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Biomedical subjects

M Yano

Publications and source records attributed to M Yano.

At least 595 records · Page 33Linked to original sources
PubMed1990

A novel hydrophobic amine, (Z)-5-methyl-2-[2-(1-naphthyl)ethenyl]-4-piperidinopyridine, as a probe of the K+ occlusion center of Na+/K(+)-ATPase.

A hydrophobic amine, (Z)-5-methyl-2-[2-(1-naphthyl)ethenyl]-4-piperidinopyridine (AU-1421), was examined as a probe of the K+ occlusion center of Na+/K(+)-ATPase. Treatment of the enzyme with AU-1421 at 37 degrees C and pH 7.0 produced irreversible inactivation of the enzyme. This inactivation was prevented, with simple competitive kinetics, by K+ or its congeners in the order of Tl+ greater than Rb+ greater than NH+4 greater than Cs+. The concentrations of these cations required for the protection, were consistent with the affinities for transport and ATPase activity. The apparent binding constant for K+ was calculated to be 0.03 mM, from the competition with AU-1421. This protection was cancelled by a high concentration of ATP or ADP. A high concentration of Na+ (Kd = 6.5-6.9 mM), as a substitute for K+, also prevented the inactivation by AU-1421. Thus, the enzyme was protected from AU-1421 when the occlusion center was occupied by a monovalent cation, irrespective of the enzyme conformation, E1 (Na(+)-bound form) or E2 (K(+)-bound form). On the other hand, the enzyme was most sensitive to AU-1421 in the presence of low concentration of Na+ (0.4-0.8 mM) or a high concentration of ATP. Tris, imidazole or choline, which favors the E1 state, also accelerated the inactivation by AU-1421. These suggest that AU-1421 reacts with the occlusion center through the E1 state.

Adenosine Diphosphate↗
PubMed1990

Hydrolysis and acyl migration of a catechol monoester of L-dopa: L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine.

Hydrolysis and acyl migration studies on L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine (1, NB-355), which produced long-lasting plasma L-dopa levels after oral dosing, have been conducted. Compound 1 exists as pure 4-O-pivaloyl-L-dopa in the solid state, but it converts rapidly to a mixture of the 3- and 4-O-isomers in solution. The rate of acyl migration increased with increases in pH and temperature, and the content of the 4-O-isomer in the equilibrium state was 53-59%. The hydrolysis rate of 1 to L-dopa (6) also increased with increases in pH and temperature, and accelerated steeply at neutral and alkaline pH. The rapid hydrolysis at neutral pH was not observed with O-pivaloyl-L-tyrosine (3), di-O-pivaloyl-L-dopa (4), or L-dopa methyl ester (5). Because of this chemical lability, 1 was hydrolyzed in rat plasma far faster than the other tested catechol esters. However, in rat intestinal homogenate at pH 6.0, 1 was hydrolyzed at the slowest rate among the tested esters, predominantly by a diisofluorophosphate (DFP)-sensitive esterase. Thus, 1 showed a unique in vitro profile on hydrolysis and acyl migration due to the existence of a neighboring hydroxyl group. The stability of 1 in the intestine might be essential for the long-lasting plasma L-dopa profile after oral dosing of 1.

Acylation↗
PubMed1990

Immunohistochemical localization of glycated protein in diabetic rat kidney.

The localization of glycated protein in the kidney of diabetic rats was examined immunohistochemically with antiserum against glucitol-lysine. In diabetic rats the brush border and basement membrane of the proximal convoluted tubules were strongly immunoreactive with the antiserum but in control rats, only the brush border was weakly reactive. The immunoreactive tubules were more abundant in diabetic rats. No immunoreaction was found in any other structures in the kidney. Glycation of the proximal convoluted tubules may be an alteration in diabetic nephropathy.

Animals↗
PubMed1990

[Comparison of myocardial perfusion assessments by digital subtraction angiography with those of left ventricular wall dynamics].

