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Biomedical subjects

D Ding

Publications and source records attributed to D Ding.

At least 19 recordsLinked to original sources

Salicylate- and quinine-induced tinnitus and effects of memantine.

CONCLUSION: Memantine, an antiglutamatergic drug, has been proposed as a treatment for tinnitus. OBJECTIVES: The purpose of this study was to determine if memantine would prevent salicylate-induced tinnitus. Local field potentials were also recorded from auditory cortex to determine what effect salicylate, memantine, and the combination of both drugs would have on evoked potential amplitudes. MATERIALS AND METHODS: Schedule induced polydipsia-avoidance conditioning was used to identify the doses of salicylate or quinine that reliably induced tinnitus in rats. Rats were trained to lick for water during quiet intervals and avoid licking during sound intervals. RESULTS: Rats injected with saline or a low dose of sodium salicylate or quinine failed to develop tinnitus-like behaviors. However, high doses of salicylate (150-300 mg/kg/day) or quinine (100-150 mg/kg/day) greatly reduced licks-in-quiet, behavior consistent with the presence of tinnitus. Licks-in-quiet increased slightly when memantine (1.5 or 3 mg/kg/day) was co-administered with salicylate; however, the effect was not statistically significant or dose-dependent. These results indicate that memantine does not completely suppress salicylate-induced tinnitus. Cortical auditory evoked potential amplitude increased after salicylate treatment; co-administration of memantine failed to block this salicylate-induced increase.

Analgesics, Non-Narcotic↗

Regulation of secretion of osteoprotegerin in rat dental follicle cells.

Tooth eruption requires alveolar bone resorption and formation, both of which appear to be regulated by the dental follicle. Osteoclastogenesis needed for this bone resorption appears to occur as a result of a reduction in the expression of the osteoprotegerin (OPG) gene in the dental follicle at a specific time. This reduction in expression is mediated in vitro in the follicle cells by colony-stimulating factor-1 (CSF-1) and parathyroid hormone-related protein (PTHrP). Using enzyme-linked immunosorbent assays and immunoblotting, this study shows that the reduction in expression of OPG after incubation of the dental follicle cells in either CSF-1 or PTHrP also results in a reduction in its secretion. We also show, by laser capture microdissection, that PTHrP is expressed in vivo in the stellate reticulum such that it could inhibit OPG expression via a paracrine effect on the follicle. Bone formation is enhanced by OPG secretion, and incubation of the follicle cells with bone morphogenetic protein-2 (BMP-2) enhances OPG secretion. Thus, a reduction in secretion of the OPG protein at defined times may promote the osteoclastogenesis and alveolar bone resorption needed for eruption, and enhancement of OPG secretion at other times may promote alveolar bone formation.

Animals↗

Pifithrin-alpha suppresses p53 and protects cochlear and vestibular hair cells from cisplatin-induced apoptosis.

Cisplatin, a commonly used antineoplastic agent, destroys the sensory hair cells in the cochlear and vestibular system leading to irreversible hearing loss and balance problems. Cisplatin-induced hair cell damage presumably occurs by apoptosis. Recent studies suggest that p53 may play an important role initiating cisplatin-induced apoptosis in some cell types. To determine if p53 plays a role in cisplatin-mediated hair cell loss, cochlear and utricular organotypic cultures were prepared from postnatal day 3-4 rats and treated with cisplatin or cisplatin plus pifithrin-alpha (PFT), a p53 inhibitor. Control cultures were devoid of p53 immunolabeling, caspase-1 and caspase-3 labeling and p53 protein was absent from Western blots. Cisplatin (1-10 microg/ml) caused a dose-dependent loss of hair cells in cochlear and utricular cultures, up-regulated phospho-p53 serine 15 immunolabeling, increased the expression of phospho-p53 serine 15 in Western blots from 6 to 48 h after the onset of cisplatin-treatment, and increased caspase-1 and caspase-3 labeling in cochlear and vestibular cultures. Addition of PFT (20-100 microM) to cisplatin-treated cochlear and utricular cultures resulted in a dose-dependent increase in hair cell survival; suppressed the expression of p53 in Western blots and eliminated caspase-1 and caspase-3 labeling in cultures. These results suggest that the tumor suppressor protein, p53, plays a critical role in initiating apoptosis in cochlear and vestibular hair cells. Temporary suppression of p53 with PFT provides significant protection against cisplatin-induced hair cell loss and offers the potential for reducing the ototoxic, vestibulotoxic and neurotoxic side effects of cisplatin.

