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1.
West Indian Med J ; 57(4): 327-31, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19566010

RESUMEN

There are emerging ethical issues with regards to the use of animals in the early stages of drug discovery for anti-inflammatory and degenerative diseases from natural products using the activity-directed isolation pathways when many compounds (eg > 100) are present in the crude extract or fraction and are to be tested The above-mentioned is the main reason for proposing the use of the in vitro anti-denaturation (stabilization) effects of heat treated (immunogenic) bovine serum albumin (BSA) as an assay. Current methods used for detecting and isolating a wide range of anti-inflammatory compounds in the early stages of the drug discovery process utilize a large number of animals. When BSA is heated and is undergoing denaturation, it expresses antigens associated to Type III hypersensitive reaction and which are related to diseases such as serum sickness, glomerulonephritis, rheumatoid arthritis and systemic lupus erythematosus. Thus, the assay that is being proposed should be applicable to the discovery of drugs for treating the above mentioned diseases and others, once the compounds stabilize the denaturation process.


Asunto(s)
Antiinflamatorios/sangre , Preparaciones de Plantas/farmacología , Desnaturalización Proteica/efectos de los fármacos , Albúmina Sérica Bovina/análisis , Animales , Bioensayo , Bovinos , Descubrimiento de Drogas , Calor/efectos adversos , Enfermedades del Sistema Inmune/tratamiento farmacológico , Técnicas In Vitro , Tamizaje Masivo
2.
West Indian Med J ; 56(6): 487-90, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18646490

RESUMEN

Mixed lymphocyte responses assays were conducted at 25.0 and 250.0 microg/mL of the crude ethanolic extract of Boehmeria jamaicensis Urb (coded as BJE) using peripheral lymphocytes obtained from individuals suffering from the common cold after four days of infection and from healthy individuals (without the common cold infection). At a concentration of 25 ug/mL, gamma interferon (IFN-gamma) was increased by 24.03 fold and interleukin 4 (IL-4) by 1.71 fold for the cells obtained from individuals with the common cold (Group A). The extract suppressed IFN-gamma by 8.3% while IL-4 was stimulated by 9.90 fold from peripheral lymphocytes obtained from healthy individuals (Group B). Gamma interferon was suppressed at 250 microg/mL while IL-4 was elevated by 1.86 fold for cells obtained from individuals suffering from the common cold (Group A). In conclusion, BJE could have implications for the treatment of the common cold.


Asunto(s)
Infecciones Bacterianas/inmunología , Infecciones Bacterianas/terapia , Boehmeria , Resfriado Común/inmunología , Resfriado Común/terapia , Interferón gamma/inmunología , Interleucina-4/inmunología , Fitoterapia/métodos , Sinusitis/inmunología , Sinusitis/terapia , Infecciones Bacterianas/complicaciones , Humanos , Sinusitis/microbiología
3.
Oncogene ; 5(3): 411-6, 1990 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-2179819

RESUMEN

The occurrence of Myelodysplastic Syndrome (MDS) and Acute Myeloblastic Leukaemia (AML) following cytotoxic therapy for neoplastic disease is well recognised. RAS mutations are common in patients with MDS and AML. To determine whether these lesions are found as early markers of secondary disease, we have studied the incidence of RAS mutations in the peripheral blood of 70 patients in complete remission from lymphoma. Patients were treated by standard chemotherapy regimes and/or localised radiotherapy. Treatment had been given 6 months to 14 1/2 years previously and no patient showed any sign of residual disease. Genomic DNA from peripheral blood leukocytes was amplified in vitro at target codons of N, K and H RAS genes, and mutations detected by hybridisation with oligonucleotide probes. RAS mutations were detected in 9 subjects. One patient with an N12 valine (Val) substitution had been in complete remission from Hodgkin's disease (HD) for 9 years. DNA from this patient registered in a nude mouse tumorigenicity assay (NMT). The N12 Val mutation was not detected in the original tumour tissue from the same patient. A second patient in remission from HD showed evidence of co-existent N12 cysteine (Cys) and N13 valine (Val) substitutions which were not detected in presentation material or unaffected tissues. All patients are currently haematologically normal, indicating that clones of mutant RAS bearing cells may be detected prior to any overt sign of disease.


