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Biomedical subjects

Y Kaneko

Publications and source records attributed to Y Kaneko.

At least 37 records · Page 2Linked to original sources

Natural IgM antibodies in sera from various animals but not the cat kill Toxoplasma gondii by activating the classical complement pathway.

Sera from swine, rabbit, and dog, that had never been exposed to Toxoplasma gondii, demonstrated significant killing of T. gondii tachyzoites in vitro, while cat serum did not. Swine and rabbit sera contained natural IgM antibody against the tachyzoites, and the classical complement pathway was activated by the binding of natural IgM antibody to the tachyzoites, leading to lysis. Anti-T. gondii antibodies, induced in swine or cat infected with T. gondii, had no killing effect by themselves but killed the tachyzoites in the presence of swine complement. However, the anti-T. gondii antibodies of swine or cat demonstrated a very low killing effect in the presence of cat complement. This suggests that T. gondii tachyzoites have an evasion mechanism to prevent lysis which is specific for cat complement.

Animals↗

Acute infection with influenza virus enhances susceptibility to fatal pneumonia following Streptococcus pneumoniae infection in mice with chronic pulmonary colonization with Pseudomonas aeruginosa.

We established a mouse model in which fatal pneumonia was induced by pneumococcal superinfection following influenza virus infection in chronic Pseudomonas aeruginosa infected mice. In this mouse model, influenza virus infection caused a significant increase in inflammatory cells, cytokines and severe tissue damage in the lungs of these P. aeruginosa infected mice, before pneumococcal infection. Intrapulmonary virus titres were significantly increased in mice with chronic P. aeruginosa infection, compared with control mice. Neutrophil function analysis showed significant reduction of myeloperoxidase (MPO) activity and lysozyme secretion by influenza virus infection in these mice. Our results suggest that influenza virus infection may play an important role in inducing pneumococcal pneumonia in chronic P. aeruginosa infected mice. Our results suggested that our mouse model is useful for investigating the pathogenesis of influenza virus infection in patients with chronic lung infection.

Acute Disease↗

Transforming growth factor-beta1 gene polymorphism modifies the histological and clinical manifestations in Japanese patients with IgA nephropathy.

Transforming growth factor (TGF)-beta1, a multifunctional cytokine, which regulates proliferation and differentiation of a variety of cell types, has the central role in the development and progression of renal injury in both animal models and human. Although it has been suggested that genetic variations in the TGF-beta1 gene are associated with the activity of the gene product, their clinical significance in glomerular disease is unknown. We investigated whether the polymorphisms of C-509T and T869C in TGF-beta1 account for interindividual variation in manifestations of IgA nephropathy (IgAN) using 626 Japanese subjects including 329 patients with histologically proven IgAN and 297 healthy controls with normal urinalysis. The frequencies of genotypes, alleles, and major haplotypes were similar between the patients and controls. The C-509T and T869C polymorphisms were in tight linkage disequilibrium, and the major haplotypes were C-C and T-T, which accounted for more than 95% of the total. In patients with -509CC and in those with the 869CC, urinary protein excretion was higher than in those with other genotypes, whereas no difference in other clinical manifestations was noted. Moreover, patients with -509CC and those with 869CC genotypes presented with a significant higher score of mesangial cell proliferation than in those with other genotypes. These results suggest that TGF-beta1 gene polymorphisms are specifically associated with heavy proteinuria and mesangial cell proliferation in Japanese patients with IgAN, although they do not confer susceptibility to this disease.

Adult↗

Immunokinetics in severe pneumonia due to influenza virus and bacteria coinfection in mice.

Coinfections of bacteria and influenza are a major cause of excessive mortality during influenza epidemics. However, the mechanism of the synergy between influenza virus and bacteria are poorly understood. In this study, mice were inoculated with influenza virus, followed 2 days later by inoculation with Streptococcus pneumoniae. The kinetics of viral titres, bacterial numbers and the immune response (cytokine and chemokine production) were also analysed. Short-term survival correlated with pathological changes in the lungs of infected mice. Influenza virus or S. pneumoniae infection alone induced moderate pneumonia; however, severe bronchopneumonia with massive haemorrhage in coinfected mice, which caused death of these mice approximately 2 days after inoculation with S. pneumoniae, was noted. Intrapulmonary levels of inflammatory cytokines/chemokines, type-1 T-helper cell cytokines and Toll-like receptors, and the related mitogen-activated protein kinase signalling molecules (phosphorylated extracellular signal-regulated kinase -1 and - 2, p38 and c-Jun N-terminal kinase), were increased in coinfected mice. These results suggest that immune mediators, including cytokines and chemokines, through Toll-like receptors/mitogen-activated protein kinase pathways, play important roles in the pathology of coinfection caused by influenza virus and Streptococcus pneumoniae.

