Search PubMed⌕ Search

Biomedical subjects

J S Han

Publications and source records attributed to J S Han.

At least 127 records · Page 7Linked to original sources
PubMed1998

Antagonistic effect of CCK-8 on morphine-inhibited electrical and contractile activities of rat jejunum in vitro.

In the present investigation, antagonistic action of cholecystokinin octapeptide (CCK-8) against morphine on the electrical and contractile activity of rat jejunum in vitro was studied. The results showed that the potentiation of acetylcholine (ACh) on both the burst of spike and the contractility were inhibited by morphine, which could be completely antagonized by CCK-8. The CCK-8 effect, again, could be suppressed by CCK-A receptor antagonist devazepide (10 nmol/L), but partially by CCK-B receptor antagonist L-365, 260 at 10 nmol/L or completely at concentration of 30 nmol/L. The above results demonstrated that the antagonism of CCK-8 on morphine was mediated by both CCK-A and CCK-B receptors.

Animals↗
PubMed1998

[Changes in the binding characteristics of central kappa-opioid receptor during the development of 100 Hz electroacupuncture (EA) tolerance in rats].

The effect of repetitive 100 Hz EA stimulation on the characteristics of binding of kappa opioid receptors in discrete brain regions and the spinal cord of rats was investigated by radioligand binding assay. 100 Hz EA was administered once a day (30 min) for 7 d. Changes in Bmax and Kd of kappa opioid receptors of 4 discrete brain regions (cortex, midbrain, pons-medulla and striatum) and spinal cord were observed at d 1, 3, 5 and 7, respectively. It was found that the numbers (Bmax) of kappa opioid receptors of all the brain regions observed were decreased during the development of 100 Hz EA tolerance with a differential time course. In rat cortex and pons-medulla, a marked down regulation of kappa opioid receptors occurred within 24 h and remained at a low level throughout the observation. The Bmax of kappa receptor in spinal cord showed a bell-shaped curve, i.e., up regulation in the first 5 days and down regulation at d 7. In contrast a slow and steady down regulation was found in the midbrain and striatum, matching the course of development of 100 Hz EA tolerance. No significant changes in Kd of [3H]-U69593 were found except for a decrease of Kd in midbrain. In conclusion, administration of 100 Hz EA 30 min per day for 7 consecutive days resulted in a significant down regulation of kappa opioid receptor in CNS, especially in midbrain and striatum.

Animals↗
PubMed1998

[Mechanisms underlying opioid addiction: new progress].

The mechanisms of opioid addiction has attracted much attention of researchers around the world. In the present review, we have discussed the recent progress in the following topics. (1) Neurotransmitters participating the mechanism of opioid addiction; (2) Roles of different opioid receptors in opioid addiction; (3) Possible involvement of learning and memory in opioid addiction; (4) The intracellular signal transductive pathways after the activation of opioid receptors. Possible method of prevention and treatment of opioid addiction are also discussed.

Animals↗
PubMed1998

Absence of H(+)-ATPase in the intercalated cells of renal tissues in classic distal renal tubular acidosis.

Proton-secretory defect is thought to be a major pathophysiologic mechanism leading to classic distal renal tubular acidosis (dRTA). However, there have been only two case reports demonstrating the absence of proton pump in renal tissues of the patients with Sjögren's syndrome. This study presents two cases of classic dRTA in which the absence of intact H(+)-ATPase was shown in their renal biopsy tissues by immunohistochemistry using a rabbit polyclonal antibody against the 70 kDa catalytic subunit of H(+)-ATPase from bovine brain clathrin-coated vesicles; one of the cases is diagnosed as subclinical Sjögren's syndrome and the other is idiopathic dRTA. A normal human kidney (NC) and the renal biopsy tissues from a patient with chronic tubulointerstitial nephritus whose proton secretory capacity was intact (DC) were compared as controls. The first patient, a 26-year-old woman, presented with quadriparesis. Her serologic tests revealed positive autoantibodies (ANA, SSA; SSB & RF), and a lower lip biopsy confirmed the diagnosis of Sjögren's syndrome. The second patient, a 43-year-old woman, who initially presented with a pathologic fracture of both femoral necks was referred for an evaluation for hypokalemia by the Department of Orthopedic Surgery. Her renal ultrasonography showed medullary calcification, and no autoantibodies were positive. Serum electrolytes and blood gas analyses of the two patients indicated severe hypokalemia and metabolic acidosis, and proton secretory defects were shown by a failure to lower the urine pH during marked acidemia induced by NH4Cl loading and an abnormally low urine-blood pCO2 difference during bicarbonate administration. While stainings with the anti-H(+)-ATPase antibody in NC and DC were strongly positive in intercalated cells in the connecting tubules and collecting ducts, the tissues from both patients with dRTA were devoid of any anti-H(+)-ATPase staining in the intercalated cells. These results support that the pathophysiologic basis of impaired H+ secretion in idiopathic classic dRTA as well as Sjögren's syndrome is the absence of intact H(+)-ATPase pumps in the intercalated cells.

