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Biomedical subjects

S C Liu

Publications and source records attributed to S C Liu.

At least 55 records · Page 3Linked to original sources

Seasonal variation of chickenpox, mumps and rubella in Taiwanese children estimated by pediatric clinics.

To determine the seasonal variation of childhood infectious diseases in Taiwan, the incidence rates of chickenpox, mumps and rubella were studied by analyzing patient's records collected from pediatric clinics in northern, central, southern and eastern Taiwan from January 1, 1993 to December 31, 1993. The study revealed that a chickenpox outbreak was most likely to occur in autumn, followed by a second peak in spring, and the lowest rate in summer. In this study, the highest monthly incidence of chickenpox was 540 cases per 100,000 population. The highest incidence of mumps occurred in the spring, the second highest in autumn, and the lowest during summer. Cases of rubella occurred in the spring, summer and autumn, but not in the winter. The data on chickenpox from this study revealed a similar seasonal pattern every year to that of the Department of Health of the National Quarantine Service on Taiwan. The chickenpox virus is known to be relatively sensitive to elevations in ambient temperature and is characterized by its occurrence mainly in slightly humid seasons.

Chickenpox↗

Markers of cell proliferation in normal epithelia and dysplastic leukoplakias of the oral cavity.

The expression of several markers of epithelial cell proliferation was analyzed to establish baseline data for future chemoprevention studies of oral premalignant lesions. Punch biopsies (n = 60) from three different sites of oral mucosa (bucca, lateral tongue, and the floor of the mouth) were obtained from 20 normal donors of both sexes. After formaldehyde fixation and paraffin embedding, immunohistochemistry was used to detect the proliferation markers Mib-1, cyclin D1, and centromere-associated protein CENP-F. Analysis of sections stained for the three markers showed similar patterns, i.e., a low labeling index (LI) in the basal layer and a high LI in the parabasal layer at all three intraoral sites. No proliferative activity was seen above the parabasal layer (superficial layer). All sites showed similar Mib-1 LI values for the proliferative markers. The tongue epithelium exhibited higher parabasal LIs of cyclin D1 and CENP-F than did the other two sites. No significant differences were detected between smokers and nonsmokers. The data from normal mucosa were compared with those from low (n = 30)- and high (n = 17)-grade dysplastic leukoplakias. The Mib-1 LI showed a very significant change, with a 9-fold increase in the basal layer LI in dysplastic leukoplakias. Cyclin D1 and CENP-F showed similar trends with increments of up to 7-fold in the basal layer of high-grade dysplasia. Although the proliferative activity of the parabasal layer was similar in normal and leukoplakic epithelia, the superficial layer showed a significant increment in proliferative activity mainly in high-grade leukoplakia. These studies suggest that proliferation markers in the basal and superficial cells of premalignant lesions may serve as surrogate end point biomarkers for chemoprevention trials.

Antigens, Nuclear↗

Expression of PACE4 in chemically induced carcinomas is associated with spindle cell tumor conversion and increased invasive ability.

Gene expression changes associated with the conversion of squamous cell carcinoma (SCC) to a more advanced malignant spindle cell carcinoma (SPCC) were determined by differential display. Using an animal model of human SCC progression, we provide evidence of increased PACE4 expression in SPCC cell lines and primary tumors induced by chemical carcinogenesis protocols, thus implicating this proprotein convertase in the process of tumor progression. Exogenous overexpression of PACE4 cDNA in mouse SCC cells of low invasive ability resulted in enhanced tumor cell invasiveness that was absent in parental or mock-transfected SCC cells. In addition, the PACE4-transfected cells acquired the ability to process prostromelysin 3 into its active enzyme form. Taken together, these results show that up-regulation of PACE4 expression is associated with SCC conversion to SPCC and suggests that activation of essential PACE4 substrates, such as the metalloproteinase stromelysin 3, is required for tumor cell invasion.

Animals↗

Red cell membranes of ankyrin-deficient nb/nb mice lack band 3 tetramers but contain normal membrane skeletons.

