RESUMEN
Serum thyroglobulin is used as part of the early postoperative assessment of differentiated thyroid cancer (DTC) since there is a clear relationship between an increased risk of recurrence and persistent disease after initial treatment and high postoperative stimulated thyroglobulin (ps-Tg) values. Thus, although ps-Tg above 10-30 ng/mL is considered an independent predictor of worse prognosis, the value that is associated with distant metastases is not defined. Thus, this was our objective. We selected 655 DTC patients from a nuclear medicine department database (Irmandade Santa Casa de Misericórdia de São Paulo, Brazil). All patients had received total thyroidectomy and radioactive iodine (RAI) therapy and had ps-Tg values higher than 10 ng/mL with negative anti-thyroglobulin antibodies. Then, we selected patients who presented post-therapy whole-body scan with pulmonary and/or bone uptake but with no mediastinum or cervical uptake. Patients with negative findings on functional imaging or any doubt on lung/bone uptake were submitted to additional exams to exclude another non-thyroid tumor. Of the 655 patients, 14.3% had pulmonary and 4.4% bone metastases. There was a significant difference in ps-Tg levels between patients with and without metastases (P<0.001). The cutoff value of ps-Tg was 117.5 ng/mL (sensitivity: 70.2%; specificity: 71.7%) for those with lung metastasis, and 150.5 ng/mL (sensitivity: 79.3%; specificity: 85%) for those with bone metastasis. The cutoff value for patients with eitherpulmonary or bone metastasis was 117.5 ng/mL (sensitivity: 70.2%; specificity: 83.7%). Our findings demonstrated that ps-Tg could predict distant metastasis in DTC patients. We identified a cutoff of 117.5 ng/mL with a high negative predictive value of 93.7%.
Asunto(s)
Neoplasias de la Tiroides , Adulto , Brasil , Femenino , Humanos , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Tiroglobulina , Neoplasias de la Tiroides/cirugíaRESUMEN
OBJECTIVE: The aim of this prospective longitudinal study is to research the amplitude of distortion product otoacoustic emissions caused by the ototoxic drugs used, between the end of the administration and from 15 to 40 days after its use. METHODS: It was a prospective longitudinal study composed by term and preterm newborns from the Santo André city hospital, in the period from July 2003 to September 2004. The first evaluation occurred on the hospital discharge day. Three groups were evaluated: control group with 33 term and healthy newborns; term study group with 19 term newborns with more than 37 weeks exposed to amikacin and/or vancomycin; and preterm study group with 15 preterm newborns from 32 to 37 weeks exposed to the same ototoxic. The newborns did not present risk factors for hearing loss according to the JCIH, 2000 concomitant to the neonatal infection. All newborns were evaluated at a corrected gestational age greater than 37 weeks. The otoacoustic emissions amplitudes obtained at the hospital discharge were compared to the ones obtained from 15 to 40 days after the discharge. RESULTS: The otoacoustic emissions amplitudes of the preterm study group were smaller than the amplitudes of the control group and the term study group in both moments of the test. The amplitude of the newborns' otoacoustic emissions increased in the second moment of the test. The otoacoustic emissions amplitudes of the control group in the second moment of the test were similar to the term study group in the first moment of the research. CONCLUSION: There are the increase of the distortion product otoacoustic emissions amplitude from the discharge moment until 15 to 40 days after in the post-natal period. The exposure to amikacin and vancomycin on the recommended dose by Neofax, 2003/2004 did not alter the amplitude of the emissions in the newborns without risk indicators concomitant with neonatal infection.
