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Biomedical subjects

D Zheng

Publications and source records attributed to D Zheng.

At least 73 records · Page 4Linked to original sources

Kindling and associated mossy fibre sprouting are not affected in mice deficient of NGFI-A/NGFI-B genes.

Kindling is an animal model of epileptogenesis, whereby repeated administration of an initially subconvulsive electrical stimulation eventually leads to the development of generalized motor seizures. Once established, the kindling effect is permanent. Although the molecular basis of kindling remains incompletely understood, emerging lines of evidence suggest that the induction of immediate-early genes could represent a link between periodic short-term stimuli and the long-lasting functional and structural alterations in the brain associated with the development of seizures. A recent study showed that null mutation of the immediate-early gene c-fos impairs the structural and functional plasticities in kindling. In the present study, we examined whether two other seizure-inducible immediate-early genes--NGFI-A (also termed EGR-1, zifl268, and Krox-24) and NGFI-B (also termed Nur77)--play requisite roles in kindling. We found that neither the rate of kindling nor seizure-induced granule cell axonal sprouting was affected in mice carrying a null mutation of NGFI-A. Furthermore, double knock-out of NGFI-A and NGFI-B genes does not result in detectable changes in kindling development and associated mossy fibre sprouting. Taken together, our observations indicate that neither constitutive nor seizure-induced expression of NGFI-A or NGFI-B is uniquely required for the establishment of kindling. These findings underscore the specificity of the immediate-early genes whose transcriptional activation contributes to kindling epileptogenesis.

Animals↗

Tachycardia alone fails to change the myocardial pharmacokinetics and dynamics of lidocaine, thiopental, and verapamil after intravenous bolus administration in sheep.

Previous reports have suggested that tachycardia alone can increase the rate of myocardial uptake of some drugs. As part of a systematic study of the determinants of the myocardial uptake and effects of drugs in critical illness, the effect of tachycardia induced by intracardiac pacing on the myocardial disposition and effects of lidocaine, verapamil, and thiopental were studied in chronically instrumented sheep. For each drug, seven sheep received either 100 mg of lidocaine, 10 mg of verapamil, or 750 mg of thiopental over 2 min in unpaced and paced (140 beats/min) states on separate occasions and in random order. Arterial and coronary sinus (effluent from the heart) blood samples were taken at regular intervals for 30 min, and the maximum rate of change of left ventricular pressure (LV dP/dtmax) was measured as an index of myocardial contractility. There were no differences between unpaced and paced studies in the time courses of arterial and coronary sinus concentrations, or the time-courses of myocardial contractility and blood flow, after bolus iv injections of these drugs. Tachycardia alone does not appear to influence the myocardial kinetics or dynamics of lipophilic drugs that can rapidly diffuse into the heart.

Animals↗

Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment.

Hearing impairment is the most commonly occurring condition that affects the ability of humans to communicate. More than 50% of the cases of profound early-onset deafness are caused by genetic factors. Over 40 loci for non-syndromic deafness have been genetically mapped, and mutations in several genes have been shown to cause hearing loss. Mutations in the gene encoding connexin 26 (GJB2) cause both autosomal recessive and dominant forms of hearing impairment. To study the possible involvement of other members of the connexin family in hereditary hearing impairment, we cloned the gene (GJB3) encoding human gap junction protein beta-3 using homologous EST searching and nested PCR. GJB3 was mapped to human chromosome 1p33-p35. Mutation analysis revealed that a missense mutation and a nonsense mutation of GJB3 were associated with high-frequency hearing loss in two families. Moreover, expression of Gjb3 was identified in rat inner ear tissue by RT-PCR. These findings suggest that mutations in GJB3 may be responsible for bilateral high-frequency hearing impairment.

Adult↗

The influence of the bolus injection rate of propofol on its cardiovascular effects and peak blood concentrations in sheep.

UNLABELLED: The influence of the bolus injection rate of propofol on its cardiovascular effects has not been extensively studied. We therefore examined the influence of the injection rate of i.v. bolus doses of propofol on its acute cardiovascular effects and peak blood concentrations in seven chronically instrumented sheep. Each received i.v. propofol (200 mg) over 2 min (slow injection) and 0.5 min (rapid injection) on separate occasions in random order. The rapid injection was associated with more profound decreases in mean arterial blood pressure than slow injection (35.7% vs 23.7% maximal reductions from baseline, respectively; P = 0.02). There were no significant differences between the injection rates for peak reductions in myocardial contractility, increases in heart rate, or degree of respiratory depression. Concurrently, the rapid injections were associated with significantly higher arterial (26.9 vs 11.9 mg/L) propofol concentrations in a manner consistent with indicator dilution principles. There were no differences in the peak coronary sinus concentrations between the injection rates. We conclude that the rapid injection of propofol in the context of the induction of anesthesia produced significantly higher peak arterial propofol concentrations and suggest that it is these higher concentrations that produced relatively greater reductions in arterial blood pressure from rapid injections. IMPLICATIONS: Propofol is injected into a vein to initiate anesthesia. It can cause a rapid decrease in blood pressure, which may be dangerous to the patient. We examined the effect of rapid and slow injection rates of propofol in sheep and found that rapid injection caused a greater decrease in blood pressure. This was because rapid injection caused higher concentrations of propofol in the blood immediately after the injection. We believe that if the same processes occur in humans, there may be little advantage in injecting propofol rapidly.

