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Biomedical subjects

N Okamoto

Publications and source records attributed to N Okamoto.

At least 19 recordsLinked to original sources
PubMed2006

Paradoxical discrepancy between the serum level and the placental intensity of PP5/TFPI-2 in preeclampsia and/or intrauterine growth restriction: possible interaction and correlation with glypican-3 hold the key.

There have been controversies whether maternal serum placental protein 5 (PP5)/tissue factor pathway inhibitor (TFPI)-2 is increased in the patients with preeclampsia and/or intrauterine growth restriction (IUGR). Here, we have estimated the serum PP5/TFPI-2 in these patients by a sandwich enzyme-linked immunosorbent assay with a newly developed monoclonal antibody, coupled with placental immunohistochemical studies of their placentae with semiquantitative scoring. Serum PP5/TFPI-2 level was significantly elevated only in the patients with preeclampsia alone (p=0.033), while PP5/TFPI-2 was detected significantly less intensely in the placentae of the same patients (p=0.035) in immunohistochemistry, as compared to Controls. A proteoglycan present on the placental villous surface, glypican-3, showed the same pattern of staining as PP5/TFPI-2, and there was a positive correlation (C.I.=0.506, p=0.004) between the immunohistochemical scores for these. Further experiments using HepG2 cells transfected with PP5/TFPI-2 suggested that glypican-3 could anchor PP5/TFPI-2 on the placental villi. A possibility that a decrease in glypican-3 in the placenta increases the outflow of PP5/TFPI-2, which in turn increases its serum level, was proposed. Preeclampsia and IUGR, often regarded to have the same pathological basis in common, showed distinct distributions of PP5/TFPI-2, which could be a clue to elucidate the pathogenesis of preeclampsia and IUGR.

Adult↗
PubMed2005

Enterocele associated with rectocele revealed by dynamic pelvic CT.

Enterocele is often associated with other pelvic floor disorders but it is not always possible to detect by clinical examination. Defecography with peritoneography and/or barium meal intake has recently been developed as a new method to identify enterocele, but this method is an invasive procedure. Multislice computed tomography was performed at rest and during simulated defecation to evaluate an 80-year-old female patient who had a defecation disorder and was diagnosed as having rectocele based on results from defecography and clinical findings. Multiplanar reconstruction images were generated for image evaluation. Using this novel method of dynamic pelvic computed tomography, a third-degree enterocele was clearly demonstrated in this case.

Aged, 80 and over↗
PubMed2005

Serious cardiac and pulmonary calcification in a young peritoneal dialysis patient: potential role of continuous correction of acidosis.

We describe a 40-month-old male infant with renal failure, treated with peritoneal dialysis, who developed massive calcification of soft tissues including the heart and lungs with subsequent cardiopulmonary insufficiency. A diagnosis of Jeune syndrome was made. After starting peritoneal dialysis, the patient exhibited an intractable metabolic acidosis of unknown etiology necessitating treatment with intravenous or oral sodium bicarbonate. Myocardial calcification was first detected by 2-dimensional echocardiography performed 3 months after starting dialysis. The patient was not suitable for renal transplantation because of his cardiac dysfunction and died of cardiac and respiratory failure at the age of 6 years. Although the patient exhibited a variety of risk factors for ectopic calcification including hyperphosphatemia, hyperparathyroidism, high calcium-phosphate product and treatment with vitamin D, the early and massive soft tissue calcification may have been accelerated by correction of the metabolic acidosis. Therefore, the use of sodium bicarbonate may be involved in the etiology of the myocardial calcification.

Acidosis↗
PubMed2005

Epitope analysis of myeloperoxidase-specific antineutrophil cytoplasmic autoantibodies (MPO-ANCA) in childhood onset Graves' disease treated with propylthiouracil.

