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81.
Bolad A Nebié I Cuzin-Ouattara N Traore A Esposito F Berzins K 《The American journal of tropical medicine and hygiene》2003,68(6):728-733
Antibody-mediated inhibition of Plasmodium falciparum parasites in vitro reflects the potential parasite-neutralizing activity of the antibodies in vivo. In this study, immunoglobulins and P. falciparum isolates were collected from children with asymptomatic malaria in Burkina Faso. We demonstrate a significantly lower in vitro growth inhibitory activity against the P. falciparum field isolates by autologous host immunoglobulin compared with that of immunoglobulin from other individuals. To gain further insight to possible mechanisms for the diverse sensitivity observed, analyses of consecutive isolates taken 14 days apart were performed with regard to polymerase chain reaction-based genotyping and sensitivity to growth inhibition in vitro. All the asymptomatic infections were composed of multiple, genotypically distinct parasite clones, and at least one new parasite clone appeared in most of the day 14 isolates compared with the corresponding day 0 isolates. Apparently persisting parasite clones, present in both the day 0 and day 14 isolates from the same person, were also frequently observed. The day 14 isolates were more effectively inhibited by autologous day 14 immunoglobulin than by the corresponding day 0 immunoglobulin in 57% of the cases. However, the frequent presence of persisting parasite clones in asymptomatic children indicates that the parasite may develop a relative resistance to neutralizing immune responses. 相似文献
82.
Purpose The use of transanal endoscopic microsurgery for local excision of rectal cancer has recently gained wide acceptance as a
valid and safe alternative for the surgical treatment of T1 tumors. The adequacy of such treatment for T2 tumors, however,
is still controversial. This study was designed to evaluate our results with local excision of T2 cancers.
Methods Patients with T2 cancer admitted to our hospital between 1995 and 2005 were offered surgery by transanal endoscopic microsurgery
if found medically unfit or were unwilling to undergo radical surgery. Patients who were preoperatively staged as T1 tumor
but were found to be pathologically T2 also were included.
Results Overall, we performed 59 transanal endoscopic microsurgery operations for rectal cancers, of which 21 were for T2 cancers.
In 16 (76 percent) of the T2 patients, the tumors were completely removed with clear margins by transanal endoscopic microsurgery
and no additional surgery was performed, except for 2 patients who developed radiation-induced complications. Radical surgery
was performed in a second operation in five patients because of involved margins and residual disease was found in two. At
a median follow-up of three years, all 12 patients who received local excision and radiotherapy remained disease free, whereas
a 50 percent recurrence rate was observed in patients who refused adjuvant radiotherapy.
Conclusions The results of this study support the feasibility of transanal endoscopic microsurgery for the treatment of selected patients
with T2 rectal cancer. The addition of radiotherapy may decrease the rates of early local recurrence. However, at present,
this treatment strategy should not be routinely considered for patients who may undergo radical procedures. 相似文献
83.
Jennifer M. Lynch Erin M. Buckley Peter J. Schwab Ann L. McCarthy Madeline E. Winters David R. Busch Rui Xiao Donna A. Goff Susan C. Nicolson Lisa M. Montenegro Stephanie Fuller J. William Gaynor Thomas L. Spray Arjun G. Yodh Maryam Y. Naim Daniel J. Licht 《The Journal of thoracic and cardiovascular surgery》2014
84.
85.
Naim Alkhouri Michael Berk Lisa Yerian Rocio Lopez Yoon-Mi Chung Renliang Zhang Thomas M. McIntyre Ariel E. Feldstein Stanley L. Hazen 《Digestive diseases and sciences》2014,59(7):1617-1624
Background and Aim
Oxidative stress is a core abnormality responsible for disease progression in nonalcoholic fatty liver disease (NAFLD). By employing a highly sensitive liquid chromatography–tandem mass spectrometry (LC/MS/MS) approach we recently were able to define the circulating profile of bioactive lipid peroxidation products characteristic of patients with nonalcoholic steatohepatitis (NASH) and developed the OxNASH score for NASH diagnosis. The aims of this study were to assess the utility of OxNASH as a predictor of NASH and study the association between OxNASH and specific histologic features of NAFLD.Methods
Our cohort consisted of 122 patients undergoing liver biopsy for clinical suspicion of NAFLD. The NAFLD activity score (NAS) was calculated for each patient. Levels of fatty acid oxidation products were quantified using stable isotope dilution LC/MS/MS, and OxNASH was calculated.Results
The mean age of our patients was 49.3 (±11.6) years, and the mean body mass index was 31.5 (±4.8) kg/m2. The majority of patients were Caucasian (82 %) and 48 % were female. OxNASH correlated with NAS and with the individual histologic features of NAFLD, namely, steatosis, inflammation, and ballooning (P < 0.05), with the strongest association being with inflammation [rho (ρ) 0.40, 95 % confidence interval 0.23, 0.57, P < 0.001]. There was also a correlation between the stage of fibrosis and OxNASH (P = 0.001). These associations remained statistically significant after adjustment for multiple confounders.Conclusions
Based on our results, in adult patients with NAFLD, OxNASH correlates with histologic features of NASH and appears to be a promising noninvasive marker. 相似文献86.
