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Biomedical subjects

W M Liu

Publications and source records attributed to W M Liu.

At least 55 records · Page 3Linked to original sources
PubMed1997

Nonlinear oscillations in models of immune responses to persistent viruses.

This paper compares several population models for HIV dynamics. The effect of perfect or nonperfect drugs proposed by Ho, Perelson, and others are considered in the more complicated models of Nowak and Bangham for immune responses to persistent viruses. It is pointed out that two models proposed by Nowak and Bangham have different dynamical behaviors. One of them can have sustained oscillations via the Hopf bifurcation and the other does not. To overcome the difficulty in symbolic computations for complicated systems, we use parameter transforms and introduce a semisymbolic method. This method is very efficient in finding Hopf bifurcation parameters and can be used for other models.

Antibody Formation↗
PubMed1997

Ureteral injury after laparoscopic surgery.

Ureteral injuries are uncommon but serious complications of laparoscopic pelvic surgery. When unrecognized, patients experience fever, abdominal pain, signs of peritonitis, and leukocytosis usually 48 to 72 hours after the surgical procedure. A 48-year-old woman underwent laparoscopic-assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and anterior and posterior colporrhapy due to a large, symptomatic uterine myoma. Postoperatively, she suffered from progressive left lower quadrant pain, with drainage of yellowish fluid from the subumbilical puncture wound 5 days after the operation. Significant urinary ascites was present. Intravenous pyelogram revealed injury to the lower third of the left ureter about 3 cm away from the ureterovesical junction. Left-sided percutaneous nephrostomy was performed after transurethral placement of a ureteral stent failed. Reanastomosis of the ureter was performed successfully 3 months later, and the patient fully recovered without compromise of the genitourinary tract.

Female↗
PubMed1997

Is there a Möbius band in closed protein beta-sheets?

Protein beta-strands can form beta-barrels and other complicated structures. This paper defines bifurcations and pseudobifurcations of beta-sheets. They are important structural elements for protein folding. This paper also presents a characteristic number that can be used to test whether the surface of a closed beta-sheet is one- or two-sided. Searching the whole Protein Data Bank released in April 1997 with the definition of beta-structures given by the DSSP program, we do not find any one-sided beta-Möbius band. However, there are interesting structures such as beta-bands with odd number of antiparallel ladders and odd number of bifurcations. There are also beta-structures that are closed only at a singular point. Adding a small patch near the singular point in different ways can make it a one- or two-sided surface. The catalytic triad of a GMP synthetase (1GPM) is near the singular point of such a beta-sheet.

Bacteriophage P22↗
PubMed1996

Diamond Blackfan anaemia: differential pattern of in vitro progenitor response to macrophage inflammatory protein 1-alpha.

The congenital disorder of erythropoiesis Diamond Blackfan anaemia (DBA) exhibits a defect in the stem/progenitor cell compartment, located at the erythroid progenitor level (CFU-GEMM, BFU-E, CFU-E). Treatment of DBA with interleukin-3 (IL-3) has had limited effect, despite in vitro studies suggesting that progenitor cells were capable of responding to IL-3. Whether IL-3 is not reaching the appropriate defective target cell, the cells cannot respond, or the marrow humoral inhibitory system is overriding it, is not clear. To investigate humoral inhibitory activities we examined the response of 15 DBA bone marrows in vitro to the inhibitory chemokine macrophage inflammatory protein 1-alpha (MIP1-alpha) in the presence of the stimulatory cytokines erythropoietin, granulocyte-macrophage colony-stimulating factor, IL-3, and stem cell factor. In vitro data agreed with our previous work showing that our patients formed three statistically different groups in response to stimulatory cytokines (type I DBA erythroid colony numbers approximately normal > type II DBA > type III DBA). Addition of MIP1-alpha to cultures caused average erythroid and myeloid suppression, which sequentially increased with DBA type (type I inhibition < type II < type III). The differential level of inhibition shown by MIP1-alpha in these DBA patients lends further evidence for the presence of distinct subgroups in this disorder.

Adolescent↗
PubMed1996

A novel approach to investigating the erythroid lineage, using both receptor analysis and haemoglobin detection.

Progenitor cell failure in the erythroid lineage is a particular problem in bone marrow failure. To provide insight into early erythopoietic development we used sensitive techniques to examine the effects of SCF, IL-3 and MIP-1 alpha on two developmentally arrested progenitor cell lines, HEL and K562. Quantitative flowcytometric analysis showed that both expressed receptors (SCF > MIP-1 alpha > IL-3). Qualitative analysis revealed HEL cells expressed more receptors than K562 cells. Clonogenic assays with sensitive haemoglobin detection showed that SCF and IL-3 did not support HEL development and reduced haemoglobin production. MIP-1 alpha reduced partially developed HEL colonies and haemoglobin in developed colonies. SCF increased development, but not haemoglobin in K562 cells, with IL-3 being more effective in both. MIP-1 alpha increased the proportion of well-developed K562 colonies but not haemoglobin. This suggests SCF, IL-3 and MIP-1 alpha all have a role to play in early erythroid cellular development, with differing actions depending on the stage of development.

