Biomedical subjects

S Kadowaki

Publications and source records attributed to S Kadowaki.

At least 37 records · Page 2Linked to original sources

PubMed1995

The urinary concentration of sialic acid is increased in non-insulin-dependent diabetic patients with microangiopathy: a possible useful marker for diabetic microangiopathy.

In order to investigate the relationship between urinary excretion of sialic acid and the severity of diabetic microangiopathy, urinary levels of sialic acid were determined in patients with non-insulin-dependent diabetes mellitus. The urinary molar ratio of sialic acid to creatinine in the diabetic patients was significantly higher than in the healthy controls (p < 0.01). Moreover, the urinary ratio was found to be gradually increased with the degree of diabetic microangiopathy. Urine molar ratio of sialic acid to creatinine in patients with proliferative diabetic retinopathy was significantly higher than in patients without retinopathy (p < 0.01). Urinary excretion in patients with macroproteinuria was also significantly higher than in patients without nephropathy (p < 0.01). Since urinary levels of sialic acid are proportionally increased with the severity of diabetic microangiopathy, the measurement of urinary sialic acid could become a useful biochemical means to monitor the degree of diabetic microangiopathy.

Adult↗

PubMed1995

Effect of polygonati rhizoma on blood glucose and facilitative glucose transporter isoform 2 (GLUT2) mRNA expression in Wistar fatty rats.

The intraperitoneal administration of the methanol extract of Polygonati Rhizoma (OM) to Wistar fatty rats caused a significant decrease in the blood glucose level 4h after its administration at 800 mg/kg (p < 0.01). The hepatic content of facilitative glucose transporter isoform 2, liver type glucose transporter (GLUT2) mRNA content from rat liver significantly decreased in the intraperitoneally OM-treated rats compared to that in the controls (p < 0.01). These results suggest that the hypoglycemic effect of OM is presumably due, at least in part, to the reduction of GLUT2 mRNA expression. Because of this unique therapeutic mechanism, OM could be a new category of therapeutic agent for non-insulin-dependent diabetes mellitus.

Animals↗

PubMed1995

Hypoglycemic effect of the rhizomes of ophiopogonis tuber in normal and diabetic mice.

The hypoglycemic effect of the rhizomes of Ophiopogonis Tuber (Liliaceae) was investigated in normal and streptozotocin-induced diabetic mice. The n-butanol extract of rhizomes of Ophiopogonis Tuber (BM) (100 mg/kg) reduced the blood glucose of normal mice from 201 +/- 13 to 151 +/- 7 mg/100 ml 4h after intraperitoneal administration (p < 0.054), and also significantly lowered the blood glucose of streptozotocin-induced diabetic mice from 590 +/- 28 to 470 +/- 37 mg/100 ml under similar conditions (p < 0.05). BM also tended to suppress epinephrine-induced hyperglycemia in mice. We concluded that the hypoglycemic effect of BM does not alter the insulin concentration.

Animals↗

PubMed1995

Effect of a major metabolite of the antiallergic drug repirinast on phosphodiesterase and adenylate cyclase activities.

MY-1250 (5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c]quinoline-2-carboxylic acid, CAS 63768-47-8), a major metabolite of the antiallergic drug repirinast (MY-5116, CAS 73080-51-0), inhibits antigen-induced histamine release from rat peritoneal mast cells. MY-1250 causes a rapid increase in cyclic adenosine monophosphate (AMP) levels in rat peritoneal mast cells. MY-1250 inhibited cyclic AMP phosphodiesterase activities from rat peritoneal cells and guinea pig lung tissue in a concentration dependent manner with IC50 values of 2000 mumol/l and 1670 mumol/l, respectively. However, MY-1250 showed no effect on adenylate cyclase activity from rat peritoneal cells. These results suggest that the inhibitory effect of MY-1250 on histamine release may be partly due to the inhibition of cyclic AMP phosphodiesterase activity.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1994

Transglycosylation activity of Mucor hiemalis endo-beta-N-acetyl-glucosaminidase which transfers complex oligosaccharides to the N-acetylglucosamine moieties of peptides.

