHD) is a rare autosomal recessive disorder. Aldosterone levels are usually low in patients with 17OHD. However, among the approximately 150 cases of 17OHD reported to date, aldosterone levels were not low in all cases. Therefore, some 17OHD cases may have been misdiagnosed as primary aldosteronism (PA) cases. Often before puberty, 17OHD is diagnosed because of abnormal genital morphology and menstrual irregularities. However, we report a very rare case of 17OHD in an elderly patient with a high aldosterone/renin ratio (ARR) similar to that in PA. CASE PRESENTATION: A 63-year-old Japanese woman was transferred to our medical facility for the evaluation of bilateral adrenal hypertrophy, which was incidentally discovered during an abdominal examination after cholecystectomy. The patient had hypokalemia and a high aldosterone/renin ratio. Her medical history included hypertension and right intracerebral capsular hemorrhage at the age of 30 years. Additional testing revealed low cortisol, high adrenocorticotropic hormone, and low testosterone and dehydroepiandrosterone sulfate, indicating congenital adrenal hyperplasia. Genetic analysis revealed a mutation in the CYP17A1 gene and a karyotype of 46, XY; hence, she was diagnosed with 17OHD. CONCLUSION: 17OHD can resemble PA. The combination of a high ARR and low cortisol level should trigger the consideration of 17OHD.


Assuntos
Hiperaldosteronismo , Doenças Metabólicas , Humanos , Idoso , Feminino , Adulto , Pessoa de Meia-Idade , Aldosterona , Hidrocortisona , Renina , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/genética , Oxigenases de Função Mista , Erros de Diagnóstico
3.
Artigo em Inglês | MEDLINE | ID: mdl-30795554

RESUMO

Numerous dietary recommendations have been made for the prevention and treatment of diabetes. However, many people with diabetes regard healthy dietary behavior as wearisome and have difficulty adhering to nutrition therapy. We, therefore, conducted a questionnaire survey concerning the restaurants that serve meals suitable for people with diabetes. We first aimed to determine the number of restaurants that were aware of the need to create special menus for people with diabetes. Second, we aimed to encourage restaurants' serving of tasty, healthy food and promote easier social living for people with diabetes. We conducted our questionnaire survey every year from 2008 to 2013 on the availability of special menus for people with diabetes at restaurants listed in Michelin Guide Tokyo. We succeeded in increasing the proportion of restaurants offering special meals for people with diabetes from 6.7% (10 of 150 restaurants) in 2008 to 13.2% (32 of 242 restaurants) in 2013. As a result of the diabetes pandemic, the market for goods and services catering to people with diabetes is increasing. Diabetologists need to inform and support the food industry to produce foods that are suitable for people with diabetes and promote the serving of such foods by restaurants. This represents a new approach in the prevention and treatment of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Rotulagem de Alimentos , Marketing , Restaurantes , Diabetes Mellitus Tipo 2/dietoterapia , Dieta , Humanos , Estudos Longitudinais , Refeições , Inquéritos e Questionários , Tóquio
4.
Disabil Rehabil Assist Technol ; 14(4): 368-378, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29522365

RESUMO

PURPOSE: With a growing proportion of elderly people in the population, the maintenance of activities of daily living (ADLs) in elderly people is crucial to keep medical costs down. We investigated the ADL measurement accuracy of KINECTTM and Kinect Studio. To eliminate the subjectivity of conventional methods, we numerically assessed motions with computer analysis. METHODS: Eighteen actions that repeated "move" and "stationary" phases, including movement of arms, legs, head and torso were measured using KINECTTM. Errors and standard deviations of joint coordinates at the stationary points outputted from KINECT Studio were evaluated. Simultaneous measurements were performed with KINECTTM using conventional high-performance motion capture, and the output was treated as a true value for comparison. RESULTS: In most motions, errors of the joint coordinates were within 100 mm; however, there were two cases where errors due to the skeleton-model estimation by KINECT Studio increased. Firstly, when a part of the body unexpectedly moved out of the infrared measurable area, and secondly, when parts of the body overlapped each other on the KINECTTM image. CONCLUSIONS: KINECTTM and Kinect Studio are effective for ADL assessment when positions that cause large errors are excluded. Since KINECTTM has sufficient precision, it should also be possible to develop a more appropriate ADL evaluation system with a new algorithm of skeleton-model estimation that does not depend on KINECT Studio. Implications for Rehabilitation The KINECTTM and Kinect Studio are effective for ADL assessment when positions that cause large errors are excluded With an increasing proportion of elderly people in the population, the maintenance of activities of daily living (ADLs) in elderly people is crucial to keep medical costs down Systems such as the KINECTTM can support these goals.