AIM: This study aimed to elucidate the relationship between epitope profiles and clinical manifestations of patients with myeloperoxidase antineutrophil cytoplasmic autoantibodies-(MPO-ANCA) positive childhood onset Graves' disease treated with propylthiouracil (PTU). METHODS: Sixteen patients were studied. The patients were grouped into ten without clinical vasculitis and nephritis (non-vasculitis group) and six with biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis (vasculitis group). Epitope analysis was performed on serum samples by an enzyme-linked immunosorbent assay (ELISA) using a panel of recombinant deletion mutants of MPO. RESULTS: The high frequency sites were region upstream of Met341 (Ha region) near the N-terminus of the heavy chain, and regions downstream of Gly598 (Hf and Hg regions) near the C-terminus. Most patients in the non-vasculitis group had polyclonal MPO-ANCA recognizing both the above linear sites and other epitope sites of the heavy chain of MPO. Only one of ten patients in the non-vasculitis group, and four of six patients in the vasculitis group had MPO-ANCA recognizing only the linear sites of the heavy chain of the MPO molecule (Ha, Hf and/or Hg). Of the four patients in the vasculitis group, two had nephritis, like rapidly progressive glomerulonephritis and one had alveolar hemorrhage. CONCLUSION: These findings suggest that most patients with childhood onset Graves' disease treated with PTU who manifest no vasculitis have polyclonal MPO-ANCA recognizing both the linear and other epitope sites of the heavy chain of MPO. However, some patients who develop nephritis have MPO-ANCA recognizing only the linear sites of the heavy chain of MPO. This clonality of MPO-ANCA may be a risk factor that induces clinical vasculitis and nephritis in patients treated with PTU. Therefore, patients exposed to PTU should be monitored for MPO-ANCA level and epitopes.

Adolescent↗
PubMed2004

Nonspecific immune response of rainbow trout (Oncorhynchus mykiss Walbaum) in relation to different status of vitamin E and highly unsaturated fatty acids.

This study was designed to examine the effects of dietary vitamin E (VE) on modulation of immune responses when supplied with two levels of n-3 highly unsaturated fatty acids (n-3 HUFA) in rainbow trout, Oncorhynchus mykiss. Six semipurified diets were prepared containing three levels of dietary VE (0, 100 or 1000 mg alpha-tocopheryl acetate kg(-1) diet) and n-3 HUFA either at 20 or 48% of dietary lipid provided from fish oil or docosahexaenoic acid (DHA) concentrated fish oil respectively. The diets were fed to rainbow trout (100 g initial mean weight) for 15 weeks. The VE, vitamin C (VC) content in plasma and tissues and the nonspecific immune responses, both humoral (alternative complement activity, total immunoglobulin) and cellular (phagocytosis, nonspecific cytotoxicity) were examined. VE contents in the kidney reflected the dietary input but were lower in fish fed 48% n-3 HUFA diets, and could have impaired some of immune responses compared to fish fed 20% n-3 HUFA. VC contents in kidney followed the same pattern as VE. Both humoral and cellular immune functions deteriorated in fish fed VE deficient diets whereas improvement in most of the parameters corresponded to its supplementation. However, the higher dose of dietary VE did not substantially enhance the responses assayed compared to the 100 mg dose. Besides clearly indicating the role of VE in maintaining the immune functions in fish in relation to dietary n-3 HUFA, this study has revealed that optimum health benefits could be achieved when VE is maintained slightly above the levels generally recommended for normal growth.

Animals↗
PubMed2004

Sensitization by glycerol for CDDP-therapy against human cultured cancer cells and tumors bearing mutated p53 gene.

To clarify effective chemotherapeutic regimens against cancer, we examined the effects of glycerol on apoptosis induced by CDDP treatment using cultured human cancer cells (in vitro) and transplanted tumor in mice (in vivo). Human tongue cell carcinoma (SAS) cells transfected with mutated p53 gene (SAS/m p53) showed CDDP-resistance compared with the cells with neo control gene (SAS/ neo). When those cultured cells were pre-treated with glycerol, CDDP-induced apoptosis was enhanced by glycerol in SAS/m p53 cells but not in SAS/ neo cells. In tumor-transplanted mice, the glycerol treatment to tumors enhanced growth delay induced by CDDP in mp53 tumors transplanted with SAS/m p53 cells, but not in wtp53 tumors transplanted with SAS/ neo cells. When transplanted tumors were treated with CDDP alone, the cells positive for active caspase-3, 85 kDa PARP and apoptosis were observed by immunohistochemical staining in wtp53 tumors but not in mp53 tumors. When the tumors were treated with CDDP combined with glycerol, positive cells were observed not only in wtp53 tumors but also in mp53 tumors. These results showed that the CDDP-induced growth inhibition of the tumors is p53 -dependent and that the enhanced growth delay by glycerol may be due to the increased apoptosis. Glycerol might be available for cancer chemotherapy in patients with mp53 tumors.

