RESUMO
Cutaneous-type adult T-cell leukemia-lymphoma is treated with antiviral or skin-directed therapy. Medications that are used to treat skin lesions of cutaneous T-cell lymphomas are also used for the cutaneous-type adult T-cell leukemia-lymphoma. Etretinate, a synthetic retinoid, has been used for treating cutaneous T-cell lymphomas; however, its clinical effectiveness for the treatment of cutaneous-type adult T-cell leukemia-lymphoma has not been fully studied. We conducted a retrospective assessment of the efficacy and safety of etretinate in 9 patients with cutaneous-type adult T-cell leukemia-lymphoma. Complete and partial responses to etretinate were observed in 1 and 7 patients, respectively. Among the responders, remission was maintained for more than 6 years in 2 patients. These results suggest that etretinate is a promising treatment option for cutaneous-type adult T-cell leukemia-lymphoma.
Assuntos
Antineoplásicos/uso terapêutico , Etretinato/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Linfoma Cutâneo de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Quimioterapia Adjuvante , Etretinato/efeitos adversos , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/patologia , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Terapia PUVA , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Fatores de Tempo , Resultado do Tratamento , Terapia UltravioletaRESUMO
BACKGROUND: The use of random skin biopsy (RSB) to diagnose intravascular large B cell lymphoma (IVLBCL) has increased. OBJECTIVE: To explore the indication for RSB to diagnose IVLBCL. METHODS: We retrospectively evaluated the medical records of 18 Japanese adults who underwent RSB between January 2008 and December 2009. RESULTS: A final diagnosis of IVLBCL was returned in 2 patients based on RSB findings and in 1 based on brain biopsy findings. All 3 patients manifested neurological symptoms, hematocytopenia, elevated levels of LDH and soluble interleukin-2 receptor (sIL-2R), and the absence of lymphadenopathy. Malignant lymphoma other than IVLBCL was diagnosed in 6 patients, and in 5 of 6 patients who underwent nodal or parenchymal biopsy diagnostic findings were made. CONCLUSION: Although RSB is useful for the early diagnosis of IVLBCL, careful selection of patients is necessary. In patients with neurological symptoms, hematocytopenia, elevated LDH and sIL-2R and no nodal involvement, RSB may be useful.
Assuntos
Biópsia/métodos , Linfoma Difuso de Grandes Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Biópsia/normas , Diagnóstico Diferencial , Feminino , Humanos , Doenças Linfáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Fabry disease is an inborn error metabolisms caused by deficiency of α-galactosidase A activity, and results in glycolipid accumulation of in multiple tissues or organs. Skin lesions occurred in Fabry disease are characterized by angiokeratoma, including acroparesthesia or hypohydrosis, among others. There are important characteristics for the diagnosis of Fabry disease.
Assuntos
Doença de Fabry/complicações , Dermatopatias/complicações , Humanos , Pele/patologia , alfa-GalactosidaseRESUMO
BACKGROUND: It has been shown that the 3G5 antigen recognized by monoclonal antibody 3G5 (mAb 3G5) is a useful marker of pericytes in normal human skin. However, most 3G5 antigen-expressing cells in capillary vessels were stained negatively for alpha-smooth muscle actin (alpha-SMA), a prominent pericyte marker. This study was designed to determine whether the expression of the 3G5 antigen is restricted to specific stages of pericyte development, or if it is expressed in other cells rather than pericytes in capillary vessels. METHODS: 3G5 antigen-expressing cells were detected in normal human skin, granulating tissues from decubitus ulcers and inflammatory psoriatic skin with extensive angiogenesis using double immunofluorescent staining with mAb 3G5 and monoclonal antibodies (mAbs) to various pericyte markers, tryptase and chymase. Furthermore, using immunoelectron microscopy, 3G5 antigen-expressing cells were observed in the granulating tissues. RESULTS: The immunoelectron microscopic findings and double immunofluorescent staining (using mAb 3G5 and either anti-tryptase or anti-chymase mAbs) showed that 3G5 antigen-expressing cells were mast cells in normal skin, granulating tissues and psoriatic skin. CONCLUSIONS: The results indicated that 3G5 antigen is a marker of mast cells, but not of pericytes in normal and diseased skin.