Assuntos
Atividades Cotidianas , Monitorização Ambulatorial/métodos , Movimento/fisiologia , Fenômenos Biomecânicos , Humanos , Raios Infravermelhos , Masculino , Reprodutibilidade dos Testes
5.
J Diabetes Investig ; 10(2): 331-338, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30175458

RESUMO

AIMS/INTRODUCTION: The present study aimed to investigate the effects of low-intensity resistance training with slow movement and tonic force generation (LST) on muscular function and glucose metabolism in older patients with type 2 diabetes. MATERIALS AND METHODS: A total of 10 patients with type 2 diabetes (age 68.2 ± 9.7 years) engaged in LST training twice a week for 16 weeks. Before the long-term intervention, they were subjected to the measurement of acute changes in blood factors relating to glycemic control as a result of a bout of LST. Body composition, muscular size and strength, and glycated hemoglobin were measured before and after the intervention. RESULTS: The magnitudes of the acute changes in the blood factors were all small and were not considered harmful for glucose metabolism. The 16-week LST training caused significant increases in thigh muscle thickness and strength, and decreases in body fat mass and glycated hemoglobin. The change in glycated hemoglobin showed a significant negative correlation with the change in the isokinetic knee extension peak torque measured at a high angular velocity (180°/s). CONCLUSIONS: The LST training was shown to be effective for gaining muscular size and strength, and improving glycemic control in older patients with type 2 diabetes. The mechanisms underlying this effect might involve the improvement of contractile function in fast glycolytic fibers.


Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/terapia , Índice Glicêmico , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Treinamento Resistido , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Composição Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
6.
Nutrients ; 10(5)2018 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-29695055

RESUMO

We previously showed that a non-calorie-restricted, moderately low-carbohydrate diet (mLCD) is more effective than caloric restriction for glycemic and lipid profile control in patients with type 2 diabetes. To determine whether mLCD intervention is sustainable, effective, and safe over a long period, we performed a 36-month observational study. We sequentially enrolled 200 patients with type 2 diabetes and taught them how to follow the mLCD. We compared the following parameters pre- and post-dietary intervention in an outpatient setting: glycated hemoglobin (HbA1c), body weight, lipid profile (total cholesterol, low and high-density lipoprotein cholesterol, triglycerides), systolic and diastolic blood pressure, liver enzymes (aspartate aminotransferase, alanine aminotransferase), and renal function (urea nitrogen, creatinine, estimated glomerular filtration rate). Data from 157 participants were analyzed (43 were lost to follow-up). The following parameters decreased over the period of study: HbA1c (from 8.0 ± 1.5% to 7.5 ± 1.3%, p < 0.0001) and alanine aminotransferase (from 29.9 ± 23.6 to 26.2 ± 18.4 IL/L, p = 0.009). Parameters that increased were high-density lipoprotein cholesterol (from 58.9 ± 15.9 to 61.2 ± 17.4 mg/dL, p = 0.001) and urea nitrogen (from 15.9 ± 5.2 to 17.0 ± 5.4 mg/dL, p = 0.003). Over 36 months, the mLCD intervention showed sustained effectiveness (without safety concerns) in improving HbA1c, lipid profile, and liver enzymes in Japanese patients with type 2 diabetes.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Dieta com Restrição de Carboidratos , Dieta para Diabéticos , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Dieta com Restrição de Carboidratos/efeitos adversos , Dieta para Diabéticos/efeitos adversos , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Japão , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
7.
Diabetol Int ; 7(3): 259-265, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30603272

