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1.
Eur Rev Med Pharmacol Sci ; 27(21): 10396-10402, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37975362

RESUMO

OBJECTIVE: To screen for geriatric syndromes in older in-hospital patients and investigate their relationship with mortality. PATIENTS AND METHODS: Demographic data, comorbidities, and medical history of the patients were recorded. Anthropometric measurements were obtained at 72 hours after hospital admission. The Mini Nutritional Assessment-Short Form, strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) sarcopenia screening questionnaire, Katz Activities of Daily Living scale, Lawton-Brody instrumental activities of daily living scale, the fatigue, resistance, ambulation, illness, and loss of weight (FRAIL) scale and the Eating Assessment Test-10 (EAT-10) screening test were used to assess geriatric syndromes. All patients were evaluated for delirium, pain, falls, polypharmacy, sleep disorders, incontinence, and pressure injury by the same researcher. RESULTS: A total of 85 patients were included in the study. The mean age was 75±7 years (range: 66-97). During hospital follow-up, 15.3% (n=13) of the patients died and 84.7% (n=72) were discharged. The median length of stay was 19 days (range: 3-126 days). In the multivariate analysis, frailty (hazard ratio: 2.67, 95% CI: 1.41-5.06, p=0.003) was found to be associated with in-hospital mortality. CONCLUSIONS: Frailty is an independent risk factor for in-hospital mortality in older adults.


Assuntos
Fragilidade , Sarcopenia , Humanos , Idoso , Idoso de 80 Anos ou mais , Fragilidade/diagnóstico , Idoso Fragilizado , Atividades Cotidianas , Mortalidade Hospitalar , Avaliação Geriátrica , Sarcopenia/diagnóstico
2.
Clin Rheumatol ; 39(12): 3707-3713, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32458244

RESUMO

BACKGROUND: There has been a substantial improvement in classifying patients with primary Sjögren's syndrome (pSS), with the new 2016 ACR/EULAR classification criteria. It was aimed to investigate the potential role of parotid elastography in the classification of patients with pSS, as well as the clinical diagnosis of those who do not otherwise fulfil the criteria. METHOD: This is a cross-sectional analysis of patients with pSS followed up in tertiary out-patient rheumatology clinic. Patients' medical records were retrospectively investigated whether or not clinically diagnosed pSS patients fulfil 2016 ACR/EULAR criteria sets. Elastographic evaluation of parotid and submandibular glands bilaterally was performed when presented for follow-up. Strain ratio, shear wave velocity and Pascal values of the glands were obtained. RESULTS: Clinical data on 179 patients with Sjögren's syndrome were investigated. Ninety-six patients with pSS and 30 gender and age-matched healthy controls were included in the study. Eighty-six percent of the clinically diagnosed patients satisfied the 2016 ACR /EULAR criteria and were considered 'criteria patients', and the remaining were considered 'non-criteria patients'. Both criteria and non-criteria patients had significantly higher parotid strain ratio and submandibular velocity compared with healthy controls (p < 0.001 and p < 0.001 for parotid strain ratio and p < 0.001 and p = 0.016 for submandibular velocity, respectively). Replacing labial gland biopsy findings with parotid strain ratio in the new classification criteria resulted in similar sensitivity and lower specificity, 91.6% and 80%, respectively. CONCLUSION: Parotid shear elastography is an easy and noninvasive method and might be a useful tool for the classification of patients with pSS, especially when labial gland biopsy is not feasible. Key Points • Salivary gland elastography (SGE) is a useful tool for the classification of patients with pSS. • SGE could be performed instead of labial biopsy without changing the diagnostic power of classification criteria.


