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Biomedical subjects

Yu-Feng Wang

Publications and source records attributed to Yu-Feng Wang.

15 recordsLinked to original sources

Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI.

In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, [corrected] and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.

Adolescent↗

Activation of adenosine A2A receptors alters postsynaptic currents and depolarizes neurons of the supraoptic nucleus.

Supraoptic nucleus (SON) neurons secrete oxytocin or vasopressin in response to various physiological stimuli (e.g., lactation/suckling, dehydration). Released near fenestrated capillaries of the neurohypophysis, these peptides enter the blood and travel to peripheral target organs. The pervasive neuromodulator adenosine, acting at A1 receptors, is an important inhibitory regulator of magnocellular neuroendocrine cell activity. Another high-affinity adenosine receptor exists in this system, however. We examined the physiological effects of adenosine A2A receptor activation and determined its localization among various cell types within the SON. In whole cell patch-clamp recordings from rat brain slices, application of the selective adenosine A2A receptor agonist CGS-21680 caused membrane depolarizations in SON neurons, often leading to increased firing activity. Membrane potential changes were persistent (>10 min) and could be blocked by the selective A2A receptor antagonist ZM-241385, or GDP-beta-S, the latter suggesting postsynaptic sites of action. However, +/--alpha-methyl-(4-carboxyphenyl)glycine or TTX also blocked CGS-21680 effects, indicating secondary actions on postsynaptic neurons. In voltage-clamp mode, application of CGS-21680 caused a slight increase (approximately 8%) in high-frequency clusters of excitatory postsynaptic currents. With the use of specific antibodies, adenosine A2A receptors were immunocytochemically localized to both the magnocellular neurons and astrocytes of the SON. Ecto-5'nucleotidase, an enzyme involved in the metabolism of ATP to adenosine, was also localized to astrocytes of the SON. These results demonstrate that adenosine acting at A2A receptors can enhance the excitability of SON neurons and modulate transmitter release from glutamatergic afferents projecting to the nucleus. We suggest that adenosine A2A receptors may function in neuroendocrine regulation through both direct neuronal mechanisms and via actions involving glia.

5'-Nucleotidase↗

Mechanisms underlying oxytocin-induced excitation of supraoptic neurons: prostaglandin mediation of actin polymerization.

In nonneuronal tissues, activation of oxytocin receptors (OTRs), like other Galpha(q/11) type G-protein-coupled receptors (Galpha(q/11)/GPCRs), increase prostaglandin (PG) expression. This is not known for the OTRs expressed by central OT neurons. We examined mechanisms underlying OT's effects on supraoptic nucleus (SON) OT and vasopressin (VP) neurons in hypothalamic slices from lactating rats. OT application (10 pM, 10 min) significantly increased firing rates of OT and VP neurons, both of which expressed OTRs. Indomethacin, an inhibitor of PG synthetases, blocked these increases. OTR (but not a V1 receptor) antagonist blocked OT effects without blocking the excitatory effect of PGE2. Tetanus toxin blocked OT effects on fast synaptic inputs and firing activity of SON neurons but not OT-evoked depolarization, suggesting involvement of both pre- and postsynaptic neurons. Indomethacin also blocked the excitatory effects of phenylephrine, another Galpha(q/11)/GPCR activating agent but not those of PGE2, a non-Galpha(q/11)/GPCR activating agent in the SON. OT or phenylephrine, but not glutamate or KCl, enhanced cyclooxygenase 2 expression at cytosolic loci in SON neurons and nearby astrocytes, as revealed by immunocytochemistry. This OT effect was not blocked by TTX. Western blot analyses showed that OT significantly increased cyclooxygenase 2 but not actin expression. OT promoted the formation of filamentous actin (F-actin) networks at membrane subcortical areas of both OT and VP neurons. Indomethacin blocked enhancement of F-actin networks by OT but not by PGE2. These results indicate that PGs serve as a common mediator of Galpha(q/11)/GPCR-activating agents in neuronal function.

Actins↗

Autofeedback effects of progressively rising oxytocin concentrations on supraoptic oxytocin neuronal activity in slices from lactating rats.

