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Biomedical subjects

Hiroyuki Kamiya

Publications and source records attributed to Hiroyuki Kamiya.

At least 73 records · Page 4Linked to original sources
PubMed2004

[Male fertility in space].

The effects of simulated microgravity on mammalian reproduction were studied using tail-suspended mice, during parabolic flight in a jet plane and in a horizontal clinostat device. In the tail-suspended mouse, which is a model of the shift of body fluid in a microgravity environment, atrophy of the testis and decrease of serum testosterone level were observed. The sperm motility decreased in the muG condition produced by the parabolic flight. There were no statistically significant differences in the efficiency of achieving normal fertilization in vitro, but there was a statistically significant decrease in the number of embryos reaching the morula and blastocyst stages after 96 hours in culture under clinostat rotation. These results suggest that the process of fertilization in vitro is not sensitive to the gravitational vector. However, the possibility exists that microgravity increases the disturbance of spermatogenesis and sperm motility or the frequency of early embryonic lethality. On the possibility of reproduction in space, there are some problems such as the cosmic radiation besides gravity. It is necessary to carry out further experiments in outer space.

Animals↗
PubMed2004

[A case of sparganosis with eosinophilic pleural effusion].

A 61 year-old man was admitted to our hospital complaining of exertional dyspnea and presented with left pleural effusion. Laboratory findings showed peripheral eosinophilia and a slightly elevated inflammatory reaction. Chest X-ray film and CT revealed left pleural effusion, but there were no particular abnormal findings on the lung fields. Pleural effusion was exudative, yellowish and contained numerous eosinophils. His detailed medical history showed that he had eaten uncooked snakes, which led us to suspect parasite diseases. Multiple-dot ELISA method was performed to detect specific anti-parasite antibody. The patient was diagnosed with sparganosis after the detection of a highly positive reaction against Spirometra erinacei-europaei in both serum and pleural effusion. Parasite disease is an important consideration on differential diagnosis of eosinophilic pleural effusion, and multiple-dot ELISA method might be helpful for screening it.

Diagnosis, Differential↗
PubMed2003

Penile apoptosis in association with p53 under lack of testosterone.

It is known that testosterone deficiency induces apoptosis in the prostate and that p53 protein is involved in this apoptosis. Therefore, p53 protein may also be involved in apoptosis induction in a testosterone-deficient state in the penis. In this study, we investigated whether castration and chemical castration induce apoptosis at penile tissue in rats, and whether p53 protein is involved in this apoptosis. Male SD rats aged 8 weeks were divided into four groups: 1) the Control group; 2) the Castration group; 3) the Estrogen group, in which rats received betaestradiol 17-(beta-D-glucuronide) injection of 500 microg/body/day; and 4) the LH-RH group, in which rats received LH-RH analogue (leuprorelin acetate) injection of 2 mg/kg. The rats were sacrificed after treatment on days 1, 3, 5, 14, and 28 by cervical dislocation. Apoptotic cells and p53 protein-positive cells were observed on the 5th day after treatment and thereafter in all castration, estrogen, and LH-RH groups. These findings showed that both castration and chemical castration induced p53 protein in vascular endothelial cells in the corpus cavernosus during the process of losing testosterone. It was also suggested that in such states, apoptosis is induced in vascular endotherial cells in the corpus cavernosus.

Animals↗
PubMed2003

Pharmacokinetic and pharmacodynamic considerations in gene therapy.

During gene therapy the concentration of plasmid DNA or oligonucleotides in the plasma can be quite different from their concentrations in the nucleus or cytosol where they exert their actions. For a better understanding of the apparent discrepancies between pharmacokinetics (PK) and pharmacodynamics (PD), a new concept for intracellular PK with an emphasis on the final efficacy of gene transcription is needed. Here, the conventional PK and intracellular PK and PD of non-viral gene delivery systems are discussed, together with a new concept, referred to as controlled intracellular disposition, which integrates these factors to gain a better understanding of gene expression in the nucleus. The importance of optimizing the system from a transcriptional point of view in the nucleus is also discussed. These new concepts must be integrated to develop an optimized non-viral gene delivery system.

Brain↗
PubMed2003

Mutagenic effects of 2-hydroxy-dATP on replication in a HeLa extract: induction of substitution and deletion mutations.

