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Biomedical subjects

A Kato

Publications and source records attributed to A Kato.

At least 325 records · Page 18Linked to original sources

The effects of calystegines isolated from edible fruits and vegetables on mammalian liver glycosidases.

The polyhydroxylated nortropane alkaloids called calystegines occur in many plants of the Convolvulaceae, Solanaceae, and Moraceae families. Certain of these alkaloids exhibit potent inhibitory activities against glycosidases and the recently demonstrated occurrence of calystegines in the leaves, skins, and sprouts of potatoes (Solanum tuberosum), and in the leaves of the eggplant (S. melongena), has raised concerns regarding the safety of these vegetables in the human diet. We have surveyed the occurrence of calystegines in edible fruits and vegetables of the families Convolvulaceae, Solanaceae, and Moraceae by GC-MS. Calystegines A3, B1, B2, and C1 were detected in all the edible fruits and vegetables tested; sweet and chili peppers, potatoes, eggplants, tomatoes, Physalis fruits, sweet potatoes, and mulberries. Calystegines B1 and C1 were potent competitive inhibitors of the bovine, human, and rat beta-glucosidase activities, with Ki values of 150, 10, and 1.9 microM, respectively for B1 and 15, 1.5, and 1 microM, respectively, for C1. Calystegine B2 was a strong competitive inhibitor of the alpha-galactosidase activity in all the livers. Human beta-xylosidase was inhibited by all four nortropanes, with calystegine C1 having a Ki of 0.13 microM. Calystegines A3 and B2 selectively inhibited the rat liver beta-glucosidase activity. The potent inhibition of mammalian beta-glucosidase and alpha-galactosidase activities in vitro raises the possibility of toxicity in humans consuming large amounts of plants that contain these compounds.

Animals↗

Conservative treatment using a methotrexate-lipiodol emulsion containing non-ionic contrast medium for a cervical ectopic pregnancy.

We present a case in which a viable cervical pregnancy was successfully treated with preservation of the uterus. A 26 year old female presented with a 6 week cervical pregnancy with acute moderate bleeding. On the day of admission the patient underwent embolization of the descending uterine artery to decrease the bleeding. The following day, 4 mEq potassium chloride and methotrexate (MTX)(1 mg/kg) dissolved in saline was injected into the amniotic cavity using transvaginal sonographic guidance. The fetal heart beat ceased; however, the urinary beta-human chorionic gonadotrophin (HCG) concentration increased and the gestational sac size also increased. After a second injection of an emulsion of MTX (1 mg/kg) dissolved in a non-ionic contrast medium, iopamidol and lipiodol, the betaHCG concentration in the urine began to decrease. After a third injection with the same emulsion, the cervical mass became necrotic. The betaHCG concentrations in the urine and serum were undetectable and the external cervix returned to normal 44 days after admission. No vaginal bleeding or significant side effects of MTX were observed throughout the treatment. An in-vitro dissolution test revealed that the dissolution rate of MTX was slower from MTX-lipiodol-iopamidol with sonication than without sonication. The present study indicates that use of an MTX emulsion enables slow release of MTX and may be applicable for conservative treatment of ectopic pregnancies, including cervical pregnancy.

Adult↗

Soluble intercellular adhesion molecule-1 level in sera is elevated in perennial allergic rhinitis.

Soluble intercellular adhesion molecule-1 (sICAM-1) in sera was measured in some allergic disorders, but serum sICAM-1 levels in perennial allergic rhinitis remain to be determined. Our study was aimed at elucidating whether the serum sICAM-1 levels in patients with perennial allergic rhinitis are different from those in nonatopic healthy volunteers and whether immunotherapy can modulate sICAM-1 levels. Serum sICAM-1 was determined in 20 nonallergic volunteers and 137 patients with perennial allergic rhinitis by a sandwich enzyme-linked immunosorbent assay. Our study demonstrated that the level of sICAM-1 in untreated patients is significantly elevated, as compared with nonatopic subjects. Immunotherapy could decrease sICAM-1 in perennial allergic rhinitis, but this suppressive effect became apparent only after many years of immunotherapy. In patients on immunotherapy, a close correlation was observed between sICAM-1 and nasal symptom scores. To take these lines of evidence together, a decrease in sICAM-1 might be related to the working mechanism of immunotherapy, and serum sICAM-1 could be used to monitor the effect of immunotherapy.

Adult↗

Effect of immunotherapy on seasonal changes in serum-specific IgE and IgG4 in patients with pollen allergic rhinitis.

