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Biomedical subjects

T Doi

Publications and source records attributed to T Doi.

At least 487 records · Page 27Linked to original sources

Analgesic effect of intrathecal morphine demonstrated in ascending nociceptive activity in the rat spinal cord an in effectiveness of caerulein and cholecystokinin octapeptide.

The effect of intrathecal injections of morphine and the two peptides, caerulein and cholecystokinin octapeptide (CCK-8), on the activity in ascending axons of the spinal cord evoked by electrical stimulation of primary nociceptive afferents was studied in spinal rats with decerebration. Morphine (20 microgram) depressed the spontaneous activity and the activity evoked from either A delta-or C-fibres. The co-activation by A delta-fibre stimulation of ascending axons activated by stimulation of C-fibres and the activity in ascending axons activated by stimulation of afferent A beta-fibres were not influenced by morphine. C-Fibre-evoked ascending activity was also depressed by morphine (10 microgram and 5 microgram). Ascending nociceptive activity was not changed by caerulein (30 ng) and CCK-8 300 ng, but it was depressed by a subsequent injection of morphine (20 microgram). The depressant effects of morphine were abolished by an intravenous injection of concluded that: (i) an intrathecal injection of morphine selectively depressed the ascending nociceptive activity; (ii) the depression produced by morphine is an equivalent for spinal analgesia following intrathecal injection of morphine to man; and (iii) the two components of the spinal nociceptive system, the motor and the sensory path, can independently be influenced by drugs.

Afferent Pathways↗

Intrathecal substance P depresses spinal motor and sensory responses to stimulation of nociceptive afferents--antagonism by naloxone.

The effect of an injection of substance P into the subarachnoid space was studied on a motor and a sensory response elicited by supramaximal stimulation of the sural nerve in spinal rats. Substance P 10 micrograms depressed the reflex activation in the electromyogram recorded from the ipsilateral tibialis anterior muscle; the depression was significant 5 and 10 min after the injection. Substance P 10 micrograms reduced the activity in ascending axons of the spinal cord evoked by stimulation of afferent C fibres; the effect developed slowly, lasted longer than 60 min and was abolished by an i.v. injection of nalaoxone 0.2 mg/kg. Only half the number of ascending axons tested showed a depression by substance P, and the administration of a higher dose (50 micrograms) did not produce an effect in a greater number of axons. Substance P did not influence the activity evoked in ascending axons by stimulation of afferent A beta and A delta fibres. The depression by substance P of ascending nocieceptive activity was antagonized by an i.v. injection of naloxone 0.2 mg/kg. When naloxone 0.2 mg/ng i.v. was administered alone, it increased the activity in ascending axons activated by afferent C fibre stimulation. It is concluded that (i) substance P depresses spinal nociceptive activity without the intermediation of endorphinergic neurons, and (ii) naloxone antagonizes tonic inhibition of the spinal nociceptive system mediated by endogenous opioid peptides and, by facilitating excitatory transmission through disinhibition, neutralizes the depression produced by substance P.

Afferent Pathways↗

Antimicrobial effect of human serum IgA.

Serum IgA, IgG and colostrum secretory IgA prepared from specimens pooled from a large number of human beings were shown to have measurable levels of antibodies against Escherichia coli, Pseudomonas aeruginosa, Klebsiella Pneumoniae, poliovirus, Coxsackie B virus, echovirus and influenza virus. Serum IgA exerted a bacteriostatic effect in vitro on E. coli and P. aeruginosa, which increased in the presence of the iron-binding proteins lactoferrin and transferrin. This bacteriostasis was reduced when the iron-binding proteins were saturated with iron. Similar results were obtained with IgG and secretory IgA. The bacteriostatic effect of serum IgA was also shown in vivo, in the peritoneal cavity of mice. The effect was suppressed by iron. Iron-chelating substances, siderophores, excreted by E. coli diminished the co-operative bacteriostatic effect of serum IgA and transferrin. Siderophore production by E. coli was inhibited in the presence of serum IgA, but not when serum IgA was deprived of specific antibody by absorption with E. coli. These results indicate that serum IgA has a potent bacteriostatic effect in co-operation with transferrin or lactoferrin because of the inhibitory effect of the specific antibody on siderophore production by E. coli.

Antibodies, Bacterial↗

Circulating immune complexes of IgG, IgA, and IgM classes in various glomerular diseases.

