Biomedical subjects

M Y Chang

Publications and source records attributed to M Y Chang.

At least 19 recordsLinked to original sources

PubMed2002

Antiviral activity of Plantago major extracts and related compounds in vitro.

Plantago major L., a popular traditional Chinese medicine, has long been used for treating various diseases varying from cold to viral hepatitis. The aim of present study was to examine the antiviral activity of aqueous extract and pure compounds of P. major. Studies were conducted on a series of viruses, namely herpesviruses (HSV-1, HSV-2) and adenoviruses (ADV-3, ADV-8, ADV-11). The antiviral activity of EC50 was defined as the concentration achieved 50% cyto-protection against virus infection and the selectivity index (SI) was determined by the ratio of CC50 (concentration of 50% cellular cytotoxicity) to EC50. Results showed that aqueous extract of P. major possessed only a slight anti-herpes virus activity. In contrast, certain pure compounds belonging to the five different classes of chemicals found in extracts of this plant exhibited potent antiviral activity. Among them, caffeic acid exhibited the strongest activity against HSV-1 (EC50=15.3 microg/ml, SI=671), HSV-2 (EC50=87.3 microg/ml, SI=118) and ADV-3 (EC50=14.2 microg/ml, SI=727), whereas chlorogenic acid possessed the strongest anti-ADV-11 (EC50=13.3 microg/ml, SI=301) activity. The present study concludes that pure compounds of P. major, which possess antiviral activities are mainly derived from the phenolic compounds, especially caffeic acid. Its mode of action against HSV-2 and ADV-3 was found to be at multiplication stages (postinfection of HSV-1: 0-12 h; ADV-3: 0-2 h), and with SI values greater than 400, suggesting the potential use of this compound for treatment of the infection by these two viruses.

Adenoviridae↗

PubMed2001

Pairing of forskolin and KCl increases differentiation of immortalized hippocampal neurons in a CREB Serine 133 phosphorylation-dependent and extracellular-regulated protein kinase-independent manner.

Although cAMP response element binding protein (CREB)- and extracellular-regulated protein kinase (ERK)-mediated pathways have been linked to each other in neuronal differentiation, involvement of these in hippocampal neuronal cell line has not been defined. Using an immortalized hippocampal cell line, HiB5, we have tried a pairing of forskolin with KCl depolarization, which acts as an ERK and CREB kinase activator in hippocampal neurons, to investigate if an activation of ERK and phosphorylation of CREB at the critical regulatory site, serine 133 might be coupled in differentiation. Differentiation toward a neuronal phenotype was synergistically and markedly increased by the pairing of forskolin and KCl depolarization. The synergistic effect was accompanied by an increase in phosphorylation of CREB Ser-133, but not phosphorylation of ERK, and was not inhibited by MEK inhibitor, PD98059. These findings indicate that phosphorylation of the transcriptional factor CREB may function to facilitate differentiation of HiB5 cells.

Animals↗

PubMed2001

Facile solid-phase synthesis of an antifreeze glycoprotein.

The antifreeze glycoproteins (AFGPs) 1 are composed of a repeating tripeptide unit (Ala-Thr-Ala) in which the threonine residue is glycosylated with the disaccharide beta-D-Gal-(1-->3)-alpha-D-GalNAc. A new procedure for synthesizing AFGPs using Fmoc-(Ac4-beta-D-Gal-(1-->3)-benzylidene- alpha-D-GalNAc)Thr-OH (10) as a building block has been developed. Total synthesis of the AFGPs (n = 4, 8) in overall yields of 61% and 33 %, respectively, has demonstrated the usefulness of the method. The synthetic AFGPs 1 (n = 4, 8) showed a similar conformation to the native AFGPs in their circular dichroism spectra.

Acetylgalactosamine↗

PubMed2001

Retrovirus-mediated transfer of prothymosin gene inhibits tumor growth and prolongs survival in murine bladder cancer.

