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Biomedical subjects

M Ogasawara

Publications and source records attributed to M Ogasawara.

At least 19 recordsLinked to original sources

Mediastinal emphysema and bilateral pneumothoraces with chronic GVHD in patients after allogeneic stem cell transplantation.

It is difficult to treat lung complications caused by chronic graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). We retrospectively analyzed the characteristics of five patients with mediastinal emphysema (ME) and bilateral pneumothoraces (BP) caused by chronic lung GVHD after allo-SCT. Four of these patients had undergone unrelated SCT, and three had had HLA-identical unrelated donors. All patients received total body irradiation (TBI) during conditioning. Immunosuppressive agents were administered as GHVD prophylaxis, but two patients developed acute GVHD and all the five developed chronic GVHD. The onset of lung complications was 99-1915 days (median, 202 days) after SCT. The onset of ME and BP was 6-48 days (median, 23 days) after the onset of lung complications. Immunosuppressive agents were initially beneficial on the lung complications, but the patients later showed no response to therapy, and all died from respiratory failure 7-195 days (median, 28 days) after the development of ME and BP. The results suggest that these complications progress rapidly, are resistant to treatment, and have a poor prognosis. It is therefore important to start prophylaxis and treatment as early as possible.

Adolescent↗

Characterization of acute somatosensory pain transmission in P/Q-type Ca(2+) channel mutant mice, leaner.

To study the role of the Ca(v)2.1/alpha(1A) (P/Q-type) Ca(2+) channel in somatosensory pain processing, behavioral and electrophysiological studies were conducted using the leaner (tg(la)/tg(la)) mouse. Behavioral analyses in tg(la)/tg(la) revealed reduced responses to mechanical stimuli, and enhanced responses to heat stimuli. Electrophysiological analyses showed that tg(la)/tg(la) had a significantly reduced ability to evoke dorsal root potentials, suggesting a functional deficit in the spinal dorsal horn local circuitry responsible for presynaptic inhibition of primary sensory fibers. These results suggest the critical importance of the P/Q-type channel in modulation of acute somatosensory pain transmission in spinal cord.

Action Potentials↗

Rhodium-catalyzed asymmetric 1,4-addition of organoboron reagents to 5,6-dihydro-2(1H)-pyridinones. Asymmetric synthesis of 4-aryl-2-piperidinones.

Catalytic asymmetric synthesis of 4-aryl-2-piperidinones was realized for the first time by asymmetric 1,4-addition of arylboron reagents to 5,6-dihydro-2(1H)-pyridinones in the presence of a chiral bisphosphine-rhodium catalyst. In the reaction introducing 4-fluorophenyl group, the use of 4-fluorophenylboroxine and 1 equiv (to boron) of water at 40 degrees C gave the highest yield of the arylation product with high enantioselectivity (98% ee). The (R)-4-(4-fluorophenyl)-2-piperidinone obtained here is a key intermediate for the synthesis of (-)-Paroxetine.

Boron Compounds↗

The membrane-type collectin CL-P1 is a scavenger receptor on vascular endothelial cells.

Collectins are a family of C-type lectins that have collagen-like sequences and carbohydrate recognition domains (CRD). They are involved in host defense through their ability to bind to carbohydrate antigens of microorganisms. The scavenger receptors type A and MARCO are classical type scavenger receptors that have internal collagen-like domains. Here we describe a new scavenger receptor that is a membrane-type collectin from placenta (collectin placenta 1 (CL-P1)), which has a typical collectin collagen-like domain and a CRD. The cDNA has an insert of about 2.2 kilobases coding for a protein containing 742 amino acid residues. The deduced amino acid sequence shows that CL-P1 is a type II membrane protein, has a coiled-coil region, a collagen-like domain, and a CRD. It resembles type A scavenger receptors because the scavenger receptor cysteine-rich domain is replaced by a CRD. Northern analyses, reverse transcription-polymerase chain reaction, and immunohistochemistry show that CL-P1 is expressed in vascular endothelial cells but not in macrophages. By immunoblotting and flow cytometry CL-P1 appears to be a membrane glycoprotein of about 140 kDa in human umbilical vein or arterial endothelial cells, placental membrane extracts, and CL-P1 transfected Chinese hamster ovary cells. We found that CL-P1 can bind and phagocytose not only bacteria (Escherichia coli and Staphylococcus aureus) but also yeast (Saccharomyces cerevisiae). Furthermore, it reacts with oxidized low density lipoprotein (OxLDL) but not with acetylated LDL (AcLDL). These binding activities are inhibited by polyanionic ligands (polyinosinic acid, polyguanylic acid, dextran sulfate) and OxLDL but not by polycationic ligands (polyadenylic acid or polycytidylic acid), LDL, or AcLDL. These results indicate that CL-P1 might play important roles in host defenses that are different from those of soluble collectins in innate immunity.