Assuntos
Anticorpos Monoclonais/imunologia , Gangliosídeos/metabolismo , Tecido de Granulação/metabolismo , Mastócitos/metabolismo , Pericitos/metabolismo , Pele/metabolismo , Biomarcadores/metabolismo , Quimases/imunologia , Técnica Indireta de Fluorescência para Anticorpo , Gangliosídeos/imunologia , Tecido de Granulação/patologia , Humanos , Mastócitos/ultraestrutura , Microscopia Imunoeletrônica , Pericitos/ultraestrutura , Úlcera por Pressão/metabolismo , Úlcera por Pressão/patologia , Psoríase/metabolismo , Psoríase/patologia , Pele/patologia , Triptases/imunologiaRESUMO
A 60-year-old man with a diagnosis of smoldering adult T-cell leukemia (ATL) had been treated successfully for 4 years with psoralen and ultraviolet A therapy, gamma-interferon, oral etoposide and sobuzoxane. He subsequently developed rapidly-growing skin nodules over his entire body. Chest X-ray and thoracic computed tomography showed nodular shadows in the right lower lung field and nodules in both lower lung lobes. Despite combined chemotherapy, he died. Upon autopsy, numerous nodules were found in the bilateral lower lobes; microscopically, the nodules were diffusely infiltrated by ATL cells. Our review of the published work found only two previously reported cases of ATL with pulmonary involvement manifested as nodular shadows. Herein, we present details on the third case.
Assuntos
Leucemia-Linfoma de Células T do Adulto/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Humanos , Leucemia-Linfoma de Células T do Adulto/terapia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Radiografia , Neoplasias Cutâneas/terapiaRESUMO
BACKGROUND: In cultured fibroblasts from I-cell disease patients the transport of many lysosomal enzymes is defective, and affected cells contain inclusion bodies filled with undegraded substrates. However, the contents of these inclusion bodies have not been well characterized yet. We attempted to identify accumulated substances in cultured I-cell disease fibroblasts cytochemically. METHODS: Cultured fibroblasts from I-cell disease patients were double-stained with a monoclonal antibody to lysosome-associated membrane protein-1 (LAMP-1) and that to GM2 ganglioside, or a series of lectins that specifically bind to sugar moieties. RESULTS: The patients' cells were granularly stained with the antibody to GM2 ganglioside and the lectins including Maakia amurensis, Datura stramonium, and concanavalin A. Their localization was coincident with that of LAMP-1. CONCLUSIONS: GM2 ganglioside and various kinds of glycoconjugates having sialic acidalpha2-3galactose, galactosebeta1-4N-acetylglucosamine and mannose residues accumulate in enlarged lysosomes in I-cell disease fibroblasts.
Assuntos
Fibroblastos/química , Gangliosídeo G(M2)/análise , Proteínas de Membrana Lisossomal/análise , Mucolipidoses/metabolismo , Células Cultivadas , Feminino , Histocitoquímica , Humanos , Lactente , Lectinas/análise , Lisossomos/enzimologia , Microscopia Eletrônica , Mucolipidoses/patologia , Pele/ultraestruturaRESUMO
beta-Catenin, a cytoplasmic protein that binds directly to the intracellular domain of cadherin, controls various functions such as cell adhesion. In many human carcinomas, E-cadherin-mediated cell-cell adhesion is lost or disturbed and related to metastasis. The purpose of this study was to compare the expression of beta-catenin in the normal epidermal keratinocytes and samples from cutaneous benign and malignant epidermal tumors in 140 patients. Our study population consisted of 140 patients with benign or malignant epidermal tumors. Using immunohistochemical methods, we compared the expression of beta-catenin in their normal epidermal keratinocytes, and in samples from 61 benign (seborrheic keratosis, n = 33; verruca vulgaris, n = 14; keratoacanthoma, n = 14), and 79 malignant (Bowen's disease, n = 18; basal cell carcinoma, n = 33; squamous cell carcinoma, n = 28) epidermal tumors. beta-Catenin was found to be expressed in the cell membrane of normal keratinocytes. Compared to other cell components of the normal epidermis, basal cells showed the strongest beta-catenin expression in all 140 patients. While absent in three of 61 benign tumors, compared to normal basal cells, the expression of beta-catenin in the other 58 tumors was not significantly different; it was reduced in 71 of 79 malignant tumors (P < 0.0001). In Bowen's disease, the expression of beta-catenin on the tumor cell membrane was reduced, however, strong expression was seen in the nuclei and cytoplasm. Our results suggest that beta-catenin expression on the membrane of keratinocytes is associated with the differentiation of normal keratinocytes but not with their stage of differentiation, nor with the proliferation ability of epidermal tumor cells.
