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1.
Genetica ; 143(1): 31-44, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25523543

ABSTRACT

Signals of selection on quantitative traits can be detected by the comparison between the genetic differentiation of molecular (neutral) markers and quantitative traits, by multivariate extensions of the same model and by the observation of the additive covariance among relatives. We studied, by three different tests, signals of occurrence of selection in Prosopis alba populations over 15 quantitative traits: three economically important life history traits: height, basal diameter and biomass, 11 leaf morphology traits that may be related with heat-tolerance and physiological responses and spine length that is very important from silvicultural purposes. We analyzed 172 G1-generation trees growing in a common garden belonging to 32 open pollinated families from eight sampling sites in Argentina. The multivariate phenotypes differ significantly among origins, and the highest differentiation corresponded to foliar traits. Molecular genetic markers (SSR) exhibited significant differentiation and allowed us to provide convincing evidence that natural selection is responsible for the patterns of morphological differentiation. The heterogeneous selection over phenotypic traits observed suggested different optima in each population and has important implications for gene resource management. The results suggest that the adaptive significance of traits should be considered together with population provenance in breeding program as a crucial point prior to any selecting program, especially in Prosopis where the first steps are under development.


Subject(s)
Adaptation, Biological , Fabaceae/genetics , Quantitative Trait, Heritable , Argentina , Climate , Environment , Gene Flow , Gene-Environment Interaction , Genetic Drift , Genetics, Population , Geography , Microsatellite Repeats , Phenotype , Selection, Genetic
2.
Ann Oncol ; 24(2): 420-428, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23028040

ABSTRACT

BACKGROUND: We previously reported results of a prospective trial evaluating the significance of circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC). This secondary analysis assessed the relationship of the CTC number with carcinoembryonic antigen (CEA) and overall survival. PATIENTS AND METHODS: Patients with mCRC had CTCs measured at baseline and specific time points after the initiation of new therapy. Patients with a baseline CEA value ≥ 10 ng/ml and CEA measurements within ± 30 days of the CTC collection were included. RESULTS: We included 217 patients with mCRC who had a CEA value of ≥ 10 ng/ml. Increased baseline CEA was associated with shorter survival (15.8 versus 20.7 months, P = 0.012). Among all patients with a baseline CEA value of ≥ 25 ng/ml, patients with low baseline CTCs (<3, n = 99) had longer survival than those with high CTCs (≥ 3, n = 58; 20.8 versus 11.7 months, P = 0.001). CTCs added prognostic information at the 3-5- and 6-12-week time points regardless of CEA. In a multivariate analysis, CTCs at baseline but not CEA independently predicted survival and both CTCs and CEA independently predicted survival at 6-12 weeks. CONCLUSIONS: This study demonstrates that both CEA and CTCs contribute prognostic information for patients with mCRC.


Subject(s)
Carcinoembryonic Antigen/blood , Colorectal Neoplasms , Neoplastic Cells, Circulating , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/mortality , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Metastasis , Prognosis , Survival , Young Adult
3.
Ann Oncol ; 20(7): 1223-9, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19282466

ABSTRACT

BACKGROUND: We demonstrated that circulating tumor cell (CTC) number at baseline and follow-up is an independent prognostic factor in metastatic colorectal cancer (mCRC). This analysis was undertaken to explore whether patient and treatment characteristics impact the prognostic value of CTCs. PATIENTS AND METHODS: CTCs were enumerated with immunomagnetic separation from the blood of 430 patients with mCRC at baseline and on therapy. Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of > or = 3 or <3 CTCs/7.5 ml, respectively. Subgroups were analyzed by line of treatment, liver involvement, receipt of oxaliplatin, irinotecan, or bevacizumab, age, and Eastern Cooperative Oncology Group performance status (ECOG PS). RESULTS: Seventy-one percent of deaths have occurred. Median follow-up for living patients is 25.8 months. For all patients, progression-free survival (PFS) and overall survival (OS) for unfavorable compared with favorable baseline CTCs is shorter (4.4 versus 7.8 m, P = 0.004 for PFS; 9.4 versus 20.6 m, P < 0.0001 for OS). In all patient subgroups, unfavorable baseline CTC was associated with inferior OS (P < 0.001). In patients receiving first- or second-line therapy (P = 0.003), irinotecan (P = 0.0001), having liver involvement (P = 0.002), >/=65 years (P = 0.0007), and ECOG PS of zero (P = 0.04), unfavorable baseline CTC was associated with inferior PFS. CONCLUSION: Baseline CTC count is an important prognostic factor within specific subgroups defined by treatment or patient characteristics.


