Search PubMed⌕ Search

Biomedical subjects

D Ding

Publications and source records attributed to D Ding.

At least 55 records · Page 3Linked to original sources

Auditory deprivation of the central auditory system resulting from selective inner hair cell loss: animal model of auditory neuropathy.

Auditory neuropathy is often characterized by normal thresholds, present otoacoustic emissions, poor speech discrimination, absent acoustic reflexes, absent or abnormal auditory brainstem response waveform, but normal late cortical potential. This paper describes an animal model that has many characteristics of auditory neuropathy. Chinchillas can be deprived of a significant portion of the neural inputs to the central auditory system by administering carboplatin, an antineoplastic agent that selectively destroys inner hair cells (IHCs) and type I auditory nerve fibers. Selective IHC loss has no effect on distortion product otoacoustic emissions or the cochlear microphonic potential, implying normal outer hair cell function. However, selective IHC loss causes the amplitude of the compound action potential to decrease in proportion to the degree of IHC loss. However, the threshold of the CAP shows little increase with mild to moderate IHC loss. Acoustically responsive auditory nerve fibers in ears with mild to moderate IHC loss have normal thresholds and tuning curves with narrowly tuned tips. Although the central auditory pathway is deprived of much of its sensory inputs, the amplitude of the local field potential in the auditory cortex was normal or enhanced, while those from the inferior colliculus were slightly reduced. The results are related to those of a patient with auditory neuropathy.

Animals↗

[The role of breathing control disorder in the development of carbon dioxide retention in patients with obesity hypoventilation syndrome].

OBJECTIVE: To define the role of breathing control in the pathogenesis of carbon dioxide (CO(2)) retention in patients with obesity hypoventilation syndrome. METHODS: 10 obese obstructive sleep apnea syndrome (OSAS) patients were studied. They were separated according to their waking arterial partial pressure of CO(2) (PaCO(2)), 5 being eucapnic and 5 hypercapnic. Both groups had similar body mass index, apnea hypopnea index and normal lung function. The hypoxic (Delta P(0.1)/Delta SaO(2), Delta V(E)/Delta SaO(2)) and the hypercapnic response (Delta P(0.1)/Delta PaCO(2), Delta V(E)/Delta PaCO(2)) were tested before and during continuous positive airway pressure (CPAP) treatment (at 2, 4, 6 weeks). RESULTS: Compared with the eucapnic patients, all the hypercapnic patients had lower Delta P(0.1)/Delta SaO(2) [(-0.04 +/- 0.02) cmH(2)O% vs (-0.14 +/- 0.03) cmH(2)O%], Delta V(E)/Delta SaO(2) [(-0.17 +/- 0.04) L x min(-1)% vs (-0.34 +/- 0.04) L x min(-1)%], Delta P(0.1)/Delta PaCO(2) [(0.23 +/- 0.1) cmH(2)O/mm Hg vs (0.49 +/- 0.1) cmH(2)O/mm Hg], Delta V(E)/Delta PaCO(2) [(1.32 +/- 0.7) L x min(-1) x mm Hg(-1) vs (2.18 +/- 0.81) L x min(-1) x mm Hg(-1)] and the Delta P(0.1)/Delta SaO(2), Delta V(E)/Delta SaO(2) were also lower than the normal value. After treatment with CPAP, the hypercapnic and the hypoxic response of the hypercapnic patients increased gradually, at about 4 approximately 6 week, both of them increased to the normal range, PaCO(2) showed a complete return to eucapnia, their weight were unchanged. CONCLUSION: The depressed breathing control play an important role in the development of CO(2) retention in OSAS patients, and the disorder in breathing control may be secondary to hypoxia, hypercapnia and sleep disorder related to the OSAS.

Adult↗

[Hemorrheological status in patients with silicosis and its clinical significance].

