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Y Niwa

Publications and source records attributed to Y Niwa.

At least 91 records · Page 5Linked to original sources

[Cytokine assessed in the serum are denatured by calcium ion and resultantly activated protease].

When we assessed cytokine levels in both plasma and serum from the patients with atopic dermatitis and healthy volunteers, we found that IL-2, 5 and 10, and IFN-gamma were significantly elevated in the plasma from atopic dermatitis patients but not in their sera and that, in an average, each cytokine level, especially IL-2 level is far higher in plasma than in serum. In order to solve the cause for this dissociation. Calcium ion was dose-dependently added in the plasma in which calcium ion had been inactivated by citrate contained in the plasma. Protease inhibitors, PMSF, aprotinin and leupeptin were added in the plasma in which each cytokine was decreased in the presence of calcium ion. Finally, in RPMI medium where cytokine IL-2 or IL-10 is present, proteases, thrombin, trypsin and chymotrypsin themselves were introduced. Results revealed that addition of calcium ion dose-dependently decreased each cytokine level in the plasma, respectively. Protease inhibitors, PMSF, aprotinin and leupeptin significantly elevated each cytokine level in the plasma where cytokines had been decreased by the presence of calcium ion, respectively. These changes were comparable between plasma and blood cell-containing plasma, attesting that the effect of enzymes released from the calcium ion-activated neutrophil granules on the decrease in cytokine levels is negligible. Cytokines, IL-2 itself was also decreased in the presence of calcium ion alone, or in the presence of both proteases, thrombin, trypsin or chymotrypsin itself, and calcium, respectively. This study suggests that calcium ion itself or calcium ion-activated protease may denature the cytokine and that for this reason, cytokine should be, in general in our laboratory, assessed in not serum but plasma.

Blood Chemical Analysis↗

Novel 31-amino-acid-length endothelins cause constriction of vascular smooth muscle.

We have reported that human chymase specifically cleaves big endothelins (ETs) at the Try31-Gly32 bond, and produces novel trachea-constricting 31-amino-acid-length ETs, ETs(1-31). In this study, we investigated the effect of synthetic ETs(1-31) on the contractile activity toward porcine coronary arteries and rat aortae. Although ETs(1-31) exhibited less potent vasoconstrictile activity in these tissues than 21-amino-acid-length ETs(1-21), or a similar extent, ET-1(1-31) caused significantly slower-developing and longer-lasting contraction than ETs(1-21). The ETA receptor antagonist, BQ485, completely inhibited the activity of ET-1(1-31). The ETB receptor antagonist, BQ788, also inhibited the activity of ET-1(1-31) toward rat aortae more efficiently than that ET-1(1-21). Therefore, trachea-constricting peptides ETs(1-31) play roles as vasoconstrictors in a different manner from ETs(1-21).

Animals↗

Nitric oxide activates Ca2+-activated K+ channels in cultured bovine adrenal chromaffin cells.

The effects of sodium nitroprusside (SNP) on Ca2+-dependent K+ (KCa) channels in cultured bovine adrenal chromaffin cells were investigated using single channel recording patch-clamp techniques. KCa channels were activated by application of 100 microM SNP to the extracellular side of cell-attached patches. Methylene blue (300 microM), an inhibitor of soluble guanylate cyclase, or H-8 (1 microM), a protein kinase inhibitor with relative specificity for cGMP-dependent protein kinase, diminished but did not completely abolish the SNP-induced KCa channel activation. Diethylamine/NO complex (DEA/NO), an NO donor, also activated KCa channels in cell-attached patches. Furthermore, application of 100 microM SNP or 100 nM DEA/NO to the intracellular surface of excised inside-out patches also activated KCa channels in the bath solution which contained 1 microM Ca2+. These results indicate that SNP is capable of activating the KCa channel via cGMP-dependent and -independent mechanisms. These studies demonstrate that NO may serve as an important regulatory mechanism for catecholamine secretion in chromaffin cells via the activation of KCa channels.

Adrenal Medulla↗

Endoscopic resection of small duodenal carcinoid tumors with strip biopsy technique.