The mutagenicity of an oxidized form of dATP, 2-hydroxydeoxyadenosine 5'-triphosphate (2-OH-dATP), was examined using an SV40 origin-dependent in vitro replication system with a HeLa extract. 2-OH-dATP induced mutations in a dose-dependent manner and elicited substitution and deletion mutations. Of the substitutions, a G.C-->A.T transition including a tandem (CC-->TT) mutation was mainly observed. This result agrees with our previous observation that mammalian DNA polymerase alpha misincorporates the oxidized nucleotide opposite C, but is in contrast to the finding that 2-OH-dATP elicits G.C-->T.A transversions in Escherichia coli. This type of mutation was also elicited, but to a lesser extent. Interestingly, the mutagenicity of 2-OH-dATP was enhanced in the presence of 2-hydroxydeoxyadenosine 5'-diphosphate, an inhibitor of the MTH1 protein, suggesting that this protein functions in the hydrolysis of 2-OH-dATP in the replication reaction mixture, and probably in living cells. These results indicate that 2-OH-dATP is mutagenic and that its mutagenicity is suppressed by the MTH1 protein in mammalian cells.

Adenosine Triphosphate↗
PubMed2003

Mutagenic potentials of damaged nucleic acids produced by reactive oxygen/nitrogen species: approaches using synthetic oligonucleotides and nucleotides: survey and summary.

DNA and DNA precursors (deoxyribonucleotides) suffer damage by reactive oxygen/nitrogen species. They are important mutagens for organisms, due to their endogenous formation. Damaged DNA and nucleotides cause alterations of the genetic information by the mispairing properties of the damaged bases, such as 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) and 2-hydroxyadenine. Here, the author reviews the mutagenic potentials of damaged bases in DNA and of damaged DNA precursors formed by reactive oxygen/nitrogen species, focusing on the results obtained with synthetic oligonucleotides and 2'-deoxyribonucleoside 5'-triphosphates.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Use of the radial artery graft after transradial catheterization: is it suitable as a bypass conduit?

BACKGROUND: The suitability of the radial artery after transradial catheterization as a bypass conduit has been of great concern to surgeons. METHODS: A total of 67 patients underwent isolated coronary artery bypass grafting using the radial artery: 22 patients received preoperative transradial catheterization (group 1) and 45 patients did not receive transradial catheterization (group 2). Those patients were retrospectively reviewed. RESULTS: Patient characteristics, operative procedures, and early clinical outcome were not different between groups. The stenosis-free graft patency rates in groups 1 and 2 were 88% (16 of 18 patients) and 90% (38 of 42 patients) in the left internal thoracic artery (p = 0.87); 77% (17 of 22 patients) and 98% (48 of 49 patients) in the radial artery (p = 0.017); and 87% (13 of 15 patients) and 84% (21 of 25 patients) in the saphenous vein (p = 0.42), respectively. Intimal hyperplasia of the radial artery was observed in 68% (11 of 16 patients) in group 1 and in 39% (14 of 34 patients) in group 2 (p = 0.046). CONCLUSIONS: Transradial catheterization reduced early graft patency and caused intimal hyperplasia, although it did not affect early clinical outcomes. We suggest that the use of the radial artery as a bypass conduit after transradial catheterization should be undertaken cautiously.

Aged↗
PubMed2003

Flow simulation of the intracoronary shunt tube for off-pump coronary artery bypass.

INTRODUCTION: To simulate blood flow provided by the intracoronary shunt tube, and to clarify whether this method is actually suitable for Off-pump coronary artery bypass (OPCAB), we investigated the efficacy of the intracoronary shunt tube in a theoretical model on the basis of fluid dynamics. METHODS: Fluid dynamics analysis was performed to simulate flow decrease after attachment on an intracoronary shunt model. RESULTS: The flow ratio in the case of turbulent flow is in proportion to the ratio of the inner diameter to the third power, and that in the case of laminar flow is in proportion to the ratio of the inner diameter to the sixth power. When this analysis is applied to commercial shunt tubes, coronary flow was estimated as approximately 2-14% of pre-attachment flow in turbulent flow, and only less than 0.1% in laminar flow. CONCLUSIONS: This result suggests that use of intracoronary shunt tubes in OPCAB may rarely contribute to maintenance of coronary flow, and they should be used carefully, especially in a jeopardized coronary artery.