Asunto(s)
Genes ras/efectos de los fármacos , Linfoma/tratamiento farmacológico , Mutación , Animales , Antineoplásicos/uso terapéutico , Transformación Celular Neoplásica , Células Cultivadas , Terapia Combinada , ADN de Neoplasias/genética , Genes ras/efectos de la radiación , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Linfoma/genética , Linfoma/radioterapia , Linfoma no Hodgkin/tratamiento farmacológico , Ratones , Ratones Endogámicos , Ratones Desnudos , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Transfección
4.
Oncogene ; 8(2): 371-8, 1993 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8426743

RESUMEN

The FMS proto-oncogene encodes for the colony-stimulating factor 1 receptor (CSF-1R), whose expression within the haematopoietic system has previously been thought to be restricted to cells of the mononuclear phagocyte lineage. We have studied the expression of the CSF-1R in peripheral blood mononuclear cells by indirect immunofluorescence and flow cytometry. FMS expression was detected on both monocytes and B lymphocytes from all samples analysed, including 14 haematologically normal individuals and 31 patients (23 in remission following cytotoxic therapy for lymphoma, six with B-cell chronic lymphocytic leukaemia and two with chronic myelomonocytic leukaemia). The level of FMS expression on B lymphocytes was lower than the level of expression detected on monocytes isolated from the same sample. FMS mRNA expression in B lymphocytes has been confirmed by a reverse transcription-polymerase chain reaction (RT-PCR)-based technique and Northern blot analysis. Thus, FMS may play a role in the normal function of B lymphocytes and, because of its potential oncogenic activity, may contribute to the pathogenesis of malignancies of this cell type.


Asunto(s)
Linfocitos B/química , Receptor de Factor Estimulante de Colonias de Macrófagos/análisis , Secuencia de Bases , Expresión Génica , Genes fms , Humanos , Linfoma/metabolismo , Datos de Secuencia Molecular , Monocitos/química , Proto-Oncogenes Mas , ARN Mensajero/análisis
5.
Leukemia ; 9(12): 2003-8, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8609709

RESUMEN

Chronic lymphatic leukaemia (CLL) is the most common leukaemia and is characterized by long-term survival. Previous studies have shown that karyotypic abnormalities are relatively stable and that certain abnormalities may be associated with a poor prognosis. In a prospective 5-year study of 45 patients with typical CLL, sequential karyotypic studies were undertaken every 6-12 months. Clonal karyotypic abnormalities were identified in 62% of patients, either at diagnosis or during the study period with 38% (17/45) exhibiting clonal evolution. In patients with no clinical disease progression, 13q abnormalities were most commonly detected compared with 11q deletions in patients with progressive disease. Karyotypic evolution was significantly associated with progressive disease (12/16, 75% vs 5/29, 17%; P < 0.001, chi2). Thus, karyotypic evolution is not uncommon in CLL, is usually associated with disease progression and deletions of 11q are the commonest detected abnormalities.


Asunto(s)
Cromosomas Humanos Par 11 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adulto , Anciano , Femenino , Eliminación de Gen , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico
6.
Leukemia ; 4(3): 216-8, 1990 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1690320

RESUMEN

Chronic lymphocytic leukemia (CLL) is a progressive disease in which chemotherapy may result in temporary suppression of the peripheral blood lymphocyte count, but cure is not usually possible. Drug resistance mechanisms and the multidrug resistant (MDR) phenotype may be relevant to the therapeutic response. We have studied 34 patients with CLL (seven untreated, 27 treated), screening both DNA and RNA with the mdr 1 gene probe. In pure lymphocyte populations from 10 normal subjects, low levels of mdr 1 RNA expression were found. Eighteen CLL patients (four untreated, 14 treated) had levels of mdr 1 RNA expression above the normal range. No evidence of mdr 1 gene amplification could be found in these patients. Sequential estimations of RNA levels in three patients suggest that malignant lymphocytes in CLL can increase mdr 1 expression in response to chemotherapy and return to basal levels on withdrawal of the treatment. Such data raise important questions about the type of timing of cytotoxic therapy in CLL.


