Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 18 de 18
Filter
1.
Genet Mol Res ; 13(3): 7123-32, 2014 Feb 21.
Article in English | MEDLINE | ID: mdl-24634300

ABSTRACT

Hawksbill sea turtles Eretmochelys imbricata are found extensively around the world, including the Atlantic, Pacific, and Indian Oceans; the Persian Gulf, and the Red and Mediterranean Seas. Populations of this species are affected by international trafficking of their shields, meat, and eggs, making it a critically endangered animal. We determined the haplotypes of 17 hawksbill foraging turtles of Islas del Rosario (Bolivar) and of the nesting beach Don Diego (Magdalena) in the Colombian Caribbean based on amplification and sequencing of the mitochondrial gene cytochrome oxidase c subunit I (COI). We identified 5 haplotypes, including EI-A1 previously reported in Puerto Rico, which was similar to 10 of the study samples. To our knowledge, the remaining 4 haplotypes have not been described. Samples EICOI11 and EICOI3 showed 0.2% divergence from EI-A1, by a single nucleotide change, and were classified as the EI-A2 haplotype. EICOI6, EICOI14, and EICOI12 samples showed 0.2% divergence from EI-A1 and 0.3% divergence from EI-A2 and were classified as EI-A3 haplotype. Samples EICOI16 and EICOI15 presented 5 nucleotide changes each and were classified as 2 different haplotypes, EI-A4 and EI-A5, respectively. The last 2 haplotypes had higher nucleotide diversity (K2P=1.7%) than that by the first 3 haplotypes. EI-A1 and EI-A2 occurred in nesting individuals, and EI-A2, EI-A3, EI-A4, and EI-A5 occurred in foraging individuals. The description of the haplotypes may be associated with reproductive migrations or foraging and could support the hypothesis of natal homing. Furthermore, they can be used in phylogeographic studies.


Subject(s)
Electron Transport Complex IV/genetics , Genes, Mitochondrial , Haplotypes , Turtles/genetics , Animals , Cluster Analysis , Computational Biology , Female , Genetic Variation , Male , Molecular Sequence Data , Phylogeny , Sequence Analysis, DNA , Turtles/classification
2.
Int Endod J ; 46(1): 71-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22788685

ABSTRACT

AIM: To determine the association of functional single nucleotide polymorphisms in genes of the pro-inflammatory cytokines tumour necrosis factor-α, interleukin-1ß, interleukin-8 and interleukin-12B with the development of two clinical forms of apical periodontitis (AP): acute suppurative and chronic nonsuppurative. METHODOLOGY: The study included 120 patients from Bucaramanga City, Colombia, 63 diagnosed with acute suppurative AP (ASAP) and 57 diagnosed with chronic nonsuppurative AP (CNAP). Genotyping for IL1B +3954 (rs1143634), IL8 / CXCL8 -251 (rs4073), IL12B +1188 (rs3212227) and TNFA -308 (rs1800629) was performed by the PCR-restriction fragment length polymorphisms method. The statistical analysis was performed using STATA 10.0 and PLINK V1.07 software. RESULTS: Significant differences in the distribution of IL8 / CXCL8 -251 A allele (P adjusted = 0.041; OR adjusted = 0.41, CI adjusted = 0.31-0.97) and IL8 / CXCL -251 TT genotype (P adjusted = 0.04; OR adjusted = 2.24, CI adjusted = 1.04-4.84) were observed comparing patients diagnosed with ASAP and CNAP. No association was observed in genotype and allele distribution for other genetic polymorphisms analysed. CONCLUSION: This study provides molecular epidemiological evidence that suggests in the present cohort that IL8 / CXCL8 -251 T allele, which is associated with higher production of IL8/CXCL8, is also associated with a higher risk of developing acute suppurative form of AP, whereas IL8 / CXCL8 -251 A allele, which is associated with lower production of IL8/CXCL8, is associated with chronic nonsuppurative form of AP. This suggests a pivotal role for IL-8/CXCL8 in periapical disease because of its ability to induce chemotaxis and modulating the directed migration of neutrophils to the site of inflammation in response to microbial infection of pulp.


