Early seizures after acute ischemic stroke]

In order to determine predictive factors of early seizures (ES) after acute stroke and to estimate prognosis, we retrospectively examined clinical data of 1,743 consecutive patients with acute ischemic stroke. The subjects were divided into two groups; an ES group (19 patients) and a non-ES group (1,724 patients). Multivariate statistical analysis revealed that the NIH-Stroke Scale score on admission (/10, OR, 1.1: 95% CI 1.04 to 1.13) and positive past history of cerebrovascular disease or brain injury (OR, 3.85: 95% CI 1.49 to 9.95) are significant factors to predict ES. There was no significant difference in the outcome between the two groups. A recurrence of seizures, after follow up for 4 to 40 months, was observed only in one patient with a history of ES.     

Endogenous tumor necrosis factor exerts its protective function intracellularly against the cytotoxicity of exogenous tumor necrosis factor.

Based on the findings that expression of endogenous tumor necrosis factor (enTNF), which is not present in TNF-susceptible cells, was generally observed in TNF-resistant cells and that TNF gene transfection gives rise to TNF resistance, the assumption was made that enTNF may be a protective protein against the cytotoxicity of exogenous TNF. However, it remains unknown whether the protection by enTNF is exerted in an intracellular or extracellular (autocrine) manner. We therefore transfected a nonsecretory human TNF gene (pTNF delta pro) into highly TNF-sensitive mouse tumorigenic fibroblasts (L-M cells) and investigated their TNF susceptibility. The transfectants expressed enTNF which was not secreted into the medium and acquired an appreciable degree of resistance to exogenous TNF. A significant increase in the manganous superoxide dismutase level was also noted in the transfectants. These findings suggest that enTNF exerts its protective function intracellularly by inducing manganous superoxide dismutase production.     

Endogenous tumor necrosis factor functions as a resistant factor against hyperthermic cytotoxicity.

One of the mechanisms of cytotoxicity by tumor necrosis factor (TNF) is the induction of reactive oxygen molecules. Cells producing endogenous tumor necrosis factor (enTNF) show resistance to the cytotoxicity of exogenous TNF by scavenging the reactive oxygen molecules. The intracellular hydroxyl radical production is also known to be involved in the heat-induced cytotoxicity. In the present study, we therefore examined the possibility that enTNF may act as a protective protein against the heat-induced cytotoxicity in a manner similar to that of exogenous TNF. Heat-sensitive L-M (mouse tumorigenic fibroblast) cells, originally expressing no enTNF, were transfected with a human TNF expression vector to produce enTNF. The stable transfectants showed apparent resistance to heat treatment. Conversely, when HeLa (human uterine cervical cancer) cells, originally producing an appreciable amount of enTNF, were transfected with an antisense TNF mRNA expression vector to inhibit enTNF synthesis, their heat sensitivity was enhanced. Furthermore, L-M cells which were transfected with nonsecretory human TNF expression vector also acquired resistance to heat treatment. In these cells, heat resistance correlated well with expression of enTNF and intracellular levels of manganous superoxide dismutase. These results indicate that enTNF exerts its intracellular protective effect against the heat-induced cytotoxicity by scavenging reactive oxygen with induced manganous superoxide dismutase in a manner similar to that found in cells treated with exogenous TNF.     

Responses of resistance and capacitance vessels in human nasal mucosa to beta-receptor agonists

To investigate the responses of nasal vessels, divided into resistance and capacitance vessels, to a beta-receptor agonist in human, mucosal blood flow of the inferior turbinate and nasal airway resistance were measured when 1.5 mg terbutaline was applied topically. Mucosal blood flow was measured by the hydrogen clearance method just beneath the site where terbutaline in physiological saline (0.02 ml) was applied on an extremely localized area of the nasal mucosa. Nasal airway resistance of the ipsilateral and contralateral nasal cavities was measured separately by anterior rhinomanometry when terbutaline in normal saline (0.1 ml) was sprayed in the unilateral nasal cavity. Topical application of terbutaline elicited neither a significant increase of mucosal blood flow of the inferior turbinate nor an increase of nasal airway resistance. beta-Receptors seem not to be as densely distributed both in the resistance vessels and in the capacitance vessels as to cause vasodilatation by their activation in the nasal mucosa.     

Platelet activating factor (PAF) involvement in endotoxin-induced thrombocytopenia in rabbits: studies with FR-900452, a specific inhibitor of PAF

PAF (1 ug/kg) injected intravenously (i.v.) into anesthetized rabbits resulted in marked loss of circulating platelets and leukocytes. Administration of FR-900452 1-methyl-3-(1-(5-methylthiomethyl-6-oxo-3-(2-oxo-3-cyclopenten-1-y lidene)- 2-piperazinyl) ethyl)-2-indolinone, a specific PAF inhibitor, at a dose of 10 mg/kg i.v. with 10 min prior to the PAF injection significantly prevented both changes. On the other hand, PAF has been considered as a mediator of endotoxin shock. Therefore, in order to determine whether endogenous PAF contributes to the occurrence of thrombocytopenia or leukopenia in endotoxin shock, we assessed the effect of FR-900452 on the thrombocytopenia and the leukopenia following bolus i.v. injection of E.coli endotoxin (0.03 mg/kg) in rabbits. As a result, pretreatment with the compound (10 mg/kg, i.v.) significantly reduced the thrombocytopenia at 60 and 180 min after the endotoxin injection. In contrast, FR-900452 did not reduced the leukopenia at any time of after endotoxin. These results indicate that PAF might be involved in the occurrence of thrombocytopenia in rabbit endotoxemia and the contribution of PAF to the leukopenia is much less extent than that to the thrombocytopenia.     

