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1.
Mouse leukemic cell subline L1210/VCR exerts expressive multidrug resistance (MDR) that is mediated by P-glycoprotein. Cells originally adapted to vincristine are also extremely resistant to doxorubicin. Resistance to both vincristine and doxorubicin is connected with depression of drug uptake. While resistance of L1210 cells to vincristine could be reversed by verapamil as chemosensitizer, resistance of cells to doxorubicin was insensitive to verapamil. Action of verapamil (well-known inhibitor of PGP activity) on multidrug resistance was often used as evidence that MDR is mediated by PGP. From this point it may be possible that the resistance of L1210/VCR cells to vincristine is mediated by PGP and the resistance to doxorubicin is mediated by other PGP-independent system. Another and more probable explanation of different effect of verapamil on resistance of L1210/VCR cells to vincristine and doxorubicin may be deduced from the following fact: Using UV spectroscopy we found that doxorubicin dissolved in water buffered medium interacts effectively with verapamil. This interaction may be responsible for the decrease of concentration of both drugs in free effective form and consequently for higher survival of cells. In contrast to doxorubicin vincristine does not give any interaction with verapamil that is measurable by UV spectroscopy and resistance of L1210/VCR cells to vincristine may be fully reversed by verapamil.  相似文献   

2.
Bifunctional agent adipic dihydrate was used to form hydrazon bond between polyglutamic acid (PGA) and pharmorubicin (PAR). Under controlled condition, a relatively high rate of conjugation was obtained with no self-condensation. The value of PGA/PAR was in positive portion with the molecular weight (MW) of PGA: per 8-11 glutamic acid monomer linking one pharmorubicin. When PGA of MW 14,300 was used as carrier, the ratio of PGA/PAR was 1:11. After conjugating with anti-hepatoma monoclonal antiboty (McAb), an immunoconjugate of McAb:PGA:PAR being 1:2:22 was obtained. The immunoconjugate retained the binding activity to targeted cell compared with the purified and the oxidized antibody. Pharmacological studies in vitro showed lower cytotoxicity of the immunoconjugate than the free drug, but selective cytotoxicity directed by antibody was observed. Consequently, the immunoconjugate McAb-PGA-PAR with high ratio of drug/McAb as well as moderate targeting cytotoxity in vitro was successfully prepared. That makes it possible for the preparation of cell-targeted drug which is expected to be benificial to tumor treatment.  相似文献   

3.
Key pecking of two pigeons was maintained under a multiple schedule of food presentation. In the presence of one keylight stimulus responding produced food according to a fixed-interval 5-min schedule. Additionally, during this component, each 50th response produced electric shock. When a different keylight stimulus was present, key pecking resulted in food delivery under a variable-interval 3-min schedule. Responding was suppressed by shock presentation (punishment) but was still positively accelerated throughout each fixed-interval cycle; steady response rates occurred during the alternate component when only the variable-interval schedule was in effect. Overall rates of punished responding were largely unchanged with d-amphetamine (0.1-3.0 mg/kg); unpunished responding was generally either increased slightly or was decreased. Pentobarbital and chlordiazepoxide (1.0-17.0 mg/kg) administered alone increased both punished and unpunished responding at most doses. Combinations of d-amphetamine with either pentobarbital or chlordiazepoxide produced increases in punished responding that exceeded those obtained with either of these drugs alone. The combined effects of d-amphetamine and either pentobarbital or chlordiazepoxide on unpunished responding depended on the individual dose combinations. Combinations of d-amphetamine with pentobarbital or chlordiazepoxide produced effects on both punished and unpunished responding that differed substantially from those obtained when any of these drugs were administered separately.  相似文献   

4.
One of the presumed effects of ethanol is the suppression of acetylcholine release at presynaptic sites. If these neuronal effects are associated with CNS depression, then administration of a cholinesterase inhibitor (physostigmine) with ethanol should result in antagonism of this CNS depression. In the present study electrophysiological measures of sleep were used to assess the degree of CNS depression in response to ethanol alone (2.0 g/kg), physostigmine (1.0 mg/kg) alone, and the combination of both drugs administered together. These results were evaluated with respect to a saline control. Our findings indicate an antagonism between ethanol and physostigmine; the shortened sleep latency observed in animals receiving ethanol was reversed to control levels with administration of physostigmine.  相似文献   