Cell Differentiation↗
PubMed1996

The use of recombinant SCF protein for rapid determination of c-kit expression in normal and abnormal erythropoiesis.

Stem cell factor (SCF) is the ligand for the dimeric c-kit tyrosine kinase receptor. Binding of SCF to c-kit is a crucial element in the developmental stimulus of late stem cells and early progenitor cells. In the erythroid lineage the SCF stimulus is important not only for proliferation and differentiation, but is also known to enhance later haemoglobin production. In an earlier report we described a rapid non-radioactive technique using the extended ester-attached labelled SCF protein itself for detecting c-kit expression in marrow and peripheral blood mononuclear populations. In the present study we have taken this a step further to analyse c-kit expression in developing erythroid cells in vitro, principally using normal donor samples. This was designed for use as a foundation for the comparison of haematological disorders. In this case we tested 4 patients with the congenital disorder of erythropoiesis, Diamond-Blackfan anaemia (DBA), finding that in all cases DBA c-kit expression was elevated over normal, in 1 case as high as 348% of the normal average. This may be indicative of the reduced state of progenitor development in these patients. These results show that the described technique is beneficial for analysis in the stem and progenitor compartment.

Adult↗
PubMed1995

RNA polymerase III promoter and terminator elements affect Alu RNA expression.

Promoter elements derived from the 7SL RNA gene stimulate RNA polymerase III (Pol III) directed Alu transcription in vitro. These elements also stimulate expression of Alus transfected into 293 cells, but transcripts from these same constructs are undetectable in HeLa cells. A terminator resembling the terminator for the 7SL RNA gene has no effect on in vitro Alu template activity, but increases expression in vivo in a position independent manner. Alu transcripts generated from templates with and without this terminator have identical half-lives, indicating that this terminator stimulates expression by increasing template activity. Together, these results show that Alu expression may be regulated at multiple levels and can respond to cis-acting elements. This new found ability to express Alu transcripts by transient transfection provides an opportunity to monitor their post-transcriptional fate. Primary Alu transcripts are not extensively adenylated or deadenylated following transcription, but are short-lived compared to 118 nt scAlu RNA. In addition to Alu RNA, transfected templates encode scAlu RNA, but very high levels of Alu RNA expression does not increase the abundance of scAluRNA. ScAluRNA is not merely a transient RNA degradation product, but is instead tightly regulated by factors other than the abundance of primary transcripts.

Base Sequence↗
PubMed1995

Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts.

The abundance of Alu RNA is transiently increased by heat shock in human cell lines. This effect is specific to Alu repeats among Pol III transcribed genes, since the abundance of 7SL, 7SK, 5S and U6 RNAs is essentially unaffected by heat shock. The rapid induction of Alu expression precedes the heat shock induction of mRNAs for the ubiquitin and HSP 70 heat shock genes. Heat shock mimetics also transiently induce Alu expression indicating that increased Alu expression is a general cell-stress response. Cycloheximide treatment rapidly and transiently increases the abundance of Alu RNA. Again, compared with other genes transcribed by Pol III, this increase is specific to Alu. However, as distinguished from the cell stress response, cycloheximide does not induce expression of HSP 70 and ubiquitin mRNAs. Puromycin also increases Alu expression, suggesting that this response is generally caused by translational inhibition. The response of mammalian SINEs to cell stress and translational inhibition is not limited to SINEs which are Alu homologues. Heat shock and cycloheximide each transiently induce Pol III directed expression of B1 and B2 RNAs in mouse cells and C-element RNA in rabbit cells. Together, these three species exemplify the known SINE composition of placental mammals, suggesting that mammalian SINEs are similarly regulated and may serve a common function.

3T3 Cells↗
PubMed1994

High-density cultivation of sporeformers.

Sporeformers are sources of a large number of industrially important biological products including enzymes, antibiotics, and bioinsecticides. Cultivation of these microorganisms to high cell densities offers potential for enhancing the rates of formation as well as the concentration of the desired products in the fermentation broths in bioreactors. With this objective, investigations have been carried out involving fed-batch cultivation of Bacillus thuringiensis, which is known to produce an insecticidal crystal protein during sporulation. With appropriate management of aeration and nutrient supply, it was possible to grow the cells to > 50 g DW/l density. Nevertheless, the achievement of high cell density did not enhance the formation of crystal protein in the same proportion as the cell concentration. Further examination of this system suggested a complex interplay of energetic requirements for protein turnover during sporulation. Energy reserve material, poly-beta-hydroxybutyric acid, appeared to be linked to formation of spores and crystal protein during the sporulation phase.

Bacillus thuringiensis↗
PubMed1994

Alu transcripts: cytoplasmic localisation and regulation by DNA methylation.