Acidosis, Renal Tubular↗
PubMed1997

Synaptojanin inhibition of phospholipase D activity by hydrolysis of phosphatidylinositol 4,5-bisphosphate.

A 150-kDa protein that inhibits phospholipase D (PLD) activity stimulated by ADP-ribosylation factor and phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2) was previously purified from rat brain. The sequences of peptides derived from the purified PLD inhibitor now identify it as synaptojanin, a nerve terminal protein that has been implicated in the endocytosis of fused synaptic vesicles and shown to be a member of the inositol polyphosphate 5-phosphatase family. Further characterization of the enzymatic properties of synaptojanin now shows that it hydrolyzes only the 5-phosphate from inositol 1,4,5-trisphosphate (I(1,4,5)P3) and that it does not catalyze the dephosphorylation of either I(1,3,4)P3 or inositol 1, 4-bisphosphate. However, synaptojanin hydrolyzes both the 4- and 5-phosphates of PI(4,5)P2 and the 4-phosphate of phosphatidylinositol 4-phosphate, converting both compounds to phosphatidylinositol. Magnesium is required for the hydrolysis of I(1,4,5)P3, but not for that of phosphoinositides, by synaptojanin. The inhibition of PLD by synaptojanin is attributable to its ability to hydrolyze PI(4,5)P2. Synaptojanin did not inhibit PLD in the absence of PI(4,5)P2, and the extent of PLD inhibition was related to the extent of PI(4,5)P2 hydrolysis in substrate vesicles. It has been proposed that the biosynthesis of PI(4,5)P2 and the activation of PLD by ADP-ribosylation factor constitute a positive loop to increase rapidly the concentrations of PI(4,5)P2 and phosphatidic acid (PA) during membrane vesiculation. The PA thus produced, probably together with PI(4,5)P2, facilitates vesicle coat assembly. The hydrolysis of PI(4,5)P2, and consequent inhibition of PLD, by synaptojanin might therefore constitute a mechanism to halt the positive loop connecting PI(4,5)P2 and PA during the endocytotic cycle of synaptic vesicles and serve as a signal for uncoating.

Amino Acid Sequence↗
PubMed1997

Inhibition of phospholipase D by clathrin assembly protein 3 (AP3).

In the accompanying paper (Chung, J.-K., Sekiya, F., Kang, H.-S., Lee, C., Han, J.-S., Kim, S. R., Bae, Y. S., Morris, A. J., and Rhee, S. G. (1997) J. Biol. Chem. 272, 15980-15985), synaptojanin is identified as a protein that inhibits phospholipase D (PLD) activity stimulated by ADP-ribosylation factor and phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2). Here, the purification from rat brain cytosol of another PLD-inhibitory protein that is immunologically distinct from synaptojanin is described, and this protein is identified as clathrin assembly protein 3 (AP3) by peptide sequencing and immunoblot analysis. AP3 binds both inositol hexakisphosphate and preassembled clathrin cages with high affinity. However, neither inositol hexakisphosphate binding nor clathrin cage binding affected the ability of AP3 to inhibit PLD. AP3 also binds to PI(4,5)P2 with low affinity. But the PI(4,5)P2 binding was not responsible for PLD inhibition, because the potency and efficacy of AP3 as an inhibitor of PLD were similar in the absence and presence of PI(4,5)P2. A bacterially expressed fusion protein, glutathione S-transferase-AP3 (GST-AP3), also inhibited PLD with a potency equal to that of brain AP3. The inhibitory effect of AP3 appeared to be the result of direct interaction between AP3 and PLD because PLD bound GST-AP3 in an in vitro binding assay. Using GST fusion proteins containing various AP3 sequences, we found that the sequence extending from residues Pro-290 to Lys-320 of AP3 is critical for both inhibition of and binding to PLD. The fact that AP3 is a synapse-specific protein indicates that the AP3-dependent inhibition of PLD might play a regulatory role that is restricted to the rapid cycling of synaptic vesicles.

Adaptor Protein Complex 3↗
PubMed1997

The role of an amygdalo-nigrostriatal pathway in associative learning.

