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1.
Ann Clin Lab Sci ; 50(3): 412-416, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32581037

RESUMO

Rhabdomyosarcoma (RMS) is a primitive embryonal mesenchymal neoplasm demonstrating skeletal muscle differentiation. Diagnosis of RMS remains difficult due to the diversity of clinical features, pathological forms, and lesion's locations. Immunohistochemistry and Fluorescence in Situ Hybridization are common methods used to aid RMS diagnosis. In this research we tested protein expression of Desmin (Clone MX046), MyoD1 (Clone MX049), MyoD1 (Clone 5.8A), MyoD1 (Clone EP212), Myogenin (Clone F5D), and cytogenetic features in 21 RMS cases, with following results: positive rates of Desmin (Clone MX046), MyoD1 (Clone MX049), MyoD1 (Clone 5.8A), MyoD1 (Clone EP212) and Myogenin (Clone F5D) were 100.00%, 100.00%, 90.48%, 95.24% and 85.71%, respectively, with cytoplasmic stains of MyoD1 (Clone 5.8A) in 38.10% (8/21) cases and only nuclear stains of MyoD1 (Clone EP212), MyoD1 (Clone MX049) in all positive cases. FOXO1 gene was detected apart in 9 alveolar RMS samples, where MyoD1 (Clone MX049), MyoD1 (Clone 5.8A) and MyoD1 (Clone EP212) were 100% positive but MyoD1 (Clone 5.8A) only 44.44% (4/9). Thus we believe MyoD1 (Clone MX049) performs more sensitive and specific than MyoD1 (Clone 5.8A) and MyoD1 (Clone EP212).


Assuntos
Anticorpos Monoclonais/imunologia , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/imunologia , Adolescente , Adulto , Anticorpos Monoclonais/metabolismo , Biomarcadores Tumorais , China , Desmina/genética , Desmina/imunologia , Diagnóstico Diferencial , Feminino , Fluorescência , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Proteína MyoD/imunologia , Proteína MyoD/metabolismo , Miogenina/genética , Miogenina/imunologia , Rabdomiossarcoma/metabolismo
2.
Vet Pathol ; 54(6): 885-891, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28812533

RESUMO

Liposarcoma, rhabdomyosarcoma, and hibernoma share some overlapping histologic and immunohistochemical features. Although immunohistochemistry (IHC) is commonly used in the diagnosis of these neoplasms, expression of muscle markers has been reported in human liposarcoma and canine hibernoma in addition to rhabdomyosarcoma. Thus, these neoplasms are a diagnostic challenge but important to distinguish because of differences in prognosis and treatment. Rhabdomyosarcoma and liposarcoma are both malignant, but rhabdomyosarcoma has a higher potential for metastasis. In contrast, hibernomas are benign with low risk of recurrence. This study investigated expression of the muscle markers desmin, myogenin, and α-smooth muscle actin (α-SMA) and the brown fat marker uncoupling protein 1 (UCP1) in 25 cases of canine liposarcoma using IHC. Oil red O histochemistry was performed to confirm the presence of lipid and the diagnosis of liposarcoma in cases that were not well-differentiated. The 25 cases included 15 well-differentiated, 5 pleomorphic, 3 myxoid, and 2 dedifferentiated subtypes of liposarcoma. By IHC, 23 of 25 expressed UCP1, 7 of 25 expressed α-SMA, 7 of 25 expressed desmin, and 3 of 25 expressed myogenin with no clear relationship of antigen expression and tumor subtype. These findings clarify the immunohistochemical profile of canine liposarcoma and suggest overlap in the expression of several muscle antigens and UCP1 between liposarcoma, hibernoma, and rhabdomyosarcoma.


Assuntos
Antígenos/imunologia , Biomarcadores Tumorais/imunologia , Doenças do Cão/imunologia , Lipossarcoma/veterinária , Actinas/imunologia , Tecido Adiposo Marrom/imunologia , Tecido Adiposo Marrom/metabolismo , Animais , Desmina/imunologia , Doenças do Cão/patologia , Cães , Feminino , Imuno-Histoquímica/veterinária , Lipossarcoma/imunologia , Lipossarcoma/patologia , Masculino , Músculo Liso/metabolismo , Miogenina/imunologia , Proteína Desacopladora 1/imunologia
3.
Pathobiology ; 83(1): 33-40, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26735863

