Biomedical subjects

K Itoh

Publications and source records attributed to K Itoh.

At least 55 records · Page 3Linked to original sources

PubMed2004

A phase I trial of cytotoxic T-lymphocyte precursor-oriented peptide vaccines for colorectal carcinoma patients.

In most protocols of peptide-based vaccination, no consideration has been paid to whether or not peptide-specific cytotoxic T-lymphocyte (CTL) precursors are pre-existent in cancer patients. Initiation of immune boosting through vaccination is better than that of immune priming to induce prompt and strong immunity. In this study, 10 human histocompatibility leukocyte antigen-A24(+) patients with advanced colorectal carcinomas were treated with up to four peptides that had been positive for pre-vaccination measurement of peptide-specific CTL precursors in the circulation (CTL precursor-oriented peptide vaccine). No severe adverse effect was observed, although local pain and fever of grade I or II were observed. Post-vaccination peripheral blood mononuclear cells (PBMCs) from five patients demonstrated an increased peptide-specific immune response to the peptides. Increased CTL response to cancer cells was detected in post-vaccination PBMCs of five patients. Antipeptide immunoglobulin G became detectable in post-vaccination sera of seven patients. Three patients developed a positive delayed-type hypersensitivity response to at least one of the peptides administrated. One patient was found to have a partial response; another had a stable disease, sustained through 6 months. These results encourage further development of CTL precursor-oriented vaccine for colorectal cancer patients.

Adult↗

PubMed2004

Usefulness of FDG-PET to diagnose intravascular lymphomatosis presenting as fever of unknown origin.

Intravascular lymphomatosis (IVL) is a rare systemic disease characterized by proliferation of lymphoid cells within the lumina of small arteries, veins, and capillaries. Diagnosis requires skin, liver, lung, bone marrow, renal, meningeal, or brain vessel biopsy but is often made only when the illness has progressed or post mortem because early involvement of organs was not evident. We report a case of IVL presenting as fever of unknown origin (FUO). In this case, gallium scintigraphy and computed tomography (CT) showed no evidence of malignancy, whereas (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased FDG uptake in the sternum, left and right vertebra, humerus, femur, and especially ilium. The diagnosis was made on iliac bone marrow biopsy examination. FDG-PET was useful for the detection of spread of disease in a patient with IVL suffering from FUO.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Magnetic resonance and biochemical studies during pentylenetetrazole-kindling development: the relationship between nitric oxide, neuronal nitric oxide synthase and seizures.

The major aim of this study was to elucidate the role of nitric oxide (NO) in the development of pentylenetetrazole (PTZ)-kindling as an animal model of primary generalized epilepsy. The daily administration of PTZ is associated with an increase in the amount of neuronal nitric oxide synthase (nNOS). NO generation was measured directly by in vivo and ex vivo electron paramagnetic resonance on rodents undergoing progressive convulsions. We found that primary generalized epilepsy is caused by NO induction during the persistent up-regulation of nNOS expression, but that NO induction is not associated with severe generalized seizures following long-term kindling phenomena after PTZ withdrawal. Morphological changes in the brain structure of rats were measured by magnetic resonance imaging during epileptic convulsions induced by repetitive administration of PTZ. Cerebellum volume for kindled rats decreased 20% but not in rats treated with the nNOS inhibitor, 3Br-7NI, suggesting that generation of NO in the cerebellum is related to decrease in cerebellum volume following PTZ-kindling.

Analysis of Variance↗

PubMed2004

Study for imaging of inside bone using FM-chirp pulse compression system.

We measured the attenuation of ultrasound in animal bone in vitro, and determined successfully the correct dynamic range for the detection of echo signals from inside the bone. It was possible to display a B-mode image of a 6-mm thick porcine rib bone using a high frequency (5 MHz) transducer. However, it was difficult to obtain the image of a large bone (20-mm thick femur). This paper describes a possibility of the improvement for the detection of echoes from inside the bone using the FM-chirp pulse. An ultrasonic wave generator that generates the FM-chirp pulse for a frequency range of 100 KHz to 5 MHz was fabricated. And the pulse was transmitted from a transducer and received by a hydrophone in the water. The received waveform and the frequency spectrum were displayed on an oscilloscope. We measured the amplitude spectrum of the received waves before and after inserting a sample bone between the transducer and the hydrophone. In the experiment, three types of focused transducers (0.5, 1 and 2.25 MHz) and three kinds of sample bones (spine, femur and rib of a pig) were used. From the results of the measurement, we could find the useful information for imaging of inside the bone.

