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Biomedical subjects

T Shimazu

Publications and source records attributed to T Shimazu.

At least 181 records · Page 10Linked to original sources
PubMed1987

Characterization of E. coli-derived recombinant human interferon-beta as compared with fibroblast human interferon-beta.

Homogeneous E. coli-derived recombinant human interferon-beta (E. coli-rHuIFN-beta) was characterized in order to elucidate its physicochemical properties, as compared with those of fibroblast human interferon-beta (fibroblast HuIFN-beta). Purified E. coli-rHuIFN-beta and fibroblast HuIFN-beta exhibited a single band of Mr 19,000 and 23,000, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The primary structure of E. coli-rHuIFN-beta was identical to the prediction from the cDNA sequence. Furthermore, both the circular dichroism (CD) spectra and the 1H nuclear magnetic resonance (NMR) spectra of E. coli-rHuIFN-beta and fibroblast HuIFN-beta at pH 6.8 were closely similar to each other. On the other hand, on reverse-phase high-performance liquid chromatography (HPLC) using a C18 column, the retention time of E. coli-rHuIFN-beta was longer than that of fibroblast HuIFN-beta. Moreover, although the isoelectric point of E. coli-rHuIFN-beta was pH 8.9, purified fibroblast HuIFN-beta exhibited multiple isoelectric points, probably due to heterogeneity of the carbohydrate moiety. These results indicate that the E. coli-rHuIFN-beta polypeptide folds similarly to fibroblast HuIFN-beta, and the carbohydrate moiety of natural HuIFN-beta has little influence on higher-order structure but does influence the hydrophobic and the electrostatic properties of the molecule.

Amino Acid Sequence↗
PubMed1987

Molecular cloning of complementary DNA for human medullasin: an inflammatory serine protease in bone marrow cells.

Medullasin, an inflammatory serine protease in bone marrow cells, modifies the functions of natural killer cells, monocytes, and granulocytes. We have cloned a medullasin cDNA from a human acute promyelocytic cell (ML3) cDNA library using oligonucleotide probes synthesized from the information of N-terminal amino acid sequence of natural medullasin. The cDNA contained a long open reading frame encoding 237 amino acid residues beginning from the second amino acid of natural meduallasin. The deduced amino acid sequence of medullasin shows a typical serine protease structure, with 41% homology with pig elastase 1.

Amino Acid Sequence↗
PubMed1987

A dose-responsive model of smoke inhalation injury. Severity-related alteration in cardiopulmonary function.

The dose responsiveness of selected physiologic indices was studied in a sheep model of smoke inhalation injury. In this model, graded severity of injury was achieved by changing the contact time with smoke (defined by "unit"), whereas other variables were kept constant. Blood gas and cardiopulmonary indices were measured in 70 sheep, including 12 controls, either 24 or 72 hours after exposure to 3, 6, 9, 12, 15, or 18 units of smoke. A 12-unit dose of smoke was fatal within 72 hours and an 18-unit dose was fatal within 24 hours. The best correlation between smoke dose and response was observed in arterial oxygen tension 24 hours after exposure. At 24 hours, most of the cardiopulmonary indices showed significant change only after a 12-unit exposure. Although the exact shape of the dose-response curve could not be defined, sigmoid or curved linear shape was suggested, reflecting the progressive deterioration.

Animals↗
PubMed1987

Hemodynamic effects of the beta 1-adrenoceptor partial agonist xamoterol in relation to plasma norepinephrine levels during exercise in patients with left ventricular dysfunction.

