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Biomedical subjects

Y Moriyama

Publications and source records attributed to Y Moriyama.

At least 19 recordsLinked to original sources

Correlation of serum pepsinogens and gross appearances combined with histology in early gastric cancer.

The correlation between serum pepsinogen (PG) levels and the gross types was investigated in 128 consecutive patients with early gastric cancer. Although there was no significant difference in age, gender, cancer location, or cancer depth among gross appearances, the distribution of histological type was significantly different between polypoid and depressed cancers: all polypoid cancers except one were intestinal type, whereas nearly a third of depressed cancers were diffuse type. All the patients in whom Helicobacter pylori status was investigated had Helicobacterpylori infection. Combination of gross appearances and histology (polypoid cancer with intestinal type, depressed cancer with intestinal type and depressed cancer with diffuse type) showed a clear difference in distribution of serum PG levels and a ratio between levels of PG I and PG II (I/II ratio). In polypoid cancer with intestinal type, a PG I level and a I/II ratio were significantly lower than those of the others. In depressed cancer with diffuse type, PG I and PG II levels were significantly higher. These findings revealed that backgrounds such as intragastric acidity and extent of gastric atrophy might differ among early gastric cancers with different morphology and histology.

Adult↗

High prevalence of quintuple mutant dhps/dhfr genes in Plasmodium falciparum infections seven years after introduction of sulfadoxine and pyrimethamine as first line treatment in Malawi.

Malawi changed its national policy for malaria treatment in 1993, becoming the first country in Africa to replace chloroquine by sulfadoxine and pyrimethamine combination (SP) as the first-line drug for uncomplicated malaria. Seven years after this change, we investigated the prevalence of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) mutations, known to be associated with decreased sensitivity to SP, in 173 asymptomatic Plasmodium falciparum infections from Salima, Malawi. A high prevalence rate (78%) of parasites with triple Asn-108/Ile-51/Arg-59 dhfr and double Gly-437/Glu-540 dhps mutations was found. This 'quintuple mutant' is considered as a molecular marker for clinical failure of SP treatment of P. falciparum malaria. A total of 11 different dhfr and dhps combinations were detected, 3 of which were not previously reported. Nineteen isolates contained the single Glu-540 mutant dhps, while no isolate contained the single Gly-437 mutant dhps, an unexpected finding since Gly-437 are mostly assumed to be one of the first mutations commonly selected under sulfadoxine pressure. Two isolates contained the dhps single or double mutant coupled with dhfr wild-type. The high prevalence rates of the three dhfr mutations in our study were consistent with a previous survey in 1995 in Karonga, Malawi, whereas the prevalences of dhps mutations had increased, most probably as a result of the wide use of SP. A total of 52 P. falciparum isolates were also investigated for pyrimethamine and sulfadoxine/pyrimethamine activity against parasite growth according to WHO in vitro standard protocol. A pyrimethamine resistant profile was found. When pyrimethamine was combined with sulfadoxine, the mean EC(50) value decreased to less than one tenth of the pyrimethamine alone level. This synergistic activity may be explained by sulfadoxine inhibition of dhps despite the double mutations in the dhps genes, which would interact with pyrimethamine acting to block the remaining folate despite dhfr mutations in the low p-aminobenzoic acid and low folic acid medium mixed with blood.

Adolescent↗

Rapid, selective digestion of mitochondrial DNA in accordance with the matA hierarchy of multiallelic mating types in the mitochondrial inheritance of Physarum polycephalum.

