Biomedical subjects

Y Kumagai

Publications and source records attributed to Y Kumagai.

At least 19 recordsLinked to original sources

PubMed2006

Naphthoquinone enhances antigen-related airway inflammation in mice.

The current authors have previously demonstrated that diesel exhaust particles (DEP) enhance antigen-related airway inflammation in mice. Furthermore, a recent study has shown that organic chemicals in DEP, rather than their carbonaceous nuclei, are important contributors to the aggravating effects of airway inflammation. However, the components in DEP responsible for the enhancing effects on the model remain to be identified. The current authors investigated the effects of naphthoquinone (NQ), one of the extractable chemical compounds of DEP, on antigen-related airway inflammation, local expression of cytokine proteins, and antigen-specific immunoglobulin (Ig) production in mice. Pulmonary exposure to NQ dose-dependently aggravated antigen-related airway inflammation, as characterised by infiltration of eosinophils and lymphocytes around the airways and an increase in goblet cells in the bronchial epithelium. Combined exposure to NQ and antigen enhanced the local expression of interleukin (IL)-4, IL-5, eotaxin, macrophage chemoattractant protein-1 and keratinocyte chemoattractant, compared with exposure to antigen or NQ alone. Also, NQ exhibited adjuvant activity for the antigen-specific production of IgG(1) and IgG(2a). These results provide the first experimental evidence that naphthoquinone can enhance antigen-related airway inflammation in vivo, and that naphthoquinone can, to some extent, partly play a role in the pathogenesis of diesel exhaust particle toxicity on the condition.

Animals↗

PubMed2005

Effects of phenanthraquinone on allergic airway inflammation in mice.

BACKGROUND: Diesel exhaust particles (DEP) enhance allergic airway inflammation in mice (Takano et al., Am J Respir Crit Care Med 1997; 156: 36-42). DEP consist of carbonaceous nuclei and a vast number of organic chemical compounds. However, it remains to be identified which component(s) from DEP are responsible for the enhancing effects. 9,10-Phenanthraquinone (PQ) is a quinone compound involved in DEP. OBJECTIVE: To investigate the effects of PQ inoculated intratracheally on allergic airway inflammation related to ovalbumin (OVA) challenge. MATERIALS AND METHODS: We evaluated effects of PQ on airway inflammation, local expression of cytokine proteins, and allergen-specific immunoglobulin production in mice in the presence or absence of OVA. Results In the presence of OVA, PQ (2.1 ng/animal) significantly increased the numbers of eosinophils and mononuclear cells in bronchoalveolar lavage fluid as compared with OVA alone. In contrast, the numbers of these cells around the airways were not significantly different between OVA challenge and OVA plus PQ challenge in lung histology. PQ exhibited adjuvant activity for the allergen-specific production of IgG1 and IgE. OVA challenge induced significant increases in the lung expression of IL-4, IL-5, eotaxin, macrophage chemoattractant protein-1, and keratinocyte chemoattractant as compared with vehicle challenge. However, the combination of PQ with OVA did not alter the expression levels of these proteins as compared with OVA alone. CONCLUSION: These results indicate that PQ can enhance the immunoglobulin production and the infiltration of inflammatory cells into alveolar spaces that are related to OVA, whereas PQ seems to be partially responsible for the DEP toxicity on the allergic airway inflammation.

Air Pollutants↗

PubMed2005

Effect of MKC-733, a 5-HT receptor partial agonist, on bowel motility and symptoms in subjects with constipation: an exploratory study.

