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Biomedical subjects

Y Jinbo

Publications and source records attributed to Y Jinbo.

14 recordsLinked to original sources
PubMed2001

Increase in the molecular weight and radius of gyration of apocalmodulin induced by binding of target peptide: evidence for complex formation.

Small-angle X-ray scattering was used to investigate a complex state of apocalmodulin induced by the binding of a Ca(2+)/calmodulin-dependent protein kinase IV calmodulin target site. Upon binding of the peptide, the molecular weight for apocalmodulin increased by 8.4%, which provides direct evidence for the formation of a calmodulin/target peptide complex. Comparison of the radius of gyration and Kratky plots of the apocalmodulin/peptide complex with those of apocalmodulin indicates that the overall conformation remains unchanged but the flexibility of the central linker decreases. An analysis of residue pairs between calmodulin and the target peptides suggests that the complex formation is induced by electrostatic interactions and subsequent van der Waals interactions.

Apoproteins↗
PubMed2000

Ca2+-bound calmodulin forms a compact globular structure on binding four trifluoperazine molecules in solution.

Small-angle X-ray scattering (SAXS), which determines the radius of gyration, R(g), and the pair distance distribution function, was used to investigate the conformational changes of calmodulin (CaM) on binding to an antagonist, trifluoperazine (TFP), with or without Ca(2+) in solution. We previously applied this SAXS method to CaM complexed with N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7) [Osawa, Kuwamoto, Izumi, Yap, Ikura, Shibanuma, Yokokura, Hidaka and Matsushima (1999) FEBS Lett. 442, 173-177] and found that the binding of two W-7 TFP molecules to one Ca(2+)-saturated CaM molecule induces structural changes from a 'dumb-bell' shape to a compact globular shape. We report here that the most compact globular shape whose size is consistent with that of the 1:2 Ca(2+)-saturated CaM-W-7 complex is formed by the binding of four TFP molecules to one Ca(2+)-saturated CaM molecule. Even in the absence of Ca(2+), the conformational changes of CaM occur on TFP binding, giving a slightly smaller R(g) than Ca(2+)-free CaM alone.

Animals↗
PubMed1998

Decreasing parasympathetic tone activity and proarrhythmic effect after radiofrequency catheter ablation--differences in ablation site.

Holter ECG was used to evaluate changes in heart rate variability (HRV), indicators of the autonomic nervous system, and arrhythmia before and after radiofrequency (RF) catheter ablation in patients with symptomatic supraventricular tachycardia. Ablation targets in 43 patients included the atrioventricular (AV) nodal pathway (AVNRT, n = 17), a right free wall accessory pathway (n = 10), a septal accessory pathway (n = 6), and a left free wall accessory pathway (n = 10). The High frequency component (0.15 - 0.40 Hz) or pNN50 of HRV analysis, indicating parasympathetic activity, significantly decreased immediately after RF ablation in the AVNRT and septal accessory pathway groups, but not in the right or left wall groups. In contrast, in all four groups, ventricular premature contractions (VPCs) significantly increased in most of the patients, and ventricular tachycardia occurred in a few of the patients immediately after RF ablation. There was no serious arrhythmia. These alterations in HRV analysis and arrhythmia returned to the control level after 1 week or more. VPCs after RF ablation did not consistently increase as a result of the reduced parasympathetic tone activity, but at the lesion near the conduction system, the increase in VPCs was inhibited by higher parasympathetic tone activity, because the parasympathetic nerve fibers and receptors were distributed in these lesions.

Adolescent↗
PubMed1997

FP-21399 blocks HIV envelope protein-mediated membrane fusion and concentrates in lymph nodes.

