RESUMO
OBJECTIVE: To study whether osteoarthritis (OA) in the knee is associated with a change of the innervation pattern in the synovial layer. DESIGN: In synovial tissue from the normal knee joint of rat and sheep we studied the presence of vessels and of nerve fibres using transmission electron microscopy and immunohistochemistry. Synovial material was also obtained from patients who underwent total knee replacement surgery. This material was examined for inflammatory changes, and the presence of vessels and nerve fibres was assessed. RESULTS: The synovium in the parapatellar region of the normal knee joint of rat and sheep exhibited a dense capillary and neuronal network. It was entered by calcitonin gene-related peptide containing sensory fibres and tyrosine hydroxylase-positive sympathetic nerve fibres. Synovial material from patients with knee OA exhibited different degrees of inflammation. Synovial material without inflammation exhibited a similar vascular and neuronal network as the normal knee joint from rat and sheep. However, in synovium with inflammatory changes we found a significant decrease of nerve fibres in depth ranges close to the synovial lining layer depending on the degree of inflammation whereas deeper regions were less affected. CONCLUSIONS: Inflammatory changes in the synovium of OA joints are associated with a massive destruction of the capillary and neuronal network which is present in normal synovium. Due to the disappearance of the sensory fibres it is unlikely that OA pain is initiated directly in the synovium. The loss of normally innervated vascularisation may have multiple consequences for the physiological functions of the synovium.
Assuntos
Articulação do Joelho/inervação , Articulação do Joelho/patologia , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/fisiopatologia , Membrana Sinovial/inervação , Membrana Sinovial/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capilares/patologia , Capilares/ultraestrutura , Feminino , Humanos , Articulação do Joelho/irrigação sanguínea , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Fibras Nervosas/ultraestrutura , Ratos , Ratos Wistar , Ovinos , Especificidade da Espécie , Membrana Sinovial/irrigação sanguíneaRESUMO
OBJECTIVES: Advanced glycation end products (AGEs) have been implicated in the pathogenesis of bone-destructive disorders. Yet reports on the influence of AGEs on human osteoblasts remain lacking. The aim of the study is to investigate the influence of AGE-modified bovine serum albumin (AGE-BSA) on cell growth and expression of osteoblastic markers associated with osteogenesis and osteoclastogenesis. METHODS: Human osteoblasts established from bone tissue specimens were stimulated with AGE-BSA and investigated in vitro. Expression of mRNA for the receptor for AGEs (RAGE), nuclear factor kappa B subunit p65 (NFκB p65), tumour necrosis factor alpha (TNF-α), matrix metallo proteinase-1 (MMP-1), receptor activator of NFκB ligand (RANKL), osteoprotegerin, collagen type I (Col1), osteocalcin (OC) and alkaline phosphatase (ALP) were measured using real-time polymerase chain reaction (PCR). Respective protein expressions were evaluated by western blot analysis or ELISA. NFκB activation was investigated by luciferase assay and electrophoretic mobility shift assay (EMSA). Cell cycle analysis, cell proliferation and markers of necrosis and early apoptosis were assessed. RESULTS: AGE-BSA was actively taken up into osteoblasts and induced cell cycle arrest and an increase in necrotic, but not apoptotic cells. The increased expression of RAGE and TNF-α together with NFκB activation indicates an AGE-mediated inflammatory response. The decreased expression of Col1, OC and ALP presumably reflects a diminished osteogenic potential, whereas upregulation of RANKL and TNF-α enhances osteoclastogenesis. CONCLUSIONS: The present study demonstrates that AGE-BSA affects the growth and function of osteoblasts. Modulation of the expression of various target genes involved in bone metabolism provides evidence that AGEs accumulated in the bone matrix have the potential to suppress osteogenic and to promote osteoclastogenic properties of osteoblasts in vivo, thereby leading to functional and structural impairment of bone.
Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese , Soroalbumina Bovina/metabolismo , Idoso , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Apoptose , Western Blotting , Ciclo Celular , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação da Expressão Gênica , Genes Reporter , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Osteoblastos/patologia , Osteocalcina/genética , Osteocalcina/metabolismo , Osteoclastos/patologia , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , RNA Mensageiro/metabolismo , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Transfecção , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Sebaceous neoplasia have been observed in members of four families exhibiting the cancer family syndrome (CFS). This disorder is characterized by adenocarcinomas, particularly involving the (proximal) colon, endometrium, and ovary; an excess of multiple primary cancer; early age of cancer onset; and autosomal dominant pattern of inheritance. Multiple adenomatous polyps are lacking in this disorder. In four patients from three of these cancer-prone kindreds, cutaneous lesions were accompanied by multiple visceral adenocarcinomas, fulfilling the criteria for Torre's syndrome, a disease that heretofore has not shown notable familial clustering characteristic of the CFS. Therefore, the coexistence of rare sebaceous neoplasia and visceral cancer in CFS supports the notion that some cases of Torre's syndrome may in fact represent the more full phenotypic expression of the gene responsible for the CFS.