Serum specific IgE and IgG4 in 70 patients with seasonal rhinitis caused by Japanese cedar pollens were determined before and during the pollen season. Seasonal increase rate in specific IgE was significantly smaller in the immunotherapy patients than the pharmacotherapy patients, and seasonal increase in specific IgG4 was significant in the immunotherapy patients only. Seasonal increase rate in specific IgE was not significantly different between the patients who responded markedly to short-term immunotherapy and those who did not. On the other hand, seasonal increase rate in specific IgG4 was significantly different between them. In contrast, seasonal increase rate in specific IgE was significantly smaller in the patients who showed marked response to the long-term immunotherapy than those who did not show marked response to the long-term immunotherapy, but seasonal increase rate in specific IgG4 was not significantly different between them. In conclusion, our results suggest that modulation of specific IgG4 response and specific IgE response might be involved in the early and late symptom relief during immunotherapy, respectively. However, further studies might be necessary to definitively establish the clinical roles of specific IgE and specific IgG4 in immunotherapy.

Adolescent↗

Creation of an infectious recombinant Sendai virus expressing the firefly luciferase gene from the 3' proximal first locus.

A genetic engineering approach was made to generate a recombinant non-segmented negative-strand RNA virus, Sendai virus (SeV) of the family Paramyxoviridae, that expresses firefly luciferase. The DNA construct containing the entire open reading frame (ORF) of the luciferase gene followed by the SeV transcription stop and restart signals connected with the conserved intergenic three nucleotides was inserted immediately before the ORF of the viral 3'-proximal nucleocapsid (N) protein gene in a full-length SeV cDNA copy. After intracellular expression of full-length antigenomic transcripts from the engineered cDNA and of the viral n ucleocapsid protein and RNA polymerase from the respective plasmids, a recombinant SeV expressing luciferase activity at a high level was recovered, although the tendency of this particular reporter gene product to aggregate in cells made it difficult to estimate the maximum level of expression. The increase in genome length brought about by inserting 1728 nucleotides into the 15,384 nucleotide parental SeV was associated with reduced plaque size, slightly slower replication kinetics and a severalfold decrease in yield of the virus. The inserted luciferase gene was stably maintained after numerous rounds of replication by serial passages in chick embryos. These results indicate the potential utility of SeV as a novel expression vector.

Animals↗

Importance of the cysteine-rich carboxyl-terminal half of V protein for Sendai virus pathogenesis.

The Sendai virus V protein is a nonstructural trans-frame protein whose cysteine-rich C-terminal half is fused to the acidic N-terminal half of the P protein via mRNA editing. We recently created a mutant by disrupting the editing motif, which is devoid of mRNA editing and hence unable to produce the V protein, and demonstrated that this V(-) virus replicated normally or even faster with augmented gene expression and cytopathogenicity in cells in vitro, but was strongly attenuated in pathogenicity for mice (A. Kato, K. Kiyotani, Y. Sakai, T. Yoshida, and Y. Nagai, EMBO J. 16:578-587, 1997). Thus, although categorized as a nonessential protein, the V protein appeared to encode a luxury function required for the viral in vivo pathogenesis. Here, we created another version of a V-deficient mutant, VdeltaC, encoding only the N-terminal half but not the V-specific C-terminal half, by introducing a stop codon in the trans-V frame, and then we compared its in vitro and in vivo phenotypes with those of the V(-) and wild-type viruses. The VdeltaC virus was found to be similar to the wild-type virus in vitro with no augmented gene expression and cytopathogenicity, but in vivo, it resembled the V(-) virus, displaying a similarly attenuated phenotype. Thus, the pathogenicity determinant in the V protein was mapped to the C-terminal half. The N-terminal half was likely sufficient to confer normal (wild-type) in vitro phenotypes.

Amino Acid Sequence↗

Hypoglycemic action of embelia madagascariensis in normal and diabetic mice.

The hypoglycemic effect of Embelia madagascariensis (Myrsinaceae) was investigated in both normal and streptozotocin-induced diabetic mice. The methanol extract of leaves of Embelia madagascariensis (EL)(500 mg/kg) reduced the blood glucose of normal mice from 206 +/- 9 to 137 +/- 10 mg/100 ml 4 hours after intraperitoneal administration (P < 0.001), and also significantly lowered the blood glucose of streptozotocin-induced diabetic mice from 570 +/- 29 to 401 +/- 59 mg/100 ml under similar conditions (P < 0.05). EL also suppressed epinephrine-induced hyperglycemia in mice (control vs EL, P < 0.01).

Animals↗

Sinus pericranii: neuroradiologic findings and clinical management.

We report an 11-year-old boy with a sinus pericranii. Magnetic resonance images demonstrated a small hole in the cranium underneath the subcutaneous mass. Magnetic resonance angiography (MRA) with sequential two-dimensional time-of-flight (2D-TOF) method demonstrated that the venous flow via the sinus pericranii was directed from the intra- to the extracranial venous system (the drainer type). This was confirmed by a combination of conventional cerebral angiography and percutaneous sinography. We advocate that both the correct diagnosis and classification of sinus pericranii can be established with a combination of current noninvasive neuroradiologic studies, especially for the pediatric age group. MRA with the 2D-TOF method is useful in the assessment of this venous anomaly.

