Subacute sclerosing panencephalitis with special reference to the ultrastructure of inclusions in the brain and lung.

A 7-year-old boy, who was diagnosed as typical SSPE by clinical data and laboratory findings, was autopsied and observed by immunofluorescent techniques, light and electron microscope. The morphological characteristics in the brain were perivascular cuffings with plasma cells, lymphocytes and mononuclear cells, gliosis and a large number of intranuclear and intracytoplasmic inclusions in the neuroglias and nerve cells. Various kinds of intranuclear inclusions were elucidated by electron microscopy and the fin structures of these inclusions were described in detail. At least five types of intranuclear inclusions were regarded as specific in SSPE. The presence of intranuclear inclusions of mononuclear cells in the lungs resembling the inclusions in the neuroglias suggested that the disease was not localized in the brain but could be disseminated throughout the body.     

Lack of association between DNA base excision repair gene XRCC1 Gln399Arg polymorphism and risk of malignant lymphoma in Japan

Growing evidence suggests that the polymorphism of DNA base excision repair gene XRCC1 Arg399Gln is associated with altered DNA repair proficiency and subsequent cancer susceptibility; however, no evidence is available for malignant lymphoma. We therefore conducted a case-control study (372 cases, 500 controls) to evaluate links with malignant lymphoma risk in Japan. The risk was evaluated in terms of odds ratio (OR) and 95% confidence interval (CI) adjusted for age and sex in an unconditional logistic regression model. There was no statistical risk change with the Arg/Gln (adjusted OR 0.89; 0.65-1.23, P = 0.492) or the Gln/Gln (0.57; 0.27-1.17, P = 0.127) compared with the Arg/Arg of the XRCC1 Arg399Gln polymorphism. The results were unchanged in analyses according to histological subtype (diffuse large lymphoma, follicular lymphoma, low-grade lymphoma of mucosa-associated lymphoid tissue, and others). These data suggest that XRCC1 Gln399Arg polymorphism plays a limited role in lymphomagenesis. Further study on the interaction between the polymorphism and environmental exposure is required.     

Direct tumor growth suppressive effect of melanoidin extracted from immunomodulator-PSK

Melanoidin, which belongs to the melanin group of molecules, was extracted from the polysaccharide biological response modifier PSK. Melanoidin was cultured together with HCT-15 cells derived from human colon cancer and with AGS cells derived from human gastric carcinoma. After four days of culture, cell count was compared with that of the control cells. Significant suppression was observed, that is, 50% suppression was shown at concentrations of melanoidin between 200 and 100 micrograms/ml. A histogram generated by flow cytometry showed elevation of the tetraploid peak and of that between diploid and tetraploid peaks, suggesting blockage of S phase and G2 to M phase of the cell cycle. Thus, melanoidins contained in the immunomodulator PSK revealed to have a direct tumor cell growth inhibitory effect.     

Algogenic mediator-induced nociceptive response in diabetic mice

The duration of the somatostatin-, bradykinin- or prostaglandin F2alpha-induced nociceptive response was significantly less in diabetic mice than in non-diabetic mice. Subcutaneous injection of 7-benzylidenenaltrexone (0.1, 0.3 and 1 mg/kg), an antagonist of delta1-opioid receptors, had no significant effect on either somatostatin-, bradykinin- or prostaglandin F2alpha-induced nociceptive responses in non-diabetic mice. 7-Benzylidenenaltrexone (0.1 and 0.3 mg/kg, s.c.) also had no significant effect on somatostatin- or prostaglandin F2alpha-induced nociceptive responses in diabetic mice. However, the bradykinin-induced nociceptive response in diabetic mice was dose-dependently and significantly increased when 7-benzylidenenaltrexone (0.1, 0.3 and 1 mg/kg, s.c.) was injected 10 min before the injection of bradykinin. These results suggest that a spinal delta1-opioid receptor-mediated endogenous antinociceptive system may inhibit the bradykinin-mediated nociceptive responses in the second phase of the formalin-induced nociceptive response in diabetic mice.     

