[Semantic processing of words in selective listening: an examination using recognition tests and event-related brain potentials].

Two experiments were conducted to investigate the degree of semantic processing for unattended words. In a dichotic listening task, each participant was required to attend selectively to either a word sequence in one ear or a speech passage in the opposite ear. The selective listening was confirmed by attenuated P1-N1 and N400 waves of the event-related brain potential to unattended words. The N400 attenuation with semantic priming was observed only for attended words. In a following recognition test with a booklet and auditory presentation, the percentage of false alarms for "new" words (or lures) semantically related to "old" words was higher when the "old" words were attended in selective listening than when unattended. These findings suggest that selective attention can act before and/or at a level of semantic processing.

Assessment of resistance to paclitaxel of murine tumors by (99m)Tc-MIBI/(201)Tl dual-radionuclide imaging.

This study investigated P-glycoprotein (Pgp) expression by murine tumors with and without resistance to paclitaxel and the role of (99m)Tc-2-methoxyisobutylisonitrile (MIBI)/(201)Tl imaging in predicting the effect of paclitaxel. Antitumor effect of paclitaxel and biodistribution of the radiopharmaceuticals were evaluated in mice bearing four tumor types. Pgp expression did not correlate with the antitumor efficacy of paclitaxel. Although the absolute uptake of (99m)Tc-MIBI did not correlate with Pgp expression, (99m)Tc-MIBI could predict paclitaxel sensitivity by its higher uptake.

Selective attention and N400 attenuation with spoken word repetition.

In two experiments, event-related brain potential were recorded to word pairs simultaneously presented to both ears, with instructions to attend to one ear and detect occasional nonwords in that ear. This attentional manipulation yielded four patterns of word repetition on successive trials: first and second presentations attended (AA), both unattended (UU), and across ears (AU and UA). A prominent attenuation of N400 due to immediate repetition of words was observed on AA trials. However, when first presentations were ignored on UU and UA trials, no repetition effect was obtained. These findings indicate that the repetition effect on N400 depends on attentional processing of first presentations.

[Phonological priming and auditory event-related brain potentials].

Phonological priming effects on auditory event-related brain potentials were compared across different numbers of syllables shared between target words and preceding prime words or pseudowords. All items of words and pseudowords consisted of 3 syllables, and the subject's task was to make a judgment whether the item belonged to a designated category. A large negative wave (N400), commencing at about 250 ms poststimulus and lasting for about 700 ms, was observed irrespective of primes and targets. When targets were preceded by word-primes that shared the first one or two syllables, the onset of N400 at the frontal site was earlier and the initial negative-going phase was steeper than in other conditions. In contrast, the magnitude of N400 to targets was reduced, when the primes were pseudowords that shared the first two syllables. These two types of early and later phonological priming effects were interpreted to reflect facilitations during spoken word recognition at the pre-lexical (phonological) and post-lexical (semantic or contextual integration) levels, respectively.

Enhanced radioresponse of paclitaxel-sensitive and -resistant tumours in vivo.

Paclitaxel is a potent chemotherapeutic drug and also has the potential to act as a radioenhancing agent. The latter is based on its ability to arrest cells in the radiosensitive G2M phases of the cell cycle; the weight of supporting evidence is derived mainly from in vitro studies. Our previous in vivo experiments identified enhanced tumour radioresponse predominantly attributable to tumour reoxygenation occurring as a result of paclitaxel-induced apoptosis. The current study investigated whether paclitaxel enhanced the radioresponse of tumours which are insensitive to apoptosis induction, but exhibited mitotic arrest, and compared the degree and kinetics of the response to that in tumours which develop apoptosis. The mouse mammary carcinoma MCa-29 (apoptosis sensitive) and the squamous cell carcinoma SCC-VII (apoptosis resistant) were used. In addition, the study investigated whether paclitaxel affected normal skin radioresponse to determine if a therapeutic gain could be achieved. Paclitaxel enhanced the radioresponse of both types of tumours. In the SCC-VII tumour, radiopotentiation occurred within 12 h of paclitaxel administration coincident with mitotic arrest, where enhancement factors (EFs) ranged from 1.15 to 1.37. In MCa-29 tumour, the effect was greater, EFs ranging from 1.59 to 1.91 and occurred between 24 and 72 h after paclitaxel when apoptosis was the predominant microscopic feature of treated tumours and when tumour oxygenation was found to be increased. The acute skin radioresponse and late leg contracture response were essentially unaffected by prior treatment with paclitaxel. Therefore, by two distinct mechanisms, paclitaxel was able to enhance the radioresponse of paclitaxel-sensitive and -resistant tumours, but not the normal tissue radioresponse, thus providing true therapeutic gain.

Effect of radiation and paclitaxel on p53 expression in murine tumors sensitive or resistant to apoptosis induction.

