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1.
O6-Alkylguanine--DNA alkyltransferase (AGT) is a protein which removes the promutagenic O6-alkylguanine lesion induced in DNA by alkylating agents. Our results demonstrate that freshly isolated organoids from reduction mammoplasty specimens contain significant levels of AGT activity. AGT activity in breast epithelial cells shows interindividual variation. Constitutive levels of AGT activity remain unchanged during short-term serum-free culture of breast epithelial cells inside three-dimensional rat-tail collagen gel matrix. In the present study, we optimized conditions for depleting AGT activity in human breast epithelial cells cultured in three-dimensional collagen gel matrix using O6-methylguanine and O6-benzylguanine which are substrates for AGT. AGT activity was efficiently inactivated by exposure of cells to O6-methylguanine or O6-benzylguanine. Inactivation with O6-benzylguanine was more rapid, of greater magnitude and consistency and occurred at lower concentrations than with O6-methylguanine. Near-complete inactivation (> 99.5%) of AGT activity was reproducibly achieved with 50 microM O6-benzylguanine. In contrast, 500 microM O6-methylguanine was needed to obtain a maximal effect and this reduced AGT activity by only 53-93% of control. Within 30 min of adding the free base, 50 microM O6-benzylguanine depleted 95% of the levels of AGT compared to 30% inhibition with 500 microM O6-methylguanine. The profile for restoration of AGT activity was different following a 24 h incubation and subsequent removal of each of the guanine derivatives. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6-benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6-benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. In contrast, following removal of 500 microM O6-methylguanine, the activity was restored from its nadir of 16% of control values reaching pretreatment levels after 5 days. These results suggest that treatment with O6-benzylguanine may be used to modulate the incidence of transforming mutations in cultured human breast epithelial cells treated with chemical carcinogens which give rise to O6-alkylguanine adducts. 相似文献
2.
E. Kimble T. Kowalski D. White A. Raychauduri G. Pastor H. Chertock W. Lee R. Neale A. Hamdan J. Wasley 《Inflammation research》1991,34(1-2):125-128
CGS 22745, and aralkyl hydroxamic acid, inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4) synthesis in guinea pig leukocytes (IC50=0.6M). The compound did not appreciably affect cyclooxygenase (ram seminal vesicles), 12-lipoxygenase and thromboxane synthase (human platelets) or 15-lipoxygenase (human neutrophils). CGS 22745 inhibited A23187-induced formation of LTB4 in blood (IC50's of 4.3, 0.56 and 3.2 M for human, dog and rat, respectively). At 1 mg/kg i.v. in dogs, it caused 96% inhibition of A23187-stimulated LTB4 formationex vivo after 5 min. Its effective biological half-life was >160 min. In dogs at 3 and 10 mg/kg p.o., CGS 22745 inhibitedex vivo A23187-stimulated LTB4 formation at 3 hr by 48% and 97%, respectively. The inhibition persisted up to 6 hr (26% at 3 mg/kg; 49% at 10 mg/kg). CGS 22745 (3, 10 and 30 mg/kg p.o.) inhibited exudate formation, mononuclear cells and PMN accumulation in a dose-dependent manner during the late phase (48 and 72 hr) of carrageenan-induced pleurisy in the rat. 相似文献
3.
Kadri Oumaima Karmous Inès Kharbech Oussama Arfaoui Hiba Chaoui Abdelilah 《Bulletin of environmental contamination and toxicology》2022,108(3):585-593
Bulletin of Environmental Contamination and Toxicology - The application of Cu and CuO nanofertilizers in horticulture has been a promising strategy to promote plants’ growth. In our study,... 相似文献
4.
