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Biomedical subjects

K Kaneko

Publications and source records attributed to K Kaneko.

At least 55 records · Page 3Linked to original sources

Diffusion-weighted magnetic resonance imaging in early stage of 5-fluorouracil-induced leukoencephalopathy.

We report a case of 5-fluorouracil (5-FU)-induced leukoencephalopathy in which magnetic resonance imaging (MRI) of the brain, including diffusion-weighted imaging (DWI), was performed serially. The initial T2-weighted and FLAIR images showed diffuse mild hyperintensity in bilateral deep cerebral white matter and corpus callosum, which on T1WI appeared as non-enhanced faint hypointensity. Isotropic DWI disclosed the abnormality as well-conspicuous diffuse hyperintensity with decreased ADC. Serial studies revealed that majority of the abnormal signal intensity on these sequences resolved, and the decreased ADC values approached normal. Some hyperintensity remained in the deep cerebral white matter and the splenium, but no further significant ADC change after normalization was noted. Measurement of ADC along the three orthogonal directions showed the presence of directional dependence of diffusion throughout the length of study. These findings suggest that early stage of 5-FU-induced leukoencephalopathy is associated with reversible restricted diffusion and preservation of anisotropy. Diffusion-weighted imaging may be useful for the diagnosis.

Adult↗

Extremely high prevalence of hypercalciuria in children living in the Aral Sea region.

UNLABELLED: The Aral Sea region is a natural area seriously polluted by human activities. In addition to the increased prevalence of diverse chronic diseases in children, the risk of developing urolithiasis is reported to be high in this region. This study was undertaken to clarify the prevalence of hypercalciuria in children of the Aral Sea region. A group of 205 children living in Kazalinsk, close to the Aral Sea, and a group of 187 children living in Zhanakorgan, far from the Aral Sea, were screened for hypercalciuria. Urinary sodium excretion (sodium per creatinine, uNa/Cr) in addition to calcium excretion (calcium per creatinine, uCa/Cr) was also calculated for each subject. Mean uCa/Cr (mmol/mmol) and uNa/Cr (mmol/mmol) excretions were significantly higher in Kazalinsk than in Zhanakorgan (uCa/Cr: 0.75 +/- 0.74 and 0.33 +/- 0.30; uNa/Cr: 3.54 +/- 2.27 and 2.89 +/- 1.69, respectively, mean +/- SD, p < 0.01). Hypercalciuria regarded as an uCa/Cr of more than 0.703 was observed in 79 out of 205 Kazalinsk children (38.6%) while this was seen in only 24 out of 187 Zhanakorgan children (12.8%). Linear regression analysis revealed a direct positive correlation between urinary calcium and sodium excretion (p < 0.01) in Kazalinsk children. CONCLUSION: The prevalence of hypercalciuria in children around the Aral Sea region is extremely high. This may be associated with excessive intake of calcium and sodium, or due to impaired renal tubular function caused by toxic chemicals. Therefore, hypercalciuria that may lead to urolithiasis should be taken into account when considering the health problems of this area.

Asia, Central↗

Th1/Th2 balance in childhood idiopathic nephrotic syndrome.

AIMS: In view of the conflicting evidence of helper T cell type 1 (Th1) or type 2 (Th2) pattern of cytokine synthesis in childhood idiopathic nephrotic syndrome (INS) this study examined the balance of Th1 and Th2 which are characterized by intracellular cytokine production of interferon-gamma (IFNgamma) and interleukin-4 (IL-4), respectively. SUBJECTS AND METHODS: Sixteen children with steroid-sensitive INS (mean age 9.0 years) were included in this study, together with 15 healthy normal children (mean age 7.9 years) for the control group. Intracellular production of both IFNgamma and IL-4 in helper T cell (CD4+ cell) was investigated by a 3-color flow cytometry. RESULTS: The cross-sectional data showed no significant differences of percentages of Th0 (IFNgamma+ IL-4+ CD4+ cell), Th1 (IFNgamma+ lL-4- CD4+ cell) and Th2 (IFNgamma- IL-4+ CD4+ cell) in CD4+ cells (p > 0.05). The Th1/Th2 ratio during nephrotic relapse did not differ from those during nephrotic remission and in normal healthy children (p > 0.05). CONCLUSION: We conclude that there is no significant skew of Th1/Th2 balance in childhood INS and that the cardinal immunological abnormality does not lie in helper T cells but in other cells, such as suppressor/cytotoxic T cells, natural killer cells or monocytes/macrophage. To clarify the pathogenesis of INS, comprehensive studies for these cells would be worthwhile.

