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51.
Identification of a second HOXA2 nonsense mutation in a family with autosomal dominant non‐syndromic microtia and distinctive ear morphology 下载免费PDF全文
F. Piceci S. Morlino M. Castori E. Buffone A. De Luca P. Grammatico V. Guida 《Clinical genetics》2017,91(5):774-779
Microtia is a congenital defect affecting external ears, which appear smaller and sometimes malformed. Here we describe a five‐generation family with isolated bilateral microtia segregating as an autosomal dominant trait. Similar features have been previously observed in an autosomal dominant family with non‐syndromic microtia and hearing loss segregating with a HOXA2 nonsense variant. HOXA2 biallelic mutations were also described in an inbreed family with autosomal recessive microtia, hearing impairment and incomplete cleft palate. In our family, sequence analysis detected a heterozygous protein truncating nonsense variant [c.670G>T, p.(Glu224*)] segregating in all affected individuals and absent in public databases. This study confirms the role of HOXA2 gene in dominant isolated microtia and contribute to further define the dysmorphogenetic effect of this gene on ear development. 相似文献
52.
D Fernandes E Guida V Koutsoubos T Harris P Vadiveloo J W Wilson A G Stewart 《American journal of respiratory cell and molecular biology》1999,21(1):77-88
We have previously shown that glucocorticoids inhibit mitogen-stimulated proliferation of human cultured airway smooth muscle (ASM) cells. The present study analyzed the effect of glucocorticoids on key regulatory pathways leading to passage of cells through the restriction point of the cell cycle, including those mediated by extracellular-regulated kinases (ERK) 1 and 2; the ERK upstream regulator MAPK kinase (MEK1); cyclin D1 levels; and levels and phosphorylation of retinoblastoma protein (pRb). Fluticasone propionate, a new inhaled glucocorticoid, was at least 10-fold more potent than dexamethasone in inhibiting thrombin-stimulated DNA synthesis and increases in cell number. Thrombin-stimulated increases in the levels and hyperphosphorylation of pRb were inhibited by glucocorticoids, which also reduced thrombin-stimulated cyclin D1 protein and messenger RNA (mRNA) levels. PD98059 (10 microM), an inhibitor of MEK1 activation, markedly attenuated thrombin stimulation of ERK activity and phosphorylation, DNA synthesis, and cyclin D1 levels. However, glucocorticoids had no effect on ERK activity or phosphorylation at 5 min, 2 h, or 12 h after addition of thrombin. In conclusion, glucocorticoid-induced reduction of cyclin D1 mRNA and protein levels, and of pRb phosphorylation, is sufficient to account for inhibition of ASM proliferation. Furthermore, these inhibitory effects of glucocorticoids on cyclin D1 and pRb occur on a component of the mitogen signaling cascade that is either downstream of or parallel to the ERK pathway. 相似文献
53.
Heraldo Lorena Guida Thiago Hernandes Diniz Sérgio Koodi Kinoshita 《Revista brasileira de otorrinolaringologia (English ed.)》2011,77(2):163-170
Police officers are exposed to impact noise coming from firearms, which may cause irreversible injuries to the hearing system.AimTo evaluate the noise exposure in shooting stands during gunfire exercises, to analyze the acoustic impact of the noise produced by the firearms and to associate it with tonal audiometry results.Study designCross-sectional.Materials and methodsTo measure noise intensity we used a digital sound level meter, and the acoustic analysis was carried out by means of the oscillations and cochlear response curves provided by the Praat software. 30 police officers were selected (27 males and 3 females).ResultsThe peak level measured was 113.1 dB(C) from a .40 pistol and 116.8 dB(C) for a .38 revolver. The values obtained for oscillation and Praat was 17.9±0.3 Barks, corresponding to the rate of 4,120 and 4,580 Hz. Audiometry indicated greater hearing loss at 4,000Hz in 86.7% of the cases.ConclusionWith the acoustic analysis it was possible to show cause and effect between the main areas of energy excitation of the cochlea (Praat cochlear response curve) and the frequencies of low hearing acuity. 相似文献
54.
Thyroidectomy appears to reduce the serotonin content in the rat brain, whereas hyperthyroidism has the opposite effect. As it is not known whether the serotonin-producing cells of the gastrointestinal tract are influenced by these conditions, the effects of thyroparathyroidectomy and induced hyperthyroidism were studied experimentally, particularly as regards the serotonin- and gastrin-immunoreactive cells of the gastrointestinal tract. Immunocytochemical and quantification techniques were used to localize and determine the numbers of serotonin and gastrin cells. In thyroparathyroidectomized rats the intestine was significantly shorter and the mucosa thinner than in sham-operated and untreated controls, whereas the converse was found in the hyperthyroid rats. Following thyroparathyroidectomy, there were fewer gastrin-immunoreactive cells in antrum and the serotonin-immunoreactive cells were significantly less dense throughout the gastrointestinal tract. In hyperthyroid rats, gastrin-immunoreactive cells were more numerous, as were the serotonin-immunoreactive cells in the small intestine, whereas these cells were fewer in antrum and caecum. In conclusion, the thyroid gland exerts a significant influence on the gastrointestinal tract and on the serotonin- and gastrin-immunoreactive cells. The observed alterations may reflect a direct effect of the thyroid hormones, although indirect factors must also be considered. 相似文献
55.
56.
