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Biomedical subjects

S C Hsu

Publications and source records attributed to S C Hsu.

At least 37 records · Page 2Linked to original sources
PubMed2001

Extreme metabolic alkalosis treated with normal bicarbonate hemodialysis.

Metabolic alkalosis (MA), defined as a primary increment in plasma bicarbonate concentration, is a common complication in hospitalized patients and is associated with high morbidity and mortality in severe cases. One of the major routes of compensation for MA (ie, the secretion of an alkaline urine) is lost in renal failure patients. We report three cases involving four episodes of extreme MA with an arterial pH value greater than 7.60, serum bicarbonate concentration greater than 55 mmol/L, and stupor or seizure. Profound vomiting or massive gastric drainage combined with concurrent oliguric renal failure was the underlying mechanism for severe MA. Hydration and normal central venous pressure failed to improve the MA. The extreme MA was reversed quickly and safely by conventional hemodialysis with normal bicarbonate dialysate of 25 to 28 mmol/L. To our knowledge, this is the first reported successful use of normal bicarbonate dialysate in the treatment of severe MA. We also found that either H(2) blockers or proton-pump inhibitors have a prophylactic effect on the formation of MA.

Adult↗
PubMed2001

Transport properties of ionic drugs in the ammonio methacrylate copolymer membranes.

PURPOSE: Ammonio methacrylate copolymer is a pharmaceutical excipient widely used as a coating material for encapsulation of pellet and tablet dosage forms. Because of the charged ammonio function groups within the polymer, ionic drugs may interact with the coating film while transporting through it. The kinetic swelling and drug permeation properties of the ammonio methacrylate copolymer membranes were studied to delineate the effect of ionic interaction between the ionic drugs and the membranes. METHODS: The pH and ionic strength of the solutions and the charged properties of drugs were varied to study the effects on the transport properties through the membranes. Ambroxol was chosen as a model cationic drug and aspirin as a model anionic drug. RESULTS: The degree of membrane swelling in the drug-free solution decreases as the ionic strength increases but it is irrelevant to the pH. With the presence of ionic drugs, the degree of membrane swelling is affected by the drug species as well as the pH of the solutions in addition to the effect of ionic strength. The degree of swelling for a membrane in a solution containing aspirin is higher at a lower pH and ambroxol is lower at a lower pH. Aspirin experiences a three-stage permeation and ambroxol a two-stage one. The ion-exchange reaction between the anionic carboxylic groups in aspirin and the cationic ammonio groups in the membranes results in a slow permeation stage during the transient state. The pseudo steady-state permeability for each drug follows the trend as the degree of membrane swelling in the drug media at various pH and ionic strengths. However, it is much higher for aspirin than ambroxol although the degree of membrane swelling is higher in an ambroxol solution than that in an aspirin solution. The permeability of ambroxol through the membrane is largely reduced because of the Donnan exclusion effect. CONCLUSIONS: The interaction between ionic drugs with the cationic groups in the membranes affects the ionic strength of the solutions and results in a pH-dependent degree of swelling. The ionic interaction also determines the drug permeation rates as well as the transient permeation behaviors.

Algorithms↗
PubMed2001

Evaluation of problem-based learning: a lecturer's perspective.

