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Biomedical subjects

D Zhang

Publications and source records attributed to D Zhang.

At least 595 records · Page 33Linked to original sources

Stimulation of human immunodeficiency virus type 1 expression by ceramide.

Ceramide, an intracellular lipid mediator of tumor necrosis factor alpha (TNF-alpha) action, was studied for its effects on the expression of the proviral human immunodeficiency virus type 1 genome in latently infected myelomonocytic cell lines U-1IIIB and OM-10.1. Ceramide treatment resulted in a 20- to 100-fold enhancement of HIV production in these cells. Ceramide also enhanced the expression of the chloramphenicol acetyltransferase gene directed by a human immunodeficiency virus type 1 long terminal repeat in transfected U-937 cells, indicating that ceramide acts at the level of viral transcription. These observations suggest that the TNF-ceramide signaling system may be involved in the regulation of HIV expression in certain myeloid cell types.

Cell Line, Transformed↗

Ligand-induced domain motion in the activation mechanism of a G-protein-coupled receptor.

Rapidly accumulating information about the structures and functions of transmembrane proteins in the class of G-protein-coupled receptors is facilitating the exploration of molecular details in the processes of cellular signal transduction. We have described recently a 3-D molecular model of the transmembrane portion of the 5-HT2A type of receptor of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT), constructed from such convergent empirical and theoretical considerations, and have used it for a computational simulation of the mechanisms of ligand-induced receptor activation and signal transduction. The molecular dynamics (MD) simulation of the interaction between the receptor model and ligands of different pharmacological efficacies pointed to a set of specific conformational changes propagated from the ligand binding site to a distal region of the receptor that is essential for signal transduction. The ligand-induced changes were found to correlate well with the known pharmacological properties, but it remained unclear how the binding of the small 5-HT2A receptor agonist molecules in the distal binding pocket could give rise to the specific conformational changes in a distant part of the receptor. As the MD simulations showed the secondary structure of the helical transmembrane domains of the receptor to be well maintained, and the conformational changes to involve mainly translations and rotations of the helices in the bundle relative to one another, an algorithm was developed to treat the ligand-induced conformational changes as rigid domain movements of transmembrane helices.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

Evaluation of a model for post-partum arthritis and the role of oestrogen in prevention of MRL-lpr associated rheumatic conditions.

Sixty-eight percent of female MRL-lpr mice developed a post-partum exacerbation of their mild spontaneous arthritis within 30 days of parturition. The flare became evident between 5 and 15 days after delivery. Histologically it was characterized by a significant increase of subsynovial inflammation and synovial hyperplasia without changes in the level of cartilage and bone erosion. Immunohistologically, marked subsynovial and frequent synovial staining of MHC class II bearing cells was noted, along with the sporadic presence of CD3, CD4, and CD43 receptor-bearing cells in the subsynovium. Injection of physiological levels (0.08 mg/kg) of estradiol on days 2, 3, 9, 15 and 20 post-partum delayed and reduced the flare to 23% of the animals. Administration of pharmacological amounts (0.4 mg/kg per day for 2 weeks following Freund's complete adjuvant injection) prevented adjuvant-enhanced arthritis, reducing the incidence from 67% to the baseline 21% level. Deleterious changes in the underlying systemic lupus erythematosus (SLE), as demonstrated by proteinuria and mortality rate increases, were elicited only by the employed pharmacological amounts of estradiol. These results indicate that the MRL-lpr mice might serve as a model for post-partum flare of arthritis in SLE and rheumatoid arthritis by providing an approach to study the complexity of the effects of pregnancy on autoimmune diseases, and to obtain further evidence for the involvement of oestrogen in arthritis.

Animals↗

Molecular cloning and expression of human EP3 receptors: evidence of three variants with differing carboxyl termini.