RESUMO

OBJECTIVES: The histological differential diagnosis between epithelioid mesothelioma (EM) and reactive mesothelial hyperplasia (RMH) is not always straightforward. The aim of the present study was to search for new immunohistochemical markers to distinguish EM from RMH. METHODS: We evaluated and compared the expression of apoptosis-related genes in EM and RMH by real-time RT-PCR array analysis followed by clustering of significant gene expression. Immunohistochemical staining and statistical analysis of Noxa expression in 81 cases of EM and 55 cases of RMH were performed and compared with the utility of other previously reported antibodies such as Desmin, EMA, GLUT-1, IMP-3 and CD146. RESULTS: Noxa mRNA expression levels were found to be increased in EM when compared to RMH by RT-PCR array analysis. In the immunohistochemical analysis, Noxa showed sensitivity of 69.0%, specificity of 93.6% and positive predictive value of 93.0% as a positive marker of EM in distinguishing it from RMH, and these values were almost similar to IMP-3. CONCLUSION: Noxa is a marker with relatively high specificity, and can be used to distinguish EM from RMH. It would be a valuable addition to the current antibody panel used for the differential diagnosis of EM and RMH.


Assuntos
Apoptose/genética , Biomarcadores Tumorais/análise , Hiperplasia/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Anticorpos , Linhagem Celular Tumoral , Desmina/análise , Desmina/imunologia , Diagnóstico Diferencial , Feminino , Perfilação da Expressão Gênica , Transportador de Glucose Tipo 1/análise , Transportador de Glucose Tipo 1/imunologia , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/ultraestrutura , Mesotelioma/ultraestrutura , Mesotelioma Maligno , Pessoa de Meia-Idade , Mucina-1/análise , Mucina-1/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade
4.
Anat Histol Embryol ; 44(3): 168-77, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24895012

RESUMO

In most avian species, only the left ovary and oviduct are developed in the adult bird. Right ovaries and oviducts usually do not mature further after hatching and remain only rudimentary. However, occurrence of a functional right ovary is frequently found in several species of birds of prey. In this study, we investigated the occurrence of the right ovaries and their morphology in these bird species. Four examined wild bird species possessed a right ovary: long-eared owl, common buzzard, sparrow hawk and goshawk. We used histological and immunohistochemical techniques to evaluate structural differences of the gonads and tried to correlate the findings with folliculogenesis and endocrine functions. The right ovaries showed different sizes and shapes. Cytoskeletal elements (tubulin and vimentin) and α-smooth muscle actin have been detected in different structures of the right ovaries, but their staining intensity was weaker compared with the left ovary. This shows that also the right ovary is mechanically able to ovulate. We could also demonstrate the expression of oestrogen receptor α and progesterone receptor in the right ovaries, which indicates that also the right ovary can respond to steroid hormone stimuli. We assume that the expression of steroid hormone receptors in the presumptive gonad is still sufficient to mediate the development of a right ovary in the studied species. We conclude that the expression of steroid hormone receptors in the right ovary is involved in its post-natal development. The histological and immunohistochemical data also imply that in the right ovary, folliculogenesis and ovulation can occur.


Assuntos
Ovário/anatomia & histologia , Aves Predatórias/anatomia & histologia , Actinas/análise , Actinas/imunologia , Animais , Desmina/análise , Desmina/imunologia , Receptor alfa de Estrogênio/análise , Receptor alfa de Estrogênio/imunologia , Falconiformes/anatomia & histologia , Feminino , Falcões/anatomia & histologia , Imuno-Histoquímica/veterinária , Ovário/química , Ovário/fisiologia , Receptores de Progesterona/análise , Receptores de Progesterona/imunologia , Estrigiformes/anatomia & histologia , Tubulina (Proteína)/análise , Tubulina (Proteína)/imunologia , Vimentina/análise , Vimentina/imunologia
5.
Transfus Apher Sci ; 48(2): 273-5, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23415411

RESUMO

BACKGROUND: Adjuvant therapeutic methods are employed when pemphigus vulgaris (PV) fails to be controlled by conventional corticosteroid treatment. OBJECTIVE: The efficacy of double filtration plasmapheresis (DFPP) was investigated in a PV patient with severe, refractory mucosal disease. METHODS: A total of 3 DFPP cycles, each cycle consisting of 5 double filtration sessions conducted on alternate days was completed. RESULTS: DFPP provided immediate clinical relief of symptoms as well as a significant decrease in anti-desmoglein antibody levels and allowed for a much lower corticosteroid dose. CONCLUSION: DFPP was an effective and safe adjuvant therapy in our patient with PV and it offers a valid treatment option in PV patients with recalcitrant disease.