INTRODUCTION: The exponential growth in medical/dental knowledge and the ever-expanding influence and sophistication of information technologies have placed a burden of responsibilities on dental educators to fashion out a curriculum that can prepare students to face the coming challenges in the new millennium. Consequently, a curriculum reform took place in the Faculty of Dentistry, National University of Singapore in 1997. Problem-based learning (PBL) was first introduced to the Faculty in 1996 as a pilot project to the 4th year. The purpose of this project was to evaluate the 4-year experience in PBL teaching and learning from the lecturers' point of view. MATERIALS AND METHODS: All 12 lecturers, who had been involved in the PBL teaching, participated in this questionnaire survey, which was composed of 17 questions with a 5-digit Likert scale. Data analysis was carried out using the Spearman's correlation, t-test, and the Mann-Whitney U test. RESULTS: Six female, 5 male and 1 unidentified lecturers were recruited into this survey with a 100% response rate. In general, lecturers learned more in teaching PBL and significantly took pleasure in the interactive learning and self-directed learning modes inherent to PBL (P = 0.004). Compared to the male lecturers, female lecturers had a greater propensity to feel that PBL teaching might not be cost-effective (P = 0.03). Senior lecturers felt more fulfilled compared with the younger ones (P = 0.026). Those lecturers who enjoyed the interactive learning experience in PBL seemed to like the self-directed learning and felt more fulfilled through teaching PBL compared to the traditional teaching (TT) (P < 0.01). They also felt that PBL may be cost-effective (P < 0.01). Lecturers did not have difficulties in being a facilitator (P = 0.04). Interestingly, lecturers who found difficulties in being a facilitator for the PBL class seemed to learn more in teaching PBL classes than in TT (P < 0.05). Overall, lecturers would like to suggest more PBL to be incorporated into the curriculum (P = 0.02). Nevertheless, lecturers were concerned about the knowledge gaps in students learning with PBL (P = 0.01) and the time constraint of students (P = 0.002). CONCLUSION: The results of this study reveal the pros and cons of the current PBL teaching method and may thus provide proper guidelines to shape the further development of PBL in our faculty.

Age Factors↗
PubMed2001

The effects on vesicourethral function following laparoscopic hysterectomy.

The aim of our study is to determine whether laparoscopic hysterectomy is associated with increased postoperative urinary symptoms and to assess the change in urodynamic parameters after operation. Forty-five women were arranged for laparoscopic hysterectomy (LH). Each patient received urinalysis, interview, and urodynamic study including uroflowmetry, filling and voiding cystometry and urethral pressure profilometry before and after hysterectomy. A total of 27 patients (60%) had urinary symptoms preoperatively. After operation, only 22 patients (48.9%) remained symptomatic. There was no significant change in the number of women with one or more voiding symptoms before and after surgery, but the incidence of urinary frequency and stress incontinence decreased significantly after laparoscopic hysterectomy (P < 0.05). In addition, maximal urethral closure pressure and maximal cystometric capacity showed significant increases after operation. They were 73.1 cm H2O (range: 49-114) vs 104.4 cm H2O (range: 60-147) (P < 0.001), and 363.3 ml (range: 287-423) vs 396.1 ml (range: 265-515) (P < 0.001), respectively. The result indicated that laparoscopic hysterectomy did not significantly increase the subjective or objective incidence of vesicourethral dysfunction. On the contrary, some patients might be cured of urinary frequency or stress incontinence postoperatively.

Adult↗
PubMed2001

Pseudo-Meigs syndrome and elevated levels of tumor markers associated with benign ovarian tumors--two case reports.

Elevated tumor markers for a post-menopausal woman presenting with a multilocular adnexal mass, ascites, and pleural effusion were interpreted as being highly suspicious of malignancy. This paper describes two cases of ovarian tumors presenting with all signs of malignancy. Following surgical excision of the masses, and histopathological assay, a benign pure struma ovarii and a mucinous cystadenoma were diagnosed by pathologists. The immediate and complete resolution of symptoms were achieved post-operatively, and the previously-evident abnormal tumor markers rapidly declined to the normal range, the two tumors were subsequently classified as pseudo-Meigs' syndromes.

Aged↗
PubMed2000

Substitution of a glycogen synthase kinase-3beta phosphorylation site in presenilin 1 separates presenilin function from beta-catenin signaling.

The majority of cases with early onset familial Alzheimer's disease have been attributed to mutations in the presenilin 1 (PS1) gene. PS1 protein is a component of a high molecular weight membrane-bound complex that also contains beta-catenin. The physiological relevance of the association between PS1 and beta-catenin remains controversial. In this study, we report the identification and functional characterization of a highly conserved glycogen synthase kinase-3beta consensus phosphorylation site within the hydrophilic loop domain of PS1. Site-directed mutagenesis, together with in vitro and in vivo phosphorylation assays, indicates that PS1 residues Ser(353) and Ser(357) are glycogen synthase kinase-3beta targets. Substitution of one or both of these residues greatly reduces the ability of PS1 to associate with beta-catenin. By disrupting this interaction, we demonstrate that the association between PS1 and beta-catenin has no effect on Abeta peptide production, beta-catenin stability, or cellular susceptibility to apoptosis. Significantly, in the absence of PS1/beta-catenin association, we found no alteration in beta-catenin signaling using induction of this pathway by exogenous expression of Wnt-1 or beta-catenin and a Tcf/Lef transcriptional assay. These results argue against a pathologically relevant role for the association between PS1 and beta-catenin in familial Alzheimer's disease.