Subject(s)
Cytokines/genetics , Inflammation Mediators/immunology , Periapical Abscess/immunology , Periapical Granuloma/immunology , Polymorphism, Single Nucleotide/genetics , Adenine , Adolescent , Adult , Alleles , Chemotaxis, Leukocyte/genetics , Cohort Studies , Colombia , Female , Genotype , Humans , Interleukin-12 Subunit p40/genetics , Interleukin-1beta/genetics , Interleukin-8/genetics , Male , Middle Aged , Neutrophil Infiltration/genetics , Polymorphism, Restriction Fragment Length/genetics , Thymine , Tumor Necrosis Factor-alpha/genetics , Young Adult
3.
Theriogenology ; 73(8): 1088-95, 2010 May.
Article in English | MEDLINE | ID: mdl-20172601

ABSTRACT

The goal of the current was to elucidate if treatment with gonadotrophins and leptin can circumvent infertility in obese mice and to establish whether reproductive effects of leptin are influenced at the hypothalamus-hypophysis or ovarian level by using a leptin deficient mouse model of obesity/type 2 diabetes (ob/ob) treated with leptin. The ovulatory response and the fertilization success were compared with the results obtained in ob/ob dams pretreated with a gonadotrophin-replacement therapy or in two groups (ob/ob and wild-type) of control non-pretreated females. The number of corpora lutea was significantly lower in control ob/ob mice than in wild-type dams. Treatment with gonadotrophin-replacement therapy did not increase significantly the ovulation rate in ob/ob, but the administration of leptin-replacement treatment allowed the authors to obtain a number of corpora lutea and oocytes/zygotes similar to those obtained in wild-type females. Furthermore, the leptin supply succeeded in producing fertilized zygotes, although in a lower number than found in the wild-type control. Thus, the hypogonadotrophic state in obese mice may be circumvented by the administration of a gonadotrophin-replacement therapy combined with a protocol for controlled ovarian stimulation, but fertile ovulations are only obtained after applying leptin-replacement therapy. Current results strongly support the existence of direct local effects of leptin on the ovary.


Subject(s)
Diabetes Mellitus, Experimental/pathology , Leptin/pharmacology , Obesity/pathology , Ovary/drug effects , Ovary/pathology , Animals , Diabetes Mellitus, Experimental/complications , Disease Models, Animal , Estrus Synchronization , Female , Injections, Subcutaneous , Leptin/administration & dosage , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Obese , Obesity/complications , Ovulation Induction , Pregnancy
4.
Rev. lab. clín ; 1(3): 94-99, jul.-dic. 2008. ilus
Article in Spanish | IBECS | ID: ibc-84581

ABSTRACT

Objetivo: analizar la validez de los anticuerpos antitransglutaminasa (tTGA) como marcador de la respuesta a la dieta libre de gluten (DLG) en pacientes celíacos y valorar la evolución de la hipertransaminasemia (HT) y ferropenia detectadas en el diagnóstico. Material y métodos: se analiza a 172 celíacos (141 niños, 31 adultos) en DLG. Se realiza control dietético-clínico, histológico, serológico y bioquímico. La valoración de tTGA se realizó utilizando anticuerpo recombinante humano. Resultados: tras un período en DLG (mediana 18 meses), 114 (81%) niños mostraron concentración normal de tTGA, 17 (12%) se mantuvieron en la zona gris y 10 (7%), valores elevados. En adultos las frecuencias eran 15 (48,3%), 11 (33,5%) y 5 (17,2%). Se realizaron 27 biopsias intestinales (26 niños, 1 adulto). La concordancia histológica con la concentración de tTGA fue elevada; índice kappa = 0,898 (0,72¿0,98). Se detectan trasgresiones en 7 pacientes (4 ocasionales, 3 frecuentes), de los cuales 6 presentaron tTGA elevada. El control de la DLG se realizó conforme a las recomendaciones establecidas en los niños, mientras que el 30% de los adultos diagnosticados de EC carece del mismo. En ambas poblaciones observamos disminución significativa de la HT y normalización de la ferropenia detectada al diagnóstico (p<0,001). Conclusiones: dado el acuerdo con los hallazgos histológicos, consideramos que la tTGA es un marcador indirecto útil para evaluar DLG al menos en población pediátrica. Sin embargo, no sustituye a la biopsia en casos de trasgresiones o de mala respuesta clínica. En nuestro medio es necesario concienciar al colectivo adulto de la importancia de la dieta y las complicaciones que conlleva su enfermedad sin tratar(AU)


