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21.
Debora M. Miranda Bernardo L. Wajchenberg† Maria R. Calsolari‡ Marcos J. Aguiar José M. C. L. Silva§ Marcia G. Ribeiro¶ Cristina Fonseca¶ Daniela Amaral¶ Wolfanga L. Boson Bruna A. Resende Luiz De Marco 《Clinical endocrinology》2009,71(4):512-517
Context Congenital generalized lipodystrophy, or Berardinelli–Seip syndrome, is a rare autosomal recessive disease caused by mutations in either the BSCL2 or AGPAT2 genes. This syndrome is characterized by an almost complete loss of adipose tissue usually diagnosed at birth or early infancy resulting in apparent muscle hypertrophy. Common clinical features are acanthosis nigricans, hepatomegaly with or without splenomegaly and high stature. Acromegaloid features, cardiomyopathy and mental retardation can also be present.
Design We investigated 11 kindreds from different geographical areas of Brazil (northeast and southeast). All coding regions as well as flanking intronic regions of both genes were examined. Polymerase chain reaction (PCR) amplifications were performed using primers described previously and PCR products were sequenced directly.
Results Four AGPAT2 and two BSCL2 families harboured the same set of mutations. BSCL2 gene mutations were found in the homozygous form in four kindreds (c.412C>T c.464T>C, c.518–519insA, IVS5-2A>G), and in two kindreds compound mutations were found (c.1363C>T, c.424A>G). In the other four families, one mutation of the AGPAT2 gene was found (IVS3-1G>C and c.299G>A).
Conclusions We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli–Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome). 相似文献
Design We investigated 11 kindreds from different geographical areas of Brazil (northeast and southeast). All coding regions as well as flanking intronic regions of both genes were examined. Polymerase chain reaction (PCR) amplifications were performed using primers described previously and PCR products were sequenced directly.
Results Four AGPAT2 and two BSCL2 families harboured the same set of mutations. BSCL2 gene mutations were found in the homozygous form in four kindreds (c.412C>T c.464T>C, c.518–519insA, IVS5-2A>G), and in two kindreds compound mutations were found (c.1363C>T, c.424A>G). In the other four families, one mutation of the AGPAT2 gene was found (IVS3-1G>C and c.299G>A).
Conclusions We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli–Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome). 相似文献
22.
Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene 总被引:7,自引:0,他引:7 下载免费PDF全文
Borrello MG Alberti L Fischer A Degl'innocenti D Ferrario C Gariboldi M Marchesi F Allavena P Greco A Collini P Pilotti S Cassinelli G Bressan P Fugazzola L Mantovani A Pierotti MA 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(41):14825-14830
Rearrangements of the RET receptor tyrosine kinase gene generating RET/PTC oncogenes are specific to papillary thyroid carcinoma (PTC), the most frequent thyroid tumor. Here, we show that the RET/PTC1 oncogene, when exogenously expressed in primary normal human thyrocytes, induces the expression of a large set of genes involved in inflammation and tumor invasion, including those encoding chemokines (CCL2, CCL20, CXCL8, and CXCL12), chemokine receptors (CXCR4), cytokines (IL1B, CSF-1, GM-CSF, and G-CSF), matrix-degrading enzymes (metalloproteases and urokinase-type plasminogen activator and its receptor), and adhesion molecules (L-selectin). This effect is strictly dependent on the presence of the RET/PTC1 Tyr-451 (corresponding to RET Tyr-1062 multidocking site). Selected relevant genes (CCL20, CCL2, CXCL8, CXCR4, L-selectin, GM-CSF, IL1B, MMP9, UPA, and SPP1/OPN) were found up-regulated also in clinical samples of PTC, particularly those characterized by RET/PTC activation, local extrathyroid spread, and lymph node metastases, when compared with normal thyroid tissue or follicular thyroid carcinoma. These results, demonstrating that the RET/PTC1 oncogene activates a proinflammatory program, provide a direct link between a transforming human oncogene, inflammation, and malignant behavior. 相似文献
23.
Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor 总被引:1,自引:0,他引:1 下载免费PDF全文
Vannini A Volpari C Filocamo G Casavola EC Brunetti M Renzoni D Chakravarty P Paolini C De Francesco R Gallinari P Steinkühler C Di Marco S 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(42):15064-15069
Histone deacetylases (HDACs) are a family of enzymes involved in the regulation of gene expression, DNA repair, and stress response. These processes often are altered in tumors, and HDAC inhibitors have had pronounced antitumor activity with promising results in clinical trials. Here, we report the crystal structure of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a eukaryotic zinc-dependent HDAC has not be described previously. Similar to bacterial HDAC-like protein, HDAC8 folds in a single alpha/beta domain. The inhibitor and the zinc-binding sites are similar in both proteins. However, significant differences are observed in the length and structure of the loops surrounding the active site, including the presence of two potassium ions in HDAC8 structure, one of which interacts with key catalytic residues. CD data suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical cancer cell lines, highlighting the importance of this HDAC subtype for tumor cell proliferation. Our findings open the way for the design and development of selective inhibitors of HDAC8 as possible antitumor agents. 相似文献
24.
de Lima Silva Alvaro Henrique Bernardo Radulski Debora Rasec Pereira Gabriela Saidel Acco Alexandra Zanoveli Janaina Menezes 《Metabolic brain disease》2022,37(4):1095-1110
Metabolic Brain Disease - Anxiety Disorders and Posttraumatic Stress Disorders (PTSD) associated with type-1 diabetes mellitus (T1DM) are increasingly common comorbidities and the treatment is... 相似文献
25.
26.