Asunto(s)
Amicacina/efectos adversos , Aminoglicósidos/efectos adversos , Enfermedades Cocleares/inducido químicamente , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , Vancomicina/efectos adversos , Amicacina/toxicidad , Aminoglicósidos/toxicidad , Enfermedades Cocleares/complicaciones , Enfermedades Cocleares/fisiopatología , Estudios de Seguimiento , Pérdida Auditiva Sensorineural/inducido químicamente , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Recién Nacido , Otitis Media/tratamiento farmacológico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Vancomicina/toxicidadRESUMEN
PURPOSE: The aim of the study was to define the prognostic role of the metastasis suppressor gene, nm23, in 106 primary ovarian cancer patients. PATIENTS AND METHODS: Northern and Western blotting analysis of nm23-H1 and nm23-H2 expression were performed in a subset of ovarian tumors. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens from 106 primary ovarian carcinomas by the antihuman nm23 monoclonal antibody. RESULTS: Northern and Western blotting analysis demonstrated a direct association between nm23-H1 and nm23-H2 levels. Moreover, an overall concordance of 86.7% between Northern blotting and immunohistochemical data was observed. Sixty-six specimens (68%) showed a positive nm23-H1 immunoreaction. The percentage of nm23-H1 positivity was higher in lymph node-negative (70%) than in lymph node-positive cases (44%) (P = .049). Moreover, the percentage of complete/partial responses to chemotherapy was higher in nm23-H1-positive (69%) than in nm23-H1-negative (44%) patients (P = .03). The percentage of epidermal growth factor receptor (EGFR) positive cases was lower in nm23-H1-positive (44%) than in nm23-H1-negative immunostained (72%) samples (P = .012). Lower ras/p21 levels (median, 1.77 absorbance units) were found in nm23-H1-positive than in nm23-H1-negative samples (median, 2.63 absorbance units) (P = .03). The 6-year progression-free survival (PFS) rate of nm23-H1-positive cases was 50% (95% confidence interval [CI], 33 to 67) versus 12% (95% CI, -2 to 26) for nm23-H1-negative patients (P = .0056). In multivariate analysis, only stage, ascites, and nm23-H1 content retained independent prognostic roles. CONCLUSION: The assessment of nm23 content may provide useful information for prognostic characterization of ovarian cancer patients.
Asunto(s)
Genes Supresores de Tumor , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Northern Blotting , Western Blotting , Supervivencia sin Enfermedad , Receptores ErbB/análisis , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , PronósticoRESUMEN
A number of cytokines modulate self-renewal and differentiation of hematopoietic elements. Among these is transforming growth factor beta1 (TGF-beta1), which regulates cell cycle and differentiation of hematopoietic cells, but has pleiotropic activities depending on the state of responsiveness of the target cells. It has been previously shown by us and other authors that TGF-beta1 maintains human CD34(+) hematopoietic progenitors in an undifferentiated state, independently of any cell cycle effects, and that depletion of TGF-beta1 triggers differentiation accompanied by a decrease in CD34 antigen expression. In the present work, we show that exogenous TGF-beta1 upregulates the human CD34 antigen in the CD34(+) cell lines TF-1 and KG-1a, but not in the more differentiated CD34(-) cell lines HL-60 and K-562. We further studied this effect in the pluripotent erythroleukemia cell line TF-1. Here, TGF-beta1 did not effect cell growth, but induced transcriptional activation of full-length CD34 and prevented differentiation induced by differentiating agents. This effect was associated with nuclear translocation of Smad-2, activation of TAK-1, and with a dramatic decrease in p38 phosphorylation. In other systems TGF-beta1 has been shown to activate a TGF-beta-activated kinase 1 (TAK1), which in turn, activates p38. The specific inhibitor of p38 phosphorylation, SB202190, also increased CD34 RNA expression, indicating the existence of a link between p-38 inhibition by TGF-beta1 and CD34 overexpression. Our data demonstrate that TGF-beta1 transcriptionally activates CD34 and prevents differentiation of TF-1 cells by acting independently through the Smad, TAK1 and p38 pathways, and thus provide important clues for the understanding of hematopoietic development and a potential tool to modify response of hematopoietic cells to mitogens or differentiating agents.