The present study examined the role of an amygdalo-nigrostriatal pathway in associative learning. An asymmetrical lesion model was used to test whether a circuit from the amygdala central nucleus to the dorsolateral striatum, via the substantia nigra, is critical for mediating conditioned orienting responses. Rats with an asymmetrical lesion, consisting of neurotoxic removal of central nucleus neurons in one hemisphere and depletion of the dopamine innervation of the dorsolateral striatum in the contralateral hemisphere, failed to acquire conditioned orienting responses. In contrast, the asymmetrical lesion had no effect on spontaneous orienting or learning another response directed to the source of the food unconditioned stimulus in the same task. A second experiment tested the effect of reversible inactivation of the dorsolateral striatum contralateral to a neurotoxic central nucleus lesion on acquisition of the conditioned orienting response. Although inactivation did not affect spontaneous orienting, rats failed to acquire the conditioned orienting response during sessions in which inactivation occurred. Immediately after the inactivation procedure was terminated, however, a significant increase in orienting to the conditioned stimulus was evident. These data support the interpretation that the dorsolateral striatum provides a route for the expression of the conditioned orienting response but is not essential for acquisition of this learned behavior.

Amygdala↗
PubMed1997

Mutagenic activity and specificity of hydrogen peroxide in the ad-3 forward-mutation test in two-component heterokaryons of Neurospora crassa.

In the ad-3 forward-mutation test, hydrogen peroxide was at best a weak mutagen in nongrowing conidia from a DNA repair-proficient heterokaryon (H-12, uvs-2+/uvs-2+) but was a moderate mutagen in nongrowing conidia from a DNA-repair-deficient heterokaryon (H-59, uvs-2/uvs-2) over a narrow range of high concentrations. H-59 also was more sensitive than H-12 to the killing activity of hydrogen peroxide at high concentrations. Thus, a DNA-repair pathway, of which the gene product of the uvs-2+ allele is a part, appears to be involved in the repair of hydrogen peroxide-induced DNA lesions at low survival in these strains. There was slightly, but significantly, more killing by hydrogen peroxide of nongrowing conidia from H-12 and H-59 in the presence of O2 than in the absence of O2 (presence of N2). Thus, the killing activity of hydrogen peroxide was enhanced by O2. The Mutational Spectra of hydrogen peroxide-induced ad-3 mutants shows that hydrogen peroxide induced mainly gene/point mutations but also some multilocus deletion mutations in H-12 and H-59. Multiple-locus mutations occurred only in H-59, but the frequency was very low. The frequencies of the 3 kinds of intracistronic complementation pattern among ad-3BR mutants (gene/point mutations) suggest that hydrogen peroxide induced both base-pair substitutions and frameshift mutations in both strains.

DNA Damage↗
PubMed1997

Involvement of endogenous orphanin FQ in electroacupuncture-induced analgesia.

Recent studies suggest that the novel opioid peptide orphanin FQ (OFQ) is involved in pain modulation. We found that intracerebroventricular (i.c.v.) administration of OFQ in the rat produced a dose-dependent antagonism of the analgesia induced by 100 Hz electroacupuncture (EA) stimulation as measured in the radiant heat tail-flick assay. Antisense oligonucleotides injected i.c.v. potentiated EA analgesia, presumably by interfering with the expression of the OFQ receptor in brain. These results suggest that endogenous OFQ exerts a tonic antagonistic effect on EA-induced analgesia. No such antagonism was observed when OFQ was injected intrathecally (i.t.). Rather, it appears that spinal OFQ produced a marked analgesic effect and enhanced EA-induced analgesia. These findings are consistent with the experimental results obtained in rats where morphine-induced analgesia is antagonized by i.c.v. OFQ and potentiated by i.t. OFQ.

Analgesia↗
PubMed1997

Rats with decreased brain cholecystokinin levels show increased responsiveness to peripheral electrical stimulation-induced analgesia.

Using the P77PMC strain of rat, which is genetically prone to audiogenic seizures, and also has decreased levels of cholecystokinin (CCK), we examined the analgesic response to peripheral electrical stimulation, which is, in part, opiate-mediated. A number of studies have suggested that CCK may function as an antagonist to endogenous opiate effects. Therefore, we hypothesized that the P77PMC animals would show an enhanced analgesic response based on their decreased CCK levels producing a diminished endogenous opiate antagonism. We found that the analgesic effect on tail flick latency produced by 100 Hz peripheral electrical stimulation was more potent and longer lasting in P77PMC rats than in control rats. Moreover, the potency of the stimulation-produced analgesia correlated with the vulnerability to audiogenic seizures in these rats. We were able to block the peripheral electrical stimulation-induced analgesia (PSIA) using a cholecystokinin octapeptide (CCK-8) administered parenterally. Radioimmunoassay showed that the content of CCK-8 in cerebral cortex, hippocampus and periaqueductal gray was much lower in P77PMC rat than in controls. These results suggest that low CCK-8 content in the central nervous system of the P77PMC rats may be related to the high analgesic response to peripheral electrical stimulation, and further support the notion that CCK may be endogenous opiate antagonist.