Cerebral Veins↗

Uninephrectomy prevents the ischemia-induced increase in renin activity.

Contralateral uninephrectomy attenuates unilateral ischemic injury. The present work was performed to elucidate whether the beneficial effect of uninephrectomy was associated with the modification of ischemia-induced changes in plasma or renal renin activity. A 60-min left renal artery occlusion was conducted in right nephrectomized (Nx) and sham-nephrectomized (Sham-Nx) rats. The decline in inulin clearance 48 h after ischemia was significantly less in Nx rats than in Sham-Nx animals (0.50 +/- 0.10 vs. 0.052 +/- 0.029 ml/min/kidney, p < 0.05). Following ischemia, plasma renin activity (PRA) significantly increased in Sham-Nx (from 5.4 +/- 0.9 to 15.5 +/- 1.4 ng AI/ml/min, p < 0.01) but not in Nx (from 3.5 +/- 0.5 to 5.0 +/- 1.0 ng AI/ml/ min) animals. PRA and renal cortical renin content (2,200 +/- 225 vs. 1,257 +/- 187 ng AI/h/mg protein, p < 0.05) were significantly less in Nx rats than in Sham-Nx animals 48 h after renal ischemia. The decrease in body weight was greater in Nx rats than in Sham-Nx animals. Plasma atrial natriuretic peptide (ANP) (195 +/- 30 vs. 302 +/- 40 pg/ml, p < 0.05) and renal dopamine (DA) content (3.2 +/- 0.5 vs. 13.7 +/- 1.3 ng/g tissue, p < 0.01) were rather lower in the Nx group when compared with the Sham-Nx group. No significant difference was found in the intrarenal content of norepinephrine (NE) between two ischemic groups. These findings suggested that uninephrectomy prevents the ischemia-induced increase in renin activity. The prevention of the increase in renin activity in Nx rats is not be mediated through the modulation of ischemia-induced changes in sodium balance, plasma ANP level and/or intrarenal contents of NE and DA.

Animals↗

Role of natriuretic peptide receptor type C in Dahl salt-sensitive hypertensive rats.

The natriuretic peptide system is suggested to be involved in the pathogenesis of salt-sensitive hypertension; a recent report indicated that disruption of the atrial natriuretic peptide precursor gene caused salt-sensitive hypertension. However, natriuretic peptide receptor (NPR)-A knockout mice did not show enhanced salt sensitivity of blood pressure. The aim of the present study was to investigate the role of NPR-C, the other receptor for atrial natriuretic peptide, in increased salt sensitivity of blood pressure. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were placed on a 0.3% or 8% NaCl diet for 4 weeks. Blood pressure was elevated by salt loading only in DS rats. RNase protection assay demonstrated that NPR-C transcript level in the kidney was reduced by chronic salt loading in both DR and DS rats, whereas expression of NPR-A and NPR-B was not altered. The reduction of NPR-C mRNA in response to salt loading was enhanced in DS compared with DR rats. In situ hybridization indicated that the salt-induced NPR-C change was attributed mainly to suppressed expression of NPR-C in the podocytes. NPR-C gene expression was regulated by salt loading in a tissue-specific manner; the marked decrease in NPR-C mRNA by salt loading was seen only in the kidney. These data suggest that the exaggerated salt-induced reduction of NPR-C in the kidney of DS rats may play an important role in the pathogenesis of salt hypertension in this animal, possibly related to impaired renal sodium excretion.

Animals↗

Effect of immunotherapy on serum levels of eosinophil cationic protein in perennial allergic rhinitis.

Eosinophil cationic protein (ECP) levels in the serum of clotted blood could reflect the rate of activation of circulating eosinophils. We investigated the serum ECP levels in patients with perennial allergic rhinitis, with special reference to the effect of immunotherapy on the serum ECP levels. Serum ECP levels in untreated patients with perennial allergic rhinitis are significantly higher than those of nonatopic volunteers. Therefore, this elevation in the untreated patients represents an ongoing inflammation occurring in allergic rhinitis. The mean serum ECP level of a 1-year immunotherapy group was significantly higher than that of the nonatopic group, and was not different from that of the untreated group. In contrast, the mean serum ECP level in patients who had more than 2 years of immunotherapy was significantly lower than that of the untreated group, and was not different from that of the nonatopic group. Additionally, serum ECP levels were significantly correlated with the duration of immunotherapy. These findings suggest that activation of circulating eosinophils decreases gradually during immunotherapy, but this inhibition becomes apparent only after 2 years of immunotherapy. The control of circulating eosinophil activation might be one of the important working mechanisms behind the clinical effect of immunotherapy.