In clinical and experimental studies we assessed images of digital subtraction coronary angiography (DSA) for evaluating regional myocardial perfusion. Myocardial perfusion was assessed by injecting contrast medium into the coronary artery, and by imaging the regional myocardium using DSA. On the time-density curve obtained from the myocardial region of interest, we calculated the time to peak concentration (TPC) and the exponential washout rate (T). TPC and T were measured in five patients with stable effort angina pectoris (AP) and left anterior descending (LAD) lesions before and after percutaneous transluminal coronary angioplasty (PTCA). The values of 1/T increased significantly from 0.09 +/- 0.02 l/sec to 0.21 +/- 0.04 l/sec (p less than 0.01) after PTCA, but l/TPC did not change. No significant difference in ejection fractions was observed between the patients with AP and the normal subjects (n = 7), while the regional percent area shrinkage in the anterolateral and apical regions supplied by the LAD was significantly decreased in the patients with AP compared with those of normal subjects (anterolateral: 39.8 +/- 8.8% vs 51.3 +/- 6.8%, apical: 36.6 +/- 8.4% vs 52.4 +/- 13.4%, both p less than 0.01). In 10 anesthetized dogs with varying degrees of reduction in the left circumflex coronary artery (LCX) blood flow (CBF: categories of stenosis (S1-S5), we compared 1/TPC and 1/T with regional myocardial function (systolic wall thickening: %WTh). With varying LCX stenosis, there were no significant changes in heart rate and mean aortic pressure and significant linear correlations were observed between %WTh and 1/TPC (r = 0.51), between %WTh and 1/T (r = 0.55). At S1 (CBF: 100-90% of the control), neither %WTh nor 1/TPC differed from that of the controls, but 1/T was significantly decreased (80% of the controls, p less than 0.01). From S3 (CBF: 79-60%) to S5 (CBF: 39-0%), %WTh, 1/TPC and 1/T were significantly decreased from those of the control levels (all p less than 0.01). However, at S5 (CBF: 39-0%) the values of 1/TPC (71% of controls) and 1/T (33%) did not differ from those at S4; whereas, %WTh was markedly reduced and the systolic thinning of the ventricular wall occurred at S5. Therefore, in critical coronary stenosis, 1/T was more sensitive than 1/TPC or wall dynamics for assessing myocardial ischemia. Both 1/TPC and 1/T, as well as %WTh, were useful for assessing moderate myocardial ischemia; however, these DSA indices had considerable limitations for evaluating the severity of myocardial ischemia when CBF was markedly reduced.

Aged↗
PubMed1990

Conversion of rat urinary prokallikrein to its active form.

A peptide derived from rat urinary prokallikrein by trypsin treatment comprised 7 amino acids, the sequence (Ala-Pro-Pro-Val-Gln-Ser-Arg) of which was identical with that of the N-terminal region in prokallikrein. Thus, with trypsin treatment, rat urinary prokallikrein is converted to the active form with the release of the N-terminal propeptide consisting of 7 amino acids. An Arg-1-Val+1 bond in the prokallikrein was found to be the site of proteolytic cleavage of the propeptide.

Amino Acid Sequence↗
PubMed1990

[Age-related modification of regional left ventricular filling in normal subjects].

Age-related reduction in global left ventricular filling has been reported. To assess how regional left ventricular filling is modified by aging, radionuclide ventriculography was conducted in 48 normal subjects aged 15 to 73 years. Left ventricular regional filling was assessed by dividing left ventricular region of interest into 4 quadrants, from which global (GLB), septal (SEP), apical (Ax) and lateral (LAT) time-activity curves and first-derivative curves were derived. Indexes of left ventricular systolic function at rest did not vary with age, but early diastolic filling significantly declined with age: peak filling rate normalized to end-diastolic volume (EDV/S), peak filling rate normalized to stroke volume (SV/s) and peak filling rate/peak ejection rate decreased (r = -0.42; p less than 0.01, r = -0.48; p less than 0.001, r = -0.47; p less than 0.001), time to peak filling rate increased (r = 0.41; p less than 0.01) with aging. Early diastolic asynchrony was measured as the sum of the absolute values of the time differences from global peak filling rate to that in each of three quadrants (delta TPFR). delta TPFR increased with age (r = 0.37; p less than 0.01). Moreover, delta TPFR correlated with global peak filling rate (EDV/s), peak filling rate (SV/s) and peak filling rate/peak ejection rate (r = -0.40; p less than 0.01, r = -0.45; p less than 0.01, r = -0.51; p less than 0.001). Time to peak filling rate of the lateral region was the shortest (163 +/- 38 ms), followed by the global (179 +/- 36 ms), apical (184 +/- 38 ms) and finally the septal region (195 +/- 35 ms). This suggested that physiologic asynchrony with regard to the sequence of regional filling exists in resting condition in normal subjects. Time to peak filling rate in the septal and apical regions increased with age (r = 0.29; p less than 0.05, r = 0.30; p less than 0.05), but that in the lateral region did not correlate with age (r = 0.11). These regional differences correlated with increase in delta TPFR. Thus, aging alter left ventricular diastolic function, with reduced rate related to increased asynchronous early diastolic filling due to prolongation of time to peak filling rate in the septal and apical regions.

