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Biomedical subjects

H Yamada

Publications and source records attributed to H Yamada.

At least 325 records · Page 18Linked to original sources

Chemokine production by the BEAS-2B human bronchial epithelial cells: differential regulation of eotaxin, IL-8, and RANTES by TH2- and TH1-derived cytokines.

BACKGROUND: Bronchial epithelial cells produce many types of chemokines and may contribute to lung inflammation by recruiting inflammatory cells. The CC chemokine eotaxin is a potent, eosinophil-specific chemoattractant that has been detected in the bronchial epithelium of patients with asthma. OBJECTIVES: The aim of this study was to investigate the regulatory mechanisms of chemokine production from bronchial epithelium by inflammatory cytokines, especially T(H)2- and T(H)1-derived cytokines, in bronchial asthma. METHODS: BEAS-2B human bronchial epithelial cells were cultured with TNF-alpha, IL-4, IL-13, and IFN-gamma alone or in combination, after which supernatants were assayed for eotaxin, IL-8, and RANTES proteins with ELISA. Reverse transcription-PCR was also performed. RESULTS: TNF-alpha induced production of eotaxin, IL-8, and RANTES in a concentration-dependent manner. Both IL-4 and IL-13 synergistically enhanced TNF-alpha-induced eotaxin production, whereas IL-8 production induced by TNF-alpha was significantly down-regulated by the T(H)2-derived cytokines. IFN-gamma, a T(H)1 cytokine, counteracted the enhancing effects of IL-4 and IL-13 on eotaxin production. RANTES production by TNF-alpha was not affected by IL-4 and IL-13 but was markedly enhanced by IFN-gamma. CONCLUSIONS: These results suggest that T(H)2 cytokines are involved in preferential recruitment of eosinophils in bronchial asthma by enhancing eotaxin and reducing IL-8 production from bronchial epithelial cells and that T(H)1 cytokines counteract the effects of T(H)2 cytokines by reducing eotaxin production.

Bronchi↗

Effects of a pectic polysaccharide from a medicinal herb, the roots of Bupleurum falcatum L. on interleukin 6 production of murine B cells and B cell lines.

The effect of T-cell-independent B cell mitogen, a pectic polysaccharide, bupleuran 2IIc, from a medicinal herb, the roots of Bupleurum falcatum L. on interleukin 6 (IL-6) production of murine B cells and B cell lines was investigated in order to clarify the mechanism of enhanced immunoglobulin (Ig) secretion from B cells. Bupleuran 2IIc enhanced IgM secretion from highly purified murine normal B cells. When normal B cells from murine spleen were cultured with bupleuran 2IIc in the presence of anti-IL-6 neutralizing antibody, the enhanced IgM secretion by bupleuran 2IIc was reduced. When B cells were stimulated with bupleuran 2IIc, their IL-6 secretion and the transcription of IL-6 mRNA were enhanced. The enhanced IL-6 secretion by bupleuran 2IIc was also observed in B cell line, Y16 cell. When bupleuran 2IIc was digested with endo-alpha-(1-->4)-D-polygalacturonase, the resulting enzyme resistant carbohydrate portion, "ramified" region (PG-1) composed of rhamnogalacturonan core containing neutral sugar side chains showed potent IL-6 secretion-enhancing activity. These results suggest that the "ramified" region of bupleuran 2IIc stimulates the secretion of IL-6 as the active site, and the resulting IL-6 may partially contribute the enhancement of IgM secretion as an autocrine and/or paracrine mechanism.

Adjuvants, Immunologic↗

Orally administered decoction of Kampo (Japanese herbal) medicine, "Juzen-Taiho-To" modulates cytokine secretion and induces NKT cells in mouse liver.

