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91.
Dominant loss of responsiveness to sweet and bitter compounds caused by a single mutation in α-gustducin
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Luis Ruiz-Avila Gwendolyn T. Wong Sami Damak Robert F. Margolskee 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(15):8868-8873
Biochemical and genetic studies have implicated alpha-gustducin as a key component in the transduction of both bitter or sweet taste. Yet, alpha-gustducin-null mice are not completely unresponsive to bitter or sweet compounds. To gain insights into how gustducin mediates responses to bitter and sweet compounds, and to elicit the nature of the gustducin-independent pathways, we generated a dominant-negative form of alpha-gustducin and expressed it as a transgene from the alpha-gustducin promoter in both wild-type and alpha-gustducin-null mice. A single mutation, G352P, introduced into the C-terminal region of alpha-gustducin critical for receptor interaction rendered the mutant protein unresponsive to activation by taste receptor, but left its other functions intact. In control experiments, expression of wild-type alpha-gustducin as a transgene in alpha-gustducin-null mice fully restored responsiveness to bitter and sweet compounds, formally proving that the targeted deletion of the alpha-gustducin gene caused the taste deficits of the null mice. In contrast, transgenic expression of the G352P mutant did not restore responsiveness of the null mice to either bitter or sweet compounds. Furthermore, in the wild-type background, the mutant transgene inhibited endogenous alpha-gustducin's interactions with taste receptors, i.e., it acted as a dominant-negative. That the mutant transgene further diminished the residual bitter and sweet taste responsiveness of the alpha-gustducin-null mice suggests that other guanine nucleotide-binding regulatory proteins expressed in the alpha-gustducin lineage of taste cells mediate these responses. 相似文献
92.
Punicic Acid a Conjugated Linolenic Acid Inhibits TNFα-Induced Neutrophil Hyperactivation and Protects from Experimental Colon Inflammation in Rats
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93.
Chollet-Martin S Lopez A Gaud C Henry D Stos B El Benna J Chedevile G Gendrel D Gougerot-Pocidalo MA Grandchamp B Gérard B 《European journal of pediatrics》2007,166(2):153-159
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by mutations of one of the subunits of phagocyte
reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase leading to decreased or complete absence of neutrophil
oxidative burst. We report the clinical and laboratory findings in two young unrelated females 14 and 9 years of age and natives
of Tahiti and Reunion Islands, respectively, with severe X-linked granulomatous disease. In both cases, the infectious pattern
was unusual, with convergent symptoms suggesting underlying mycobacterial infection. Functional analysis revealed low residual
NADPH oxidase activity with about 5–10% of normal neutrophil population. De novo null mutations affecting the CYBB gene that encodes the gp91 protein were found in both cases in the heterozygous state (in patient 1, p.Arg130X in exon 5,
and in patient 2, a novel insertion in exon 6, c.632_633insCATC). Methylation analysis confirmed that phenotype expression
was linked to skewed X inactivation and showed that the de novo mutation arose on the maternally inherited chromosome in one
case and on the paternally inherited chromosome in the other case. In conclusion, X-linked CGD carriers could therefore be
at risk for severe infectious diseases depending on the skewed X inactivation pattern and the infectious context. 相似文献
94.
Hela Elloumi Mériam Sabbah Norsaf Bibani Dorra Trad Nour Elleuch Dalila Gargouri Asma Ouakaa Jamel Kharrat 《Arab Journal Of Gastroenterology》2019,20(4):205-208
Background and Study AimsCurrent guidelines favour albumin administration during spontaneous bacterial peritonitis (SBP). However, its use is limited in clinical practice and low doses are preferred. The aim of our study was to determine the effect of low dose albumin perfusion during SBP on mortality and prevention of hepatorenal syndrome (HRS) in cirrhotic patients.Patients and methodsA retrospective study including consecutive patients with SBP hospitalized from 2002 to 2015 was performed. All patients were treated by intravenous empiric antibiotics associated with albumin infusion (30 g/day the first and third day) irrespective of patient's weight. The diagnosis of HRS was assessed according to the International Ascites Club criteria. The survival, the frequency of HRS and any disturbance in renal function were recorded.ResultsFourty nine patients (sex ratio = 0.81, mean age 60.6 years [23–89]) were included. Main cause of cirrhosis was hepatitis B and C in 42.9% of cases. 63.3% were of Child Pugh C score%. The first line intravenous antibiotic treatment was based on cefotaxime in 87.8% of cases, followed by ofloxacin in 6.1% of cases. The outcome was favourable in 85.7% of cases. HRS was observed in 9 patients (18.3%) within 18 months [1–55]. Otherwise, 10 patients (20.4%) experienced an increase in creatinine level despite of albumin perfusion. The immediate mortality was 4%, and the six months survival was of 81.8%.ConclusionDespite even a low dose administration of albumin during SBP, renal dysfunction and HRS occurred less than described in literature. These results associated with cost considerations could suggest to use such an intervention during SBP or to select high risk patients who must receive albumin perfusion during SBP. 相似文献
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98.
Kchaou-Ouakaa A Belhadjbrik N Elloumi H Gargouri D Kochlef A Kilani A Romani M Kharrat J Ghorbel A 《La Tunisie médicale》2007,85(10):866-870
BACKGROUND: The surveillance of cirrhotic patients for early detection of hepatocellular carcinoma is recommended but its efficacy is now discussed. The aim of our study was to present the results of a screening program in 110 patients. METHODS: it is a retrospective study that included 110 patients with cirrhosis in a screening program of hepatocellular carcinoma, based on the realization of abdominal ultrasound exam and the determination of alpha-fetoprotein amount every 6 months in 95 patients and every 3 months in 15 patients. RESULTS: the mean duration of the surveillance was 36 months. A hepatocellular carcinoma was diagnosed in 13 patients. Curative treatment was done in only 3 cases and consisted in a hepatic resection in 1 patient and an alcoolisation in 2 cases. Ten patients had new treatment : for 8 patients the discussed was very agressive and 2 patients had a server hepotic failure. The cost of this study was 37.500 Tunisian dinars. CONCLUSIONS: systematic screening for hepatocellular carcinoma offer a limited cost effectiveness ratio. 相似文献
99.
Wala Ben Kridis Jihène Feki Lobna Ayedi Afef Khanfir Nabil Toumi Mohamed Abdelmoula Tahia Boudawra Jamel Daoud Mounir Frikha 《Journal of maxillofacial and oral surgery》2016,15(2):287-290
Primary melanoma of the mandibular gingiva is extremely rare. It is often misinterpreted as a benign pigmented process. The prognosis of this entity is very poor. We report here the first case of primary gingival melanoma described in the Tunisian literature about a 55-year-old smoker having cerebral and pulmonary metastases from gingival melanoma at diagnosis. Our patient underwent brain radiotherapy at a dose of 18 Gy in three sessions but he died with a decline of 3 months before starting systemic therapy. Therefore, each new case should be illustrated to make clinicians aware about the importance of the early diagnosis to improve the poor diagnosis of this entity. 相似文献
100.
Imen Rejeb Houweyda Jilani Yasmina Elaribi Syrine Hizem Lamia Hila Julia Lauer Zillahrdt Jamel Chelly Lamia Benjemaa 《BMC medical genetics》2017,18(1):134