Alzheimer Disease↗
PubMed2000

Lead in the southern East China Sea.

At present, in most oceans the lead (Pb) biogeochemical cycling has been disturbed by anthropogenic Pb through atmospheric input. The Pb concentrations in the upper water positively correlate with atmospheric input fluxes of Pb. The North Pacific is affected greatly by atmospheric substances via long-range transport from eastern Asia, especially from Mainland China. Mainland China may export considerable amounts of pollutants into the seas via rivers and the atmosphere owing to its recent fast growth in industry and economy. The East China Sea lies in an important geographical position--a transit between Mainland China and the western North Pacific. However, no data are available for seawater concentrations of Pb, a representative element with anthropogenic origin. In this work seawater samples from both 5 and 30-50 m water layers of 15 stations occupied over a cyclonic eddy in the southern East China Sea were analyzed for particulate Pb (PPb) and dissolved Pb (DPb). The Mean concentration of DPb (approximately 128 ng/l) in the southern East China Sea upper waters (< or = 50 m) is approximately several times higher than those in the Pacific; the high DPb concentrations in the southern East China Sea waters correspond to much higher atmospheric supplies of Pb to the East China Sea. Thus, this study partly fills the 'data gap' of the marginal seas. Also, it indicates that the East China Sea may be considerably contaminated by deposited polluted aerosols. Spatial distributions of DPb in the surface water show a tendency of increasing concentrations with distance offshore, that depends on the magnitudes of atmospheric Pb inputs and on particle scavenging processes. In contrast to DPb, spatial distributions of PPb basically display an 'omega'-like picture and a tendency of decreasing concentrations with distance offshore. These are related to riverine and scavenging sources and to the drive by the eddy. Additionally, the residence times of DPb in the surface water were estimated to be about 2 years, agreeing well with the reported data.

Lead↗
PubMed2000

Characterization of a strain-specific monoclonal antibody to hepatitis delta virus antigen.

Sequences of the hepatitis delta virus (HDV) vary to different degrees among isolates. A monoclonal antibody, designated as HP6A1, against the antigen of HDV (HDAg) has been characterized for its specificity. HP6A1 bound to HDAg of isolate 25 (genotype I) that was used for immunization, but not to others of both genotypes I and II. The epitope recognized by HP6A1 was then determined by a phage library displaying various heptapeptides. A consensus peptide deduced has the best match with that of residues 4-10 of HDAg (isolate 25). To confirm the phage mapping result, Escherichia coli recombinant proteins containing different lengths and various segments of HDAg (isolate 25) were constructed. The shortest HDAg segment contained in the fusion protein that reacted with HP6A1 was residues 1-10. When this peptide was added to the N-terminus of a heterologous protein engineered for eucaryotic expression, the fusion protein was detected by HP6A1. It is concluded that HP6A1 recognizes an epitope located at the N-terminus of HDAg (isolate 25). Since viruses of quasi-species exist in natural infections, a question of how different viral strains interact in vivo remains to be explored. The highly specific MAb opens a possibility to examine the fate of one strain in the presence of other related species in a cell transfection system.

Amino Acid Sequence↗
PubMed2000

Immunohistochemical differentiation of hepatitis D virus genotypes.

