RESUMEN
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.
Asunto(s)
Enfermedad de Fabry/complicaciones , Enfermedades de la Piel/complicaciones , Humanos , Piel/patología , alfa-GalactosidasaRESUMEN
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.
Asunto(s)
Antineoplásicos/uso terapéutico , Etretinato/uso terapéutico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Linfoma Cutáneo de Células T/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Quimioterapia Adyuvante , Etretinato/efectos adversos , Femenino , Humanos , Leucemia-Linfoma de Células T del Adulto/patología , Linfoma Cutáneo de Células T/patología , Masculino , Persona de Mediana Edad , Terapia PUVA , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Factores de Tiempo , Resultado del Tratamiento , Terapia UltravioletaAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Erupciones por Medicamentos/etiología , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Erupciones por Medicamentos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Adult T-cell leukemia-lymphoma (ATL), characterized by various clinicopathological features, is divided into four clinical subtypes, namely, acute, lymphoma, chronic and smoldering types, and the treatment strategy differs according to the clinical subtype. The designation cutaneous type ATL has been proposed to describe a peculiar subgroup of smoldering type ATL in which the skin is predominantly affected. However, diagnostic criteria and prognostic factors for cutaneous type ATL remain to be determined. Therefore, we performed a retrospective study to obtain a precise method for subtype classification and to clearly define cutaneous type ATL. A total of 87 ATL patients (acute, n = 31; lymphoma, n = 6; chronic, n = 24; smoldering, n = 26) were enrolled. The human T-lymphotropic virus type I (HTLV-1) proviral load in peripheral blood and the serum soluble interleukin-2 receptor (sIL-2R) level were evaluated with respect to the clinical features of the different types of ATL. The HTLV-1 proviral load was significantly increased in the acute and chronic type and the serum sIL-2R level was increased in the acute and lymphoma type. The HTLV-1 proviral load was significantly lower in cutaneous than other smoldering types of ATL without skin lesions. The clinical findings of cutaneous type ATL were also different from other subtypes. These results indicate that, in combination, determination of the HTLV-1 proviral load and the serum sIL-2R level is useful for distinguishing among the different types of ATL, and strongly suggest that cutaneous type ATL is a distinct clinical entity.
Asunto(s)
Leucemia-Linfoma de Células T del Adulto/virología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Leucemia-Linfoma de Células T del Adulto/clasificación , Leucemia-Linfoma de Células T del Adulto/inmunología , Linfoma Cutáneo de Células T/clasificación , Linfoma Cutáneo de Células T/inmunología , Linfoma Cutáneo de Células T/virología , Masculino , Persona de Mediana Edad , Provirus/aislamiento & purificación , Receptores de Interleucina-2/sangre , Estudios Retrospectivos , Neoplasias Cutáneas/clasificación , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/virología , Carga Viral , Adulto JovenRESUMEN
Trichothiodystrophy group A (TTD-A) is one of the three types of photosensitive TTD and is a very rare genodermatosis with deficient post-ultraviolet (UV) DNA repair. We herein describe the first Japanese case with a novel mutation in the GTF2H5 gene responsible for TTD-A. A 5-year-old male, born as a collodion baby from healthy non-consanguineous parents, exhibited sun sensitivity, brittle hair, ichthyosis, cataracts and mental/physical retardation. He demonstrated neither neurological abnormalities nor pigmentary changes following sun exposure. The patient's primary fibroblasts were hypersensitive to killing by UV (D0 = 1.5 J/m(2) ), and the post-UV unscheduled DNA synthesis was 13% of normal. A host cell reactivation complementation analysis showed a decreased DNA capacity without recovery after transfecting any xeroderma pigmentosum genes. We identified a novel homozygous mutation (c.166G>T) in the coding region of the GTF2H5 gene that resulted in a predicted amino acid change: p.E55X. Thus far, only one Japanese case of TTD with a mutation of the XPD gene had been reported. The present case is the first of TTD-A and the second case of TTD in Japan, suggesting that it is necessary to differentiate TTD from other photosensitive disorders, although the incidence of TTD is very low in Japan compared to that observed in Western countries.