5.
OBJECTIVES: The purpose of this prospective study was to evaluate the immediate results and the 6-month angiographic recurrent restenosis rate after balloon angioplasty for in-stent restenosis. BACKGROUND: Despite excellent immediate and mid-term results, 20% to 30% of patients with coronary stent implantation will present an angiographic restenosis and may require additional treatment. The optimal treatment for in-stent restenosis is still unclear. METHODS: Quantitative coronary angiography (QCA) analyses were performed before and after stent implantation, before and after balloon angioplasty for in-stent restenosis and on a 6-month systematic coronary angiogram to assess the recurrent angiographic restenosis rate. RESULTS: Balloon angioplasty was performed in 52 patients presenting in-stent restenosis. In-stent restenosis was either diffuse (> or =10 mm) inside the stent (71%) or focal (29%). Mean stent length was 16+/-7 mm. Balloon diameter of 2.98+/-0.37 mm and maximal inflation pressure of 10+/-3 atm were used for balloon angioplasty. Angiographic success rate was 100% without any complication. Acute gain was lower after balloon angioplasty for in-stent restenosis than after stent implantation: 1.19+/-0.60 mm vs. 1.75+/-0.68 mm (p=0.0002). At 6-month follow-up, 60% of patients were asymptomatic and no patient died. Eighteen patients (35%) had repeat target vessel revascularization. Angiographic restenosis rate was 54%. Recurrent restenosis rate was higher when in-stent restenosis was diffuse: 63% vs. 31% when focal, p=0.046. CONCLUSIONS: Although balloon angioplasty for in-stent restenosis can be safely and successfully performed, it leads to less immediate stenosis improvement than at time of stent implantation and carries a high recurrent angiographic restenosis rate at 6 months, in particular in diffuse in-stent restenosis lesions.  相似文献   

6.
OBJECTIVE: We examined whether the proliferative index of luteinized granulosa cells, as determined by flow cytometry, varied as a function of a woman's ovarian reserve, as reserve, as reflected by follicular-phase day 3 serum follicle-stimulating hormone. STUDY DESIGN: This prospective cohort study consisted of 19 women of similar chronologic age preparing for in vitro fertilization-embryo who met specific day 3 serum follicle-stimulating hormone criteria. The "low follicle-stimulating hormone" group consisted of 11 women with day 3 serum follicle-stimulating hormone levels < or = 6 IU/L. The "high follicle-stimulating hormone" group consisted of eight women with day 3 serum follicle-stimulating hormone levels > or = 18 IU/L. A total of 56 preovulatory follicles containing > or = 10(4) luteinized granulosa cells were examined by flow cytometry. The low follicle-stimulating hormone group was compared with the high follicle-stimulating hormone group to examine proliferative index as a function of serum day 3 follicle-stimulating hormone levels. RESULTS: The low follicle-stimulating hormone group had a greater proliferative index (11.1% +/- 0.4%) than did the high follicle-stimulating hormone group (8.3% +/- 0.6%), p < 0.001). This study demonstrates that in spite of the same chronologic age, luteinized granulosa cells from preovulatory follicles of women with day 3 serum follicle-stimulating hormone levels > or = 18 IU/L have a 25% decreased proliferative index compared with luteinized granulosa cells from women with day 3 serum follicle-stimulating hormone levels < or = 6. CONCLUSIONS: This suggests that granulosa cell proliferation is influenced by ovarian reserve and may explain in part the more favorable response to ovulation induction protocols that younger women demonstrate compared with women of more advanced reproductive age.  相似文献   