BACKGROUND: MKC-733, a 5-HT(3) receptor partial agonist, is a novel enteroprokinetic compound. OBJECTIVE: The aim of this study was to explore the effects of MKC-733 on bowel motility and symptoms in a small group of subjects with constipation. Tolerability was also examined. METHODS: The study was conducted in a single-blind and dose-escalation manner on 14 male and female subjects with constipation aged 22-67 years. After a 1 week run-in period, subjects were treated with placebo (b.i.d.) for 1 week, and 0.2 and 0.5 mg of MKC-733 (b.i.d.) for 2 weeks sequentially. Geometric mean and per cent elimination of surrogate markers of bowel motility were measured by a radio-opaque marker technique at the end of each treatment period. They were analysed on the whole group and subgroups with low (n = 6) and high (n = 8) bowel motility based upon the geometric mean value after placebo treatment. Subjects kept diaries of their bowel habits and gastrointestinal symptoms. RESULTS: Percent elimination increased after treatment with 0.5 mg MKC-733 compared with placebo treatment in the whole group (70.4 +/- 33.5% vs. 47.1 +/- 36.6%, mean +/- SD, P < 0.05). In the low bowel motility group, both geometric mean and percent elimination increased after treatment with 0.5 mg MKC-733 compared with placebo (7.1 +/- 0.9 vs. 5.9 +/- 0.5, P < 0.05; 60.0 +/- 35.8% vs. 13.3 +/- 19.4%, P < 0.05). Stool frequency increased after the first-week treatment with MKC-733 compared with placebo (P < 0.05). Numbers of sensation of incomplete evacuation and gastrointestinal symptoms decreased to half and less after the treatment with MKC-733. No serious adverse effect was noted. CONCLUSION: Multiple doses of 0.5 mg MKC-733 improve bowel motility, which was clearly demonstrated in the subjects with decreased bowel motility. MKC-733 at the doses studied might be effective in increasing stool frequency and reduce gastrointestinal symptoms related to constipation. MKC-733 was well tolerated. Further studies will be needed to clarify efficacy and safety of MKC-733 on a larger population.

Adult↗

PubMed2004

A fragment of the hypophosphatemic factor, MEPE, requires inducible cyclooxygenase-2 to exert potent anabolic effects on normal human marrow osteoblast precursors.

MEPE, 56.6 kDa protein isolated from tumors associated with hypophosphatemic osteomalacia, increases renal phosphate excretion and is expressed in normal human bone cells. AC-100, a central 23-amino acid fragment of MEPE, contains motifs that are important in regulating cellular activities in the bone microenvironment. Thus, we assessed in vitro effects of AC-100 on multipotential normal human marrow stromal (hMS) cells that have the capacity to differentiate into mature osteoblasts. Proliferation was quantified by [H3]thymidine uptake and cell counting and differentiation by the levels of mRNA for the alpha2-chain of type I procollagen (COL1A2), alkaline phosphatase (AP), and osteocalcin (OC) measured using real time reverse transcriptase PCR (RT-PCR) and by the formation of mineralized nodules. AC-100 increased proliferation by 257 +/- 89% (P < 0.005), increased gene expression of COL1A2 by 339 +/- 85% (P < 0.005), AP by 1,437 +/- 40% (P < 0.001), and OC by 1,962 +/- 337% (P < 0.001). In addition, it increased mineralized nodule formation by 81 +/- 14% (P < 0.001) in a dose- and time-dependent fashion. In equimolar dosages, the parent compound, MEPE, had the full activity of the AC-100 fragment. AC-100 elicited a comparable response to both IGF-I and BMP-2 with respect to proliferation and differentiation of hMS cells. Using gene expression microarray analysis, we demonstrated that AC-100 increased (by approximately 3-fold) the mRNA for cyclooxgenase-2 (COX-2), an inducible enzyme required for prostaglandin synthesis. Moreover, NS-398, a specific inhibitor of COX-2 action completely blocked AC-100-induced increases in proliferation and differentiation. Thus, AC-100 has potent anabolic activity on osteoblast precursor cells in vitro and these effects require the induction of COX-2.

Biomarkers↗

PubMed2004

MEPE has the properties of an osteoblastic phosphatonin and minhibin.

