Etoposide-induced PC12 cell death: apoptotic morphology without oligonucleosomal DNA fragmentation or dependency upon de novo protein synthesis

Etoposide, a topoisomerase II inhibitor used in cancer therapy, has been shown to induce apoptosis in vitro in a variety of cell types. In the present study, we have characterized the effects of etoposide on undifferentiated rat pheochromocytoma PC12 cells. Etoposide killed PC12 cells in a time- and concentration-dependent manner. 20-24 h incubation with 10 micrograms/ml etoposide induced 25-50% cell death. Hoechst 33258 staining revealed apoptotic morphology in dying cells. No evidence was found of either oligonucleosomal DNA fragmentation, as shown by agarose gel electrophoresis, or endonuclease involvement, as shown by the inability of aurintricarboxylic acid to prevent cell death. Cycloheximide and actinomycin-D were unable to prevent etoposide cytotoxicity indicating that the process is not dependent upon de novo protein or mRNA synthesis. NGF (5 ng/ml) prevented etoposide-induced PC12 cell death. These results offer an example of how the morphological features of apoptosis are not necessarily associated with oligonucleosomal DNA fragmentation or with de novo macromolecule synthesis.     

Lipoprotein(a) in android obesity and NIDDM

OBJECTIVE: To assess the level of serum lipoprotein(a) [Lp(a)] in nonobese and obese NIDDM subjects with android body distribution. RESEARCH DESIGN AND METHODS: Serum Lp(a) levels were measured in 30 long-standing NIDDM patients (duration of diabetes 12.5 +/- 3 years, mean +/- SD), with 15 of the patients being obese of android distribution (BMI > 30 kg/m2 and waist-to-hip ratio > 0.8). In addition, there were 15 android obese nondiabetic subjects and 10 healthy subjects serving as the control group. RESULTS: All groups of patients in this study (diabetic, obese, and obese diabetic) showed significantly higher levels of Lp(a) than the healthy control group. Lp(a) concentrations were significantly higher in NIDDM patients with android type of obesity than in nondiabetic androids (24.1 +/- 5.6 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Significantly greater levels of Lp(a) were found in nonobese subjects with diabetes when compared with obese subjects without diabetes (22.3 +/- 4.1 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Furthermore, Lp(a) serum concentrations were not dependent on the degree of glycemic control (controlled NIDDM 23.6 +/- 5.0 vs. uncontrolled NIDDM 21.4 +/- 2.7 mg/dl, NS), but were much greater in subjects with diabetes complicated by vascular disease (complicated 26.3 +/- 5.0 vs. uncomplicated 20.5 +/- 2.7 mg/dl, P < 0.001). No correlation was found between Lp(a) and other lipid parameters in this study. CONCLUSIONS: Lp(a) levels are significantly elevated in both android-obese and nonobese NIDDM patients regardless of the degree of glycemic control. Lp(a) is an independent risk factor showing greater elevations in those subjects complicated with diabetic vascular diseases.     

From particle-mass to multibody systems: graph-theoretic modeling

The distinction between geometry and dynamic interactions is fundamental for the consistent dynamic analysis of physical systems. A unified treatment of such systems is possible when we adopt a hierarchical mathematical model with a consistent set of embedded abstractions. This new view is adopted in the general formulation strategy for obtaining a simplified dynamics model of mechanical systems. We show that there exists a consistent general extension from the model of constrained particle-mass systems (PMS) to the model of multibody systems (MBS) based entirely on graph-theoretic concepts     

Linear B-cell epitopes in the N-terminus of L2 of bovine papillomavirus type 4

In vivo dosimetry performed with semiconductor detectors is a reliable method for patient dose control. The purpose of this study is to evaluate the perturbations introduced in the patient's absorbed dose distribution by three types of commercially available diodes (Isorad, Sun Nuclear Corp.; model 114200, 114300 and 114400) from the same company and to present possible solutions for minimizing this side-effect.     

Procedural memory stimulation in Alzheimer''s disease: impact of a training programme

The operative results of 23 patients with a specific or unspecific spondylodiscitis were documented over 2 years after the focus of the inflammation had been eradicated, bone chip had been interposed and a CDH instrumentation had been performed by an anterior approach only. These outcomes were compared with the results of 32 patients in whom the focus had been removed and the defect had been filled with bone graft from an anterior approach, followed by stabilisation with CD instrumentation through an additional dorsal approach. In the cases where CDH instrumentation was applied, the range of fusion averaged 1.3 segments. This was clearly less extensive than in dorsoventral stabilisation, in which on average 3.5 segments were fused. In 47 of 55 cases mobilisation was achieved without orthesis. Eight months after the operations bony fusion could be observed radiologically in all patients. The mean preoperative kyphotic angle of the affected segments was 14.4 degrees, compared to 4 degrees after the operation. The mean loss of reposition was measured to be about 2.7 degrees in both groups. Average operation time and blood loss were about 50% higher in the patients treated dorsoventrally. We conclude that even in the case of florid spondylodiscitis, a short-range anterior fusion of the affected spinal segment may be performed by use of a stable-angle implant without an increased risk of infection-related loosening.     

