RESUMEN
Acute graft-versus-host disease (GVHD) is a major complication of bone marrow transplantation (BMT) and is characterized by hematopoietic dysfunction, immunosuppression, and tissue injury in the skin, liver, and intestinal mucosa. Hepatocyte growth factor (HGF), originally identified and cloned as a potent mitogen for hepatocytes, induces mitogenic and antiapoptotic activity in various epithelial cells and promotes hematopoiesis. Working in a murine model of acute GVHD, we performed repeated transfection of the human HGF cDNA into skeletal muscle and showed that this treatment inhibited apoptosis of intestinal epithelial cells and donor T-cell infiltration into the liver, thereby ameliorating the enteropathy and liver injury caused by acute GVHD. HGF also markedly suppressed IFN-gamma and TNF-alpha expression in the intestine and liver and decreased the serum IL-12. Furthermore, extramedullary hematopoiesis by donor cells was increased, and the survival rate was improved. These results suggest that HGF may be useful for controlling acute GVHD after allogeneic BMT.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/terapia , Hematopoyesis Extramedular/fisiología , Factor de Crecimiento de Hepatocito/uso terapéutico , Transfección , Animales , Modelos Animales de Enfermedad , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/fisiopatología , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Interferón gamma/genética , Interferón gamma/metabolismo , Interleucina-12/sangre , Intestinos/patología , Liposomas , Hígado/patología , Hígado/fisiología , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/fisiología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapéutico , Bazo/citología , Bazo/fisiología , Timo/citología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
TP67.14 established by somatic hybridization is a 2,4,6-trinitrobenzenesulfonic acid (trinitrophenyl, TNP)-specific B cell clone with a receptor molecule for TNP on the cell membrane, and MS202 is an interleukin-2 (IL-2)-dependent T helper (Th) cell clone reactive to auto-MHC class II antigens (IAk and IEk) as previously reported. In the present study it was shown that MS202 considerably induced the maturation of TP67.14 into anti-TNP plaque-forming cells (PFCs), and this response was markedly augmented by the addition of TNP-keyhole limpet hemocyanin (KLH). Recombinant cytokines and the culture supernatant of MS202 with TP67.14 did not affect the generation of anti-TNP antibodies by TP67.14. Also, neither anti-IL-4 nor anti-IL-5 monoclonal antibody (mAb) inhibited the maturation of TP67.14 mediated by MS202. The differentiative effect of MS202 on TP67.14 was completely lost when each cell was separately cultured using a semipermeable membrane. Monoclonal antibodies against LFA-1 beta molecules significantly blocked the development of anti-TNP PFCs induced by MS202, as well as anti-IAk and anti-IEk mAbs. Interestingly, the plasma membrane-enriched fraction (PM) derived from MS202 exhibited much more differentiative effects on TP67.14 treated with TNP-KLH than PM from other T cell lines and concanavalin A-induced T lymphoblasts. In addition, TNP-conjugated PM from MS202 by itself induced a great number of anti-TNP PFCs. The present findings indicate that MS202 is capable of inducing the maturation of TP67.14, which is considered to represent a population of B cells with antigen specificity in a late lineage of B cell maturation, through direct cell contact but not soluble factors. This suggests that B cells with antigen specificity, in the presence of antigen, can be induced to mature into antibody-secreting cells through direct contact with Th cells; in this process surface major histocompatibility complex class II and lymphocyte function-associated antigen 1 (LFA-1) molecules are directly involved and the cell membrane derived from Th cells provides a transductional signal for maturation of B cells with antigen specificity in the presence of antigen.
