Biomedical subjects
Publications and source records attributed to T Takaya.
The synthesis and biological properties of some 3-vinylthio- and 3-vinylthiomethylcephem derivatives are described. Both series possess potent antibacterial activity. Among them, 3-[(Z)-2-cyanovinylthiomethyl]cephem derivative was found to have an expanded antibacterial spectrum.
The synthesis and antibacterial activity of several 7 beta-[1-(2-aminothiazol-4-yl)-1-cyclopropanecarboxyamido]cep hem derivatives (1) are described. The structure-activity relationships of 1 are also presented.
During the ventricular slow-filling period, both the left atrium and left ventricle fill passively, and their respective internal pressures equalize, becoming evenly elevated. If the diastolic chamber compliance of the left atrium is smaller than that of the left ventricle, we expect the inflowing blood to be distributed more to the left ventricle than to the left atrium during this period. We examined the magnitude of the diastolic compliance of the left atrium and the left ventricle at the end of the slow-filling period. We studied 10 patients, mostly with a mild degree of coronary artery disease, in whom hemodynamic variables were almost within normal limits. To estimate the compliance of the left atrium, we recorded the left atrial pressure directly (by the Brockenbrough technique) and determined the left atrial volume by biplane cineatriography. We determined the diastolic compliance of the left atrium from the pressure-volume relations between the nadir of the x trough and the peak of the v wave by fitting them to an exponential equation. P = b.eaV (P = pressure, V = volume, a, b = constants). The diastolic compliance of the left ventricle was determined from the pressure-volume relations during the ventricular slow-filling period. The compliances of the left atrium and the left ventricle at the pressure at the end of the ventricular slow-filling period were 1.60 +/- 0.41 (mean +/- SD) ml.mmHg-1.m-2 and 4.22 +/- 1.12, respectively. The ratio of compliance of the left ventricle to that of the left atrium was 2.60 +/- 0.71.(ABSTRACT TRUNCATED AT 250 WORDS)
A series of 7 alpha-hydroxyethyl-1-oxacephems (1) was synthesized. The main focus of this study was to investigate biological activity relationships between 1-oxacephems (1) and the corresponding cephems (2). Replacement of the sulfur atom of 2 by the oxygen atom caused an enhancement of antibacterial activity, although the antibacterial activity of 1 was not high enough. Additionally 1 showed beta-lactamase inhibitory activity, especially against cephalosporinase. However, the potency was lower than that of 2.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
FK482 is a new orally active cephem antibiotic which offers some advantages over the commercially available oral beta-lactam antibiotics. It displayed a broad spectrum of activity in vitro against stock strains of Gram-positive and Gram-negative aerobes and anaerobes. FK482 was more active in vitro than cefixime (CFIX), cefaclor (CCL) or cephalexin (CEX) against clinical isolates of Gram-positive organisms such as methicillin-sensitive Staphylococcus aureus, coagulase-negative Staphylococci including Staphylococcus epidermidis and strains of the Streptococcus group. Moderate activity was found against methicillin-resistant S. aureus and Enterococcus faecalis. Against clinical isolates of many Gram-negative species, including opportunistic pathogens, FK482 had good in vitro activity similar or slightly inferior to that of CFIX but superior to that of CCL or CEX. However, it was clearly inferior to CFIX in activity against Serratia marcescens, and was inactive against Pseudomonas aeruginosa. Strains of S. aureus resistant to methicillin were moderately susceptible to FK482. All tested strains of Klebsiella pneumoniae resistant to CCL and CEX were susceptible to FK482, as were all the strains of Escherichia coli, Proteus mirabilis, Haemophilus influenzae and Branhamella catarrhalis resistant to amoxicillin (AMPC). FK482, like CFIX, was relatively stable to all type of beta-lactamases except Bacteroides fragilis and its stability was superior to that of CCL or CEX. The antibacterial activity of FK482 against CSH2 strains containing ampicillin-resistance plasmids was not affected by the presence of the ampicillin resistance determinants. FK482 showed higher affinity for the penicillin-binding proteins (PBPs) (3, 2 and 1) of S. aureus than did CFIX, CCL and CEX. FK482 also showed very high affinity for the PBPs (2 and 3) of E. faecalis and PBPs (3, 1a, 4, 2 and 1 bs) of E. coli. The bactericidal activity of FK482 against S. aureus was almost as strong as that of AMPC and superior to that of CCL or CEX. Against Gram-negative bacteria such as E. coli, K. pneumoniae and P. mirabilis, FK482 was similar to CFIX and superior to CCL and CEX in bactericidal activity.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We estimated the magnitude of the left atrial contraction in 28 patients with ischemic heart disease by calculating the biplane cineangiographic volumes of the left atrium. The left atrial contraction contribution to the left ventricular stroke volume (ml/m2, Y axis) correlated inversely with the left ventricular ejection fraction (%, X axis), yielding an equation: Y = -0.31X + 43.7 (n = 28, r = -0.56, p less than 0.001). The result indicates that the left ventricular filling is compensated by the augmented atrial contraction in case of impaired left ventricular function. We defined the left atrial volume at the beginning of the atrial contraction (LAVd, ml/m2) as the "preload" of the left atrium, and we also defined the volume expelled by the active atrial contraction (delta LAVa, ml/m2) as the stroke volume of the left atrium. The stroke volume (Y) correlated positively with the "preload" (X), yielding an equation: Y = 0.48X - 1.3 (n = 28, r = 0.80, p less than 0.001). We then defined the left ventricular end-diastolic pressure, the peak of the a-wave, as the "afterload" of the left atrium, and we studied the "afterload"-stroke volume relations in the left atrium. However as expected, a reasonable relationship between them was difficult to form. Consequently, we showed that an increase in the "preload" of the left atrium augmented the stroke volume of the left atrium, which means that Frank-Starling mechanism is operative in the left atrium.