Amino Acid Sequence↗

Expression of thyroid transcription factor-1 (TTF-1) gene in the ventral forebrain and endostyle of the agnathan vertebrate, Lampetra japonica.

The Thyroid transcription factor-1 (TTF-1) gene belongs to the Nkx-2.1 subfamily and encodes a transcription factor containing an NK-2-type homeodomain. In our study, we isolated and characterized cDNA clones for the TTF-1/Nkx-2.1 orthologue (LjTTF-1) from the agnathan vertebrate Lampetra japonica. Spatial and temporal expression patterns assessed by in situ hybridization revealed the expression of LjTTF-1 in the anterior nerve cord and anteroventral region of the pharynx. The neural expression was subsequently restricted to the ventral diencephalon. The pharyngeal expression, on the other hand, extended posteriorly to the fourth pharyngeal-pouch level and was finally localized in the endostyle anlage. In the differentiated endostyle of ammocoete larvae, the expression of LjTTF-1 was chiefly detected in type 2a, 2b, and 2c cells, which develop adjacent to glandular cells. These expression patterns of LjTTF-1 support the idea that this gene family plays an important role in the development of the rostral brain and endostyle equivalent organs. Furthermore, histological comparisons between TTF-1/Nkx-2.1 expression in the endostyles of ammocoetes and ascidians suggested the possibility that the organogenetic architecture of the endostyle is conserved among chordates.

Amino Acid Sequence↗

Relation between body composition and age in healthy Japanese subjects.

OBJECTIVE: To describe the relation between body composition and age measured by dual-energy X-ray absorptiometry (DXA) in healthy Japanese adults. DESIGN: Cross-sectional study. SUBJECTS AND MEASUREMENTS: The subjects were 2411 healthy Japanese adults (males 625, females 1786, age 20--79 y) who attended the Fukuoka Health Promotion Center, Fukuoka, Japan for health check-up. Body composition was determined by DXA (QDR-2000, Hologic) for the whole body and three anatomical regions of arms, legs and trunk. RESULTS: The mean values of body mass index (BMI) and percentage fat mass (%FM) were 23.2+/-3.1 (s.d.) kg/m(2) and 21.8+/-6.8% for males and 22.1+/-3.3 kg/m(2) and 32.0+/-7.5% for females, respectively. For males, curvilinear relations with the peaks in their forties or fifties were seen for the variables associated adiposity, ie BMI, waist and hip circumference, waist-hip ratio, total or regional fat mass (FM), %FM and ratio of trunk FM to leg FM. For females, most of these variables increased linearly in older subjects. Lean mass (LM), bone mineral content (BMC) and bone mineral density (BMD) of the whole body and appendicular LM were relatively constant until the forties and then decreased in both sexes. The rates of decrease in the total or appendicular LM were larger for males than for females, whereas those in BMC or BMD were larger for females than for males. CONCLUSIONS: This study presents the first detailed data on body composition in Japanese, which may be useful when comparing with populations of different racial and ethnic backgrounds and studying ill subjects.

Absorptiometry, Photon↗

Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia.

