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Biomedical subjects

H Nagayama

Publications and source records attributed to H Nagayama.

At least 73 records · Page 4Linked to original sources
PubMed1997

Circadian rhythm in the hypothermic response to serotonin1A receptor agonist 8-OH-DPAT in rats.

In a recent study, we found a circadian rhythm in the serotonin (5-HT) syndrome (forepaw treading, head weaving, and flat body posture) in the response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The present study examined the rhythm in the responsiveness to 8-OH-DPAT by observing hypothermia, another index of the 5-HT1A receptor function. Rats standardized to L(1800-0600) : D(0600-1800) were subcutaneously administered with 0.16 mg/kg 8-OH-DPAT at one of the following times of day: 00:00, 04:00, 08:00, 12:00, 16:00, 20:00 h. Two parameters of assessing the hypothermic response, the maximum decrease in temperature after the administration (MAXDT) and the area under the curve of the decrease in temperature (AUCDT), displayed significant circadian rhythms with the peaks in the middark phase (12:00 h). The waveform of the rhythms observed was similar to that of the rhythms that we observed previously in the 5-HT syndrome. The evidence presented here further supports that the central postsynaptic 5-HT1A receptor function exhibits a circadian rhythm.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Effects of antidepressants on intracellular Ca2+ mobilization in CHO cells transfected with the human 5-HT2C receptors.

Serotonin 5-HT2C receptor-mediated intracellular Ca2+ mobilization was investigated in 5-HT2C receptors expressed in Chinese hamster ovary (CHO) cells; and fura-2/AM was used to investigate the regulation of 5-HT2C receptor function. CHO cells, transfected with a cDNA clone for the 5-HT2C receptor, expressed 287 fmol/mg of the receptor protein as determined by mianserin-sensitive [3H]-mesulergine binding (kd = 0.49 nM). The addition of 5-HT mobilized intracellular Ca2+ in a dose-dependent fashion, ranging from basal level of 99 +/- 1.8 nM up to 246 +/- 21.2 nM, with an EC50 value for 5-HT of .015 microM. Exposure to 5-HT, a 5-HT receptor agonist, mCPP [1-(3-chlorophenyl)piperazine dihydrochloride], a 5-HT2C agonist, and DOI [1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane], a 5-HT2C and 5-HT2 agonist, resulted in increased intracellular Ca2+ levels. Mianserin, mesulergine, ritanserin, and ketanserin each blocked 5-HT-mediated intracellular Ca2+ mobilization more effectively than spiperone. Mianserin and amoxapine inhibited 5-HT-mediated intracellular Ca2+ mobilization completely; amitriptyline, nortriptyline, and imipramine reduced it about 50%. These results suggest that antagonism in CHO cells transfected with human 5-HT2C receptors is a component of the serotonergic properties of a number of established antidepressants.

Animals↗
PubMed1996

Circadian rhythm in the response of central 5-HT1A receptors to 8-OH-DPAT in rats.

Circadian rhythm in the behavioral responsiveness to the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was studied in rats. Rats were subcutaneously injected with 8-OH-DPAT at one of the following times of day: 0000, 0400, 0800, 1200, 1600, 2000 hours. The post-synaptic 5-HT1A receptor behavioral syndrome, that is, forepaw treading, head weaving, and flat body posture, were measured after the administration of 8-OH-DPAT. Circadian rhythms were found in each of the behavioral responses to 8-OH-DPAT. Peak responses were observed in the mid-dark phase (1200 hours) while the weakest responses were observed in the mid-light phase (0000 hours). In a subsequent experiment, 8-OH-DPAT was administered intracerebroventricularly during the mid-dark phase and the mid-light phase. The behavioral responses to the drug in the mid-dark phase were significantly higher than those in the mid-light phase. These results suggest that the function of central postsynaptic 5-HT1A receptor exhibits circadian rhythm.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Circadian rhythm in the responsiveness of central 5-HT2A receptor to DOI in rats.

The present study investigated the circadian variation in the behavioral response to the selective 5-HT2A/2C receptor agonist (+/-)-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI). Rats were subcutaneously injected with DOI at 0000, 0400, 0800, 1200, 1600, or 2000 hours. The wet-dog shake (WDS) response was counted following administration of DOI. A circadian rhythm that peaked during the late light period (0400 hours) and reached the lowest point during the late dark period (1600 hours), was observed in the DOI-induced WDS response. In a separate experiment, DOI was administered intra-cerebroventricularly at either 0400 or 1600 hours. The WDS response to the drug at 0400 hours was significantly higher than the response at 1600 hours. These results suggest that the function of the central 5-HT2A receptor exhibits a circadian rhythm.

