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1.
Lasers Med Sci ; 35(8): 1821-1830, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32372237

RESUMO

Pseudoxanthoma elasticum (PXE, OMIM 264800) is a rare autosomal recessive disorder with ectopic mineralization and fragmentation of elastin fibers. It is caused by mutations of the ABCC6 gene that leads to decreased serum levels of inorganic pyrophosphate (PPi) anti-mineralization factor. The occurrence of severe complications among PXE patients highlights the importance of early diagnosis so that prompt multidisciplinary care can be provided to patients. We aimed to examine dermal connective tissue with nonlinear optical (NLO) techniques, as collagen emits second-harmonic generation (SHG) signal, while elastin can be excited by two-photon excitation fluorescence (TPF). We performed molecular genetic analysis, ophthalmological and cardiovascular assessment, plasma PPi measurement, conventional histopathological examination, and ex vivo SHG and TPF imaging in five patients with PXE and five age- and gender-matched healthy controls. Pathological mutations including one new variant were found in the ABCC6 gene in all PXE patients and their plasma PPi level was significantly lower compared with controls. Degradation and mineralization of elastin fibers and extensive calcium deposition in the mid-dermis was visualized and quantified together with the alterations of the collagen structure in PXE. Our data suggests that NLO provides high-resolution imaging of the specific histopathological features of PXE-affected skin. In vivo NLO may be a promising tool in the assessment of PXE, promoting early diagnosis and follow-up.


Assuntos
Microscopia Óptica não Linear/métodos , Pseudoxantoma Elástico/diagnóstico por imagem , Pele/diagnóstico por imagem , Estudos de Casos e Controles , Colágeno/metabolismo , Tecido Conjuntivo/patologia , Elastina/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pseudoxantoma Elástico/metabolismo , Pseudoxantoma Elástico/patologia , Pele/metabolismo , Pele/patologia
2.
Biochim Biophys Acta Rev Cancer ; 1873(2): 188354, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32119940

RESUMO

Fibrillins constitute a family of large extracellular glycoproteins which multimerize to form microfibrils, an important structure in the extracellular matrix. It has long been assumed that fibrillin-2 was barely present during postnatal life, but it is now clear that fibrillin-2 molecules form the structural core of microfibrils, and are masked by an outer layer of fibrillin-1. Mutations in fibrillins give rise to heritable connective tissue disorders, including Marfan syndrome and congenital contractural arachnodactyly. Fibrillins also play an important role in matrix sequestering of members of the transforming growth factor-ß family, and in context of Marfan syndrome excessive TGF-ß activation has been observed. TGF-ß activation is highly dependent on integrin binding, including integrin αvß8 and αvß6, which are upregulated upon TGF-ß exposure. TGF-ß is also involved in tumor progression, metastasis, epithelial-to-mesenchymal transition and tumor angiogenesis. In several highly vascularized types of cancer such as hepatocellular carcinoma, a positive correlation was found between increased TGF-ß plasma concentrations and tumor vascularity. Interestingly, fibrillin-1 has a higher affinity to TGF-ß and, therefore, has a higher capacity to sequester TGF-ß compared to fibrillin-2. The previously reported downregulation of fibrillin-1 in tumor endothelium affects the fibrillin-1/fibrillin-2 ratio in the microfibrils, exposing the normally hidden fibrillin-2. We postulate that fibrillin-2 exposure in the tumor endothelium directly stimulates tumor angiogenesis by influencing TGF-ß sequestering by microfibrils, leading to a locally higher active TGF-ß concentration in the tumor microenvironment. From a therapeutic perspective, fibrillin-2 might serve as a potential target for future anti-cancer therapies.