Assuntos
Autoanticorpos , Desmina/imunologia , Doenças da Boca , Mucosa Bucal , Pênfigo , Plasmaferese , Corticosteroides/administração & dosagem , Autoanticorpos/sangue , Autoanticorpos/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Doenças da Boca/sangue , Doenças da Boca/imunologia , Doenças da Boca/patologia , Doenças da Boca/terapia , Mucosa Bucal/imunologia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Pênfigo/sangue , Pênfigo/imunologia , Pênfigo/patologia , Pênfigo/terapia , Turquia
6.
PLoS One ; 7(10): e46709, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23071619

RESUMO

Inclusion body myositis (IBM) belongs to a group of muscle diseases known as the inflammatory myopathies. The presence of antibody-secreting plasma cells in IBM muscle implicates the humoral immune response in this disease. However, whether the humoral immune response actively contributes to IBM pathology has not been established. We sought to investigate whether the humoral immune response in IBM both in the periphery and at the site of tissue damage was directed towards self-antigens. Peripheral autoantibodies present in IBM serum but not control serum recognized self-antigens in both muscle tissue and human-derived cell lines. To study the humoral immune response at the site of tissue damage in IBM patients, we isolated single plasma cells directly from IBM-derived muscle tissue sections and from these cells, reconstructed a series of recombinant immunoglobulins (rIgG). These rIgG, each representing a single muscle-associated plasma cell, were examined for reactivity to self-antigens. Both, flow cytometry and immunoblotting revealed that these rIgG recognized antigens expressed by cell lines and in muscle tissue homogenates. Using a mass spectrometry-based approach, Desmin, a major intermediate filament protein, expressed abundantly in muscle tissue, was identified as the target of one IBM muscle-derived rIgG. Collectively, these data support the view that IBM includes a humoral immune response in both the periphery and at the site of tissue damage that is directed towards self-antigens.


Assuntos
Autoanticorpos/sangue , Autoimunidade , Imunidade Humoral , Imunoglobulina G/sangue , Miosite de Corpos de Inclusão/imunologia , Animais , Autoanticorpos/química , Autoanticorpos/isolamento & purificação , Autoantígenos/imunologia , Autoantígenos/isolamento & purificação , Estudos de Casos e Controles , Linhagem Celular , Desmina/imunologia , Desmina/isolamento & purificação , Humanos , Imunoglobulina G/química , Imunoglobulina G/isolamento & purificação , Camundongos , Proteínas Musculares/imunologia , Proteínas Musculares/isolamento & purificação , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Miosite de Corpos de Inclusão/sangue , Ligação Proteica
7.
Lab Invest ; 92(10): 1440-50, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22890553

RESUMO

Hepatic myofibroblasts (MFB) show increased proliferation, migration and collagen production, which are crucial for hepatic fibrogenesis. Atorvastatin treatment inhibits proliferation, apoptosis and cytokine production of MFB in bile duct-ligated (BDL) rats in vivo. Here, we have further investigated the underlying mechanisms. Primary rat hepatic stellate cells (HSC) were isolated and culture-activated to hepatic MFB. Following 3 days of incubation with atorvastatin (10(-4), 10(-5) and 10(-6) M), transcription levels of profibrotic cytokines (transforming growth factor-ß1, connective tissue growth factor and TIMP1) and procollagen Ia were analyzed by real time PCR. Proliferation was investigated by 5'-bromo-2'-deoxyuridine assays. α-Smooth muscle actin protein expression was examined by western blotting. Fluorescence-activated cell sorting analysis of Annexin V and propidium iodide were used to measure apoptosis. Furthermore, p21 western blotting and ß-galactosidase staining were investigated in MFB as senescence markers. Subsequently, hepatic expression of desmin and senescence markers were analyzed in the livers of rats receiving atorvastatin (15 mg/kg*d) for 1 week starting 3 and 5 weeks after BDL. Atorvastatin inhibited the activation of HSC to MFB and decreased cytokine and collagen production in MFB in vitro. In addition, proliferation, cytokine and collagen production of MFB were reduced by atorvastatin. Atorvastatin initiated apoptosis at 10(-4) M and attenuated it at 10(-5) M. Atorvastatin induced p21 protein expression and ß-galactosidase staining of MFB in vitro and in vivo. Atorvastatin elicits similiar effects on MFB as previously seen in vivo: it decreases MFB turnover and fibrogenesis. We suggest that a further mechanism explaining these effects is senescence of cells.