Acoustic Stimulation↗
PubMed1997

Biomechanical changes of the wrist flexor and extensor tendons following loss of scaphoid integrity.

Loss of integrity of the scaphoid may change the motion center of the entire carpus, and deformities from scaphoid fractures may alter the location of motor tendons of the wrist, thus altering their biomechanics. The goal of this study was to clarify biomechanical changes in these tendons following loss of scaphoid integrity. Excursions and moment arms of the principal flexor and extensor tendons of the wrist were investigated in seven cadaveric upper extremities in intact wrists after simulation of scaphoid waist fracture and after removal of the proximal scaphoid. Excursions of the flexor carpi radialis and ulnaris, extensor carpi radialis longus and brevis, and extensor carpi ulnaris tendons were measured with rotary potentiometers during wrist flexion-extension and radioulnar deviation. Simultaneously, wrist joint angulation was recorded. Moment arms of the tendons were derived from tendon excursions and joint motion. After scaphoid fracture, the moment arms of the flexor carpi radialis and extensor carpi ulnaris tendons increased significantly during wrist flexion-extension, whereas the moment arms of the extensor carpi radialis longus and brevis tendons decreased significantly. After proximal scaphoid excision, the moment arms of the extensor carpi radialis longus and brevis tendons again decreased significantly during wrist flexion-extension. The moment arms of the flexor carpi radialis and extensor carpi radialis brevis tendons increased significantly during radioulnar deviation, whereas those of the wrist motors on the ulnar side decreased. These findings indicate the importance of the integrity of the scaphoid in maintaining normal biomechanics of motor tendons of the wrist. An increase in the moment arm of the radial wrist flexor along with a decrease in moment arms of the radial extensors constitutes as etiology for persistent angulation of the scaphoid and the humpback deformity. In addition, disturbing the biomechanics of the wrist motor tendons predisposes the carpal joints to abnormal loading, potentially contributing to the development of carpal joint degeneration.

Aged↗
PubMed1997

Temporal changes and reversibility of carbamylated hemoglobin in renal failure.

The detection of carbamylated hemoglobin (CarHb) is known to be useful in determination of the chronicity of uremia. However, the time course of the in vivo reaction between isocyanic acid and terminal valine residues of the hemoglobin chain is not clearly defined. To assess the temporal relationship and reversibility of carbamylation, we prospectively measured CarHb as micrograms of valine hydantoin per gram of hemoglobin (microg VH/g Hb) by high-performance liquid chromatography in 37 patients with acute renal failure (ARF), 53 patients with chronic renal failure (CRF), and six patients with successful kidney transplant. Patients with ARF had a lower median CarHb concentration (53.2 microg VH/g Hb; range, 24.6 to 97.1 microg VH/g Hb) than those with CRF (115.0 microg VH/g Hb; range, 34.6 to 286.5 microg VH/g Hb; P < 0.01), but had a higher value (53.2 microg VH/g Hb; range, 24.6 to 97.1 microg VH/g Hb) than 31 normal controls (36.6 microg VH/g Hb; range, 19.9 to 62.9 microg VH/g Hb; P < 0.05). In patients with ARF, the CarHb concentration positively correlated with the number of days of illness (r = 0.74; P < 0.01). The patients with ARF of 10 or more days' duration had a higher CarHb concentration (68.7 microg VH/g Hb; range, 36.0 to 93.9 microg VH/g Hb) than those with a shorter duration of ARF (33.7 microg VH/g Hb; range, 24.6 to 55.8 microg VH/g Hb; P < 0.01) despite similar blood urea nitrogen and serum creatinine values. However, they had a lower concentration of CarHb (68.7 microg VH/g Hb; range, 36.0 to 93.9 microg VH/g Hb) than CRF patients with comparable serum creatinine values (112.5 microg VH/g Hb; range, 34.6 to 286.5 microg VH/g Hb; P < 0.01). In patients with a kidney transplant, CarHb concentration declined by 19.7% (range, 12.3% to 35.6%) within 2 to 3 weeks after receiving the graft, while the level of hemoglobin increased by 25% (range, 4.0% to 46.6%) during the same period. Therefore, the total blood CarHb (CarHb x hemoglobin concentration) was not significantly changed. We concluded that the in vivo reaction of carbamylation of hemoglobin progressed during the period of uremia, and there might exist some irreversible preformed CarHb in advanced stages of CRF.

