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Biomedical subjects

M Takemura

Publications and source records attributed to M Takemura.

At least 37 records · Page 2Linked to original sources
PubMed2002

Prognostic factors after oesophagectomy and extended lymphadenectomy for squamous oesophageal cancer.

BACKGROUND: The prognosis of patients without nodal metastasis of oesophageal cancer is generally good, but recurrence develops in some cases. METHODS: Data on 88 consecutive patients with squamous oesophageal cancer who underwent three-field lymph node dissection from 1986 to September 1998 and who had no evidence of nodal disease were reviewed retrospectively. Disease status was based on histological examination of the section of each node with the largest surface area, stained with haematoxylin and eosin. RESULTS: The 3- and 5-year survival rates of patients without lymph node metastasis were 85 and 81 per cent respectively, better than in patients with metastasis. Twelve patients died from recurrence. Recurrence was haematogenous in nine patients and locoregional in three. Survival was worse in men, for patients with lesions located in the upper thoracic oesophagus, and in those with lymphatic or blood vessel invasion. Only the presence of lymphatic invasion correlated with survival on multivariate analysis (P = 0.04). CONCLUSION: Although survival was generally good in patients without nodal metastasis from oesophageal cancer following three-field lymph node dissection, patients with lymphatic invasion remained at risk for haematogenous dissemination.

Adult↗
PubMed2002

Role of leptin in pregnancy--a review.

Leptin is an adipocyte-derived hormone that decreases food intake and body weight via its receptor in the hypothalamus. In rodents, it also modulates glucose metabolism by increasing insulin sensitivity. We previously reported that leptin is produced by human placental trophoblasts. We also revealed that leptin gene expression in the placenta was augmented in severe pre-eclampsia, and suggested that placental hypoxia may play a role in this augmentation. Maternal plasma leptin levels correlated well with mean blood pressure, but not with body mass index. Plasma leptin levels in pre-eclamptic women with IUGR were higher than those without IUGR (P< 0.05). We further examined the effects of hyperleptinemia on the course of pregnancy by using transgenic mice (Tg) overexpressing leptin. In pregnant Tg mice, food intake was significantly less than non-Tg, and the fetal body weights were reduced to approximately 70 per cent of those of non-Tg. Resistin is a novel adipocyte-derived hormone that decreases insulin sensitivity and increases plasma glucose concentration, thus contributing the development of obesity-related type II diabetes mellitus. We recently found that resistin gene is expressed in the human placenta as well as adipose tissue. In this review, possible roles of placental leptin and resistin are discussed.

Adult↗
PubMed2002

Significant reduction of 125 I-meta-iodobenzylguanidine accumulation directly caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine, a toxic agent for inducing experimental Parkinson's disease.

A significant reduction of cardiac 123I-meta-iodobenzylguanidine (MIBG) accumulation has been reported in patients with idiopathic Parkinson's disease. However, it is unclear whether this reduction in cardiac sympathetic nerve is caused primarily or secondarily to the degeneration of sympathetic nerve centres which occurs in Parkinson's disease. Therefore, we examined neuronal 125I-MIBG accumulation in mice hearts of an experimental Parkinson's disease model and in sympathetic cells without any neuronal innervation. Cardiac accumulation of 125I-MIBG was determined 4h after intravenous injection of 125I-MIBG in mice pretreated with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP), an inducer of Parkinson's disease. In an in vitro study, uptake of 125I-MIBG was determined in a cultured pheochromocytoma cell line (PC-12), which was pretreated with MPTP. MPTP reduced MIBG accumulation mainly in its neuronal component of mice hearts, suggesting that MPTP impairs cardiac sympathetic nerves to uptake MIBG. Application of MPTP also caused near-complete blockade of 125I-MIBG accumulation in PC-12 cells. In the experimental PD models, it was shown that neuronal accumulation of MIBG was impaired by the direct action of MPTP to the sympathetic cells. These findings support the idea that cardiac sympathetic nerves are primarily impaired in Parkinson's disease despite the presence or absence of systemic autonomic failure.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Stimulation of DNA polymerase alpha by hypergravity generated by centrifugal acceleration.