A new cardioselective beta 1-adrenoceptor partial agonist, xamoterol, has been developed for the treatment of heart failure, especially that associated with ischemic heart disease. To investigate the hemodynamic effect of xamoterol in relation to sympathetic nervous activity, hemodynamic variables and plasma norepinephrine (NE) levels were measured at rest and during three graded bicycle exercise tests before and after a single intravenous dose of 0.15 mg/kg xamoterol in 10 patients with mild-to-moderate left ventricular dysfunction. Plasma NE increased with increasing grade of exercise and a linear correlation between plasma NE and heart rate was observed at four time points (at rest and three exercise levels) before and after xamoterol. After administration of xamoterol, the slope of the regression line of plasma NE-heart rate relation was significantly less steep than that before drug. Predose and postdose regression lines crossed at 440 pg/ml of plasma NE. Similar effects were observed on the plasma NE-cardiac index and plasma NE-systolic blood pressure relations (regression lines crossed at 380 and 530 pg/ml of plasma NE, respectively). Thus, xamoterol had a dual agonist-antagonist effect in relation to plasma NE, and the crossover point lay approximately between 400 pg/ml and 500 pg/ml. This level of plasma NE was achieved at a low exercise level and at a heart rate of about 100 beats/min. These results indicate that xamoterol has intrinsic sympathomimetic activity comparable to relatively low sympathetic activity (400 to 500 pg/ml of plasma NE) and therefore acts as a beta 1-agonist when sympathetic nervous activity is below this level and as an antagonist when sympathetic activity is above this level.

Adrenergic beta-Antagonists↗
PubMed1986

Chronic infusion of norepinephrine into the ventromedial hypothalamus induces obesity in rats.

To examine whether chronic increase in the local concentration of certain neurotransmitters in the hypothalamus might lead to some metabolic disorders in peripheral organs, several neurotransmitters and neuropeptides were infused continuously at a rate of 0.48 microliter/h for up to 20 weeks into the unilateral ventromedial (VMH), lateral or paraventricular hypothalamic nucleus of rats. A massive obesity with marked increase in body weight was observed after about 10 weeks when norepinephrine (NE) was infused chronically into the VMH, but not into other hypothalamic loci. Plasma insulin level went up markedly at the early stage of NE infusion and remained high during the infusion period, but plasma glucose did not change appreciably. Similar, but less pronounced effects were observed with epinephrine infusion into the VMH. However, other neurotransmitters and neuropeptides tested had no such effects. The NE-induced obese rats showed hyperphagia and an arrhythmic feeding pattern with increased daytime feeding. Chemical composition and the rate of fatty acid synthesis in the interscapular brown adipose tissue (BAT) were also altered after NE infusion into the VMH: although the triglyceride content was increased, the rate of fatty acid synthesis was decreased, indicating that triglyceride turnover in BAT was greatly reduced. The latter observation suggests that energy dissipation in BAT is impaired and this functional abnormality in BAT may also contribute to the development or maintenance of a new type of hypothalamic obesity induced by NE infusion.

Adipose Tissue, Brown↗
PubMed1986

Metabolic and morphological alterations of brown adipose tissue after sympathetic denervation in rats.

Effects of sympathetic denervation on biochemical and morphological changes of brown adipose tissue (BAT) were studied in rats after severing 5 intercostal nerve bundles that enter the unilateral interscapular BAT, the contralateral BAT being used as the control. Four weeks after denervation, there was no appreciable change in BAT weight or its DNA and protein contents, whereas the triglyceride content was increased significantly. However, the rate of fatty acid synthesis was decreased to about half the rate in controls. The denervated BAT was much paler than controls and contained lots of adipocytes filled with large lipid droplets, some of which were unilocular. The results are discussed with reference to changes in BAT seen after bilateral lesions of the ventromedial hypothalamus.

Adipose Tissue, Brown↗
PubMed1986

Clinical assessment of elastic properties of large coronary arteries: pressure-diameter relationship and dynamic incremental elastic modulus.

Vascular elastic properties in vivo (dynamic incremental elastic modulus [Ep(dyn)]) of large coronary arteries were assessed from the pressure-diameter relationships of the large coronary arteries in 46 patients with suspected ischemic heart disease. Ep(dyn) represents the vascular stiffness primarily determined by the organic sclerotic changes of the vascular wall and the vascular smooth muscle tone. Coronary arterial diameter was obtained from the magnified cine coronary arteriograms by using a computerized caliber measurement technique. The mean Ep(dyn) of the left main coronary artery and the proximal portions of the left anterior descending and circumflex coronary arteries with apparently normal angiograms were significantly (P less than 0.01) increased as the number of involved coronary vessels was increased. Mean Ep(dyn) values in multi-vessel disease were comparable with those of dilated segment by the percutaneous transluminal coronary angioplasty, indicating that the vascular sclerotic changes are not localized to the narrowed segments but diffusely distributed to the angiographically normal vascular wall. In 4 patients who had successful percutaneous transluminal coronary angioplasty, Ep(dyn) of the dilated coronary segment showed markedly higher values (0.21-0.30 X 10(6) Nm-2) than the normal values (0.16 +/- 0.06 X 10(6) Nm-2 in left anterior descending coronary artery). In contrast, there was no significant difference in Ep(dyn) values of the angiographically normal left main coronary trunk, proximal portions of left anterior descending and circumflex arteries between patients with and without vasospastic angina. During myocardial ischemia induced by ergonovine maleate, vasospastic response of the non-diseased segment was comparable with that in patients who did not have an anginal attack during the ergonovine test. Thus, in contrast to the sclerotic change, abnormal vasoconstrictive property of the coronary artery may be localized to the diseased segment.

