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Biomedical subjects

Shinya Sakai

Publications and source records attributed to Shinya Sakai.

15 recordsLinked to original sources

Macrophage-mediated inhibitory effect of Zingiber officinale Rosc, a traditional oriental herbal medicine, on the growth of influenza A/Aichi/2/68 virus.

The inhibitory effect of Zingiber officinale Rosc (ZOR), an Oriental traditional herbal medicine, on the growth of influenza A/Aichi/2/68 (Aichi) virus was investigated in Madin-Darby canine kidney (MDCK) cells. Direct addition of ZOR (0.1 approximately 100 microg/ml) to the infected cells did not have any inhibitory effect. However, the ZOR-induced conditioned medium (ZOR-CM) of RAW cells, a murine macrophage (Mphi) cell line, exhibited an apparent inhibitory effect on MDCK cells without cytotoxicity. In accordance with the time-dependent inhibitory effect of ZOR-CM, it has been demonstrated that tumor necrosis factor (TNF)-alpha was gradually accumulated in ZOR-CM by the induction of TNF-alpha mRNA expression in ZOR-stimulated RAW cells. Conversely, the inhibitory effect of ZOR-CM was reduced significantly by the removal of TNF-alpha after the formation of an immune complex with anti-TNF-alpha monoclonal antibody. These data suggested that ZOR itself has no inhibitory effect on the growth of influenza virus, but could exert its effect via macrophage activation leading to production of TNF-alpha.

Animals↗

Induction of inducible nitric oxide (NO) synthase mRNA and NO production in macrophages infected with influenza A/PR/8 virus and stimulated with its ether-split product.

We investigated the inductive activity of infective influenza A/PR/8/34 (PR8) virus and its ether-split product (ESP) on the expression of inducible nitric oxide (NO) synthase (iNOS) and NO production in RAW264.7 (RAW) cells, a murine macrophage (M psi) cell line, and thioglycolate-elicited peritoneal M psi (TPM). In both cells, PR8 virus infection induced iNOS mRNA between 4 hr and 24 hr, attaining a peak value at 12 hr. In correlation with induction of iNOS mRNA, NO amounts increased significantly from 12 to 24 hr. Moreover, this study demonstrated that ESP with the same hemagglutination titer as PR8 virus could induce iNOS mRNA and NO production, although the inductive activity of ESP was weaker than that of PR8 virus. Considering the dual role (beneficial and detrimental roles) of NO on certain inflammatory disorders and virus infections, the inductive activity of influenza virus on the iNOS-mediated NO production independent of its infectivity might contribute to a modification of influenza virus infection.

Animals↗

Suppressive effects of Stephania tetrandra on the neutrophil function in patients with rheumatoid arthritis.

Crude preparations of Stephania tetrandra (ST), a traditional herbal medicine, have been used safely for arthritis and silicosis in China. The concentration of granulocyte elastase - alpha 1 protease inhibitor complex in plasma is enhanced in inflammatory processes, e.g. in septicaemia and rheumatoid arthritis (RA), being an expression of granulocyte activation during inflammatory response. It has previously been reported that ST showed beneficial and immunomodulatory effects in the treatment of relatively mild RA. After the administration of ST for 12 weeks, the proportion of granulocytes and the granulocyte count in peripheral blood decreased significantly. The lipid peroxide and human granulocyte elastase levels of stored plasma declined significantly. Furthermore, both the leukocyte/elastase ratio and granulocyte/elastase ratio increased significantly. The findings of this study suggest that the suppressive effect of ST administration on excessive granulocyte activation resulted in the improvement of inflammation with rheumatoid arthritis.

Adjuvants, Immunologic↗

Inducible activity of ginger rhizome (Zingiber offifinale Rosc.) on the mRNA expression of macrophage-inducible nitric oxide (NO) synthase and NO production in a macrophage cell line, RAW264.7 cells.

