Search PubMed⌕ Search

Biomedical subjects

T Sakurai

Publications and source records attributed to T Sakurai.

At least 739 records · Page 41Linked to original sources

New fluorescence of nonenzymatically glucosylated human serum albumin.

Glucosylated human serum albumin (G-HSA) obtained under incubation with glucose at 37 degrees C for 8 days showed a new fluorescence with a maximum at 430 nm, resulting in quenching of the fluorescence of only one tryptophan residue on HSA. The quantum yield of new fluorescence is 0.024 at 25 degrees C. The analysis of the excitation spectra allowed us to conclude the absence of energy transfer. In G-HSA, non-disulfide cross-linking hexamer was confirmed by SDS-PAGE.

Energy Transfer↗

Nonenzymatic glucosylation of human serum albumin and its influence on binding capacity of sulfonylureas.

To estimate the functional change occurring in human serum albumin by nonenzymatic glucosylation, glucosylated human serum albumin was prepared by in vitro incubation with glucose. The rate of glucosylation proceeded as a first-order reaction. The binding of sulfonylureas to serum albumin was determined by equilibrium gel filtration. Through this method, it was possible to estimate the binding capacity of a low water solubility drug with a high affinity to protein. The amounts of the sulfonylureas bound to glucosylated HSA decreased by 44% with tolazamide and acetohexamide, 50% with glibenclamide, and 52% with tolbutamide, compared to human serum albumin (HSA). This suggests that a high concentration of glucosylated HSA in diabetic patients may possibly cause an increase in free drug concentration exceeding normal levels. This study shows that the decrease in the binding capacity of sulfonylureas with protein is due to the modification of albumin molecules by the covalent binding of glucose.

Chromatography, Affinity↗

Characterization of microenvironments of 2-(4'-hydroxyphenylazo)benzoic acid bound to bovine serum albumin by studying the solvent effects.

The binding and thermodynamic parameters of the two binding forms of 2-(4'-hydroxyphenylazo)benzoic acid to bovine serum albumin were estimated. The number of the binding sites of the azo form was 3.2 and that of the hydrazone form was 0.7. The binding of the hydrazone form was affected only by enthalpy changes, in contrast to that of the azo form which was affected by both enthalpy and entropy changes. To estimate the complex microenvironments of 2-(4'-hydroxyphenylazo)benzoic acid molecules on bovine serum albumin, the solvent effects were studied. The 2-carboxyl group of 2-(4'-hydroxyphenylazo)benzoic acid participates in the azo-hydrazone tautomerism . The 2-carboxylate ion forms an ion pair with triethylamine in ethylene dichloride, chloroform, and benzene, resulting in the appearance of the hydrazone form. The hydrazone formation in the system of 2-(4'-hydroxyphenylazo)benzoic acid-triethylamine (1:1) in chloroform was affected only by enthalpy changes, in the same manner as in the system of 2-(4'-hydroxyphenylazo)benzoic acid-bovine serum albumin. We speculate the presence of the two kinds of ion pairs on the basis of the changes of the azo-hydrazone tautomerism in chloroform, and that the azo form takes the contact ion pair and the hydrazone form takes the solvent-separated ion pair. A new possible model for the interaction of the azo and hydrazone forms and bovine serum albumin is proposed.

Animals↗

Preliminary evaluation of dose-effect relationships for vibration induced white finger in Japan.

Habitual use of many vibrating tools has been found to be connected with the appearance of various disorders affecting the blood vessels, nerves, bones, joints, muscles or connective tissues of the hand and forearm. The vibration exposures required to cause these diseases are not known exactly, either with respect to vibration intensity and the vibration frequency spectrum, or with respect to daily exposure time and total exposure period. The purpose of this study is to investigate available data on the physical conditions in Japan that have caused vibration induced white finger (VWF) and attempt to establish approximate relationships between vibration conditions and prevalence of VWF. The vibration conditions were evaluated using the method of vibration assessment recommended by the International Standardized Organization, which uses the weighted vibration level of the frequency weighted, dominant, single axis component of vibration directed into the hand. A clear correlation between level, prevalence of VWF and exposure period can be found. The results also suggest the relationship between the weighted levels and latent intervals. These dose-effect relationships enable the prediction of the average latent interval for a population group and the range of progression of the disorders--all from a measurement of the vibration entering the hands. In Japanese cases, 4, 8, and 15% of VWF prevalence correspond with 10, 20, and 40% of VWF prevalence in the Draft International Standard ISO/DIS 5349 (1982) within the weighted vibration level range of 2 to 50m X s-2.