Adult↗
PubMed1986

Determination of the complete amino acid sequence of recombinant human gamma-interferon produced in Escherichia coli.

The complete amino acid sequence of recombinant human gamma-interferon (HuIFN-gamma) produced in Escherichia coli was determined using a gas-phase protein sequencer. The sequence was established by automated Edman degradation on the intact protein and its peptides obtained after Staphylococcus aureus V8 protease or trypsin digestion. The result was identical to the amino acid sequence predicted from the nucleotide sequence of the cloned HuIFN-gamma cDNA except that it was missing the four carboxy-terminal residues, Arg-Ala-Ser-Gln.

Amino Acid Sequence↗
PubMed1986

Sympathetic denervation impairs responses of brown adipose tissue to VMH stimulation.

Effects of unilateral surgical denervation of the interscapular brown adipose tissue (IBAT) on its thermogenic and lipogenic responses to electrical stimulation of the ventromedial hypothalamic (VMH) nucleus were studied in anesthetized rats. The rapid rise in IBAT temperature in response to VMH stimulation was greatly suppressed in the denervated IBAT, whereas the temperature response was not impaired in the contralateral innervated IBAT in the same animals. Similarly, the increased rates of conversion of [14C] glucose and [3H]H2O to fatty acids and glyceride glycerol in vivo in IBAT after VMH stimulation were almost completely inhibited by sympathetic denervation. These results indicate clearly that the increases in lipogenic and thermogenic activities in IBAT in response to VMH stimulation are mediated by the sympathetic nerve supply of this tissue.

Adipose Tissue, Brown↗
PubMed1986

[Quantitative integrated backscatter characteristics in the normal and infarcted canine myocardium].

To develop ultrasonic cardiac tissue characterization, serial changes in intensity of backscattered ultrasound from the normal and infarcted myocardium were studied in vitro, with frequency-domain analysis. As an index of backscattered signal intensity, quantitative integrated backscatter [(10 X log-S2/S1)] (dB), S1 and S2 = areas of power spectra of digitized (sample rate = 100 MHz, 8 bits) ultrasonic signals from a perfect reflector and good specimens) were calculated for 60 regions of the myocardium (N = 20, MI = 40) excised from 10 dogs 3 days, 1, 2, and 4 weeks after coronary artery ligation in 2, 3, 3, and 2 dogs, respectively. The myocardial specimens and a stainless steel reflector were mounted at the focal distance of a newly-developed wide-band transducer having a center frequency of 4.0 MHz, in a water bath filled with degassed physiological saline. Tissue concentrations of hydroxyproline (HP) were also established using a HPLC (Hitachi amino acid analyzer model 835). The results obtained were as follows: 1. No significant changes in the integrated backscatter of the normal myocardium were observed throughout the experimental period (3 days = -52.5 +/- 0.7, one week = -53.6 +/- 1.8, two weeks = -51.6 +/- 0.8, four weeks = -52.8 +/- 1.4 (dB) (mean +/- SE). 2. Integrated backscatter of the infarcted myocardium [3 days = -47.3 +/- 0.6, one week = -49.2 +/- 1.3, two weeks = -40.7 +/- 1.3, four weeks = -39.6 +/- 2.0 (dB)] was significantly increased compared with the integrated backscatter of the normal myocardium in the early stage of myocardial infarction, before tissue concentrations of hydroxyproline increased, as well as in the chronic stage of myocardial infarction. 3. Results of histological examinations suggest that minute changes in structure, such as interstitial edema or neovascular proliferations, may be the cause of an early increase in integrated backscatter. The results suggest that quantitative integrated backscatter is a sensitive parameter for detecting both early and old myocardial infarction by cardiac tissue characterization.