Case-Control Studies↗

[A resected case of solitary fibrous tumor of the pleura].

A 45-year-old female with solitary fibrous tumor (SFT) of the pleura was reported. Chest X-ray and CT scan on admission showed a large tumor in the right thoracic cavity. A preoperative needle biopsy was performed. The microscopic appearance of biopsied specimen revealed many spindle cells. And an immunohistochemical study was positive for CD 34 and negative for keratin, epithelial membrane antigen, alpha-smooth muscle actin, S-100 protein. So SFT was strongly suspected and an operation was performed. A tumor arised from the visceral pleura of right middle lobe and was pedunculated. The tumor was 13 x 10 x 7.5 cm in size. An immunohistochemical study of the tumor was positive for CD 34, and negative for SMA, ki-67. From these immunohistochemical stainings and microscopic findings, the tumor was diagnosed as SFT. An immunohistochemical study of the tumor seems to be very useful for the diagnosis of SFT.

Female↗

Dscam is associated with axonal and dendritic features of neuronal cells.

Dscam, a novel cell-adhesion molecule belonging to the Ig-superfamily mediates homophilic intercellular adhesion and is expressed abundantly in the nervous system during development. To gain better understanding on the role of Dscam in neuronal differentiation, we raised an antibody and characterized its protein product. Anti-Dscam antibody detected an approximately 200-kDa protein band in human and mouse brain lysates. Immunohistochemical studies showed that during embryonic development of mice, mouse Dscam is expressed throughout the neuronal tissues and also in nonneuronal tissues such as lung, liver, and limb buds. In adult brain Dscam expression is predominant in the cerebellum, hippocampus, and olfactory bulb. Immunofluorescence double labeling of hippocampal and cerebellar primary cultures revealed that Dscam is associated with axonal and dendritic processes. In view of its cellular localization and spatiotemporal expression pattern, we suggest that Dscam is involved in cell-cell interactions during axonal-dendritic development, and maintenance of functional neuronal networks.

Aging↗

Relaxation, the Boltzmann-Jeans conjecture, and chaos.

Slow (logarithmic) relaxation from a highly excited state is studied in a Hamiltonian system with many degrees of freedom. The relaxation time is shown to increase as the exponential of the square root of the energy of excitation, in agreement with the Boltzmann-Jeans conjecture, while it is found to be inversely proportional to residual Kolmogorov-Sinai entropy, introduced in this Rapid Communication. The increase of the thermodynamic entropy through this relaxation process is found to be proportional to this quantity.

Journal Article↗

Solid-state NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration.

The secondary structure of a 55-residue fragment of the mouse prion protein, MoPrP(89-143), was studied in randomly aggregated (dried from water) and fibrillar (precipitated from water/acetonitrile) forms by (13)C solid-state NMR. Recent studies have shown that the fibrillar form of the P101L mutant of MoPrP(89-143) is capable of inducing prion disease in transgenic mice, whereas unaggregated or randomly aggregated samples do not provoke disease. Through analysis of (13)C chemical shifts, we have determined that both wild-type and mutant sequence MoPrP(89-143) form a mixture of beta-sheet and alpha-helical conformations in the randomly aggregated state although the beta-sheet content in MoPrP(89-143, P101L) is significantly higher than in the wild-type peptide. In a fibrillar state, MoPrP(89-143, P101L) is completely converted into beta-sheet, suggesting that the formation of a specific beta-sheet structure may be required for the peptide to induce disease. Studies of an analogous peptide from Syrian hamster PrP verify that sequence alterations in residues 101-117 affect the conformation of aggregated forms of the peptides.

