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Biomedical subjects

T F Lee

Publications and source records attributed to T F Lee.

At least 19 recordsLinked to original sources
PubMed2001

Effect of ginseng saponins on beta-amyloid-suppressed acetylcholine release from rat hippocampal slices.

In view of the facts that ginseng has been shown to improve age-related memory deficits and beta-amyloid-related peptides have been suggested to play a significant role in memory degeneration in the elderly, the present study was carried out to examine the effect of various ginsenosides on beta-amyloid peptides-modulated acetylcholine (ACh) release, a key neurotransmitter in memory processing, from the hippocampal slices. Addition of beta-amyloid fragment(25 - 35) (0.01 - 1 microM) in the superfusion medium suppressed the K(+)-evoked [(3)H]-ACh release from the rat hippocampal slices in a concentration-related manner and about 40 % reduction in ACh outflow was observed when incubating with the highest concentration of an amyloid fragment (1 microM). Inclusion of the ginsenoside components Rb(1) (0.1 microM), but not Rg(1), caused a rightward shift of the concentration-response curve of beta-amyloid. The reversal of the beta-amyloid-inhibited ACh release by Rb(1) was not blocked by tetrodotoxin (1 microM) indicating that an interaction occurs at the cholinergic synapse. These results suggest that Rb(1) may elicit its anti-amnesic effect by minimizing the inhibitory effect of beta-amyloid peptides.

Acetylcholine↗
PubMed2000

Effect of ginseng saponins on cold tolerance in young and elderly rats.

Acute systemic injection of ginseng saponin (GS) significantly elevated both the total and maximum heat production in young rats (3-6 months) and improved their cold tolerance under severe cold (-10 degrees C under helium-oxygen). However, pretreating the animal with the optimal dose (10 mg/kg) of GS devoid of Rg1 and Rb1 failed to elicit any beneficial effect in improving the cold tolerance. Pretreating the animal with Rb1, but not Rg1, increased thermogenesis as well as cold tolerance in young rats. A similar beneficial effect in improving cold tolerance was also observed when old rats (26-28 months) were pretreated with the same doses of Rb1 (2.5 and 5.0 mg/kg). Our results indicate that Rb1 is the key ingredient in GS-mediated enhancement in thermogenic capacity and that both young and old rats can benefit from this treatment for enhanced cold tolerance.

Adaptation, Physiological↗
PubMed2000

Complete genomic organization and promoter analysis of the round-spotted pufferfish JAK1, JAK2, JAK3, and TYK2 genes.

We have previously reported the isolation of the JAK1 gene from the round-spotted pufferfish. In the present study, we cloned and characterized genomic sequences encoding pufferfish JAK2, JAK3, and TYK2, which are other members of JAK family. To our knowledge, this is the first report to demonstrate the existence of four JAK genes in fish. All pufferfish JAK genes except JAK1 are composed of 24 exons; JAK1 has an additional exon. A comparison of the exon-intron organization of these genes revealed that the splice sites of JAK genes are nearly identical. In addition, all pufferfish JAK genes have one intron in the 5' untranslated region. Taken together, these data suggest that the pufferfish JAK genes may have evolved from a common ancestor. By 5' rapid amplification of cDNA ends and sequence analysis, we deduced the promoter regions for all JAK genes and found they do not contain typical TATA or CCAAT boxes but rather numerous other potential binding sites for transcription factors. Interestingly, the TYK2 gene is linked to CDC37 in a head-to-tail manner with a small intergenic region of 292 bp. Within this region, there are two potential binding sites for transcriptional factors such as c-Myb and NF-IL6. The putative promoter regions of all JAK genes were tested either in a carp CF cell line or in zebrafish embryos using CAT or lacZ as reporter genes. Both assays confirmed the transcriptional activities of these promoters in vitro and in vivo.

Amino Acid Sequence↗
PubMed2000

Effects of hetastarch and mannitol on prolonging survival in stable hypothermia in rats.

In rats, prolonged stable hypothermia ( approximately 24 h at body temperature of 19 degrees C) is characterized by a time-dependent increase in hematocrit, plasma osmolality, and red blood cell fragility and a decrease in plasma volume. These changes impede tissue microcirculation and could limit survival. As a countermeasure, we used plasma volume expanders of both long (hetastarch)- and short-lasting (mannitol) characteristics to improve microcirculation and hopefully hypothermia survival. Infusion of 6% hetastarch at hour 3 in hypothermia significantly (P < 0.05) enhanced survival over saline control (33.5 vs. 23.8 h); a significant delay in the increases of hematocrit and cell fragility was also observed compared with those in saline controls. Treating the animal with 6% hetastarch at hour 20 during hypothermia caused a similar but less-effective improvement in survival. In contrast, treating the rats with 6% mannitol at hour 3 or 20 during hypothermia failed to enhance survival over saline control, although transient improvement in plasma volume was observed. Our results indicate that by using a long-lasting volume expander, which tends to better maintain plasma volume and rheological parameters governing microcirculation than does saline or a short-lasting volume expander, hypothermia survival can be significantly improved.

