Effective treatment with topical cyclosporin A of a patient with Cogan syndrome.

The purpose of this report is to describe the effective treatment of severe anterior segment inflammation due to Cogan syndrome through the use of topical administration of cyclosporin A. A 47-year-old female patient had been experiencing headaches and difficulties with her vision. Subsequent examination revealed the sudden onset of bilateral conjunctival injection and swelling of bilateral auricles. Despite the multiple treatment (systemic and topical corticosteroid and antibiotic therapy), necrotizing scleritis had appeared bilaterally and the scleral wall was thinning. Topical administration of 1% cyclosporin A was applied to both eyes 4 times a day. After 2 months of this therapy, the epithelial tissue covered the necrotizing tissue and her symptom of ocular pain was relieved and her corrected visual acuity was improved. This is the first case exhibiting that topical cyclosporin A is an effective treatment for severe anterior segment inflammation associated with Cogan syndrome.

Cerebroside elicitors found in diverse phytopathogens activate defense responses in rice plants.

Cerebrosides A and C, compounds categorized as glycosphingolipids, were isolated in our previous study from the rice blast fungus (Magnaporthe grisea) as novel elicitors which induce the synthesis of rice phytoalexins. In this paper, these cerebroside elicitors showed phytoalexin-inducing activity when applied to plants by spray treatment and also induced the expression of pathogenesis-related (PR) proteins in rice leaves. This elicitor activity of the cerebrosides showed the structural specificity as that for the induction of phytoalexins. Ceramides prepared from the cerebrosides by removal of glucose also showed the elicitor activity even in lower level compared to the cerebrosides. In field experiments, the cerebroside elicitors effectively protected rice plants against the rice blast fungus, an economically devastating agent of disease of rice in Japan. The cerebrosides elicitors protected rice plants from other disease as well and were found to occur in a wide range of different phytopathogens, indicating that cerebrosides function as general elicitors in a wide variety of rice-pathogen interactions.

Inhibition of Vpr-induced cell cycle abnormality by quercetin: a novel strategy for searching compounds targeting Vpr.

Vpr, an accessory gene product of HIV-1 which induces cell cycle abnormality leading to the increased HIV replication, is supposed to be a possible target for anti-AIDS drugs. We recently established a cell line (MIT-23) in which Vpr-induced cell cycle perturbation could be manipulated by a tetracycline promoter. Here, we screened anti-Vpr activity in 27 kinds of herb drugs using MIT-23 cells. One of the extracts prepared from Houttuyniae herba showed an inhibitory activity. Quercetin (QCT), a compound of this crude drug, efficiently inhibited Vpr function without affecting its expression. Furthermore, data suggested that Vpr-induced transcription from HIV-LTR was considerably abrogated by QCT. These data indicate that QCT, a flavonoid previously reported to inhibit HIV replication, also targets Vpr, implicating that MIT-23 cell provides a novel strategy for screening compounds possessing anti-Vpr activity which would be in turn utilized for clarifying the mechanism of Vpr function.

The effect of electro-acupuncture stimulation on the muscle blood flow of the hindlimb in anesthetized rats.

The effect of electro-acupuncture stimulation (EAS) on blood flow in the muscle biceps femoris (MBF) and on mean arterial pressure (MAP) was investigated in anesthetized, artificially ventilated rats. EAS was applied to a hindpaw for 30 s at intensities of 0.1-10.0 mA and at frequencies of 1-20 Hz, and MBF was measured by laser Doppler flowmetry. EAS at less than 1.0 mA, which excited group II fibers maximally and III fibers partially in a saphenous nerve, had no significant effect on MBF or MAP, although both revealed variable responses. EAS at 1.5 mA, which additionally excited group III fibers almost maximally and was subthreshold for group IV fibers, produced a small but significant increase in MBF and MAP. These responses were further increased at 2.0 mA or more, which was suprathreshold for group IV fibers. The increased response of MBF at 10.0 mA was followed by a small decrease in MBF. EAS at 1.5 mA or more also elicited a decrease in renal blood flow (RBF) and an arterial pressor response. Following severance of the bilateral splanchnic nerves, EAS at 10.0 mA induced only a slight increase in MAP and a decrease in MBF. The decrease in MBF was abolished following further severance of the bilateral lumbar sympathetic trunks (LSTs). In conclusion, EAS to a hindpaw at a stimulus strength sufficient to excite group III and IV afferent fibers, particularly group IV afferent fibers, can produce a reflex decrease in MBF via a reflex activation of muscle sympathetic activity, although this decrease in MBF is overridden by an increase in MBF caused passively by a reflex MAP pressor response elicited by a reflex increase, at least in splanchnic sympathetic activity.

Cerebrosides A and C, sphingolipid elicitors of hypersensitive cell death and phytoalexin accumulation in rice plants.

When plants interact with certain pathogens, they protect themselves by generating various chemical and physical barriers called the hypersensitive response. These barriers are induced by molecules called elicitors that are produced by pathogens. In the present study, the most active elicitors of the hypersensitive response in rice were isolated from the rice pathogenic fungus Magnaporthe grisea, and their structures were identified as cerebrosides A and C, sphingolipids that were previously isolated as inducers of cell differentiation in the fungus Schizophyllum commune. Treatment of rice leaves with cerebroside A induced the accumulation of antimicrobial compounds (phytoalexins), cell death, and increased resistance to subsequent infection by compatible pathogens. The degradation products of cerebroside A (fatty acid methyl ester, sphingoid base, and glucosyl sphingoid base) showed no elicitor activity. Hydrogenation of the 8E-double bond in the sphingoid base moiety or the 3E-double bond in the fatty acid moiety of cerebroside A did not alter the elicitor activity, whereas hydrogenation of the 4E-double bond in the sphingoid base moiety led to a 12-fold decrease in elicitor activity. Furthermore, glucocerebrosides from Gaucher's spleen consisting of (E)-4-sphingenine and cerebrosides from rice bran mainly consisting of (4E,8E)-4,8-sphingadienine and (4E,8Z)-4,8-sphingadienine showed no elicitor activity. These results indicate that the methyl group at C-9 and the 4E-double bond in the sphingoid base moiety of cerebrosides A and C are the key elements determining the elicitor activity of these compounds. This study is the first to show that sphingolipids have elicitor activity in plants.