Animals↗

Epi-inositol regulates expression of the yeast INO1 gene encoding inositol-1-P synthase.

Myo-inositol exerts behavioral effects in animal models of psychiatric disorders and is effective in clinical trials in psychiatric patients. Interestingly, epi-inositol exerts behavioral effects similar to myo-inositol, even though epi-inositol is not a substrate for synthesis of phosphatidylinositol. We postulated that the behavioral effects of epi-inositol may be due to its effects on gene expression. Yeast INO1expression was measured in northern blots. INM1 was determined by beta-galactosidase activity in a strain containing the fusion gene INM1-lacZintegrated into the genome. Epi-inositol affects regulation of expression of the INO1 gene (encoding inositol-1-P synthase), even though it cannot support growth of an inositol auxotroph (suggesting that, as in mammalian cells, it is not incorporated into phosphatidylinositol). Like myo-inositol, although to a lesser extent, epi-inositol causes a significant reduction in INO1 expression, and reverses the lithium- or valproate-induced increase in INO1 expression. However, it does not affect regulation of INM1 (encoding inositol monophosphatase), the expression of which is up-regulated by myo-inositol. The observed regulatory effects of epi-inositol on expression of the most highly regulated gene in the inositol biosynthetic pathway may help to explain how this inositol isomer can exert behavioral effects without being incorporated into phosphatidylinositol.

Anticonvulsants↗

Childhood narcolepsy in North China.

STUDY OBJECTIVES: The purpose is to report the results of an effort to diagnose children with narcolepsy in a pediatric referral clinic. DESIGN: Between September 1998 and December 1999, a program was implemented to emphasize recognition of childhood narcolepsy. Patients underwent brain computed tomography (CT) scan and magnetic resonance imaging (MRI) testing. All children received a MSLT test following a routine night's sleep, and serological HLA typing for HLA DR2. Three who reported occasional snoring also underwent nocturnal PSG prior to the MSLT. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: 29 (21 male, 8 female) children were identified with sleepiness and cataplexy. There was no evidence for brain functional or structural disease or for drug use. Sleep paralysis was elicited in 41%; hypnagogic hallucinations, in 59%. Psychosocial problems including emotional irritability and social isolation were present in 93% of the patients. Mean sleep latency on MSLT was 2.0+/-1.3 minutes; sleep-onset rapid eye movement (SOREM) occurred during 2/5 naps in 28 of 29 patients and 3/5 in 26/29 patients. The average number and latency of SOREM episodes were 4.2+/-0.9 episodes and 4.0+/-1.7 minutes, respectively. In those with snoring, a nocturnal PSG did not disclose sleep apneas/hypopneas. All patients but one were HLA DR2 positive. The estimated clinic incidence was 0.04%. CONCLUSIONS: A program for recognition in a referral neurology clinic combined with an availability of the MSLT and HLA testing resulted in the new identification in North China of a number of children with narcolepsy syndromes.

Adolescent↗

Lithium and valproate decrease inositol mass and increase expression of the yeast INO1 and INO2 genes for inositol biosynthesis.

