Prediction of survival in patients with esophageal carcinoma using artificial neural networks

BACKGROUND: Accurate estimation of outcome in patients with malignant disease is an important component of the clinical decision-making process. To create a comprehensive prognostic model for esophageal carcinoma, artificial neural networks (ANNs) were applied to the analysis of a range of patient-related and tumor-related variables. METHODS: Clinical and pathologic data were collected from 418 patients with esophageal carcinoma who underwent resection with curative intent. A data base that included 199 variables was constructed. Using ANN-based sensitivity analysis, the optimal combination of variables was determined to allow creation of a survival prediction model. The accuracy (area under the receiver operator characteristic curve [AUR]) of this ANN model subsequently was compared with the accuracy of the conventional statistical technique: linear discriminant analysis (LDA). RESULTS: The optimal ANN models for predicting outcomes at 1 year and 5 years consisted of 65 variables (AUR = 0.883) and 60 variables (AUR = 0.884), respectively. These filtered, optimal data sets were significantly more accurate (P < 0.0001) than the original data set of 199 variables. The majority of ANN models demonstrated improved accuracy compared with corresponding LDA models for 1-year and 5-year survival predictions. Furthermore, ANN models based on the optimal data set were superior predictors of survival compared with a model based solely on TNM staging criteria (P < 0.0001). CONCLUSIONS: ANNs can be used to construct a highly accurate prognostic model for patients with esophageal carcinoma. Sensitivity analysis based on ANNs is a powerful tool for seeking optimal data sets.     

Glutamate transporters as drug targets

The L-glutamate (Glu) has been hypothesized as an excitatory amino acid neurotransmitter in the mammalian central nervous system after successful cloning and identification of a number of genes encoding signaling machineries required for the neurocrine at synapses in the brain. These include excitatory amino acid transporters (EAATs) for signal termination and vesicular Glu transporters (VGLUTs) for signal output through exocytotic release, in addition to Glu receptors (GluRs) for signal input. These Glu signaling molecules not only play key roles in mechanisms associated with synaptic plasticity such as learning and memory, but also participate in the etiology and pathology of different neuropsychiatric disorders and neuronal cell death seen in various neurodegenerative diseases. Of the aforementioned Glu signaling molecules, EAATs are essential for the termination of signal transmission mediated by Glu as well as for the prevention of neurotoxicity mediated by this endogenous excitotoxin, while VGLUTs are crucial for the storage of Glu in synaptic vesicles to suffice for the definition of a glutamatergic phenotype. Many early desperate efforts were devoted to the search and development of novel compounds with a therapeutic window toward GluRs, while relatively little attention was paid to either EAATs or VGLUTs in this aspect. In this review, therefore, we will summarize the classification and functionality of EAATs and VGLUTs with a focus on their possibilities as potential therapeutic targets for different neurodegenerative and neuropsychiatric disorders related to malfunction of Glu signaling in human beings.     

Efficacy of biventricular pacing for dialysis-related hypotension due to idiopathic dilated cardiomyopathy

A 45-year-old man who had been undergoing maintenance hemodialysis for end-stage renal failure, caused by chronic glomerulonephritis 4 years before, was admitted to our hospital for biventricular pacemaker implantation (BVP). Ten years ago, he was diagnosed with idiopathic dilated cardiomyopathy, and had been suffering from dialysis-related hypotension (DRH) due to low cardiac function over the past year. An electrocardiogram revealed complete left bundle branch block with a QRS duration of 180 ms, and echocardiography showed moderate hypokinesis of the left ventricular wall and systolic asynchronized motion of the septum and free wall. After BVP, the left ventricular ejection fraction had increased from 29% to 40%, and the transmitral rapid left ventricular filling (E wave) and atrial contraction (A wave) ratio (E/A) had improved from 1.3 to 1.0. Before and after BVP, we measured hemodynamic parameters during hemodialysis by successive echocardiography. Before BVP, systemic vascular resistance had decreased, cardiac output had not changed, and hypotension was noted. In contrast, after BVP, cardiac output had increased and systemic vascular resistance had not changed, which caused an increase in blood pressure. We conclude that BVP improved the cardiac function which resulted in an improvement in dialysis-related hypotension (DRH).     

