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Biomedical subjects

Y Morimoto

Publications and source records attributed to Y Morimoto.

At least 73 records · Page 4Linked to original sources
PubMed2001

Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos.

We examined 8-hydroxyguanine (8-OH-Gua) formation and 8-OH-Gua repair enzyme activity in pulmonary type-II-like epithelial cells to determine whether oxidative stress induced by asbestos plays a role in its carcinogenic mechanism. A549 cells were incubated with crocidolite asbestos at concentrations of 0, 10, 50 and 100 microg/ml over 27 h. We then evaluated 8-OH-Gua formation, 8-OH-Gua repair enzyme activity and gene expression of 8-oxoguanine-DNA glycosylase 1 (hOGG1) and human MUtT homologue (hMTH1). This was done using a high-performance liquid chromatography system equipped with an electrochemical detector, endonuclease nicking assay and reverse transcription polymerase chain reaction, respectively. Crocidolite induced the formation of 8-OH-Gua in DNA at concentrations of 50 and 100 microg/ml. 8-OH-Gua levels increased at 9 h and had declined to near baseline at 27 h, whereas 8-OH-Gua repair enzyme activity peaked at 18 h post-crocidolite exposure. hOGG1 and hMTH1 mRNA levels were also increased by crocidolite exposure. These data suggest that crocidolite asbestos is associated with epithelial cell injury in the process of carcinogenesis through oxidative stress.

Actins↗
PubMed2001

The clp1 gene of the mushroom Coprinus cinereus is essential for A-regulated sexual development.

Sexual development in the mushroom Coprinus cinereus is under the control of the A and B mating-type loci, both of which must be different for a compatible, dikaryotic mycelium to form between two parents. The A genes, encoding proteins with homeodomain motifs, regulate conjugate division of the two nuclei from each mating partner and promote the formation of clamp connections. The latter are hyphal configurations required for the maintenance of the nuclear status in the dikaryotic phase of basidiomycetes. The B genes encode pheromones and pheromone receptors. They regulate the cellular fusions that complete clamp connections during growth, as well as the nuclear migration required for dikaryosis. The AmutBmut strain (326) of C. cinereus, in which both A- and B-regulated pathways are constitutively activated by mutations, produces, without mating, dikaryon-like, fertile hyphae with clamp connections. In this study we isolated and characterized clampless1-1 (clp1-1), a mutation that blocks clamp formation, an essential step in A-regulated sexual development, in the AmutBmut background. A genomic DNA fragment that rescues the clp1-1 mutation was identified by transformations. Sequencing of the genomic DNA, together with RACE experiments, identified an ORF interrupted by one intron, encoding a novel protein of 365 amino acids. The clp1-1 mutant allele carries a deletion of four nucleotides, which is predicted to cause elimination of codon 128 and frameshifts thereafter. The clp1 transcript was normally detected only in the presence of the A protein heterodimer formed when homokaryons with compatible A genes were mated. Forced expression of clp1 by promoter replacements induced clamp development without the need for a compatible A gene combination. These results indicate that expression of clp1 is necessary and sufficient for induction of the A-regulated pathway that leads to clamp development.

Amino Acid Sequence↗
PubMed2001

Tissue factor pathway inhibitor response does not correlate with tissue factor-induced disseminated intravascular coagulation and multiple organ dysfunction syndrome in trauma patients.

OBJECTIVE: To determine the precise relationship between tissue factor and tissue factor pathway inhibitor (TFPI) after trauma, as well as to test the hypothesis that low TFPI levels are not sufficient to prevent tissue factor-dependent intravascular coagulation, leading to multiple organ dysfunction syndrome (MODS). DESIGN: Prospective, observational cohort study. SETTING: Emergency room and intensive care unit in a university hospital. PATIENTS: Thirty-three trauma patients, 18 with disseminated intravascular coagulation (DIC) and 15 without DIC were studied. Ten normal, healthy volunteers served as control subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Antigen concentration of tissue factor and TFPI, and global parameters of coagulation and fibrinolysis were measured on the day of admission, and on days 1-4 after admission. The number of systemic inflammatory response syndrome (SIRS) criteria that patients met and the DIC score were determined, simultaneously. The results of these measurements, incidence of MODS, and outcome were compared between the DIC patients and those without DIC. In the DIC patients, significantly higher tissue factor levels (p =.0049) and lower platelet counts (p =.0016) were found compared with the non-DIC patients and control subjects. However, the TFPI values remained at normal levels during the study period. No correlation was found between the peak levels of tissue factor and TFPI. The mean duration of SIRS and the maximum number of the SIRS criteria being met by the patients in the DIC group were statistically longer and higher than those in the non-DIC patients. The incidence of MODS and the number of the dysfunctioning organs were higher in the DIC patients compared with those in the non-DIC patients, and the DIC patients had a poor outcome. CONCLUSIONS: We systematically elucidated the relationship between tissue factor and TFPI in post-trauma patients. Highly activated tissue factor-dependent coagulation pathway is not sufficiently prevented by the normal TFPI levels in patients with DIC. The DIC associated with thrombotic and inflammatory responses causes MODS, and leads to poor outcome in post-trauma patients.

