[International expert consensus on gene therapy for hereditary hearing loss: based on clinical trials].
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Journal Article↗
Biomedical subjects
D Zhang
Publications and source records attributed to D Zhang.
Blockade of NMDA receptor-mediated mobilization of intracellular Ca2+ prevents neurotoxicity.
NMDA receptor activation leads to elevated Ca2+ in cultured rat cortical and retinal ganglion cell neurons. If excessive, this Ca2+ response is associated with delayed neurotoxicity. We used dantrolene and ionomycin to test if the Ca2+ response to NMDA was due to mobilization of intracellular Ca2+ stores rather than merely to Ca2+ influx. In the presence of EGTA, ionomycin resulted in release and subsequent depletion of intracellular Ca2+ stores. Henceforth, despite normal extracellular Ca2+, NMDA elicited only about half of its former Ca2+ response. Similarly, when dantrolene was used to block Ca2+ release from intracellular stores, we observed > 50% smaller NMDA-evoked Ca2+ responses. These results quite surprisingly indicate that at least half the Ca2+ response to NMDA is due to release of intracellular Ca2+, a process triggered by influx of extracellular Ca2+. Dantrolene also protected neurons from NMDA receptor-mediated neurotoxicity. Release of intracellular Ca2+ may therefore be a necessary step in the cascade leading to neuronal damage induced by excessive NMDA receptor stimulation and may be amenable to pharmacological intervention.
Animals↗
Colocalization of enkephalin-, glucagon-, and corticotropin-releasing factor-like immunoreactivity in GABAergic amacrine cells in turtle retina.
The large number of amacrine cells which contain gamma-aminobutyric acid (GABA) in the turtle retina makes it difficult to examine specific GABAergic cell types. In order to selectively label subpopulations of GABAergic neurons, we have used fluorescent double-labeling immunocytochemical techniques to examine the localization of GABA-like immunoreactivity (LI) in amacrine cells which contain antigens resembling the neuropeptides glucagon (GLUC), corticotropin-releasing factor (CRF) or enkephalin (ENK). GABA-LI was found in 41% of the cells with GLUC-, 100% of the cells with CRF-, and 69% of the cells with ENK-LI. There were regional differences in the presence of GABA-LI in amacrine cell populations with ENK-LI. GABA-LI was present in about 80% of the cells with ENK-LI outside of the visual streak, while only 37% of the cells within the streak had GABA-LI. Based on the distinct morphologies and regional distributions of these peptidergic amacrine cells, we conclude that they represent different subpopulations of GABAergic amacrine cells in the turtle retina. Future studies can now utilize existing information regarding the synaptic connectivity of these peptidergic amacrine cells to help delineate the functions of GABAergic amacrine cells in the turtle retina.
Animals↗
Glutamate-immunoreactive terminals synapse on primate spinothalamic tract cells.
Glutamate has been shown to excite spinothalamic tract (STT) neurons and has been localized to primary afferent neurons, spinal cord projection neurons, and interneurons in the spinal cord dorsal horn. The likelihood that glutamate-immunoreactive (GLU-IR) terminals directly innervate STT neurons was investigated. For these studies three lamina IV or V STT cells in the lumbar spinal cords of three monkeys (Macaca fascicularis) were identified electrophysiologically and characterized. Two were identified as high threshold neurons and one as a wide dynamic range neuron. Following intracellular injection of the cells with HRP and reaction to give the cells a Golgi-like appearance, the tissues were processed for electron microscopy. Postembedding immunogold methods with antibodies specific for glutamate were used to identify GLU-IR terminals apposing the somata and dendrites of the STT neurons, including dendrites that extended into laminae IV and III. The GLU-IR terminals were numerous and constituted a mean of 46% of the population counted that appose the STT soma and 50% of the profiles apposing the dendrites. Fifty-four percent of the somatic and 50% of the dendritic surface length was contacted by GLU-IR terminals. Most terminals contained round clear vesicles and some contained a variable number of large dense core vesicles. For one of the three cells examined it was determined that 45% of the terminals apposing the soma were GLU-IR and 30% of the terminals were gamma aminobutyric acid-immunoreactive (GABA-IR). In an additional monkey, a lamina I cell retrogradely labeled from the ventral posterolateral nucleus of the thalamus was found to be ensheathed in glial processes.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
GABA-immunoreactive terminals synapse on primate spinothalamic tract cells.