In order to examine the correlation between immunoglobulin (Ig) classes of immunoglobulins in circulating immune complexes (CIC) and immunoglobulins in glomerular deposits, we have measured CIC of IgG, IgA and IgM classes in various glomerular diseases. Serum CIC were measured using a modified conglutinin binding assay (K assay) using 125I-labeled anti-gamma, anti-alpha and anti-mu antisera. IgA class CIC were detected in more patients with IgA nephropathy than patients with non-IgA nephropathy. There was an association between the presence of IgG deposits in kidneys and the presence of IgG in CIC. Patients with IgA deposits in their kidneys also had IgA class CIC. There was also an association between the presence of IgM deposits in kidneys and the presence of IgM in CIC. These results suggest that the Ig class in CIC and the Ig class in glomerular deposits were correlated, and that in IgA nephropathy the mesangial IgA deposits may be derived from IgA class CIC.

Antigen-Antibody Complex↗

Non-IgG1 nature of cutaneous basophil hypersensitivity factor in contact sensitivity.

Cutaneous basophil hypersensitivity (CBH)-inducing factor was demonstrated in immune sera obtained from dinitrofluorobenzene (DNFB)-sensitized animals 2 weeks after sensitization (DNP-GPS-2W). It showed hapten specificity and worked dose dependently. It was fractionated into a non-gamma-globulin fraction by Sephadex G-150 gel filtration following ammonium sulfate desalting and CM-cellulose chromatography. The factor was eluted into a fraction of a little smaller molecular weight than bovine serum albumin on Sephadex G-150 gel filtration. It passed through an antiguinea pig IgG1 column and was absorbed to a DNP-BGG column. On SDS-PAGE it failed to show any staining band because of low protein concentration. From these results CBH factor appearing in circulation in contact-sensitized animals was thought to be a somewhat different molecule from that of Askenase's factor, i.e. IgG1 antibody.

Animals↗

Oxygen--insensitive nitrofuran reductases in Salmonella typhimurium TA100.

The present study demonstrated by DEAE-cellulose column chromatography that oxygen-insensitive nitrofuran reductases in Salmonella typhimurium TA100 consisted of at least two reductases, NADPH- and NAD(P)H-linked enzymes. The NADPH- and NADH-linked activities of the latter enzyme seemed to originate from a single enzyme, because both activities were similarly inactivated by heat and urea treatments, and also inhibited by dicumarol. On the other hand, the NADPH-linked enzyme was less sensitive to heat, urea and dicumarol. Furthermore, the study showed that the NAD(P)H-linked enzyme was a flavoenzyme which could be inactivated by dialysis against 1 M potassium bromide and reactivated by FMN.

Apoenzymes↗

Correlation between pharmacological and opiate receptor binding activities of tetrapeptide acylhydrazide analogs of enkephalin.

The pharmacological and opiate receptor binding activities of four synthetic tetrapeptide acylhydrazide analogs of enkephalin (EK compound) were compared with those of reference compounds. EK-159 administered subcutaneously was less analgesic, while EK-209, EK-259 and EK-272 were more potent than morphine in the hot plate, Haffner's and phenylquinone writhing tests in mice. EK-272 being the most active was comparable to what was found with FK-33824. IC50 values of EK compounds in a sodium-free medium in the opiate receptor binding assay were lower than the values seen with morphine. The binding activities of EK compounds in 100 mM NaCl medium showed a clearer correlation with their analgesic activities than was seen in the absence of sodium ion. The binding affinity of EK-272 was the highest and the sodium response ratio (IC50 + NaCl/IC50-NaCl) was slightly lower than that of pentazocine. The analgesic action in rodents, respiratory inhibition in rabbits, inhibition of intestinal movement in mice, and hyperthermic action in rats, were all qualitatively, but not quantitatively similar to the effects seen with morphine. The analgesic action of EK compounds was relatively resistant to the antagonizing effect of naloxone and the EK compounds modified the analgesic action of morphine. These properties were inversely correlated with the sodium response ratios.

Analgesics↗

Intrathecal substance P depresses the tail-flick response - antagonism by naloxone.

Substance P injected into the lumbar subarachnoid space of rats depressed the tail-flick response to radiant heat in a dose-dependent way. The effective doses ranged from 0.1 microgram to 100 micrograms per rat (ED 50: 1.5 microgram/rat). The maximum of the effect was reached 20 min after intrathecal injection and the effect lasted for about 30 min. An antinociceptive effect was also observed after intrathecal injection of substance P 1 microgram to spinal rats. The depression of the tail-flick response produced by intrathecal administration of substance P was abolished by intrathecal (5 micrograms/rat) or i.p. (0.5 mg/kg) injections of naloxone.