Blood Flow Velocity↗
PubMed2003

Erroneous incorporation of oxidized DNA precursors by Y-family DNA polymerases.

Deranged oxidative metabolism is a property of many tumour cells. Oxidation of the deoxynucleotide triphosphate (dNTP) pool, as well as DNA, is a major cause of genome instability. Here, we report that two Y-family DNA polymerases of the archaeon Sulfolobus solfataricus strains P1 and P2 incorporate oxidized dNTPs into nascent DNA in an erroneous manner: the polymerases exclusively incorporate 8-OH-dGTP opposite adenine in the template, and incorporate 2-OH-dATP opposite guanine more efficiently than opposite thymine. The rate of extension of the nascent DNA chain following on from these incorporated analogues is only slightly reduced. These DNA polymerases have been shown to bypass a variety of DNA lesions. Thus, our results suggest that the Y-family DNA polymerases promote mutagenesis through the erroneous incorporation of oxidized dNTPs during DNA synthesis, in addition to facilitating translesion DNA synthesis. We also report that human DNA polymerase eta, a human Y-family DNA polymerase, incorporates the oxidized dNTPs in a similar erroneous manner.

DNA, Archaeal↗
PubMed2003

Suppression of spontaneous and hydrogen peroxide-induced mutations by a MutT-type nucleotide pool sanitization enzyme, the Escherichia coli Orf135 protein.

BACKGROUND: We recently found that the Escherichia coli Orf135 protein, a MutT-type enzyme, hydrolysed 2-hydroxy-dATP (2-OH-dATP), and less efficiently, 8-hydroxy-dGTP. RESULTS: In this study, we examined the effects of the absence of the orf135 gene. Frequencies of spontaneous and H2O2-induced mutations were two- to three-fold higher in the orf135- strain than in the wild-type strain. These mutations include various mutations involving a G:C-->T:A transversion, the same type of mutation elicited by 2-OH-dATP. Over-expression of the Orf135 protein suppressed mutations even in the wild-type strain, as well as in the orf135- strain. CONCLUSIONS: The mutator phenotype of bacteria lacking the Orf135 protein suggests that this protein is involved in the suppression of mutations induced by oxidized deoxynucleotides in vivo and that various MutT-type enzymes contribute to nucleotide pool sanitization.

Base Sequence↗
PubMed2003

Utilization efficiency of the oxidized purine nucleotide analogs by DNA polymerase eta.

To elucidate the behavior of DNA polymerase eta against the oxidized purine nucleotides, we determined the utilization efficiency of 2-hydroxy-dATP and 8-hydroxy-dGTP by the recombinant yeast DNA polymerase eta using the primer extension assay with the synthetic oligonucleotide template-primers, and compared those by DNA polymerase alpha. Results indicate that DNA polymerase eta incorporates 2-hydroxy-dATP opposite template G in addition to template T and 8-hydroxy-dGTP opposite A in addition to C, respectively. Kinetic analysis revealed that the rate of mutation caused by 2-OH-dATP and 8-OH-dGTP with DNA polymerase eta should be much higher than those with DNA polymerase alpha.

Base Sequence↗
PubMed2003

Mutations induced by 2-hydroxy-dATP during in vitro replication with a HeLa extract.

The mutagenicity of oxidized dATP, 2-hydroxydeoxyadenosine 5'-triphosphate (2-OH-dATP), was examined using an SV40 origin-dependent in vitro replication system with a HeLa extract. 2-OH-dATP mainly elicited a G x C to A x T transition, and a G x C to T x A transversion to a lesser extent. Interestingly, the mutagenicity of 2-OH-dATP was enhanced in the presence of 2-hydroxydeoxyadenosine 5'-diphosphate, an inhibitor of the MTH1 protein, suggesting that this protein functions in the hydrolysis of 2-OH-dATP in the replication reaction mixture. These results indicate that 2-OH-dATP is mutagenic and that its mutagenicity is suppressed by the MTH1 protein in mammalian cells.

Adenosine Triphosphate↗
PubMed2003

Calpain 10 as a predictive gene for type 2 diabetes: evidence from a novel screening system using white blood cells of Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

The mRNA expression of type 2 diabetes-related genes in white blood cells (WBC) was examined before and after onset in Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The level of the calpain 10 (CAPN10) transcript was significantly decreased compared to control animals in WBC before and after onset. Significant decreases in this gene expression were also found in the major insulin-target tissues as well as WBC before onset. These results suggest that gene expression in WBC could be a useful screening system for predicting the incidence of type 2 diabetes before onset in OLETF rats, and that CAPN10 represents a potential candidate gene for predicting type 2 diabetes in human.