Gamma-aminobutyric acid (GABA) is a putative inhibitory neurotransmitter in the vertebrate nervous system. Several lines of evidence suggest that GABA plays an important role in the processing and modulation of sensory input in the spinal cord dorsal horn. In the present study, the relationship between GABA-immunoreactive (GABA-IR) terminals and spinothalamic tract (STT) cells in the monkey lumbar cord was investigated. Physiologically characterized STT cells, one located in lamina V and two located in lateral lamina IV, were intracellularly injected with horseradish peroxidase (HRP). A fourth STT cell, located in lamina I, was retrogradely labeled following injection of HRP into the contralateral thalamus. Immunogold labeling of ultrathin sections through the cell bodies and proximal dendrites of the STT neurons demonstrated that the percentage of the GABA-IR terminals in contact with these profiles was 24.7% and 36%, respectively. The average STT surface length contacted by GABA-IR terminals for cell bodies and proximal dendrites was 18.2% and 26.7%, respectively. For the lamina I cell, 7 out of 35 (20%) of the terminals were GABA-IR and they covered 9.6% of the surface analyzed. These data demonstrate that GABA-IR terminals synapse directly on STT cells, constituting a substantial proportion of the terminal population on these cells. Furthermore, compared to the cell bodies, a greater percentage of the input on the proximal dendrites is GABAergic. These anatomical data are consistent with the findings of a previously published iontophoretic study that demonstrated that GABA can exert a strong inhibitory influence on STT cells. These findings are discussed in relation to GABAergic involvement in tonic and phasic inhibition of STT neurons.
Animals↗
Isolated cardiomyocytes in conjunction with NMR spectroscopy techniques to study metabolism and ion flux.
To distinguish cellular from vascular responses to physiological and pathophysiological stimuli, we developed methods to perform NMR spectroscopy on isolated ventricular cardiomyocytes. Isolated adult rat cardiomyocytes, placed in agarose beads and superfused with phosphate-free buffer (Media 199 (GIBCO 400-1100) gassed with 95% O2, 5% CO2), were used to evaluate a variety of cellular processes during different pharmacological and physiological interventions. Bioenergetic function was monitored with 31P NMR. Intermediary metabolism, gluconeogenesis, and glycolysis were monitored with 13C NMR. Sodium flux was monitored with 23Na NMR. Calcium flux was monitored with 19F NMR in conjunction with an intracellular calcium-chelating agent, 5F-1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid. Creatine kinase kinetics (forward rate constant (Kf) and flux of phosphocreatine to ATP) were estimated with 31P NMR saturation transfer data. Various combinations of NMR parameters were monitored simultaneously so that the interaction of metabolism and ion flux could be evaluated. We have demonstrated that it is possible to simultaneously monitor a variety of cellular processes in intact heart cells in real time, without the confounding influences of perfusion, contractile function, and extrinsic blood-borne neurohumoral agents. This model will be useful for longitudinal studies of myocyte metabolism and ion flux.
Acetylcholine↗
Substance-P-like immunoreactive amacrine cells in the adult and the developing rat retina.
Substance-P-like immunoreactivity (SP-LI) cells in the Long-Evans rat retina were investigated by combining immunohistochemistry with [3H]thymidine autoradiography. Two subpopulations of SP-LI amacrine cells, with cell bodies in either the proximal portion of the inner nuclear layer (INL) or the ganglion cell layer (GCL), were identified based on morphology, pattern of distribution and development. In the INL, SP-LI cells were found scattered throughout the retina. However, in the GCL, they were limited to the superio-temporal region. Such a contrast in distribution specific to nuclear layers was present upon first detection of SP-LI amacrine cells and persisted throughout development. Birthdating revealed a temporal lag in the histogenesis of SP-LI cells situated in the GCL relative to that in the INL, suggesting that the two subpopulations developed separately. Overall, unique anatomical features of the SP-LI amacrine cells in the rat retina were observed which could only have been uncovered through detailed analyses in the adult as well as during postnatal development.
Animals↗
L-homocysteic acid selectively activates N-methyl-D-aspartate receptors of rat retinal ganglion cells.