Suckling stimuli induce somatodendritic oxytocin (OT) release from supraoptic nucleus (SON) neurons, which raises intranuclear OT concentrations and contributes to the effectiveness of the milk-ejection reflex. To clarify how such changes in OT concentrations modulate the activity of OT neurons, we examined OT effects using whole cell patch-clamp recordings from SON neurons in slices from lactating rats. Progressive increases from extremely low OT concentrations (0.1-10 fM) to high concentrations (0.1-10 nM) induced excitation and subsequent spike frequency reduction (SFR) in OT neurons. Significant effects of OT on firing rates were observed starting at 1 fM, reached peak level from 1 fM to 1 pM before SFR occurred in most neurons. The buildup of OT concentrations progressively promoted depolarization of membrane potential, spike broadening, decreases in spike amplitude, and increases in the rise time of spike afterhyperpolarizations, which were unrelated to firing rate. However, intermittent application of OT (1 fM, 1 pM, and 1 nM, each for 5 min) evoked dose-dependent excitation but not the SFR. Application of 1 pM OT for 40 min simulated the effects of progressively increasing OT concentrations. Vasopressin neurons were also activated by OT but did not show SFR. Consistent with presynaptic loci of OT action, ionotropic glutamate receptor antagonists reduced OT effects on firing rate, whereas bicuculline did not change the excitatory effects. These results suggest that the specific autoregulatory effects of OT, and perhaps other neuropeptides as well, are time and concentration dependent.

Animals↗

Burst firing of oxytocin neurons in male rat hypothalamic slices.

Burst firing and single spike activity play different roles in the modulation of local neuronal circuit activity and neurosecretion. In hypothalamic oxytocin (OT) neurons in vivo, burst firing is associated with pulsatile secretion of OT in the milk ejection reflex, and can be observed in slices from both immature and lactating rats in vitro. Whether OT neurons from male rats also possess burst firing capability is still an open question. To examine this possibility, whole-cell patch clamp recordings were made in supraoptic nucleus OT neurons in brain slices from male rats. In low Ca(2+) medium, the alpha(1)-adrenoceptor agonist, phenylephrine evoked bursts that were highly similar to those from lactating rats in vivo and in vitro: explosive onset, short-duration, quickly reaching peak firing rate and displaying an exponential decay in returning to the pre-burst rate. During bursts, spike durations increased, and spike amplitudes decreased, while riding on an arc of depolarization around peak rate. In comparison to those from lactating rats in vitro, the rising phase of male bursts was more rapid, the decay phase was slower, and the rising phase of the spike after hyperpolarization was faster. No significant differences, however, were seen in burst characteristics that are most important in determining the amount of peptide release: burst amplitudes (the number of spikes in a burst), firing frequency within bursts or peak firing rate. Thus, we conclude that OT neurons in males are capable of burst firing highly similar to that seen in lactating rats.

Action Potentials↗

Selective sensing of Cu(II) at ng ml(-1) level based on phosphorescence quenching of 1-bromo-2-methylnaphthalene sandwiched in sodium deoxycholate dimer.

Using sodium deoxycholate as a protective medium, the selective recognition of Cu(II) at ng ml(-1) level is realized through dynamic phosphorescence quenching of 1-bromo-2-methylnaphthalene (BMN) without deoxygenation. The limit of detection is 4.32 ng ml(-1), and the relative standard deviation is 1% at 10 microM, linear up to 1 x 10(-5) M.

Acetals↗

Functional MRI in attention-deficit hyperactivity disorder: evidence for hypofrontality.

Using event-related functional magnetic resonance imaging to study the Stroop effect on both behavioral and brain activation of ADHD children off or on methylphenidate (MPH). Nine ADHD boys (aged 9.8-14.5 years) and 9 age-matched normal controls were included. A Stroop-like paradigm was used. AFNI (Analysis of Functional NeuroImaging) and its Deconvolution Analysis were used in a descriptive comparison between ADHD and control groups. (1) Both behavioral reaction time and brain activation showed Stroop effect in controls but neither was found in ADHD children off MPH. When MPH was administered, the Stroop effect tended to appear. (2) The activation volume (AV) of prefrontal cortex (PFC) in both the neutral (NC) and interference conditions (IC) in ADHD children off MPH was smaller than in controls. AV of anterior cingulate cortex in the IC in ADHD children off MPH was smaller than that in controls, but was similar in the NC to that in controls. AV of the basal ganglia, insula and cerebellum was also smaller in the IC, but was larger in the NC for ADHD children off MPH compared with controls. These findings are consistent with prior findings of hypofrontality in ADHD children and implicate a compensatory network including basal ganglia, insula and cerebellum for relative lower cognitive load tasks.