Assuntos
Envelhecimento/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácidos Heptanoicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Cirrose Hepática/tratamento farmacológico , Miofibroblastos/efeitos dos fármacos , Pirróis/farmacologia , Actinas/imunologia , Actinas/metabolismo , Animais , Atorvastatina , Colágeno/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Desmina/imunologia , Desmina/metabolismo , Relação Dose-Resposta a Droga , Citometria de Fluxo , Células Estreladas do Fígado/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , beta-Galactosidase/análise , beta-Galactosidase/metabolismo
8.
J Pharmacol Exp Ther ; 342(3): 835-42, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22711911

RESUMO

Platelet-derived growth factor B (PDGF-B) plays an essential role in hepatic fibrosis. Inhibition of the PDGF-B signaling in chronically injured livers might represent a potential therapeutic measure for hepatic fibrosis. In this study, we assessed the effects of vaccination against PDGF-B on CCl4-induced liver fibrosis in BALB/c mice. The PDGF-B kinoid immunogens were prepared by cross-linking two PDGF-B-derived B-cell epitope peptides [PDGF-B¹6-(23-38) and PDGF-B¹6-(72-83)] to ovalbumin and keyhole limpet hemocyanin, respectively. Enzyme-linked immunosorbent assay, Western blotting, and NIH3T3 cell proliferation assay verified that immunization with the PDGF-B kinoids elicited the production of high levels of neutralizing anti-PDGF-B autoantibodies. The vaccination markedly alleviated CCl4-induced hepatic fibrosis, as indicated by the lessened morphological alternations and reduced hydroxyproline contents in the mouse livers. Moreover, immunohistochemical staining for proliferating cell nuclear antigen, α-smooth muscle actin, and desmin demonstrated that neutralization of PDGF-B inhibited both the proliferation and the activation of hepatic stellate cells in the fibrotic mouse livers. Taken together, this study demonstrated that vaccination with PDGF-B kinoids significantly suppressed CCl4-induced hepatic fibrosis in mice. Our results suggest that vaccination against PDGF-B might be developed into an effective, convenient, and safe therapeutic measure for the treatment of hepatic fibrosis.


Assuntos
Tetracloreto de Carbono/antagonistas & inibidores , Tetracloreto de Carbono/toxicidade , Cirrose Hepática/imunologia , Cirrose Hepática/prevenção & controle , Proteínas Proto-Oncogênicas c-sis/imunologia , Actinas/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Neutralizantes/imunologia , Autoanticorpos/imunologia , Processos de Crescimento Celular/imunologia , Células Cultivadas , Desmina/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Epitopos de Linfócito B/imunologia , Células Estreladas do Fígado/imunologia , Humanos , Imunização/métodos , Fígado/imunologia , Cirrose Hepática/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Células NIH 3T3 , Antígeno Nuclear de Célula em Proliferação/imunologia , Vacinação/métodos
9.
Anat Histol Embryol ; 41(3): 190-201, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22250786

RESUMO

The cellular cytoskeleton is composed of three fibrillar systems, namely actin microfilaments, microtubules and intermediate filaments (IFs). It not only is a structural system, which mediates functional compartmentalization, but also contributes to many cellular processes such as transport, mitosis, secretion, formation of cell extensions, intercellular communication and apoptosis. In this study, we have examined the distribution of four groups of IFs [cytokeratins (CKs), vimentin, desmin and lamins] in the somatic and germinal cells of the bovine ovary using RT-PCR and immunohistochemical techniques. Using RT-PCR, specific transcripts for all intermediate proteins studied (CK8, CK18, desmin, vimentin, lamin A/C and lamin B1) were detected. A characteristic immunohistochemical staining pattern was observed for the different IFs within the ovary. In this study, we used antibodies against type I CK (acidic CKs: CK14, CK18 and CK19) and type II CK (basic CKs: CK5 and CK8). Among these, only antibodies against CK18 gave a characteristic pattern of immunostaining in the ovary, which included the surface epithelium, the follicle cells, the endothelium of blood vessels and rete ovarii. Antibodies against all other CKs resulted in a weak staining of a limited number of cellular structures (CK5 and CK19) or were completely negative (CK8 and CK14, apart from the surface epithelium). Vimentin antibodies resulted occasionally in a weak staining of the granulosa cells of primary and secondary follicles. In late secondary follicles, the basal and the most apical follicle cells contacting the zona pellucida usually showed a marked immunostaining for vimentin. In antral follicles, three different immunostaining patterns for vimentin were observed. Desmin immunostaining was confined to the smooth muscle cells of blood vessels. Although mRNA for lamin A/C and lamin B1 could be demonstrated using RT-PCR, no immunostaining was found for lamins, neither in the follicle cells nor in the oocytes.


