Biomedical subjects

T Sekiguchi

Publications and source records attributed to T Sekiguchi.

At least 91 records · Page 5Linked to original sources

PubMed1995

[Clinical studies on SY5555 in pediatrics].

SY5555 in dry syrup (powder which is dissolved before use) or tablet form was given orally to 21 children with acute bacterial infections including 4 with acute pharyngitis, 5 with acute tonsillitis, 7 with acute bronchitis, 2 with acute gastroenteritis, 1 each with scarlet fever, acute lymphadenitis and urinary tract infection. Good to excellent clinical responses were obtained in all of the 21 patients and 8 of 11 strains found as causative organisms in these cases were eradicated and 3 strains were decreased. Loose stools were observed in 3 cases and eosinophilia was observed in 1 case. From the above clinical results, it appears that SY5555 is a useful antibiotic for the treatment of pediatric patients with various bacterial infections.

Administration, Oral↗

PubMed1994

Structure of the human CCG1 gene: relationship between the exons/introns and functional domain/modules of the protein.

The human CCG1 gene, encoding CCG1/TAFII250/p250, was isolated by complementing tsBN462, a mutant BHK21 cell line that shows cell-cycle arrest at high temperature. Using the cDNA as a probe, the locations of exon-intron junctions were determined in the genomic DNA. Thirty-eight exons ranging from 68 to 219 bp in size were found. All the exon-intron junctions followed the GT-AG rule. Using a newly developed method, we performed a module analysis of the CCG1 protein. The functional domain previously predicted in CCG1 was further confirmed to be encoded in a single predicted module that is the minimal functional unit in the protein. The boundaries of the predicted modules show a close correlation to the intron/exon junction of CCG1. The entire gene, at least 110 kb long, has been recovered in a YAC, which provides a route to the further study of module function.

Base Sequence↗

PubMed1994

The CCG1/TAFII250 gene is mutated in thermosensitive G1 mutants of the BHK21 cell line derived from golden hamster.

The CCG1 cDNA encoding a general transcription factor, TAFII250, complements a thermosensitive (ts) cell cycle mutant, tsBN462, of the BHK21 cell line, which arrests in the G1 phase at the restrictive temperature. In order to clarify whether the CCG1 is mutated in tsBN462 cells or a suppressor of tsBN462 mutation, CCG1 cDNAs isolated from parental wild-type (wt) BHK21 and tsBN462 cell lines were sequenced. Comparison of the nucleotide (nt) sequences showed a single transition: G-->A in the second base of codon 690 of the tsBN462 CCG1 cDNA, resulting in a Gly690-->Asp change. The BHK CCG1 cDNA, but not the tsBN462 CCG1 cDNA, complemented the tsBN462 mutation, proving that the CCG1 is mutated in the tsBN462 cell line. Thus, the defect of general transcription factor, TAFII250, is suggested to cause a G1 arrest in the cell cycle.

Amino Acid Sequence↗

PubMed1994

Inhibition of free radical generation by biotin.

To assess the inhibitory effect of biotin on free radical generation, we used a spectrophotometric assay of cytochrome c reduction and determined the 2-methyl-6-phenyl-3,7-dihydroimidazo[1,3-a]-pyrazin-3-one (CLA)-dependent chemiluminescence response of human neutrophils or a hypoxanthine-xanthine oxidase (XOD) system. In the spectrophotometric assay of cytochrome c reduction, superoxide (O2-) generation by neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine (f-MLP) was reduced significantly when biotin was added. In the CLA-dependent chemiluminescence test of neutrophils stimulated by f-MLP, biotin significantly reduced the generation of free radical species, including O2-, in a concentration-dependent manner, the concentration corresponding to 50% inhibition (IC50) of biotin for free radical generation was 1.12 x 10(-7) mol. However, biotin did not exert an inhibitory effect on oxidative metabolism by directly scavenging superoxide anion, as shown by the study using the hypoxanthine-XOD system.

Adult↗

PubMed1994

Minimum essential region of CCG1/TAFII250 required for complementing the temperature-sensitive cell cycle mutants, tsBN462 and ts13 cells, of hamster BHK21 cells.

