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Biomedical subjects

F Zhou

Publications and source records attributed to F Zhou.

At least 109 records · Page 6Linked to original sources
PubMed1996

Biodistribution of clodronate and liposomes used in the liposome mediated macrophage 'suicide' approach.

Clodronate (Cl2MBP; dichloromethylene-bisphosphonate)-containing liposomes are used to investigate the role of macrophages in immune and non-immune defense mechanisms by elimination of these macrophages followed by functional studies. The present studies characterize such liposomes in terms of the leakage of clodronate and the biodistribution of both the encapsulated drug and the liposomal carrier. The distribution of liposomes was studied using a radioactively labelled lipid phase marker (111In-DTPA-SA) and the distribution of the encapsulated drug was examined following injection of radioactively labelled clodronate (99mTc-Cl2MBP). Furthermore, the biodistribution of variously composed multilamellar liposomes (EPC/Chol molar ratio 7:1.3 or 7:7; EPC/Chol/PS 7:1.3:1 or 7:7:1; EPC/Chol/M 7:2:1; EPC/Chol/M-PE 7:2:1) after intravenous injection was investigated. The findings suggest that only one third of the originally entrapped clodronate was still encapsulated in the liposomes at the time of ingestion by the macrophages in the liver and spleen after intravenous injection of the clodronate containing liposomes. 3 h after injection no clodronate could be detected in the circulation.

Animals↗
PubMed1996

Fibroblast growth factor receptor 3 is a negative regulator of bone growth.

Endochondral ossification is a major mode of bone that occurs as chondrocytes undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. We have identified a role for fibroblast growth factor receptor 3 (FGFR-3) in this process by disrupting the murine Fgfr-3 gene to produce severe and progressive bone dysplasia with enhanced and prolonged endochondral bone growth. This growth is accompanied by expansion of proliferating and hypertrophic chondrocytes within the cartilaginous growth plate. Thus, FGFR-3 appears to regulate endochondral ossification by an essentially negative mechanism, limiting rather than promoting osteogenesis. In light of these mouse results, certain human disorders, such as achondroplasia, can be interpreted as gain-of-function mutations that activate the fundamentally negative growth control exerted by the FGFR-3 kinase.

Animals↗
PubMed1996

Molecular dynamics study of phospholipase A2 on a membrane surface.

The desolvation of lipid molecules in a complex of the enzyme human synovial phospholipase A2 with a lipid membrane is investigated as a mechanism that enhances the overall activity of the enzyme. For this purpose the interaction of the enzyme phospholipase A2 with a dilauryl-phosphatityl-ethanolamin (DLPE) membrane monolayer surface has been studied by means of molecular dynamics simulations. Two enzyme-membrane complexes, a loose and a tight complex, are considered. For comparison, simulations are also carried out for the enzyme in aqueous solution. The conformation, dynamics, and energetics of the three systems are compared, and the interactions between the protein and lipid molecules are analyzed. Free energies of solvation are calculated for the lipid molecules in the enzyme-membrane interface. Along with the calculated dielectric susceptibility at this interface, the results show the desolvation of lipids in a tightly bound, but not in a loosely bound protein-membrane complex. The desolvated lipids are found to interact mainly with hydrophobic protein residues, including Leu-2, Val-3, Ala-18, Leu-19, Phe-24, Val-31, and Phe-70. The results also explain why the turnover rate of phospholipase A2 complexed to a membrane is enhanced after a critical amount of negatively charged reaction product is accumulated.

Algorithms↗
PubMed1996

Role of c-jun induction in the glucocorticoid-evoked apoptotic pathway in human leukemic lymphoblasts.