PRAME (Preferentially expressed antigen of melanoma) has been previously identified as a melanoma antigen recognized by cytotoxic T cells (CTLs) and found to be expressed in a variety of cancer cells including leukaemic cells. We have screened 98 Japanese patients with leukaemia and lymphoma for expression of the PRAME gene using semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Forty-one patients (42%) showed high levels of PRAME expression. Eight of these patients were then monitored using real-time PCR for a period of 10-37 months. Significant reductions in the PRAME expression were observed in all patients after chemotherapy. An increased expression was detected in the two patients who relapsed, one of which was before cytological diagnosis. These changes were correlated with those of other known genetic markers, such as the bcr-abl gene. Therefore, quantitative monitoring of the PRAME gene using real-time PCR method may be useful for detecting minimal residual disease and to predict subsequent relapse, especially in patients without known genetic markers. In addition, a PRAME-positive leukaemia cell line and fresh leukaemic cells were found to be susceptible to lysis by PRAME-specific CTLs established from a patient with melanoma, suggesting that the PRAME peptide can also be a target leukaemia antigen for T cells.

Adult↗

Association of serum tumour necrosis factor-alpha with serum low-density lipoprotein-cholesterol and blood pressure in apparently healthy Japanese women.

1. The pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha is considered to be involved in the development of atherosclerosis by inducing local inflammatory responses in the vascular wall. Because TNF-alpha is also known to affect lipid and glucose metabolism, the association between the circulating concentration of TNF-alpha and atherogenic risk factors was examined in 82 apparently healthy Japanese women (aged 19-69 years; mean age 48.5 years). 2. The mean (+/-SD) serum TNF-alpha concentration was 2.7+/-0.9 pg/mL (range 1.4-5.9 pg/mL). The TNF-alpha concentration showed significant correlations with age (r = 0.28; P = 0.01), body mass index (r = 0.27; P = 0.01), the waist-hip ratio (r = 0.41; P = 0.0002), percentage body fat (r = 0.30; P = 0.006), systolic (r = 0.32; P = 0.004) and diastolic (r = 0.24; P = 0.03) blood pressure, total cholesterol (r = 0.27; P = 0.02) and low-density lipoprotein-cholesterol (LDL-C; r = 0.36; P = 0.001), while the correlations with high-density lipoprotein-cholesterol (r = -0.20; P = 0.08) and insulin resistance estimated by the homeostasis model assessment (HOMA(IR); r = 0.16; P = 0.15) were not statistically significant. 3. When adjusted for age and menopause, TNF-alpha was significantly associated with systolic blood pressure (r = 0.25; P = 0.02) and LDL-C (r = 0.27; P = 0.02). The association between TNF-alpha and LDL-C remained significant when adjustment was made for age, menopause and the waist-hip ratio (r = 0.24; P = 0.03). 4. Our results indicate that TNF-alpha may play a role in modulating blood pressure and LDL-C.

Adult↗

Effect of prostatic neuropeptides on migration of prostate cancer cell lines.

BACKGROUND: A previous study by the same authors demonstrated that among various neuropeptides in the prostate, calcitonin gene-related peptide (CGRP) and gastrin-releasing peptide (GRP) increased the invasive capacity of PC-3 prostate cancer cells through enhancement of cell motility, while substance P (SP) inhibited the invasiveness through suppression of motile response. METHODS: The effect of 10 kinds of neuropeptides were investigated, including CGRP, GRP, SP, neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), methionine-enkephalin (M-ENK), glucagon and parathyroid hormone-related protein (PTH-rP), on the invasion of DU-145 prostate cancer cells through a reconstituted basement membrane (Matrigel) and the haptotactic migration of DU-145, TSU-pr1 and LNCaP prostate cancer cells using a Transwell cell culture chamber assay. RESULTS: It was found that GRP, CGRP and PTH-rP increased the invasive capacity of tumor cells. In contrast, SP, VIP, CT, L-ENK, M-ENK, NPY and glucagon had no significant effect. These three neuropeptides also increased the haptotactic migration of tumor cells to fibronectin. In addition VIP, CGRP and GRP increased the haptotactic migration of LNCaP prostate cancer cells and GRP and PTH-rP increased the migration of TSU-pr1 cells. CONCLUSION: The results indicated that some prostatic neuropeptides increased the invasive potential of prostate cancer cells partially through enhancement of cell motility.