Anesthetics, Intravenous↗

[8-chloro-adenosine induced apoptosis in various human tumor cell lines].

OBJECTIVE: To study the effect of 8-Chloro-adenosine (8CA) on tumor cell growth and apoptosis. METHODS: Tumor and normal cell lines were treated with 8CA at different concentrations and cell growth was analysed by MTT assay. Cell apoptosis was evaluated by light microscopy, flow cytometry and chromosome DNA fragmentation. RESULTS: Treatment with 8CA at 10 mumol/L remarkably inhibited tumor cell growth. HL-60 promyelocytic leukemia cell line was more sensitive to 8CA than MGc-803 gastric mucoid adenocarcinoma cell line. NIH3T3 cells were relatively resistant to 8CA. The IC50 of HL-60 and MGc-803 cells was 1.2 mumol/L and 1.8 mumol/L, respectively, while that of NIH3T3 cells was 12 mumol/L. Further study showed that 8CA induced HL-60 and MGc-803 cell death characterized by apoptotic phenotypes, DNA content changes and chromosome DNA fragmentation. CONCLUSION: 8CA is a potential agent for tumor chemotherapy.

2-Chloroadenosine↗

[Rheumatoid arthritis synoviocyte hyperplasia and expression of fas and bcl-2 genes].

OBJECTIVE: To determine whether apoptosis occurs in the proliferative synovial tissue and cells from patients with rheumatoid arthritis (RA). METHODS: In situ hybridization was carried out by using labeled RNA probes of fas, fasL, and bcl-2 synthesized by in vitro transcription. Apoptosis was examined by DNA electrophoresis and flow cytometry. RESULTS: fas mRNAs were expressed in 6 of 7 patients with RA. bcl-2 mRNAs were positive in 5 of 7 patients with RA. fasL mRNAs were not detectable in all the patients. bcl-2 mRNAs were always coexpressed with fas in RA synovial lining cells. The positive rates of fas and bcl-2 expression in RA synovial tissues were significantly higher than those of patients with osteoarthritis (OA) and normal synovial tissues (P < 0.05). Immunochemistry staining showed that Fas and Bcl-2 proteins were expressed in the synovial lining cells. Nucleic DNA extracted from the synovial tissues of 6 patients with RA, 4 patients with OA and 2 normal controls. Agarose gel electrophoresis demonstrated that DNA ladders occurred in only one OA synovial tissue. The spontaneous apoptosis in cultured synoviocytes from patients with RA and OA was lower as analyzed by immunofluorescence staining and flow cytometry. CONCLUSION: The phenomena of apoptosis in RA synoviocytes was not significant and overexpression of bcl-2 perhaps inhibited apoptosis in these cells, leading to hyperplasia of RA synoviocytes.

Apoptosis↗

[Histologic study on the pulpal response after complete crown preparation].

Protecting pulp health during preparation procedures is one of the key factors for prosthesis success. The histological sections of dental pulp showed the disruption of odontoblastic layer, blood vessels hyperemia and local bleeding. Dental histological sections of 40 healthy teeth which would need to be detracted because of orthodontical treatment were made to observe the pulp response in vivo during different tooth preparation time, including four groups: before preparation, after preparation, one week after being covered with temporary crown and two weeks after being covered with temporary crown. when air-water spray was used during crown preparation, Healing of the pulp was apparent 2 weeks following preparation, when the prepared teeth were covered with temporary crown and cemented with zinc oxide eugenol.

Crowns↗

[Observation of complications at the operative and early postoperative stages of phacoemulsification].