Although mitochondria are inherited uniparentally in nearly all eukaryotes, the mechanism for this is unclear. When zygotes of the isogamous protist Physarum polycephalum were stained with DAPI, the fluorescence of mtDNA in half of the mitochondria decreased simultaneously to give small spots and then disappeared completely approximately 1.5 hr after nuclear fusion, while the other mitochondrial nucleoids and all of the mitochondrial sheaths remained unchanged. PCR analysis of single zygote cells confirmed that the loss was limited to mtDNA from one parent. The vacant mitochondrial sheaths were gradually eliminated by 60 hr after mating. Using six mating types, the transmission patterns of mtDNA were examined in all possible crosses. In 39 of 60 crosses, strict uniparental inheritance was confirmed in accordance with a hierarchy of relative sexuality. In the other crosses, however, mtDNA from both parents was transmitted to plasmodia. The ratio of parental mtDNA was estimated to be from 1:1 to 1:10(-4). Nevertheless, the matA hierarchy was followed. In these crosses, the mtDNA was incompletely digested, and mtDNA replicated during subsequent plasmodial development. We conclude that the rapid, selective digestion of mtDNA promotes the uniparental inheritance of mitochondria; when this fails, biparental inheritance occurs.

Animals↗

[Successful surgical treatment in a nonagenarian with aortic arch aneurysm].

Surgical treatment in a nonagenarian with thoracic aortic aneurysm is challenging, and the surgical indication in such patients is controversial. A 92-year-old female patient with severe chest and back pain was transferred to our hospital because of impending rupture of an aortic arch aneurysm with normal mental activity. Physical and laboratory examinations were within normal limits. The patients underwent urgent graft replacement of the total aortic arch. Postoperative course was uneventful and the patient remains well with no disability 8 months after the operation.

Aged↗

Differentiation-associated Na+-dependent inorganic phosphate cotransporter (DNPI) is a vesicular glutamate transporter in endocrine glutamatergic systems.

Vesicular glutamate transporter is present in neuronal synaptic vesicles and endocrine synaptic-like microvesicles and is responsible for vesicular storage of L-glutamate. A brain-specific Na(+)-dependent inorganic phosphate transporter (BNPI) functions as a vesicular glutamate transporter in synaptic vesicles, and the expression of this BNPI defines the glutamatergic phenotype in the central nervous system (Bellocchio, E. E., Reimer, R. J., Fremeau, R. T., Jr., and Edwards, R. H. (2000) Science 289, 957-960; Takamori, S., Rhee, J. S., Rosenmund, C., and Jahn, R. (2000) Nature 407, 189-194). However, since not all glutamatergic neurons contain BNPI, an additional transporter(s) responsible for vesicular glutamate uptake has been postulated. Here we report that differentiation-associated Na(+)-dependent inorganic phosphate cotransporter (DNPI), an isoform of BNPI (Aihara, Y., Mashima, H., Onda, H., Hisano, S., Kasuya, H., Hori, T., Yamada, S., Tomura, H., Yamada, Y., Inoue, I., Kojima, I., and Takeda, J. (2000) J. Neurochem. 74, 2622-2625), also transports L-glutamate at the expense of an electrochemical gradient of protons established by the vacuolar proton pump when expressed in COS7 cells. Molecular, biological, and immunohistochemical studies have indicated that besides its presence in neuronal cells DNPI is preferentially expressed in mammalian pinealocytes, alphaTC6 cells, clonal pancreatic alpha cells, and alpha cells of Langerhans islets, these cells being proven to secrete L-glutamate through Ca(2+)-dependent regulated exocytosis followed by its vesicular storage. Pancreatic polypeptide-secreting F cells of Langerhans islets also expressed DNPI. These results constitute evidence that DNPI functions as another vesicular transporter in glutamatergic endocrine cells as well as in neurons.

Adenosine Triphosphate↗

Cloning of a lymphatic peptide/histidine transporter.