Asunto(s)
Resistencia a Medicamentos/genética , Leucemia Linfocítica Crónica de Células B/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Glicoproteínas de Membrana/genética , ARN/análisis
7.
Leukemia ; 9(1): 155-8, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7845011

RESUMEN

The FMS proto-oncogene encodes a polypeptide growth factor receptor expressed on the cell surface of monocytes and B lymphocytes within the haematological system. Mutations of the FMS gene at codons 301 and 969 have been detected in a number of haematological disorders. Mutations at these codons are thought to be important in the pathogenesis of leukaemia in cells expressing a mutant receptor. Following our finding that the colony stimulating factor-1 receptor (CSF-1R) was expressed on B cells, we have assessed DNA from 17 patients with B-cell chronic lymphocytic leukaemia (CLL), 15 with acute lymphoblastic leukaemias (ALL), two samples from patients with B-cell non-Hodgkin's lymphoma (B-NHL), and 20 haematologically normal individuals for the presence of C-terminal mutations of the FMS gene. Using single stranded conformational polymorphism analysis (SSCP), a single band shift was detected resulting from a nucleotide insertion at codon 965 in the DNA isolated from a patient with B-NHL. These results indicate that mutations of the FMS gene in this region are rare in B-cell malignancy but may contribute to the pathogenesis of leukaemias and lymphomas in a small subset of patients. However, the presence of other mutations not detected using this type of analysis cannot be excluded.


Asunto(s)
Genes fms , Leucemia Linfocítica Crónica de Células B/genética , Mutación , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Secuencia de Aminoácidos , Secuencia de Bases , Linfoma de Células B/genética , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple
8.
Leukemia ; 5(12): 1050-3, 1991 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-1685551

RESUMEN

The ability of cyclosporin to modify drug accumulation in vitro, measured by the cellular accumulation of daunorubicin, was examined. In 42 patients with chronic lymphatic leukaemia this correlates well with the levels of P-glycoprotein (Pgp) measured by immunofluorescent labelling of Pgp after treatment of the cells with neuraminidase to unmask the epitope recognized by the monoclonal antibody MRK 16. It is shown that flow cytometric analysis using MRK 16 to detect Pgp expression levels together with drug accumulation studies can rapidly assess the multidrug-resistant phenotype of patients' cells, and enable selection of those suitable for therapy with agents known to circumvent mdr-1 mediated drug resistance.


Asunto(s)
Ciclosporina/farmacología , Resistencia a Medicamentos , Glicoproteínas de Membrana/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Transporte Biológico/efectos de los fármacos , Clorambucilo/farmacología , Daunorrubicina/metabolismo , Humanos , Técnicas In Vitro , Glicoproteínas de Membrana/química , Neuraminidasa/farmacología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatología , Células Tumorales Cultivadas
9.
Leukemia ; 8(9): 1498-502, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8090029

RESUMEN

The treatment of acute myeloid leukaemia (AML) is often complicated by resistance to chemotherapeutic drugs. Many of the most effective drugs used to treat haematological malignancies target the nuclear enzyme topoisomerase II. Resistance to these drugs in vitro has been associated with quantitative and qualitative changes in the enzyme. In this study, we have investigated topoisomerase II mRNA expression in leukaemic blasts from 23 AML patients. Expression levels ranged from 1-47% relative to the haemopoietic cell line HL60 in 16 evaluable patients. Thirteen of 16 patients achieved complete remission (CR). We have therefore chosen ease of entry into CR as the most sensitive clinical correlate. Decreased topoisomerase II mRNA expression in vitro results in drug resistance. The clinical relevance of reduced expression is not known. All cases of AML and de novo AML have been studied separately. We are unable to identify a correlation between topoisomerase II mRNA levels and ease of entry into CR in either of these groups. Taking these findings into account, group size calculations have been undertaken and indicate that a multi-centre study of this question is warranted.


Asunto(s)
ADN-Topoisomerasas de Tipo II , ADN-Topoisomerasas de Tipo II/metabolismo , Isoenzimas/metabolismo , Leucemia Mieloide Aguda/enzimología , Adolescente , Adulto , Anciano , Antígenos de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , ADN-Topoisomerasas de Tipo II/genética , Proteínas de Unión al ADN , Resistencia a Medicamentos , Femenino , Humanos , Isoenzimas/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , ARN Mensajero/metabolismo , Inducción de Remisión
10.
Leukemia ; 7(8): 1199-203, 1993 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8394482

RESUMEN

Chronic lymphocytic leukaemia (CLL) is a progressive disease, commonly treated in its early stage with alkylating agents. A multi-agent regimen which includes anthracyclines is used to treat advanced disease. Despite chemotherapy, the disease remains incurable. There is now considerable evidence to suggest that anthracyclines exert their effect via the nuclear enzyme topoisomerase II and that alterations in amount or activity of this enzyme may mediate drug resistance. We have investigated topoisomerase II mRNA expression in 34 CLL patients and in haemopoietic cells from 10 normal donors. Expression was found to be low but detectable in all patients and normals. Such low levels may contribute to the toxicity of alkylating agents, but could severely limit the effect of anthracyclines.