Bipolar affective disorder (manic-depressive illness) is a chronic, severe, debilitating illness affecting 1-2% of the population. The Food and Drug Administration-approved drugs lithium and valproate are not completely effective in the treatment of this disorder, and the mechanisms underlying their therapeutic effects have not been established. We are employing genetic and molecular approaches to identify common targets of lithium and valproate in the yeast Saccharomyces cerevisiae. We show that both drugs affect molecular targets in the inositol metabolic pathway. Lithium and valproate cause a decrease in intracellular myo-inositol mass and an increase in expression of both a structural (INO1) and a regulatory (INO2) gene required for inositol biosynthesis. The opi1 mutant, which exhibits constitutive expression of INO1, is more resistant to inhibition of growth by lithium but not by valproate, suggesting that valproate may inhibit the Ino1p-catalyzed synthesis of inositol 1-phosphate. Consistent with this possibility, growth in valproate leads to decreased synthesis of inositol monophosphate. Thus, both lithium and valproate perturb regulation of the inositol biosynthetic pathway, albeit via different mechanisms. This is the first demonstration of increased expression of genes in the inositol biosynthetic pathway by both lithium and valproate. Because inositol is a key regulator of many cellular processes, the effects of lithium and valproate on inositol synthesis have far-reaching implications for predicting genetic determinants of responsiveness and resistance to these agents.

Basic Helix-Loop-Helix Proteins↗

Effect of inner and outer hair cell lesions on electrically evoked otoacoustic emissions.

When the cochlea is stimulated by a sinusoidal current, the inner ear emits an acoustic signal at the stimulus frequency, termed the electrically evoked otoacoustic emission (EEOAE). Recent studies have found EEOAEs in birds lacking outer hair cells (OHCs), raising the possibility that other types of hair cells, including inner hair cells (IHCs), may generate EEOAEs. To determine the relative contribution of IHCs and OHCs to the generation of the EEOAE, we measured the amplitude of EEOAEs, distortion product otoacoustic emissions (DPOAEs), the cochlear microphonic (CM) and the compound action potential (CAP) in normal chinchillas and chinchillas with IHC lesions or IHC plus OHC lesions induced by carboplatin. Selective IHC loss had little or no effect on CM amplitude and caused a slight reduction in mean DPOAE amplitude. However, IHC loss resulted in a massive reduction in CAP amplitude. Importantly, selective IHC lesions did not reduce EEOAE amplitude, but instead, EEOAE amplitude increased at high frequencies. When both IHCs and OHCs were destroyed, the amplitude of the CM, DPOAE and EEOAE all decreased. The increase in EEOAE amplitude seen with IHC loss may be due to (1) loss of tonic efferent activity to the OHCs, (2) change in the mechanical properties of the cochlea or (3) elimination of EEOAEs produced by IHCs in phase opposition to those from OHCs.

Action Potentials↗

Treatment effects on carbon dioxide retention in patients with obstructive sleep apnea-hypopnea syndrome.

OBJECTIVES: This study was designed to examine respiratory control in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), with or without CO(2) retention. METHODS: We recruited 10 body mass index-matched, apnea-hypopnea index-matched, age-matched, and lung function-matched OSAHS patients, according to their awake PaCO(2). Five patients were hypercapnic (PaCO(2), > or = 45 mm Hg), and five patients were eucapnic. Hypoxic responses (the ratio of the change in minute ventilation [DeltaV(E)] to the change in arterial oxygen saturation [DeltaSaO(2)] and the ratio of the change in mouth occlusion pressure over the first 100 ms of inspiration against an occluded airway [DeltaP(0.1)] to DeltaSaO(2)) and hypercapnic responses (DeltaV(E)/DeltaPCO(2) ratio and DeltaP(0.1)/DeltaPCO(2) ratio) were tested during wakefulness before treatment in all 10 patients, and before and during treatment (at 2, 4, and 6 weeks) with pressure support in the hypercapnic group. RESULTS: Hypercapnic patients had lower mean (+/- SD) DeltaV(E)/DeltaSaO(2) ratio than eucapnic patients (-0.17 +/- 0.04 vs -0.34 +/- 0.04 L /min/%SaO(2), respectively), lower mean DeltaP(0.1)/DeltaSaO(2) ratio (-0.04 +/- 0.02 vs -0.14 +/- 0.03 cm H(2)O/%SaO(2), respectively), and lower DeltaP(0.1)/DeltaPCO(2) ratio (0.23 +/- 0.1 vs 0.49 +/- 0.1 cm H(2)O/mm Hg, respectively) [p < 0.05]. After receiving noninvasive ventilation treatment, the hypercapnic and hypoxic responses of the hypercapnic patients increased. At 4 to 6 weeks, values for both responses had increased to within the normal range and PaCO(2) had fallen to < 45 mm Hg, while weight was unchanged. CONCLUSIONS: Depressed chemoresponsiveness plays a role that is independent of obesity in the development of CO(2) retention in some OSAHS patients, and it may be a response to sleep-disordered breathing.

