[Mechanism of hypoglycemic phenomenon in alloxan diabetic rat with renal damage by nephrotoxin. Studies on enzymatic activities of carbohydrate metabolism in liver].
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Animals↗
Biomedical subjects
A Matsuda
Publications and source records attributed to A Matsuda.
Early gastric carcinomas in the cardiac region: diagnosis with double-contrast x-ray studies.
BACKGROUND: The ratio of early to advanced gastric carcinomas in the cardiac region is significantly low. It is necessary to establish methods of early diagnosis of gastric carcinomas in the cardiac region. METHODS: Twenty cases (21 lesions) of early gastric carcinomas in the cardiac region were resected between 1997 and 2001. We studied the macroscopic characteristics of the specimens, films of double-contrast upper gastrointestinal studies before operations, and the detectabilities of findings in each projection. RESULTS: Four of 21 early gastric carcinomas in the cardiac region were on the anterior wall, 10 were on the lesser curvature, and seven were on the posterior wall. In seven of 21 lesions the carcinomas were not detected in the resected specimens macroscopically; in five, the area of carcinoma was not clearly traced in the resected specimens; and in nine, the area of carcinomas was clearly traced. In the morphologic study, 16 (76.2%), two (9.5%), two (9.5%), and one (4.8%) of the 21 lesions showed the superficial depressed type (IIc), superficial elevated type (IIa), superficial elevated and superficial depressed type (IIa + IIc), flat and superficial depressed type (IIb + IIc), respectively. Mucosal reddening was seen in 11, and mucosal discoloration was seen in one; change of color was not seen in the remaining nine lesions. Twenty lesions were diagnosed as differentiated adenocarcinomas, and one lesion was diagnosed as undifferentiated adenocarcinoma. Radiologically, early gastric carcinomas in the cardiac region had the following features: localized shallow barium deposits, localized abnormal barium coating, and niche and radiolucent lesions. Four (100%) of four lesions on the anterior wall, 10 (100%) of 10 lesions on the lesser curvature, and seven (100%) of seven lesions on the posterior wall were detected in the half-standing, prone, right anterior, oblique projection. Seven (100%) of seven lesions on the posterior wall and 10 (100%) of 10 lesions on the lesser curvature were detected in the half-standing, supine, left anterior, oblique projection. CONCLUSION: Even though most early gastric carcinomas in the cardiac region demonstrate few macroscopic findings, the half-standing, prone, right anterior, oblique projection and the half-standing, supine, left anterior, oblique projection are useful in the double-contrast studies.
Adenocarcinoma↗
Non-radioactive DNA diagnosis for the fragile X syndrome in mentally retarded Japanese males.
A rapid screening test was developed to detect CGG repeat expansion of the FMR-1 gene causing the fragile X syndrome by a non-radioisotope PCR technique. A biotin-labeled primer was initially used and the biotin-labeled PCR product was detected by means of chemiluminescence. The normal PCR product of around 300 bp was not created in the abnormal FMR-1 gene sample with this method. Four positive samples were found among those from 226 mentally retarded males, but the CGG repeat expansion was shown on Southern blot analysis in only one sample. To eliminate false-positive samples, a hybridization method involving a biotin-labeled (CGG)s oligonucleotide was developed for the PCR product and the CGG repeat expansion could be detected. Finally, 256 mentally retarded males in Japan were examined and only 2 abnormal samples were detected. The prevalence of this abnormality was less than 1%, which is relatively lower than those reported previously.
Base Sequence↗
TGF-beta2, tenascin, and integrin beta1 expression in superior limbic keratoconjunctivitis.