Matrix extracellular phosphoglycoprotein (MEPE) is expressed exclusively in osteoblasts, osteocytes and odontoblasts with markedly elevated expression found in X-linked hypophosphatemic rickets (Hyp) osteoblasts and in oncogenic hypophosphatemic osteomalacia (OHO) tumors. Because these syndromes are associated with abnormalities in mineralization and renal phosphate excretion, we examined the effects of insect-expressed full-length human-MEPE (Hu-MEPE) on serum and urinary phosphate in vivo, (33)PO(4) uptake in renal proximal tubule cultures and mineralization of osteoblast cultures. Dose-dependent hypophosphatemia and hyperphosphaturia occurred in mice following intraperitoneal (IP) administration of Hu-MEPE (up to 400 microg kg(-1) 31 h(-1)), similar to mice given the phosphaturic hormone PTH (80 microg kg(-1) 31 h(-1)). Also the fractional excretion of phosphate (FEP) was stimulated by MEPE [65.0% (P < 0.001)] and PTH groups [53.3% (P < 0.001)] relative to the vehicle group [28.7% (SEM 3.97)]. In addition, Hu-MEPE significantly inhibited (33)PO(4) uptake in primary human proximal tubule renal cells (RPTEC) and a human renal cell line (Hu-CL8) in vitro (V(max) 53.4% inhibition; K(m) 27.4 ng/ml, and V(max) 9.1% inhibition; K(m) 23.8 ng/ml, respectively). Moreover, Hu-MEPE dose dependently (50-800 ng/ml) inhibited BMP2-mediated mineralization of a murine osteoblast cell line (2T3) in vitro. Inhibition of mineralization was localized to a small (2 kDa) cathepsin B released carboxy-terminal MEPE peptide (protease-resistant) containing the acidic serine-aspartate-rich motif (ASARM peptide). We conclude that MEPE promotes renal phosphate excretion and modulates mineralization.

Amino Acid Sequence↗

PubMed2004

Magnifying chromoendoscopy of the esophagus: in-vivo pathological diagnosis using an endocytoscopy system.

BACKGROUND AND STUDY AIMS: The aim of the present study was to observe the endoscopic characteristics of cells on the surface layer of superficial esophageal carcinomas in vivo using an endocytoscopy system and to compare the findings with those in normal squamous epithelium. PATIENTS AND METHODS: Superficial esophageal cancers in 12 patients were examined with methylene blue staining using an endocytoscopy system. RESULTS: The endocytoscopy system and methylene blue staining made it possible to observe cells on the surface of the squamous epithelium in normal esophageal mucosa. Normal cells were arranged homogeneously, and the nucleus cytoplasm ratio was uniform and low. In esophageal cancers, the density of cells was found to be much greater than that in normal squamous epithelium. The cell distribution was also irregular and the cells were extremely heterogeneous, with the nuclei having different staining, size, and shape characteristics. The nucleus cytoplasm ratio was also very irregular. CONCLUSIONS: Examining esophageal tissue using the endocytoscopy system described here makes it possible to observe detailed histological alterations in esophageal lesions in vivo.

Carcinoma, Squamous Cell↗

PubMed2004

Dentonin, a fragment of MEPE, enhanced dental pulp stem cell proliferation.

Matrix extracellular phosphoglycoprotein (MEPE) is a SIBLING protein, found in bone and dental tissues. The purpose of this study was to determine whether a 23-amino-acid peptide derived from MEPE (Dentonin or AC-100) could stimulate dental pulp stem cell (DPSC) proliferation and/or differentiation. DPSCs were isolated from erupted human molars, and the mitogenic potential of Dentonin in DPSCs was measured by BrdU immunoassay and cell-cycle gene SuperArray. Differentiation of DPSCs with Dentonin was characterized by Western blot and by osteogenesis gene SuperArray. Dentonin enhanced DPSC proliferation by down-regulating P16, accompanied by up-regulation of ubiquitin protein ligase E3A and human ubiquitin-related protein SUMO-1. Enhanced cell proliferation required intact RGD and SGDG motifs in the peptide. This study shows that Dentonin can promote DPSC proliferation, with a potential role in pulp repair. Further studies are required to determine the usefulness of this material in vivo.

Amino Acid Sequence↗

PubMed2003

Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis.