Animals↗
PubMed1998

Effect of ginseng saponins on exercise performance in non-trained rats.

Short-term (4 days), but not acute, treatment with ginseng saponin (GS, 10 and 20 mg/kg/day) significantly prolonged the aerobic endurance of non-trained rats exercising at approximately 70% VO2max. Compared to the saline controls, GS treatment significantly increased the plasma free fatty acid (FFA) level and maintained plasma glucose level during exercise. Both the liver and skeletal muscle glycogen levels of the GS-treated rats were slightly higher than those of saline-treated controls after exhaustive exercise. These results indicate that GS enhances exercise endurance by altering fuel homeostasis during prolonged exercise, presumably by increasing FFA utilization in preference over glucose for cellular energy demands. To further search for the active components responsible for the ergogenic effect of GS, it was found that a GS preparation devoid of Rg1 and Rb1 failed, whereas injection of either Rg1 or Rb1 enhanced aerobic exercise performance. These results indicate that both Rg1 and Rb1 are key ingredients in GS-mediated enhancement in aerobic endurance.

Animals↗
PubMed1997

Autoradiographic determination of changes in opioid receptor binding in the limbic system of the Columbian ground squirrel at different hibernation states.

To localize and quantify the state-dependent changes in various opioid receptor subtypes in the limbic system of non-hibernating and hibernating Columbian ground squirrels, quantitative receptor-binding autoradiography was used. Compared to the non-hibernating animals, the binding density of [3H]-[D-Pen2,5]-enkephalin (DPDPE) to the delta receptor in the lateral septum, CA3, and the hippocampal fissure of the hippocampal formation was significantly decreased in the hibernating ground squirrels. A significant reduction in the binding density of [3H]-[D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAGO) to mu receptor was also observed in the medial septum and the CA3 region of the hippocampus of the hibernating animals. In contrast, a decrease in [3H]ethylketocyclazocine (EKC) binding to the kappa receptor was only observed in the claustrum and CA3 of the hippocampus during hibernation. The differential changes in binding to various opioid receptors suggest that different opioid subtypes may exert different physiological roles in regulating the specific states (entrance, maintenance and arousal) of a hibernation bout.

Animals↗
PubMed1997

Calcitriol enhancement of TPA-induced tumorigenic transformation is mediated through vitamin D receptor-dependent and -independent pathways.

We previously showed that 1alpha,25-dihydroxyvitamin D3, calcitriol, enhanced phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced tumorigenic transformation of mouse epidermal JB6 Cl41.5a cells. To determine if calcitriol regulates this enhancement through a nuclear vitamin D receptor (VDR)-dependent or -independent pathway, we used vitamin D analogs which induce biological responses by either of these mechanisms. In JB6 Cl41.5a cells, 1alpha,24-dihydroxy-22-ene-24-cyclopropyl-vitamin D3 (BT), which like calcitriol binds to VDR and regulates transcription, inhibited cell growth, stimulated expression of nonphosphorylated osteopontin (OPN), and enhanced TPA-induced anchorage-independent growth (AIG, an in vitro assay which highly correlates with tumorigenicity of these cells). 25-Hydroxy-16-ene-23-yne-vitamin D3 (AT), which stimulates calcium influx but has low affinity for VDR, had moderate effects on cell growth and expression of OPN. However, it enhanced TPA-induced tumorigenic transformation, though to a lesser extent than BT, thus suggesting that a VDR-independent mechanism is involved. Since 1alpha-hydroxylase activity was detected in JB6 cells, AT could be converted into 1alpha,25-dihydroxy-16-ene-23-yne-vitamin D3 (V), an analog which binds with high affinity to VDR, and could subsequently enhance TPA-induced AIG. To verify whether the VDR-independent pathway is involved in calcitriol enhancement of tumorigenic transformation, two additional VDR-independent analogs, 1alpha,25-dihydroxy-lumisterol3 (JN) and 24R,25-dihydroxyvitamin D3 (AS), were tested. The analog JN, which stimulates calcium transport and cannot be further hydroxylated at 1-carbon position, increased TPA-induced AIG, while AS, which inhibits calcium influx, did not. These studies suggest that a VDR-independent pathway, perhaps stimulation of calcium influx, and a VDR-dependent mechanism, which directly affects transcription, are involved in calcitriol's enhancement of TPA-induced tumorigenic transformation in JB6 Cl41.5a cells.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1996

In vivo microdialysis study on changes in septal dynorphin and beta-endorphin activities in active and hibernating Columbian ground squirrels.