APACHE↗
PubMed2001

Inhibition of experimental vasospasm by pretreatment with ultraviolet light irradiation in a rat femoral artery model.

OBJECTIVE: Chronic cerebral vasospasm is resistant to conventional treatments despite recent advances in treatment modalities. We studied the preventive effect of ultraviolet (UV) irradiation on development of vasospasm and its mechanism in a rat femoral artery model. METHODS: The rat femoral artery model for vasospasm was used in this investigation (n = 108). The femoral arteries were divided into four groups: empty and no irradiation (control), UV irradiation (UV group), blood placement (VS group), and blood placement after UV irradiation (VS + UV group). Luminal area was measured, and smooth muscle cell counts in the medial layer of the vessel wall were obtained. An immunohistochemical study was performed with cross sections of fixed femoral arteries at 12 hours and 1, 3, 5, 7, and 49 days after blood placement. The rings of femoral arteries on Day 7 were subjected to pharmacological study. RESULTS: Pretreatment with UV irradiation (VS + UV group) resulted not only in significant inhibition of chronic vasospasm but also in a significant decrease in smooth muscle cells compared with the VS group on Days 5 and 7. The UV-treated arteries (UV and VS + UV groups) exhibited a significant number of Bax- and Bcl-2-positive cells on Days 5 and 7, but few CPP-32 positive cells were observed at the same time points. In the pharmacological study, contractile response to KCI or phenylephrine was reduced significantly in the UV-treated arteries. CONCLUSION: These results imply that UV irradiation prevents chronic vasospasm and suggest that UV-induced cell death plays an important role in the preventive effect without causing complications during the chronic period.

Animals↗
PubMed2001

Effects of profound anemia on brain tissue oxygen tension, carbon dioxide tension, and pH in rabbits.

This study sought to determine the maximum tolerable limit of anemia for the brain during halothane anesthesia. Using a multiparameter sensor, we continuously monitored brain tissue oxygen tension (PO2), carbon dioxide tension (PCO2), and pH during profound hemodilution and subsequent transfusion. Twelve New Zealand White rabbits were anesthetized, intubated, and mechanically ventilated at a fraction of inspired oxygen (FiO2) of 21% to produce an arterial carbon dioxide tension (PaCO2) of 35 to 40 mm Hg. The femoral artery was cannulated to continuously monitor arterial blood pressure and to intermittently measure arterial blood gases. The electroencephalogram (EEG) was recorded throughout the course of the study. A fiberoptic sensor was inserted into the brain for the continuous measurement of brain PO2, PCO2, pH, and temperature. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. Severe anemia was induced by repeatedly withdrawing 50-mL aliquots of blood and infusing an equal volume of 6% hetastarch. This procedure was performed four times for each rabbit. After the forth blood draw and fluid infusion, a total of 60 mL of packed red blood cells were transfused. Upon completion of the hemodilution, the hemoglobin concentration was 2.4 +/- 0.3 g/dL (mean +/- SEM). Brain tissue PO2 decreased from 27 +/- 3 mm Hg to a minimum of 12 +/- 2 mm Hg. Brain tissue pH also decreased from 7.22 +/- 0.03 to 7.12 +/- 0.05 and returned to the baseline value with transfusion. Brain PCO2 did not change significantly during the experiment. Cerebral blood flow increased from 37 +/- 3 to 66 +/- 15 mL x 100 g(-1) x min(-1) during hemodilution and returned to baseline after infusion of red blood cells. There was some loss of EEG amplitude and the calculated cerebral metabolic rate (CMRO2) decreased from 4.3 +/- 0.6 to 1.9 +/- 0.3 mL x 100 g(-1) x min(-1) at the most profound level of anemia. This is the first report of which the authors are aware of continuous monitoring of brain tissue pH, PCO2, and PO2 during profound hemodilution and transfusion. Hemodilution results in a decrease in brain tissue PO2. Increases in CBF and oxygen extraction can only partially compensate for the decreased oxygen carrying capacity of the blood. Decreases in brain tissue PO2, pH, CMRO2, and a loss of EEG amplitude suggest that the maximum tolerable limit of hemodilution was achieved in this study.

