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1.
Sci Rep ; 8(1): 6501, 2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29679027

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

2.
Sci Rep ; 7(1): 14264, 2017 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-29079835

RESUMO

Haptoglobin (Hp) is an acute phase protein that has recently been linked to components of the metabolic syndrome (MetS). We aimed to evaluate Hp as marker of MetS, and to assess its association with long-term outcome in renal transplant recipients (RTR). We measured plasma Hp in a prospective cohort of 699 stable RTR and 149 healthy controls. Median plasma Hp concentration in RTR was 1.4 [interquartile range (IQR), 1.0-1.8] g/L, which was higher compared to 1.1 [0.9-1.4] g/L in controls (P < 0.001). Hp was independently associated with the MetS (ß = 0.10) (P = 0.005). During follow-up of 5.4 [4.8-6.1] years, 150 (21%) recipients died, of whom 60 (9%) due to cardiovascular causes, and 83 (12%) RTR developed graft failure. High (≥2.0 g/L) and low (≤0.9 g/L) plasma Hp were associated with increased risk of mortality (HR's 2.3 [1.3-4.1] and 1.9 [1.0-3.5], resp.), predominantly cardiovascular. The association of high Hp lost significance upon adjustment for inflammation markers (HR 1.5 [0.8-2.7]), while low Hp was independently associated with mortality (HR 2.2 [1.2-4.0]). Hp was not associated with graft failure (P = 0.49). In conclusion, plasma Hp is independently associated with MetS in RTR. Importantly, high and low Hp are associated with increased mortality risk, independent of MetS.


Assuntos
Haptoglobinas/metabolismo , Transplante de Rim , Síndrome Metabólica/sangue , Síndrome Metabólica/terapia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
5.
Horm Res Paediatr ; 76 Suppl 1: 2-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21778740

RESUMO

BACKGROUND: The paradox of pituitary tumours is that persistent growth is so atypical. By definition, all pituitary microadenomas regain complete trophic stability after an initial period of deregulated growth. Unlike tumours in many other organ systems, concern about significant growth of macroadenoma remnants after debulking is minimal. Despite reports of a relatively high prevalence of aneuploidy and clonal skewing in these tumours, prolonged efforts to implicate classical proto-oncogene activation and tumour suppressor mutations have been of limited success. No histological or molecular markers reliably predict behaviour. To date, the number of molecular genetic factors unequivocally linked to pituitary tumours can be counted on the fingers of one hand: (1) GNAS1 activation in acromegaly; (2) the MENIN and p27Kip1 (CDKN1B) mutations associated with multiple endocrine neoplasia type 1; (3) mutations of PRKA1RA with loss of 17q22-24 in Carney complex, and (4) aryl hydrocarbon receptor interacting protein gene mutations in 15% of familial isolated pituitary adenomas and 50% of familial isolated acromegaly. Together, these account for only a small proportion (<5%) of sporadic pituitary macroadenomas. CONCLUSION: In most instances, we still do not know what causes quantitative aberrations in trophic behaviour.


Assuntos
Adenoma/genética , Neoplasias Hipofisárias/genética , Acromegalia/genética , Adenoma/patologia , Animais , Complexo de Carney/genética , Cromograninas , Epigênese Genética , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Neoplasia Endócrina Múltipla Tipo 1/genética , Hipófise/patologia , Neoplasias Hipofisárias/patologia , Proto-Oncogene Mas
6.
J Endocrinol ; 205(1): 49-60, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20139144

RESUMO

In rats, a shift from somatotroph dominance to lactotroph dominance during pregnancy and lactation is well reported. Somatotroph to lactotroph transdifferentiation and increased lactotroph mitotic activity are believed to account for this and associated pituitary hypertrophy. A combination of cell death and transdifferentiation away from the lactotroph phenotype has been reported to restore non-pregnant pituitary proportions after weaning. To attempt to confirm that a similar process occurs in mice, we generated and used a transgenic reporter mouse model (prolactin (PRL)-Cre/ROSA26-expression of yellow fluorescent protein (EYFP)) in which PRL promoter activity at any time resulted in permanent, stable, and highly specific EYFP. Triple immunochemistry for GH, PRL, and EYFP was used to quantify EYFP+ve, PRL-ve, and GH+ve cell populations during pregnancy and lactation, and for up to 3 weeks after weaning, and concurrent changes in cell size were estimated. At all stages, the EYFP reporter was expressed in 80% of the lactotrophs, but in fewer than 1% of other pituitary cell types, indicating that transdifferentiation from those lactotrophs where reporter expression was activated is extremely rare. Contrary to expectations, no increase in the lactotroph/somatotroph ratio was seen during pregnancy and lactation, whether assessed by immunochemistry for the reporter or PRL: findings confirmed by PRL immunochemistry in non-transgenic mice. Mammosomatotrophs were rarely encountered at the age group studied. Individual EYFP+ve cell volumes increased significantly by mid-lactation compared with virgin animals. This, in combination with a modest and non-cell type-specific estrogen-induced increase in mitotic activity, could account for pregnancy-induced changes in overall pituitary size.