BACKGROUND: The authors reported a mutation, P1158S, of the human skeletal muscle sodium channel gene (SCN4A) in a family with cold-induced hypokalemic periodic paralysis (hypoKPP) and myotonia. OBJECTIVE: To identify mechanisms of temperature dependency in this channelopathy. METHODS: Using the amphotericin B perforated patch clamp method, sodium currents were recorded at 22 and 32 degrees C from the wild-type (WT) and P1158S mutant SCN4A expressed in tsA201 cells. Computer simulation was performed, incorporating the gating parameters of the P1158S mutant SCN4A. RESULTS: P1158S mutant SCN4A exhibited hyperpolarizing shifts in voltage dependence of both activation and inactivation curves at a cold temperature and a slower rate of inactivation than the WT. Computer simulation reproduced the abnormal skeletal muscle electrical activities of both paralysis at a low potassium concentration in the cold and myotonia at a normal potassium concentration. CONCLUSIONS: Both paralysis and myotonia are attributable to the biophysical properties of the SCN4A mutation associated with hypoKPP. This is the first report of an SCN4A mutation that exhibits temperature-dependent shifts of voltage dependence in sodium channel gating.

Action Potentials↗

PubMed2003

Enhancement of acute lung injury related to bacterial endotoxin by components of diesel exhaust particles.

BACKGROUND: Diesel exhaust particles (DEP) synergistically aggravate acute lung injury related to lipopolysaccharide (LPS) in mice, but the components in DEP responsible for this have not been identified. A study was undertaken to examine the effects of the organic chemicals (DEP-OC) and residual carbonaceous nuclei (washed DEP) derived from DEP on LPS related lung injury. METHODS: ICR mice were divided into experimental groups and vehicle, LPS, washed DEP, DEP-OC, washed DEP+LPS, and DEP-OC+LPS were administered intratracheally. The cellular profile of the bronchoalveolar lavage (BAL) fluid, pulmonary oedema, lung histology, and expression of proinflammatory molecules and Toll-like receptors in the lung were evaluated. RESULTS: Both DEP-OC and washed DEP enhanced the infiltration of neutrophils into BAL fluid in the presence of LPS. Washed DEP combined with LPS synergistically exacerbated pulmonary oedema and induced alveolar haemorrhage, which was concomitant with the enhanced lung expression of interleukin-1beta, macrophage inflammatory protein-1alpha, macrophage chemoattractant protein-1, and keratinocyte chemoattractant, whereas DEP-OC combined with LPS did not. Gene expression of Toll-like receptors 2 and 4 was increased by combined treatment with washed DEP and LPS. The enhancement effects of washed DEP on LPS related changes were comparable to those of whole DEP. CONCLUSIONS: These results suggest that the residual carbonaceous nuclei of DEP rather than the extracted organic chemicals predominantly contribute to the aggravation of LPS related lung injury. This may be mediated through the expression of proinflammatory cytokines, chemokines, and Toll-like receptors.

Animals↗

PubMed2002

Magnifying endoscopy, stereoscopic microscopy, and the microvascular architecture of superficial esophageal carcinoma.

BACKGROUND AND STUDY AIMS: In this study we clarify the microvascular architecture of superficial esophageal carcinoma as observed by ultra-high magnification endoscopy and stereoscopic microscopy with Microfil injection. PATIENTS AND METHODS: We observed two surgically resected specimens of superficial esophageal cancer under stereoscopic microscopy with Microfil injection. In addition, in the histological investigation, we measured the caliber of the vessels at the surface of the tumor. We carried out ultra-high magnification before treatment in 82 patients with superficial esophageal neoplasms. We classified the depth of tumor penetration of superficial esophageal carcinoma into four categories: m1 to m3 (mucosal cancer) and sm (submucosal cancer). RESULTS: By observing the normal esophageal mucosa under a stereoscopic microscope and an ultra-high magnification endoscope, we were able to visualize the intrapapillary capillary loops (IPCL). In cancer lesions, we observed characteristic changes in the superficial microvascular architecture according to the depth of tumor invasion. In m1 invasion, there was dilatation of the IPCL; in m2 invasion, there was dilatation and elongation of the IPCL; in m3, there was a mixed appearance of the IPCL and tumor vessels; and in sm invasion, complete replacement by tumor vessels. On the basis of the above criteria, ultra-high magnification endoscopic observation before treatment showed a rate of agreement between histological depth of invasion and magnified appearance of 60/72 cases (83.3 %) for which satisfactory pictures were obtained. The histological investigation showed the caliber of the IPCL of the m1 cancer lesions (12.9 +/- 3.9 microm) to be significantly greater than that of the normal esophageal mucosa (6.9 +/- 1.5 microm) (P < 0.0001). CONCLUSIONS: Observation of the microvascular architecture of superficial esophageal carcinoma is useful in the diagnosis of the depth of invasion.

