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Biomedical subjects

S F Fan

Publications and source records attributed to S F Fan.

At least 19 recordsLinked to original sources
PubMed2003

Zinc-induced apoptosis in substantia nigra of rat brain: neuroprotection by vitamin D3.

Accumulation of transition metals has been suggested to be responsible for the deteriorated nigrostriatal dopaminergic system in Parkinson's patients. In the present study, the mechanism underlying the zinc-induced neurotoxicity was investigated in the nigrostriatal dopaminergic system in vivo. Our 6-methoxy-8-paratoluene sulfonamide quinoline fluorescence study showed zinc translocation in the infused nigral cells after intranigral infusion of zinc. Furthermore, lipid peroxidation in the zinc-infused substantia nigra was consistently elevated 4 h to 7 d after the infusion. At the same time, an abrupt increase in cytosolic cytochrome c content in the infused substantia nigra was observed 4 h after zinc infusion and gradually decreased to basal levels 7 d after infusion. Both TUNEL-positive neurons and DNA fragmentation, indicatives of apoptosis, were detected in the zinc-infused substantia nigra. Furthermore, striatal dopamine content was reduced 7 d after the infusion. In attempt to prevent zinc-induced neurotoxicity, vitamin D3 was systemically administered. Zinc-induced increases in lipid peroxidation and cytosolic cytochrome c in the infused substantia nigra were prevented by this treatment. Moreover, zinc-induced reduction in striatal dopamine content was attenuated after vitamin D3 treatment. Our in vivo data suggest that zinc-induced oxidative stress may result in apoptosis followed by reduced dopaminergic function in the nigrostriatal dopaminergic system. Furthermore, vitamin D3 prevented zinc-induced oxidative injuries in the rat brain.

Animals↗
PubMed2001

Case report: MR findings of malignant melanoma of the vagina.

We report a case in which malignant melanoma of the vagina showed some MR signal changes after radiotherapy. Before radiotherapy, the tumour had slightly high signal intensity on T(1) weighted images and was enhanced after gadolinium-DTPA administration. After radiotherapy, the signal intensity of the tumour increased conspicuously on both T(1) weighted images and fat suppression T(1) weighted images.

Contrast Media↗
PubMed1999

A stretch-sensitive Cl- channel in human corpus cavernosal myocytes.

With the patch clamp method we demonstrate a stretch-sensitive Cl- currents as well as stretch-sensitive Cl- channels in a small group (5%,n 117) of cultured human corpus cavernosal muscle cells. The current and the channel activities had the following characteristics: (1) Their equilibrium potentials changed with extracellular Cl- concentration close to that predicted by Nernst equation provided that the relevant channels had high permeability to Cl- but low permeability to acetate ions; (2) They were blocked by mM concentrations of Zn2+; (3) The i-v relation of single channel current was almost linear for holding potentials varied from -70 to +60 mV; and (4) The channels had unitary conductances of approximately 140-170 pS.

Acetates↗
PubMed1997

Electrogenic hyperpolarization-elicited chloride transporter current in blue cones of zebrafish retinal slices.

Voltage-activated currents in blue cones of the retinal slice of zebrafish were characterized using whole cell recording techniques. Depolarizing-elicited currents were recorded: an outward tetraethylammonium (TEA)-sensitive K+ current (IKx), an outward Ca(2+)-activated Cl- current (ICl(Ca)), from which we inferred an inward Ca2+ current (ICa) as well as a hyperpolarizing-elicited nonselective inward cation current (Ih). In addition, hyperpolarizing steps elicited an outward current (Iout-h) in about one-third of the blue cones. Iout-h seems to be carried by inward transported Cl- because it was abolished by equimolar substitution of bath Cl- with acetate; equimolar substitution of Na+ with choline or TEA had no effect; it was not affected by Cl- channel blockers, anthracene-9-carboxylic acid, 4,4'-diisothiocyanostilbene-2.2'-disulfonic acid, N-phenylanthranilic acid (DPC), niflumic acid, and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid but was suppressed by Cl- transporter blockers acetalzolamide, bumetanide, N-ethylmaleimide, furosemide, and vanadate, and no reversal potential was found. In addition, this current was suppressed by ouabains but unrelated to their Na(+)-K(+)-ATPase inhibitory effect, was not suppressed by Co2+ or nifedipine, was not affected by the gap junction decoupler, 2-octanol, was increased by bath application of Cs+, presumably due to suppression of Ih, which was masked by Iout-h, and was suppressed by intensive light. Similar current also was found in the short cones and double cones. As Iout-h operates over the same voltage range, and with similar magnitude and time course as Ih, we suggest that Iout-h contributes to the modulation of the photoresponse of cones.

Animals↗
PubMed1997

Genotypic characterization and multivariate survival analysis of chronic lymphocytic leukemia in Taiwan.