Asunto(s)
Antígenos CD34/biosíntesis , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Leucemia Eritroblástica Aguda/patología , Transcripción Genética/efectos de los fármacos , Factor de Crecimiento Transformador beta/farmacología , Antígenos CD34/genética , Ciclo Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Medio de Cultivo Libre de Suero , Citocinas/farmacología , Proteínas de Unión al ADN/fisiología , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Genes bcl-2 , Células HL-60/efectos de los fármacos , Células HL-60/metabolismo , Células Madre Hematopoyéticas/metabolismo , Humanos , Imidazoles/farmacología , Células K562/efectos de los fármacos , Células K562/metabolismo , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/metabolismo , Quinasas Quinasa Quinasa PAM/fisiología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiología , Fosforilación/efectos de los fármacos , Proteínas Quinasas/metabolismo , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Piridinas/farmacología , ARN Mensajero/biosíntesis , ARN Neoplásico/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína Smad2 , Transactivadores/fisiología , Factor de Crecimiento Transformador beta1 , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismo , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
The bcl-2 family of proteins includes some important regulators of apoptosis. Among these, bcl-2 and bcl-xL prevent cells from entering apoptosis, whereas bax and bcl-xS can induce cell death. Alterations in the control of this process can lead to a decrease in cell death, thus contributing to neoplastic growth. Diminished susceptibility to chemotherapy has also been attributed, in in vitro systems, to alterations in the levels of bcl-2, bax, or bcl-x. We analyzed the expression of bcl-2, bax, bcl-xL, and bcl-xS in normal and neoplastic ovarian tissues by reverse transcriptase-PCR and Western blotting. The RNA and protein levels were significantly correlated for all genes. Interestingly, the levels of these genes in normal and neoplastic tissues were significantly different: bcl-2 was higher in normal tissue (P < 0.002), whereas bax and bcl-xL were higher in carcinoma (P < 0.018 and P < 0.030, respectively). bcl-xS was present at low levels in 83% of neoplastic samples and was undetectable in normal tissue. Reverse transcriptase-PCR analysis of 74 tumors showed no major correlation with clinicopathological parameters or with response to chemotherapy. Only bax and bcl-xL were correlated with progesterone receptor levels (n = 29, r = +0.44, P < 0.0189, and r = -0.40, P < 0.035, respectively). No correlation was found with estrogen receptor levels or with p53 immunostaining. Our data indicate that the regulation of the bcl-2 family of proteins differs between normal and neoplastic ovarian tissues. Moreover, the modulation of these genes in ovarian carcinoma is different compared to other tissues; therefore, tissue specificity is very important in regulation of the bcl-2 family of proteins.
Asunto(s)
Neoplasias Ováricas/metabolismo , Ovario/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Femenino , Humanos , Persona de Mediana Edad , ARN/metabolismo , ARN Neoplásico/metabolismo , Valores de Referencia , Proteína bcl-XRESUMEN
Peripheral blood progenitor cells (PBPC) mobilized by granulocyte colony-stimulating factor (G-CSF) promptly engraft allogeneic recipients after myeloablative chemotherapy for hematologic malignancies. Surprisingly, no exacerbation of acute graft-vs-host disease has been observed despite a 10-fold higher T-cell content in PBPC compared with bone marrow allografts. Because G-CSF can suppress T-cell proliferation in response to mitogens and enhance their activation-induced apoptosis, we examined the molecular mechanisms underlying G-CSF-induced immune dysfunction. Normal allogeneic lymphocytes were challenged with phytohemagglutinin in the presence of serum collected after G-CSF administration (postG) to healthy PBPC donors, and the expression of key components of the cell cycle and apoptotic machineries was investigated by flow cytometry and Western blotting. Lymphocyte stimulation was associated with collapse of mitochondrial transmembrane potential, hypergeneration of reactive oxygen intermediates, and activation of caspase-3 and DNA fragmentation. Lymphocytes were arrested in a