RESUMO

OBJECTIVE: Our aims were to compare diabetic patients' evaluations of straight 32- and tapered 34-gauge 4-mm needles for usability and preference as well as the frequency of injection adverse events during insulin self-injection and to analyze the relationship between patients' preferences and their background characteristics including thumb force measured by manual muscle testing. METHODS: We enrolled 60 insulin-treated patients and measured their maximum thumb force. Patients were randomized into two groups (32- and 34-gauge) with reverse order of needle use: 1 week with one type of needle and the next week with the other. The usability of and preference for the needles were measured using the visual analog scale (VAS), and the frequency of injection adverse events was evaluated. RESULTS: Mean maximum thumb strength was 83.5 ± 25.4 N, tended to decrease with age and was significantly lower in females than in males. The mean VAS scores regarding smooth insertion and pain during insulin delivery were significantly different, favoring the 34-gauge needle. However, the mean VAS scores regarding ease of pushing an injection button and overall preference showed no significant difference between the two needles. There was no significant difference in the frequency of injection adverse events including breaking needles. CONCLUSION: Our patients had sufficient thumb force to push the injection button regardless of needle type. Although significant differences regarding smooth insertion or pain during insulin delivery were perceived, there was no difference in overall preference between the two needles, indicating the usability and safety of the two needles are not different in clinical use.

8.
J Diabetes Sci Technol ; 9(3): 632-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25526758

RESUMO

BACKGROUND: The study presents a comparison of the glucose-lowering effects, glycemic variability, and insulin doses during treatment with insulin degludec or insulin glargine. METHODS: In this open-label, single-center, 2-way crossover study, 13 Japanese diabetic outpatients in the insulin-dependent state on basal-bolus therapy were assigned to receive either insulin glargine followed by insulin degludec, or insulin degludec followed by insulin glargine. Basal insulin doses were fixed in principle, and patients self-adjusted their bolus insulin doses. Seventy-two-hour continuous glucose monitoring was performed 2 weeks after switching the basal insulin. RESULTS: Mean blood glucose (mg/dL) was not significantly different between insulin degludec and insulin glargine over 48 hours (141.8 ± 35.2 vs 151.8 ± 43.3), at nighttime (125.6 ± 40.0 vs 124.7 ± 50.4), or at daytime (149.3 ± 37.1 vs 163.3 ± 44.5). The standard deviation (mg/dL) was also similar (for 48 hours: 48.9 ± 19.4 vs 50.3 ± 17.3; nighttime: 18.7 ± 14.3 vs 13.7 ± 6.7; daytime: 49.3 ± 20.0 vs 44.3 ± 17.7). Other indices of glycemic control, glycemic variability, and hypoglycemia were similar for both insulin analogs. Total daily insulin dose (TDD) and total daily bolus insulin dose (TDBD) were significantly lower with insulin degludec than with insulin glargine (TDD: 0.42 ± 0.20 vs 0.46 ± 0.22 U/kg/day, P = .028; TDBD: 0.27 ± 0.13 vs 0.30 ± 0.14 U/kg/day, P = .036). CONCLUSIONS: Insulin degludec and insulin glargine provided effective and stable glycemic control. Insulin degludec required lower TDD and TDBD in this population of patients.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Insulina Glargina/administração & dosagem , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/uso terapêutico , Povo Asiático , Glicemia/análise , Estudos Cross-Over , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos
9.
Intern Med ; 53(1): 13-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24390522