Objective: To analyze the validity of antitransglutaminase antibodies (tTGA) as a serological marker of response to the gluten-free diet (GFD) in celiac patients and to determine the outcome of hypertransaminasemia (HT) and ferropenia found at the time of diagnosis. Material and methods: We have retrospectively analyzed the data from 172 patients with celiac disease (CD) (141 children and 31 adults) following a GFD. We have collected clinical and diet information and also histological, biochemical and serological data. The tTGA was measured with a human recombinant antibody. Results: After a median follow-up time of 1.5 years in GFD, 114 (81%) of the children had normal levels of tTGA, 17 (12%) showed values in the ‘‘grey zone’’ and only 10 (7%) had elevated levels of this marker. This contrasts with the figures found in adults, corresponding to 15 (48.3%), 11 (33.5%) and 5 (17.2%), respectively. In our series we have performed 27 intestinal biopsies during follow-up (26 children and 1 adult). The concordance rate between the results of this biopsy and the tTGA determination was high, with a Kappa Index ¼ 0.898. We have detected dietary transgressions in 7 patients (4 occasional and 3 frequently) and 6 of these 7 patients showed high levels of tTGA. The GFD was correctly followed by children according to the international recommendations, but only 40% of the adults followed the GFD adequately. In both populations we have found a significant decrease in HTand normalization of the ferropenia found at diagnosis (Po0.001). Conclusions: tTGA is a useful indirect marker for evaluation of GFD in a pediatric population, with a high concordance between serum levels of the marker and histological findings in the intestinal biopsy. However, tTGA cannot substitute biopsy in cases of diet transgressions or unfavourable clinical evolution. In our environment it is still essential to increase the awareness of the adult population regarding the importance of diet in CD and also of the serious complications associated with untreated disease(AU)


Subject(s)
Humans , Male , Female , Child , Adult , Celiac Disease/diet therapy , Celiac Disease/diagnosis , Immunoglobulin A , Glutens/analysis , Glutens/metabolism , Intestinal Secretions , Biopsy/methods , Intestinal Mucosa , Serology/methods , 28599
5.
Cytopathology ; 19(6): 381-4, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18540878

ABSTRACT

INTRODUCTION: The Department of Clinical Chemistry of the General Hospital of Móstoles (Madrid, Spain) has for many years diagnosed the presence of atypical cells in the urinary sediment (ACUS), but this finding only led to a comment in the final report of the urinalysis, informing the clinician of this fact in case he/she decided to perform further studies in these patients. METHODS: Since 2004, the Clinical Chemistry Department has implemented a new protocol together with the Department of Surgical Pathology of the Hospital, according to which all the urinary sediment samples with ACUS are sent for cytological analysis. In this report, we comment on the results corresponding to 99 samples. RESULTS: With this new strategy, we can directly diagnose if the ACUS correspond to a carcinoma or to another process, and this has allowed us to reduce time until diagnosis in our patients and also to avoid unnecessary studies in negative cases. We comment on our results with this new management strategy.