Asunto(s)
Linfocitos B/citología , Antígenos de Histocompatibilidad Clase II/análisis , Linfocitos T Colaboradores-Inductores/citología , Animales , Formación de Anticuerpos , Células Productoras de Anticuerpos/fisiología , Antígenos de Superficie/inmunología , Linfocitos B/inmunología , Comunicación Celular , Diferenciación Celular/efectos de los fármacos , Membrana Celular/fisiología , Células Clonales , Citocinas/farmacología , Epítopos , Humanos , Antígeno-1 Asociado a Función de Linfocito/fisiología , Linfocitos T Colaboradores-Inductores/inmunología , Trinitrobencenos/inmunologíaRESUMEN
Decay-accelerating factor (DAF), a complement-regulating glycoprotein, has been shown to be expressed on hematopoietic progenitors and their progeny cells in normal individuals but not on abnormal cells in patients with paroxysmal nocturnal hemoglobinuria (PNH). Fluorescence histograms of bone marrow cells showed the heterogeneity of DAF expression on their cell membranes, suggesting mixed hematopoietic cell populations in PNH. We have previously shown that DAF is a maturational protein expressed on normal hematopoietic cells. In order to elucidate the relationship between DAF expression and cell maturity in PNH, we fractionated bone marrow cells according to amount of DAF and cultured these cells in methylcellulose for clonal assay of erythroid burst-forming units (BFU-E) and granulocyte-macrophage colony-forming units (CFU-GM), followed by reanalysis of DAF expression on their progeny. The matured cells from the bursts/colonies in cultures with DAF-negative PNH marrow cells had no or little DAF, but those grown from DAF-positive PNH progenitors showed nearly as much of this factor as those grown from normal progenitors. These results clearly indicate that there are at least two distinct populations of hematopoietic progenitors with respect to the membrane expression of DAF and that abnormalities occur at the level of the stem cell in PNH.
Asunto(s)
Médula Ósea/patología , Células Madre Hematopoyéticas/metabolismo , Hemoglobinuria Paroxística/patología , Proteínas de la Membrana/metabolismo , Antígenos CD55 , Membrana Celular/metabolismo , Separación Celular , Células Cultivadas , Células Precursoras Eritroides/metabolismo , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Granulocitos/metabolismo , Humanos , Macrófagos/metabolismoRESUMEN
Intestinal graft-versus-host disease (GVHD) can readily easily induce generalized metabolic disturbance that influences morbidity and mortality after allogeneic bone marrow transplantation. Although adding a new drug or increasing the doses of immunosuppressive agents will probably be effective for controlling intestinal GVHD, the systemic side effects of such therapy cannot be ignored. In this study, we used betamethasone retention enemas as a local treatment for eight patients with refractory and/or severe intestinal GVHD. Six of the eight patients showed improvement of diarrhea and/or abdominal pain, with a reduction in the stage of GVHD. When treatment with betamethasone enemas was continued for 10 to 27 days in the 6 responding patients, no severe toxicity was observed. One patient failed to respond to treatment and another could not tolerate the enemas. Despite some uncertainty regarding the indications and duration of treatment, betamethasone enemas seem to be a potential alternative method for the management of intestinal GVHD.
Asunto(s)
Antiinflamatorios/administración & dosificación , Betametasona/administración & dosificación , Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedades Intestinales/tratamiento farmacológico , Administración Tópica , Adulto , Recuento de Linfocito CD4 , Enema , Femenino , Glucocorticoides , Humanos , Masculino , Trasplante HomólogoRESUMEN
BACKGROUND: Adult respiratory distress syndrome-like respiratory disorders are a serious, but uncommon, complication of bone marrow transplantation. METHODS: We measured various cytokines in 2 patients with respiratory disorders and 11 patients without respiratory problems after allogeneic bone marrow transplantation. RESULTS: The patients with respiratory disorders had elevated levels of interferon-gamma and interleukin-2 in the aplastic phase, and elevation of tumor necrosis factor-alpha, intercellular adhesion molecule-1, and interleukin-8 at the time of leukocyte recovery. Both patients with respiratory disorders developed fever during the aplastic phase, whereas none of the patients without fever had respiratory disorders. Among patients who had fever during the aplastic phase but no respiratory disorders, there was no elevation of cytokines from the aplastic phase to the recovery phase. CONCLUSIONS: Respiratory disorders may occur after bone marrow transplantation when an inflammatory response during the aplastic phase stimulates cytokines that cause vascular endothelial damage and increases the levels of chemokines and adhesive molecules along with elevation of the leukocyte count.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Síndrome de Dificultad Respiratoria/etiología , Adulto , Femenino , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-8/sangre , Masculino , Trasplante Homólogo , Factor de Necrosis Tumoral alfa/análisisRESUMEN
We investigated the effect of staphylokinase (SAK), which has specific thrombolytic properties, on human platelet aggregation. Platelet aggregation induced with collagen was observed following preincubation of platelets in platelet-rich plasma (PRP) or washed platelet suspension (WP) with SAK at 37 degrees C for 30 min. SAK inhibited platelet aggregation in PRP only at the highest examined concentration (1 x 10(-4) g/ml). Although SAK did not inhibit platelet aggregation in WP which contained fibrinogen, it did when the platelets had been preincubated with SAK and plasminogen. The most effective concentration in WP was 1 x 10(-6) g/ml. The effect could be inhibited by adding aprotinin or alpha 2-antiplasmin. The highest generation of plasmin in the same preincubation fluid was detected at 1 x 10(-6) g/ml SAK. We concluded that SAK can inhibit platelet aggregation in WP by generating plasmin and/or fibrinogen degradation products, but is only partially effective in PRP because of the existence of alpha 2-antiplasmin.
