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INK4a/ARF locus alterations in human non-Hodgkin's lymphomas mainly occur in tumors with wild-type p53 gene 总被引:3,自引:0,他引:3
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Pinyol M Hernández L Martínez A Cobo F Hernández S Beà S López-Guillermo A Nayach I Palacín A Nadal A Fernández PL Montserrat E Cardesa A Campo E 《The American journal of pathology》2000,156(6):1987-1996
INK4a/ARF locus codes for two different proteins, p16(INK4a) and p14(ARF), involved in cell cycle regulation. p14(ARF) is considered an upstream regulator of p53 function. To determine the role of these genes in the pathogenesis of human non-Hodgkin's lymphomas we have analyzed exon 1beta, 1alpha, and 2 of the INK4a/ARF locus and p53 gene aberrations in 97 tumors previously characterized for p16(INK4a) alterations. p53 alterations were detected in four of 51 (8%) indolent lymphomas but in 15 of 46 (33%) aggressive tumors. Inactivation of p14(ARF) was always associated with p16(INK4a) alterations. Exon 1beta was concomitantly deleted with exon 1alpha and 2 in eight tumors. One additional lymphoblastic lymphoma showed deletion of exon 1alpha and 2 but retained exon 1beta. No mutations were detected in exon 1alpha and 1beta in any case. Two of the three mutations detected in exon 2 caused a nonsense mutation in the p16(INK4a) reading frame and a missense mutation in the ARF reading frame involving the nucleolar transport domain of the protein. The third mutation was a missense mutation in the p16(INK4a) reading frame, but it was outside the coding region of p14(ARF). Aggressive lymphomas with p14(ARF) inactivation and p53 wild type showed a significantly lower p53 protein expression than tumors with no alteration in any of these genes. In this series of tumors, inactivation of the INK4a/ARF locus mainly occurred in tumors with a wild-type p53 gene because only two lymphomas showed simultaneous aberrations in these genes. Tumors with concomitant alterations of p16(INK4a) and p14(ARF)/p53 genes seem to exhibit a worse clinical behavior than lymphomas with no alterations or isolated inactivation of any of these genes. These findings indicate that p14(ARF) genetic alterations occur in a subset of aggressive NHLs, but they are always associated with p16(INK4a) aberrations. Concomitant disruption of p16(INK4a) and p14(ARF)/p53 regulatory pathways may have a cooperative effect in the progression of these tumors. 相似文献
6.
Contribution of molecular analyses to the estimation of the risk of congenital myotonic dystrophy.
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A M Cobo J J Poza L Martorell A López de Munain J I Emparanza M Baiget 《Journal of medical genetics》1995,32(2):105-108
A molecular analysis of the maternal and child CTG repeat size and intergenerational amplification was performed in order to estimate the risk of having a child with congenital myotonic dystrophy (CMD). In a study of 124 affected mother-child pairs (42 mother-CMD and 82 mother-non-CMD) the mean maternal CTG allele in CMD cases was three times higher (700 repeats) than in non-CMD cases (236 repeats). When the maternal allele was in the 50-300 repeats range, 90% of children were non-CMD. In contrast, when the maternal allele was greater than 300 repeats, 59% inherited the congenital form. Furthermore, the risk of having a CMD child is also related to the intergenerational amplification, which was significantly greater in the mother-CMD pairs than in the mother-non-CMD pairs. Although the risk of giving birth to a CMD child always exists for affected mothers, our data show that such a risk is considerably higher if the maternal allele is greater than 300 repeats. 相似文献
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A López de Munain A M Cobo J J Poza D Navarrete L Martorell F Palau J I Emparanza M Baiget 《Journal of medical genetics》1995,32(9):689-691