BACKGROUND: Most cases of duodenal carcinoid have conventionally been treated by surgical resection. The aim of our study was to explore the feasibility of endoscopic resection in small duodenal carcinoids. METHODS: The study population consisted of seven patients with small duodenal carcinoids. The diagnosis was confirmed by preoperative biopsies. The depth of tumor invasion was evaluated by endosonography. RESULTS: The carcinoid was detected by endosonography in all cases. Size ranged ultrasonographically from 1.5 mm to 7 mm. Tumor invasion was confined to the submucosa in all patients. Endoscopic resection was performed with the strip biopsy technique using a two-channel endoscope. In six patients, the specimens were resected without severe complications. Five of them were confirmed histologically to be typical carcinoids. In one patient, carcinoid was not detected histologically in the specimen. In the remaining patient, a perforation occurred. However, the huge ulcer was managed conservatively. Follow-up endoscopy revealed no evidence of recurrent or residual tumor in any patient. CONCLUSION: Small duodenal carcinoids confined to the submucosa can be resected endoscopically and preoperative endosonography is necessary for the determination of endoscopic resectability.

Aged↗

Endothelin-1 stimulates sodium-dependent calcium efflux from bovine adrenal chromaffin cells in culture.

1. The effect of endothelin (ET)-1 on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. ET-1 (10(-7) M) significantly increased intracellular free Ca2+ level ([Ca2+]i), 45Ca2+ uptake and catecholamine secretion in the cells. 2. ET-1 stimulated the efflux of 45Ca2+ from the cells preloaded with 45Ca2+ in a concentration-dependent manner (10(-9)-10(-7) M). This stimulatory effect was inhibited by ET(B) receptor antagonist BQ788, but not by ET(A) receptor antagonist BQ123. Selective ET(B) receptor agonists Suc-[Glu9, Ala11.5]-ET-1 and sarafotoxin S6c (SRTX) also stimulated 45Ca2+ efflux from the cells. 3. ET-1, Suc-[Glu9 Ala11.15]-ET-1 and SRTX increased the level of cyclic GMP in the adrenal chromaffin cells. ET-1 induced an increase in the nitric oxide (NO) level in the cells. The stimulatory effects by which ET- increases NO level and 45Ca2+ efflux were inhibited by NG-monomethyl-L-arginine acetate (L-NMMA), a competitive inhibitor of NO synthase. 4. The 45Ca2+ efflux stimulated by ET-1 was inhibited by deprivation of extracellular Na+, but not by deprivation of Ca2+. 5. These results suggest that ET-1 stimulates an extracellular Na+-dependent Ca2+ efflux through the activation of NO synthase in cultured bovine adrenal chromaffin cells.

Adrenal Glands↗

Effects of gamma-glutamylcysteine ethyl ester in cisplatin-induced changes in prostanoid concentrations in rat gastric and colonic mucosa.

We evaluated changes in gastric and colonic mucosal prostanoid contents in rats treated with cisplatin. We also determined effects of gamma-glutamylcysteine ethyl ester (GCE), a pro-drug of glutathione, on cisplatin-induced changes in prostanoid concentrations. Rats were divided into three groups--the control: 0.5 ml of physiological saline was administered intraperitoneally (i.p.); the cisplatin group: 0.5 ml of cisplatin, 10 mg/kg, was administered i.p.; the GCE + cisplatin group: GCE, 30 min before cisplatin injection. In each group, rat gastric and colonic mucosa were isolated and their prostanoid concentrations were determined using high-performance liquid chromatography. 6-Keto-PGF1 alpha, PGF2 alpha, PGE2 were detected in gastric mucosa. In addition to these prostaglandins (PGs), thromboxane (TX) B2 was also detected in the colonic mucosa. In the cisplatin group, gastric mucosal 6-keto-PGF1 alpha concentration decreased significantly 24 h after administration, while PGE2 and PGD2 concentrations were increased significantly after 12 and 24 h, respectively. In colonic mucosa, cisplatin increased PGE2 and PGD2 concentrations, while it decreased TXB2 concentration. 6-Keto-PGF1 alpha concentration was not affected by cisplatin in colonic mucosa. GCE canceled out these changes in prostanoid concentrations in both gastric and colonic mucosa. Changes in prostanoid concentrations might be implicated in the adverse gastrointestinal effects of cisplatin, and clinical application of GCE could be expected.

