Endothelin-1 concentrations and optimisation of arterial oxygenation and venous admixture by selective pulmonary artery infusion of prostaglandin E1 during thoracotomy

PURPOSE: To demonstrate a superselective intraarterial chemotherapy as a therapeutic alternative in the treatment of previously treated recurrent lymph node metastases in breast cancer. METHODS: 14 patients with recurrent lymph node metastases in cases of breast cancer were presented to be treated by intraarterial chemotherapy of 25 mg mitoxantrone/m2 over a period of 24 hours. In two patients with superclavicular lymph node involvement an intraarterial therapy could not be carried out because of a vascular connection to the anterior spinal artery. Involved lymph stations could be reached in superselective technique by side branches of the subclavian artery. Heparin coverage was given intravenously. Every patient had had surgery, radiation, systemic chemo- and hormonal therapy before and was now graded as inoperable. Therapy indication was given by local tumour-induced symptoms. RESULTS: In the 12 treated cases complete remission was seen in three, partial remission in 4, a steady state in two and a progressive disease in three. There were no complications or severe side effects. CONCLUSION: Intraarterial chemotherapy is an effective and well tolerated treatment in recurrent lymph node metastases in cases of breast cancer even if conventional therapies can no longer be used.     

Flavopiridol: a cytotoxic flavone that induces cell death in noncycling A549 human lung carcinoma cells

Flavopiridol (NSC 649890, L86-8275), a potent inhibitor of cyclin-dependent kinase 1/p34cdc2 phosphorylation and kinase activity, is currently undergoing Phase I clinical testing as a potential antineoplastic agent. Previous studies have suggested that flavopiridol is cytostatic but not cytotoxic when applied to exponentially growing cells. In the present study, various human tumor cell lines were assayed for trypan blue exclusion and ability to form colonies after exposure to flavopiridol under a variety of growth conditions. When log phase A549 non-small cell lung cancer cells were examined 72 h after the start of a 24-h flavopiridol exposure, as many as 90% of the cells accumulated trypan blue. A 24-h exposure to 250-300 nM resulted in trypan blue uptake in 50% of A549 cells at 72 h and a 50% reduction in colony formation. Similar results were observed in HCT8 ileocecal adenocarcinoma, T98G glioblastoma, MCF-7 breast adenocarcinoma, and HL-60 leukemia cells. With A549 cells, identical results were obtained in actively growing logarithmic phase cells and growth-arrested confluent cells. Treatment with the DNA synthesis inhibitor aphidicolin only minimally affected the cytotoxicity of flavopiridol. In contrast, the RNA synthesis inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole or the protein synthesis inhibitor cycloheximide reduced the cytotoxicity of flavopiridol. These results suggest that: (a) flavopiridol is not only cytostatic, but also cytotoxic to a variety of human tumor cell lines; (b) flavopiridol is equally active against cycling and noncycling A549 cells; and (c) RNA and protein synthesis appear to play a role in flavopiridol-induced cytotoxicity.     

Adaptive control of arterial blood pressure with a learningcontroller based on multilayer neural networks

The authors discuss a two-model multilayer neural network controller for adaptive control of mean arterial blood pressure (MABP) using sodium nitroprusside. A model with an autoregressive moving average (ARMA), representing the dynamics of the system, and a modified backpropagation training algorithm are used to design the control system to meet specified objectives of design (settling time and undershoot/overshoot) and clinical constraints. The controller is associated with a weighting-determinant unit (WDU) to determine and update the output weighting factor of the parallel two-model neural network for adequate control action and a control-signal modification unit (CMU) to comply with clinical constraints and to suppress the effect of adverse noise and to improve the WDU performance. Extensive computer simulations indicate satisfactory performance and robustness of the proposed controller in the presence of much noise, over the full range of plant parameters, uncertainties, and large variations of parameters     

Erbium-doped fiber amplifier second-order distortion in analog links and electronic compensation