Assuntos
Técnicas de Imagem por Elasticidade , Síndrome de Sjogren , Biópsia , Estudos Transversais , Humanos , Glândula Parótida/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e Especificidade , Síndrome de Sjogren/diagnóstico por imagem
3.
Scand J Rheumatol ; 48(4): 315-319, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30786810

RESUMO

Background: Chronic inflammation, as determined by persistently elevated acute-phase reactants in attack-free periods, can occasionally be observed in patients with familial Mediterranean fever (FMF) and is suggested to be a risk factor for the development of amyloidosis. We aimed to investigate the underlying causes of chronic inflammation in FMF patients and its association with amyloidosis in long-term follow-up. Method: Electronic medical records of FMF patients who had regular follow-up for ≥ 5 years in our cohort were utilized. As part of routine evaluation, detailed history, physical examination, and pertinent laboratory and radiographic investigations were performed in all patients to determine potential causes of elevated C-reactive protein (CRP) levels. Results: The study included 146 FMF patients who had no evidence of amyloidosis at baseline and had regular follow-up for ≥ 5 years. Thirty-seven patients (25.3%) were found to have chronic inflammation in the disease course. Twenty-five (67.5%) of them had either very frequent attacks or chronic manifestations of disease. In the entire study group, amyloidosis developed in five patients (3.42%) during the 5 year follow-up, four in the FMF with chronic inflammation group (10.8%), and only one of the 109 patients without chronic inflammation (odds ratio 13.09, 95% confidence interval 1.41-121.2). Conclusions: The results suggest that persistently high CRP levels during the attack-free periods may be a strong risk factor for the development of amyloidosis in patients with FMF. The vast majority of FMF patients with chronic inflammation had active FMF.


Assuntos
Proteínas de Fase Aguda/imunologia , Amiloidose , Febre Familiar do Mediterrâneo , Inflamação/sangue , Adulto , Amiloidose/diagnóstico , Amiloidose/etiologia , Amiloidose/imunologia , Proteína C-Reativa/análise , Registros Eletrônicos de Saúde/estatística & dados numéricos , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/imunologia , Feminino , Seguimentos , Humanos , Masculino , Monitorização Fisiológica/métodos , Monitorização Fisiológica/estatística & dados numéricos , Medição de Risco , Fatores de Risco
4.
Z Rheumatol ; 76(5): 458-460, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28197771

RESUMO

Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic and plasmacytic infiltration of the exocrine glands. Tubulointerstitial nephritis (TIN) is the most common type of renal involvement in pSS. However, clinically significant renal involvement is uncommon. Granulomatous interstitial nephritis (GIN) is a rare histopathological entity characterized by the presence of granulomas against a background of interstitial inflammation. GIN is not a typical and commonly seen form of TIN in pSS. Herein, we report on a patient who was concurrently diagnosed with pSS and GIN and was treated successfully with rituximab (RTX). pSS should be considered in the differential diagnosis of GIN, and RTX may be a good option in the treatment of this patient group.


Assuntos
Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/patologia , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/patologia , Rituximab/administração & dosagem , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/patologia , Adulto , Anti-Inflamatórios/administração & dosagem , Diagnóstico Diferencial , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Resultado do Tratamento
5.
J Wound Care ; 24(12): 606, 608-11, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26654742

RESUMO

OBJECTIVE: N-acetyl cysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties. It has multiple potential uses-including as an aid to wound healing-supported by varying levels of evidence. Pressure ulcers (PUs) are a major problem affecting older and bed-bound patients, and are associated with significant morbidity, mortality, and health-care costs. We aimed to study whether topical NAC treatment may be useful in non-healing PUs in a prospective case study in two debilitated nursing home residents suffering from a total of three treatment-resistant PUs. METHOD: PUs were staged as described by the National Pressure Ulcer Advisory Panel. The ulcers were measured at the beginning and weekly thereafter with a standard wound measuring paper ruler. RESULTS: The first patient had a category 3 pressure ulcer and the second patient had one category 3 and one category 4 ulcer. Topical NAC vial administration significantly improved healing in all three PUs without any side effects. CONCLUSION: Our data indicate that NAC may be used in treatment-resistant PUs successfully.