The role of ankyrin in the formation and stabilization of the spectrin-based skeletal meshwork and of band 3 oligomers was studied by characterizing, in nb/nb mouse red cells, the effect of ankyrin deficiency on skeletal ultrastructure, band 3-skeleton associations, and band 3 oligomeric states. Despite severe ankyrin deficiency, nb/nb mouse red cell skeletal components formed a relatively uniform two-dimensional hexagonal array of junctional complexes cross-linked by spectrin tetramers. Treatment of nb/nb ghosts with the nonionic detergent C12E8 (octaethylene glycol n-dodecyl monoether) resulted in nearly complete extraction of band 3. The extracted band 3 was present exclusively as band 3 dimers. Fluorescence photobleaching recovery and polarized fluorescence depletion measurements showed increases in the laterally (33% vs 10%) and rotationally (90% vs 76%) mobile fractions of band 3 in intact nb/nb compared to control red cells. The rotational correlation time of the major fraction of band 3 molecules was 10-fold shorter in nb/nb compared to control red cells, indicating a significant relaxation of rotational constraints in nb/nb cells. These data suggest that, although ankyrin plays a major role in strengthening the attachment of the skeleton to the membrane bilayer, ankyrin is not required for the formation of a stable two-dimensional spectrin-based skeleton. The absence of band 3 tetramers in the membrane of ankyrin-deficient red cells suggests that ankyrin is required for the formation of stable band 3 tetramers.

Animals↗

Developmental expression of chick cortical GABA(A) receptor alpha1 subunits in vivo and in vitro.

In order to examine the expression of the GABA(A) receptor alpha1 subunit during chick cortical development in vivo and in vitro, we have utilized a polyclonal antibody (RP4) directed against an alpha1(331-381) fusion protein. This antibody exhibits a high titer for precipitation of [3H]flunitrazepam binding sites in chick cortical extracts, no significant cross-reactivity with GABA(A) receptor beta2- or beta4-subunit fusion proteins, and a robust reaction with a single 51-kDa polypeptide on immunoblots of cortical membranes. This indicates monospecificity of the RP4 antiserum for the GABA(A) receptor alpha1 subunit. The alpha1-subunit antibody also showed strong immunocytochemical reactions with neurons in the embryonic mediodorsal cortex and Purkinje cells of the chick cerebellum. The ontogeny of the alpha1 subunit in chick cortex and in derived neuronal cultures was examined by quantitative Western blotting. The level of the alpha1 polypeptide increased from day 2 to day 6 in culture, acquiring 50% of the maximum expression at day 4. Expression of the cortical GABA(A) receptor alpha1 subunit increased in vivo from embryonic day 8 (E8) to day 7 post-hatching, reaching 50% of adult levels at E16. Levels of the corresponding alpha1-subunit mRNA, analyzed from E8 to E20 by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR), showed a corresponding incline. These findings correlated well with previous developmental studies of GABA(A) receptor ligand binding sites both in vivo and in vitro. The parallel increase of the alpha1 subunit transcript and polypeptide with [3H]flunitrazepam binding sites suggests that this subunit may be an important component of GABA(A) receptors early in cortical ontogeny. This was investigated further by quantitative immunoprecipitation. At saturation, the RP4 antiserum consistently precipitated 50-65% of the central [3H]flunitrazepam binding sites in the developing cortex from E12 through P7, despite a 5-fold increase in the binding level. The data suggest that during cortical development the fraction of GABA(A) receptors containing alpha1 subunits remains relatively constant. Furthermore, the alpha1 polypeptide appears to be a major component of GABA(A) receptor oligomers at all stages of cortical maturation.

Animals↗

Aberrant expression of GABAA receptor subunits in the tottering mouse: an animal model for absence seizures.

The single-locus mutant mouse tottering (tg) is an established model for absence seizures. We have previously reported an impairment in GABA-induced chloride uptake in tg brain [Tehrani and Barnes, Epilepsy Res. 1995;22:13-21]. In order to determine if this alteration in GABAA receptor function can be related to specific receptor isoforms, we examined the radioligand binding properties of GABAA receptors and the expression of GABAA receptor subunit mRNAs in the cerebral cortex. Saturation binding of [3H]flunitrazepam revealed a significantly lower Kd value in tg cortical tissues (1.77 +/- 0.05 nM) in comparison to that for the background C57BL/6J strain (3.23 +/- 0.23 nM), while the Bmax values were indistinguishable. Biphasic displacement of [3H]flunitrazepam binding by 2-oxoquazepam showed that low affinity binding sites account for 36 +/- 7.6 and 51 +/- 7.5% of the total in control and tg, respectively. The level of [35S]-t-butylbicyclophosphorothionate (TBPS) binding to tg cortical membranes was 73.6 +/- 5.8% of that in controls. Paired measurements by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) revealed no significant differences in the levels of GABAA receptor alpha 1, alpha 3, alpha 5, beta 2, beta 3, gamma 2 or gamma 3 subunit mRNAs between tg and control cortex. However, tg tissues showed elevated levels of alpha 2- and beta 1-subunit mRNAs, representing 256 and 177%, respectively, those of controls. For the tg cortex, the enhanced expression of GABAA receptor alpha 2 and beta 1 subunits correlates with recombinant subtypes known to have low affinity for 2-oxoquazepam and impaired binding of TBPS. These aberrant properties of GABAA receptors could influence the development or propagation of phenotypic seizures in the tottering mouse.