Adult↗

Three-dimensional analysis of regional myocardial function in response to nitroglycerin in patients with coronary artery disease.

Biplane cineventriculography was performed at rest and after sublingual nitroglycerin in 13 patients with coronary artery disease. In six patients (responders), there was a significant increase in ejection fraction [40 +/- 5 to 52 +/- 4% (p less than 0.001)], while in the other seven (nonresponders), there was no alteration in ejection fraction. To evaluate the extent of regional myocardial response to nitroglycerin, the contractile pattern of the regional myocardium over the entire ventricular surface was analyzed using a computer-generated three-dimensional model. The spatial coordinates that define the elliptic ventricular surface on a given horizontal plane cross section of the chamber were determined by four counter values in the two orthogonal silhouettes. Then, 32 points at equal angles around the center of gravity of the end-diastolic cavity were generated to form the border image. Repetition of this process for 16 successive cross sections allowed for reconstruction of the ventricular surface by the sequence of 32 X 16 (512) points. The regional wall motion was expressed as the percent change of the radial length, drawn from the center of gravity to each surface point. There was significant heterogeneity in regional response to nitroglycerin. In the responders, the normally contracting area was significantly increased (from 16.5 +/- 16.0 to 36.2 +/- 14.9% of the total surface area, p less than 0.001), largely mediated by the greater improvement in segmental shortening of each graded contractile pattern relative to its deterioration. In the nonresponders, a lessening of the severe dysfunction of the given area was associated with significant deterioration of segmental shortening of the other normally contracting area (49.1 +/- 19.7% of the area with a contractile pattern of grade 5 had deteriorated, p less than 0.05). Thus, the ratio of the area with respective graded segmental shortening was virtually unchanged. These differences in response of the ischemic ventricle to nitroglycerin appeared to be related to the development of adequate coronary collateral vessels as well as to an interaction of changes in preload and afterload.

Cineradiography↗

Analysis of asynchronous wall motion by regional pressure-length loops in patients with coronary artery disease.

The progression of regional dysfunction during angina pectoris was studied in eight patients with coronary artery disease. Single plane left ventriculograms were obtained using a high fidelity micromanometer-tipped catheter both at rest and immediately after rapid cardiac pacing. Each image of the left ventriculogram was digitized and transferred to a computer. The boundary of the ventricular cavity was automatically determined and sequentially superimposed. Regional shortening was quantified by a radial coordinate system originating at the center of gravity of the end-diastolic silhouette. Thirty-two radial grids were drawn around the center of gravity, and the length of each radial grid was measured to characterize the centripetal motion of a given surface point. Each radial length was then plotted simultaneously and continuously against left ventricular pressure to generate a pressure-length loop. The area of the pressure-length loop provided an index of regional myocardial work. In the ischemic ventricle, the loops exhibited a striking deformity in configuration. Prolonged relaxation of ischemic segments was associated with outward motion of the normal segments. Shortening of the normal segment occurred earlier than that of the ischemic segment associated with its stretch. Thus, the loops of the two areas inclined in opposite directions. Pacing stress increased the magnitude of hypofunction in the potentially ischemic area, the average extent of shortening being reduced by 30% and the segmental work by 25% (p less than 0.005). In the normal area, contrary to the significant increase in segmental shortening (20% above control values [p less than 0.005]), the average segmental work remained at 7% below control values because of an augmented deformation of the loop.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Characterization of nitrite reductase from a denitrifier, Alcaligenes sp. NCIB 11015. A novel copper protein.

A copper-containing dissimilatory nitrite reductase [nitric-oxide: ferricytochrome c oxidoreductase, EC 1.7.2.1] was purified from a denitrifier, Alcaligenes sp. NCIB 11015, by ion-exchange chromatography on CM-cellulose, gel filtration on Sephadex G-150, and adsorption on hydroxyapatite. The preparation was homogeneous by SDS-polyacrylamide gel electrophoretic criteria, and its enzymatic activity increased considerably by freezing (at -20 degrees C) and thawing. The enzyme consists of two subunits with a molecular weight of 37,000, and the isoelectric point and redox potential are 8.4 and +260 mV (pH 7.2), respectively. The EPR spectrum and copper analysis clearly indicated that the enzyme contains two type I copper atoms per molecule but no other types of copper. This is the first blue copper protein that exhibits catalytic activity despite possessing only type I copper.