7.
Since its introduction, the multiple sleep latency test (MSLT) has played a major role in the diagnosis of narcolepsy. We assessed its diagnostic value in a series of 2,083 subjects of whom 170 (8.2%) were diagnosed with narcolepsy. The sensitivity of the combination of two or more sleep onset rapid eye movement (REM) periods (SOREMPs) with a mean sleep latency of < 5 minutes on an initial MSLT was 70% with a specificity of 97%, but 30% of all subjects with this combination of findings did not have narcolepsy. In some narcoleptics who had more than one MSLT, the proportion of naps with SOREMPs varied substantially from the initial MSLT to the follow-up test. The highest specificity (99.2%) and positive predictive value (PPV) (87%) for MSLT findings was obtained with the criteria of three or more SOREMPs combined with a mean sleep latency of < 5 minutes, but the sensitivity of this combination was only 46%. The combination of a SOREMP with a sleep latency < 10 minutes on polysomnography yielded a specificity (98.9%) and PPV (73%) almost equal to those obtained from combinations of MSLT findings, but the sensitivity was much lower. Our results suggest that the MSLT cannot be used in isolation to confirm or exclude narcolepsy, is indicated only in selected patients with excessive daytime sleepiness, and is most valuable when interpreted in conjunction with clinical findings.  相似文献   

8.
PURPOSE: This prospective study was undertaken to determine the incremental yield of combined abdominal and pelvic CT in searching for clinically suspected postoperative abscess in oncologic patients. METHOD: One hundred seventeen oncologic patients underwent CT to exclude a clinically suspected abscess within 30 days of abdominal or pelvic surgery during an 8 month period. Scans were evaluated for the presence of ascites, loculated fluid collections, or other possible sources of fever. The clinical course and any intervention in the abdomen or pelvis within 30 days after CT were recorded. RESULTS: After abdominal surgery, 44 of 69 [64%; confidence interval (CI) 51-75%] patients had loculated fluid collections in the abdomen; no patient (0%; CI 0-5%) had a loculated fluid collection present only in the pelvis. After pelvic surgery, 22 of 48 (46%; CI 31-61%) patients had loculated fluid collections in the pelvis; no patient (0%; CI 0-7%) had a loculated collection present only in the abdomen. Loculated collections were present in both the abdomen and the pelvis in 4 of 69 (6%; CI 1.6-14%) patients after abdominal surgery and 3 of 48 (6%; CI 1.3-17%) after pelvic surgery. CONCLUSION: Isolated pelvic abscesses after abdominal surgery and isolated abdominal abscesses after pelvic surgery appear to be very uncommon in oncologic patients. CT initially need be directed only to the region of surgery in this particular patient population.  相似文献   

9.
Mentation reports collected from sleep onset, Stage 2 and REM Stage awakenings, in the first part and in the second part of the night were analyzed both with systematic psycholinguistic and global measures. Results confirm the relationship between activation and the length of sleep mentation report shown by Antrobus. Length of the report increases with sleep time, but time does not modulate qualitative inter-stage differences. By partialling out the length of the report, many inter-stage differences disappeared; however significant differences remain in the global measure of bizarreness and in the psycholinguistic measure of visual imagery. These results cannot be explained entirely by differences in attention and memory and point to more basic differences in mental activity.  相似文献   

10.
The Computer Science Application (CSA) accelerometer uses integrated circuitry and memory to provide a continuous recording of minute-by-minute movement counts. It has been previously validated as an objective monitor of children's physical activity in field and laboratory settings. Our purpose was to derive accelerometry summary variables reflective of different physical activity intensity levels, evaluate the stability of these summary variables, and define the number of days needed to adequately measure usual physical activity. A secondary study purpose was to compare three self-report questionnaires to accelerometry. Thirty children (7-15 yr) wore accelerometers for 12 h.d-1 for 6 d. Daily summary variables of average movement count (total physical activity) and daily frequency of sedentary through vigorous activity were constructed. Intraclass correlation coefficients (R) and 95% confidence intervals (CI) were used to analyze the data. Accelerometry stability using 1 monitored day to represent usual physical activity was R = 0.42-0.47. When 6 d were used, stability increased to R = 0.81-0.84. Acceptable intraclass correlations and CI were achieved with 4 d of monitoring (R = 0.75-0.78, CI = 0.60-0.88). The self-report questionnaires were poorly to moderately correlated to accelerometry variables (r = -0.03-0.51). Data indicate that in field settings: 1) accelerometry can be used to assess the intensity of children's activity and 2) 4 or more days of activity monitoring are needed to achieve satisfactory reliability.  相似文献   