The identification of fusin and other chemokine receptors as coreceptors for HIV-1 has renewed the interest in agents that may prevent viral entry. Polyanionic compounds such as dextran sulfate, curdian sulfate, and suramin act on the V3 loop of the viral envelope and may prevent its interaction with fusin. These agents show activity against a wide range of HIV-1 strains, but have undesirable circulating half-life, bioavailability, and toxicity. We have developed a small molecule inhibitor of HIV-1 that has several advantages over these other agents. FP-21399 is a novel compound of the bis(disulfonaphthalene) dimethoxybenzene class that blocks entry of HIV into CD4+ cells and blocks fusion of infected and noninfected CD4+ cells. This compound only weakly inhibits binding of CD4 and gp120, at concentrations much greater than are required to block viral entry. Furthermore, FP-21399 can block the interaction between gp120 and antibodies directed against the V3 loop, but does not block binding of antibodies directed against the V4 loop. Animal studies demonstrate that FP-21399 is concentrated in lymph nodes, making it a promising compound for anti-HIV therapy. In SCID mice reconstituted with human immune cells, maintenance of HIV-1 infection was blocked by a 5-day treatment with low doses of FP-21399, suggesting that lymph node accumulation may contribute to antiviral activity. Finally, attempts to generate drug-resistant virus in cell culture resulted in only weakly resistant variants with IC90 values that are much lower than concentrations of FP-21399 found in lymph nodes.

Animals↗
PubMed1997

Effects of adenosine triphosphate on ventriculoatrial conduction--usefulness and problems in assessment of catheter ablation of accessory pathways.

The effects of adenosine triphosphate (ATP) on ventriculoatrial (VA) conduction were examined before and after accessory pathway (AP) ablation, with emphasis on assessment of the complication of dual atrioventricular (AV) node pathway. By evaluating the differences in the response to ATP of APs and other pathways, we assessed the usefulness and problems of this method. Of 59 patients who underwent AP ablation, 31 showed pre-excitation and 28 had concealed APs. A dual AV node pathway was found in 9 patients (15.3%) before ablation. After ablation, a dual AV node pathway was newly found in 9 patients. Thus, the total number of patients with a dual AV node pathway was 18 (30.5%). VA conduction over APs was not blocked in 26 of 29 patients, but the remaining 3 APs were blocked transiently by ATP. ATP caused VA block over the AV node in 15 of 16 patients and a dual AV node pathway in all 11 patients. In contrast, VA conduction over the retrograde fast pathway was blocked in 9 of 14 patients with AV node re-entrant tachycardia. ATP has little effect on APs, so observation of the response to ATP provides a more reliable and useful means of evaluating successful ablation. With this method, however, it is important to consider the possibility of the presence of ATP-sensitive APs and ATP-resistant retrograde fast pathways. The influence of ablation-induced injury has not been fully clarified. It is therefore essential to take into account various data, including the comparison between data obtained before and after ablation.

Adenosine Triphosphate↗
PubMed1996

Dipyridamole suppresses catecholamine- and Ca++ influx-sensitive ventricular arrhythmias.

To study the mechanism of ventricular arrhythmias, the effect of dipyridamole (DIP; 300 mg/day), an adenosine transport inhibitor, on ventricular premature contractions (VPCs) was assessed in 12 patients who showed VPCs (21312 +/- 12314/day) on Holter ECG in a controlled setting. The effects were compared with those of verapamil (240 mg/day) and bisoprolol (5 mg/day). DIP suppressed more than one-half the VPCs in 5 patients. The mean degree of reduction in these DIP-responders was 75 +/- 18%. Both verapamil and bisoprolol inhibited VPCs in all of the DIP-responders (verapamil: 71 +/- 15%, bisoprolol: 88 +/- 16%). Two of the 5 DIP-responders had sustained ventricular tachycardias (VT) that were terminated by intravenous DIP, ATP, acetylcholine, verapamil, and propranolol. In contrast, verapamil did not inhibit VPCs in any of the DIP-nonresponders. Bisoprolol also did not suppress VPCs in 3 of 6 DIP-non responders. heart rate was unaffected by DIP, but was suppressed by both verapamil and bisoprolol. In addition, DIP increased the serum concentration of adenosine (control 16.3 +/- 17.1 vs 22.3 +/- 19.0 pmol/ml after DIP, p < 0.05). The inhibitory effect of DIP may involve suppression of Ca+2 current through an extracellular increase in adenosine.

Adult↗
PubMed1996

Selective slow pathway ablation in atrioventricular nodal reentrant tachycardia--comparison of different methods and the site of slow pathway ablation.

