Biomedical subjects

K Hirota

Publications and source records attributed to K Hirota.

At least 361 records · Page 20Linked to original sources

PubMed1991

Interleukin-1 alpha enhances hepatotoxicity of tumor necrosis factor-alpha in galactosamine-sensitized mice.

The possible involvement of interleukin-1 alpha (IL-1 alpha) in the pathogenesis of murine hepatitis model induced with galactosamine and lipopolysaccharide (LPS) was investigated. The injection of 10 ng/mouse of LPS in combination with 10 mg/mouse of galactosamine into mice induced hepatic damage at 24 hours. Treatment with anti-mouse IL-1 alpha antiserum 30 min before galactosamine/LPS injection showed a tendency to reduce the liver injury, while pretreatment with anti-mouse tumor necrosis factor-alpha (TNF) antiserum significantly protected mice from liver injury. The use of recombinant murine TNF, instead of LPS, in combination with galactosamine could elicit hepatic damage, whereas recombinant murine IL-1 alpha could not substitute for LPS. However, recombinant murine IL-1 alpha enhanced the hepatotoxic effect of recombinant murine TNF in galactosamine-sensitized mice. These results suggest that TNF plays a major role in the pathogenesis of galactosamine/LPS hepatitis in mice and that IL-1 alpha acts synergistically with TNF in this hepatitis model.

Animals↗

PubMed1991

Inhibitory effect of N3-methyl derivative of 3'-azido-3'-deoxythymidine 5'-triphosphate on the activity of HIV-1 reverse transcriptase.

N3-Methyl derivative of 3'-azido-3'-deoxythymidine 5'-triphosphate (Me-AZTTP) showed a potent inhibitory effect on HIV-1 reverse transcriptase using MS2 phage RNA as the template. The inhibition mechanism of MeAZTTP was noncompetitive with respect to any of the template MS2 RNA, dATP and dCTP. On the other hand, MeAZTTP showed a mixed-type inhibition with respect to dGTP and dTTP. These results indicate that MeAZTTP competes not only with dTTP but also with dGTP.

Antiviral Agents↗

PubMed1991

[Effects of isoflurane on membrane potentials, refractory periods and membrane ionic currents in rabbit single ventricular myocytes].

In order to analyze direct action of isoflurane on myocardium, we studied effects of isoflurane on membrane potentials and transmembrane ionic currents in single ventricular myocytes isolated enzymatically from rabbit hearts. Membrane potentials were recorded with a suction microelectrode technique, and an action potential was elicited by a brief intracellular stimulus. Isoflurane 3% depressed the action potential overshoot, plateau phase and duration without changing resting potential. Isoflurane decreased the refractory period of the action potential and prolonged the time-constant (tau) of the recovery process. In corresponding voltage clamp experiments, isoflurane significantly depressed the Ca2+ current (ICa), which generates the plateau phase. However, isoflurane had no effect on the transient outward current (I(t)), which triggers repolarization of the action potential. In rabbit ventricular cells, the time- and voltage-dependent outward K+ current (IK) was nearly absent. In conclusion, the depression of the action potential plateau by isoflurane is due to the decrease of ICa. Since isoflurane has no effect on It, the depression of the plateau phase by isoflurane may explain the shortening in the duration and the refractory period of the action potential.

Action Potentials↗

PubMed1991

[Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--11. Effect on epidural pressure].

We have developed a new method of total intravenous anesthesia using ketamine, fentanyl and droperidol (NLA-FK). There are many reports describing a significant increase in cerebrospinal fluid pressure (CSFP) during ketamine administration, but little is known about changes in CSFP during NLA-FK. As epidural pressure (EP) is considered as a good index for CSFP, we measured it in 12 patients under either NLA-FK or isoflurane anesthesia, who underwent gastrectomy. In the NLA-FK group the EP increased significantly by 26% at the induction of anesthesia as compared with the preinduction level, and it decreased to the preinduction level 30 minutes after the induction. Thereafter the pressure was not appreciably changed. In the isoflurane group EP significantly decreased by 16% at induction, but the pressure significantly increased by 29% 30 minutes after the induction as compared with the preinduction level. The change was similar to that of the NLA-FK group. Although the increase in the EP during the induction of NLA-FK is significant, it is considered to be within normal ranges. However, further detailed clinical study is needed to attenuate the significant increase in the EP during the induction of NLA-FK.