In Taiwan, as in other areas of Asia, the incidence of chronic lymphocytic leukemia (CLL) is low. A retrospective analysis was conducted to elucidate the clinicopathologic features of CLL patients in Taiwan. Of the 47 cases of CLL enrolled in this study, 45 were immunophenotyped as B-CLL; the other 2 were T-CLL. It was found that the lower the Binet and Rai stages of the B-CLL, the longer patients survive (p = 0.0131 and 0.0142, respectively). Univariate analysis showed that fatigue, splenomegaly, hepatomegaly and anemia are associated with poor survival with p values of 0.0203, 0.0184, 0.0001 and 0.171, respectively. By multivariate analysis with Cox's proportional hazard model, hepatomegaly and decrease in body weight were the two most significant predictors of survival. However, molecular parameters of kappa or lambda immunoglobulin (Ig) gene rearrangement or double allele rearrangement of Ig gene did not significantly increase the predictability of the prognosis.

Adult↗
PubMed1997

[Study on the operational method for the treatment of CRF with enteroclysis (chronic renal failure)].

The enteroclysis used for chronic renal failure (CRF) is very effective in the clinical therapy and is developed by professor Zhang Da-ning, a famous specialist in nephrosis in China. In order to find the most effective treatment, we observed 300 patients with CRF who received enteroclysis therapy in the past five years. We focused on the study of the operational method about conservative enteroclysis by multiple cross-transverse comparative method. The results show that proper temperature for enteroclysis (37-39 C), suitable depth for intubation (15-20 cm) as well as right prone position for patients enable the enteroclysis medicine exert the most effective action and ease the patient's suffering as possible as it can. This optimum operational method for conservative enteroclysis will provide scientific basis for improving regular enteroclysis technique and nursing quality.

Adult↗
PubMed1995

Chronic opioid treatment of neuroblastoma x dorsal root ganglion neuron hybrid F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate levels and onset of naloxone-evoked decreases in membrane K+ currents.

Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via Gs regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (microM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K+ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the Gs/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiate addiction in vivo.

Animals↗
PubMed1995

Dual regulation by mu, delta and kappa opioid receptor agonists of K+ conductance of DRG neurons and neuroblastoma X DRG neuron hybrid F11 cells.

The effects of the mu opioid receptor agonists, morphine and Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol (DAGO), the delta opioid receptor agonist, Tyr-D-Pen-Gly-Phe-D-penicillamine (DPDPE) and the kappa-opioid receptor agonist, dynorphin A-(1-13) on the whole-cell K+ currents (IK) of cultured mouse DRG neurons and neuroblastoma X DRG neuron hybrid F11 cells were studied. These opioid ligands all elicited dual effects. Low concentrations (< nM) usually elicited a transient increase in IK (within 1 min), followed by a sustained decrease in IK. In contrast, microM concentrations rapidly elicited a sustained increase in IK. After brief treatment with cholera toxin subunit B (CTX-B), the usual sustained decrease in IK evoked by < nM opioid agonists no longer occurred. Low concentrations then elicited only a sustained increase in IK. On the other hand, after chronic treatment with pertussis toxin (PTX), the usual microM opioid-induced increases in IK no longer occurred and more than half of the cells responded with a sustained decrease of IK to microM as well as nM opioids. The results suggest that mu, delta and kappa opioid receptors are each coupled to K+ channels through CTX-B- and PTX-sensitive transduction systems. Both systems have similar threshold concentrations to opioids. Activation of the CTX-B-sensitive opioid receptor/transduction system resulted in a decrease in K+ conductance of the cell which is generally associated with an increase in neuronal excitability. Activation of the other system resulted in an increase in K+ conductance which will, in general, decrease neuronal excitability. The net change in the IK depends upon which effect predominates. The dominance at different opioid concentrations may depend on the relative efficacies of the coupling of these two systems to K+ channels.

Amino Acid Sequence↗
PubMed1995

An analysis of the Maxi-K+ (KCa) channel in cultured human corporal smooth muscle cells.