The effects of orally administered decoction of Juzen-Taiho-To (JTT; Si-Quan-Da-Bu-Tang in Chinese) on cytokine production in hepatic lymphocytes were studied in mice. JTT was found to increase interferon gamma (IFN-gamma), as well as interleukin-4 (IL-4), IL-5 and IL-6 secretion from stimulated hepatic lymphocytes, whereas IL-2 secretion was reduced. The number of IFN-gamma- and IL-4-spot forming cells (SFC) were not changed by administration of JTT. These results suggest that modulation of cytokine secretion by JTT might not be due to changes in the number of cytokine secreting cells within liver lymphocytes. CD4/CD8 ratio and alphabeta/gammadelta T cell receptor (TCR) ratio in hepatic lymphocytes were not changed. However, flow cytometric analysis revealed that the population of CD3 positive intermediate cells in NK positive cells (NKT cells) was increased after oral administration of JTT. The population of CD3int IL-2Rbeta+ cells was also increased. The induction of NKT cells by JTT was reduced by injection of 2-chloroadenosine. JTT enhanced transcription of IL-12 mRNA in liver. From these results, it may be concluded that a rise in NKT cell population contributes, at least partially, to the modulating effect of JTT on cytokine production in liver lymphocytes, and macrophages. The production of IL-12 in liver may also contribute to this NKT induction.

Administration, Oral↗

Difference in the metabolic response to photic stimulation of the lateral geniculate nucleus and the primary visual cortex of infants: a fMRI study.

The metabolic change that occurs during early development of the human brain was studied with functional magnetic resonance imaging (fMRI), in which the signal change reflects the balance between the supply and the demand of oxygen during stimulus-related neuronal activation. The subjects were 16 infants, aged < 1 year. They were sedated with pentobarbital, and 8-Hz flickering light was intermittently projected onto their eyelids. Two age groups were analyzed: infants < 60 days old and > 60 days old (corrected for gestational age at birth). The stimulus-related signal change was positive in the lateral geniculate nucleus regardless of the infants' age, but in the primary visual cortex reversed from positive in the younger group to negative in the older group. It is known that synaptogenesis in the lateral geniculate nucleus peaks before birth, and in the primary visual cortex accelerates in the second month after birth. Hence, the inversion of the stimulus-related signal change in the primary visual cortex may be due to an increased demand for oxygen owing to rapid synaptogenesis.

Aging↗

Neurogenesis in the superior olivary complex in the rat.

In a previous paper we provided evidence that crossed projection neurons are generated earlier than uncrossed projection neurons in the lateral superior olive. The aim of the present study was to determine if other major nuclei of the superior olivary complex (SOC), the medial superior olivary (MSO), the superior paraolivary (SPN) and the medial trapezoid (MTB) nuclei, are distinguished by their neuronal constitutions of birthdates. Pregnant rats were injected intraperitoneally with 5-bromodeoxyuridine (BrdU), the thymidine analogue, to label the neurons on one of the embryonic (E) days E11-E16. When the progeny rats reached adulthood, the brains were processed for BrdU immunohistochemistry. The MSO was mostly composed of neurons generated on E12 (95%). The remaining neurons in the MSO completed their neurogenesis by E13. The SPN neurons were generated from E12 to E14 with a peak on E13 (80%). Regardless of the morphological heterogeneity, the SPN consisted of a single population of neurons in terms of neurogenesis. The MTB neurons were generated from E13 to E16 with a peak on E14 (73%). In contrast to the previous assumption, no topographical relationship existed between neurogenesis and tonotopicity within each nucleus of the SOC.

Animals↗

Ganglioside patterns in neuroepithelial tumors of childhood.

To elucidate a relationship between neuronal anaplasia, tumor proliferation, and ganglioside contents, we quantified gangliosides by HPTLC in tumors of neuroepithelial tissues at different grade, i. e. peripheral primitive neuroectodermal tumor (PPNET, grade IV), ependymoma (EPEN, grade III), neuroblastoma (NB, grade IV), and dysembryoplastic neuroepithelial tumor (DNT, grade I). PPNET, the most undifferentiated tumor examined had lowest concentration of total lipid-bound sialic acid. GM3 was the major ganglioside in all undifferentiated tumors (46-72.7% of total lipid-bound sialic acid). GD3 was an another component in PPNET and EPEN (7.2-17.3%). Concentration of a complex gangliosides GM1 was decreased in all tumor tissues and those of GT1a, GD1b and GT1b were decreased in tumors of high grade. The results suggest that the composition of gangliosides could be of considerable value in refining the classification of neuroepithelial tumors in infancy and childhood.

Adolescent↗

Subendocardial motion in hypertrophic cardiomyopathy: assessment from long- and short-axis views by pulsed tissue Doppler imaging.