Neural mechanism of pupillary dilation elicited by electro-acupuncture stimulation in anesthetized rats.

The neural mechanisms to reflex dilation elicited by electro-acupuncture stimulation were investigated in anesthetized rats. Two needles, with 160 microns diameter and about 5 mm apart, were inserted into the skin and underlying muscle of a hindpaw. Repetitive 20 Hz, 0.5 ms electrical pulses at various intensities were used for stimulation for 30s. The pupil size was magnified about 44 times via a microscope and was continuously recorded on a videotape. Electro-acupuncture stimulation at more than 0.5 up to 6 mA induced stimulus intensity-dependent pupil dilation. These responses were abolished by the severance of the sciatic and saphenous nerve of the stimulated hindlimb. Compound action potentials were recorded from the distal cut end of the tibial of a saphenous nerve following electro-acupuncture stimulation of the hindpaw. The mean threshold of the compound action potentials of the myelinated fibers in saphenous nerves was 0.18 mA, while that of unmyelinated fibers was 3.0 mA. The mean threshold of the compound action potentials of the myelinated fibers in the tibial nerve was 0.20 mA of unmyelinated fibers was 3.3 mA. Severance of bilateral trunks did not affect the response, while severance of the third cranial nerves abolished the responses. In conclusion, electro-acupuncture stimulation applied to the hindpaws of the anesthetized rats induced excitation of myelinated or of both myelinated and unmyelinated afferent fibers of the tibial and saphenous nerve, and involved a reflex response of pupil dilation through the third cranial parasympathetic efferent nerve.

Determination of the optimal walking speed for neural relaxation in healthy elderly women using electromyogram and electroencephalogram analyses.

The purpose of this study was to determine the walking speed which has the greatest influence on neural relaxation in healthy elderly women as determined by electromyogram (EMG) and electroencephalogram (EEG) analyses. Seven elderly female volunteers [mean age 68.5 (SD 3.95) years] served as subjects for this study. The EMG signals were recorded from the gastrocnemius (MG), soleus (SL) and tibialis anterior (TA) muscles while walking on a treadmill, starting at 40 m.min-1 and increasing 6 m.min-1 incrementally for 10 min. The turning point of muscle activities (by integrated EMG. iEMGtp) was determined as the walking speed at the point at which the mean rate of change of iEMG (MG + SL + TA) abruptly increased. After the determination of iEMGtp. the treadmill was set at three constant speeds, one corresponding to the speed for the iEMGtp and two others 20% higher or lower than that for the iEMGtp. The subjects then walked for 20 min at each of these speeds on 3 separate days and their EEG power spectrum data were obtained for frequencies from the 8 to 13 Hz (z-wave component, AWC). The mean of iEMGtp for our subjects was at a mean walking speed of 64.7 (SD 7.9) m.min-1. Considering the subjects' age and height, iEMGtp was somewhat faster than their expected self-paced normal walking speed. There were no differences between the mean AWC values of the subjects prior to exercising at each of the three speeds. The mean AWC values after exercise were significantly (P < 0.01) greater than before. The extent of the increase in AWC at iEMGtp was greater than those at slower speeds. Our data would suggest that walking exercise at the speed which corresponds with EMG evidence of iEMGtp may induce the most significant relaxing effects in elderly women.

Accumulation of mutant p53 and hsp72 by heat treatment, and their association in a human glioblastoma cell line.

The cellular content of mutant p53 and hsp72 proteins following gamma-ray irradiation, UV irradiation, and heat treatment was studied in A-7 cells, a human glioblastoma cell line. A-7 was found to contain a mutant p53 gene in which the arginine codon at position 175 was substituted by a histidine codon. Although the p53 gene was mutant, the phenotype of the p53 protein appeared wild-type since the cellular content of the p53 protein was limited under normal culturing conditions. The quantity of mutant p53 and hsp72 proteins in A-7 was increased by heat treatment as well as gamma-ray and UV irradiation. Furthermore, the mutant p53 protein was coimmunoprecipitated with anti-hsp72/hsc73 antibody. Additionally, hsp72 and hsc73 were coimmunoprecipitated with anti-p53 antibody. These results suggest that in A-7, p53 protein accumulation may be caused as a result of response to stressors, such as gamma-ray, UV and heat and that mutant p53 protein and hsp72/hsc73 may manage biological functions cooperatively after gamma-ray, UV and also heat treatments.

Spa bathing activates fibrinolysis in patients with cerebral infarction.

The effects of spa bathing on blood coagulation and fibrinolysis were studied in 20 patients with chronic cerebral infarction. Blood was obtained before and after a 10-minute period of spa bathing at 41 degrees C. Prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII activity, von Willebrand factor activity, and antithrombin III activity did not show significant changes after bathing, but euglobulin lysis time was significantly reduced (p < 0.01) and fibrin lysis activity was increased (p < 0.05). These findings suggest that spa bathing activates fibrinolysis without markedly changing blood coagulation in patients with chronic cerebral infarction. It is thought that the activation of fibrinolysis without the activation of coagulation has a favorable effect on blood circulation. The results of fibrin-plate assays using C1 inactivator indicated that tissue-type plasminogen activator was the major contributor to the activation of fibrinolysis during spa bathing.