87.
Jeff N. Borchert Jordan W. Tappero Robert Downing Trevor Shoemaker Prosper Behumbiize Jane Aceng Issa Makumbi Melissa Dahlke Bassam Jarrar Briana Lozano Sam Kasozi Mark Austin Dru Phillippe Ian D. Watson Tom J. Evans Timothy Stotish Scott F. Dowell Michael F. Iademarco Raymond Ransom Arunmozhi Balajee Kristin Becknell Denise Beauvais Tadesse Wuhib 《MMWR. Morbidity and mortality weekly report》2014,63(4):73-76
88.
Sébastien Brot Hinda Smaoune Mina Youssef‐Issa Céline Malleval Claire Benetollo Roger Besançon Carole Auger Mahnaz Moradi‐Améli Jérôme Honnorat 《The European journal of neuroscience》2014,40(7):3010-3020
The collapsin response‐mediator proteins (CRMPs) are multifunctional proteins highly expressed during brain development but down‐regulated in the adult brain. They are involved in axon guidance and neurite outgrowth signalling. Among these, the intensively studied CRMP2 has been identified as an important actor in axon outgrowth, this activity being correlated with the reorganisation of cytoskeletal proteins via the phosphorylation state of CRMP2. Another member, CRMP5, restricts the growth‐promotional effects of CRMP2 by inhibiting dendrite outgrowth at early developmental stages. This inhibition occurs when CRMP5 binds to tubulin and the microtubule‐associated protein MAP2, but the role of CRMP5 phosphorylation is still unknown. Here, we have studied the role of CRMP5 phosphorylation by mutational analysis. Using non‐phosphorylatable truncated constructs of CRMP5 we have demonstrated that, among the four previously identified CRMP5 phosphorylation sites (T509, T514, T516 and S534), only the phosphorylation at T516 residue was needed for neurite outgrowth inhibition in PC12 cells and in cultured C57BL/6J mouse hippocampal neurons. Indeed, the expression of the CRMP5 non‐phosphorylated form induced a loss of function of CRMP5 and the mutant mimicking the phosphorylated form induced the growth inhibition function seen in wildtype CRMP5. The T516 phosphorylation was achieved by the glycogen synthase kinase‐3β (GSK‐3β), which can phosphorylate the wildtype protein but not the non‐phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin‐binding property of CRMP5. Therefore, CRMP5‐induced growth inhibition is dependent on T516 phosphorylation through the GSK‐3β pathway. The findings provide new insights into the mechanisms underlying neurite outgrowth. 相似文献
89.
90.
Tawfiq Froukh Omar Nafie Sana' A. S. Al Hait Lucia Laugwitz Julia Sommerfeld Marc Sturm Aya Baraghiti Tala Issa Anis Al-Nazer Philipp A. Koch Johannes Hanselmann Beate Kootz Peter Bauer Wael Al-Ameri Rami Abou Jamra Ayman J. Alfrook Moath Hamadallah Linda Sofan Angelika Riess Tobias B. Haack Olaf Riess Rebecca Buchert 《Clinical genetics》2020,97(4):621-627
We recruited 103 families from Jordan with neurodevelopmental disorders (NDD) and patterns of inheritance mostly suggestive of autosomal recessive inheritance. In each family, we investigated at least one affected individual using exome sequencing and an in-house diagnostic variant interpretation pipeline including a search for copy number variation. This approach led us to identify the likely molecular defect in established disease genes in 37 families. We could identify 25 pathogenic nonsense and 11 missense variants as well as 3 pathogenic copy number variants and 1 repeat expansion. Notably, 11 of the disease-causal variants occurred de novo. In addition, we prioritized a homozygous frameshift variant in PUS3 in two sisters with intellectual disability. To our knowledge, PUS3 has been postulated only recently as a candidate disease gene for intellectual disability in a single family with three affected siblings. Our findings provide additional evidence to establish loss of PUS3 function as a cause of intellectual disability. 相似文献