Assuntos
Neoplasias Primárias Múltiplas/genética , Neoplasias das Glândulas Sebáceas/genética , Adenocarcinoma/genética , Adulto , Neoplasias do Colo/genética , Feminino , Ligação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Linhagem , Fenótipo , Neoplasias das Glândulas Sebáceas/patologia , SíndromeRESUMO
BACKGROUND: Non-destructive techniques for the detection and classification of pathological changes of cartilage in the early stages of osteoarthritis are required for arthroscopic and open surgery of joints. Biochemical and histological changes in cartilage with different degrees of destruction were analysed and correlated to changes in the spectroscopic characteristics of cartilage. PATIENTS, MATERIAL AND METHODS: 24 patients (n = 25 knees) with severely destructed knee joints received total knee replacement. The cartilage of the resected joints was classified according to the ICRS system. Defined cartilage specimens were investigated spectroscopically employing NIRS (near-infrared spectroscopy). In the following the cartilage specimens were harvested to determine the content of proteoglycan (GAG) and hydroxyproline (HP) as an essential part of collagen. Histological evaluation of the Mankin score and Otte score was performed using haematoxylin/eosin and safranin-O staining. Spearman's rank correlation coefficient was used to characterise links between the parameters investigated. RESULTS: We found significant correlations between spectroscopic, histological and biochemical characteristics. NIRS corresponded to the content of GAG (ρ = 0.58) and HP (ρ = 0.59), as well as to the Mankin (ρ = 0.55) and Otte (ρ = 0.5) scores. Furthermore, the ICRS classification correlated with histological evaluation (Mankin score ρ = 0.725 and Otte score ρ = 0.736), as to be expected. CONCLUSION: Characteristic cartilage changes in different degrees of osteoarthritis can be detected and evaluated by the spectroscopic method NIRS as a non-destructive technique. However, the quality of this technical evaluation cannot compete with biochemical and histological analysis.
Assuntos
Cartilagem Articular/química , Cartilagem Articular/patologia , Hidroxiprolina/análise , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/metabolismo , Proteoglicanas/análise , Análise Espectral/métodos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Cartilagem Articular/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite , Osteoartrite do Joelho/cirurgia , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeAssuntos
Neoplasias/genética , Dermatopatias/genética , Adenocarcinoma/genética , Neoplasias do Colo/genética , Feminino , Humanos , Neoplasias Ovarianas/genética , Fenótipo , Neoplasias Retais/genética , Risco , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Síndrome , Telangiectasia/genética , Neoplasias Uterinas/genéticaRESUMO
For almost two decades we have followed a kindred with the familial, atypical, multiple-mole melanoma (FAMMM) syndrome. We first evaluated the proband's 14-year-old daughter when she was age 5 years. We documented the evolution, both clinically and histologically, of the FAMMM phenotype in this girl for eight years.
Assuntos
Melanoma/genética , Nevo Pigmentado/patologia , Neoplasias Cutâneas/genética , Adolescente , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Melanoma/patologia , Fenótipo , Pele/patologia , Neoplasias Cutâneas/patologia , Síndrome , Fatores de TempoRESUMO
The Leser-Trelat sign is the sudden appearance and rapid increase in size and number of seborrhoeic keratoses in association with cancer. Twenty cases of this unusual phenomenon have so far been reported in the world literature. More than half involve adenocarcinomas and none was shown to be familial. We report a unique example of a 41-year-old black female and her 74-year-old black mother, both of whom have demonstrated classical clinical-pathological evidence of the Leser-Trelat sign and adenocarcinoma of the breast. The remainder of the family history was negative for cutaneous lesions and cancer. The aetiological and pathogenetic significance of the Leser-Trelat sign in association with carcinoma of the breast in this mother and daughter remains obscure.