Assuntos
Aracnodactilia/genética , Contratura/genética , Fibrilina-2/genética , Síndrome de Marfan/genética , Neoplasias/genética , Neovascularização Patológica/genética , Animais , Aracnodactilia/patologia , Tecido Conjuntivo/patologia , Contratura/patologia , Modelos Animais de Doenças , Endotélio Vascular/patologia , Fibrilina-2/metabolismo , Humanos , Síndrome de Marfan/patologia , Mutação , Neoplasias/irrigação sanguínea , Neoplasias/patologia , Neovascularização Patológica/patologia , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral/genética
3.
Folia Histochem Cytobiol ; 58(1): 37-45, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176314

RESUMO

INTRODUCTION: Graves' orbitopathy (GO) is a complication in Graves' disease (GD) that causes disfigurement and sometimes blindness. The pathogenesis of GO remains unknown, while its symptoms demonstrate dependence between the thyroid gland and the orbit. The ongoing inflammatory process in retrobulbar tissue results in its remodeling characterized by increased volume of the orbital contents involving adipose tissue, with fibrosis and adipogenesis as predominant features. This study was aimed at the immunohistochemical verification of potential contribution and correlation between orbital expressions of IGF-1R, CD34, Foxp-3, PPAR-γ and CD4, CD68, TGF-ß, FGF-ß in severe and mild (long-lasting) GO. MATERIAL AND METHODS: Forty-one orbital tissue specimens - 22 patients with severe GO, 9 patients with mild GO and 10 patients undergoing blepharoplasty as a control group - were processed by routine immunohistochemistry. RESULTS: Increased IGF-1R, CD34 and Foxp-3 expression was found in both severe and mild GO, yet a significant correlation between CD34 and CD4, CD68, TGF-ß, FGF-ß expressions was observed in long-lasting GO. CONCLUSIONS: CD34 expression is proposed to be the marker of orbital tissue remodeling in the course of mild GO.


Assuntos
Biomarcadores/metabolismo , Oftalmopatia de Graves/metabolismo , Órbita/metabolismo , Adulto , Tecido Conjuntivo/metabolismo , Tecido Conjuntivo/patologia , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Oftalmopatia de Graves/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Órbita/patologia
4.
Am J Sports Med ; 48(5): 1168-1174, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32150441

RESUMO

BACKGROUND: Recently, a hypertrophic labrum has been reported in the absence of hip dysplasia, which can possibly contribute to an acetabular labral tear. PURPOSE: To compare the clinical outcomes and complications, including the incidence of iatrogenic acetabular labrum and cartilage injury, in patients with tears of hypertrophic versus morphologically normal acetabular labra over a minimum follow-up period of 2 years and to assess the morphologic changes at follow-up computed tomography arthrography in the 2 groups. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Between January 2010 and December 2016, 20 patients (22 hips) with a hypertrophic labrum underwent arthroscopic hip surgery. A total of 22 patients (22 hips) without a hypertrophic labrum were assigned to the control group based on matching criteria, including age, sex, body mass index, labral tear, and labral repair. Clinical outcomes were assessed with the visual analog scale score, UCLA activity scale score (University of California, Los Angeles), and modified Harris Hip Score. Radiologic outcomes were assessed through serial radiography. Patients were followed for at least 2 years. RESULTS: The mean age at surgery was 42 years. The most common cause of arthroscopic surgery in the study group was an isolated acetabular labral tear without any bony structural abnormalities (68.2%, 15 of 22 hips). All improvements in both groups were statistically significant at the last postoperative follow-up (P < .001). Although the radiologic and clinical outcomes were not significantly different between the groups, the complication rates, including iatrogenic labral perforations and cartilage injury, were significantly higher in patients with hypertrophic acetabular labral tears (9 vs 3, P = .042). The patient-reported satisfaction scores at the last postoperative follow-up were 8.4 and 7.9 in the study and control groups, respectively (P = .351). CONCLUSION: The high rates of patient-reported satisfaction and the clinical outcomes after arthroscopic repair in both groups are encouraging. Arthroscopic treatment in patients with hypertrophic acetabular labral tears should be carefully performed to prevent iatrogenic injury during the surgery, and isolated hypertrophic labral tears can have good results after repair.