Accumulated evidence suggests tI AP-1 family in CEM cell clones exposed to the glucocorticoid dexamethasone (Dex) has been investigated. Dex is known to cause apoptosis of lymphoid cells in general and of sensitive human lymphoid CEM cell clones in particular. This study finds that Dex induces c-jun mRNA and cJun protein in cells of the sensitive clone CEM-C7 and of the lysis-sensitive OEM hybrid clone H10. CEM-O7 cells were screened for several other Jun/Fos family proteins. Both cFos and JunD were expressed but were unaffected by the steroid, and JunB was not detected. In the continual presence of Dex the induction of cJun began about 6 h after addition of Dex, reached a maximum by 24 h, and plateaued for 72 h, while cell death did not begin until 24-48 h. In clone OEM-Cl cells, which contain glucocorticoid receptor (GR) but are resistant to lysis by Dex, the basal, and even the fully induced, cJun levels are below the basal levels in OEM-07 and H10 cells. To test the hypothesis that cJun plays an important role in steroid-evoked apoptosis, stable transfectants expressing Dex-regulable antisense c-jun RNA were established. Mass cultures of these cells showed reduced sensitivity to Dex, and in three of three clones tested, complete resistance to Dex was obtained. This occurred even though endogenous genes (GR, c-jun) normally responsive to Dex were still inducible, indicating that the GR and basic glucocorticoid response apparatus were intact. It is concluded that Dex induces cJun levels in sensitive OEM cells before cell death and that this induction plays a role in the apoptotic process.

Apoptosis↗
PubMed1996

[Effects of assisted ovarian stimulation with leuprolide acetate on alterations of plasma estradiol levels and newly synthesized endometrial proteins].

OBJECTIVE: To evaluate the effects of leuprolide acetate (LA)-assisted ovarian stimulation on endometrial protein synthesis in hamsters. METHODS: Hamsters were treated separately with three different regimens: (1) 40 IU of pregnant mare's serum gonadotropin (PMSG) followed by 100 IU of hCG after 52 hours (PMSG alone group). (2) Same volumes of normal saline on the same schedule (control group). (3) 40 micrograms of LA daily prior to the same regimen of PMSG-hCG treatment in order to down-regulate the pituitary-ovarian functions (LA-PMSG group). The newly synthesized endometrial proteins were characterized and quantitated in vitro by 3H-leucine incorporation test and 10% SDS-PAGE technique. RESULTS: The levels of newly synthesized 3H-labelled endometrial proteins were not different between LA-PMSG and control groups. However, those of low and middle molecular weight (< 31,000 and 45,000) proteins in the PMSG alone group were significantly lower than the levels in both LA-PMSG and control groups (P < 0.05, P < 0.01). CONCLUSIONS: The addition of LA in ovarian stimulation protocol resulted in more physiological endometrial protein synthesis. This phenomenon may causally related to higher pregnancy rate when applied in vitro fertilization-embryo transfer programs.

Animals↗
PubMed1996

[Effects of clomiphene citrate treatment on endometrial estrogen and progesterone receptors expressions].

OBJECTIVE: To assess the effects of clomiphene citrate (CC) on estrogen receptors (ER) and progesterone receptors (PR) expressions in glandular, epithelial and stromal cells of endometrium. METHODS: Endometrium samples of 16 normal ovulatory women (11 with unexplained and 5 female infertility) were taken in the late proliferative phase (12th day) and late secretory phase (10 days after ovulation), both in spontaneous and CC-induced cycles. ER and PR in glandular, epithelial and stromal cells of endometrium were localized and their histological score (H-score) were measured semi-quantitatively by monoclonal antibodies immunohistochemical analysis. RESULTS: The H-score of ER and PR contents were significantly lower in late proliferative phase and secretory phase of CC cycles when compared with that in spontaneous cycles (P < 0.01, P < 0.05). The decrease of receptor contents in glandular cells was significantly pronounced than that in stromal cells (P < 0.05). In late proliferative phase the decrease of ER was significantly severe than that of PR. On the contrary in late secretory phase the decline of PR was more significant. CONCLUSIONS: Based on these data, we suggested that CC inhibited the ER and PR induction in endometrium and affected endometrial development. These may be one of the causes of low pregnancy rate in CC-induced cycles.

