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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 829 records · Page 46Linked to original sources

Structural evaluation of anorectic action induced by 1,5-anhydro-D-glucitol.

In previous studies, 1,5-anhydro-D-glucitol (1-DG), an endogenous glucose analog, was found to significantly influence physiological feeding behavior. The relationships between the hydroxyl group positions on the pyranose ring carbons and the anorectic action induced by 1-DG and its analogs are discussed. To investigate the effects of these glucose analogs on ingestive behavior, 24 mumole of test solution was injected into the rat third cerebral ventricle immediately before normal eating time, which starts at the beginning of the dark. After initial transient hyperphagia, 1-DG suppressed feeding during the first 12-hr dark period. It prolonged postprandial intermeal interval beginning shortly after injection, but eating rate was not affected and meal size did not decrease until near the end of the normal feeding period. The incidence of drinking episodes decreased concomitant with feeding suppression. Feeding and drinking suppression were also produced by 1,2-dideoxy-D-glucose, 1,3-dideoxy-D-glucose, and 1,4-dideoxy-D-glucose, although they were less potent than 1-DG. They suppressed feeding by prolonging the postprandial intermeal interval, but did not change meal size or eating rate. The anorectic effects of 1-DG were abolished by removal of the hydroxyl group at carbon 6 and by epimerization at carbons 2, 3, and 4. These findings indicate that feeding suppression induced by 1-DG and its analogs is induced mainly by prolongation of the postprandial intermeal interval, and the presence or absence of a hydroxyl group on each carbon of 1-DG is important for its feeding suppression.

Animals↗

In vitro and in vivo inhibitory effects of propentofylline on cyclic AMP phosphodiesterase activity.

1-(5'-Oxohexyl)-3-methyl-7-propylxanthine (propentofylline), a vasoactive agent, was investigated for its in vitro and in vivo inhibitory effects on cyclic AMP phosphodiesterases activity. Soluble cyclic AMP phosphodiesterases from the cerebral cortex, heart muscle, descending aorta and platelet showed two Km values, high and low. The low Km values were in the range of 2.1-3.0 mumol/l and the high Km values were 111, 28.7, 30.2 and 18.7 mumol/l, respectively. Propentofylline inhibited the enzyme from the 4 tissues noncompetitively. Ki values for the low and high Km cyclic AMP phosphodiesterases were 83.4-135 and 107-188 mumol/l, respectively. In the four tissues, the enzyme inhibitory effect of propentofylline was 1/4 to 1/10 times that of 3-isobutyl-1-methylxanthine (IBMX) but 3-9 and 6-17 times as potent as those of theophylline and caffeine, respectively. The in vivo cyclic AMP phosphodiesterase inhibitory effect of propentofylline was determined in mice using an elevation of plasma cyclic AMP levels as a measure. When given both singly and in combination with isoprenaline (isoproterenol), propentofylline was a potent inhibitor of cyclic AMP phosphodiesterase in the case of intravenous administration.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Electrophysiological identification of neurons of the substantia innominata].

Recently in senile dementia of Alzheimer type, neuronal loss of cholinergic neurons in the substantia innominata is described. However these findings are based on morphological studies and, so far, these neurons have not been identified physiologically. In this study we tried to record these neurons electrophysiologically by antidromic activation. Cats were anesthetized with sodium pentobarbital and paralyzed with gallamine triethiodide. Three arreys of 3 or 4 silver-ball stimulating electrodes were fixed to the surface of the cerebral cortex. Each electrode was stimulated by rectangular pulses of 1 msec duration. Recording electrodes were glass micropipettes filled with 2 M NaCl saturated with fast green FCF and inserted into the ipsilateral substantia innominata stereotaxically. Twenty-eight neurons were constituted of mainly negative component; suggesting that they were recorded from cell bodies, not from axons. Also they responded in an all-or-none manner and showed constant latencies when stimulus intensities were at threshold level. When paired stimuli were applied, the latency of the action potential to the second stimulus was equal to that of the first one. These neurons were, therefore, considered to be activated antidromically. These neurons had axons of very slow conduction velocities. They are divided into two groups according to conduction velocities. The first group had mean conduction velocity of 2.3 m/sec and they responded to rather high frequency stimuli. The second group had mean conduction velocity of 1.0 m/sec and neurons belonging to this group showed quite long refractory periods. Based on conduction velocity analysis, the former is thought to include neurons with myelinated axons and the latter those with unmyelinated ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Synthesis and expression of the native RNase T1 gene and several mutant genes.

RNase T1 gene and several mutant genes were constructed by joining of chemically synthesized deoxyoligonucleotides. These genes were inserted into an expression vector and expressed as fused protein in E. coli. RNase T1 and its mutant enzymes were liberated by cyanogen bromide treatment and their activities were measured.