The aim of the work is the evaluation of the microbial content of soft cheese when it comes on the table of the consumer. To reach this purpose we have bought, as simple clients, the product in the small and average distributions that apply the HACCP (Hazard Analysis Critical Control Point) plain and in the small distributions which don't apply it, the collecting and the microbiological analysis of the product has been performed on the different pieces that belong to the whole form of cheese during the days of the week, observing a progressive increase of the bacterial number; besides we have found in the bought cheese that when the form of cheese was at the end, values overcame the limits of law. The increase of the bacterial numbers was greater in the products purchased in the average distributions in order with the application of the self-control, and in the small ones that don't effect this type of selling. The deduction was that the HACCP system has not been correctly applied in all the shops tested and in the exercises without the HACCP plain the contamination levels are higher. The health risk connected with not correct manipulation by the employees still results very elevated. 相似文献
57.
Causes of cognitive impairment after stroke are not yet clear because a large number of sociodemographic and clinical variables
complicate the understanding of the phenomenon. We aim to evaluate sociodemographic and clinical predictors of cognitive level
and depression in subjects with different lesion laterality. We assessed 153 right (n = 87) and left (n = 66) unilateral first-ever
stroke patients within the first year of illness with the Structured Clinical Interview for DSM-IV-Patient Edition, the Hamilton
Depression Rating Scale, the Hamilton Anxiety Rating Scale, the State Trait Anger Expression Inventory, the Barthel Index,
and the Mini Mental State Examination (MMSE). Sociodemographic variables were also measured. Sixty-two (41 %) patients suffered
from Major Depression (MDD), and 26 (17 %) suffered from Minor Depression (MIND). An univariate analysis of variance showed
that MMSE scores were different throughout the groups of left and right stroke patients with MDD, MIND and without depression.
Left stroke patients with MDD were more cognitively impaired than all the other groups. This result was valid after controlling
for the effect of lesion location on cognitive level difference between the groups. A series of stepwise multiple regression
analyses indicated that depression severity was a predictor of cognitive level and vice-versa in left hemispheric stroke patients only. Moreover, educational level in right hemispheric stroke patients and state-anger
and number of regions affected in left hemispheric stroke patients were other predictors of cognitive level.
The study confirms the hypothesis that predictors of cognitive level and depression severity are different in subjects with
different laterality of lesion and that MDD is associated with cognitive impairment in left stroke patients.
Received: 4 February 2002, Received in revised form: 14 May 2002, Accepted: 22 May 2002
Correspondence to Gianfranco Spaletta, MD 相似文献
58.
Carlomagno F Vitagliano D Guida T Napolitano M Vecchio G Fusco A Gazit A Levitzki A Santoro M 《Cancer research》2002,62(4):1077-1082
Oncogenic activation of the RET receptor tyrosine kinase is common in different human cancers. We found that the pyrazolo-pyrimidine PP1 inhibited RET-derived oncoproteins with a half maximal inhibitor concentration of 80 nM. Furthermore, RET/PTC3-transformed cells treated with 5 microM of PP1 lost proliferative autonomy and showed morphological reversion. PP1 prevented the growth of two human papillary thyroid carcinoma cell lines that carry spontaneous RET/PTC1 rearrangements and blocked anchorage-independent growth and tumorigenicity in nude mice of NIH3T3 fibroblasts expressing the RET/PTC3 oncogene. These findings suggest targeting RET oncogenes with PP1 or related compounds as a novel treatment strategy for RET-associated neoplasms. 相似文献
59.
M ODowd T Geoghegan PL Munk G McAuley WC Torreggiani 《Journal of Medical Imaging and Radiation Oncology》2006,50(4):386-388
Osseous haemophilic pseudotumours are uncommon. The commonest sites of involvement are the femur and the pelvis. Trauma is the initiating factor in most reported cases and repeated bleeding into the lesion contributes to their growth. Most lesions grow slowly and are often asymptomatic. Complications include massive haemorrhage, infection and pathological fracture. We present an extremely unusual presentation where a large haemophilic pseudotumour of the pelvis extended to impinge the adjacent colon, resulting in large bowel obstruction. 相似文献
60.
Ruggero Ridolfi Vanna Chiarion-Sileni Michele Guida Antonella Romanini Roberto Labianca Andrea Freschi Giovanni Lo Re Rolando Nortilli Sonia Brugnara Patrizia Vitali Oriana Nanni 《Journal of clinical oncology》2002,20(6):1600-1607
PURPOSE: Phase II and III studies have shown that the addition of interleukin-2 (IL-2) and interferon alpha-2b (IFN alpha-2b) in multiagent chemotherapy (CT) for advanced melanoma increases overall response (OR), albeit without clear evidence of an improvement in overall survival (OS). Treatment with high-dose IL-2 can cause severe toxicity and is normally administered in an inpatient setting. We conducted a multicenter prospective randomized clinical trial in outpatients with metastatic melanoma to compare CT with biochemotherapy (bioCT) using immunomodulant doses of IL-2 and IFN alpha-2b. PATIENTS AND METHODS: One hundred seventy-six eligible patients with advanced melanoma were randomized to receive CT (cisplatin and dacarbazine with or without carmustine every 21 days) or bioCT comprising the same CT regimen followed by low-dose subcutaneous IL-2 for 8 days and IFN alpha-2b three times a week, both for six cycles. RESULTS: At a median follow-up of 18 (CT) and 16 (bioCT) months, median OS was 9.5 versus 11.0 months (P =.51), respectively. In the 89 CT-arm patients, 18 ORs (20.2%) (three complete responders [CRs] and 15 partial responders [PRs]) were observed according to World Health Organization criteria. In the 87 bioCT-arm patients, 22 ORs (25.3%) (three CRs and 19 PRs) (P =.70) were recorded. Treatment-related toxicity was fairly similar in both arms. CONCLUSION: The addition of low-dose immunotherapy did not produce a statistically significant advantage in OS, time to progression, or OR. However, the 11-month median OS in the bioCT arm does not differ greatly from the best results with high-dose IL-2-containing regimens reported in the literature. Furthermore, our treatment schedule was carried out on outpatients and had an acceptable level of toxicity. 相似文献