A novel endo-beta-N-acetylglucosaminidase in the culture fluid of Mucor hiemalis isolated from soil was found to have transglycosylation activity. This endo-beta-N-acetylglucosaminidase, Endo-M, could liberate the complex type of asparagine-linked oligosaccharides by hydrolysis of diacetylchitobiose linkage from glycoproteins. The treatment of Endo-M with N-acetyl-glucosamine and asialotransferrin glycopeptide having the complex type of oligosaccharides resulted in the transfer of the released oligosaccharide from the glycopeptide to N-acetyl-glucosamine. The structure of the product after transfer was deduced to be (GlcNAc)2-Man-(Gal-GlcNAc-Man)2 by a combination method of pyridylamination and high performance liquid chromatography, and mass-spectrometry. The enzyme could transfer the complex type of oligosaccharide from asialotransferrin glycopeptide to bovine ribonuclease with the high-mannose type of oligosaccharide. This will lead to the construction of neoglycoproteins containing different types of oligosaccharides.

Acetylglucosamine↗

PubMed1994

Novel specificities of Mucor hiemalis endo-beta-N-acetylglucosaminidase acting complex asparagine-linked oligosaccharides.

Mucor hiemalis endo-beta-N-acetylglucosaminidase (Endo-M) was proved to act on complex type biantennary oligosaccharides of glycoproteins by using dansylated asparagine-linked and pyridylaminated oligosaccharides, as the substrate. The enzyme could act on both asialo- and sialo-biantennary oligosaccharides. This is the only endo-beta-N-acetylglucosaminidase known to act on sialo glycans, though their activity for them was weak. The enzyme could liberate complex type biantennary oligosaccharides from native human asialotransferrin, which was ascertained by a combination of the pyridylaminated method and HPLC. The enzyme had substrate specificity for high-mannose type oligosaccharides different from those of the endo-beta-N-acetylglucosaminidases of other microorganisms: ovalbumin glycopeptide-IV was a better substrate for Endo-M than glycopeptide-V. The enzyme could act on complex type triantennary oligosaccharides of dansylated glycopeptide prepared from calf fetuin. The enzyme had various novel specificities in regard to activities on complex type and high-mannose type oligosaccharides in glycoproteins.

Asialoglycoproteins↗

PubMed1994

Effects of anti-CD44 monoclonal antibody on adhesion of erythroid leukemic cells (ELM-I-1) to hematopoietic supportive cells (MS-5): CD44, but not hyaluronate-mediated, cell-cell adhesion.

Cocultivation of erythroid leukemic cells (ELM-I-1) with hemopoietic supportive cells (MS-5) resulted in a specific adhesion of ELM-I-1 cells to MS-5 cells. This phenomenon was designated as rosette formation. After induction of differentiation of ELM-I-1 cells, rosette formation was reduced, and no rosette formation was observed between erythrocytes and MS-5 cells. Studies on anti-adhesion molecule antibody treatment have revealed that CD44 plays a key role in rosette formation. Expression of CD44 on (the membrane of) ELM-I-1 cells was reduced after differentiation, and no CD44 expression was detected on erythrocytes. CD44 was also expressed on MS-5. Hyaluronate is known as the ligand of CD44, but neither hyaluronidase treatment nor addition of excess hyaluronate to the assay system affected rosette formation. These data indicate that hyaluronate is not responsible for rosette formation. Anti-CD44 antibody (KM81), which recognized the hyaluronate binding site of CD44, inhibited rosette formation. But other monoclonal antibodies against different epitopes except for the hyaluronate binding site, even those against CD44's hyaluronate binding site, did not inhibit rosette formation. Thus, rosette formation between MS-5 cells and ELM-I-1 cells is mediated by CD44 but not by the hyaluronate binding site of CD44.

Animals↗

PubMed1994

Pharmacological profile of the novel, potent and selective peptide leukotriene antagonist (E)-2,2-diethyl-3'-[2-[2-(4-isopropyl)thiazolyl]ethenyl]succinanilic acid.

