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Biomedical subjects

Takashi Oka

Publications and source records attributed to Takashi Oka.

At least 19 recordsLinked to original sources

State-dependent changes in intrahemispheric EEG coherence for patients with acute exacerbation of schizophrenia.

Abnormalities of electroencephalographic (EEG) coherence in schizophrenia are thought to reflect functional disconnections between different brain regions associated with the onset of this disease. To clarify whether these abnormalities change in a symptom-dependent manner in individual patients, we analyzed the coherence of resting EEGs recorded at two time points with a 36.6-day interval during the course of treatment for 14 patients who had been hospitalized for acute exacerbation of schizophrenia. Symptom severity was quantitatively measured by means of the Brief Psychiatric Rating Scale (BPRS). Beta (13-20 Hz) coherence for the left frontal (F7)-temporal (T5) electrode pair was less than that for the corresponding right pair (F8-T6) at the initial test. At the second test, when symptoms had improved, the left frontal-temporal beta coherence had increased, resulting in disappearance of the laterality. This change in beta coherence for the left frontal-temporal pair correlated negatively with the change in the total BPRS score, particularly the positive symptom score. Similar correlations were found for eight patients who had been drug-free at the first examination. These results suggest that a functional disconnection between the frontal and the temporal lobe in the left hemisphere may be associated with the generation of acute psychotic symptoms in schizophrenia.

Acute Disease↗

Down-regulation of ASY/Nogo transcription associated with progression of adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive form of human leukemia/lymphoma. Although this disease is initiated by infection with human T-lymphotropic virus type 1 (HTLV-1), many HTLV-1 carriers survive for a long period without aggressive illness, suggesting that other factors may play roles in the progression of ATLL to an aggressive state. However, the mechanism involved in this progression still remains unclear. Previously, we have reported that ASY/Nogo mRNA was markedly down-regulated in human small-cell lung carcinomas, whereas it was expressed in normal tissues and other lung carcinomas, such as adenocarcinoma and squamous cell carcinoma. To understand whether or not ASY/Nogo gene is involved in the progression of ATLL, we examined the expression of ASY/Nogo mRNA in smoldering, chronic and aggressive ATLL, and found that the expression level of ASY/Nogo mRNA was markedly reduced in clinically aggressive ATLL. HTLV-1 Tax expression was not affected by the down-regulation of ASY/Nogo mRNA. These results indicate that the ASY/Nogo gene may act as a suppressor against ATLL progression, independent of Tax expression.

Adult↗

Dendritic cells interacting mainly with B cells in the lymphoepithelial symbiosis of the human palatine tonsil.

The lymphoepithelial symbiosis (LES) of the human palatine tonsil is composed of spindle- or star-shaped epithelial cells forming a loose meshwork, containing numerous lymphocytes and dendritic cells (DCs). In the present study, we immunohistochemically characterized DCs in the LES (LES-DCs). LES-DCs were phenotypically immature DCs that were S100beta+, fascin-, HLA-DR+, CD1a-, CD80-, CD83-, CD86-, and CD123-. The most characteristic feature of LES-DCs was that they contacted many B cells, which were mostly IgM+ IgD+ resting naive B cells. Langerhans cells (LCs) located in the nonsymbiotic squamous epithelium were immature DCs that were S100beta+, fascin-, and CD1a+ and did not contact lymphocytes. In contrast to LES-DCs, interdigitating dendritic cells (IDCs) in the T zone were mature DCs that were HLA-DR+, CD1a-, fascin+, CD80+, CD83+, and CD86+ and contacted numerous CD4+ T cells. Two subsets of IDC, S100beta+ fascin+ IDC (IDC-1) and S100beta- fascin+ IDC (IDC-2), were identified, and the majority of IDCs are IDC-2. In contrast to IDCs, which were distributed in the T-cell area in groups, LES-DCs were distributed along the crypt as if forming a barrier. These findings suggest that LES-DCs are a novel type of DC playing an important role in the induction of humoral immune response against incoming air- or food-borne pathogenic antigens.

B-Lymphocytes↗

Development of an orthotopic transplantation model in nude mice that simulates the clinical features of human lung cancer.