The modulatory effect of (+)-TAN-67 on the antinociceptive effects of the nociceptin/orphanin FQ in mice

To clarify the pharmacological properties of (+)2-Methyl-4aalpha-(3-hydroxyphenyl)-1, 2, 3, 4, 4a, 5, 12, 12aalpha-octahydro-quinolino[2, 3, 3-g]isoquinoline ((+)-TAN-67), the effect of (+)-TAN-67 on the antinociception induced by the intrathecal (i.t.) administration of nociceptin/orphanin FQ was studied in mice using the tail-flick test and the formalin test. I.t. administration of (+)-TAN-67, at doses of 1 to 10 ng, facilitated the tail-flick response in a dose-dependent manner in mice. In addition, i.t. administration of (+)-TAN-67 (1 to 10 ng) in mice produced a marked pain-like aversive responses. I.t. pretreatment with D-Pro(9)-[spiro-gamma-lactam]-Leu(10)-Trp(11)-physalaemin(1-11) (GR82334, 0.1-1.0 nmol), a potent and selective tachykinin NK(1) receptor antagonist, dose-dependently blocked the reduction of the tail-flick response induced by (+)-TAN-67. Furthermore, (+)-TAN-67-induced facilitation of the tail-flick response was abolished in capsaicin-treated mice. On the other hand, (+)-TAN-67-induced flinching responses were dose-dependently and significantly reduced by i.t. pretreatment with GR82334 (0.1-1.0 nmol). The duration of i.t. (+)-TAN-67-induced flinching responses was significantly reduced in capsaicin-treated mice as compared with naive mice. I.t. administration of nociceptin/orphanin FQ (1-10 nmol) dose-dependently increased the tail-flick latency. I.t. administration of nociceptin/orphanin FQ (0.1-1.0 nmol) significantly and dose-dependently reduced the first-phase nociceptive response, but not the second-phase nociceptive response. I.t. pretreatment with (+)-TAN-67 (0.3-3.0 microg) for 30 min dose-dependently attenuated the antinociception induced by i.t. nociceptin (10 nmol) in the tail-flick test. Furthermore, the antinociceptive effect of nociceptin/orphanin FQ (1 nmol, i.t.) on the first-phase response in the formalin test was dose-dependently attenuated by s.c. pretreatment with (+)-TAN-67 (0.3-3.0 microg). (+)-TAN-67 (0.3-3.0 microg, i.t.), by itself, did not facilitate the tail-flick response or produce apparent behavioral changes. It is possible that (+)-TAN-67 has an antagonistic effect on nociceptin/orphanin FQ-induced antinociception.     

Inhibition of cell growth in culture by quinones

Quinones were studied for their growth inhibitory effect on cultured malignant cells. HCT-15 cells derived from human colon carcinoma were used for these experiments. Quinones used were arbutin in the benzoquinone group, juglone and lawsone in the naphthaquinone group, alizarin, emodin, 1,8-dihydroxyanthraquinone, and anthraquinone in the anthraquinone group, and xanthone. Cultured cells were incubated with various concentrations of the quinones for four days in a 5% CO2 incubator, after which cell numbers were counted and significance of differences was analyzed by Student's t test. Anthraquinones and naphthaquinones used in these experiments were more effective than the monocyclic quinone. The 50% suppression dose was less than 12.5 micrograms/ml for them. The number of OH groups seemed to play an important role in the degree of the cell growth inhibition: anthraquinones with 2 or 3 OH groups were more effective than those with no OH group like, 9,10-dioxoanthracene and xanthone. In fact, anthraquinones with no OH group and xanthone were not significantly effective. Flow cytometric histograms revealed a specific pattern; that is, lawsone and juglone in the naphthaquinone group and alizarin and 1,8-dihydroxy-anthraquinone in the anthraquinone group blocked mainly the S phase, and emodin in the anthraquinone group blocked the G1 to S phase of the cell cycle.     