Assuntos
Antioxidantes/uso terapêutico , Cisteína/uso terapêutico , Úlcera por Pressão/tratamento farmacológico , Vasodilatadores/uso terapêutico , Cicatrização/efeitos dos fármacos , Administração Tópica , Idoso de 80 Anos ou mais , Feminino , Instituição de Longa Permanência para Idosos , Humanos , Casas de Saúde , Estudos Prospectivos , Resultado do Tratamento
7.
Mol Biol Rep ; 41(9): 5549-55, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24934313

RESUMO

C-type natriuretic peptide (CNP) signaling has been implicated as an important regulator of chondrogenic differentiation during endochondral bone development. This preliminary study further investigated the putative effectors and/or targets of CNP signaling in transforming growth factor (TGF)-ß induced in vitro chondrogenic differentiation of mesenchymal stem cells (MSCs). Previously characterized human trabecular bone derived MSCs were induced either with only TGF-ß1 or with a combination of TGF-ß1 and CNP in micromass culture for 10 or 20 days. Genome wide gene expression profile changes in between these two groups were analyzed on day-10 or day-20 of culture. Results revealed that there were only 7 genes, whose expression change was fourfolds or higher in TGF-ß1 and CNP fed group in comparison to only TGF-ß1 fed group. The up-regulated genes included matrilin-3 (MATN3), engulfment and cell motility 1 (ELMO1), CD24, and DCN1, defective in cullin neddylation 1, domain containing 1 (DCUN1D1). The down-regulated genes, on the other hand, included LIM domain kinase 2 (LIMK2), Ewing sarcoma breakpoint region 1, and guanine nucleotide binding protein (G protein), gamma 12 (GNG12). The up-regulation of MATN3 was confirmed on the basis of RT-PCR. The known literature on both CNP signaling and MATN3 function in chondrogenesis match with each other and suggest MATN3 as a putative effector and/or target of CNP signaling during this process.


Assuntos
Diferenciação Celular , Proteínas Matrilinas/metabolismo , Células-Tronco Mesenquimais/citologia , Peptídeo Natriurético Tipo C/farmacologia , Fator de Crescimento Transformador beta1/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Osso e Ossos/citologia , Osso e Ossos/metabolismo , Antígeno CD24/genética , Antígeno CD24/metabolismo , Proteínas de Ligação a Calmodulina/genética , Proteínas de Ligação a Calmodulina/metabolismo , Condrogênese/genética , Análise por Conglomerados , Biologia Computacional , Regulação para Baixo , Subunidades gama da Proteína de Ligação ao GTP/genética , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Humanos , Quinases Lim/genética , Quinases Lim/metabolismo , Proteínas Matrilinas/genética , Análise em Microsséries , Proteína EWS de Ligação a RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Regulação para Cima
8.
Biotech Histochem ; 89(1): 23-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23848547

RESUMO

Copper sulfate can cause different pathologies in different organ systems during development. We determined the effects of toxic levels of copper sulfate on brain development in term Hubbard broiler chicks using stereological and biochemical analyses. Hubbard broiler chicken eggs were divided into three groups: controls with no treatment, sham-treated animals and an experimental group. On day 1, 0.1 ml saline was injected into the air chambers of the sham and experimental groups. The experimental group received also 50 µg copper sulfate. At term (day 21), all chick brains were removed and their volumes were determined using the Cavalieri volume estimation. Parallel biochemical analyses were carried out for glutathione and malondialdehyde levels in the brain tissues as indicators of oxidative damage. With copper treatment, the mean brain volume (8079 µm(3)) was significantly decreased compared to both the control (10075 µm(3)) and sham (9547 µm(3)) groups. Copper treatment (143.8 nmol/g tissue) showed significantly decreased malondialdehyde levels compared to the control (293.6 nmol/g tissue) and sham groups (268.8 nmol/g tissue). Copper treatment (404.5 nmol/g tissue) showed significantly increased malondialdehyde levels compared to the control (158.6 nmol/g tissue) and sham (142.8 nmol/g tissue) groups. The morphological and biochemical parameters we measured demonstrated that in term Hubbard broiler chicks, toxic levels of copper sulfate cause developmental and oxidative brain damage.