Assuntos
Acetábulo/cirurgia , Tecido Conjuntivo/lesões , Tecido Conjuntivo/patologia , Lesões do Quadril/cirurgia , Acetábulo/diagnóstico por imagem , Acetábulo/lesões , Adulto , Artroscopia , Tecido Conjuntivo/cirurgia , Articulação do Quadril , Humanos , Los Angeles , Estudos Retrospectivos , Resultado do Tratamento
5.
BMC Pulm Med ; 20(1): 21, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964365

RESUMO

BACKGROUND: Lung fibrosis is a serious life-threatening condition whose manifestation varies according to the localization and characteristics of fibroblasts, which are considered heterogeneous. Therefore, to better understand the pathology and improve diagnosis and treatment of this disease, it is necessary to elucidate the nature of this heterogeneity and identify markers for the accurate classification of human lung fibroblast subtypes. METHODS: We characterized distinct mouse lung fibroblast subpopulations isolated by fluorescence-activated cell sorting (FACS) and performed microarray analysis to identify molecular markers that could be useful for human lung fibroblast classification. Based on the expression of these markers, we evaluated the fibroblast-like cell subtype localization in normal human lung samples and lung samples from patients with idiopathic pulmonary fibrosis (IPF). RESULTS: Mouse lung fibroblasts were classified into Sca-1high fibroblasts and Sca-1low fibroblasts by in vitro biological analyses. Through microarray analysis, we demonstrated CD248 and integrin alpha-8 (ITGA8) as cell surface markers for Sca-1high fibroblasts and Sca-1low fibroblasts, respectively. In mouse lungs, Sca-1high fibroblasts and Sca-1low fibroblasts were localized in the collagen fiber-rich connective tissue and elastic fiber-rich connective tissue, respectively. In normal human lungs and IPF lungs, two corresponding major fibroblast-like cell subtypes were identified: CD248highITGA8low fibroblast-like cells and CD248lowITGA8high fibroblast-like cells, localized in the collagen fiber-rich connective tissue and in the elastic fiber-rich connective tissue, respectively. CONCLUSION: CD248highITGA8low fibroblast-like cells and CD248lowITGA8high fibroblast-like cells were localized in an almost exclusive manner in human lung specimens. This human lung fibroblast classification using two cell surface markers may be helpful for further detailed investigations of the functions of lung fibroblast subtypes, which can provide new insights into lung development and the pathological processes underlying fibrotic lung diseases.


Assuntos
Antígenos CD/metabolismo , Antígenos de Neoplasias/metabolismo , Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/patologia , Cadeias alfa de Integrinas/metabolismo , Pulmão/citologia , Idoso , Animais , Antígenos Ly/metabolismo , Tecido Conjuntivo/patologia , Células do Tecido Conjuntivo , Tecido Elástico , Fibroblastos/classificação , Citometria de Fluxo , Humanos , Técnicas In Vitro , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Pessoa de Meia-Idade , Análise Serial de Tecidos
6.
J Neuropathol Exp Neurol ; 79(1): 102-112, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31803918

RESUMO

Myopathies during chronic graft-versus-host disease (cGvHD) are syndromes for which tissue targets and mechanisms of muscle damage remain incompletely defined. This study reviewed, and pathologically analyzed, 14 cGvHD myopathies, comparing myopathology to other immune myopathies. Clinical features in cGvHD myopathy included symmetric, proximal weakness, associated skin, gastrointestinal and lung disorders, a high serum aldolase (77%), and a 38% 2-year survival. Muscle showed noninflammatory pathology involving all 3 tissue components. Perimysial connective tissue had damaged structure and histiocytic cells. Vessel pathology included capillary loss, and reduced α-l-fucosyl and chondroitin sulfate moieties on endothelial cells. Muscle fibers often had surface pathology. Posttranslational glycosylation moieties on α-dystroglycan had reduced staining and abnormal distribution in 86%. Chondroitin-SO4 was reduced in 50%, a subgroup with 3-fold longer times from transplant to myopathy, and more distal weakness. cGvHD myopathies have noninflammatory pathology involving all 3 tissue components in muscle, connective tissue, small vessels, and myofibers. Abnormal cell surface glycosylation moieties are common in cGvHD myopathies, distinguishing them from other immune myopathies. This is the first report of molecular classes that may be immune targets in cGvHD. Disordered cell surface glycosylation moieties could produce disease-related tissue and cell damage, and be biomarkers for cGvHD features and activity.