PURPOSE: To determine the pathophysiological etiology of superior limbic keratoconjunctivitis (SLK), we compared the superior limbic conjunctivae of SLK patients and normal controls. METHODS: Frozen sections of conjunctival specimens from five SLK patients and two controls were examined by immunohistochemical methods. Transforming growth factor (TGF)-beta2, integrin beta1, and tenascin (TN) were chosen for analysis because their expression is known to be affected by mechanical stress or injury. The staining pattern was observed by confocal laser scanning microscopy. RESULTS: Prominent positive TGF-beta2 staining on the surface region and heterogeneous staining in the suprabasal region were observed in the SLK specimens. TN expression was markedly up-regulated in the subepithelial stroma. In addition, suprabasal expression of integrin beta1 was observed. CONCLUSIONS: Up-regulation of TGF-beta2 and TN suggested that an increased amount of mechanical stress existed in the conjunctivae of the SLK patients. In addition, deposition of TN and suprabasal expression of integrin beta1 suggested that chronic minor injury contributed to the pathogenesis of SLK.
Aged↗
The effect of short-term basal insulin supplementation with human ultralente insulin on diurnal glycemic control in NIDDM patients.
The effect of short-term insulin treatment with a long-acting insulin preparation, Ultratard HM (U-HM) was investigated in eight non-insulin-dependent diabetes mellitus (NIDDM) patients whose previous glycemic control using diet was judged unsatisfactory. The treatment consisted of one daily pre-breakfast injection of U-HM (0.3 IU/kg) for 8 days. Glycemic control, assessed by mean plasma glucose (PG) daily profile and M-value, was improved significantly after U-HM treatment (mean PG and M-value, before: 223 +/- 19 mg/dl, 38.2; on the last day of U-HM: 151 +/- 11 mg/dl, 16.3; P less than 0.001; P less than 0.05). Serum insulin (IRI) reached a peak at 14:30 h during U-HM treatment, and mean IRI level increased during U-HM treatment (before: 14.0 +/- 2.8; during U-HM: 19.9 +/- 2.7 microU/ml). The mean C-peptide (CP) level decreased during U-HM treatment. Daily urinary CP excretion also decreased during U-HM treatment (before: 52.7 +/- 4.2; during U-HM: 34.8 +/- 4.2 micrograms/24 h). The data indicated that a single daily injection of U-HM was effective to improve whole-day glycemic control in NIDDM patients.
Adult↗
Nucleosides and nucleotides. 204. Synthesis of oligodeoxynucleotides containing 6'alpha-[N-(Aminoalkyl)carbamoyloxy]-carbocyclic-thymidines and the thermal stability of the duplexes and their nuclease-resistance properties.
To construct the nuclease-resistant oligodeoxynucleotides (ODNs) with natural phosphodiester linkages, we synthesized ODNs that contain 6'alpha-[N-(aminoalkyl)carbamoyloxy]-carbocyclic-thymidines (4, 5, and 6). The stability of these ODNs to nuclease hydrolysis was examined by using snake venom phosphodiesterase (3'-exonuclease) and nuclease S1 (endonuclease). It was found that the ODNs containing 4, 5, or 6 were more resistant to both the enzymes than the unmodified ODN. These nuclease-resistant properties are noteworthy, since they have natural phosphodiester linkages. Next, the thermal stabilities of duplexes consisting of these ODNs and either the complementary DNA or RNA were studied by thermal denaturation. The ODNs that contain 4 were found to enhance the thermal stability of the duplexes with the complementary DNA, while those containing 5 or 6 decreased the thermal stability of the ODN-DNA duplexes. On the other hand, all ODNs that contained 4, 5, or 6 decreased the thermal stability of the ODN-RNA duplexes.
Base Sequence↗
Significance of substrate hydrophobicity for recognition by an oligopeptide transporter (PEPT1).