Adipose Tissue↗
PubMed2003

Efficacy and adverse effects of the coronary active perfusion system--from a viewpoint of perfusional timing.

We developed a coronary active perfusion system (CAPS) to avoid myocardial ischemia during off-pump coronary artery bypass (OPCAB). The purpose of this study was to determine the optimal timing of CAPS perfusion, and to investigate any adverse effects when it is driven within the systolic phase. Twenty-four pigs were divided into four groups: (A) systolic, (B) early-diastolic, (C) middle-diastolic, and (D) late-diastolic perfusion. Myocardial blood flow (MBF), hemodynamic and mechanical data were measured during 30 minutes of CAPS perfusion. MBF in group A was lower than in the other groups (p<0.001), but no significant differences were observed among groups B to D. End-systolic pressure-volume relation (Mw) and preload recruitable stroke work relation (Ees) in group A was lower than in groups B to D (p<0.01 and p<0.05, respectively), but no significant differences were observed among groups B to D. CAPS could maintain regional MBF and left ventricular function if it was driven only within the diastolic phase and required no strict adjustment, but CAPS has an adverse effect when it is driven in the systolic phase.

Animals↗
PubMed2002

Visualization of intracellular trafficking of exogenous DNA delivered by cationic liposomes.

To visualize the intracellular trafficking of exogenous DNAs delivered by cationic liposomes, rhodamine-labeled DNAs were transfected into NIH3T3 cells and observed by confocal laser microscopy. After 0.5- to 1-h incubations, the DNAs reached the nucleus with a much higher frequency than that expected from the cell division rate. This result suggests that DNAs can enter the nucleus in the presence of the nuclear membrane. Interestingly, some DNAs appeared to extend through the nuclear membrane in the aggregated form which were much larger than the nuclear pore complex. The DNAs which have passed through the nuclear membrane were stained with SYTO 24, a DNA labeling reagent. The stained part may be "naked" DNA that is free of lipids or proteins. This observation indicates that a complex containing DNA fuses with the nuclear membrane and then naked DNA is released into the nucleus.

3T3 Cells↗
PubMed2002

Troglitazone suppresses cell growth of KU812 cells independently of PPARgamma.

We examined the effects of troglitazone, one of thiazolidinedione derivatives on human basophilic leukemia cell line KU812. Troglitazone caused the suppression of cell growth, which was suggested to result from the decrease in cyclin E and the hyperphosphorylated form of retinoblastoma tumor suppressor gene product (pRb). In addition, troglitazone caused a decrease in histamine secretion due to the reduced expression of histidine decarboxylase mRNA. Peroxisome proliferator-activated receptor (PPAR)-gamma mRNA was undetectable by reverse transcription-polymerase chain reaction (RT-PCR) in KU812 cells. These findings suggested that troglitazone suppressed cell growth and histamine synthesis independently of PPARgamma.

Antineoplastic Agents↗
PubMed2002

Induction of T --> G and T --> A transversions by 5-formyluracil in mammalian cells.

Oxidatively damaged thymine, 5-formyluracil (5-fU), was incorporated into a predetermined site of double-stranded shuttle vectors. The nucleotide sequences in which the modified base was incorporated were 5'-CFTAAG-3' and 5'-CTFAAG-3' (F represents 5-fU), the recognition site for the restriction enzyme AflII (5'-CTTAAG-3'). The 5-fU was incorporated into a template strand of either the leading or lagging strand of DNA replication. The modified DNAs were transfected into simian COS-7 cells, and the DNAs replicated in the cells were recovered and were analyzed after the second transfection into Escherichia coli. The 5-fU did not block DNA replication in mammalian cells. The 5-fU residues were weakly mutagenic, and their mutation frequencies in double-stranded vectors were 0.01-0.04%. The T --> G and T --> A transversions were the mutations found most frequently, suggesting the formation of 5-fU.C and 5-fU.T base pairs, respectively. This is the first report that clearly shows the induction of transversion mutations by an oxidized pyrimidine base in DNA in mammalian cells.

Animals↗