Assuntos
Encéfalo/efeitos dos fármacos , Galinhas/fisiologia , Sulfato de Cobre/toxicidade , Animais , Apoptose/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Glutationa/análise , Malondialdeído/análise , Tamanho do Órgão/efeitos dos fármacos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos
9.
West Indian med. j ; 61(9): 870-872, Dec. 2012. ilus, tab
Artigo em Inglês | LILACS | ID: lil-694358

RESUMO

OBJECTIVE: In this study, we aimed to investigate endothelial functions in primary Sjögren syndrome. METHODS: Thirty-five patients with primary Sjögren syndrome and 20 age and sexmatched healthy volunteers were recruited to the present study. Flow mediated dilatation of brachial artery and carotid intimamedia thickness were measured in the study population. RESULTS: Carotid intimamedia thickness values were similar between groups (0.50 ± 0.10, 0.53 ± 0.08, p > 0.05). Flow mediated dilatation of the brachial artery was disrupted in the primary Sjögren syndrome group (7% vs 12%, p = 0.002). CONCLUSION: There is endothelial dysfunction in patients with primary Sjögren syndrome, although they had comparable carotid intimamedia thickness with the healthy control group.


OBJETIVO: Este estudio se encaminó a investigar las funciones endoteliales en el síndrome de Sjögren primario. MÉTODOS: Para el presente estudio, se reclutaron treinta y cinco pacientes con síndrome de Sjögren primario y 20 voluntarios sanos apareados por edad y sexo. La dilatación mediada por flujo observada en la arteria braquial, y el espesor íntimamedia carotídeo fueron medidos en la población bajo estudio. RESULTADOS: Los valores del espesor íntimamedia carotídeo fueron similares entre los grupos (0.50 ± 0.10, 0.53 ± 0.08, p > 0.05). La dilatación mediada por flujo de la arteria braquial, estaba alterada en el grupo de síndrome del Sjögren primario (7% frente a 12%, p = 0.002). CONCLUSIÓN: Hay una disfunción endotelial en los pacientes con el síndrome de Sjögren primario, aunque estos tenían un espesor íntimamedia carotídeo comparable con el grupo de control saludable.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Braquial/fisiopatologia , Espessura Intima-Media Carotídea , Endotélio Vascular/fisiopatologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/fisiopatologia , Vasodilatação/fisiologia , Hiperemia/fisiopatologia , Valores de Referência
10.
J Mol Histol ; 43(5): 497-508, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22714108

RESUMO

This study investigated the involvement of CNP-3, chick homologue for human C-type natriuretic peptide (CNP), in TGF-ß1 induced chondrogenic differentiation of chicken bone marrow-derived mesenchymal stem cells (MSCs). Chondrogenic differentiation of MSCs in pellet cultures was induced by TGF-ß1. Chondrogenic differentiation and glycosaminoglycan synthesis were analyzed on the basis of basic histology, collagen type II expression, and Alcian blue staining. Antibodies against CNP and NPR-B were used to block their function during these processes. Results revealed that expression of CNP-3 and NPR-B in MSCs were regulated by TGF-ß1 in monolayer cultures at mRNA level. In pellet cultures of MSCs, TGF-ß1 successfully induced chondrogenic differentiation and glycosaminoglycan synthesis. Addition of CNP into the TGF-ß1 supplemented chondrogenic differentiation medium further induced the glycosaminoglycan synthesis and hypertrophy of differentiated chondrocytes in these pellets. Pellets induced with TGF-ß1 and treated with antibodies against CNP and NPR-B, did show collagen type II expression, however, Alcian blue staining showing glycosaminoglycan synthesis was significantly suppressed. In conclusion, CNP-3/NPR-B signaling may strongly be involved in synthesis of glycosaminoglycans of the chondrogenic matrix and hypertrophy of differentiated chondrocytes during TGF-ß1 induced chondrogenic differentiation of MSCs.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Condrócitos , Glicosaminoglicanos/biossíntese , Peptídeo Natriurético Tipo C , Receptores do Fator Natriurético Atrial/metabolismo , Animais , Células da Medula Óssea , Embrião de Galinha , Galinhas/metabolismo , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Condrogênese/genética , Colágeno Tipo X/metabolismo , Hipertrofia/metabolismo , Células-Tronco Mesenquimais , Peptídeo Natriurético Tipo C/genética , Peptídeo Natriurético Tipo C/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/administração & dosagem , Fator de Crescimento Transformador beta1/genética
11.
J Mol Histol ; 41(4-5): 247-58, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20721606

