Biomedical subjects

S Oh

Publications and source records attributed to S Oh.

At least 91 records · Page 5Linked to original sources

PubMed1998

Effects of ginseng total saponin on morphine-induced hyperactivity and conditioned place preference in mice.

A single or repeated administration of morphine in mice produced hyperactivity, conditioned place preference (CPP) and postsynaptic dopamine (DA) receptor supersensitivity. The hyperactivity induced by morphine was evidenced by measuring the enhanced ambulatory activity using a tilting-type ambulometer. CPP effects were evaluated assessing the increased time spent by the mice to morphine and the inhibition of CPP by the decreased time spent by the mice in the white compartment. Postsynaptic DA receptor supersensitivity in mice displaying a morphine-induced CPP was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine (2 mg/kg, s.c.). The intraperitoneal injection of ginseng total saponin (GTS) from the root of Panax ginseng C.A. Meyer (Araliaceae), prior to and during the morphine treatment in mice inhibited morphine-induced hyperactivity and CPP. GTS inhibited the development of postsynaptic DA receptor supersensitivity. A single dose administration of GTS also inhibited apomorphine-induced climbing behavior, showing the antidopaminergic action of GTS at the postsynaptic DA receptor. These results suggest that the development of morphine-induced CPP may be associated with the enhanced DA receptor sensitivity and that GTS inhibition of the morphine-induced hyperactivity and CPP may be closely related with the inhibition of dopaminergic activation induced by morphine.

Animals↗

PubMed1998

Changes in NMDAR2 subunit mRNA levels during pentobarbital tolerance/withdrawal in the rat brain: an in situ hybridization study.

Little is known about the functional modulation of NMDA receptor subunits at the molecular level. Therefore, a series of experiments were conducted to elucidate more fully the role of NMDA receptor subtypes in pentobarbital tolerance and withdrawal. We investigated the influence of centrally administered pentobarbital on the regulation of mRNA levels of the family of NMDA receptor 2 (NR2) subtypes (NR2A, NR2B, and NR2C) by in situ hybridization histochemistry in rat brain. Animals were rendered tolerant by continuous intracerebroventricular (i.c.v.) infusion with pentobarbital (300 microg/10 microl/hr for 6 days) through pre-implanted cannulae connected to osmotic mini-pumps, and dependent, by abrupt withdrawal from pentobarbital. The NR2A subunit mRNA was increased in cortical areas in pentobarbital tolerant and withdrawal rats. In contrast, the NR2B mRNA was decreased in parietal cortex and hippocampus in both tolerance and withdrawal rats. The level of NR2C mRNA was increased in withdrawal rats, while there was no change in tolerant rats. These results indicate that continuous i.c.v. infusion with pentobarbital alters NR2 subunit mRNA expression in the rat brain, suggesting that NR2 subunits may play an important role in the development of tolerance to and withdrawal from pentobarbital.

Animals↗

PubMed1998

Changes in [3H]forskolin binding to adenylate cyclase and [3H]phorbol dibutyrate binding to protein kinase C in pentobarbital tolerant/dependent rats.

These studies were designed to examine the effect of chronic administration of pentobarbital on activity of adenylate cyclase (AC) and protein kinase C (PKC) in the rat brain by autoradiography. Recently, it has been suggested that the phosphorylation of specific proteins may be involved in the development of physical dependence. An experimental model of barbiturate tolerance and dependence was developed using i.c.v. infusion of pentobarbital (300 microg/10 microl/hr for 7 days) by osmotic minipumps and abrupt withdrawal from pentobarbital. The levels of [3H]forskolin binding were elevated (28-67%) in cortex, thalamus, dentate gyrus, hippocampal CA3 and cerebellum of the pentobarbital withdrawal animals, while these changes were not observed in tolerant rats. The levels of [3H]phorbol dibutyrate binding were highly elevated (38-65%) in the region of cortex, caudate putamen, septum, thalamus, dentate gyrus, and cerebellum of rats withdrawal from pentobarbital. These results show that the levels of AC and PKC were significantly elevated in pentobarbital withdrawal rats, and suggest that the levels of AC and PKC are altered in a region-specific manner during pentobarbital withdrawal.

Adenylyl Cyclases↗

PubMed1998

The conditional binomial test revisited for clinical trials.