In this report, the in vitro and in vivo pharmacological profile of MCI-826 ((E)-2,2-diethyl-3'-[2-[2-(4-isopropyl) thiazolyl]ethenyl]succinanilic acid, CAS 121230-22-6) is described. In isolated guinea pig ileum, MCI-826 inhibited LTD4 (a peptide leukotriene, 10(-9) mol/l)-induced contraction in a concentration-dependent manner with an IC50 of 6.8 x 10(-12) mol/l. It had no effect on histamine (10(-5) mol/l)-, serotonin (2.5 x 10(-5) mol/l)-, or acetylcholine (5.5 x 10(-6) mol/l)- induced contractions in isolated guinea pig ileum. In isolated guinea pig trachea, MCI-826 demonstrated competitive antagonism of the contractile activity of LTD4 and LTE4 with pA2 values of 9.0 and 8.8, respectively. MCI-826 inhibited LTC4-induced contraction in a concentration-dependent manner. However, in the presence of an inhibitor of the metabolism of LTC4 to LTD4, MCI-826 (10(-6) mol/l) produced no effect on LTC4 concentration-response curves in guinea pig trachea. In the in vivo study, the oral administration of MCI-826 caused a dose-dependent inhibition of LTC4- and LTD4-induced bronchoconstrictions in guinea pigs with an ED50 of 0.049 and 0.013 mg/kg, respectively. However, MCI-826 (3 mg/kg p.o.) showed no effect on histamine-induced bronchoconstriction in guinea pigs. The pharmacological half-life of orally administered MCI-826 as assessed by LTD4-induced bronchoconstriction was more than 12 h in guinea pigs. MCI-826 also inhibited antigen-induced bronchoconstriction in a dose-dependent manner with a MID (minimum dose that causes significant inhibition) of 0.1 mg/kg p.o. in guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1993

Application of poly(L-lactic acid) particles for the suppression of genetic resistance to bone marrow allografts by reticuloendothelial system-blockade.

We have recently successfully achieved bone marrow allografts by reticuloendothelial system (RES)-blockade. Long-term survival of the recipient mice after BMT was achieved without apparent evidence of graft-versus-host disease (GVHD), although T-cells were not depleted from donor marrow cells. Hemopoietic system of these recipient mice was replaced by that of donor origin [7]. As a first step to the application of this technique for human patients, we tested poly(L-lactic acid) (PLLA) particles as biodegradable particles. PLLA particles were phagocytized by macrophages when injected intravenously, and degraded slowly. PLLA has already been in clinical use as a bioresorbable suture material and matrix for drug release. We found that administration of PLLA prior to bone marrow transplantation resulted in a successful take of the allografts. In addition, PLLA was found not to show any antigenicity in normal mice.

Animals↗

PubMed1993

Abnormal facilitative glucose transporter gene expression in human islet cell tumors.

Our previous studies have shown that increased expression of GLUT1/erythrocyte and GLUT3/brain type glucose transporter genes in human tumors is associated with cellular transformation. We have now determined the levels of messenger RNAs (mRNAs) encoding these two glucose transporter isoforms as well as that of GLUT2/liver isoform in insulin-, glucagon-, and gastrin-secreting islet cell tumors. Northern blot analysis and reverse transcriptase-polymerase chain reaction revealed the presence of GLUT1 and GLUT3 mRNA in all human islet cell tumors and normal islets examined. In contrast, GLUT2 mRNA, which is present at high levels in normal islets, was not detected in insulinomas or other types of islet cell tumors. These results imply that GLUT1 and GLUT3 are primarily responsible for glucose uptake by these tumors.

Base Sequence↗

PubMed1993

Possible compensatory role of parathyroid hormone-related peptide on maintenance of calcium homeostasis in patients with non-insulin-dependent diabetes mellitus.

Recent studies have revealed that altered mineral and vitamin D metabolism is observed in diabetic patients with the complication of osteopenia. In order to elucidate the role of parathyroid hormone-related peptide (PTHrP) on calcium homeostasis in diabetes, we have measured the serum level and urinary excretion of PTHrP as well as other serum calcium-regulating hormones in 106 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 43 control subjects. The serum concentration of intact PTH was 2.34 +/- 0.13 (mean +/- SEM) pmol/l in NIDDM patients, which is significantly lower than the value of 3.11 +/- 0.14 pmol/l in the controls (p < 0.01). Both serum calcium and calcitonin, however, were not statistically different from controls. On the other hand, circulating PTHrP in NIDDM was 40.1 +/- 1.4 pmol/l, which is significantly elevated when compared to 27.3 +/- 1.3 pmol/l in the controls (p < 0.01). Moreover, urinary excretion of PTHrP also was significantly higher in NIDDM (p < 0.01). In the present study, the circulating calcium level was well preserved in NIDDM patients, although the PTH levels were shown to be decreased. The elevated serum PTHrP might, therefore, have a physiologically compensatory role on the calcium regulatory systems in NIDDM. Furthermore, this elevation is most likely due to the excess production of this peptide and not to the decrease in urinary excretion.

Adaptation, Physiological↗

PubMed1992

MY-1250, a major metabolite of the anti-allergic drug repirinast, induces phosphorylation of a 78-kDa protein in rat mast cells.

