Threshold-dependent effects on peripheral nerve in vivo excitability properties in the rat

Various factors, including maturity, have been shown to influence peripheral nerve excitability measures, but little is known about differences in these properties between axons with different stimulation thresholds. Multiple nerve excitability tests were performed on the caudal motor axons of immature and mature female rats, recording from tail muscles at three target compound muscle action potential (CMAP) levels: 10%, 40% (“standard” level), and 60% of the maximum CMAP amplitude. Compared to lower target levels, axons at high target levels have the following characteristics: lower strength-duration time constant, less threshold reduction during depolarizing currents and greater threshold increase to hyperpolarizing currents, most notably to long hyperpolarizing currents in mature rats. Threshold-dependent effects on peripheral nerve excitability properties depend on the maturation stage, especially inward rectification (Ih), which becomes inversely related to threshold level. Performing nerve excitability tests at different target levels is useful in understanding the variation in membrane properties between different axons within a nerve. Because of the threshold effects on nerve excitability and the possibility of increased variability between axons and altered electric recruitment order in disease conditions, excitability parameters measured only at the “standard” target level should be interpreted with caution, especially the responses to hyperpolarizing currents.     

Surgical Outcomes in Esophageal Cancer Patients with Tumor Recurrence After Curative Esophagectomy

This study aimed to identify predictive factors and to evaluate appropriate treatments for recurrence of esophageal cancer after curative esophagectomy. About 166 consecutive patients, who underwent curative esophagectomy, were enrolled between April 1994 and March 2003. Recurrence was classified as loco-regional or distant. Logistic regression analysis was used to identify predictive factors for recurrence. Prognostic factors were evaluated by Log-rank test and Cox proportional hazard regression analysis. The disease-specific 5-year survival was 56.8%. Recurrence was observed in 72 patients (43.4%), with 64 of these occurring within 3 years. The number of metastatic lymph nodes and lymphatic invasion independently predicted recurrence. There were significant differences in time to recurrence and survival time between loco-regional, distant recurrence, and combined recurrence. The 5-year survival time in patients with recurrence was 11.9%, and median survival time was 24 months. There was also a significant difference in survival after recurrence between treatment methods (no treatment vs chemo-radiotherapy, p = 0.0063; chemotherapy, p = 0.0247; and radiotherapy, p < 0.0001). Meticulous, long-term follow-up is particularly necessary in patients with four or more metastatic lymph nodes to achieve early detection of recurrence. Randomized controlled trials should be used to develop effective modalities for each recurrence pattern to improve therapeutic outcomes.     

Regional Expression of CXCL12/CXCR4 in Liver and Hepatocellular Carcinoma and Cell-cycle Variation during in vitro Differentiation

The CXCL12/CXCR4 system may be important in carcinoma. Expression of the a‐chemokine SDF‐lα (stromal cell derived factor‐lα)/CXCL12 mRNA is reduced in many carcinomas, yet its tissue protein expression may guide metastasis. Here we first compare the mRNA and protein expression of CXCL12 and its receptor CXCR4 in human liver, hepatocellular carcinoma, and malignant cell lines, and then assess cell cycle variation in CXCR4 expression. CXCR4 mRNA was present in most normal human tissues and malignant cell lines; it was only marginally reduced in hepatomas, while CXCL12 was markedly reduced, P<0.0001. Immuno‐histochemical staining of adjacent non‐malignant liver showed regional CXCR4 cytoplasmic and cell‐surface staining, limited to those hepatocytes around the central vein, a distribution resembling that of CXCL12. CXCL12 protein was not present in hepatocellular carcinoma cells in vivo, nor was cytoplasmic CXCR4 staining; nuclear CXCR4 protein expression in some malignant hepatocytes and CXCR4 staining of capillary endothelial cells around tumor cells were noted. In some malignant cell lines that had no CXCL12 on northern blots CXCL12 was weakly detectable by RT‐PCR or protein staining in the cytoplasm of a few cells. With a view to future manipulation of CXCL12/CXCR4 expression and growth we noted that in HT‐29 cells CXCR4 protein expression was less on confluent than on non‐confluent cells and varied during the cell cycle. Higher expression was associated most closely with the percentage of cells in the S‐phase and inversely with the percentage of cells in the G1‐phase. Treatment of HT‐29 cells with butyrate reduced CXCR4 cell surface expression and reduced the percentage of cells in S‐phase. In summary, CXCL12 protein expression parallels its mRNA, being markedly reduced in malignant cell lines and hepatomas; in liver, the regional distributions of CXCL12 and cytoplasmic CXCR4 are similar; finally, in HT‐29, CXCR4 expression correlates with the S‐phase of the cell cycle and is reduced during butyrate‐induced differentiation.     