Animals↗

PubMed2004

Supraclavicular approach without thoracotomy for posterior mediastinal tumor.

Using a right-sided supraclavicular approach, we operated on a 15-year-old girl with a posterior mediastinal neurogenic tumor and von Recklinghausen's disease. The encapsulated 95 x 65 x 40 mm neurofibroma was removed safely and completely without thoracotomy. No peripheral neurologic defect such as Horner's syndrome, paralysis of accessory nerve, or palsy of the right upper extremity was observed after operation. The postoperative course was uneventful and the patient was discharged on the third postoperative day with no symptoms. Today, various adaptations of video-assisted thoracic surgery are frequently utilized for many lesions. However, more direct, safer, and less invasive approaches should be selected based on local anatomy, such as the supraclavicular approach without thoracotomy that we utilized.

Adolescent↗

PubMed2004

New multiplexed flow cytometric assay to measure anti-peptide antibody: a novel tool for monitoring immune responses to peptides used for immunization.

Peptide-based vaccination has a great potential for the prevention and treatment of various diseases. There is, however, no appropriate monitoring system to measure immune responses to vaccinated peptides, which hampers the development of therapeutically effective vaccine regimens to various diseases. In this study a new multiplexed flow cytometric assay using the Luminex system to monitor humoral immune responses to vaccinated peptides is described. Although the sensitivity is mostly equal to that of the traditional enzyme-linked immunosorbent assay (ELISA), the new assay has several advantages over ELISA in that it minimizes the amount of sera needed, running costs and working periods, and thus will be a novel tool for monitoring immune responses to vaccinated peptides.

Antibodies↗

PubMed2004

Japanese multicenter phase II and pharmacokinetic study of rituximab in relapsed or refractory patients with aggressive B-cell lymphoma.

BACKGROUND: To evaluate the efficacy and feasibility of rituximab monotherapy in Japanese patients with relapsed or refractory aggressive B-cell lymphoma. PATIENTS AND METHODS: Sixty-eight patients were treated with rituximab at 375 mg/m(2) by eight consecutive weekly infusions. Pretreatment variables affecting overall response rate (ORR) and progression-free survival (PFS) and the relationship between pharmacokinetic parameters and efficacy were analyzed. RESULTS: The ORRs of 68 enrolled patients and 57 eligible patients were 35% [95% confidence interval (CI) 24% to 48%] and 37% (95% CI 25% to 51%), respectively. Median PFS of 53 evaluable patients was 52 days, whereas time to progression of 21 eligible responders was 245 days. Mild to moderate infusion-related toxicities were observed frequently at the first infusion, but all of them were reversible. Elevated lactate dehydrogenase (LDH) and refractoriness to prior chemotherapy were unfavorable factors affecting ORR and PFS (P <0.01). Serum trough levels of rituximab and area under the concentration-time curve for responders were higher than for non-responders (P <0.05). CONCLUSIONS: Eight consecutive weekly infusions of rituximab have significant anti-lymphoma activity for relapsed or refractory aggressive B-cell lymphoma. Several pretreatment variables and serum rituximab levels are useful for predicting its efficacy.

Adult↗

PubMed2004

Helicobacter pylori eradication decreases blood neutrophil and monocyte counts.

BACKGROUND: The effect of Helicobacter pylori infection on systemic disorders is not well understood. AIM: The purpose of this study was to elucidate the systemic effects of H. pylori infection by comparing differential counts of leukocytes and platelets in peripheral blood before and after eradication of H. pylori. METHODS: A total of 164 H. pylori-positive patients underwent eradication therapy, and populations of peripheral blood leukocytes and platelets before and 0 (just after therapy), 1, 3 and 12 months after eradication were retrospectively analysed. RESULTS: In the eradicated group (n = 138), blood leukocytes, neutrophils and monocytes decreased significantly after eradication, but there was no significant change in eosinophils, basophils, lymphocytes or platelets. In the non-eradicated group (n = 26), there was no significant change in any studied parameter. With regard to smoking status, although leukocytes and neutrophils did not decrease after eradication in the smoking group, they significantly decreased after eradication in the nonsmoking group. CONCLUSIONS: These findings suggest that: (1) H. pylori infection increases neutrophil and monocyte counts in the peripheral blood, which indicates a significant role of H. pylori infection in systemic disorders; and (2) Smoking may mask the effect of H. pylori eradication on peripheral leukocytes, which would explain the controversy in previous reports concerning H. pylori infection and peripheral leukocytes.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2004

An association study using AFLP markers and application to a beef cattle breeding population.