Assuntos
Bovinos/fisiologia , Filamentos Intermediários/genética , Filamentos Intermediários/metabolismo , Folículo Ovariano/fisiologia , Animais , Anticorpos/imunologia , Desmina/análise , Desmina/imunologia , Feminino , Células da Granulosa , Imuno-Histoquímica , Queratinas/análise , Queratinas/imunologia , Laminas/análise , Laminas/imunologia , Oócitos , Vimentina/análise , Vimentina/imunologia
10.
Anat Histol Embryol ; 41(2): 79-86, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21919950

RESUMO

The early post-hatch development of immunoreactivity to vimentin, desmin, smooth muscle actin (SMA) and laminin, in relation to follicle histogenesis, was described in this study. Ovigerous cords in day old quails contained pre-granulosa cells and oocytes. Pre-granulosa cells at the cortico-medullary junction were vimentin immunopositive. A laminin immunopositive basement membrane and desmin immunopositive mesenchymal cells lined the ovigerous cords. Ovigerous cords in 3-day-old quails contained developing primordial follicles, the vimentin immunopositive pre-granulosa cells of which were partially encircled by a basement membrane and desmin immunopositive mesenchymal cells. In 5- to 7-day-old quails, ovigerous cords formed an outer cortical region, while primordial follicles formed the inner cortical region. Early pre-vitellogenic follicles were present in 9- to 13-day-old quails. Underlying the granulosa cells of these follicles was a laminin immunopositive basement membrane and a layer of desmin immunopositive thecal cells. Early and late pre-vitellogenic follicles dominated the ovary in 15- to 17-day-old quails. The thecal layer in these follicles was desmin immunopositive, but SMA immunonegative. The results of the study have shown that the process of primordial follicle development in the Japanese quail is similar to that reported in mammals. The study suggests that in the quail pre-granulosa cells originate predominantly from the medulla. The study has shown that, in the Japanese quail, thecal cells are derived from desmin immunopositive mesenchymal cells lining the ovigerous cords.


Assuntos
Coturnix/crescimento & desenvolvimento , Coturnix/fisiologia , Folículo Ovariano/crescimento & desenvolvimento , Actinas/análise , Actinas/imunologia , Animais , Coturnix/imunologia , Desmina/análise , Desmina/imunologia , Feminino , Células da Granulosa , Imuno-Histoquímica , Laminina/imunologia , Folículo Ovariano/fisiologia , Células Tecais , Vimentina/análise , Vimentina/imunologia
11.
Lymphology ; 40(3): 114-21, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18062612

RESUMO

This case report presents a hydroptic trisomy 21 fetus affected by lymphatic dysplasia with no other malformations. Our studies using CD31, CD34, smooth muscle actin, desmin, and D2-40 antibodies immunohistochemistry confirm the diagnosis of severe pulmonary lymphangiectasia associated with lymphangiectasia ih the mediastinum and small bowel.


Assuntos
Anormalidades Múltiplas/patologia , Síndrome de Down , Hidropisia Fetal/patologia , Linfangiectasia/patologia , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/metabolismo , Actinas/imunologia , Adulto , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Murinos , Antígenos CD34/imunologia , Desmina/imunologia , Evolução Fatal , Feminino , Morte Fetal , Feto , Idade Gestacional , Humanos , Hidropisia Fetal/metabolismo , Imuno-Histoquímica , Linfangiectasia/metabolismo , Masculino , Molécula-1 de Adesão Celular Endotelial a Plaquetas/imunologia , Gravidez
13.
Vestn Oftalmol ; 123(2): 9-17, 2007.
Artigo em Russo | MEDLINE | ID: mdl-17650602

RESUMO

The authors present the results of comparison of clinical, instrumental and histological, immunohistochemical and electron microscopic data on two pigment-free ciliochoroidal tumors. Differential diagnosis was made at each of the above stages of diagnosis. There is evidence that despite the similarity of the clinical syndrome, the spindle-cell type of the histological structure of both tumors, the latter were of various histogenesis. This was confirmed by the results of immunohistochemical and electron microscopic studies. Retrospective analysis of the data of immunohistochemical and echographic studies revealed the distinctive signs that could differentiate these two types of tumors at the stage of clinical and instrumental diagnosis.