Adolescent↗
PubMed1990

[A case of right renal pelvic and ureter cancer with hepatic metastasis showing complete response by M-VAC].

A 69-year-old man was admitted for further examination of right hydronephrosis in November 1988. Radiologically, excretory urography showed right non-functional kidney and antegrade pyelography revealed filling defect of right renal pelvis and ureter. Cytology findings of right renal urine indicated transitional cell carcinoma. Computed tomography revealed multiple mass of liver. The patient was administered M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) combination chemotherapy. After the 4 courses of treatment, the mass of the primary lesion and hepatic metastasis disappeared and he achieved complete remission. The side effects noted were mild myelosuppression, alopecia and gastrointestinal symptoms such as nausea and vomiting.

Aged↗
PubMed1990

[Intra-arterial infusion chemotherapy in bladder cancer].

Between 1976 and 1985, 35 patients with bladder cancer were preoperatively treated with intra-arterial doxorubicin (ADM) chemotherapy. We separated these patients into 2 groups according to regimen: A) 1-3 shots of ADM infusion with or without radiotherapy, and B) 3-day courses of ADM infusion with low-dose radiotherapy. The 5-year actual survival rate according to stage (T category) was 100% in T1-2, 37.5% in T3 and 23.3% in T4. In T1-2, bladder preservative operations were done on 50% of the patients in group A and 100% in group B. In T3-4, the 5-year actual survival rate in group A was 22.5%, while in group B it was 52.8% (p less than 0.01). The bladder preservative operations were done on 33.3% of the patients in group A and 73.3% in group B. The patients who received ADM intra-arterial chemotherapy combined with low-dose radiotherapy for bladder cancers, who achieved complete or partial remission, might be able to preserve their bladder.

Aged↗
PubMed1989

Lens protein glycation and the subsequent degree of opacity in streptozotocin-diabetic rats.

We measured how much glycated protein there was in rat eye lenses with different degrees of cataract, using an antibody against glucitol-lysine. Streptozotocin-diabetic (STZ) rats were in some cases treated with insulin (STZ + INS); control rats were normal. We graded the cataracts from 0 (transparent) to 3 (entirely opaque). STZ rats had significantly more grade 3 cataracts, and STZ + INS rats more grade 1 cataracts, than other groups. Grade 3 lenses had significantly more glycated protein than those of grade 0 (10.8 +/- 2.7 vs. 1.0 +/- 0.4 nmol/mg protein), grades 1 and 2 being intermediate. Glycosylated hemoglobin levels correlated similarly with severity of cataract. These data are consistent with the greater incidence of cataract among diabetics than among non-diabetics, and suggest that lens protein glycation contributes to the development of cataract.

Animals↗
PubMed1989

Decreased activation of carcinogens in the liver of carcinogen-resistant rats.

We have developed a new strain of rats (resistant rat) which exhibit resistance against the carcinogenic action of several carcinogenic compounds. In the present study, we compared the ability of resistant rat liver to activate 3'-methyl-4-dimethylaminoazobenzene and 2-acetylaminofluorene to highly reactive metabolites, which can covalently bind to DNA, with that of carcinogen-sensitive parent strain rats (sensitive rat), using in vitro DNA binding assay. The covalent binding of these carcinogens to calf thymus DNA, catalyzed by the hepatic 9000 x g supernatant fraction from resistant rats pretreated with 3-methylcholanthrene, was about one-half of that catalyzed by the 9000 x g supernatant from sensitive rats which had received the same treatment. These results suggest that the ability of resistant rat liver to activate the carcinogens decreases compared to sensitive rat liver. Further experiments revealed that this decreased activation of the carcinogens in resistant rat livers is due to a low inducibility of 3-methylcholanthrene-inducible forms of cytochrome P-450 mRNA. The hepatic cytosolic Ah receptor concentrations in resistant rats were shown to be significantly lower than those of sensitive rats. Scatchard plot analysis demonstrated, however, that there is no significant difference between the affinity of Ah receptors for 2,3,7,8-tetrachlorodibenzo-p-dioxin in these two strains. These data implicate that the hepatic Ah receptor level may be an important factor in determining carcinogen sensitivity in rats.