Assuntos
Integrases/metabolismo , Lactação/metabolismo , Lactotrofos/metabolismo , Prolactina/metabolismo , Proteínas/metabolismo , Somatotrofos/metabolismo , Animais , Morte Celular , Diferenciação Celular , Transdiferenciação Celular , Feminino , Hormônio do Crescimento/metabolismo , Integrases/genética , Lactotrofos/citologia , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Transgênicos , Modelos Animais , Fenótipo , Gravidez , Prolactina/genética , Proteínas/genética , RNA não Traduzido , Somatotrofos/citologia , Desmame
7.
Science ; 326(5956): 1112-5, 2009 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-19965430

RESUMO

We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.


Assuntos
Variação Genética , Genoma de Planta , Análise de Sequência de DNA , Zea mays/genética , Sequência de Bases , Centrômero/genética , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Produtos Agrícolas/genética , Variações do Número de Cópias de DNA , Metilação de DNA , Elementos de DNA Transponíveis , DNA de Plantas/genética , Genes de Plantas , Endogamia , MicroRNAs/genética , Dados de Sequência Molecular , Ploidias , RNA de Plantas/genética , Recombinação Genética , Retroelementos
8.
Endocrinol Metab Clin North Am ; 37(1): 23-50, vii, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18226729

RESUMO

A significant proportion of pituitary macroadenomas, and by definition all microadenomas, regain trophic stability after an initial period of deregulated growth. Classical proto-oncogene activation and tumor suppressor mutation are rarely responsible, and no histologic or molecular markers reliably predict behavior. GNAS1 activation and the mutations associated with multiple endocrine neoplasia type 1 and Carney complex, aryl hydrocarbon receptor interacting protein gene mutations, and a narrowing region of chromosome 11q13 in familial isolated acromegaly together account for such a small proportion of pituitary adenomas that the pituitary adenoma pathogenic epiphany is surely yet to come.


Assuntos
Transformação Celular Neoplásica/patologia , Neoplasias Hipofisárias/patologia , Animais , Transformação Celular Neoplásica/genética , Cromograninas , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/fisiologia , Humanos , Fenótipo , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/genética , Proto-Oncogene Mas
9.
J Neuroendocrinol ; 20(1): 139-40, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18081562

RESUMO

We still do not understand the pathogenesis of the majority of pituitary adenomas or why, once formed, their behaviour tends to be so benign. Understanding trophic activity in the normal pituitary may be the key. Despite the fact that changes in indices of cell division and programmed cell death that are too small to measure can produce highly significant fluxes in cell populations, little by little, the fascinating patterns of integrated responses of pituitary cells to hormonal stimuli are now being revealed.


Assuntos
Adenoma/etiologia , Hormônios Hipofisários/fisiologia , Neoplasias Hipofisárias/etiologia , Células-Tronco/fisiologia , Feminino , Humanos , Mitose/fisiologia , Gravidez
11.
Front Neuroendocrinol ; 24(2): 94-127, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12763000

RESUMO

The majority of pituitary adenomas are trophically stable and change relatively little in size over many years. A comparatively small proportion behave more aggressively and come to clinical attention through inappropriate hormone secretion or adverse effects on surrounding structures. True malignant behaviour with metastatic spread is very atypical. Pituitary adenomas that come to surgery are predominantly monoclonal in origin and roughly half are aneuploid, indicating either ongoing genetic instability or transition through a period of genetic instability at some time during their development. Few are associated with the classical mechanisms of tumour formation but it is generally believed that the majority harbour quantitative if not qualitative differences in molecular composition compared to the normal pituitary. Despite their prevalence and the ready availability of biopsy material, at the present time, the precise molecular pathogenesis of the majority of pituitary adenomas remains unclear. This review summarizes current thinking.


Assuntos
Adenoma/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hipofisárias/genética , Aneuploidia , Animais , Biomarcadores Tumorais/genética , Células Clonais , Genes cdc , Humanos , Adeno-Hipófise/patologia , Proto-Oncogenes/genética , Receptores de Superfície Celular/genética , Transdução de Sinais/genética
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