RESUMO

OBJECTIVE: Although caloric restriction is a widely used intervention to reduce body weight and insulin resistance, many patients are unable to comply with such dietary therapy for long periods. The clinical effectiveness of low-carbohydrate diets was recently described in a position statement of Diabetes UK and a scientific review conducted by the American Diabetes Association. However, randomised trials of dietary interventions in Japanese patients with type 2 diabetes are scarce. Therefore, the aim of this study was to examine the effects of a non-calorie-restricted, low-carbohydrate diet in Japanese patients unable to adhere to a calorie-restricted diet. METHODS: The enrolled patients were randomly allocated to receive a conventional calorie-restricted diet or low-carbohydrate diet. The patients received consultations every two months from a registered dietician for six months. We compared the effects of the two dietary interventions on glycaemic control and metabolic profiles. RESULTS: The HbA1c levels decreased significantly from baseline to six months in the low-carbohydrate diet group (baseline 7.6±0.4%, six months 7.0±0.7%, p=0.03) but not in the calorie-restricted group (baseline 7.7±0.6%, six months 7.5±1.0%, n.s.), (between-group comparison, p=0.03). The patients in the former group also experienced improvements in their triglyceride levels, without experiencing any major adverse effects or a decline in the quality of life. CONCLUSION: Our findings suggest that a low-carbohydrate diet is effective in lowering the HbA1c and triglyceride levels in patients with type 2 diabetes who are unable to adhere to a calorie-restricted diet.


Assuntos
Terapias Complementares/métodos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/dietoterapia , Dieta com Restrição de Carboidratos/métodos , Ingestão de Energia/fisiologia , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Redução de Peso/fisiologia
10.
Magn Reson Med Sci ; 11(4): 243-52, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23269011

RESUMO

PURPOSE: We present and demonstrate a new compressed sensing (CS) method to improve the image quality obtained in magnetic resonance CS. The sparsifying function, which transforms the image function to sparsified domain, is very important since it controls the quality of reconstructed image. We investigate the utility of a multi-step directional transform for improving the quality of reconstructed images in CS reconstruction. METHODS: As a sparsifying function, we used the Fresnel domain band split transformation (FREBAS), a method to decompose images with highly directional representation and optional scaling of the decomposition. Our image reconstruction algorithm involved linear and nonlinear operations, such as projection onto a convex set and hard thresholding in the transform domain. RESULTS: Several numerical experiments demonstrated the acquisition of images of better quality using multi-step successive thresholding and different scaling parameters in the FREBAS domain rather than single-step FREBAS thresholding. Reconstruction experiments showed much more detail of the imaging subject with fewer artifacts in CS images based on the FREBAS transform compared to CS based on the wavelet transform. CONCLUSION: The proposed method using multi-step FREBAS as the sparsifying transformation function is suitable for CS magnetic resonance imaging.


Assuntos
Compressão de Dados/métodos , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Algoritmos , Artefatos , Encéfalo/anatomia & histologia , Humanos , Aumento da Imagem/métodos , Imageamento Tridimensional/métodos , Masculino , Valores de Referência , Razão Sinal-Ruído , Adulto Jovem
11.
Diabetes Metab Res Rev ; 27(8): 951-3, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22069291

RESUMO

BACKGROUND: It has been reported that intervention with insulin in slowly progressive type 1 diabetic (SPIDDM) patients delays the progression to an insulin-dependent state compared to that with sulfonylureas. However, the rate of progression to SPIDDM with the use of insulin-sensitizing agents is unknown. The aim of this study was to determine the effect of insulin-sensitizing agents on SPIDDM patients. METHODS: The enrolled SPIDDM patients were randomly allocated to a pioglitazone or metformin group. When the haemoglobin A1C level was more than 8% on two consecutive occasions, the case was considered to reach the end point. RESULTS: By 4 years post-intervention, all patients had reached the end point in the pioglitazone group, whereas only 20% of patients had reached the end point in the metformin group (p<0.05). CONCLUSIONS: Pioglitazone may accelerate the disease course of SPIDDM.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Tiazolidinedionas/efeitos adversos , Adulto , Idade de Início , Progressão da Doença , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pioglitazona
12.
J Immunol ; 187(10): 4947-53, 2011 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-21967896