To explore the possible role of L-homocysteic acid (HCA) as a retinal transmitter, whole-cell recordings with patch electrodes were performed on isolated rat retinal ganglion cells (RGCs) in culture. HCA elicited an inward current at -60 mV. Similar to currents evoked at this potential in RGCs by N-methyl-D-aspartate (NMDA), HCA-activated currents were of relatively small amplitude (10-150 pA), and the noise level increased dramatically during the response. When HCA was co-applied with concentrations of NMDA that elicited a maximal response, the current was not increased over that of NMDA alone. HCA-evoked currents were almost completely blocked by the NMDA antagonists D-2-amino-5-phosphonovalerate (D-AP5), Mg2+, or 7-chlorokynurenate (7-Cl KYN). Unlike its effects on other preparations, even millimolar concentrations of HCA did not activate kainate-like currents. These observations suggest that HCA specifically activates the NMDA receptor-channel complex of rat RGCs.
2-Amino-5-phosphonovalerate↗
Effect of helium-neon laser irradiation on serum lipid peroxide concentrations in burnt mice.
The effect of helium-neon irradiation on serum lipid peroxide concentrations in mice following 6-7% body surface area burns was investigated in a controlled study. Immediately following injury by an 8-sec 100 degrees C scalding, 25 mice were irradiated by a helium-neon laser at 0.05 J/cm2. A control group of the same size underwent identical treatment but received only sham irradiation. Serum lipid peroxide concentrations increased markedly in the control group at 0.5-4 h (P less than 0.0001, two sample t-test). In the laser treated group, the lipid peroxide concentrations remained relatively constant and were significantly depressed relative to the control group 4 h following burning (P less than 0.0001, two-sample t-test).
Animals↗
Effect of coprophagy on bioavailability of iron from plant foods fed to anemic rats.
Effects of coprophagy and coprophagy preventing device on iron bioavailability were evaluated in two experiments. In Experiment 1, rats were fed diets with FeSO4, spinach, bran cereal or cornmeal as the iron source. The rats in each diet group were fitted with collars, sham-collars or not fitted with collars (control). In Experiment 2, rats were fed diets with FeSO4 or green peas as the iron source and were fitted with collars, tail cups, sham-collars or not fitted with any device (control). Preventing coprophagy reduced hemoglobin regeneration efficiency (HRE) of rats fed bran cereal, green peas, spinach or cornmeal diets by 26 (P less than .05), 24(P less than .05), 22(P less than .05) and 11% (not significant), respectively. Preventing coprophagy in rats fed FeSO4 diet did not significantly reduce HRE. Sham-collaring reduced (P less than .05) HRE of rats fed the FeSO4 diet by 12 and 13% but did not significantly affect HRE in rats fed food iron sources. It was more convenient and effective to prevent coprophagy with collars than with tail cups. Differences in bioavailability between food and FeSO4 iron due to coprophagy may be explained based on two gastrointestinal nonheme iron pools, complexed and highly soluble.
Absorption↗
Heterozygosity of the major histocompatibility complex controls the autoimmune disease in (NZW x BXSB) F1 mice.
In the F1 hybrid of phenotypically normal NZW (H-2z) and systemic lupus erythematosus (SLE)-prone BXSB mice (H-2b), features of the disease became more severe than those seen in the BXSB mice, regardless of the presence or absence of the Yaa (Y-chromosome-linked autoimmune acceleration) mutant gene. To determine whether the gene(s) linked to the major histocompatibility complex (MHC) of NZW mice is involved in this event, we developed the H-2-congenic NZW.H-2d strain and compared the severity of autoimmune disease between (NZW x BXSB) F1 (H-2z/b) and (NZW.H-2d x BXSB) F1 mice (H-2d/b). The H-2z/b, but not H-2d/b, heterozygous F1 mice of both sexes showed an accelerated, higher incidence of proteinuria and a more severe thrombocytopenia than did the BXSB mice. In NZW x (NZW x BXSB) F1 backcross mice, the H-2z/b heterozygous progeny showed more severe disease than did the H-2z/z homozygotes. Thus, disease-accelerating events in (NZW x BXSB) F1 mice are linked to the H-2z/b heterozygosity. Because H-2d/z heterozygosity plays a crucial role for SLE in (NZB x NZW) F1 mice, in which SLE features differ from those in (NZW x BXSB) F1 mice, the present observations may imply that the different but related MHC heterozygosity acts as a predisposing genetic element in these different SLE syndromes.