11.
One-wk prose retention was examined as a function of 4 activities immediately following reading. 24 Ss served in each of 7 conditions. Completion questions as an immediate activity with knowledge of results produced significantly better delayed retention than did questions without knowledge of results or presentation of statements equivalent in information to the questions with knowledge of results. These 3 conditions yielded performance significantly superior to the nonactivity control. Knowledge of results did not increase retention for correctly answered immediate questions, and it significantly increased delayed performance for immediate questions incorrectly answered. The immediate activity facilitation findings were attributed to 2 processes, practice at retrieval of stored information and addition of answers to items not recallable immediately after reading. No delayed retention difference occurred between passage information and equivalent randomly presented statements. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

12.
13.
Three experiments investigated the effects of a prior test trial on the subsequent long-term forgetting of paired-associates lists. The pattern of findings was consistent with a learning hypothesis that views a prior test as promoting the overlearning of remembered items and as mediating an efficient learning strategy on the next study trial, but leaving the forgetting rate intact. The learning hypothesis was upheld when pitted against the contrasting predictions of a retrieval-based notion, and it also provided an interpretation of extant data from the method of successive relearning. The main conclusion was that, although a prior test has substantial performance consequences, there is no evidence that it influences the rate of forgetting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

14.
The present study investigated the attitude of 243 patients with Multiple Sclerosis (MS) as a function of their perceived disease state. Data was collected via a closed-format questionnaire developed through the Fishbein and Ajzen [1-3] Theory of Reasoned Action. Results indicated clearly that patients with MS are not an homogenous group and vary in characteristics across disease states and that disease state differentially affects the psycho-social attitudes of patients. Results also indicated that persons in remission were more positive in their attitude associated with their disease state than persons with a chronic progressive form of the disease.  相似文献   

15.
Surface energies of copper at 1027°C were determined as a function of oxygen fugacity. The value of the surface energy was 1.49 J/m2 below 10-18 N/m2 oxygen and decreased linearly from 10-18 to 10-11 N/m2. The region of linear decrease fitted the Gibbs adsorption isotherm and gave a surface coverage of 0.24 monolayers of oxygen. The surface energy apparently increased with oxygen fugacity in the range from 10-11 to 10-7 N/m2, but this was associated with effects introduced by a precursor oxide on creep rate rather than a true effect on surface energy. Formerly a student.  相似文献   

16.
The aim of the present study was to determine the extent of genome evolution among methicillin-resistant Staghylococcus aureus (MRSA) strains. Three different collections of strains were analysed, comprising locally, nationally and internationally disseminated genotypes. Various genotyping assays displaying different levels of resolution were used. Geographically and temporally diverse MRSA strains comprised the international group. MRSA strains recovered during an outbreak in a New York City hospital and Portuguese MRSA isolates, all resembling the so-called Iberian clone, were included in the local and national collections, respectively. Genotypes were determined by genome scanning typing techniques and procedures which analyse specific DNA elements only. The outbreak strains showed subclonal variation, whereas the Portuguese isolates displayed an increased number of genotypes. Among the epidemiologically unrelated MRSA strains, the different genotyping techniques revealed a wide heterogeneity of types. Different typing techniques appeared to show different levels of resolution, which could be correlated with the extent of geographic spread; the more pronounced the spread, the higher the degree of genome evolution. Binary typing and randomly amplified polymorphic DNA analysis are the typing methods of choice for determining (non)identity among strains that have a recent common ancestor and have undergone yet limited dissemination.  相似文献   