Subject(s)
Cell Biology , Urinalysis/methods , Urine/cytology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cytodiagnosis/methods , Female , Humans , Male , Middle Aged , Young Adult
6.
Nutr Hosp ; 22(5): 602-6, 2007.
Article in Spanish | MEDLINE | ID: mdl-17970546

ABSTRACT

OBJECTIVES: The objectives of the present study are: 1) to assess protein changes in patients diagnosed with morbid obesity (MO) and non-alcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH); 2) to assess the likely reversibility of these entities after bariatric surgery, and 3) to analyze their progression seven years after the gastric bypass. MATERIAL AND METHODS: We retrospectively analyzed the data from 190 patients, 150 women (79%) and 40 men (21%) diagnosed with MO and surgically treated at our Hospital (Capella's gastric bypass). Mean age of the patients was 36.5 years (range: 18.5-54.5). Anthropometric values are gathered: body mass index (BMI), waist circumference (WC) and biochemistry: insulin (INS), glucose (GLU), total proteins (TP), albumin (ALB), transferrin (TRF), ferritin (FER), prealbumin (PBA), retinol binding protein (RBP) and C reactive protein (CRP). The HOMA index was calculated before the bypass and at the following follow-up periods after bypass: 6, 12, 60 and 84 months. RESULTS: Abdominal ultrasound suggesting NAFLD or NASH was found in 34.7% (n = 66; 52 women and 14 men) of MO patients surgically treated. Ninety patients (47.3%; 67 women and 23 men) presented risk factors for metabolic syndrome (MS). All patients with possible liver dysfunction had MS. Before the bypass, we found increased levels of: BMI, WC, CRP, GLU, INS and HOMA index and changes in TP, ALB, PBA, RBP, FER and TRF levels. The first set of parameters start to decrease within 6 months after surgical bypass and at the same time the changes in protein levels start to face off and remain stable at 84 months. CONCLUSIONS: Weight loss due to bariatric surgery represents an effective method of fighting MO and its associated comorbidities (NAFLD, NASH, hyperinsulinemia, hyperglycemia, dyslipidemia and components of the metabolic syndrome).


Subject(s)
Bariatric Surgery/statistics & numerical data , Fatty Liver/epidemiology , Metabolic Syndrome/epidemiology , Obesity, Morbid/surgery , Adolescent , Adult , Biomarkers , Fatty Liver/diagnostic imaging , Female , Follow-Up Studies , Humans , Male , Metabolic Syndrome/blood , Middle Aged , Obesity, Morbid/epidemiology , Remission Induction , Retrospective Studies , Ultrasonography
7.
Nutr. hosp ; 22(5): 602-606, sept.-oct. 2007. ilus, tab
Article in Es | IBECS | ID: ibc-057465

ABSTRACT

Objetivos: Los objetivos del presente estudio son: 1) evaluar las alteraciones proteicas en pacientes: diagnosticados de obesidad mórbida (OM) y portadores de hígado graso no alcohólico (NAFLD) o esteatohepatitis (NASH); 2) valorar la posible reversibilidad de las mismas tras cirugía bariátrica, y 3) analizar su evolución tras siete años de realizado el bypass gástrico. Material y métodos: Evaluamos retrospectivamente los datos de 190 pacientes, 150 mujeres (79%) y 40 hombres (21%) diagnosticados de OM e intervenidos quirúrgicamente en nuestro Hospital (bypass gástrico de Capella). La edad media de los pacientes fue de 36,5 años (rango: 18,5-54,5). Se recogen variables antropométricas: índice de masa corporal (IMC), circunferencia de la cintura (CC) y bioquímicas: niveles de insulina (INS), glucosa (GLU), proteína totales (PT), albúmina (ALB), transferrina (TRF), ferritina (FER), prealbúmina (PBA), proteína ligadora de retinol (RBP) y proteína C reactiva (PCR). Se calcula el índice HOMA previo al bypass y con tiempos de seguimiento de 6, 12, 60 y 84 meses de realizado el bypass. Resultados: La ecografía abdominal sugestiva de sufrir NAFLD o NASH se encontró en el 34,7% (n = 66; 52 mujeres y 14 hombres) de los pacientes con OM intervenidos quirúrgicamente. En 90 pacientes (47,3%; 67 mujeres y 23 hombres) se pudo demostrar que eran portadores de los factores de riesgo de síndrome metabólico (SM). Todos los pacientes con posible disfunción hepática eran portadores del SM. Previo al bypass encontramos niveles elevados de: IMC, CC, PCR, GLU, INS e índice HOMA y alteraciones en los niveles de PT, ALB, PBA, RBP, FER y TRF. Los primeros, comienzan a descender a los 6 meses de realizado el bypass al mismo tiempo las alteraciones de los niveles proteicos comienzan a desaparecer y continúan estables a los 84 meses de realizado. Conclusiones: La pérdida de peso por la cirugía bariátrica constituye el método más eficaz en la lucha contra la OM y sus comorbilidades (NAFLD, NASH, hiperinsulinemia, hiperglucemia, dislipemia y componentes del síndrome metabólico)


