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Biomedical subjects

H Zheng

Publications and source records attributed to H Zheng.

At least 325 records · Page 18Linked to original sources

beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity.

In several pedigrees of early onset familial Alzheimer's disease (FAD), point mutations in the beta-amyloid precursor protein (APP) gene are genetically linked to the disease. This finding implicates APP in the pathogenesis of Alzheimer's disease in these individuals. To understand the in vivo function of APP and its processing, we have generated an APP-null mutation in mice. Homozygous APP-deficient mice were viable and fertile. However, the mutant animals weighed 15%-20% less than age-matched wild-type controls. Neurological evaluation showed that the APP-deficient mice exhibited a decreased locomotor activity and forelimb grip strength, indicating a compromised neuronal or muscular function. In addition, four out of six homozygous mice showed reactive gliosis at 14 weeks of age, suggesting an impaired neuronal function as a result of the APP-null mutation.

Amyloid beta-Protein Precursor↗

Chemical modulation of metallothionein I and III mRNA in mouse brain.

Metallothioneins (MTs) are sulfhydryl-rich proteins. MT-I and MT-II are found in all tissues of the body, while MT-III exists only in brain. Regulation of MT-I and MT-III mRNA was studied in brain and liver of control C57BL/6J mice and mice given chemicals known to increase MT-I, namely, lipopolysaccharide (LPS), zinc chloride (Zn), cadmium chloride (Cd), dexamethasone (Dex), ethanol, and kainic acid (KA). Northern blot analysis revealed that MT-I mRNA levels in liver were induced dramatically (12-27-fold over basal levels) by all of the chemicals, while in brain only LPS produced an increase in MT-I mRNA (2-fold). Interestingly, the MT-I inducers, Cd, Dex, ethanol, and KA, down-regulated brain MT-III mRNA levels by approx. 30%. Because brain is such a heterogenous tissue, in situ hybridization was used to localize MT-I and MT-III mRNA in control and treated mice. MT-I mRNA signal, which was most abundant in the glial cells of the Purkinje cell layer of the cerebellum in control mice, appeared to be enhanced in mice given the MT-I inducers (LPS, Zn, Cd, Dex, ethanol, and KA). MT-I mRNA hybridization signal was also enhanced in the olfactory bulbs from LPS- and Cd-treated mice, while this signal was present but weak in control brains. MT-III mRNA hybridization signals were localized in hippocampus and co-localized with MT-I message in the glial cells of the Purkinje cell layer of the cerebellum. In addition, diffuse MT-III mRNA signals were visible in areas of the cerebral cortex, and in the molecular layer of the cerebellum. Signals for MT-III in hippocampus appeared to be reduced by KA, Dex and LPS treatment, while in the cortical region, MT-III mRNA signals appeared to be enhanced by KA, Cd, and ethanol treatment. In conclusion, both MT-I and MT-III expression in brain appears to be modulated by exogenous treatment, however, the changes are small in relation to those observed in liver. Chemical-induced alterations of MT mRNA are non-uniform throughout the brain, and thus best studied in a region-specific manner.

Animals↗

Resistance to fever induction and impaired acute-phase response in interleukin-1 beta-deficient mice.

We used gene targeting in embryonic stem cells to introduce an IL-1 beta null allele in mice. The IL-1 beta-deficient mice develop normally and are apparently healthy and fertile. The IL-1 beta null mice responded normally in models of contact and delayed-type hypersensitivity or following bacterial endotoxin LPS-induced inflammation. The IL-1 beta-deficient mice showed equivalent resistance to Listeria monocytogenes compared with wild-type controls. In contrast, when challenged with turpentine, which causes localized inflammation and tissue injury, the IL-1 beta mutant mice exhibited an impaired acute-phase inflammatory response and were completely resistant to fever development and anorexia. These results highlight a central role for IL-1 beta as a pyrogen and a mediator of the acute-phase response in a subset of inflammatory disease models, and support the notion that blocking the action of a single key cytokine can alter the course of specific immune and inflammatory responses.

Acute-Phase Reaction↗

Nasal natural killer (NK) cell lymphoma: report of a case with activated NK cells containing Epstein-Barr virus and expressing CD21 antigen, and comparative studies of their phenotype and cytotoxicity with normal NK cells.