PURPOSE: The study was designed to investigate the reason and management of the complications at the initial stage of studying the technique of phacoemulsification. METHODS: Observing the complications at the operative and early postoperative stages of phacoemulsification used in situ nuclear fracture technique or in iridial plain fracture technique on 233 eyes of 212 patients with cataract. RESULTS: During the operations the rate of vitreous loss was 8.6% (20 eyes); iridial damage was 5.6% (13 eyes); hemorrhage in the anterior chamber was 0.4% (1 eye). After the operations the rate of continued corneal edema was 1.3% (3 eyes); posterior capsular opacity was 3.0% (7 eyes); inflammation was 0.9% (2 eyes); discentral location of intraocular lens was 0.4% (1 eye); leakage of wound was 0.9% (2 eyes); hemorrhage in the anterior chamber was 0.4% (1 eye). CONCLUSION: Vitreous loss and iridial damage were the frequent complications at the initial stage of studying the technique of phacoemusification. The rate of the complications was lower in situ nuclear fracture technique than in iridial plain fracture technique.

Adult↗

The enantiomer-specific kinetics and dynamics of verapamil after rapid intravenous administration to sheep: physiological analysis and modeling.

The lung, myocardial and systemic kinetics of the enantiomers of verapamil, and their myocardial effects, were measured after administration of 10 mg of racemic verapamil during 2 min to chronically instrumented sheep; the data were used to develop a physiological model of the process. Verapamil was characterized by relatively slow transit through the lungs and heart. The lung kinetic values were membrane limited, whereas the tissue/blood equilibrium half-life for the heart was approximately 8 min. There was little difference between the kinetic values of the enantiomers, with the exception of their extent of deep distribution into the lung. The time course of the increase in myocardial blood flow caused by verapamil was best related to the time course of the arterial verapamil concentrations, whereas the time course of increases in the interval between P and R waves of the electrocardiogram and decreases in the maximum rate of rise of left ventricular pressure were best related to the time course of its myocardial concentrations. Thus, the observed hysteresis for these effects compared with arterial blood was largely caused by the time required for the myocardial equilibration. The model predicted that the myocardial concentrations of verapamil were relatively insensitive to the duration of injection of a given bolus dose, but that rapid injection caused transient, high arterial concentrations. It also predicted that the bolus dose of verapamil should be modified over a 2-fold range to account for physiologically plausible variations in base-line cardiac output and myocardial blood flow.

Animals↗

Overview of the Diabetes Initiative of South Carolina.

Implementation is underway for many of these programs, and there are descriptions of activities elsewhere in this symposium. The Board recognizes that in dealing with the complications of a chronic disease like diabetes, many years of intense effort will be needed before significant results may be appreciated. Progress will be monitored regularly by the Surveillance Council and SCDCP/DHEC, and modifications of the plan will be made by the Board at intervals after review of the data. We are optimistic that over the next decade, this system will make a significant impact to reduce mortality, morbidity, and costs of diabetes, and the result will be an increased quality of life for people affected by diabetes in South Carolina.

Diabetes Mellitus↗

Diabetes patient education.

Not all medical practices are equipped to provide diabetes self-management training. Physicians can incorporate a team approach in their practice by establishing collaborative relationships with recognized diabetes education programs. The ADA's education recognition program has identified diabetes education programs that meet the National Standards for Diabetes Self-Management Education Programs. This list is available on the ADA's web site at http://www.diabetes.org/recognition and is printed twice a year in Diabetes Forecast. The National Certification Board for Diabetes Educators (NDEA) can provide a list of CDEs in your area. The South Carolina Model Diabetes Patient Education Program of DSC and SCDCP/DHEC is an excellent critical step towards obtaining ADA recognition.

Diabetes Mellitus↗

Tyrosine phosphorylation of the CD3-epsilon subunit of the T cell antigen receptor mediates enhanced association with phosphatidylinositol 3-kinase in Jurkat T cells.

T cell receptor signaling results both in T cell proliferation and apoptosis. A key enzyme at the intersection of these downstream pathways is phosphatidylinositol 3'-kinase (PI 3-kinase). In a previous report, we showed that the p85alpha subunit of the PI 3-kinase preferentially associated with the CD3-zeta membrane-proximal immunoreceptor tyrosine-based activation motif of the zeta chain (zetaA-ITAM) (Exley, M., Varticovski, L., Peter, M., Sancho, J., and Terhorst, C. (1994) J. Biol. Chem. 269, 15140-15146). Here, we demonstrate that tyrosine phosphorylation of CD3-epsilon can recruit the PI 3-kinase enzyme in a T cell activation-dependent manner. In vivo studies with Jurkat cells stably transfected with a CD8-CD3-epsilon chimera (termed CD8-epsilon) shows that ligation of endogenous CD3-epsilon or CD8-epsilon by specific antibodies induces tyrosine phosphorylation of CD3-epsilon or CD8-epsilon, respectively. Increased tyrosine phosphorylation correlates with increased binding of p85alpha PI 3-kinase and recruitment of PI 3-kinase enzymatic activity to CD3-epsilon or CD8-epsilon proteins. Mutagenesis studies in COS-7 cells, transiently transfected with CD8-epsilon, p85alpha, and Fyn cDNAs in various combinations, show that both Tyr170 and Tyr181 within the CD3-epsilon-ITAM are required for efficient binding of p85alpha PI 3-kinase. Thus, replacement of Tyr170 by Phe (Y170F), or Tyr181 by Phe (Y181F) significantly reduces binding of p85alpha PI 3-kinase, whereas it does not affect binding of Fyn. Further in vitro experiments suggest that a direct binding of the tandem SH2 domains of p85alpha PI 3-kinase to the two phosphorylated tyrosines in a single CD3-epsilon-ITAM may occur. The data also support a model in which a single CD3 subunit can recruit distinct effector molecules by means of TCR-mediated differential ITAM phosphorylation.