Calcitonin Gene-Related Peptide↗

Participation of type I interferon in the decreased virulence of the UL13 gene-deleted mutant of herpes simplex virus type 1.

We isolated a UL13 gene-deleted mutant of the herpes simplex virus type 1 (HSV-1) strain VR3 (VRDelta13) and its revertant virus (VRDelta13R). This deletion mutant still had virus host shutoff (vhs) activity, although a previous report had suggested the possibility of a functional relation between the UL13 product, that is protein kinase (PK), and vhs activity. We compared the in vivo growth of these viruses in BALB/c mice. VRDelta13 was cleared in the early period of intraperitoneal infection. VRDelta13 had a higher sensitivity to the mouse type I interferon (IFN) and showed a higher level of IFN induction in the study period of infection than did VR3 and VRDelta13R. These results suggest that a nonspecific antiviral response (i.e., the IFN system) may contribute to this rapid inhibition of viral replication in vivo.

3T3 Cells↗

Increased concentrations of cathepsin D in peritoneal fluid from women with endometriosis.

To assess the release of the proteolytic enzyme cathepsin D in endometriosis, concentrations in peritoneal fluid and serum were measured by ELISA in 54 women with (n = 33) and without (n = 21) endometriosis. Surgery was scheduled in either the proliferative or secretory phase of the menstrual cycle. The concentrations of cathepsin D in the peritoneal fluid were markedly elevated in the endometriosis patients (median 58 ng/ml, interquartile range 0-166 ng/ml) as compared to the controls (5 ng/ml, 0-86 ng/ml), especially in women with late stage disease (n = 19, stages III/IV) and in those not undergoing gonadotrophin-releasing hormone (GnRH) agonist therapy (n = 15). No significant difference was determined in cathepsin D concentrations of the serum from women with and without endometriosis. We conclude that cathepsin D is an important factor that may contribute to the pathogenesis of endometriosis, possibly by promoting digestion of extracellular matrix proteins. These results have implications for the therapeutic efficacy of GnRH agonists.

Adult↗

Role of the UL25 gene product in packaging DNA into the herpes simplex virus capsid: location of UL25 product in the capsid and demonstration that it binds DNA.

Recent studies have suggested that the herpes simplex type 1 (HSV-1) UL25 gene product, a minor capsid protein, is required for encapsidation but not cleavage of replicated viral DNA. This study set out to investigate the potential interactions of UL25 protein with other virus proteins and determine what properties it has for playing a role in DNA encapsidation. The UL25 protein is found in 42 +/- 17 copies per B capsid and is present in both pentons and hexons. We introduced green fluorescent protein (GFP) as a fluorescent tag into the N terminus of UL25 protein to identify its location in HSV-1-infected cells and demonstrated the relocation of UL25 protein from the cytoplasm into the nucleus at the late stage of HSV-1 infection. To clarify the cause of this relocation, we analyzed the interactions of UL25 protein with other virus proteins. The UL25 protein associates with VP5 and VP19C of virus capsids, especially of the penton structures, and the association with VP19C causes its relocation into the nucleus. Gel mobility shift analysis shows that UL25 protein has the potential to bind DNA. Moreover, the amino-terminal one-third of the UL25 protein is particularly important in DNA binding and forms a homo-oligomer. In conclusion, the UL25 gene product forms a tight connection with the capsid being linked with VP5 and VP19C, and it may play a role in anchoring the genomic DNA.

Animals↗

Results of vitrectomy performed at the time of phacoemulsification complicated by intravitreal lens fragments.