The authors study the second-order distortion when an erbium-doped fiber amplifier (EDFA) is used to amplify the analog optical AM cable TV (CATV) multiple carrier signal from a directly modulated distributed feedback (DFB) semiconductor laser. Experimentally, it was seen that this second order distortion depends critically on the gain of the EDFA fiber amplifier. The authors attribute this distortion to the interaction between the frequency chirping of the DFB laser and the variable gain with wavelength of the amplifier. The authors describe an electronic predistorter that compensates the nonlinearity produced by the DFB-laser-EDFA combination. As a result, the high power advantage of the EDFA can be fully realized in spite of the potential for second-order distortion in the system.<>     

Physiological and theoretical analysis of K+ currents controlling discharge in neonatal rat mesencephalic trigeminal neurons

Whole cell voltage- and current-clamp recordings were obtained from mesencephalic trigeminal sensory (Mes 5) neurons identified visually in thin brain stem slices of neonatal rats with the use of infrared video microscopy. These cells exhibited accommodation in spike discharge responses to depolarizing current injection protocols whose duration differed as a function of holding potential (-50 vs. -65 mV). Several spikes were elicited before the membrane response accommodated from -50 mV, whereas from -65 mV only single action potentials were evoked. In response to similar protocols, application of the K+ channel blocker 4-aminopyridine (4-AP) (50 microM to 2 mM) caused sustained repetitive spiking whereas tetraethylammonium (TEA) (10-30 mM) did not cause repetitive spiking. In voltage clamp, 4-AP application (100 microM) revealed a sustained outward current (I4-AP) that was active between -60 and -30 mV. I4-AP was responsible for suppressing sustained repetitive spiking behavior, producing accommodation under normal circumstances. TEA application in voltage clamp revealed a sustained outward current evoked positive to -40 mV. Two transient outward currents (TOCs) were identified by prepulse protocols typically used to characterize A-type currents: a 4-AP-insensitive fast TOC, and a slow TOC (ITOC-S) sensitive to 4-AP (> 500 microM). A Ca(2+)-dependent outward current that activated positive to -30 mV was also characterized. A mathematical model of a Mes 5 neuron was assembled from our voltage-clamp records to simulate the dynamic interaction of outward currents during membrane excitation. We conclude that in Mes 5 neurons, the 4-AP-sensitive currents ITOC-S and I4-AP determine the duration of spike trains. In particular, the noninactivating I4-AP determines whether cells exhibit sustained repetitive discharge or accommodate in response to depolarizing current. Neurotransmitter modulation of this current or modulation of the resting membrane potential could modify the output properties of Mes 5 neurons, and therefore the properties of these currents must be incorporated into our current understanding of how these cells contribute to shaping oral-motor pattern generation.     

Substrate transport and cocaine binding of human dopamine transporter is reduced by substitution of carboxyl tail with that of bovine dopamine transporter

A chimeric dopamine transporter (DAT) cDNA encoding mutant human DAT (hDAT) protein in which the intracellular carboxyl-terminal tail is replaced by that of the bovine dopamine transporter (bDAT) was constructed. The chimeric hDAT cDNA was expressed in COS-7 cells, and [3H]dopamine and [3H]MPP+ uptake and [3H]CFT binding capacities were assessed. Substrate transport and ligand binding of bDAT were reduced by 32-43% as a result of substitution of the carboxyl tail in hDAT, suggesting that the functional characteristics of bDAT arise from differences in the carboxyl tail between human and bovine DAT. Thus, it appears that the sequences encoded within the carboxyl terminal of DAT would be one of the important determinants for its functions.     

Single nucleotide polymorphism data analysis - State-of-the-art review on this emerging field from a signal processing viewpoint

The basic structural units of the genome are nucleotides. A single nucleotide polymorphism (SNP) is a mutation at a single nucleotide position. This paper discusses several major problems in SNP data analysis and review some existing solutions in this work. Generally speaking, a rich set of SNP analysis problems are cast in the signal processing framework. Our objective is to offer a state-of-the art review on this topic from a signal processing viewpoint so that researchers in the signal processing field can grasp the important domain knowledge to overcome the barrier between the two fields