Subject(s)
Colorectal Neoplasms/pathology , Neoplasm Metastasis/pathology , Neoplastic Cells, Circulating/pathology , Aged , Aged, 80 and over , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Bevacizumab , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Colorectal Neoplasms/drug therapy , Disease Progression , Disease-Free Survival , Female , Follow-Up Studies , Humans , Irinotecan , Kaplan-Meier Estimate , Male , Middle Aged , Organoplatinum Compounds/therapeutic use , Oxaliplatin , Predictive Value of Tests , Prognosis , Survival Rate , Time Factors , Treatment Outcome
4.
Chest ; 118(2): 550-1, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10936156

ABSTRACT

Thallium (Tl) 201 and technetium (Tc) 99m tetrofosmin single-photon emission CT are routinely used in the evaluation of coronary artery disease. Mediastinal tumors demonstrate Tl 201 and Tc 99m tetrofosmin uptake. We report a 56-year-old man who developed chest pain after a previously successful angioplasty and stent of the left anterior descending coronary artery. He underwent a Tl 201, Tc 99m tetrofosmin exercise study. Abnormal mediastinal activity was visualized in both the Tl 201 and Tc 99m tetrofosmin images. Subsequently, the patient underwent resection of a stage II thymoma. Unanticipated focal extracardiac accumulation during myocardial scintiscanning should lead to further investigation to exclude mediastinal tumor.


Subject(s)
Coronary Disease/diagnosis , Neoplasms, Unknown Primary/diagnostic imaging , Organophosphorus Compounds , Organotechnetium Compounds , Radiopharmaceuticals , Thymoma/secondary , Thymus Neoplasms/secondary , Tomography, Emission-Computed, Single-Photon , Exercise Test , Humans , Male , Middle Aged , Neoplasms, Unknown Primary/surgery , Thallium Radioisotopes , Thymectomy , Thymoma/diagnostic imaging , Thymoma/surgery , Thymus Neoplasms/diagnostic imaging , Thymus Neoplasms/surgery
5.
Hereditas ; 132(1): 19-27, 2000.
Article in English | MEDLINE | ID: mdl-10857255

ABSTRACT

The section Algarobia of genus Prosopis involves important natural resources in arid and semiarid regions of the world. Their rationale use requires a better knowledge of their biology, genetics and mating system. There are contradictory information about their mating system. Some authors claim they are protogynous and obligate outcrosser. However, some evidence have been shown indicating that they might not be protogynous and that they might be somewhat self-fertile. The current paper analyses genetic structure and mating system parameters in populations of seven species of this section from South and North America based on isozyme data. In all species a significant homozygote excess was found in the offspring population but not in mother plant genotypes. Multilocus and mean single locus outcrossing rates (tm, ts) indicated that about 15% selfing can occur in the studied populations. The heterogeneity between pollen and ovule allele frequencies was low suggesting population structuration, in agreement with the estimates of correlation of tm within progeny (rt) and correlation of outcrossed paternity (rp). The difference of FIS estimates between offspring and mother plants suggest some selection favouring heterozygotes between seedling and adult stages.