Adolescent↗

[Association between dopamine beta hydroxylase gene and attention deficit hyperactivity disorder complicated with disruptive behavior disorder].

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD), a common behavior disorder of childhood, is a highly heterogeneous disease frequently accompanied by various mental disorders, including disruptive behavior disorder (DBD). Studies show that children suffering from ADHD with DBD are at higher risk of antisocial personality, substance abuse, and social adaptations disorder at their adulthood. The dopamine beta hydroxylase (DbetaH) is the key enzyme to ADHD since it catalyzes the conversion of dopamine to norepinephrine, and dysfunction there of is believed to be one of the causes of the disorder. To explore the association between DBH gene and ADHD complicated with or without DBD, the authors analyzed the transmission of a novel polymorphism DBH -1021C-->T, which is found associated with plasma DbetaH activity, in ADHD nuclear families using transmission disequilibrium test (TDT). METHODS: Consensus diagnoses were based on the DSM-IV. The samples included those from 292 Chinese Han nuclear families with ADHD probands. Genotypes of DBH -1021C-->T polymorphism were determined by PCR amplification, endonuclease digesting and electrophoresis. The transmission of DBH -1021C-->T polymorphism in ADHD nuclear families with or without DBD was analyzed by TDT. RESULTS: The results showed that there was transmission disequilibrium between DBH-1021C-->T polymorphism and ADHD with or without DBD. In ADHD comorbid with DBD, T allele was preferentially transmitted (P < 0.05); and in ADHD without DBD, so was the C allele (P < 0.05). Among the three subtypes of ADHD, only ADHD-C subtype with DBD had an increased transmission of T allele (P < 0.05). CONCLUSION: There is an association between DBH gene and ADHD comorbid with or without DBD, but the preferential transmission alleles are different. The low activity T allele is increased to transmit in ADHD with DBD, while the high activity C allele is preferentially transmitted in ADHD without DBD. The results support the proposition that the genetic mechanism is different between ADHD comorbid with or without DBD. We also found that only ADHD-C subtype with DBD is associated with DBH -1021C-->T polymorphism in three subtypes of ADHD, which may suggest that there is a more intense relationship between DBD and ADHD-C subtype.

Alleles↗

[Hira gene and development: from yeast to human].

HIR/HIRA, one of the histone chaperones, encoded by Hir/Hira (histone regulation) genes, were initially identified in yeast as negative regulators of histone gene expression. It has been confirmed that HIRA contains a conserved family of proteins found in various species including low eukaryotes, invertebrates and vertebrates. It is essential for proper development. Mutations of Hir/Hira genes result in very serious defects in normal development not only in yeast but also in advanced eukaryotes. Combined with the work in our group, the roles of Hir/Hira genes in the development in different species are reviewed, and the recent advances concerning the mechanisms of HIRA functioning are also summarized in an attempt to promote the research further on the exact roles of hira genes in development of eukaryotes and on their deeply operating mechanisms.

Animals↗

[The clinical analysis of free patellar implantation in repairing the defect of the knee of giant cell tumors].

OBJECTIVE: To analysis the clinical effects of free patellar implantation in treating the defect of the knee joint after the excision of giant cell tumor in the distal femur and the proximal tibia. METHODS: If the giant cell tumor in the distal femur and the proximal tibia invaded the articular surface, we resected the condyle of femur or tibia including the tumor, dissociated the patella and placed it in the condyle horizontally to repair the articular surface. The cruciate ligament was reserved in all the patients. The condyle of femur or tibia was replaced by the anterior surface or the articular surface of the patella respectively. The implanted patella was fixed by the screw to the contralateral condyle, and the remaining defect was filled by autogenous cancellous illium. RESULTS: Nine patients were followed up 3 to 121 months, the average was 65 months. None of them recurred or metastated. The excellent and good rate of the functional evaluation of knee joints was 88.9%. CONCLUSION: After resecting the condyle of femur or tibia including the tumors which invade the articular surface, we find that free patellar implantation is a suitable way to repair the defect of the knee.

Adult↗

Milk ejection burst-like electrical activity evoked in supraoptic oxytocin neurons in slices from lactating rats.