Anemia↗
PubMed2001

The combination of lamotrigine and mild hypothermia prevents ischemia-induced increase in hippocampal glutamate.

The excessive release of glutamate during cerebral ischemia may play an important role in subsequent neuronal injury. Both lamotrigine and hypothermia have independently been shown to attenuate the release of glutamate. In this study, the authors sought to determine whether these effects were additive. Thirty-five New Zealand White rabbits were randomized to one of six groups: a normothermic control group; a lamotrigine-treated group; two hypothermic groups at 33 degreesC or 34.5 degreesC; or two groups treated with both hypothermia at 33 degreesC or 34.5 degreesC plus lamotrigine. Animals were anesthetized before implanting microdialysis probes in the hippocampus. Esophageal temperature was maintained at 38 degreesC in the control and lamotrigine groups, while the temperatures of animals in the hypothermia and hypothermia-plus-lamotrigine groups were cooled to 33 degreesC or 34.5 degreesC. Two 10 minute periods of global cerebral ischemia were produced by inflating a neck tourniquet. Levels of glutamate in the microdialysate were then determined using high-performance liquid chromatography. Extracellular glutamate concentrations increased only slightly from baseline during the first ischemic period. Glutamate levels during the second ischemic episode in the hypothermia-plus-lamotrigine group (34.5 degreesC) were significantly lower than those in the hypothermia group alone (34.5 degreesC), lamotrigine, or control groups (P < .01). The fact that mild hypothermia (34.5 degreesC) plus lamotrigine (20 mg/kg) together were more effective in inhibiting extracellular glutamate accumulation than hypothermia (34.5 degreesC) or lamotrigine (20 mg/kg) alone, suggests the potential for increased neuroprotection by the addition of lamotrigine to mild hypothermia.

Animals↗
PubMed2001

Influence of breast-feeding on the production of cytokines.

PROBLEM: Recently, we reported increases in the production of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and IL-4 during the postpartum period. The present study was undertaken to investigate whether these increases might be explained by increased prolactin while breast-feeding. METHOD: Whole blood from 41 women who were breast-feeding, 13 women not breast-feeding, and 31 healthy non-pregnant women was stimulated with phorbol 12-myristate 13-acetate and ionomycin, and the levels of cytokines in the supernatant were measured by enzyme-linked immunosorbent assay. Their serum levels of prolactin were measured by enzyme immunoassay. RESULTS: Increases in IFN-gamma, IL-2, IL-4, and IL-10 production were observed in women who were breast-feeding but not in women who were not breast-feeding. Serum levels of prolactin correlated with the levels of IFN-gamma in culture supernatant. CONCLUSIONS: These results suggest that breast-feeding induces production of cytokines and that IFN-gamma production is enhanced by physiological concentrations of prolactin.

Breast Feeding↗
PubMed2001

Real-time measurements of endogenous CO production from vascular cells using an ultrasensitive laser sensor.

Carbon monoxide (CO) has been implicated as a biological messenger molecule analogous to nitric oxide. A compact gas sensor based on a midinfrared laser absorption spectroscopy was developed for direct and real-time measurement of trace levels (in approximate pmol) of CO release by vascular cells. The midinfrared light is generated by difference frequency mixing of two nearinfrared lasers in a nonlinear optical crystal. A strong infrared absorption line of CO (4.61 microm) is chosen for convenient CO detection without interference from other gas species. The generation of CO from cultured vascular smooth muscle cells was detected every 20 s without any chemical modification to the CO. The sensitivity of the sensor reached 6.9 pmol CO. CO synthesis was measured from untreated control cells (0.25 nmol per 10(7) cells/h), sodium nitroprusside-treated cells (0.29 nmol per 10(7) cells/h), and hemin-treated cells (0.49 nmol per 10(7) cells/h). The sensor also detected decreases in CO production after the addition of the heme oxygenase (HO) inhibitor tin protoporphyrin-IX (from 0.49 to 0.02 nmol per 10(7) cells/h) and increases after the administration of the HO substrate hemin (from 0.27 to 0.64 nmol per 10(7) cells/h). These results demonstrate that midinfrared laser absorption spectroscopy is a useful technique for the noninvasive and real-time detection of trace levels of CO from biological tissues.