2-Acetylaminofluorene↗
PubMed1989

A model for bacterial flagellar motor: free energy transduction and self-organization of rotational motion.

A bacterial flagellar motor is an energy transducing molecular machine which shows some attractive characteristics. First, this motor is driven by a protonmotive force (PMF) across the membrane, two components of which, electric potential delta psi and chemical potential -(2.3RT/F)delta pH, are equivalently transduced to the mechanical work of the motor rotation. Second, a PMF threshold for rotation is observed. Third, this motor can rotate reversibly either counterclockwise (CCW) or clockwise (CW) at almost the same speed. To clarify the osmomechanical coupling of this motor, these characteristics must be explained consistently at the molecular level. In this paper, in order to allow quantitative analyses of the above characteristics, a theoretical model of a bacterial flagellar motor is constructed assuming that the torque generating sites are electrodes which can be charged by protons and that the electrostatic interaction between the electrodes generates the rotation torque. Electrode reaction reasonably derives the equivalence of delta psi and -(2.3RT/F)delta pH. In this model, rates of charging and discharging of protons are influenced by the motor rotation rate, so that the torque generating sites co-operatively work through the motor rotation. We named this kind of co-operativity among them "dynamic co-operativity" in torque generation. This co-operativity causes autocatalytic generation of motor torque and the existence of the rotation threshold. In this model, the appearance of the stable rotational states can be described by phase transition caused by the dynamic co-operativity among torque generating sites. According to this model, the flagellar motor has two stable rotational states corresponding to CCW and CW, which show the same torques. The motor selects one direction from them to rotate, and that is self-organization of rotational motion. Interpretation of the transition between the two stable rotational states as the chemotactic reversals of the flagellar motor is also discussed.

Bacterial Physiological Phenomena↗
PubMed1989

Inhibitory action of gliclazide on platelet functions.

Gliclazide (GC), an oral hypoglycemic agent, inhibits platelet functions, but its effective concentration is reported to be much higher in vitro than in vivo. To determine why, we compared its inhibitory effect measured by impedance aggregometry using citrated whole blood with that measured by turbidometry using platelet-rich plasma. In addition, to see how GC inhibits platelet functions, we examined its effects on arachidonic acid metabolism in platelets in an in vitro system. Impedance aggregometry was found to be more sensitive than turbidometry for detecting the inhibition of platelet aggregation, and revealed significant inhibition at 1 x 10(-4) M GC. GC reduced the amount of prostaglandin I2 (PGI2) needed to inhibit ADP-induced platelet aggregation and the adhesiveness of platelets to a rabbit vessel wall after their preincubation with 1 x 10(-3) M GC for 10 min. GC (1 x 10(-4) -1 x 10(-2) M) had no effect on platelet cyclo-oxygenase activity. GC inhibited thromboxane A2 (TXA2)-induced platelet aggregation, but had no effect on the aggregation triggered by addition of mixtures of arachidonic acid (AA) and inhibitors of key enzymes regulating various steps of AA metabolism in platelets. GC had no significant effect on PGI2-stimulated cyclic AMP (cAMP) production in platelets. These results show that the difference in the effective concentrations of GC reported to modulate platelet functions in vivo and in vitro is partly due to differences in the methods used to evaluate its effect: turbidometry evaluates platelet aggregability, but not other platelet functions modulated by GC in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1989

Analysis of digital subtraction coronary angiography for estimation of flow reserve in critical coronary stenosis.

To examine the accuracy of digital subtraction angiographic assessment of coronary flow reserve in critical coronary stenosis, time-density curves were obtained from digital angiograms for a myocardial region of interest. Time-to-peak contrast (TPC) and contrast washout rate (T) were measured in 11 patients with critical 1-vessel lesions before and after percutaneous transluminal coronary angioplasty (PTCA). Collectively, the values of TPC and T were significantly shortened, from 5.8 +/- 1.1 to 4.4 +/- 1.0 seconds (p less than 0.01) and from 11.3 +/- 4.0 to 5.2 +/- 1.2 seconds (p less than 0.001) after PTCA, respectively. All 11 patients except 1 showed shortened T after PTCA; however, in 5 of the 11 patients, TPC after PTCA had approximately the same values as those before PTCA. In experiments in dogs with critical circumflex stenosis, coronary flow and posterior wall thickening at rest were not different from control; however, contrast media-induced hyperemia was markedly attenuated, accompanied by a significant prolongation of T (7.7 +/- 4.5 vs 15.8 +/- 1.9 seconds, p less than 0.01) and completely unchanged TPC (both 6.8 seconds). With simultaneous tracings of coronary flow and time-density curves, TPC and the washout phase on the curve corresponded with contrast-induced transient flow reduction and hyperemic phases, respectively. It is concluded that T appears more sensitive than TPC when basal coronary flow is maintained to almost normal levels, as in patients with stable effort angina pectoris having critical coronary stenosis.