To examine the mechanisms underlying milk-ejection bursts of oxytocin (OT) neurons during suckling, both in vivo and in vitro studies were performed on supraoptic OT neurons from lactating rats. The bursts were first recorded extracellularly in anesthetized rats. Burst-related electrical parameters were essentially the same as previous reports except for a trend toward transient decreases in basal firing rates immediately preceding the burst. From putative OT neurons in slices with extracellular recordings, bursts that closely mimicked the in vivo bursts were elicited by phenylephrine, an alpha1-adrenoceptor agonist, in a low-Ca(2+) medium. Moreover, in whole cell patch-clamp recordings, the in vitro bursts were recorded from immunocytochemically identified OT neurons. After a transient decrease in the basal firing rate, the in vitro bursts started with a sudden increase in the firing rate, quickly reaching a peak level, then gradually decaying, and ended with a postburst inhibition. A brief depolarization of the membrane potential and an increase in membrane conductance appeared after the onset of the burst. Spikes during a burst were characterized by a significant increase in the duration and decrease in the amplitude around the peak rate firing. These bursts were significantly different from short-lasting burst firing of vasopressin neurons in membrane potential changes, time to reach peak firing rate, spike amplitude and duration during peak rate firing. Our extensive analysis of these results suggests that the in vitro burst is a useful model for further study of mechanisms underlying milk-ejection bursts of OT neurons in vivo.

Action Potentials↗

Association of norepinephrine transporter gene with methylphenidate response.

OBJECTIVE: This study aimed to explore the association between alleles of the norepinephrine transporter gene and the methylphenidate response. METHOD: Chinese Han youths with attention-deficit/hyperactivity disorder recruited in the Outpatient Department of the Institute of Mental Health from 2001 to 2004 were treated with methylphenidate in doses of 0.45 to 0.60 mg/kg per day. Behavior changes were measured by the ADHD Rating Scale-IV when optimal doses were reached. The single-nucleotide polymorphic allele of norepinephrine transporter gene G1287A was used as the genetic marker, and the genotypes were identified by restriction fragment length polymorphism analysis. RESULTS: A significant association was found between norepinephrine transporter gene G1287A genotypes and response to methylphenidate for hyperactive-impulsive subscale scores (mean score reduction was 7.15 and 6.94 for G/G and G/A genotype, respectively, and 2.13 for A/A; p = .012) but not inattentive scores. CONCLUSIONS: These findings suggest an association between the G1287A polymorphism of the norepinephrine transporter gene and variation in methylphenidate response. Further work is needed to confirm this finding and to assess its generalization to other ethnic groups.

Adolescent↗

The relationship among the polymorphisms of SULT1A1, 1A2 and different types of cancers in Taiwanese.

Sulfotransferase (SULT) enzymes play an important role in the detoxification, metabolism and bioactivation of numerous xenobiotics, many dietary and environmental mutagens, drugs, neurotransmitters and hormones. The genes for SULT1A1 and SULT1A2 contain common genetic polymorphisms that are associated with individual variations in the level of enzyme activities as well as variations of biochemical and physical properties. We developed a PCR-RFLP method to analyze the frequencies of SULT1A1 and SULT1A2 alleles among cancerous patients and normal controls in Taiwan. The results showed that SULT1A1*1 and SULT1A2*1 were in positive linkage disequilibrium. Neither SULT1A1*3 nor SULT1A2*3 were found in this study. The frequencies of SULT1A1*2 and SULT1A2*2 for hepatic, colon, lung, oral, gastric, renal and cervical cancerous patients were 3.95, 5.56, 4.92, 3.84, 2.70, 7.41 and 4.50%, respectively. No statistical significance was found for these cancer patients after comparison with normal controls (4.0%) for the allelic frequencies of SULT1A1*2 and SULT1A2*2.

Arylsulfotransferase↗

Phosphorescent pH sensors and switches with substitutionally tunable response range based on photo-induced electron transfer.

According to the principle of photo-induced electron transfer (PET), five aminomethyl-bromonaphthalene phosphoroionophores with long lifetimes (to ms) were synthesized, all of them working well in beta-cyclodextrin (beta-CD) aqueous solutions. They form a family of phosphorescent sensors with pH-dependent spectral properties. For all the compounds, the fully protonated form exhibits the highest phosphorescence emission intensity and the proton-free form of the sensor is weakly emissive, due to the designed PET process. The sensors also show the expected pH dependence of phosphorescence quantum yields. Responses of the sensors are tuned by variation of substituent. The pH response ranges for 1-5 were 4.3-6.5, 3.5-10.5, 3.4-10.5, 3.4-10.5 and 3.4-6.1, respectively.

Cations↗