Although peptide transport across the plasma membrane has been characterized well in the kidney and the intestine, the functional relevance of this transport in other organs has not been addressed. Here we report the cloning of a cDNA for a novel peptide/histidine transporter found in the rat (rPHT2), whose mRNA is expressed mainly in the lymphatic system. rPHT2 encodes a protein of 582 amino acids and showed 49% identity with the brain PHT (PHT1) [Yamashita, Shimada, Guo, Sato, Kohmura, Hayakawa, Takagi and Tohyama (1997) J. Biol. Chem. 272, 10205-10211]. rPHT2 mRNA was abundant in lung, spleen and thymus, and detected faintly in brain, liver, adrenal gland and heart by Northern-blot analysis and reverse transcriptase PCR (RT-PCR). Intense signals for the gene were found in immunocytes using in situ hybridization. Ectopic expression of rPHT2 protein in HEK-293T cells and BHK cells was not found on the cell surface, but was found on the lysosomal membrane using light- and electron-microscopic analysis. Recombinant rPHT2 protein reconstituted into liposomes showed proton-dependent transport activity with histidine and histidyl-leucine. These findings suggest that rPHT2 is involved in the protein catabolic pathway in the lymphatic system.

Amino Acid Sequence↗

D-Aspartate is stored in secretory granules and released through a Ca(2+)-dependent pathway in a subset of rat pheochromocytoma PC12 cells.

D-Aspartate in mammalian neuronal and neuroendocrine cells is suggested to play a regulatory role(s) in the neuroendocrine function. Although D-aspartate is known to be released from neuroendocrine cells, the mechanism underlying the release is less understood. Rat pheochromocytoma PC12 cells contain an appreciable amount of D-aspartate (257 +/- 31 pmol/10(7) cells). Indirect immunofluorescence microscopy with specific antibodies against d-aspartate indicated that the amino acid is present within a particulate structure, which is co-localized with dopamine and chromogranin A, markers for secretory granules, but not with synaptophysin, a marker for synaptic-like microvesicles. After sucrose density gradient centrifugation of the postnuclear particulate fraction, about 80% of the d-aspartate was recovered in the secretory granule fraction. Upon the addition of KCl, an appreciable amount of D-aspartate (about 40 pmol/10(7) cells at 10 min) was released from cultured cells on incubation in the presence of Ca(2+) in the medium. The addition of also triggered d-aspartate release. Botulinum neurotoxin type E inhibited about 40% of KCl- and Ca(2+)-dependent d-aspartate release followed by specific cleavage of 25-kDa synaptosomal-associated protein. alpha-Latrotoxin increased the intracellular [Ca(2+)] and caused the Ca(2+)-dependent d-aspartate release. Bafilomycin A1 dissipated the intracellular acidic regions and inhibited 40% of the Ca(2+)-dependent D-aspartate release. These properties are similar to those of the exocytosis of dopamine. Furthermore, digitonin-permeabilized cells took up radiolabeled d-aspartate depending on MgATP, which is sensitive to bafilomycin A1 or 3,5-di-tert-butyl-4-hydroxybenzylidene-malononitrile. Taken together, these results strongly suggest that d-aspartate is stored in secretory granules and then secreted through a Ca(2+)-dependent exocytotic mechanism. Exocytosis of D-aspartate further supports the role(s) of D-aspartate as a chemical transmitter in neuroendocrine cells.

Adrenal Gland Neoplasms↗

A homologue of N-ethylmaleimide-sensitive factor in the malaria parasite Plasmodium falciparum is exported and localized in vesicular structures in the cytoplasm of infected erythrocytes in the brefeldin A-sensitive pathway.

N-Ethylmaleimide-sensitive factor (NSF) and its homologues play a central role in vesicular trafficking in eukaryotic cells. We have identified a NSF homologue in Plasmodium falciparum (PfNSF). The reported PfNSF gene sequence (GenBank accession number CAB10575) indicated that PfNSF comprises 783 amino acids with a calculated molecular weight of 89,133. The overall identities of its gene and amino acid sequences with those of rat NSF are 50.9 and 48.8%, respectively. Reverse transcription-polymerase chain reaction analysis and Northern blotting with total P. falciparum RNA indicated expression of the PfNSF gene. Polyclonal antibodies against a conserved region of NSF specifically recognized an 89-kDa polypeptide in the parasite cells. After homogenization of the parasite cells, approximately 90% of an 89-kDa polypeptide is associated with particulate fraction, suggesting membrane-bound nature of PfNSF. PfNSF was present within both the parasite cells and the vesicular structure outside of the parasite cells. The export of PfNSF outside of the parasite cells appears to occur at the early trophozoite stage and to terminate at the merozoite stage. The export of PfNSF is inhibited by brefeldin A, with 9 microM causing 50% inhibition. Immunoelectromicroscopy indicated that intracellular PfNSF was associated with organelles such as food vacuoles and that extracellular PfNSF was associated with vesicular structures in the erythrocyte cytoplasm. These results indicate that PfNSF expressed in the malaria parasite is exported to the extracellular space and then localized in intraerythrocytic vesicles in a brefeldin A-sensitive manner. It is suggested that a vesicular transport mechanism is involved in protein export targeted to erythrocyte membranes during intraerythrocytic development of the malaria parasite.