Amino Acid Sequence↗

[Antiemetic combination of metoclopramide and methylprednisolone for cisplatin-induced vomiting].

An antiemetic combination of metoclopramide and methylprednisolone was administered to 16 lung cancer patients receiving cisplatin (80 cmg/m2) alone or in combination with other drugs. Metoclopramide was administered four times intravenously at a dose of 1.5 mg/kg. Methylprednisolone was administered three times intravenously at a dose of 125 mg. Sixteen patients received a total of 34 chemotherapy courses. No vomiting occurred in 70% of 34 chemotherapy courses and mild emesis (one or two vomiting episodes) occurred in 18% of chemotherapy courses. Side effects were minimal and included mild sleepiness (nine patients), diarrhea (three patients), and hiccups (three patients). It is concluded that a combination of metoclopramide and methylprednisolone is very effective in preventing cisplatin-induced vomiting.

Aged↗

The reaction of DNA with lipid oxidation products, metals and reducing agents.

The interaction of lipid hydroperoxides and secondary oxidation products with DNA was investigated by evaluating the fluorescence formed in the presence of metals and reducing agents. We also investigated the effect of malonaldehyde, because it has been generally considered responsible for the formation of fluorescence with DNA. However, malonaldehyde usually has been estimated by the notoriously unspecific thiobarbituric acid test. At low concentration of oxidation products (1 mM), fluorescence formation required the presence of metals and ascorbic acid. In contrast, a positive thiobarbituric acid reaction was obtained with many lipid oxidation products without metals or ascorbic acid. Monohydroperoxides from autoxidized methyl linoleate and linolenate produced the highest level of fluorescence. Hydroperoxy epidioxides of linolenate and dihydroperoxides of linoleate and linolenate were among the most active secondary products in forming fluorescence with DNA. In contrast, malonaldehyde produced very little fluorescence under our conditions. The thiobarbituric acid values did not correlate with fluorescence formation. This study showed that, in our model reaction system, DNA forms fluorescent products by the breakdown of lipid oxidation products in the presence of metals and ascorbic acid into reactive materials other than malonaldehyde. Therefore, the importance of malonaldehyde in its crosslinking properties with DNA may have been exaggerated in the literature.

Ascorbic Acid↗

Treatment of inferior vena cava obstruction producing Budd-Chiari syndrome.

We treated a patient who had an inferior vena cava (IVC) obstruction associated with Budd-Chiari syndrome. All of the right, middle, and left hepatic veins were completely obstructed. The IVC was obstructed by a membranous substance and thrombus at the hepatic portion and was completely occluded by a fibrous septum at the site of a suprahepatic coarctation. A cavotomy was performed transversely at the suprahepatic level and then longitudinally to the level just above the renal veins, and the obstructing tissue was removed. An additional vertical incision was made in the IVC over the coarctation, and an autologous pericardial patch was sutured in place to widen the IVC. The patient was discharged with the patency of the IVC restored.

Adult↗

Short-chain polyhydroxymonocarboxylic acids as physiological signals for food intake.

In order to clarify the effects of endogenous organic acids on short and long-term feeding behavior, ingestive behavior was monitored for 2 hr before and after intra-third ventricular infusions of 3,4-dihydroxybutyric acid (2-deoxytetronic acid, 2-DTA), 2,4,5-trihydroxypentanoic acid (3-deoxypentonic acid, 3-DPA), and 3-hydroxybutyric acid (3-HBA). In addition, meal patterns were recorded for 2 days before and after the ventricular infusions. 2-DTA suppressed both short and long-term feeding by decreasing meal size (MS). 3-DPA elicited transient feeding behavior, but caused no change in long-term feeding. 3-HBA initially stimulated feeding, but subsequently suppressed long-term feeding by decreasing MS and prolonging postprandial intermeal interval (IMI). The suppressive effects of 3-HBA on feeding behavior lasted about 24 hr longer than those of 2-DTA. Based upon these observations as well as our previous reports, it appears that some of the processes affecting hunger and satiation are mediated by changes in central and peripheral concentrations of these organic acids.

3-Hydroxybutyric Acid↗

A comparative study of body surface isopotential mapping and the electrocardiogram in diagnosing of myocardial infarction.