Animals↗
PubMed2003

Low-loss polymeric optical waveguides with large cores fabricated by hot embossing.

A simple low-cost method of fabricating polymeric optical waveguides with large core sizes for plastic optical fibers is presented. The waveguides are fabricated by hot embossing with an ultraviolet-cured epoxy resin stamper. The stamper is fabricated by replication of a rectangular groove mold that is made from silicone rubber replicated from a ridged original silicon master. The master is fabricated by anisotropic etching of (110) single-crystal silicon. Optical waveguides with large core sizes of 100-500 microm have been fabricated, and a low propagation loss of 0.19 dB/cm at 650 nm was achieved.

Journal Article↗
PubMed2003

[Local advanced lung cancer invaded thoracic vertebral bodies with unruptured cerebral aneurysm].

A 57-year-old man presented with the chief complaint of left shoulder pain in June 2001, and paridrosis of left upper trunk and left upper limb in July 2001. Head magnetic resonance imaging (MRI) showed 8 mm sized unrupture aneurysm of left middle cerebral artery, and chest computed tomography (CT) showed the lung tumor invaded thoracic vertebral bodies. The local advanced lung carcinoma (cT4N0M0) and unrupture aneurysm of left middle cerebral artery was diagnosed. The prevented clipping of unrupture aneurysm was performed at 11th September 2001, and left upper lobectomy, hemivertebrectomy and reconstruction of thoracic vertebral body (Th 3-5) with Modul' ICS at 12th October 2001. The pathological findings revealed squamous cell carcinoma. The staging was pT4N0M0, IIIB. The postoperative course was uneventful. After the radiotherapy (50 Gy), chemotherapy (gemcitabine and vinorelbine) was performed. But the radiation pneumonia was occurred and chemotherapy was intermitted. The steroid was administrated due to the radiation pneumonia, and the complication was improved. He discharged at 17th April 2002 and had no recurrence. The prevented clipping of unrupture cerebral aneurysm and the reconstruction of thoracic vertebral body (Th 3-5) with Modul' ICS were useful for the radical operation of the local advanced lung cancer.

Carcinoma, Squamous Cell↗
PubMed2002

Cytotoxic T cell function in fish.

Fish possess immunoglobulins, major histocompatibility complex (MHC), T-cell receptors, and lymphocyte populations analogous to B and T cells and can evoke specific immune responses against a variety of antigens. However, T-cell subsets have yet to be demonstrated and the information on cell-mediated immunity is limited. Here we briefly review our recent studies on specific cell-mediated immunity, particularly on cytotoxic T-cell function employing isogeneic fish and cell lines. Analyses of the graft-versus host reaction (GVHR) and cell-mediated cytotoxicity (CMC) against allogeneic erythrocytes or cell lines show alloantigen-specific cytotoxicity in clonal ginbuna crucian carp. We also describe specific cytotoxicity against virus-infected cells using clonal ginbuna and a syngeneic cell line. Lastly, we report MHC-restriction in CMC against virus-infected cells using homozygous clonal rainbow trout and trout cell line which share the same MHC class I allele. These studies on CMC strongly suggest the presence of antigen specific cytotoxic T cells in teleosts and functional similarities between the immune systems of fish and higher vertebrates. Experimental model systems established in these studies can be applied to the investigation of protective antigens to induce cell-mediated immunity for the development of fish vaccines.

Animals↗
PubMed2002

The proportion of cells with functional X disomy is associated with the severity of mental retardation in mosaic ring X Turner syndrome females.

Turner syndrome females (45,X) do not have mental retardation (MR), whereas some mosaic ring X Turner syndrome females, with 45,X/46,X,r(X), have severe MR. The MR is believed to be caused by a failure of X chromosome inactivation (XCI) of the small ring X chromosome, which leads to functional X disomy (FXD), To explore this hypothesis, we examined the proportion of FXD cells in the peripheral blood of four ring X Turner syndrome females with various levels of MR, using two newly developed XCI assays based on DNA methylation of X-linked genes. As a result, the two patients with extremely severe MR showed complete FXD patterns, whereas the remaining two patients with relatively milder MR showed partial FXD patterns. These results indicate that the proportion of FXD cells may be associated with the severity of MR in mosaic ring X Turner syndrome females, although this association should be confirmed by examining brain cells during development. One of the cases with severe MR and a complete FXD pattern neither lacked the XIST gene nor had uniparental X isodisomy, and we discuss the mechanism of the failure of XCI in this case.

