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Y Kumagai

Publications and source records attributed to Y Kumagai.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Phenanthraquinone inhibits eNOS activity and suppresses vasorelaxation.

Diesel exhaust particles cause an impairment of endothelium-dependent vasorelaxation and are associated with cardiopulmonary-related diseases and mortality, but the mechanistic details are poorly understood. Since we reported previously that phenanthraquinone, an environmental chemical contained in diesel exhaust particles, suppresses neuronal nitric oxide synthase (nNOS) activity by shunting electrons away from the normal catalytic pathway, it was hypothesized that phenanthraquinone inhibits endothelial NOS (eNOS) activity and affects vascular tone. Therefore, the effects of phenanthraquinone on eNOS activity, endothelium-dependent relaxation, and blood pressure were examined in the present study. Phenanthraquinone inhibited NO formation evaluated by citrulline formed by total membrane fraction of bovine aortic endothelial cells with an IC(50) value of 0.6 microM. A kinetic study revealed that phenanthraquinone is a competitive inhibitor with respect to NADPH and a noncompetitive inhibitor with respect to L-arginine. Endothelium-dependent relaxation of rat aortic rings by ACh was significantly inhibited by phenanthraquinone (5 microM), whereas the endothelium-independent relaxation by nitroglycerin was not. Furthermore, an intraperitoneal injection of phenanthraquinone (0.36 mmol/kg) to rats resulted in an elevation of blood pressure (1.4-fold, P < 0.01); under this condition, plasma levels of stable NO metabolites, nitrite/nitrate, in phenanthraquinone-treated rats was reduced to 68% of control levels. The present findings suggest that phenanthraquinone has a potent inhibitory action on eNOS activity via a similar mechanism reported for nNOS, thereby causing the suppression of NO-mediated vasorelaxation and elevation of blood pressure.

Air Pollutants↗

Incidence of genetic subgroups of hereditary spinocerebellar ataxia in Fukushima Prefecture.

The prevalence of each type of hereditary spinocerebellar ataxias (SCAs) was genetically determined in Fukushima Prefecture, and the results were compared to those in other areas of Japan. The genetic analyses were done in 29 patients with dominant SCA and 5 patients with SCA with negative family history. Machado-Joseph disease was identified in 41.3% of the cases, SCA6 17.2%, dentatorubral-pallidoluysian atrophy (DRPLA) 6.9% and unknown 34.5%. The incidence is clearly different from those of Miyagi and Yamagata Prefectures as SCA1 has not been identified in our region, and is in fact similar to that of Hokuriku or Kanto Provinces. An apparent difference in the incidence of each SCA may be attributed to the historical and geographic regional difference in the distribution of inhabitants and also to the small size of the SCA population we have so far investigated. In addition, 2 of the 3 genetically identified DRPLA in this study were not clinically diagnosed, and one of them was thought to be sporadic. Late onset DRPLA may thus be misdiagnosed to other disease categories, when dementia was not apparent at the time of onset.

Genetic Diseases, Inborn↗

Ecological co-inhabitance index (ECI) as a management tool for ecosystem preservation in rivers.

The number of novel man-made hazardous substances produced by industries is increasing year after year, resulting in conventional discharge standards ineffective to preserve the natural ecological environment. A novel index, ecological co-inhabitance index (ECI), was proposed in order to evaluate the river ecosystem sensitively. The river benthic community with a high value of ECI is formed in the healthy ecosystem where benthic animals can share resources in the river environment efficiently, keep the ecosystem functioning, and give the least adverse effect to lower reaches of the river. In order to clarify the characteristic of ECI, the relationship between ECI and water quality in the river was investigated using the data on benthic animals obtained from 17 various rivers. Results of this investigation indicated that ECI could synthetically evaluate the river environment without a bias toward a specific water quality. Moreover, ECI had the significant correlation coefficients with diversity index, biotic index and pollution index at significance level 0.05, respectively. Therefore, ECI is a promising index for managing the river ecosystem.

Animals↗

Inhibitory effect of low density lipoprotein on the inflammation-inducing activity of calcium pyrophosphate dihydrate crystals.

