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51.
T-maze learning, spontaneous activity and food intake recovery following systemic administration of the noradrenaline neurotoxin, DSP4 总被引:4,自引:0,他引:4
Trevor Archer Abdul K. Mohammed Svante B. Ross Ulf Söderberg 《Pharmacology, biochemistry, and behavior》1983,19(1):121-130
Following systemic administration of the noradrenaline (NA) neurotoxin, DSP4 (50 mg/kg), rats were found to be retarded in the rate at which they acquired the "right-turn" running response in a modified T-maze choice situation, as measured by the total number of errors per session and median latency to reach the goal box. Desipramine (DMI, 20 mg/kg), injected 30 min before DSP4 blocked the acquisition retardation. DSP4 was found to have a short-lasting effect upon spontaneous motor activity, while food and water intake recovery was complete within 7 days of the injection. Both the NA-accumulation data and endogenous NA concentrations indicated profound NA, but not 5-hydroxytryptamine (5-HT) and dopamine (DA), depletions in the cortex, hippocampus and cerebellum. These data seem to confirm the role of the locus coeruleus-noradrenaline (LC-NA) system in an instrumental learning situation. 相似文献
52.
53.
Neil E Martin Thomas B Brunner Krystina D Kiel Thomas F DeLaney William F Regine Mohammed Mohiuddin Ernest F Rosato Daniel G Haller James P Stevenson Debbie Smith Barnali Pramanik Joel Tepper Wesley K Tanaka Briggs Morrison Paul Deutsch Anjali K Gupta Ruth J Muschel W Gillies McKenna Eric J Bernhard Stephen M Hahn 《Clinical cancer research》2004,10(16):5447-5454
PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed. 相似文献
54.
Carl Morrison Michael Radmacher Nehad Mohammed David Suster Herbert Auer Susie Jones Judy Riggenbach Nicole Kelbick Gary Bos Joel Mayerson 《Journal of clinical oncology》2005,23(36):9369-9376
PURPOSE: To identify recurrent regions of genomic gain or loss in chondrosarcoma in a clinically relevant and statistically valid fashion. Materials and METHODS: Array comparative genomic hybridization (CGH) results of 15 frozen tumor samples of high-grade chondrosarcoma for chromosome 8 are presented. A separate subset of 116 cartilaginous tumors with outcome data was used for validation. RESULTS: Array CGH identified gain at 8q24.12-q24.13, the region of the MYC (c-Myc) oncogene, as a frequent change in high-grade chondrosarcoma. In the validation arm of 116 cartilaginous tumors, MYC was frequently amplified in G2 (15%), G3 (20%), and dedifferentiated (21%) chondrosarcomas. No amplification was identified in samples of enchondroma and grade 1 chondrosarcoma. In samples without MYC amplification, polysomy 8 was a frequent finding in grade 1 (18%), grade 2 (31%), grade 3 (80%), and dedifferentiated (29%) chondrosarcomas, but was not found in any samples of enchondroma. MYC protein expression was identified in all samples with amplification, but was also frequent in the remaining samples without amplification or polysomy 8. Kaplan-Meier survival curves for overall survival showed a statistically significant difference for patients with MYC amplification or polysomy 8 (P = .034). Univariate analysis involving Cox proportional hazards models showed that grade (P = .003), polysomy 8 (P = .045), and MYC amplification (P = .053) correlated with shorter overall survival. By multivariate analysis, grade of chondrosarcoma (P = .026) was the only factor to reach statistical significance. CONCLUSION: MYC amplification and polysomy 8 can be used as markers of prognostic importance in chondrosarcoma. Molecular targeting of MYC expression may have therapeutic potential in the future for subsets of chondrosarcoma. 相似文献
55.
WBG Macdonald AP Patrikeos RI Thompson BD Adler AA Van Der Schaaf 《Journal of Medical Imaging and Radiation Oncology》2005,49(1):32-38
The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses. 相似文献
56.