Objectives: The objectives of the present study are: 1) to assess protein changes in patients diagnosed with morbid obesity (MO) and non-alcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH); 2) to assess the likely reversibility of these entities after bariatric surgery, and 3) to analyze their progression seven years after the gastric bypass. Material and methods: We retrospectively analyzed the data from 190 patients, 150 women (79%) and 40 men (21%) diagnosed with MO and surgically treated at our Hospital (Capella’s gastric bypass). Mean age of the patients was 36.5 years (range: 18.5-54.5). Anthropometric values are gathered: body mass index (BMI), waist circumference (WC) and biochemistry: insulin (INS), glucose (GLU), total proteins (TP), albumin (ALB), transferrin (TRF), ferritin (FER), prealbumin (PBA), retinol binding protein (RBP) and C reactive protein (CRP). The HOMA index was calculated before the bypass and at the following follow-up periods after bypass: 6, 12, 60 and 84 months. Results: Abdominal ultrasound suggesting NAFLD or NASH was found in 34.7% (n = 66; 52 women and 14 men) of MO patients surgically treated. Ninety patients (47.3%; 67 women and 23 men) presented risk factors for metabolic syndrome (MS). All patients with possible liver dysfunction had MS. Before the bypass, we found increased levels of: BMI, WC, CRP, GLU, INS and HOMA index and changes in TP, ALB, PBA, RBP, FER and TRF levels. The first set of parameters start to decrease within 6 months after surgical bypass and at the same time the changes in protein levels start to face off and remain stable at 84 months. Conclusions: Weight loss due to bariatric surgery represents an effective method of fighting MO and its associated comorbidities (NAFLD, NASH, hyperinsulinemia, hyperglycemia, dyslipidemia and components of the metabolic syndrome)


Subject(s)
Male , Female , Humans , Obesity, Morbid/surgery , Gastric Bypass , Obesity, Morbid/complications , Fatty Liver/complications , Retrospective Studies , Biomarkers/analysis , Metabolic Syndrome/epidemiology , Anthropometry
8.
Oncogene ; 26(12): 1673-80, 2007 Mar 15.
Article in English | MEDLINE | ID: mdl-16964279

ABSTRACT

Oncogenic Ras triggers a permanent cell-cycle arrest known as oncogene-induced senescence (OIS) that constitutes a relevant tumor suppressor mechanism. Ris1 (Ras-induced senescence-1) is a novel gene that was identified in a screen as specifically upregulated during Ras-induced senescence, and that is located at a chromosomal region, 3p21.3, frequently lost in human cancer. Moreover, Ris1 is highly conserved in vertebrates, does not present paralogs, and its sequence does not reveal similarities with other proteins or domains. To analyse the physiological function of Ris1 and test its putative role as a tumor suppressor gene, we have generated mutant mice deficient for this gene. Ris1-null mice are viable, fertile, develop normally and do not display any obvious abnormalities. Of relevance, Ris1-deficient mice had a normal lifespan and did not exhibit predisposition to spontaneous tumors or to tumors induced by chemical carcinogens. Finally, Ris1-deficient embryonic fibroblasts were indistinguishable from wild-type cells regarding their proliferation properties, immortalization, senescence and oncogenic transformation. These findings do not support a role of Ris1 in tumor suppression or in OIS.