Asunto(s)
Factores de Transcripción/genética , Síndromes de Tricotiodistrofia/genética , Pueblo Asiatico/genética , Secuencia de Bases , Preescolar , Codón sin Sentido , ADN/genética , Reparación del ADN/genética , Femenino , Homocigoto , Humanos , Japón , Masculino , LinajeRESUMEN
Adult T-cell leukemia-lymphoma (ATL) is one of the most malignant lymphomas with poor prognosis. ATL cells express CC chemokine receptor 4 (CCR4) and mogamulizumab, a monoclonal antibody against CCR4 that exhibits very strong cytotoxicity for ATL cells via antibody-dependent cellular cytotoxicity. Although its effect is dramatic in ATL, serious adverse reactions such as Stevens-Johnson syndrome have been reported. However, these eruptions can appear as therapeutic signs of mogamulizumab. We evaluated the effectiveness of mogamulizumab in five acute-type ATL patients. Peripheral blood (PB) and lymph nodes (LN) were affected in three and four patients, respectively. In PB, complete response (CR) was obtained in all three patients and partial response (PR) was recorded in LN of one patient. In skin lesions, four of five patients manifested CR; in two, the lesions worsened after the start of mogamulizumab treatment and subsequently improved. In these lesions, CD4(+) 8(-) 25(+) ATL cells were replaced by CD3(+) 8(+) cytotoxic T cells. Cutaneous adverse reactions (CAR) developed in two patients with CR; they did not show a relapse of ATL over the course of 9 months. Our findings suggest that mogamulizumab should be continued and surface marker evaluation should be performed even in patients whose skin lesions show aggravation, and that CAR may be a marker for a favorable prognosis.
Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Erupciones por Medicamentos/etiología , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Anciano , Erupciones por Medicamentos/patología , Femenino , Humanos , Leucemia-Linfoma de Células T del Adulto/patología , Masculino , Persona de Mediana Edad , Pronóstico , Receptores CCR4/antagonistas & inhibidores , Recurrencia , Piel/patologíaRESUMEN
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.
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Biopsia/métodos , Linfoma de Células B Grandes Difuso/patología , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Biopsia/normas , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades Linfáticas/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
The pathogenesis of systemic sclerosis (SSc) is not fully understood and there is no effective treatment for this disease. Retinoic acid (RA) can modulate connective tissue metabolism, exhibit anti-fibrotic activity, and improve the clinical symptoms of SSc. However, the mechanisms by which RA elicits its anti-fibrotic actions remain to be determined. The aim of this study was to elucidate the underlying mechanisms by which RA exerts beneficial effects on scleroderma. Cultured skin fibroblasts from patients with scleroderma were treated with RA and their effect on the expression of 5-lipoxygenase (LOX), transforming growth factor (TGF)-ß1, connective tissue growth factor (CTGF), type I and type III collagen was tested by reverse transcription polymerase chain reaction (RT-PCR) and western immunoblotting. The effect of MK886, a 5-LOX-specific inhibitor, on the expression of TGF-ß1, CTGF, type I and type III collagen was also examined by RT-PCR. In cultured scleroderma fibroblasts, the expression of 5-LOX was elevated compared with normal human dermal fibroblasts. RA significantly inhibited the expression of 5-LOX and of TGF-ß1, CTGF, type I and type III collagen. We further found that the expression of TGF-ß1, CTGF and type I and type III collagen mRNA was inhibited by MK886 in scleroderma fibroblasts. In vitro, RA reduced 5-LOX expression in scleroderma fibroblasts and downregulated TGF-ß1 and CTGF expression, leading to the inhibition of type I and type III collagen synthesis. Our results indicate that the clinical effects of RA on scleroderma are, at least in part, attributable to the reduction of 5-LOX expression and the subsequent suppression of TGF-ß1 and CTGF expression that results in the blockade of collagenogenesis.