Amino Acid Sequence↗

Antibodies inhibit prion propagation and clear cell cultures of prion infectivity.

Prions are the transmissible pathogenic agents responsible for diseases such as scrapie and bovine spongiform encephalopathy. In the favoured model of prion replication, direct interaction between the pathogenic prion protein (PrPSc) template and endogenous cellular prion protein (PrPC) is proposed to drive the formation of nascent infectious prions. Reagents specifically binding either prion-protein conformer may interrupt prion production by inhibiting this interaction. We examined the ability of several recombinant antibody antigen-binding fragments (Fabs) to inhibit prion propagation in cultured mouse neuroblastoma cells (ScN2a) infected with PrPSc. Here we show that antibodies binding cell-surface PrPC inhibit PrPSc formation in a dose-dependent manner. In cells treated with the most potent antibody, Fab D18, prion replication is abolished and pre-existing PrPSc is rapidly cleared, suggesting that this antibody may cure established infection. The potent activity of Fab D18 is associated with its ability to better recognize the total population of PrPC molecules on the cell surface, and with the location of its epitope on PrPC. Our observations support the use of antibodies in the prevention and treatment of prion diseases and identify a region of PrPC for drug targeting.

Animals↗

Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors.

BACKGROUND: Survivin is a new member of the inhibitor of apoptosis family of antiapoptotic proteins. This protein was expressed selectively in all the most common human carcinomas but not in normal adult tissues. To our knowledge, the relation between survivin expression and apoptosis or tumorigenesis has not yet been studied in pancreatic neoplasms. METHODS: The authors investigated the expression of survivin in 4 pancreatic carcinoma cell lines and 56 human pancreatic tissues (5 cases of normal, 12 cases of chronic pancreatitis [CP], 26 cases of pancreatic duct cell adenocarcinoma [PDC], 16 lesions of 13 intraductal papillary-mucinous tumor [IPMT] by immunohistochemistry, immunoblotting, and reverse transcription-polymerase chain reaction (RT-PCR) to examine the association of its expression with tumor apoptosis and/or tumorigenesis. RESULTS: Survivin expression was found in the tumor cells but not in the nonneoplastic pancreatic tissues (normal and CP tissues). Survivin expression was observed in 20 of 26 cases of PDC (76.9%) and in 9 of 16 IPMT lesions that ranged from adenoma to invasive (56.3%) by immunohistochemistry. Survivin was more frequently expressed in malignant tumors than in benign tumors (P = 0.0089). In PDC, high levels of survivin expression were associated significantly with a reduction in the apoptotic index of the tumor cells (0.445% +/- 0.150% vs. 0.961% +/- 0.378%; P < 0.0001). CONCLUSIONS: These data suggest that the expression of survivin may be upregulated during an early step of tumorigenesis and during the development of cancer by reducing the cancer cell apoptosis.

Adenocarcinoma↗

Detection of peritoneal micrometastases of gastric carcinoma with green fluorescent protein and carcinoembryonic antigen promoter.