Asunto(s)
Metaloendopeptidasas/farmacología , Agregación Plaquetaria/efectos de los fármacos , Secuencia de Aminoácidos , Aprotinina/farmacología , Colágeno/farmacología , Productos de Degradación de Fibrina-Fibrinógeno/biosíntesis , Fibrinolisina/biosíntesis , Fibrinolisina/farmacología , Humanos , Datos de Secuencia Molecular , Plasminógeno/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , alfa 2-Antiplasmina/farmacologíaRESUMEN
An analytical method was devised to determine the entire course of the adenosine-triphosphate (ATP) release from blood platelets based on a continuous measurement of firefly luciferase luminescence. The equation of the release reaction was derived after due consideration of substrate (ATP) consumption and product (oxyluciferin) inhibition on the luciferase reaction as follows: Ct = Vt X (Km/Vmax) X (1 + It/Ki) + It, where Ct is the total concentration of the released ATP at time t, vt is the velocity of the luciferase reaction at time t and is directly measured, It is the concentration of oxyluciferin at time t, and Vmax, Km and Ki are constants. Ct of the gel-filtered platelet suspension (GFP) could be determined by substituting vt and It as functions of t. The effects of albumin and temperature on the reaction were also studied.
Asunto(s)
Adenosina Trifosfato/sangre , Plaquetas/metabolismo , Luciferasas , Adenosina Trifosfato/metabolismo , Animales , Humanos , Técnicas In Vitro , Cinética , Mediciones Luminiscentes , Conejos , Albúmina Sérica/farmacología , TemperaturaRESUMEN
Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder, which is caused by deficiency or decrease of the platelet GPIb/IX/V complex. Analysis of two patients with BSS by flow cytometry of the blood revealed different expression patterns of the components of the GPIb/IX/V complex. In case 1, GPIX was completely absent but residual amounts of GPIb alpha and GPV were detectable; in case 2, GPIb alpha was completely absent. We amplified the coding regions of GPIb alpha, GPIb beta, GPV, and GPIX from the patients' genomic DNA with the polymerase chain reaction (PCR) and sequenced the PCR products. in case 1, we identified a point mutation in the GPIX coding region that changes the codon for tryptophan-126 (TGG) to a nonsense codon (TGA). In case 2, we found a deletion of nucleotide within seven adenine repeats at the position of 1932 to 1938 in the coding region of GPIb alpha, which causes a frame shift that results in 58 altered amino acids and a premature stop codon. These genetic changes alter the transmembrane domain of GPIX or GPIb alpha and, therefore, would prevent proper insertion of the proteins in the plasma membrane. Thus, abnormality of a single component protein (GPIX or GPIb alpha) alters the assembly of the GPIb/IX/V complex and causes heterogeneous surface expression of GPIb alpha, GPV and GPIX.
Asunto(s)
Síndrome de Bernard-Soulier/sangre , Plaquetas/metabolismo , Aberraciones Cromosómicas/sangre , Complejo GPIb-IX de Glicoproteína Plaquetaria/biosíntesis , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Síndrome de Bernard-Soulier/genética , Western Blotting , Trastornos de los Cromosomas , ADN/genética , Femenino , Citometría de Flujo , Humanos , Datos de Secuencia MolecularRESUMEN
To investigate the relationships of personal hair dye use and environmental factors to myelodysplastic syndromes (MDS), we conducted a case-control study in Japan. A total of 111 MDS cases and 830 controls randomly selected from the residents in the same prefecture of cases using telephone directories responded to a health questionnaire. The odds ratio (OR) for ever having used hair dye was 1.99 (95% confidence interval (CI) 1.17-3.38) and there were statistically significant trends in risk with increasing duration and number of hair dye use. Occupational exposure to organic solvents was marginally associated with the risk of MDS (OR = 1.99; 95% CI 0.97-4.10).