Effects of phenytoin on cell-mediated immunity

Phenytoin is a highly effective anticonvulsant agent that is widely administrated to prevent some kinds of patients with brain tumor. But it has been said that phenytoin may have some immunosuppresive potential for hosts. In this study, we evaluated the effects of phenytoin upon cellular immunity such as NK, CTL and LAK activity in murine models. Fresh splenocytes were taken out from mice (CBA/J, C 3 H/HeN, C 57 BL/6) into which phenytoin had been injected intraperitoneally at a daily dose of 1,000 micrograms for 28 days. The serum concentration of phenytoin in the experimental models was 10-20 micrograms/ml. The cytotoxic activities were estimated by a 4-hr 51Cr release assay. The mitogen-stimulated lymphocyte function was evaluated by 3H-thymidine incorporation into DNA. The NK activity was estimated by cytotoxicity of splenocytes of CBA/J mice against NK-sensitive YAC-1 cells. The cytotoxic T-lymphocyte (CTL) activity was estimated by cytotoxicity of splenocytes of C 57 BL/6 mice which were stimulated in vitro for 5 days by splenocytes of C 3H/HeN treated with mitomycin C, against RSV-M glioma cells. Lymphokine-activated killer (LAK) activity was estimated by cytotoxicity of LAK cells, which were induced from splenocytes of C 3 H/HeN mice by human recombinant interleukin-2 (rIL-2), against syngeneic RSV glioma and allogeneic 203 glioma cells. 3H-thymidine incorporation of splenocytes of C 57 BL/6 mice was reduced significantly (p less than 0.01) in phenytoin-treated mice. The cytotoxicity of splenocytes of non-treated CBA/J mice against YAC-1 cells was 75%, but that of phenytoin-treated CBL/J mice was a few %.(ABSTRACT TRUNCATED AT 250 WORDS)     

The anti-inflammatory effects of phenolic dental medicaments as determined by mouse ear edema assay

The anti-inflammatory effects of phenolic dental medicaments were evaluated by mouse ear edema assay. p-Chlorophenol (PCP) inhibited edema when applied topically in dosages of 0.2 and 0.5 mg per site at 15 min before or 1.0 and 2.0 mg per site at 60 min after the application of croton oil. The inhibitory effects were also noted with eugenol, guaiacol, o-cresol, phenol and orally administered indomethacin (10 mg/kg). The involvement of the effects on prostaglandin biosynthesis in the anti-inflammatory effects of these compounds is discussed.     

Chemotherapy-induced anemia in patients with primary lung cancer.

To elucidate the factors which influence the value of hemoglobin, the nadir value of hemoglobin, frequency of blood transfusion and prognostic value of blood transfusion in patients with primary lung cancer during intensive chemotherapy, the hematological features of 124 patients entered into a randomized phase III study containing cisplatin were retrospectively analyzed. There was no difference in the percent nadir hemoglobin value of the first course of chemotherapy (% of pretreatment value) in any of the subgroups with respect to sex, body weight loss, performance status, age, stage, number of metastatic sites or treatment arms. The only predictive indicator for the nadir hemoglobin value in the first course of chemotherapy was the pretreatment value of hemoglobin. The equation for the regression line was y = 1.07 + 0.73x (R2 = 0.663, p < 0.001). The lowest nadir hemoglobin value (% of pretreatment value) during all chemotherapy courses was significantly lower in the subgroups older than 60 years and those with body weight loss. There was an inverse correlation between the accumulated dose of cisplatin and the lowest nadir hemoglobin value (p < 0.05). The frequency of blood transfusion in patients with more than two metastatic sites was significantly higher than in those with one or no metastatic sites (p < 0.05). Survival of patients who had required blood transfusion after chemotherapy was significantly shorter than that of patients who had not (p < 0.05).     

Presence of ghost cells and the Wnt signaling pathway in odontomas

BACKGROUND: Although it has been reported that ghost cells are present in odontomas, the generation mechanism of these cells is unclear. To evaluate the presence of ghost cells and involvement of the Wnt signaling pathway, we examined the expression of hard keratins, beta-catenin and Lef-1 in odontomas. METHODS: Sixty-nine cases of odontoma were examined immunohistochemically with the use of antibodies against human hair proteins, beta-catenin and Lef-1. RESULTS: Expression of hard keratins was found only in the cytoplasm of ghost cells in 46 (66.7%) of the 69 odontomas. Compound odontomas (78.8%) showed a higher incidence of ghost cells than complex odontomas (29.4%). Histopathologically, ghost cells were found within odontogenic epithelium adjacent to immature enamel and in the centre of Liesegang-ring-like calcified materials. Expression of beta-catenin and Lef-1 was observed in the cytoplasm and nucleus of odontogenic epithelial cells adjacent to the ghost cells in immature odontomas. CONCLUSION: These findings suggest that odontoma is a hard keratin-expressing tumor-like lesion, and that the Wnt signaling pathway may be involved in the formation of ghost cells in odontomas.     

A case of middle-aged onset sialidosis type I]

We reported a patient with middle-aged onset sialidosis type I. A 52-year-old Japanese man was referred to our hospital because of dysarthria, involuntary movement of his extremities and gait disturbance since the age of 46 years. On admission, neurological examination revealed scanning speech, action myoclonus, cerebellar ataxia and cherry-red spots. Vacuolated lymphocytes were found in peripheral blood. Brain 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) showed decreased glucose metabolism in the cerebellum. Enzymological analysis using his skin fibroblasts revealed primary deficiency of sialidase activity. Sialidase gene analysis identified compound heterozygotes for base substitusions of 239T-to-C and 649G-to-A, which resulted in amino acid alterations of P80L and V217M, respectively. These mutations have been reported in Japanese sialidosis type II (P80L) and I (V217M). Further studies are required to reveal effects of gene mutations on residual enzyme activities and phenotypes.