The objective of the present study was to establish an orthotopic tumor transplantation model in nude mice that closely resembles the clinical features of human lung cancer. The human lung adenocarcinoma A549 cell line and the squamous cell carcinoma SQ5 cell line were used. Tumor cells suspended in serum-free medium were injected directly into the main bronchi of anesthetized female Balb/c athymic nude mice (7-9 weeks old) with or without simultaneous administration of 0.01 M ethylenediaminetetracetic acid (EDTA). In some experiments, lung carcinoma cells harvested from tumors transplanted subcutaneously were recultured and used for intratracheal implantation. Tumor nodules that formed in the lung were counted and confirmed by histological examination. Administration of A549 cells with EDTA resulted in a 70% engraftment rate (n = 10). Recultured A549 cells without and with EDTA resulted in 20% (n = 5) and 80% (n = 5) engraftment rates, respectively. Administration of SQ5 cells without or with EDTA formed 50% (n = 4) and 67% (n = 6) engraftment rates, respectively. Recultured SQ5 cells with EDTA further increased the engraftment rate to 100% (n = 6). Multiple tumors formed mainly in the left lung and the upper lobe of the right lung. Simultaneous administration of EDTA resulted in greater numbers of tumor nodules in the lung. Histological findings revealed that A549 tumor nodules were distributed primarily in alveoli. The SQ5 solid tumors invaded bronchioles and occupied the alveoli. This reproducible orthotopic transplantation model produced tumor growth that simulated the clinical features of human lung cancer.

Adenocarcinoma, Bronchiolo-Alveolar↗

p27(Kip1) is detected on most gastric MALT lymphomas, but not large cell lymphomas.

We investigated the relationship of gastric mucosa-associated lymphoid tissue (MALT) lymphoma tumorigenesis to Helicobacter pylori infection, the t (11;18) translocation, and alterations in cell cycle regulators. We sought to assess the implications of altered expression of p27(Kip1), a cyclin-dependent kinase inhibitor, on high-grade transformation and responsiveness to eradication therapy. We used immunohistochemistry to examine p27(Kip1), p53, and Ki-67 expression in 23 MALT lymphomas, five diffuse large B-cell lymphomas (DLBCLs), and four DLBCLs with associated MALT lymphoma. All of the MALT lymphomas were positive for p27(Kip1) expression and negative for p53 with a low Ki-67 index, regardless of the sensitivity of these cells to eradication. All DLBCLs were negative for p27(Kip1) and positive for p53, exhibiting a high Ki-67 index. In DLBCLs with MALT lymphoma, p27(Kip1) expression was absent from both the MALT and large cells components. In all of these lymphomas, the MALT components were negative for p53 and displayed a low Ki-67 index, while the large cell components were positive for p53 with a high Ki-67 index. The expression patterns of the DLBCLs differed significantly from those of the MALT lymphomas. p27(Kip1) was not detected in either component of DLBCL with MALT lymphoma, suggesting that decreased expression of p27(Kip1) in the MALT component may be related to high-grade transformation. Thus, p27(Kip1) expression in morphological MALT lymphomas could be useful tool to predict high-grade transformation to DLBCL.

Aged↗

Interfaces of correlated electron systems: proposed mechanism for colossal electroresistance.

Mott's metal-insulator transition at an interface due to band bending is studied by the density matrix renormalization group approach. We show that the result can be recovered by a simple modification of the conventional Poisson's equation approach used in semiconductor heterojunctions. A novel mechanism of colossal electroresistance is proposed, which incorporates the hysteretic behavior of the transition in higher dimensions.

Journal Article↗

Expression of phosphorylated Ser70 of Bcl-2 correlates with malignancy in human colorectal neoplasms.

PURPOSE: Bcl-2 is a model apoptosis suppressor postulated to promote tumorigenesis. Recently, it has been reported that Bcl-2 undergoes phosphoregulation of its Ser70 to substantially alter its molecular function. Previous studies further suggest that such phospho-Bcl-2 regulation may influence tumor progression in colorectal and other cancers; however, phosphorylation status of the Ser70 of Bcl-2 (pSer70) in vivo in tumors remains obscure. To elucidate this question that may suggest the biological role, we molecularly screened a panel of human colorectal adenomas and adenocarcinomas for endogenous expression of pSer70 Bcl-2. EXPERIMENTAL DESIGN: An antibody specific against pSer70 Bcl-2 was generated for thorough immunohistochemical examination of paraffin-embedded tumor specimens, allowing detection of the endogenously expressed antigen among a range of Bcl-2-positive colorectal neoplasms, including 75 tubular adenomas, 114 adenocarcinomas, and 15 cases of cancer in adenomas. RESULTS: Loss of pSer70 Bcl-2 expression was observed in adenocarcinomas in a differentiation-dependent manner (positivities: well differentiated 63%, moderately differentiated 52%, and poorly differentiated 12%), whereas tubular adenomas maintained their expression (positivity 88%). Interestingly, an inverse correlation was found between expression of pSer70 Bcl-2 and Ki-67 antigen in those cases of cancer in adenoma (P < 0.01). It was further observed that loss of pSer70 Bcl-2 expression was associated with significantly shorter survival (P < 0.05) and correlated with clinical stages and lymph node metastasis (P < 0.05 and P < 0.05, respectively). CONCLUSIONS: Loss of pSer70 Bcl-2 expression is closely linked to biological aggressiveness in colorectal tumors and represents a statistically significant molecular index for prognosis of patients with these tumors.