Adult↗
PubMed1996

[Study on some susceptible genes of systemic lupus erythematosus in Han nationality of China].

In order to explore the allelic polymorphism of HLA-DR and TNF B loci and susceptibility to systemic lupus erythematosus (SLE) in the Han nationality of northern China with the aid of methods of polymerase chain reaction/sequence specific primers (PCR/SSP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. The findings from a case-control study on 151 blood samples (45 from the cases and 106 from the controls) indicated that there were significantly higher frequency of DR2 (P < 0.05, RR = 1.56) and DR3 (P < 0.01, RR = 2.69), which represent candidate susceptible genes or useful markers for SLE. The DR5 allele in the samples (P < 0.05, RR = 0.43) might be an antagonistic or protective allele, or a marker for such allele. The frequency of TNF B * 1 and TNF B * 2 alleles was investigated in 45 SLE patients and 80 healthy controls and it was found that the frequency of TNF B * 2 allele was significantly higher in the patient group (P < 0.05, RR = 1.84). It might also be a suspicious susceptible allele or a marker for such allele. The frequency of HLA polymorphisms in various clinical/immunological subsets of our patient population was also determined. Clinical findings used include plasma SC5b-9 level, SSA, SSB, Sm, RNP, ANA antibodies, and SLE complications (SLE nephritis, pneumonia & encephalopathy). It turned out that there was a positive association between HLA-DR2 allele and SLE nephritis (P < 0.05, RR = 1.32).

Alleles↗
PubMed1996

Anchoring of c-myc on nuclear matrix proteins in process of mouse thymic T lymphocyte proliferation induced by ConA.

Isolation and characterization of functional nuclear matrix proteins involved in DNA anchoring and gene expression is one of the major subjects of current nuclear matrix research. Southwestern blotting (DNA-protein hybridization) was applied to studying the anchoring of c-myc on the nuclear matrix proteins in mouse thymic T lymphocytes. The results showed that c-myc bound to the lamin, p34 and p36 nuclear matrix proteins specifically. In the process of mouse thymic PNA-T lymphocytes proliferation induced by ConA, the anchoring of c-myc on p34 and p36 nuclear matrix proteins changed dynamically.

Animals↗
PubMed1995

Induction of vascular endothelial growth factor gene expression by interleukin-1 beta in rat aortic smooth muscle cells.

Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells and promotes neovascularization in vivo. To determine whether interleukin-1 beta (IL-1 beta), which is present in atherosclerotic lesions, induces VEGF gene expression in vascular smooth muscle cells, we performed RNA blot analysis on rat aortic smooth muscle cells (RASMC) with a rat VEGF cDNA probe. IL-1 beta increased VEGF mRNA levels in RASMC in a time- and dose-dependent manner. As little as 0.1 ng/ml IL-1 beta increased VEGF mRNA levels by 2-fold and 10 ng/ml IL-1 beta increased VEGF mRNA by 4-fold. We also measured the half-life of VEGF mRNA and performed nuclear run-on experiments before and after addition of IL-1 beta to see if IL-1 beta increased VEGF mRNA levels by stabilizing the mRNA or by increasing its rate of transcription. The normal, 2-h half-life of VEGF mRNA in RASMC was lengthened to 3.2 h (60%) by IL-1 beta, and IL-1 beta increased the rate of VEGF gene transcription by 2.1-fold. In immunoblot experiments with an antibody specific for VEGF, we found that IL-1 beta increased VEGF protein levels in RASMC by 3.3-fold. Together these data indicate that IL-1 beta induces VEGF gene expression in smooth muscle cells. This IL-1 beta-induced expression of VEGF may accelerate the progression of atherosclerotic lesions by promoting the development of new blood vessels.

Animals↗
PubMed1995

Mucosal IgA response to rectally administered antigen formulated in IgA-coated liposomes.