Asunto(s)
Antineoplásicos/uso terapéutico , ADN-Topoisomerasas de Tipo II/sangre , Células Madre Hematopoyéticas/enzimología , Leucemia Linfocítica Crónica de Células B/enzimología , ADN-Topoisomerasas de Tipo II/genética , Resistencia a Medicamentos , Expresión Génica , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , ARN Mensajero/sangre
11.
Leukemia ; 11(11): 1929-32, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9369428

RESUMEN

Eighty-four patients with typical chronic lymphocytic leukemia (CLL) (by morphological and immunophenotypic criteria) on whom karyotypes were available were studied. Binet stage at diagnosis and follow-up were defined. Survival was calculated from diagnosis. Fifty-one percent of patients had a karyotypic abnormality, the commonest being abnormalities at 13q14 (16%); these patients did not have significantly different survival from patients with normal karyotype. The second commonest abnormality was del(11q) (13%); these patients had significantly worse survival when compared both with patients with normal karyotype (P < 0.0001) and with other patients with karyotypic abnormality (P = 0.0012). All patients with del(11q) had progressed to stage C at follow-up while only 20% of the other patients had shown any disease progression (P < 0.0001). Del(11q) may identify a subset of patients with typical CLL who have worse survival and consistent disease progression and in future may help define a group of patients with CLL who could benefit from earlier or more intensive therapy.


Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 11/genética , Leucemia Linfocítica Crónica de Células B/genética , Adulto , Anciano , Anciano de 80 o más Años , Aberraciones Cromosómicas , Trastornos de los Cromosomas , Progresión de la Enfermedad , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia
12.
Leukemia ; 8(4): 677-81, 1994 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8152265

RESUMEN

Patients successfully treated for a malignancy with cytotoxic therapy have an increased risk of developing secondary myelodysplasia (MDS) and acute myeloid leukemia (AML). We report a patient in remission from Hodgkin's disease (HD) who remains hematologically normal 4 years after combination chemotherapy, but who has biological and genetic abnormalities characteristic of myelodysplasia. X-inactivation analysis using a 5' phosphoglycerate kinase (PGK) probe demonstrates polyclonal hematopoiesis, but cytogenetic analysis reveals a clonal population with a minority of metaphases having a 7q-deletion. NRAS mutations are not detectable 1 year after treatment, but are present in two separate clones (at codons 12 and 15) analyzed by single-stranded conformational polymorphism (SSCP), followed by cloning and sequencing 4 years after treatment. The presence of an activated NRAS with the same codon 12 mutation was independently confirmed by the nude mouse tumorigenicity assay. In vitro peripheral blood granulocyte-macrophage colony-forming units (CFU-GM) have changed from normal to undetectable levels while erythroid burst forming units (BFU-E) were significantly reduced on two occasions during the period of observation. These abnormalities are characteristic of MDS. Continued clinical follow-up will determine whether these evolving genetic and biological abnormalities pre-date the onset of clinical and morphological features of MDS.


Asunto(s)
Enfermedad de Hodgkin/terapia , Síndromes Mielodisplásicos/genética , Adulto , Secuencia de Aminoácidos , Animales , Terapia Combinada , Compensación de Dosificación (Genética) , Femenino , Genes ras/genética , Humanos , Ratones , Ratones Desnudos , Datos de Secuencia Molecular , Neoplasias Primarias Secundarias/genética , Mutación Puntual
13.
Leukemia ; 7(6): 795-800, 1993 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8501974

