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- Diab, Asim, et al.
(författare)
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Neutralization of macrophage inflammatory protein 2 (MIP-2) and MIP-1α attenuates neutrophil recruitment in the central nervous system during experimental bacterial meningitis
- 1999
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 67:5, s. 2590-2601
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Tidskriftsartikel (refereegranskat)abstract
- Chemokines are low-molecular-weight chemotactic cytokines that have been shown to play a central role in the perivascular transmigration and accumulation of specific subsets of leukocytes at sites of tissue damage. Using in situ hybridization (ISH), we investigated the mRNA induction of macrophage inflammatory protein 2 (MIP-2), MIP-1α, monocyte chemoattractant protein 1 (MCP-1), and RANTES. Challenge of infant rats’ brains with Haemophilus influenzae type b intraperitoneally resulted in the time-dependent expression of MIP-2, MIP-1α, MCP-1, and RANTES, which was maximal 24 to 48 h postinoculation. Immunohistochemistry showed significant increases in neutrophils and macrophages infiltrating the meninges, the ventricular system, and the periventricular area. The kinetics of MIP-2, MIP-1α, MCP-1, and RANTES mRNA expression paralleled those of the recruitment of inflammatory cells and disease severity. Administration of anti-MIP-2 or anti-MIP-1α antibodies (Abs) resulted in significant reduction of neutrophils. Administration of anti-MCP-1 Abs significantly decreased macrophage infiltration. Combined studies of ISH and immunohistochemistry showed that MIP-2- and MIP-1α-positive cells were neutrophils and macrophages. MCP-1-positive cells were neutrophils, macrophages, and astrocytes. Expression of RANTES was localized predominantly to resident astrocytes and microglia. The present study indicates that blocking of MIP-2 or MIP-1α bioactivity in vivo results in decreased neutrophil influx. These data are also the first demonstration that the C-C chemokine MIP-1α is involved in neutrophil recruitment in vivo.
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| 2. |
- Hu, Li-Fu
(författare)
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Nasopharyngeal carcinoma and Epstein-Barr virus
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nasopharyngeal carcinoma (NPC) is the most common tumor in southern China and also quite frequent among the Eskimos and in Alaska. NPC is invariably associated with Epstein-Barr virus (EBV). Our primary aim was to investigate the potential contribution of the EBV-encoded latent membrane protein (LMP) in the development of NPC, particularly its tumorigenic and immunogenic properties and the possible prognostic value of LMPI expression in NPC. Analysis of EBV gene expression in 125 NPC biopsies has revealed that viral gene expression was limited to one nuclear protein (EBNAI), three latent membrane proteins (LMPI, LMP2A and LMP2B) and three additional transcripts (EBER 1, EBER2 and BamHlA). EBNAI, required for the maintenance of viral episomes, was consistently detected in all tumor biopsies and the transcription of this gene originated exclusively from the F/Q promoter whereas the C and W promoters were inactive. None of the NPC biopsies or control tissues expressed detectable amounts of EBNA2-6.In 65% of the biopsies, LMPI protein was detected by immunoblotting and a Xhol restriction site polymorphismlocated in the coding sequence of the LMPI gene was found (36/37 positive cases). LMP2A and BamHlA transcripts were detected in the majority of NPC specimens and expression of LMP2B and LMPI were coupled. This pattern suggested that expression of the EBV genome is regulated in a tissue specific fashion. Sequence analysis of the B95-8 (EBV prototype) virus-derived LMPI and a Chinese NPC-derived LMPI (C-LMPI) indicated that a variant virus strain is prevalent in China. We found that the expression of C-LMPI was inversely correlated with the degree of CpG methylation within its transcription control region whereas all EBV coding genes including the LMPI region were highly methylated, suggesting that disease-associated hypo-methylation plays a role in regulating the expression of this gene. A clinical study of 74 NPC cases suggested that LMPI positive tumors grow faster and more invasively than LMPI negative tumors, and functional studies showed that the C-LMPI gene had higher clonability and tumorigenicity than B95-8-derived LMPI. Using a murine model in vivo system, C-LMPI was non-immunogenic, in contrast to a B-cell derived homologue, B-LMPI. In addition, we also explored the possible contribution of inactivation of tumor suppressor genes in NPC development. Using CA repeat polymorphic markers, allelic loss was observed in 11 of 17 patients. Two separate regions of allelic deletion were found on the short arm of chromosome 3: 3p21.1-pl4.3 and 3pl4.2-pl4.1. Taken together, our findings demonstrate that a substrain of EBV is prevalent in China and its LMPI may be more tumorigenic and less immunogenic than the corresponding gene isolated from B-lymphocytes. Multiple additional factors, such as inactivation of suppressor gene function by chromosomal deletion are likely to underlie the many steps that lead to oncogenic transformation, and the development of NPC.
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| 3. |
- Tang, C. A., et al.
(författare)
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A theoretical model for Kaiser effect in rocks
- 1997
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Ingår i: Pure and Applied Geophysics. - : Springer Science and Business Media LLC. - 0033-4553 .- 1420-9136. ; 150:2, s. 203-215
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism of Kaiser effect was studied with the aid of a damage model for rock. Recognizing that the AE counts are transient elastic waves due to local damage of the rock, the quantitative relation between AE counts and statistical distribution of the local strength of the rock has been established. Subsequently, according to Damage Theory, an expression for Kaiser Effect under uniaxial stress state was derived from the model. This is found to be in good agreement with the experimental results.
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