RESUMO

Human fulminant type 1 diabetes (FT1D) is an extremely aggressive disease. The delay of proper diagnosis results in high mortality. However, the pathophysiology of this disease remains unclear. We took advantage of CD28-deficient NOD (CD28(-/-) NOD) mice, which have limited numbers of regulatory T cells and develop aggressive autoimmune diabetes, to create a FT1D model that mimicked the disease in humans. Young CD28(-/-) NOD mice were injected with polyinosinic-polycytidylic acid to activate innate immunity in an effort to induce diabetes onset. In this model, innate immune cell activation precedes the onset of diabetes similar to ∼70% of FT1D patients. Eighty-three percent of CD28(-/-) NOD mice developed diabetes within 1-6 d after injection of polyinosinic-polycytidylic acid. Moreover, T cells infiltrated the pancreatic exocrine tissue and destroyed α cells, an observation characteristic of human FT1D. We conclude that an FT1D-like phenotype can be induced in the background of autoimmune diabetes by a mimic of viral dsRNA, and this model is useful for understanding human FT1D.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Linfopenia/imunologia , Mimetismo Molecular/imunologia , RNA de Cadeia Dupla/imunologia , RNA Viral/imunologia , Linfócitos T Reguladores/imunologia , Animais , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Modelos Animais de Doenças , Enterovirus/genética , Enterovirus/imunologia , Feminino , Linfopenia/genética , Linfopenia/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Mimetismo Molecular/genética , Síndrome , Linfócitos T Reguladores/patologia
13.
Rev Diabet Stud ; 7(3): 209-24, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21409313

RESUMO

OBJECTIVE: Complete Freund's Adjuvant (CFA) is known to arrest autoimmune diabetes development in non-obese diabetic (NOD) mice. However, CFA alone cannot induce effective remission in diabetic NOD mice. Previously, we reported that anti-CXC chemokine ligand 10 (CXCL10) antibody can promote beta-cell proliferation in NOD mice. In the present study, we aimed to examine whether anti-CXCL10 plus CFA treatment can effectively reverse autoimmune diabetes development. METHODS: Systemic supply of anti-CXCL10 antibody by CXCL10 DNA vaccination in combination with CFA injection was performed in new-onset diabetic NOD mice. Remission rate of diabetes, histological characteristics of residual insulitis lesions, residual beta-cell mass, and regulatory T cell population in local pancreas were examined. RESULTS: A high frequency of diabetes reversal was observed after combination treatment with anti-CXCL10 plus CFA. In mice showing diabetes reversal, residual beta-cell mass was significantly increased, and some beta-cells were in a proliferative state. Although systemic cytokine profiles were unaffected, the frequency of "hybrid regulatory T cells", i.e. regulatory T cells expressing CXCR3, was significantly increased in local pancreatic lesions. This was possibly associated with the regulation of anti-islet autoimmunity. CONCLUSIONS: Anti-CXCL10 plus appropriate immune adjuvant therapy arrested, and reversed, type 1 diabetes development.


Assuntos
Quimiocina CXCL10/imunologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Adjuvante de Freund/uso terapêutico , Hiperglicemia/tratamento farmacológico , Vacinas de DNA/uso terapêutico , Animais , Anticorpos/uso terapêutico , Quimiocina CXCL10/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/prevenção & controle , Modelos Animais de Doenças , Feminino , Humanos , Hiperglicemia/imunologia , Hiperglicemia/prevenção & controle , Camundongos , Camundongos Endogâmicos NOD , Ratos , Vacinação , Vacinas de DNA/imunologia
14.
Rev Diabet Stud ; 6(2): 81-4, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19806237

RESUMO

Despite intervention with insulin, type 1 diabetes gradually deteriorates the patients' quality of life. The disease is characterized by an immune-mediated destruction of pancreatic beta-cells. Its etiology, however, remains controversial. Some studies argue that glutamic acid decarboxylase (GAD) antigen and GAD-reactive T cells are critical players in the development of diabetes by affecting the Th cell balance. A T-helper 1 (Th1)-dominant immune response is considered to be important in beta-cell failure in both human and animal models of type 1 diabetes. The Th1-type chemokine, CXCL10, and its receptor, CXCR3, are involved not only in the immune response, but also in the suppression of beta-cell proliferation. Thus, understanding the CXCL10/CXCR3 system may be important for finding a cure. In this short review, we discuss the role of the CXCL10/CXCR3 system in type 1 diabetes and propose relevant treatment options.

