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841.
The proposed mechanism of action of the antineoplastic drug 3-nitrobenzothiazolo[3,2-alpha]quinolinium chloride (NBQ-2) involves its interaction with DNA by intercalation and inhibition of topoisomerase II activity by arresting the enzyme in a covalent cleavage complex. In an attempt to identify some structural determinants for activity and develop a molecular structure/cytotoxicity correlation, four new structural analogs of the antitumor NBQ-2 were prepared and their cytotoxic activity and DNA binding properties were investigated. The cytotoxic activity was evaluated against six different human tumor cell lines: U937, K-562, HL-60, HT-29, HeLa, and A431. The results showed that these new drugs elicit pronounced cytotoxic effects against U937, K-562, HL-60 and A431 while HeLa and HT-29 were less sensitive to the new drugs. This apparent selectivity was different to that of m-AMSA, a drug currently used for cancer treatment. Since the interaction of NBQ-2 to DNA by intercalation has been proposed as the initial step leading to its antineoplastic activity, DNA binding and changes in DNA contour length induced by the new NBQ-2 structural analogs were also investigated using calf thymus and human DNA. The drug, 7-(1-propenyl)-3-nitrobenzimidazolo[3,2-alpha]quinolinium chloride (NBQ-59) was the most cytotoxic agent of the analog series (IC50 = 16 microM for HL-60 cells), however, it demonstrated the weakest binding to DNA (Kint = 0.9 x 10[5] M-1 for calf thymus DNA). NBQ-59 was also found to be a poor intercalator into the DNA double helix. Therefore, our results suggest that DNA binding is not the primary mechanism of drug action for this family of compounds. In addition structural determinants important for cytotoxicity of the benzazolo quinolinium chlorides were suggested by our results. In particular, the nitro group in the 3 position does not seem to be necessary for bioactivity, while substitutions in the benzazolo moiety have striking effects on the biological activity of the drugs. 相似文献
842.
1. Supramedullary structures including the ventral medial prefrontal cortex (MPFC) and the midbrain cuneiform nucleus (CnF) project directly and indirectly to premotor sympatho-excitatory neurons of the rostral ventrolateral medulla (RVLM) that are critically involved in the generation of sympathetic vasomotor tone. 2. Electrophysiological studies have demonstrated that activation of depressor sites within the MPFC is associated with splanchnic sympathetic vasomotor inhibition and inhibition of the activity of RVLM sympathoexcitatory neurons. 3. Antidromic mapping and anatomical studies support the notion that a relay in the nucleus tractus solitarius is involved in the cardiovascular response to MPFC stimulation. 4. The midbrain CnF, which lies adjacent to the midbrain periaqueductal grey, is a sympathoexcitatory region of the midbrain reticular formation. Sympathoexcitatory responses evoked from the CnF are associated with short-latency excitation of RVLM neurons. 5. Cuneiform nucleus stimulation induces the expression of mRNA for the immediate early genes c-fos and NGFI-A in mid-brain, pontine and hypothalamic structures. 6. The MPFC and CnF are supramedullary structures with opposing modulatory influences on sympathetic vasomotor drive, whose roles in cardiovascular control mechanisms warrant further investigation. 相似文献
843.
O. N. Shablovskii 《Journal of Engineering Physics and Thermophysics》1997,70(2):319-327
A set of divergent forms of heat-transfer equations are presented. New laws are established that govern the behavior of the
temperature field behind the front of a strong discontinuity. Comparison of theoretical and experimental data on the propagation
of nonlinear waves in a sapphire crystal and liquid helium is carried out.
Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 70, No. 2, pp. 318–325, March–April 1997. 相似文献
844.
BACKGROUND: Diabetic patients with end-stage renal failure (ESRD) have a high cardiovascular morbidity and mortality. The underlying mechanisms are not completely elucidated. The aim of our study was to define predictors of death in diabetic patients with end-stage renal disease. PATIENTS AND METHODS: We performed a prospective study in 35 dialysis centres in Germany between 1985 and 1994. To evaluate predictors and risk factors in this population we examined 412 diabetic patients at the time of admission to dialysis treatment (peritoneal dialysis (PD) or haemodialysis (HD)). Classification of the type of diabetes was done according the criteria of the National Diabetes Data Group [1,2]. Items assessed at the time of admission were coronary artery disease (CAD), peripheral occlusive disease (POD), and stroke. CAD was defined as a history of myocardial infarction with the corresponding changes in the ECG or luminal narrowing by more than 50% in at least one coronary artery upon coronarangiography; POD was defined as claudication and/or brachial-tibial ratio (BTR) less than 0.9 or a history of amputation. Assessment of the nutritional state comprised body mass index, skinfold thickness of the upper arm and lateral thorax area, and urea concentration. Cholesterol, HDL, LDL, apolipoprotein A (ApoA-I) and B (ApoB), triglycerides, lipoprotein(a) (Lp(a)), and fibrinogen were measured. As an index of disturbed cardiac innervation beat-to-beat variation was measured. Outcome measurements were causes of death (i.e. cardiac and non-cardiac) and time of survival. RESULTS: One hundred and eighty of 412 (44%) patients died during the observation period. Patients who died were older (61 +/- 12 versus 53 +/- 15 years P < 0.0001), had lower skin fold thickness (13.1 +/- 6.0 versus 15.1 +/- 7.3 mm P < 0.04), lower ApoA-I (100 +/- 35 versus 111 +/- 32 mg/dl P < 0.005) and higher fibrinogen (515 +/- 146 versus 451 +/- 155 mg/dl P < 0.02). Type II diabetic patients had a lower mean survival time than type I (34 versus 66 months P < 0.0006). The mode of renal replacement therapy (PD or HD) had no adverse effect on survival time. Survivors less frequently had a history of CAD, POD and stroke than non-survivors. In multivariate analysis ApoA-I, fibrinogen, age and stroke were independent predictors of cardiac and non-cardiac death in diabetic patients with end-stage renal failure. Lipid values and nutritional state did not independently predict the overall and cardiovascular mortality. CONCLUSION: This study in dialysed diabetic patients identifies several predictors of death, some of which are susceptible to intervention. 相似文献
845.