State-dependent changes in extracellular concentration of endogenous opioids in the septum of Columbian ground squirrels were examined in the hibernating and euthermic states using in vivo microdialysis. The order of estimated extracellular concentration was found to be: hibernating > interbout euthermia > non-hibernating euthermia for dynorphin A and interbout euthermia > hibernating > non-hibernating euthermia for beta-endorphin. The apparent turnover rates of dynorphin A during hibernation was 15 times greater than that during euthermic non-hibernation phase and that of beta-endorphin was 8-fold greater. These results demonstrate that subfamilies of endogenous opioids may vary differentially in their activities at different stages of an annual hibernation cycle and may reflect their different roles in the regulation of hibernation.

Animals↗
PubMed1996

State-dependent changes of brain endogenous opioids in mammalian hibernation.

Endogenous opioids belonging to three opioid families were measured in different states of the hibernation cycle in brain of the Columbian ground squirrels. Using high-performance liquid chromatography-EC detection, the hypothalamic and septal concentrations of met-enkephalin were found to be significantly higher (p < 0.05) in the hibernating state than that in the nonhibernating state. In contrast, met-enkephalin content in the medulla decreased significantly during hibernation. Leuenkephalin content was only increased in the hypothalamus of hibernating animals. Using radioimmunoassay, dynorphin A-like immunoreactivity was observed to increase in the claustrum and striatum, whereas beta-endorphin-like peptides showed a significant increase in the hypothalamus during hibernation. It is evident that the changes in endogenous opioids in brain during hibernation are state dependent, type specific and region specific. These specific alterations of various endogenous opioids may imply their different roles in hibernation.

Animals↗
PubMed1996

Acute care of myocardial infarction.

Patients with acute myocardial infarct (AMI) need rapid diagnosis and prompt initiation of thrombolytic therapy. Patients with suspected cardiac ischemia must receive a coordinated team response by the emergency room staff including rapid electrocardiographic analysis and a quick but thorough history and physical examination to diagnose AMI. Thrombolysis and adjunct therapies should be administered promptly when indicated. The choice of thrombolytics is predicated by the location of the infarct.

Algorithms↗
PubMed1995

Modulatory effects of magnolol on potassium-stimulated 5-hydroxytryptamine release from rat cortical and hippocampal slices.

Magnolol, a phenolic constituent of magnolia bark, is a known central nervous system depressant. To examine the possibility that magnolol may elicit its depressant effect by modulating central serotonergic activity, its effect on 35 mM K(+)-stimulated 5-[3H]HT release from rat hippocampal and frontal cortical slices were examined. Inclusion of magnolol (1-100 microM) had no effect on 5-HT release in hippocampal slices but elicited a dose-related inhibition on 5-HT release from cortical slices. The inhibitory effect of magnolol on K(+)-stimulated 5-HT release from the cortex was not affected by either antagonists (metergoline, propranolol, and cyproheptadine) (0.01-10 microM) of various 5-HT receptor subtypes or the voltage-dependent sodium channel blocker tetrodotoxin (1 microM). It is concluded that the suppression of brain 5-HT release by magnolol is site-specific, and the suppression of cortical 5-HT release by magnolol is not via the 5-HT autoreceptors at the 5-HT terminals.

Animals↗
PubMed1995

Thermoregulatory effects of alkaloids isolated from Wu-chu-yu in afebrile and febrile rats.

Dehydroevodiamine (DeHE) and evodiamine (EVO), alkaloids isolated from a Chinese medicinal herb, Wu-chu-yu, exhibit calcium antagonistic activity. Intraperitoneal injections of DeHE (5-20 mg/kg) and EVO (2.5-10 mg/kg) caused a dose-related hypothermia in afebrile rats at an ambient temperature (Ta) of 20 degrees C. Because the heat production of alkaloid-injected rats did not differ from that of the controls, the hypothermic effect likely resulted from increased peripheral heat loss. This suggestion is supported by the finding that both DeHE and EVO did not affect the thermoregulatory response of rats exposed to a Ta of 35 degrees C, at which heat loss was maximized. Injection of the same doses of DeHE and EVO attenuated the febrile response in a dose-related manner, induced by intrahypothalamic injection of exogenous pyrogen. The attenuation of the febrile response was associated with a reduction in heat production. Because DeHE and EVO did not affect HP in afebrile rats at a Ta of either 20 or 35 degrees C, but suppressed the metabolic rate of febrile rats at 20 degrees C, the thermoregulatory effect of DeHE and EVO could involve both a calcium-dependent increase in heat loss and a suppression in heat production; the latter may only be manifested when the set point for thermoregulation is elevated.

Alkaloids↗
PubMed1995

Effects of honokiol and magnolol on acetylcholine release from rat hippocampal slices.