Anesthesia, Intravenous↗

PubMed1991

Oxidative cyclization of 2',3'-O-isopropylideneadenosines to 5'-O,8-cycloadenosines: considerations of N6-substituent effects and mechanism.

Oxidative cyclization of 2',3'-O-isopropylideneadenosines to the corresponding 5'-O,8-cyclo-2',3'-O-isopropylideneadenosines was achieved by using by lead tetraacetate, cupric chloride, and N-halogeno-succinimide as an oxidant, and by irradiation with a uv-visible light in the presence of pyrimido[5,4-g]pteridinetetrone 5-oxide. The reaction modes for the oxidative cyclization were investigated and discussed. In particular, N6-substituent effects on the oxidative cyclization provided a positive proof supporting the respective reaction mode.

Adenosine↗

PubMed1991

[Methods of anesthesia in canine heart-lung transplants].

Hypothermia has many valuable merits compared with under cardiopulmonary bypass using pump oxygenator, as known. But, on the contrary, it has some weak points, such as, long time required for cooling and rewarming. We have developed the device for rapid cooling and rewarming by using jet water blows. It appeared that the key point in hypothermia was control of ether inhalation and timing of rewarming. We demonstrated that mongrel dog could survive for at least 72 hours after transplantation of heart-lung under simple deep hypothermia with ether anesthesia. The dog was breathing 50-100 percent oxygen gas under control through respiratory ventilator. Postoperative arterial blood gases were maintained between pH 7.3-7.5 and PO2 80-200mmHg on the other hand, PCO2 was unstable from 14 to 63mmHg. It seemed that the anesthesia in canine heart-lung transplants using profound surface hypothermia with either anesthesia was useful methods.

Anesthesia, Closed-Circuit↗

PubMed1991

[Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--4. Control of intraoperative hypertension with nicardipine].

Intraoperative hypertension over 160 mmHg systolic observed during total intravenous anesthesia with droperidol, fentanyl and ketamine was treated with intravenous nicardipine in 50 surgical patients. Nicardipine was given intravenously in a bolus of either 0.5 mg or 1.0 mg to treat the intraoperative hypertension. Systolic and diastolic blood pressures decreased soon after administration of nicardipine without simultaneous sinus tachycardia. Thus rate pressure product was also reduced significantly. Neither preoperative hypertension, nor systolic blood pressure just before the administration of nicardipine had any significant relationship with hypotensive effect of intravenous nicardipine. We did not experience any adverse reaction with the drug. We conclude that intravenous nicardipine in a dose of 0.5-1.0mg can be given repeatedly to overcome hypertension observed during this method of anesthesia.

Adolescent↗

PubMed1991

[Effect of induced hypotension with prostaglandin E1 or trimetaphan on endocrine functions in surgical patients].

Twenty patients who underwent surgery of hip joint under enflurane anesthesia were studied to evaluate the effect of induced hypotension with prostaglandin E1 or trimetaphan on endocrine functions. Ten patients were given prostaglandin E1 and the remaining ten patients were given trimetaphan intravenously to maintain systolic blood pressure at about 80 mmHg. There were no significant differences between the two groups concerning plasma level of ACTH, cortisol, TSH, T3, T4, epinephrine and dopamine. However a significant difference in plasma norepinephrine levels was observed between them. Plasma norepinephrine levels after start of hypotension increased by 50% in the prostaglandin E1 group, but decreased by 50% in the trimetaphan group, when compared with each pre-hypotensive level. The data obtained suggest that the prostaglandin E1 would not influence ACTH-cortisol and thyroid functions, but may have a tendency to increase plasma norepinephrine levels in hypertensive patients complicated with pheochromocytoma.

Endocrine Glands↗

PubMed1990

Ultrasensitive enzyme immunoassay.