Animals↗

Repression of c-myc gene expression by the thiol and disulfide forms of the cytoprotector amifostine.

The clinically approved cytoprotector amifostine, designated WR-2721, [S-2-(3-aminopropylamino)ethylphosphorothioic acid], protects against both radiation and drug-induced mutagenesis in animal systems. These effects extend over a wide concentration range making amifostine a strong candidate for evaluation as a possible cancer chemopreventive agent. To better identify and develop potential intermediate biomarkers for chemoprevention at the molecular level we applied the technique of differential display RT-PCR to assess the effects of both the thiol (SH), i.e. WR1065 and the disulfide (SS), i.e. WR-33278, metabolites of amifostine on gene expression in CHO-AA8 cells. Cells were exposed to either 40 microM or 4 mM of each agent for 30 min, and subsequent changes in gene expression were identified and contrasted to that found in corresponding untreated control cells. One band that showed a differential response was sequenced and was found to have 78% homology with a segment of the human pHL-1 cDNA clone contained in GenBank. This clone contains a COX III mitochondrial DNA insert and two exons of human c-myc. Northern blot analyses were performed by using the cloned human c-myc exon 1 probe to confirm whether c-myc gene expression was affected. Repression of c-myc expression was observed under all of the conditions evaluated. An exposure of cells to 40 microM of the disulfide form of amifostine was the most effective in repressing c-myc, i.e. 27% of control level. A concentration of 4 mM of the disulfide form reduced gene expression to 45% of the control level, while the thiol form was less effective, with 4 mM and 40 microM concentrations reducing c-myc gene expression to 65% and 46% of control levels, respectively.

Amifostine↗

Erythrocyte membrane alterations in Plasmodium falciparum malaria sequestration.

Plasmodium falciparum malaria, the most lethal form of human malaria, claims at least 2 million lives worldwide each year. Recently, there has been a significant advance in our understanding of the molecular basis of P. falciparum sequestration, a distinctive pathologic feature that often leads to fatal human cerebral malaria. Parasite-derived VAR proteins (Plasmodium falciparum-infected erythrocyte membrane protein 1) have been cloned and identified as antigenically diverse cytoadherent receptors localized to the knob protrusions that act as attachment points in parasite sequestration. Evidence now supports the hypothesis that cryptic regions of band 3 protein are parasite-induced, host-derived erythrocyte receptors mediating parasite sequestration. Knob structures have been localized to spectrin-actin-protein 4.1 junctions in intact spread membrane skeletons. A recombinant domain of knob-associated histidine-rich protein, a major protein found in both membrane-intact and isolated knobs, has been shown to associate with filamentous actin and spectrin. Parasite- and host-derived erythrocyte membrane proteins involved in P. falciparum sequestration are discussed in this review.

Animals↗

Hepatitis B vaccination in preterm infants.

AIM: To investigate the immunogenicity and safety of existing recommendations for hepatitis B vaccination in preterm infants. METHODS: Recombinant hepatitis B vaccine (H-B-VAX II, 5 micrograms per dose) was given to 85 preterm infants divided into two groups, using two different schedules. Forty four group A infants with birthweights of < 2000 g received three doses at 1, 2, and 7 months of age. Forty one group B infants with birthweights of > or = 2000 g received three doses at 0, 1, and 6 months of age. RESULTS: After vaccination, 42 infants from group A (95%) and 37 infants from group B (90%) developed protective levels of antibody. The final seropositive rate and the geometric mean concentration of hepatitis B surface antibody between the two groups were not significantly different. The immune response of preterm infants to hepatitis B vaccines was similar to that of term infants in a previous study. CONCLUSIONS: Preterm infants can be given hepatitis B vaccines using one of the above two different schedules, at a cutoff birthweight of 2000 g.

Antibodies, Viral↗

Increased expression of G1 cyclins and cyclin-dependent kinases during tumor progression of chemically induced mouse skin neoplasms.