CCG1/TAFII250, the largest subunit of the TFIID complex, is mutated in ts cell cycle mutants of BHK21 cells, ts13 and tsBN462, which have a promoter-selective transcriptional defect. A series of deletion mutants of CCG1 cDNA were prepared and transfected into these mutants, in order to identify functional domains of CCG1 required for the complementation of ts 13/BN462 mutation. We determined the minimum size of CCG1:CCG1ME, essential for complementing the ts mutation, which possessed one proline cluster, an HMG1-like domain, and a nuclear localization signal, but which lacked the bromo domains and the acidic phosphorylation sites for casein kinase II common to transcriptional activators. It encodes a protein of 140 kDa. These characteristics of CCG1ME correspond to yeast TAFII145, the yeast homolog of human TAFII250. CCG1ME bound to TBP, creating its own TFIID complex different from that of the endogenous mutated CCG1 in ts+ transformants of tsBN462 cells.

Animals↗

PubMed1994

Preliminary findings of chromosomal alterations and expression of cell cycle genes in head an neck tumors.

The genesis and progression of malignant tumors may be related to certain somatic mutations and the accumulation of multiple chromosomal alterations. Using four freshly resected malignant tumors, we investigated the relationship between chromosomal alteration and expression of cell cycle regulatory genes. Specimens of thyroid hyperplasia and normal thyroid tissue were also investigated. As cell cycle regulating genes, we chose the cdc2 gene that encodes the p34cdc2 protein kinase, a major kinase of the cell cycle, and the RCC1 gene that is essential for coupling between S and M phases. Three of the malignant tumors contained cells with chromosomal alterations, including one polyploid and two aneuploid. The DNA content of cells in thyroid hyperplasia was the same as in the normal gland. The amount of p34cdc2 protein was very low in cells of both normal thyroid and hyperplastic tissue, and grew very slowly as compared with malignant tumors. There was no significant relationship between the amount of RCC1 and ploidy pattern.

Adaptor Proteins, Signal Transducing↗

PubMed1994

Cooling-induced retrograde amnesia reflexes Pavlovian conditioning associations in Limax flavus.

The relationships between cooling-induced retrograde amnesia and associations in Pavlovian conditioning in the terrestrial mollusk Limax flavus were studied. In the first experiment, the slugs were conditioned to avoid carrot odor and the experimental conditions required for amnesia induction were studied. Memory reactivation before cooling was found to be necessary for amnesia induction and the induced amnesia was selective for the reactivated memory. In the subsequent experiments, slugs were conditioned to avoid both carrot and cucumber odors using one of three Pavlovian conditioning paradigms, namely two-independent first-order conditioning, phase-2-sequential second-order conditioning and phase-2-simultaneous second-order conditioning, after which amnesia was induced by cooling immediately after presentation of one of the conditioning odors. The amnesia pattern induced differed depending upon the conditioning procedure used, which indicated that amnesia induction was related closely to stimulus associations in slugs. The possible role of cooling-induced retrograde amnesia as a tool for studying memory associations is also discussed.

Amnesia, Retrograde↗

PubMed1994

Hyaluronan, cartilage destruction and hydrarthrosis in traumatic arthritis.

The concentrations of hyaluronan (HA) and chondroitin sulfate (CS) in synovial fluids from patients with traumatic arthritis (TA) with and without hydrarthrosis were measured. The CS in synovial fluids was determined as a marker of cartilage destruction by high performance liquid chromotography. The concentration of HA in synovial fluids was lower in patients with hydrarthrosis than in healthy volunteers and patients with TA without hydrarthrosis, whereas the total amounts of HA and CS and the concentration of CS were higher in patients with hydrarthrosis. To investigate the relation between hydrarthrosis and production of HA in synovial tissues, TA synovial tissue biopsies were stained for HA with biotinylated HA binding region. The intensity of HA staining was higher in specimens from patients with hydrarthrosis than in normal and TA without hydrarthrosis specimens. Thus, there may be a correlation between hyperproduction of HA, cartilage destruction and increase in fluid volume in TA.

Adolescent↗

PubMed1994

Mammalian cells have two functional RCC1 proteins produced by alternative splicing.