Gravity alteration is known to influence cell proliferation. Here we tested the effects of hypergravity on the action of DNA polymerase alpha, one of the DNA replication enzymes in eukaryotes. Hypergravity was produced by horizontal centrifugal acceleration with a hand-made rotator. The reaction rate of DNA polymerase alpha in centrifuge tubes increased along with the acceleration up to 4g, when a plateau was reached. In contrast, no stimulation was observed with primase, DNA polymerase epsilon, and the E. coli DNA polymerase I Klenow fragment. Kinetic analysis of DNA polymerase alpha reactions revealed that, under high gravity conditions, the K(m) value for template DNA decreased while the V(max) stayed constant. In contrast, the centrifugal acceleration did not affect the K(m) values for deoxyribonucleoside triphosphates. These results suggest that the hypergravity enhances the activity of DNA polymerase alpha by increasing the affinity of the enzyme for template DNA. Such enhancement was more prominent with a low concentration of DNA polymerase alpha under low ionic conditions.

Animals↗
PubMed2001

Nitric oxide synthase/nicotinamide adenine dinucleotide phosphate-diaphorase in the brainstem trigeminal nuclei after transection of the masseteric nerve in rats.

In this study, the responses of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and neuronal nitric oxide synthase (nNOS) activities were quantitatively analyzed at different times in both ipsilateral and contralateral sides of trigeminal nuclei, after unilateral trigeminal muscle nerve transection, in Sprague Dawley rats. In the control animals, both NADPH-d- and nNOS-positive neurons were constitutively distributed in the rostrolateral solitary tract nucleus, dorsomedial part of trigeminal nucleus oralis (Vo/Sn), and superficial layers (VcI/II) of the trigeminal nucleus caudalis (Vc). NADPH-d-positive neurons appeared in the trigeminal mesencephalic nucleus ipsilaterally at 5 days (mean +/- SEM: 30.5 +/- 5.6) and were maintained until 8 weeks (33 +/- 10.6) after the denervation. In the trigeminal motor nucleus, NADPH-d-positive neurons appeared transiently and bilaterally, peaking at 1 week (663.5 +/- 156.2, ipsilateral side; 687.5 +/- 118.6, contralateral side) after unilateral denervation of the masseteric nerve. In both Vo/Sn and Vc, the number of NADPH-d-positive neurons in the control animals showed a decrease at 3 days but significantly increased from 5 days to 1 week and gradually fell to the control values by 8 weeks after the denervation. There were no significant differences observed between the two sides in either Vo/Sn or Vc. nNOS-positive neurons were similarly distributed and the numbers of labeled neurons were similar to those of NADPH-d-positive neurons after the denervation, although the changes were delayed by approximately 1 week. In conclusion, after unilateral nerve transection, the peak NADPH-d activity occurs 1 week prior to nNOS activity.

Animals↗
PubMed2001

Structural requirements of sphingosine molecules for inhibition of DNA primase: biochemical and computational analyses.