OBJECTIVE: To study relationship between silicosis and hemorrheology and its clinical significance. METHODS: Varied indices for hemorrheology were measured in 85 male patients with silicosis, 45 male patients with chronic bronchitis and 100 healthy male subjects. RESULTS: Compared with the control group and the chronic bronchitis patient group, average hematocrit (Hct), whole blood apparent viscosity (eta(a)) at 4 s(-1) - 200 s(-1) shear rates, plasma viscosity (eta(p)), erythrocyte electrophoresis time (EET) and platelet electrophoresis time (PET) all significantly increased in patients with silicosis (P < 0.001). Hemorrheological indices in patients with silicosis increased with severity of disease, increased with decrease in their pulmonary function, and were all significantly higher than those in the control group (P < 0.01 approximately equal 0.001). Stepwise regression analysis showed that severity of disease correlated closely to Hct, eta(a) at 4 s(-1) - 200 s(-1), EET and PET, and that pulmonary function status in patients with silicosis and their courses correlated closely to Hct, eta(a) at 4 s(-1) - 200 s(-1), eta(p), EET and PET. CONCLUSIONS: Blood of patients with silicosis was in highly viscose status, which was easy to be complicated with multiple diseases.

Aged↗

[Cochleogram for assessing hair cells and efferent fibers in carboplatin-treated ear].

OBJECTIVE: This paper describes a convenient histochemical technique that allows one to simultaneously assess the cochlear efferent neurons and inner (IHCs) and outer hair cells (OHCs). METHOD: Selective labeling of the sensory cells and efferent fibers was carried out by first labeling the hair cells for dehydrogenase activity and then staining the efferent fibers for acetylcholinesterase activity. Double-labeled specimens were prepared as a surface preparation and counts were made of the number of hair cells and the number of discreate fiber bundles crossing the tunnel of Corti along the entire length of the cochlea. RESULT: The utility of this technique for assessing ototoxic damage was demonstrated by constructing cochleograms showing the percentage of missing hair cells and tunnel-crossing efferent fibers in chinchillas treated with carboplatin. In the region of the cochlea associated with most IHC loss and a part of OHC missing showed by succinate dehydrogenase in the region of hair cells; however, the loss of tunnel-crossing efferent fibers showed by acetylcholinesterase staining was closely correlated with the percentage of OHC loss. But, if only damage the IHC, the efferent fibers showed normal. CONCLUSION: These results suggest that carboplatin damaged efferent systems may be due to the damage of OHC.

Animals↗

NMR solution structure of the N3' --> P5' phosphoramidate duplex d(CGCGAATTCGCG)2 by the iterative relaxation matrix approach.

High-resolution 2D NMR spectra of the duplex CGCGAATTCGCG with deoxyribose sugars but with the normal phosphodiester linker replaced by an N3' --> P5' phosphoramidate (NP) group have been used to establish a solution structure for the duplex. Distance, angle, and base pair hydrogen-bonding constraints were used to refine the structure by use of the iterative relaxation matrix approach (IRMA). The phosphoramidate NH proton signal could be observed in DMSO at low temperature but not in H2O and D2O. For this reason, the structure was refined with the -NH in each of the two possible low-energy configurations. The structure with the nitrogen lone pair located between the nonbridging oxygen atoms of the 5'-phosphate group consistently had the lowest energy and RMSD values, consistent with an X-ray analysis of the same duplex [Tereshko, V., Gryaznov, S. , and Egli, M. (1998) J. Am. Chem. Soc. 120, 269-283]. In the refined structure, the sugars are in the C3'-endo conformation with the change from the normal C2'-endo conformation of deoxyribose apparently being driven by the gauche effect and the change in electronegativity from the 3'O to the 3'NH group. In agreement with preliminary studies [Ding, D., Gryaznov, S. M., Lloyd, D. H., Chandrasekaran, S., Yao, S., Ratmeyer, L., Pan, Y., and Wilson, W. D. (1996) Nucleic Acids Res. 24, 354-360], the backbone conformation in the NP duplex is very close to classical A-form values. Comparison of phosphodiester and phosphoramidate structures suggests that their backbones have global conformations that are primarily a function of the low-energy state of the sugar ring. A somewhat more complex situation arises when base pair conformation is analyzed with many of the base pairs having a conformation between those of classical A- and B-form helices. The effects of the 2' substituent are obviously important in specifying the final conformation of the stacked bases in either an A-form or B-form helix. It is clear, however, that conversion of the normal phosphodiester of DNA into a phosphoramidate linkage yields a nucleic acid that behaves much more like RNA than DNA, and it has been shown that NP sequences can bind to RNA-directed proteins [Rigl, C. T., Lloyd, D. H., Tsou, D. S., Gryaznov, S. M., and Wilson, W. D. (1997) Biochemistry 36, 650-659].