Child↗
PubMed2001

B cell adaptor containing src homology 2 domain (BASH) links B cell receptor signaling to the activation of hematopoietic progenitor kinase 1.

The B cell adaptor containing src homology 2 domain (BASH; also termed BLNK or SLP-65), is crucial for B cell antigen receptor (BCR)-mediated activation, proliferation, and differentiation of B cells. BCR-mediated tyrosine-phosphorylation of BASH creates binding sites for signaling effectors such as phospholipase Cgamma (PLCgamma)2 and Vav, while the function of its COOH-terminal src homology 2 domain is unknown. We have now identified hematopoietic progenitor kinase (HPK)1, a STE20-related serine/threonine kinase, as a protein that inducibly interacts with the BASH SH2 domain. BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379 within HPK1 which we identified as a Syk-phosphorylation site were both necessary for interaction of both proteins and efficient HPK1 activation after BCR stimulation. Furthermore, HPK1 augmented, whereas its kinase-dead mutant inhibited IkappaB kinase beta (IKKbeta) activation by BCR engagement. These results reveal a novel BCR signaling pathway leading to the activation of HPK1 and subsequently IKKbeta, in which BASH recruits tyrosine-phosphorylated HPK1 into the BCR signaling complex.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Elucidation of the differences between the 430- and 455-nm absorbing forms of P450-isocyanide adducts by resonance Raman spectroscopy.

Alkylisocyanide adducts of microsomal P450 exist in two interconvertible forms, each giving the Soret maximum around 430 or 455 nm. This is demonstrated with a rabbit liver P450 2B4. Resonance Raman spectra of the 430- and 455-nm forms were examined for typical P450s of the two types as well as for P450 2B4 because the 430-nm form of P450 2B4 is liable to change into P420. P450cam and P450nor were selected as a model of the 430- and 455-nm forms, respectively. For the n-butyl isocyanide (CNBu) adduct, the Fe(II)-CNBu stretching band was observed for the first time at 480/467 cm(-1) for P450cam and at 471/459 cm(-1) for P450nor with their (12)CNBu/(13)CNBu derivatives. For P450cam, but not P450nor, other (13)C isotope-sensitive bands were observed at 412/402, 844/835, and 940/926 cm(-1). The C-N stretching mode was identified by Fourier transform IR spectroscopy at 2116/2080 cm(-1) for P450cam and at 2148/2108 cm(-1) for P450nor for the (12)C/(13)C derivatives. These findings suggest that the binding geometry of isocyanide differs between the two forms-bent and linear structures for P450cam-CNBu and P450nor-CNBu, respectively. In contrast, in the ferric state, the Raman (13)C isotopic frequency shifts, and the IR C-N stretching frequencies (2213/2170 and 2215/2172 cm(-1)) were similar between P450cam and P450nor, suggesting similar bent structures for both.

Animals↗
PubMed2001

Differential expression of max and two types of c-myc genes in a tetraploid fish, the common carp (Cyprinus carpio).

We cloned the full-length cDNA of max gene from the common carp (Cyprinus carpio). The cDNA clone of carp max consists of 1209 bp and contained an ATG-initiated ORF consisting of 156 aa. The carp MAX share 76.7-93.8% aa identity with those of human, mouse, rat, chicken, Xenopus and zebrafish, respectively. The 15 bp alternative splicing was observed in the loop region of helix-loop-helix and is not previously described in mammalian max sequences. Transcripts of max gene were observed in all of the tissues of carp investigated in this study. The highest expression was found in the ovary, and the transcripts in hepatopancreas and heart were low. Two carp c-myc genes (CAM1 and CAM2) showed differential expression pattern. The expression of max was concomitant with CAM2 expression, but not with CAM1. It has been reported that MYC/MAX heterodimer as a regulator of gene expression has been maintained throughout vertebrate evolution, and the expression of c-myc has been concomitant with max expression. In addition, according to phylogenetic analysis, CAM1 is evolving faster than CAM2 after gene duplication. Therefore, this result suggests that CAM1 may evolve to obtain a new function different from c-myc.

Amino Acid Sequence↗