Adult↗

Primary studies on heroin abuse and injury induced by oxidation and lipoperoxidation.

OBJECTIVE: To further reveal serious risks of heroin abuse to human body and clarify grave injuries of oxidation, peroxidation and lipoperoxidation induced by nitric oxide and other free radicals to heroin abusers. METHODS: Determined and compared plasma levels of nitric oxide (P-NO), vitamin C (P-VC), vitamin E (P-VE), beta-carotene (P-beta-CAR), lipoperoxides (P-LPO) and erythrocyte activities of superoxide dismutase (E-SOD), catalase (E-CAT), glutathione peroxidase (E-GSH-Px) and erythrocyte level of lipoperoxides (E-LPO) in 137 cases of heroin abusers (HAs) and 100 cases of healthy volunteers (HVs), used linear regression and correlation, stepwise regression and correlation to analyze correlation among heroin-abusing-duration (HAD), daily-heroin-abusing-quantity (DHAQ) with above determination values in the HAs. RESULTS: Compared with the above average values in the HVs group, the average values of P-NO, P-LPO, E-LPO in the HAs group were significantly increased (P < 0.0001), the average values of P-VC, P-VE, P-beta-CAR, E-SOD, E-CAT and E-GSH-Px were significantly decreased (P < 0.0001); the analysis of linear regression and correlation showed that with ascending of the HAD and DHAQ in the HAs, the values of P-NO, P-LPO, E-LPO were gradually increased (P < 0.0001), the values of P-VC, P-VE, P-beta-CAR, E-SOD, E-CAT, E-GSH-Px were gradually decreased (P < 0.0001); the analysis of stepwise regression and correlation suggested that the correlation among the HAD, DHAQ with the values of P-NO, P-VC, P-VE was the closest. CONCLUSION: The balance between oxidation and antioxidation in the HAs was seriously destroyed, and the injuries induced by nitric oxide and other free radicals, oxidation, peroxidation and lipoperoxidation reactions to the body of HAs gravely exacerbated. In the abstaining from heroin dependence, therefore, it should consider that sufficient quantum antioxidants such as VC, VE and beta-CAR are dosed to the HAs so as to abate the injuries to their bodies.

Adult↗

[The effects of the polysaccharides from Dermatocarpon miniatum on oxygen radicals and lipid peroxidation].

OBJECTIVE: To study the effects of Dermatocarpon miniatum (DEM) polysaccharides scavenging oxygen radicals and inhibiting lipid peroxidation. METHODS: .OH was produced by Fenton reaction and O2-. was produced by the oxidation of pyrogallol. The inhibition to LPO was determined by the colorimetry for testing the relative content of MDA. RESULTS: DEM polysaccharides could scavenge oxygen radical. The amounts of scavenging 50% (EC50) .OH was 1.72 mg/ml, the EC50 for O2-. was 2.12 mg/ml. DEM polysaccharides could also decrease the content of MDA. CONCLUSION: DEM polysaccharides has the effects of scavenging oxygen radicals and the inhibition to LPO. Its activities showed positive correlation with the amounts.

Antioxidants↗

[The study of intrapleural urokinase in the prevention of pleural thickening and loculated effusions by tuberculous pleurisy].