Age Factors↗
Ultrasonic attenuation estimation in-vivo using the difference ratio correction method.
In recent years, B scanners have been widely used clinically. Obviously, it is of particular importance to use the commercial B scanners to characterize tissue by estimating its ultrasonic attenuation in vivo. However, there are a lot of difficulties in doing so because the output of a B scanner is affected by many unknown factors. In this paper, a time domain method named the difference ratio correction (DRC) method is proposed to estimate the ultrasonic attenuation of tissue in vivo. In this method, three tissue-mimicking phantoms with known acoustical properties were employed to eliminate the instrumentation errors of the B scanner and the measuring system and to correct beam diffraction for correct attenuation estimation. Other advantages of this method are that it is very convenient to apply this method clinically and there is no need to change the inner construction of the B scanner because this method only utilizes the video output. Experimental and clinical results have proved the validity of this method.
Biophysical Phenomena↗
Changes in the response states of primate spinothalamic tract cells caused by mechanical damage of the skin or activation of descending controls.
1. The responses of a population of 318 spinothalamic tract (STT) cells to mechanical stimulation of the skin were recorded in anesthetized macaque monkeys by several teams of investigators. The responses were subjected to k-means cluster analysis, a multivariate statistical procedure. 2. For an analysis that pertained to the responsiveness of the neurons, the mean responses to four standard mechanical stimuli (Brush, Pressure, Pinch, and Squeeze) were used. Although no true clusters were found, the cells could be partitioned into four groups (called clusters a, b, c, and d) that responded progressively more vigorously to the stimuli. 3. For an analysis that pertained to the selectivity of the cells for various stimulus intensities, from innocuous to highly noxious, the data were normalized by taking the ratio of the mean response evoked by each stimulus to the sum of the responses and multiplying by 100. This procedure does not have a bias toward selection of any particular number of clusters and resulted in three clusters of STT cells. 4. Cluster 1 STT cells responded best to Brush. Cluster 2 cells responded weakly to Brush and Pressure and maximally to Pinch. Cluster 3 cells responded weakly to Brush, Pressure, and Pinch and maximally to Squeeze. 5. The response states of STT cells with respect to mechanical stimulation of the skin can be defined by their cluster assignments on the basis of the responsiveness (clusters a-d) and selectivity (clusters 1-3) of the cells. The response states of newly recorded STT cells can be determined by discriminant analysis from the nearest centroids of the two types of clusters in the reference population of STT cells. 6. No consistent changes in response state were detected when a second series of mechanical stimuli was applied 1 cm from the site stimulated initially or when the stimulus series was alternately repeated at the initial site and at progressively more proximal sites. However, when the stimulus series was applied five times to the initial site, the response state of five of eight cells tested showed a change. Although a change in response state required repetitive damage, even a single stimulus series increased background activity and responses to Brush at undamaged sites. 7. The background activity and responses to Brush and Pressure of all five STT cells recorded in the superficial laminae increased after repeated testing. The background activity of five STT cells recorded in the nucleus proprius also increased, but the responses of only three of the cells to Brush and Pressure increased.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Creatine and cyclocreatine effects on ischemic myocardium: 31P nuclear magnetic resonance evaluation of intact heart.