Amphetamines↗
PubMed1996

A case of drug eruption due to simultaneous sensitization with three different kinds of drugs.

We reported a case of drug eruption induced by combined treatment with three different kinds of drugs, amoxapine, mexiletine hydrochloride and cefaclor. A 63-year-old Japanese woman suffering from 11 years of standing reflex sympathetic dystrophy developed multiple erythematous papules on her trunk and extremities after taking 14 kinds of drugs. The provocation challenge produced positive reactions to amoxapine, mexiletine hydrochloride, and cefaclor, but was negative to the other drugs. We discussed the mechanism of simultaneous sensitization to three different kinds of drugs in our case.

Amoxapine↗
PubMed1996

Chronic administration of imipramine and lithium changes the phase-angle relationship between the activity and core body temperature circadian rhythms in rats.

Evidence suggests that there is an association between the pathophysiology of depression and a disturbance of circadian rhythms. Accordingly, attention has focused on the possible effects of antidepressants on circadian rhythms. In the present study, we examined the effects of chronic administration of two clinically effective antidepressant agents, imipramine and lithium, on several circadian rhythms in the rat. Activity, core body temperature, and drinking rhythms were assessed in constant darkness (DD) and light-dark (LD) conditions. In DD, lithium significantly lengthened the circadian period of the activity, temperature, and drinking rhythms, while imipramine had no effect. In LD, both drugs significantly delayed the phase of the activity rhythm, but did not change that of the other two rhythms. As a result, the phase-angle differences between the activity and temperature rhythms significantly increased. Neither lithium nor imipramine produced any effect on the resynchronization of these rhythms after an 8-h delay in the LD cycle. These results indicate that although both drugs produced different effects on the circadian period of individual rhythms, both caused a relative phase advance of the temperature rhythm as compared to the activity rhythm, and this effect may be related to the similarity in their antidepressant effects.

Animals↗
PubMed1996

[Bronchiolitis obliterans organizing pneumonia (BOOP) after allogeneic bone marrow transplantation].

We report a patient who underwent allogeneic bone marrow transplantation for ALL. The patient presented low grade fever, cough and dyspnea at day 3 after after bone marrow transplantation. Imaging studies showed bilateral patchy infiltrates on chest X-ray and chest CT. Though treated by antibiotics, chest auscultation recognized marked bilateral inspiratory crackles. Transbronchial lung biopsy performed on day 34 showed bronchiolitis obliterans and an organizing interstitial pneumonia. The patient was treated with methylprednisolone and follow up computed tomography findings improved.

Administration, Oral↗
PubMed1995

Effects of 8-OH-DPAT on corticosterone after acute and chronic administration of antidepressants.

1. Serotonin has a facilitary role in the role of corticosterone secretion. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A agonist, dose dependently (0.25- 1.0 mg/kg i.p.) increased rat plasma corticosterone concentration. 2. 3 days parachlorophenylalanine (PCPA) (150 mg/kg) administration did not effect the 8-OH-DPAT-induced corticosterone secretion. 3. Corticosterone responses to 8-OH-DPAT (0.5 mg/kg) were significantly attenuated by pretreatment with propranolol (5 mg/kg). Ketanserin (2 mg/kg), haloperidol (0.2 mg/kg), prazosin (0.1 mg/kg), and ICS-205930 (30 mu/kg) failed to antagonize the corticosterone response to 8-OH-DPAT. 4. 8-OH-DPAT-induced corticosterone were investigated in male rats after treatment with mianserin (2, 10 mg/kg), imipramine (5 mg/kg), desipramine (5 mg/kg), doxepine (5 mg/kg) for 1 day or 3 weeks. Chronic mianserin (10 mg/kg) and doxepine (5 mg/kg) did significantly increase 8-OH-DPAT-induced corticosterone response. Acute antidepressant, chronic imipramine, desipramine and mianserin (2 mg/kg) treatment did not change it. 5. These findings demonstrate that chronic treatment of some antidepressants potentiates 8-OH-DPAT-induced increase in plasma corticosterone, by actions at 5-HT-1A receptors located postsynaptically on 5-HT neurones.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Rapid desensitization of serotonin 5-HT2C receptor-stimulated intracellular calcium mobilization in CHO cells transfected with cloned human 5-HT2C receptors.