Asunto(s)
Tinturas para el Cabello/efectos adversos , Síndromes Mielodisplásicos/etiología , Exposición Profesional/efectos adversos , Solventes/efectos adversos , Adulto , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Factores Sexuales , Fumar/efectos adversos , Encuestas y CuestionariosRESUMEN
Characteristics of karyotypes were analyzed in de novo acute myeloid leukemia (AML) with trilineage myelodysplasia (AML/TMDS) at initial diagnosis and compared with myelodysplastic syndrome (MDS) cases that had evolved to AML (MDS/AML). Abnormal karyotypes were seen in 11 of 19 patients with AML/TMDS and 13 of 16 MDS/AML cases. Trisomy 8 was observed in 3 AML/TMDS cases as a sole anomaly and was also present in 3 MDS/AML cases but not as a sole finding. Although MDS/AML frequently displayed monosomies or long-arm deletions of chromosome 5, 7 and 9, only one case exhibited long-arm deletion (of chromosome 7) in AML/TMDS. Two or more chromosome aberrations were found in some cases in both groups. These findings suggest that AML/TMDS had passed through several preleukemic stages at diagnosis, as has been well documented in MDS and MDS/AML. Additionally, clonal evolution may have already occurred in AML/TMDS, as MDS transformed to AML is associated with clonal evolution.
Asunto(s)
Leucemia Mieloide/genética , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/genética , Enfermedad Aguda , Adolescente , Adulto , Factores de Edad , Anciano , Aberraciones Cromosómicas , Deleción Cromosómica , Trastornos de los Cromosomas , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 16 , Cromosomas Humanos Par 21 , Cromosomas Humanos Par 5 , Cromosomas Humanos Par 7 , Cromosomas Humanos Par 8 , Cromosomas Humanos Par 9 , Femenino , Humanos , Cariotipificación , Leucemia Mieloide/complicaciones , Leucemia Mieloide/etiología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/fisiopatología , Translocación Genética , TrisomíaRESUMEN
We examined the expression and the regulation of p21(waf1) and p27(kip1) cdk inhibitors in P19 mouse embryonal carcinoma (EC) cells following treatment with all-trans retinoic acid (ATRA) to induce neuronal differentiation. The levels of p27 mRNA and protein increased within 24 h of treatment with ATRA, reaching a plateau 4-5 days later prior to neurite formation. In contrast, levels of p21 expression remained low until after neurites were extensively formed. Induction of muscle differentiation from P19 cells by treatment with dimethyl sulfoxide caused only transient increases in p27 levels. In a mutant P19 cell line, RAC65, treatment with ATRA induced neither p27 accumulation nor neuronal differentiation, but p21 mRNA expression increased markedly. In contrast, treatment of RAC65 cells with 9-cis retinoic acid induced both p27 expression and neuronal differentiation. Correlation between p27 expression and neuronal differentiation was also observed in NT2/D1 human EC cells. Luciferase reporter assays showed that p27 promoter activity increased in ATRA-treated cells, consistent with the elevation of p27 mRNA levels. Arrest of neuronal differentiation of P19 cells by okadaic acid resulted in inhibition of p27 expression, whereas p21 mRNA expression was greatly enhanced. Conversely, inhibition of p27 expression by antisense p27 oligonucleotides resulted in blockade of neuronal differentiation. Taken together, these results strongly suggest that the expression of p27 is indispensable for neuronal differentiation of EC cells.