BACKGROUND: Tissue Doppler imaging (TDI) is a recently developed technique that allows the instantaneous measurement of intrinsic regional myocardial motion velocity. Pulsed TDI is capable of separately assessing left ventricular (LV) regional motion velocity caused by circumferential and longitudinal fiber contraction. This particular feature of function is still controversial in patients with hypertrophic cardiomyopathy (HC). METHODS: To better characterize intrinsic circumferential and longitudinal LV systolic myocardial function in HC, we used pulsed TDI to measure short- and long-axis LV motion velocities, respectively. The subendocardial motion velocity patterns at the middle of the LV posterior wall (PW) and ventricular septum (IVS) in LV parasternal and apical long-axis views were recorded by pulsed TDI in 19 patients with nonobstructive HC and in 21 normal controls (NC). RESULTS: Peak short- and long-axis systolic subendocardial velocities in both the LV PW and IVS were significantly smaller in the HC group than in the NC group, and the time to peak velocity was significantly delayed. Furthermore, peak PW systolic velocity was significantly greater along the long axis than along the short axis in the NC group (8.8 +/- 1.5 cm/s vs 8.2 +/- 1.4 cm/s, P <.05), whereas the opposite was observed in the HC group (6.1 +/- 1.2 cm/s vs 7.5 +/- 1.0 cm/s, P <.0001). No significant differences were found in either group between the long- and short-axis IVS velocities (HC: 5.9 +/- 1.4 cm/s vs 5.5 +/- 1.3 cm/s; NC: 7.8 +/- 1.3 cm/s vs 7.9 +/- 1.6 cm/s). CONCLUSIONS: By using the capability of pulsed TDI for the evaluation of intrinsic myocardial velocity instantaneously in a specific region and direction, we found impairment of LV myocardial systolic function in patients with HC not only in the hypertrophied IVS but also in the nonhypertrophied LV PW. We also found a greater decrease in LV PW velocities along the long axis than the short axis, suggesting greater impairment of long-axis contraction in patients with HC. Because our HC patients did not appear to have excessive intracavitary pressure, these results suggest that the relatively normal-appearing PW is directly affected by the HC pathologic process.

Adult↗

Functional asymmetry of human prefrontal cortex in verbal and non-verbal episodic memory as revealed by fMRI.

Functional neuroimaging studies have demonstrated preferential involvement of bilateral prefrontal cortex during episodic memory encoding and retrieval. The aim of the present study is to address the question whether left prefrontal model for encoding holds when highly non-verbal material is used, and which region of the brain is critically related to successful retrieval. To do this, seven normal subjects were investigated using functional magnetic resonance imaging (fMRI) during encoding and retrieval of word and checkerboard pattern. Our results revealed that word encoding activated the left prefrontal cortices and right cerebellum, whereas pattern encoding activated the bilateral middle frontal gyrus, superior parietal lobule, premotor area, and occipital visual cortex. Word-specific activation was found in the ventral prefrontal cortices, and pattern-specific activation located in the right dorsal prefrontal cortex. Conjunction analysis during encoding of word and pattern showed that activity in the left dorsal prefrontal cortex and the right cerebellum might relate to common neural network for encoding regardless of the type of material. Finally, the present study demonstrates strong association between the left ventral prefrontal cortex and retrieval success for word. The evidence, that both encoding and retrieval of words activated the left ventral prefrontal cortex, indicates that this area is involved in active and strategic operation of the mnemonic representation. A lack of the right prefrontal activation during retrieval was interpreted as that activity in this region might relate to retrieval effort rather than success.

Adult↗

Potentiation of brain acetylcholine neurons by Kami-Untan-To (KUT) in aged mice: implications for a possible antidementia drug.

The effects of a traditional Japanese herbal medicine, Kami-Untan-To (KUT), on brain choline (Ch) and Acetylcholine (ACh) levels in aged mice were examined. Further, the expression of choline acetyltransferase (ChAT) in the medial septum (MS), the vertical limbs of the diagonal band of Broca (VDB), and the nucleus basalis Meynert (NBM) was examined by immunohistochemistry. Following an oral administration of KUT to the aged mice for 3 months, ACh levels in the cortex, striatum and hippocampus were increased significantly. The density of ChAT-immunoreactive cells located in MS, VDB, and NBM in the KUT-treated group was increased significantly as compared to the non-treatment group. The survival rate of aged mice was significantly higher in the KUT-treated group as compared to that in the nontreated group. Our results suggest that KUT potentiates the brain acetylcholinergic system, and may become a possible anti-dementia drug.