Carcinoma↗

PubMed2001

Impairment of spermatogenesis in rats by methylmercury: involvement of stage- and cell- specific germ cell apoptosis.

Methylmercury has been shown to affect the male reproductive organs. However, the specific mode of impairment of spermatogenesis during methylmercury exposure remains unknown. In this study, we characterized the induction of germ cell apoptosis and reproductive toxicity in Wistar male rats that had been exposed to methylmercuric chloride (MMC). Subcutaneous injection of MMC at a dose of 10 mg/kg per day for 8 days resulted in a 28% testicular weight loss at 14 days after the first injection. In addition, the ventral and dorso-lateral prostatic lobes showed a 65 and 52% decrease, respectively, at 14 days, although no effects were observed in the epididymis. Sperm production also was suppressed by the administration of MMC. After exposure to MMC, fragmentation of testicular DNA was found to be increased at 3 days after the first injection, with a 20-fold increase over control levels at 14 days. In situ detection of apoptosis by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) staining revealed that spermatocytes and spermatids at stages VII-VIII and IX-XI, respectively, steps which are considered to be highly sensitive to testosterone, were the major cell types affected. Consequently, a marked cell loss in elongated spermatids at stages XII-XIV and I was observed at 14 days. In addition, plasma testosterone levels were reduced at 6 days after exposure to MMC, and remained at approximately 20% of control levels during the 14-day observation period. Our results suggest that methylmercury impairs spermatogenesis by germ cell deletion via cell- and stage- specific apoptosis.

Animals↗

PubMed2001

Effects of exercise training of 8 weeks and detraining on plasma levels of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans.

Vascular endothelial cells produce nitric oxide (NO), which is a potent vasodilator substance and has been proposed as having antiatherosclerotic property. Vascular endothelial cells also produce endothelin-1 (ET-1), which is a potent vasoconstrictor peptide and has potent proliferating activity on vascular smooth muscle cells. Therefore, ET-1 has been implicated in the progression of atheromatous vascular disease. Because exercise training has been reported to produce an alteration in the function of vascular endothelial cells in animals, we hypothesized that exercise training influences the production of NO and ET-1 in humans. The purpose of the present study was to examine whether chronic exercise could influence the plasma levels of NO (measured as the stable end product of NO, i.e., nitrite/nitrate [NOx]) and ET-1 in humans. Eight healthy young subjects (20.3 +/- 0.5 yr old) participated in the study and exercised by cycling on a leg ergometer (70% VO2max for 1 hour, 3-4 days/week) for 8 weeks. Venous plasma concentrations of NOx and ET-1 were measured before and after (immediately before the end of 8-week exercise training) the exercise training, and also after the 4th and 8th week after the cessation of training. The VO2max significantly increased after exercise training. After the exercise training, the plasma concentration of NOx significantly increased (30.69 +/- 3.20 vs. 48.64 +/- 8.16 micromol/L, p < 0.05), and the plasma concentration of ET-1 significantly decreased (1.65 +/- 0.14 vs. 1.23 +/- 0.12 pg/mL, p < 0.05). The increase in NOx level and the decrease in ET-1 level lasted to the 4th week after the cessation of exercise training and these levels (levels of NOx and ET-1) returned to the basal levels (the levels before the exercise training) in the 8th week after the cessation of exercise training. There was a significant negative correlation between plasma NOx concentration and plasma ET-1 concentration. The present study suggests that chronic exercise causes an increase in production of NO and a decrease in production of ET-1 in humans, which may produce beneficial effects (i.e., vasodilative and antiatherosclerotic) on the cardiovascular system.