A wideband wattmeter for measuring active power over a frequency range of dc to 500 kHz is described. The wattmeter is based on the three-voltmeter method in which three rms voltage measurements are used to calculate power. The wattmeter active power uncertainty is estimated to be within 0.03% from dc to 20 kHz and within 1.5% to 500 kHz 相似文献
846.
A Konstantinidou E Patsouris N Kavantzas PM Pavlopoulos V Bouropoulou P Davaris 《Canadian Metallurgical Quarterly》1997,142(5-6):311-316
Proliferating cell nuclear antigen (PCNA) expression has been proven to be a significant marker of cell proliferation in meningiomas, which correlates with growth rate and, as shown by several authors, possibly provides prognostic information concerning biologic behavior. However, the current method for determining PCNA labeling index (LI) is tedious and time consuming like all the nonautomated methods for evaluating cell kinetics, presenting high interobserver and interlaboratory variability and low reproducibility. In the present study, we introduce a semi-automated computer-assisted image analysis method for determining PCNA LI in 38 meningiomas, in parallel with the current nonautomated method. Image analysis technique permits unbiased cell counting, standardizes the degree of staining intensity and provides instant results. By calculating coefficient of variability, the method proved to be highly reproducible. The correlation between the results provided by the nonautomated and the semiautomated image analysis method showed a high agreement between them, with a correlation coefficient, r, of 0.82. In conclusion, we consider that image analysis contributes to the accuracy, reproducibility, and practicality of PCNA LI determination so that along with other useful parameters this significant marker may serve to predict the clinical behavior in meningiomas. 相似文献
847.
848.
Tamasevicius A. Cenys A. Mykolaitis G. Namajunas A. Lindberg E. 《Electronics letters》1997,33(24):2025-2026
The authors present three different examples demonstrating the possibility of synchronising hyperchaotic oscillators via a single variable 相似文献
849.
The present study determined tumorigenicity, tumor classification and DNA damage induced in infant mice by benzo[a]pyrene (B[a]P) or Manufactured Gas Plant (MGP) residues after a single exposure. Male and female B6C3F1 mice were exposed to B[a]P or MGP residue from a single environmental site (MGP-4) and males were also exposed to MGP residue composite from seven different sites (MGP-M7). At 26, 39 and 52 weeks after exposure tumorigenesis was assessed in lung, forestomach and liver. Formation and persistence of DNA adducts were quantified by 32P-postlabeling. Exposure of males to B[a]P induced liver tumors in a dose and time dependent manner. MGP induced more advanced tumors than B[a]P. Only a single liver tumor was found in MGP-4 treated females. No forestomach and few pulmonary adenomas were induced in males or females. MGP-4, MGP-M7 or B[a]P induced DNA adducts in males and females. Adducts in liver, lung and forestomach peaked on different days and decreased at different rates. At 24 h post-exposure, no significant differences in initial DNA adduct levels occurred in males and females exposed to MGP-4 or B[a]P. Lack of DNA damage (adducted DNA) did not account for non-responsiveness of lung and forestomach in B6C3F1 genders as well as in liver in females. MGP tumorigenicity could not be accounted for solely by B[a]P content nor did it reflect additivity of B[a]P and other carcinogenic polycyclic aromatic hydrocarbons (PAHs) in MGP. Synergy among MGP-PAHs, presence of unidentified carcinogens and/or promoters in MGP may account for MGP potency. The B6C3F1 infant male model is a convenient and rapid assay for assessing MGP liver tumorigenicity and potency. 相似文献
850.
Faccio F. Anghinolfi F. Heijne E.H.M. Jarron P. Cristoloveanu S. 《Electron Devices, IEEE Transactions on》1998,45(5):1033-1038
An additional noise component is observed in the noise spectrum of transistors in a partially-depleted (PD) medium-thickness SOI-CMOS technology. We identify the origin of this additional noise in the noisy resistance of the body film. This resistance, coupled to the gate capacitance, forms an RC filter and generates the hump-shape of the additional noise component. Several experimental observations that support this model are presented 相似文献