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Biomedical subjects

Kenji Matsumoto

Publications and source records attributed to Kenji Matsumoto.

98 records · Page 6Linked to original sources

Intratracheal delivery of a single major histocompatibility complex class I peptide induced prolonged survival of fully allogeneic cardiac grafts and generated regulatory cells.

We have previously reported that intratracheal delivery of donor splenocytes in mice induces hyporesponsiveness to fully allogeneic cardiac grafts and generates regulatory cells. Here, we examined whether an allopeptide would produce the same results. A 15-mer (54-68) peptide corresponding to a hypervariable region of the K(b) molecule was given intratracheally or intravenously to CBA (H2(k)) mice 7 days before transplantation of a C57BL/10 (H2(b)) or BALB/c (H2(d)) heart and was also used in adoptive transfer experiments. Cardiac grafts in recipients given K(b) peptide intratracheally experienced a median survival time (MST) of 56 days, whereas those in recipients given the peptide intravenously were rejected acutely (MST=7.5 days). Adoptive transfer of splenocytes from mice pretreated intratracheally with K(b) peptide to naïve secondary recipients prolonged survival of cardiac grafts (MST = 35 days). Intratracheal delivery of a single major histocompatibility complex class I peptide induced hyporesponsiveness to allogeneic cardiac grafts and generated regulatory cells.

Adoptive Transfer↗

Effect of extracellular matrix proteins on platelet-activating factor-induced eosinophil chemotaxis.

BACKGROUND: Eosinophils accumulate in tissues during various allergic inflammatory processes. Selective eosinophil recruitment is the result of orchestrated events involving cell adhesion molecules and chemoattractants. However, the exact mechanism of the regulation of integrin avidity during interstitial migration is poorly understood. OBJECTIVE: The purpose of this study was to investigate whether extracellular matrix proteins might activate human eosinophil chemotaxis and, if so, to clarify the mechanism in terms of integrin avidity. METHOD: Eosinophils were purified from the peripheral blood of healthy donors. Eosinophil migration was measured using Boyden chambers with filter membranes coated with fibronectin (Fn), vitronectin (Vn), laminin (Ln), hyaluronic acid, collagen type IV, or bovine serum albumin (BSA) overnight. Platelet-activating factor (PAF) was introduced into the lower chamber of each well. Eosinophils were placed in the upper chamber after incubation with IL-5 for 15 min. The number of eosinophils that transmigrated into the lower chamber was calculated by measuring the eosinophil peroxidase activity. RESULTS: Fn, Ln and BSA enhanced PAF-induced chemotaxis of eosinophils. Inhibition experiments using blocking monoclonal antibodies showed that in the early phase of chemotaxis, Fn and Ln facilitated eosinophil chemotaxis that was mediated by alpha4 and alpha6 integrins, respectively. In the late phase of chemotaxis, BSA, but not other matrix proteins, facilitated both chemokinesis and chemotaxis that was mediated by beta2 integrin. CONCLUSION: Our data strongly suggest that during chemotaxis, matrix proteins might activate eosinophils via binding with integrins to facilitate PAF-induced chemotaxis, and that such a mechanism might participate in allergic inflammatory processes.

Animals↗

Pepsin-resistant 16-kD buckwheat protein is associated with immediate hypersensitivity reaction in patients with buckwheat allergy.