Animals↗

Widespread crystalline inclusions affecting podocytes, tubular cells and interstitial histiocytes in the myeloma kidney.

Numerous crystalline inclusions were observed in glomerular and tubular epithelial cells in a 46-year-old female patient with multiple myeloma and renal dysfunction. On light microscopy, epithelial cells were filled with homogenous materials and were remarkably swollen. Infiltrations of histiocytes with expanded cytoplasm were also seen in the interstitium of the kidney and bone marrow. On electron microscopy, cytoplasmic inclusions had crystalline structure showing rhomboid and oval shapes. Immunofluorescence study revealed that these cells were positive for IgG-kappa. The combination chemotherapy followed by autologous stem cell transplantation led to a partial resolution of her renal dysfunction, continued by a slight reduction in the number of crystalline-containing podocytes at the second renal biopsy. Crystal inclusions in the kidney are rarely found and cause renal impairment in multiple myeloma.

Bone Marrow Cells↗

A gamma-ray burst with a high-energy spectral component inconsistent with the synchrotron shock model.

Gamma-ray bursts are among the most powerful events in nature. These events release most of their energy as photons with energies in the range from 30 keV to a few MeV, with a smaller fraction of the energy radiated in radio, optical, and soft X-ray afterglows. The data are in general agreement with a relativistic shock model, where the prompt and afterglow emissions correspond to synchrotron radiation from shock-accelerated electrons. Here we report an observation of a high-energy (multi-MeV) spectral component in the burst of 17 October 1994 that is distinct from the previously observed lower-energy gamma-ray component. The flux of the high-energy component decays more slowly and its fluence is greater than the lower-energy component; it is described by a power law of differential photon number index approximately -1 up to about 200 MeV. This observation is difficult to explain with the standard synchrotron shock model, suggesting the presence of new phenomena such as a different non-thermal electron process, or the interaction of relativistic protons with photons at the source.

Journal Article↗

Change of electronic structure in Ca2RuO4 induced by orbital ordering.

Optical conductivity spectra sigma(omega) were used to investigate the effect of orbital ordering on the electronic structure of Ca2RuO4. Our LDA+U calculation predicts Ru 4d(xy) ferro-orbital ordering at the ground state, and well explains the present sigma(omega) as well as the reported O 1s x-ray absorption spectra. Variation of temperature (T) causes a large change of spectral weight over several eV as well as collapse of a charge gap accompanied by elongation of the c-axis Ru-O bond length. These results clearly indicate that the d(xy) orbital ordering plays a crucial role in the metal-insulator transition and the T-dependent electronic structure on a large energy scale.

Journal Article↗

Congenital pulmonary-systemic collateral vein without obstructed left atrial egress is associated with conotruncal anomalies.

We present a case of congenital pulmonary systemic collateral vein associated with truncus arteriosus. Pulmonary systemic collateral vein with nonobstructed left atrial egress is different from those with obstructed left atrial egress in that it is functionally redundant. Including this case, 8 patients among 33 reported cases with pulmonary systemic collateral veins have had nonobstructed left atrial egress. Association with conotruncal anomalies in 4 of these 8 patients, as well as the reported finding that neural crest cells are distributed not only in the conotruncus but also in the cardinal vein, indicates that neural crest cells play roles in remodeling of the systemic venous system.

Collateral Circulation↗

Merging of multiple signals regulating delta9 fatty acid desaturase gene transcription in Saccharomyces cerevisiae.