We have investigated the effect of Zingiber offifinale Rosc. (ZOR) on macrophage-inducible nitric oxide (NO) synthase (macNOS) mRNA expression and NO production in RAW264.7 cells, a murine macrophage cell line; 100 microg/ml ZOR can induce macNOS mRNA expression, but induction effects at a dose below 10 microg/ml were weak or negligible. Kinetic studies showed that macNOS mRNA can be detected from 4 hours to 24 hours after dosing, with a peak at 8 hours. In accordance with the induction of macNOS mRNA expression, NO concentrations increased from 3.4 microM at 2 hours to almost 150 microM at 24 hours, reflecting a longer period of macNOS mRNA expression. The activity of ZOR can be considered to contribute, at least in part, to the beneficial effects of ZOR through the macNOS-mediated activation of the biodefense mechanism.

Animals↗

[Visual search training for a case of homonymous field defect with multiple visual dysfunctions].

A 72-year-old right handed man developed right homonymous hemianopia without macular sparing, left homonymous lower quadranopia with macular sparing, cerebral amblyopia, cerebral achromatopsia, impaired form vision, and mild right hemispatial neglect, after multiple cerebral infarctions, involving bilateral occipital cortices. His intelligence and memory were deteriorated moderately. He failed to notice objects located in the affected visual field, because of his severely impaired visual search. When ordinary lighting was used, he showed severe right-sided omissions on the line cancellation test. However, omissions were less marked under the brighter lighting. By using a modified method of Kerkhoff and Vianen (1994), he was trained to make saccadic eye movements toward affected regions to find a target and to search and point at targets arranged randomly. As the sensitivity for contrast of isoluminante red and green stimuli was preserved well at high spatial frequencies despite the decreaced contrast sensitivity for brightness, we used green targets as the training stimuli. After the training, search field and pointing range that could be covered by the patient increased in size for both green and white targets, and daily activities improved. Moreover, after the training, he no longer showed discrepancy in line cancellation performances between ordinary and brighter lighting conditions. In the follow up period, the search field and the performance on the line cancellation test were maintained, while the performance of pointing targets array declined. The family members complained of mild re-deterioration of daily activities. Then, the training for searching and pointing re-introduced at home. After the training, his pointing performance and daily activities, evaluated by questionnaires to his family members, improved again. In conclusion, it was suggested that disordered visual search after a homonymous field defect can be treated effectively, even if multiple visual dysfunctions were associated.

Aged↗

Natural killer cytolytic activity is associated with the expression of killer cell immunoglobulin-like receptors on peripheral lymphocytes in human.

Although it has been shown that killer cell immunoglobulin-like receptors (KIRs) on peripheral lymphocytes are upregulated by interleukin-2 (IL-2), which activates natural killer (NK) activity, it has not been demonstrated whether the expression of KIRs is related to NK activity. Therefore, we investigated the association between the KIR expression on lymphocytes and NK activity. CD158a/b expression on lymphocytes obtained from 37 subjects was analyzed using flow cytometry. Simultaneously, NK activity was measured each sample using a 51Cr-release assay. Additionally, lymphocytes were cultured in RPMI 1640 medium with or without IL-2 for 48 h, and then their CD158a/b expression and NK activity was analyzed. CD158a/b expression was significantly correlated with NK activity. Especially, the percentage of CD16+CD158a+ and CD8+CD158a/b+ cells in lymphocytes showed a highly significant correlation with NK activity. However, analysis of CD8+ and CD16+ cells revealed that there was only a significant correlation between the percentage of CD8+CD158a+ cells among only CD8+ cells and NK activity. The upregulation of CD16+CD158a+/b+ cells in response to IL-2 tended to be related to the increase of NK activity, but the relationship was not significant. In conclusion, the level of KIR expression was correlated with NK activity, and IL-2 treatment resulted in an increase of NK activity as well as KIR expression, suggesting that upregulation of KIRs enhances the ability to sort target cells, such as virus-infected cells from uninfected cells, according to major histocompatibility complex class I expression.

Adult↗

Reexamination of the relation between menstrual cycle and kampo diagnosis, yin-yang.

