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Biomedical subjects

Takeshi Mori

Publications and source records attributed to Takeshi Mori.

At least 19 recordsLinked to original sources
PubMed2026

A transient, B cell-targeted tolerance switch using nanoparticles loaded with metabolizable AhR agonists for antigen-specific immune regulation.

Achieving antigen-specific immune tolerance without systemic immunosuppression remains a major challenge in biomaterial-based immunotherapy. Here, we report a simple nanoparticle (NP)-based platform that enables a transient, B cell-targeted tolerance switch. NPs encapsulating metabolizable aryl hydrocarbon receptor (AhR) agonists-FICZ or ITE-preferentially accumulate in splenic marginal zone B cells and convert them into IL-10-producing regulatory B cells (Bregs). This study provides the first in vivo evidence that Bregs can directly present antigen and induce regulatory T cells (Tregs), establishing a NP-controlled Breg-Treg pathway. These Bregs promote antigen-specific Tregs expansion only when co-exposed to antigen, establishing time-gated, antigen-restricted immune regulation. By exploiting the rapid metabolism of AhR agonists, this system provides precise temporal control of tolerance induction while preserving vaccine responses. In mouse models, co-administration of FICZ-containing NP with antigen suppressed anti-drug antibody formation and ameliorated allergic inflammation. This NP platform demonstrates a strategy for safe, antigen-specific immunomodulation and offers a clinically adaptable framework for allergy and biotherapeutic tolerance.

Animals↗
PubMed2006

Mass-tag technology responding to intracellular signals as a novel assay system for the diagnosis of tumor.

A novel mass spectrometry-based assay system for determining protein kinase activity employing mass-tagged substrate peptide probes was used for the diagnosis of tumors. Two peptide probes (H-type and D-type) were synthesized containing the same substrate peptide sequence for protein kinase C (PKC). The molecular weights of the two probes differ because of the incorporation of deuterium into the acetyl groups of the D-type probe. The lysates of the normal and tumor tissue were prepared and reacted with the H- and D-type peptide probes, respectively. The PKC activities of the normal and tumor tissues can be compared simply and directly by calculating the phosphorylated ratio to each peptide probe, obtained from the peak intensity of the mass spectrum after mixing of the two reaction solutions. The phosphorylation ratio for the reaction of the H-type peptide probe with the tumor tissue lysate (B16 melanoma) was more than three times higher than that of the D type peptide probe with the normal skin tissue lysate. These results show that the novel assay system for detecting protein kinase activity using mass-tag technology can be a simple and useful means to profile protein kinase activity for cell or tissue lysate samples, and can be applied to the diagnosis of tumors.

Animals↗
PubMed2006

Structural advantage of dendritic poly(L-lysine) for gene delivery into cells.

This study aimed to investigate the relationships between structures of gene carrier molecules and their activities for gene delivery into cells. We compared 2 types of poly(L-lysine) as carriers, that is, dendritic poly(L-lysine) (KG6) and linear poly(L-lysine) (PLL). KG6 formed a neutral DNA complex, and its DNA compaction level was weaker than that of PLL. The amount of DNA binding and uptake into cells mediated by PLL was 4-fold higher than that with KG6. However, KG6-mediated gene expression was 100-fold higher than that by PLL. Since pK(a) values of terminal amines of KG6 were lowered even though small amounts of DNA were internalized into cells, sufficient DNA amounts for effective gene expression escaped to the cytosol due to the proton sponge effect in the endosome. In addition, weakly compacted DNA with KG6 was advantageous in accessing RNA polymerase in the cell nucleus. On the other hand, PLL did not show the proton sponge effect in the endosome and resulted in strong compaction of DNA. Even though large DNA amounts were internalized into cells, most of the DNA would not take part in gene expression systems in the nucleus. Amount of induced cytokine production after intravenous injection of DNA complexes with KG6 and PLL was low, and was similar to the case when DNA was injected alone. Therefore, no significant difference in effects on cytokine production was observed between KG6 and PLL.