McNemar's test is used to test the hypothesis that one treatment is better than another in a matched-pair design for binary outcomes. The conditional binomial test in such a matched-pair design is the exact McNemar test. However, in many clinical trials, one wants to establish equivalency between two treatments. We discuss how to use a conditional binomial test to establish equivalency between two treatments in a matched-pair design. Sample size and power determination for each conditional binomial test are calculated. Some statistical properties of the tests are analyzed through Monte Carlo simulation.

Binomial Distribution↗

PubMed1998

Optimization of intensity modulated beams with volume constraints using two methods: cost function minimization and projections onto convex sets.

For accurate prediction of normal tissue tolerance, it is important that the volumetric information of dose distribution be considered. However, in dosimetric optimization of intensity modulated beams, the dose-volume factor is usually neglected. In this paper we describe two methods of volume-dependent optimization for intensity modulated beams such as those generated by computer-controlled multileaf collimators. The first method uses a volume sensitive penalty function in which fast simulated annealing is used for cost function minimization (CFM). The second technique is based on the theory of projections onto convex sets (POCS) in which the dose-volume constraint is replaced by a limit on integral dose. The ability of the methods to respect the dose-volume relationship was demonstrated by using a prostate example involving partial volume constraints to the bladder and the rectum. The volume sensitive penalty function used in the CFM method can be easily adopted by existing optimization programs. The convex projection method can find solutions in much shorter time with minimal user interaction.

Dose-Response Relationship, Radiation↗

PubMed1998

Impaired G protein function in gallbladder muscle from progesterone-treated guinea pigs.

This study was designed to elucidate the mechanism of action of progesterone on gallbladder smooth muscle in guinea pigs. Adult male guinea pigs were treated with either progesterone (2 mg.kg-1.day-1) or saline for 7 days. Gallbladder muscle cells were isolated by enzymatic digestion with collagenase. Contractile responses to agonists were expressed as percent shortening from control cell length. [35S]guanosine 5'-O-(3-thiotriphosphate) ([35S]GTP gamma S)-binding properties of G proteins were assessed in crude membranes of gallbladder muscle with or without cholecystokinin octapeptide (CCK-8) stimulation. Gallbladder muscle cells from progesterone-treated guinea pigs exhibited an impaired contractile response to CCK-8, GTP gamma S, or aluminum fluoride but a normal response to potassium chloride or D-myo-inositol 1,4,5-trisphosphate compared with controls. Western blot analysis of gallbladder muscle revealed the presence of Gi1-2, Gi3, Gq/11, and Gs proteins. The maximal contraction induced by CCK-8 was blocked by pertussis toxin and Gi alpha 3-specific antibodies, but not by Gi alpha 1-2 or Gq/11 alpha antibodies. CCK-8 caused a significant increase in [35S]GTP gamma S binding to Gi alpha 3, but not to Gq/11 alpha or Gi alpha 1-2. The stimulation of Gi alpha 3 binding, however, was significantly reduced in gallbladder muscle membranes from progesterone-treated guinea pigs compared with that in control animals. In conclusion, progesterone might cause gallbladder hypomotility by downregulating Gi3 proteins.

Aluminum Compounds↗

PubMed1997

Differential modulation of short and long latency sensory responses in the SI cortex by IL-6.

The effects of topical application of interleukin-6 (IL-6) on the short and long latency evoked unit responses of the neurones in the primary somatosensory (SI) cortex were determined quantitatively in anaesthetized rats. IL-6 (0.01, 0.1, 1.0 units) significantly suppressed (-15.13 +/- 3.4%) short latency afferent sensory responses, while it induced profound facilitation (+464.74 +/- 132.7%) of long latency responses in a dose-dependent manner. IL-6-induced afferent modulations fully recovered by 60 min after drug administration. In control experiments, saline solution containing 0.2% bovine serum albumin, used as a vehicle, did not affect afferent sensory transmission. Implications of these results are discussed with reference to the different somatosensory functions of short and long latency response components in the SI cortex.

Administration, Topical↗

PubMed1997

Interhemispheric modulation of sensory transmission in the primary somatosensory cortex of rats.

