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Biomedical subjects

K Miki

Publications and source records attributed to K Miki.

At least 199 records · Page 11Linked to original sources

Specific arrangement of three amino acid residues for flavin-binding barrel structures in NADH-cytochrome b5 reductase and the other flavin-dependent reductases.

The structure of NADH-cytochrome b5 reductase from pig liver microsomes has been refined to a crystallographic R factor of 0.223 at 2.4 A resolution. A structural comparison between the flavin-binding beta barrel domain of NADH-cytochrome b5 reductase and those of the other flavin-dependent reductases, ferredoxin-NADP+ reductase, phthalate dioxygenase reductase and nitrate reductase, indicated that the overall barrel foldings are similar to each other and that the specific arrangement of three amino acid residues (Arg, Tyr and Ser/Thr) is usually necessary for flavin-binding. These conserved residues overlap each other in their three-dimensional structures and stabilize the flavin-binding site in the four flavin-dependent reductases.

Amino Acid Sequence↗

Crystal structure of NADH-cytochrome b5 reductase from pig liver at 2.4 A resolution.

The three-dimensional structure of NADH-cytochrome b5 reductase from pig liver microsomes has been determined at 2.4 A resolution by X-ray crystallography. The molecular structure reveals two domains, the FAD binding domain and the NADH domain. A large cleft lies between these two domains and contains the binding site for the FAD prosthetic group. The backbone structure of the FAD binding domain has a great similarity to that of ferredoxin-NADP+ reductase [Karplus, P. A., Daniels, M. J., & Herriott, J. R. (1991) Science 251, 60-65], in spite of the relatively low sequence homology (about 15%) between the two enzymes. On the other hand, the structure of the NADH domain has several structural differences from that of the NADP+ domain of ferredoxin-NADP+ reductase. The size of the cleft between the two domains is larger in NADH-cytochrome b5 reductase than in ferredoxin-NADP+ reductase, which may be responsible for the observed difference in the nucleotide accessibility in the two enzymes.

Animals↗

Esophageal body and lower esophageal sphincter function in healthy premature infants.

BACKGROUND & AIMS: Gastroesophageal reflux is a common problem in premature infants. The aim of this study was to use a novel manometric technique to measure esophageal body and lower esophageal sphincter pressures in premature infants. METHODS: Micromanometric feeding assemblies (OD, < or = 2 mm) incorporating 4-9 manometric channels were used in 49 studies of 27 premature neonates. Esophageal body motility was recorded at three sites for 20 minutes after feeding. Twenty attempts (one per minute) were made to stimulate swallowing via facial stimulation (Santmyer reflex). In 32 studies lower esophageal sphincter pressures were recorded (sleeve) for 15 minutes before and after feeding. RESULTS: Peristaltic motor patterns were less common than non-peristaltic motor patterns (26.6% vs. 73.4%; P < 0.0001) that comprised 31.1% synchronous, 34.6% incomplete, and 6.3% retrograde pressure waves. Reflex swallowing was elicited more frequently in neonates older than 34 weeks postconceptional age than in younger infants (33.4% vs. 20.4%; P < 0.05). Mean lower esophageal sphincter pressure was 20.5 +/- 1.7 mm Hg before and 13.7 +/- 1.3 mm Hg after feeding (P < 0.0005). CONCLUSIONS: Premature infants show nonperistaltic esophageal motility that may contribute to poor clearance of refluxed material. In contrast, the lower esophageal sphincter mechanisms seem well developed.

Deglutition↗

Inhibitory effect of a single local probucol administration on neointimal formation in balloon-injured rat carotid artery.

The aim of this study was to determine whether a single local probucol administration could suppress neointimal formation in balloon-injured rat carotid artery. Rats were divided into four groups; (i) rats receiving no probucol (control group); (ii) rats receiving topical application of 50 mg probucol at the time of ballooning (p-top group); (iii) rats fed chow containing 1% probucol (p-fed group; (iv) rats receiving both topical application of 50 mg probucol and chow containing 1% probucol (p-top/fed group). Although serum total cholesterol levels did not significantly differ between the control and the p-top groups at two weeks after balloon injury, the p-top group had a smaller intimal/medial ratio or intimal area than the control group (0.97 +/- 0.11 vs. 0.53 +/- 0.08 or 0.15 +/- 0.02 mm2 vs. 0.08 +/- 0.02 mm2 respectively, P < 0.01). Neointimal formation was suppressed to a similar extent in the p-fed group, in which serum total cholesterol level was approximately 40% lower than that in the control group. Thus, a single local delivery of probucol can suppress neointimal formation in balloon-injured rat carotid artery without altering serum lipid level.

Administration, Topical↗

The association of smoking and drinking habits with serum pepsinogens.