Assuntos
Neoplasias do Nervo Óptico/diagnóstico , Pigmentação , Actinas/imunologia , Actinas/metabolismo , Anticorpos Antineoplásicos/análise , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Desmina/imunologia , Desmina/metabolismo , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica/métodos , Masculino , Melaninas/imunologia , Melaninas/metabolismo , Microscopia Eletrônica , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/imunologia , Monofenol Mono-Oxigenase/metabolismo , Estadiamento de Neoplasias , Neoplasias do Nervo Óptico/metabolismo , Reprodutibilidade dos Testes , Estudos Retrospectivos , Proteínas S100/imunologia , Proteínas S100/metabolismo , Vimentina/imunologia , Vimentina/metabolismo
14.
Folia Neuropathol ; 44(3): 191-6, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17039414

RESUMO

Aetiology and pathogenesis of amyotrophic lateral sclerosis (ALS) is still a mystery. Among several hypotheses autoimmune mechanisms are also taken into account. We report here our investigations of auto-antibodies against proteins of spinal cord cells in the cerebrospinal fluid (CSF) and serum of ALS patients. The results were correlated with the severity of disease course. The subjects were 57 ALS patients (29 severe, 28 mild) and 10 normal controls. The major finding in CSF was the presence of antibodies against a 70 kD protein in the majority of ALS patients. This protein was identified as neurofilament 68. The second protein of high reactivity and frequency of appearance was a 82 kD protein, which was identified as a-actinin. Less reactive and less frequent were antibodies directed against 55 kD and 40 kD proteins. They were immunologically defined to be related to desmin and actin, resp. The difference between the reactivity of anti-neurofilament and anti-desmin related protein in the severe and mild ALS groups was significant. More frequent were the anti-neurofilament antibodies in the severe ALS cases as compared to the milder ones. In normal CSF, antibodies directed against 55 kD, 70 kD and 82 kD proteins were present in traces and appeared in 5%, 20% and 10% of cases, respectively. In the serum of 30% of severe ALS patients traces of antibodies against 70 kD protein were detected. The morphological studies in the presence of CSF of ALS patients revealed pronounced immunoreactivity of spinal cord neurons, mainly within anterior horns. The significance of the presence of auto-antibodies in CSF of ALS patients against cellular proteins of the spinal cord is hard to define. It is conceivable that they appear as a secondary immunological consequence of neuronal death. It is also possible that they may accelerate the course of neuronal degeneration.


Assuntos
Esclerose Lateral Amiotrófica/imunologia , Autoanticorpos/líquido cefalorraquidiano , Autoantígenos/imunologia , Neurônios/imunologia , Medula Espinal/imunologia , Actinina/imunologia , Adulto , Idoso , Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Autoanticorpos/sangue , Desmina/imunologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/imunologia , Neurônios/metabolismo , Medula Espinal/metabolismo
16.
Eur J Heart Fail ; 8(5): 477-83, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16376610

RESUMO

BACKGROUND: Primary desminopathies are caused by desmin gene [DES (MIM*125660)] mutations. The clinical spectrum includes pure myopathies, cardiomuscular diseases and cardiomyopathies. Patients with restrictive cardiomyopathy (RCM) plus atrioventricular block (AVB) due to DES defects are frequently unrecognized unless desmin accumulation is specifically investigated in endomyocardial biopsy (EMB) by ultrastructural study. AIMS: To describe a cardiological phenotype characterized by RCM plus AVB due to desmin accumulation caused by DES defects. METHODS AND RESULTS: Desmin accumulation was diagnosed by means of ultrastructural and immunocytochemical studies of EMB in four unrelated probands with RCM and AVB. Candidate genes [DES and alphaB-crystallin (CRYAB)] were screened using sequence analysis. Four DES gene mutations were identified: three new (R16C, T453I and a 10 bp deletion at the exon-intron boundary of exon 3 disrupting the donor splice site) and one known (R406W). The disease was autosomal dominant in two families, recessive in one and associated with a de novo mutation in one. The mutations cosegregated with phenotype in all patients. CRYAB gene screening was negative. CONCLUSIONS: A cardiac phenotype characterized by RCM and AVB caused by desmin accumulation is associated with DES mutations. Although the mutations affected different domains, the cardiac phenotype was identical.