Using amplified fragment length polymorphism (AFLP) fingerprinting, selective genotyping was performed to determine if this method was effective for selecting superior breeding stock. Forty-eight cows with extreme genetic merit for beef marbling score (BMS) were selected from a population of Japanese Black cattle (n = 4462), including 25 with the highest for predicted breeding value (PBV) and 23 with the lowest. Sixteen AFLP fragments were selected for further analysis based on fragment frequency differences between the high and low groups. A linear discriminant analysis using these AFLP fragments was applied in order to derive a discriminant function that classified the cows into high and low groups. Seven of the 16 fragments were included in the resulting function and the discriminant scores (general genetic values, GGV) of the 48 cows were calculated using the function. These cows were clearly separated into high and low groups by GGV with a correlation ratio of 0.91 (discriminative error of 2.1%). The same function was then applied to 121 additional cows that were randomly selected from the original population. A significant regression coefficient of GGV on BMS-PBV (R2 = 0.45) was obtained, which indicates that the GGV can be used as a selection criterion for BMS in this population. These results suggest that AFLP fingerprinting can be used for animal breeding without identifying the underlying genes affecting the trait of interest.

Agriculture↗

PubMed2004

Endotoxin stimulates monocyte-endothelial cell interactions in mouse intestinal Peyer's patches and villus mucosa.

Although monocyte-endothelial cell interactions represent an initial step in controlling the recruitment of monocytes in inflamed tissues, their dynamic processes in microvessels of lymphoid (Peyer's patches) and non-lymphoid (villus) regions in gut-associated lymphoid tissue remain poorly understood. We monitored the migration of fluorescence-labelled monocytes derived from the spleen in intestinal microvessels with or without lipopolysaccharide (LPS) treatment and investigated the role of adhesion molecules, P-selectin, vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). In control mice, there were few interactions between infused monocytes and the endothelium of intestinal microvessels. The monocyte-endothelial interactions (both rolling and adhesion) were significantly increased in intestinal microvessels of LPS-treated mice compared with those in controls. Anti-P-selectin monoclonal antibody (MoAb) significantly suppressed the LPS-induced increase in monocyte rolling in postcapillary venules of Peyer's patches and submucosal venules. Anti-VCAM-1 MoAbs significantly suppressed the LPS-induced increase in monocyte adhesion to postcapillary venules (PCVs) of Peyer's patches, submucosal venules, and villus capillaries. In contrast, anti-ICAM-1 MoAb significantly suppressed the number of adherent monocytes in PCV of Peyer's patches but not in submucosal venules or villus capillaries. These observations demonstrated that LPS treatment resulted in a significant increase in recruitment of monocytes both in microvessels of lymphoid and non-lymphoid regions and that P-selectin, VCAM-1 and ICAM-1 appeared to play important roles in LPS-induced interactions.

Animals↗

PubMed2004

A comparison and validation of amorphous sensor condylar movement analysis to MRI diagnosis of anterior disc displacement.

This study compared temporomandibular joint condylar movements in a sample of six patients with clinically normal joints, with those of nine patients with joints diagnosed by magnetic resonance imaging (MRI) to have anterior disc displacement with reduction (ADD). The aim of this study was to compare and validate the use of the amorphous sensor to MRI diagnosis in condylar movement analysis. The measuring device consisted of an amorphous sensor and a small magnet. Condylar and jaw movements were recorded simultaneously over the course of 10 open-close cycles. Maximum velocity of condylar movement during the opening phase in the ADD joints was significantly higher than the normal joints. The degree of jaw opening at the turning point of condylar movement in the ADD joints was significantly larger than the normal joints. The diagnostic sensitivity and specificity of the maximum velocity of condylar movement during the opening phase was 75.0 and 75.0%, respectively, while those of the degree of jaw opening at the turning point of condylar movement were 91.7 and 91.7%, respectively. These results suggest that the analysis of condylar movement, employing the amorphous sensor may be a reliable method for diagnosis of ADD.