Adult↗

PubMed2001

Structure of microbial communities in activated sludge: potential implications for assessing the biodegradability of chemicals.

Various methods used to assess the biodegradability of chemicals often employ activated sludge as an inoculum since chemicals that ultimately enter the environment are often discharged through wastewater. Differences in the structure and function of activated sludge microbial communities that may complicate interpretation of biodegradation tests could arise from differences in wastewater composition, wastewater treatment plant (WWTP) operation, or manipulations done after collection of the activated sludge. In this study, various methods were used to characterize the structure of microbial communities found in freshly collected activated sludge from WWTPs in Japan, Europe, and the United States, as well as sludge that had been continuously fed either sewage or a glucose-peptone mixture for several weeks after collection. Comparisons of biomass levels, whole-community substrate utilization (determined using Biolog GN and GP plates), and phospholipid fatty acid (PLFA) profiles indicated there were both geographical and temporal differences among freshly collected activated sludge samples. Moreover, marked shifts in the structure of activated sludge microbial communities occurred upon continuous cultivation in the laboratory for 5 weeks using a glucose-peptone feed. These shifts were evident from whole-community substrate utilization and PLFA profiles as well as differences in the profiles of 16S rDNA genes from numerically dominant populations obtained by denaturing gradient gel electrophoresis and terminal restriction fragment analyses. Further studies are needed to better define the variability within and between activated sludge from wastewater treatment plants and laboratory reactors and to assess the impact of such differences on the outcome of biodegradability tests.

Bacteria↗

PubMed2001

Multiple primary cancers associated with esophageal carcinoma.

This study was conducted to examine the characteristics of esophageal cancers with primary synchronous or metachronous cancer in another organ. We retrospectively evaluated 744 patients who underwent esophagectomy for esophageal cancers between 1985 and 1998. The patients were divided into two groups according to whether they had multiple primary cancer (MPC) or nonmultiple primary cancer (NPC). Stage I cancer was significantly more frequent among patients with MPC than among those with NPC (P < 0.0001). Among patients with MPC, another primary cancer was found in the head and neck region in 70 (42.4%), in the stomach in 51 (30.9%), and in the colon, lung, breast, and other locations in the remaining patients. Of the 70 patients with another primary cancer in the head and neck region, 32 (45.7%) had pharyngeal cancer. Furthermore, the incidence of intraesophageal multiple cancer in the patients with primary cancer in the head and neck region was significantly higher than that in those whose other primary cancers were gastric cancer or in those with NPC (P = 0.0135. P < 0.0001). The 5-year survival rate of the patients with MPC was 51.28%, which was significantly higher than that of those with NPC (P = 0.019). In conclusion, a better knowledge of the relationships between esophageal carcinoma and cancers in other organs may lead to earlier detection of other primary cancers and improved therapeutic results.

Carcinoma, Squamous Cell↗

PubMed2001

Telemedical support using real-time ultrasonography and endoscopy images.

We developed a telecommunications apparatus (TMS-6101, NIHON KOHDEN WELLNESS CORPORATION, Tokyo, Japan) and evaluated its clinical utility as a telemedical support system. It is capable of transmitting on a real-time basis such vital signs as blood pressure, arterial O2 saturation and ECG recordings, which are measured at bedside using the Life-Mate monitor (NIHON KOHDEN WELLNESS Co.). It is also capable of transmitting moving video-camera pictures in real time. In this study we assessed its application for telemedical supports with particular emphasis on ultrasonography and endoscopy images since reports of such applications are lacking. Employing this system, several kinds of technically demanding endoscopic procedures were supported successfully under the supervision of at least one off-site specialist physician. The system proved to be a very useful medical resource, since it facilitated high quality medical care and specialist consultation at any location without those specialists traveling to the scene.