OBJECTIVE: It has been proposed that low density lipoprotein (LDL) plays a role in the self-limiting nature of pseudogout inflammation. We investigated changes of LDL concentration in rat air pouch fluid during periods of acute and subsiding inflammation to evaluate whether LDL contributes to inhibiting inflammation of pseudogout. We examined whether LDL binds to calcium pyrophosphate dihydrate (CPPD) crystals as a possible mechanism for reduction of inflammation. METHODS: In this in vivo study, 5 mg suspensions of CPPD crystals and saline were injected into the rat air pouch. Fluid samples were taken from rat air pouch at 0, 3, 6, 12, 24, and 48 h after injection. White blood cells in the samples were counted; the remaining fluid was centrifuged and concentrations of beta-glucuronidase and PGE2 in the supernatant were measured as inflammatory markers. LDL in the supernatant was immunochemically identified by Western blotting, then pellets containing crystals were examined by the same technique. RESULTS: LDL was identified in the air pouch 3 h after CPPD crystal injection, and its concentration increased and reached a peak level after 24 h. Inflammatory markers reached maximal level from 6 to 12 h, then decreased after 24 h. In the pellets containing crystals, LDL could not be identified in every specimen. CONCLUSION: LDL in the rat air pouch increased during the inflammatory course induced by CPPD crystal and the inflammation subsided as the LDL increased. Since some reports indicate LDL was related to reduction of crystal induced inflammation such as gout or pseudogout, we concluded that LDL could contribute to the resolution of acute pseudogout arthritis in vivo with or without binding to CPPD crystals.

Animals↗

Zeta-crystallin catalyzes the reductive activation of 2,4,6-trinitrotoluene to generate reactive oxygen species: a proposed mechanism for the induction of cataracts.

Exposure to 2,4,6-trinitrotoluene (TNT) has been shown to cause induction of cataract in which oxidative stress plays a critical role. From bovine lens we purified to homogeneity and identified an enzyme that catalyzes the reduction of TNT, resulting in the production of reactive oxygen species. The final preparation of TNT reductase showed a single band with a subunit molecular weight of 38 kDa on SDS-PAGE. Sequence data from peptides obtained by digestion with lysylendopeptidase Achromobacter protease I (API) revealed that TNT reductase is identical to zeta-crystallin. Superoxide anions were formed during reduction of TNT by zeta-crystallin, though negligible enzyme activity or protein content for superoxide dismutase, a superoxide scavenging enzyme, was found in the lens. Thus, the present results suggest that the induction of cataracts by TNT may be associated with increased oxidative stress, as a result of reductive activation of TNT generating superoxide anions, there being minimal antioxidant enzyme activity for defense against reactive oxygen species exogenously produced in the lens.

Amino Acid Sequence↗

Involvement of the renal kallikrein-kinin system in K(+)-induced diuresis and natriuresis in anesthetized rats.

Intravenous infusion of a high-K(+) solution (67.5 mM KCl, 67.5 mM NaCl) to anesthetized rats increased urine volume by 47.6% after 60 min, compared with infusion of a Na(+) solution (135 mM NaCl). This treatment also increased urinary excretion of Na(+) by 32.2%, in parallel with an increase in excretion of K(+) or Cl(-). Urinary excretion of kallikrein increased within 60 min after the start of K(+) infusion. A bradykinin B(2) receptor antagonist, 8-[3-[N-[(E)-3-(6-acetamidopyridin-3-yl)acryloylglycyl]-N-me thylamino ]-2,6-dichlorobenzyloxy]-2-methylquinoline (FR173657; 1.0 mg/kg, i.v. ), inhibited the K(+)-induced diuresis and natriuresis by 41.0% and 26.7%, respectively. These results indicate that K(+) load induces diuresis and natriuresis through the renal kallikrein-kinin system in rats.

Anesthesia↗

Improved method for simultaneous determination of L-arginine and its mono- and dimethylated metabolites in biological samples by high-performance liquid chromatography.