Repirinast (MY-5116; isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c]quinoline-2-carboxylate) is an anti-allergic drug of demonstrated effectiveness for treating bronchial asthma in humans. MY-1250 (5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c]quinoline-2-carboxylic acid), the major active metabolite of repirinast, inhibits antigen-induced histamine release from sensitized rat peritoneal exudate cells (PEC). When purified rat mast cells were treated with MY-1250 (2.5 x 10(-5) M) for 1 min, phosphorylation of a specific mast cell protein of apparent molecular mass of 78 kDa was observed as previously reported for sodium cromoglycate (SCG). Phosphorylation of this protein induced by MY-1250 and SCG occurred in a concentration-dependent manner with IC50 values of 2.0 x 10(-7) and 1.4 x 10(-5) M, respectively. MY-1250 did not inhibit calcium ionophore A23187 (1 microgram/mL)-induced histamine release from rat PEC. In the presence of calcium ionophore A23187 (1 microgram/mL), phosphorylation of this protein induced by MY-1250 was not evident. In conclusion, MY-1250 induced phosphorylation of a 78-kDa protein in rat mast cells and MY-1250 may inhibit histamine release by regulating phosphorylation of this protein in rat mast cells.

Animals↗

PubMed1992

Development of an animal model of late asthmatic response in guinea pigs and effects of anti-asthmatic drugs.

We developed an animal model of late asthmatic response (LAR) in guinea pigs and examined the effects of anti-asthmatic drugs and peptide leukotriene antagonist, MCI-826, on this model. Bronchial challenge of DNP-As (Dinitrophenylated-Ascaris suum extract)-sensitized guinea pigs induced a biphasic increase in pulmonary resistance (RL) with the maximal increase being observed immediately (IAR, immediate asthmatic response) and 3 to 5 hr after antigen inhalation (LAR). Twelve of 22 guinea pigs showed both IAR and LAR. The average increases in RL for all 22 guinea pigs at IAR and LAR, were 168 +/- 13 and 207 +/- 16 (% of baseline value), respectively. Bronchoalveolar lavage (BAL) fluid of guinea pigs that received antigen, revealed increases in the numbers of eosinophils (7.3-fold compared to animals receiving saline) and neutrophils (5.3-fold compared to animals receiving saline) 4 hr after antigen inhalation. When DSCG (disodium cromoglycate) was administered (10 mg/kg, i.v.) before antigen challenge, DSCG significantly inhibited IAR (p less than 0.05) and slightly inhibited LAR (p less than 0.2). Theophylline (30 mg/kg, p.o.) administered before antigen, slightly inhibited both IAR and LAR (p less than 0.2). Salbutamol (3 mg/kg, i.p.) administered before antigen, significantly inhibited IAR (p less than 0.05), but did not affect LAR. These results were correlated with clinical trials. Moreover, peptide leukotriene antagonist, MCI-826, (E)-2,2-Diethyl-3'-[2-[2-(4- isopropyl)thiazolyl] ethenyl]succinanilic acid (0.1 mg/kg, p.o.) administered 1 hr before antigen challenge, significantly inhibited both IAR and LAR (p less than 0.05). MCI-826 (0.1 mg/kg, p.o.) administered 1.5 hr after antigen inhalation, also inhibited LAR (p less than 0.05). Analysis of BAL fluid revealed that DSCG and MCI-826 significantly inhibited the increase in eosinophils (p less than 0.05). These data suggest that leukotriene plays an important role in the development of the pathogenesis of LAR, and that our model is an useful experimental model for investigating the mechanisms of LAR and examining the effects of several anti-asthmatic drugs on LAR.

Albuterol↗

PubMed1992

Magnetic resonance imaging for the diagnosis of esophago-aneurysmal fistula.

A 77-year-old woman who complained of dysphagia was found to have an aneurysm in the descending aorta. Magnetic resonance imaging (MRI) demonstrated the state of thrombi, a thin and irregular soft tissue signal between the aneurysm and the esophagus, which suggested an esophago-aneurysmal fistula revealed by the operation. MRI was effective in the evaluation of the status of aneurysm.

Aged↗

PubMed1992

A successful therapy with plasma exchange for interstitial pneumonia of progressive systemic sclerosis.