Serotonin 5-HT2C receptor-mediated intracellular Ca2+ mobilization was investigated in Chinese hamster ovary (CHO) cells transfected with 5-HT2C receptors. Fura-2 acetoxymethyl ester was used to investigate the regulation of 5-HT2C receptor function. CHO cells, transfected with a cDNA clone for the 5-HT2C receptor, expressed 287 fmol/mg of the receptor protein as determined by mianserin-sensitive [3H]mesulergine binding (KD = 0.49 nM). The addition of 5-HT mobilized intracellular Ca2+ in a dose-dependent fashion, ranging from a basal level of 99 +/- 1.8 up to 379 +/- 18 nM, with an EC50 value for 5-HT of 0.029 microM. Exposure to 5-HT, 1-(3-chlorophenyl)piperazine dihydrochloride (a 5-HT2C agonist), and 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (a 5-HT2C and 5-HT2A agonist) resulted in increased intracellular Ca2+ levels. Mianserin, mesulergine, ritanserin, and ketanserin each blocked 5-HT-mediated intracellular Ca2+ mobilization more effectively than spiperone. The receptor was rapidly desensitized by preexposure to 5-HT in a time- and concentration-dependent manner. Mezerein and phorbol 12-myristate 13-acetate, protein kinase C activators, weakly inhibited the intracellular Ca2+ mobilization induced by 10 microM 5-HT. Furthermore, the protein kinase C inhibitor H-7 partially prevented the protein kinase C activator-induced inhibition of the 5-HT-mediated increase in intracellular Ca2+ concentration. The desensitization induced by pretreatment with 5-HT was blocked by W-7, added in conjunction with 5-HT, and partially inhibited by W-5, a nonselective inhibitor of protein kinases and weak analogue of W-7.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Transduction of LacZ gene into leukemia cells using viral vectors of retrovirus and adenovirus.

Recent developments in gene therapy techniques enable us to introduce new genetic information into hematopoietic cells. Among the various techniques, we focused on two viral vector systems, one using a retrovirus and the other an adenovirus. By using an adenoviral vector we could transduce and highly express bacterial beta-galactosidase (LacZ) gene under the control of the CAG (cytomegalovirus enhancer with chicken beta-actin promoter) promoter in various hematopoietic cells, although the expression persisted for only two weeks. The retroviral vector (MFG) could transduce the LacZ gene into hematopoietic cells almost as well as the adenoviral vector using the repetitive infection protocol. The retroviral system could maintain the expression of transduced cells quite longer than the adenoviral system. Differential use of these two vector systems may be helpful for the gene transduction into various kinds of hematopoietic cells (Lin et al., manuscript in preparation).

Actins↗
PubMed1994

Effects of chronic mianserin administration on serotonin metabolism and receptors in the 5-hydroxytryptophan depression model.

1. To further investigate a previous postulate that increased serotonergic activity may cause depression, the effects of chronic mianserin administration on 5-HT, its metabolites, and the subtypes of 5-HT receptors were studied. 2. The levels of 5-HT, 5-hydroxyindoleacetic acid, 5-HTP, 5-HT turnover and their response to 5-HTP administration all exhibited no change following mianserin treatment. 3. The Bmax value of the high affinity site of the 5-HT-1A receptor increased and the Bmax value of 5-HT-2 receptor decreased with no change in the low affinity site of the 5-HT-1A receptor nor in the 5-HT-1B receptor. 4. The response to 5-HTP administration showed no change in any of these receptors. 5. These results suggest that the chronic mianserin administration might block both the 5-HT-2 and 5-HT-1A receptors in the 5-hydroxytryptophan depression model.

5-Hydroxytryptophan↗
PubMed1994

The effect of chronic administration of antidepressants and electroconvulsive shock on the 5-HT1A receptor mediated hypothermic response induced by 8-OH-DPAT in the rat.

