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Biomedical subjects

T Yoshino

Publications and source records attributed to T Yoshino.

At least 37 records · Page 2Linked to original sources
PubMed2002

Carbohydrates expressed on Aspergillus fumigatus induce in vivo allergic Th2-type response.

BACKGROUND: The mould Aspergillus fumigatus (Af) causes several forms of Th2-biased diseases such as Type I respiratory allergies. This mould contains abundant carbohydrates including glucan, chitin and galactomannan. However, little is known on whether these carbohydrates directly drive Th2 responses in vivo. OBJECTIVE: We sought to determine the relative role of carbohydrates expressed on crude extracts of Af in the induction of Th2-type antibody production and local eosinophila in mice. METHODS: Carbohydrates on native Af were destroyed by sodium metaperiodate under mild conditions. CBA/J mice were sensitized intranasally with native, periodate-treated or mock-treated Af. Histologic changes and production of Af-specific IgE, IgG1 and IgG2a, as well as serum total IgE were determined. Inhibition ELISA for Af-specific IgE was performed using periodate-treated Af as an inhibitor. RESULTS: Mice sensitized with periodate-treated Af displayed significant decreases in both total and specific IgE levels in comparison to mice sensitized with native or mock-treated Af. Furthermore, sensitization and subsequent challenge with periodate-treated Af significantly reduced the degree of eosinophil recruitment into the nasal mucosa, compared to the controls. On the other hand, competitive inhibition showed that periodate-treated Af could inhibit binding between native Af and specific IgE in a similar manner to that of native and mock-treated Af. CONCLUSION: These results suggest that carbohydrates on Af play a key role as internal adjuvants in inducing the allergic Th2-type response and are not the targets of the induced IgE response.

Animals↗
PubMed2002

Intranasal application of purified protein derivative suppresses the initiation but not the exacerbation of allergic rhinitis in mice.

BACKGROUND: Several epidemiological and experimental studies have demonstrated that exposure to pathogens such as those from the genus Mycobacterium leads to the suppression of allergic sensitization and inflammation. However, little is known as to whether pathogen-derived soluble antigens have the potential to modulate the pathogenesis of allergic rhinitis. OBJECTIVE: We sought to determine whether application of purified protein derivative (PPD) from Mycobacterium tuberculosis can suppress the initiation and/or exacerbation of allergic rhinitis using a recently developed murine model. METHODS: First, we investigated whether a single intranasal application of PPD could elicit cytokine production in the nose by RT-PCR. BALB/c mice were repeatedly sensitized with Schistosoma mansoni egg antigen (SEA) intranasally without an adjuvant. PPD was applied through different routes either before or after sensitization. The production of SEA-specific antibodies, nasal eosinophilia and cytokines by nasal lymphocytes was compared among mice that had or had not received PPD treatment. RESULTS: IFN-gamma, but not IL-4, was detected in the nasal tissue 12 to 48 h after a single intranasal application of 10 microg PPD. Repeated intranasal application of PPD prior to and during sensitization with SEA significantly inhibited the production of both SEA-specific IgE/IgG1 and nasal eosinophilia. Moreover, it partially inhibited the production of IL-4 by nasal lymphocytes in response to SEA. Conversely, this treatment led to a significant increase in IFN-gamma production. On the other hand, PPD applied through the footpad had no effect over the same period. Repeated intranasal application of PPD after sensitization with SEA had no exacerbative effect on allergic inflammation. CONCLUSION: These results indicate that the local application of PPD, and the subsequent induction of IFN-gamma, inhibits the initiation, but not the exacerbation, of allergic rhinitis in mice. This suggests that pathogen-derived antigens have potential for use in the prevention and prophylaxis of allergic rhinitis.

Administration, Intranasal↗
PubMed2002

Correlation between elevator muscle activity and direction of sagittal closing pathway during unilateral chewing.

The closing pathway of masticatory movement in the vicinity of the intercuspal position (ICP) is considered as a functional movement in reconstructing the occlusal guidance. The purpose of this study was to examine a correlation between elevator muscle activity and direction of the closing pathway in the vicinity of the ICP during mastication. Fifty subjects (18 male and 32 female subjects aged from 21 to 34 years) were selected randomly from the students of the Kanagawa Dental College. The measurements of jaw movement during mastication were recorded using a Sirognathograph instrument and surface electromyography (EMG) of the anterior temporalis and masseter muscles simultaneously. The muscle activity and the direction of the closing pathway were calculated on the working and non-working sides during unilateral chewing and analysed at the sections of ICP-2 mm and 2-4 mm in sagittal view. The direction of the closing pathway was expressed by the angle to a vertical reference axis. The direction of the closing pathway correlated significantly with the activity of the anterior temporalis muscles on the non-working side and the masseter muscles on the working side at ICP-2 mm. From the results of this study, it was suggested that the elevator muscle activity may be associated with the direction of the closing pathway during mastication.