Animals↗
PubMed2006

A protein kinase signal-responsive gene carrier modified RGD peptide.

We have previously reported artificial gene-regulation systems responding to cyclic AMP-dependent protein kinase (PKA) using a cationic polymer. However, this polymer alone cannot deliver any gene into living cells. In the present work, we modified the signal-responsive polymer to the RGD peptide for the introduction of a polymer/DNA complex into living cells and succeeded in regulating the gene expression responding to intracellular PKA activation.

Cell Line, Tumor↗
PubMed2006

Phosphorylation of Rho-associated kinase (Rho-kinase/ROCK/ROK) substrates by protein kinases A and C.

Rho-associated kinase (Rho-kinase/ROCK/ROK) is a serine/threonine kinase and plays an important role in various cellular functions. The cAMP-dependent protein kinase (protein kinase A/PKA) and protein kinase C (PKC) are also serine/threonine kinases, and directly and/or indirectly take part in the signal transduction pathways of Rho-kinase. They have similar phosphorylation site motifs, RXXS/T and RXS/T. The purpose of this study was to identify whether sites phosphorylated by Rho-kinase could be targets for PKA and PKC and to find peptide substrates that are specific to Rho-kinase, i.e., with no phosphorylation by PKA and PKC. A total of 18 substrates for Rho-kinase were tested for phosphorylation by PKA and PKC. Twelve of these sites were easily phosphorylated. These results mean that Rho-kinase substrates can be good substrates for PKA and/or PKC. On the other hand, six Rho-kinase substrates showing no or very low phosphorylation efficiency (<20%) for PKA and PKC were identified. Kinetic parameters (K(m) and k(cat)) showed that two of these peptides could be useful as substrates specific to Rho-kinase phosphorylation.

Amino Acid Motifs↗
PubMed2006

Guanine nitration in idiopathic pulmonary fibrosis and its implication for carcinogenesis.

RATIONALE: Nitric oxide (NO)-induced nitrative stress of nucleic acids, as evidenced by guanine nitration, appears to be involved in inflammation-induced carcinogenesis. A high incidence of lung cancer in idiopathic pulmonary fibrosis (IPF) is the major reason for poor prognosis in patients with IPF. OBJECTIVES AND METHODS: We immunohistochemically analyzed the formation and localization of 8-nitroguanine in lung tissues from control subjects, patients with IPF, and patients with lung cancer. MAIN RESULTS: Immunohistochemical analysis of control smoker and nonsmoker lungs showed weak immunoreactivity for 8-nitroguanine, mainly in cytoplasm of bronchial epithelial cells. In addition to the bronchial epithelial cells, metaplastic regenerated epithelial cells overlying dense fibrotic lesions in IPF showed strong 8-nitroguanine staining in the cytoplasm. The staining in these metaplastic cells colocalized with staining of inducible and endothelial NO synthases and 8-oxodeoxyguanosine, as evidenced by double-immunostaining analysis. Confocal and immunoelectron microscopy revealed localization of 8-nitroguanine in metaplastic epithelial cytoplasm, mostly in mitochondria. Appreciable 8-nitroguanine immunostaining was also observed in both nuclei and cytoplasm of malignant epithelial cells in squamous cell carcinoma. No significant difference was found in the epithelial 8-nitroguanine formation between control smokers and nonsmokers, but much higher guanine nitration was observed in patients with IPF than in control subjects and patients with lung cancer, via a quantitative immunofluorescence image analysis. CONCLUSIONS: The present study indicates that not only oxidative stress but also nitrative stress induced by NO may participate in the pathogenesis of epithelial cell damage and aberrant regeneration occurring in IPF. Thus, guanine nitration may be a major risk factor for lung cancer development in IPF.

Adult↗
PubMed2006

Soluble-insoluble-soluble transitions of aqueous poly(N-vinylacetamide-co-acrylic acid) solutions.