Calculi from 45 Moroccan children aged between 2 and 15 years underwent morphological and infrared spectrometric analysis. The stones were three times more frequent in males than females (M/F = 3.09). Whewellite was the main component in 51.1% of cases and in 44.4% of stone nuclei, wheddellite in 8.9% of stones and nuclei, carbapatite in 6.7% of stones and 8.9% of nuclei, struvite in 15.6% of stones and 11.1% of nuclei. Ammonium hydrogen urate and uric acid were predominant respectively in 8.9% and 6.7% of stones and in 15.6% and 11.1% of nuclei. In addition to whewellite, struvite and ammonium hydrogen urate were the main components of bladder stones from both sexes. With respect to their calculi, whewellite was present in 84.4% of cases and wheddellite in 26.7%. Purines were present in 46% of calculi, especially as ammonium urate (28.9%) and uric acid (15.6%). Calcium phosphates as the main components were infrequent. In contrast, they were frequently identified in urinary calculi from children, respectively 64.4% and 40% for carbapatite and amorphous carbonated calcium phosphate. 相似文献
5.
Frequency and outcome of pediatric acute lymphoblastic leukemia with ZNF384 gene rearrangements including a novel translocation resulting in an ARID1B/ZNF384 gene fusion 下载免费PDF全文
Mary Shago Oussama Abla Johann Hitzler Sheila Weitzman Mohamed Abdelhaleem 《Pediatric blood & cancer》2016,63(11):1915-1921
6.
Hypophosphatemic rickets/osteomalacia in linear sebaceous nevus syndrome: a variant of tumor-induced osteomalacia 总被引:1,自引:0,他引:1
D E Carey M K Drezner J A Hamdan M Mange M S Ahmad S Mubarak W L Nyhan 《The Journal of pediatrics》1986,109(6):994-1000
A severe form of vitamin D-resistant rickets is associated with the linear sebaceous nevus syndrome. We investigated the pathophysiology underlying defective bone mineralization in two individuals and examined the effects of 1,25-dihydroxyvitamin D (1,25(OH)2D, calcitriol) therapy on the clinical and biochemical abnormalities. Both patients had fasting hypophosphatemia, markedly diminished TmP/GFR, and elevated alkaline phosphase activity in the presence of normocalcemia. Before treatment with calcitriol, serum 1,25(OH)2D concentrations were reduced but serum 25-hydroxyvitamin D (25(OH)D) concentrations were normal. Administration of calcitriol increased serum 1,25(OH)2D concentrations and led to an increase in TmP/GFR and serum phosphorus levels and to a decrease in alkaline phosphatase activity. However, the renal tubular maximum for reabsorption of inorganic phosphate, normalized according to glomerular filtration rate, and serum phosphorus levels remained abnormally low even in the patient who also received phosphate supplementation. Bone histomorphologic studies in the adult patient showed extreme osteomalacia, which partially improved with calcitriol. These data demonstrate that the putative skin lesion-derived factor results in both a renal tubular defect in phosphate reabsorption and in 1,25-(OH)2 D deficiency. The vitamin D-resistant rickets of linear sebaceous nevus syndrome is a variant of tumor-induced osteomalacia. 相似文献
7.