Using 28 chemically well-defined compounds containing D-erythro-sphingosine and its analogues, we analyzed structure-activity relationships for DNA primase inhibition. Biochemical studies demonstrated a positively charged amino group at C2 and a long aliphatic chain to be absolutely required for inhibition. Whereas C2-amino group is intact, sphingosine 1-phosphate was totally inactive. This result could be due to cancellation of positive charge of the amino group by the interaction with negatively charged C1-phosphate, since simulations with the software INSIGHT II showed these two groups to be close enough to interact. The hydroxyl group at C3 and trans-double bond at C4-C5 were also found to be important for the inhibition. Dehydroxylation of C3, as well as saturation or cis-conversion of the trans-double bond led to decrease of inhibitory activity. Despite saturation of the double bond, introduction of a hydroxyl group into C4 of dihydrosphingosine resulted in restoration of inhibition. Conversion of the double bond into a triple bond did not abolish but rather enhanced the inhibitory activity. Among sphingosine stereoisomers, the naturally occurring D-erythro-sphingosine proved to be the strongest inhibitor. To ascertain the contribution of the total conformation to the inhibition, especially of the long aliphatic chain, we constructed a 3D-quantitative structure-activity relationship model using the computer program Catalyst/HipHop on the basis of information described above. Analysis of the hypothesis model for active compounds revealed that the orientation of aliphatic chain, represented by the dihedral angle of C2-3-4-5, correlated well with the inhibition. Modifications such as deletion of the hydroxyl group at C3 or saturation of the C4-C5 double bond caused shifts in the dihedral angle of C2-3-4-5, with concomitant decrease in inhibitory activity.

Animals↗
PubMed2001

Histamine N-methyltransferase regulates histamine-induced phosphoinositide hydrolysis in guinea pig cerebellum.

We report here that the dose-response curve of the histamine-stimulated phosphoinositide hydrolysis in the guinea pig cerebellar slices was shifted to the left when the slices were pretreated with SKF 91488 (100 microM), a specific inhibitor of histamine N-methyltransferase (HMT). In contrast, the pretreatment of the cerebellar slices with aminoguanidine (100 microM - 1 mM), an inhibitor of diamine oxidase, had no effect on histamine-induced phosphoinositide hydrolysis. HMT mRNA was expressed abundantly in cerebellum, especially in Purkinje cells. These observations suggest that HMT regulates histaminergic neurotransmission in guinea pig cerebellum more predominantly than diamine oxidase in histamine degradation.

Animals↗
PubMed2001

Secondary somatosensory cortex stimulation facilitates the antinociceptive effect of the NO synthase inhibitor through suppression of spinal nociceptive neurons in the rat.

Electrical stimulation of the secondary somatosensory cortex (S-II), which is clinically effective in some chronic pain patients, produces a weak antinociception by itself and also strongly facilitates the antinociceptive effect of the neuronal NO synthase inhibitor 7-nitro-indazole in laboratory animals (rats). The present study thus investigated the mechanisms by which S-II stimulation facilitates the 7-nitro-indazole-induced antinociception. S-II stimulation in combination with 7-nitro-indazole at a subeffective dose, 5 mg/kg, synergistically reduced the number of cells expressing c-Fos in response to intraplantar injection of formalin in the superficial regions (laminae I and II) of the L4 and L5 spinal dorsal horn in conscious rats, although each had no significant effect. A similar synergism produced by S-II stimulation and 7-nitro-indazole was also confirmed in both the first and second phases in the formalin-induced behavioral nociception test. The synergistic antinociception exerted by S-II stimulation in combination with 7-nitro-indazole was resistant to systemic administration of the opioid antagonist naloxone or the alpha-adrenoceptor antagonist phentolamine. In contrast, intrathecally administered methysergide, a serotonin receptor antagonist, at 20 microg/rat, abolished the first-phase, but not the second-phase, antinociception following S-II stimulation in combination with 7-nitro-indazole. These findings suggest that S-II stimulation, in combination with inhibition of neuronal NO synthase, can suppress spinal nociceptive neurons, at least in part through the descending spinal serotonergic pathway, resulting in antinociception.

Adrenergic alpha-Antagonists↗
PubMed2001

Stimulation of DNA polymerase alpha activity by cdk2-phosphorylated Rb protein.

We propose a new role of retinoblastoma protein as a cell growth activator in its phosphorylated form. The hyper-phosphorylated retinoblastoma protein generated by the action of cdk2/cyclin E strongly stimulated the activity of DNA polymerase alpha, but did not stimulate DNA polymerases delta, epsilon, or primase. But, cdk4/cyclin D-phosphorylated retinoblastoma protein showed little stimulation. Hyper-phosphorylated retinoblastoma protein interacted with the catalytic subunit of DNA polymerase alpha, and stabilised DNA polymerase alpha from heat inactivation at 45 degrees C. These results suggest that in G1 phase, hypo-phosphorylated retinoblastoma protein suppresses the progression of cell cycle as a transcription inhibitor, but that after phosphorylation by cdk2/cyclin E at the G1/S boundary, hyper-phosphorylated retinoblastoma protein acts as a cell-cycle promoter by optimising the DNA polymerase alpha reaction.