The synthesis and antiviral activity of various aminoglycoside derivatives having a palmitoyl group are described. All of these aminoglycoside derivatives exhibited almost the same excellent antiviral activity against herpes simplex virus type I and influenza virus.
Explore the source record for details and available documents.
In relation to the synthesis of antipseudomonal drugs, namely, gentamicin C2 and 3-de-O-methylsporaricin A, a protected purpurosamine B (15) and 6-epipurpurosamine B (13) were synthesized. The key intermediate, methyl 2,3,4,7- tetradeoxy-6-O-(methylsulfonyl)-2-phthalimido-beta-L-lyxo-++ +heptopyranoside (8), was obtained in 48% yield by Grignard addition to methyl 2,3,4-trideoxy-2-phthalimido-alpha-D-erythro-hexodialdo-1,5-pyrano side (7) proceeding in accordance with Cram's chelate rule, followed by methylsulfonylation. From 8, compound 15 was readily obtained by introduction of the azide group with inversion of configuration at C-6. Compound 13 was obtained by introduction of the azide group with retention of configuration.
Explore the source record for details and available documents.
By definition, the pulmonary "venous" system consists of the pulmonary veins and the left atrium. The stiffness of the pulmonary "venous" (P'V') system and the left ventricle (LV) at the end of the slow filling period (at the point of pre-a) were estimated sequentially in a total of 26 patients, divided into a control group and mitral stenosis (MS), angina pectoris (AP), hypertrophic cardiomyopathy (HCM) groups. The stiffness (delta P/delta V) of the P'V' system was estimated from the pulmonary artery wedge (PAW) pressure tracings and the stroke volume. The stiffness (dP/dV) of LV was obtained from the pressure-volume (P-V) relationship of LV with a model of P = beaV. The present study is aimed primarily at obtaining factual information. The stiffness of the P'V' system was 0.063 +/- 0.022 mmHg/ml (mean +/- SD) in the control group and 0.052 +/- 0.006 mmHg/ml in the HCM group (p greater than 0.1). The stiffness of LV in diastole was 0.091 +/- 0.016 mmHg/ml in the control group and 0.199 +/- 0.056 mmHg/ml in the HCM group (p less than 0.01). The ratio of the stiffness of LV in diastole to that of the P'V' system was 1.6 +/- 0.6 in the control group and 3.8 +/- 0.7 in the HCM group. The volume elastic constant (a) of the P'V' system was 0.008 +/- 0.005 ml-1 in the control group and the values of (a) occupied a range of 0.007 to 0.008 ml-1 in the remaining 3 groups of patients. The values of (a) of LV were 0.011 +/- 0.004 ml-1 in the control group and 0.022 +/- 0.007 ml-1 in the HCM group (p less than 0.01). The present study suggests that the P'V' system is usually 2 to 3 times more complaint than LV in diastole. On the other hand, the P'V' system remained compliant in spite of the decreased compliance of LV in diastole in the HCM group, maintaining the reservoir function with which pulmonary edema is prevented.
In order to evaluate the magnitude of pulmonary "systolic runoff", we studied the pulmonary vein blood flow velocity waveform by positioning a catheter-tip velocity-pressure transducer into the extraparenchymal pulmonary vein just distal to the left atrium. We recorded blood flow velocity and pressure simultaneously, and subsequently identified the zero blood flow velocity with blood flow velocity level of the pulmonary artery in diastole. Patients with atrial septal defect were used as subjects because of the technical ease although the altered hemodynamics were present. Two kinds of flow velocity waveforms were consistently demonstrated. One was a waveform of two peaks with the first peak in late systole and the second peak in early diastole (n = 9). The other was a waveform of one peak with a summit near the end of systole (n = 5). On the assumption that the blood flow velocity waveform obtained with this method is roughly equivalent to the flow volume waveform, we initiated the second study. The area encompassed between the actual flow velocity waveform and the line of zero flow velocity was divided into two compartments, i.e., ventricular systole (S) and diastole (D). The ratios of the area in systole to the sum of the areas in systole and diastole, i.e., (S)/[S) + (D], which are analogous to the pulmonary "systolic runoff", were 0.45 +/- 0.07 (mean +/- SD, n = 13). This suggests that about 40% of the right ventricular stroke volume flows into the pulmonary veins, the left atrium and a portion of the right atrium through the atrial septal defect during ventricular systole.
The synthesis of 7 beta-([Z) -2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino) acetamido]-cephalosporins (2a-h) modified at the C-3 position of a cephem nucleus and the effect of the C-3 substituents on the antibacterial activity, oral absorptivity and therapeutic activity are discussed. The cephems (2a and 2b) having a C-3 substituent such as hydrogen or vinyl were more potent than other cephalosporins against Gram-negative bacteria. However, the cephalosporin (2f) having methylthio group at the 3-position showed the highest absorption rate in rats. These three cephalosporins (2a, b and f) exhibited equally good protective activities in mice infected. Furthermore, the serum levels of these cephalosporins (2a, b and f) were examined in dogs, and 2b and 2f showed outstanding high and prolonged serum levels.
Explore the source record for details and available documents.