Single unit responses of the primary somatosensory (SI) cortical neurons to the stimulation of the forepaw single digit were monitored in anesthetized rats before and after subcutaneous injection of lidocaine to an ipsilateral homologous receptive field (IHRF). Quantitative determination of the temporal changes of afferent sensory transmission was done by analyzing poststimulus time histograms of unit responses. Temporary deafferentation to the IHRF induced immediate, but reversible suppression of afferent sensory transmission in the SI cortex and this suppression lasts up to 35 min post-deafferentation period (during 10-15 min, -21.81 +/- 5.9%, P < 0.01). This result suggests that temporary absence of afferent inflow from the digit to the SI cortex may exert interhemispheric modulation of afferent sensory transmission in the opposite somatosensory cortex of anesthetized rats.

Afferent Pathways↗

PubMed1997

Identification of the autophosphorylation sites of the Xenopus laevis Pim-1 proto-oncogene-encoded protein kinase.

Pim-1 is an oncogene-encoded serine/threonine kinase expressed primarily in cells of the hematopoietic and germ line lineages. Previously identified only in mammals, pim-1 cDNA was cloned and sequenced from the African clawed frog Xenopus laevis. The coding region of Xenopus pim-1 encoded a protein of 324 residues, which exhibited 64% amino acid identity with the full-length human cognate. Xenopus Pim-1 was expressed in bacteria as a glutathione S-transferase (GST) fusion protein and in COS cells. Phosphoamino acid analysis revealed that recombinant Pim-1 autophosphorylated on serine and threonine and to a more limited extent on tyrosine. Electrospray ionization mass spectroscopy was undertaken to locate these phosphorylation sites, and the primary autophosphorylation site of GST-Pim-1 was identified as Ser-190 with Thr-205 and Ser-4 being minor sites. Ser-190, which immediately follows the high conserved Asp-Phe-Gly motif in catalytic subdomain VII, is also featured in more than 20 other protein kinases. To evaluate the importance of the Ser-190 site on the phosphotransferase activity of Pim-1, Ser-190 was mutated to either alanine or glutamic acid, and the constructs were expressed in bacteria as GST fusion proteins and in COS cells. These mutants confirmed that Ser-190 is a major autophosphorylation site of Pim-1 and indicated that phosphorylation of Pim-1 on the Ser-190 residue may serve to activate this kinase.

Amino Acid Sequence↗

PubMed1997

Increased release of excitatory amino acids in rat locus coeruleus in kappa-opioid agonist dependent rats precipitated by nor-binaltorphimine.

Extracellular fluid levels of glutamate and aspartate in the locus coeruleus (LC) during nor-binaltorphimine (nor-BNI)-precipitated withdrawal from butorphanol, (5alpha,7alpha,8beta)-(+)-N-methyl-N-[7-(1-pyrrolidiny l)-1-oxaspiro [4,5] dec-8-yl]-benzeneacetamide (U-69,593), or morphine were measured in rats. When the microdialysis probe was located in the core of the LC, increases in glutamate and aspartate were noted after nor-BNI (48 nmol/50 microl, LC)-precipitated withdrawal in rats that had been intracerebroventricularly infused with butorphanol (26 nmol/1 microl/h) or U-69,593 (26 nmol/10 microl/h) for 3 days. The glutamate and aspartate levels in the LC markedly increased in the butorphanol- or U-69,593-dependent rats within 60 min following administration of nor-BNI. However, there was no significant increase in levels of glutamate, and only a slight increase in levels of aspartate, after nor-BNI treatment of the morphine (26 nmol/1 microl/h)-infused rats. Behavioral signs of withdrawal (teeth-chattering, wet-dog shakes, etc.) were observed following nor-BNI challenge in the butorphanol- or U-69,593-infused rats, with only minimal signs in the morphine-infused rats, and none in the saline-infused controls. These results directly suggest that kappa-opioid receptors and excitatory amino acids within the LC mediate withdrawal in animals dependent on butorphanol or U-69,593, but not on morphine.

Animals↗

PubMed1997

cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein.