Acetylcholine↗

Orally administered Kampo (Japanese herbal) medicine, "Juzen-Taiho-To" modulates cytokine secretion in gut associated lymphoreticular tissues in mice.

The influence of the oral administration of Juzen-Taiho-To (JTT; Si-Quan-Da-Bu-Tang in Chinese), a Kampo (Japanese herbal) medicine, on the cytokine production in mice were investigated. Lymphocytes from spleen (SPN), mesenteric lymph node (MLN) and Peyer's patches (PP) from mice, which received orally administered JTT for 2 weeks, were stimulated with concanavalin A (Con A), and the resulting conditioned medium was tested for cytokine production by ELISA. Administration of JTT caused enhancement of interferon g (IFN-gamma) and interleukin-4 (IL-4) production to some extent but decreased IL-5 production from the SPN. On the other hand, notable changes in cytokine production were observed in lymphocytes from MLN and PP. Administration of JTT increased IFN-gamma production remarkably, as well as IL-5 secretion from both MLN and PP, whereas IL-2 secretion was plainly reduced. The ratio of IFN-gamma and IL-4 was shifted to Th1 dominant in MLN and PP, however changed little in SPN. The flow cytometric analysis revealed that the population of CD3+, CD4+, CD45R/B220+, and CD45RBlowCD4+ cells in each lymphocyte was not changed significantly after oral administration of JTT. These findings demonstrate that the lymphocytes from gut associated lymphoreticular tissues (GALT) are more sensitive to produce cytokines on cytokine production than those from SPN by oral administration of JTT, and that the modulation of cytokine production may be due to functional change of lymphocytes but not change in lymphocytes population.

Administration, Oral↗

Genetic instability in intestinal metaplasia is a frequent event leading to well-differentiated early adenocarcinoma of the stomach.

To understand the development of well-differentiated adenocarcinoma in the stomach, we examined genetic instability in 31 patients with stage Ia gastric cancer. Triplets of tissue specimens (normal/metaplasia/tumour) from 33 lesions were examined for microsatellite instability (MSI) and loss of heterozygosity (LOH), using nine microsatellite loci. Frameshift mutations in the transforming growth factor beta receptor type II (TGF-betaRII) (A)(10), Bcl-2-associated X protein (BAX) (G)(8), hMSH3 (A)(8) and hMSH6 (C)(8) genes were also studied. In this study, a high incidence of MSI (MSI-H) was defined as samples containing 30% or more MSI positive loci, and a low incidence of MSI (MSI-L) as samples which had less than 30% MSI. MSI-L was observed in 19 cancerous lesions (58%), and MSI-H in three (9%). Eleven intestinal metaplasia lesions (33%) showed MSI-L, but no metaplasia lesions exhibited MSI-H. Frameshift mutation was observed in only one cancerous lesion (3%) at the (A)(10) tract of TGF-betaRII. In contrast, LOH was observed in 24 cancerous lesions (73%), and in 15 (45%) of intestinal metaplasia lesions. Intriguingly, these alterations tend to be coincident between metaplasia and cancerous lesions in the same sets of specimens, and there was no case that showed alterations in metaplasia, but not in cancerous lesions. These findings suggest that metaplasia and well-differentiated adenocarcinoma in the stomach may have the same molecular backgrounds, and that these two lesions may be chronologically connected.

Adenocarcinoma↗

In vivo antioxidative activity of propolis evaluated by the interaction with vitamins C and E and the level of lipid hydroperoxides in rats.