Jamal M. Arif Mohammed Kunhi Yunus M. Siddiqui Khalid A. El Sayed Khaled Y. Orabi Amal Al-Hazzani Mohammed N. Al-Ahdal Fahad M. Al-Khodairy 《Medicinal chemistry research》2004,13(6-7):553-562
In the present study, two of the probable an umor marine compounds, manzamine A and sarcophine, were screened using benzo[a]pyrene (BP)-derived DNA adduct formation in MCF-7 cells as intermediary biomarker. Briefly, MCF-7 cells were treated with
the compounds for 24 h followed by treatment with BP (0.5 μM). After 24h incubation, cellular DNA was isolated and analyzed
for BP-derived DNA adducts by 32P-postlabeling technique. Manzamine A and sarcophine increased the BP-DNA adducts by 2 to 4-folds. Further, manzamine A (50
μM) substantially down regulated the expression of p53 while sarcophine (50 μM) slightly induced the level of p21. The residual
DNA repair ability was almost completely abolished by manzamine A while sarcophine was ineffective. Based on our preliminary
results, these compounds may be classified as potential genotoxic. 相似文献
57.
Anood Alassaf Khaled Ellithy Tejas Mehta Walid Aljbawi Hossamaldein Ali Ashraf Soliman Mohammed Al Amri Abdulqadir J. Nashwan 《Clinical Case Reports》2022,10(8)
Our patient is a 3‐week‐old female neonate, presented with complaints of low‐grade fever and a congested nose for one day. Eventually, she developed progressive desaturation, hypotension, and poor perfusion due to severe pulmonary hemorrhage. Then, she developed cardiac arrest and was declared dead. 相似文献
58.
Aeshah Ibrahim Alhosain Ghedeir M. Alshammari Barakat Lafi Almoteri Mohammed A. Mohammed Manal Abdulaziz Binobead Mohammed Abdo Yahya 《Nutrients》2022,14(10)
This cross-sectional study examines the influence of long-term gluten-free diet (GFD) consumption on nutritional status, body composition, and associated factors in adult Saudi females with celiac diseases (CD). Fifty-one patients who have been diagnosed with CD and have been on GFD for more than 1 year were included in this study where data regarding their dietary pattern, as well as a complete analysis of their anthropometric parameters, vitamins B12 and D levels, and complete blood count (CBC), were collected. Data have shown that all included patients showed a reduced intake in all micro and macro-nutrients, as well as vitamin D, folate, calcium, and iron. However, the vast majority of all measured hematological parameters and blood indices were within the expected reference range. In addition, 51%, 43.1%, and 60.8% of the patients showed low waist/hip ratio (WHR), decreased level of total body fat (BF), and decreased level of visceral fat (VF), respectively, whereas 33.3% were slim. The poor educational level and some psychosocial factors were associated with the poor nutritional status of the patients. In conclusion, the GFD-dependent intake by female patients with CD adversely affects their nutritional intake and anthropometric indices and leads to a deficiency in major nutrients, vitamins, and ions. 相似文献
59.
Zuhier A. Awan Shareefa A. AlGhamdi Nabil A. Alhakamy Solomon Z. Okbazghi Mohamed A. Alfaleh Shaimaa M. Badr-Eldin Hibah M. Aldawsari Mohammed A. S. Abourehab Hani Z. Asfour Shadi A. Zakai Mohammad W. Alrabia Aya A. Negm Mohamed A. El-Moselhy Sara S. Sharkawi Waleed Y. Rizg 《Drug delivery》2022,29(1):1536
Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC50 of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC50 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses. 相似文献
60.
Granular materials are widespread in nature and human production, and their macro-mechanical behavior is significantly affected by granule movement. The development of computer vision has brought some new ideas for measuring the numerical information (including the amount of translation, the rotation angle, velocity, acceleration, etc.) of dynamic granular materials. In this paper, we propose a numerical measurement method for dynamic granular materials based on computer vision. Firstly, an improved video instance segmentation (VIS) network is introduced to perform end-to-end multi-task learning, and its temporal feature fusion module and tracking head with long-sequence external memory can improve the problems of poor video data quality and high similarity in appearance of granular materials, respectively. Secondly, the numerical information can be extracted through a series of post-processing steps. Finally, the effectiveness of the measurement method is verified by comparing the numerical measurement results with the real values. The experimental results indicate that our improved VIS obtains an average precision (AP) of 76.6, the relative errors and standard deviations are maintained at a low level, and this method can effectively be used to measure the numerical information of dynamic granular materials. This study provides an intelligent proposal for the task of measuring numerical information of dynamic granular materials, which is of great significance for studying the spatial distribution, motion mode and macro-mechanical behavior of granular materials. 相似文献