Growth factor receptor expression during in vitro differentiation of partially purified populations containing murine stem cells

The Word Accentuation Test assesses the accentuation of 30 infrequent Spanish words written without the accentuation mark and is an easy-to-use tool for estimating premorbid intelligence of Spanish-speaking people. Its intraobserver (0.97) and interobserver (0.93) reliabilities and its correlation with the Wechsler Adult Intelligence Scale (.837) and Raven's Progressive Matrices (.655) are high, offering a good prediction of general intelligence. It is resistant to mental deterioration; 20 demented and 40 controls matched by sex, age, and education obtained similar scores. The discrepancies between current and predicted scores in Raven's scale can diagnose mild-moderate dementia with 0.79 accuracy (sensitivity, 0.78; specificity, 0.82).     

Microfabricated Lamb wave device based on PZT sol-gel thin film formechanical transport of solid particles and liquids

The fabrication using silicon micromachining and characterization of an acoustic Lamb wave actuator is presented. The intended use of the device is for mass transport and sensor applications. The device consists of dual interdigitated transducers patterned on a thin-film composite membrane of silicon nitride, platinum, and a sol-gel-derived piezoelectric ceramic (PZT) thin film. The acoustic properties of the device are presented along with preliminary applications to mechanical transport and liquid delivery systems. Improved acoustic signals and improved mass transport are achieved with PZT over present Lamb wave devices utilizing ZnO or AlN as the piezoelectric transducer     

1.04 GBd low EMI digital video interface system using small swingserial link technique

In a high-resolution flat panel system, a conventional interface that directly connects a liquid crystal display (LCD) controller to a flat panel cannot overcome the problems of excess EMI (electromagnetic interference) and power caused by full-swing transmission signals in parallel lines. This paper presents a high-speed digital video interface system implemented with a low-cost standard CMOS (complimentary metal-oxide-semiconductor) technology that can mitigate EMI and power problems in high-resolution flat panel display systems. The combined architecture of the high-speed, small number of parallel lines and low-voltage swing serial interface can support resolutions from VGA (640×480 pixels) up to XGA (1024×768 pixels) with significant power improvement and drastic EMI reduction. To support high-speed, low-voltage swing signaling and overcome channel-to-channel skew problems, a robust data recovery system is required. The proposed digital phase-locked loop enables robust skew-insensitive data recovery of up to 1.04 GBd     

The expression of CD4 and CD8 molecules conditions the behavior of V beta + murine thymocytes upon superantigenic challenge

We investigated the capacity of the Staphylococcal enterotoxin (SE) B, a superantigen (SAg) specific for TCR V beta domain, to modulate V beta 8+ thymocytes selection in adult mice. Thymocytes were collected at various time intervals after SEB injection (10 and 100 micrograms) and V beta 8+ modulation was analysed by three color flow cytometry. SEB failed to affect V beta 8+ thymocytes comprised in the less mature compartments, namely, CD4+8+ and CD4-CD8-, whereas it selectively affected V beta 8+CD4+8+ (downward modulation) and V beta 8+CD4-8+ thymocytes (upward modulation). The different response to SEB challenge between CD4+8- and CD4-8+ thymocytes appeared dependent on the CD4/MHC class II interaction, as V beta 8+CD4-8+ thymocytes carrying a transgenic CD4 molecule capable of interacting with MHC class II showed the same response of V beta 8+CD4+8- thymocytes. At variance with thymocytes, however, V beta 8+CD4+8- and V beta 8+CD4-8+ splenic T lymphocytes responded to SAg challenge in identical manner (upward modulation) highlighting the importance of maturation status and/or microenvironment in SAg response. V beta 8+ thymocytes remaining in the thymus were assessed for their capacity to respond to a SAg challenge. Thus, thymocytes were obtained at various time intervals after SEB injection and cultured in the presence of SEB or SEA, a Sag specific for V beta 10 as control. A reduced mitotic response to SEB but not to SEA was noticed irrespective of the number of V beta 8+ responding cells present in culture. It is concluded that SAgs affect TCR specific thymocytes by conditioning their redistribution and inducing an anergic status.     

Comorbidity of drug dependence and other mental disorders: a two-phase study of prevalence at outpatient treatment centres in Italy

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.