Ultrasensitive enzyme immunoassay methods not only for antigens but also for antibodies and haptens are reviewed. These methods are based on a noncompetitive type of assay using solid phase rather than a competitive one. One of the greatest obstacles limiting the sensitivity of noncompetitive immunoassay methods using solid phase is the nonspecific binding of labeled reactants to solid phase. A novel method (immune complex transfer immunoassay method) to overcome this difficulty has been developed. In the initially developed method, antibodies in test serum were reacted with dinitrophenylated biotinylated antigen. The complex formed was trapped onto (anti-dinitrophenyl group) IgG-coated solid phase. The solid phase was washed to eliminate nonspecific immunoglobulins. The complex was eluted from the solid phase with dinitrophenyl-L-lysine, again trapped onto avidin(streptavidin)-coated solid phase and finally measured by reaction with (anti-immunoglobulin) Fab'-enzyme conjugate. Namely, the complex of antibodies and dinitrophenylated biotinylated antigen was transferred from one solid to another, effectively eliminating nonspecific immunoglobulins nonspecifically adsorbed onto the first solid phase. By this method with and without further modifications, the sensitivity for antibodies in serum has been considerably improved. The same principle of immune complex transfer has been applied to the detection of antigens, and one milliattomole (600 molecules) of human ferritin has been detected. Ultrasensitive, noncompetitive immunoassay methods to measure haptens with amino groups have also been developed to measure attomole amounts of haptens.

Animals↗

PubMed1990

Involvement of tumor necrosis factor-alpha in development of hepatic injury in galactosamine-sensitized mice.

Intravenous injection of lipopolysaccharide and D-galactosamine, at doses of 0.2 micrograms/kg and 800 mg/kg, respectively, elicited massive hepatic necrosis within 24 hr in C3H/HeN mice. The plasma L-alanine aminotransferase (ALT, E.C. 2.6.1.2) or L-aspartate aminotransferase (AST, E.C. 2.6.1.1) activities at this point reached more than 2,000 IU/L. However, overt hepatic injury as evaluated by the plasma aminotransferase activities did not develop in mice in which only lipopolysaccharide or only D-galactosamine was injected. No tumor necrosis factor-like activities could be detected in the plasma of galactosamine- and lipopolysaccharide-injected mice as determined by the assay of cytotoxicity to highly tumor necrosis factor-sensitive L-P3 cells through the experimental period of 24 hr. However, passive immunization against mouse tumor necrosis factor-alpha with polyvalent rabbit anti-mouse tumor necrosis factor-alpha antiserum, which was able to neutralize the cytotoxic effects of recombinant mouse tumor necrosis factor-alpha on L-P3 cells, could protect the mice from the development of hepatic injury in a dose-dependent manner. Simultaneous injection of recombinant human tumor necrosis factor-alpha, instead of lipopolysaccharide, with 800 mg/kg of D-galactosamine in lipopolysaccharide-resistant C3H/HeJ mice sensitized the animals more than one thousand-fold to the development of hepatic injury. The livers appeared to be morphologically similar to those of galactosamine- and lipopolysaccharide-injected C3H/HeN mice.

Alanine Transaminase↗

PubMed1990

Involvement of tumor necrosis factor-alpha in the pathogenesis of activated macrophage-mediated hepatitis in mice.

The possible involvement of tumor necrosis factor-alpha in the pathogenesis of an experimentally induced hepatitis was investigated. Balb/c mice were primed with Propionibacterium acnes to induce the infiltration of mononuclear cells into the liver. Immunohistochemical study showed that most of the accumulated mononuclear cells at 7 days were Mac-2 positive, suggesting that they were activated macrophages. An injection of lipopolysaccharide resulted in massive hepatic necrosis and high mortality in the mice within 24 hours. Plasma tumor necrosis factor-alpha activity initially rose sharply and then declined over 3 hours. The increase in plasma aminotransferase activity correlated well with the elevation of plasma tumor necrosis factor-alpha activity. Pretreatment with dexamethasone or 16,16-dimethyl-prostaglandin E2 attenuated not only the elevation of plasma tumor necrosis factor-alpha activity but also the increase in plasma aminotransferase activity and improved the survival rate. Passive immunization against tumor necrosis factor-alpha showed protective effects. These findings suggest that tumor necrosis factor-alpha released from activated macrophages may play a crucial role in the pathogenesis of this murine hepatitis.