The aim of this study was to specifically visualize micrometastases in the peritoneal cavity, which cannot be detected by conventional methods, by using enhanced Green Fluorescent Protein (EGFP) containing carcinoembryonic antigen (CEA) promoter in an upstream position. In in vitro experiments, two cell lines from human gastric cancer, MKN45 and MKN1, and a cell line from human fibrosarcoma, HT1080, were transduced with pCEA-EGFP, which contains the CEA promoter region. MKN45 and MKN1, which expressed CEA mRNA, showed positive fluorescence after transduction of pCEA-EGFP, whereas HT1080 did not. In in vivo experiments, 7 days after 10(7) MKN45 had been injected into the peritoneal cavity of BALB/c nude mice, pCEA-EGFP was transduced in the peritoneal cavity using a fusogenic liposome with the envelope protein of Hemagglutinating Virus of Japan on the surface. On the peritoneum of the abdominal wall, fluorescent nodules were detected by fluorescence stereomicroscopy. These nodules had a minimal size of approximately 0.15 mm and could not be detected by conventional stereomicroscopy or macroscopy. They were histologically confirmed to be cancer cells by H&E staining. The results suggest that visualization of peritoneal micrometastasis of gastric cancer using CEA promoter and EGFP can offer a new strategy for diagnosis of micrometastasis.

Animals↗

A correlation between magnetic resonance imaging and electrophysiological findings in cervical spondylotic myelopathy.

STUDY DESIGN: Correlation between compressed spinal cords on magnetic resonance imaging (MRI) and electrophysiological findings in cervical spondylotic myelopathy patients. OBJECTIVE: To clarify the correlation between spinal-cord-evoked potentials and MRI measurements of compressed spinal cords in patients with cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: Compression of the spinal cord does not always cause clinical symptoms and it is difficult to infer the degree of dysfunction of the spinal cord from MRI findings. METHODS: Seventeen patients with cervical spondylotic myelopathy were examined with MRI and spinal-cord-evoked potentials before surgery. Using abnormality in spinal-cord-evoked potentials as indicators of spinal cord morphology, spinal-cord transverse area and compression ratios (central and 1/4-lateral) were measured on T1-weighted axial imaging. The correlations between these dimensions and electrophysiological findings were investigated. RESULTS: The mean preoperative transverse area of the spinal cord was 47.13 mm2. The mean preoperative central compression ratio of the spinal cord was 34.4%. The mean preoperative 1/4-lateral compression ratio of the spinal cord was 27.5%. A correlation (Spearman r=0.65, P < 0.01) was observed between the 1/4-lateral compression ratio of the spinal cord and the amplitude ratio of spinal-cord-evoked potentials after electric stimulation of the brain (Br(E)-SCEPs). CONCLUSIONS: The preoperative 1/4-lateral compression ratio of the spinal cord was found to reflect the degree of dysfunction of the corticospinal tracts.

Adult↗

Differential recording of upper and lower cervical N13 responses and their contribution to scalp recorded responses in median nerve somatosensory evoked potentials.

To distinguish the different origins of cervical N13 potentials in median nerve somatosensory evoked potentials (SSEPs), cervical N13 potentials were recorded by two different montages. The abnormal patterns of the SSEPs were compared to the abnormal evoked spinal cord responses (ESCPs) recorded from posterior epidural space in 13 patients with various cervical lesions. SSEPs from the posterior cervical surface were recorded from the mid-cervical level with anterior neck reference (Cv5-AN) and from the upper cervical level with inion reference (Cv2-IN). Scalp responses were recorded from the parietal region contralateral to the stimulating side with non-cephalic reference (shoulder contralateral to stimulating side). ESCPs were recorded from the posterior epidural space using catheter electrodes or needle electrodes inserted into the ligamentum flavum. Lower cervical N13 (LC-N13) recorded from the Cv5-AN montage showed similar latency to upper cervical N13 (UC-N13) recorded from the Cv2-IN montage. The latency of the early part of the P13-P14 complex in the scalp montage was similar to that of the UC-N13 and the negative peak latency of the ESCPs recorded at the C2-3 level. Attenuation of the LC-N13 and relatively preserved UC-N13 and P13-P14 were characteristic in patients with cervical syringomyelia and compression cervical myelopathy at the mid-cervical levels. Attenuation of the UC-N13 with normal LC-N13 was characteristic in patients with cervical spondylotic myelopathy who showed conduction blockade of the ESCPs at the C3-4 level. In a patient with schwannoma at the C1-2 level, conduction blockade of the ESCPs was observed at the C1-2 level. P13 was normal but P14 was prolonged. UC-N13 and P13 latencies were similar to the negative peak latency of the ESCPs at the C2-3 level. We demonstrated that two different cervical N13 potentials can be recorded by two different montages and they represent different behavior in various spinal cord lesions. In addition, at least the early part of the P13-P14 complex originates in the upper cervical region. To distinguish two different cervical N13, it is useful to detect not only the cervical pathology but also the symptomatic cervical cord compression level in patients with cervical myelopathy.