Clinical evaluation of tumor scanning with 169-Yb-citrate.

169-Yb-citrate was used as the tumor-scanning agent in 360 patients with malignant tumors and in 55 others with benign lesions and the results compared with 67-Ga-citrate studies in other series. In malignant tumors, the overall positive detection rate for ytterbium was 65.3%; in benign lesions, the false-positive rate was 29.1%. Good results were obtained in the extremities, head and neck, and pelvic area. Of all tumors visualized, squamous cell carcinoma was detected most effectively (77.5%). 169-Yb-citrate has a long shelf life, photon peaks of 178 and 198 kev, clears from the blood more rapidly than 67-Ga-citrate and has an extremely low soft-tissue background uptake. Its main disadvantage is its high radiation dose: 1.74 R/500 muCi whole-body and 5.77 R to the bone.     

Change in relative mobility of M protein following neuraminidase treatment in patients with multiple myeloma and monoclonal gammopathy of undetermined significance

The aim of this study was to clarify the relationship between the relative mobility of M protein in various disease states using cellulose acetate membrane electrophoresis. To examine the carbohydrate chain of the M protein, sera from patients with multiple myeloma (MM), various cancers, and benign disease were treated with neuraminidase.The relative mobility in benign disease and MM patient sera following neuraminidase treatment varied among individuals, while that of IgG M protein in sera from cancer patients was from 0.2 to 0.3. Thus, the relative mobility in cancer patients was narrower than in those with MM or benign disease.However, after neuraminidase treatment, there was no significant difference between relative mobility in cancer patient's sera and those in other disease patients.     

Selective electro-thermolysis in aesthetic medicine: a review

The use of radiofrequency (RF) for selective electro-thermolysis has been found to produce a highly efficient thermal effect on biological tissue. Different from optical energy, RF energy is dependent on the electrical properties of the tissue rather than on concentration of chromophores in the skin for selective thermal destruction of targeted sites. Good results have been obtained with systems that use RF current alone for skin resurfacing, with efficacy comparable to laser resurfacing but with potentially more rapid healing. A related adverse effect is pain accompanying the procedure, due to a high depth of penetration. Another technology integrates RF energy together with optical energy (using lower energies of both forms of energies). These systems have shown efficacy in hair removal for all hair colors and skin types, as well as wrinkle reduction; and may reduce the risk of side effects associated with either RF or optical treatments alone. This article discusses the properties of electrical current in medicine and reviews the studies to date that have evaluated RF energy for dermatological applications.     

Intake and excretion of cadmium and iron balance and influence of dietary habits among young women

OBJECTIVE: Absorption of cadmium is increased by deficiency of iron in animals, but it is uncertain that the same phenomenon occurs in humans. The purpose of this study is to investigate the relationship between cadmium and iron in the body and to evaluate the influence of dietary habits. METHODS: Twenty-five healthy women, aged 20-23 years, were selected by excluding those with renal disease and habitual constipation. They participated in the dietary intervention study to estimate tolerable weekly intake of Cd for 3 weeks in the same dormitory. At 3 months before, at 0 Day, at the 12th Day of the study and 9 months after the study, health check-ups were performed, and Cd in the blood and urine, hemoglobin (Hb), serum iron (iron) and serum ferritin (ferritin) were measured. RESULTS: Cd concentration in the blood (B-Cd) showed a significant correlation with Cd concentration in the urine (U-Cd), and inverse correlation with the body iron storage, such as Hb, iron and ferritin. A food frequency questionnaire showed that no subject showed insufficient dietary intake of iron. Subjects who had eaten grain, millet and brown rice showed higher levels of B-Cd and U-Cd and low levels of Hb, iron and ferritin. CONCLUSION: Absorption of Cd tended to increase according to a low level of body iron storage among healthy young women.     