To study the possible mechanism through which honokiol and magnolol elicit their central depressant effects, we examined the influence of these two phenolic compounds on 25 mM K(+)-stimulated release of [3H]acetylcholine (ACh) from the rat's hippocampal slices. Honokiol, but not magnolol, elicited a concentration-dependent enhancement of K+-evoked ACh release. Addition of either tetrodotoxin, pilocarpine, or methoctramine had no effect on honokiol-enhanced ACh release. These results suggest that honokiol enhanced K(+)-evoked ACh release directly on hippocampal cholinergic terminals via receptors other than the M2 cholinergic subtypes.

Acetylcholine↗
PubMed1993

The modulatory effects of mu and kappa opioid agonists on 5-HT release from hippocampal and hypothalamic slices of euthermic and hibernating ground squirrels.

To elucidate the role of opioids in regulating hibernation, the modulatory effects of different opioids on 35 mM K(+)-stimulated [3H]-5-HT release from brain slices were examined in the Richardson's ground squirrels. DAGO ([D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin), a specific mu agonist, evoked a significant dose-dependent (10(-7)-10(-5) M) inhibition of K(+)-stimulated 5-HT release from hippocampal slices of the non-hibernating squirrels. The inhibitory effect of DAGO was attenuated by either the opioid antagonist naloxone (10(-6) M) or the voltage dependent sodium channel blocker tetrodotoxin (TTX, 10(-6) M). The inhibitory effect of DAGO persisted in the hibernating squirrels; however, a ten fold higher concentration of DAGO (10(-6)-10(-5) M) was required to elicit a significant inhibition. In contrast, kappa agonist U50488 (10(-5) M) exerted a significant enhancement of K(+)-stimulated 5-HT release from hippocampal slices of the non-hibernating squirrels. This enhancement was blocked by either the specific kappa antagonist nor-binaltorphimine (10(-6) M) or TTX (10(-6) M). However, in the hibernating squirrels, the stimulatory effect of U50488 (10(-5) M) on 5-HT release was absent. DAGO and U50488 had no modulatory effects on K(+)-stimulated 5-HT release from the hypothalamic slices of either the non-hibernating or hibernating squirrels. These results demonstrate that the modulatory effects of opioids on 5-HT release are receptor-specific and state-dependent, indicating the complex nature of the roles of different opioids in regulating hibernation.

Amino Acid Sequence↗
PubMed1993

Thermoregulatory responses following injection of 5-hydroxytryptamine into the septohippocampal complex in rats.

The present study investigated the change in thermoregulatory responses following microinjection of 5-hydroxytryptamine (5-HT) into the lateral septum and the hippocampus of unanesthetized, unrestrained rats. Intraseptal injection of 5-HT (5 to 20 micrograms) caused a dose-related fall in core temperature (Tb), which was associated with a decrease in heat production (HP). As the decrease in HP can not completely account for the magnitude of the decrease in Tb, increase in heat loss may also be involved in the 5-HT-induced hypothermia. In contrast to observed changes following intraseptal injection, no significant change in either Tb or HP was observed after microinjection of the same doses of 5-HT into the hippocampal areas, indicating that the hypothermic response to intraseptal injection of 5-HT is site specific. Further, the hypothermic response to intraseptal injection of 5-HT was only attenuated by systemic pretreatment with cyproheptadine, but not by naloxone or scopolamine, indicating that the hypothermic response is mediated by 5-HT receptor, but not by endogenous opioid and cholinergic systems.

Animals↗
PubMed1993

Age-dependent change in the inhibitory effect of an adenosine agonist on hippocampal acetylcholine release in rats.

To investigate the possibility that age-dependent deficits in acetylcholine (ACh) release are precipitated by the alteration of endogenous purinergic activities, the effects of (-)N6-phenylisopropyladenosine (PIA), an adenosine agonist, in modulating K+ (25 mM)-induced [3H]ACh release from the hippocampal slices of young (3-6 months old) and old rats (26-30 months old) were examined. In young rats, PIA (0.1-10 microM) caused a dose-related inhibition of [3H]ACh release from the hippocampal slices and a significant reduction in [3H]ACh release was observed in the presence of 1 microM PIA. In old rats, a similar pattern of PIA suppression of K(+)-induced [3H]ACh release was observed; however, a 10-fold higher concentration of PIA (10 microM) was required to elicit a significant inhibition. This age-dependent reduction in responsiveness to PIA may be due to an enhanced endogenous adenosine activity in aged rats leading to downregulation of the adenosine receptors. This notion is supported by the finding that both the adenosine concentration and activity of 5'-nucleotidase, an enzyme partially governing adenosine synthesis, were increased in the hippocampus of old rats as compared to their younger counterparts.

Acetylcholine↗