Adult↗

Neuronal plasticity in hippocampal mossy fiber-CA3 synapses of mice lacking the inositol-1,4,5-trisphosphate type 1 receptor.

In the present study, we used inositol-1,4,5-trisphosphate (IP3) type 1 receptor (IP3R1) knockout mice to examine the role of this receptor in the induction of LTP, LTD, and DP at mossy fiber-CA3 synapses. No difference in synaptically induced field-EPSPs was seen between the wild-type (IP3R1(+/+)) and IP3R1 knockout mice (IP3R1(-/-)), showing that basic synaptic transmission does not involve IP3R1 activation. Tetanus induced LTP in both wild-type and IP(3)R1(-/-) mice, but the magnitude of LTP was significantly greater in IP3R1(-/-) mice (149.8+/-3.5%, mean+/-S.E.M., n=15) than in wild-type mice (132.4+/-1.5%, n=17), suggesting that the IP3R1 has a suppressive effect on LTP induction. To determine whether this effect involved N-methyl-D-aspartate receptor (NMDAR)-dependent LTP, the effect of tetanus was tested in the present of the NMDAR antagonist, D,L-AP5 (50 microM); under these conditions, the LTP in both IP3R1(-/-) and IP3R1(+/+) mice was not significantly reduced. In addition, group I mGluR activation was shown to be necessary for LTP induction, as the LTP was almost blocked by the group I mGluR antagonist, RS-4CPG (500 microM) in both IP3R1(-/-) (117.6+/-1.7%, n=8) and IP3R1(+/+) (116.9+/-1.8%, n=5) mice. The IP3R1 also plays an essential role in LTD induction, as low-frequency stimulation (LFS) failed to induce LTD in the mutant mice (104.5+/-2.1%, n=10). DP was induced in both IP3R1(-/-) and wild-type mice.

Animals↗

Theory of robustness of irreversible differentiation in a stem cell system: chaos hypothesis.

Based on an extensive study of a dynamical systems model of the development of a cell society, a novel theory for stem cell differentiation and its regulation is proposed as the "chaos hypothesis". Two fundamental features of stem cell systems-stochastic differentiation of stem cells and the robustness of a system due to regulation of this differentiation-are found to be general properties of a system of interacting cells exhibiting chaotic intra-cellular reaction dynamics and cell division, whose presence does not depend on the detail of the model. It is found that stem cells differentiate into other cell types stochastically due to a dynamical instability caused by cell-cell interactions, in a manner described by the Isologous Diversification theory. This developmental process is shown to be stable not only with respect to molecular fluctuations but also with respect to the removal of cells. With this developmental process, the irreversible loss of multipotency accompanying the change from a stem cell to a differentiated cell is shown to be characterized by a decrease in the chemical diversity in the cell and of the complexity of the cellular dynamics. The relationship between the division speed and the loss of multipotency is also discussed. Using our model, some predictions that can be tested experimentally are made for a stem cell system.

Animals↗

Transitions induced by the discreteness of molecules in a small autocatalytic system.

The autocatalytic reaction system with a small number of molecules is studied numerically by stochastic particle simulations. A novel state due to fluctuation and discreteness in molecular numbers is found, characterized as an extinction of molecule species alternately in the autocatalytic reaction loop. Phase transition to this state with changes of the system size and flow is studied, while a single-molecule switch of the molecule distributions is reported. The relevance of the results to intracellular processes is briefly discussed.