NHE3 is the Na+/H+ exchanger located on the intestinal and renal brush border membrane, where it functions in transepithelial Na+ absorption. The brush border Na+ absorptive process is acutely inhibited by activation of cAMP-dependent protein kinase, but the molecular mechanism of this inhibitory effect is poorly understood. We have identified two regulatory proteins, E3KARP and NHERF, that interact with NHE3 to enable cAMP to inhibit NHE3. The two regulatory proteins are structurally related, sharing approximately 50% identity in amino acid sequences. It has been previously shown that when NHE3 is transfected into PS120 fibroblasts or Caco-2 cells, cAMP failed to inhibit NHE3 activity. Northern blot analysis showed that both PS120 and Caco-2 cells lacked the expression of both E3KARP and NHERF. In contrast, other cell lines in which cAMP inhibits NHE3, including OK, CHO, and LLC-PK1 cells, expressed NHERF-related regulatory proteins. To determine their functions in cAMP-dependent inhibition of NHE3, E3KARP and NHERF were transfected into PS120/NHE3 fibroblasts. Transfection in PS120/NHE3 fibroblasts with either NHERF or E3KARP reconstituted cAMP-induced inhibition of NHE3, resulting in 25-30% inhibition in these cells.

Amino Acid Sequence↗

PubMed1997

Gallbladder relaxation in patients with pigment and cholesterol stones.

BACKGROUND & AIMS: Gallbladders with cholesterol stones show a defective contraction in response to agonists. The aim of this study was to investigate the muscle relaxation of human gallbladders with cholesterol or black pigment gallstones. METHODS: Gallbladder relaxation was measured in vitro using muscle strips and single muscle cells. Relaxation was expressed as percent inhibition of either basal active tension in strips or maximal cell contraction induced by diacylglycerol. The production of cyclic nucleotides was determined using a 125I-labeled radioimmunoassay kit. RESULTS: Frequency-dependent relaxation evoked by electrical field stimulation was significantly lower in gallbladders with cholesterol stones than in gallbladders with pigment stones. Relaxation and adenosine 3',5'-cyclic monophosphate (cAMP) production induced by isoproterenol, vasoactive intestinal peptide, and forskolin were also significantly decreased in gallbladders with cholesterol stones. However, the relaxation in response to 8-bromo-cAMP, nitric oxide (NO), and the NO donor S-nitroso-N-acetylpenicillamine (SNAP), which circumvent plasma membrane receptors and directly activate intracellular mechanisms, was similar in gallbladders with cholesterol and pigment stones. Guanosine 3',5'-cyclic monophosphate production induced by NO and SNAP was also similar. CONCLUSIONS: Human gallbladder muscle from specimens with cholesterol stones show an impaired relaxation and lower cAMP production compared with specimens with pigment stones. The muscle defect(s) responsible for this impairment seem to be in the plasma membranes.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1997

Blockade by naloxone of cocaine-induced hyperactivity, reverse tolerance and conditioned place preference in mice.

Cocaine-induced hyperactivity was inhibited by a single administration of naloxone (2 and 5 mg/kg, i.p.), an opioid receptor antagonist, and naloxone administered prior to and during the chronic injection of cocaine attenuated the development of both cocaine-induced reverse tolerance and conditioned place preference (CPP). Dopamine (DA) receptor supersensitivity which developed in cocaine-induced reverse tolerant or CPP mice, was also inhibited by naloxone. Furthermore, naloxone reduced an apomorphine-induced striatal dopaminergic action, climbing behavior. Therefore, the present studies suggest that cocaine-induced dopaminergic behaviors, such as hyperactivity, reverse tolerance and CPP, may be commonly produced via activation of an opioid receptor. The development of DA receptor supersensitivity may be a possible common mechanism of cocaine-induced reverse tolerance and CPP, since cocaine-induced changes in sensitivity to apomorphine, as well as apomorphine-induced climbing behavior in mice, were both inhibited by naloxone.

Animals↗

PubMed1997

Dual effects of NMDA-induced intracellular Ca2+ elevations on cGMP levels in cultured cerebellar granule neurons.

1. Cyclic GMP (cGMP) levels were markedly elevated by N-methyl-D-aspartate (NMDA) within 1-3 min of incubation, then gradually decreased with incubation time. 2. The NMDA-induced intracellular Ca2+ elevations showed maximal levels just after adding NMDA and were maintained for 60 min. 3. NMDA did not show augmentation of cGMP elevation with sodium nitroprusside (SNP), rather it decreased the SNP-induced cGMP elevation after exposure for 60 min. 4. The NMDA-induced elevation of cGMP was remarkably augmented with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 1mM), after 60 min of incubation.

1-Methyl-3-isobutylxanthine↗

PubMed1997

Changes in permeability caused by connexin 32 mutations underlie X-linked Charcot-Marie-Tooth disease.

