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101.
102.
This report describes the intracellular metabolism of 5-methyltetrahydrofolate (5-methyl-H4PteGlu) and 5-formyltetrahydrofolate (5-formyl-H4PteGlu) to the various folate forms and their respective polyglutamated states in the MCF-7 human breast-cancer cell line. The intracellular folate distribution observed in MCF-7 cells treated with 5-methyl-H4PteGlu was similar to that seen in cells treated with 5-formyl-H4PteGlu. In cells exposed to 5-formyl-H4PteGlu for 24 h, the folate pool consisted of 103±10 pmol/mg 10-formyl-H4PteGlu, 120±18 pmol/mg H4PteGlu, and 71±18 pmol/mg 5-methyl-H4PteGlu versus 88±5, 54±20 and 87±10 pmol/mg, respectively, for cells exposed to 5-methyl-H4PteGlu. Only the difference seen in H4PteGlu levels between cells exposed to either 5-methyl-H4PteGlu or 5-formyl-H4PteGlu reached statistical significance (P<0.05). In the absence of vitamin B12, exposure to 5-methyl-H4PteGlu resulted in 154±17 pmol/mg 5-methyl-H4PteGlu along with only 8±5 pmol/mg 10-formyl-H4PteGlu and 4±2 pmol/mg H4PteGlu, thus demonstrating the marked dependence on vitamin B12 for the metabolism of 5-methyl-H4PteGlu to the other intracellular folates. 5–10-Methylene-H4PteGlu (2±1.3 pmol/mg) was detected only in cells exposed to 5-formyl-H4PteGlu for 24 h, not in cells treated with 5-methyl-H4PteGlu. The profile of polyglutamates detected in cells treated with either 5-formyl-H4PteGlu or 5-methyl-H4PteGlu for 24 h was not significantly different, although cells treated with 5-methyl-H4PteGlu tended to have less conversion to the higher polyglutamates (Glu3–Glu5) as compared with those treated with 5-formyl-H4PteGlu. In 5-methyl-H4PteGlu-treated cells grown in the absence of vitamin B12, the pentaglutamate was the only polyglutamate form detected, accounting for only 11% of the total folate pool. Since there does not appear to be a greater formation of the optimal reduced-folate forms necessary to achieve enhanced thymidylate synthase (TS) inhibition through ternary-complex formation in cells exposed to 5-methyl-H4PteGlu versus 5-formyl-H4PteGlu, these studies suggest that the use of 5-methyl-H4PteGlu would not be advantageous over that of 5-formyl-H4PteGlu in combination regimens with the fluoropyrimidines. 相似文献
103.
Cryptorchidism in meningomyelocele 总被引:1,自引:0,他引:1
104.
Rationale: There are increasing reports of sex differences in the etiology of drug abuse in humans. A nonhuman primate model is useful
for examining sex as a variable in drug abuse. Objectives: To determine whether there are sex differences in the acquisition of oral phencyclidine (PCP) self-administration and to
compare the effect of altered feeding conditions on drug self-administration in male and female monkeys. Methods: Acquisition of orally delivered PCP was studied using 7 female and 11 male adult rhesus monkeys. Initially, the monkeys were
not food restricted, and they were given access to water under concurrent fixed-ratio (FR) 1 schedules during daily 3-h sessions.
Each lip-contact response on a drinking spout resulted in a 0.3 ml liquid delivery. After baseline levels of water intake
were obtained for 5 days, water was replaced with PCP (0.125 mg/ml) at both drinking spouts. Body weights were then reduced
to 85% of free-feeding weights, and the monkeys were fed 30 min before the session began. The FR value was increased from
1 to 2, 4, and 8, at both drinking spouts. As a final step in the procedure, water and PCP were concurrently available at
the two spouts under FR 8 schedules. Acquisition of PCP-reinforced behavior was considered to have occurred if PCP intake
was consistently greater than water intake. Results: Lip-contact responses and liquid deliveries were not significantly different between the females and males throughout the
acquisition period, but there was a significant increase in responding and decrease in liquid intake as FR increased, and
a significant increase in PCP consumption due to food restriction that did not differ in males and females. On a milligram
per kilogram basis, female monkeys consumed nearly twice as much PCP as the males; however, this effect was not significant.
The females showed significantly higher PCP than water intake while the males consumed approximately equal amounts of PCP
and water. Of the seven females, 100% met the acquisition criterion of significantly greater PCP than water intake, while
only 36.4% of the males met the criterion. Conclusion: These results concur with previous rat studies and indicate that female monkeys are more likely than males to acquire drug-reinforced
behavior.
Received: 4 October 1999 / Final version: 20 January 2000 相似文献
105.
Incisional hernia 总被引:3,自引:0,他引:3
Voeller GR Ramshaw B Park AE Heniford BT 《Journal of the American College of Surgeons》1999,189(6):635-637
106.