Fatty acid desaturation, which requires molecular oxygen (O2) as an electron acceptor, is catalyzed by delta9 fatty acid desaturase, which is encoded by OLE1 in Saccharomyces cerevisiae. Transcription of the OLE1 gene is repressed by unsaturated fatty acids (UFAs) and activated by hypoxia and low temperatures via the endoplasmic reticulum membrane protein Mga2p. We previously reported the isolation of the nfo3-1 (negative factor for OLE1) mutant, which exhibits enhanced expression of OLE1 in the presence of UFA and under aerobic conditions. In this work, we demonstrated that the NFO3 gene is identical to OLE1 and that the nfo3-1 mutation (renamed ole1-101) alters arginine-346, in the vicinity of the conserved histidine-rich motif essential for the catalytic function of the Ole1 protein, to lysine. The ratio of UFAs to total fatty acids in the ole1-101 mutant was 60%, compared to 75% in the wild type, suggesting that the reduction in relative levels of intracellular UFAs activates OLE1 transcription. However, in ole1-101 cells grown in the presence of oleic acid, the level of OLE1 expression remained high, although the relative amount of UFAs in the ole1-101 mutant cells was almost the same as that in wild-type cells growing under the same conditions. By contrast, when cells were grown with linoleic acid, which has a lower melting point than oleic acid, the elevation of the OLE1 expression level due to the ole1-101 mutation was almost completely suppressed. These observations suggest that the ole1-101 cells activate OLE1 transcription by sensing not only the intracellular UFA level, but also membrane fluidity or the nature of the UFA species itself. Furthermore, we found that not only the fatty acid- regulated (FAR) element but also the O2- regulated (O2R) element in the OLE1 promoter was involved in the activation of OLE1 transcription by the ole1-101 mutation, and that the effects of the low-oxygen signal and the ole1-101-generated signal on OLE1 expression were not additive. Taken together, these findings suggest that signals associated with hypoxia, low temperatures and intracellular UFA depletion activate OLE1 transcription by a common pathway.

Amino Acid Sequence↗

Cryptic insertion and translocation or nondividing leukemic cells disclosed by FISH analysis in infant acute leukemia with discrepant molecular and cytogenetic findings.

Of 51 infants with acute leukemia, 13 (25%) had contradictory findings on 11q23/MLL rearrangements that were analyzed by cytogenetic and Southern blot methods: seven had rearranged MLL and normal karyotype, four had rearranged MLL and abnormal karyotype with no 11q23 translocation, and two had germline MLL and 11q23 translocations. Fluorescent in situ hybridization (FISH) analysis using an MLL probe that was performed to elucidate the discrepancy disclosed the presence of normal dividing cells and nondividing leukemic cells in the same bone marrow in five patients, and cryptic insertion or translocation in another five. Subsequent FISH and reverse transcription-polymerase chain reaction analysis identified the MLL-AF10, MLL-AF4, or MLL-AF1q fusions that were produced by the cryptic rearrangements in four of the five patients. In the remaining three patients, the breakpoint of 11q23 translocation was located distal to the MLL locus in one, and the discrepancy was unresolved in two. Thus, FISH should complement cytogenetic analysis when cytogenetic and molecular genetic findings are contradictory in infant leukemia, and when infant leukemia does not show 11q23 translocations or other specific translocations including t(7;12), t(1;22), etc that are recurrently found in infant leukemia.

Blotting, Southern↗

Distinct methylated profiles in Helicobacter pylori dependent and independent gastric MALT lymphomas.

BACKGROUND: Gastric mucosa associated lymphoid tissue (MALT) lymphomas are clinically subdivided into Helicobacter pylori dependent and independent, according to H. pylori infection and the therapeutic course. In previous reports it has been suggested that H. pylori independent cases develop from H. pylori dependent cases, and sometimes transform into high grade diffuse large B cell lymphomas (DLBCLs). METHODS: To better understand the pathogenesis of H. pylori dependent and independent MALT lymphomas, we analysed the methylation profiles of eight independent CpG islands, including p15, p16, p73, hMLH1, death associated protein kinase, MINT1, MINT2, and MINT31 in H. pylori dependent and independent MALT lymphomas, DLBCLs, and H. pylori associated chronic gastritis. RESULTS: We first confirmed that H. pylori independent cases had a high incidence of t(11;18)(q21;q21) (4/8 cases) and aberrant BCL10 expression (7/8 cases) compared with H. pylori dependent cases and gastric DLBCLs. In the methylation pattern study, all 13 H. pylori dependent MALT lymphomas had more than four methylated loci while H. pylori independent cases had less than two. According to the previous criterion, all H. pylori dependent MALT lymphomas (13/13, 100%) and five of 10 (50%) DLBCLs were classified as CpG island methylator phenotype positive (CIMP+). In contrast, all H. pylori independent MALT lymphomas were CIMP-. CONCLUSION: The distinct methylation pattern together with lack of chromosomal translocation in H. pylori dependent MALT lymphomas suggest that H. pylori dependent and independent MALT lymphomas have a different pathogenesis.