Previously we cloned two human RCC1 cDNAs that differed in their noncoding region. In this study, we have found new human and hamster RCC1 cDNAs, which have an even more different coding region from that of the previously cloned RCC1 cDNAs yet can complement the RCC1 mutation in the tsBN2 cell line. The newly found RCC1 cDNAs encode a protein (designated as RCC1-I) that has an insertion of 31 (human) and 13 (hamster) amino acids at valine25 in the N-terminal region outside the RCC1-seven repeat. The inserted nucleotide sequence was searched for, within the human RCC1 genomic sequence that had already been determined, and was found to be located between the 6th and 7th exons, designated as the 6' exon. Both the 5' and 3' ends of the 6' exon correspond to the GT-AG rules for splicing, indicating that human RCC1-I mRNAs are produced by alternative splicing. The finding that both humans and hamsters have the insertion at the same RCC1 site suggests that the pattern of alternative splicing in the RCC1 gene has been conserved through evolution.

Alternative Splicing↗

PubMed1994

Effect of H2-receptor antagonists cimetidine and famotidine on interdigestive gastric motor activity and lower esophageal sphincter pressure in progressive systemic sclerosis.

The effect of the H2-receptor antagonists cimetidine and famotidine on interdigestive gastric motor activity and lower esophageal sphincter pressure was assessed in 41 patients with uncomplicated progressive systemic sclerosis. There was no significant change in gastric phasic motor activity after the intravenous administration of cimetidine (n = 6), famotidine (n = 13), and physiological saline (n = 15), or the intragastric infusion of 7% sodium bicarbonate (n = 7). The lower esophageal sphincter pressure was increased significantly by both cimetidine and famotidine, but only famotidine caused a significant pressure rise in patients without an increase of gastric motility. Cimetidine and physiological saline produced a similar pattern of change in the esophageal sphincter pressure, as did famotidine and sodium bicarbonate. These findings suggest that the inhibition of acetylcholinesterase activity and gastric acid secretion may be involved in the respective mechanisms of action of cimetidine and famotidine.

Cimetidine↗

PubMed1994

[Clinical studies on cefozopran in pediatrics].

Cefozopran (CZOP, SCE-2787) was given intravenously to 12 children with acute bacterial infections including 9 with acute pneumonia, 1 each with acute pyothorax, impetigo and staphylococcal scalded skin syndrome. Good or excellent clinical responses were obtained in all of the 12 patients and bacterial eradications were achieved for all 10 strains identified in these cases. No side effects were noted. Eosinophilia was observed in one case, however. From the above clinical results, it appears that CZOP is a useful antibiotic for treatment of pediatric patients with various bacterial infections.

Bacteria↗

PubMed1994

[The CCG1 gene].

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Animals↗

PubMed1993

Molecular cloning and identification of two types of hamster cyclin-dependent kinases: cdk2 and cdk2L.

We isolated two types of hamster cyclin-dependent kinase 2 (cdk2) cDNAs from BHK21 cells derived from Golden hamsters. One type of cdk2 (cdk2hm) encodes the 32 kDa protein consisting of 298 predicted amino acids and shows strong homology to the cdk2 cDNAs of humans and Xenopus. The other cdk2 (cdk2Lhm) encodes the 38 kDa protein containing the insertion of 48 amino acids in the cdk2hm protein. Immunoblotting analysis suggested that these two types of cdk2 protein exist in mammalian cells. The cdk2hm has the activity of protein kinase, while the cdk2Lhm does not, however, both bind with cyclin E.

3T3 Cells↗

PubMed1993

Inflammatory polyarthritis in mice transgenic for human T cell leukemia virus type I.

OBJECTIVE: We have recently reported that arthropathy develops in high incidence among transgenic mice carrying the pX region of human T cell leukemia virus type I (HTLV-I). In the present study, the histopathologic features of the joints in these mice were examined in order to compare the animal disease with rheumatoid arthritis (RA) in humans. METHODS: Paraffin sections of limbs (right and left fingers, wrists, elbows, shoulders, toes, knees, and ankles) were stained with hematoxylin and eosin, periodic acid-Schiff, azan-Mallory, or phosphotungstic acid hematoxylin, and examined by light microscopy. RESULTS: Abnormalities of the limbs began to occur as early as 3 weeks of age, and the incidence gradually increased until the mice were 12 months old. The incidence of arthropathy was 22% (48 of 217) at 3 months of age and 28% (18 of 64) at 6 months. The severity of the histopathologic changes in the joints of the transgenic mice ranged from grade I to grade IV. CONCLUSION: The major histopathologic features in the joints of HTLV-I transgenic mice are similar to those in humans with RA. Thus, these mice may represent a useful model for the study of the disease in humans.