Amino Acid Sequence↗

A 7.5-kbp region of the maize (T cytoplasm) mitochondrial genome contains a chloroplast-like trnI (CAT) pseudo gene and many short segments homologous to chloroplast and other known genes.

The DNA sequence of a 7.5-kbp region from the maize cmsT mt genome was determined. Nucleotide-sequence analysis of this region reveals the presence of a ct-like trnI (CAT) gene, orf31 and orf48 which are respectively homologous to the trnI (CAT) gene in the maize and rice chloroplast genomes, and to orf28 and orf64 in the rice chloroplast genome. Northern-blot analysis indicates that the ct-like trnI (CAT) gene is likely to be a pseudo gene in the maize cmsT mt genome because it is not transcribed. A nucleotide-sequence homology search of this 7.5-kbp region reveals several short segments homologous to portions of chloroplast (ct), mitochondrial (mt) and other known genes. These segments range from 17 bp to 187 bp in length with homology from 71 to 100%. These observations also suggest that the transfer of DNA fragments from the ct genome to the mt genome may have occurred at different times during the evolution of the maize mt genome, and that multiple recombination events and rearrangements in both mt and ct genomes have occurred after the transfer of DNA fragments from the ct to the mt genome. A few segments were identified by their homology to be portions of genes from sources other than the ct genome. While it is known that large fragments of ctDNA have been transferred to maize mt genomes, this is the first report of the presence of numerous short ctDNA, or other foreign DNA segments, in the maize cmsT mt genome. These segments may provide valuable information regarding the evolution of plant mt genomes.

Base Sequence↗

Characterization of the mitochondrial cytochrome b gene from Venturia inaequalis.

A new class of agricultural fungicides derived from the group of antifungal strobilurins acts as specific respiration inhibitors by binding to mitochondrial cytochrome b. The cytochrome b gene was cloned and sequenced from the mitochondrial genome of Venturia inaequalis, the causal agent of apple scab. The gene was 10.65 kbp in size and contained seven exons and six introns. The exons encoded a protein of 393 amino acids. Comparison of the deduced amino-acid sequence with cytochrome b proteins from other fungi revealed highest homologies to the respective proteins of Aspergillus nidulans, Podospora anserina and Neurospora crassa. All amino acids of the V. inaequalis cytochrome b at positions altered in mutants of Saccharomyces cerevisiae resistant to strobilurins, and other fungi with reduced sensitivities to strobilurins, were identical to wild-type isolates of several fungi. The cloning and characterization of the V. inaequalis cytochrome b gene is the initial step in the assessment of resistance risks inherent to the strobilurin fungicides.

Amino Acid Sequence↗

Major depression and all-cause mortality among white adults in the United States.

PURPOSE: Depression is the most common psychiatric illness affecting adults. Despite the importance of a potential link between major depression and mortality, research has been surprisingly sparse. METHODS: Information on 57,897 white adults aged 25 years and older who were included in the mental health supplement of the 1989 National Health Interview Survey was linked with the National Death Index to examine the relationship of major depression to mortality. Death status was obtained through December 1991. Sex-specific hazard rate ratios for mortality were calculated by Cox proportional hazards regression and Poisson regression to adjust for potential confounders (age, education, marital status, body mass index, and whether the target subject or a family member completed the survey about the subject). RESULTS: Major depression was reported for 223 (0.8%) of 27,345 men and 392 (1.3%) of 30,552 women. During the 2.5-year follow-up, death certificate data were obtained for 848 (3.1%) men and 651 (2.1%) women. The adjusted hazard rate ratios for all-cause mortality associated with major depression were 3.1 (95% confidence interval; 2.0-4.9) for men and 1.7 (95% confidence interval; 0.9-3.1) for women. CONCLUSIONS: These results suggest that major depression increases risk of all-cause mortality, particularly among men. Further research is needed to explain the mechanism.

Adult↗