Adult↗
PubMed2002

Spontaneous recurrence of methamphetamine-induced paranoid-hallucinatory states in female subjects: susceptibility to psychotic states and implications for relapse of schizophrenia.

In this study, we examined the relationship between increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes, and susceptibility to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (i.e., flashbacks). The subjects were 81 physically healthy females. Plasma monoamine metabolite levels were assayed in: 19 flashbackers, of whom 11 experienced a single flashback and 8 exhibited subsequent flashbacks; 20 non-flashbackers with a history of MAP psychosis; 8 subjects with persistent MAP psychosis; and 23 MAP users and 11 non-user controls. All 19 flashbackers had undergone frightening and stressful experiences during previous MAP use. Mild psychosocial stressors then triggered their flashbacks. During flashbacks, plasma norepinephrine levels increased, with a small increase in plasma levels of 3-methoxytyramine, which is an index of dopamine release. Among the 19 flashbackers, the 8 with subsequent episodes had increased NE levels and slightly increased 3-methoxytyramine levels, while the 11 with a single episode displayed small increases in norepinephrine and 3-methoxytyramine levels. Thus, noradrenergic hyperactivity and increased dopamine release in response to mild psychosocial stressors may be responsible for the development of flashbacks. Robust noradrenergic hyperactivity with slightly increased DA release in response to mild stress may induce susceptibility to subsequent flashbacks. Flashbacks and schizophrenia may share the pathophysiology of susceptibility to recurrence of paranoid-hallucinatory states such as stress sensitization, and also noradrenergic hyperactivity and enhanced DA release. Thus, flashbacks may provide an appropriate model of susceptibility to paranoid-hallucinatory states of schizophrenia. The model psychosis is a potential tool for validating basic neurobiological concepts thought to be related to the schizophrenia. A better understanding of the neurobiological mechanisms of susceptibility to recurrence could provide useful information in the development of strategies for preventing relapse.

Adult↗
PubMed2002

Eimeria organisms develop in the epithelial cells of equine small intestine.

Histopathologic and immunohistochemical examinations were performed to determine the origin of host cells parasitized by Eimeria in the small intestines collected from five foals. Eimeria organisms at various stages (mainly microgametes and macrogametes) were frequently found in the cytoplasm of hypertrophied host cells in the lamina propria at the tips of villi of the jejunum and ileum. The cytoplasm of the host cell was immunohistochemically positive for cytokeratin AE1/AE3 and cytokeratin 13 and was negative for vimentin, desmin, alpha-smooth muscle actin, chromogranin A, neuron-specific enolase, and factor VIII. The host cells parasitized by Eimeria species had the immunostaining characteristics of epithelial cells but not of mesenchymal cells, endothelial cells of lacteals or capillaries, smooth muscle cells or neuroendocrine cells. These results suggest that the host cell of Eimeria species is possibly derived from intestinal epithelial cells and then displaced into the lamina propria of the small intestine.

Actins↗
PubMed2002

Gene expression analysis from nuclear Poly(A) RNA.

Quantitation of the level of specific mRNA involves the isolation of total RNA or poly(A)+ RNA as a starting materiaL Thus, this result is the sum of the transcription and degradation of mRNA. Here we report a rapid, sensitive, and high-throughput methodology for gene expression analysis from nuclear poly(A)+ RNA via the reduction of the cytosolic components. The cells were first trapped on the glass fiber membranes of 96-well filter plates and subsequently exposed to non-ionic detergent to achieve cell membrane permeation. The cytosolic components, which contain preexisting mRNA, were removed by washing with the appropriate buffer, while nuclei remained in the filter plates. Lysis buffer was then used to release nuclear mRNA, which was collected on oligo(dT)-immobilized PCR plates for the capture of poly(A)+ RNA, on which RT-PCR was performed. The reduction of the cytosolic components and the preservation of the nuclear components were confirmed by electron microscopy, agarose gel electrophoresis, PCR of mtDNA, and RT-PCR of pre-splicing immature beta-actin poly(A)+ RNA. Using this method, we clearly identified UVC-induced p21 gene expression that is not detectable with conventional whole cell methods.