An improved method has been developed for the determination of L-arginine and its methylated metabolites, N(G)-monomethyl-L-arginine (L-NMMA), N(G),N(G)-dimethyl-L-arginine (asymmetric DMA, ADMA) and N(G),N(G)'-dimethyl-L-arginine (symmetric DMA, SDMA) in biological samples. Extraction of these compounds with a strong cation-exchange resin AG50W-X8 with L-homoarginine (2-amino-6-guanidinohexanoic acid) as an internal standard gave a recovery of more than 70% except for SDMA from plasma samples. After extracted samples were converted to fluorescent derivatives with o-phthalaldehyde (OPA) in an alkaline medium, the following high-performance liquid chromatographic separation with a ODS column (wide-pore size, 300 A) was successfully performed with an isocratic mobile phase system. The method permits quantitative determination of L-arginine and its methylated metabolites at concentrations as low as 4 microM and 0.18 microM, respectively. Using this method, the levels of L-arginine, L-NMMA, ADMA and SDMA in human plasma, urine and rat tissue were determined.

Adult↗

Decreased serum concentrations of nitric oxide metabolites among Chinese in an endemic area of chronic arsenic poisoning in inner Mongolia.

Prolonged exposure to arsenic results in peripheral and cardiovascular manifestations, as does impaired production of endothelial nitric oxide (NO). In vitro studies have indicated that endothelial cells undergo damage by arsenic. However, no information has been available on the relationship between NO synthesis and chronic arsenic poisoning in humans. The present study was designed to reveal this question. The subjects were 33 habitants who continued to drink well water containing high concentrations of inorganic arsenic (mean value = 0.41 microg/ml) for about 18 years in Inner Mongolia, China, and 10 other people who lived in this area but exposed to minimal concentrations of arsenic (mean value = 0.02 microg/ml) were employed as controls. Mean blood concentration of total arsenic was six times higher in exposed subjects than controls; 42.1 vs. 7.3 ng/ml, p <.001. Mean serum concentration of nitrite/nitrate, stable metabolites of endogenous NO, was lower in arsenic-exposed subjects than in controls: 24.7 vs. 51.6 microM, p<.001. In total samples, an inverse correlation with serum nitrite/nitrate levels was strong for blood inorganic arsenic (r = -0.52, p <.001) and less strong for its metabolites, monomethyl arsenic (r = -0.45, p<.005) and dimethyl arsenic (r = -0.37, p<.05). Furthermore, serum nitrite/nitrate concentration was significantly correlated with nonprotein sulfhydryl level in whole blood (r = 0.58, p<.001). In an in vitro study, we demonstrated that inorganic arsenite or arsenate suppresses the activity of endothelial NO synthase in human umbilical vein endothelial cells. These results suggest that long-term exposure to arsenic by drinking well water possibly reduces NO production in endothelial cells, resulting in a decrease in reduced nitrite/nitrate concentrations. Peripheral vascular disorders caused by arsenic may be attributable in part to impairment of NO production in vivo.

Adolescent↗

Primary response of naive CD4(+) T cells to amino acid-substituted analogs of an antigenic peptide can show distinct activation patterns: Th1- and Th2-type cytokine secretion, and helper activity for antibody production without apparent cytokine secretion.

Naive CD4(+) T cells differentiate into two types of helper T cells showing an interferon-gamma-predominant (Th1) or an interleukin-4-predominant (Th2) cytokine secretion profile after repeated antigenic stimulation. Their differentiation can be influenced by slight differences in the interaction between the T cell receptor (TCR) and its ligand at the time of primary activation. However, the primary response of freshly isolated naive CD4(+) T cells to altered TCR ligands is still unclear. Here, we investigated the primary response of splenic naive CD4(+) T cells derived from transgenic mice expressing TCR specific for residues 323-339 of ovalbumin (OVA323-339) bound to I-A(d) molecules. Naive CD4(+) T cells secreted either Th1- or Th2-type cytokines immediately after stimulation with OVA323-339 or its single amino acid-substituted analogs. Helper activity for antibody secretion by co-cultured resting B cells was also found in the primary response, accompanied by either low-level Th2-type cytokine secretion or no apparent cytokine secretion. Our results clearly indicate that dichotomy of the Th1/Th2 cytokine secretion profile can be elicited upon primary activation of naive CD4(+) T cells. We also demonstrate that the helper activity of naive CD4(+) T cells for antibody production does not correspond to the amounts of the relevant cytokines secreted.

Amino Acid Sequence↗