Adenocarcinoma↗

Ground-state decay rate for the Zener breakdown in band and Mott insulators.

Nonlinear transport of electrons in strong electric fields, as typified by dielectric breakdown, is reformulated in terms of the ground-state decay rate originally studied by Schwinger in nonlinear QED. We discuss the effect of electron interaction on Zener tunneling by comparing the dielectric breakdown of the band insulator and the Mott insulator, where the latter is studied by the time-dependent density-matrix renormalization group. The relation with the Berry's phase theory of polarization is also established.

Journal Article↗

Neuropsychological correlates of an attention-related negative component elicited in an auditory oddball paradigm in schizophrenia.

An attention-related, negative component can be detected between the N100 peak and 200 ms after stimulus by subtracting event-related potentials (ERPs) elicited to background tones when subjects ignore tones, from ERPs elicited to background tones when subjects attend to tones to detect target tones in an oddball paradigm. To clarify the cognitive significance of this component in schizophrenia, we examined the correlations of 24 patients between the amplitude and latency of the negative component and results obtained using neuropsychological measurement methods, including the Wisconsin Card Sorting Test, the Trail Making Test, the Verbal Fluency Test and some subtests from the Wechsler Memory Scale. The latency prolongation of the negative component correlated positively with the difference in performance time between parts A and B of the Trail Making Test, which estimates set shift, a frontal-lobe executive function, but not with any other neuropsychological measurements, while the amplitude showed no such correlation. These results suggest that the latency prolongation of the attention-related, negative component induced in an auditory oddball paradigm may serve as an index for frontal dysfunction in schizophrenia.

Acoustic Stimulation↗

Breakdown of an electric-field driven system: a mapping to a quantum walk.

Quantum transport properties of electron systems driven by strong electric fields are studied by mapping the Landau-Zener transition dynamics to a quantum walk on a semi-infinite one-dimensional lattice with a reflecting boundary, where the sites correspond to energy levels and the boundary the ground state. Quantum interference induces a distribution localized around the ground state, and a delocalization transition occurs when the electric field is increased, which describes the dielectric breakdown in the original electron system.

Journal Article↗

Prostate cancer: a comparative study of 11C-choline PET and MR imaging combined with proton MR spectroscopy.

PURPOSE: Prostate cancer is difficult to visualise in its early stages using current imaging technology. The present study aimed to clarify the utility of 11C-choline PET for localising and evaluating cancer lesions in patients with prostate cancer by conducting a prospective comparison with magnetic resonance (MR) imaging combined with proton MR spectroscopy. METHODS: PET and MR imaging combined with proton MR spectroscopy were performed in 20 patients with prostate cancer. Correlations among the metabolite ratio of choline + creatine to citrate (Cho+Cr/Ci) on MR spectroscopy, serum PSA and maximum standardised uptake value (SUVmax) of (11)C-choline were assessed. The location of the primary lesion was assessed by the site of SUVmax and the laterality of the highest Cho+Cr/Ci ratio and confirmed by examination of surgical pathology specimens (n=16). RESULTS: PET exhibited a diagnostic sensitivity of 100% (20/20) for primary lesions, while the sensitivities of MR imaging and MR spectroscopy were 60% (12/20) and 65% (13/20), respectively. Weak linear correlations were observed between SUVmax and serum PSA (r=0.52, p<0.05), and between SUVmax and Cho+Cr/Ci ratio (r=0.49, p<0.05). Regarding the localisation of main primary lesions, PET results agreed with pathological findings in 13 patients (81%) (kappa=0.59), while MR spectroscopy results were in accordance with pathological findings in eight patients (50%) (kappa=0.11). CONCLUSION: This preliminary study suggests that 11C-choline PET may provide more accurate information regarding the localisation of main primary prostate cancer lesions than MR imaging/MR spectroscopy. A further clinical study of 11C-choline PET in a large number of patients suspected of prostate cancer will be necessary to determine the clinical utility of 11C-choline PET in patients who clinically require biopsy.