Adolescent↗

Cardiotonic activity of the rhizome of Polygonatum sibiricum in rats.

The cardiotonic effect of the rhizome of Polygonatum sibiricum was investigated in the left atria of rats. The methanol extract of the rhizome of Polygonatum sibiricum (OM) (1-7 mg/ml) concentration-dependently increased the developed tension of the left atrium. It also strongly inhibited cAMP phosphodiesterase. The increase cAMP level correlated the increase in left atrial contraction. On the other hand, OM did not inhibit Na+, K+-ATPase. The cardiotonic effect of OM was strongly inhibited by reserpine, a sympatholytic agent. Furthermore, OM-treated left atria inhibited the tension produced by propranolol, a beta adrenocepter antagonist. These findings suggested that the cardiotonic effect is due to stimulating beta adrenoceptors through activation of sympathetic nerves.

3',5'-Cyclic-AMP Phosphodiesterases↗

First-pass metabolism of ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]benzoyl]aminoacetic acid), a novel elastase inhibitor, in rats.

The first-pass metabolism in the intestine and liver of ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy)-phenylsulfonylamino]benz oyl]aminoacetic acid), a newly synthesized elastase inhibitor, was separately estimated in rats. When ONO-5046 solution was administered into the whole intestine via the bile duct at a dose of 5 mumol/rat, the extent of bioavailability was only 1.5%. A small but significant increase in the bioavailability with an increase in the dose suggested marked first-pass metabolism with a saturable process. Hepatic first-pass metabolism was estimated by determining the hepatic extraction ratio of ONO-5046 after administration into the portal vein at two different infusion rates (5 mumol/kg/9 min or 5 mumol/kg/20s). The extraction ratio was relatively small and constant (about 20%) under 2 different infusion rates of the drug. Intestinal first-pass metabolism was estimated by determining the drug recovery in the mesenteric plasma after administering the drug into the intestinal loop in situ (mesenteric blood collecting method in situ). The recovery percentage of ONO-5046 in the mesenteric plasma was small (2.58 +/- 0.04% at a dose of 1 mumol/rat), and the remaining ONO-5046 recovered in the mesenteric plasma and in the intestinal loop was a metabolite of ONO-5046 (El-601, N-[2-[(4-hydroxyphenyl)sulfonylamino]benzoyl]amino-acetic acid). Recovery percentage of ONO-5046 in the mesenteric plasma increased significantly with an increase in the dose, although the recovery percentage was still low, even at a higher dose (9.55 +/- 1.17% of dose at a dose of 5 mumol/rat). These results indicate that the low oral bioavailability of ONO-5046 in vivo is mainly due to the marked intestinal first-pass metabolism, including the metabolism in the intestinal fluid, and the dose-dependent oral bioavailability was derived from the saturable intestinal first-pass metabolism.

Animals↗

Hypoglycemic effect of the rhizomes of Smilax glabra in normal and diabetic mice.

The hypoglycemic effect of the rhizomes of Smilax glabra ROXBURGH (Liliaceae) was investigated in normal and KK-Ay mice, one of the animal models of non-insulin dependent diabetes mellitus (NIDDM) with hyperinsulinemia. The methanol extract of rhizomes of Smilax glabra ROXBURGH (SM, 100 mg/kg body weight) reduced the blood glucose of normal mice 4 h after intraperitoneal administration (p<0.05), and also significantly lowered the blood glucose of KK-Ay mice under similar conditions (p<0.001). However, SM did not affect the blood glucose in streptozotocin-induced diabetic mice, one of the animal models of insulin-dependent diabetes mellitus (IDDM) with hypoinsulinemia. SM also suppressed epinephrine-induced hyperglycemia in mice. SM-treated KK-Ay mice significantly decreased the blood glucose in an insulin tolerance test. We concluded that the hypoglycemic effect of SM raised insulin sensitivity.

Animals↗

Activation of macrophages by sulfated glycopeptides in ovomucin, yolk membrane, and chalazae in chicken eggs.

Sulfated glycopeptides in ovomucin, chalazae and yolk membrane were found to activate cultured macrophage-like cells, J774.1, and TGC-induced macrophages from the peritoneal cavity of male mice. The macrophage-stimulating activity was estimated by the growth and morphology of the cells, H2O2 generation, and interleukin-1 (IL-1) production from the cells. The in vitro culture assay with macrophages showed that the protease digests of ovomucin, yolk membrane, and chalazae induced morphologic alteration and increased H2O2 generation and IL-1 production in lower concentration (100 micrograms/ml). The isolation of the components having macrophage-stimulating activity was attempted to elucidate the molecular mechanism. The O-linked carbohydrate chains, consisting of N-acetylgalactosamine, galactose, N-acetylneuraminic acid and sulfate, in the sulfated glycopeptide were identified as a component having macrophage-stimulating activity.

Animals↗