To analyse the influence of the sex of the transmitting grandparents on the occurrence of the congenital form of myotonic dystrophy (CDM), we have studied complete three generation pedigrees of 49 CDM cases, analysing: (1) the sex distribution in the grandparents' generation, and (2) the intergenerational amplification of the CTG repeat, measured in its absolute and relative values, between grandparents and the mothers of CDM patients and between the latter and their CDM children. The mean relative intergenerational increase in the 32 grandparent-mother pairs was significantly greater than in the 56 mother-CDM pairs (Mann-Whitney U test, p < 0.001). The mean expansion of the grandfathers (103 CTG repeats) was also significantly different from that seen in the grandmothers' group (154 CTG repeats) (Mann-Whitney U test, p < 0.01). This excess of non-manifesting males between the CDM grandparents' generation with a smaller CTG length than the grandmothers could suggest that the premutation has to be transmitted by a male to reach the degree of instability responsible for subsequent intergenerational CTG expansions without size constraints characteristic of the CDM range. 相似文献
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Carlos Jiménez Romero Laura Alonso Murillo Paula Rioja Conde Alberto Marcacuzco Quinto Óscar Caso Maestro Anisa Nutu Isabel Pérez Moreiras Iago Justo Alonso 《Cirugía espa?ola》2021,99(6):440-449
IntroductionThere is controversy regarding the ideal pancreaticojejunostomy technique after pancreaticoduodenectomy. Many authors consider the external Wirsung stenting technique to be associated with a low incidence of fistula, morbidity and mortality. We analyse our experience with this technique.Patients and methodsA retrospective analysis of the morbidity and mortality of a series of 80 consecutive patients who had been treated surgically over a 6.5-year period for pancreatic head or periampullary tumors, performing pancreaticoduodenectomy and pancreaticojejunostomy with external Wirsung duct stenting.ResultsMean patient age was 68.3 ± 9 years, and the resectability rate was 78%. The texture of the pancreas was soft in 51.2% of patients and hard in 48.8%. Pylorus-preserving resection was performed in 43.8%. Adenocarcinoma was the most frequent tumor (68.8%), and R0 was confirmed in 70% of patients. Biochemical fistula was observed in 11.2%, pancreatic fistula grade B in 12.5% and C in 2.5%, whereas the abdominal reoperation rate was 10%. Median postoperative hospital stay was 16 days, and postoperative and 90-day mortality was 2.5%. Delayed gastric emptying was observed in 36.3% of patients, de novo diabetes in 12.5%, and exocrine insufficiency in 3. Patient survival rates after 1, 3 and 5 years were 80.2, 53.6 and 19.2%, respectively.ConclusionsAlthough our low rates of postoperative complications and mortality using external Wirsung duct stenting coincides with other more numerous recent series, it is necessary to perform a comparative analysis with other techniques, including more cases, to choose the best reconstruction technique after pancreaticoduodenectomy. 相似文献
9.
Acidic Amino Acids and Self-stimulation of the Prefrontal Cortex in the Rat: A Pharmacological Study
The effects of intraventricular and intracortical microinjections of acidic amino acid antagonists on self-stimulation (SS) of the medial prefrontal cortex (MPC) were investigated. Self-stimulation was measured by depressing a lever in a standard chamber. Spontaneous motor activity of the animal and SS of the contralateral non-injected MPC were used as control for non-specific effects of the drugs. Intraventricular microinjections of gamma-d-glutamylglycine (DGG), an antagonist of NMDA, kainate and quisqualate receptors, or 2-amino-5-phosphonovalerate (AP-5), a specific antagonist of NMDA receptors, produced a dose-related decrease of SS in the MPC. Spontaneous motor activity of the animal was not significantly affected. Unilateral microinjections into the medial prefrontal cortex of DGG or AP-5 produced a decrease of SS in the ipsilateral side while no effects were found on the contralateral MPC. On the contrary, intraventricular microinjections of gamma-d-glutamyltaurine (Glu-tau), an antagonist with more relative affinity for kainate and quisqualate receptors, produced a dose-related decrease of both self-stimulation and spontaneous motor activity of the rats. Moreover, intracortical microinjections of Glu-tau had no effect on self-stimulation of this cortical area. These results suggest that acidic amino acids through NMDA, but not kainate or quisqualate, receptors could be part of the neurochemical substrate underlying SS of the MPC in the rat. 相似文献
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