Crystallography, X-Ray↗

The relationship between synonymous codon usage and protein structure.

The hypothesis that synonymous codon usage is related to protein three-dimensional structure is examined by investigating the correlation between synonymous codon usage and protein secondary structure. All except two codons in E. coli show the same secondary structural preference for alpha-helix, beta-strand or coil as that of amino acids to be encoded by the respective codons, while 17 codons show secondary structural bias in mammalian proteins. The results indicate that there is no significant correlation between synonymous codon usage and protein secondary structure in E. coli, but there is a correlation in mammals. It could be deduced that synonymous codons carry much less structural information in prokaryotes than in eukaryotes due to their divergent evolutionary mechanism.

Animals↗

The BALB/c mouse as an animal model for progressive sensorineural hearing loss.

To develop the BALB/c mouse strain as an animal model for the study of progressive sensorineural hearing loss, mice ranging in age from young adult through middle age were studied. Auditory brainstem response thresholds, histopathology [cytocochleograms for hair cells, the packing density of spiral ganglion cells (SGCs), the number of neurons and overall size of the anterior ventral cochlear nucleus (AVCN)], and behavioral paradigms (prepulse inhibition, fear-potentiated startle) were compared with previous data from C57BL/6J (C57) and DBA/2J (DBA) mouse strains. Progressive high frequency hearing loss in BALB/c mice was generally more rapid than C57 and slower than DBA (e.g. mean thresholds for 16 kHz: 10-month-old BALB/c mice = 71 dB SPL; 55-day-old DBA mice = 79 dB SPL; 12-month-old C57 mice = 50 dB SPL). Like the other strains, BALB/c exhibited a progressive loss of hair cells and SGCs that was most severe in the cochlear base and least severe in the middle turns; however, BALB/c mice had relatively more SGC loss in the apex. Unlike C57 and DBA, no loss of neurons was observed in the AVCN following cochlear pathology (although AVCN volume was reduced). Like the other strains, successful fear conditioning was obtained with a 12 kHz conditioned stimulus. Prepulse inhibition showed that middle and low frequency tones (4-12 kHz) became more salient as high frequency hearing declined. Similar results had been previously obtained with C57 and DBA mice and were interpreted as reflecting hearing-loss-induced plasticity in the central auditory system.

Acoustic Stimulation↗

Effects of noise on inferior colliculus evoked potentials and cochlear anatomy in young and aged chinchillas.

Like many aging humans, the aging chinchilla tends to lose high-frequency sensitivity at a faster rate than low-frequency sensitivity. This feature, combined with its excellent low-frequency hearing, makes the chinchilla attractive as an animal model for studying the relationship between noise-induced hearing loss (NIHL) and age-related hearing loss (AHL). In the present study, we examined susceptibility to noise in 15 aged (10-15 years old) and 15 young chinchillas. Two levels of noise were used, with the aim of determining whether age-related differences exist in the magnitude and rate of recovery from temporary threshold shifts produced by a moderate-level (95 dB) noise exposure, or in susceptibility to permanent threshold shifts and cochlear damage caused by a high-level (106 dB) noise exposure. Thresholds and response amplitudes at 0.5, 1, 2, 4, 8 and 16 kHz were determined from evoked potentials recorded from the inferior colliculus. Cochlear histology was performed on animals exposed to high-level noise. The results suggest that older animals are equally vulnerable to moderate-level noise, but may be slightly more vulnerable to high-level noise. For moderate-level exposures, there appears to be a simple additive relationship (in dB) between AHL and NIHL. For high-level exposures, the relationship may be more complex.

Acoustic Stimulation↗

Effects of inner hair cell loss on inferior colliculus evoked potential thresholds, amplitudes and forward masking functions in chinchillas.