RESUMEN

Patients successfully treated for lymphoma by conventional cytotoxic therapy are at increased risk of developing treatment-related myelodysplasia and acute myeloid leukaemia. In this study we have investigated a group of haematologically normal females in remission from lymphoma for evidence of clonal haemopoiesis as a possible marker for the development of clonal haemopoietic disorders. Unilateral X-inactivation, and hence clonality, can be determined in females heterozygous for X-linked restriction fragment length polymorphisms by differences in methylation between active and inactive X-chromosomes. We have studied methylation patterns at the DXS255 locus and the phosphoglycerate kinase (PGK) gene in 25 females in remission from lymphoma and compared them to 35 normal females. Unilateral X-inactivation was detected in 4/15 patients in remission from lymphoma versus 2/27 normals at the DXS255 locus and in 4/13 treated lymphoma patients versus 0/11 normals at the PGK locus. Six individuals were analysed by both techniques with complete concordance. Unilateral X-inactivation was more common following cytotoxic therapy for lymphoma (7/25) than in normals (2/35) (p < 0.025) and in the lymphoma cohort was associated with increasing time from the end of therapy (p = 0.03). Patients in remission from lymphoma have an increased incidence of clonal haemopoiesis compared to normal individuals. This may be due to either the clonal expansion of an abnormal genetically damaged stem cell or a variation of normal haemopoiesis. Prospective studies will establish whether this finding is associated with an increased risk of developing treatment-related myelodysplasia and acute myeloid leukaemia.


Asunto(s)
Hematopoyesis , Linfoma/genética , Neoplasias Primarias Secundarias/patología , Secuencia de Bases , Células Clonales , Compensación de Dosificación (Genética) , Femenino , Amplificación de Genes , Reordenamiento Génico de Cadena Pesada de Linfocito B , Marcadores Genéticos , Humanos , Linfoma/terapia , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos/química , Fosfoglicerato Quinasa/genética , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Mapeo Restrictivo , Cromosoma X
14.
Leukemia ; 14(8): 1371-7, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10942231

RESUMEN

First results of a randomized trial (APL91 trial) and other randomized or non-randomized studies have shown that ATRA followed by chemotherapy significantly increased event-free survival (EFS) and survival, and decreased the incidence of relapse by comparison to chemotherapy alone in newly diagnosed APL. We present here long-term follow-up of the APL91 trial. In this trial, 101 patients had been randomized between ATRA followed by three courses of daunorubicin-AraC chemotherapy (ATRA group) and the same chemotherapy alone (chemotherapy group). Results were reanalyzed 73 months after closing of patient entry. Updated results of APL 91 trial found a Kaplan-Meier estimate of EFS and relapse rate at 4 years of 63% and 31% in the ATRA group, as compared to 17% and 78% in the chemotherapy group (P= 10(-4) and relative risk 2.95, P= 10(-4) and relative risk 3.68, respectively). Kaplan-Meier survival at 4 years was 76% in the ATRA group and 49% in the chemotherapy group (P= 0.026, relative risk 2.7). In the chemotherapy group, seven of the 27 relapses occurred after 18 months, but no relapse was seen after 43 months. In the ATRA group, four of the 17 relapses occurred after 18 months, including two late relapses (at 58 and 74 months). In the chemotherapy group, 23 of the 25 patients who relapsed achieved a second CR with ATRA, and the Kaplan-Meier estimate of second relapse was 40% at 30 months. In the ATRA group, the 10 patients who relapsed and were retreated with ATRA achieved a second CR. In conclusion, long-term results of APL91 trial confirm the superiority of the combination of ATRA and chemotherapy over chemotherapy alone in newly diagnosed APL, and that ATRA should be incorporated in the front-line treatment of APL.


Asunto(s)
Antineoplásicos/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/uso terapéutico , Humanos , Recuento de Leucocitos , Pronóstico
15.
Endocrinology ; 142(9): 4076-85, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11517187