RESUMO

Recent investigations credited important roles to C-type natriuretic peptide (CNP) signaling during chondrogenesis. This study investigated the putative role of CNP in transforming growth factor (TGF)-ß1 induced in vitro chondrogenic differentiation of mesenchymal stem cells (MSCs) in pellet culture. MSCs were derived from human trabecular bone and were characterized on the basis of their cell surface antigens and adipogenic, osteogenic, and chondrogenic differentiation potential. TGF-ß1 induced chondrogenic differentiation and glycosaminoglycan (GAG) synthesis was analyzed on the basis of basic histology, collagen type II, Sox 9 and aggrecan expressions, and Alcian blue staining. Results revealed that human trabecular bone-derived MSCs express CNP and NPR-B analyzed on the basis of RT-PCR and immunohistochemistry. In pellet cultures of MSCs TGF-ß1 successfully induced chondrogenic differentiation and GAG synthesis. RT-PCR analyses of both CNP and NPR-B during this process revealed an activation of this signaling pathway in response to TGF-ß1. Similar cultures induced with TGF-ß1 and treated with different doses of CNP showed that CNP supplementation at 10(-8) and 10(-7) M concentrations significantly increased GAG synthesis in a dose dependent manner, whereas at 10(-6) M concentration this stimulatory effect was diminished. In conclusion, CNP/NPR-B signaling pathway is activated during TGF-ß1 induced chondrogenic differentiation of human trabecular bone-derived MSCs and may strongly be involved in GAG synthesis during this process. This effect is likely to be a dose-dependent effect.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Glicosaminoglicanos/biossíntese , Células-Tronco Mesenquimais/citologia , Peptídeo Natriurético Tipo C/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Idoso , Antígenos de Superfície/metabolismo , Osso e Ossos/citologia , Separação Celular , Humanos , Imuno-Histoquímica , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Peptídeo Natriurético Tipo C/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
Biol Trace Elem Res ; 133(3): 335-41, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19597723

RESUMO

Copper is an essential trace element that is extremely toxic to organisms and organs at high doses. We have investigated the histological and biochemical effects of a toxic dose of copper sulfate on the liver of term Ross broiler chicks. Fertilized eggs were divided into three groups: experimental, injected with 50 mcg/0.1 ml copper sulfate in the air chambers on day 1; sham, injected with 0.1 ml saline; and control, no injection. Term chicks were killed and their livers investigated histologically, with hematoxylin-eosin-stained sections examined under light microscopy, and biochemically, for malondialdehyde and glutathione levels. Histological examinations showed copper-treated samples with granular degeneration and necrosis of hepatocytes and impairment to the cell lining of the remark cords. The samples had a congestive appearance, with blood in the vena centralis and sinusoids, slight connective tissue increase, and lymphocyte infiltration. Control and sham group sections had normal appearances. As oxidative damage parameters, in the copper-treated group, malondialdehyde levels were increased and glutathione levels decreased. In the sham and control groups, there were no significant differences. At this toxic dose, copper sulfate shows oxidative damage according to the histology of term chick liver that are confirmed biochemically by the changes in malondialdehyde and glutathione levels.