Our previous paper [(1999) Bioconjugate Chem. 10, 24-31] pointed out that hydrophobicity of substrates/inhibitors plays an important role in the recognition by an oligopeptide transporter (PEPT1) expressed in the human intestinal epithelial cell line Caco-2. To determine the significance of that hydrophobicity, we have now synthesized dipeptide analogues conjugating the epsilon-amino group of Lys in Val-Lys with aliphatic carboxylic acids: acetic acid (C2), propanoic acid (C3), pentanoic acid (C5), hexanoic acid (C6), and decanoic acid (C10). The affinities of these conjugates were estimated by their inhibition of the accumulation rate of Gly-Sar, a well-established substrate for PEPT1. With the increase in length of the hydrocarbon chain of the conjugates, i.e., in the hydrophobicity of the conjugates, the inhibition strengthened. Dixon-Webb plot analysis of the inhibition by the C10-conjugated dipeptide showed competitive inhibition. The trans-stimulation effect of Val-Lys conjugated to C10 or C5 on the uptake of Ceftibuten was observed using rat brush border membrane vesicles. This findings showed that these conjugates are transportable substrates. These results confirmed that the hydrophobicity of substrates/inhibitor is one of the factors in the recognition by PEPT1.
Animals↗
Nucleosides and nucleotides. 121. Synthesis of oligonucleotides carrying linker groups at the 1'-position of sugar residues.
Novel 2'-deoxyuridine analogues carrying aminoalkyl linkers at the 1'-position of the sugar residues were synthesized and incorporated into oligonucleotides, then intercalating groups such as an anthraquinone derivative and a pyrene derivative were attached to the amino groups. Duplexes consisting of the oligonucleotides carrying the linker groups and a complementary ribonucleotide were more stable than an unmodified parent duplex, but the duplexes consisting of the oligonucleotides and a complementary deoxyribonucleotide were less stable. The oligonucleotides carrying the linker groups were more resistant to nuclease P1 and venom phosphodiesterase than an unmodified oligonucleotide. Furthermore, a duplex formed by the oligonucleotide analogue and the complementary ribonucleotide was a substrate for ribonuclease H.
Carbohydrate Metabolism↗
Nucleosides and nucleotides. 135. DNA duplex and triplex formation and resistance to nucleolytic degradation of oligodeoxynucleotides containing syn-norspermidine at the 5-position of 2'-deoxyuridine.
A novel 2'-deoxyuridine analogue with syn-norspermidine at the 5-position, 5-[4-[N,N-bis(3-amino-propyl)amino]butyl]-2'-deoxyuridine (1), has been synthesized from 5-iodo-2'-deoxyuridine. This nucleoside 1 was incorporated into heptadecadeoxynucleotides 5'-d[1(MT)8]-3' and 5'-[(TM)(4)1(MT)4]-3'(M = 5-methyl-2'-deoxycytidine). The triamine group stabilized duplex and triplex formation of the heptadecadeoxynucleotides with a complementary strand and a target duplex, respectively. The oligonucleotides containing 1 were more resistant to nuclease P1 and snake venom phosphodiesterase than an unmodified heptadecadeoxynucleotide, 5'-d[T(MT)8]-3'.
DNA↗
Nucleosides and nucleotides. 208. Alternate-strand triple-helix formation by the 3'-3'-linked oligodeoxynucleotides with the anthraquinonyl group at the junction point.
The synthesis of 3'-3'-linked oligodeoxynucleotides (ODNs) with the anthraquinonyl group at the junction point is described. The ODNs were synthesized on a DNA synthesizer using a controlled pore glass (CPG) carrying pentaerythritol that has an intercalator at one of the four hydroxymethyl groups. Stability of the triplexes with the target duplexes was studied by thermal denaturation. The 3'-3'-linked ODNs with the anthraquinonyl group enhanced the thermal stability of the triplexes when compared with those without the intercalator and the unmodified nonamer 10. It was found that the ODNs 12 and 13 carrying the anthraquinonyl groups can form thermally stable triplexes by skipping two or three extra base pairs between two binding domains of the target duplexes. The ability of the 3'-3'-linked ODNs to inhibit cleavage of the target DNA 22 by the restriction enzyme Hind III was tested. It was found that the 3'-3'-linked ODN 16 with the anthraquinonyl group at the junction point inhibited the cleavage by the enzyme more effectively than the nonamer 14 and the 3'-3'-linked ODN 15 without the intercalator.