Assuntos
Epiderme/metabolismo , Queratinócitos/metabolismo , Dermatopatias/metabolismo , Neoplasias Cutâneas/metabolismo , beta Catenina/metabolismo , Doença de Bowen/metabolismo , Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/metabolismo , Células Epidérmicas , Humanos , Imuno-Histoquímica , Ceratoacantoma/metabolismo , Ceratose Seborreica/metabolismo , Verrugas/metabolismo , Verrugas/patologiaRESUMO
Merkel cell carcinoma (MCC) is a malignant neuroendocrine tumor with a high rate of recurrence and metastasis. Despite its high degree of malignancy, spontaneous regression has been documented. We report an 87-year-old woman who presented with recurrent MCC on her left cheek and regional lymph node metastasis. Although she received no treatment due to her poor condition, the recurrent metastatic lesion regressed spontaneously within 2 months.
Assuntos
Carcinoma de Célula de Merkel/secundário , Recidiva Local de Neoplasia/patologia , Regressão Neoplásica Espontânea/patologia , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Apoptose , Carcinoma de Célula de Merkel/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Metástase Linfática , Microscopia Eletrônica , Recidiva Local de Neoplasia/ultraestrutura , Neoplasias Cutâneas/ultraestruturaRESUMO
In the present study, we have shown that granulocyte and monocyte adsorption apheresis (GCAP), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is useful for skin diseases attributable to activated granulocytes and psoriatic arthritis (PsA). We assessed the clinical effectiveness of GCAP and investigated the mechanisms underlying the adsorption of pathogenic granulocytes. The effect of GCAP was assessed in 14 patients with neutrophilic dermatoses and 16 with PsA. The mechanisms by which the instrument adsorbs activated granulocytes were investigated using an in vitro mini-column system that mimics the GCAP. Skin lesions and arthropathy improved in 22 of 29 patients (75.9%) and 14 of 18 (77.8%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral neutrophils, increased compared with normal subjects, was reduced by GCAP. In the mini-column system, CA beads adsorbed 50% neutrophils; and adsorption was inhibited significantly by treating plasma with EDTA and blood cells with antihuman CD11b monoclonal antibody. GCAP was useful for treating neutrophilic dermatoses and PsA. GCAP adsorbs Mac-1-expressing neutrophils to the CA beads by the binding of complement component (iC3b) on CA beads and CD11b expressed on activated neutrophils.