Ferritin, a soluble model antigen, was used to test whether liposomes can provide an effective delivery vehicle for mucosal immunization via the rectum, and whether the local colonic/rectal secretory immune response to antigen in liposomes can be enhanced by immunoadjuvants. The colonic/rectal IgA response to liposomal ferritin was significantly enhanced over the response to free ferritin but only when cholera toxin (CT) was present as adjuvant. The presence of IgA on the liposome surface increased the uptake of liposomes into Peyer's patch mucosa, and the local rectal/colonic immune response to ferritin about 5-fold over uncoated liposomes. These results show that (1) liposomes co-administered with immunoadjuvants can be used for mucosal immunization via the rectum. (2) Cholera toxin is an effective immunoadjuvant in the rectal/colonic mucosa. (3) IgA can enhance the local secretory immune response to antigen in liposomes, apparently by increasing liposome uptake via M cells.

Adjuvants, Immunologic↗
PubMed1995

The ATF site mediates downregulation of the cyclin A gene during contact inhibition in vascular endothelial cells.

Contact inhibition mediates monolayer formation and withdrawal from the cell cycle in vascular endothelial cells. In studying the cyclins--key regulators of the cell cycle--in bovine aortic endothelial cells (BAEC), we found that levels of cyclin A mRNA decreased in confluent BAEC despite the presence of 10% fetal calf serum. We then transfected into BAEC a series of plasmids containing various lengths of the human cyclin A 5' flanking sequence and the luciferase gene. Plasmids containing 3,200, 516, 406, 266, or 133 bp of the human cyclin A promoter directed high luciferase activity in growing but not confluent BAEC. In contrast, a plasmid containing 23 bp of the cyclin A promoter was associated with a 65-fold reduction in activity in growing BAEC, and the promoter activities of this plasmid were identical in both growing and confluent BAEC. Mutation of the activating transcription factor (ATF) consensus sequence at bp -80 to -73 of the cyclin A promoter decreased its activity, indicating the critical role of the ATF site. We identified by gel mobility shift analysis protein complexes that bound to the ATF site in nuclear extracts from growing but not confluent BAEC and identified (with antibodies) ATF-1 as a binding protein in nuclear extracts from growing cells. Also, ATF-1 mRNA levels decreased in confluent BAEC. Taken together, these data suggest that the ATF site and its cognate binding proteins play an important role in the downregulation of cyclin A gene expression during contact inhibition.

Activating Transcription Factor 1↗
PubMed1995

Delivery of protein antigen to the major histocompatibility complex class I-restricted antigen presentation pathway.

Major histocompatibility complex (MHC) class I-restricted antigen presentation normally requires a protein antigen to be synthesized in the cytosol of the antigen presenting cell (APC). Exogenous protein antigen could gain access to the class I presentation pathway if the protein is introduced into the cytosolic compartment of the APC. Approaches which release the protein antigen from endocytic vesicles have been employed to deliver protein antigen for the recognition by class I-restricted cytotoxic T lymphocytes (CTL). These include osmotic shock, electroporation, cationic and pH-sensitive liposomes. An alternative approach is to deliver a gene that encodes the protein antigen. In this case, the APC is transfected with a gene which synthesizes the "exogenous protein" in the cytosol. Delivery of protein antigen targeted for CTL induction in vivo follows a different strategy and generally requires an antigen carrier of lipidic/membranous nature, such as liposomes, immunostimulating complexes, and/or lipid conjugates. Macrophages that are responsible for scavenging the antigen play an important role in CTL induction. An optimal CTL inductive vaccine must contain other immuno-modulatory activities in addition to its activity in delivering antigen to the class I pathway. Attempts to attenuate viral infection and to improve anti-tumor immunity have been successful by delivering the exogenous antigen entrapped in liposomes. These animal model studies should be of great value in the development of potential vaccine formulation.

Amino Acid Sequence↗