To explore the potential use of prothymosin alpha(ProT), a putative thymic hormone, in gene therapy for bladder cancer, we generated a replication-defective recombinant retroviral vector encoding ProT and tested its antitumor effect on the MBT-2 murine bladder cancer. C3H/HeN mice injected with MBT-2 cells in conjunction with retroviruses encoding ProT exhibited smaller tumor mass, lower tumor incidence and higher survival rate, as well as higher antitumor cytotoxic activities compared with those injected with control viruses. However, such effects were not observed in severe combined immunodeficiency mice, suggesting that ProT exerts antitumor effects through its immunomodulatory activities. Cell growth in monolayer culture and colony formation in soft agar were enhanced in ProT gene-modified MBT-2 clones, and such growth-promoting activities of ProT could be reversed if its nuclear localization signal (NLS) was deleted. To circumvent the proliferation-promoting effect of ProT on tumor cells, a retroviral vector encoding ProT lacking NLS was constructed. Our results showed that retroviruses encoding NLS-deleted ProT was more efficacious than those encoding wild-type ProT in prolonging survival of tumor-bearing mice. This is the first report indicating that ProT, in particular NLS-deleted ProT, delivered by retroviral vectors may be further explored for the treatment of bladder cancer.

Animals↗

PubMed2001

Protein kinase C-mediated functional regulation of dopamine transporter is not achieved by direct phosphorylation of the dopamine transporter protein.

Dopaminergic neurotransmission is terminated by the action of the presynaptic dopamine transporter (DAT). It mediates Na(+)/Cl(-) -dependent re-uptake of extracellular dopamine (DA) into the cell, and is regarded as a major regulatory mechanism for synaptic transmission. Previous works have documented that protein kinase C (PKC) activator or inhibitor alters DA uptake by DAT, suggesting that PKC phosphorylation plays an important regulatory mechanism in DAT function. Based on the existence of consensus amino acid sequences for PKC phosphorylation, it has been postulated that PKC regulation of DAT is mediated by the direct phosphorylation of DAT protein. In this study, we try to discover whether the functional regulation of DAT by PKC is due to direct phosphorylation of DAT. The PKC null mutant hDAT, where all putative PKC phosphorylation sites are eliminated, has been constructed by the replacement of serine/threonine residues with glycines. The mutation itself showed no effect on the functional activities of DAT. The DA uptake activity of PKC null mutant was equivalent to those of wild-type hDAT (80-110% of wild-type). Phorbol ester activation of PKC inhibited DA uptake of wild-type hDAT by 35%, and staurosphorine blocked the effect of phorbol ester on DA uptake. The same phenomena was observed in PKC null mutant DAT, although no significant phosphorylation was observed by PKC activation. Confocal microscopic analysis using EGFP-fused DAT revealed that the activation of PKC by phorbol ester elicited fluorescent DAT to be internalized into the intracellular space both in wild-type and PKC null mutant DAT in a similar way. These results suggest that PKC-mediated regulation of DAT function is achieved in an indirect manner, such as phosphorylation of a mediator protein or activation of a clathrin-mediated pathway.

Animals↗

PubMed2001

Women's perceptions of helpful and unhelpful nursing behaviors during labor: a study in Taiwan.

BACKGROUND: The job of the nurse in labor and delivery is not only to ensure a safe delivery but also to create a positive and satisfying childbirth experience. Few studies have been conducted of women's perceptions about the ideal image of the obstetric nurse during labor, and most previous studies involved only North American or European women. The purpose of this study was to assess Taiwanese women's perspectives about their encounters with obstetric nurses during labor. METHODS: Interviews of a convenience sample of 50 mothers experiencing normal childbirth in Taiwan were conducted. The interviews were tape recorded and transcribed, and the transcriptions were analyzed to develop coding categories and identify themes. RESULTS: Sixty percent of the participants reported having received helpful nursing behaviors only; 38 percent reported having received both helpful and unhelpful nursing behaviors. Helpful labor-coping measures that were valued by participants included performing roles of emotional support providers, comforters, information/advice providers, professional technical skills providers, and advocates. Forty percent of the participants reported that some nurses had hindered their labor-coping ability by failing to provide emotional support, comfort measures, adequate or correct information/advice, or to perform technical duties. CONCLUSIONS: The ideal nursing image encompasses the roles of emotional supporter, comforter, information/advice provider, professional/technical skill provider, and advocate. The findings may help obstetric team members better understand patients' needs, and enable them to provide better support during labor and to prevent unhelpful nursing behaviors.