Amino Acid Sequence↗

The complete DNA sequence of the mitochondrial genome of Physarum polycephalum.

The complete sequence of the mitochondrial DNA (mtDNA) of the true slime mold Physarun polycephalum has been determined. The mtDNA is a circular 62,862-bp molecule with an A+T content of 74.1%. A search with the program BLAST X identified the protein-coding regions. The mitochondrial genome of P. polycephalum was predicted to contain genes coding for 12 known proteins [for three cytochrome c oxidase subunits, apocytochrome b, two F1Fo-ATPase subunits, five NADH dehydrogenase (nad) subunits, and one ribosomal protein], two rRNA genes, and five tRNA genes. However, the predicted ORFs are not all in the same frame, because mitochondrial RNA in P. polycephalum undergoes RNA editing to produce functional RNAs. The nucleotide sequence of an nad7 cDNA showed that 51 nucleotides were inserted at 46 sites in the mRNA. No guide RNA-like sequences were observed in the mtDNA of P. polycephalum. Comparison with reported Physarum mtDNA sequences suggested that sites of RNA editing vary among strains. In the Physarum mtDNA, 20 ORFs of over 300 nucleotides were found and ORFs 14 19 are transcribed.

Amino Acid Sequence↗

Penetrating atherosclerotic ulcer.

The pathogenesis of penetrating atherosclerotic ulcer (PAU) in aortic disease remains controversial. Between January 1995 and April 1999, five patients underwent treatment for a PAU in our hospital. All were men, ranging in age from 46 to 74 years, with a mean age of 66.2 years. The PAU was located on the thoracic descending aorta in three patients and on the abdominal aorta in two. Preoperative diagnosis was established by contrast-enhanced computed tomographic scan and aortogram. Surgery was performed in four patients, as graft replacement in three, and patch plasty in one. The remaining patient is being carefully observed on antihypertensive therapy. No connective tissue disorder, trauma, dissection, or infection was seen in any of the patients who underwent surgery, all of whom had uneventful postoperative courses with no perioperative complications or enlargement of the aorta. We conclude that surgical treatment should be performed for patients with PAU to prevent an aortic catastrophe caused by rapid development of the lesion. This report might provide further evidence of the importance of PAU.

Aged↗

Thoracic and thoracoabdominal aneurysm repair under deep hypothermia using subclavian arterial perfusion.

BACKGROUND: Hypothermic circulatory arrest is a valuable adjunct for thoracic and thoracoabdominal aortic aneurysm repair. Retrograde aortic perfusion through the femoral artery, however, carries a risk of cerebral embolism or malperfusion. To avoid these complications we adopted antegrade aortic perfusion through a prosthetic graft attached to the left subclavian artery through a left thoracotomy. METHODS: Ten patients had repair of descending thoracic and thoracoabdominal aortic aneurysm under deep hypothermia with antegrade aortic perfusion through the left subclavian artery. Hypothermic circulatory arrest was used because proximal aortic control was hazardous due to rupture or intraluminal disease, or for spinal cord protection. RESULTS: There was no brain injury and one hospital death. The cause of death was massive bleeding from the gastrointestinal tract not related to deep hypothermia or the perfusion method. All 9 survivors were alive and well after a mean follow-up period of 9 months. CONCLUSIONS: Using the left subclavian artery as a site of aortic perfusion can avoid retrograde aortic perfusion, hence reducing the potential for brain injury due to embolic stroke or malperfusion through a dissected thoracoabdominal aorta.