The optimum potential of the slow pathway (SP) was investigated by determining the effectiveness and safety of high-radiofrequency catheter ablation to treat atrioventricular nodal reentrant tachycardia (AVNRT). The subjects consisted of 29 patients with AVNRT (11 men, with a mean age of 54 +/- 15 years). Three ablation methods were used: a) Method A used the earliest atrial activation site, which is retrograde to the slow pathway, b) Method SP used the SP potential, and c) Method SW, in which ablation was performed stepwise starting from the coronary sinus and moving toward the recording site of the His bundle potential. Five, 20, and 4 patients underwent Methods A, SP, and SW, respectively. The fewest number of applications was needed with Method SP (11 +/- 9, 6 +/- 4, and 13 +/- 9), and the delivered energy was also lowest with Method SP (9151 +/- 6119, 3712 +/- 2168, and 12183 +/- 4090 J, with Methods A, SP, and SW, respectively). In Method SP, the interval between the atrium and SP was significantly longer at sites which cured tachycardia, than at sites at which ablation was ineffective (88 +/- 26 vs 66 +/- 22 msec, p < 0.05). The SP potential showed a humped shape in 18 of 20 patients. Method SP was the most efficient ablation method for treating AVNRT.

Adult↗
PubMed1994

Synthesis and antibacterial activity of thiazolopyrazine-incorporated tetracyclic quinolone antibacterial agents. 2.

A novel series of 8-(2-substituted morpholino)-9,1-[(N-methylimino) methano]-7-fluoro-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids, designated 8a-j, with a unique tetracyclic structure were synthesized, and the in vitro and in vivo antibacterial activities against Gram-positive strains, including methicillin-resistant Staphylococcus aureus isolates (MRSA), and Gram-negative strains were evaluated. These morpholino derivatives, 8a-j, showed excellent in vitro antibacterial activities against Gram-positive bacteria. The substitutions at the C-2 position of the 8-morpholino moiety of compound 8 play an important role in the enhancement of in vivo antibacterial activity. The unsubstituted morpholino derivative 8a, the 2,6-dimethyl derivative 8c, and the 2-ethylmorpholino derivative 8d showed poor in vivo antibacterial activity, while 8b, 8f-h, and 8j exhibited good activities. The 2-(methoxymethyl)morpholino derivative, 8h, showed the most potent activity in vivo. The therapeutic effects of 8h on systemic infection against S. aureus IID 803 were over 10-fold more potent than that of ofloxacin. Compound 8h, which showed superior oral bioavailability, has a chiral center. The enantiomers of 8h were synthesized, and the in vitro and in vivo antibacterial activities were evaluated. Both enantiomers, (S)-8h and (R)-8h, and the racemic compound 8 exhibited similar activities in vitro and in vivo. Compounds 8b and 8f-h also showed good levels of antibacterial activity against MRSA strains. The morpholino derivatives with unique tetracyclic structures are characterized by strong antibacterial activities against MRSA strains.

4-Quinolones↗
PubMed1994

Synthesis and antibacterial activity of thiazolopyrazine-incorporated tetracyclic quinolone antibacterials.

A novel series of 8-substituted-9,1-[(N-methylimino)methano]- 7-fluoro-5-oxo-5H-thiazolo[3,2-alpha]-quinoline-4-carboxylic acids 5a-q having a unique thiazolopyrazine-incorporated tetracyclic structure were synthesized, and the in vitro and in vivo activities were determined against Gram-positive and Gram-negative bacteria. All compounds 5a-q had more potent activity than ofloxacin (6), which is one of the most popular quinolones, against Gram-positive and Gram-negative bacteria. The 8-pyrrolidinyl, 5a-e, and 8-morpholino, 5p, derivatives showed the most potent activity against Gram-positive bacteria. It is also significant that these compounds, 5a-q, showed more potent antibacterial activity against methicillin-resistant Staphylococcus aureus isolates (MRSA) than ofloxacin (6). The combination of the morpholino group and this unique tetracyclic thiazolopyrazine skeleton contributes to the enhancement of the antibacterial activity against MRSA isolates. The in vivo antibacterial activities of these compounds, 5a-q, were limited and depended on the structure of the 8-substituent. The 8-(4-alkyl-1-piperazinyl) derivatives 5g, 5h, 5j, and 5n provided good oral efficacy and exhibited more potent activity than ofloxacin (6) against the systematic infection with S. aureus IID 803 in mice.

Animals↗
PubMed1993

Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic acids.