Assuntos
Artrite Psoriásica/terapia , Granulócitos/metabolismo , Leucaférese/métodos , Antígeno de Macrófago 1/efeitos adversos , Pioderma/terapia , Adsorção , Adulto , Idoso , Artrite Psoriásica/complicações , Celulose/análogos & derivados , Celulose/química , Feminino , Hemoperfusão , Humanos , Leucaférese/instrumentação , Antígeno de Macrófago 1/sangue , Antígeno de Macrófago 1/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Infiltração de Neutrófilos , Projetos Piloto , Pioderma/imunologia , Resultado do TratamentoRESUMO
Cutaneous allergic vasculitis (CAV) is characterized clinically by purpuric patches with secondary ulcerations, and histologically by leukocytoclastic vasculitis with neutrophil infiltrates. Granulocyte and monocyte adsorption apheresis (GCAP) is an extracorporeal apheresis instrument using a column containing cellulose acetate beads designed to remove pathogenic granulocytes. Here we report our assessment of the efficacy of GCAP for recurrent leg ulcers in a 49-year-old woman with CAV. She underwent five GCAP treatments at one-week intervals. In each treatment session, 1800 mL of blood was processed. Her leg ulcers responded well and her white blood cell and neutrophil counts and the expression level of CD11b/CD18, a marker for activated neutrophils, on her peripheral neutrophils were reduced from 7500/microL to 6500/microL, 4350/microL to 3315/microL, and 64.9 MFI (mean fluorescence intensity) to 27.0 MFI (normal controls: 10.5 +/- 1.2 MFI) by GCAP, respectively. These results suggest that GCAP is useful for skin disorders with leucocytoclastic vasculitis.
Assuntos
Remoção de Componentes Sanguíneos/métodos , Hemoperfusão/métodos , Vasculite Leucocitoclástica Cutânea/terapia , Feminino , Humanos , Antígeno de Macrófago 1/sangue , Antígeno de Macrófago 1/metabolismo , Pessoa de Meia-Idade , Monócitos/imunologia , Neutrófilos/imunologia , Resultado do TratamentoRESUMO
We report a 45-year-old woman with breast cancer who had undergone surgery and radiation and anti-estrogen therapy and presented with many reddish papules in the irradiated breast area. Skin biopsy of the affected area disclosed proliferation of eccrine sweat ducts and cystic structures; the clinical and histopathological features were consistent with syringoma-like eccrine sweat duct proliferation. The lesions spread rapidly on her chest during radiation therapy and regressed spontaneously 3 weeks after its completion. We postulate that the lesions were induced by radiation, and promoted by anti-estrogen therapy.
Assuntos
Glândulas Écrinas/patologia , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias das Glândulas Sudoríparas/diagnóstico , Siringoma/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/patologia , Radioterapia/efeitos adversos , Neoplasias das Glândulas Sudoríparas/etiologia , Neoplasias das Glândulas Sudoríparas/patologia , Siringoma/etiologia , Siringoma/patologiaRESUMO
A 64-year-old male who cultivated orchids as a hobby, had noticed itchy erythematous lesions on both hands since 6 months earlier. His eruptions had gradually worsened and scales and fissures had appeared. Although he was treated with topical corticosteroids by a doctor, his erythema showed no improvement. Patch tests with the orchids he cultivated, fertilizers, antiseptics and insecticides showed positive reactions to the stems of Cymbidium and Oncidium orchids. A diagnosis of contact dermatitis attributable to the cultivated orchids was made.
Assuntos
Dermatite Alérgica de Contato/etiologia , Exposição Ocupacional/efeitos adversos , Orchidaceae/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Seguimentos , Dermatoses da Mão/diagnóstico , Dermatoses da Mão/etiologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Testes do Emplastro , Medição de Risco , Índice de Gravidade de DoençaRESUMO
We report an adult T-cell leukemia/lymphoma (ATL) patient whose crusted scabies was successfully treated with oral ivermectin. This 63-year-old man had previously been treated with oral prednisolone, sobuzoxane and etoposide for approximately 1 year. When he developed crusted scabies, he received two doses of oral ivermectin (200 microg/kg) 10 days apart and the concomitant topical application of crotamiton containing 30% benzyl benzoate. This produced remarkable results, suggesting that oral ivermectin should be considered for the treatment of crusted scabies even in immunocompromised patients. While ivermectin may be useful for treating intractable scabies, attention must be paid to the possible appearance of ivermectin-resistant mites.