Assuntos
Adenocarcinoma/genética , Neoplasias da Mama/genética , Ceratose/genética , Adulto , Idoso , Carcinoma Intraductal não Infiltrante/genética , Dermatite Seborreica/genética , Feminino , Humanos , Ceratose/diagnóstico , Manifestações CutâneasRESUMO
Clinical-pathologic-genetic studies were performed on 3 kindreds showing the familial atypical multiple mole-melanoma syndrome (FAMMM). Findings showed vertical transmission, including father-to-son, of cutaneous malignant melanoma and/or FAMMM moles with no sex predilection. A broad spectrum of clinical signs characterizing the phenotype ranged from an apparent lack of disease expression through minimal, moderate, and florid manifestations. An extreme example was a patient with 9 separate primary melanomas in 18 years. The FAMMM moles were histologically compound nevocellular nevi with varying degrees of dysplasia of the melanocytes, an increased occurrence of fibroplasia, and chronic inflammation within the papillary dermis. Of further interest was marked variation in the degree of dysplasia in moles between and within families. These observations, when coupled with recent reports by others, are consistent with an autosomal dominant gene showing markedly variable expressivity. Management of these patients is difficult, as one cannot be certain which moles require biopsy and then, following histological study, which will require wider excision. Studies of the FAMMM syndrome should deal carefully with its natural history, including the patient's lifelong susceptibility to multiply malignant melanomas, and the possibility that cancer of other anatomic sites may be integral components of this hereditary cancer syndrome.
Assuntos
Melanoma/genética , Neoplasias Primárias Múltiplas/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Feminino , Genes Dominantes , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Linhagem , Fenótipo , Fatores Sexuais , Neoplasias Cutâneas/patologiaRESUMO
A case report of a 56-year-old man with the characteristic clinical and histologic features of multiple neurofibromatosis is presented. This patient was also diagnosed as having a malignant fibrous histiocytoma involving the right thigh with metastasis to the lung. A definite association between Von Recklinghausen's disease and various sarcomas (most commonly neurofibrosarcomas) of the peripheral nerves and the somatic soft tissues is well-known. This is apparently the first report in the literature of a malignant fibrous histiocytoma arising in a patient with multiple neurofibromatosis. The phenomenon of sarcomatous change in Von Recklinghausen's disease and the clinical and pathologic features of malignant fibrous histiocytoma are also discussed.
Assuntos
Histiocitoma Fibroso Benigno/complicações , Neoplasias Primárias Múltiplas , Neurofibromatose 1/complicações , Histiocitoma Fibroso Benigno/patologia , Histiocitoma Fibroso Benigno/secundário , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Coxa da PernaRESUMO
The familial atypical multiple mole-melanoma syndrome (FAMMM) is characterised by an autosomal dominantly inherited susceptibility to multiple atypical moles which show variable colouration ranging from black to brown, tan, red, or pink, with occasional variegation. These compound naevi may be macular or papular, with regular or irregular borders, and measure 1 cm or more in size. They may be few in number or absent or may exceed 100 in a given patient. They are located predominantly on areas not exposed to the sun. Dysplastic changes in melanocytes, fibroplasia, focal chronic inflammatory cell infiltrate, and new blood vessel formation of the papillary dermis characterise their histopathology. These findings are not uniformly present. Because of these distinctive features, coupled with their propensity for transformation to cutaneous malignant melanoma, little attention has been given to the possibility of either minimal or absent cutaneous expression of the phenotype or more diverse neoplastic involvement in this disease. These latter phenomena, which we ascribe to the pleiotropic effects of the cancer-prone FAMMM genotype, were observed in a single FAMMM kindred, the subject of this report.
Assuntos
Melanoma/genética , Neoplasias Primárias Múltiplas/genética , Nevo Pigmentado/genética , Fenótipo , Neoplasias Cutâneas/genética , Adulto , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , SíndromeRESUMO
The Familial Atypical Multiple Mole-Melanoma Syndrome (FAMMM) is characterized by an autosomal dominantly inherited susceptibility to multiple atypical naevi. Patients with this hereditary phenotype show a strong susceptibility to cutaneous malignant melanoma (CMM). Our investigation of an extended Dutch kindred showing the FAMMM phenotype revealed a proband with bilateral intraocular malignant melanoma (IOM) and multiple CMM. The family revealed an array of tumours which included carcinoma of the lung, skin, larynx, and breast in addition to CMM and IOM, which were transmitted vertically through 3 generations. There was male-to-male transmission, and the number of affected males and females was about the same, which was consistent with an autosomal dominant inheritance. Thus the FAMMM syndrome not only indicates a potential for CMM, but a susceptibility to other systemic cancers as well. These observations, though limited to a single kindred, merit a painstaking evaluation of cancer of all anatomical sites in other kindreds showing the FAMMM syndrome. Such studies could yield clues to cancer aetiology, pathogenesis, and control.