RESUMEN
Various angiogenic factors, such as vascular endothelial growth factor (VEGF) and an associated molecule, placenta growth factor (PlGF), are thought to be important for normal and malignant hematopoiesis. This study examined mRNA expression of VEGF, PlGF and receptors for these molecules in AML cells and identified the disease-specific patterns of expression. AML M3 having t(15;17) abnormality showed highest expression of VEGF and VEGF receptor type 1 (VEGFR1), suggesting the autocrine pathway of VEGF-VEGFR1. Then, t(8;21) AML demonstrated augmented expression of VEGF and VEGF receptor type 2 (VEGFR2), suggesting VEGF-VEGFR2 autocrine pathway. Then, addition of VEGFR2 kinase inhibitor in Kasumi-1, a t(8;21) AML cell line, resulted in marked inhibition of cell growth, although growth inhibitory effect of R2 kinase inhibitor to HL-60 was marginal. In addition, cell cycle analysis study showed S-phase cell population reduction by R2 kinase inhibitor in Kasumi-1, but not in HL-60. This observation is thought to be the rationale for novel molecular target therapy directed to angiogenic molecules.
Asunto(s)
Comunicación Autocrina/genética , Leucemia Mieloide Aguda/genética , Translocación Genética/genética , Factor A de Crecimiento Endotelial Vascular/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Aberraciones Cromosómicas , Cromosomas Humanos Par 15/genética , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 8/genética , Enfermedad , Inhibidores Enzimáticos/farmacología , Regulación Leucémica de la Expresión Génica/genética , Células HL-60 , Humanos , Leucemia Mieloide Aguda/metabolismo , Persona de Mediana Edad , Factor de Crecimiento Placentario , Proteínas Gestacionales/biosíntesis , Proteínas Gestacionales/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Receptor 1 de Factores de Crecimiento Endotelial Vascular/biosíntesis , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) is a transcription factor that is activated as a result of t(6;14)(p25;q32) in multiple myeloma. MUM1 expression is seen in various B-cell lymphomas and predicts an unfavorable outcome in some lymphoma subtypes. To elucidate its role in B-cell malignancies, we prepared MUM1-expressing Ba/F3 cells, which proliferated until higher cellular density than the parental cells, and performed cDNA microarray analysis to identify genes whose expression is regulated by MUM1. We found that the expression of four genes including FK506-binding protein 3 (FKBP3), the monokine induced by interferon-gamma(MIG), Fas apoptotic inhibitory molecule (Faim) and Zinc-finger protein 94 was altered in the MUM1-expressing cells. We then focused on MIG since its expression was immediately upregulated by MUM1. In reporter assays, MUM1 activated the MIG promoter in cooperation with PU.1, and the interaction between MUM1 and the MIG promoter sequence was confirmed. The expression of MIG was correlated with that of MUM1 in B-CLL cell lines, and treatment with neutralizing antibodies against MIG and its receptor, CXCR3, slightly inhibited the proliferation of two MUM1-expressing lines. These results suggest that MUM1 plays roles in the progression of B-cell lymphoma/leukemia by regulating the expression of various genes including MIG. Leukemia (2005) 19, 1471-1478. doi:10.1038/sj.leu.2403833; published online 16 June 2005.