The relation between the current underlying pacemaker activity and beta-adrenoceptors in cardiac Purkinje fibres: A study using adrenaline,procaine, atenolol and penbutolol

Summary The pacemaker current — i _K2 — in cardiac Purkinje fibres was analysed using the voltage clamp technique described by Deck et al. (1964). (–)-Adrenaline (5.5 · 10^–6 M) causes the wellknown shift of the Hodkin-Huxley kinetics in the depolarizing direction. Procaine (7.3·10^–4 M) does not cause any further shift of s in the presence of adrenaline. Atenolol (3.8·10^–5 M) causes a backshift of the kinetics in the negative direction in the presence of adrenaline and procaine. The instantaneous current-voltage relationship ( ) is altered neither with adrenaline, nor with procaine or atenolol. The results exclude the possibility that the local anaesthetic side effect of many beta-adrenoceptor blocking agents may be involved in the backshift of the s-kinetics. The voltage dependence of the reciprocals of the time constants is shifted in a similar way as s by the sympathomimetic or blocking drugs. Following the application of (–)-adrenaline (5.5·10^–6 M) the (–)-isomere of penbutolol (1.7 and 3.5·10^–6 M) is about equally effective in shifting the kinetics back as the (+)-isomere (3.5·10^–5 M). In the presence of (–)-adrenaline, the (+)- and (–)-forms of penubutolol cause virtually no change of the instantaneous current-voltage relationship, . Thus, (–)-adrenaline and (+)- and (–)-penbutolol are aiming for the s-kinetics whose voltage dependence is controlled by the electric field near the i _K2-channel of the membrane and do not influence the number of the i _K2-channels. These findings suggest that the sympathomimetic or blocking agents influence the s-kinetics of the pacemaker current i _K2 by altering the electric field; the fully activated current-voltage relationship which is proportional to the number of the open i _K2-channels is not subject to any appreciable modification. The results conclusively show that the kinetics of the pacemaker current can be controlled by beta-adrenoceptors.     

Influence of lateral head tilting on head-shaking nystagmus

We conducted a trial to determine whether or not head-shaking nystagmus (HSN) was influenced by lateral head tilting. Twenty-two patients with unilateral peripheral vestibular lesions were examined between July 1990 and June 1996. All of the patients were found to have horizontal HSN following horizontal head shaking in the upright head position. Eye movements were recorded by electronystagmography with the eyes open in complete darkness. Patients voluntarily tilted their heads to the lateral head positions with the assistance of the examiner as quickly as possible immediately after head shaking in the upright head position. Findings showed that monophasic horizontal HSN and the first phase of biphasic horizontal HSN were suppressed by lateral head tilting. The second phase of biphasic horizontal HSN was influenced differently by head tilting when compared with the first phase. Vertical (down-beating) components in horizontal HSN may appear in the peripheral vestibular lesions, but seem to have no definite relation to head positions.     

Severity of trauma changes expression of TNF-alpha mRNA in the brain of mice

BACKGROUND: The greater nitrogen loss that occurs with increasing severity of trauma is believed to occur because activation of the hypothalamus-pituitary axis is greater with severe injury. Cytokines in the brain stimulate the hypothalamus-pituitary-adrenal axis. This study was carried out to investigate whether the brain would recognize severity of trauma via TNF-alpha mRNA synthesis in the brain. METHODS: Male C57BL/6 mice (n = 70, BW: 20-28 g) were randomly assigned into four groups, (1) control (no anesthesia or incision), (2) anesthesia alone, (3) anesthesia plus laparotomy by short incision (short), and (4) anesthesia plus laparotomy by long incision (long). A laparotomy was carried out in the short and long groups by a 1.2-cm vertical incision and by a horizontal plus a vertical incision (2.4 x 2.4 cm), respectively. Exactly either 3 or 24 h after surgery, the animals were decapitated. TNF-alpha mRNA levels in the tissues were determined by semi-quantitative PCR. RESULTS: Nitrogen and catecholamine excretion were increased in the long wound group compared with the short wound group. Expression of TNF-alpha mRNA in the brain was greater in the long group after surgery than in the control, anesthesia, and short groups (brain, long: 0.150 +/- 0.005; P < 0.01 vs control, anesthesia alone, and short groups), but TNF-alpha levels in the plasma were the same in the short and long groups after surgery. CONCLUSION: Levels of TNF-alpha mRNA in the brain were enhanced according to the length of the wound probably because of greater neural stimuli from the wound site, and this elevation was involved in the greater nitrogen loss.