15.
Anal Biochem ; 387(2): 249-56, 2009 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-19454241

RESUMO

To estimate the transcriptional activity of p53 in individual living mammalian cells, we constructed the enhanced green fluorescent protein-red fluorescent protein (EGFP-DsRed) reporter system with the EGFP-p53 expression vector and the reporter plasmid, which carried a p53-dependent promoter. The expression level and transcriptional activity of EGFP-p53 were determined simultaneously by green and red fluorescence signals, respectively. In this system, we could target only the cells expressing p53 at endogenous levels, as observed in UV- or adriamycin-stimulated A549 cells. Using this system, we investigated the transcriptional activity of mutant p53s in tetramerization domain. Transcriptional activities were nearly abolished by seven mutations and significantly reduced in several mutant p53s. However, under overexpression conditions, the latter mutant p53s showed activity similar to that observed in wild-type p53. These results indicated the importance of physiological concentration for p53 proteins in cells so as to analyze their activities. Fluorescence intensity distribution analysis indicated that the mutant p53s lacking transcriptional activity presented as monomer forms in the cellular extract. In most of the mutant p53s, the decrease in transcriptional activity correlated with an increase in the fraction of monomers. This reporter system can be used for estimating the transcriptional activity of mutant p53s without contribution of the cells overexpressing p53.


Assuntos
Transcrição Gênica , Proteína Supressora de Tumor p53/análise , Proteínas de Fluorescência Verde/análise , Humanos , Proteínas Luminescentes , Mutação , Estrutura Terciária de Proteína , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/fisiologia , Proteína Vermelha Fluorescente
16.
Magn Reson Med ; 60(2): 422-30, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18666133

RESUMO

An image reconstruction technique that reduces aliasing artifacts by scalable image reconstruction in magnetic resonance imaging (MRI) is proposed. The signal obtained by the phase-scrambling Fourier transform (PSFT) imaging technique can be transformed to the signal described in the Fresnel transform equation of the objects. Therefore, image reconstruction can be performed not only by inverse FT but also by inverse Fresnel transform. When a phase-scrambling coefficient is given in a certain range, image reconstruction by inverse Fresnel transform allows shrinking of images over rather wide scales. Thus, reduced aliasing images can be reconstructed even from signals that produce serious aliasing artifacts by standard inverse FT reconstruction. Simulation and experimental studies reveal that the proposed method can be used to produce reduced aliasing images.


Assuntos
Algoritmos , Artefatos , Encéfalo/anatomia & histologia , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Análise de Fourier , Humanos , Imageamento por Ressonância Magnética/instrumentação , Modelos Biológicos , Modelos Estatísticos , Imagens de Fantasmas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
J Nanosci Nanotechnol ; 8(5): 2308-15, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18572642

RESUMO

Oligoarginine conjugates are highly efficient vectors for the delivery of plasmid DNA into cells. Decaarginine-conjugated lipid (Arg10-PEG-lipid) was synthesized and the effects of Arg10-PEG-lipid concentration at a fixed DNA concentration on transfection efficiency and the structure of the complexes were studied below and above critical micelle concentration (CMC), and at the lipid nitrogen/DNA phosphate (N/P) ratio corresponding to transfection, respectively. Arg10-PEG-lipid at the concentration below CMC showed stronger interaction with DNA by fluorescence intensity distribution analysis, and significantly higher luciferase and green fluorescent protein expression than that above CMC. A phase-contrast cryo-transmission electron microscope (cryo-TEM) experiment showed that the morphology of the complexes depended on the N/P ratio. At a low N/P ratio corresponding to that in transfection at a lipid concentration below CMC, a net-like structure developed in which plasmid DNA was involved. A further increase in the N/P ratio, a large fibrous nanostructure of complexes, was also observed. Without DNA, these structures were not obtained. The cellular uptake mechanism of complexes using flow cytometry with inhibitors suggested that complexes with two different morphologies showed similar cellular uptake and uptake mechanism, macropinocytosis. Differences in transfection efficiency of the complexes may be explained by a large fibrous nanostructure inhibiting the cellular internalization of complexes or the release of DNA from macropinosomes into cytoplasm. Arg10-PEG-lipid/DNA complexes formed a favorable nanostructure for gene delivery, depending on the N/P ratio in water.


