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81.
Voutetakis A Maniati-Christidi M Kanaka-Gantenbein C Dracopoulou M Argyropoulou M Livadas S Dacou-Voutetakis C Sertedaki A 《European journal of endocrinology / European Federation of Endocrine Societies》2004,150(3):257-264
OBJECTIVE: To identify the genetic defect in a neonate presented with prolonged jaundice and central hypothyroidism. DESIGN: Central hypothyroidism was detected in a neonate initially examined for prolonged jaundice, and levothyroxine therapy was initiated. Direct sequencing of the Prop1 gene was carried out and pituitary function and morphology were evaluated using hormonal testing and magnetic resonance imaging (MRI) respectively. METHODS: Dynamic hormonal testing was carried out using established methodologies. Hormones were determined by RIA or chemiluminescence immunoassays. Genomic analysis of the Prop1 gene was performed by direct sequencing. MRI protocol: sagittal spin echo T2-weighted scans 2500/90 (TR/TE), plain and contrast-enhanced sagittal and coronal spin echo T1-weighted scans 500/20 (TR/TE). RESULTS: Low thyroid hormones (coupled with lack of TSH rise), low GH, normal cortisol and normal prolactin values were detected. Direct sequencing revealed the presence of two mutations in the Prop1 gene: GA296del and Q83X. The Q83X was further confirmed by PvuII restriction digestion and represented a novel Prop1 gene mutation, which was not detected in 100 controls tested. Pituitary enlargement was detected, with respect to normal-for-age controls. CONCLUSIONS: (i) The Q83X mutation extends the spectrum of Prop1 gene mutations; (ii) central hypothyroidism in a neonate might constitute the initial sign of Prop1 gene defect; (iii) the patient is the youngest individual with Prop1 gene defect and pituitary enlargement presented to date; and (iv) early detection of Prop1 gene mutations facilitates genetic counseling and ensures prompt management of the anticipated hormonal insufficiencies. 相似文献
82.
Metallothionein prevents neurodegeneration and central nervous system cell death after treatment with gliotoxin 6-aminonicotinamide 总被引:1,自引:0,他引:1
Penkowa M Quintana A Carrasco J Giralt M Molinero A Hidalgo J 《Journal of neuroscience research》2004,77(1):35-53
Transgenic expression of interleukin-6 (IL-6) in the CNS under the control of the glial fibrillary acidic protein (GFAP) gene promoter (GFAP-IL6 mice) induces significant inflammation and neurodegeneration but also affords neuroprotection against acute traumatic brain injury. This neuroprotection is likely mediated by the IL-6-induced protective factors metallothioneins-I and -II (MT-I+II). Here we evaluate the neuroprotective roles of IL-6 vs. MT-I+II during 6-aminonicotinamide (6-AN)-induced neurotoxicity, by using GFAP-IL6 mice and transgenic mice overexpressing MT-I (TgMT) as well as GFAP-IL6 mice crossed with TgMT mice (GFAP-IL6 x TgMT). 6-AN caused acute damage of brainstem gray matter areas identified by necrosis of astrocytes, followed by inflammatory responses. After 6-AN-induced toxicity, secondary damage was observed, consisting of oxidative stress, neurodegeneration, and apoptotic cell death. We hereby show that the primary injury caused by 6-AN was comparable in wild-type and GFAP-IL6 mice, but MT-I overexpression could significantly protect the brain tissue. As expected, GFAP-IL6 mice showed increased CNS inflammation with more gliosis, macrophages, and lymphocytes, including increased cytokine expression, relative to the other mice. However, GFAP-IL6 mice showed reduced oxidative stress (judged from nitrotyrosine, malondialdehyde, and 8-oxoguanine stainings), neurodegeneration (accumulation of neurofibrillary tangles), and apoptosis (determined from TUNEL and caspase-3). MT-I+II expression was significantly higher in GFAP-IL6 mice than in wild types, which may contribute to the IL-6-induced neuroprotection. In support of this, overexpression of MT-I in GFAP-IL6 x TgMT as well as TgMT mice protected the brainstem tissue significantly from 6-AN-induced toxicity and secondary brain tissue damage. Overall, the results demonstrate that brain MT-I+II proteins are fundamental neuroprotective factors, which in the future may become therapeutic agents. 相似文献
83.
Laborde A 《Toxicology》2004,198(1-3):273-277
84.
85.