Biophysical Phenomena↗

Adsorptive properties of metal oxide dispersed carbon materials and characterization of metal oxide fine particles by XAFS.

Surface modification of activated carbon fiber (ACF) with metal oxide increases the adsorptivity of the ACF for supercritical gas such as NO and CH4. In this study, pitch-based activated carbon fibers (P20) were modified with nickel oxide particles. The adsorptive properties and micropore structures of NiO dispersed P20 (NiO-P20) were investigated by nitrogen adsorption isotherms at 77 K. The isotherm was of type 1, suggesting that the NiO-P20 has microporosity. The micropore volume and surface area for NiO-dispersed P20 were smaller than that of P20 by about 15%. The Ni K-edge X-ray absorption fine structure of NiO-P20 has been investigated in order to characterize the species dispersed on P20. The local structure of the NiO particles on the P20 showed some different features compared with the local structure of powdered NiO.

Journal Article↗

Sensitive boundary condition dependence of noise-sustained structure.

Sensitive boundary condition dependence (BCD) is reported in a convectively unstable system with noise, where the amplitude of generated oscillatory dynamics in the downstream depends sensitively on the boundary value. This BCD is explained in terms of the decrease (relaxation) of the comoving Lyapunov exponent (characterizing the convective instability) from upstream to downstream [K. Fujimoto and K. Kaneko, Physica D 129, 203 (1999)]. It is shown that a fractal BCD appears if the dynamics that represent the spatial change of the fixed point includes transient chaotic dynamics, and if appropriate intensity of noise is presented. By considering as an example a one-way-coupled map lattice, this theory for BCD is demonstrated.

Journal Article↗

Comparison of MET-PET and FDG-PET for differentiation between benign lesions and malignant tumors of the lung.

OBJECTIVE: We retrospectively assessed and compared the usefulness of 11C-methionine (MET)-PET with that of 18F-FDG-PET for the differentiation between benign lesions and malignant tumors of the lung. METHODS: We examined 101 patients with a suspected lung tumor including 79 patients with primary lung cancer and 22 patients with benign lesions. One hundred and forty PET studies (46 studies with MET-PET and 94 studies with FDG-PET) were performed. Both MET-PET and FDG-PET were performed on 39 patients. The MET-PET was performed 15 minutes after the administration of 67-740 MBq of MET, and FDG-PET 45 minutes after the administration of 30-437 MBq of FDG. The results were then evaluated by the standardized uptake value (SUV). RESULTS: The MET uptake in lung cancer was 3.69+/-1.22 (n = 37) which was significantly higher than that in benign lesions 1.81+/-1.04 (n = 9) (p < 0.001). The sensitivity, specificity and accuracy of MET-PET were 83.8%, 88.9% and 84.8%, respectively, when 2.66 of SUV was used as the cutoff value. The FDG uptake in lung cancer was 5.94+/-2.89 (n = 75) and was also significantly larger than that in benign lesions 2.46+/-1.01 (n = 19) (p < 0.001). The sensitivity, specificity and accuracy of FDG-PET were 81.3%, 78.9% and 80.9%, respectively (cutoff = 3.20). The MET uptake in the lesions correlated significantly with FDG uptake (r = 0.71, p < 0.001). According to an ROC analysis, the area under the curve for MET-PET (area = 0. 833) was higher than that for FDG-PET (area = 0.828), but the difference was not statistically significant. Furthermore, the combined use of MET-PET and FDG-PET did not improve the diagnostic ability. CONCLUSIONS: In conclusion, both MET-PET and FDG-PET were considered to be equally useful for the differential diagnosis of lung tumors. Furthermore, MET uptake in lung lesions was found to correlate significantly with FDG uptake.

Adult↗