G(1)-like phase of the cell cycle, as measured by G(1)-phase cyclin expression and bromodeoxyuridine (BrdUrd) incorporation. Cell tracking experiments confirmed the occurrence of a lower number of population doublings in postG compared with preG cultures. Unexpectedly, the phosphorylation state of the protein encoded by the retinoblastoma susceptibility gene (pRB) was unaltered in postG cultures, and the inhibition of cell cycle progression occurred without the recruitment of the cyclin-dependent kinase inhibitors p15(INK4B), p16(INK4A), and p27(Kip1). We eventually evaluated the ability of antioxidant/cytoprotectant agents to prevent the G-CSF-induced mitochondrial dysfunction and inhibition of cell cycle progression. Of interest, both N-acetylcysteine and amifostine reduced apoptotic cell death by 45% on average, inhibited the activation/processing of caspase-3, and increased BrdUrd incorporation in postG cultures. Based on these experimental findings, a model is proposed in which T-cell activation in the presence of serum immunoregulatory factor(s) induced by G-CSF is associated with a molecular phenotype mimicking the G(1)-S transition and consisting of pRB phosphorylation, lack of CDKI recruitment, and reduced cyclin-E expression. The putative relationship between lymphocyte mitogenic unresponsiveness and apoptosis induction would occur at the level of key molecules shared by the cell cycle and apoptotic machineries. Whether the G-CSF-mediated modulation of lymphocyte functions in vitro is beneficial in transplantation medicine remains to be determined.
Asunto(s)
Apoptosis , Proteínas de Ciclo Celular , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Expresión Génica , Factor Estimulante de Colonias de Granulocitos/farmacología , Proteína de Retinoblastoma/metabolismo , Linfocitos T/fisiología , Proteínas Supresoras de Tumor , Acetilcisteína/farmacología , Adulto , Amifostina/farmacología , Antioxidantes/farmacología , Proteínas Portadoras/genética , Caspasa 3 , Caspasas/metabolismo , División Celular , Inhibidor p15 de las Quinasas Dependientes de la Ciclina , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Quinasas Ciclina-Dependientes/metabolismo , Fragmentación del ADN , Inhibidores Enzimáticos , Femenino , Fase G1 , Humanos , Recuento de Linfocitos , Masculino , Proteínas Asociadas a Microtúbulos/genética , Mitocondrias/fisiología , Mitocondrias/ultraestructura , Fosforilación , Especies Reactivas de Oxígeno/metabolismo , Linfocitos T/inmunología , Linfocitos T/ultraestructuraRESUMEN
OBJECTIVE: A fusion protein made of human granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO), referred to as MEN 11303, has been tested for biologic activity using mobilized CD34(+) cells. METHODS AND RESULTS: MEN 11303 and a combination of GM-CSF/EPO produced the same amount of colony-forming unit granulocyte-macrophage (CFU-GM), of burst-forming unit erythroid (BFU-E), and of multipotent CFU-mixed. After 15 days, liquid cultures of CD34(+) cells exposed to MEN 11303 yielded a total cell number larger than that obtained with an equimolar mixture of GM-CSF and EPO, with a clear prevalence of cells exhibiting an erythroid phenotype. A colony-forming cell assay established from CD34(+) cells precultured with MEN 11303 for 7 days yielded a greater amount of BFU-E than GM-CSF/EPO combination. Exposing CD34(+) cells to MEN 11303 for 7 days in liquid culture resulted in higher recoveries of cells expressing a comparatively less differentiated hematopoietic phenotype and of long-term culture initiating cells. A cell-based binding-competition assay using the human EPO-receptor (EPO-R) transfected murine Ba/F3EPOR cell line showed that MEN 11303 bound to EPO-R with a sixfold lower affinity but induced a more sustained receptor phosphorylation. MEN 11303 supported the growth of Ba/F3EPOR cells more efficiently than EPO and remained detectable in the spent culture medium for a longer time. CONCLUSIONS: MEN 11303 and the combination of GM-CSF/EPO are equally potent in recruiting hematopoietic progenitors into cycle, but the fusion protein is superior in promoting the expansion of committed erythroid percursors. Primitive hematopoiesis is less affected by MEN110303 than GM-CSF/EPO combination. Part of these effects may reflect the peculiar interaction of the EPO moiety of MEN 11303 with the EPO-R.