Assuntos
Defeitos Congênitos da Glicosilação/patologia , Doença Enxerto-Hospedeiro/patologia , Inflamação/patologia , Doenças Musculares/patologia , Adulto , Idoso , Biomarcadores/metabolismo , Capilares/patologia , Tecido Conjuntivo/patologia , Feminino , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Histiócitos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Debilidade Muscular/patologia , Músculo Esquelético/patologia , Análise de Sobrevida
7.
Updates Surg ; 71(4): 701-704, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586312

RESUMO

To assess the utility of mutational markers in determining the most appropriate initial surgery for patients with thyroglossal duct cyst carcinoma (TGDCCa) and a normal thyroid gland. Our sample comprised 15 patients with a diagnosis of TGDCCa and a thyroid gland histologically negative for any malignant involvement, who underwent surgery between the years 1994 and 2017. Clinical records were reviewed and tissue specimens were genetically tested for the presence of the most commonly encountered mutational markers in differentiated thyroid cancer: BRAF, N-RAS, and H-RAS. The primary outcome of interest was the correlation between mutational marker positivity and the T-stage of the primary tumor and its potential implication on therapeutic decision making. All 15 cases were papillary carcinomas with a mean tumor size of 17 mm (2-40 mm). According to the 7th edition of the American Joint Committee on Cancer TNM staging system, these represented: T1 (n = 3), T2 (n = 1), and T3 (n = 11). Cancerous invasion of the pericystic soft tissue and/or hyoid bone was considered T3. BRAFV600E was the only mutational marker identified (7 in 15 cases). All BRAFV600E-positive lesions were T3, necessitating radioactive iodine ablation (RIA) therapy, therefore, total thyroidectomy. The correlation between BRAFV600E positivity and extracystic cancerous extension was statistically significant [1.0 (7/7) vs. 0.5 (4/8); p value = 0.0035]. BRAFV600E positivity seems to be predictive of locally advanced disease mandating RIA therapy. Therefore, it could serve as a preoperative tool that predicts the need for total thyroidectomy, in addition to Sistrunk's procedure.


Assuntos
Biomarcadores Tumorais/genética , Proteínas Proto-Oncogênicas B-raf/genética , Cisto Tireoglosso/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Biomarcadores Tumorais/análise , Tomada de Decisão Clínica , Tecido Conjuntivo/patologia , Humanos , Osso Hioide/patologia , Invasividade Neoplásica , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas B-raf/análise , Cisto Tireoglosso/patologia , Cisto Tireoglosso/cirurgia , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Glândula Tireoide/anatomia & histologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
9.
Dis Model Mech ; 12(8)2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31416928

RESUMO

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease, and patients with active or recurrent bone inflammation at multiple sites are diagnosed with chronic recurrent multifocal osteomyelitis (CRMO). The Chronic multifocal osteomyelitis (CMO) mouse model develops IL-1ß-driven sterile bone lesions reminiscent of severe CRMO. The goal of this study was to evaluate the potential involvement of mast cells in CMO/CRMO. Here, we show that mast cells accumulate in inflamed tissues from CMO mice and that mast cell protease Mcpt1 can be detected in the peripheral blood. A transgenic model of connective tissue mast cell depletion (Mcpt5-Cre:Rosa26-Stop fl/fl -DTa) was crossed with CMO mice and the resulting mice (referred to as CMO/MC-) showed a significant delay in disease onset compared with age-matched CMO mice. At 5-6 months of age, CMO/MC- mice had fewer bone lesions and immune infiltration in the popliteal lymph nodes that drain the affected tissues. In bone marrow-derived mast cell cultures from CMO mice, cytokine production in response to the alarmin IL-33 was elevated compared with wild-type cultures. To test the relevance of mast cells to human CRMO, we tested serum samples from a cohort of healthy controls and from CRMO patients at diagnosis. Interestingly, mast cell chymase was elevated in CRMO patients as well as in patients with oligoarticular juvenile arthritis. Tryptase-positive mast cells were also detected in bone lesions from CRMO patients and patients with bacterial osteomyelitis. Together, our results identify mast cells as cellular contributors to bone inflammation in CMO/CRMO and provide rationale for further study of mast cells as therapeutic targets.