Aged↗

Analysis of genomic homology of murine gammaherpesvirus (MHV)-72 to MHV-68 and impact of MHV-72 on the survival and tumorigenesis in the MHV-72-infected CB17 scid/scid and CB17+/+ mice.

Murine gammaherpesvirus (MHV)-68-infected mice are well-known as models for Epstein-Barr virus (EBV)-related lymphoproliferative diseases. MHV-72 may be a relative of MHV-68, but any genetic comparison between the two (except for the M7 gene) has never been reported. The genetic compositions of MHV-72 and MHV-68 were compared and the pathology of MHV-72 infection studied in CB-17 severe combined immunodeficiency (scid/scid; SCID) and CB17 wild-type (CB17+/+) mice. The MHV-72 DNA sequence was almost identical to MHV-68 except for approximately 7000 bp corresponding to the MHV-68 M1-M3 genes. Twenty-seven of 30 MHV-72-infected SCID mice (90%) died from generalized infection with intranuclear viral inclusions for approximately 1 month, while MHV-72-infected CB17+/+ mice recovered from acute infection. Long observation and pathological study of 68 MHV-72-infected mice for up to 24 months revealed that the survival rate (29.4%) and survival time (21.3 months) of MHV-72-infected CB17+/+ mice were significantly lower (P = 0.0127) and shorter (P = 0.0065) than those of the controls (61.1% and 22.9 months), respectively. The malignancy development rate (60.3%) of the infected CB17+/+ mice was also significantly higher (P = 0.004) than those of the controls (22.2%). However, no MHV-72 DNA was detected in the tumors of infected mice. MHV-72 may have some tumor-promoting effects but the tumorigenesis in infected CB17+/+ mice is different from EBV-associated tumors.

Animals↗

The clinical relevance of thymic fluorodeoxyglucose uptake in pediatric patients after chemotherapy.

The purpose of this study was to clarify the clinical implications of thymic fluorodeoxyglucose (FDG) uptake after chemotherapy in pediatric patients with malignant disease. Twenty-two pediatric patients, aged 0-17 years (mean 7.0 years), who had undergone FDG positron emission tomography (PET) were examined retrospectively. A total of 48 FDG-PET scans of the 22 patients were reviewed. Seven PET scans were recorded before the initial chemotherapy, and the remaining 41 scans were conducted during and after chemotherapy. Thymic FDG uptake was evaluated using standardized uptake value (SUV) analysis. The effect of chemotherapy on thymic FDG uptake was assessed by comparing SUV before, during, and after chemotherapy. The change in thymic FDG uptake with increasing time after the completion of chemotherapy was also assessed. Clinical laboratory data including number of white blood cells (WBCs), erythrocytes (RBCs), platelets, plasma glucose level and differential white blood count were analyzed for their association with thymic FDG uptake. Thymic FDG uptake in patients during chemotherapy was significantly lower than that in patients before chemotherapy (mean+/-SD 1.71+/-0.48 vs 2.27+/-0.32, respectively, P<0.01). Thymic FDG uptake in patients after chemotherapy was significantly higher than that in patients during chemotherapy (mean+/-SD 2.74+/-0.70 vs 1.71+/-0.48, respectively, P<0.01). A significant relationship between thymic FDG uptake and interval after completion of chemotherapy (r=0.74, P<0.0001) was observed. Significant relationships between blood counts (WBCs, RBCs, and platelets) and thymic FDG uptake were also observed. Comparison of the differential white blood count and thymic FDG uptake revealed a significant relationship only with lymphocyte count. Thymic FDG uptake in pediatric patients after completion of chemotherapy should not be mistaken as recurrent or metastatic thymic malignancy. Thymic FDG uptake appears to be associated with thymic function or hematopoietic function in bone marrow. Interpretation of FDG-PET must be made with this consideration in mind.

Adolescent↗

Thymic myoid cells as a myasthenogenic antigen and antigen-presenting cells.