The effects of outer hair cell (OHC) loss on evoked potential (EVP) thresholds, amplitudes and forward masking (FWM) functions have been fairly well characterized. In contrast, the effects of inner hair cell (IHC) losses are largely unknown, primarily due to the difficulty of producing selective IHC lesions. Recent studies have shown that IHCs of the chinchilla are preferentially damaged by the anticancer drug, carboplatin. In this study, we administered a single 100 mg/kg dose of carboplatin to four chinchillas, to examine the effects of IHC lesions on EVPs measured from the inferior colliculus (IC-EVPs). Thresholds and amplitude functions were measured for 0.25-16 kHz tone bursts, and FWM functions were measured at 1, 2 and 4 kHz, using masker probe intervals of 2, 5, 10, 20, 40 and 80 ms, before and 1-2 months after carboplatin treatment. Histology revealed IHC lesions ranging from approximately 15 to 90%, with virtually no loss of OHCs. Surprisingly, even massive IHC lesions were not associated with elevations of IC-EVP thresholds. IC-EVP amplitudes at suprathreshold levels were sometimes depressed, sometimes enhanced, and in some cases unchanged. IHC lesions increased susceptibility to FWM, particularly at intermediate (10-20 ms) masker-probe intervals, without significantly changing the overall time course of FWM. The results provide new perspectives on the contribution of IHCs to FWM, and on the ability of the central auditory system to adapt to a significant reduction of neural input from the cochlea.

Acoustic Stimulation↗

Protecting the Inner Ear from Acoustic Trauma.

Calcium activated proteases, or calpains, play an important role in neurodegeneration. In some cases, neural degeneration can be significantly reduced by leupeptin, a potent calpain inhibitor. To determine if leupeptin could protect against noise-induced hearing loss and hair cell loss, we infused leupeptin into scala tympani of one cochlea before, during and after a 14-day exposure to a 100 dB SPL, octave band noise centered at 4.0 kHz. Hearing loss, assessed with the auditory evoked response, was less in the leupeptin-treated ear than in the control ear during the early stage of recovery from acoustic trauma. In addition, hair cell loss in the leupeptin-treated ear was significantly less than in the control ear. These preliminary results suggest that leupeptin may protect against noise-induced hearing loss.

Journal Article↗

[Glycogenosis in cochlea of aging mice].

CBA/Caj mice and C57BL/6Nsd mice (animal models widely used for study of presbycusis) were used to study glycogen metabolic changes in the aging cochlea by a quantitative analysis of histochemistry. Glycogen contents in both hair cells and stria vascularis were significantly increased in CBA aged mice (18 and 36 months) as compared with those in CBA young animals (6 weeks), indicating a glycogenosis in the cochlea within naturally aging CBA mice. The glycogen contents in the stria vascularis in C57BL mice (6 weeks) was higher than in CBA (6 weeks) mice, whereas no significant difference could be discerned in the hair cell glycogen level. The results suggest that the glycogen metabolic changes in the CBA mice, a model of the natural aging cochlea, were different from in the C57 mice, a model of the cochlear genetic defect.

Aging↗

[Study on hepatitis G virus infection in 63 posttransfusion patients with hematological diseases].

OBJECTIVE: To study the hepatitis G virus(HGV) infection in posttransfusion patients. METHODS: HGV RNA and HCV RNA were detected by RT-PCR, and anti-HGV and HBsAg were assayed by ELISA in 63 posttransfusion patients with blood diseases. RESULTS: The positive rates of HGV RNA, HCV RNA and anti-HGV were 7.9%, 46.0% and 6.3%, respectively. HGV infection was usually accompanied by HCV infection and elevation of ALT. CONCLUSION: HGV as well as HCV may transmitted by blood transfusion.

Flaviviridae↗

[Quantitation of nerve fibers in habenula perforata in chinchilla].

OBJECTIVE: To examine the number of nerve fibers in the habenula perforata of the cochlea in normal and carboplatin-treated chinchillas. METHODS: Three months following administration of carboplatin (100 mg/kg x 2), six carboplatin-treated animals, together with 6 controls, were sacrificed, prepared for semi-thin sectioning of the cochlea. The sections were stained with toluidine blue and basic fuchsin, examined under a light microscope and photographed. RESULTS: In normal chinchillas, the numbers of the nerve fibers in each habenula opening varied across the cochlea, with 93.7 +/- 12.2(mean +/- s) fibers at the hook, 181.5 +/- 30.4 at the upper of basal turn, 129.7 +/- 27.8 at the second turn and 75.8 +/- 13.2 at the apical turn. In cochlear devoid of type I ganglion cells and inner hair cells as a result of carboplatin treatment, only one-seventh of the fiber population remained. CONCLUSION: Approximately six-seventh of the nerve fibers in the habenula are type I afferent axons that innervate the inner hair cells. The remaining fibers are type II afferents and surviving efferents.