Assuntos
Cardiomiopatia Restritiva/genética , Desmina/genética , Bloqueio Cardíaco/genética , Adolescente , Adulto , Anticorpos/metabolismo , Biópsia , Cardiomiopatia Restritiva/sangue , Análise Mutacional de DNA , Desmina/sangue , Desmina/imunologia , Endocárdio/patologia , Feminino , Bloqueio Cardíaco/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Miocárdio/metabolismo , Miocárdio/patologia , Linhagem , Fenótipo , Análise de Sequência , Cadeia B de alfa-Cristalina/genética
17.
J Pathol ; 208(1): 26-34, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16278817

RESUMO

Chondromyxoid fibroma (CMF) is a rare benign cartilaginous bone tumour with a lobular architecture containing stellate and myofibroblast-like spindle cells. The aim of this study was to investigate the presence, spatial distribution, and extent of myoid differentiation in CMF and to evaluate a possible causative role for TGF-beta1 signalling, which is known to promote smooth muscle actin (SMA) expression. Twenty cases were studied for immunoreactivity for muscle-specific actin (MSA), SMA, desmin, h-caldesmon, calponin, TGF-beta1, and plasminogen activator inhibitor type 1 (PAI-1). The extent of myofibroblastic differentiation was further investigated ultrastructurally, including immuno-electron microscopy using antibodies against MSA and SMA, focusing upon the different cell types in CMF. The expression of potential genes driving this process was quantified by Q-RT-PCR (TGF-beta1, fibronectin, its EDA splice variant, and PAI-1). Tumour cells, especially those with a spindled morphology, showed diffuse immunoreactivity for MSA, SMA, TGF-beta1, and PAI-1, while desmin, h-caldesmon, and calponin were absent. Ultrastructurally, neoplastic cells showed the presence of myofilaments and rare dense bodies, which were more prominent in spindle cells and less so in chondroblast-like cells. Immuno-electron microscopy confirmed the actin nature of these myofilaments. No fibronexus was identified. The functional activity of TGF-beta1 was demonstrated by the identification of PAI-1, a related downstream molecule both immunohistochemically as well as by Q-RT-PCR. There was a linear correlation between TGF-beta1 and PAI-1 expression. Fibronectin-EDA levels were low. We have therefore substantiated the presence of morphological, immunohistochemical, and immuno-electron microscopic partial myofibroblastic differentiation in CMF, driven by TGF-beta1 signalling.


Assuntos
Neoplasias Ósseas/patologia , Condroblastoma/patologia , Fator de Crescimento Transformador beta/metabolismo , Actinas/imunologia , Adolescente , Adulto , Neoplasias Ósseas/genética , Neoplasias Ósseas/ultraestrutura , Proteínas de Ligação ao Cálcio/imunologia , Proteínas de Ligação a Calmodulina/imunologia , Transformação Celular Neoplásica , Criança , Condroblastoma/genética , Condroblastoma/ultraestrutura , Condrócitos/patologia , Condrócitos/ultraestrutura , Desmina/imunologia , Feminino , Fibroblastos/patologia , Fibroblastos/ultraestrutura , Fibronectinas/genética , Fibronectinas/imunologia , Genes Neoplásicos/genética , Humanos , Imuno-Histoquímica/métodos , Masculino , Proteínas dos Microfilamentos , Microscopia Eletrônica/métodos , Microscopia Imunoeletrônica/métodos , Pessoa de Meia-Idade , Proteínas Musculares/imunologia , Músculo Liso/imunologia , Proteínas de Neoplasias/imunologia , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta1 , Calponinas
18.
Vet Pathol ; 42(3): 306-14, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15872376

RESUMO

The transgenic adenocarcinoma mouse prostate (TRAMP) model, designed for researching human prostatic cancer, was genetically engineered to harbor a transgene composed of the simian virus 40 Large-T/small-t antigen promoted by the rat probasin gene. In addition to prostatic neoplasms, the TRAMP mouse develops tumors in the seminal vesicles. This study was conducted to evaluate the pathology and histogenesis of TRAMP seminal vesicle neoplasms. Tissues of accessory sex organs harvested from 72 TRAMP mice of various ages (11-40 weeks of age) were fixed in neutral buffered formalin and stained with hematoxylin and eosin, desmin, 5-bromo-2'-deoxyuridine (BrdU, treated animals only), and SV40 Large-T antigen (SV40-Tag). In the seminal vesicles, we found neoplastic stromal cells that emerged multicentrically just beneath the epithelium, densely packed between the epithelium and the smooth muscle layer. These stromal cells frequently exhibited mitotic figures and showed BrdU incorporation and SV40-Tag protein expression in the nuclei and immunopositivity for desmin. The proliferative mesenchymal cells were lined by cuboidal to columnar epithelium. Some of the larger papillary, polypoid lesions exhibited a phyllodes pattern resembling that seen in mixed epithelial-stromal tumors of the breast, prostate, and seminal vesicles of humans. Although the epithelium was negative for SV40-Tag and showed only occasional incorporation of BrdU, it clearly participated in the biphasic proliferation, forming papillary, cystic, and tubuloglandular structures. No conclusive evidence of malignancy (invasion or metastasis) was identified. Our recommended diagnosis of this lesion in the seminal vesicles is epithelial-stromal tumor.