We investigated immune property of a myoid cell line, established from Fisher rat thymus. Immunization of syngeneic rats with the myoid cells induced anti-rat acetylcholine receptor (AChR). Implantation of them into the thymus failed to induce typical thymic pathology of human myasthenia gravis (MG) or anti-AChR responses. We also demonstrated that the myoid cells were able to present exogenous antigens to T cells and induce antigen-specific T cell proliferation. These results suggest that myoid cells have the potential antigenicity to induce anti-AChR and the functions of antigen-presenting cells, but their expansion in the thymus may not directly cause MG.

Animals↗

Event-related potentials elicited by non-target tones in an auditory oddball paradigm in schizophrenia.

It has been reported that in event-related potentials (ERPs) elicited by non-target tones in oddball paradigms, the superimposition of a negative component on the descending slope of N100 depends on subjects' attention to the task. We tested the possibility that this attention-related change is abnormal for patients with schizophrenia. ERPs induced by non-target, frequent tones were measured for 52 patients and 31 healthy controls under two oddball conditions: a passive condition where the subjects were told to disregard the tones, and an active condition where they were instructed to respond to infrequent tones. For both groups, a negative component was superimposed from the descending slope of N100 to the end of P150 (latency, 120-200 ms) for the active condition. The peak latency of this attention-related negative component was longer for the patients than for the controls, while the amplitude showed no group difference. In addition, the active P150 for the patients was more enlarged than that for the controls. Furthermore, the active P150 amplitude for the patients correlated positively with the score for the negative symptom factor of the Positive and Negative Syndrome Scale. These findings suggest that the enlargement of non-target P150 observed in conjunction with the latency prolongation of the attention-related negative component may be a biological marker for the severity of the negative symptoms in schizophrenia.

Acoustic Stimulation↗

Induction and prevention of virus-associated malignant lymphoma by serial transmission of EBV-related virus from cynomolgus by blood transfusion in rabbits.

Epstein-Barr virus (EBV)-related herpesvirus (Si-IIA-EBV) was serially transmitted for 3 passages from rabbit to rabbit of the opposite sex by blood transfusion, which subsequently induced virus-associated rabbit lymphomas. The virus could be transmitted by transfusion with 15-20 ml of whole blood (7/7) or irradiated blood (1/6) from the EBV-related virus-infected rabbits, but there was no transmission with transfusion of cell-free plasma (0/6) from the infected rabbits. Passive anti-EBV-VCA IgG (x 20 approximately x 10) titers decreased during the first 1-2 weeks in the transfused rabbits. The virus-transmitted rabbits showed a gradual increase in antibody titers ranging from peak titers of x 640 to x 2560 after 3 weeks of transfusion. The recipient origin of malignant lymphoma that developed in the first rabbit transfused by infected blood was confirmed by chromosomal analysis. This rabbit model thus shows that EBV-related herpesvirus is serially transmissible by blood transfusion and that transmission can not be completely prevented by irradiation of blood, but removal of blood cells is the best way to prevent transmission of EBV-related virus. Therefore, this animal model provides a convenient in vivo system for studies of the prevention and therapy of transfusion-related transmission of EBV and EBV-associated lymphoproliferative diseases in immunocompromised human beings.

Animals↗

FDG-PET scanning after radiation can predict tumor regrowth three months later.

PURPOSE: Positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) is well known for providing excellent clinical information regarding malignant tumors. We investigated whether dual-time FDG-PET performed immediately post radiation could predict early regrowth of malignant tumors. MATERIALS AND METHODS: Twenty patients with malignant tumors were included in this study. All patients received radiation, and each underwent FDG-PET before the initiation of therapy and within 10 days of completing their course of irradiation. PET images after irradiation were obtained at 60 min and 180 min post FDG injection. For 26 lesions in 20 patients, standardized uptake value (SUV) before and after treatment was calculated and then correlated with postradiation tumor response and outcome at 3 months status post irradiation. RESULTS: Retention index [RI = (SUV on delayed image - SUV on early image)/SUV on early image] after irradiation showed a significant difference between patients with residual tumor and those without residual tumor at 3 months status post irradiation (p < 0.0025). All 9 lesions in 6 patients with residual tumors showed more than 0.1 of RI, whereas none of the lesions with less than 0.1 of RI revealed residual tumors. CONCLUSIONS: Dual-time FDG-PET imaging just after irradiation is potentially useful for predicting early regrowth of malignant tumors.

Adult↗