Alcaligenes↗

A phage-resistant mutant of Lactobacillus casei which permits phage adsorption but not genome injection.

A phage-resistant mutant of Lactobacillus casei (strain YIT 9021) was capable of adsorbing both PL-1 and J-1 phages, but did not yield phage-infected cells. The mutant and wild-type strains were identical in morphology and sugar composition of the cell walls. Attempts to induce prophages from strain YIT 9021 were unsuccessful. Electron microscopic examination of negatively stained mixtures of phage PL-1 and YIT 9021 bacteria revealed that the phages were adsorbed to the cells in a tail-first orientation. All the absorbed phages had DNA-filled heads. It was concluded that PL-1 adsorbed normally but was blocked in the injection of the phage genome into the cell.

Bacteriophages↗

Bladder inhibition by penile electrical stimulation.

Transcutaneous electrical stimulation was applied to the penis in 22 patients complaining of frequency, urgency and/or urge incontinence. Detrusor activity was suppressed with this stimulation, causing decreased bladder spasticity and/or increased cystometric capacity in 10 of 22 patients. Clinical success was noted in four patients with a portable stimulator.

Adolescent↗

Quinidine-induced rise in ajmaline plasma concentration.

A high-performance liquid chromatographic method is described for the simultaneous determination of ajmaline and quinidine in human plasma. With 0.5 ml plasma sample of a ajmaline and quinidine, concentrations as low as 0.001 and 0.01 micrograms ml-1, respectively, could be detected and the technique could be used to investigate the effect of quinidine on the pharmacokinetics of ajmaline. Four healthy subjects were given oral ajmaline (50 mg) alone or in combination with quinidine sulphate (200 mg) on separate occasions. When ajmaline was administered alone, its plasma concentrations were less than 0.03 micrograms ml-1. Quinidine induced a marked increase to give a mean peak concentration of ajmaline which increased from 0.018 micrograms ml-1 after a single administration to 0.141 micrograms ml-1 in combination with quinidine. the area under the ajmaline concentration-time curves was increased 10 to 30-fold by the concurrent administration of quinidine. According to the one compartment open model, the absorption rate constant of ajmaline did not change appreciably, but the elimination rate constant was reduced to approximately 50% of the value in the absence of quinidine. The results indicate the existence of a significant interaction between oral ajmaline and quinidine.

Adult↗

A novel method to predict the elimination half-lives and the renal excretion mechanisms of cephalosporins.

A novel method was proposed to predict the elimination half-lives of cephalosporins from plasma protein binding (unbound fraction, f) and fraction of the dose excreted into urine (f*) on the basis of the following four assumptions. 1) The drug is only distributed to the extracellular fluid, 2) the bound fraction of the drug in plasma is independent of the plasma drug concentration, 3) the binding protein of the drug is albumin, 4) the unbound drug in plasma is excreted by the glomerular filtration and the contribution of active secretion and reabsorption is negligible. The VSS's and t1/2 beta's of MT-141, one of cephalosporins, in rabbits, dogs and healthy human subjects were well predicted, whereas in rats, the prediction of the both values was failed. The t1/2 beta's of various cephalosporins in healthy subjects were calculated from f and f*, in reasonably good agreement with the observed ones, except for some cephalosporins which have been reported to be secreted actively in the renal tubules. Thus, the comparison of the calculated t1/2 beta's with the observed ones makes it possible to presume the renal excretion mechanism. Moreover, this method will be applicable to other drugs which satisfy the above four assumptions.

Animals↗

Effect of prostacyclin and prazosin in the treatment of congestive heart failure; with special reference to the sympathetic nervous system.