Subject(s)
Cellular Senescence/genetics , Genetic Predisposition to Disease , Membrane Proteins/physiology , Neoplasms, Experimental/pathology , Animals , Base Sequence , Cell Proliferation , Cell Transformation, Neoplastic , Chromosome Mapping , DNA Primers , Embryonic Development , Membrane Proteins/genetics , Mice , Mice, Knockout , Neoplasms, Experimental/genetics , Reverse Transcriptase Polymerase Chain Reaction
9.
Actas Esp Psiquiatr ; 31(5): 239-43, 2003.
Article in Spanish | MEDLINE | ID: mdl-14557947

ABSTRACT

INTRODUCTION: Based on several contributions and studies on evolutive aspects of grief, this study aims to focus on the two-year follow-up of patients from the Community Mental Health Service of Pa rla who came to the clinic in relationship with grief. METHODS: Based upon a previous research, the authors have performed a follow-up study at two years in a sample of 51 patients, carried out by a telephone interview that examined subjective improvement, coping strategies and grieving process, biographical continuity and later life events. RESULTS: Two years after the first visit, most of the patients considered that they had coped well with the loss and were able to resume their normal activities. They ranked their clinical situation as <>. One out of every four reported a partial or marked detention in their biographical course. CONCLUSIONS: In the long term evolution of a visit due to grief, a positive outcome might be expected in the most of the cases. Factors associated with a worst outcome are a problematic bond with the deceased, and the son/daughter loss. Positive outcome was associated with social support and psychotherapy.


Subject(s)
Grief , Patient Acceptance of Health Care , Adaptation, Psychological , Adult , Aged , Aged, 80 and over , Continuity of Patient Care , Female , Follow-Up Studies , Humans , Life Change Events , Male , Middle Aged
10.
Cell Death Differ ; 10(11): 1226-33, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14576774

ABSTRACT

Members of the inhibitor of apoptosis protein family are involved not only in suppressing apoptosis, but also in signal transduction, cell division, and are associated with some types of cancers. Here we show that transgenic expression of the inhibitor of apoptosis protein OpIAP in murine T lymphocytes leads to a significant increase in T-cell receptor-induced cell activation, proliferation and cytokine production. Transgenic T lymphocytes expressing OpIAP have a lower proliferation threshold in response to T-cell receptor stimulation. Unstimulated OpIAP transgenic T lymphocytes show elevated nuclear levels of NF-kappaB transcription factor that increase after in vivo antigen peptide treatment. OpIAP transgenic animals present an exacerbated inflammatory response in an experimental contact hypersensitivity model, suggesting increased T-cell activation in vivo. These data indicate a new role for the inhibitor of apoptosis proteins in T-lymphocyte activation and proliferation.


Subject(s)
Inflammation Mediators/metabolism , Inflammation/metabolism , Lymphocyte Activation/genetics , T-Lymphocytes/metabolism , Viral Proteins/metabolism , Animals , Cell Division/genetics , Cells, Cultured , Cytokines/metabolism , Dermatitis, Contact/genetics , Disease Models, Animal , Female , Inflammation/immunology , Inflammation Mediators/immunology , Inhibitor of Apoptosis Proteins , Male , Mice , Mice, Transgenic , NF-kappa B/metabolism , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes/immunology , Up-Regulation/genetics , Viral Proteins/genetics , Viral Proteins/immunology
11.
Actas esp. psiquiatr ; 31(5): 239-243, sept. 2003.
Article in Es | IBECS | ID: ibc-25174

ABSTRACT

Introducción. Partiendo de diversas aportaciones y estudios sobre aspectos evolutivos del duelo, el presente trabajo se centra en el seguimiento a los 2 años de pacientes del Servicio de Salud Mental de Parla que consultaban en relación a un duelo. Métodos. A partir de una investigación anterior se realizó un estudio de seguimiento a los 2 años a una muestra de 51 personas mediante una encuesta de aplicación telefónica que exploraba mejoría subjetiva, afrontamiento de la pérdida, continuidad del curso biográfico y circunstancias posteriores. Resultados. A los 2 años de la primera consulta la mayoría de los pacientes afirmaban una mejoría clínica, así como haber podido afrontar total o parcialmente la pérdida y continuar sus actividades con normalidad, si bien una cuarta parte refería una parcial o marcada detención del curso biográfico. Conclusiones. En la evolución a largo plazo de una consulta por duelo es mayoritaria la remisión de sintomatología asociada. Asimismo influyen negativamente en este proceso variable como la calidad del vínculo con el fallecido y el hecho de que el fallecido sea un hijo, y positivamente factores como el apoyo social y la psicoterapia (AU)


