New algorithmic-based digital filter processing system for real-time continuous blood pressure measurement and analysis in conscious rats

A new algorithmic-based digital filter processing system for real-time continuous blood pressure (BP) measurement and analysis in freely-moving conscious rats has been developed. Real-time recognition of BP waveforms, real-time noise rejection and determination of representative waveform indexes (WIs) at indicated time points using digital filters and Smirnov's rejection test were realized with this system. Digital filters were applied for two different purposes: waveform segmentation and smoothing the calculations of representative WIs. Smirnov's rejection test was used for real-time noise rejection and yielded an accurate rejection rate of 99.99%. The result was that the digital filter processing and Smirnov's rejection test realized accurate real-time BP measurement and analysis in freely-moving conscious rats using a personal computer.     

Influence of polymorphisms in the genes for cytokines and glutathione S-transferase omega on sporadic Alzheimer's disease

We studied promoter region polymorphisms in the interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, tumor necrosis factor, and transforming growth factor (TGF)-beta1 genes in Japanese patients with Alzheimer's disease (AD) (n = 172) and normal controls (n = 163). We also examined an association of a polymorphism located in the glutathione S-transferase omega 1 (GSTO-1) gene region with AD patients. None of these genotypes or allele frequencies showed a significant difference between AD patients and controls. We also failed to detect any difference in the disease onset between each genotype of the seven polymorphisms. Although AD patients carrying high producer alleles of TGF-beta1 and IL-1beta or TGF-beta1 and IL-6 showed a tendency for an early onset of the disease, neither of these combined effects reached a significant level after multiple comparisons. Our findings suggest that genetic polymorphisms in the cytokines and GSTO do not play a major role in Japanese AD patients.     

Prostaglandin E1-initiated immune regulation during human mixed lymphocyte reaction

Prostaglandin E1 (PGE1) has therapeutic value for transplantations due to its microvascular activity. Interleukin (IL)-18, which is elevated in plasma during the acute rejection after organ transplantation, elicits the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) on monocytes as well as the production of interferon (IFN)-gamma and IL-12 and proliferation of T-cells during the human mixed lymphocyte reaction (MLR) in an in vitro model of acute rejection. In contrast, PGE1 inhibits all the adhesion molecule expression, cytokine production and T-cell proliferation in the presence of IL-18. The effects of PGE1 depend on stimulation of the IP/EP2/EP4-receptor, and thus, PGE1 might have therapeutic potential for treating acute rejection due to its immune regulatory effect.     

Histamine downregulates CD14 expression via H2 receptors on human monocytes

Lipopolysaccharide (LPS) binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14 on human monocyte. LPS is transferred to the transmembrane signaling receptor toll-like receptor (TLR) 4. In the present study, the effect of histamine on the expression of CD14 on human monocytes was investigated. Histamine concentration- and time-dependently decreased the expression of cell surface CD14, whereas histamine did not decrease mRNA for CD14 nor increase soluble CD14 (sCD14). The inhibitory effects of histamine on CD14 expression were antagonized by H2-receptor antagonist, but not by H1 and H3/H4 antagonist. The effects of selective H2-receptor agonists, 4-methylhistamine and dimaprit, on CD14 expression mimicked that of histamine indicating that histamine regulated CD14 expression through the stimulation of H2-receptors. The pretreatment with histamine partially inhibited the LPS-induced TNF-alpha production in human peripheral blood mononuclear cells (PBMC). Such inhibition might be due to the down-regulation of CD14 expression on monocytes by histamine.     

Successful treatment of tracheomalacia associated with esophageal atresia without a tracheoesophageal fistula by aortopexy: Report of a case

Tracheomalacia (TM) is well known as a complication associated with esophageal atresia (EA) and tracheoesophageal fistula (TEF); however, the occurrence of TM requiring surgical treatment in a patient having EA without a tracheoesophageal fistula has never been reported. We describe herein a rare case of TM associated with EA without TEF. Respiratory distress was caused by compression of the trachea by a severely dilated upper esophageal pouch with weakness of the tracheal wall. Aortopexy was performed, and an excellent postoperative result was achieved.     