Animals↗
PubMed2001

Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair.

Nucleotide excision repair (NER) is carried out by xeroderma pigmentosum (XP) factors. Before the excision reaction, DNA damage is recognized by a complex originally thought to contain the XP group C responsible gene product (XPC) and the human homologue of Rad23 B (HR23B). Here, we show that centrin 2/caltractin 1 (CEN2) is also a component of the XPC repair complex. We demonstrate that nearly all XPC complexes contain CEN2, that CEN2 interacts directly with XPC, and that CEN2, in cooperation with HR23B, stabilizes XPC, which stimulates XPC NER activity in vitro. CEN2 has been shown to play an important role in centrosome duplication. Thus, those findings suggest that the XPC-CEN2 interaction may reflect coupling of cell division and NER.

Calcium-Binding Proteins↗
PubMed2001

Hip fracture prevention trial using hip protectors in Japanese nursing homes.

A method to protect the hips during falls could effectively reduce the incidence of hip fractures. We report the results of the first hip protector trial in Japan, performed between July 1996, and September 1999. One hundred and sixty-four elderly female residents of nursing homes, with Activities of Daily Living above the wheelchair level, agreed to participate in this study. Among them, 88 were randomly selected to wear a hip protector and 76 controls did not. All falls and resulting injuries were recorded daily. In anthropometric measurements and ultrasonic bone evaluation, no significant differences were found between the two groups, except in height. During an average of 377 days, the wearers and the non-wearers fell a total of 131 and 90 times, respectively. Among the wearers, there were two non-hip fractures and one hip fracture, so the annual hip fracture rate was calculated at 1.2%, against 8 hip fractures among the non-wearers, or 9.7% per year. The hip fracture rate was significantly lower among the wearers than non-wearers, while the annual number of falls per subject and the distribution of fallers remained the same. According to Cox's proportional hazard regression analysis, the effect of the hip protector on hip fracture prevention was independent of anthropometric data, ultrasonic bone assessment values or number of falls. Moreover, even after limiting the subjects to fallers only, the annual hip fracture rate in non-wearers was higher than in wearers (19.8% vs 2.0%) and the annual hip fracture rate per fall in wearers was lower than that in non-wearers (0.8% vs 8.2%). It was thus concluded that the hip protector is a beneficial device for the prevention of hip fractures.

Accidental Falls↗
PubMed2001

Effects of intrathecal c-fos antisense oligodeoxynucleotide on adjuvant-induced thermal hyperalgesia.

We examined the effects of intrathecally preadministered injections of a phosphorothioate analog of c-fos antisense and mismatch oligodeoxynucleotides (ODNs) on the withdrawal latency to a thermal stimulus following unilateral injection of complete Freund's adjuvant (CFA) into the hind footpad of rats. Pretreatment with the c-fos antisense ODN significantly decreased the CFA-induced expression of c-Fos protein dose-dependently in ipsilateral laminae I/II (LI/II) of the dorsal horn (mean +/- SEM per section: 10 nM ODN, 43.9+/-1.3; 25 nM ODN, 19.4+/-4.1) compared with pretreatment with the mismatch ODN (63.6+/-2.9; 60.6+/-4.0) or saline (56.6+/-5.5). Animals pre-treated with 25 nM of the c-fos antisense ODN significantly increased the withdrawal latency to the noxious thermal stimulation (63.0-70.5%; compared with contralateral to the CFA injection) compared with animals pretreated with mismatch ODN (28.5-42.6%) or saline (26.4-45.3%) from 0 to 5 h after unilateral injection of CFA into the hind footpad. Pretreatment with 10 nM antisense ODN had a less significant effect. These results indicate that the expression of CFA-induced c-Fos in the dorsal horn might facilitate thermal nociception.