Adult↗

PubMed2001

Ticlopidine-induced thrombotic thrombocytopenic purpura: two case reports treated with plasma exchange plus steroids.

Thrombotic thrombocytopenic purpura (TTP) has a high mortality rate if left untreated with plasma exchange promptly. We report two cases of ticlopidine-induced TTP, which lesser dosages of ticlopidine (200-250 mg/day) were prescribed and were treated with plasma exchange (PE) plus steroids. The first case was treated successfully, but the second case did not respond to our treatment and died of a progressive disease complicated with pneumonia. In sum, we recommend careful use of ticlopidine, regardless of the dosages prescribe and regardless of how long the drug is used. Moreover, the adverse effect of ticlopidine should be closely monitored.

Aged↗

PubMed2001

Oxidized LDL bind to nonproteoglycan components of smooth muscle extracellular matrices.

Arterial wall lipid retention is believed to be due primarily to ionic interactions between lipoproteins and proteoglycans. Thus, oxidized low density lipoproteins (LDL), with decreased positive charge relative to native LDL, should have decreased interaction with negatively charged proteoglycans. However, oxidized LDL does accumulate within arterial lesions. Therefore, this study investigated the binding of native and oxidized LDL to a complex smooth muscle extracellular matrix and the role of ionic charge interactions in their binding. LDL was modified with 2,2-azo-bis(2-amidinopropane)-2HCl, hypochlorite, soybean lipoxygenase, and phospholipase or copper sulfate. The extracellular matrix had 15- to 45-fold greater binding capacity for the different forms of oxidized LDL than for native LDL. However, the affinity of binding for all forms of oxidized LDL was high (K(a) = approximately 10(-9) M) and was similar to that for native LDL. Preincubation of the lipoproteins with chondroitin sulfate decreased the binding of native LDL, but had no effect on the binding of oxidized LDL. Digestion of matrices with chondroitin ABC lyase and heparinase decreased the binding of native LDL, but increased the binding of oxidized LDL; matrix digestion with pronase or trypsin markedly reduced the binding of both native and oxidized LDL.Thus, the binding of native LDL involves matrix proteoglycans, whereas the binding of oxidized LDL involves a nonproteoglycan component(s) of the matrix. The markedly enhanced retention of oxidized LDL compared with native LDL may play an important role in the progression of atherosclerosis.

Animals↗

PubMed2000

Cationic lipid:bacterial DNA complexes elicit adaptive cellular immunity in murine intraperitoneal tumor models.