Asunto(s)
Eritropoyesis/efectos de los fármacos , Eritropoyetina/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Células Madre Hematopoyéticas/efectos de los fármacos , Antígenos CD34/sangre , Neoplasias de la Mama/sangre , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Ensayo de Unidades Formadoras de Colonias , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Femenino , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/patología , Humanos , Inmunofenotipificación , Glicoproteínas de Membrana/metabolismo , Neoplasias Ováricas/sangre , Fenotipo , Fosforilación , Receptores Inmunológicos/metabolismo , Lectina 1 Similar a Ig de Unión al Ácido SiálicoRESUMEN
The changes in chemical attributes and aromatic profile of espresso coffee (EC) were studied taking into account the extraction time and grinding level as independent variables. Particularly, using an electronic nose system, the changes of the global aromatic profile of EC were highlighted. The results shown as the major amounts of organic acids, solids, and caffeine were extracted in the first 8 s of percolation. The grinding grade significantly affected the quality of EC probably as an effect of the particle size distribution and the percolation pathways of water through the coffee cake. The use of an electronic nose system allowed us to discriminate the fractions of the brew as a function of the percolation time and also the regular coffee obtained from different grinding grades. Particularly, the aromatic profile of a regular coffee (25 mL) was significantly affected by the grinding level of the coffee grounds and percolation time, which are two variables under the control of the bar operator.
Asunto(s)
Coffea/química , Café/química , Manipulación de Alimentos/métodos , Compuestos Orgánicos Volátiles/química , Nariz Electrónica , Calor , Odorantes/análisis , Tamaño de la PartículaRESUMEN
Serum thyroglobulin is used as part of the early postoperative assessment of differentiated thyroid cancer (DTC) since there is a clear relationship between an increased risk of recurrence and persistent disease after initial treatment and high postoperative stimulated thyroglobulin (ps-Tg) values. Thus, although ps-Tg above 10-30 ng/mL is considered an independent predictor of worse prognosis, the value that is associated with distant metastases is not defined. Thus, this was our objective. We selected 655 DTC patients from a nuclear medicine department database (Irmandade Santa Casa de Misericórdia de São Paulo, Brazil). All patients had received total thyroidectomy and radioactive iodine (RAI) therapy and had ps-Tg values higher than 10 ng/mL with negative anti-thyroglobulin antibodies. Then, we selected patients who presented post-therapy whole-body scan with pulmonary and/or bone uptake but with no mediastinum or cervical uptake. Patients with negative findings on functional imaging or any doubt on lung/bone uptake were submitted to additional exams to exclude another non-thyroid tumor. Of the 655 patients, 14.3% had pulmonary and 4.4% bone metastases. There was a significant difference in ps-Tg levels between patients with and without metastases (P<0.001). The cutoff value of ps-Tg was 117.5 ng/mL (sensitivity: 70.2%; specificity: 71.7%) for those with lung metastasis, and 150.5 ng/mL (sensitivity: 79.3%; specificity: 85%) for those with bone metastasis. The cutoff value for patients with eitherpulmonary or bone metastasis was 117.5 ng/mL (sensitivity: 70.2%; specificity: 83.7%). Our findings demonstrated that ps-Tg could predict distant metastasis in DTC patients. We identified a cutoff of 117.5 ng/mL with a high negative predictive value of 93.7%.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Neoplasias de la Tiroides/cirugía , Tiroglobulina , Brasil , Radioisótopos de Yodo , Recurrencia Local de NeoplasiaRESUMEN