E. Jason Abel R. Houston Thompson Vitaly Margulis Jennifer E. Heckman Megan M. Merril Oussama M. Darwish Laura-Maria Krabbe Stephen A. Boorjian Bradley C. Leibovich Christopher G. Wood 《European urology》2014
Background
Surgery for renal cell carcinoma (RCC) patients with inferior vena cava (IVC) thrombus above the hepatic veins is technically complex and associated with an increased risk of perioperative morbidity and mortality. However, minimal data exist that describe contemporary perioperative outcomes at major referral centers or the prognostic factors associated with poor outcomes.Objective
To determine the preoperative predictors of major complications and 90-d mortality after surgery in RCC patients who have IVC thrombus above the hepatic veins.Design, setting, and participants
We reviewed medical records of all RCC patients who had IVC tumor thrombus above hepatic veins and had had surgery between January 2000 and December 2012 at the Mayo Clinic, M.D. Anderson Cancer Center, University of Texas Southwestern Medical Center, and the University of Wisconsin Hospital.Outcome measurement and statistical analysis
Major complications recorded were defined as ≥3A according to the Clavien-Dindo system within 90 d of surgery. Univariate and multivariate analyses were used to evaluate associations of preoperative variables with risk of major complications or 90-d mortality.Results and limitations
A total of 162 patients were identified for study (level 3, 4 in 69, 93 patients, respectively, according to the Neves classification). Cardiopulmonary bypass was used in 60 of 162 patients (37.5%), and 40 patients (24.7%) had preoperative angioembolization. Major complications were reported in 55 patients (34.0%), with the most common being respiratory, cardiac, and hematologic issues. After multivariate analysis, preoperative systemic symptoms and level 4 thrombus were independently associated with increased risk of major complications. Mortality was reported in 17 patients (10.5%) within 90 d after surgery. After multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and low serum albumin were preoperative factors independently associated with increased risk of 90-d mortality.Conclusions
Contemporary perioperative mortality and major complication rates for RCC patients who have upper-level thrombus are 10% and 34%, respectively. Patients who have ECOG PS >1 or low serum albumin have increased risk for perioperative mortality. 相似文献8.
Righab Hamdan Ricardo Garcia Gonzalez Christophe Caussin Said Ghostine 《Cardiovascular Revascularization Medicine》2012,13(3):202.e5-202.e6
We report the case of a young female with embolic myocardial infarction. The embolic etiology was confirmed by Fourier Domain Optical Coherence Tomography as well as histo-pathology. 相似文献
9.
To look at the prevalence of phonatory symptoms in patients with type 2 diabetes mellitus. The correlation between these symptoms with duration of the disease, glycemic control, and neuropathy will be described. A total of 105 consecutive patients diagnosed with type 2 diabetes mellitus by their primary endocrinologist were evaluated. A control group consisting of 33 healthy subjects was recruited for this study. Demographic data included: age, gender, allergy, smoking, duration of the disease, glycemic control, and presence or absence of neuropathy. Subjects were also asked about the presence or absence of the following symptoms: hoarseness, vocal tiring or fatigue, vocal straining, and aphonia or complete loss of voice. Patients were also asked to fill out the Voice Handicap Index 10. The mean age of patients with diabetes was 53.21 + 9.68 years with male-to-female ratio of 2/3. The most common phonatory symptoms were vocal tiring or fatigue and hoarseness (34.3 and 33.3 %). There was a significant difference in the prevalence of hoarseness and vocal straining (p value 0.045 and 0.015, respectively) compared to controls. There was a significant correlation between glycemic control, neuropathy, and hoarseness (p value 0.030 and 0.001, respectively). Vocal straining and aphonia also correlated significantly with the presence of neuropathy. Close to 16 % of diabetic patients had a VHI-10 above or equal to 7. Diabetic patients are more likely to have phonatory symptoms compared to controls, namely straining and hoarseness. One out of seven patients with diabetes has reported that phonatory symptoms had a significant impact on their quality of life. The presence of neuropathy and poor glycemic control should alert the treating physician to these vocal complaints. 相似文献
10.
Hoi-Poh Tee Crispin Corte Hamdan Al-Ghamdi Emilia Prakoso John Darke Raman Chettiar Wassim Rahman Scott Davison Sean P Griffin Warwick S Selby Arthur J Kaffes 《World journal of gastroenterology : WJG》2010,16(31):3905-3910
AIM: To study the significance of cap-fitted colonoscopy in improving cecal intubation time and polyp detection rate. METHODS: This study was a prospective randomized controlled trial conducted from March 2008 to February 2009 in a tertiary referral hospital at Sydney. The primary end point was cecal intubation time and the secondary endpoint was polyp detection rate. Consecutive cases of total colonoscopy over a 1-year period were recruited. Randomization into either standard colonoscopy (SC) or cap-assist... 相似文献