Subject(s)
Middle Aged , Adult , Aged , Aged, 80 and over , Male , Female , Humans , Patient Acceptance of Health Care , Grief , Continuity of Patient Care , Adaptation, Psychological , Life Change Events , Follow-Up Studies
13.
FASEB J ; 14(7): 895-903, 2000 May.
Article in English | MEDLINE | ID: mdl-10783143

ABSTRACT

Alterations in the cell division:cell death ratio induce multiple autoimmune and transformation processes. Phosphoinositide 3-kinase (PI3K) controls cell division and cell death in vitro, but its effect on the function of the cellular immune system and on tumor formation in mammals is poorly characterized. Here we show that transgenic mice expressing in T lymphocytes an active form of PI3K derived from a thymic lymphoma, p65(PI3K), developed an infiltrating lymphoproliferative disorder and autoimmune renal disease with an increased number of T lymphocytes exhibiting a memory phenotype and reduced apoptosis. This pathology was strikingly similar to that described in mice exhibiting heterozygous loss of the tumor suppressor PTEN, a lipid and protein phosphatase. We show that overexpression of PTEN selectively blocks p65(PI3K)-induced 3T3 fibroblast transformation. Moreover, the early development of T cell lymphomas in p65(PI3K) Tg p53(-/-) mice indicated that PI3K contributes to tumor development. These observations demonstrate that constitutive activation of PI3K extends T cell survival in vivo, affects T cell homeostasis, and contributes to tumor generation, supporting a model in which selective increases in one type of PTEN substrate, the PI3K-derived lipid products, induce tumorigenesis. PI3K thus emerges as a potential target in autoimmune disease and cancer therapy.


Subject(s)
Cell Transformation, Neoplastic/genetics , Lymphoproliferative Disorders/enzymology , Phosphatidylinositol 3-Kinases/metabolism , Tumor Suppressor Proteins , Animals , Autoimmune Diseases/genetics , CD4-Positive T-Lymphocytes/enzymology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Genes, Tumor Suppressor , Kidney Diseases/genetics , Loss of Heterozygosity , Mice , Mice, Transgenic , PTEN Phosphohydrolase , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositols/metabolism , Phosphoric Monoester Hydrolases/genetics , Phosphoric Monoester Hydrolases/metabolism
14.
EMBO J ; 18(1): 156-66, 1999 Jan 04.
Article in English | MEDLINE | ID: mdl-9878059

ABSTRACT

Clonal deletion in the thymus by apoptosis is involved in purging the immune system of self-reactive T lymphocytes (negative selection). Cysteine proteases (caspases) belonging to the CPP32 family are activated during this process. We have produced transgenic mice expressing baculovirus p35, a broad-range caspase inhibitor. Thymocytes from p35 transgenic mice were resistant in vitro to several apoptosis-inducing agents; this resistance correlated with the inhibition of CPP32-like activity. Negative selection in vivo of thymocytes triggered by two exogenous antigens, staphylococcal enterotoxin B superantigen and an antigenic peptide in the F5 T-cell receptor transgenic model, was specifically inhibited in p35 transgenic mice. Our results provide direct evidence for caspase involvement in negative selection during thymocyte development.