Animals↗
PubMed1986

Influence of the increased uterine tonus on maternal hemodynamics.

In an experiment using 103 late pregnant rabbits, the resting uterine tonus was increased by inserting a balloon into the amniotic cavity on the cervical side (n = 71) or the ovarian side (n = 52) and the effects of this increase on the maternal blood pressure, renal cortical blood flow (measured by a thermocouple method), renal arterial and carotid arterial blood flow (measured with an electromagnetic flowmeter) were studied. The findings are briefly described, as follows: The maternal blood pressure was slightly increased on both sides (by 12.0 +/- 3.5% on the cervical and by 12.0 +/- 3.8% on the ovarian side). However, there was a hemodynamic difference between the renal cortical and renal arterial blood flow on the cervical side and those on the ovarian side: They were slightly increased on the cervical side and slightly decreased on the ovarian side. On the basis of these findings, the following may be proposed: An increase in resting uterine tonus causes a rise in maternal blood pressure associated with blood redistribution from the uteroplacental vascular bed. However, the fact that the renal blood flow was decreased consequently upon the increase in resting uterine tonus raised a possibility of neurotransmission via the ovarian plexus as well as utero-renal reflex.

Animals↗
PubMed1985

Assay of inorganic phosphate in the mild pH range, suitable for measurement of glycogen phosphorylase activity.

A spectrophotometric assay of orthophosphate at mild pH is described. Phosphomolybdate complex is reduced by ascorbic acid at pH 5.0 in the presence of Zn2+. The chromophore produced is measured at 850 nm. The method is simple and sensitive, and the reaction proceeds normally in the presence of "interfering substances" such as metal-chelating agents and thiol compounds. The method could be widely employed for the assay of phosphate-releasing reaction from labile organic phosphates, such as for the assay of glycogen phosphorylase.

Acetates↗
PubMed1985

Isolation and properties of two phospholipases A2 from the venom of an Australian elapid snake (Pseudechis australis).

Two phospholipases A2 (Pa-11 and Pa-13) were purified from the venom of an Australian elapid snake (subfamily Acanthophiinae) Pseudechis australis (king brown snake) by chromatography on CM-cellulose CM-52 followed by gel filtration on a Sephadex G-75 column. The apparent molecular weights of the two phospholipases A2 (Pa-11 and Pa-13) were 14,000 and 13,500, respectively, by gel filtration analysis on a Sephadex G-75 column. Each enzyme molecule consists of a single polypeptide chain of 118 amino acid residues. The isoelectric points of Pa-11 and Pa-13 were 10.5 and 10.0, respectively. The optimum pH values of Pa-11 and Pa-13 for hydrolysis of egg-yolk phosphatidylcholine were 7.8 and 7.5, respectively. Pa-11 was lethal to mice (LD50 0.23 micrograms/g body weight), whereas Pa-13 showed no lethal activity at a dose level of 7.4 micrograms/g mouse. Each enzyme was inactivated by reaction with p-bromophenacylbromide on the sole histidine residue (Pa-11) or on one of the two histidine residues (Pa-13). Oxidation of the tryptophan residues in Pa-11 and Pa-13 with N-bromosuccinimide led to a decrease in the phospholipase A activity. A complete loss of both enzymic and lethal activities of Pa-11 was observed upon oxidation of one of the two tryptophan residues of the molecule.

Acetophenones↗
PubMed1985

Transesophageal echocardiographic dimensional analysis of four cardiac chambers during positive end-expiratory pressure.