16,16-Dimethylprostaglandin E2↗

PubMed1990

Receptive fields and gustatory responsiveness of frog glossopharyngeal nerve. A single fiber analysis.

Receptive fields and responsiveness of single fibers of the glossopharyngeal (IXth) nerve were investigated using electrical, gustatory (NaCl, quinine HCl, acetic acid, water, sucrose, and CaCl2), thermal, and mechanical stimulation of the single fungiform papillae distributed on the dorsal tongue surface in frogs. 172 single fibers were isolated. 58% of these fibers (99/172) were responsive to at least one of the gustatory stimuli (taste fibers), and the remaining 42% (73/172) were responsive only to touch (touch fibers). The number of papillae innervated by a single fiber (receptive field) was between 1 and 17 for taste fibers and between 1 and 10 for touch fibers. The mean receptive field of taste fibers (X = 6.6, n = 99) was significantly larger than that of touch fibers (X = 3.6, n = 73) (two-tailed t test, P less than 0.001). In experiments with natural stimulation of single fungiform papillae, it was found that every branch of a single fiber has a similar responsiveness. Taste fibers were classified into 14 types (Type N, Q, A, NA, NCa, NCaA, NCaW, NCaAW, NCaWS, NQ, NQA, NQAS, NQWarm, Multiple) on the basis of their responses to gustatory and thermal stimuli. The time course of the response in taste fibers was found to be characteristic of their types. For example, the fibers belonging to Type NQA showed phasic responses, those in Type NCa showed tonic responses, etc. These results indicate that there are several groups of fibers in the frog IXth nerve and that every branch of an individual fiber has a similar responsiveness to the parent fiber.

Action Potentials↗

PubMed1990

Dopamine inhibits the arachidonate and prolactin release stimulated by thyrotropin-releasing hormone through an islet-activating protein-sensitive GTP-binding protein in anterior pituitary cells.

Coupling of the dopamine (DA) receptor to the pathway of arachidonate (AA) through the islet-activating protein (IAP)-sensitive GTP-binding (G) protein was examined in primary cultures of anterior pituitary cells. The inhibitions by 1 microM DA of the stimulations of prolactin (PRL) release by 100 nM thyrotropin-releasing hormone and by 10 microM calcium ionophore A23187 were blocked by 100 ng/ml IAP. DA at 1 microM did not inhibit the release of [3H]-AA induced by 100 mU/ml phospholipase A2 (PLA2), but it inhibited the release of PRL induced by 100 mU/ml PLA2. This inhibition was blocked by 100 ng/ml IAP. IAP also blocked the inhibitions by DA of the releases of PRL by 5 microM AA and by 5 microM 5-hydroxyeicosatetraenoic acid. These results suggest that the DA receptor on lactotrophs is coupled to the pathway following the release of AA (lipoxygenase) through the IAP-sensitive G protein.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1990

Adenosine 3',5'-cyclic monophosphate enhances dopamine accumulation in rat hypothalamic cell culture containing dopaminergic neurons.

The regulation of dopamine accumulation in cultured rat hypothalamic cells by adenosine 3',5'-cyclic monophosphate (cAMP) was investigated in cultures of newborn rat hypothalamic cells. Both dibutyryl cAMP, (Bu)2-cAMP, and forskolin enhanced [3H]dopamine accumulation in a dose-dependent manner. cAMP also enhanced [3H]dopamine accumulation, but to a lesser degree. Neither n-butyrate nor adenosine alone enhanced [3H]dopamine accumulation. (Bu)2-cAMP had no effect on basal efflux of [3H]radioactivity. The effect of (Bu)2-cAMP appeared on day 5 of culture, reached a maximum on day 6, and then rapidly decreased. These results suggest that dopamine uptake by cultured rat hypothalamic cells is regulated by intracellular cAMP.

Adenosine↗

PubMed1990

Synthesis and anti-human immunodeficiency virus (HIV-1) activity of 3'-deoxy-3'-(triazol-1-yl)thymidines and 2',3'-dideoxy-3'-(triazol-1-yl)uridines and inhibition of reverse transcriptase by their 5'-triphosphates.