Asunto(s)
Inhibidores de la Lipooxigenasa/farmacología , Esclerodermia Sistémica/tratamiento farmacológico , Esclerodermia Sistémica/metabolismo , Tretinoina/farmacología , Adulto , Anciano , Araquidonato 5-Lipooxigenasa/genética , Araquidonato 5-Lipooxigenasa/metabolismo , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , Indoles/farmacología , Masculino , Persona de Mediana Edad , Esclerodermia Sistémica/genética , Piel/efectos de los fármacos , Piel/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Thymidine phosphorylase (TP) is an enzyme involved in reversible conversion of thymidine to thymine. TP is identical to an angiogenic factor, pletelet-derived endothelial cell growth factor (PD-ECGF) and the expression levels of TP in a variety of malignant tumors were higher than the adjacent non-neoplastic tissues. To investigate the molecular basis for the effect of TP on the metabolic process and the anticancer effect of 5-fluorouracil (5-FU), human gastric carcinoma AZ521 cells and epidermoid carcinoma KB cells were transfected with TP cDNA, and AZ521/TP and KB/TP were cloned. AZ521/TP and KB/TP cells overexpressed TP and were more sensitive to 5-FU than the counterpart parental cells. TPI, a newly synthesized inhibitor for TP (Ki=2.36 x 10(-9) M), decreased the sensitivity to 5-FU of the TP expressing cells but not of the parental cells. 5-Formyl-tetrahydrofolate (leucovorin; LV) stabilized the complex of thymidylate synthase (TS) and 5-fluoro-deoxyuridine-monophosphate (FdUMP), increased the sensitivity to 5-FU of TP expressing AZ521 cells, but not of the parental cells. The levels of FdUMP in TP expressing cells were significantly higher than in parental cells and TPI considerably decreased FdUMP to the level comparable to that in the parental cells. 5-FU increased the expression of early growth response protein-1 (Egr-1) and an angiogenesis inhibitor, thrombospondin-1 (TSP-1), in KB/TP cells but only slightly in KB/CV cells, if any. TPI attenuated the induction of Egr-1 and TSP-1 mRNA by 5-FU, while LV increased the expression of Egr-1 and TSP-1 mRNA in KB/TP cells. These findings demonstrate that the TP has a principal role in the production of FdUMP and the enhanced responses to 5-FU by leucovorin in TP-overexpressing KB and AZ521 cells, and FdUMP but not FUTP is implicated in the induction of Egr-1 and TSP-1 in KB cells.
Asunto(s)
Carcinoma/tratamiento farmacológico , Proteína 1 de la Respuesta de Crecimiento Precoz/biosíntesis , Fluorouracilo/farmacología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Trombospondina 1/biosíntesis , Timidina Fosforilasa/metabolismo , Antimetabolitos Antineoplásicos/farmacología , Carcinoma/enzimología , Línea Celular Tumoral , Didesoxinucleótidos/farmacología , Fluorodesoxiuridilato/farmacología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Cutáneas/enzimología , Neoplasias Gástricas/enzimología , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/farmacologíaRESUMEN
To examine the uptake of a recombinant human alpha-L-iduronidase (laronidase) by cultured fibroblasts from a patient with mucopolysaccharidosis I (MPS I) and its effect on the cleavage of accumulated substrates, we performed enzymological, Western blotting, immunocytochemical and morphological studies. Laronidase was incorporated into the MPS I cells dose-dependently mainly via mannose 6-phosphate (M6P) receptors. Then the incorporated enzyme was transported to lysosomes and processed to the mature form, the pathological changes of the cells being improved. Furthermore, we compared the uptake of laronidase by cultured mouse osteoblasts with that by cultured mouse fibroblasts. The enzyme was incorporated into the cultured mouse osteoblasts mainly via M6P receptors, although mannose (Man) receptors were partially involved in the uptake of the enzyme, as in the cultured fibroblasts. But the uptake by the former was apparently lower than that by the latter. The administration of a high dose of the enzyme or development of a recombinant alpha-L-iduronidase containing many M6P residues is required for further improvement of enzyme replacement therapy for skeletal disorders caused by MPS I.
Asunto(s)
Fibroblastos/metabolismo , Iduronidasa/metabolismo , Osteoblastos/metabolismo , Animales , Células Cultivadas , Fibroblastos/ultraestructura , Humanos , Cinética , Ratones , Mucopolisacaridosis I/metabolismo , Osteoblastos/ultraestructura , Receptor IGF Tipo 2/metabolismo , Proteínas Recombinantes/metabolismoRESUMEN
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.
Asunto(s)
Leucemia-Linfoma de Células T del Adulto/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Cutáneas/patología , Humanos , Leucemia-Linfoma de Células T del Adulto/terapia , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Radiografía , Neoplasias Cutáneas/terapiaRESUMEN
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.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Gangliósidos/metabolismo , Tejido de Granulación/metabolismo , Mastocitos/metabolismo , Pericitos/metabolismo , Piel/metabolismo , Biomarcadores/metabolismo , Quimasas/inmunología , Técnica del Anticuerpo Fluorescente Indirecta , Gangliósidos/inmunología , Tejido de Granulación/patología , Humanos , Mastocitos/ultraestructura , Microscopía Inmunoelectrónica , Pericitos/ultraestructura , Úlcera por Presión/metabolismo , Úlcera por Presión/patología , Psoriasis/metabolismo , Psoriasis/patología , Piel/patología , Triptasas/inmunologíaRESUMEN
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.