BACKGROUND: Buckwheat is becoming popular in many countries as a health food and the incidence of buckwheat allergy is increasing in Asia. The ingestion of small amounts sometimes provokes an anaphylactic reaction. However, it remains controversial which is the major allergen responsible for such reactions. METHODS: The patients whose sera are positive for buckwheat-specific IgE antibody measured by the CAP system fluorescein-enzyme immunoassay (CAP-FEIA) were classified into two subgroups depending on the history of immediate hypersensitivity reactions (IHR). Major buckwheat allergens were identified with immunoblotting, ELISA and N-terminal amino acid sequencing. Various treatments such as pepsin digestion were added to characterize the proteins. RESULTS: We found that the 24-kD protein that had previously been reported to be a major allergen reacted to IgE antibodies present in sera from almost all subjects (19/20) regardless of symptoms. On the other hand, 16- and 19-kD proteins were bound with IgE antibodies present in sera from 9 of the 10 patients with IHR including 8 patients with anaphylaxis but not in sera from buckwheat-specific IgE-positive subjects without IHR. After pepsin treatment, the 16-kD protein but not the 19- and 24-kD proteins remained undigested and preserved the capacity of IgE binding. This pepsin-resistant 16-kD protein had no homology with the 24-kD protein by the N-terminal amino acid sequencing. CONCLUSIONS: The 16-kD buckwheat protein was resistant to pepsin digestion and appeared to be responsible for IHR including anaphylaxis, while the pepsin-sensitive 24-kD protein was responsible for CAP-FEIA but not IHR.

Adolescent↗

Nutrition during pregnancy may be associated with allergic diseases in infants.

The prevalence of allergic diseases is high in Japan, even in infants. Their risk for developing allergies is influenced by the antigens in the mother's diet during pregnancy. We hypothesized that, apart from the antigens, hypersensitivity induced through high energy and nutrient intake by mothers during pregnancy may be a factor for allergic diseases in their babies. In this study, we tried to confirm our hypothesis. Allergy histories of parents and their infants, body characteristics and food and nutrient intake were measured by a questionnaire and a food frequency questionnaire, respectively. A total of 2,642 responses were obtained (return rate, 94.7%). The major allergic diseases in the infants were atopic dermatitis (6.0%), food allergy (3.7%) and bronchial asthma or asthmatic bronchitis (3.2%). About 60% of the infants with allergies had a family history of allergies. Family history of allergy, age of infant, order of birth, head and chest circumferences of infants, BMI of mothers before pregnancy and delivery and intake of lipids (fat and vegetable oil) and vegetables by mothers related positively, and the intake of protein, carbohydrates and milk and its products correlated negatively with allergic diseases in the infants (p < 0.05). The results, together with previous reports, suggest that a high intake of energy and lipids (fat and vegetable oil) during pregnancy may accelerate allergic diseases in infants.

Adult↗

[Accuracy of dynamic multileaf position and influence of beam profile according to change in dose monitor unit in QA plan of intensity modulated radiotherapy].

The number of dose monitor units in IMRT QA plans differs form the actual conditions of IMRT in dosimetry for verification of dynamic multileaf-IMRT (DMLC-IMRT). We measured the accuracy of the position of the dynamic multileaf collimator and the dose profile for various numbers of dose monitor units, and verified the accuracy of dosimetry in an IMRT QA plan. The accuracy of the position of the dynamic multileaf collimator was measured by using the software of the external irradiation device, and the dose profile was measured by using the semiconductor profiler. Deviation in the position of the dynamic multileaf collimator increased as the number of dose monitor units decreased. When deviation in the position of the dynamic multileaf collimator was large and the gap width of the multileaf collimator was narrow, the change in dose profile was large. Therefore, verification of IMRT QA plans requires a phantom and measurement device close to the actual conditions of IMRT.

Phantoms, Imaging↗

Antitumor effect of stilbenoids from Vateria indica against allografted sarcoma S-180 in animal model.