Assuntos
Carcinoma/patologia , Neoplasias dos Genitais Masculinos/patologia , Glândulas Seminais/patologia , Animais , Antígenos Transformantes de Poliomavirus/metabolismo , Bromodesoxiuridina , Carcinoma/diagnóstico , Desmina/imunologia , Neoplasias dos Genitais Masculinos/diagnóstico , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Transgênicos , Glândulas Seminais/citologia , Células Estromais/patologia
19.
Ophthalmic Plast Reconstr Surg ; 21(1): 16-22, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15677948

RESUMO

PURPOSE: Leiomyomas are exceedingly rare tumors of the orbit and periorbital region. Our objective is to describe the clinical, histopathologic, and radiologic features and the management of 4 cases of orbital leiomyomas and to summarize the cases from the literature. METHODS: This retrospective review describes 4 patients with orbital leiomyoma diagnosed by clinical and histopathologic studies. Electron microscopy was performed in 2 cases. Immunohistochemical techniques were performed with 5 monoclonal antibodies. Selected papers describing well-documented cases of orbital leiomyoma in the English literature published since 1960 were reviewed. RESULTS: CT and MRI showed well-circumscribed contrast-enhancing mass lesions. Three tumors were completely excised and 1 had subtotal excision. All 4 tumors showed immunoreactivity for actin, desmin, and vimentin. Follow-up examination showed no evidence of recurrence in 3 patients. One patient was lost to follow-up. CONCLUSIONS: Leiomyoma should be considered in the differential diagnosis of a well-circumscribed mass lesion involving the orbit and periorbital region. Immunohistochemistry provides conclusive evidence to confirm the diagnosis.


Assuntos
Leiomioma/diagnóstico , Neoplasias Orbitárias/diagnóstico , Actinas/imunologia , Adolescente , Adulto , Anticorpos Antineoplásicos/análise , Criança , Desmina/imunologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Leiomioma/imunologia , Leiomioma/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Orbitárias/imunologia , Neoplasias Orbitárias/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vimentina/imunologia
20.
Malays J Pathol ; 27(1): 9-16, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16676687

RESUMO

AIM: To study the clinical features, histology and immunohistochemical properties of gastrointestinal stromal tumours (GISTs); and establish any parameters that can help prognosticate the malignant potential. METHODS: Twenty-six patients with GISTs who were seen in Sultanah Aminah Hospital Johor, Malaysia from 1999 to 2003 were selected for study. Patient, clinical characteristics and outcome based on surgical records were analysed. Tumour variables (tumour size, cellularity, mitotic count, necrosis and haemorrhage) were compared between very low to low risk groups and intermediate to high risk groups. The immunohistochemical properties of GISTs were also studied. RESULTS: Patients with GISTs presented mainly with pain, palpable mass or gastrointestinal tract bleeding. The tumours were seen in stomach (50%) followed by small intestine (38.5%) and rectum (11.5%). In the period of study, six patients had metastasis, mainly in the liver or peritoneum. Immunoreactivity for CD117, CD34, vimentin, S100, neuron specific enolase, alpha-smooth-muscle-actin and desmin were observed in 100%, 76.9%, 61.5%, 46.1%, 80.8%, 11.5% and 0% of tumours respectively. The behaviour of GISTs was largely dependent on tumour size and number of mitosis. Necrosis and haemorrhage were seen in tumours with high risk potential.


Assuntos
Tumores do Estroma Gastrointestinal/metabolismo , Imuno-Histoquímica , Actinas/imunologia , Actinas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/imunologia , Antígenos CD34/metabolismo , Desmina/imunologia , Desmina/metabolismo , Feminino , Tumores do Estroma Gastrointestinal/patologia , Hemorragia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mitose , Músculo Liso/metabolismo , Necrose/patologia , Metástase Neoplásica , Fosfopiruvato Hidratase/imunologia , Fosfopiruvato Hidratase/metabolismo , Proteínas Proto-Oncogênicas c-kit/imunologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Estudos Retrospectivos , Fatores de Risco , Proteínas S100/imunologia , Proteínas S100/metabolismo , Carga Tumoral , Vimentina/metabolismo
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