Several poly(N-vinylacetamide-co-acrylic acid)s with various copolymer compositions have been synthesized, and their unique phase-transition behavior in aqueous salt (Na2SO4 or NaCl) solutions was investigated. Copolymers containing more than 51 mol % N-vinylacetamide (NVA) show reentrant soluble-insoluble-soluble transitions with increasing temperature. The soluble-insoluble transition temperature (T(p1)) increased linearly with increasing NVA content, whereas the insoluble-soluble transition temperature (T(p2)) was almost constant irrespective of the NVA content. Potentiometric titration of the copolymer solutions suggested that the acrylic acid (AA) carboxyl groups form hydrogen bonds with the NVA amide groups even under soluble conditions. Dehydration of the NVA amides and their consequent hydrogen bonding with the AA carboxyl groups during the soluble-insoluble transition process was indicated by FTIR measurements. Addition of salt (Na2SO4 or NaCl) to the aqueous media reduces the solvent quality and enhances the intra- and interchain interactions of the copolymers. Thus, T(p1) was observed to decrease and T(p2) was observed to increase with increasing salt concentration. However, the addition of urea to the media reverses the concentration dependence of T(p1) and T(p2) by disturbing the intra- and interchain interactions of the copolymers.

Journal Article↗
PubMed2006

Successful treatment of severe pouchitis with rebamipide refractory to antibiotics and corticosteroids: a case report.

The antibiotics, metronidazole and ciprofloxacin, are the first-line treatment for pouchitis. Patients who do not respond to antibiotics or conventional medications represent a major challenge to therapy. In this report, we have described a successful treatment of severe refractory pouchitis with a novel agent, rebamipide, known to promote epithelial cell regeneration and angiogenesis. A 27-year-old male with ileo-anal pouch surgery presented with worsening anal pain, diarrhea, and abdominal pain. The patient was diagnosed to have pouchitis and was given metronidazole together with betamethasone enema (3.95 mg/dose). However, despite this intensive therapy, the patient did not improve. On endoscopy, ulceration and inflammation were seen in the ileal pouch together with contact bleeding and mucous discharge. The patient was treated with rebamipide enema (150 mg/dose) twice a day for 8 wk without additional drug therapy. Two weeks after the rebamipide therapy, stool frequency started to decrease and fecal hemoglobin became negative at the 4th wk. At the end of the therapy, endoscopy revealed that ulcers in the ileal pouch had healed with no obvious inflammation. The effect of rebamipide enema was dramatic and was maintained throughout the 11-mo follow-up. The patient continued to be in remission. No adverse effects were observed during the treatment or the follow-up period. The sustained response seen in this case with severe and refractory pouchitis indicates that agents, which promote epithelial cell growth, angiogenesis and mucosal tissue regeneration, are potential therapeutic agents for the treatment of refractory colorectal lesions.

Adrenal Cortex Hormones↗
PubMed2006

Extrapleural pneumonectomy via a lower door open thoracotomy with reconstruction of the diaphragm and pericardium using autologous materials for mesothelioma.

We performed extrapleural pneumonectomy (EPP) with combined resection of the diaphragm and pericardium via a lower door open (LDO) thoracotomy to treat right malignant pleural mesothelioma (MPM) in a 57-year-old man. Specifically, we extended the standard posterolateral thoracotomy skin incision along the anterior costal arch, and performed the thoracotomy by cutting into the 6th to 9th costal cartilage. The resulting defect of the diaphragm and pericardium were reconstructed with a reversed latissimus dorsi (LD) muscle flap and a fascia lata graft, respectively. The patient had an uneventful postoperative course without dyspnea or dysfunction of the extremities. The LDO thoracotomy provided a good operative field, especially for the costo- and cardiophrenic angles, allowing a complete resection of the diaphragm to be performed easily. Furthermore, the reversed LD muscle flap and fascia lata graft proved to be ideal autologous materials for reconstruction of both the diaphragm and the pericardium.