Pilot study on gastric electrical stimulation on surgery-associated gastroparesis: long-term outcome
Oubre B Luo J Al-Juburi A Voeller G Familoni B Abell TL 《Southern medical journal》2005,98(7):693-697
OBJECTIVES: Patients with postgastric surgery gastroparesis are often unresponsive to conventional medical therapy. Gastric electrical stimulation (GES) with the use of high-frequency and low-energy neural stimulation is an approved technique for patients with idiopathic and diabetic gastroparesis. METHODS: We hypothesized that GES would improve symptoms, health resource utilization, and gastric emptying in six patients with postsurgical gastroparesis from a variety of surgical procedures. Patients were evaluated by means of the following criteria: symptoms, health-related quality of life, and gastric emptying tests at baseline over time. RESULTS: All patients noted improvements after device implantation for up to 46 months: the frequency score for weekly vomiting went from a baseline of 3.2 down to 0.4 immediately after treatment before settling at 1.4 by the long-term follow up. Total gastrointestinal symptom score went from 36.5 at baseline down to 12.3 before settling at 20.5 at long-term follow up. Improvements were also seen in health-related quality of life and solid and liquid gastric emptying. CONCLUSIONS: We conclude that GES is associated with clinical improvements in this group of patients with either postsurgical or surgery-associated gastroparesis. This pilot study with long-term outcomes offers evidence for a new therapy for otherwise refractory patients with gastroparesis associated with previous surgery. 相似文献
107.
R Krempien MW Muenter PE Huber S Nill H Friess C Timke B Didinger P Buechler S Heeger KK Herfarth A Abdollahi MW Buchler J Debus 《BMC cancer》2005,5(1):1-11
Background
Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR.Methods/design
The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrolment.Discussion
The primary objective of this study is to evaluate the feasibility and the toxicity profile of trimodal therapy in pancreatic adenocarcinoma with chemoradiation therapy with gemcitabine and intensity modulated radiation therapy (IMRT) and EGFR-targeted therapy using cetuximab and to compare between two different methods of cetuximab treatment schedules (concomitant versus concomitant and sequential cetuximab treatment). Secondary objectives are to determine the role and the mechanism of cetuximab in patient's chemoradiation regimen, the response rate, the potential of this combined modality treatment to concert locally advanced lesions to potentially resectable lesions, the time to progression interval and the quality of life. 相似文献108.
Gadolinium enhanced Magnetic Resonance Imaging (MRI) for the evaluation of the post operative lumbo-sacral spine is a sensitive and specific imaging technique. A need for establishing a specific protocol for Failed Back Surgery Syndrome (FBSS) for use in the service hospitals is highlighted for convenience of patient management and preservation of active manpower. The MR scan of 50 patients performed over a span of six months, who complained of persistent low backache even after surgery, were retrospectively analysed. The specificity of this series using MRI in indicating the exact cause of FBSS was clocked at only 30%. The conditions diagnosed were rectifiable. The balance of the patients who could not be offered any specific diagnosis towards the cause, were being managed conservatively / placed in low medical category for a considerable period. It was noted with concern that there was non prevalence of sequence like the fast spin echo with gadolinium enhancement as a routine.KEY WORDS: Gadolinium, Magnetic Resonance Imaging, Post-operative spine 相似文献
109.
Lau EMC; Cooper C; Fung H; Lam D; Tsang KK 《Journal of public health (Oxford, England)》1999,21(3):249-250
110.
4-S-(5″-烃基-4″-氨基-1″,2″,4″-三唑-3″-基)-4-去氧-4′-去甲基表鬼臼毒素衍生物的合成及抗肿瘤活性 总被引:1,自引:0,他引:1
许多有显著抗肿瘤活性的鬼臼毒素类化合物,其母核C-4侧链上往往连接有刚性较强的脂环或芳香环结构,而且侧链多含有一定数量的杂原子[1~3]。另外,三氮唑类化合物大都有广泛的生物活性,如抗菌[4~5]、抗病毒[6]、抗肿瘤[7]等,据此,我们设计并合成了8个三氮唑杂环取代的表鬼臼毒素衍生物,以期寻找活性高、毒副作用小的鬼臼毒素类药物,并进一步考察此类化合物的构效关系。 合成路线如图1所示,三氮唑3a~3h和4′-去甲基-表鬼臼毒2分别按文献[8,9]方法合成;我们选择三氟乙酸作为缩合剂,基于它不仅能催化缩合反应,而且能保护三唑上的氨基官能团,使其不能充当进攻基团;最后一步缩合反应显然经历了一个SN1历程,4′-去甲基-表鬼臼毒
的C-4位上很容易形成一个苄基型碳正离子,由于C-1位有庞大的芳环,加之,进攻的基团也较大,可以预料,这个反应有很强的立体选择性,使C-4β-构型成为主要产物,事实确实如此,在TLC上几乎看不到C-4α-构型的产物。 相似文献