RESUMEN

Prohibitin is an evolutionary conserved protein that is associated with cellular differentiation, atresia, and luteolysis in the rat ovary. However, the specific cellular location and function of prohibitin in ovarian cells has not been clearly elucidated. To characterize the expression of prohibitin during cell proliferation, differentiation, and cell death, we have successfully established a temperature-sensitive granulosa cell line, designated RGA-1. At a permissive temperature of 33 C, RGA-1 cells proliferate, but revert to a differentiated phenotype at a nonpermissive temperature of 39 C. Significant inductions of prohibitin mRNA and protein expression were observed in the differentiated phenotype when compared with proliferating cells. Differentiated RGA-1 cells were found to express inhibin alpha- and beta-transcripts, as well as steroidogenic acute regulatory protein and peripheral-type benzodiazepine receptor proteins in a manner reminiscent of steroidogenic functional responses observed in primary differentiated granulosa cells. Prohibitin expression correlated well with the expression of these steroidogenic proteins. At 39 C, RGA-1 cells also displayed increases in p53 protein levels, indicative of growth arrest in the nonproliferating cells. Confocal and electron microscopic examinations revealed increased prohibitin localization to the mitochondria at 39 C, along with changes in mitochondrial size and shape. These changes were accompanied by marked reductions in cytochrome c oxidase subunit II levels and in unit mitochondrial transmembrane potential. In addition, cell fractionation studies demonstrated that the prohibitin protein was mainly localized to the mitochondrial membrane. Collectively, these findings suggest a role for prohibitin in mitochondrial structure and function during growth and differentiation in ovarian granulosa cells. Prohibitin expression may also be indicative of mitochondrial destabilization during apoptosis-related events.


Asunto(s)
Células de la Granulosa/metabolismo , Proteínas/metabolismo , Proteínas Represoras , Animales , Apoptosis/fisiología , Diferenciación Celular , División Celular , Línea Celular , Femenino , Antagonistas de Receptores de GABA-A , Células de la Granulosa/citología , Células de la Granulosa/fisiología , Inhibinas/antagonistas & inhibidores , Mitocondrias/metabolismo , Mitocondrias/fisiología , Mitocondrias/ultraestructura , Fosfoproteínas/antagonistas & inhibidores , Prohibitinas , Ratas , Fracciones Subcelulares/metabolismo , Distribución Tisular
16.
Transplantation ; 49(3): 547-53, 1990 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-2180150

RESUMEN

Retrospectively we analyzed the histocompatibility data and clinical results of bone marrow transplantation in 51 patients who received marrow from unrelated donors (UD) from 1977 to 1987 at one of four UK BMT centers. We compared the results with those obtained in 51 transplants carried out at the same centers using HLA-identical (ID) sibling donors. Of the UD/recipient pairs 32 (63%) were serologically identical for HLA A, B, and DR antigens, and 37% showed varying degrees of mismatch. UD-BMT primary diagnoses were: severe aplastic anemia or Fanconi's anemia (n = 17), acute leukemia (n = 11), chronic myeloid leukemia (n = 21), and other conditions (n = 2). T cell depletion of the graft was associated with a significant improvement in survival in both UD and ID-BMT. Graft failure was more common in recipients of UD than of ID transplants (13 [25%] vs. 5 [10%] P = 0.05) but there was no significant difference in the frequency of acute or chronic graft-versus-host disease. Actuarial survival was superior for recipients of ID transplants (UD vs. ID: 49% vs. 78%, respectively, at 3 months; 32% vs. 63% at one year). Reduced survival for recipients of UD-BMT was confirmed in case control regression analysis (relative risk 3.0, P = 0.01). Nevertheless in patients whose only alternative is a partially mismatched family donor we think that UD-BMT is justified.


Asunto(s)
Trasplante de Médula Ósea/inmunología , Supervivencia de Injerto , Antígenos HLA/análisis , Antígenos HLA-DR/análisis , Histocompatibilidad , Humanos , Estudios Multicéntricos como Asunto , Análisis Multivariante , Análisis de Regresión , Estudios Retrospectivos , Análisis de Supervivencia , Reino Unido
17.
J Histochem Cytochem ; 47(6): 769-76, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10330453

RESUMEN

This study was designed to determine the pattern of expression and cellular distribution of the steroidogenic acute regulatory protein (StAR) during the transitional stages of follicular differentiation in rat ovary. Using specific antisera against the StAR, immunohistochemistry, Western blotting, and immunoprecipitation analyses provide evidence confirming the localization and expression of StAR in granulosa cells (GCs) of juvenile rat ovaries before and after PMSG treatment. The results also show that StAR expression occurs in theca intersitial cells surrounding preantral, antral, and larger antral follicles in adult diestrous ovaries. Furthermore, we have demonstrated heterogenous StAR immunoreactivity in the granulosa cell layers and cells of the corpora lutea. A novel finding presented here is that, during ongoing growth and differentiation of the follicle, the immunoreactivity of StAR tends to shift from the GC of early antral follicles to the theca cell layers in the adult. The spatiotemporal changes or shifts in StAR expression and cellular localization also coincide with the appearance of more acidic isoforms of the 30-kD protein, as determined by two-dimensional gel electrophoresis. Although the functional implications of these observations remain unclear, the acute temporal changes in StAR expression and localization may not only reflect the dynamic steroidogenic capacity of follicular cells but may also support a possible role for FSH in the induction of follicular maturation.