Determination of hepatitis D virus (HDV) genotypes is epidemiologically and clinically important. Phylogenic analysis based on sequencing analysis of multiple HDV strains isolated from sera of patients is not convenient for mass screening in routine laboratories. This study was designed to develop genotype-specific antibodies against hepatitis delta antigen (HDAg) and to apply these antibodies for immunohistochemical differentiation of HDV genotypes in formalin-fixed, paraffin-embedded liver biopsies of patients. Divergence in the carboxyl-terminal 19 amino acids of the large HDAg between genotypes I and II is more than 70%. Peptides covering these residues were conjugated to keyhole limpet hemocyanin and were used for immunization. The generated antibodies were confirmed for their specificity by binding to type-specific HDAgs expressed in DNA-transfected Huh-7 hepatoma cells. Liver biopsies from 6 patients who had dominant genotype I HDV and 33 patients who had dominant genotype II HDV in sera were stained with these antibodies. The accuracy for these antibodies was 94.9%, and the agreement between dominant HDV genotypes in serum and dominant hepatic HDV genotypes based on HDAg staining was nearly perfect (kappa = 0.83). In summary, the carboxyl-terminal 19 amino acids of the large HDAg can be used as immunogens to generate genotype-specific antibodies. These antibodies were proven to be useful in immunohistochemical differentiation of HDV genotypes in liver biopsies.

Amino Acid Sequence↗
PubMed2000

DNA-Based immunization produces Th1 immune responses to hepatitis delta virus in a mouse model.

Hepatitis delta virus (HDV) superinfection is one of the major causes of fulminant hepatitis in endemic areas of hepatitis B virus (HBV) infection. Currently, there is no effective treatment or vaccine against HDV superinfection. DNA-based immunization is a promising antiviral strategy to prevent or treat persistent viral infections. In this study, we investigated the immunological effects of DNA vaccines against HDV in BALB/c mice. Plasmid (pD) encoding large hepatitis D antigen (L-HDAg), or plasmid (pS/pD) coexpressing hepatitis B surface antigen (HBsAg) and L-HDAg, were injected into mice intramuscularly. The seroconversion rate, anti-HBs levels, anti-HDV titers, T-cell proliferation responses, and T-helper (Th)-release cytokine profiles were analyzed. Mice immunized with plasmids, pS/pD or pD, produced low, but significant, titers of anti-HDV antibodies. In contrast, pS/pD induced much stronger anti-HBs titers in the immunized animals. Interestingly, splenic lymphocytes derived from pS/pD-inoculated mice demonstrated significant proliferation responses to recombinant HBsAg and HDAg, and resulted in a Th1-like immune response as suggested by the production of interferon gamma (INF-gamma) and interleukin-2 (IL-2), but not IL-4. The splenic lymphocyte derived from the pD-inoculated mice showed a similar Th1 response to the stimulation of HDAg, but not to HBsAg. In conclusion, our results suggest that DNA vaccines against HDV can induce significant cellular immune responses with a Th1 preference. HBV and HDV coimmunization can be performed by DNA vaccines. These results are promising for the future development of prophylactic and therapeutic HDV vaccines.

Animals↗
PubMed1999

p38 mitogen-activated protein kinase is involved in Fas ligand expression.

p38 mitogen-activated protein kinase (MAPK) is activated by T cell receptor engagement. Here we showed that T cell receptor activated p38alpha but not p38delta. Inhibition of p38alpha by the specific inhibitor SB 203580 prevented activation-induced cell death in T cells. SB 203580 had no effect on Fas-initiated apoptosis. Instead, SB 203580 preferentially inhibited activation-induced Fas ligand (FasL) expression. The inhibition on FasL expression by SB 203580 was correlated with the suppression on the FasL promoter activation. Overexpression of active MAPK kinase 3b, the activator of p38 MAPK, led to activation of FasL promoter and induction of FasL transcripts in T cells. Stress stimulation of T cells by anisomycin also induced FasL expression in a p38 MAPK-dependent manner. The induction of FasL expression in nonlymphoid cells such as 293T also required activation of p38 MAPK. Our results suggest that p38 MAPK is essential for FasL expression.

Apoptosis↗
PubMed1999

The sec6/8 complex is located at neurite outgrowth and axonal synapse-assembly domains.