Previous studies have demonstrated that cultured corporal smooth muscle cells have prominent outward K currents composed of several different K channel subtypes. The goals of the present investigation were (1) to assert the nature of these channels and to evaluate the characteristics of the most predominant of these channel subtypes, the Maxi-K+ (KCa) channel, and (2) to compare KCa channel behavior in cultured corporal smooth muscle cells derived from the human corpus cavernosum of two distinct patient populations. The patient population was subdivided into two broad diagnostic categories: Group 1: 4 patients without evidence of organic disease of the corpus cavernosum, 3 of whom had documented erections; and Group 2: 4 patients with organic erectile dysfunction. Consistent with previous observations, 3 different K channel subtypes were detected in both patient populations, with corresponding conductances of 180, 100 and 40 pS, respectively. The approximately 183 pS channel was identified as the KCa channel based on its selective permeability to K+ and the fact that its open probability was modulated by both membrane potential and intracellular calcium levels. Specifically, the relative permeability of the 183 pS KCa channel to K+, Rb+, and NH4+ was 1.00:0.64:0.46. The channel was virtually impermeable to Na+ and Li+ (relative permeability < 0.02). In addition, the KCa channel was responsible for more than 90% of the outward K+ current passed through the cell membrane when depolarized. Furthermore, pharmacological studies using the K channel blocker tetraethylammonium ion (TEA) revealed that the sensitivity of KCa channels to TEA inhibition (as judged by the [TEA] required to block one-half of the outward whole cell current induced by a 90 mV depolarizing pulse) in cells from Group 1 patients was 1.05 +/- 0.22 mM. (n = 10 cells), while in sharp contrast the observed value for cells from Group 2 patients was 12.7 +/- 3.8 (n = 9 cells). The difference between the two groups was highly significant. These observations confirm and extend our previous studies to suggest that the KCa channel plays an important role in corporal smooth muscle physiology and, moreover, that alterations in the function/regulation of KCa channels may be an important feature of organic erectile dysfunction. As such, altered KCa channel behavior may contribute to an impaired hyperpolarizing ability of corporal smooth muscle, possibly altering intracellular calcium homeostasis and, perhaps, corporal smooth muscle reactivity and tone.

Calcium↗
PubMed1994

Dynamic laser light scattering studies of the effects of pyrophosphate on cyclic motions of cross-bridges in isolated thick myofilaments from Limulus striated muscle.

Pyrophosphate (PPi) is a non-hydrolyzable ATP analogue known to affect the binding between myosin heads and actin. By using a dynamic laser light scattering method, we have shown that 1-2 mM PPi enhances the increase in gamma values induced by Ca2+ in isolated thick myofilaments from Limulus striated muscle. However, similar treatment has no effect on the gamma values of filaments suspended in either relaxing solution or ATP-free solution. gamma is the average linewidth of the photoelectron count autocorrelation function of the light scattered. PPi had no effect on the increase of gamma values by Sr2+ but it substantially increased the gamma values of the thick myofilaments suspended in Ba(2+)-substituted Ca2+ activating solution. The results show that PPi also affects the energy-requiring cyclic cross-bridge motions.

Actin Cytoskeleton↗
PubMed1994

Release of TEA blockade of maxi-K+ channels by isoproterenol.

The outward K+ current induced by step depolarization of freshly dispersed myocytes of guinea-pig taenia coli decreased about 80% upon treatment with 3 mM tetraethylammonium chloride (TEA). Isoproterenol (ISO, 2-5 microM) restored it to a large extent. This restoration did not occur in the presence of propranolol (2 microM). In single-channel recordings from cell-attached patches, the activity of maxi-K+ channel is dominant. When 3 mM TEA is incorporated in the pipette solution, the dominant channel-openings observed had much smaller unitary conductance. On the addition of ISO (2 microM) to the bath solution, but not to the pipette solution, K(+)-channel openings with unitary conductance similar to that without TEA treatment appeared. Cyclic AMP incorporated into the cytoplasm through the pipette was ineffective. These results indicate that ISO release TEA decrease of maxi-K+ channel conductance through some intracellular second messenger system other than adenylyl cyclase-protein kinase A system.

Animals↗
PubMed1994

Enhancement of beta-adrenergic receptor activation of maxi-K+ channels by GM1 ganglioside.

In freshly dispersed guinea-pig taenia coli myocytes, beta-adrenergic receptor agonist isoproterenol (ISO, 2-5 microM) increased the open probability (po) of the maxi-K+ channels through the G-protein, G. Subunit B of cholera toxin (0.1 nM) suppressed the ISO-induced increase of po of maxi-Ks+ channels but did not affect that induced by forskolin. Brief (20 min) treatment of the myocytes with GM1 ganglioside (GM1, 0.1-1.0 microM) enhanced the effectiveness of ISO-induced increase of po. This effect was blocked by 0.5% trypsin, which is known to prevent the incorporation of exogeneous GM1 into the membrane. The effect of GM1 was not shared by GM2 and GM3 gangliosides. These results suggest that the membrane-bound endogeneous GM1 may participate in the regulation of cellular response to beta-adrenergic agents.

Animals↗
PubMed1993

mu and delta opioid agonists at low concentrations decrease voltage-dependent K+ currents in F11 neuroblastoma x DRG neuron hybrid cells via cholera toxin-sensitive receptors.