OBJECTIVE: To investigate the effects of intrapleural urokinase in the prevention of pleural thickening and loculated pleural effusions by tuberculous pleural effusion. METHOD: Eighty-one patients with tuberculous pleural effusion were randomized into 2 groups, intrapleural urokinase group (group I) and conventional group (group C). The patients in group I were injected with urokinase 100 000 IU intrapleurally after each thoracocentesis on twice a week basis, other therapies were similar to group C. RESULTS: The mean volume of fluid drained in group I was (3 981 +/- 573) ml, while it was (3 045 +/- 498) ml in group C (P < 0.01). The mean thickness of pleura in group I was (1.10 +/- 0.20) mm, but it was (1.40 +/- 0.30) mm in group C (P < 0.01), the incidence of pleural adhesion and location in group I was 10%, while it was 36% in group C (P < 0.01). The mean number of injection was (4.6 +/- 1.4) (ranged 3 approximately 8). The resolution time of pleural effusion was prolonged slightly, but there was no significant difference between two groups. CONCLUSION: Intrapleural urokinase can evidently increase the volume of pleural effusion drained and prevent pleural thickening and adhesion.

Adolescent↗

[The effects of low birth weight, gestational age on lung function in childhood].

OBJECTIVE: To evaluate the effects of low birth weight, gestational age on lung function in later childhood. METHODS: Height, body weight and lung function were measured in a cohort of 35 children with low birth weight (aged 6 approximately 9 y) and 35 healthy controls matched for sex and age with normal birth weight. At the same time, we inquired their gestational age and passive smoking history. The correlation analysis was used to analyze the relationship between lung function in these children and birth weight and gestational age. RESULTS: FVC, FEV(1), FEV(1)% pred, V(75), V(50), V(50%) Pred, (V(25%) Pred in children with low birth weight were significantly lower than those in children with normal birth weight (P < 0.05). The lung function statistically positively correlated with birth weight (r = 0.245 approximately 0.365, P < 0.05), but not with gestational age (P > 0.05). CONCLUSION: Low birth weight was positively correlated with most lung function parameters in childhood.

Case-Control Studies↗

[Study on voltage-sensitive current of spiral ganglion cells in mice organ of Corti culture].

OBJECTIVE: To investigate the property of voltage-sensitive current in cochlear spiral ganglion cells of the C57BL/10J mice, an inbred strain which develops early onset hearing loss. METHODS: Organotypic cultures of organ of Corti were prepared from neonatal mice 0-5 days of age. Whole-cell current and voltage clamp techniques were used to study Na+, K+ and Ca2+ currents of the spiral ganglion cells in culture. RESULTS: Cultures were maintained for 8-48 hours before use. Ganglion cells were identified first through their anatomical positions and finally through fast negative Na+ current. Spontaneous action potentials were recorded from some ganglion cells (4 out of 39). When present, spontaneous rates were around 20 spikes/sec, and might be as high as 135 spikes/sec. The mean resting potential was (-55 +/- 5) mV (n = 39). Under voltage clamp conditions, transient inward currents (negative) and outward (positive), steady-state voltage-dependent currents were recorded in normal HBSS. Rapid inward currents were totally blocked by 300 nM TTX applied locally to the culture. Inward currents recovered quickly after TTX wash out suggesting that the transient inward current was carried by Na+. The mean maximum amplitude of Na+ current was (-2.0 +/- 1.1) nA (n = 39) recorded in HBSS. Adding TEA (10 mmol/L) and 4-AP (0.15 mmol/L) to the bath solution or replacing K+ with Ca+ in the pipette solution partly blocked the sustained outward current. This suggests that the outward current was carried by K+. The mean maximum amplitude of K+ was (3.0 +/- 1.3) nA (n = 39) with 140 mM K+ in the pipette. Inward Ca2+ current was recorded in Ba2+ solution which mean peak amplitude was (-1.0 +/- 0.7) nA (n = 20). Ca2+ currents were reversibly blocked by 100 microM Cd2+. CONCLUSION: Whole cell recordings from spiral ganglion neurons can be obtained from organotypic cultures of the organ of Corti. Fast Na+ current, sustained K+ current and L-type Ca2+ current were recorded in the spiral ganglion cells cultured for 1-2 days. Whole cell recording showed that cochlea spiral ganglion cells can generate spontaneous action potential one day after birth and the firing rates could reach levels equal to those recorded in vivo.