Aged↗

A leukocyte depleting filter reduces endothelial cell dysfunction and improves transplanted canine heart function.

BACKGROUND: To date leukocytes have been known to play a major role in reperfusion injury and have directed attention to leukocyte-endothelium interaction. This study was designed to investigate how much graft viability and the coronary microcirculatory function could be preserved by leukocyte depletion (LD) in a model of orthotopic cardiac transplantation. METHODS: The heart in 10 beagle dogs was arrested by introducing a 4 degrees C St. Thomas' cardioplegic solution. They were harvested, immersed in the cold saline for 3 hours, and then orthotopically transplanted. Five recipients underwent LD (LD group) at reperfusion with the use of a Pall BC1B leukocyte depleting filter inserted into the cardiopulmonary bypass (CPB) circuit. The other 5 dogs without filtration served as a control group. RESULTS: Leukocytes were about 80% filtrated and neutrophils were also 85% filtrated during the first 30 minutes of reperfusion in the LD group. A high level of adenosine triphosphate was maintained after transplantation in the LD group. The polymorphonuclear elastase level was significantly lower in the LD group. The cardiac function assessed by the slopes of the end-systolic pressure volume relation after transplantation was significantly higher in the LD group than in the control group (p < 0.05). The coronary vascular resistance responses to acetylcholine and nitroglycerin after transplantation were preserved significantly better in the LD group than in the control group (p < 0.05). CONCLUSIONS: These results suggest that a leukocyte depleting filter placed in the CPB circuit would prevent leukocyte-mediated endothelial cell injury, improve microcirculation of the myocardium, and lead to excellent graft function.

Animals↗

Effect of a neutrophil elastase inhibitor (ONO-5046 Na) on ischemia/reperfusion injury using the left-sided heterotopic canine heart transplantation model.

BACKGROUND: Ischemia/reperfusion injury is a major cause of transplanted heart dysfunction. Several reports have demonstrated that polymorphonuclear neutrophil (PMN) elastase derived from the activated neutrophils might play an important role in this injury. Herein, we investigated the protective effects of PMN elastase inhibitor (ONO-5046 Na) on ischemia/reperfusion injury using a left-sided canine heterotopic heart transplantation model. METHODS: We used 10 pairs of adult beagle dogs. The donor heart was transplanted heterotopically into the left thoracic cavity of the recipient without cardiopulmonary bypass. A bolus of ONO-5046 Na (10 mg/kg) was introduced intravenously to 5 recipients (group II) at 15 minutes before reperfusion and was followed by continuous infusion (10 mg/kg per hour) for 180 minutes. Five dogs (group I) did not receive ONO-5046 Na and thus served as a control. After reperfusion, we evaluated transplanted heart function and obtained blood samples from the coronary sinus over a 360-minute period. RESULTS: E(max) and pre-load recruitable stroke work in group II showed significantly better recovery than group I. Blood levels of PMN elastase, creatine kinase MB, lactate and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-8) were significantly lower in group II. Depletion of myocardial concentration of adenosine triphosphate at 120 minutes after reperfusion and myocardial water content was significantly lower in group II. CONCLUSIONS: ONO-5046 Na, which inhibits PMN elastase, could reduce ischemia/reperfusion injury in heart transplantation. These results indicate that clinical application of ONO-5046 Na should be considered.

Animals↗

Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation.

