Biomedical subjects

Gewei Lian

Publications and source records attributed to Gewei Lian.

4 recordsLinked to original sources

PubMed2006

Failure of hepatocyte marker-expressing hematopoietic progenitor cells to efficiently convert into hepatocytes in vitro.

OBJECTIVE: Whether bone marrow (BM) hematopoietic stem/progenitor cells can directly differentiate into nonhematopoietic cells remains controversial. The aim of this study is to further investigate the potentiality of BM hematopoietic progenitor cells to convert into hepatocytes in vitro. MATERIALS AND METHODS: Different subsets of BM cells from C57/BL6 mice were isolated using markers of hematopoietic stem cells by magnetic cell sorting and by flow cytometry. These cells were induced to transdifferentiate to hepatocytes in vitro in the presence of various cytokines or of hepatocytes (or tissue) from damaged liver, which have been reported to stimulate the conversion. Hepatic gene markers in freshly isolated or cultured BM cells were determined by reverse transcriptase polymerase chain reaction and immunofluorescence. RESULTS: Freshly isolated hematopoietic progenitor cells (HPC) expressed a low level of messenger RNAs of hepatic cell-specific markers including albumin and alpha-fetoprotein (AFP), but did not significantly upregulate expression of these markers, even in the presence of cytokines or cocultured hepatocytes (or tissue). HPCs induced in vitro did not express the message of alpha-anti-trypsin-a mature hepatocyte marker. At protein level, the specific staining of AFP was not detected in the HPCs, either freshly isolated or in vitro induced. Albumin protein was detected in freshly isolated albumin mRNA-positive and -negative BM cell subpopulations. Albumin-stained BM cells disappeared after being induced for 5 days, but restained if mouse serum was supplemented in medium for a 24-hour extended culture, suggesting that albumin was absorbed by BM cells instead of de novo expression. CONCLUSIONS: HPCs expressed mRNAs of hepatic cell markers, but could not efficiently convert into hepatocytes in vitro under our experimental conditions. Our observation raises a cautionary note in determining whether in vitro transdifferentiation of BM cells to hepatocytes can actually take place.

Animals↗

PubMed2006

Cerebral developmental disorders.

PURPOSE OF REVIEW: The development of the cerebral cortex progresses through defined stages including neural proliferation, neuroblast migration and neuronal differentiation. Disruptions in each of these developmental stages can lead to characteristic cerebral cortical malformations. This review provides an overview of the known genetic causes of human cerebral developmental disorders and discusses the potential molecular mechanisms that contribute to these malformations. RECENT FINDINGS: Mutations in genes that are involved in neural proliferation give rise to microcephaly (small brain). Mutations in genes that direct the onset of neuroblast migration give rise to periventricular heterotopia (clusters of neurons along the ventricles of the brain). Mutations in genes that are required for neuroblast migration cause type I lissencephaly (smooth brain) and subcortical band heterotopia (smooth brain with a band of neurons beneath the cortex). Mutations in genes that direct migratory neurons to arrest in the cortex lead to type II lissencephaly (smooth brain with clusters of neurons along the surface of the brain). SUMMARY: The identification of causative genes involved in the formation of the cerebral cortex now allows for a rational approach with which to interpret the underlying mechanistic basis for many of these disorders.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2004

Neutralizing antibodies in patients with severe acute respiratory syndrome-associated coronavirus infection.

BACKGROUND: Severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is the principal etiologic agent of SARS. We analyzed serum samples obtained from 623 patients with SARS in Beijing, to determine whether infection with SARS-CoV can elicit neutralizing antibodies (NAbs). METHODS: We developed a highly sensitive and safe neutralization assay using the SARS-CoV pseudotyped virus and used this assay to determine the titers of the NAbs in serum samples from patients with SARS. RESULTS: We found that 85.9% of serum samples contained NAbs against SARS-CoV and that most of the NAb activities could be attributed to immunoglobulin G. The NAbs became detectable first at 5-10 days after the onset of symptoms, and their levels peaked at 20-30 days and then were sustained for >150 days. The serum samples could neutralize the pseudotype particles bearing the spike glycoproteins from different SARS-CoV strains, suggesting that the NAbs to SARS-CoV were broadly reactive. CONCLUSIONS: NAbs to SARS-CoV are broadly elicited in patients with SARS and, according to their kinetics, may correlate with viral load during the early stages of the disease. These results suggest that it is possible to develop effective vaccines against SARS and that NAbs provide a potential strategy for treating patients with SARS.

Antibodies, Viral↗

PubMed2004

Identification of an antigenic determinant on the S2 domain of the severe acute respiratory syndrome coronavirus spike glycoprotein capable of inducing neutralizing antibodies.

Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by a newly identified coronavirus (CoV), SARS-CoV. The spike (S) glycoprotein of CoV is the major structural protein responsible for induction of host immune response and virus neutralization by antibodies. Hence, knowledge of neutralization determinants on the S protein is helpful for designing protective vaccines. To analyze the antigenic structure of the SARS-CoV S2 domain, the carboxyl-terminal half of the S protein, we first used sera from convalescent SARS patients to test the antigenicity of 12 overlapping fragments spanning the entire S2 and identified two antigenic determinants (Leu 803 to Ala 828 and Pro 1061 to Ser 1093). To determine whether neutralizing antibodies can be elicited by these two determinants, we immunized animals and found that both of them could induce the S2-specific antisera. In some animals, however, only one determinant (Leu 803 to Ala 828) was able to induce the antisera with the binding ability to the native S protein and the neutralizing activity to the SARS-CoV pseudovirus. This determinant is highly conserved across different SARS-CoV isolates. Identification of a conserved antigenic determinant on the S2 domain of the SARS-CoV S protein, which has the potential for inducing neutralizing antibodies, has implications in the development of effective vaccines against SARS-CoV.

Amino Acid Sequence↗