Assuntos
Inflamação/patologia , Mastócitos/patologia , Osteomielite/patologia , Animais , Osso e Ossos/patologia , Doença Crônica , Tecido Conjuntivo/patologia , Humanos , Interleucina-1beta/metabolismo , Linfonodos/patologia , Camundongos Endogâmicos BALB C , Modelos Biológicos
10.
Khirurgiia (Mosk) ; (8): 12-16, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31464268

RESUMO

OBJECTIVE: To define the indication for preventive mesh implantation in patients scheduled for laparotomy. MATERIAL AND METHODS: There were 108 patients divided into the control (52 patients without anterior abdominal wall hernia) and the main (56 patients with ventral hernia) groups. RESULTS: Predominance of collagen type III over type I was observed in patients older 60 years in the main group. The maximum ratio of collagen types I and III was 1.4 in the main group. The minimum number of inter-fiber spaces (n=5) was noted in patients aged 30-40 years. The maximum density of connective tissue was 250 pixels per inch. CONCLUSION: Analysis of connective tissue structures revealed some important age-related features and markers of connective tissue dysplasia in the main group. An indication for preventive mesh implantation in patients scheduled for laparotomy was determined.


Assuntos
Colágeno/análise , Doenças do Tecido Conjuntivo/complicações , Hérnia Ventral/prevenção & controle , Hérnia Incisional/prevenção & controle , Laparotomia/efeitos adversos , Telas Cirúrgicas , Parede Abdominal/patologia , Parede Abdominal/cirurgia , Adulto , Tecido Conjuntivo/química , Tecido Conjuntivo/patologia , Doenças do Tecido Conjuntivo/patologia , Hérnia Ventral/etiologia , Hérnia Ventral/patologia , Herniorrafia/métodos , Humanos , Hérnia Incisional/etiologia , Hérnia Incisional/patologia , Pessoa de Meia-Idade
11.
Presse Med ; 48(7-8 Pt 2): e219-e231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447333

RESUMO

Image-guided ablation is performed by percutaneously introducing ablation probes to deliver energy into a tumor to destroy it in a controlled and localized fashion. Ablation modalities can be broadly classified as thermal or non-thermal based on the mechanism of tumor destruction and are performed using different types of image guidance for planning, delivering and follow-up of the treatment. Ablation is performed in a minimally invasive fashion, providing greater residual organ preservation with minimal morbidity to the patient. Image-guided ablation is being used in the clinic for the treatment of primary and metastatic tumors, and this article reviews state of the art for the treatment of malignancies in the liver, lung, kidney and musculoskeletal tissue.


Assuntos
Ablação por Cateter/métodos , Neoplasias/cirurgia , Cirurgia Assistida por Computador/métodos , Ablação por Cateter/efeitos adversos , Tecido Conjuntivo/patologia , Tecido Conjuntivo/cirurgia , Humanos , Rim/patologia , Rim/cirurgia , Fígado/patologia , Fígado/cirurgia , Pulmão/patologia , Pulmão/cirurgia , Sistema Musculoesquelético/patologia , Sistema Musculoesquelético/cirurgia , Neoplasias/diagnóstico , Neoplasias/patologia , Especificidade de Órgãos , Complicações Pós-Operatórias/etiologia , Cirurgia Assistida por Computador/efeitos adversos , Resultado do Tratamento
12.
Cell Prolif ; 52(5): e12667, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31373101

RESUMO

OBJECTIVE: Interstitial fluid in extracellular matrices may not be totally fixed but partially flow through long-distance oriented fibrous connective tissues via physical mechanisms. We hypothesized there is a long-distance interstitial fluid transport network beyond vascular circulations. MATERIALS AND METHODS: We first used 20 volunteers to determine hypodermic entrant points to visualize long-distance extravascular pathway by MRI. We then investigated the extravascular pathways initiating from the point of thumb in cadavers by chest compressor. The distributions and structures of long-distance pathways from extremity ending to associated visceral structures were identified. RESULTS: Using fluorescent tracer, the pathways from right thumb to right atrium wall near chest were visualized in seven of 10 subjects. The cutaneous pathways were found in dermic, hypodermic and fascial tissues of hand and forearm. The perivascular pathways were along the veins of arm, axillary sheath, superior vena cava and into the superficial tissues on right atrium. Histological and micro-CT data showed these pathways were neither blood nor lymphatic vessels but long-distance oriented fibrous matrices, which contained the longitudinally assembled micro-scale fibres consistently from thumb to superficial tissues on right atrium. CONCLUSIONS: These data revealed the structural framework of the fibrous extracellular matrices in oriented fibrous connective tissues was of the long-distance assembled fibres throughout human body. Along fibres, interstitial fluid can systemically transport by certain driving-transfer mechanisms beyond vascular circulations.