Sheiner E Levy A Menes TS Silverberg D Katz M Mazor M 《Paediatric and perinatal epidemiology》2004,18(3):196-201
The present study was aimed to investigate pregnancy outcome among obese women and specifically the correlation between maternal obesity and incidence of caesarean section (CS) while controlling for the potential confounding effects of other variables associated with obesity. A population-based study was performed comparing all pregnancies of obese (maternal pre-pregnancy body mass index (BMI) of 30 kg/m2 or more) and non-obese patients, between the years 1988 and 2002. Patients with hypertensive disorders and diabetes mellitus as well as patients lacking prenatal care were excluded from the analysis. Stratified analyses, using the Mantel-Haenszel technique, and a multiple logistic regression model were performed to control for confounders. During the study period there were 126,080 deliveries meeting the inclusion criteria, of which 1769 (1.4%) occurred in obese patients. Using a multivariable analysis, the following conditions were significantly associated with maternal obesity: failure to progress during the first stage (odds ratio (OR) = 3.1; 95% confidence interval [CI] 2.5, 3.8; P < 0.001), fertility treatments (OR = 2.0; [95% CI 1.6, 2.5]; P < 0.001), previous CS (OR = 1.7; [95% CI 1.5, 1.9]; P < 0.001), malpresentations (OR = 1.4; [95% CI 1.2, 1.6]; P < 0.001), recurrent miscarriages (OR = 1.4; [95% CI 1.2, 1.7]; P < 0.001) and fetal macrosomia (OR = 1.4; [95% CI 1.2, 1.7]; P < 0.001). Higher rates of caesarean deliveries were found among obese parturients (27.8% vs. 10.8%; OR = 3.2; [95% CI 2.9, 3.5]; P < 0.001). When controlling for possible confounders, using the Mantel-Haenszel technique, the association between maternal obesity and CS remained significant. No significant differences were noted between the groups regarding perinatal complications such as perinatal mortality, congenital malformations, shoulder dystocia and low Apgar scores. In conclusion, a significant association was found between obesity and CS even after the exclusion of hypertensive disorders and diabetes mellitus. Importantly, obesity alone was not associated with adverse perinatal outcome. Obstetricians should be encouraged to allow obese patients not suffering from diabetes or hypertensive disorders an adequate trial of labour. 相似文献
86.
Espinosa AB Tabernero MD García-Macías MC Primo D Bernal AG Cruz JJ Ramos M Font de Mora J Gómez Alonso A Orfao A 《American journal of clinical pathology》2003,120(6):917-927
We compared the incidence of Her-2/neu amplification in patients with and without a family history of breast cancer and correlated gene status with clinicobiologic and prognostic features in sporadic and familial cases. Of 108 patients, 28.7% had gene amplification. Among 96 cases with family history information available, 28 had an affected first-degree relative. The gene was amplified more frequently in familial than in sporadic cases (13/28 [46%] vs 14/68 [21%]; P = .01). Among familial cases, amplification was associated with adverse clinicobiologic features (poorly differentiated tumors [P = .05], larger tumors [P = .05], more lymph nodes involved [P = .04], and DNA aneuploid [P = .02] and highly proliferative tumors [P = .005]), and the relapse (P = .02) and disease-related death (P = .05) rates were higher than in cases without amplification. Among sporadic cases, amplification was not associated with significantly different disease features, except for a higher incidence of DNA aneuploid tumors (P = .01), percentage of S-phase tumor cells (P = .006), and lower proportion of estrogen (P = .001) and progesterone (P = .002) receptors. Her-2/neu amplification was observed more frequently among patients with a family history of breast cancer, in whom it was associated with adverse clinicobiologic features and a worse clinical outcome. 相似文献
87.