Animals↗

PubMed1993

Effect of erythromycin derivative EM523L on human interdigestive gastrointestinal tract.

We investigated the effect of an erythromycin derivative, EM523L, on interdigestive gastrointestinal motor activity and plasma motilin concentrations in three healthy volunteers using an infused catheter system. We administered doses of 500, 1000, and 2000 micrograms of EM523L to each subject as well as physiological saline. EM523L induced interdigestive migrating contractions (IMCs) that originated in the stomach and migrated to the duodenum. This response was noted in all three subjects after each dose of EM523L, while no IMCs were induced by saline. There were no significant differences in the characteristics of the EM523L-induced IMC and the spontaneous IMC. The initiation time, ie, the interval between the start of EM523L infusion and the onset of the IMC became shorter in a dose-dependent manner. Plasma motilin concentrations increased significantly after EM523L administration, suggesting that motilin is involved in the mechanism of IMC induction by this drug.

Adult↗

PubMed1993

Gastric acid inhibits antral phase III activity in duodenal ulcer patients.

Fourteen patients with duodenal ulcers and eight healthy volunteers were examined to measure interdigestive gastroduodenal motility and plasma motilin. In order to study the effects of gastric acid on the gastroduodenal motility, 20 mg of famotidine was administered intravenously. The motility index of the gastric antrum and the duodenum, as well as the pH in the duodenal bulb were calculated. The duodenal pH was significantly lower and the gastric motility index was significantly weaker before the duodenal interdigestive migrating complex (IMC) in the ulcer patients than in the controls. Motilin levels increased before the duodenal IMC and decreased afterwards in both groups. Famotidine significantly increased the duodenal pH and the gastric motility index before the IMC, but no changes in the motilin level were noted. We conclude that duodenal ulcer patients have duodenal hyperacidity that results from increased inflow from the antrum and antral hypomotility during the gastric IMC and that these changes are normalized by the administration of famotidine. These results suggest that gastric acid inhibits antral contraction during the gastric IMC.

Adult↗

PubMed1993

Effect of erythromycin on interdigestive gastrointestinal contractile activity and plasma motilin concentration in humans.

The effects of erythromycin (EM) on gastrointestinal contractile activity during the interdigestive period were investigated in seven healthy subjects using an infused catheter system, and the changes in the plasma motilin concentration were also determined. Graded EM doses (0.1-1.5 mg/kg) were administered intravenously over 5 min, usually during gastric phase I. EM induced interdigestive migrating contractions (IMCs). Their induction rate was low after low doses of EM, but gradually increased as the dose increased to reach 71.4% at an EM dose of 0.375 mg/kg. Strong contractions, which were quite similar to phase III activity of the stomach but did not migrate or migrated incompletely to the duodenum, were observed at EM doses above 0.375 mg/kg. Therefore, the optimum dose of EM for inducing an IMC was established to be 0.375 mg/kg. In comparison with spontaneous IMCs, EM-induced IMCs had a significantly longer duration in the stomach and a significantly lower amplitude in the duodenum. These observations indicate that EM induced phase III activity more intensively in the stomach than in the duodenum. The plasma motilin concentration increased significantly during EM-induced IMCs, and this suggested a close relationship between this hormone and induction of the IMC. The increase in motilin levels was also observed of the strong gastric contractions which did not migrate or migrated incompletely to the duodenum. Therefore, it seems reasonable to suggest that motilin is involved in phase III activity of the stomach rather than in that of the duodenum.

Adolescent↗

PubMed1993

Histopathological observation of joint lesions of extremities in mice transferred genome.

Pathological examination of arthritic lesions in transgenic mice produced by the pX region of the human T-cell leukemia virus type-1 (HTLV-1) was carried out. Clinically, erythema, swelling and/or ataxia of the limb joints were observed in many transgenic mice about 1 month-old. Histopathologically, proliferation of synovial lining cells, infiltration of inflammatory cells with lymphoid structures and formation of pannus with cartilage and/or subchondral bone destructions were observed in various joints of transgenic mice. The frequency of abnormalities in the joints was higher in females than in males. These histopathological findings were very similar to those of human rheumatoid arthritis (RA). Present results indicate that the pX genome of the HTLV-1 is an etiological agent for the incidence of arthritic lesions in the transgenic mice.

Animals↗