Assuntos
Sulfato de Cobre/farmacologia , Fígado/efeitos dos fármacos , Ciências da Nutrição Animal , Animais , Bioquímica/métodos , Galinhas , Glutationa/química , Fígado/metabolismo , Fígado/patologia , Linfócitos/efeitos dos fármacos , Malondialdeído/química , Oxirredução , Estresse Oxidativo , Oxigênio/química , Oligoelementos/farmacologia
13.
World J Gastroenterol ; 13(23): 3183-8, 2007 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-17589896

RESUMO

AIM: To investigate the apoptotic process of cells within the intestinal metaplasia areas co-localizing with chronic gastritis and gastric carcinomas and to analyze the involvement of proteins regulating apoptosis in the process of intestinal metaplasia related gastric carcinogenesis. METHODS: Forty-two gastric carcinoma and seventeen chronic gastritis cases were included in this study. All cases were examined for the existence of intestinal metaplasia. Ten cases randomly selected from each group were processed for TUNEL assay. TUNEL positive cells within the intestinal metaplasia areas, co-localizing either to gastric carcinoma or chronic gastritis, were counted and converted to apoptotic indices. In addition, p53, bcl-2 and bax expression patterns within these tissues were analyzed on the basis of immunohistochemistry. RESULTS: Twenty-eight of the cases were intestinal and 14 of the cases were diffuse type adenocarcinomas. 64% (27/42) of the gastric carcinoma cases had intestinal metaplasia. Intestinal metaplasia co-localized more with intestinal type carcinomas compared with diffuse type carcinomas [75% (21/28) vs 42% (6/14), respectively; P

Assuntos
Apoptose , Neoplasias Gástricas/patologia , Adulto , Idoso , Feminino , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Metaplasia , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/análise , Neoplasias Gástricas/química , Proteína Supressora de Tumor p53/análise , Proteína X Associada a bcl-2/análise
14.
Eur J Hum Genet ; 15(10): 1023-8, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17579668

RESUMO

Pseudoachondroplasia (PSACH) is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein (COMP). Clinical diagnosis of PSACH is based primarily on family history, physical examination, and radiographic evaluation, and is sometimes extremely difficult, particularly in adult patients. Genetic diagnosis based on DNA sequencing, on the other hand, can be expensive, time-consuming, and intensive because COMP mutations may be scattered throughout the gene. However, there is evidence that decreased plasma COMP concentration may serve as a diagnostic marker in PSACH, particularly in adult patients. Here, we report the serum and/or plasma COMP concentration-based differential diagnosis of a family with affected adult members. The mean serum and/or plasma COMP concentrations of the three affected family members alive (0.69+/-0.15 and/or 0.81+/-0.08 microg/ml, respectively) were significantly lower than those of an age-compatible control group of 21 adults (1.52+/-0.37 and/or 1.37+/-0.36 microg/ml, respectively; P<0.0001). Bidirectional fluorescent DNA sequencing-based genetic diagnosis of these patients revealed a heterozygous mutation for the nucleotide change 1532A>G in exon 14 of the COMP gene, resulting in a substitution of amino acid 511 from aspartic acid to glycine in COMP. Thus, serum and/or plasma COMP concentration may be suggested as an additional diagnostic marker to aid clinical and radiographic findings in suspected cases of PSACH.


Assuntos
Proteínas da Matriz Extracelular/sangue , Glicoproteínas/sangue , Osteocondrodisplasias/sangue , Osteocondrodisplasias/diagnóstico , Acondroplasia/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Biomarcadores/sangue , Proteína de Matriz Oligomérica de Cartilagem , Consanguinidade , DNA/genética , Diagnóstico Diferencial , Nanismo/diagnóstico , Proteínas da Matriz Extracelular/genética , Feminino , Genes Dominantes , Glicoproteínas/genética , Humanos , Masculino , Proteínas Matrilinas , Pessoa de Meia-Idade , Osteocondrodisplasias/genética , Linhagem , Mutação Puntual
15.
Tohoku J Exp Med ; 208(2): 103-7, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16434832