In a previous study, we showed that microM concentrations of mu or delta opioid agonists increase voltage-dependent outward K+ currents in neuroblastoma x DRG neuron hybrid F11 cells via pertussis toxin-sensitive receptors. The present study demonstrates that much lower concentrations (fM to nM) of these opioids (DAGO and DPDPE) decreased voltage-dependent outward K+ currents during step depolarization. The opioid antagonist, naloxone (3 nM) prevented these decreases in K+ current as did the cholera toxin subunits A or B (ca. 1 nM). Furthermore, the specific mu opioid receptor antagonist, beta-funaltrexamine (5 nM) blocked the decrease by DAGO and the specific delta antagonist, naltrindole (1 nM) blocked that by DPDPE. Acute GM1 ganglioside (1 microM) treatment markedly enhanced the efficacy of opioid-induced decrease in K+ current. After treating the cells with pertussis toxin (1 microgram/ml) for 2 days or more, these opioids decreased the K+ current even when tested at concentrations as high as 1 microM. These results indicate that the decrease in K+ current elicited in F11 cells by low concentrations of mu and delta opioid agonists resembles the opioid-induced prolongation of the action potential duration and decrease in voltage-dependent K+ conductance that occur in DRG neurons in primary cultures. The F11 cell line provides therefore a valuable model system for correlative pharmacologic, electrophysiologic and biochemical analyses of Gs-coupled, GM1 ganglioside-regulated excitatory opioid receptor functions, in addition to G(i)/G(o)-coupled inhibitory receptor functions, in sensory neurons.

Animals↗
PubMed1993

The transduction system in the isoproterenol activation of the Ca(2+)-activated K+ channel in guinea pig taenia coli myocytes.

In freshly dispersed guinea pig taenia coli myocytes the activity of the large conductance Ca(2+)-activated K+ channel (maxi-K+ channel) predominates. The open probability (Po) of this channel is increased by micromolar concentrations of the beta-adrenergic agonist isoproterenol (ISO). Low concentrations of cholera toxin (CTX, 1 pM) and guanosine 5'-O-2-thiodiphosphate (GDP beta S, 0.5 mM) suppress the ISO-induced increase of Po. Higher concentrations of CTX (e.g., 0.5 nM) as well as forskolin and dibutyryl cAMP increase the Po. 1,9-Dideoxyforskolin, the forskolin analogue, which lacks the adenylate cyclase-stimulating effect, does not. A specific protein kinase A inhibitor (Wiptide), applied intracellularly via diffusion from the patch electrode, suppresses the ISO-induced increase of whole-cell outward K+ current during step depolarization. In contrast, intracellularly applied protein kinase C (19-36), a specific protein kinase C inhibitor, has no effect on the whole-cell current. TMB-8, an inhibitor of intracellular calcium mobilization, does not affect either the whole-cell outward K+ current during step depolarization or the Po. These observations show that ISO increases the Po of the maxi-K+ channels in the guinea pig taenia coli myocytes through the G protein-adenylate cyclase-protein kinase A system.

Adenylyl Cyclases↗
PubMed1993

On the apparent absence of maxi-K+ channel in rat aortic myocyte.

In cultured rat aortic myocytes, no high-conductance Ca(2+)-and voltage-dependent K+ channels (maxi-K+ channels) such as those found in the human and rabbit were observed. However, we have found that in freshly dissociated rat aortic myocytes, the activities of high-conductance Ca(2+)-and voltage-dependent channels were present and predominant. In cell-attached patches measured with pipettes filled with normal saline solution, their single channel conductances were 139.6 +/- 2.5 picosiemens (mean +/- SE). Under the 140-mM symmetrical K+ condition (both bath and pipette solutions contained 140 mM KCl), that measurement became 207.2 +/- 3.6 picosiemens and increased by about 50% with detaching of the membrane patch. The relative conductances of the channel to K+, NH4+, and Rb+ were 1:0.61:0.48. The conductance of these channels can readily be reduced by more than 90% by extracellularly applied 0.5 mM tetraethylammonium chloride. These characteristics show that they were maxi-K+ channels.

Ammonia↗
PubMed1992

Difference in the effects of verapamil on Ca(2+)-activated K+ channels of smooth myocytes of aorta and taenia coli.

In freshly dispersed taenia coli myocytes of guinea pig, verapamil decreased the whole-cell outward current during depolarization. In aortic myocytes it has the opposite effect. In cell-attached patches, verapamil increased the frequency of opening of the maxi-K+ channel of both taenia coli and aortic myocytes at the expense of the mean open time. In taenia coli myocytes, the greater frequency did not fully compensate for the reduced open time, and the overall open probability of the channel was reduced. In aortic myocytes, the increase in open frequency overwhelmed the effect of the decrease in mean open time. None of the effects could be reproduced with nifedipine or diltiazem in either cell type.

Animals↗