Asunto(s)
Proteínas de Ciclo Celular , Diferenciación Celular , Regulación de la Expresión Génica , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Células Madre Neoplásicas/citología , Neuronas/citología , Proteínas Supresoras de Tumor , Animales , Diferenciación Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Ciclinas/genética , Ciclinas/metabolismo , Dimetilsulfóxido/farmacología , Células Madre de Carcinoma Embrionario , Regulación de la Expresión Génica/efectos de los fármacos , Inmunohistoquímica , Ratones , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Neuritas/efectos de los fármacos , Neuritas/metabolismo , Proteínas de Neurofilamentos/genética , Proteínas de Neurofilamentos/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ácido Ocadaico/farmacología , Oligonucleótidos Antisentido/genética , Regiones Promotoras Genéticas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor trkB/genética , Receptor trkB/metabolismo , Activación Transcripcional/efectos de los fármacos , Tretinoina/farmacología , Células Tumorales CultivadasRESUMEN
A male patient with CML received a BMT from his sister and developed chronic GVHD. The host-origin normal karyotype (46,XY) was identified for the first time in the 60th month after BMT. Detection of Y-chromosome-specific DNA in BM and peripheral blood (PB) showed that all BM samples obtained 6 months from BMT were positive for Y-specific DNA, while PB became positive in the 60th month after BMT. The BCR-ABL mRNA derived from leukemic cells was detected in the 36th month post-BMT, but not in the 60th month or thereafter. Fluorescence in situ hybridization revealed that 1.5% and 0.6% in BM and PB cells were Y-positive in the 70th month post-BMT, respectively. DNA analysis of hematopoietic progenitor colonies revealed 1 of 42 erythroid colonies to be host derived. These results indicate that host-origin hematopoietic cells survive chronic GVHD, while the Ph1 clone was eliminated.
Asunto(s)
Trasplante de Médula Ósea , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Adulto , Secuencia de Bases , Trasplante de Médula Ósea/efectos adversos , Enfermedad Crónica , ADN de Neoplasias/genética , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/genética , Hematopoyesis , Células Madre Hematopoyéticas/ultraestructura , Humanos , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Datos de Secuencia Molecular , Cromosoma Filadelfia , ARN Mensajero/genética , Quimera por Radiación , Donantes de TejidosRESUMEN
Urinary trypsin inhibitor has attracted attention as an index of the systemic inflammatory response syndrome. In this study, the urine concentration of trypsin inhibitor was measured to compare the immunological insult of conventional chemotherapy and conditioning chemotherapy for bone marrow transplantation. We also investigated whether urinary trypsin inhibitor was a useful index of the complications and outcome of bone marrow transplantation. Urinary trypsin inhibitor concentration was determined before chemotherapy, on the day after finishing chemotherapy (day 0 of transplantation), and during recovery of the white cell count, in 17 patients (seven receiving conventional chemotherapy and 10 receiving conditioning for bone marrow transplantation). Urinary trypsin inhibitor concentrations were significantly higher after conditioning for bone marrow transplantation than after conventional chemotherapy (P < 0.001), indicating that conditioning was more invasive. After bone marrow transplantation, the incidence of severe complications and the mortality rate were higher in patients whose urinary trypsin inhibitor concentrations rose during recovery of the white cell count. Comparison of urinary trypsin inhibitor concentrations suggested that conditioning for bone marrow transplantation was more invasive than conventional chemotherapy. This study also suggested that the urine concentration of trypsin inhibitor could be useful for predicting the risk of complications and outcome of bone marrow transplantation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , Glicoproteínas/orina , Neoplasias Hematológicas/terapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/inmunología , Biomarcadores , Femenino , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/orina , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Inmunología del TrasplanteRESUMEN
Intestinal graft-versus-host disease (GVHD) produces clinical manifestations and histological changes resembling those of ulcerative colitis and has been treated with drugs which are used for ulcerative colitis. These two conditions also resemble each other with respect to changes of cytokines. Accordingly, we investigated whether the level of leukotriene B4, a risk factor for ulcerative colitis, was also a risk factor or prognostic indicator for intestinal GVHD. The pre-conditioning leukotriene B4 level was significantly related to the grade of intestinal GVHD in 42 patients (P < 0.01). Compared with patients who did not develop severe intestinal GVHD after bone marrow transplantation, those who did had significantly higher interleukin-2 and interferon-gamma levels during the aplastic phase (P <0.01), followed by higher tumor necrosis factor-alpha levels during the recovery phase (P < 0.0001), with significant elevation of tumor necrosis factor-alpha and interferon-gamma occurring in association with exacerbations of intestinal GVHD (P < 0.001). These findings suggest a similarity between the pathogenesis of ulcerative colitis and intestinal GVHD and raise the possibility that leukotriene B4 may be a useful prognostic indicator for intestinal GVHD.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedades Intestinales/diagnóstico , Leucotrieno B4/sangre , Adolescente , Adulto , Biomarcadores/sangre , Colitis Ulcerosa/sangre , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/etiología , Citocinas/sangre , Diagnóstico Diferencial , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/etiología , Humanos , Enfermedades Intestinales/sangre , Enfermedades Intestinales/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