Assuntos
Tecido Conjuntivo/metabolismo , Matriz Extracelular/metabolismo , Pontos de Acupuntura , Adulto , Cadáver , Tecido Conjuntivo/química , Tecido Conjuntivo/patologia , Meios de Contraste/química , Meios de Contraste/metabolismo , Feminino , Fluoresceína/química , Fluoresceína/metabolismo , Pé/diagnóstico por imagem , Mãos/diagnóstico por imagem , Humanos , Vasos Linfáticos/anatomia & histologia , Vasos Linfáticos/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Microscopia Confocal , Pontos Quânticos/química , Pontos Quânticos/metabolismo , Adulto Jovem
13.
Am J Physiol Renal Physiol ; 317(4): F1047-F1057, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31411077

RESUMO

Stress urinary incontinence (SUI) is more prevalent among women who deliver vaginally than women who have had a cesarean section, suggesting that tissue repair after vaginal delivery is insufficient. A single dose of mesenchymal stem cells (MSCs) has been shown to partially restore urethral function in a model of SUI. The aim of the present study was to determine if increasing the number of doses of MSCs improves urethral and pudendal nerve function and anatomy. We hypothesized that increasing the number of MSC doses would accelerate recovery from SUI compared with vehicle treatment. Rats underwent pudendal nerve crush and vaginal distension or a sham injury and were treated intravenously with vehicle or one, two, or three doses of 2 × 106 MSCs at 1 h, 7 days, and 14 days after injury. Urethral leak point pressure testing with simultaneous external urethral sphincter electromyography and pudendal nerve electroneurography were performed 21 days after injury, and the urethrovaginal complex and pudendal nerve were harvested for semiquantitative morphometry of the external urethral sphincter, urethral elastin, and pudendal nerve. Two and three doses of MSCs significantly improved peak pressure; however, a single dose of MSCs did not. Single, as well as repeated, MSC doses improved urethral integrity by restoring urethral connective tissue composition and neuromuscular structures. MSC treatment improved elastogenesis, prevented disruption of the external urethral sphincter, and enhanced pudendal nerve morphology. These results suggest that MSC therapy for postpartum incontinence and SUI can be enhanced with multiple doses.


Assuntos
Doenças Neuromusculares/terapia , Transplante de Células-Tronco/métodos , Uretra/fisiopatologia , Incontinência Urinária por Estresse/terapia , Animais , Transplante de Medula Óssea/métodos , Tecido Conjuntivo/patologia , Elastina/metabolismo , Feminino , Transplante de Células-Tronco Mesenquimais/métodos , Compressão Nervosa , Doenças Neuromusculares/complicações , Doenças Neuromusculares/fisiopatologia , Período Pós-Parto , Nervo Pudendo/fisiopatologia , Ratos , Ratos Sprague-Dawley , Uretra/inervação , Incontinência Urinária por Estresse/etiologia , Incontinência Urinária por Estresse/fisiopatologia , Vagina/lesões
14.
Genes (Basel) ; 10(6)2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185693

RESUMO

FBN1 encodes fibrillin 1, a key structural component of the extracellular matrix, and its variants are associated with a wide range of hereditary connective tissues disorders, such as Marfan syndrome (MFS) and mitral valve-aorta-skeleton-skin (MASS) syndrome. Interpretations of the genomic data and possible genotype-phenotype correlations in FBN1 are complicated by the high rate of intronic variants of unknown significance. Here, we report two unrelated individuals with the FBN1 deep intronic variants c.6872-24T>A and c.7571-12T>A, clinically associated with MFS and MASS syndrome, respectively. The individual carrying the c.6872-24T>A variant is positive for aortic disease. Both individuals lacked ectopia lentis. In silico analysis and subsequent mRNA study by RT-PCR demonstrated the effect of the identified variant on the splicing process in both cases. The c.6872-24T>A and c.7571-12T>A variants generate the retention of intronic nucleotides and lead to the introduction of a premature stop codon. This study enlarges the mutation spectrum of FBN1 and points out the importance of intronic sequence analysis and the need for integrative functional studies in FBN1 diagnostics.