1. The polymerase chain reaction (PCR) was used in combination with plaque hybridization analysis to clone four variants of the EP3 prostaglandin receptor from a human small intestine cDNA library. 2. Three of these variants, i.e. the EP3A, EP3E and EP3D, share the same primary amino acid sequence except for their carboxyl termini, which diverge from one another at the same point, approximately 10 amino acids away from the end of the seventh membrane spanning domain of the receptor. The fourth variant (EP3A1) has a nucleotide coding sequence identical to EP3A but has a completely different 3' untranslated sequence. 3. The carboxyl termini of the three isoforms differ most obviously in length with the EP3A being the longest (41 amino acids) and the EP3E being the shortest (16 amino acids). They also differ in content with the EP3A containing 9 serine and threonines in its carboxyl terminus and the EP3E none. 4. Transient expression in eukaryotic cells showed that the human EP3 receptor variants had similar but not identical radioligand binding properties and differed in their functional coupling to second messenger pathways. Up to 3 pmol mg-1 protein of [3H]-prostaglandin E2 binding could be obtained with more than 95% specific binding. Using a reporter gene assay, as a measure of intracellular cyclic AMP levels, the EP3A coupled more efficiently to the inhibition of adenylyl cyclase than did the EP3E. 5. PCR was used to confirm the presence of mRNAs encoding the four human EP3 receptor variants in tissues of the human small intestine, heart and pancreas. These findings indicate that the EP3 receptor variants identified here are likely to be expressed in tissues. The differences in the carboxyl termini at the protein level, and in the 3' untranslated regions at the mRNA level, could be profound in terms of the regulation and functional coupling of these receptor isoforms.

Adenylyl Cyclases↗

Resistance to 2',3'-dideoxycytidine conferred by a mutation in codon 65 of the human immunodeficiency virus type 1 reverse transcriptase.

A human immunodeficiency virus type 1 variant resistant to zalcitabine (2',3'-dideoxycytidine [ddC]) was selected by sequential passage in the presence of increasing concentrations of ddC in peripheral blood mononuclear cell cultures. A mutation causing a lysine-to-arginine substitution was noted in reverse transcriptase (RT) codon 65 of this ddC-selected virus. A cloned mutant virus with this codon 65 mutation was constructed by using a novel PCR approach for site-directed mutagenesis. Characterization of this virus confirmed that the RT Lys-65-->Arg substitution was necessary and sufficient for a fourfold increase in the ddC 50% inhibitory concentration, as well as for resistance to didanosine (2',3'-dideoxyinosine [ddI]). Lys-65-->Arg and virus resistance to ddC and ddI also developed during therapy in isolates from one ddC-treated patient and two ddI-treated patients. Recombinant-expressed codon 65 mutant RT enzyme was resistant to ddCTP and ddATP in cell-free polymerase assays. Results of mutant enzyme studies are consistent with Lys-65-->Arg leading to changes in binding of the triphosphate forms of these nucleoside analogs to the RT. These data have implications for future studies of ddC resistance, particularly those aimed at defining its clinical relevance.

Arginine↗

Platelet-activating factor: a candidate human immunodeficiency virus type 1-induced neurotoxin.

The pathogenesis of central nervous system disease during human immunodeficiency virus type 1 (HIV-1) infection revolves around productive viral infection of brain macrophages and microglia. Neuronal losses in the cortex and subcortical gray matter accompany macrophage infection. The question of how viral infection of brain macrophages ultimately leads to central nervous system (CNS) pathology remains unanswered. Our previous work demonstrated high-level production of tumor necrosis factor alpha, interleukin 1 beta, arachidonic acid metabolites, and platelet-activating factor (PAF) from HIV-infected monocytes and astroglia (H. E. Gendelman, P. Genis, M. Jett, and H. S. L. M. Nottet, in E. Major, ed., Technical Advances in AIDS Research in the Nervous System, in press; P. Genis, M. Jett, E. W. Bernton, H. A. Gelbard, K. Dzenko, R. Keane, L. Resnick, D. J. Volsky, L. G. Epstein, and H. E. Gendelman, J. Exp. Med. 176:1703-1718, 1992). These factors, together, were neurotoxic. The relative role(s) of each of these candidate neurotoxins in HIV-1-related CNS dysfunction was not unraveled by these initial experiments. We now report that PAF is produced during HIV-1-infected monocyte-astroglia interactions. PAF was detected at high levels in CSF of HIV-1-infected patients with immunosuppression and signs of CNS dysfunction. The biologic significance of the results for neurological disease was determined by addition of PAF to cultures of primary human fetal cortical or rat postnatal retinal ganglion neurons. Here, PAF at concentrations of > or = 300 pg/ml produced neuronal death. The N-methyl-D-aspartate receptor antagonist MK-801 or memantine partially blocked the neurotoxic effects of PAF. The identification of PAF as an HIV-1-induced neurotoxin provides new insights into how HIV-1 causes neurological impairment and how it may ultimately be ameliorated.