The 'systemic inflammatory response syndrome' (SIRS) may represent the underlying cause of complications after bone marrow transplantation (BMT). This study was conducted to determine whether blocking the etiologic factors of SIRS could improve the complications of BMT. Sixteen consecutive patients with unrelated donors were allocated alternately to two groups. Seven patients received 1.8 g/day of eicosapentaenoic acid (EPA) orally from 3 weeks before to about 180 days after transplantation, while nine patients did not. These two groups were compared with respect to complications, survival, and various cytokines and factors causing vascular endothelial damage. All seven patients receiving EPA survived and only two had grade III graft-versus-host disease (GVHD). Among the nine patients not receiving EPA, three had grade III or IV GVHD. In addition, thrombotic microangiopathy developed in four patients and cytomegalovirus disease occurred in four. Five patients died in this group. The levels of leukotriene B(4), thromboxane A(2), and prostaglandin I(2) were significantly lower in patients receiving EPA than in those not receiving it (all P < 0.01). Cytokines such as tumor necrosis factor-alpha, interferon-gamma, and interleukin-10 were also significantly decreased by EPA (P < 0.05), as were factors causing vascular endothelial damage such as thrombomodulin and plasminogen activator inhibitor-1 (P < 0.05). The survival rate was significantly higher in the group given EPA (P < 0.01). EPA significantly reduced the complications of BMT, indicating that these complications may be manifestations of the systemic inflammatory response syndrome.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Citocinas/sangre , Ácido Eicosapentaenoico/uso terapéutico , Inmunosupresores/uso terapéutico , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , 6-Cetoprostaglandina F1 alfa/sangre , Administración Oral , Adulto , Anemia Aplásica/terapia , Infecciones por Citomegalovirus/etiología , Ácido Eicosapentaenoico/administración & dosificación , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Inmunosupresores/administración & dosificación , Molécula 1 de Adhesión Intercelular/sangre , Interferón gamma/sangre , Interleucinas/sangre , Leucemia/terapia , Tablas de Vida , Enfermedades Pulmonares Intersticiales/etiología , Masculino , Análisis de Supervivencia , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Síndrome de Respuesta Inflamatoria Sistémica/prevención & control , Trasplante Homólogo , Factor de Necrosis Tumoral alfa/análisis , Enfermedades Vasculares/etiologíaRESUMEN
We monitored the levels of various cytokines and chemokines, as well as an adhesion molecule and factors related to vascular endothelial damage, in three patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome after bone marrow transplantation. Measurements were done at the onset of this condition and during plasma exchange for treatment. At the onset of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, the levels of interleukin-8, thrombomodulin, and plasminogen activator inhibitor-1 were all markedly increased. A close relationship was observed between improvement in symptoms by plasma exchange and a decrease in interleukin-8 level, suggesting that this chemokine may be related to the development of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome after bone marrow transplantation.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Síndrome Hemolítico-Urémico/sangre , Púrpura Trombocitopénica Trombótica/sangre , Adulto , Biomarcadores/sangre , Factores de Coagulación Sanguínea/metabolismo , Moléculas de Adhesión Celular/sangre , Citocinas/sangre , Endotelio Vascular/patología , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Síndrome Hemolítico-Urémico/etiología , Humanos , Interleucina-8/sangre , Masculino , Púrpura Trombocitopénica Trombótica/etiología , Trasplante Homólogo/efectos adversosRESUMEN
Hepatocyte growth factor (HGF) was reported to be effective in preventing acute graft-versus-host disease (GVHD) in a murine model. We examined serum HGF concentrations in 38 patients receiving allogeneic bone marrow transplants, and investigated the relationship of serum HGF concentrations to severity of acute GVHD. More HGF was present in sera from patients with than without acute GVHD. Serum HGF correlated significantly with grade of acute GVHD. Furthermore, serum HGF correlated with serum concentrations of C-reactive protein, gamma-glutamyltranspeptidase (GTP), and aspartate aminotransferase (AST). Serum concentrations of HGF in transplanted patients without GVHD were consistently low, while those in patients with acute GVHD increased with exacerbation. We conclude that HGF was produced during induction of the GVH reaction, and probably increased as a physiological response.