Difference of visual attention between smokers and never-smokers]

Nicotine is known to improve cognitive performance such as attention, concentration and working memory in humans and animals. Previous research suggests that nicotine enhances visuospatial attention. But it could be hypothesized that nicotine intake alleviate a withdrawal-induced deficit in smokers. To evaluate the cognitive performance in smokers and never-smokers, we investigate eye movement while 4-points saccade task is performed. 5 smokers and 6 never-smokers are matched for age and education. Eye movement was investigated by using TKK2920 (Takei Co.) which determines the direction of gaze over a two-dimensional visual field without attachments to the eye. We found that a tendency which Mean Gazing Time is prolonged in smokers. These data suggest that impairment of visual attention in smokers is not significant.     

Thirty-One Autopsy Cases of Trisomy 18: Clinical Features and Pathological Findings

The clinical features and morphological findings in 31 Japanese infants with trisomy 18 are presented. The majority were small-for-date infants. There was no sex predominance in our series, as opposed to male female ratios of 1:3 reported in the literature. The average age at death was greater in females than in males. Cardiovascular anomalies were consistently present; ventricular septar defect and patent ductus arteriosus being the most common malformations. Various other internal malformations including the Arnold-Chiari malformation were observed.     

MR imaging of the thyroid: correlation between apparent diffusion coefficient and thyroid gland scintigraphy

PURPOSE: To evaluate the usefulness of echo-planar MR imaging for assessing the thyroid function and confirm the clinical use of MR imaging for thyroid diseases. MATERIALS AND METHODS: Thirty-four patients with a variety of thyroid disorders (24 Graves disease; five subacute thyroiditis; five Hashimoto thyroiditis) were examined using T1-, T2-, and diffusion-weighted magnetic resonance (MR) imaging and thyroid scintigraphy with Tc-99m pertechnetate. RESULTS: The ADC values obtained from the diffusion-weighted images of the patients with Graves disease were significantly higher than those of patients with subacute hyroiditis and Hashimoto thyroiditis, though no difference among those disorders was observed on T1- and T2-weighted images. Based on the ADC value, anisotropy was not observed in the thyroid gland. An ADC value of 1.82 x 10(-3) mm(2)/second or higher indicated the presence of Graves disease (sensitivity 75%, specificity 80%). CONCLUSION: Diffusion-weighted MR images may be of value for the diagnosis of thyroid diseases and could be clinically important in the evaluation of thyroid function.     

Clinical scale electroloading of mature dendritic cells with melanoma whole tumor cell lysate is superior to conventional lysate co-incubation in triggering robust in vitro expansion of functional antigen-specific CTL

Recent commercial approval of cancer vaccine, demonstrating statistically significant improvement in overall survival of prostate cancer patients has spurred renewed interest in active immunotherapies; specifically, strategies that lead to enhanced biological activity and robust efficacy for dendritic cell vaccines. A simple, widely used approach to generating multivalent cancer vaccines is to load tumor whole cell lysates into dendritic cells (DCs). Current DC vaccine manufacturing processes require co-incubation of tumor lysate antigens with immature DCs and their subsequent maturation. We compared electroloading of tumor cell lysates directly into mature DCs with the traditional method of lysate co-incubation with immature DCs. Electroloaded mature DCs were more potent in vitro, as judged by their ability to elicit significantly (p < 0.05) greater expansion of peptide antigen-specific CD8⁺ T cells, than either lysate-electroloaded immature DCs or lysate-co-incubated immature DCs, both of which must be subsequently matured. Expanded CD8⁺ T cells were functional as judged by their ability to produce IFN-γ upon antigen-specific re-stimulation. The electroloading technology used herein is an automated, scalable, functionally closed cGMP-compliant manufacturing technology supported by a Master File at CBER, FDA and represents an opportunity for translation of enhanced potency DC vaccines at clinical/commercial scale.