Animals↗

[A study on the nutrient physiology of Ophiopogon japonicus (Thunb.) Ker-Gawl].

By means of observing at regular intervals and on tixed plants, the growth stages, organogenetic habits, content of nutrient elements and its changing regularity, storage habit of dry matter, relationship between aerial and subterraneous parts, and fertilizer requirements have been studied for Ophiopogen japonicus.

Drugs, Chinese Herbal↗

A new type of DNA minor-groove complex: carbazole dication-DNA interactions.

The effect of opportunistic infections (OI) on immune-compromised populations has been known for decades, but the recent AIDS epidemic has sparked renewed interest in the development of new anti-OI agents. The mechanism of action of a series of cationic unfused-aromatic anti-OI drugs is believed to involve binding of the drug to AT sequences in the minor groove of DNA. Some new anti-OI drug candidates have been synthesized with fused aromatic ring systems (e.g. carbazoles) that do not resemble the classical paradigm for minor-groove interactions at AT sequences in DNA. To characterize the DNA interactions of these compounds, we have used UV-vis absorbance, fluorescence, kinetic measurements, and circular dichroism in conjunction with NMR spectroscopy to evaluate the structure of the complexes formed between the carbazoles and DNA. Application of these methods to carbazoles substituted at either the 3,6 or 2,7 positions with cationic imidazoline groups gave conclusive, but very surprising, evidence that both compounds bind strongly in the minor groove at AT DNA sequences. NMR and molecular modeling of the complexes formed between the 3,6- and 2,7-carbazoles and the self-complementary oligomer d(GCGAATTCGC) have been used to establish structural details for the minor-groove complex. These results have been used as constraints for molecular modeling calculations to construct models of the minor-groove-carbazole complexes and to draw conclusions regarding the molecular basis for the effects of substituent position on carbazole-DNA affinities. The surprising result is that the 2,7 carbazole binds in AT sequences with hydrogen bonds involving one imidazoline group and the carbazole NH. The 3,6-carbazole compound binds in a more "classical" model that uses both imidazoline groups for H-bonding while the carbazole NH points out of the minor groove. The carbazoles thus form a new type of DNA minor groove complex and their excellent biological activities indicate that a variety of fused-ring minor-groove binding agents should be investigated.

Binding Sites↗

Effects of selective inner hair cell loss on auditory nerve fiber threshold, tuning and spontaneous and driven discharge rate.

Current theories assume that the outer hair cells (OHC) are responsible for the sharp tuning and exquisite sensitivity of the ear whereas inner hair cells (IHC) are mainly responsible for transmitting acoustic information to the central nervous system. To further evaluate this model, we used a single (38 mg/kg) or double dose (38 mg/kg, 2 times) of carboplatin to produce a moderate (20-28%) or severe (60-95%) IHC loss while sparing a large proportion of the OHCs. The surviving OHCs were functionally intact as indicated by normal cochlear microphonic (CM) potentials and distortion product otoacoustic emissions (DPOAE). Single-unit responses were recorded from auditory nerve fibers to determine the effects of the moderate or severe IHC loss on the output of the surviving IHCs. Most neurons that responded to sound in the single-dose group had normal or near-normal thresholds and normal tuning. Relatively few neurons in the double-dose group responded to sound because of the severe IHC loss. The neurons that did respond to sound had narrow tuning curves. Some neurons in the double-dose group also had thresholds that were within the normal range, but most had thresholds that were elevated a mild-to-moderate degree. These results indicate that intact IHCs can retain relatively normal sensitivity and tuning despite massive IHC loss in surrounding regions of the cochlea. However, the spontaneous and driven discharge rates of neurons in the carboplatin-treated animals were significantly lower than normal. These changes could conceivably be due to sublethal damage to surviving IHCs or to postsynaptic dysfunction in the auditory nerve.

Action Potentials↗