We studied vertebral morphometry and its relation to bone mineral density (BMD) in normal Brazilian women (n = 605). All women (age 22-97 years) were ambulatory and healthy. A lateral spine scan was done for morphometric X-ray absorptiometry using an imaging densitometer. In 429 of these women, BMD of the spine and proximal femur also were measured using dual-energy X-ray absorptiometry. All women were white with mean (+/- 1 SD) age of 53.7 (+/- 9.5) years. About 21% of the women over 50 years had a T score for spine BMD lower than -2.5 SD, and 7% had a femoral neck BMD below this osteoporosis threshold. Vertebral heights (anterior, HA; middle, HM; and posterior, HP) and ratios (HA/HP and HM/HP) were assessed. There was no systematic difference between younger (20-49 years) and older (50+ years) women in heights or ratios. The vertebral heights were normalized for those observed in each individual case for the L2-L4 sequence. This normalization was adequate for all vertebral heights; the Z score averaged about +0.1. The average Z score for HA/HP was +0.01, but that for the HM/HP was -0.72, indicating that the latter ratio might differ from the reference population used (white American and European women). We observed a small positive correlation between vertebral heights and spine or femur BMD, but this was due entirely to the influence of body size on BMD. On a group basis, the HM/HP showed a significant association with axial BMD; the 1 SD difference between the lowest and highest quartile was associated with a difference of 8-15% (0.5-1.0 SD) in axial BMD.
Asunto(s)
Densidad Ósea , Columna Vertebral/diagnóstico por imagen , Absorciometría de Fotón , Adulto , Anciano , Anciano de 80 o más Años , Estatura , Brasil , Femenino , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Body composition determined by dual energy x-ray absorptiometry and the abdominal visceral fat component determined by computed tomographic scanning were examined in women with Cushing's disease and compared with those in obese women with the same anthropometric parameters and those in nonobese women. Patients with Cushing's had no increase in total body fat or the trunk region (android) component, but had a higher intraabdominal fat area compared to the obese subjects. The total lean tissue mass was slightly reduced in Cushing's compared to that in the obese subjects due to a significant decrease in the muscle of the legs and arms; the reduced amounts of fat and lean tissue masses in the arms were the most significant findings in hypercortisolism. The body mineral and bone calcium contents were slightly reduced in Cushing's compared to those in the obese controls. Thus, although obese subjects had more fat and lean tissue and mineral masses than their normal weight counterparts, the Cushing's patients, with the same total fat mass and its components (except in the arms) as obese individuals, present total lean tissue and fractions, including body mineral and bone calcium contents, similar to those in nonobese subjects due to the depletion of the protein depots, as seen in hypercortisolism.
Asunto(s)
Tejido Adiposo/patología , Composición Corporal , Síndrome de Cushing/diagnóstico , Radiografía Abdominal , Tomografía Computarizada por Rayos X , Absorciometría de Fotón , Adulto , Densidad Ósea , Femenino , Humanos , Persona de Mediana Edad , Minerales/metabolismo , Obesidad/patología , Valores de Referencia , VíscerasRESUMEN
We simultaneously assessed bcl-2, bax, bcl-x(L) and bcl-x(S) expression levels by Western blotting on 53 primary untreated cervical cancers and 15 normal samples. Bcl-2 showed a trend to be lower in neoplastic than in normal samples (P<0.01), while no significant difference was observed for bax and bcl-x(L). Bcl-x(S) was barely detectable in only a few samples. Interestingly, in cervical cancer, bcl-2 and bcl-x(L) were directly correlated (P<0. 01). A significant association of bcl-2 levels with age (P<0.021) and menopausal status (P<0.041) in cervical cancer patients as well as in control patients was observed. Bcl-2, bax and bcl-x(L) levels in responding and non-responding patients were not differently distributed. Bcl-2, bax and bcl-x(L) are likely to play a role in the natural history of cervical tumors, but their clinical significance in predicting response to treatment and clinical outcome needs long-term follow-up studies.