Previous studies with a mycobacterial heat shock protein (hsp-65) have demonstrated some efficacy using cationic liposome-mediated gene transfer in murine i.p. sarcoma models. To further analyze the efficacy of hsp-65 immunotherapy in clinically relevant models of localized cancer, immunocompetent mice bearing i.p. murine mesothelioma were treated with four i.p. doses of a cationic lipid complexed with plasmid DNA (pDNA) containing hsp65, LacZ, or a null plasmid. We observed >90% long-term survival (median survival, 150 days versus approximately 25 days, treated versus saline control, respectively) in a syngeneic, i.p. murine mesothelioma model (AC29). Long-term survivors were observed in all groups treated with lipid complexed with any pDNA. Lipid alone or DNA alone provided no demonstrable survival advantage. In a more aggressive i.p. model of mesothelioma (AB12), we observed >40% long-term survival in groups treated with lipid:pDNA complexes, again irrespective of the transgene. To ask whether these antitumor effects had led to an adaptive immune response against the tumor cell, we rechallenged long-term survivors in both murine models s.c. with the parental tumor cell line. Specific, long-lasting systemic immunity against the tumor was readily demonstrated in both models (AB12 and AC29). Consistent with these results, splenocytes from long-term survivors specifically lysed the parental tumor cell lines. Depleting the CD8+ T-cells from the splenocyte pool eliminated this lytic activity. Lipid:pDNA treatment of athymic, SCID, and SCID/Beige mice bearing a murine i.p. mesothelioma (AC29) resulted in only a slight survival advantage, but there were no long-term survivors. Treatment of immunocompetent mice depleted of specific immune effector cells demonstrated roles for CD8+ and natural killer cells. Although the exact mechanism(s) responsible for these antitumor effects is unclear, the results are consistent with roles for both innate and adaptive immune responses. An initial tumor cell killing stimulated by cationic lipid:pDNA complexes appears to be translated into long-term, systemic immunity against the tumor cell. These results are the first to demonstrate that adaptive immunity against a tumor cell can be induced by the administration of lipid:pDNA complexes. Multiple administrations of cationic lipid complexed with pDNA lacking an expressed transgene could provide a promising generalized immune-mediated modality for treating cancer.

Animals↗

PubMed2000

Oxidized low density lipoproteins regulate synthesis of monkey aortic smooth muscle cell proteoglycans that have enhanced native low density lipoprotein binding properties.

Oxidized low density lipoproteins (Ox-LDL) affect several biological processes involved in atherogenesis. However, it is not known whether Ox-LDL can regulate proteoglycan expression and thus affect arterial wall lipoprotein retention. This study evaluated whether Ox-LDL, as compared with native LDL, regulates proteoglycan expression by monkey arterial smooth muscle cells in vitro and whether proteoglycans synthesized in the presence of Ox-LDL exhibit altered lipoprotein binding properties. Ox-LDL stimulated glycosaminoglycan synthesis, as measured by (35)SO(4) incorporation, by 30-50% over that of native LDL. The effect was maximal after 72 h of exposure to 5 microg/ml of Ox-LDL. The molecular sizes of versican, biglycan, and decorin increased in response to Ox-LDL, as indicated by size exclusion chromatography and SDS-polyacrylamide gel electrophoresis. These effects could be mimicked by the lipid extract of Ox-LDL. These size increases were largely due to chain elongation and not to alterations in the ratio of (35)SO(4) to [(3)H]glucosamine incorporation. Affinity chromatography indicated that Ox-LDL stimulated the synthesis of proteoglycans with high affinity for native LDL. Ox-LDL also specifically stimulated mRNA expression for biglycan (but not versican or decorin), which was correlated with increased expression of secreted biglycan. Thus, Ox-LDL may influence lipoprotein retention by regulating synthesis of biglycan and also by altering glycosaminoglycan synthesis of vascular proteoglycans so as to enhance lipoprotein binding properties.

Animals↗

PubMed2000

Salivary cotinine levels in children presenting with wheezing to an emergency department.

We set out to evaluate salivary cotinine concentrations to judge tobacco smoke exposure among infants and children, and to examine the results in relation to age and wheezing. This was a case-control study of wheezing children (n = 165) and children without respiratory tract symptoms (n = 106) who were enrolled in the Pediatric Emergency Department at the University of Virginia. The age range of both wheezing and control patients was 2 months to 16 years. Questionnaires were combined with cotinine assays in saliva to evaluate exposure to environmental tobacco smoke (ETS) for each child. The prevalence of exposure to one or more smokers at home was high (68%); and 43% of the children enrolled were exposed to ETS from their mothers. According to the questionnaires, and after adjusting for age and race, a wheezing child in this study was more likely than a control to be exposed to at least one smoker at home (odds ratio = 1.9; 95% CI = 1.1-3.4). However, the odds of exposure to ETS from smoking mothers did not differ significantly between wheezing and control patients, and no significant association was found between the presence of wheezing and salivary cotinine levels. Among children exposed to ETS at home, cotinine levels were significantly higher in saliva from those under the age of two years, and from toddlers aged 2 and 3 years, compared to values from children over age 4 years. Moreover, the number of smokers in the home strongly influenced cotinine levels from children under age 4 years. In addition, higher cotinine levels were observed in saliva from children under age 2 years who were exposed to ETS from their mothers. Cotinine levels were similar and significantly correlated in paired samples of saliva and serum from children under 4 years of age (n = 54), (r = 0.92, P < 0.001). Based on information gathered from questionnaires, the results indicate that wheezing children were more likely than controls to be exposed to ETS at home. However, significant differences in ETS exposure between wheezing and control groups with respect to maternal smoke exposure or comparisons of salivary cotinine levels were not apparent. It was clear that determinations of salivary cotinine for monitoring the prevalence and intensity of household smoke exposure in this study were most valuable during the first 4 years of life.