Animals↗
PubMed2001

Temperature measurement for energy-efficient ablation by thermal radiation with a microsecond time constant from the corneal surface during ArF excimer laser ablation.

Measurement of the temperature of the corneal surface during photorefractive keratectomy (PRK) is thought to be useful for monitoring the corneal ablation process, since the photothermal process has been proposed as the major mechanism of ArF excimer laser ablation. For temperature measurement, we measured thermal radiation from the corneal surface during ArF excimer laser ablation using a mercury-cadmium-telluride detector with a 1-micros time constant. To investigate the effects of temperature on ablation depth, the ablation depth of the cornea was measured by microscopy. When corneal ablation was initiated at the fluence of 65 mJ/cm2, the corneal surface temperature rose to 60-70 degrees C. The energy required for a unit-depth ablation (degrees C/microm) was lowest at 120 micro C. Monitoring of transient temperature during PRK provides important information on energy-efficient ablation, which may enable rapid and safe corneal incisions.

Animals↗
PubMed2001

A protective effect against undesirable increase of dihydroetorphine permeation through damaged skin by using pressure-sensitive adhesive tape with an ethylene-vinyl acetate co-polymer membrane.

The release kinetics of dihydroetorphine (DHE) from pressure-sensitive adhesive (PSA) tape with an ethylene-vinyl acetate co-polymer (EVA) membrane as a diffusion-controlling membrane and its protective effect from an unpredictable increase in skin permeation of DHE caused by stratum corneum damage were investigated. The DHE flux through the EVA membrane was enhanced with the increase of vinyl acetate content. Although the DHE release from the PSA tape was proportional to the square root of the time, the release from the PSA tape covered with the EVA membrane was dominated by zero-order rate. The release rate increased by the addition of isopropyl myristate to the PSA layer, due to the increase of solubility and diffusivity of DHE in the PSA layer, and not a decrease of permeation resistance in the EVA membrane. When using the PSA tape with the EVA membrane, the steady-state flux of DHE through hairless rat skin with stratum corneum damage was not 2-fold more than that through non-damaged skin. Plasma DHE concentration rose promptly above 5 ng/ml after the application of the PSA tape onto the damaged skin in hairless rat. In contrast, when the PSA tape with the EVA membrane was applied onto the damaged or non-damaged skin, plasma concentrations in the both cases were maintained in the therapeutic range (0.2-1.2 ng/ml). These results suggest that the PSA tape with the EVA membrane can be used to protect from the unpredictable increase in skin permeation of DHE due to stratum corneum damage.

Adhesives↗
PubMed2001

[Effects of bofu-tsusho-san, a traditional Chinese medicine, on body fat accumulation in fructose-loaded rats].

The effects of Bofu-tsusho-san (BOF), a traditional Chinese medicine, on fructose-induced hypertriglyceridemia and body fat accumulation were investigated in female SD rats. Rats were allowed to drink ad libitum 25% (w/w) fructose solution for 6 weeks. BOF was administered to the rats as an experimental diet containing 1.5% or 4.5% (w/w) of BOF during the fructose-loading period. BOF suppressed body weight gain and prevented the elevation of serum triglyceride levels and body fat accumulation in fructose-loaded rats without affecting food and fructose intake. Furthermore, BOF prevented the increase of triglyceride content in the liver and the reduction of mitochondrial cytochome c oxidase activity in the brown adipose tissue induced by fructose. From these results, it has been suggested that BOF has a preventive effect against the body fat accumulation caused by excess intake of sugar or other fructose-containing foods. The inhibition of triglyceride synthesis in the liver, and the enhancement of lipolysis in adipocytes and of thermogenesis in brown adipose tissue have been presumed as the mechanisms of action of BOF.

Adipose Tissue↗
PubMed2001

Increased expression of matrix metalloproteinase in Clara cell-ablated mice inhaling crystalline silica.

We investigated the function of Clara cells in vivo during exposure to inhaled crystalline silica by examining pulmonary matrix metalloproteinase (MMP)-2 and MMP-9 mRNA levels in mice. The Clara cells of male FVB/n mice (8-12 weeks old) were ablated by intraperitoneal administration of naphthalene (300 mg/kg) in a corn oil vehicle. The mice were then exposed to crystalline silica (Min-U-Sil-5 silica, 97.1 +/- 9.5 mg/m(2), 6 hr/day, 5 days/week) for up to 2 weeks. Transcriptional levels of mRNA extracted from the lungs were assessed by reverse transcription-polymerase chain reaction. Gene expression of both MMP-2 and MMP-9 was significantly more marked in the Clara cell-ablated group than in the group with Clara cells, indicating that Clara cells inhibit MMP expression. Our findings suggest that Clara cells inhibit pulmonary inflammation induced by crystalline silica via MMPs in vivo.