In vivo antioxidative activity of propolis was evaluated on the basis of ameliorative effects on the oxidative stress induced by vitamin E deficiency in rats. The control group was fed vitamin E-deficient diet, and the propolis group was fed vitamin E-deficient diet supplemented with 1% of propolis for 4 and 8 weeks. Comparisons were made in tissue concentrations of vitamin C, vitamin E, and lipid hydroperoxides between these groups. No significant difference was observed in tissue vitamin E concentration between these groups after both 4 and 8 weeks. After 4 weeks, the plasma vitamin C concentration of the propolis group was significantly higher than that of the control group. After 8 weeks, the tissue concentrations of vitamin C in the kidney, stomach, small intestine, and large intestine of the propolis group were significantly higher than those of the control group. These results suggest that some components of propolis are absorbed to circulate in the blood and behave as a hydrophilic antioxidant that saves vitamin C. The concentration of lipid hydroperoxides in the large intestine of the propolis group was significantly lower than that of the control group after 8 weeks. These results suggest that propolis exerts its antioxidative effect where it is assumed to accumulate, such as on the kidney, where it is excreted, and on the gastrointestinal tract, where propolis influences these tissues even from the outside of the cell.

Animals↗

Induction of choline acetyltransferase activity in cholinergic neurons by stolonidiol: structure-activity relationship.

The effect of stolonidiol (1), a bioactive marine diterpenoid from the Japanese soft coral Clavularia sp., on choline acetyltransferase (ChAT) activity was examined using cultured cholinergic neurons. Stolonidiol (1) showed potent ChAT inducible activity in primary cultured basal forebrain cells and clonal septal SN49 cells, suggesting that it may act as a potent neurotrophic factor-like agent on the cholinergic nervous system. Further expansion of the structure-activity relationship to include stolonidiol (1) and its derivatives demonstrated that the exo-methylene group and the epoxide group are essential for ChAT-inducing activity. Stolonidiol (1) showed the highest activity among the test samples.

Animals↗

Differential responses of Bcl-2 family genes to etoposide in chronic myeloid leukemia K562 cells.

Etoposide is a potent anticancer agent that is used to treat various tumors. We have investigated the dose-dependent effect of etoposide on apoptosis using chronic myeloid leukemia K562 cells treated with low (5 microM) or high (100 microM) concentrations of the drug. At a low concentration, etoposide induced little apoptosis at 24 h, while about 20% of the cells showed apoptosis morphologically at a high concentration. Processing of caspase-3 was slightly detected from 12 h and became obvious at 24 h with 100 microM etoposide. Caspase-3-like protease activity was detected at 24 h with a high concentration. Moreover, these changes were accompanied by cleavage of poly ADP ribose polymerase (PARP). Changes of the mRNA levels of most apoptosis-regulating genes were not prominent at both concentrations, except for the rapid induction of c-IAP-2/HIAP-1 and the down-regulation of Bcl-X(L) by 100 microM etoposide. The downregulation of Bcl-X(L) protein occurred from 6 h, while Bax protein conversely showed a slight increase from 6 h. Taken together, the present findings show that the dose-dependent apoptotic effect of etoposide is based on a change in the balance between Bcl-X(L) and Bax, which precedes the activation of caspase-3.

Antineoplastic Agents, Phytogenic↗

Pressure effect on the dynamics of an isolated alpha-helix studied by 15N-1H NMR relaxation.

Dynamics and structure of (1-36)bacteriorhodopsin solubilized in chloroform/methanol mixture (1:1) were investigated by 1H-15N NMR spectroscopy under a hydrostatic pressure of 2000 bar. It was shown that the peptide retains its spatial structure at high pressure. 15N transverse and longitudinal relaxation times, 15N[1H] nuclear Overhauser effects, chemical shifts and the translation diffusion rate of the peptide at 2000 bar were compared with the respective data at ambient pressure [Orekhov et al. (1999) J. Biomol. NMR, 14, 345-356]. The model free analysis of the relaxation data for the helical 9-31 fragment revealed that the high pressure decreases the overall rotation and translation diffusion, as well as apparent order parameters of fast picosecond internal motions (S2) but has no effect on internal nanosecond motions (S2 and taus) of the peptide. The decrease of translation and overall rotation diffusion was attributed to the increase in solvent viscosity and the decrease of apparent order parameters S2f to a compression of hydrogen bonds. It is suggested that this compression causes an elongation of H-N bonds and a decrease of absolute values of chemical shift anisotropy (CSA). In particular, the observed decrease of S2f at 2000 bar can be explained by 0.001 nm increase of N-H bond lengths and 10 ppm decrease of 15N CSA values.

Anisotropy↗