Full length Alu transcripts in HeLa cells are detected by primer extension using reverse transcriptase and are also analyzed as cloned cDNA sequences. The 5' end of these transcripts corresponds to the transcriptional start site for RNA polymerase III indicating that these RNAs are transcribed from their internal polymerase III promoters. The Alu transcripts found in cytoplasmic poly A+ RNAs appear to be organized into RNPs as assayed by sucrose gradient sedimentation. Present at about one hundred to one thousand copies per cell, the Alu transcripts are rare as compared to 7SL RNA. In agreement with previous reports that methylation inhibits Pol III-directed transcription of Alu in vitro, treatment of HeLa cells with 5-azacytidine results in Alu DNA hypomethylation and an increase in the abundance of the Alu transcript. Sequence analysis shows that many different Alu repeats including members of all subfamilies are transcribed by Pol III in vivo. cDNA sequences of the Pol III-directed transcripts exactly match the A box of the Pol III promoter element whereas in other Alu transcripts this element is not faithfully conserved.

Azacitidine↗
PubMed1994

Nonlinear forecasting of hepatitis and AIDS incidence.

The simplex methods of nonlinear forecasting are used to study the data sets of hepatitis A and AIDS in various regions of the United States. The results are compared with those obtained from the traditional ARIMA methods. In many regions, the simplex methods developed from nonlinear dynamical system theory give smaller errors for the data of hepatitis A. A combination of the simplex methods and the traditional ARIMA methods can produce better results for the AIDS data sets.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A new pharmacodynamic model of antiarrhythmic drugs.

A new model using rational functions is proposed for the pharmacodynamics of antiarrhythmic drugs. It can describe both positive and negative effects, as well as different asymptotic effect levels. The method for determining parameters is presented and applied to experimental data. This model fits data better than traditional models.

Anti-Arrhythmia Agents↗
PubMed1993

Proposed roles for DNA methylation in Alu transcriptional repression and mutational inactivation.

Methylation at CpG dinucleotides to produce 5 methyl cytosine (5me-C) has been proposed to regulate the transcriptional expression of human Alu repeats. Similarly, methylation has been proposed to indirectly favor the transpositional activity of young Alu repeats by transcriptionally inactivating older Alu's through the very rapid transition of 5me-C to T. Both hypotheses are examined here by RNA polymerase III (Pol III) in vitro transcription of Alu templates using HeLa cell extracts. A limiting factor represses the template activity of methylated Alu repeats. Competition by methylated prokaryotic vector DNA's relieves repression, showing that the factor is not sequence specific. This competitor has no effect on the activity of unmethylated templates showing that the repressor is highly specific toward methylated DNA. While methylation of a single pair of CpG dinucleotides in the A box of the Poll III promoter is sufficient to cause repression, methylation elsewhere within the template also causes repression. The repressor causing these effects on the Pol III directed transcription of Alu repeats is thought to be a previously reported, repressor for Pol II directed templates. Young Alu repeats are transcriptionally more active templates than a representative older Alu subfamily member. Also, younger Alu's form stable transcriptional complexes faster, potentially giving them an additional advantage. The mutation of three CpG's to CpA's within and near the A box drastically decreases both the template activity and rate of stable complex formation by a young Alu member. The sensitivity of Alu template activity to CpG transitions within the A box partially explains the selective transpositional advantage enjoyed by young Alu members.

5-Methylcytosine↗
PubMed1993

Phylogenetic isolation of a human Alu founder gene: drift to new subfamily identity [corrected].

A severe bottleneck in the size of the PV Alu subfamily in the common ancestor of human and gorilla has been used to isolate an Alu source gene. The human PV Alu subfamily consists of about one thousand members which are absent in gorilla and chimpanzee DNA. Exhaustive library screening shows that there are as few as two PV Alus in the gorilla genome. One is gorilla-specific, i.e., absent in the orthologous loci in both human and chimpanzee, suggesting the independent retrotranspositional activity of the PV subfamily in the gorilla lineage. The second of these two gorilla PV Alus is present in both human and chimpanzee DNAs and is the single PV Alu known to precede the radiation of these three species. The orthologous Alu in gibbon DNA resembles the next older Alu subfamily. Thus, this Alu locus is originally templated by a non-PV source gene and acquired characteristic PV sequence variants by mutational drift in situ, consequently becoming the first member and presumptive founder of this PV subfamily.

Animals↗
PubMed1992

Unusual sequences of two old, inactive human Alu repeats.

Two human Alu repeats terminating in an oligo(T) run rather than the usual A-rich 3' tail were isolated by library screening. Base sequence comparisons reveal that these unusual Alus are also exceptionally divergent from other Alu family members implying that they are evolutionarily old. Unlike other members of the family, they are not transcribed in vitro by RNA polymerase III (Pol III) suggesting a partial explanation for how Alu source genes might become inactive with age.

Base Sequence↗