Asunto(s)
Quimiocinas CXC/genética , Proteínas de Unión al ADN/fisiología , Regulación Neoplásica de la Expresión Génica , Leucemia de Células B/genética , Factores de Transcripción/fisiología , Regulación hacia Arriba/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Quimiocina CXCL9 , Perfilación de la Expresión Génica , Humanos , Factores Reguladores del Interferón , Leucemia de Células B/patología , Linfoma de Células B/genética , Linfoma de Células B/patología , Ratones , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas , TransactivadoresRESUMEN
ABO-incompatible renal transplantation (ABOIRTx) tend to lead to blood type antibody-mediated rejection, the so-called delayed hyperacute rejection (DHAR), which results in short-term graft loss. To clarify the accurate incidence and prognostic value of DHAR among ABOIRTx, we reviewed biopsy specimens obtained from ABOKTx allografts with abrupt dysfunction during the early period after transplantation. Among 74 ABOIRTx patients, 34 patients displayed allograft dysfunction within 14 days following transplantation. The biopsy specimens were classified based on the Banff schema. The pathological diagnosis of ABO blood type antibody-mediated humoral rejection (ABO-AMHR) was made by the following 3 findings: Specimens with all of above-mentioned findings were categorized as severe ABO-AMHR; those with at least one findings, were categorized as mild ABO-AMHR. All patients were treated with steroid pulse therapy and/or modification of other immunosuppressants. Group 1 consisted of severe ABO-AMHR (n = 6); group 2 consisted of mild ABO-AMHR (n = 5); group 3 consisted of acute cellular rejection (n = 3); group 4 consisted of recovery phase of ATN (n = 11); group 5 consisted of calcineurin inhibitor toxicity (n = 2); and group 6 consisted of normal histology (n = 5). One of 6 patients (16%) in group 1 lost the graft because of DHAR irreversible by antirejection and anticoagulation therapy. However, there has been no clear definition of histpathological criteria for DHAR after ABO-incompatible kidney transplantation. The definition must prognosticate whether the rejection process is reversible.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Rechazo de Injerto/inmunología , Trasplante de Riñón/inmunología , Trasplante de Riñón/patología , Adulto , Biopsia , Femenino , Rechazo de Injerto/epidemiología , Humanos , Incidencia , Isoanticuerpos/sangre , Masculino , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/inmunología , Estudios Retrospectivos , Esplenectomía , Trasplante Homólogo/inmunología , Trasplante Homólogo/patologíaAsunto(s)
Ciclosporina/farmacocinética , Trasplante de Riñón/inmunología , Área Bajo la Curva , Ciclosporina/sangre , Ciclosporina/uso terapéutico , Monitoreo de Drogas/métodos , Estudios de Seguimiento , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/sangre , Inmunosupresores/farmacocinética , Inmunosupresores/uso terapéutico , Japón , Donadores Vivos , Análisis de Regresión , Factores de TiempoRESUMEN
BACKGROUND: Due to a severe shortage of suitable cadaveric allografts for children awaiting kidney transplants, we have performed a series of ABO-incompatible living kidney transplantations (LKT) at our institution. METHODS: Between July 1989 and March 2000, 16 pediatric patients (3 female, 13 male) underwent ABO-incompatible LKT. The mean age at transplantation was 10.9+/-4.3 years (range 5.1-15.0 years). The donor to recipient ABO blood antigen incompatibility was as follows: A1-->O, 5 patients; B-->O, 6 patients; A1B-->B, 2 patients; and A1B -->B, A1-->B, or B-->A1, 1 patient each. The median pretransplantation anti-A1 titers of eight A-incompatible recipients were 1:128 (IgM, range 1:16 to 1:512) and 1:32 (IgG, range 1:2 to 1:128). Median anti-B titers of seven B-incompatible recipients were 1:32 (IgM, range 1:4 to 1:128) and 1:8 (IgG, range 1:2 to 1:64). All patients received three or four sessions of plasmapheresis (PP) and/or immunoadsorption (IA) to remove the anti-A and/or anti-B antibodies before transplantation. Immunosuppression initially consisted of cyclosporine, methylprednisolone, cyclophosphamide, and antilymphocyte globulin. Splenectomy was performed on all recipients at the time of transplantation. RESULTS: The patients were followed for 6 to 122 months with a mean follow-up of 63 months. All 16 recipients who underwent ABO-incompatible LKT achieved a pretransplant isoagglutinin titer less than 1:8 with 3-4 sessions of PP/IA treatment. Of 16 patients, 10 patients had rebound increase in their IgM and/or IgG anti-A/B titers to greater than 1:64 or predepletion levels within 10 days posttransplantation. In addition, nine patients developed renal dysfunction in association with the rebound increase in their anti-A/B. One patient lost his graft because of uncontrolled delayed hyperacute rejection, whereas