BACKGROUND: The influence of smoking on serum pepsinogen I has been assessed. However, still to be assessed are the influences of smoking on pepsinogen II and drinking on serum pepsinogens. METHODS: Data were collected from 13,381 employees by questionnaire and serum tests. Multiple regression analyses were done with logarithms of serum pepsinogen I (LPI), pepsinogen II (LPII) or pepsinogen I/II ratio (LI/II) as a criterion variable and as categorized explanatory variables, sex, age, subjective symptoms in the stomach, past history of peptic ulcer, current smoking dose, past smoking amount, drinking habit and current drinking dose. RESULTS: Current smoking dose showed dose-dependent positive associations with LPI and LI/II: Past smoking amount yielded weakly dose-dependent negative associations with LPI and LI/II: Current drinking dose showed dose-dependent negative associations with LPI and LPII. CONCLUSION: Current smoking elevates pepsinogen I and the I/II ratio, and it may be necessary to consider the effect of smoking when pepsinogens are used as markers for gastric cancer. Drinking reduced pepsinogen I and II, but the effect was not so large.

Adult↗

Crystal structure determination of a flavoprotein FP390 from a luminescent bacterium, Photobacterium phosphoreum.

The three-dimensional structure of a flavoprotein, FP390, purified from a luminescent bacterium, Photobacterium phosphoreum, has been determined at 3 A resolution by X-ray crystallography. Crystallographic refinements of the structural model have led to an R-factor of 0.24 for the intensity data between 6 to 3 A resolution collected with synchrotron radiation. It was found that a homodimer of the FP390 molecules related by a non-crystallographic 2-fold axis is comprised in the asymmetric unit. Two homodimers are arranged around a crystallographic 2-fold axis to form a tetrameric assembly. The monomer molecule of FP390, to which two molecules of the flavin cofactor (Q-flavin) are bound, consists of a seven-stranded parallel beta-sheet which forms a half of the beta-barrel structure and seven alpha-helices which surround one side of the beta-barrel. We suggest that the reason why the Q-flavin sample prepared from FP390 is always a mixture of two components is connected with the fact that the monomer molecules has two flavin binding sites, at the dimer interface and at the molecular surface.

Bacterial Proteins↗

Lansoprazole versus famotidine in symptomatic reflux esophagitis: a randomized, multicenter study.

We compared the usefulness of lansoprazole and famotidine for treatment of reflux esophagitis. Fifty-four subjects with moderate to severe reflux esophagitis were divided into two groups. The lansoprazole group (LPZ) received lansoprazole 30 mg once daily for 4 weeks, followed by famotidine 20 mg twice daily for 4 weeks. The famotidine group (FAM) received the same medications in the reverse order. Patient evaluation was based on six factors found on endoscopy, and on patient reports of heartburn. Evaluations were done before the start of the study and at 4 and 8 weeks. The improvement rates in the grade of GI classification at 4 weeks were 57.7% in the LPZ group and 38.5% in the FAM group; there was no significant difference between the two groups. However, after drugs were switched, more patients who switched to famotidine experienced a deterioration of their condition than did those who switched to lansoprazole. The percentages of "useful" or "very useful" were not significantly different between the two groups, but the percentage of "very useful" in the LPZ group (46.2%) was significantly higher than that in the FAM group (14.3%) (p < 0.05). These results suggest that lansoprazole is the first drug of choice for treatment of moderate to severe reflux esophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Lansoprazole for maintenance therapy of peptic ulcer disease: weekend full-dose or everyday half-dose administration?

Seventy-one patients with peptic ulcer (44 gastric ulcer and 27 duodenal ulcer patients) were enrolled in this study. After the ulcers had healed with 2 months of treatment with lansoprazole (LPZ) 30 mg/day, patients were divided into two groups: 43 in the half-dose q.d. group and 28 in the weekend full-dose group. Fourteen (23%) of the 43 patients in the half-dose q.d. group and 14 of the 28 (50%) in the weekend full-dose group failed to continue taking the drug for 6 months owing to poor compliance (p < 0.05). None of the 30 patients who continued to take the maintenance dose of LPZ experienced ulcer recurrence during the 6-month follow-up period, whereas 71% of the patients who stopped taking LPZ experienced recurrence (p < 0.01). In conclusion, maintenance therapy using the half-dose q.d. administration schedule was superior to weekend full-dose administration because of the better patient compliance and a lower ulcer recurrence rate.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Utility of duplex Doppler ultrasound in evaluating portal hypertension in children.

We measured the maximal velocity of the blood flow in the main portal trunk by duplex Doppler ultrasound in children suffering from a variety of liver diseases. The maximal velocity of the main portal vein in children with chronic active hepatitis and liver cirrhosis was decreased significantly as compared to those in control children (p < 0.01). The maximal velocity of the main portal trunk and K indocyanine green (ICG) had no significant correlation (r = 0.25, n = 27). The patient with the lowest portal velocity had esophageal and gastric varices with red color sign. We conclude that the measurement of the maximal velocity of the main portal trunk with duplex Doppler ultrasound is useful in evaluating portal hypertension in children.

Adolescent↗