Cell Nucleus↗
PubMed2002

Allelic imbalance and microsatellite instability in plasma DNA released from polyclonal pancreatic adenocarcinoma.

Evidence of circulating soluble DNA in blood-stream of cancer patients has emerged. Because the plasma DNA is largely derived from cancer cells, genetic analysis of plasma DNA is important to understand the molecular events occurred in cancer patient. Seven microsatellite markers in the soluble plasma DNA from patients with pancreatic adenocarcinoma and other pancreato-biliary malignant tumors were examined for microsatellite instability (MSI) and allelic imbalance (AI). A variety of genetic alterations including MSI and AI were detected in the plasma DNA. Some alterations were detected before recurrence of the tumor was verified. Analysis of five primary pancreatic adenocarcinomas by microdissection revealed that the heterogeneous nature of pancreatic tumors is associated with both MSI and AI in the same tumor. The presence of altered plasma DNA including MSI and/or AI from the same pancreatic cancer patient may be important evidence for the presence of these alterations in heterogeneous primary tumors. Analysis of plasma DNA could become one of the diagnostic or therapeutic measures for this type of pancreatic adenocarcinoma.

Aged↗
PubMed2001

High frequency of low-level microsatellite instability in early colorectal cancer.

Molecular events in early colorectal cancers (CRCs) have not been well elucidated because of the low incidence of early CRCs in clinical practice. Therefore, we studied 104 sporadic early CRCs with invasion limited to submucosa compared with 116 advanced CRCs. Loss of heterozygosity as well as microsatellite instability (MSI) status was examined. A significantly high frequency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs, samples with MSI-L phenotype differed from microsatellite stable (MSS) phenotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L is a frequent genetic event in early CRCs and may be a novel pathway in colorectal carcinogenesis distinct from both MSI-H and MSS.

Aged↗
PubMed2001

Differential role of CD80 and CD86 molecules in the induction and the effector phases of allergic rhinitis in mice.

Selective involvement of CD80 and/or CD86 in the differentiation of T-helper (Th)1 and Th2 was seen in several diseases. In this study, we sought to determine the differential roles of CD80 and CD86 in the induction and effector phase of allergic rhinitis using Schistosoma mansoni egg antigen (SEA) as a specific Ag. Intranasal sensitization with SEA in BALB/c mice elicited a strong Th2 response including SEA-specific IgE production, nasal eosinophilia, and IL-4 and IL-5 production by nasal lymphocytes after Ag challenge. Blockade of CD80 at the induction phase significantly inhibited these manifestations, whereas no effect was observed by CD86 blockade. In contrast, the simultaneous blockade of both CD80 and CD86 during the effector phase partially inhibited IgE and IgG(1) production and nasal eosinophilia, although either blockade of CD80 or CD86 during the phase failed to inhibit these responses. Flow cytometric analysis on nasal mononuclear cells showed that CD80 but not CD86 was preferentially expressed on non-B cells by in vitro SEA stimulation in unsensitized mice. However, both CD80 and CD86 expression were significantly augmented by in vitro SEA stimulation in sensitized mice. Our results suggest the differential roles and expression of CD80 and CD86 in the development of allergic rhinitis.

Animals↗
PubMed2001

Susceptibility to subsequent episodes of spontaneous recurrence of methamphetamine psychosis.

We examine susceptibility to subsequent spontaneous recurrences of methamphetamine psychosis (i.e. flashbacks) in 11 flashbackers with a single episode and in nine flashbackers with subsequent episodes. All had undergone frightening stressful experiences during previous MAP use. Mild psychosocial stressors then triggered flashbacks. During flashbacks, the nine flashbackers with subsequent episodes had more markedly increased norepinephrine levels, with slightly increased 3-methoxytyramine levels. The duration of imprisonment in this subgroup approached significantly long levels than in the 11 flashbackers with a single episode. Robust noradrenergic hyperactivity with slightly increased dopamine release may therefore predict subsequent flashbacks. Longer exposure to distressing situations may also contribute to robust noradrenergic hyperactivity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Tumor-specific cytotoxic T lymphocyte responses against chondrosarcoma with HLA haplotype loss restricted by the remaining HLA class I allele.