Animals↗

Preliminary results of fine needle aspiration biopsy histology in upper gastrointestinal submucosal tumors.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) has recently been reported to be useful in the diagnosis of submucosal tumors, but there are some cases in which the EUS diagnosis is questionable. We evaluated the diagnostic usefulness of endoscopic ultrasonography-guided fine needle aspiration biopsy (EUS-FNAB) in such cases. PATIENTS AND METHODS: From October 1993 to May 1997, EUS-FNAB was performed in 22 patients with upper gastrointestinal submucosal tumors who had also undergone EUS. We analyzed the capability of EUS-FNAB diagnosis compared to that of EUS imaging alone (presumptive diagnosis). RESULTS: Adequate specimens for histological diagnosis by EUS-FNAB were obtained in 18 of the 22 patients (82%). In 15 cases the final diagnosis was based on surgery. EUS-FNAB was correct in 14 of 15 lesions. In contrast, EUS alone suggested a correct diagnosis in only nine lesions. CONCLUSIONS: EUS-FNAB may be able to establish a histologic diagnosis, and whenever histology is deemed necessary EUS-FNAB would be an option. EUS-FNAB may increase the diagnostic capability of EUS in differentiating between submucosal tumors.

Adult↗

The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions.

UNLABELLED: We investigated the effect of thiopental, midazolam, and ketamine (at clinically relevant concentrations and at 0.1 and 10 times these concentrations) on several aspects of human neutrophil functions. The three intravenous (i.v.) anesthetics significantly decreased chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, thiopental and midazolam significantly depressed these neutrophil functions. However, ketamine at the clinical plasma concentration did not impair chemotaxis or ROS production, except phagocytosis. In contrast, the three anesthetics had no effect on the levels of ROS production by a cell-free ROS generating system. In addition, intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucil-L-phenylalanine were dose-dependently decreased in the presence of each of the three anesthetics. The suppression of an increase in intracellular calcium concentrations may be responsible for the inhibition of neutrophil functions by the i.v. anesthetics. IMPLICATIONS: Neutrophils play an important role in the antibacterial host defense system and autotissue injury. We found that thiopental and midazolam (but not ketamine), at clinically relevant concentrations, impaired the neutrophil functions.

Anesthetics↗

Propofol inhibits human neutrophil functions.

UNLABELLED: Neutrophils play important roles in the antibacterial host defense mechanism and in the pathogenesis of tissue injury. Propofol has been reported to impair the production of reactive oxygen species from neutrophils. We examined the effect of propofol (2,6-diisopropylphenol), at clinically relevant concentrations and at 10 and 100 times this concentration, on several aspects of human neutrophil functions using an in vitro system. Propofol significantly inhibited chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, propofol suppressed these neutrophil functions, but it did not decrease ROS generation by the cell-free (xanthine-xanthine oxidase) system. Increase in intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine was dose-dependently attenuated by propofol. This decreasing effect on [Ca2+]i in neutrophils may represent one of the mechanisms responsible for the inhibition of neutrophil functions by propofol. IMPLICATIONS: Neutrophils play a pivotal role in the antibacterial host defense system and tissue injury. We found that at clinically relevant concentrations, propofol impaired neutrophil functions. Further studies may determine whether this impairment, observed in vitro, leads to clinical immunological suppression.

Anesthetics, General↗

Familial occurrence of gastric carcinoid tumors associated with type A chronic atrophic gastritis.

We present here familial occurrence of two patients with gastric carcinoid. Both patients, a sister and older sister, had type A chronic atrophic gastritis with hypergastrinemia. This is the first case report of familial occurrence of gastric carcinoid associated with type A chronic atrophic gastritis in the world literature. The possible mechanism of familial occurrence in the patients is discussed.

Adult↗

Does prolonged exercise alter diet-induced thermogenesis?

Diet-induced thermogenesis (DIT) is mainly an insulin-mediated response and the result of fat and glycogen synthesis. We investigated DIT at rest and after exercise to clarify the mechanism of exercise-induced changes in DIT in 6 healthy men (mean age 36 +/- 16 years). Subjects exercised for 1 h at 58% of maximal O2 consumption on a bicycle ergometer and then rested for 8 h sitting in a comfortable chair (exercise experiment). On a different day, subjects rested for 8 h without preceding exercising (non-exercise experiment). At 12.30 h, the subjects were given their second meal. DIT to individual meal did not differ significantly between the exercise and non-exercise days. Increased insulin sensitivity and increased free fatty acid oxidation by exercise may facilitate the conversion of glucose to glycogen in muscle. On the other hand, insulin secretion expressed as the ratio of plasma levels of insulin to glucose after the meal was significantly decreased in the exercise experiment (p < 0.05). Study of heart rate variability showed that sympathetic tone, a primary hormonal determinant of glucose metabolism during exercise, was increased and parasympathetic tone was decreased during the recovery period in the exercise experiment (p < 0.05). These findings suggest that changes in DIT are affected by many factors and may be related to the balance between these counteracting factors.