Asunto(s)
Epidermis/metabolismo , Queratinocitos/metabolismo , Enfermedades de la Piel/metabolismo , Neoplasias Cutáneas/metabolismo , beta Catenina/metabolismo , Enfermedad de Bowen/metabolismo , Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/metabolismo , Células Epidérmicas , Humanos , Inmunohistoquímica , Queratoacantoma/metabolismo , Queratosis Seborreica/metabolismo , Verrugas/metabolismo , Verrugas/patologíaRESUMEN
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.
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Carcinoma de Células de Merkel/secundario , Recurrencia Local de Neoplasia/patología , Regresión Neoplásica Espontánea/patología , Neoplasias Cutáneas/patología , Anciano de 80 o más Años , Apoptosis , Carcinoma de Células de Merkel/ultraestructura , Femenino , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Metástasis Linfática , Microscopía Electrónica , Recurrencia Local de Neoplasia/ultraestructura , Neoplasias Cutáneas/ultraestructuraAsunto(s)
Técnicas Cosméticas/efectos adversos , Dermatosis Facial/inducido químicamente , Granuloma de Cuerpo Extraño/inducido químicamente , Parafina/efectos adversos , Anciano , Femenino , Granuloma de Cuerpo Extraño/patología , Humanos , Inyecciones , Microscopía Electrónica , Parafina/administración & dosificación , Piel/patología , Piel/ultraestructuraAsunto(s)
Antineoplásicos/efectos adversos , Dapsona/efectos adversos , Linfohistiocitosis Hemofagocítica/inducido químicamente , Adulto , Antineoplásicos/uso terapéutico , Células de la Médula Ósea/patología , Dapsona/uso terapéutico , Humanos , Masculino , Síndrome de Sézary/tratamiento farmacológicoRESUMEN
Peripheral neuropathy is one of the important manifestations of Fabry disease. Enzyme replacement therapy with presently available recombinant alpha-galactosidases does not always improve the Fabry neuropathy. But the reason has not been determined yet. We established a Schwann cell line from Fabry mice, characterized it, and then examined the uptake of alpha-galactosidase by cells and its effect on the degradation of accumulated substrate. The cells exhibited a distinct Schwann cell morphology and biochemical phenotype (alpha-Galactosidase activity was deficient, and numerous cytoplasmic inclusion bodies were present in the cells). A recombinant alpha-galactosidase added to the culture medium was incorporated into the cultured Fabry Schwann cells dose dependently. But the increase in cell-associated enzyme activity was less than that in the cases of human and mouse Fabry fibroblasts. The administration of a high dose of the enzyme improved the pathological changes in cells, although a low dose of it did not. Cellular uptake of the enzyme was strongly inhibited in the presence of mannose 6-phosphate. This suggests that the enzyme is incorporated via cation-independent mannose 6-phosphate receptors in Schwann cells. The low expression of cation-independent mannose 6-phosphate receptors in Schwann cells must be one of the reasons their uptake of the present enzymes was low. The administration of a high dose of the enzyme or the development of an enzyme containing many mannose 6-phosphate residues is required to improve Fabry neuropathy.
Asunto(s)
Enfermedad de Fabry/tratamiento farmacológico , Células de Schwann/metabolismo , alfa-Galactosidasa/farmacocinética , Animales , Transporte Biológico , Relación Dosis-Respuesta a Droga , Enfermedad de Fabry/enzimología , Enfermedad de Fabry/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Receptor IGF Tipo 2 , Proteínas Recombinantes , Células de Schwann/efectos de los fármacos , alfa-Galactosidasa/antagonistas & inhibidoresRESUMEN
We report 2 patients with multicentric Castleman disease. Both presented with multiple, indurated, hyperpigmented plaques, generalized lymphadenopathy and polyclonal hypergammaglobulinemia. Biopsy specimens showed infiltration of mature plasma cells and lymphocytes in the dermis and lymph nodes. Skin specimens were negative for human herpesvirus 8, latent nuclear antigen 1 and Epstein-Barr virus by in situ hybridization. PCR disclosed clonal T-cell receptor gene rearrangement in the bone marrow cells of 1 patient. We discuss the possible relationship between multicentric Castleman disease and systemic plasmacytosis as well as plasma cell proliferation.
Asunto(s)
Enfermedad de Castleman/patología , Células Plasmáticas/patología , Enfermedades de la Piel/patología , Piel/patología , Adulto , Biopsia , Enfermedad de Castleman/diagnóstico , Proliferación Celular , Femenino , Humanos , Enfermedades Linfáticas/diagnóstico , Enfermedades Linfáticas/patología , Linfocitos/patología , Masculino , Persona de Mediana Edad , Enfermedades de la Piel/diagnósticoRESUMEN
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.