Therapy to decrease the load in congestive heart failure is now classified as acute and chronic vasodilator therapy. In this symposium, we presented prostacyclin (PG I2) as an acute and prazosin as a chronic vasodilator. Their hemodynamic and clinical effectiveness were evaluated and their effect on the sympathetic nervous system was also studied. We studied the effect of intravenous prostacyclin infusion in doses of 22 +/- 11 ng/kg/min in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean pulmonary capillary wedge pressure decreased from 21.0 +/- 7.9 to 15.0 +/- 6.6 mmHg (p less than 0.001), mean arterial pressure from 98.9 +/- 12.8 to 76.2 +/- 7.0 mmHg (p less than 0.001), systemic vascular resistance from 2,574 +/- 384 to 1,368 +/- 283 dynes X sec X cm-5 (p less than 0.001), pulmonary vascular resistance from 1,008 +/- 451 to 443 +/- 135 dynes X sec X cm-5 (p less than 0.001) and pulmonary arteriolar resistance from 330 +/- 111 to 189 +/- 73 dynes X sec X cm-5 (p less than 0.001). The cardiac index increased from 2.0 +/- 0.37 to 3.2 +/- 0.59 l/min/m2 (p less than 0.001), and the stroke index from 27.6 +/- 8.69 to 42.0 +/- 0.62 ml/m2 (p less than 0.001). Moreover, prostacyclin therapy counteracted the sensation of coldness of the limbs and face, and patients felt warmth and mild flushing of the face. The effect of prazosin on the exercise duration time until dyspnea was evaluated by the treadmill test.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Intravenous left ventriculography utilizing digital subtraction technique.

To detect the left ventricular boundary in the intravenous ventriculography, we used a subtraction technique for background suppression. Images containing contrast medium and reference mask images were transferred to a computer through a flying spot scanner and stored on the digital disc. Stored reference mask images were subtracted from the digitized contrast images. The resulting images were then electronically enhanced to extract the left ventricular (LV) image. The LV boundary was delineated with an algorithm we have developed and the volume of the LV cavity was calculated automatically. The validity of this method was compared with data obtained from conventional left ventriculogram (LVG). In 11 patients, values for end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) calculated from the intravenous LVG were correlated closely with those from the conventional LVG (128 +/- 38 (SD) vs 133 +/- 39 ml, r = 0.95; 50 +/- 28 vs 53 +/- 30 ml, r = 0.98; 63 +/- 10 vs 62 +/- 12%, r = 0.96, respectively). Nine patients with valvular regurgitation were followed up serially after valve replacement. EDV index fell significantly after corrective surgery (145 +/- 50 to 81 +/- 33 ml/m2, p less than 0.02), whereas, EF was affected variably depending upon the preoperative state (58 +/- 13 to 61 +/- 11%, not significant). Thus, this method is less invasive than conventional LVG and has successfully allowed for sequential determination of ventricular function on an outpatient basis.

Adult↗

Effect of hypothermia upon the electrocochleogram and auditory evoked brainstem response.

The effects of hypothermia upon electrocochleogram (ECochG) and auditory evoked brainstem response (ABR) were studied in 10 children who underwent the open heart surgery under hypothermic anesthesia. The latencies of N1, waves III and V in response to click of 115 dB p.e. SPL were prolonged at the rate of 0.12 +/- 0.02, 0.25 +/- 0.04 and 0.43 +/- 0.05 msec/degree C, respectively. The N1 amplitude was initially increased, returned to the precooling value at about 26 degrees C and decreased thereafter. SP was increased in amplitude by hypothermia and never disappeared throughout the observation. At the time of rewarming, SP appeared first, followed by N1 and finally by waves III and V. The results obtained in the present study were discussed in the light of the sensitivity of the sensory hair cells, peripheral nerves and CNS to the hypothermic condition.

Anesthesia, General↗

Amegakaryocytic thrombocytopenia associated with systemic lupus erythematosus successfully treated by a high-dose prednisolone therapy.

A patient with systemic lupus erythematosus (SLE) developed amegakaryocytic thrombocytopenic purpura. The absence of a drug relationship or other identifiable underlying cause made us consider this to be a rare manifestation of SLE. Her thrombocytopenia, which initially appeared to be steroid-resistant, ultimately improved following a prolonged high-dose prednisolone therapy. To our knowledge, this is the second case of amegakaryocytic thrombocytopenia associated with SLE in the literature. The possibility that amegakaryocytic thrombocytopenia in SLE can be caused by cellular rather than humoral immunologic mechanism was discussed.

Bone Marrow↗