A novel tetracyclic pyridone carboxylic acid with a thiazolidine ring, 1,2-dihydro-9,1-(epoxymethano)-7-fluoro-8-(4-methyl-1-piperazinyl)-5-oxo -5H- thiazolo[3,2-a]quinoline-4-carboxylic acid (4a), and variants with a nitrogen atom (4b) or carbonyl group (4c) in the place of the 10-position oxygen atom of 4a were prepared and tested for antibacterial activity and inhibitory activity on DNA gyrase from Escherichia coli KL-16. The in vitro antibacterial potency with regard to the 10-position atom was found to be of the following order; O > NCH3 = C = O. The IC50 values for DNA gyrase inhibition activity for the 4a, 4b, and 4c compounds were 0.33, 0.53, and 0.67 g/mL, respectively. The activity of 4a, in which the C-3 methyl group and C-5 of ofloxacin (2a) were connected with a sulfur atom to restrict the conformation of 2a, was more potent than that of 2a against both Gram-positive and -negative bacteria, except for Pseudomonas aeruginosa. Compared to the tetracyclic pyridone carboxylic acid 1a, which has a flat thiazole ring, compound 4a showed comparable or slightly more potent activity against both Gram-positive and -negative bacteria, except for P. aeruginosa.

Anti-Infective Agents↗
PubMed1993

Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic acids.

A series of novel tetracyclic pyridone carboxylic acids replacing the 10-position oxygen atom of 9,1-(epoxymethano)-7-fluoro-8-(4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo [3,2-alpha]quinoline-4-carboxylic acid by imino groups (NR; R = Me, Et, c-Pr, allyl, Ph, benzyl), a sulfur atom, or a carbonyl group was prepared and evaluated for antibacterial activity and inhibitory activity on DNA gyrase isolated from E. coli KL-16. The in vitro antibacterial potency and DNA gyrase inhibitory activity were found to be in the following order: NMe > or = O > S >> C = O. Moreover, a methyl group was the optimal alkyl substituent at the 10-position nitrogen atom for antibacterial activity and for DNA gyrase inhibitory activity. 7-Fluoro-9,1-[(N-methylimino)methano]-8- (4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo[3,2-alpha]quinoline-4-carboxy lic acid (10-NCH3) showed potent in vivo antibacterial activity.

Animals↗
PubMed1993

Visualization of the morphology of purple membrane surfaces by monoclonal antibody techniques.

A monoclonal antibody technique for determining the surface morphology of the purple membrane (PM) has been developed. Two types of antibodies for distinguishing the extracellular surface and the cytoplasmic surface of PM were produced by immunizing the corresponding synthetic peptides to mice. The Langmuir-Blodgett (LB) method was employed to form a single-layer two-dimensional array of PM fragments on an electron microscope grid. The LB film was then treated with the antibodies which had been labeled with colloidal gold particles. Electron microscope observations visualized the morphology of the two surfaces of PM to be rough and smooth regions, respectively; thus the orientation of PM fragments was determined.

Amino Acid Sequence↗
PubMed1992

Synthesis and antibacterial activity of new tetracyclic quinolone antibacterials.

A series of 8-substituted-9,1-(epoxymethano)-7-fluoro-5-oxo-5H- thiazolo[3,2-a]quinoline-4-carboxylic acids having a novel tetracyclic structure was synthesized and tested for antibacterial activity. The nature of the heteroatom (N, O, or S) substituted at the 8-position had little influence on the antibacterial activity. Among the six pyrrolidinyl derivatives and the five piperazinyl derivatives, the 8-(3-hydroxy-1-pyrrolidinyl) derivative 6h and the hydrochloride of the 8-(4-methyl-1-piperazinyl) derivative 6l showed the most potent activity against both Gram-positive and Gram-negative bacteria. Against nalidixic acid resistant strains, isolated from Escherichia coli KC-14, compound 6h was less potent than 6l. Replacement of the piperazinyl nitrogen atom by a carbon atom, an oxygen atom, or a sulfur atom (corresponding to the piperidino, morpholino, or thiomorpholino group, respectively) enhanced the activity against Gram-positive bacteria, but reduced the activity against Gram-negative bacteria. Compound 6l also showed potent in vivo antibacterial activity against Gram-positive and Gram-negative bacteria, and did not cause convulsions in mice with the concomitant administration of fenbufen. Replacement of the carboxy group by a sulfonic acid group in 6l resulted in a complete loss of antibacterial activity.

Animals↗