Cyclins and cyclin-dependent kinases (Cdks) are central to regulation of the cell cycle. Their abnormal expression may cause loss of cell-cycle control and result in autonomous cell growth, a critical feature of neoplasias. In this study, using immunoblotting, we analyzed the protein levels of several G1/S cyclins (cyclins D1, D2, D3, A, and E) and their respective Cdks (Cdk 2, 4, and 6) in 17 mouse squamous cell carcinomas (SCCs) and 18 mouse skin tumor cell lines. Overexpression of these cell cycle-related genes was frequent in tumors and cell lines. Of special interest was the fact that a group of cell lines that became more aggressive after animal passaging expressed more cyclins D2 and D3 than their respective parental lines did. In addition, SCCs had higher cyclin D3 expression levels than papillomas, and metastases had higher levels than the respective primary tumors, indicating that overexpression of cyclin D3 may be associated with increased aggressiveness of mouse SCC. Interestingly, overexpression of cyclin E was seen in most SCCs induced by a complete carcinogenesis protocol with benzo[a]pyrene (B(a)P) and only in a few SCCs induced by a two-stage carcinogenesis protocol using 7,12-dimethylbenz[a]anthracene as initiator. In contrast, more of the latter tumors overexpressed cyclin D1 and D2 than those induced by B(a)P. Thus, it is possible that different components of the cell-cycle machinery are involved in proliferative dysfunctions that take place during tumor development with different carcinogenesis protocols. Taken together, these results indicate that overexpression of G1 cyclins and their related Cdks is a significant molecular abnormality that could be involved in the process of tumor progression.

9,10-Dimethyl-1,2-benzanthracene↗

Penicillin-resistant pneumococcal infections in children.

Penicillin-resistant pneumococcal infections have been reported worldwide, but rarely reported in Taiwan. From 1990 to 1995, the rate of penicillin-resistant Streptococcus pneumoniae (PRSP) infections in our hospital increased from less than 10% during the first 2 years (1990-91) to 45% during the last 2 years (1994-95). From 1990 to 1995, twenty-four patients with systemic pneumococcal infections were diagnosed in the Department of Pediatrics at Mackay Memorial Hospital. Pneumococci were isolated from blood in 20 patients, cerebrospinal fluid in 12 patients, joint fluid in one patient and pleural effusion in one patient. Four patients had underlying diseases, including ileal atresia, Wiskott-Aldrich syndrome, congenital heart disease, and perilymph fistula. Of the 24 isolates of S. pneumoniae, 17 (70.8%) were intermediately penicillin resistant (minimum inhibitory concentrations between 0.1 and 1.0 microgram/mL), and 7 (29.2%) were highly resistant (minimum inhibitory concentrations > 1.0 microgram/ml). Fourteen patients recovered completely, two had minor sequelae, two had major sequelae, and six died. Four of the 12 patients with meningitis died. In this study, both the rate of PRSP as well as the mortality of patients with PRSP meningitis were high, as compared to previous reports. To reduce the mortality and morbidity of systemic pneumococcal infections, the oxacillin disc diffusion test is important in addition to appropriate antibiotic therapy.

Child, Preschool↗

Cardiac perforation and tamponade induced by external cardiac massage: a case report.

A 76-year-old woman suffered from sudden loss of consciousness while sitting in a chair. She was sent to a local hospital and found to be in shock. After a brief period of external cardiac massage, she was transferred to our hospital. In our emergency department she was lethargic with cool, clammy extremities. Her blood pressure dropped from 113/53 mmHg on arrival to 72/42 mmHg 2 hours later. Echocardiography showed massive pericardial effusion, fair left ventricular contractility and no abnormal segmental motion. The echocardiographic appearance suggested fibrin-like substance in the pericardial space, which was felt to indicate the presence of blood. Enhanced chest computerized tomography showed extravasation of contrast medium from the right ventricular outflow tract. At surgery, a small perforation was found at the infundibular area of the right ventricle, and a total of 500 mL of blood had accumulated in the pericardial space. She was discharged 7 days postoperatively, having made an uneventful recovery. External cardiac massage may cause cardiac disruption, and this should be considered in patients who have secondary hemodynamic instability following successful cardiopulmonary resuscitation.

Aged↗

Anion exchanger 1 (band 3) is required to prevent erythrocyte membrane surface loss but not to form the membrane skeleton.

The red blood cell (RBC) membrane protein AE1 provides high affinity binding sites for the membrane skeleton, a structure critical to RBC integrity. AE1 biosynthesis is postulated to be required for terminal erythropoiesis and membrane skeleton assembly. We used targeted mutagenesis to assess AE1 function in vivo. RBCs lacking AE1 spontaneously shed membrane vesicles and tubules, leading to severe spherocytosis and hemolysis, but the levels of the major skeleton components, the synthesis of spectrin in mutant erythroblasts, and skeletal architecture are normal or nearly normal. The results indicate that AE1 does not regulate RBC membrane skeleton assembly in vivo but is essential for membrane stability. We postulate that stabilization is achieved through AE1-lipid interactions and that loss of these interactions is a key pathogenic event in hereditary spherocytosis.