Animals↗

Total synthesis of a RNA molecule with sequence identical to that of Escherichia coli formylmethionine tRNA.

A RNA molecule has been synthesized that is identical in sequence to Escherichia coli tRNAfMet except that it lacks the base modifications present in the E. coli tRNA. This was achieved by enzymatic joining of chemically synthesized oligonucleotides with chain lengths of 3-10 which were synthesized by the phosphodiester or phosphotriester method. First, quarter molecules of tRNA were constructed by joining of chemically synthesized fragments with RNA ligase. The 5'-quarter molecule (bases 1-20) served as an acceptor in joining reactions with the 3',5'-bisphosphorylated donor molecule (bases 21-34). The 5'-half molecule thus obtained was treated with phosphatase and joined to the 3'-half molecule which was prepared by ligation of the other quarter molecules (bases 35-60, acceptor; bases 61-77, donor) followed by 5'-phosphorylation with polynucleotide kinase. The synthetic tRNA was characterized by oligonucleotide pattern and was partially active in aminoacylation with E. coli methionyl-tRNA synthetase.

Base Sequence↗

Studies on oxygen-insensitive nitrofuran reductase in Escherichia coli B/r.

Oxygen-insensitive nitrofuran reductase in Escherichia coli B/r was clearly resolved by DEAE-cellulose column chromatography into two components, one NADPH-linked, and the other both NADPH- and NADH-linked. It is known that the strain requires resistance to nitrofurazone in two mutational steps. It is known that the the first step mutants had no NADPH-linked component and the second step ones had neither this component nor the NAD(P)-H-linked one. The NADPH- and NADH-linked activities of the latter component were similarly inactivated by heat or urea treatment. In addition, it was found that these activities were significantly inhibited by dicoumarol, an NAD(P)H dehydrogenase inhibitor, to similar extents. These results suggest that the activities of the NAD(P)H-linked component originate from a single enzyme. On the other hand, the NADPH-linked component was less sensitive to heat, urea and dicoumarol.

Cell-Free System↗

Joint force analysis in degenerative varus or valgus knees during standing -importance of tibial tilt to the floor-.

A two-dimensional skeletal model of the knee was constructed to estimate joint compression force in varus of valgus osteoarthrotic knees. Angle and length constants and variables were measured for 100 X-ray films of normal and osteoarthrotic subjects while they were standing on one foot. The results showed that the tibial tilting angle to the floor primarily determined the joint forces in the deformed knees. The angle has mechanically more significance than the femoro-tibial tilting angle which has been widely used clinically. The results have some clinical implications.

Body Weight↗

Comparison of substrate base sequences for RNA ligase reactions in the synthesis of a tetradecanucleotide corresponding to bases 21-34 of E. coli tRNAfMet 1.

A tetradecanucleotide U-A-G-C(U-C-G)2G-G-C-Up corresponding to bases 21-34 of a nascent sequence of formylmethionyl tRNA of E. coli has been synthesized by the joining of two combinations of chemically synthesized oligonucleotides: 1) U-A-G-C + U-C-G-U-C-G + G-G-C-Up and 2) U-A-G-C + U-C-G-U + C-G-G-G-C-Up. In reaction 1) and the extent of joining *pG-G-C-Up to U-C-G-U-C-G was only 15.4% and the last ligation of the decamer to U-A-G-U proceeded to 27%. In reaction 2) joining between U-A-G-C and pU-C-G-Up gave a high yield (88%). The ligation of this octamer and *pC-G-G-G-C-Up also gave a satisfactory yield (52%). These reactions suggest that sequence preferences in RNA ligase reactions may arise from the structure of the 3'-end of acceptor molecules.

Base Sequence↗

Antagonistic effects of psycholeptic drugs on stress-induced analgesia.

Stress-induced analgesia was significantly antagonized by naloxone and was dose-dependently reduced by diazepam, chlordiazepoxide, flurazepam, medazepam, nitrazepam, estazolam, phenobarbital, chlorpromazine, levomepromazine, haloperidol and propranolol. In contrast to psycholeptics, morphine substantially increased in threshold of nociceptive response in the post-stress session. Centrally acting muscle relaxants, tolperisone and carosiprodol had no substantial anti-stress effects. These results suggest that the stress-induced analgesia is probably mediated through endogenous opioids in the central nervous system. The approach used in our study provides a simple method for assessing the anti-stress action of psycholeptics.

Analgesia↗