Assuntos
Fibrilina-1/genética , Predisposição Genética para Doença , Síndrome de Marfan/genética , Prolapso da Valva Mitral/genética , Miopia/genética , Dermatopatias/genética , Adulto , Processamento Alternativo/genética , Tecido Conjuntivo/metabolismo , Tecido Conjuntivo/patologia , Matriz Extracelular/genética , Feminino , Genótipo , Humanos , Íntrons/genética , Masculino , Síndrome de Marfan/fisiopatologia , Pessoa de Meia-Idade , Prolapso da Valva Mitral/fisiopatologia , Mutação/genética , Miopia/fisiopatologia , Dermatopatias/fisiopatologia
15.
Sud Med Ekspert ; 62(3): 9-11, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31198197

RESUMO

Diagnosis of sudden death in the young is based on the results of a set of research methods. Immunohistochemical, histochemical and histochemical methods are fundamental to the diagnosis of hidden forms of connective tissue pathology. These methods allow the sequence of initial and irreversible changes in connective tissue structures to be determined. The aim of this study was to determine the abnormalities of the vascular wall structure when using immunohistochemical and histological methods for the verification of congenital anomalies of various types of vessels, which expand the criteria for the diagnostic detection of individuals with connective tissue dysplasia. These investigation methods allow the diagnosis of hidden forms of congenital connective tissue pathology in the young. The main morphological signs of pathology of the aorta, carotid arteries, coronary and cerebral arteries are the disturbance of structural elements of the connective tissue.


Assuntos
Vasos Sanguíneos/patologia , Tecido Conjuntivo/patologia , Morte Súbita , Humanos
16.
Chin J Traumatol ; 22(2): 93-98, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30928194

RESUMO

The clinical treatment of joint contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca2+-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-ß1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.


Assuntos
Contratura/etiologia , Imobilização/efeitos adversos , Articulações , Músculo Esquelético , Transdução de Sinais/fisiologia , Atrofia , Autofagia , Cálcio/metabolismo , Caspases/metabolismo , Tecido Conjuntivo/metabolismo , Tecido Conjuntivo/patologia , Contratura/metabolismo , Contratura/patologia , Contratura/terapia , Fibrose , Humanos , Lisossomos/metabolismo , Metaloproteinases da Matriz/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Fator de Crescimento Transformador beta1/metabolismo , Ubiquitina/metabolismo
17.
Bull Exp Biol Med ; 166(6): 722-725, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31020583

RESUMO

It was shown that the intensity of morphological changes in the dental system tissues (periodontium and pulp) of ISIAH rats depends on the mode of stress exposure. Acute stress was associated with a significant increase in the area of periodontal and pulp vessels, a decrease in the area of connective tissue of these components, and an increase in the thickness of the vascular endothelium. Chronic stress in these animals induced an increase in the thickness of the endothelial layer of the periodontal and pulp vessels, fibromatosis (increase in the number of fibroblasts), and a sharp decrease in the level of odontoblasts.


Assuntos
Polpa Dentária/patologia , Células Endoteliais/patologia , Fibroblastos/patologia , Hipertensão/patologia , Periodonto/patologia , Estresse Fisiológico , Animais , Contagem de Células , Tecido Conjuntivo/irrigação sanguínea , Tecido Conjuntivo/patologia , Polpa Dentária/irrigação sanguínea , Endotélio Vascular/patologia , Imobilização , Masculino , Odontoblastos/patologia , Periodonto/irrigação sanguínea , Ratos , Ratos Endogâmicos
18.
Eur J Radiol ; 113: 24-31, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30927954