Animals↗

Reduced invasion and growth of Plasmodium falciparum into elliptocytic red blood cells with a combined deficiency of protein 4.1, glycophorin C, and p55.

In this investigation, we have measured the invasion and growth of the malaria parasite Plasmodium falciparum into elliptocytic red blood cells (RBCs) obtained from subjects with homozygous hereditary elliptocytosis. These elliptocytic RBCs have been previously characterized to possess molecular defects in protein 4.1 and glycophorin C. Our results show that the invasion of Plasmodium falciparum into these protein 4.1 (-) RBCs is significantly reduced. Glycophorin C (-) Leach RBCs were similarly resistant to parasite invasion in vitro. The intracellular development of parasites that invaded protein 4.1 (-) RBCs was also dramatically reduced. In contrast, no such reduction of intracellular parasite growth was observed in the glycophorin C (-) Leach RBCs. In conjunction with our recent finding that a third protein termed p55 is also deficient in protein 4.1 (-) and glycophorin C (-) RBCs, the present data underscore the importance of the membrane-associated ternary complex between protein 4.1, glycophorin C, and p55 during the invasion and growth of malaria parasites into human RBCs.

Animals↗

Red cell membrane remodeling in sickle cell anemia. Sequestration of membrane lipids and proteins in Heinz bodies.

In red cells from patients with sickle cell anemia, hemoglobin S denatures and forms Heinz bodies. Binding of Heinz bodies to the inner surface of the sickle cell membrane promotes clustering and colocalization of the membrane protein band 3, outer surface-bound autologous IgG and, to some extent, the membrane proteins glycophorin and ankyrin. Loss of transbilayer lipid asymmetry is also found in certain populations of sickle red cells. The lateral distribution of sickle cell membrane lipids has not been examined, however. In this report, we examine by fluorescence microscopy the incorporation and distribution of the fluorescent phospholipid analogues 7-nitro-2,1,3-benzoxadiazol-4-yl (NBD)-phosphatidylserine and NBD-phosphatidylcholine in sickle red cells. Both phospholipid analogues are observed to accumulate prominently at sites of Heinz bodies. Accumulation at sites of Heinz bodies is also shown by 1,'1-dihexadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate, a fluorescent lipid analogue that readily crosses membranes, but not by fluorescein-phosphatidylethanolamine, an analogue that is localized to the outer leaflet of the membrane. Double labeling and confocal microscopy techniques show that NBD-lipids, band 3 protein, protein 4.1, ankyrin, and spectrin are all sequestered within sickle red cells and colocalized at sites of Heinz bodies. We propose that Heinz bodies provide a hydrophobic surface on which sickle red cell membrane lipids and proteins are sequestered.

4-Chloro-7-nitrobenzofurazan↗

Genome-wide high-resolution mapping by recurrent intermating using Arabidopsis thaliana as a model.

We demonstrate a method for developing populations suitable for genome-wide high-resolution genetic linkage mapping, by recurrent intermating among F2 individuals derived from crosses between homozygous parents. Comparison of intermated progenies to F2 and "recombinant inbred" (RI) populations from the same pedigree corroborate theoretical expectations that progenies intermated for four generations harbor about threefold more information for estimating recombination fraction between closely linked markers than either RI-selfed or F2 individuals (which are, in fact, equivalent in this regard). Although intermated populations are heterozygous, homozygous "intermated recombinant inbred" (IRI) populations can readily be generated, combining additional information afforded by intermating with the permanence of RI populations. Intermated populations permit fine-mapping of genetic markers throughout a genome, helping to bridge the gap between genetic map resolution and the DNA-carrying capacity of modern cloning vectors, thus facilitating merger of genetic and physical maps. Intermating can also facilitate high-resolution mapping of genes and QTLs, accelerating mapbased cloning. Finally, intermated populations will facilitate investigation of other fundamental genetic questions requiring a genome-wide high-resolution analysis, such as comparative mapping of distantly related species, and the genetic basis of heterosis.

Arabidopsis↗

Detection of congenital cytomegalovirus infection in Chinese newborn infants using polymerase chain reaction.

Polymerase chain reaction (PCR) amplification was used to detect cytomegalovirus (CMV) in 1000 urine specimens from Chinese newborns for defining the incidence of congenital CMV infection in the Chinese population. The major immediate-early and the late antigen genes of CMV were amplified and detected by gel electrophoresis. There were 18 congenitally infected infants found when tests were performed with one or both primer pairs. Comparing with tissue culture, PCR of both primer sets provided a sensitivity of 94%, a specificity of 100% and a predictive value of positive result of 100%.

China↗