Several Chinese herbal medicine textbooks describe that a short menstrual cycle indicates "yang" status and a long cycle indicates "yin" status. However, we sometimes encounter yang patients with a long cycle or yin patients with a short cycle in daily practice. Therefore, we reviewed the relationship between yin-yang and length of menstrual cycle. A questionnaire addressing both menstrual cycle and several parameters for determining yin-yang was completed at the time of the patients' visit to the hospital. Patients were divided into yang or yin groups, and menstrual cycle was compared between the two groups. A short menstrual cycle was mostly observed in yin patients (27.42 +/- 1.73, 95% CI: 26.32-28.52, n = 12) and a long cycle was mostly observed in yang patients (31.63 +/- 3.96, 95% C.I: 29.51-33.74, n = 16). The difference in menstrual cycle between the two groups was significant (p = 0.002), and this result was entirely opposite to the traditional theory. This study identified a discrepancy between the traditional theory and the actual menstrual cycle findings in this small population. Current reexamination of the relationship between yin-yang and menstruation in a larger population is warranted.

Adult↗

[Unawareness for homonymous visual field defect].

BACKGROUND: There was no report which dealt with the relationship between emotional state, degree of defective visual search, severity of hemianopic dyslexia, the episode when the patient became aware of the defect, and unawareness of visual loss in homonymous hemifield. OBJECTIVE: To investigate the relationship between degree of awareness and those factors that might be responsible for the unawareness, including the aspects listed above. METHODS: Four patients with visual field defects caused by a brain lesion after a stroke was investigated. Self rating of emotional state, search performance for an object among many placed on a table, and for text reading, as well as visual field, visual positive phenomena, and hemispatial neglect were evaluated. Degree of unawareness for field loss was evaluated by modified version of the method of Bisiach et al. (1985). In addition, the episodes when the patient became aware of the defect were asked. RESULT: In accordance with the previous studies, we found no relationship between the degree of awareness of field defect and anatomic lesions, co-existence of hemispatial neglect, or the degree of awareness of hemiplegia. However, the patient with neglect was unaware of their troubles in vision at all, whereas the patients without neglect were aware of the troubles but misinterpreted them as problems of the eyes including acuity. In accordance with previous studies, co-existence of visual hallucinations or illusions seemed to be associated with awareness of visual field defect. No relationship was found between the degree of awareness of field defect and emotional state, degree of field loss, degree of defective visual search, or severity of hemianopic dyslexia. Their responses to the inquiry about the degree of awareness of field defect were not consistent. Thus, the awareness of the field defect seemed to be difficult to be kept firmly in their mind. On the other hand, the patients could remember the episode when they became aware of the defect for the first time, being able to specify time, place, and situation. CONCLUSION: Levine (1990) suggested that the sensory loss in this sort of patients was never phenomenally immediate but instead must be discovered by observation and inference. Non-specificity of the lesion, qualitative difference in awareness between the patient with and without hemispatial neglect, association of positive visual phenomena and awareness, fluctuation of awareness, and dependence of awareness on personal experiences found in our patients, can be explained with this 'discovery' hypothesis.

Aged↗

Gene expression of cell surface antigens in the early phase of murine influenza pneumonia determined by a cDNA expression array technique.

BACKGROUND: Influenza virus is a worldwide health problem with significant economic consequences. To study the gene expression pattern induced by influenza virus infection, it is useful to reveal the pathogenesis of influenza virus infection; but this has not been well examined, especially in vivo study. AIMS: To assess the influence of influenza virus infection on gene expression in mice, mRNA levels in the lung and tracheal tissue 48 h after infection were investigated by cDNA array analysis. METHODS: Four-week-old outbred, specific pathogen free strain, ICR female mice were infected by intra-nasal inoculation of a virus solution under ether anesthesia. The mice were sacrificed 48 h after infection and the tracheas and lungs were removed. To determine gene expression, the membrane-based microtechnique with an Atlas cDNA expression array (mouse 1.2 array II) was performed in accordance with the manual provided. RESULTS AND CONCLUSIONS: We focused on the expression of 46 mRNAs for cell surface antigens. Of these 46 mRNAs that we examined, four (CD1d2 antigen, CD39 antigen-like 1, CD39 antigen-like 3, CD68 antigen) were up-regulated and one (CD36 antigen) was down-regulated. Although further studies are required, these data suggest that these molecules play an important role in influenza virus infection, especially the phase before specific immunity.

Adenosine Triphosphatases↗

The efficacy of herbal medicine (kampo) in reducing the adverse effects of IFN-beta in chronic hepatitis C.