Malignant lymphomas arising from the nasal cavity have been considered to be derived from T cells, but recent surface marker studies suggest that more than half of the lymphomas are derived from natural killer (NK) cells. Here we describe a case of nasal lymphoma whose lymphoma cells were identified as NK cells by morphological, phenotypic, immunogenotypic, and functional studies. We believe this is the first study with functional evidence of NK activity. When compared with normal freshly isolated NK cells or activated NK cells, the surface phenotypes and NK activity of the patient tumour cells were those of the activated, but not resting, NK cells. Also, Epstein-Barr virus (EBV) was detected in the tumour cells and the lymphoma cells were found to be monoclonally expanded. The patient's lymphoma cells also expressed EBV receptor CD21 (CR2) and CD30 (Ki-1) that have not been described on normal NK cells. We therefore examined highly enriched NK cells of normal donors, and found that some resting and/or activated NK cells express these antigens.

Antigens, CD↗

Thermal and behavioral effects of lipopolysaccharide and influenza in interleukin-1 beta-deficient mice.

This study characterized body temperature (Tb), locomotor activity (Act), and feeding behavior under normal conditions and following injection with lipopolysaccharide (LPS) or inoculation with live influenza virus of transgenic C57/black mice deficient in interleukin-1 beta (IL-1 beta). Tb and Act in freely moving mice were measured by biotelemetry. Mice deficient in IL-1 beta had normal circadian rhythm of Tb but were less active than their control counterparts. Mice injected with LPS (2.5 mg/kg i.p.) responded with a prompt decrease of Tb, which lasted approximately 10 h, followed by a fever in which Tb reached a peak at approximately 24 h postinjection. There was no difference between groups in the early drop of Tb after the LPS; however, the 24-h peak of Tb was lower in IL-1 beta-deficient mice. The anorexic effects of LPS and influenza infection were similar in both groups of mice. In mice given influenza virus (17.5 plaque-forming units, median lethal dose), Tb and Act gradually decreased. The fall of Tb was smaller in the transgenic mice. The mice deficient in IL-1 beta displayed a higher mortality rate due to influenza infection than the control mice. We conclude that deficiency in IL-1 beta results in lower fever following the LPS injection and in impairment of the defense response to infection with influenza.

Animals↗

[Electromyographic study of human extrinsic laryngeal muscles].

Seven cases of human extrinsic laryngeal muscles were studied to determine the electrical activities during phonation, coughing, swallowing, fixation of thorax and respiration. The activities of these muscles all fired during phonation which were synchronous with discharge of the thyroarytenoid muscle (TAM) and increased with increasing volume of voice. They also fired during cough reflex and sphincteric action of larynx, and were basically synchronous with the TAM. They were weak during normal respiration. Although stronger electrical activities were recorded during inspiration in dyspnea, they were weaker than discharge during phonation, cough reflex and sphincteric action of larynx.

Adult↗

High expression of synthetic human interferon-gamma cDNA in E. coli.

Human interferon-gamma (IFN-gamma) cDNA was synthesized, and it makes the usage of favorable codons in E. coli. The authors got 9 different expression plasmids which contain the synthetic IFN-gamma-cDNA and have different spaces between SD sequence and ATG. The free energies G0f298 in the formation of stable secondary structure in the translation initiation region (TIR) are different in various expression plasmids. One of them, pLY4-gamma 5, can highly yield INF-gamma which will be about 60%-80% of the total bacterial proteins, such a high expression was hardly noted in literature. The reasons of high expression in this work are optimal spaces between SD and ATC, favorable delta G0f298, favourable condons usage for E. coli.

Amino Acid Sequence↗

[Textual study and resource investigation on traditional Chinese drugs duhuo, jiuyanduhuo and qianghuo].

By means of Bencaological study on traditional Chinese drugs Duhuo, Jiuyanduhuo and Qianghuo, it has been found out that the Duhuo recorded in earlier Bencao works should be Qianghuo, and Duhuo was first used medically in the South-North Dynasty period, whereas Jiuy-anduhuo's medical use started in the Ming Dynasty. Resources of the three drugs were investigated and their main species were found out.

Drug Contamination↗

[Studies of drugs for osteoporosis (3): synthesis of quinolinone derivatives and their treatment of osteoporosis].

In order to obtain more effective drugs with less side effects for the treatment of osteoporosis, we designed and synthesized fourteen quinolinone derivatives. The 14 title compounds have not been reported in literature. Their structures were confirmed by elemental analysis, IR, MS and 1H-NMR. Initial pharmacological test showed that target compound TM-11 could stimulate bone formation in Wistar rat embryo in culture and showed higher activity in stimulating bone formation than ipriflavone.

Animals↗

[Ultrastructural changes in pulmonary microvascular damage in rats inflicted with burn, blast and combined burn-blast injury].