Animals↗
PubMed2001

Poxviruses and the origin of the eukaryotic nucleus.

A number of molecular forms of DNA polymerases have been reported to be involved in eukaryotic nuclear DNA replication, with contributions from alpha-, delta-, and epsilon-polymerases. It has been reported that delta-polymerase possessed a central role in DNA replication in archaea, whose ancestry are thought to be closely related to the ancestor of eukaryotes. Indeed, in vitro experiment shown here suggests that delta-polymerase has the potential ability to start DNA synthesis immediately after RNA primer synthesis. Therefore, the question arises, where did the alpha-polymerase come from? Phylogenetic analysis based on the nucleotide sequence of several conserved regions reveals that two poxviruses, vaccinia and variola viruses, have polymerases similar to eukaryotic alpha-polymerase rather than delta-polymerase, while adenovirus, herpes family viruses, and archaeotes have eukaryotic delta-like polymerases, suggesting that the eukaryotic alpha-polymerase gene is derived from a poxvirus-like organism, which had some eukaryote-like characteristics. Furthermore, the poxvirus's proliferation independent from the host-cell nucleus suggests the possibility that this virus could infect non-nucleated cells, such as ancestral eukaryotes. I wish to propose here a new hypothesis for the origin of the eukaryotic nucleus, posing symbiotic contact of an orthopoxvirus ancestor with an archaebacterium, whose genome already had a delta-like polymerase gene.

Amino Acid Sequence↗
PubMed2001

GABA B receptor-mediated effects on expression of c-Fos in rat trigeminal nucleus following high- and low-intensity afferent stimulation.

We examined the effects of systemic administration of a GABA(B) receptor agonist, baclofen, or antagonist, phaclofen, on the expression of c-Fos protein induced 3h after electrical stimulation of the trigeminal ganglion at low (0.1 mA) or high intensities (1.0 mA) in the urethane-anesthetized rat. In saline-treated rats, 10 min stimulation of the trigeminal ganglion induced c-Fos-immunopositive neurons throughout the full extent of the ipsilateral superficial layers of the trigeminal nucleus caudalis, and dorsal or dorsomedial part of the nuclei rostral to obex (trigeminal nucleus principalis, dorsomedial nucleus of trigeminal nucleus oralis and dorsomedial nucleus of trigeminal nucleus interpolaris). Animals stimulated at 1.0 mA induced a significantly higher number of labeled neurons in all the trigeminal sensory nuclei than animals stimulated at 0.1 mA. In rats treated with 20mg/kg i.p. baclofen and stimulated at 0.1 mA, the numbers of Fos-positive neurons in all the trigeminal sensory nuclei were significantly decreased compared to saline-treated controls. After stimulation at 1.0 mA in rats treated with baclofen, the numbers of Fos-positive neurons in all the trigeminal sensory nuclei were also significantly decreased. In rats treated with 2mg/kg i.p. phaclofen and stimulated at 1.0 mA, the numbers of Fos-positive neurons were significantly increased in all the trigeminal sensory nuclei. However, after stimulation at 0.1 mA in rats treated with phaclofen, the numbers of Fos-positive neurons were significantly decreased in the superficial layers and magnocellular zone of trigeminal nucleus caudalis and dorsomedial nucleus of trigeminal nucleus oralis. These results indicate that the expression of c-Fos in the trigeminal sensory nucleus is differentially regulated through GABAB receptors in a manner that is dependent on the nucleus and the type of primary afferents that are activated by different stimulus intensities. Systemic administration of baclofen could inhibit both nociceptive and non-nociceptive sensory activity in the trigeminal sensory nucleus. Systemic administration of phaclofen could enhance nociceptive sensory activity but not non-nociceptive activity.