Common and rare side-effects of low-dose thalidomide in multiple myeloma: focus on the dose-minimizing peripheral neuropathy 总被引:1,自引:0,他引:1
Offidani M Corvatta L Marconi M Malerba L Mele A Olivieri A Brunori M Catarini M Candela M Capelli D Montanari M Rupoli S Leoni P 《European journal of haematology》2004,72(6):403-409
OBJECTIVES: Thalidomide has demonstrated a remarkable efficacy in the treatment of multiple myeloma but its use may cause several toxicities. We have investigated the common and rare side-effects, especially analysing peripheral neuropathy, in order to optimise the thalidomide dose for minimizing this harmful side-effect. METHODS: Fifty-nine patients were treated with thalidomide alone or combined with oral melphalan. The median age was 69 yr. The initial dose of thalidomide was 100 mg/day increasing weekly by 100 mg increments until a maximum dose of 400 mg was attained. Melphalan was administered at a dose of 0.20 mg/kg/d for 4 d every 28 d. RESULTS AND CONCLUSIONS: Nearly one-fourth of patients discontinued thalidomide because of toxicity. Constipation (71%), somnolence (36%) and fatigue (20%) were the most common side-effects and they were not dose dependent. Peripheral neuropathy occurred in 39% of patients and a thalidomide median daily dose of more than 150 mg was significantly associated with higher frequency and actuarial risk of peripheral neuropathy without improving the response rate. Deep venous thrombosis was observed in 7% of patients and other side-effects were rare. In patients with advanced multiple myeloma we found that a thalidomide daily dose of 150 mg minimizes peripheral neuropathy without jeopardizing response and survival. 相似文献
27.
Monica Terenziani MD Paolo D'Angelo MD Alessandro Inserra MD Renata Boldrini MD Gianni Bisogno MD Gian Luca Babbo MD Massimo Conte MD Patrizia Dall' Igna MD Maria Debora De Pasquale MD Paolo Indolfi MD Luigi Piva MD Giovanna Riccipetitoni MD Fortunato Siracusa MD Filippo Spreafico MD Paolo Tamaro MD Giovanni Cecchetto MD 《Pediatric blood & cancer》2015,62(7):1202-1208
28.
Derjung M. Tarn Debora A. Paterniti Neil S. Wenger 《Journal of general internal medicine》2016,31(8):909-917
BACKGROUND
Little is known about how providers communicate recommendations when scientific uncertainty exists.OBJECTIVES
To compare provider recommendations to those in the scientific literature, with a focus on whether uncertainty was communicated.DESIGN
Qualitative (inductive systematic content analysis) and quantitative analysis of previously collected audio-recorded provider–patient office visits.PARTICIPANTS
Sixty-one providers and a socio-economically diverse convenience sample of 603 of their patients from outpatient community- and academic-based primary care, integrative medicine, and complementary and alternative medicine provider offices in Southern California.MAIN MEASURES
Comparison of provider information-giving about vitamin D to professional guidelines and scientific information for which conflicting recommendations or insufficient scientific evidence exists; certainty with which information was conveyed.RESULTS
Ninety-two (15.3 %) of 603 visit discussions touched upon issues related to vitamin D testing, management and benefits. Vitamin D deficiency screening was discussed with 23 (25 %) patients, the definition of vitamin D deficiency with 21 (22.8 %), the optimal range for vitamin D levels with 26 (28.3 %), vitamin D supplementation dosing with 50 (54.3 %), and benefits of supplementation with 46 (50 %). For each of the professional guidelines/scientific information examined, providers conveyed information that deviated from professional guidelines and the existing scientific evidence. Of 166 statements made about vitamin D in this study, providers conveyed 160 (96.4 %) with certainty, without mention of any equivocal or contradictory evidence in the scientific literature. No uncertainty was mentioned when vitamin D dosing was discussed, even when recommended dosing was higher than guideline recommendations.CONCLUSIONS AND RELEVANCE
Providers convey the vast majority of information and recommendations about vitamin D with certainty, even though the scientific literature contains inconsistent recommendations and declarations of inadequate evidence. Not communicating uncertainty blurs the contrast between evidence-based recommendations and those without evidence. Providers should explore best practices for involving patients in decision-making by acknowledging the uncertainty behind their recommendations.29.
Benefits and Burdens of Using a SNP Array in Pregnancies at Increased Risk for the Common Aneuploidies 下载免费PDF全文
Diane Van Opstal Femke de Vries Lutgarde Govaerts Marjan Boter Debora Lont Stefanie van Veen Marieke Joosten Karin Diderich Robert‐Jan Galjaard Malgorzata I. Srebniak 《Human mutation》2015,36(3):319-326
We present the nature of pathogenic SNP array findings in pregnancies without ultrasound (US) abnormalities and show the additional diagnostic value of SNP array as compared with rapid aneuploidy detection and karyotyping. 1,330 prenatal samples were investigated with a 0.5‐Mb SNP array after the exclusion of the most common aneuploidies. In 2.7% (36/1,330) of the cases, pathogenic chromosome aberrations were found; a microscopically detectable abnormality in 0.7% and a submicroscopic aberration in 2%. Our results show that in addition to the age‐ or screening‐related aneuploidy risk, in pregnancies without US abnormalities, there is a risk of 1:148 (9/1,330) for a (sub)microscopic abnormality associated with an early‐onset often severe disease, 1:222 (6/1,330) for a submicroscopic aberration causing an early‐onset disease, 1:74 (18/1,330) for carrying a susceptibility locus for a neurodevelopmental disorder, and 1:443 (3/1,330) for a late‐onset disorder (hereditary neuropathy with liability to pressure palsies in all three cases). These risk figures are important for adequate pretest counseling so that prospective parents can make informed individualized choices between targeted prenatal testing and broad testing with SNP array. Based on our results, we believe if invasive testing is performed, SNP array should be the preferred cytogenetic technique irrespective of the indication. 相似文献
30.