Animals↗
PubMed2001

Inhaled corticosteroids reduce bone mineral density in early postmenopausal but not premenopausal asthmatic women.

Inhaled corticosteroids are widely used in the treatment of bronchial asthma, but it is still uncertain whether long-term use of the inhaled corticosteroids affects bone metabolism in asthmatic patients. In this study, we examined the effect of inhaled beclomethasone dipropionate (BDP) on bone mineral density (BMD) and biochemical markers of bone metabolism in pre- and early postmenopausal asthmatic women. Thirty-six (17 premenopausal and 19 early postmenopausal) asthmatic women and 45 healthy control (24 premenopausal and 21 early postmenopausal) women were investigated. All the asthmatic patients were treated with BDP (542 +/- 298 microg/day; 100-1200 microg/day) without any systemic administration of corticosteroids for at least 1 year. In premenopausal women, BMD as well as the biochemical markers of bone metabolism did not differ between control subjects and BDP-treated asthmatic patients. By contrast, in early postmenopausal women, BMD was significantly lower in BDP-treated asthmatic patients than in control subjects. In these early postmenopausal women, serum intact osteocalcin concentration was lower in the BDP-treated asthmatic patients than in the control subjects whereas urinary free pyridinoline (F-PYD) and free deoxypyridinoline (F-DPD) concentrations did not differ between the groups. Thus, early postmenopausal, but not premenopausal, asthmatic patients who were treated with inhaled BDP had reduced BMD, which was associated with a decreased level of the bone formation marker. Ovarian hormones may be protective against the adverse effect of inhaled BDP on bone metabolism in the premenopausal patients.

Absorptiometry, Photon↗
PubMed2001

Successful resection of rectal carcinoma in an Evans' syndrome patient followed by predonisolone and high-dose immunoglobulin: report of a case.

A 69-year-old woman was admitted to our hospital because of anal bleeding and fatigue. The patient was previously diagnosed as having Evans' syndrome on the basis of hematological examination and had been treated with predonisolone for 8 years. On admission, severe anemia and thrombocytopenia were noted. Colonoscopy and Barium enema studies demonstrated an irregular tumor with hemorrhagic ulceration in the rectum, which was histopathologically confirmed as an adenocarcinoma. After red blood cells and platelets were transfused, and the patient was treated with high-dose gammaglobulin, predonisolone, and camostat mesylate, the platelet count gradually increased and hemolysis was well controlled. The patient then underwent Hartmann's operation and splenectomy without any postoperative complications. Predonisolone and high-dose immunoglobulin therapy in a rectal cancer burdened patient with Evans' syndrome is considered useful in combination with surgical treatment. This is the first case report of rectal carcinoma resection in a patient with Evans' syndrome.

Adenocarcinoma↗
PubMed2001

Modest overexpression of neuropeptide Y in the brain leads to obesity after high-sucrose feeding.

Neuropeptide Y (NPY), one of the most abundant peptide transmitters in the mammalian brain, is assumed to play an important role in feeding and body weight regulation. However, there is little genetic evidence that overexpression or knockout of the NPY gene leads to altered body weight regulation. Previously, we developed NPY-overexpressing mice by using the Thy-1 promoter, which restricts NPY expression strictly within neurons in the central nervous system, but we failed to observe the obese phenotype in the heterozygote. Here we report that in the homozygous mice, overexpression of NPY leads to an obese phenotype, but only after appropriate dietary exposure. NPY-overexpressing mice exhibited significantly increased body weight gain with transiently increased food intake after 50% sucrose--loaded diet, and later they developed hyperglycemia and hyperinsulinemia without altered glucose excursion during 1 year of our observation period.

Aging↗
PubMed2001

In vivo studies of man-made mineral fibers--fibrosis-related factors.

Pneumoconiosis that pursues a chronic course may result from repeated injury and repair caused by dust particles that remain in the lungs, leading to fibrosis. We will introduce in vivo studies concerning these processes using animals exposed to man-made mineral fibers and asbestos. We will report on whether there are developmental changes with the mineral fiber and animal model in proinflammatory cytokine, chemokine, free radicals, proteinase and other genes that lead to injury, as well as in genes that effect repair such as growth factor, and we will also report on the effects of surfactant protein and clara cell secretory protein on fibrosis.

Animals↗