Subject(s)
Caspase Inhibitors , Cysteine Proteinase Inhibitors/genetics , Nucleopolyhedroviruses/genetics , T-Lymphocytes/cytology , T-Lymphocytes/enzymology , Viral Proteins/genetics , Amino Acid Sequence , Animals , Antigens/administration & dosage , Apoptosis , Base Sequence , Caspase 3 , DNA Primers/genetics , Gene Expression , Inhibitor of Apoptosis Proteins , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Transgenic , T-Lymphocytes/immunology
15.
Arch Esp Urol ; 50(9): 943-6, 1997 Nov.
Article in Spanish | MEDLINE | ID: mdl-9527823

ABSTRACT

OBJECTIVE: To report on our experience in the diagnosis and surgical treatment of distal urethral stenosis arising from fibrous periurethritis in women. METHODS: 9 patients who had undergone surgery for distal urethral stenosis caused by fibrous periurethritis are described. Patient history, clinical symptoms, the surgical technique employed, complications and post-operative course are presented. RESULTS: All 9 patients had a history of recurrent urinary infection and alteration of the urinary stream. The results obtained by surgery were satisfactory in all cases. CONCLUSIONS: Distal urethral stenosis arising from fibrous periurethritis is uncommon, but not rare. Diagnosis is principally based on the clinical symptoms, characterized by low urinary obstructive symptoms, and the finding at physical examination of a narrow meatus and periurethral enlargement caused by fibrous tissue surrounding the distal urethra. The Richardson urethrolysis technique achieved satisfactory results in these patients.


Subject(s)
Urethral Stricture/diagnosis , Urethral Stricture/surgery , Urethritis/complications , Adult , Female , Humans , Middle Aged , Surgical Procedures, Operative/methods , Urethral Stricture/etiology
16.
Gene ; 126(1): 135-9, 1993 Apr 15.
Article in English | MEDLINE | ID: mdl-8472954

ABSTRACT

The nucleotide (nt) sequence of the gene (pab) encoding p-aminobenzoic acid (PABA) synthase, a key enzyme in the biosynthesis of candicidin by Streptomyces griseus IMRU3570, was determined and an open reading frame (ORF) of 2171 nt was found. The predicted amino acid sequence demonstrated extensive sequence identity with PABA synthases (Pab) from Gram-negative Enterobacteria. The protein encoded by ORF pab shows a clear relationship at the N terminus with PabA and at the C terminus with PabB from Escherichia coli, Serratia and Klebsiella. We also determined the extent of a spontaneous deletion that removed the ORF located upstream from pab near the 5' end of the cloned fragment. The deletion occurred when the gene was cloned in the BamHI site of pBR322 and allowed pab expression in E. coli.


Subject(s)
Candicidin/biosynthesis , Genes, Bacterial , Streptomyces griseus/genetics , Transaminases/genetics , Amino Acid Sequence , Animals , Base Sequence , Chromosome Mapping , DNA, Bacterial , Molecular Sequence Data , Sequence Homology, Amino Acid , Streptomyces griseus/enzymology , Transaminases/metabolism
17.
FEMS Microbiol Lett ; 58(1): 15-8, 1990 Jun 15.
Article in English | MEDLINE | ID: mdl-2397878

ABSTRACT

A p-aminobenzoic synthase gene (pabS) from Streptomyces griseus IMRU 3570 involved in candicidin production was used as probe to find new aromatic polyene producing Streptomyces strains. The pab gene hybridizes with 6 out of 16 Streptomyces strains, and those strains which hybridize turned out to be polyene producers. Such strains were never before described as polyene producers.


Subject(s)
Anti-Bacterial Agents/biosynthesis , Candicidin/biosynthesis , Streptomyces/genetics , Transaminases/genetics , Blotting, Southern , Cloning, Molecular , DNA, Bacterial , Genes, Bacterial , Plasmids , Restriction Mapping , Streptomyces/metabolism , Transformation, Bacterial
18.
J Radiol ; 70(11): 617-9, 1989 Nov.
Article in French | MEDLINE | ID: mdl-2693698

ABSTRACT

Two cases of human fasciolasis in which the presence of the parasite in the gallbladder could be demonstrated by ultrasonography, are presented.


Subject(s)
Fascioliasis/diagnosis , Gallbladder Diseases/diagnosis , Ultrasonography , Adult , Animals , Fasciola hepatica , Female , Humans , Male , Middle Aged
SELECTION OF CITATIONS
SEARCH DETAIL
...