The authors examined the effects of positive end-expiratory pressure (PEEP) on cardiac function by dimensional analysis of the four heart chambers using M-mode transesophageal echocardiography (TEE). The accuracy of cardiac output (CO) calculated from TEE was confirmed by its close correlation (r = 0.97) with CO, determined by the thermodilution technique. The reliability of TEE also was confirmed by excellent correlation (r = 0.95) between left ventricular end-diastolic (LVEDD) and end-systolic (LVESD) dimensions measured by the two-dimensional precordial echocardiography and those by TEE. With 10 cmH2O PEEP LVEDD decreased from its level during zero end-expiratory pressure (ZEEP), and the calculated stroke volume also decreased. These decreases were greater during 15 cmH2O PEEP, where heart rate increased slightly but significantly. Ejection fraction (EF) and fractional shortening (FS), as a whole, did not change significantly. Mean velocity of circumferential fiber shortening (mean Vcf) significantly increased and LVESD significantly decreased with PEEP. Although systolic blood pressure (SBP) significantly decreased, the (SBP-PEEP value)/LVESD ratio was not changed with PEEP. Such measures of left ventricular systolic function as EF, FS, mean Vcf, and (SBP-PEEP value)/LVESD were not decreased. Right ventricular end-diastolic dimension decreased with PEEP. Right atrial end-diastolic dimension began to decrease immediately after PEEP was initiated, whereas left atrial end-diastolic dimension began to decrease a few seconds later, suggesting that left ventricular preload decreased as a result of a decrease in right ventricular preload. The authors therefore conclude that CO was decreased as a result of the decrease in right and left ventricular preloads.

Adolescent↗
PubMed1985

Brown adipose tissue after ventromedial hypothalamic lesions in rats.

The interscapular brown adipose tissue (IBAT) from obese rats with lesions of the ventromedial hypothalamus (VMH) was approximately 5 times heavier than those from controls. This hypertrophy of IBAT was associated with a marked enlargement of constituent adipocytes and their apparent transformation from multiloculated structure of lipid droplets into the uniloculated structure. The rate of fatty acid synthesis in IBAT of the obese rats was less than one-tenth of that in control rats and approximated the value in white adipose tissue (WAT) when they were starved for 24 h. When rats were fed, the synthetic rate was increased, but the lipogenic response of IBAT in the obese rats was much greater than that in controls, the extent of the response being comparable to that of WAT. The IBAT temperature rose rapidly on electrical stimulation of the sympathetic nerves to the tissue in control rats, whereas the temperature response was reduced markedly in the obese rats. It was suggested that thermogenesis in BAT was impaired in obese rats with VMH lesions by decreasing triglyceride turnover in BAT, probably due to dysfunction of the sympathetic nervous system and a consequent transformation of BAT into WAT.

Adipose Tissue, Brown↗
PubMed1985

[Evaluation of myocardial perfusion by intravenous contrast echomyocardiography].

For the echocardiographic assessment of intramyocardial blood flow distribution by intravenous contrast echocardiographic technique, we measured the echo intensity of a point (phi 6 mm) in the interventricular septum using a lightmeter in end-diastole before and after the intravenous injection of various dosages of ether or hydrogen peroxide in one open-chest and four closed-chest dogs. Before the injection of contrast media, the echo intensity of the myocardium varied within a range of 6.1 +/- 4.6% After the injection of ether or hydrogen peroxide, the echo intensity of the myocardium increased. After the occlusion of the left anterior descending artery, echo enhancement of the left ventricular wall occurred, except for the left ventricular anterior wall and the interventricular septum. Between dosage (x) and % increase (y), relations of y = 127x - 3, in ether and y = 1.17x + 1.11, in hydrogen peroxide were observed. We found that the intravenous injection of at least 0.2 ml ether or 15 mg hydrogen peroxide was necessary to achieve effective echo enhancement of the myocardium in dogs.

Animals↗
PubMed1984

Decreased rate of fatty acid synthesis in brown adipose tissue of hypothalamic obese rats.

Obese rats with lesions of the ventromedial hypothalamus (VMH) exhibited a 3-fold increase in the wet weight of interscapular brown adipose tissue (IBAT), due to an increased triglyceride content, compared with lean controls. The rate of lipogenesis in IBAT was much higher than that in white adipose tissues in control rats, but decreased greatly in rats with VMH lesions and approximated the value in white adipose tissues. It was suggested that thermogenesis in BAT was impaired after VMH lesions by decreasing triglyceride turnover in BAT.

Adipose Tissue, Brown↗