The molecules that specify domains on the neuronal plasma membrane for the delivery and accumulation of vesicles during neurite outgrowth and synapse formation are unknown. We investigated the role of the sec6/8 complex, a set of proteins that specifies vesicle targeting sites in yeast and epithelial cells, in neuronal membrane trafficking. This complex was found in layers of developing rat brain undergoing synaptogenesis. In cultured hippocampal neurons, the sec6/8 complex was present in regions of ongoing membrane addition: the tips of growing neurites, filopodia, and growth cones. In young axons, the sec6/8 complex was also confined to periodic domains of the plasma membrane. The distribution of synaptotagmin, synapsin1, sec6, and FM1-43 labeling in cultured neurons suggested that the plasma membrane localization of the sec6/8 complex preceded the arrival of synaptic markers and was downregulated in mature synapses. We propose that the sec6/8 complex specifies sites for targeting vesicles at domains of neurite outgrowth and potential active zones during synaptogenesis.

Animals↗
PubMed1999

NF-kappa B-dependent Fas ligand expression.

Apoptosis of lymphocytes is triggered by different stimuli through the induced expression of Fas and Fas ligand (FasL). Using T cell activation-induced Fas/FasL expression as a model system, we observed a differential regulation of the induction of Fas and FasL. cAMP inhibited activation-induced apoptosis by an effective suppression of TCR-coupled FasL expres sion. In contrast, cAMP weakly interfered with activation-induced Fas expression, and the remaining Fas molecules on cAMP-treated T cells still mediated apoptosis. Among the major transcription elements on the FasL promoter, the activation of NF-kappaB, but not of NF-AT and AP-1, was suppressed by cAMP. The prominent role of NF-kappaB was further demonstrated by a better activation of the FasL promoter and an elevated expression of FasL induced by p65 (RelA) overexpression than those induced by AP-1 or NF-AT. Our results demonstrate the essential role of NF-kappaB for the expression of the death receptor ligand FasL, and suggest a direct link between NF-kappaB activation and the expression of FasL. NF-kappaB may be the common mediator in the induction of FasL through TCR activation and by various stress stimuli.

Antibodies, Monoclonal↗
PubMed1999

Targeting vesicles to specific sites on the plasma membrane: the role of the sec6/8 complex.

The delivery of secretory vesicles to appropriate docking and fusion sites on the plasma membrane is crucial for many cellular functions, including formation of synapses, exocytosis of neurotransmitter, establishment and maintenance of cell polarity, cell growth and plasma membrane wound healing. Cell-biological, genetic and biochemical approaches have identified crucial proteins and protein interactions important for vesicle docking and fusion. However, a description of the molecular mechanisms underlying vesicle targeting to specific membrane-fusion sites remains elusive. This review discusses a set of proteins that might direct vesicles to specific domains of the plasma membrane.

Animals↗
PubMed1999

Localization of isoprenylated antigen of hepatitis delta virus by anti-farnesyl antibodies.

Hepatitis delta virus (HDV) is a subviral pathogen that requires pre-existing or concurrent infection with hepatitis B virus (HBV). HDV expresses two forms of a single protein, the delta antigen (HDAg), which are identical except for an additional 19 residues at the C terminus of the large form. Within this C-terminal extension a cysteine residue is isoprenylated; this isoprenylation is critical for interaction with HBV envelope proteins to enable virus assembly and release into the medium. Therefore, large HDAg must be recruited to an extracellular compartment. However, immuno-staining with HDAg-specific antibodies has localized the large antigen mainly to the nucleus and supports the notion that large HDAg suppresses virus replication in the nucleus. Since isoprenylation would increase the hydrophobicity of the protein and may favour transport towards specific membranes, the question remains whether the large HDAg detected in the nucleus carries an isoprenyl group. To address this issue, antibodies against the farnesyl modification were generated to allow direct visualization of the antigen by immunofluorescence microscopy. The anti-farnesyl antibodies specifically stained large HDAg expressed in Huh-7 cells, and the signal was largely restricted to the nucleus; the staining pattern could be superimposed on those of cells stained for large HDAg. The large HDAg translocated into the nucleus was therefore isoprenylated. In addition, antibodies specific for the farnesyl modification should be applicable to the study of other similarly isoprenylated proteins.

Amino Acid Sequence↗