RESUMO

AIM: Radiographs (X-rays) are used for the preoperative assessment of hallux valgus (HV). Our purpose was to determine how well quantitative measurements of HV on radiographs and MRI correlate with the qualitative soft tissue and internal derangement findings on MRI. MATERIALS AND METHODS: After IRB approval, 56 consecutive patients with MRI and radiographs of the foot were retrospectively reviewed. Two trained readers independently evaluated radiographs, measuring hallux valgus angle (HVA) and intermetatarsal angle (IMA). Two separate readers assessed qualitative MRI data by evaluating 21 different soft tissue and bony features. Statistical analysis included inter-reader reliability (IRR) and correlation of quantitative and qualitative findings. RESULTS: Excellent IRR (ICC = 0.89-0.96) was observed for radiograph and MRI measurements of the hallux valgus severity. For qualitative assessments on MRI, IRR was good to excellent for all features (ICC = 0.63-0.9). No significant difference was found for HVA or IMA between normal and abnormal qualitative MRI features. No statistically significant correlation between the severity of hallux valgus and injury to hallux joints and supporting structures was found. CONCLUSION: Hallux valgus measurements are reliable on x-rays and MRI and qualitative findings of 1st MTP joint show good to excellent inter-reader agreement on MRI. No statistically significant correlations exist between the severity of hallux valgus and qualitative MRI findings.


Assuntos
Hallux Valgus/patologia , Adulto , Idoso , Tecido Conjuntivo/diagnóstico por imagem , Tecido Conjuntivo/patologia , Feminino , , Hallux Valgus/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Radiografia/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Raios X
19.
Analyst ; 144(8): 2635-2642, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30839958

RESUMO

Infrared (IR) spectroscopic imaging, utilizing both the molecular and structural disease signatures, enables extensive profiling of tumors and their microenvironments. Here, we examine the relative merits of using either the fingerprint or the high frequency regions of the IR spectrum for tissue histopathology. We selected a complex model as a test case, evaluating both stromal and epithelial segmentation for various breast pathologies. IR spectral classification in each of these spectral windows is quantitatively assessed by estimating area under the curve (AUC) of the receiver operating characteristic curve (ROC) for pixel level accuracy and images for diagnostic ability. We found only small differences, though some that may be sufficiently important in diagnostic tasks to be clinically significant, between the two regions with the fingerprint region-based classifiers consistently emerging as more accurate. The work provides added evidence and comparison with fingerprint region, complex models, and previously untested tissue type (breast) - that the use of restricted spectral regions can provide high accuracy. Our study indicates that the fingerprint region is ideal for epithelial and stromal models to obtain high pixel level accuracies. Glass slides provide a limited spectral feature set but provides accurate information at the patient level.


Assuntos
Mama/anatomia & histologia , Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Tecido Conjuntivo/anatomia & histologia , Tecido Conjuntivo/patologia , Epitélio/anatomia & histologia , Epitélio/patologia , Humanos , Hiperplasia/patologia , Modelos Biológicos , Curva ROC , Espectrofotometria Infravermelho/métodos
20.
Subcell Biochem ; 91: 281-310, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30888657

RESUMO

We begin this chapter by describing normal characteristics of several pertinent connective tissue components, and some of the basic changes they undergo with ageing. These alterations are not necessarily tied to any specific disease or disorders, but rather an essential part of the normal ageing process. The general features of age-induced changes, such as skin wrinkles, in selected organs with high content of connective or soft tissues are discussed in the next part of the chapter. This is followed by a section dealing with age-related changes in specific diseases that fall into at least two categories. The first category encompasses common diseases with high prevalence among mostly ageing populations where both genetic and environmental factors play roles. They include but may not be limited to atherosclerosis and coronary heart disease, type II diabetes, osteopenia and osteoporosis, osteoarthritis, tendon dysfunction and injury, age-related disorders of spine and joints. Disorders where genetics plays the primary role in pathogenesis and progression include certain types of progeria, such as Werner syndrome and Hutchinson-Gilford progeria belong to the second category discussed in this chapter. These disorders are characterized by accelerated signs and symptoms of ageing. Other hereditary diseases or syndromes that arise from mutations of genes encoding for components of connective tissue and are less common than diseases included in the first group will be discussed briefly as well, though they may not be directly associated with ageing, but their connective tissue undergoes some changes compatible with ageing. Marfan and Ehlers-Danlos syndromes are primary examples of such disorders. We will probe the role of specific components of connective tissue and extracellular matrix if not in each of the diseases, then at least in the main representatives of these disorders.


Assuntos
Envelhecimento/patologia , Doenças do Tecido Conjuntivo/patologia , Envelhecimento/genética , Tecido Conjuntivo/metabolismo , Tecido Conjuntivo/patologia , Doenças do Tecido Conjuntivo/genética , Humanos , Progéria/genética , Progéria/patologia
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