Adult↗

PubMed2004

Bonding efficacy and side effects of the high purity glyceryl mono-methacrylate.

The purpose of this study was to examine the efficacy of experimentally developed high purity glyceryl mono-methacrylate (GM) as a dentine primer and to evaluate the possibility of allergic reaction. The efficacy of experimental dentine primers was evaluated by measuring the polymerization contraction gap width and the tensile bond strength. Allergic reaction was evaluated by the guinea-pig maximization test. The skin reaction was evaluated according to the criteria of the International Contact Dermatitis Research Group. Contraction gap formation was completely prevented and the tensile bond strength was not significantly affected by priming with GM on high-purity GM. The allergic response decreased when high-purity GM was employed as the challenger. It was concluded that the clinical use of the high-purity GM is beneficial as the delayed allergic reaction could be avoided with no detrimental effect on the dentine bonding.

Animals↗

PubMed2004

An autopsy case of bacterial septic shock 12 years following ABO-incompatible renal transplantation.

We report the case of an ABO-incompatible kidney transplant recipient who died suddenly following a good transplant course of 12 years. For 10 years after transplantation, the graft function had been stable (s-Cr: 1.0-1.5 mg/dL), although chronic hepatitis C had developed, with elevation of transaminase. In the 11th year, he was admitted into the hospital with low-grade fever and general fatigue. Jaundice and anaemia progressed, and he died 2 months after admission. The autopsy diagnosis was: (1) post-renal transplantation state, (2) phlegmonous enterocolitis with septic infarction, (3) cellulitis and necrotic myositis, and (4) sepsis. The transplanted kidney graft showed well-preserved glomeruli and tubules, corresponding to chronic allograft nephropathy (CAN) grade Iota (ci1, ct1, cv1), according to the Banff classification. The pathological changes observed in this long-surviving ABO-incompatible kidney graft were similar to those of an ABO-compatible graft, although its degree was milder.

ABO Blood-Group System↗

PubMed2004

Assessment of synthetic peptides of severe acute respiratory syndrome coronavirus recognized by long-lasting immunity.

In order to determine highly immunogenic severe acute respiratory syndrome coronavirus (SARS-CoV) epitope peptides capable of inducing long-lasting immunity, we first screened immunoglobulin-G (IgG) antibodies reactive to 197 different overlapping 15-mers from the SARS-CoV proteins in the sera of three infected patients. Forty-two peptides among them were reactive to the sera from all three patients. Consequently, we tested for the reactivity of these 42 peptides to patients' sera (n = 45) at 6-month post-infection. The significantly higher levels of IgG antibodies specific to three (S791, M207 and N161) of 42 peptides were detectable in the post-infection sera from 23 (51%), 27 (60%) and 19 (42%) of 45 patients, respectively. These three peptides, recognized by their long-lasting immunity, may provide a better understanding of the immunogenicity of SARS-CoV.

Enzyme-Linked Immunosorbent Assay↗

PubMed2004

Local administration of IGF-I stimulates the growth of mandibular condyle in mature rats.

AIM: To evaluate the effects of local injection of insulin-like growth factor I (IGF-I) on the growth of mandibular condyle in mature rats. MATERIALS AND METHODS: Sixteen 15 week-old male rats were used in this study. In the experimental group, IGF-I at a concentration of 50 microg/ml was injected into articular capsules of the condyle, while rats in the control group were injected with equal volume of physiological saline. These injections were performed three times at 7 day intervals, and all of the rats were killed on the 7th day after the last injection. Tetracycline and calcein were used for vital staining. After death, the condyles were extracted and undecalcified ground sections were prepared for histological and histomorphometric observations. The thickness of the cartilaginous layer of the condyle, the percentage of bone area in the subchondral cancellous bone layer and the amount of endochondral bone growth in the condyle were measured. The significance of the difference in these measurements between IGF-I and control group was evaluated. RESULTS: An increase in the thickness of the cartilaginous layer, and a decrease in the percentage of bone area in the subchondral cancellous bone layer was recognized in IGF-I treated condyle. The amount of endochondral bone growth in the experimental group was greater than that in the control group. CONCLUSION: The local injection of IGF-I into mature condyle seemed to reactivate the process of endochondral bone formation and induced actual bone growth in mature condyle.

