Effects of ISI and stimulus probability on event-related go/nogo potentials after somatosensory stimulation

The present study investigated the characteristics of the middle-latency negative potential of event-related potentials (ERPs) using somatosensory go/nogo tasks. We manipulated interstimulus interval (ISI) in Experiment 1 and stimulus probability in Experiment 2 and analyzed the subtracted difference waveform resulting from subtraction of the ERP evoked by the go stimulation from that evoked by the nogo stimulation. In Experiment 1, the peak latency of negativity became significantly longer as the ISI increased, but the peak amplitude was unchanged. The reaction time (RT) was longer with increasing ISI. In Experiment 2, manipulation of the stimulus probability yielded an increase in peak amplitude with decreasing probability of the nogo stimulus, but did not affect the latency. The RT increased as the probability of a nogo stimulus rose. Because manipulation of the ISI and stimulus probability elicited different brain activities, we hypothesized that manipulation of the ISI elicited a delay of the stimulus evaluation process including response inhibition, and that stimulus probability significantly affected the strength of the response inhibition process.     

Refined mapping of eight cosmid markers on human chromosome 22

Summary Eight cosmid clones were regionally assigned to small subregions of chromosome 22 by hybridization with a total of 22 somatic cell hybrids. One cosmid was localized to the proximal part of 22q which contained the region commonly deleted in the DiGeorge syndrome. Seven cosmids showing restriction fragment length polymorphisms were localized to the telomeric region distal to the MB locus, which was reported to be frequently deleted in sporadic meningioma. These cosmids, when finely mapped and ordered, are considered useful for the identification of genetic alterations on this chromosome arm.     

Alteration of T cell maturation and proliferation in the mouse thymus induced by serum factors from patients with ulcerative colitis.

Recently it has been reported that patients with ulcerative colitis (UC) often have thymus abnormalities, although the precise mechanisms which induce those abnormalities remain unclear. We have examined the effect of serum fractions from patients with UC and other colonic diseases on mouse thymus to clarify the possible existence of factors which have thymus growth activity. These fractions were separated from sera of patients with UC by gel filtration and anion exchange high performance liquid chromatography. In mice given UC serum fractions; (i) remarkable increases in weight and total cell number of the thymus were observed from day 4 to day 9; (ii) a significant increase in the number of peanut agglutinin (PNA)+ thymus cells was demonstrated using flow cytometry on day 9; (iii) on quantitative analysis of surface antigens the percentage of Lyt-2+ thymus cells decreased and that of L3T4+ thymus cells increased remarkably on day 13; the number of bright Thy-1.2+ cells and of dull Lyt-1+ cells increased. In contrast, the serum fractions from patients with other colonic diseases and from normal persons caused little change in mouse thymus throughout the study. The results suggest that factors fractionated from the serum of patients with UC disturb intra-thymic T cell maturation and enhance the proliferation of thymus cells.     

Expression of cytoplasmic TFF2 is a marker of tumor metastasis and negative prognostic factor in gastric cancer

Trefoil factor family 2 (TFF2) is a small peptide constitutively expressed in the gastric mucosa, where it plays a protective role in restitution of gastric mucosa. TFF2 has also been shown to be expressed in some gastric cancers, but its role in tumor metastasis and patient prognosis has not been examined. In this study, we examined TFF2 expression at both the mRNA and protein levels and correlated these results with the clinicopathologic characteristics and prognosis of gastric cancer patients. Among the 144 curatively resected samples, 43 (30%) were positive for TFF2. TFF2 expression was preferentially observed in the infiltrating tumor cells sparing the superficial cells. Significantly increased expression of TFF2 was noted in large tumors of the diffuse type. An increased prevalence of TFF2 expression was also found in tumors with advanced T and N stage and in patients with lymphatic and venous invasion. Accordingly, patients with TFF2-expressing tumors had a significantly worse disease-free survival, and in multivariate analysis, this finding remained significant as an independent prognostic factor. Taken together, our results suggest that TFF2 expression may play a role in gastric cancer invasion and as such could be a useful target for therapeutic intervention.     

Biological properties and gene expression associated with metastatic potential of human osteosarcoma

Lung metastasis has a great influence on the prognosis of patients with osteosarcoma. We previously established two high-metastatic sublines, M112 and M132, from the HuO9 human osteosarcoma cell line by in vivo selection. In this study, we newly isolated a high-metastatic subline, H3, and three low-metastatic sublines, L6, L12 and L13, from HuO9 by the dilution plating method. Three high-metastatic sublines produced more than 200 metastatic nodules in the lung, while three low-metastatic sublines produced no or few nodules after injection of 2 × 10⁶ cells into the tail vein of nude mice. There were significant differences in the motility and invasiveness between high- and low-metastatic sublines, whereas the growth rates in vitro and the tumorigenicity in vivo showed no correlation with their metastatic abilities. Early adherence to culture plates was significantly lower in two of three low-metastatic sublines, which occupied smaller surface areas on the culture plates than other sublines did. Comparison of the expression of 637 cancer-related genes by cDNA microarray revealed that seven genes were differentially expressed between high- and low-metastatic sublines. Among them, five genes (AXL, TGFA, COLL7A1, WNT5A, and MKK6) were associated with adherence, motility, and/or invasiveness. These results suggest that the differences in motility/invasiveness and adhesive abilities are key determinants of lung metastasis in osteosarcoma. This revised version was published online in July 2006 with corrections to the Cover Date.     

WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production

WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi. WSX-1-/- mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1-/- splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1-/- mice, and IFN-gamma that was overproduced in WSX-1-/- mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-alpha, were produced by liver mononuclear cells in WSX-1-/- mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production.     

Intracellular Ca antagonist TMB-8 blocks catecholamine secretion evoked by caffeine and acetylcholine from perfused cat adrenal glands in the absence of extracellular Ca

Unlike acetylcholine, caffeine was much more effective in releasing catecholamine in the absence of extracellular Ca²⁺ than in its presence in perfused cat adrenal glands. The intracellular Ca²⁺ antagonist, TMB-8 (10⁻⁴ M), inhibited reversibly the catecholamine secretion evoked by caffeine (40 mM) and that induced by acetylcholine (10⁻⁴ M) in the presence of hexamethonium (10⁻³ M) during perfusion with Ca²⁺-free Locke solution containing EGTA (10⁻⁵ M). These results support our view that muscarinic receptor activation causes catecholamine secretion by mobilizing Ca²⁺ from an intracellular pool just as caffeine does.     

Immunohistochemical studies on oncogene products (EGF-R,c-erbB-2) and growth factors (EGF,TGF-α) in human breast cancer: their relationship to oestrogen receptor status,histological grade,mitotic index and nodal status

Summary In this investigation, 83 human mammary carcinomas were examined for the expression of oestrogen receptor (ER), epidermal growth factor receptor (EGF-R), epidermal growth factor (EGF), transforming growth factor alpha (TGF-), c-erbB-2, histological grade, mitotic index and nodal status, all of which are reportedly prognostically significant factors (Bloom and Richardson 1957; Baak et al. 1985; Wright et al. 1989). ER expression was biochemically recognized in 43.4% of mammary carcinomas, and EGF-R, EGF, TGF- and c-erbB-2 were histochemically recognized in 25.3, 14.5, 27.7 and 18.0% of mammary carcinomas examined respectively, using conventional sections of buffered formalin-fixed, paraffin-embedded tissue and monoclonal or polyclonal antibodies. There were significant relationships between negative ER and positive EGF-R or TGF-; positive EGF-R and TGF-; positive EGF-R and c-erbB-2; and positive c-erbB-2 and TGF-. The single changes which were the negative ER and the positive c-erbB-2 correlated with histological grade and mitotic index. Co-expression of EGF-R and TGF- correlated with positive nodal status. Therefore, the present investigation indicates that the negative ER, single expression of c-erbB-2 and co-expression of EGF-R and TGF- are important markers which contribute indirectly to prognosis, which reconfirms previous findings on the former two while adding the new finding that immuno-histochemical demonstration of expression of EGF-R and TGF- may provide useful information for selecting the appropriate treatment.     

Construction of radiation-reduced hybrids and their use in mapping of microclones from chromosome 10p11.2-q11.2

Summary Radiation-reduced hybrids for mapping of DNA markers in the pericentromeric region of chromosome 10 were developed. A Chinese hamster/human somatic cell hybrid (762-8A) carrying chromosomes 10 and Y as the only human material were exposed to 40,000 rads of irradiation and then rescued by fusion with non-irradiated recipient Chinese hamster cells (GM459). Southern hybridization analyses revealed that 10 of 128 HAT-resistant clones contained human chromosomal fragments corresponding to at least one marker locus betweenFNRB (10p-11.2) andRBP3 (10q11.2). These hybrids were then used to map microdissection clones previously isolated and roughly mapped to this chromosomal region by fluorescencein situ hybridization (FISH). Two of the six microclones studied could be mapped to the proximity of the D10-S102 locus. These radiation hybrids are useful for the construction of refined genetic maps of the pericentromeric region of chromosome 10.     

Expression of transforming growth factor alpha in human tissues: Immunohistochemical study and Northern blot analysis

Summary The expression of transforming growth factor alpha (TGF-) was examined in various human tissues and the fetus, using immunohistochemistry and Northern blot analysis. TGF- immunoreactivity was detected mainly in the epithelial cells of the digestive tract, liver, pancreas, kidney, thyroid, adrenal, skin, mammary gland and genital organs. In the digestive tract, epithelial cells with regenerative change or hyperplastic change showed strong immunoreactivity to TGF-. Peripheral nerve, vessels, megakaryocytes and macrophages in the lung and spleen were also positive for TGF-. By Northern blot analysis the expression of TGF- mRNA was confirmed in the digestive tract, salivary gland, thyroid, kidney and mammary gland. In the human fetus, the nerve tissues, liver, adrenal and kidney were positive for TGF-. Strong immunoreactivity to TGF- was observed in the hepatocytes of the fetus. These findings indicate that TGF- is produced by a variety of nonneoplastic cells in both adult and fetal tissues.