AIM: To evaluate outcome of vitrectomy performed at the time of phacoemulsification complicated by intravitreal lens material. METHODS: Clinical records associated with consecutive 8536 phacoemulsification procedures were reviewed retrospectively. RESULTS: 17 (0.20%) eyes had a posterior capsule rupture with retained lens material in the vitreous cavity that required vitrectomy. Final visual acuity was 0.5 or better in 14 eyes (82%) and 0.4 to 0.1 in three eyes (18%). Retinal detachment occurred in one eye during vitrectomy and two after the surgery. Cystoid macular oedema was observed in two eyes and none developed glaucoma. The corneal endothelial cell loss was 5.7% (SD 6.8 %) (n=15) at 3-6 months postoperatively. CONCLUSIONS: Combined vitrectomy and intraocular lens implantation at the time of phacoemulsification complicated by intravitreal lens material is an option to be considered to reduce the risk of postoperative complications including secondary glaucoma and corneal endothelial cell damage.

Aged↗

Large-scale cDNA analysis of the maternal genetic information in the egg of Halocynthia roretzi for a gene expression catalog of ascidian development.

The ascidian egg is a well-known mosaic egg. In order to investigate the molecular nature of the maternal genetic information stored in the egg, we have prepared cDNAs from the mRNAs in the fertilized eggs of the ascidian, Halocynthia roretzi. The cDNAs of the ascidian embryo were sequenced, and the localization of individual mRNA was examined in staged embryos by whole-mount in situ hybridization. The data obtained were stored in the database MAGEST (http://www.genome.ad.jp/magest) and further analyzed. A total of 4240 cDNA clones were found to represent 2221 gene transcripts, including at least 934 different protein-coding sequences. The mRNA population of the egg consisted of a low prevalence, high complexity sequence set. The majority of the clones were of the rare sequence class, and of these, 42% of the clones showed significant matches with known peptides, mainly consisting of proteins with housekeeping functions such as metabolism and cell division. In addition, we found cDNAs encoding components involved in different signal transduction pathways and cDNAs encoding nucleotide-binding proteins. Large-scale analyses of the distribution of the RNA corresponding to each cDNA in the eight-cell, 110-cell and early tailbud embryos were simultaneously carried out. These analyses revealed that a small fraction of the maternal RNAs were localized in the eight-cell embryo, and that 7.9% of the clones were exclusively maternal, while 40.6% of the maternal clones showed expression in the later stages. This study provides global insights about the genes expressed during early development.

Animals↗

Identification and expression of the lamprey Pax6 gene: evolutionary origin of the segmented brain of vertebrates.

The Pax6 gene plays a developmental role in various metazoans as the master regulatory gene for eye patterning. Pax6 is also spatially regulated in particular regions of the neural tube. Because the amphioxus has no neuromeres, an understanding of Pax6 expression in the agnathans is crucial for an insight into the origin of neuromerism in the vertebrates. We have isolated a single cognate cDNA of the Pax6 gene, LjPax6, from a Lampetra japonica cDNA library and observed the pattern of its expression using in situ hybridization. Phylogenetic analysis revealed that LjPax6 occurs as an sister group of gnathostome Pax6. In lamprey embryos, LjPax6 is expressed in the eye, the nasohypophysial plate, the oral ectoderm and the brain. In the central nervous system, LjPax6 is expressed in clearly delineated domains in the hindbrain, midbrain and forebrain. We compared the pattern of LjPax6 expression with that of other brain-specific regulatory genes, including LjOtxA, LjPax2/5/8, LjDlx1/6, LjEmx and LjTTF1. Most of the gene expression domains showed conserved pattern, which reflects the situation in the gnathostomes, conforming partly to the neuromeric patterns proposed for the gnathostomes. We conclude that most of the segmented domains of the vertebrate brain were already established in the ancestor common to all vertebrates. Major evolutionary changes in the vertebrate brain may have involved local restriction of cell lineages, leading to the establishment of neuromeres.

Amino Acid Sequence↗