Assuntos
Ivermectina/administração & dosagem , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Escabiose/diagnóstico , Administração Oral , Animais , Relação Dose-Resposta a Droga , Esquema de Medicação , Seguimentos , Humanos , Leucemia-Linfoma de Células T do Adulto/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Escabiose/complicações , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Bidens pilosa (BP) Linn. var. radiata is a plant used in traditional folk medicine. It is clinically effective in various diseases; the pathogenesis of most of these involves cyclooxygenase (COX)-2. To investigate the mechanism on which the clinical effectiveness of BP is based, we examined its effects on COX-2 expression and its major product, prostaglandin (PG)E(2), under conditions of inflammation. We induced inflammation in normal human dermal fibroblasts with interleukin (IL)-1beta and examined the effects of BP on COX-2 expression and PGE(2) production using Western blotting and competitive enzyme immunoassay, respectively. The functional involvements of mitogen activated protein kinases (MAPK) ERK1/2, p38, and JNK in COX-2 expression were also examined by Western blotting. IL-1beta-induced COX-2 expression was regulated by MAPK pathways, especially by p38. BP inhibited the phosphorylation of MAPKs, COX-2 expression, and subsequent PGE(2) production. The physiological activities and clinical effectiveness of BP observed under diverse conditions may be partly attributable to its ability to inhibit MAPK, mainly p38, activity, COX-2 expression, and subsequent PGE(2) production.
Assuntos
Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Bidens , Técnicas de Cultura de Células , Derme/citologia , Humanos , Interleucina-1beta , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
Leuprorelin acetate, a chemotherapeutic agent used to treat prostate cancer, is a synthetic luteinizing hormone-releasing hormone (LHRH) agonist. We report a 75-year-old man who presented with several large subcutaneous nodules at the site of leuprorelin acetate injections for his prostatic cancer. A biopsy of the nodules disclosed epithelioid granulomatous inflammation and resulted in a diagnosis of drug-induced granulomatous reaction to leuprorelin acetate.
Assuntos
Antineoplásicos Hormonais/efeitos adversos , Hormônio Liberador de Gonadotropina/agonistas , Granuloma/diagnóstico , Leuprolida/efeitos adversos , Neoplasias Cutâneas/diagnóstico , Abdome , Idoso , Antineoplásicos Hormonais/administração & dosagem , Diagnóstico Diferencial , Granuloma/induzido quimicamente , Granuloma/patologia , Humanos , Injeções Subcutâneas , Leuprolida/administração & dosagem , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologiaRESUMO
We report a 74-year-old Japanese man with squamous cell carcinoma (SCC) originating in the frontal sinus. It presented as a cutaneous nodule on his right forehead. Magnetic resonance imaging (MRI) revealed invasion of the anterior wall of the ethmoid sinus, the frontal bone, and possibly the meninx by a frontal sinus carcinoma. Despite right fronto craniotomy with en bloc resection followed by two courses of radiation therapy and chemotherapy with 5-fluorouracil and nedaplatin or TS-1 he died of disease-related causes 20 months later. Herein, we present a detailed description of this patient and a review of the published work.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Seio Frontal/patologia , Neoplasias dos Seios Paranasais/diagnóstico , Idoso , Diagnóstico Diferencial , Seio Etmoidal/patologia , Neoplasias Faciais/diagnóstico , Evolução Fatal , Osso Frontal/patologia , Humanos , Masculino , Invasividade Neoplásica , Neoplasias Cranianas/diagnósticoRESUMO
A decrease in the activity of ferrochelatase (FECH; EC 4.99.1.1), the terminal enzyme of the heme biosynthetic pathway, results in erythropoietic protoporphyria (EPP; MIM 177000). We analyzed the FECHgene in eight Japanese EPP patients from seven non-consanguineous families and found two distinct genomic DNA abnormalities. In six patients from five families, there was a G-to-A point-mutation at the first position of the intron 9 donor site; it resulted in aberrant splicing and skipping of exon 9 in FECH mRNA. In one patient, we found an A-to-G point-mutation 4 bases from the 3" terminus of intron 4 that led to the in-frame insertion of 3 bases in mRNA. No allelic anomalies, except for 3 single nucleotide polymorphisms were detected in another patient. We analyzed intron polymorphism at IVS3-48, known to be associated with the phenotypic expression of EPP, in these eight patients and 152 healthy Japanese volunteers. All patients were C/C homozygous for IVS3-48. The allelic frequency of IVS3-48C polymorphism in the healthy Japanese volunteers was 67.8% (103/152).