The relationship between the loss of connexin 32 function and clinical manifestations of X-linked Charcot-Marie-Tooth (CMTX) disease is unknown. Here, we report that eight of nine CMTX mutations investigated form channels with measurable electrical conductance. Single-channel studies of two mutations demonstrate reduced junctional permeability caused by a decrease in either pore size (S26L) or open channel probability (M34T) that favors residency in a low-conductance substate. Permeation of second messengers such as cAMP through reflexive gap junctions between adjacent cytoplasmic loops of myelinating Schwann cells is likely to be reduced or absent in these channels. We propose that CMTX mutations impair the transduction of signals arising from normal glial-neuronal interactions and thereby cause demyelination and axonal degeneration.

Animals↗

PubMed1997

Role of NMDA receptors in pentobarbital tolerance/dependence.

Effects of continuous pentobarbital administration on binding characteristics of [3H]MK-801 in the rat brain were examined by autoradiography. Animals were rendered tolerant to pentobarbital using i.c.v. infusion of pentobarbital (300 micrograms/10 microliters/hr for 7 days) by osmotic minipumps and dependent by abrupt withdrawal from pentobarbital. The levels of [3H]MK-801 binding were elevated in rats 24-hr after withdrawal from pentobarbital while there were no changes except in septum and anterior ventral nuclei in tolerant rats. For assessing the role of NMDA receptor in barbiturate action, an NMDA receptor antagonist (MK-801, 2.7 femto g/10 microliters/hr) was co-infused with pentobarbital. The pentobarbital-infused group had a shorter duration of pentobarbital-induced loss of righting reflex (sleeping time) than that of the control group, and MK-801 alone did not affect the righting reflex. However, co-infusion of MK-801 blocked hyperthermia, and prolonged the onset of convulsions induced by t-butylbicyclophosphorothionate (TBPS) in pentobarbital withdrawal rats. In addition, elevated [35S]TBPS binding was significantly attenuated by co-infusion with MK-801. These results suggest the involvement of NMDA receptor up-regulation in pentobarbital withdrawal and that the development of dependence can be attenuated by the treatment of subtoxic dose of MK-801.

Animals↗

PubMed1997

Conformal radiotherapy computation by the method of alternating projections onto convex sets.

Synthesis of beam profiles for a given dose prescription is a central problem in radiotherapy. Care must be taken in the beam design to expose the tumour volume at a high level, to avoid significant irradiation of critical organs, and to minimize exposure of all other tissue. Use of the synthesis procedure known as alternating projections onto convex sets (POCS) is shown to be a viable approach to beam design. POCS is a powerful tool for signal and image restoration and synthesis. Convex sets of signals obeying desired constraint sets are first specified. Then, by repeated projections onto these sets, convergence is to a signal obeying all desired constraints if the constraint sets have a finite intersection. In this paper we apply the method of POCS to conformal radiotherapy dose computation. The performance of the method is shown through three representative examples.

Algorithms↗

PubMed1997

Force-frequency effect is a powerful determinant of myocardial contractility in the mouse.

The effects of heart rate (HR) on myocardial contractility in the mouse heart in situ were first investigated in open-chest mice (n = 7) by left ventricular (LV) catheter-tip micromanometry. HR was first slowed with a sinus node inhibitor (zatebradine), and atrial pacing to progressively increase the HR caused a positive inotropic response (assessed by maximum positive first derivative of LV pressure, LV dP/dtmax) up to a HR of 282 beats/min with the onset of a descending limb of the force-frequency relation (FFR) at 332 beats/min. beta-Adrenergic receptor stimulation (dobutamine) shifted upward and significantly steepened the positive FFR and increased HR at the onset of the descending limb to 402 beats/min. HR and LV dP/dtmax were then studied in closed-chest mice without pacing during recovery from anesthesia (n = 7), and during rest and intermittent physical activity the FFR was linear and positive up to 600 beats/min. HR was then progressively slowed with zatebradine, and the points at rest and during activity fell on the same linear relation. Thus we conclude the following: 1) in the open-chest anesthetized mouse, a positive FFR was amplified by beta-adrenergic receptor stimulation, and 20 in the mouse recovering from anesthesia the sinus node rate remained a critical determinant of myocardial contractility, without a descending limb of the FFR.

Anesthesia, General↗