1. The effect of chronic administration of antidepressants and electroconvulsive shock (ESC) on the hypothermic response (HTR) induced by 8-hydroxy-2-(di-n-propyramino) tetralin (8-OH-DPAT) as an index of the function of 5-HT1A receptors was investigated in the rat. 2. 8-OH-DPAT dose-dependently decreased the rectal temperature. 3. Pretreatment with parachlorophenylalanine increased HTR. 4. Chronic administration of the antidepressants, trazodone, imipramine, amitriptyline, and fluoxetine had no effect on HTR, whereas administration of clorgyline attenuated HTR significantly. 5. Repeated ECS had no effect on HTR. 6. These results suggest that the action site of 8-OH-DPAT is post-synaptic 5-HT1A receptors and that the chronic administration of some antidepressants and ECS has no direct action on these receptors. 7. Therefore, the antidepressant effects of these drugs are not produced by direct action on postsynaptic 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

A method for analyzing biological rhythms in healthy subjects and depressed patients.

Rectal temperature rhythms of healthy subjects and patients with depression were fitted to a waveform having cosine components of periods 8, 12, and 24 hours using the least squares method. The nadir was then used as an index of phase. The results suggest that this method gives more exact data than the conventional method of analyzing biological rhythms, which uses a least squares fit to a single, 24-hour-period cosine waveform.

Adolescent↗
PubMed1993

Angiographic findings of Meckel's diverticulum: the characteristic appearance of the vitelline artery.

Angiographic findings of the vitelline artery in five patients with surgically proven Meckel's diverticulum were reviewed retrospectively. Superselective vitelline arteriography was performed in two patients and superior mesenteric arteriography in three. Arteriography showed the elongated artery without branching originating from the distal ileal artery and a group of tortuous vessels at the distal portion of this artery in all patients. A dense capillary staining of the vitelline artery was exclusively shown in patients with ectopic gastric mucosa. In one patient, injection of methylene blue intraoperatively through a previously placed angiographic catheter into the vitelline artery stained only the vitelline artery and Meckel's diverticulum in blue but neither the mesentery nor the ileum. Demonstration of a nonbranching artery from the ileal artery and a group of dilated tortuous vessels at the distal portion of this artery should suggest the possibility of Meckel's diverticulum and can be confirmed by selective injection of the artery. It should be emphasized that angiography can detect Meckel's diverticulum even in the absence of acute bleeding.

Adolescent↗
PubMed1993

Chronopharmacology of psychotropic drugs: circadian rhythms in drug effects and its implications to rhythms in the brain.

The effects of many kinds of psychotropic drugs have been shown in animal studies to follow a circadian rhythm. Trials for the clinical application of this circadian rhythm have already been undertaken. Although the mechanisms underlying this phenomenon are still unclear, chronological changes in the levels of drugs in the blood and brain suggest that it is primarily due to rhythms in the brain's susceptibility to drugs. Rhythms are present in the level of intracerebral neurotransmitters, receptors and second messengers. Each of these rhythms may cause other rhythms within each system of neurotransmitters, which in turn induces a rhythm in the susceptibility to drugs.

Absorption↗
PubMed1993

Free combined composite flaps using the lateral circumflex femoral system for repair of massive defects of the head and neck regions: an introduction to the chimeric flap principle.

Chimeric composite flaps combined using microanastomoses consist of two or more flaps or tissues, each with an isolated pedicle and a single vascular source. Free combined chimeric flaps using the lateral circumflex femoral system were used to treat massive composite defects of the head and neck in 10 cases. A combined anterolateral thigh flap and vascularized iliac bone graft based on the lateral circumflex femoral system and the deep circumflex iliac system was the most commonly used combination. An anteromedial thigh flap and a paraumbilical perforator-based flap were also combined with this principal combination. The advantages of this chimeric flap over other osteocutaneous flaps are: (1) The flap is relatively thin and the pedicle vessels are up to 10 cm longer and are wider than those of other flaps for easier harvesting of the flap. (2) It is unnecessary to reposition the patient. (3) The vascular pedicle to the skin can be separated from that of the bone. (4) The donor site is not close to the recipient site. (5) The donor scar is in an unexposed area. (6) The skin territory of this flap is extremely wide. (7) A combined anterolateral and anteromedial thigh flap and vascularized iliac bone graft can be easily obtained as an extended combined osteocutaneous flap. (8) Other neighboring skin flaps, such as a groin flap, a paraumbilical perforator-based flap, or a medial thigh flap, can be combined with this chimeric flap because several major muscle branches to be anastomosed derive from the lateral circumflex femoral system. Chimeric composite flaps using the lateral circumflex femoral system are considered suitable for the repair of massive composite defects of the head and neck.

Adult↗