Endoscopy↗

PubMed2001

Proinflammatory characteristics of a nonpeptide bradykinin mimic, FR190997, in vivo.

1. Proinflammatory potency of the nonpeptide bradykinin (BK) B(2) receptor agonist FR190997 (8-[2,6-dichloro-3-[N-[(E)-4-(N-methylcarbamoyl)cinnamidoacetyl]-N-methylamino]benzyloxy]-2-methyl-4-(2-pyridylmethoxy)quinoline) was investigated. 2. Intradermal injection of FR190997 (0.03 - 3 nmol site(-1)) into dorsal skin of rats increased vascular permeability in a dose-dependent manner. The effect was less than that of BK, but it was long-acting and was inhibited by treatment with FR173657 (3 mg kg(-1), p.o.). Captopril (10 mg kg(-1), i.p.) did not enhance the plasma extravasation by FR190997 (0.3 nmol site(-1)) in the presence of soybean trypsin inhibitor (SBTI, 30 microg site(-1)). 3. Subcutaneous injection of FR190997 (3 nmol site(-1)) into the hindpaw of mice markedly induced paw swelling. The oedema lasted up to 3 h after the injection. Administration of indomethacin or NS-398 (10 mg kg(-1), i.p.) significantly reduced it at 3 h after the injection. 4. Simultaneous i.p. injection of prostaglandin (PG) E(2) (1 nmol site(-1)) or beraprost sodium (0.5 nmol site(-1)) with FR190997 (5 nmol site(-1)) greatly enhanced frequency of writhing reactions in mice. 5. FR190997 (0.3 - 30 nmol kg(-1), i.v.) showed less increase in airway opening pressure (Pao) in the guinea-pig after i.v. injection. Furthermore, FR190997 (0.03 - 30 nmol) resulted in a very weak contraction of tracheal ring strips and lung parenchymal sections in vitro. 6. In mice sponge implants, topical application of FR190997 increased angiogenesis and granulation with enhanced expressions of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) mRNAs. 7. These results indicate that FR190997 has proinflammatory long-lasting characteristics and it might be 'a stable tool' for studying the role of BK B(2) receptor in vivo.

Animals↗

PubMed2001

Characteristics of a column suitable for capacity gradient chromatography with a borate eluent.

In capacity gradient elution, the gradient separation of ionic species is achieved by decreasing the ion-exchange capacity of a column during the course of the separation. Diol-type hydroxy groups on the resin surface form anionic complexes with borate as an eluting reagent. Thus, a chemically bonded anion-exchange column enriched with residual hydroxy groups allows the creation of a capacity gradient. An increase in the amount of the complex formed gradually brings about a decrease in the ion-exchange capacity of the column, and strongly bound analyte ions are eluted. We investigated the characteristics of a column suitable for this eluent system. The concentration of borate eluent required to remove the ion-exchange capacity depended inversely on the ratio of the residual hydroxy groups to functional groups. On a column in which this ratio was approximately 100, the ion-exchange capacity could easily be adjusted by using a low concentration of mannitol as a competing reagent. Use of this column led to very small baseline shifts during the borate-mannitol gradients, and to the simultaneous determination of anions with widely varying retention times.

Borates↗

PubMed2001

Histopathological studies on virulence of dipeptidyl aminopeptidase IV (DPPIV) of Porphyromonas gingivalis in a mouse abscess model: use of a DPPIV-deficient mutant.

To elucidate the role of dipeptidyl aminopeptidase IV (DPPIV) in the virulence of Porphyromonas gingivalis, mice were infected with either a wild-type strain or a DPPIV-deficient mutant using an abscess model. Histopathological analysis of the resulting lesions indicated that DPPIV participates in virulence through the destruction of connective tissue and the less effective mobilization of inflammatory cells.

Abscess↗