Asunto(s)
Cuello del Útero/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas/biosíntesis , Neoplasias del Cuello Uterino/metabolismo , Adulto , Factores de Edad , Anciano , Western Blotting , Supervivencia sin Enfermedad , Femenino , Humanos , Menopausia , Persona de Mediana Edad , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/mortalidad , Proteína X Asociada a bcl-2 , Proteína bcl-XRESUMEN
Endoglin (CD105) is a component of the transforming growth factor-beta (TGF-beta) receptor (TGF-betaR) complex. Together with betaglycan, CD105 is considered as a TGF-betaR accessory molecule (also called TGF-betaRIII), but its functions in the receptor-ligand interactions are still poorly understood. A small subset of human CD34+ hematopoietic stem/progenitor cells that has phenotypic and functional features suggestive of very primitive hematopoietic cells expresses the CD105 antigen. CD34+/CD105+ cells recirculate in the peripheral blood of mobilized subjects and can be purified by immunomagnetic isolation strategies. The hematopoietic potential of these CD34+/CD105+ cells appears to be sustained by a combination of hematopoietic and non-hematopoietic cytokines, which comprises Flt3 ligand, erythropoietin, interleukin-15 and vascular endothelial growth factor. Endogenous TGF-beta1 is a crucial factor for the maintenance of CD34+/CD105+ immaturity acting through positive modulation of both CD105 and CD34 molecules in the absence of relevant effects on the cell cycle profile. CD105 is absent on very primitive CD34-/lineage-/CD45+ (CD34-Lin-) human hematopoietic cells isolated from cord blood. However, in vitro exposure of CD34-Lin- cells to exogenous TGF-beta1 causes the appearance of a discrete population of CD34+/CD105+ cells. Collectively, available data on CD105 expression and function in primitive hematopoiesis indicate that this molecule could cooperate with the dissociation of TGF-beta1 cell cycle effects from its other effects on cell survival and differentiation.
Asunto(s)
Células Madre Hematopoyéticas/química , Molécula 1 de Adhesión Celular Vascular/análisis , Antígenos CD , Antígenos CD34/análisis , Endoglina , Humanos , Proteínas Serina-Treonina Quinasas , Receptor Tipo II de Factor de Crecimiento Transformador beta , Receptores de Superficie Celular , Receptores de Factores de Crecimiento Transformadores beta/análisis , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
Western blotting is utilized to detect and quantify the amount of a specific protein in a complex mixture of proteins and at the same time to determine its molecular weight. In particular, by Western blotting it is also possible to detect and discriminate the two isoforms of nm23, H1, and H2 (1, 2). nm23-H1 is about 18.5 kD (3) and nm23-H2 is 17 kD (4), hence, they migrate as two distinct bands on a standard SDS polyacrylamide gel. Because the two isoforms are very highly conserved (4), they retain most of the same epitopes; thus any polyclonal antibody raised against one of the two isoforms or a monoclonal antibody against a conserved epitope will recognize both nm23-H1 and -H2 at the same time. Analysis by immunohistochemistry, on the other hand would require two distinct reactions with two specific antibodies for H1 and H2 raised against the least conserved epitopes to avoid crossreaction.
RESUMEN
A useful correlation between maximum thyroid uptake and radioiodine urine levels at different times after exposure was developed in order to determine when the intervention with an adequate blocking agent might still be effective. In an animal model (dog), six different doses were administered in the range of 100-600 kBq. The best correlation was found between the 125I uptake after 48 h (T-48) and urine radioactivity 4-6 h (U-4, U-5, U-6) after exposure. For the case of U-4, the equation Y(T-48) = 0.790 X(U-4) + 2.973 (r = 0.974 with a level of significance of p < 0.001) was obtained. An analogous study, carried out in humans (n = 20) to whom 1311 was administered, showed a similar correlation and level of significance: Y(T-24) = 1.162 X(U-4)+3.263 (r = 0.926; p < 0.001). The validity of this correlation was confirmed in four volunteers who received small doses of 125I(25-100 kBq), with good agreement between measured and extrapolated thyroid uptake and a mean difference of less than 10% (CV = 16.2%). Three different blocking agents were then tested in the same dog: potassium iodide, potassium perchlorate, and a thionamide (Tapazole). The blocking action of the first two compounds was about 90%, as opposed to only 48% for the third compound. Potassium iodide was chosen for its limited side effects and more universal utilization. The final study, carried out with four different doses, indicated that 25 mg of KI is the ideal amount to be administered to the dog. This corresponds to approximately 100 mg for a 70 kg human being (i.e., 1.4 mg kg(-1)). This dose, when administered to a volunteer 4 h after exposure, provided a thyroid blocking of 68%.