Anthraquinones↗
Nucleosides and nucleotides. 160. Synthesis of oligodeoxyribonucleotides containing 5-(N-aminoalkyl)carbamoyl-2'-deoxyuridines by a new postsynthetic modification method and their thermal stability and nuclease-resistance properties.
Heptadecadeoxynucleotides containing 5-(N-aminoethyl- or N-aminohexyl)carbamoyl-2'-deoxyuridines (E or H) were synthesized using a newly developed postsynthetic modification method. As a convertible nucleoside unit, 5-methoxycarbonyl-2'-deoxyuridine (1) was initially incorporated into oligodeoxynucleotides (ODNs) according to the phosphoramidite method at various positions using a DNA synthesizer. Fully protected ODNs attached to a solid support were treated with alkyldiamines such as ethylenediamine and 1,6-hexanediamine to give the above modified ODNs. The thermal stability, resistance toward nuclease digestion, and stability in fetal calf serum of the modified ODNs were studied. An increase in the number of 5-(N-aminohexyl)carbamoyl-2'-deoxyuridines (H) in the ODNs was found to effectively stabilize duplex formation with both the corresponding complementary DNA and RNA and protect against nucleolytic hydrolysis by snake venom phosphodiesterase. In particular, the half-life of ODN 19, which contained four H residues, was about 162 h in the presence of the nuclease. Furthermore, 19 was also stable in medium containing 10% fetal calf serum with a t1/2 of about 48 h, while t1/2 for the corresponding unmodified ODN was 13 min.
Deoxyuridine↗
Nucleosides and nucleotides. 170. Synthesis and properties of oligodeoxynucleotides containing 5-[N-[2-[N,N-bis(2-aminoethyl)- amino]ethyl]carbamoyl]-2'-deoxyuridine and 5-[N-[3-[N,N-bis(3-aminopropyl) amino]propyl]carbamoyl]-2'-deoxyuridine.
The synthesis of oligodeoxynucleotides (ODNs) containing 5-[N-[2-[N,N-bis(2-aminoethyl)amino]ethyl]-carbamoyl]-2'-deoxyuridine (BAE) and 5-[N-[3-[N,N-bis(3-aminopropyl)amino]propyl]carbamoyl]-2'- deoxyuridine (BAP) is described. The thermal stabilities of duplexes containing these ODNs and either the complementary DNA or RNA strand and of triplexes consisting of these ODNs and the target duplex were studied by thermal denaturation. ODNs containing BAE or BAP stabilize duplex formation with either the complementary DNA or RNA strands but destabilize triplex formation with the target duplex. Furthermore, the resistance of these ODNs to nuclease hydrolysis was studied by using snake venom phosphodiesterase (a 3'-exonuclease) and nuclease S1 (an endonuclease). It was found that ODNs containing either BAE or BAP were more resistant to nucleolytic hydrolysis by either of the nucleases than the unmodified ODN.
Base Sequence↗
Conjugation of dipeptide to fluorescent dyes enhances its affinity for a dipeptide transporter (PEPT1) in human intestinal Caco-2 cells.