Subject(s)
Isoenzymes/genetics , Rosales/genetics , Alleles , Gene Frequency , Genotype , Heterozygote , Inbreeding , Models, Genetic , Pollen , Reproduction
6.
Genetica ; 109(3): 255-66, 2000.
Article in English | MEDLINE | ID: mdl-11430489

ABSTRACT

The Chaqueña Biogeographic Province, in South America, is the main diversity centre of Prosopis. A group of sympatric species of Section Algarobia in this region constitutes a syngameon, characterised by frequent hybridization and introgression. These processes have been postulated as responsible for the low genetic differentiation observed among species within this group. In this study genetic variability and differentiation among geographically isolated species of the same section was analysed through isoenzyme electrophoresis. Variability parameters and fixation indices were estimated to determine the genetic structure of populations. Two Argentinean, P. ruscifolia ('vinal') and P. flexuosa ('algarrobo amarillo'), and one North American species, P. glandulosa (honey mesquite) were studied. All of them showed, similarly to other species of the same section, high genetic variability and exhibit homozygote excess, probably due to population substructure and low rates of selfing. In contrast to our hypothesis, genetic similarity among species is not related to geographic distance. Genetic distances between P. glandulosa and South American species are similar to those observed among species of this subcontinent. The results obtained suggest that the high genetic similarity among the species of the section Algarobia studied is not due to hybridization.


Subject(s)
Fabaceae/genetics , Plants, Medicinal , Alleles , Fabaceae/enzymology , Gene Frequency , Genes, Plant , Genetic Variation , Isoenzymes/genetics
7.
Arch Pathol Lab Med ; 120(4): 389-92, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8619753

ABSTRACT

We report herein a case of extramedullary myeloid tumor arising bilaterally in the testes of a 66-year-old man, who had previously been diagnosed with myelodysplastic syndrome. Light microscopy of the testicular neoplasm demonstrated a tumor composed of large, slightly polygonal cells with pale blue to weakly eosinophilic cytoplasm. The tumor cells were immunoreactive for CD45, myeloperoxidase, lysozyme, CD43, and MB2. Many of the cells also expressed chloroacetate esterase. Peripheral blood and bone marrow findings were consistent with chronic myelomonocytic leukemia (FAB-CMML), particularly in the most recent material, which showed clear cellular dysplasia and an increase in the percentage of blasts in the bone marrow (15% to 20% of all nucleated cells). This case of extramedullary myeloid tumor is unusual in view of the patient's age and the testicular location. It emphasizes the importance of including extramedullary myeloid tumor in the differential diagnosis of histologically undifferentiated large-cell tumors, as well as a need to use a broad panel of immunohistochemical stains in such cases.


Subject(s)
Leukemia, Myelomonocytic, Chronic/pathology , Leukemic Infiltration/pathology , Myelodysplastic Syndromes/pathology , Testis/pathology , Aged , Cell Nucleus/pathology , Humans , Immunophenotyping , Leukemia, Myelomonocytic, Chronic/complications , Leukemic Infiltration/complications , Male , Mitosis , Myelodysplastic Syndromes/complications
8.
Cancer ; 71(7): 2335-41, 1993 Apr 01.
Article in English | MEDLINE | ID: mdl-8453556

ABSTRACT

BACKGROUND: Cyclosporine (cyclosporin A, CSA) prolongs the survival of transplanted organs by reducing the transcription of cytokines, especially interleukin-2, that are thought to mediate T-cell expansion and subsequent graft rejection. Recently, CSA has been suggested as a potentially effective agent in the treatment of T-cell neoplasms. As a result, a Phase II trial of CSA was done in patients with refractory T-cell lymphomas. METHODS: Patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who had disease progression after at least one previous therapy were eligible for participation. CSA was administered orally at a dose of 7.5 mg/kg twice daily, and the patients were followed for disease response and toxicity. RESULTS: A total of 16 patients were treated. Five patients had PTCL, and 11 had CTCL. Most patients were pretreated extensively with chemotherapy and/or radiation therapy. No responses occurred in patients with PTCL. Two of 11 patients with CTCL responded to therapy. Both patients who responded to CSA had recurrent disease that approached baseline levels within 1 week of discontinuing therapy. A second response occurred in both patients after reinstitution of therapy. Although most patients were removed from the study because of disease progression, renal toxicity was significant. CONCLUSIONS: Most patients with refractory T-cell lymphomas did not respond to CSA, suggesting that these malignancies are not interleukin-2 dependent or, alternatively, that CSA did not reach its intracellular target. In the two responding patients, the pattern of repeated rapid regression of disease after CSA administration and subsequent rapid recurrence after a temporary halt in therapy suggested that CSA was cytostatic rather than cytocidal or that the clinical remissions were mediated by the antiinflammatory effects of the drug.