Asunto(s)
Folículo Ovárico/metabolismo , Fosfoproteínas/biosíntesis , Fosfoproteínas/metabolismo , Animales , Western Blotting , Diferenciación Celular , Femenino , Células de la Granulosa/metabolismo , Proteínas de la Membrana/metabolismo , Microscopía Confocal , Folículo Ovárico/crecimiento & desarrollo , Ratas , Ratas Sprague-Dawley
18.
Leuk Res ; 15(7): 543-9, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1907341

RESUMEN

Histocompatibility antigen (HLA) frequencies in chronic lymphatic leukaemia (CLL) patients and control subjects were compared with respect to disease susceptibility and prognosis. Additionally, HLA and full blood count data were compared in relatives of 25 patients and 31 controls. We found no association of HLA with susceptibility although the presence of HLA B12, alone or in combination with HLA A2, indicated better prognosis. Relatives HLA identical with the patients showed no evidence of white cell disorder when compared with haplo- or non-identical relatives, or controls. As a group, however, relatives of patients had fewer lymphocytes than relatives of controls.


Asunto(s)
Antígenos HLA/análisis , Leucemia Linfocítica Crónica de Células B/sangre , Antígenos de Diferenciación de Linfocitos T/análisis , Antígenos CD4/análisis , Antígenos CD8 , Salud de la Familia , Femenino , Antígenos HLA/genética , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/inmunología , Recuento de Leucocitos , Linfocitos/citología , Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Neutrófilos/citología , Neutrófilos/inmunología , Pronóstico , Factores de Riesgo
19.
Leuk Res ; 19(12): 985-8, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8632669

RESUMEN

The inhibition of [3H]-thymidine incorporation into the DNA of mitogen-stimulated chronic lymphocytic leukaemia lymphocytes by chlorambucil or gamma-irradiation in vitro was measured in a series of patients, some of whom were untreated, some treated and some who were showing resistance to first-line or second-line treatment. There was evidence of resistance to irradiation developing in parallel with that to chlorambucil. The resistance to chlorambucil in chronic lymphocytic leukaemia (CLL) is not necessarily due to altered drug transport or metabolism but to a more fundamental process affecting DNA damage.


Asunto(s)
Leucemia Linfocítica Crónica de Células B/patología , Linfocitos/efectos de la radiación , Antineoplásicos Alquilantes/farmacología , Clorambucilo/farmacología , ADN de Neoplasias/biosíntesis , Resistencia a Antineoplásicos , Femenino , Rayos gamma , Humanos , Leucemia Linfocítica Crónica de Células B/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Masculino , Tolerancia a Radiación , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismo , Células Tumorales Cultivadas/efectos de la radiación
20.
Leuk Res ; 8(4): 667-79, 1984.
Artículo en Inglés | MEDLINE | ID: mdl-6590934

RESUMEN

The prognostic usefulness of a range of factors has been examined for patients with acute myeloid leukaemia. Although there was a statistical association between some of these factors and remission rate, the association was only partial. To improve the usefulness of the data, multiple logistic regressional analysis was used. The features selected for use in the analysis were age, blood blast count, FAB classification and colony growth pattern. The last three features could be used as categorical variables, since blood blast counts of greater than 100 X 10(9)/1, FAB group 1 and a prolific pattern of colony growth were associated with a low remission rate. Age was used as a continuous variable. Using these features, eight regression groups were defined. Thus when this data for an individual patient is analysed, it is possible to obtain a value for the probability of that patient achieving remission.


Asunto(s)
Leucemia Mieloide Aguda/diagnóstico , Adulto , Factores de Edad , Anciano , División Celular , Ensayo de Unidades Formadoras de Colonias , Humanos , Leucemia Mieloide Aguda/patología , Recuento de Leucocitos , Persona de Mediana Edad , Probabilidad , Pronóstico , Estadística como Asunto
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