Although loss of HLA expression by malignant cells has also been demonstrated, it has not been clarified how the loss of HLA expression observed in vitro actually results in immune escape. We demonstrated two major findings: (i) a part of chromosome 6 coding for HLA haplotypes was deleted from the genome of chondrosarcoma cell line, OUMS-27; furthermore, immunohistostaining for HLA-A11 showed that the original chondrosarcoma tissue lost the expression of HLA-A11, implicating that HLA haplotype loss was already present in the original tumor tissue and (2) HLA class I-restricted and autologous tumor-specific cytotoxic T cells (CTL) were generated from peripheral blood lymphocytes of the patient with chondrosarcoma, from whom OUMS-27 originated. This CTL line was maintained by weekly stimulation with OUMS-27, and lysed OUMS-27 in an HLA-A24 dependent manner but did not either K562 or autologous (EBV)-transformed B cells. These observations indicated that OUMS-27 and its original tumor are still immunogenic and can present antigen peptides with the remaining HLA-A24, even if HLA expression is partially lost. Tumor specific immunotherapy can be applied to the treatment of malignancies, even if HLA expression is partially lost.

Aged↗
PubMed2001

IL-18-induced expression of intercellular adhesion molecule-1 in human monocytes: involvement in IL-12 and IFN-gamma production in PBMC.

IL-18 time- and concentration-dependently upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) in a monocyte population in human PBMC as determined by FACS analysis while the expression of CD11a, CD18, CD29, CD44, and CD62L in monocytes and that of ICAM-1, CD11a, CD18, CD29, CD44, and CD62L in T cells was not influenced by IL-18. IL-18 in the same concentration range stimulated the production of IL-12, TNF-alpha, and IFN-gamma in culture of PBMC; however, IL-18-induced expression of ICAM-1 in monocytes was not inhibited by anti-IL-12, anti-TNF-alpha, or anti-IFN-gamma Ab, suggesting the independence of the upregulating effect of IL-18 on endogenous IL-12, TNF-alpha, and IFN-gamma production. IL-18 also induced the aggregation of PBMC, which was prevented by anti-ICAM-1 and anti-LFA-1 Abs. On the other hand, anti-ICAM-1 and anti-LFA-1 Abs inhibited IL-18-induced production of three cytokines, IL-12, IFN-gamma, and TNF-alpha, by 60 and 40%, respectively. These results strongly suggested that the IL-18-induced upregulation of ICAM-1 and the subsequent adhesive interaction through ICAM-1 on monocytes and LFA-1 on T/NK cells generate an additional stimulatory signaling as well as an efficient paracrine environment for the IL-18-initiated cytokine cascade.

Antibodies, Monoclonal↗
PubMed2001

Genetic alterations of candidate tumor suppressor ING1 in human esophageal squamous cell cancer.

Overexpression of ING1, a candidate tumor suppressor gene, efficiently blocks cell growth or induces apoptosis in different experimental systems. ING1 maps to chromosome 13q33-34, and because loss of the terminal region of chromosome 13q has been implicated in esophageal squamous cell cancer (ESCC), we examined ESCC for genetic alterations of ING1. Among 31 informative cases of ESCC, 58.9% of the tumors showed allelic loss at chromosome 13q33-34, and we detected four tumor-specific missense nucleotide changes. These alterations were found within the PHD finger domain and nuclear localization motif of the ING1 and may be functionally involved in the development of ESCC. Because immunohistochemical study revealed that all of the ESCC samples showed loss of ING1 protein expression, genetic or epigenetic alterations that abrogate the normal function of ING1 may contribute to esophageal squamous cell carcinogenesis.

Aged↗
PubMed2001

Orally active docetaxel analogue: synthesis of 10-deoxy-10-C-morpholinoethyl docetaxel analogues.

To improve cytotoxicity of 10-deoxy-10-C-morpholinoethyl docetaxel analogues against various tumor cell lines including resistant cells expressing P-glycoprotein (P-gp), we modified the 7-hydroxyl group to hydrophobic groups (methoxy, deoxy, 6,7-olefin, alpha-F, 7-beta-8-beta-methano, fluoromethoxy). Among these analogues, the 7-methoxy analogue showed the strongest cytotoxicity. This analogue showed potent activity against B16 melanoma BL6 in vivo by oral administration.

Administration, Oral↗
PubMed2001

Potent serotonin (5-HT)(2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome.