It is important to determine the location of the infarcted area by body surface isopotential mapping (MAP), but at present there is no definite method to accomplish this. The present authors reported that they were able to estimate the infarcted area by MAP, and so it became necessary to confirm the reliability of their method. Initially, in a retrospective study using 50 cases, a comparison was made between the location of the infarcted area estimated by MAP and that estimated by 12-lead ECG to determine the size of the infarcted area of a region in which positive findings were obtained to determine the location of infarction. Criterion A (the infarcted area occupies more than half of a region in which positive findings are obtained by MAP) in a previous study was too severe for MAP, and Criterion B (the infarcted area occupies more than one third of a region in which positive findings are obtained) was adequate as a positive finding by MAP after comparison with the 12-lead ECG. This was confirmed in 40 cases in a prospective study. Secondly, in order to assess the superiority of MAP to the 12-lead ECG, the sensitivity, specificity and others of MAP and those of the 12-lead ECG to a scintigram using thallium-201 (SCG) were calculated. The sensitivity and negative predictive value of MAP to SCG were superior to that of ECG to SCG in the lateral, inferior and posterior walls, and it was suggested that MAP was more sensitive than 12-lead ECG in detecting the location of myocardial infarction.

Electrocardiography↗

Cost evaluation of control measures for indoor radon progeny.

Based on assumed conditions within a typical U.S. home, annualized costs for reducing indoor airborne radon progeny concentrations have been calculated for a variety of methods of control. These analyses were limited to methods for control in existing homes. Control through modified construction techniques was not evaluated. Methods assessed included increased air circulation, increased ventilation, particle removal using electrostatic precipitation and unipolar ion generation, and the application of sealants to room surfaces. Although surface sealants proved to be reasonably cost-effective per person- sievert dose reduction, such sealants are prone to cracking and the durability of their effectiveness is questionable. Use of ceiling fans for increased air circulation and particle deposition appears to be least cost-effective, but this method may be attractive in some cases for reasons of comfort. The use of unipolar ion generators appears to be the best approach from the standpoint of cost effectiveness. These devices are also easy to install and are esthetically readily acceptable.

Air Ionization↗

The acetylation of 6'-amino group of amikacin by a new enzyme prepared from serratia sp.

It was found that Serratia marcescens 43, Serratia proteamaculans 48 and Serratia sp. 45, all of which were clinically isolated, produced a new type of aminoglycoside acetyltransferase which acetylated amikacin at the 6'-amino group. 1-N-[(S)-3-Amino-2-hydroxypropionyl]-gentamicin B (HAPA-B, SCH 21420) and gentamicin C2 were hardly inactivated by the enzymes and had effective antimicrobial activities against these strains both in vitro and in vivo. This kind of aminoglycoside acetyltransferase should be classified into a new group other than previously reported AAC(6') enzymes.

Acetylation↗

In vitro antibacterial activity and beta-lactamase stability of cefodizime, a new cephalosporin antibiotic.

The in vitro activity and beta-lactamase stability of cefodizime (HR 221), a new cephalosporin, were compared with those of other cephem antibiotics. HR 221 was highly active against Gram-negative bacteria. The compound inhibited growth of all tested Haemophilus influenzae strains at 0.10 microgram/ml and showed strong activity even against penicillin-resistant Neisseria gonorrhoeae strains, but it was less effective against Pseudomonas aeruginosa than the other antibiotics tested. Against Gram-positive bacteria, HR 221 showed 100% inhibition of growth of Streptococcus pneumoniae at 0.39 microgram/ml, and it was slightly less active against Staphylococcus aureus (MIC90:12.5 micrograms/ml) than other antibiotics such as cefotaxime (CTX). The bactericidal activity of HR 221 against E. coli was dose-related and comparable to that of CTX, cefoperazone and latamoxef. The bactericidal activity of the compound at medium concentrations simulating human serum levels was higher than that of CTX and cefmetazole, and no cell regrowth was noted after beta-lactamase-induced inactivation of the compound. HR 221 was stable to most drug-inactivating enzyme preparations from various bacterial species.

Cefoperazone↗

In vivo antibacterial activity of cefodizime, a new cephalosporin antibiotic.

The in vivo activity of cefodizime (HR 221) was compared with that of cefotaxime (CTX), cefmenoxime, latamoxef, cefazolin and cefmetazole (CMZ). The protective effects of HR 221 on experimental infections in mice caused by Staphylococcus aureus Smith, Escherichia coli C-11, Proteus vulgaris GN-76 and Serratia marcescens No. 2 were directly related to its in vitro activity against these strains. In contrast, the compound showed the smallest ED50 values, among the 5 antibiotics tested (not including CMZ), for Klebsiella pneumoniae 3K-25 and Pseudomonas aeruginosa PI 67 against which it had relatively low in vitro activity, and its ED50 for Citrobacter freundii GN-346 was as small as 1.821 mg/mouse in spite of its MIC of greater than 100 micrograms/ml. HR 221 exerted potent bactericidal activity against Streptococcus pneumoniae Sp-1 inoculated into the mouse lung; the duration of action was prolonged. When tested against the E. coli Ec-89 infection induced in the rat uterus, the activity of HR 221 given to rats once daily was equal to that of CTX or CMZ given at the same dose twice daily.

Animals↗