17.
An outward current (Iout) was produced by stereoisomers of beta-hydroxy-L-glutamic acid (L-BHGA), an L-glutamic acid (L-Glu) derivative, applied by brief pneumatic pressure ejection on an identifiable neurone type, v-LCDN (ventral-left cerebral distinct neurone), of Achatina fulica Férussac. However, L- and D-Glu were almost ineffective on this neurone type. The pharmacological features of this Iout caused by L-BHGA were elucidated in the present study. According to the dose (pressure duration)-response studies on the L-BHGA stereoisomers that produced the Iout, the effective potency of threo-L-BHGA was approximately similar to that of erythro-L-BHGA. The dose (pressure duration)-response curve of quisqualic acid was shifted towards the left direction from those of threo-and erythro-L-BHGA, suggesting that the binding activity of quisqualic acid to the receptors would be stronger than those of the L-BHGA stereoisomers. GABA, glycine and L-homocysteic acid showed an inward current (Iin) on this neurone type, in contrast to the Iout caused by L-BHGA. beta-Alanine and taurine had absolutely no effect. Therefore, no amino acid inhibitory neurotransmitter candidate was found for this neurone type except for L-BHGA. It was assumed that L-BHGA, in either threo-or erythro-configuration, would be an inhibitory neurotransmitter for this neurone type. Mammalian L-Glu receptor antagonists. D(-)-AP-5, (+/-)-CPP, CNQX and L(+)-AP-3, applied by perfusion, showed no effect on the Iout of v-LCDN caused by threo-L-BHGA, indicating that the features of the inhibitory receptor activated by L-BHGA were much different from those of any type of the mammalian L-Glu receptors. Among the inhibitors of ATP-sensitive K+ channel, glipizide significantly inhibited the Iout caused by threo-L-BHGA, whereas tolbutamide did not. Inhibitors of intracellular signal transduction systems, H-7, H-8, H-9, staurosporine, calphostin C, KT5823 and W-7, had no effect on the Iout caused by threo-L-BHGA, suggesting that the receptors activated by threo-L-BHGA would be ionotropic.  相似文献   

18.
A rat thyroid cell line (FRTL-5) was used to study the phagocytic activity of thyroid follicular cells using fluorescent latex beads and flow cytometric analysis. Morphologic studies demonstrated that latex beads were engulfed and located within cytoplasmic vacuoles of thyrocytes. Flow cytometric evaluation of cell suspensions revealed high levels of fluorescence in cells engulfing latex beads. Using thyrotropin (TSH) as a stimulator of thyroid function and human interleukin-1 beta as an inhibitor, protocols were established for measuring the effects of these substances on either basal or TSH-induced phagocytosis. Cells exposed to latex beads over time in basal (0H) or TSH-containing medium had an increase in time-dependent phagocytic activity which was maximal after 24 or 8 h, respectively. Treatment of FRTL-5 cells with either a stimulator or an inhibitor revealed maximal change in phagocytic activity after 72 h as measured by the percentage of phagocytic cells as well as the mean fluorescence intensity. Phagocytic activity and iodide trapping by FRTL-5 cells were qualitatively similar in both sensitivity and magnitude of change in the assays used in this study. Phagocytosis of fluorescent latex beads represents a sensitive nonradioactive assay of thyrocyte function whose regulation is similar to iodide trapping.  相似文献   

19.
20.
There is abundant evidence for the premise that oxygen-derived free radicals (OFR) mediate ischemia/reperfusion injury to the myocardium. OFR scavengers such as superoxide dismutase can effectively reduce damage through lipid peroxidation during ischemia/reperfusion. Enhanced chemiluminescence, which has been used to measure OFR, was used to measure the antioxidant activity of fatty acids (palmitic and linoleic acid) and triglycerides (triolein, tristearin) and natural plant antioxidants (magnolol, catechin, trilinolein). Trilinolein, which has recently been isolated from natural products, as well as the well-known water soluble analogue of vitamin E-Trolox, were used as control. During pretreatment with chemicals, at concentrations of 10(-9) to 10(-7) M, enhanced chemiluminescence of linoleic acid (C 18:2) showed a dose-responsive reduction of OFR with a maximal mean reduction of -31.9% when compared to baseline. A saturated fatty acid such as palmitic acid (C 16:0) showed only relatively weak antioxidant activity at concentrations of 10(-7) to 10(-6) M with a maximum reduction of OFR of- 15.2% only. control chemicals such as trilinolein and Trolox showed significant antioxidant activity. At concentrations between 10(-10) and 10(-6) M and trilinolein has the most potent antioxidant activity with a maximal mean reduction of OFR of -48.0%, whereas Trolox showed only -39.2%. As for the natural plant antioxidants, only catechin showed potent antioxidant activity (-40%). Polyunsaturated triglycerides such as triolein (oleic acid, C 18:1) also possess significant OFR scavenging effect (-31.9%) whilst saturated triglycerides such as tristearin (stearic acid, C 18:0) had only relatively weak antioxidant activity (-15.2%). Generally, the antioxidant activity of unsaturated compounds is stronger than saturated compounds; double-bond existence may partially explain this phenomenon.  相似文献   

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