Dipeptide transporters in small intestine have a very wide substrate specificity, so that the transporter sometimes serves as a carrier for peptide-like compounds. We have synthesized dipeptide analogues conjugated at an epsilon-amino group of Lys in Val-Lys or Lys-Sar with fluorescent compounds such as fluorescein isothiocyanate and coumarin-3-carboxylic acid. Uptakes of these peptide analogues were examined by measuring intracellular accumulations into monolayers of the human intestinal epithelial cell line Caco-2 expressing the dipeptide transporter PEPT1. Kinetic analysis and effects of addition either of uncoupler (protonophore) or by Gly-Sar, one of the good substrates of PEPT1, revealed that fluorescent dipeptides were taken up by passive diffusion. In contrast, these analogues remarkably inhibited the Gly-Sar uptake by Caco-2 cells. Among the fluorescent analogues synthesized in this paper, Val-Lys(Flu) was the most potent competitive inhibitor against the Gly-Sar uptake with an inhibition constant of 5 microM. This value is the smallest among those ever reported: Val-Lys(Flu) has the highest affinity for PEPT1 among chemicals ever reported. The importance of the hydrophobic part of the substrate was pointed out.
Biological Transport↗
Stereospecificity of 6'-C-neplanocin A analogues as inhibitors of S-adenosylhomocysteine hydrolase activity and human immunodeficiency virus replication.
The R- and S-isomers of 6'-C-neplanocin A analogues, which are all known as inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase, were studied for their inhibitory effects on Human Immunodeficiency Virus type 1 (HIV-1) replication and HIV-1 Tat-mediated transactivation. The R-isomers showed much greater activity against AdoHcy hydrolase than the S-isomers. The same differential activity was observed against the HIV-1 replication and the Tat transactivation.
Adenosine↗
Nucleosides and nucleotides. 192. Toward the total synthesis of cyclic ADP-carbocyclic-ribose. Formation of the intramolecular pyrophosphate linkage by a conformation-restriction strategy in a syn-form using a halogen substitution at the 8-position of the adenine ring.
The synthesis of cyclic ADP-carbocyclic-ribose (2), as a stable mimic for cyclic ADP-ribose, was investigated. Construction of the 18-membered backbone structure was successfully achieved by condensation of the two phosphate groups of 19, possibly due to restriction of the conformation of the substrate in a syn-form using an 8-chloro substituent at the adenine moiety. SN2 reactions between an optically active carbocyclic unit 8, which was constructed by a previously developed method, and 8-bromo-N6-trichloroacetyl-2',3'-O-isopropylideneadenosine 9c gave N-1-carbocyclic derivative, which was deprotected to give 5'-5"-diol derivatives 18. When 18 was treated with POCl3 in PO(OEt)3, the bromo group at the 8-position was replaced to give N-1-carbocyclic-8-chloroadenosine 5',5"-diphosphate derivative 19 in 43% yield. Treatment of 19 with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride gave the desired intramolecular condensation product 20 in 10% yield. This is the first chemical construction of the 18-membered backbone structure containing an intramolecular pyrophosphate linkage of a cADPR-related compound with an adenine base.
Adenine↗
A new antitumor nucleoside, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd), is a potent inhibitor of RNA synthesis.
The antitumor activity, metabolism, and mechanism of action of a newly developed antitumor nucleoside, 1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd) are described.
Animals↗
Intracellular Ca(2+)-mobilizing adenine nucleotides. Synthesis and biological activity of cyclic ADP-carbocyclic-ribose and C-glycosidic analog of adenophostin A.
We designed novel Ca(2+)-mobilizing purine nucleotides, cyclic ADP-carbocyclicribose 4, and its inosine congener 5, and C-glycosidic adenophostin A 6. In the synthesis of cADPR analogs, the intramolecular condensation to form the pyrophosphate linkage should be the key step. We developed an efficient method for forming such an intramolecular pyrophosphate linkage by the activation of the phenylthiophosphate group with I2 or AgNO3. Using this method, we achieved to synthesize the target compounds 4 and 5. The synthesis of C-glycosidic analog 6 of adenophostin A was achieved using a temporary silicon-tethered radical coupling reaction for constructing (3'alpha, 1" alpha)-C-glycosidic structure as the key step.
Adenine Nucleotides↗
1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106)1: antitumor effect and mechanism of action.
The antitumor activity, cellular metabolism and mechanism of action of the antitumor nucleoside analog, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd) are described.
Animals↗