eight other recipients recovered completely with pulse steroids and PP/IA therapy. After the third week posttransplant, there was no correlation between the occurrence of AR and their isoagglutinin titers. Moreover, no antibody-mediated rejection was observed, even in recipients with continued high titer anti-A and/or anti-B antibodies. Patient survival is 100% to date. The actuarial 1-year and 5-year graft survival rates are 87% and 85%, respectively. No fatal infectious complications occurred despite the combination of splenectomy and immunosuppressive drugs. CONCLUSIONS: We have demonstrated that with adequate pre- and posttransplant management, successful kidney transplantation across the ABO barrier is possible in the pediatric population. "Accommodation" of the allografts occurred within 2 weeks of transplantation. Subsequently, the long-term graft outcome of ABO-incompatible LKT was comparable to that of ABO-compatible LKT.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Trasplante de Riñón , Donadores Vivos , Adolescente , Niño , Femenino , Humanos , Técnicas de Inmunoadsorción , Inmunosupresores/uso terapéutico , Masculino , Plasmaféresis , Esplenectomía , Factores de Tiempo , Trasplante Homólogo , Resultado del TratamientoAsunto(s)
Inmunosupresores/farmacocinética , Trasplante de Riñón , Tacrolimus/farmacocinética , Administración Oral , Adolescente , Área Bajo la Curva , Niño , Preescolar , Femenino , Rechazo de Injerto/metabolismo , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/administración & dosificación , Inyecciones Intravenosas , Masculino , Tacrolimus/administración & dosificaciónRESUMEN
OBJECTIVE: To investigate the relative importance of wife abuse as a risk factor for physical child abuse, physical punishment, and verbal child abuse. The study explored the importance of wife abuse relative to blocks of parent, child, and family characteristics and also relative to specific risk factors. METHOD: This study re-analyzed a sub-sample (N = 2,733) of data from the 1985 National Family Violence Survey. Hierarchical logistic regressions were conducted, using five different criterion variables measuring physical child abuse, physical punishment, and verbal abuse separately and in combination. RESULTS: Blocks of parent, child, and family characteristics were more important predictors of violence towards children than was wife abuse, though the presence of wife abuse in the home was a consistently significant specific risk factor for all forms of violence against children. Of specific risk factors, a respondent's history of having been hit as an adolescent was a larger risk factor for physical child abuse than was wife abuse. Wife abuse was an important predictor of physical punishment. Non-violent marital discord was a greater factor in predicting likelihood of verbal child abuse than was wife abuse. CONCLUSIONS: Though this study confirms the association between wife abuse and violence towards children, it cautions us not to overlook the contribution of other factors in our attempts to understand the increased risk attributed to wife abuse.
Asunto(s)
Maltrato a los Niños , Maltrato Conyugal , Adulto , Niño , Estudios de Cohortes , Recolección de Datos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , ViolenciaRESUMEN
Congenital vesicovaginal fistula is a very rare entity, the etiology of which has not been clearly elucidated because pathologic features have not been mentioned in previous reports. The case of a 4-year-old girl having incontinence resulting from a congenital vesicovaginal fistula joining with the left ectopic ureter from the hypoplastic kidney is described. This is thought to be the first presentation of congenital vesicovaginal fistula joining with ectopic ureter. A microscopic examination revealed the fistula consisting of transitional cell epithelium, suggesting an abnormal fusion of the ureteral bud and caudal end of the müllerian duct with the urogenital sinus.
Asunto(s)
Fístula Vesicovaginal/congénito , Preescolar , Femenino , Humanos , Riñón/anomalías , Incontinencia Urinaria/etiología , Urografía , Fístula Vesicovaginal/diagnóstico por imagen , Fístula Vesicovaginal/patologíaRESUMEN
This report describes a successful renal Tx in a patient with chronic renal failure, caused by dysplastic kidneys, who received a cadaveric kidney with post-infectious glomerulonephritis. Sequential renal biopsies were performed at 12 h before Tx, and at 1 h and on days 8 and 58 post-Tx. Post-operative hematuria disappeared on day 9 and proteinuria on day 13. Normal graft function was observed within 1 month, with histologic resolution. Our study suggests that while the donor kidney facilitates deposition of certain immune reactants, this is a host (environmental) problem and when transplanted into a new host (new environment), the problem is no longer sustained.