Adult↗

Respiratory quotient in patients with non-insulin-dependent diabetes mellitus treated with insulin and oral hypoglycemic agents.

The respiratory quotient (RQ) reflects the amount of energy derived from carbohydrate as apposed to fat metabolism. To assess the metabolic state of patients with non-insulin-dependent diabetes mellitus, the RQ was measured five times a day (at 09.00, 11.00, 13. 00, 14.00, and 17.00 h) in 20 healthy subjects and 60 diabetic patients. Diabetic patients treated with insulin or sulfonylurea showed significantly higher RQ values than normal subjects and nontreated diabetic patients. Diabetic patients without treatment showed higher glucose levels, and their RQ values were significantly lower than those of treated patients. There was a significant inverse correlation between RQ and blood glucose levels at 11.00 h (r = -0.361, p < 0.01) in diabetic patients, but no significant relation with HbA1c. Treated diabetic patients with a higher body mass index tended to show a higher RQ than those with a lower one (r = -0.269, p = 0.083). Within 1 year, 7 of 13 patients, who had RQ > 1.0, gained more than 3 kg, while only 5 of the remaining 32 treated diabetic patients gained more than 3 kg (p < 0.05). This demonstrates that diabetic patients with a higher RQ tended to gain weight despite the use of insulin or oral hypoglycemia agents. The RQ increased by infusing both insulin and glucose in normal subjects. These results suggest that a high RQ results from excess insulin and excess food. The RQ is a good predictor of weight gain in diabetic patients treated with either insulin or oral hypoglycemic agents.

Calorimetry, Indirect↗

Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous NIDDM.

We investigated whether endothelial function may be impaired in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. The effect of exercise training and food restriction on endothelial function was also studied. OLETF rats were divided into three groups at age 16 weeks: sedentary, exercise trained, and food restricted (70% of the food intake of sedentary rats). Otsuka Long-Evans Tokushima rats were used as the age-matched nondiabetic controls. Endothelium-dependent relaxation of the thoracic aorta induced by histamine was significantly attenuated in the sedentary or food-restricted rats, and exercise training improved endothelial function. Relaxation induced by sodium nitroprusside, a donor of nitric oxide, did not differ significantly among groups. Both exercise training and food restriction significantly suppressed plasma levels of glucose and insulin and serum levels of triacylglycerol and cholesterol and reduced the accumulation of abdominal fat. Insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique, was significantly decreased in sedentary rats but was enhanced in exercise-trained and food-restricted rats. The urinary excretion of nitrite was significantly decreased in sedentary and food-restricted rats compared with nondiabetic rats and was significantly increased in exercise-trained rats. These results indicate that exercise training, but not food restriction, prevents endothelial dysfunction in NIDDM rats, presumably due to the exercise-induced increase in the production of nitric oxide.

Abdomen↗

[The effect of carbon dioxide on intraorbital hemodynamics in glaucoma determined by color Doppler imaging].

We developed a new system to safely supply carbon dioxide (CO2) to man to investigate the effect of the gas vasodilator on orbital blood flow in open angle glaucoma (OAG) patients. Using the system, we determined orbital hemodynamics in OAG by color Doppler imaging (CDI) at baseline conditions and during CO2 supplementation sufficient to increase end-tidal CO2% by 10%. Seven OAG patients (mean age, 60.9 +/- 16.4 years; normal-tension glaucoma/primary open-angle glaucoma = 5/2) were included in the study. CDI was performed to measure resistance index (RI), and peak-systolic and end-diastolic blood flow velocities (PSV & EDV) of the ophthalmic artery (OA) and the central retinal artery (CRA). Systemic conditions including oxygen saturation and blood pressure were monitored throughout the period of the CO2 inhalation. CO2 significantly increased PSV and EDV in the CRA (p = 0.0273, p = 0.0094, respectively; Wilcoxon signed-rank test), but not in the OA. Other parameters were not altered. The results suggest that CO2 inhalation increases blood flow velocities in distal arteries in OAG patients without affecting proximal vessels. The new system enables us to supply CO2 in a safe and controlled manner in glaucoma patients and to modify orbital hemodynamics.