Diaphragm↗
PubMed2006

Sparganum mansoni parasitic infection in the lung showing a nodule.

Reported herein is a 57-year-old man infected by Sparganum mansoni, a kind of tapeworm, showing a solitary nodule of the middle lobe of the right lung. Because a transbronchial biopsy could not diagnose the nodule, a right middle lobectomy was performed on suspicion of malignant tumor. The lesion was diagnosed as sparganosis by histological and immuno-serological examinations. Histological examination revealed granulomatous inflammation with neutrophil and eosinophil infiltration around the worm and interstitial pneumonia surrounding the nodule. Moreover, vasculitis with foreign body giant cell was seen around the lesion. To the authors' knowledge this is the second case of sparganosis limited in the lung, and the current report presents the first detailed histological description of a pulmonary sparganosis case.

Animals↗
PubMed2006

Kissing pleural metastases from metastatic osteosarcoma of the lung.

Two patients with osteosarcoma lung metastases of which migrated to the parietal pleura due to contact are reported. The first patient was a 16-year-old male who had a pleural metastasis in the diaphragm within an area in contact with a single lung metastasis. Both of the tumors were resected, followed by systemic chemotherapy. Nine months after the resection of the first metastases, two other lung metastases were found which were resected after chemotherapy. The patient is alive without recurrence 84 months after the first resection of the metastases. The second patient was an 11-year-old female with a pleural metastasis of osteosarcoma which was within an area in contact with a single lung metastasis, which had been resected 4 months before. We concluded (1) that a lung metastasis of osteosarcoma occasionally metastasizes to the pleura due to contact; and (2) that because this kissing metastases of osteosarcoma could be cured by a complete resection, the intrathoracic cavity should be thoroughly observed.

Adolescent↗
PubMed2006

The efficacy of epidural analgesia after video-assisted thoracoscopic surgery: a randomized control study.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) is known to reduce the severity of pain after surgery. However, it has not yet been established whether epidural anesthesia/analgesia (EA) is necessary after VATS. We therefore conducted a randomized control study to examine whether or not EA is necessary for pain control after VATS. PATIENTS AND METHODS: Forty-six patients undergoing VATS were randomly allocated to one of 2 groups: 24 who were given EA after the procedure (EA group) and 22 who were not (NEA group). Patients in the EA group received a continuous infusion of fentanyl and bupivacaine via an epidural catheter for 2 days after VATS. The degree of postoperative pain was assessed on the total dose of additional analgesics administered, a visual analog scale (VAS), a verbal pain score at rest (VPS-R) and on movement (VPS-M), from the day of surgery to the 2nd postoperative day (2 POD). RESULTS: Additional use of rectal diclofenac sodium and intramuscular pentazocine was more frequent in the NEA group than in the EA group (p<0.05). The VAS, VPS-R, and VPS-M scores were significantly lower in the EA group than in the NEA group at 0 POD, from 0 to 1 POD, and from 0 to 2 POD, respectively (p<0.0001-0.05). Stepwise regression analysis revealed that EA was a significant independent variable of VPS-R and VPS-M from 0 to 1 POD (p<0.05). However, the incidence of nausea/vomiting in the EA group was 29%, which was more frequent than in the NEA group (5%) (p<0.05). CONCLUSION: While EA causes nausea/vomiting in some patients, it is effective for pain control until 1 POD after VATS, especially for pain on movements.

Analgesia, Epidural↗
PubMed2005

Synthesis and characterization of beta-haloalkenyl-lambda3-bromanes: stereoselective Markovnikov addition of difluoro(aryl)-lambda3-bromane to terminal acetylenes.

