Changes of cancer diagnosis disclosure to children in Japan in the last 20 years

International Journal of Clinical Oncology - The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change...     

Analysis of variance study of the rat cortical layer 4 barrel and layer 5b neurones

Unique formation of rodent cortical barrels by layer 4 neurones attracts study of the sensory function of cortical input stage neurones (layer 4) compared with that of output stage neurones (layer 5). We have recorded extracellular responses from rat somatosensory cortical neurones to deflections of contralateral vibrissae. Thirty-two layer 4 barrel neurones and 29 layer 5b neurones were studied. Whisker stimulations were ramp-and-hold deflections with one of six different ramp velocities (100–2.5 mm s⁻¹) and one of four different plateau amplitudes (2000–200 μm). Twenty-four (6 × 4) different stimulus forms were applied to the tip of a whisker trimmed to 10 mm in a predetermined order in stimulus cycles of 20–50 repetitions. Spike counts for a period of 2560 ms in 10 ms bins were summed to construct a matrix of 24 peristimulus histograms for each neurone. Twenty-four amplitude and 24 velocity values were computed from counts during the plateau and ramp phases, respectively. To determine the amplitude- and velocity dependence of a neurone, an amplitude F value (the ratio of variations among-/within-amplitude of the amplitude value) and a velocity F value (ratio of variations among-/within-velocity of the velocity value) were derived by analysis of variance. The amplitude F value of the layer 4 barrel neurones was greater than that of the layer 5b neurones ( P < 0.0001). The velocity F value of the barrel neurones was smaller than that of the layer 5b neurones ( P = 0.0226). The results suggests that barrel neurones and layer 5b neurones tend to detect amplitude and velocity components of whisker deflection, respectively.     

Fractalkine and inflammatory diseases]

The migration of leukocytes into inflamed peripheral tissues and lymphoid organs involves a cascade of molecular events finely regulated by cell adhesion molecules and chemokines. Fractalkine/CX3CL1 is a membrane-bound chemokine that functions not only as a chemoattractant but also as an adhesion molecule, and is expressed on endothelial cells activated by proinflammatory cytokines. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes including NK cells and cytotoxic effector T cells (T(CE)), mature monocytes/macrophages, and mucosal dendritic cells, all of which play important roles in elimination of pathogens and cancer cells. Recently, accumulating evidence in both clinical studies and animal disease models has shown that fractalkine is also involved in the pathogenesis of various chronic inflammatory diseases, such as rheumatoid arthritis and atherosclerosis. This article reviews the unique functions of fractalkine and its pathophysiological roles in various clinical conditions.     

Association of the GNAS1 gene variant with hypertension is dependent on alcohol consumption.

The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension.     

Fluid-fluid levels in cavernous hemangioma of soft tissue

Five cases of cavernous hemangioma with fluid-fluid levels on magnetic resonance imaging and/or computed tomography are reported. The signal characteristics were those of blood and histological analysis of the fluid-fluid levels showed that they were blood-filled cavities in the tumor. Although this finding itself is not specific, it may help in confirming the diagnosis of cavernous hemangioma.     

Mucin expression profile in pancreatic cancer and the precursor lesions

In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary–mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.     

Immunology: Diversity of the blocking effects of antisperm antibodies on fertilization in human and mouse

The blocking effects of complement-dependent sperm immobilizingantibodies in the sera of infertile women and monoclonal antispermantibodies against humans and mice on fertilization were investigated.The hemizona assay (HZA) and sperm penetration assay (SPA) wereused to study the inhibitory effects of sera from 22 infertilepatients positive for sperm immobilizing antibodies. Use ofthese tests allowed us to differentiate whether the antibodyblocked sperm—zona pellucida tight binding and/or spermpenetration into the ooplasm. The zona pellucida penetrationassay (ZPA) was also used to study the effects of four monoclonalantibodies (mAbs) on human sperm penetration into the zona pellucida.Seven mAbs against murine spermatozoa were tested for theirinhibitory effects on in-vitro fertilization (IVF) and HZA inmice. Of 22 patient sera with sperm immobilizing antibodies,21 (95.5%) inhibited HZA attachment and penetration, whereasthis did not occur in any of 13 patient sera without these antibodies.However, 19 of 22 (86.4%) patient sera with sperm immobilizingantibodies and eight of 13 (61.5%) patient sera without theseantibodies inhibited the SPA. Two (2C6, 1G12) of four mAbs againsthuman spermatozoa showed strong inhibitory effects in all theassays (HZA, ZPA and SPA). One mAb (3B10) did not inhibit HZAbut blocked ZPA and SPA. Another mAb (H6-3C4) seemed to haveno inhibitory effects on fertilization. Two (Vx 5 and Vx 8)of seven mAbs against murine spermatozoa inhibited IVF in micebut did not block mouse HZA. These findings suggest that antispermantibodies block fertilization at specific stages. Some of themmay inhibit sperm capacitation and thus prevent all processesof fertilization that follow. Some other antibodies may notaffect capacitation and sperm binding to zona pellucida butinhibit the acrosome reaction, followed by the blocking of spermpenetration through zona pellucida and ooplasm.     

Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells

BACKGROUND: Inflammation has been proposed to play essential roles in the pathophysiology of endometriosis, in which neutrophils and mast cells have been suggested to be involved. We studied whether the protease-activated receptor 2 (PAR2), which is activated by enzymes from neutrophils and mast cells, in endometriotic stromal cells (ESC) has any implication in the development of the disease. METHODS: Cultured ESC were stimulated with various concentrations of a specific PAR2 agonist peptide. Proliferating activity of the cells was determined using immunostaining of proliferating cell nuclear antigen (a cell proliferation marker), 5-bromo-2'-deoxyuridine incorporation into DNA and cell count. The concentrations of interleukin (IL)-6 and IL-8 were measured using specific enzyme-linked immunosorbent assay kits. The phosphorylation of three mitogen-activated protein kinases (MAPK), i.e. p38 MAPK, p42/44 MAPK and stress-activated protein Kinase/c-jun N terminal Kinase, in ESC was examined with Western blot analysis. RESULTS: Activation of PAR2 stimulated the proliferation of ESC and the secretion of IL-6 and IL-8 from ESC in a dose-dependent manner. Activation of PAR2 stimulated the phosphorylation of all three MAPK, and inhibitors of each MAPK suppressed the PAR2 activation-induced proliferation of ESC. CONCLUSIONS: The activation of PAR2 in ESC may be involved in the pathophysiology of endometriosis by inducing the growth and inflammation of endometriotic lesions.     

Development of enrofloxacin ELISA using a monoclonal antibody tolerating an organic solvent with broad cross-reactivity to other newquinolones

Antibacterial reagents, especially quinolones, are widely used in animals and humans, and have caused serious problems to human health because of their residual contaminants in food. In order to screen for different kinds of newquinolones at the same time, a sensitive and specific enzyme-linked immunoassay (ELISA) has been developed. The anti-enrofloxacin monoclonal antibody was selected because of its ability to react with structurally related newquinolones in organic solvent. The antibody has 100% cross-reactivity with norfloxacin, ciprofloxacin and other newquinolones at 50% inhibition of control values IC₅₀, but not with nitroflazone, sulphadimethoxine. The lowest detection limit of this ELISA was 0.7 ng/ml (ppb) when enrofloxacin was used as the calibrator. Eel extracts were spiked with enrofloxacin and the average recoveries at 10, 50, 100 ng/ml were 98, 102 and 91%, respectively. The proposed ELISA is a useful method for the practical microquantitation of various newquinolones in biological and environmental specimens.