Animals↗

PubMed2004

Analysis of cellular localization of SART3 tumor antigen by a newly established monoclonal antibody: heterotopic expression of SART3 on the surface of B-lineage leukemic cells.

SART3 has been identified as a tumor antigen recognized by cytotoxic T-lymphocytes. Subcellular localization of SART3 is still controversial, although it has been studied extensively. In this study, we established an anti-SART3 monoclonal antibody (mAb) to analyze the subcellular localization of SART3 in tumor specimens. Immunohistochemical analysis demonstrated that SART3 was preferentially expressed in the nucleus of cancer cells. Flow cytometric analysis indicated that SART3 was not expressed on the cell surface of tumor cells, except for B-lineage cells. SART3 was detected on the cell surface of several B-lineage leukemic cells with different maturation stages, but not on normal peripheral blood B cells. These results suggest that heterotopically expressed SART3 is a tumor-associated antigen rather than a differentiation antigen on B-lineage cells.

Animals↗

PubMed2003

Central role of mitochondria and p53 in Fas-mediated apoptosis of rheumatoid synovial fibroblasts.

OBJECTIVE: Fas-mediated apoptosis is preferentially observed in synoviocytes of patients with rheumatoid arthritis (RA) and is associated with the pathophysiological process of RA. To clarify the molecular mechanisms of Fas-mediated apoptosis of RA synoviocytes, we investigated the role of the mitochondrial pathway and tumour suppressor p53 in this process. METHODS: Cultured synovial fibroblasts were prepared from RA patients. After treatment of RA synovial fibroblasts with anti-Fas monoclonal antibody, the expression levels of activated caspase-9 and -3, Bid cleavage, cytochrome c release and phosphorylation of p53 at Ser15 were assessed using immunoblot analysis. The mitochondrial membrane potential (DeltaPsim) was evaluated with a fluorescence-based detection assay. Apoptotic cells were determined by a DNA fragmentation assay in the presence or absence of caspase inhibitors. Expression of p53-regulated apoptosis-inducing protein 1 (p53AIP1) was measured by real-time PCR. RA synovial fibroblasts stably transfected with a dominant-negative (DN) p53 were prepared in order to investigate the role of p53 during Fas-induced apoptosis. RESULTS: Fas ligation induced Bid cleavage, loss of DeltaPsim, cytochrome c release to the cytosol and activation of caspase-9 and -3 in RA synovial fibroblasts. Treatment with a caspase-9-specific inhibitor almost completely inhibited Fas-mediated apoptosis. Moreover, p53 activation after Fas ligation was evidenced by its phosphorylation at Ser15 and up-regulation of the p53 target gene p53AIP1. Fas-mediated apoptosis was significantly suppressed by anti-sense p53 oligonucleotides and by p53DN. CONCLUSION: Our findings strongly suggest the involvement of mitochondria and p53 in Fas-mediated apoptosis of RA synovial fibroblasts.

Apoptosis↗

PubMed2003

Heat shock cognate protein 70 encodes antigenic epitopes recognised by HLA-B4601-restricted cytotoxic T lymphocytes from cancer patients.

Heat shock cognate protein 70 (HSC70), a highly conserved protein and a member of the family of molecular chaperones, has the ability to induce cytotoxic T lymphocyte (CTL) responses through binding and carrying antigenic peptides. We demonstrated in this study that the HSC70 gene encodes two antigenic peptides recognised by HLA-B46-restricted and tumour-reactive CTLs established from tumour-infiltrating lymphocytes of a colon cancer. These HSC70-derived peptides, at amino-acid positions 106-114 and 233-241, had the ability to induce HLA-B46-restricted and peptide-specific CTLs, which are reactive to tumour cells, from peripheral blood mononuclear cells of the majority of epithelial cancer patients tested. These results, along with those from the previous studies, indicate the two ways of HSC70 involvement in the immune responses to tumours: chaperones and antigens, and thus may provide a new insight for the development of HSC70-directed cancer-specific immunotherapy.

Animals↗