RESUMO

Achondroplasia is the most common genetic form of dwarfism inherited as an autosomal dominant disorder. Individuals affected with achondroplasia have impaired ability to form bone from cartilage (endochondral bone formation). Homozygous achondroplasia is a neonatal lethal condition. The vast majority of patients with achondroplasia have a G-to-A transition at position 1138 of the fibroblast growth factor receptor 3 (FGFR3) cDNA sequence, resulting in the Gly-to-Arg substitution at position 380 of the FGFR3 protein. This mutation has been diagnosed by SfcI digestion of amplified genomic DNA. However, it has also been demonstrated that the SfcI digestion protocol does not consistently distinguish between DNA samples heterozygous and homozygous for the G1138A substitution. This study was designed to improve the molecular diagnosis based on the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques for the FGFR3 G1138A mutation. The newly designed forward primer contains one mismatch (G at position 1136) from the FGFR3 cDNA sequence (A at position 1136), thereby creating a PstI site (CTGCAG at positions 1134 to 1139) in the amplified DNA from alleles containing the G1138A mutation. The PCR-RFLP technique based on the PstI digestion of amplified genomic DNA with a novel forward primer shows 100% accuracy in diagnosis of the G1138A mutation in heterozygous and homozygous individuals.


Assuntos
Acondroplasia/diagnóstico , Mutação , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Sequência de Bases , Triagem de Portadores Genéticos , Homozigoto , Humanos , Técnicas de Diagnóstico Molecular , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição
16.
Curr Cancer Drug Targets ; 5(4): 249-66, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15975046

RESUMO

Angiogenesis, the formation of new blood vessels, is essential for tumor growth, progression and metastasis. The development of agents that target tumor vasculature is ultimately dependent on the availability of appropriate preclinical screening assays. The chorioallantoic membrane (CAM) assay is well established and widely used as a model to examine angiogenesis, and anti-angiogenesis. This review 1) summarizes the currently used angiogenesis assays and the importance of CAM model among them; 2) summarizes the current knowledge about the development and structure of the CAM's capillary bed; 3) reports findings regarding the role played by molecular signaling pathways in angiogenesis process; 4) discusses the use, advantages and limitations of the CAM as a model for studying tumor angiogenesis and invasiveness, as well as development of angiogenic and/or anti-angiogenic agents; 5) discusses the importance of standardization of the major methodologies for all aspects of the use of the CAM in angiogenesis-related studies; 6) and finally, summarizes major findings regarding the agents developed by the use of CAM model in the study of tumor angiogenesis, invasion and development of anti-angiogenic agents.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Membrana Corioalantoide/irrigação sanguínea , Invasividade Neoplásica/fisiopatologia , Neoplasias/irrigação sanguínea , Neovascularização Patológica/fisiopatologia , Inibidores da Angiogênese/química , Animais , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/instrumentação , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Modelos Biológicos , Invasividade Neoplásica/prevenção & controle , Neoplasias/prevenção & controle , Neovascularização Patológica/embriologia , Neovascularização Patológica/prevenção & controle
17.
Dev Dyn ; 223(2): 241-53, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11836788

RESUMO

Products of the Frizzled family of tissue polarity genes have been identified as putative receptors for the Wnt family of signaling molecules. Wnt-signaling is implicated in the regulation of limb mesenchymal chondrogenesis, and our recent study indicates that N-cadherin and related activities are functionally involved in Wnt-7a-mediated inhibition of chondrogenesis. By using an in vitro high-density micromass culture system of chick limb mesenchymal cells, we have analyzed the spatiotemporal expression patterns and the effects on chondrogenesis of RCAS retroviral-mediated misexpression of Chfz-1 and Chfz-7, two Frizzled genes implicated in chondrogenic regulation. Chfz-1 expression was localized at areas surrounding the cartilaginous nodules at all time points examined, whereas Chfz-7 expression was limited to cellular aggregates during initial mesenchymal condensation, and subsequently was down-regulated from the centers toward the periphery of cartilage nodules at the time of chondrogenic differentiation, resembling the pattern of N-cadherin expression. Chondrogenesis in vitro was inhibited and limited to a smaller area of the culture upon misexpression of Chfz-7, but not affected by Chfz-1 misexpression. Analyses of cellular condensation and chondrogenic differentiation showed that the inhibitory action of Chfz-7 is unlikely to be at the chondrogenic differentiation step, but instead affects the earlier precartilage aggregate formation event. At 24 hr, expression of N-cadherin, a key component of the cellular condensation phase of chondrogenesis, was delayed/suppressed in Chfz-7 misexpressing cultures, and was limited to a significantly smaller cellular condensation area within the entire culture at 48 hr, when compared with control cultures. Chfz-1 misexpressing cultures appeared similar to control cultures at all time points. However, neither Chfz-1 nor Chfz-7 misexpression affected mesenchymal cell proliferation in vitro. These results suggest that Chfz-7 is active in regulating N-cadherin expression during the process of limb mesenchymal chondrogenesis and that Chfz-1 and Chfz-7 are involved in different Wnt-signaling pathways.