Contrast sensitivity of patients with severe motor and intellectual disabilities and cerebral visual impairment

We attempt to evaluate the residual visual capacities of nine patients (seven males and two females; age range 4 to 35 years, mean 13.8 +/- 9.98) with cerebral visual impairment coupled with severe motor and intellectual disabilities by their contrast sensitivities to sine-wave gratings. Two methods were used for detecting the occurrence of ocular responses to stimuli: (1) detection of optokinetic nystagmus to drifting sinusoidal gratings by naked-eye observation and electronystagmography and (2) detection of ocular pursuit for a drifting Gabor patch by naked-eye observation. We succeeded in measuring the sensitivities of eight cases. For the remaining one case, only the Gabor method could be applied. Most cases showed low contrast sensitivity in both higher (2 and 4 cycles/degree) and lower (0.125 and 0.25 cycles/degree) spatial frequencies and relatively high contrast sensitivity in the middle (0.5 and 1 cycle/degree) range of spatial frequencies. We conclude that the residual visual capacities of patients with severe motor and intellectual disabilities and cerebral visual impairment can be measured fairly accurately by these behavioral methods.     

Validity of attentional-style subscales for the Japanese version of the Test of Attentional and Interpersonal Style (TAIS)

The six attentional-style subscales of the Test of Attentional and Interpersonal Style (TAIS, Nideffer, 1976) have been used mainly in the sport psychology area to investigate the relationship between attentional abilities and performance. This study assessed the validity of the Japanese version of the TAIS attentional-style subscales with 157 male and 163 female students. A confirmatory factor analysis failed to validate Nideffer's attentional dimension of bandwidth (narrow to broad attention) and direction (internal to external). The findings replicate previous studies which showed that the structure of the TAIS attention-related subscales is not reasonable and its factorial validity does not meet the needs of psychometrics.     

Rapid development of nitric oxide-induced hyperalgesia depends on an alternate to the cGMP-mediated pathway in the rat neuropathic pain model

Intrathecal injection of a nitric oxide releasing compound, NOC-18, was used to define the role of nitric oxide (NO) in the spinal mechanism of neuropathic pain caused by unilateral chronic constriction injury to rat sciatic nerves. Paw withdrawal latency was used to evaluate nociception induced by thermal stimuli before surgery and afterwards at 1, 3, and 6 h, and on days 1, 2, 3, 4, 5, 8, and 12 after the nerve ligature. In the sham-surgery control groups, intrathecal injection of 10 or 100 μg of NOC-18 did not produce any change in withdrawal latencies. In rats with unilateral nerve ligation, however, administration of 1 or 10 μg, but not 0.1 μg, of NOC-18 significantly shortened the time in which thermal hyperalgesia developed after nerve injury. Injection of 1 μg of NOC-18 decreased the onset time of thermal hyperalgesia from 2 days to 3 h and with 10 μg hyperalgesia developed within 1 h after the nerve injury. The effects of intrathecal injection of MK-801, a N-methyl-

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-aspartate (NMDA) receptor antagonist, N-nitro-

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-arginine methyl ester (

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-NAME), a NO synthase inhibitor, methylene blue (MB), a soluble guanylate cyclase inhibitor, and hemoglobin (Hb), a NO scavenger, on the development of thermal hyperalgesia after the sciatic nerve ligature were examined in the presence and absence of 1 and 10 μg of NOC-18. Acceleration of the development of thermal hyperalgesia induced by 1 and 10 μg NOC-18 was completely inhibited by Hb, but was not affected by either MK-801,

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-NAME or MB. These findings indicate that NO plays an important role in the rapid development of thermal hyperalgesia after the nerve injury, but that facilitation of nociceptive processing in the spinal cord may entail an alternate to the NO–cyclic guanosine 3′,5′-monophosphate (cGMP) pathway.     