Asunto(s)
Radioisótopos de Yodo/farmacocinética , Glándula Tiroides/metabolismo , Administración Oral , Animales , Perros , Humanos , Radioisótopos de Yodo/administración & dosificación , Radioisótopos de Yodo/orina , Masculino , Tasa de Depuración Metabólica , Análisis de Regresión , Urinálisis/métodosRESUMEN
AIMS: To investigate the influence of body weight (BW), fat mass (FM) and lean mass (LM) on the bone mineral density (BMD) of several areas of the skeleton. PARTICIPANTS: Sixty one white postmenopausal women (50.1 +/- 4.8 years). MEASUREMENTS: Measurement of BMD by dual energy x-ray absorptiometry. The results were analyzed by linear regression and the slopes of each curve were compared. RESULTS: The results showed that the correlations between BW, FM and LM to BMD were positive, whilst the correlations between age and years since menopause to BMD were negative. LM was the main factor that influence BMD in almost all areas. CONCLUSIONS: FM and LM present a positive effect on BMD, although LM is the main determinant of bone mass. Moreover, higher values of LM and FM present a protective effect against the reduction of BMD combined with menopause. Therefore postmenopausal women with low BW, especially low LM, present serious risk for developing osteoporosis.
Asunto(s)
Composición Corporal , Densidad Ósea , Posmenopausia/metabolismo , Absorciometría de Fotón , Adulto , Factores de Edad , Peso Corporal , Femenino , Humanos , Modelos Lineales , Persona de Mediana Edad , Osteoporosis Posmenopáusica/etiología , Osteoporosis Posmenopáusica/metabolismo , Factores de RiesgoRESUMEN
OBJECTIVE: To study the vertebral (L2-L4) and femoral (neck) bone mineral density (BMD) of normal white women. MATERIAL AND METHOD: We measured the BMD of 724 women (40-79 kg; 20-69 years-age) by dual-energy X-ray absorptiometry. Data were analysed as a function of age and body weight (BW). RESULTS: Thinner women (40-49 kg) attained maximal vertebral and femoral BMD (mBMD) at ages between 30-39 years, while heavier women (60-79 kg) already had the mBMD by the age of 20. At the femur, there was a significant mBMD-BW correlation (r = 0.97; p < 0.001; slope = 0.72%/kg). At the spine, only the 40-49 Kg women exhibited lower mBMD when compared to the others (p < 0.001). The decrease of the vertebral BMD was more intense (-8.3 vs. -5.7%/decade) and started earlier (fourth vs. fifth decade) in women weighting 40-59 kg, as compared to those weighting 60-79 kg. The decrease of the femoral BMD was initiated just after mBMD was achieved and, at the age of 69, heavier women showed a decrease that was 5.3% lower than those weighting 40-49 kg. The vertebral BMD of the Brazilian women was practically the same as reported for a North-American population. CONCLUSIONS: (i) Vertebral and femoral BMD of this Brazilian population varied with age similarly to other white female populations; (ii) provided that appropriate corrections are made for BW, the BMD of Brazilian women is comparable to the BMD of North-Americans; and (iii) the BW is important both in acquisition and decline of bone mass, as it influences the relation BMD-age.