A 47-year-old woman who was diagnosed as progressive systemic sclerosis (PSS) had acute and severe interstitial pneumonia. Based on the results of her chest roentgenogram, computed tomography, transbronchial lung biopsy (TBLB) and bronchoalveolar lavage (BAL), her interstitial pneumonia was considered to be atypical of PSS. Although she was treated with corticosteroid, methylprednisolone pulse therapy and immunosuppressive drug, the effect of these drugs was insufficient as treatment for the interstitial pneumonia. Therefore, plasma exchange was attempted. After plasma exchange was carried out for three days, her symptoms improved as well as the laboratory data and chest roentgenogram without any severe side effects. We recommend plasma exchange for interstitial pneumonia of PSS as an effective treatment.

Adrenal Cortex Hormones↗

PubMed1991

Prevention of genetic resistance to bone marrow allografts by reticuloendothelial system blockade.

Agents which are toxic to macrophages such as silica and caragheenan suppress genetic resistance to bone marrow allografts. However, these agents may also be toxic to other tissues and cannot be used for the establishment of long-term bone marrow chimerism. In this study, we used chemically insert carbon particles to blockade phagocytic cells, and succeeded in carrying out bone marrow allografts. Long-term survival of the recipient mice after bone marrow transplantation (BMT) was achieved without apparent evidence of graft-versus-host reaction (GVHR), although T-cells were not depleted in donor marrow cells. The hemopoietic system of the recipient mice was replaced by that of donor origin. These results indicate that phagocytic cells play an essential role, probably as effector cells in genetic resistance to bone marrow allograft.

Animals↗

PubMed1991

Microbial endo-beta-N-acetylglucosaminidases acting on complex-type sugar chains of glycoproteins.

The activity and substrate specificity of endo-beta-N-acetylglucosaminidase [glycopeptide-D-mannosyl-N4-(N-acetyl-D-glucosaminyl)2-asparagine 1,4-N-acetyl-beta-glucosamino-hydrolase, EC 3.2.1.96] obtained from Mucor hiemalis (Endo-M) was compared with that of the enzyme obtained from Flavobacterium meningosepticum (Endo-F), which is the only enzyme available that acts on the complex oligosaccharides of asparagine-linked sugar chains in glycoproteins. They showed almost the same activities toward DNS-ovalbumin glycopeptide containing high-mannose and hybrid asparagine-linked oligosaccharides. However, Endo-M showed high activity towards DNS-asialotransferrin and DNS-transferrin glycopeptides, which contain complex biantennary oligosaccharides. Endo-M could weakly act even on DNS-asialofetuin glycopeptide containing complex triantennary oligosaccharides, while Endo-F could not. SDS-denatured asialotransferrin was deglycosylated by both enzymes in the presence of non-ionic detergent (NP-40) and EDTA, and the deglycosylated protein migrated to a lower molecular weight position than asialotransferrin on SDS-PAGE. However, even in the absence of detergent, Endo-M deglycosylated native asialotransferrin and transferrin. Deglycosylation of asialotransferrin was confirmed by means of Con A-Sepharose 4B column chromatography and SDS-PAGE.

Asialoglycoproteins↗

PubMed1990

Colony promoting activity: differences from interleukin-3 and similarities to interleukin-6.

The supernatant of long-term bone marrow culture contains colony promoting activity (CPA) which does not have granulocyte-macrophage colony stimulating activity (CSF) but which enhances granulocyte-macrophage (GM) colony formation in the presence of CSF. CPA might consist of IL-3 or IL-3-like activity, since CPA stimulates proliferation and differentiation of more immature cells to CSF-responding granulocytes-macrophage progenitors (GM-CFC), and since IL-3 also stimulates immature hemopoietic cells to proliferate and differentiate to functional blood cells. IL-1 and IL-6 are also known to enhance GM colony formation. One or both of these molecules can accordingly be another candidate for CPA. In the present study, GM-CSF activity of IL-3 was dependent on the batch of serum: it was negative in the presence of fetal calf serum, but positive in the presence of horse serum. In contrast, GM-CSF and CPA showed no such dependence on the batch of serum. The addition of IL-3 to GM colony assay system did not enhance but rather suppressed GM colony formation. The supernatant of long-term bone marrow culture which contains substantial levels of CPA did not stimulate proliferation of IL-3 dependent DA-1 cells, but facilitated the proliferation of IL-6 dependent, MH60.BSF2 cells. No detectable level of IL-1 activity was found in the supernatant. These results indicate that CPA is different from IL-1, IL-3 or GM-CSF, but similar to or the same as IL-6.

Animals↗