Assuntos
Proteínas Aviárias , Caderinas/fisiologia , Condrogênese/fisiologia , Extremidades/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Mesoderma/metabolismo , Proteínas Proto-Oncogênicas , Receptores de Superfície Celular/fisiologia , Receptores Acoplados a Proteínas G , Animais , Caderinas/biossíntese , Caderinas/genética , Divisão Celular , Células Cultivadas/metabolismo , Embrião de Galinha , Condrócitos/citologia , Condrócitos/metabolismo , Condrogênese/genética , Colágeno Tipo II/biossíntese , Receptores Frizzled , Técnicas de Cultura de Órgãos , Proteínas/fisiologia , RNA Mensageiro/biossíntese , Receptores de Superfície Celular/biossíntese , Receptores de Superfície Celular/genética , Receptores de Neurotransmissores/biossíntese , Receptores de Neurotransmissores/genética , Receptores de Neurotransmissores/fisiologia , Proteínas Recombinantes de Fusão/fisiologia , Transfecção , Proteínas Wnt
18.
Exp Cell Res ; 273(2): 197-203, 2002 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-11822875

RESUMO

Wnt signaling has been implicated in the regulation of limb mesenchymal chondrogenesis. In this study, we have analyzed the molecular mechanism of Wnt-7a inhibition of chondrogenic differentiation by examining the involvement of mitogen-activated protein kinase (MAPK) pathways, i.e., Erk and p38. The combination of Wnt-7a misexpression and Erk inhibition partially recovers Wnt-7a inhibition of chondrogenic differentiation, whereas the combination of Wnt-7a misexpression and p38 inhibition acts in a synergistic chondro-inhibitory fashion. Although Wnt-7a misexpression has no direct effect on Erk signaling, it increases the activity of one of the ultimate targets of the MAPK pathway, c-jun, a major component of the activator protein-1 (AP-1) transcription factor complex. In addition, Wnt-7a misexpression enhances the activity of an AP-1 promoter-luciferase reporter construct by approximately 2.3-fold in vitro. Interestingly, misexpression of wild-type N-cadherin in these micromass cultures suppresses the activity of the same AP-1 promoter by approximately 40%, whereas misexpression of an extracellular 390-amino-acid N-terminal deletion mutant of N-cadherin has a stimulatory effect on the AP-1 promoter activity by approximately 2.6-fold. Thus, our results suggest that at least a part of the chondro-inhibitory effect of Wnt-7a misexpression may involve AP-1 transcription factor stimulation. Furthermore, a very tightly regulated level of AP-1 activity is necessary for the process of limb mesenchymal chondrogenesis, and signals from Wnt-ligands (e.g., Wnt-7a), cell adhesion molecules (e.g., N-cadherin), and MAPK pathways (e.g., Erk and p38) are interactively involved in this regulation.


Assuntos
Proteínas Aviárias , Caderinas/metabolismo , Condrogênese/fisiologia , Regulação da Expressão Gênica , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas/metabolismo , Fator de Transcrição AP-1/genética , Animais , Caderinas/genética , Adesão Celular , Embrião de Galinha , Ativação Enzimática , Mesoderma/citologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Proteínas Wnt , Proteínas Quinases p38 Ativadas por Mitógeno
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