Action Potentials↗

[Simultaneous determination of three components in antongding injection by Kalman filtering method].

Kalman filtering method was applied to determine three components in antongding injection without separation. The average recovery and relative standard deviation of amidopyrine, phenazone, barbital obtained by Kalman filtering method were 99.8%, 0.93%, 99.7%, 0.82%, 99.7%, 1.5% respectively. It was showed by t-test that there was no significant difference between the results of Kalman filtering method and standard method.

Aminopyrine↗

Investigating 42 candidate orthologous protein groups by molecular evolutionary analysis on genome scale.

It is one of key problems for comparative genomics to accurately identify orthologous genes/proteins. Here 42 quartettes of human, yeast Saccharomyces cerevisiae, nematode Caenorhabditis elegans, and fruit fly Drosophila melanogaster candidate orthologs, defined by using similarity-based highest hit criteria (Mushegian et al., 1998 Genome Res. 8: 590-598), were reconsidered according to molecular evolutionary analysis. We found that only 14 of the 42 candidate orthologous groups can be identified to have truly one-to-one orthologous relationships, whereas other groups were characterized by one (many)-to-many orthologous relationships or even more complex scenarios involving gene duplications and/or gene losses. The result could imply that the classical one-to-one orthology might be not as common as typically accepted and automated similarity-based methods should be used with caution when accurate orthology/paralogy discrimination is required.

Animals↗

Effects of compound structure on carbazole dication-DNA complexes: tests of the minor-groove complex models.

Carbazole dications have shown excellent activity against opportunistic infections, but they are quite different in structure from previously studied unfused aromatic cations that function by targeting the DNA minor groove. In a previous report [Tanious, F. A., Ding, D., Patrick, D. A., Tidwell, R. R., and Wilson, W. D. (1997) Biochemistry 36, 15315-15325] we showed that, despite their fused ring structure, the carbazoles also bind in A/T sequences of the DNA minor groove and we proposed models for the carbazole-DNA complexes with the carbazole nitrogen facing out of the groove for 3,6 substituted compounds but into the groove in 2,7 carbazoles. To test and refine the models, carbazole-N-methyl substituted derivatives have been synthesized in both the 3,6 and 2,7 series as well as a new 2,6 substituted NH derivative that is intermediate in structure. Footprinting results indicate a broad AT specificity of carbazole binding and a pattern in agreement with a minor groove complex. Surface plasmon resonance biosensor analysis of carbazole binding to an oligomer with an AATT central sequence indicated that the 2,7 NH compound has the largest binding constant. Both the 3,6 NH and NMe compounds bind with similar equilibrium constants that are less than for the 2,7 NH compound. The 2,7 NMe compound has the lowest binding constant of all the carbazoles. Spectroscopic results are also similar for the two 3,6 derivatives but are quite different for the 2,7 NH and NMe carbazole dications. Structural analysis of carbazole complexes with an AATT sequence by 2D NMR methods also supported a minor groove complex of the carbazoles in orientations in agreement with the previously proposed models. From these results, it is clear that the fused ring carbazoles can bind strongly in the DNA minor groove with a broad A/T specificity and that the 2,7 and 3,6 substituted carbazoles bind to the minor groove in opposite orientations.

Binding Sites↗

Radiative and relativistic effects in the decay of highly excited states in helium

A recent experimental study [J.-E. Rubensson et al., Phys. Rev. Lett. 83, 947 (1999)] measured a significant fluorescence yield of the He( 2lnl(')) photoexcited resonances, showing major qualitative differences from nonrelativistic predictions. We present a further theoretical study of these states, and perform R-matrix multichannel quantum defect theory calculations to extract fluorescence and ionization cross sections. These theoretical results are in excellent agreement with newer, higher-resolution measurements. Radiative and spin-orbit effects are quantified and shown to play an important role in the overall characterization of highly excited states.

Journal Article↗