PURPOSE: Tumors are thought to differ in their response to cytotoxic agents for a variety of reasons including cell cycle kinetics, degree of hypoxia, differential repair, and ability to survive when stressed. Our previous studies showed that murine mammary carcinoma MCA-4 tumors are relatively sensitive to both radiation and paclitaxel and exhibit a significant apoptotic response following treatment in vivo. In contrast, murine squamous cell carcinoma SCC-VII tumors are relatively resistant to radiation and paclitaxel and exhibit relatively little apoptosis following treatment. Since dysfunctional p53 has been shown to be associated with tumor resistance, perhaps through a dysregulated cell loss mechanism, we examined the role of p53 expression in the differential apoptotic response of these two tumors following cytotoxic treatment in vivo. METHODS AND MATERIALS: Mice bearing 8-mm tumors were treated with 40 mg/kg paclitaxel i.v. or 15 Gy local tumor irradiation, and tumors were harvested at several time points up to 2 days following treatment. Histological sections of the tumors were then assessed micromorphometrically for mitotic arrest and apoptosis and immunohistochemically for p53 and p21 expression. RESULTS: In the apoptosis-sensitive MCA-4 tumors, p53 expression increased rapidly following radiation from 13% at baseline to a peak of 45% within 3 h, and expression remained elevated for more than 24 h. Radiation also upregulated p21 suggesting that radiation-induced apoptosis in MCA-4 tumor is p53 dependent. Paclitaxel also induced an increase in both p53 and p21 expression in MCA-4 cells; however, the increase was delayed compared to that after irradiation. This upregulation occurred after the onset of apoptosis which would suggest that paclitaxel-induced apoptosis is p53 independent. Both radiation and paclitaxel caused p53 upregulation in the apoptosis-resistant SCC-VII tumors. The untreated SCC-VII tumor has 25% cells p53 positive and has a very high level of p21 (87% cells positive) which suggests a downstream defect in p53 response. CONCLUSION: These results show that tumor responsiveness to paclitaxel and radiation, measured by tumor growth delay, was associated with apoptotic response. However, although both agents upregulated p53 expression in these tumors, the association between this upregulation and induction of apoptosis was not clear. Additional studies using these and other tumors are warranted to elucidate the role of p53 and its downstream effectors in the in vivo responsiveness of tumors to paclitaxel and radiation.

Antimetastatic activity of lipopolysaccharide against a NK-resistant murine fibrosarcoma.

An intravenous injection of bacterial lipopolysaccharide (LPS) into mice exerted prominent antimetastatic activities against a NK-resistant weakly immunogenic NFSa fibrosarcoma. The number of visible metastases in the lung was increased by a pretreatment of anti-asialoGM1 (asGM1) antibody or silica, but pretreatment of asGM1 antibody or silica scarcely affected the antimetastatic activities of LPS. The pulmonary retention of radiolabeled tumor cells showed that LPS accelerated the detachment of the tumor cells from the lung, and that this acceleration was not suppressed by anti-asGM1 antibody. Sialic acids of lung endothelial cell surface, essential components of various receptors, was diminished by the i.v. injection of LPS. These results suggested that the antimetastatic effect of LPS against NK-resistant NFSa cells was partly the result of modulations of lung endothelial cell surface.

Significance of platelets in an antimetastatic activity of bacterial lipopolysaccharide.

Recently we reported an antimetastatic activity of bacterial lipopolysaccharide (LPS) on a NK-cell-resistant murine fibrosarcoma (NFSa). Here we investigate and report the mechanistic significance of platelets in this activity. The number of circulating platelets was reduced to 63% of the control 3 days after an i.v. injection of 1.0 micrograms LPS, and then recovered to the level of control at day 10. Aggregation efficiency of platelets was impaired by LPS. The number of metastatic lung colonies after an i.v. injection of tumor cells was maximally reduced to 2.2% of the control at day 3 and increased in proportion to the recovery of platelet number. Neuraminidase (Ndase), which caused a non-immunological thrombocytopenia, also inhibited lung metastasis when injected prior to an i.v. tumor cell challenge. LPS and Ndase showed an identical pattern against five other syngeneic tumors; these agents inhibited lung metastases of the FSa fibrosarcoma and the SCC VII squamous cell carcinoma but failed to inhibit those of the NR-S1 squamous cell carcinoma, the MMCa#4 mammary adenocarcinoma and the NR-PG parotid gland tumor. All the three cells which were not responsive to any agents possessed a high aggregating activity of platelets while the other three tumors responsive to both agents did not show a detectable level of this activity. Platelet transfusion failed to modify the antimetastatic activity of LPS. These results suggest that platelets play an important role in the antimetastatic activity of LPS, though whether the role is principal or assistant remains to be seen.

Active components of intestinal bacteria for abdominal irradiation-induced inhibition of lung metastases.

We have previously reported that abdominal irradiation of mice inhibited lung metastases of a weakly immunogenic fibrosarcoma, and that transmigration after the irradiation of Enterobacter cloacae into mesenteric lymph nodes coincided with this phenomenon. In this paper, we show that Escherichia coli as well as E. cloacae reduce the number of metastatic lung colonies when these bacteria were intravenously injected into mice prior to the tumour cell challenge. The inhibition was caused not only by the administration of living bacteria but also by that of killed bacteria. Bacterial lipopolysaccharide (LPS), a component of membrane, replaced at least in part the effect of whole bacteria. Transfer of spleen cells from LPS-treated mice into intact recipients prominently inhibited metastatic development in the recipient mice. 'Cross transfer' between LPS high responders and LPS low responders suggested an indirect activity of transferred spleen cells. The antimetastatic activity of LPS depended on the tumour cell type; metastasis of fibrosarcomas was extensively inhibited by LPS irrespective of tumour immunogenicity while that of adenocarcinomas was only slightly inhibited. These results suggest that non-immunological mechanisms are involved in the antimetastatic activity of LPS.