The pathological changes in pulmonary microvasculature in rats inflicted with overpressure blast, 15% third degree burns and combined burn-blast injury, respectively, were studied with electron microscopy and ultrastructural morphometry. Results indicated that the pathological changes in pulmonary microvasculature in 15% third degree burns were slight, and mainly restricted to ultrastructural level. While in severe blast and burn-blast injuries, the damage of pulmonary microvasculature including endothelial swelling and regeneration and dispersal of arteriole wall structure, was prominent. These changes form the basis of pulmonary hemorrhage and edema. Apart from vessel structural damages, arteriole constriction and capillary closure were also observed during 2 to 4 h postinjury. The vessel damage and dysfunction were more severe in combined injury than in blast injury alone. The mechanisms needed to be studied further.

Animals↗

[Ansa cervicalis to the adductor division of the recurrent laryngeal nerve anastomosis for unilateral vocal cord paralysis].

The main trunk of ansa cervicalis was anastomosed to the adductor division of the recurrent laryngeal nerve in seven patients to reinnvervate the vocal cord for unilateral vocal cord paralysis. Although the reinnervated vocal cord neither abducted nor adducted, it presented itself in midline for precise apposition with the nonparalyzed cord. Normal phonatory quality was achieved after the procedure. Electroacoustic analysis indicated that this technique might produce normal phonatory function in paralyzed larynx. Laryngeal electromyography demonstrated that the procedure seemed to induce satisfactory reinnervation of the adductor musculature. Therefore, we think this technique may be recommended as an alternative to Teflon injection or thyroplasty in selected cases.

Adult↗

[A study on the viability of corneal endothelium in rabbit by dual staining with trypan blue and alizanin red S].

PURPOSE: We study the viability of preserved rabbit corneal endothelium by dual staining with trypan blue and alizanin red S. METHOD: We randomly divided New Zealand white rabbit eyes into four groups, each with 5 eyes. The eye balls were preserved in moist chambers with aqueous remorad and C3F8 temponade for 5, 7, 10 and 14 days. Then we got the corneal Bottons with sclera ring. Isolated corneas were placed with the endothelial side up in a corneal cup, and trypan blue (0.25%) was added drop-wise to cover the endothelium. After 1.5 minutes the stain was poured out. The endothelial layer was then covered with aliznin red S (0.2%) for 1.5 minutes and pouring away the staining reagent. After staining, the corneas were immensec in glutaraldehyde fixative solution for 10 minutes. Finally, the endothelium was examinated and taken photoes with light microscope. RESULTS: Changed cells that have become permeable to trypan blue show deep blue staining of their nuclei in contrast to the unstained condition of normal cells. All the intercellular borders of endothelial cells were purple. The survival rate of the endothelium preserved for 5 and 7 day is more than 95%, for 10 days is 75-80%, and for 14 days about 70%. CONCLUSION: This technique allows a proportion cout of damaged and undamaged cells in the endothelial monolayer, makes it possible to observe their structures clearly and gives advantage to take pathelage photos.

Animals↗

Purification of a 24-kD protease from apoptotic tumor cells that activates DNA fragmentation.

We report the purification of a protease from tumor cells undergoing apoptosis that is involved in activating DNA fragmentation. Initial studies revealed that two inhibitors of serine proteases, N-1-tosylamide-2-phenylethylchloromethyl ketone and carbobenzoxy-Ala-Ala-borophe (DK120), suppressed tumor necrosis factor or ultraviolet (UV) light-induced DNA fragmentation in the U937 histiocytic lymphoma as well as UV light-induced DNA fragmentation in the BT-20 breast carcinoma, HL-60 myelocytic leukemia, and 3T3 fibroblasts. The protease was purified by affinity chromatography with DK120 as ligand and showed high activity on a synthetic substrate preferred by elastase-like enzymes (Ala-Ala-Pro-Val p-nitroanilide), but was inactive on the trypsin substrate, N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester, or the chymotrypsin substrate, Ala-Ala-Pro-Phe p-nitroanilide. The activity of the DK120-binding protease purified from U937 cells undergoing apoptosis was increased approximately 10-fold over that recovered from normal cells. Further purification to homogeneity by heparin-Sepharose affinity chromatography followed by reverse phase high-performance liquid chromatography revealed a single band of 24 kD on a silver-stained sodium dodecyl sulfate gel. In addition to protease activity, the purified enzyme induced DNA fragmentation into multiples of 180 basepairs in isolated U937 nuclei. These findings suggest the 24-kD protease is a novel enzyme that activates DNA fragmentation in U937 cells undergoing apoptosis.

3T3 Cells↗

Chimerism in PCR products from a multigene family.

This paper describes a potential hazard in obtaining sequences of a multigene family by amplifying the mixed population by the polymerase chain reaction with primers from conserved sequences. We describe a product which appears to be a chimera formed during the PCR reaction from two different but related sequences.

Base Sequence↗