The serotonin (5-HT) syndrome is the most serious side effect of antidepressants, and it often necessitates pharmacotherapy. In the present study, the efficacy of several drugs was evaluated in an animal model of the 5-HT syndrome. When 2 mg/kg of clorgyline, a type-A monoamine oxidase inhibiting antidepressant, and 100 mg/kg of 5-hydroxy-L-tryptophan, a precursor of 5-HT, were administered intraperitoneally to rats to induce the 5-HT syndrome, the rectal temperature of the rats increased to more than 40 degrees C, and all of the animals died by 90 min after the drug administration. The noradrenaline (NA) levels in the anterior hypothalamus, measured by microdialysis, increased to 15.9 times the preadministration level. Pretreatment with propranolol (10 mg/kg), a 5-HT(1A) receptor antagonist as well as a beta-blocker, and dantrolene (20 mg/kg), a peripheral muscle relaxant, did not prevent the death of the animals, even though these two drugs suppressed the increase in rectal temperature to some extent. Chlorpromazine and cyproheptadine prevented the lethality associated with the 5-HT syndrome only at high doses. By contrast, pretreatment with ritanserin (3 mg/kg) and pipamperone (20 mg/kg), both potent 5-HT(2A) receptor antagonists, completely prevented the increase in rectal temperature and death of the animals, and the hypothalamic NA levels in these two groups increased less than that in the other groups. These results suggest that potent 5-HT(2A) receptor antagonists are the most effective drugs for treatment of the 5-HT syndrome, and that NA hyperactivity occurs in the 5-HT syndrome.

5-Hydroxytryptophan↗
PubMed2001

Multiple organ mucosa-associated lymphoid tissue lymphomas often involve the intestine.

BACKGROUND: Low grade mucosa-associated lymphoid tissue (MALT) lymphomas usually are confined to single extranodal organs. Although some case reports have been published, clinicopathologic characteristics of multiorgan MALT lymphomas remain unclear. METHODS: The authors evaluated 7 MALT lymphoma cases involving multiorgans in the past 7 years. In this period, they experienced 304 cases of MALT lymphomas. They analyzed the clinicopathologic features of these cases, including examination of clonal comparison among the lesions. RESULTS: The patients, 4 females and 3 males, were aged 55-68 years old (average, 60.1 years). Four cases showed multiple organ involvement at the initial diagnosis or after a short period. In the other three cases, primary foci were the stomach, thyroid gland, and ocular adnexa; after a rather long period (3 years or more), distant metastases were found. Although intestinal primary lymphomas are rather rare, six of the seven cases showed large intestinal involvement. Lymph node involvement was proven in only three cases. The patients were rather resistant to the various therapeutic approaches. Although six patients are alive, five are with disease. DNA analyses revealed that in five of the cases evaluated, identical clones were detected among the different affected organs. CONCLUSIONS: Multiorgan MALT lymphomas are rather rare. Most cases probably derived from a single clone, and lymphoma cells may selectively move among MALTs via a homing system with preferential involvement of the colon. Because multiorgan MALT lymphomas rarely achieve complete remission by treatment with combination chemotherapy or irradiation, MALT lymphomatous lesions should be checked carefully, especially in the large intestine.

Aged↗
PubMed2001

Differential involvement of p38 MAP kinase pathway and Bax translocation in the mitochondria-mediated cell death in TCR- and dexamethasone-stimulated thymocytes.

Mitochondria play a central role in many apoptotic reactions. Although mitochondrial apoptotic changes and caspase activation have been demonstrated in the apoptotic thymocytes, cell death signal through mitochondria in TCR-stimulated thymocytes has not been fully understood. In this study, we show that TCR stimulation induced disruption of mitochondrial transmembrane potential (Delta Psi(m)), the cytochrome c release from mitochondira, capase-3 activation, and the cell death of thymocytes. Bongkrekic acid, an inhibitor of Delta Psi(m) disruption, blocked the cytochrome c release from mitochondria and the following caspase-3-mediated cell death. Furthermore, a pro-apoptotic Bcl-2 family protein, Bax, but not Bad or Bid, was translocated from cytosol to mitochondria in TCR-stimulated thymocytes. This translocation and the following apoptotic changes were inhibited by SB203580, a p38 kinase inhibitor, in a specific manner. These results suggest that activated p38 kinase pathway by TCR stimulation induces translocation of Bax to mitochondria, causing Delta Psi(m) disruption, and the release of cytochrome c, which finally induces caspase-3-mediated apoptosis in thymocytes.

Animals↗