The purpose of this study was to investigate the effects of prior dietary supplementation with creatine (Cr) or cyclocreatine (Cy, a synthetic analogue of Cr) on high energy phosphate metabolism of the ischemic myocardium. To this end, 48 rats were fed the following powdered rat chow diet for 21 days: 16 were fed chow without additives (CON); 16 were fed a diet containing 1% Cr by weight (CR); 16 were fed a diet containing 1% Cy by weight (CY). At the end of the feeding period, rats were anesthetized, hearts harvested and perfused in the Langendorff mode using Krebs-Henseleit buffer (maintained at 37 degrees C, equilibrated with 95% O2/5% CO2) to which 11 mM glucose was added. 31P nuclear magnetic resonance (NMR) studies of myocardial bioenergetics were done using a Bruker AM 500 spectrometer. After acquisition of preischemic spectra, global ischemia was produced by clamping aortic inflow. Ischemia was maintained until adenosine triphosphate (ATP) became NMR invisible (CON = 34 +/- 11 min; CR = 32 +/- 13 min; CY = 56 +/- 13 min; p less than 0.05 CY vs. CR and CON). Half-lives of ATP were 19 min for CON and CR and 37.5 min for CY; half-lives of phosphagen were 4 min for CON and CR and 11 min for CY. Time for return of mechanical function (heart rate x systolic pressure) after ischemia was similar for all three groups (CON = 28 +/- 28, CR = 34 +/- 22, and CY = 22 +/- 15 min), even though the CY group was subjected to longer periods of ischemia). These data indicate that CY, but not CR, pretreatment provides myocardial protection either during and/or after ischemia and allows return of mechanical function after much longer episodes of ischemia than in CON and CR. One factor in the mechanism of protection may be the prolonged maintenance of phosphagen due to the higher equilibrium concentration of phosphocyclocreatine which in turn provides substrate for continued synthesis of ATP during and after ischemia, thus defining Cy as a bioenergetic protective agent. Other mechanisms of protection remain to be defined.
Adenosine Triphosphate↗
Dietary zinc methionine effect on eggshell quality of hens drinking saline water.
In two experiments individually caged 60-wk-old laying hens were exposed to daily temperatures ranging between 18 and 35 C and given various dietary and drinking water treatments. In Experiment 1 these were: 1) basal diet and town water; 2) basal diet and town water supplemented with 2 g NaCl/L; 3) basal diet supplemented with .2 g zinc methionine (Zinpro-200)/kg diet and town water; or 4) basal diet supplemented with .2 g zinc methionine/kg and town water supplemented with 2 g NaCl/L. In Experiment 2, Treatments 1 and 2 were the same as in Experiment 1. Birds on Treatments 3 and 4 received the town water supplemented with 2 g NaCl/L and the basal diet supplemented with either .5 g zinc methionine/kg (Treatment 3) or .28 g ZnSO4H2O/kg to approximate the same dietary zinc concentration in Treatment 3 (Treatment 4). In both experiments, dietary zinc methionine plus 2 g NaCl/L in the drinking water significantly improved shell breaking strength over those birds on the 2 g NaCl/L with no zinc methionine supplementation. This same pattern occurred for shell weight, shell weight per unit of surface area, and percentage of shell defects. There were no improvements in the parameters measured from the supplementation of ZnSO4. The zinc methionine compound apparently was effective in overcoming the negative influence of the added 2 g NaCl/L of town water.
Animal Feed↗
Calcium and carbonate supply in the shell gland of hens laying eggs with strong and weak shells and during and after a rest from lay.
The concentration of calcium-binding protein (CaBP) and the activities of calcium adenosine triphosphatase (Ca(2+)-ATPase) and carbonic anhydrase (CA) were determined in the shell gland mucosa of hens in two experiments. In Experiment 1, laying hens on a proprietary layer mash were compared with hens rested from lay by the feeding of whole grain barley. In Experiment 2 comparisons were made of laying hens fed the proprietary layer mash and producing eggs with either strong or weak shells. These latter comparisons were also made when the shell gland was quiescent or active with respect to daily eggshell formation. Feeding whole grain barley reduced egg production to zero after 11 days. This reduction in rate of lay was accompanied by significant reductions in all three markers, the effect on Ca(2+)-ATPase and CaBP being less than for CA. Control values were regained between 10 and 16 days after the barley was replaced with the layer mash. Relative shell strength and the physiological status of the shell gland with respect to time of daily eggshell formation had no significant effect on any marker in Experiment 2.
Animal Feed↗
[Application of infrared thermography for study of acupuncture and meridians].
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Acupuncture Therapy↗
[The experimental research on the changes in the amount of prostaglandins in rat alveolar bone during tooth movement].
In this paper, the author observed that in different time the changes of the amount of endogenous prostaglandins in rat alveolar bone under continuous orthodontic force, and confirmed that there are certain amount of PGE1. PGE2 in the rat alveolar bone even without orthodontic force, and the amount is no difference between right and left side. After several hours when the orthodontic force was applied the amount of PGE1 and PGE2 in rat alveolar bone rose significantly. But it is transient and does not last 24 hours.
Alprostadil↗