Animals↗
PubMed2001

IFN-gamma production in response to IL-18 or IL-12 stimulation by peripheral blood mononuclear cells of atopic patients.

BACKGROUND: Several studies have shown that interleukin (IL)-4 and interferon-gamma (IFN-gamma) are important for the regulation of immunoglobulin E (IgE) production and that IL-18 and IL-12 induce IFN-gamma. OBJECTIVE: IFN-gamma production in response to IL-18 or IL-12 stimulation was investigated in peripheral blood mononuclear cells (PBMCs) of atopic patients with various levels of serum IgE. METHODS: Cytokine production from PBMCs was measured following stimulation with a non-specific stimulator (phytohemagglutinin: PHA), IL-18 or IL-12 in 12 healthy controls and 26 atopic patients with various serum IgE levels. RESULTS: IFN-gamma production by IL-18-stimulated PBMCs was positively correlated with IFN-gamma production by IL-12-stimulated PBMCs (P < 0.05). However some atopic patients showed discrepancy between the levels of IFN-gamma production stimulated by IL-12 and by IL-18. CONCLUSIONS: The results shown here suggest the presence of abnormalities in the IL-12 and/or IL-18 signalling pathways, such as genetic defects in the atopic patients.

Adolescent↗
PubMed2001

Relationship between osteoprotegerin/osteoclastogenesis inhibitory factor concentration in synovial fluid and disease severity in individuals with osteoarthritis of the knee.

We studied the relationship between osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) concentration in synovial fluid from individuals with osteoarthritis (OA) of the knee and the severity of this condition. The study population included 111 Japanese women with knee OA (153 knees) and 23 normal controls. Osteoarthritic changes were graded according to the system of Kellgren and Lawrence. The concentration of OPG/OCIF in synovial fluid increased with severity of knee OA and was significantly higher in individuals with OA of grade IV than in those with OA of grade 0 or grade 1. It has been shown in a previous study that administration of OPG/OCIF prevents cartilage destruction in adjuvant-induced arthritis in rats. The increase in the concentration OPG/OCIF in synovial fluid of individuals with knee OA might thus reflect a compensatory response to degeneration of articular cartilage and serve to protect cartilage rather than be a cause of OA.

Aged↗
PubMed2001

Fate of the mutated IgG2 heavy chain: lack of expression of mutated membrane-bound IgG2 on the B cell surface in selective IgG2 deficiency.

IgG2 deficiency is clinically characterized by sinopulmonary infections caused by pneumococcus and Hemophilus. We reported homozygous one-base insertion (1793insG) in the C(gamma)2 gene in two Japanese siblings in whom serum IgG2 levels were under detection limits. The 1793insG was present in exon 4, just upstream from the alternative splice site for M exons; the result being a complete amino acid change in transmembrane and cytosolic parts of membrane-bound gamma2 heavy chain (m gamma 2HC). To determine why this mutation caused selective and complete IgG2 deficiency, we constructed expression vectors of normal and mutant membrane-bound chimeric IgG heavy chain cDNAs. Stable transformants, Ag8N-L and Ag8M-L, expressing either normal and mutant chimeric IgG heavy chain with light chain respectively were obtained using P3X63Ag8653 as recipient cells. Of the Ag8N-L, 22.1% were surface IgG+; however, none of the Ag8M-L were surface IgG+. Addition of an anti-human IgG antibody induced cell death of Ag8N-L and we considered that the expressed chimeric IgG protein on Ag8N-L might function as the Ig receptor for signal transduction. However, Ag8M-L did not express mutant IgG on its surface nor did it secrete this mutant into culture medium. The mutant chimeric IgG protein was rapidly degraded within Ag8M-L. Thus, the mutated IgG2 heavy chain in our patient could not be expressed on the cell surface because of loss of the transmembrane domain and the evolutionally conserved cytoplasmic domain. In humans, B cells expressing surface IgG are indispensable for secretion of IgG.

Amino Acid Sequence↗