AIDS Dementia Complex↗

Actin microfilaments are associated with the migrating nucleus and the cell cortex in the green alga Micrasterias. Studies on living cells.

Rhodamine-phalloidin or FITC-phalloidin has been injected in small amounts into living, developing cells of Micrasterias denticulata and the stained microfilaments visualized by confocal laser scanning microscopy. The results reveal that two different actin filament systems are present in a growing cell: a cortical actin network that covers the inner surface of the cell and is extended far into the tips of the lobes in both the growing and the nongrowing semicell; it is also associated with the surface of the chloroplast. The second actin system ensheathes the nucleus at the isthmus-facing side during nuclear migration. Its arrangement corresponds to that of the microtubule system that has been described in earlier electron microscopic investigations. The spatial correspondence between the distribution of actin filaments and microtubules suggests a cooperation between both cytoskeleton elements in generating the motive force for nuclear migration. The function of the cortical actin network is not yet clear. It may be involved in processes like transport and fusion of secretory vesicles and may also function in shaping and anchoring the chloroplast.

Actin Cytoskeleton↗

Physicochemical damage to liposomal membrane induced by iron- or copper-mediated lipid peroxidation.

A carboxyfluorescein (CF)-enveloping soybean phosphatidylcholine liposome was used as a model of physicochemical damage of biomembranes. The liposomes were exposed to a metal-chelate complex [2 mM of ferric nitrilotriacetate (FeNTA) or cupric nitrilotriacetate (CuNTA)] plus a reductant (2 mM of ascorbate or various concentrations of reduced glutathione), and CF release from damaged liposomal membranes and the generation of thiobarbituric acid-reactive substances (TBARS) were measured. In the presence of a reducing agent, both FeNTA and CuNTA stimulated markedly CF release and an increase in the TBARS level, while in the absence of a reducing agent both of the chelate complexes showed little CF release and TBARS. The effects of H2O2 addition to the reaction system containing liposome with FeNTA or CuNTA plus ascorbate were also examined. The CF release was slightly increased by the addition of a smaller dose (0.5 mM) of H2O2 and it was inhibited by 8 mM of H2O2. A similar result was obtained in the TBARS test. These results suggest that FeNTA- or CuNTA-mediated lipid peroxidation can damage liposomal membranes physicochemically, and the redox reaction of the chelated metal itself is more important than a Fenton-type reaction in the process.

Ferric Compounds↗

[The uniformity of medical terms in early period: a review on the work of China Medical Missionary Association].

Translation in medical terminology was a subject the medical missionaries encountered in China. The medical missionaries had done a lot of useful work in standardizing medical terms. Their work impelled the spread and development of Western medicine in China. It also laid a foundation for the uniformity of medical nomenclature. Unfortunately, this complex task was far beyond the reach of medical missionaries and had to leave it to those Chinese physicians who were well educated in modern medicine.

China↗

Establishment of a human malignant T lymphoma cell line carrying retrovirus-like particles with RT activity.

We have established an IL-2 independent malignant lymphoma line (CM-1) from peripheral T lymphocytes donated by a female patient with nervous system disease, the biological characteristics of CM-1 cells was studied in this paper. Another T lymphocytes, such as peripheral T lymphocytes donated by a male patient with multiple sclerosis, could be transformed into a malignant lymphoma line by using filtered supernatant of the CM-1 cultured medium, thus the CM-2 cell line was established. The CM-1 and CM-2 cells were transplanted by subcutaneous inoculation into nude mice, and could cause the occurrence of typical malignant lymphoma. The observation of electron micrographs suggested the existence of virions in the CM-1 and CM-2 cells, and these virions were similar to retrovirus in the ultra-structure characteristics. It was found that this virus possesses reverse transcriptase activity. Results obtained from serological assay, molecular hybridization and PCR excluded the existence of other human viruses, which were commonly used in our laboratory. The unknown virus possesses strong transformation activity, and probably is a new retrovirus. Meanwhile, the work on the clone and sequence analysis of this virus are being carried out.