Comparative genomics on Dkk1 orthologs

WNT family proteins bind to transmembrane proteins FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, FZD10, LRP5, LRP6, ROR1, ROR2, RYK, and also secreted proteins SFRP1, SFRP2, SFRP3, SFRP4, SFRP5, and DAND4 (CER1). DKK family members antagonize WNT binding to LRPs, while SFRP family members antagonize WNT binding to FZDs. Here, we identified and characterized rat Dkk1 gene and cow Dkk1 gene by using bioinformatics. Rat and cow Dkk1 genes, consisting of four exons, were located within AC095296.4 and AC157142.1 genome sequences, respectively. Dkk1 gene at rat chromosome 1q52 was found to encode a 270-aa protein, showing 94.1, 81.5, 78.9, 53.7 and 48.1% total-amino-acid identity with mouse Dkk1, human DKK1, cow Dkk1, Xenopus dkk1 and zebrafish dkk1, respectively. Vertebrate Dkk1 orthologs were secreted proteins with two Cys rich regions, each containing ten conserved Cys residues. The C-terminal Cys rich region was well conserved among vertebrate Dkk1 orthologs. Nucleotide position 148898-147860 of AC009986.10 human genome sequence was identified as evolutionarily conserved human DKK1 promoter, and nucleotide position 55266-56301 of AC095296.4 rat genome sequence as evolutionarily conserved rat Dkk1 promoter. Human DKK1 promoter and rat Dkk1 promoter, showing 66.2% total nucleotide identity, were well conserved. TCF/LEF, CP2, POU2F1 (OCT1), HNF1 and FOXJ2-binding sites and TATA-box were conserved among human DKK1, rat Dkk1, mouse Dkk1, and cow Dkk1 promoters. Double TCF/LEF-binding sites within the proximal promoter region of mammalian Dkk1 orthologs are implicated in the negative feed back mechanism of WNT/beta-catenin signaling pathway.     

Comparative genomics on Fzd8 orthologs

WNT signaling pathway networks with Hedgehog, Notch and FGF signaling pathways during carcinogenesis and embryogenesis. FZD8 is up-regulated in HeLa S3 and A549 cells. Here we identified and characterized rat Fzd8 gene by using bioinformatics. Rat Fzd8 gene was identified within AC131883.2 genome sequence. Rat Fzd8 (684 aa) showed 99.1, 96.8, 71.8 and 71.6% total amino-acid identity with mouse Fzd8, human FZD8, zebrafish fzd8 and Xenopus fzd8, respectively. Vertebrate Fzd8 orthologs were seven-transmembrane receptors with Frizzled (Fz) domain within the N-terminal extracellular region, leucine zipper motif around the fifth transmembrane domain, and Dishevelled (Dvl)-binding motif within the C-terminal cytoplasmic region. Two Asn-linked glycosylation sites within the N-terminal extracellular region were conserved among vertebrate Fzd8 orhologs. One Asn-linked glycosylation site within the second extracellular loop was conserved among mammalian Fzd8 orthologs, but not in Xenopus and zebrafish fzd8 orthologs. These facts indicate the molecular evolution of Fzd8 orthologs. The 5'-flanking region and exonic region were well conserved among mammalian Fzd8 orthologs. Nucleotide position 92950-94221 of AC131883.2 genome sequence was identified as the evolutionarily conserved promoter region of rat Fzd8 gene, and nucleotide position 133421-132134 of AL121749.14 genome sequence as the evolutionarily conserved promoter region of human FZD8 gene. Match program revealed that ELK1- and PAX4-binding sites were conserved between rat Fzd8 and human FZD8 promoters. This is the first report on the rat Fzd8 gene as well as on comparative genomics for Fzd8 orthologs.