Administration, Inhalation↗

In situ hybridization with biotinylated tyramide amplification: detection of human papillomavirus DNA in cervical neoplastic lesions.

A novel peroxidase-mediated amplification system, which is based on the deposition of biotinylated tyramide (BT) molecules, was recently described for immunohistochemistry and in situ hybridization (ISH). We report here a highly sensitive ISH system combined with a microwave prehybridization treatment and BT enhancement after hybridization. Our ISH with BT amplification can detect human papillomavirus (HPV) 16 DNA signals in the fixed SiHa cell, suggesting the ability to detect single or few copies of HPV DNA. To confirm its diagnostic usefulness, we used our ISH with BT amplification to detect HPV 16 DNA in 81 cases of cervical neoplastic lesions, which had been used for routine pathologic diagnosis. Of 81 tumors, 47 (58%) showed HPV 16 DNA, of which 29 and 18 were cervical intraepithelial neoplasia (CINs) and invasive cancers, respectively. In almost all of the invasive cancers positive for HPV 16 DNA, ISH revealed a basic dot signal pattern in the nuclei, suggesting that HPV DNA integrated into tumor cell DNA. On the other hand, low-grade CINs displayed a diffuse, mainly episomal, signal pattern, which decreased in frequency with increased grade of CIN. Our ISH with BT amplification is highly sensitive and can be used to detect various genes and their expressions.

DNA, Viral↗

[Anaphylactic shock associated with a central venous catheter impregnated with chlorhexidine and silver sulfadiazine].

A 28 year-old male patient developed anaphylactic shock on separate occasions, possibly due to the contact with a central venous catheter impregnated with chlorhexidine and silver sulfadiazine. He was successfully resuscitated. On the second operation, blood basophils disappeared and plasma histamine level increased extremely up to 80 ng.ml-1 soon after anaphylactic shock. One year after the first shock, he did not develop anaphylactic shock following the insertion of a central venous catheter without the impregnation. Pin prick test and scratch test showed positive reactions only to chlorhexidine. Latex-specific anti-IgE antibody was not detected. Therefore, chlorhexidine was confirmed as the causative agent of anaphylactic shock. Because chlorhexidine is extensively used as an antiseptic drug in emergency rooms and intensive care units, we should be aware of the possibility of chlorhexidine induced anaphylactic reactions.

Adult↗

Successful treatment of severe atopic dermatitis-complicated cataract and male infertility with a natural product antioxidant.

There has been a recent dramatic change in the features of atopic dermatitis and male infertility, including a marked increased prevalence of severe and treatment-resistant atopic dermatitis; an increase in severe atopic dermatitis complicated by cataracts, especially in urban and industrial areas; and an increase in the number of infertile men with poor sperm motility. Previously we have attributed these changes to the increased free radicals produced by environmental toxicity. We have reported the increase in lipid peroxide levels and decrease in superoxide dismutase inducibility in severe atopic dermatitis patients, and shown that lipid peroxides attach to the stratum corneum, promoting loss of skin moisturization and resulting in the worsening of atopic dermatitis. Cataracts which occur with severe atopic dermatitis are also formed by the diffusing of lipid peroxides through the posterior lens. Regarding aspermia, the standard levels of sperm motility according to the World Health Organization Guidelines have been reduced to 50% from 60%, but nonetheless the prevalence of infertile men is increasing. It has been reported that antioxidants such as ascorbate, catalase and glutathione-Px can reverse the decrease in sperm motility in the seminal plasma of infertile men. We have developed an oral antioxidant, named AOA, which is produced from natural plants and seeds (e.g., soybean, sesame, wheat germ), treated by heating with far infrared rays (4-14 microns wavelength), brewed with Aspergillus oryzae, and lipophilized with similarly heated sesame oil. These procedures liberate low-molecular-weight antioxidants that exist naturally in an inactive form of repeating subunits of polymers, to produce free, activated forms of antioxidants. This natural medicinal product, AOA, has been applied to the treatment of both cataract complicated with atopic dermatitis and male infertility. Approximately half the patients tested have shown marked improvement.

Administration, Oral↗