Dipterocarpaceous plants contain various resveratrol oligomers that exhibit a variety of biological activities, such as antibacterial and antitumor effects. Previously, we found that vaticanol C, a resveratrol tetramer, exhibits strong cytotoxicity against various tumor cell lines. In the present study, we examined the antitumor activity of the ethanol extract from the stem bark of Vateria indica, which has been traditionally used for health and healing diseases as Ayurveda in India. High-performance liquid chromatography analysis showed that the extract contains bergenin, hopeaphenol, vaticanol B, vaticanol C, and epsilon-viniferin. The in vitro assay displayed the extract's anti-cancer activity against mouse sarcoma 180 cells (IC50=29.5 microM). In the animal study, the tumor growth of sarcoma S-180 cells subcutaneously allografted in DDY mice was significantly retarded by oral administration of the extract (30 or 100 mg/kg body weight: P < 0.001). The extract did not show significant toxicity to mice even at a dosage of 1000 mg/kg body weight by daily oral administration for 28 days. These results demonstrated that the ethanol extract containing various stilbenoids from the stem bark of V. indica has the potent antitumor activity.

Animals↗

Selective cancer cell apoptosis induced by FTY720; evidence for a Bcl-dependent pathway and impairment in ERK activity.

BACKGROUND: FTY720 is a unique immunosuppressant that induces apoptosis in activated lymphocytes, but not in other hematopoietic cells. We conducted the present study to investigate its anticancer effect and molecular pathway in inducing apoptosis using murine breast cancer models. MATERIALS AND METHODS: The difference in drug susceptibility to FTY720 between cancer cells and non-cancer cells was examined by MTT assay and cell growth assay. FTY720-induced apoptosis was determined by electron microscopy and DNA electrophoresis, and its molecular pathway was evaluated by Western blot analysis. We then tested in vivo the effect of this agent using two murine breast cancer models. RESULTS: FTY720 treatment induced selective cancer cell apoptosis in vitro at a concentration of less than 10 microM. In vivo tumor growth was significantly prevented with induction of apoptosis in both models without any severe systemic adverse reactions. The evaluation of intracellular protease activity demonstrated that FTY720-induced apoptosis was mediated by a Fas-independent, Bcl-associated signal transduction pathway. Inhibition of extracellular signal-regulated kinase (ERK) activity may be involved in its underlying mechanism of action. CONCLUSION: FTY720 may be a promising candidate for a new anticancer therapy, which potentially induces selective apoptosis in cancer cells.

Animals↗

Inhibitory effects of crude alpha-mangostin, a xanthone derivative, on two different categories of colon preneoplastic lesions induced by 1, 2-dimethylhydrazine in the rat.

The purpose of this study was to examine whether crude alpha-mangostin (a major xanthone derivative in mangosteen pericarp (Garcinia mangostana)) has short-term chemopreventive effects on putative preneoplastic lesions involved in rat colon carcinogenesis. The crude preparation was obtained by simple recrystallization of an ethylacetate extract of mangosteen pericarps. A total of 33 five-week-old male F344 rats were randomly divided into 5 experimental groups. Rats in groups 1-3 were given a subcutaneous injection of 1,2-dimethylhydrazine (DMH)(40 mg/kg body weight) once a week for 2 weeks. Starting one week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 0.02% and 0.05% crude alpha-mangostin, respectively, for 5 weeks. Rats in group 4 also received the diet containing 0.05% crude alpha-mangostin, while rats in group 5 served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary administration of crude alpha-mangostin at both doses significantly inhibited the induction and/or development of aberrant crypt foci (ACF) (P<0.05 for 0.02% crude alpha-mangostin, P<0.01 for 0.05% crude alpha-mangostin), when compared to the DMH-treated group (group 1). Moreover, treatment of rats with 0.05% crude alpha-mangostin significantly decreased dysplastic foci (DF) (P<0.05) and beta-catenin accumulated crypts (BCAC) (P<0.05), to below the group 1 values. The proliferating cell nuclear antigen (PCNA) labeling indices of colon epithelium and focal lesions in groups 2 and 3 were also significantly lower than in group 1 and this effect occurred in a dose dependent manner of the crude alpha-mangostin. This finding that crude alpha-mangostin has potent chemopreventive effects in our short-term colon carcinogenesis bioassay system suggests that longer exposure might result in suppression of tumor development.

1,2-Dimethylhydrazine↗