We report the results of a phase III trial comparing tacrolimus (FK506) with cyclosporine for GVHD prophylaxis after allogeneic BMT. From February 1995 to July 1996, 136 patients were enrolled and followed up to September 1997. During the first 100 days post-transplant the incidence of grade II-IV acute GVHD (the primary end-point) was lower in the tacrolimus group (17.5%) compared with the cyclosporine group (48.0%, P < 0.0001). A significant difference was observed between the tacrolimus and cyclosporine groups when subset analyses were performed based on recipients from HLA-matched siblings (13.3% vs 41.3%, P = 0.015) or donors other than HLA-matched siblings (21.4% vs 53.8%, P= 0.0029). The incidence of chronic GVHD (47.3% and 47.8%) and Kaplan-Meier estimate of overall survival (62.9% and 65.2%) were similar between the tacrolimus and cyclosporine groups, respectively. The overall leukemia relapse rate was not significantly different between the tacrolimus and cyclosporine groups (19.6% and 11.4%, respectively). However, the relapse rate among recipients from HLA-matched siblings was significantly higher in the tacrolimus group (30.9%) compared with the cyclosporine group (3.6%, P = 0.013). These results suggest the merit of tacrolimus for the prophylaxis of acute GVHD, but a lack of merit for a graft-versus-leukemia effect among recipients from HLA-matched sibling donors.

Adolescent↗

Effects of CYP2C19 genotypic differences in the metabolism of omeprazole and rabeprazole on intragastric pH.

BACKGROUND: Omeprazole is mainly metabolized in the liver by CYP2C19, a genetically determined enzyme, whereas rabeprazole is mainly reduced non-enzymatically and partially metabolized by CYP2C19. The therapeutic effects of rabeprazole are therefore assumed to be less affected by an individual's CYP2C19 status. AIM: To investigate the acid inhibitory effects and plasma levels of omeprazole and rabeprazole with reference to different CYP2C19 genotypes. METHODS: Fifteen healthy volunteers took a daily dose of 20 mg of omeprazole or rabeprazole for 8 days. On post-dose days 1 and 8, 24-h profiles of intragastric pH were recorded and plasma concentrations of omeprazole, rabeprazole and their metabolites were determined. RESULTS: After single and repeated doses of omeprazole, the intragastric pH values and plasma concentrations of omeprazole and its metabolites were significantly dependent on the CYP2C19 genotype. Significant differences in the same kinetic and dynamic parameters were also observed after single doses of rabeprazole. Although the plasma levels of rabeprazole differed among the different CYP2C19 genotype groups after repeated doses, no significant differences in intragastric pH values were observed. CONCLUSIONS: The acid inhibitory effects of omeprazole and rabeprazole are significantly dependent on the CYP2C19 genotype status, as well as on their intrinsic pharmacokinetic and pharmacodynamic characteristics and dosing schemes.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Acute effects of melatonin administration on cardiovascular autonomic regulation in healthy men.

BACKGROUND: Previous studies have suggested that melatonin, a major pineal hormone, possibly modulates the autonomic nervous system in animals. The aim of this study was to examine the effects of melatonin administration on heart rate variability (HRV) in human beings. METHODS: In 26 healthy men, melatonin (2 mg) or placebo was randomly administered. Power spectral analysis of HRV and blood pressure monitoring were performed in the supine position before and 60 minutes after administration and in the standing position 60 minutes after administration. Plasma catecholamine levels were also assessed. RESULTS: No differences in any baseline parameters were found between the two groups. Compared with placebo, melatonin administration within 60 minutes increased R-R interval, the square root of the mean of the squared differences between adjacent normal R-R intervals, high-frequency power, and low-frequency power of HRV and decreased the low-frequency to high-frequency ratio and blood pressure in the supine position (all P <.01). Plasma norepinephrine and dopamine levels in the supine position 60 minutes after melatonin administration were lower compared with placebo (P <.05 and P <.01, respectively). Standing up resulted in the decrease of HRV and the increase of blood pressure and plasma catecholamine levels in both administration groups, and the differences between the groups found in the supine position disappeared. CONCLUSIONS: These findings indicate that melatonin administration increased cardiac vagal tone in the supine position in awake men. Melatonin administration also may exert suppressive effects on sympathetic tone.

Blood Pressure↗