Adult↗

[Cyclic changes of serum reproductive hormone levels on patients with endometriosis and infertility].

Fourteen cases of endometriosis (Em) with infertility were studied by laparoscopy in our hospital from Dec. 1988 to Oct. 1989. 2 cases were minimal, 6 cases were moderate and 6 cases were severe. The salpingo examinations of 13 cases were normal by laparoscopy. There were no stigma on ovaries in 7 cases (LUFS). Levels of hormone (E2,P,LH,FSH) were compared in Em with normal women. The level of E2 during the follicle phase in Em was lower (86.4 +/- 6.9 pg/ml) than in normal women (119.9 +/- 7.7 pg/ml, P < 0.01). The LUFS group was compared with the no-LUFS group in Em. During the mid-late follicle phase and ovulatory phase, the E2 values in the LUFS group was significantly lower than in the non-LUFS group (P < 0.05), while the FSH value in LUFS group was significantly higher than in non-LUFS group (P < 0.05).

Adult↗

[Effects of acupuncture on antral G cells in patients with gastric disease].

It is well known that acupuncture is effective for treatment of gastric disease in human. We have observed the effect of acupuncturing "Zhongwan" "Neiguan" "Zusanli" on fluorohistochemical changes of G cells of antral mucosa in 42 patients with gastric disease. The results show that after acupuncture treatment the amount of fluorescent G cells and the fluorescent intensity of gastrin in the G cells were obviously decreased in patients with duodenal ulcer, as compared with that before acupuncture treatment. However, the amount of G cells was increased by acupuncture treatment in patients with chronic atrophic gastritis. These data indicate the acupuncture may regulate G cell from abnormal to normal condition in gastric mucosa of gastric disease.

Acupuncture Therapy↗

[An experimental study on cultivation of human trigeminal ganglionic cell in vitro and its sensitivity to infection of herpes simplex virus type 1].

We firstly report an experimental study on the sensitivity of primary cultural human trigeminal ganglionic cells infected by herpes simplex virus type 1 (HSV-1) in different time-points. The results indicate that the neuron of human trigeminal ganglia is the most sensitive cell type, the antigen of HSV-1 replicates rapidly within the cytoplasm and cell nucleus, the fibroblasts and glia cells are infected partly by the virus. Therefore, perhaps the neuron is the main harboring cell type.

Antigens, Viral↗

Perforated colonic carcinoma mimicking perforated peptic ulcer: an argument for full exploration of the stomach and duodenum.

Perforated peptic ulcer is one of the commonest types of hollow-viscus perforation. Because many of these ulcers are found at laparotomy to be sealed off, some authors believe it is unnecessary to dissect the surrounding tissue from the presumed site of perforation. A patient with a long history of peptic ulcer disease experienced the sudden onset of signs and symptoms of perforated peptic ulcer. On exploration, the omentum appeared to be densely adherent to the pylorus and duodenum. However, no perforation was found when the omentum was dissected free from the stomach and duodenum. Further exploration revealed a walled-off, perforated carcinoma of the transverse colon adjacent to the mesenteric border. As a result of this experience, the authors emphasize that when the findings at operation do not fit the clinical presentation in a patient with a presumed perforated peptic ulcer, a thorough exploration of the abdominal viscera is mandatory to identify the pathologic process.

Adenocarcinoma↗

[Surgical correction of Crouzon syndrome using LeFort III advancement osteotomy].

Crouzon syndrome is one of craniosynostosis syndromes (or craniofacial dysostosis). It consists of multiple craniofacial deformities including severe midface retrusion, exorbitism and close bite. In 11 cases LeFort III advancement osteotomy to move the midface segments was performed in past eight years. We evaluate the result of reconstructive and postoperative aesthetic improvement using measurements of lateral cephalograms and exophthalmetry. Changes in midface horizontal view are obvious postoperatively, and SNA is increased from 70.9 degree to 74.5 degree, SNB decrease from 85.1 degree to 80.8 degree, and ANB increase from -14.2 degree to -6.3 degree. Midface segment is brought forward (average 10mm) and downward (average 2mm) postoperatively. The distance from the posterior nasal spine to the posterior pharyngeal wall on cephalograms is increased from 9.1mm to 19mm. Complications are discussed.

Adolescent↗