Aged↗
PubMed1989

A new potential prodrug to improve the duration of L-dopa: L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine.

L-3-(3-Hydroxy-4-pivaloyloxyphenyl)alanine (1, NB-355) is a novel L-dopa prodrug. After oral administration with carbidopa in rats, 1 demonstrated 2.3 times longer duration (MRT) and 1.4 times larger bioavailability (AUC) on plasma L-dopa concentrations than those of L-dopa itself. Similar results were obtained in dogs. The prolonged profile of L-dopa was parallel to that of carbidopa, and the intact ester was undetectable in rat plasma. After intravenous administration in rats, 1 was converted quickly and completely to L-dopa in the systemic circulation. It was also noted that the oral LD50 value of 1 was greater than 6 g/kg in mice. These data suggest that 1 will offer long-lasting L-dopa therapy for the treatment of Parkinson's disease with little concern about toxicity.

Animals↗
PubMed1989

A multicenter randomized controlled clinical trial of Shosaiko-to in chronic active hepatitis.

The efficacy of Shosaiko-to (SST) on 222 patients with chronic active hepatitis was studied in a double-blind multicenter clinical study. One hundred and sixteen patients received SST in a daily oral dose of 5.4 g for 12 weeks, followed by the same dose for a further 12 weeks. One hundred and six patients received a placebo containing 0.5 g of SST for 12 weeks, followed by a cross-over to SST for a further 12 weeks. Among the liver tests, serum AST and ALT values decreased significantly with the administration of SST. The difference of the mean value between the SST group and the placebo group was significant after 12 weeks. In patients with chronic active type B hepatitis, a tendency towards a decrease of HBeAg and an increase of Anti-HBe antibodies was also observed. No remarkable side effects were noticed.

Adult↗
PubMed1989

Evaluation of the human T-cell leukemia virus type I seropositivity of blood donors by the particle agglutination inhibition test.

In the HTLV-I seroscreening of blood donor sera by gelatin particle agglutination (PA), more than 50% (55.6%) of the PA-positive sera were negative by immunofluorescence assay (IF). However, when donors were divided into age groups, there were increasing numbers of IF-positive/PA-positive donors with age. Among the PA-positive donors in the 50-64 age group, 65.9% were IF-positive compared to 16.0% in the 16-19 age group. The serological specificities of the IF-negative/PA-positive specimens were tested by using a newly developed PA inhibition (PAI) test. The HTLV-I specificity of the PAI test was confirmed by the observation that agglutinations with anti-HTLV-I p19 and gp21 monoclonal antibodies as well as IF-positive sera were specifically inhibited with HTLV-I preparations or HTLV-I-positive cell extracts and not with HTLV-I-negative cell extracts. Sixty of the 104 specimens collected randomly from the IF-negative/PA-positive donors were PAI-positive. The majority (80%) of such PAI-positive sera showed more than two bands of HTLV-I gag-encoded polypeptide, p19, p24, p28 and p53 on Western blotting. Some of the PAI-positive sera were also positive by enzyme immunoassay. These results indicate that at least some of the IF-negative/PA-positive donors possess HTLV-I-specific antibody and may be potential HTLV-I carriers who will become IF-positive at a later age.

Adolescent↗
PubMed1989

Expression of the Arthrobacter viscosus penicillin G acylase gene in Escherichia coli and Bacillus subtilis.

The penicillin G acylase gene cloned from Arthrobacter viscosus 8895GU was subcloned into vectors, and the recombinant plasmids were transferred into Escherichia coli or Bacillus subtilis. Both E. coli and B. subtilis transformants expressed the A. viscosus penicillin G acylase. The enzyme activity was found in the intracellular portion of the E. coli transformants or in the cultured medium of the B. subtilis transformants. Penicillin G acylase production in the B. subtilis transformants was 7.2 times higher than that in the parent A. viscosus. The A. viscosus penicillin G acylase was induced by phenylacetic acid in A. viscosus, whereas the enzyme was produced constitutively in both the E. coli and B. subtilis transformants carrying the A. viscosus penicillin G acylase gene.

Amidohydrolases↗