Assuntos
Povo Asiático/genética , Ferroquelatase/genética , Mutação/genética , Protoporfiria Eritropoética/enzimologia , Protoporfiria Eritropoética/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Íntrons/genética , Masculino , Polimorfismo Genético/genéticaRESUMO
Thymidine phosphorylase (TP), an enzyme involved in the reversible conversion of thymidine to thymine, is identical to an angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF). Both TP and one of the TP-degradation products of thymidine 2-deoxy-D-ribose (dRib) display endothelial cell chemotactic activity in vitro and angiogenic activity in vivo. Recently, we demonstrated that 2-deoxy-L-ribose (lRib) could abolish the inhibitory effect of dRib on hypoxia-induced apoptosis. This suggested that lRib may be a useful inhibitor of dRib and thereby of TP functions. Therefore, we investigated the ability of lRib to inhibit the range of biological activities of TP and dRib. lRib suppressed both dRib-induced endothelial cell migration in a chemotaxis assay and endothelial tube formation induced by dRib in a collagen gel. lRib could also suppress the biological effects of TP in vivo assays of angiogenesis and tumor growth. Thus, in a corneal assay of angiogenesis, lRib inhibited angiogenesis induced by the implantation of recombinant TP. In a dorsal air sac assay of angiogenesis, lRib inhibited angiogenesis induced by the implantation of KB cells overexpressing TP (KB/TP). In a tumor growth assay, lRib treatment considerably decreased the growth rate of KB/TP cells xenografted into nude mice and also resulted in an increase in the proportion of apoptotic cells in KB/TP tumors. These findings demonstrate that TP and dRib play an important role in angiogenesis and tumor growth, and that these effects can be inhibited by lRib. Thus, lRib is a potentially useful agent for the suppression of TP-dependent angiogenesis and tumor growth.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Desoxirribose/farmacologia , Inibidores Enzimáticos/farmacologia , Neovascularização Patológica/tratamento farmacológico , Timidina Fosforilase/antagonistas & inibidores , Animais , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Quimiotaxia/efeitos dos fármacos , Desoxirribose/antagonistas & inibidores , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/enzimologia , Neovascularização Fisiológica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Timidina Fosforilase/fisiologia , Células Tumorais CultivadasRESUMO
To clarify the pathogenesis of cardiac hypertrophy in carnitine-deficient juvenile visceral steatosis (JVS) mice, we performed differential mRNA display analysis with the ventricles of control and JVS mice. We found a novel up-regulated gene, designated as carnitine deficiency-associated gene expressed in ventricle (CDV)-3. Northern blot analysis with a cDNA probe derived from the novel gene revealed two substantial mRNA species of prominent 4.1- and faint 3.5-kb in examined tissues of control and JVS mice. In spite of their widely expressed features, up-regulation of the gene was found predominantly in the ventricles and slightly in the auricles and skeletal muscles of JVS mice. The up-regulation of CDV-3 gene in the ventricles of JVS mice was significantly relieved by carnitine administration within 6 h. The entire cDNA nucleotide sequences showed that two kinds of cDNA, long and short versions (CDV-3A and -3B), corresponding to the detected mRNAs, are different in a 711 base fragment. Analysis of genomic DNA revealed that the two mRNAs were derived from a single CDV-3 gene with five exons by alternative splicing. The deduced amino acid sequences indicated that the isoforms consist of 236 and 281 residues, differing at regions near the carboxy-terminus but sharing 231 residues of the amino-terminal regions. A BLAST search revealed that they show a high similarity to a human predicted nuclear protein (H41), which has been reported to be up-regulated in breast cancer cells overexpressing cellular-erythroblastosis B-2 (c-erbB-2, a kind of tyrosine kinase).We report the identification and characterization of novel transcripts that may be involved in the development of cardiac hypertrophy caused by carnitine deficiency.