Augmentation of c-fos and c-jun expression in transgenic mice carrying the human T-cell leukemia virus type-Itax gene

To analyze the effect of human T-cell leukemia virus type I (HTLV-I) on cellular gene expression and its relation to tumorigenesis, two lines of transgenic mice carrying the long terminal repeat (LTR)-env-pX-LTR regions of the HTLV-I genome were produced. The transgene was expressed in many organs, including the brain, salivary gland, spleen, thymus, skin, muscle, and mammary gland. We found that the expression of the c-fos and c-jun genes, but not of thelyn and c-myc genes, was augmented 2- to 20-fold in histologically normal skin and muscle of these mice. The augmentation was tissue specific, suggesting the involvement of a cellular factor in the transgene action. In these mice, a three to seven times higher incidence of tumors was seen as compared with the control mice. These tumors included mesenchymal tumors, such as fibrosarcoma, neurofibroma, and lipoma, and adenocarcinomas of the mammary gland, salivary gland, and lung. The c-fos and c-jun genes were also activated in these tumors. The possible roles of elevated c-fos and c-jun gene expression in tumorigensis are discussed.The abbreviations used are ATL, adult T-cell leukemia; HTLV-I, human T-cell leukemia virus type I; IL-2, interleukin 2; IL-2R, interleukin 2 receptor; IL-6, interleukin 6; LTR, long terminal repeat.     

Neuraminidase activity and syncytial formation in variants of parainfluenza 3 virus.

By a sensitive fluorometric assay method, we could definitely demonstrate neuraminidase activity for two variants of parainfluenza 3 virus, M and SC, which were previously shown to have no detectable neuraminidase activity. The enzyme activities of these viruses were very similar to each other, showing a much lower catalytic rate, a much higher Km value, and a more acidic pH optimum than those of the virus variants of high neuraminidase activity, 910N, LT, and MR. M and SC viruses eluted from guinea pig erythrocytes very poorly, whereas 910N and LT viruses eluted readily. M virus required the aid of a bacterial neuraminidase for effective growth and plaque formation in MDBK cells, but the virus grew well and formed plaques in R66 and Vero cells without the enzyme. SC virus required no exogenous neuraminidase for growth in all of these cell types. Depending on cell type, SC virus induced slight to extensive syncytial formation which was greatly inhibited by exogenous neuraminidase. In contrast, M virus induced extensive syncytial formation in all these cells regardless of the presence or absence of exogenous neuraminidase, although development and disintegration of the syncytia were more or less retarded by the enzyme, especially in MDBK cells. These results indicate that M virus possesses highly potent inducibility of syncytial formation which is further fortified by being low in viral neuraminidase activity.     

Clinical significance of matrix metalloproteinase-7 expression in esophageal carcinoma.

Matrix metalloproteinase-7 (MMP-7) is a member of MMP family and has a wide variety of substrate spectra. It is reported to play an important role in carcinoma invasion and metastasis. There is, however, little information on the clinical significance of MMP-7 in human esophageal carcinoma. We thus studied 48 tumor/normal pair samples of human esophagus by Northern blot analysis. The results demonstrated that the tumor tissue (T) of esophageal carcinoma showed a higher expression of MMP-7 mRNA than the corresponding normal tissue (N) in 31 cases (65%). We also statistically evaluated tumor MMP-7 value (T value) corrected for MMP-7-positive control (KYSE150 transfected with the MMP-7 gene). Fourteen cases with T value > or = 0.3 showed a higher frequency of lymph node metastasis than 34 cases with T value < 0.3 (P < 0.05). The cases with T value > or = 0.3 showed a significantly poorer prognosis than those with T value < 0.3 (P < 0.01). Multivariate analysis demonstrated that the MMP-7 expression status was the independent factor relating to the prognosis (P = 0.0005). The findings indicated that MMP-7 might be a novel prognostic factor for patients with esophageal carcinoma.