3'-Deoxy-3'-(1,2,3-triazol-1-yl)thymidines (5a, 6a, 8a, 11a, and 12a) and 2',3'-dideoxy-3'-(1,2,3-triazol-1-yl)uridines (5b, 6b, 8b, 11b, and 12b) were synthesized as cyclic analogues of 3'-azido-3'-deoxythymidine (AZT) and 3'-azido-2',3'-dideoxyuridine (CS-87) by the cyclization of 5'-trityl derivatives (1a, b) of AZT and CS-87 using alpha-ketophosphorus ylides and with acetylenic compounds followed by deprotection of the 5'-trityl group. It was hypothesized that the triazole nitrogen atoms could mimic and distorted azido group. However, no significant activity against human immunodeficiency virus type 1 (HIV-1) was observed with any of these compounds. 5'-Triphosphates (17a and 18a, b), prepared from 5a and 6a, b, were inactive against HIV-1 and Rauscher murine leukemia virus (RLV) reverse transcriptases.

Acquired Immunodeficiency Syndrome↗

PubMed1990

5-Hydroxyeicosatetraenoic acid and phorbol ester stimulate prolactin release from rat anterior pituitary cells by different mechanisms.

The relationship between 5-hydroxyeicosatetraenoic acid (5-HETE) and calcium-activated, phospholipid-dependent protein kinase (protein kinase C) in prolactin (PRL) release was investigated in rat anterior pituitary cells. Arachidonic acid or 5-HETE, a 5-lipoxygenase metabolite of arachidonic acid, is known to cause a significant concentration-dependent increase in PRL release. Phorbol 12-myristate 13-acetate (PMA) and dioctanoyglycerol (diC8) have also been known to stimulate PRL release from pituitary cells, so we showed that these PRL releases were correlated with the activation of protein kinase C, that is, they induced dose-dependent translocation of protein kinase C from the cytosol to the membrane. Arachidonic acid, however, did not cause a significant change in the distribution of protein kinase C. We also showed that the PRL release induced by arachidonic acid and that induced by 5-HETE were additional to that by 100 nM PMA. Thus we suggested that the signals for the stimulation of PRL release sent by arachidonic acid and 5-HETE would be different from the signal sent through protein kinase C by PMA.

Animals↗

PubMed1990

Interleukin 6 possibly induced by interleukin 1 beta in the pituitary gland stimulates the release of gonadotropins and prolactin.

The abilities of recombinant human interleukin 1 (IL-1) and IL-6 to induce release of FSH, LH and PRL from rat pituitary cells in vitro were examined. IL-1 and IL-6 induced significant releases of FSH, LH and PRL within 3 h. The extents of release of these compounds induced by IL-1 and IL-6 were similar to those induced by GnRH and TRH. Rat anterior pituitary cells released IL-6 spontaneously, and its release was enhanced by IL-1 beta. This effect of IL-1 beta was inhibited significantly by a rabbit anti-IL-1 beta antiserum. These findings suggest that IL-1 induced the release of IL-6 from rat pituitary, and that the released IL-6 stimulated the secretions of FSH, LH and PRL.

Animals↗

PubMed1990

Interleukin 1 beta and tumour necrosis factor alpha stimulate the release of gonadotropin-releasing hormone and interleukin 6 by primary cultured rat hypothalamic cells.

The abilities of recombinant human interleukin 1 beta and tumour necrosis factor alpha to induce release of GnRH and interleukin 6 from primary culture of rat hypothalamic cells were examined. The effect of estradiol on the release of interleukin 6 by these cells was also tested. Both interleukin 1 beta and tumour necrosis factor alpha caused significant stimulation of GnRH secretion from the hypothalamic cells within 5 min. The hypothalamic cells secreted interleukin 6 spontaneously, and their secretion over 24 h was stimulated dose-dependently by interleukin 1 beta, tumour necrosis factor alpha and estradiol. These results suggest that interleukin 1 beta and tumour necrosis factor alpha stimulate the secretions of GnRH and interleukin 6 in the hypothalamus, and that these cytokines may be involved in the mechanism of GnRH secretion in the hypothalamus.

Animals↗