Acute Kidney Injury↗
PubMed1997

Cholecystokinin antisense RNA increases the analgesic effect induced by electroacupuncture or low dose morphine: conversion of low responder rats into high responders.

The analgesic effects of the rat in response to electroacupuncture (EA) or low-dose morphine (3 mg/kg) show marked individual variations. In the midbrain periaqueductal gray (PAG) of the rat, the content of the neuropeptide cholecystokinin octapeptide (CCK-8) was found to be significantly higher in the low responder (LR) rats as compared to that in the high responders (HR). Since PAG has been shown to be a strategic site for CCK-8 to exert an anti-opioid action, a high CCK content in PAG may account for the low analgesic responsiveness to EA and morphine. In order to block the expression of the gene encoding preproCCK in the brain, antisense CCK expression vector pSV2-CCKAS was microinjected into the lateral cerebral ventricle of the rat, leading to a decrease of the CCK-mRNA as well as the CCK-8 content in rat brain. This effect started 4 days after the intracerebroventricular (i.c.v.) injection of the antisense expression vector, and lasted no more than 1 week. This procedure was shown to be very effective in converting LR rats into HR for EA analgesia and morphine analgesia, and also delayed the development of tolerance elicited by prolonged EA stimulation or repeated morphine administration. The time course of the augmentation of opioid analgesia (4-6 days after the i.c.v. injection of the expression vector) paralleled the decrease of the brain CCK-8 content. The results argue that blocking the CCK gene expression in the brain may tilt the balance between opioid and anti-opioid peptides in favor of the former, thus strengthening the EA analgesia and morphine analgesia, and delaying the development of opioid tolerance.

Acupuncture Analgesia↗
PubMed1997

Lipofectin-facilitated transfer of cholecystokinin gene corrects behavioral abnormalities of rats with audiogenic seizures.

To evaluate the potential for lipofectin-mediated central nervous system gene transfer, the plasmid coding for cholecystokinin was administered intracerebroventricularly to rats, which have congenital audiogenic seizures and high responses to peripheral electric stimulation-induced analgesia. Previous studies had shown that low brain cholecystokinin levels may be the neurochemical variable of rat's audiogenic seizure and high responses to the analgesia because cholecystokinin is an anticonvulsant and anti-opioid neuropeptide. Gene transfer of cholecystokinin corrected the increased susceptibility to audiogenic seizures and the high responses to analgesia for about one week. Similar administration of plasmid expressing beta-galactosidase indicated that the vector mainly transfected ependymal cells lining the ventricle and pia mater cells. The increased cholecystokinin messenger RNA and immunoreactivity in the hippocampus following stereotactic intrahippocampal administration of cholecystokinin plasmid was also demonstrated with in situ hybridization and immunohistochemistry techniques. These results suggest that lipofectin-mediated gene transfer will be useful for studies of brain function, the modification of behavior and gene therapy for central nervous system disorders.

Acoustic Stimulation↗
PubMed1997

Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat.

1. The present study was designed to investigate further the effects of the newly discovered orphanin FQ (OFQ)-the endogenous ligand for the orphan opioid receptor (called, e.g., ORL, and LC132)-on pain modulation in the rat. We used the tail-flick assay as a nociceptive index. 2. When injected into a cerebral ventricle, OFQ (4 fmol-10 nmol) has no effect on basal tail-flick latency by itself at any dose, but dose-dependently antagonizes systemic morphine analgesia (400 fmol 50 nmol). 3. Injected intrathecally, OFQ (3 and 10 nmol) displayed an analgesic effect without producing motor dysfunction, and potentiated morphine analgesia (1 and 10 nmol). 4. The anti-opioid effect of OFQ in rat brain and the high level of expression of LC132/ORL, receptor in the locus coeruleus indicated a possible role of OFQ in the precipitation of opiate withdrawal symptoms. However, no such precipitation was observed by OFQ in morphine-dependent rats.

Analgesia↗
PubMed1997

Magnetic resonance imaging of the kidney in hemorrhagic fever with renal syndrome: its histopathologic correlation.

We present 2 cases of magnetic resonance imaging in hemorrhagic fever with renal syndrome and their histopathologic findings. The low signal intensities along the renal outer medulla in T2-weighted images are persistent ex vivo as well as in vivo, and these are the radiologic counterpart of medullary congestion and hemorrhage. We will discuss the significance of the imaging in the fields of the medical renal disease such as acute renal failure and review the mechanisms of acute renal failure in hemorrhagic fever with renal syndrome.

Adult↗