Adaptor Proteins, Signal Transducing↗

Three-dimensional volumetric visualization of arteriovenous malformation of the maxilla.

The appearance of an arteriovenous malformation is described from images derived from spiral CT and reconstructed in three dimensions using computer graphics. The existence and shape of a vascular malformation is demonstrated using a vascular protocol. This three-dimensional CT technique is an important adjunct to diagnosis using CT, MRI and conventional radiography.

Adult↗

Younger onset myeloperoxidase-specific antineutrophil cytoplasmic antibody- (MPO-ANCA) related glomerulonephritis accompanied with nephrotic syndrome.

It is known that nephrotic syndrome rarely accompanies myeloperoxidase-specific antineutrophil cytoplasmic antibody- (MPO-ANCA) related glomerulonephritis. We present a case of younger onset MPO-ANCA-related glomerulonephritis accompanied with nephrotic syndrome in a female patient. It was diagnosed through the renal biopsy and the detection of a high titer of MPO-ANCA and steroid therapy (intravenous steroid pulse therapy and oral administration), anticoagulant therapy and antiplatelet therapy were initiated. Since her nephrotic syndrome persisted in spite of the decrease of MPO-ANCA, we conducted a second renal biopsy. We found active necrotizing crescentic glomerulonephritis with a small deposition of immunoglobulin and fibrinogen on the glomeruli. To suppress her disease activity, we administered second steroid-pulse therapy and MPO-ANCA titer disappeared. However, as her nephrotic syndrome, which was accompanied by severe hyperlipidemia, persisted, we tried to treat her using low-density lipoprotein (LDL) apheresis. It was effective temporarily, but she finally fell into end-stage renal failure. We discuss here the possibility of double nephropathy by considering her clinical and renal pathologic features.

Adult↗

Hepatic vein-to-azygos vein connection in a patient with interrupted inferior vena cava.

Massive systemic-to-hepatic venous collaterals developed in a 8-year-old boy with left isomerism and azygos connection of the inferior vena cava who had undergone total cavopulmonary shunt leaving the hepatic vein connected to the common atrium 5 years previously. A hepatic vein-to-azygos vein connection via an autologous pericardial roll successfully ameliorated cyanosis and physical activity. Hepatic vein-to-azygos vein connection is technically easy and is favorable in providing balanced distribution of hepatic venous blood to both lungs. We recommend this technique as an effective alternative to hepatic vein-to-pulmonary artery connection in patients developing collateral vessels after total cavopulmonary shunt.

Azygos Vein↗

Effects of 5-campestenone (24-methylcholest-5-en-3-one) on the type 2 diabetes mellitus model animal C57BL/KsJ-db/db mice.

We examined the therapeutic effects of dietary exposure to 5-campestenone (24-methylcholest-5-en-3-one), an enone derivative of campesterol, in C57BL/KsJ-db/db mice, which are an animal model of obese type 2 diabetes. Blood glucose levels of db/db mice linearly increased from 270 to 720 mg/dl in 10 weeks, an approximately 7-fold difference from the levels of db/+m mice. The 0.3 % dietary exposure to 5-campestenone caused a marked reduction in blood glucose levels of 330 mg/dl after 10 weeks of feeding with a concomitant inhibition of glucose excretion in urine. Only slight efficacy was observed with 0.1 % dietary exposure to this chemical in db/db mice. Significant decreases of plasma triglyceride and plasma free fatty acid were also observed in db/db mice at a 0.3 % dose. However, feed efficiency and body-weight gain in db/db mice was improved by 5-campestenone. No obvious anomaly due to consumption of 5-campestenone was detected by necropsy or clinical observation.

Animals↗