Asunto(s)
Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/diagnóstico , Factor de Crecimiento de Hepatocito/sangre , Enfermedad Aguda , Adulto , Anemia Aplásica/terapia , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Leucemia/terapia , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/terapia , Trasplante Homólogo , gamma-Glutamiltransferasa/sangreRESUMEN
This study was performed to investigate whether measurement of cyclic GMP (cGMP), a marker for nitric oxide production, before and after allogeneic bone marrow transplantation (BMT) with total body irradiation (TBI) conditioning was of prognostic value. cGMP levels were monitored in 23 consecutive patients who received TBI as conditioning for BMT, and were compared with the outcome. cGMP became positive during the aplastic phase after BMT in 12 patients. In nine of these 12 patients, cGMP level decreased during the recovery phase. Eight of the nine patients survived, one dying after relapse. In three other patients, the cGMP level continued to increase even during the recovery phase and they died of severe complications. cGMP became positive on day 0 of BMT and during the leukocyte recovery phase after BMT in two and seven of the 23 patients, respectively. Subsequently, all patients died of severe complications. The two patients who were negative for cGMP both before and after BMT survived without complications. These results suggest that monitoring cGMP from early after BMT may be useful for predicting outcome and that it may be a useful prognostic marker.
Asunto(s)
Trasplante de Médula Ósea , GMP Cíclico/sangre , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/fisiología , Irradiación Corporal Total/métodos , Adolescente , Adulto , Biomarcadores/sangre , Crisis Blástica/cirugía , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/cirugía , Masculino , Metotrexato/uso terapéutico , Metilprednisolona/uso terapéutico , Monitoreo Fisiológico/métodos , Síndromes Mielodisplásicos/patología , Síndromes Mielodisplásicos/cirugía , Estadificación de Neoplasias , Óxido Nítrico/metabolismo , Pronóstico , Trasplante Homólogo/inmunología , Resultado del TratamientoRESUMEN
This study was performed to clarify the influence of Helicobacter pylori on the platelet count in patients undergoing bone marrow transplantation (BMT) from unrelated donors. Of 23 consecutive patients undergoing BMT from unrelated donors, the H. pylori antibody test did not change from before conditioning until recovery of the platelet count in 15 patients. These patients were classified into H. pylori antibody-positive (n=8) and -negative (n=7) groups. In the H. pylori antibody-positive group, the platelet count exceeded 20 x 10(9)/l significantly faster after BMT, than in the H. pylori antibody-negative group. When myelosuppression was most severe, the interleukin-6 (IL-6) level was significantly higher in the positive group than in the negative group (67.0+/-10.6 vs 9.9+/-2.4 pg/ml, P<0.05). In addition, the thrombopoietin level was significantly lower in the positive group than in the negative (510.1+/-313.9 vs 3209.1+/-2006.7 pg/ml, P<0.01). These data suggest that H. pylori infection accelerates recovery of the platelet count after BMT from unrelated donors, possibly by stimulating IL-6 production.
Asunto(s)
Plaquetas/microbiología , Trasplante de Médula Ósea , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Trasplante de Células Madre Hematopoyéticas , Adulto , Plaquetas/citología , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Humanos , Interleucina-6/sangre , Masculino , Recuento de Plaquetas , Estudios Retrospectivos , Trombopoyetina/sangre , Donantes de TejidosRESUMEN
Cyclosporine A (CsA) may increase the incidence of thrombotic events, but whether tacrolimus (Tc) has such effects is still unclear. The serotonergic system has been linked to the thrombotic effects of CsA, but a direct effect of CsA on serotonin-induced platelet aggregation has not been demonstrated because of methodological difficulties. We measured the effects of CsA and Tc on serotonin-induced platelet aggregate formation by particle counting using light scattering. CsA and Tc both enhanced serotonin-induced formation of small platelet aggregates, however, neither CsA nor Tc affected aggregation induced by high or low concentrations of ADP, with or without addition of a serotonin receptor antagonist. Both CsA and Tc enhance platelet aggregation induced via the serotonin pathway.