Subject(s)
Cyclosporine/therapeutic use , Lymphoma, T-Cell, Cutaneous/drug therapy , Lymphoma, T-Cell, Peripheral/drug therapy , Adult , Aged , Cyclosporine/adverse effects , Cyclosporine/blood , Female , Humans , Male , Middle Aged
9.
Fam Plann Perspect ; 15(5): 244, 249-50, 1983.
Article in English | MEDLINE | ID: mdl-6653743

ABSTRACT

The effects of spermicide use around the time of conception on fetal loss, birth weight and sex were examined using data from the 1976 National Survey of Family Growth (NSFG). There was no evidence that cessation of spermicide use at least one month prior to conception had any effect on the pregnancy outcomes examined. However, the proportion of female births was approximately 25 percent higher among women who used spermicides around the time of conception than among nonusers of spermicides. In addition, women who used spermicides after conception were found to have approximately double the rate of fetal loss experienced by former users, including those who had used spermicides close to the time of conception. The effects of spermicides on birth weight were not statistically significant.


Subject(s)
Pregnancy/drug effects , Spermatocidal Agents , Birth Weight/drug effects , Female , Fetal Death , Humans , Infant, Newborn , Male , Sex Factors , Spermatocidal Agents/pharmacology , Vagina
10.
Naunyn Schmiedebergs Arch Pharmacol ; 297(1): 39-46, 1977 Mar.
Article in English | MEDLINE | ID: mdl-193047

ABSTRACT

The contractile responses to transmural stimulation of, and the overflow of tritium from the rat portal vein prelabelled with 3H-noradrenaline were studied. The contractile responses of the rat portal vein were sustained throughout the period of stimulation. The tension developed did not decline when two consecutive periods of stimulation were compared. In contrast, the tritium overflow decreased during the second period of stimulation. Preincubation with 3 micronM phenoxybenzamine during 30 min increased 3-fold the tritium overflow during stimulation. Phentolamine and phenoxybenzamine were nearly equipotent in reducing the vascular response to stimulation. In contrast, phentolamine was less potent than phenoxybenzamine in increasing the 3H-noradrenaline overflow elicited by stimulation. The results obtained with phentolamine are interpreted in terms of a different potency of phentolamine to produce blockade of prejunctional and postjunctional alpha-adrenoceptors in the rat portal vein. ATP inhibited by 70% the tritium overflow induced by stimulation. The potency of ATP in inhibiting the overflow increased when the prejunction alpha-adrenoceptors were blocked. The purine compounds ATP, ADP, AMP and adenosine were roughly equipotent in inhibiting stimulation-induced tritium overflow. The tritium released by stimulation decreased when uptake and metabolism of adenosine were inhibited. Under physiological conditions, a prejunctional purinergic inhibition of noradrenaline release might be involved in an endogenously mediated negative feed-back regulatory mechanism. It is possible that the purinergic inhibition of the noradrenaline liberation elicited by stimulation plays a physiological role in tissues with both purinergic and adrenergic innervation.


Subject(s)
Norepinephrine/metabolism , Purines/physiology , Vasomotor System/metabolism , Adenine Nucleotides/pharmacology , Adenosine/pharmacology , Animals , Electric Stimulation , Feedback , Female , Male , Muscle Contraction/drug effects , Neural Inhibition , Phenoxybenzamine/pharmacology , Phentolamine/pharmacology , Rats , Receptors, Adrenergic, alpha/drug effects
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