Reported here for the first time are the synthesis, isolation, and characterization of hypervalent beta-haloalkenyl-lambda3-bromanes. Exposure of terminal alkynes to p-trifluoromethylphenyl(difluoro)-lambda3-bromane activated by BF3-i-Pr2O resulted in fluoro-lambda3-bromanation of the triple bonds in a Markovnikov fashion, yielding (E)-beta-fluoroalkenyl-lambda3-bromanes stereoselectively in good yields. 5-Chloro-1-pentynes undergo domino lambda3-bromanation-chlorine shift-fluorination or lambda3-bromanation-chlorine shift-alkyl shift-fluorination reaction, depending on the substituents and afford (E)-beta-chloroalkenyl-lambda3-bromanes stereoselectively in high yields. The beta-chloroalkenyl-lambda3-bromanes contain three kinds of halogen atoms, F, Cl, and Br, in the molecule.

Journal Article↗
PubMed2005

Rebamipide enemas-new effective treatment for patients with corticosteroid dependent or resistant ulcerative colitis.

In this study we investigated the effect of rebamipide enema in patients with steroid-resistant and/or dependent ulcerative colitis. Rebamipide enemas were administered twice daily for a 12-week period; this treatment was further continued longer in patients who requested this. Disease activity index as reflecting the clinical condition and endoscopic index with histological grading were determined before and after the treatment period. Nine of 11 (81.8%) patients on 12-week treatment with rebamipide approved and were classified as colitis in remission. Moreover, seven of 11 patients requested long-term medication, the longest medication term being 80 weeks. These results medicated that rebamipide enemas may be effective in patients with steroid-resistant and/or dependent ulcerative colitis.

Adolescent↗
PubMed2005

The relationship between ambulation ability before surgery and the D-dimer value after total hip arthroplasty: the evaluation of ambulation ability by the timed "Up & Go" test.

We examined whether ambulatory ability before surgery might influence the post-operative D-dimer level after total hip arthroplasty (THA). One hundred two patients with hip osteoarthritis receiving THA were included in the current study. The patients were all female, and their ages ranged from 45 to 81 (average 65.0 +- 9.3 years). Age, operated side, body mass index (BMI), disease duration before surgery, pre-operative pain evaluated by visual analogue scale (VAS), total cholesterol value, maximal circumference of the lower leg of the operated side, and timed "Up & Go"test (TUG) before surgery, were retrospectively investigated to examine their relationship with D-dimer levels on post-operative day 7. Patients were divided into 2 groups according to the D-dimer value: over 10 microg/ml (Group D), and under (Group N). Patients in group D (N= 52)were older, had a higher BMI, and had less ambulatory ability than patients in group N (N= 50). As age showed a relationship with the D-dimer value on the 7th day and TUG results, patients in the 2 groups were further subdivided into 50's, 60's, and 70's age brackets. In the 50's bracket, patients in group D had higher BMI than patients in group N, but time for TUG was not significantly different. In the 60's and 70's bracket, patients in group D had less ambulatory ability than patients in group N, but the time for TUG was not directly correlated with the D-dimer value. The results suggest that pre-operative low ambulatory ability in patients with osteoarthritis over 60 years might influence the postoperative D-dimer after THA, indicating the potential risk for post-operative deep venous thrombosis.

Aged↗
PubMed2005

[Hemothorax following intraabdominal bleeding due to pedicle torsion of ovarian tumor via a small pore in the diaphragm: report of a case].

On February 25, 2004, 59-year-old woman visited a local clinic due to lower abdominal pain. On February 28, she was admitted to the clinic due to severe abdominal pain. Computed tomography (CT) showed a mass in the lower abdomen and plural effusion and athelectasis of the right lung. She had severe anemia (Hb 6.9 g/dl). On March 1, she was transferred to our hospital. Pleural fluid was revealed to be sanguineous by thoracentasis. She underwent thoracotomy on the day of admission. There was no source of bleeding in the pleural space. A small pore, 3 mm in diameter, was found in the tendinous portion of the diaphragm. An influx of bloody fluid from the abdomen via the pore caused hemothorax. Laparotomy was performed, followed by closure of the pore using direct suture. The origin of the abdominal bleeding was pedicle torsion of the right ovarian tumor. Seven months after surgery she was uneventful with no pleural effusion.

Abdominal Cavity↗