Asunto(s)
Cadáver , Glomerulonefritis , Trasplante de Riñón , Donantes de Tejidos , Adolescente , Niño , Femenino , Glomerulonefritis/etiología , Glomerulonefritis/patología , Humanos , Infecciones/complicaciones , Riñón/patologíaRESUMEN
Inflammatory pseudotumors of the bladder are rare in children. We describe a 7-day-old male neonate with inflammatory pseudotumor of the bladder. He presented with a 3-day history of macroscopic hematuria. Ultrasonography, computed tomography and cystoscopy showed an intravesical mass arising from the right lateral wall. Pathologic findings obtained by open excision revealed that the tumor had spindle-shaped cells without significant atypia infiltrating into submucosal fibrous tissue. There has been no evidence of recurrent tumor 12 months post-operatively. To our knowledge our case is the first presentation in a neonate among the reported pediatric cases.
Asunto(s)
Granuloma de Células Plasmáticas/diagnóstico , Enfermedades de la Vejiga Urinaria/diagnóstico , Humanos , Recién Nacido , MasculinoRESUMEN
BACKGROUND: Recent advance of perinatal ultrasound screening and/or physician's awareness of renal damage from recurrent pyelonephritis has brought about the increasing number of infants with primary vesicoureteral reflux (VUR) including refluxing megaureter which should be conceptually differentiated from simple high grade VUR. We evaluated the clinical outcome of infants diagnosed with refluxing megaureter. PATIENTS AND METHODS: We retrospectively reviewed the clinical records of 15 infants (17 ureters) diagnosed as refluxing megaureter (max caliber > or = 10 mm) at our institution from 1988 to 1997. We compared the clinical outcome of refluxing megaureter with that of high grade VUR. (Results) Patients were 13 boys and 2 girls. Megaureter was unilateral in 13 patients and bilateral in 2. Fourteen infants (93.3%) presented with febrile urinary tract infection (UTI). The diameter of megaureter was 10-21 mm (average: 13.6 +/- 4.0 mm) at excretory urogram. Nine of 15 infants (60.0%) had breakthrough urinary infection. Its incidence was significantly higher than that of high grade VUR (21.3%) (p = 0.02). In 13 cases surgical treatments were performed, however 2 cases (max caliber: 16 mm, 21 mm) by Politano-Leadbetter or Paquin procedure required re-ureteroneocystostomy by Psoas-hitch procedure because of persistent reflux and recurrent UTI. On the other hand no patient required re-ureteroneocystostomy in high grade VUR. CONCLUSION: It is important to differentiate refluxing megaureter from high grade VUR due to high incidence of breakthrough UTI. Ureteral remodeling and/or Psoas-hitch procedure are strongly recommended for adequate length of submucosal tunnel in refluxing megaureter.
Asunto(s)
Uréter/patología , Reflujo Vesicoureteral/diagnóstico , Cistostomía , Diagnóstico Diferencial , Dilatación Patológica/diagnóstico , Dilatación Patológica/cirugía , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Reoperación , Resultado del Tratamiento , Uréter/cirugía , UreterostomíaRESUMEN
PURPOSE: We analyzed the presentation, treatment and survival of 4 children with renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the pathological and hospital records of 4 Japanese children diagnosed with renal cell carcinoma at our hospital from 1970 to 1998. RESULTS: In the 1 boy and 3 girls with an average age of 8 years 7 months at diagnosis the most common presenting complaints were gross hematuria in 75% and a palpable abdominal mass in 50%. Computerized tomography revealed characteristic calcification within the tumor in 3 of the 4 patients (75%). In the remaining case the lesion had high density areas with microcalcification, as confirmed by histopathological study. In 2 patients with regional lymph node metastasis calcification was also observed in the metastatic lesions. Disease was stages I to III in 1, 1 and 2 patients, respectively. All patients underwent transabdominal nephrectomy with regional lymphadenectomy. One patient with stage I disease had multiple metastases 15 months later and died of disease 55 months postoperatively. However, the remaining 3 patients received adjuvant interferon therapy and they are without evidence of recurrence a mean of 51.3 months postoperatively. CONCLUSIONS: Calcification within the tumor and/or metastatic lesions or high density areas in the tumor on screening computerized tomography are characteristic findings suggestive of pediatric renal cell carcinoma. Adjuvant therapy with interferon may provide some benefit in select pediatric patients. Further studies of a larger number of pediatric renal cell carcinoma cases may be necessary to establish the optimal diagnostic and therapeutic regimen.