Sheiner E Levy A Feinstein U Hallak M Mazor M 《Acta obstetricia et gynecologica Scandinavica》2002,81(3):222-226
BACKGROUND: One of the major indications for Cesarean section (CS) is failure of labor to progress. This study was aimed at defining obstetric risk factors for failure of labor to progress during the first stage, and to determine pregnancy outcome. METHODS: A population-based study comparing all singleton, vertex, term deliveries between the years 1988 and 1999 with an unscarred uterus, complicated with failure of labor to progress during the first stage with deliveries without non-progressive labor (NPL). Multiple logistic regression analysis was performed to investigate independent obstetric risk factors associated with failure of labor to progress during the first stage. RESULTS: Failure to progress during the first stage of labor complicated 1.3% (n = 1197) of all deliveries included in the study (n = 92 918), and resulted in CS. Independent risk factors for failure of labor to progress during the first stage, using a multivariable analysis, were premature rupture of membranes (PROM; OR = 3.8, 95% CI 3.2-4.5), nulliparity (OR = 3.8, 95% CI 3.3-4.3), labor induction (OR = 3.3, 95% CI 2.9-3.7), maternal age > 35 years (OR = 3.0, 95% CI 2.6-3.6), birth weight > 4 kg (OR = 2.2, 95% CI 1.8-2.7), hypertensive disorders (OR = 2.1, 95% CI 1.8-2.6), hydramnios (OR = 1.9, 95% CI 1.5-2.3), fertility treatment (OR = 1.8, 95% CI 1.4-2.4), epidural analgesia (OR = 1.6, 95% CI 1.4-1.8) and gestational diabetes (OR = 1.4, 95% CI 1.1-1.7). Although newborns delivered after failure of labor to progress during the first stage had significantly higher rates of Apgar scores lower than 7 at 1 and 5 min as compared with the controls (18.2% vs. 2.1%; P < 0.001 and 1.3% vs. 0.2%; P < 0.001, respectively), no significant differences were noted between the groups regarding perinatal mortality (0.3% vs. 0.4%; P = O.329). Maternal anemia and accordingly packed cells transfusion (47.4% vs. 22.8%; P < 0.001 and 5.6% vs. 1.0%; P < 0.001, respectively) were higher among pregnancies complicated with failure of labor to progress during the first stage as compared with the controls. CONCLUSIONS: Major risk factors for failure of labor to progress during the first stage were PROM, nulliparity, induction of labor and older maternal age. Indications for labor induction should be carefully evaluated in order to decrease the rate of operative deliveries. 相似文献
88.
Giamarellos-Bourboulis EJ Plachouras D Skiathitis S Raftogiannis M Dionyssiou-Asteriou A Dontas I Karayannacos PE Giamarellou H 《The Journal of antimicrobial chemotherapy》2003,51(2):423-426
Three multidrug-resistant strains of Pseudomonas aeruginosa were incubated ex vivo with sera sampled after a 10 min intravenous infusion of 25 mg/kg of arachidonic acid (AA) in 10 rabbits in the presence of ceftazidime and amikacin. Lipid peroxidation was assessed during bacterial growth. A statistically significant decrease in bacterial cells was found by the interaction of antimicrobials and serum sampled in the middle of infusion and 15 and 30 min after infusion of AA and was accompanied by elevated levels of malonodialdehyde. This effect of AA is probably attributed to lipid peroxidation and raises the possibility of its application in experimental infections. 相似文献
89.
Sertedaki A Papadimitriou A Voutetakis A Dracopoulou M Maniati-Christidi M Dacou-Voutetakis C 《Pediatric research》2002,52(6):935-941
Isolated congenital hypothyroidism resulting from mutation of the TSH beta-subunit gene, has rarely been reported. In the present article, we report a new mutation (C85R) in exon 3 of the TSH beta-subunit gene in one sporadic case and the mutation Q49stop in two siblings with congenital hypothyroidism. The novel mutation is a T to C transition at codon 85, resulting in a change of cysteine to arginine (C85R) of the ss-subunit. Because the cysteine residues of all glycoproteins are highly conserved, this mutation is expected to result in conformational changes of the ss-subunit, rendering it incapable to form a functional heterodimer with the alpha-subunit. The second mutation described is a C to T transition resulting in a premature stop at codon 49 (Q49stop), leading to the formation of a truncated protein. Although the two siblings reported herein carried the same mutation, they had slightly modified clinical and biochemical phenotype. The mutation C85R and the previously described E11stop have, thus far, exclusively been detected in Greek patients. The Q49stop mutation initially detected in Greek patients was subsequently identified in an Egyptian girl and most recently in two Turkish siblings. These three reports possibly indicate the presence of a mutational hot spot on the TSH beta-subunit gene. Hence, with the novel mutation herein reported, a total of five mutations of the TSH beta-subunit gene are recognized as a cause of low-TSH congenital hypothyroidism worldwide. 相似文献
90.
Issa AM 《Journal of the American Geriatrics Society》2002,50(5):946-948
The challenges inherent in physicians treating members of their own families are well known. However, the issues related to physicians acting as surrogate decision-makers on behalf of relatives have not been addressed. The growing number of older persons will increase the need not only for healthcare resources, but also for physicians to act on behalf of incapacitated family members as surrogate decision-makers. In this paper, some of the clinical and ethical tensions evoked by physicians serving as surrogate decision-makers for family members are explored. Some recommendations for managing these tensions are suggested. 相似文献