The purpose of this study was to determine if the adverse effects of interferon (IFN) in hepatitis C patients could be reduced by treatment with Japanese Oriental (Kampo) medicine. Twelve patients with chronic hepatitis C were treated with a combination of IFN-beta and either Mao-to or Dai-seiryu-to (groups A and B), and 16 patients were treated with IFN-beta alone (group C). Mao-to was administered to eight patients and Dai-seiryu-to was administered to four in groups A and B, respectively. Adverse effects were evaluated by clinical and laboratory examinations. The severity of symptoms was daily self-classified into four categories (1: none, 2: very slight, 3: moderate, and 4: serious), using a questionnaire consisting of 29 items. Scores of symptom such as discomfort and fever in group A, and discomfort, general malaise, paresthesia and arthralgia in group B were significantly lower than those in group C (p < 0.05). In all patients, HCV-RNA was negative at the end of the treatment, and serum alanine aminotransferase (ALT) levels had normalized transiently in all group A and B patients with genotype 1b by 2 weeks after cessation of IFN treatment. This study indicates that Kampo medicines are useful for reducing the adverse effects accompanying IFN treatment in patients with chronic hepatitis C without reducing the antiviral effects.

Adult↗

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.

Adolescent↗

Herbal medicine and false-positive results on lymphocyte transformation test.

In vitro mitogenic activity of 16 herbs and 3 Kampo (herbal medicine) formulae have been reported in experimental studies. It is not known how many herbs and Kampo formulae in total have mitogenic activity. Lymphocyte transformation test (LTT) is generally utilized to diagnose drug-induced liver injury. In LTT, mitogenic activity is assessed by measuring 3H-thymidine incorporation. The objective of the present study was to determine which herbs and which Kampo formulae caused false-positivity on LTT. We examined 2496 summaries of all admission records from 1979 to 1999 in our department. We selected patients in whom liver injuries were diagnosed as definitely unrelated to Kampo medication. In these patients, LTT was performed for some herbs contained in the suspect Kampo medicines, resulting in positive LTT for 17 herbs: Evodiae Fructus (Goshuyu), Zizyphi Fructus (Taiso), Ginseng Radix (Ninjin), Zingiberis Rhizoma (Shokyo), Hoelen (Bukuryo), Aconiti Tuber (Bushi), Angelicae Radix (Toki), Cnidii Rhizoma (Senkyu), Rehmanniae Radix (Jio), Ephedrae Herba (Mao), Anemarrhenae Rhizoma (Chimo), Cinnamomi Cortex (Keihi), Bupleuri Radix (Saiko), Artemisiae Capillari Spica (Inchinko), Persicae Semen (Tonin), Moutan Cortex (Botanpi) and Paeoniae Radix (Shakuyaku). These results were considered false-positive, because the results were observed in the "definitely unrelated" patients. Mitogenic activity inherent to some herbs and Kampo formulae may sometimes cause false-positivity on LTT in clinical situations. These examples suggest that LTT for Kampo formulae may be unreliable as a diagnostic method for drug-induced liver injury.

Chemical and Drug Induced Liver Injury↗

Rhubarb use in patients treated with Kampo medicines--a risk for gastric cancer?

In vitro mutagenic effects have been reported for ingredients contained in rhubarb. Therefore, rhubarb (Rhei Rhizoma) as an anthranoid laxative could be associated with a risk of developing gastric cancer as well as colorectal cancer. We are not aware of any reports that have examined the relationship between the use of rhubarb and the development of gastric cancer. During the period between 1979 and 1999, we treated 14,616 patients using various Kampo medicines, which sometimes contained rhubarb. In the present study, we determined whether patients, diagnosed with gastric cancer during the period between 1979 and 1999, had been administered rhubarb before the development of gastric cancer. Among the 10 enrolled patients, only 2 patients had been administered rhubarb before the development of gastric carcinoma. The other 8 patients had never received rhubarb before the development of gastric carcinoma. Rhubarb use may have little connection with the development of gastric cancer in practice, even if some ingredients in rhubarb have shown carcinogenic activity in experimental studies.

Aged↗