Assuntos
Arginina/química , DNA/química , Lipídeos/química , Nanoestruturas , Polietilenoglicóis/química , Transfecção , Fluorescência , Células HeLa , Humanos , Microscopia Eletrônica
18.
J Org Chem ; 72(9): 3242-6, 2007 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-17397223

RESUMO

Tetrakis(4-hydroxyphenyl)-cavitand 1 and tetra(4-pyridyl)-cavitand 2 self-assemble into a heterodimeric capsule 1.2 via four ArOH...pyridyl hydrogen bonds in CDCl3. The 1.2 expresses the orientational isomerism of an encapsulated unsymmetrical guest with high orientational selectivity because the electronic environment of the 1 unit is different from that of the 2 unit. For p-ethoxyiodobenzene and 2-iodo-6-methoxynaphthalene encapsulated in 1.2, the iodo group is specifically oriented to the cavity of the 2 unit. The orientational isomeric selectivity for methyl p-acetoxybenzoate and methyl p-ethoxybenzoate within 1.2 is 1:0.11 and 1:<0.05, respectively, wherein the methyl ester group is preferentially oriented to the cavity of the 2 unit. The delicate balance among electrostatic potential repulsion, CH-pi interaction, or CH-halogen (halogen-pi) interaction, in 1.2-guest assembly influences the orientational isomeric selectivity of unsymmetrical guests within 1.2.


Assuntos
Nanoestruturas/química , Dimerização , Elétrons , Éteres Cíclicos/química , Ligação de Hidrogênio , Isomerismo , Espectroscopia de Ressonância Magnética , Resorcinóis/química
19.
Bioorg Med Chem Lett ; 17(10): 2904-7, 2007 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-17350836

RESUMO

The design and solid-phase synthesis of effective fluorescent-labeled aeruginosin derivatives and their application to the fluorescence correlation spectroscopy (FCS)-based competitive binding assay of an aeruginosin library are described. The phenolic hydroxyl group on the (R)-3-(4-hydroxyphenyl)lactic acid (d-Hpla) residue was observed to be suitable for connecting Rhodamine green derivative with minimum loss of biological activity. In addition, the FCS-based binding assay of the library using fluorescent-labeled chemical probes was also achieved.


Assuntos
Leucina/análogos & derivados , Espectrometria de Fluorescência/métodos , Corantes Fluorescentes , Leucina/síntese química , Leucina/química , Estrutura Molecular , Espectrofotometria Ultravioleta
20.
J Org Chem ; 71(23): 8800-6, 2006 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-17081009

RESUMO

Fine and/or drastic tuning of capsule space has been attained by alteration of the hydrogen-bonding linker and/or hemispherical cavitand, respectively. Two molecules of tetracarboxyl-cavitand 1 or tetrakis(4-carboxyphenyl)-cavitand 2 as a hemisphere and four molecules of 2-aminopyrimidine (2-AP) or tetrahydro-2-pyrimidinone (THP) as an equatorial hydrogen-bonding linker self-assemble into a capsule [(1)2.(2-AP)4] (3), [(1)2.(THP)4] (4), [(2)2.(2-AP)4] (5), or [(2)2.(THP)4] (6), respectively, via 16 hydrogen bonds. These capsules provide isolated nanospace and can encapsulate one guest molecule (7-13) in solution. Each capsule has a different cavity size and shows particular guest selectivity on the competitive encapsulation experiments.

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