Adolescent↗

PubMed2000

Spleen laceration, a rare complication of laparoscopy.

A 31-year-old woman had secondary infertility of 4 years' duration. Hysterosalpingography revealed bilateral distal tubal occlusion with bilateral hydrosalpinx-like appearance. At laparoscopy, both oviducts were occluded with marked hydropic change. Salpingoplasty was performed to correct bilateral hydrosalpinges and reform the fimbriated tubal ends. The procedure was performed uneventfully by an experienced surgeon in 45 minutes. Nine hours after the operation an emergency exploratory laparotomy was performed due to massive intraabdominal bleeding. The cause was a small tear, 3 cm long and 1 cm deep, with active bleeding in the inferior splenic tail. The laceration was repaired successfully with 1-0 chromic suture. The etiology of splenic laceration during laparoscopic surgery is uncertain. Many complications of laparoscopy are physiologic, and this one might have occurred while establishing pneumoperitoneum. Distortion and stretching of small vascular adhesions of the spleen with the abdominal wall also may have played a role. Gynecologists must be aware of the physiologic insult to patients during laparoscopy.

Adult↗

PubMed2000

Prediction of pregnancy rate of in vitro fertilization and embryo transfer in women aged 40 and over with basal uterine artery pulsatility index.

PURPOSE: The purpose was to determine the effect of basal uterine perfusion on the pregnancy rates of in vitro fertilization and embryo transfer (IVF-ET) in women aged 40 and above. METHODS: A total of 47 patient aged 40 and over underwent IVF-ET. The conception cycles and the nonconception cycles were compared. RESULTS: Of the 47 patients, 4 patients were pregnant (8.5%). The mean age, basal follicle stimulating hormone (FSH), basal estradiol (E2) level, antral follicle count (AFC), number of ampoules of gonadotropin used, E2 levels and endometrial thickness on the day of human chorionic gonadotropin (hCG) administration, number of retrieved and fertilized oocytes, and number of transferred embryos were not statistically significant between the conception and nonconception cycles. However, the basal uterine artery pulsatility index (UA PI) was significantly lower in the conception cycles (P < 0.001). The receiver operating characteristics (ROC) curve analysis for basal FSH, AFC, and basal UA PI in predicting the pregnancy rate of IVF in patients aged > or = 40 were demonstrated. The best prediction rate was achieved by a pulsatility index cutoff of < 2.0 for a receptive uterus. CONCLUSIONS: Increased uterine perfusion in the early follicular phase enhanced the pregnancy rate of IVF in women aged 40 and above. It is therefore essential that patients aged > or = 40 with poor basal uterine perfusion should be identified early in the early follicular phase of the menstrual cycle to apply appropriate intervention to improve the uterine circulation for the subsequent chance of pregnancy.

Adult↗

PubMed2000

Direct peripheral venopuncture: another new choice of temporary vascular access.

BACKGROUND: Femoral, subclavian, and internal jugular veins access have been widely used for temporary vascular access for hemodialysis, but their use has been associated with a significant complication rate. We report in three selected hemodialysis patients with the procedure of direct peripheral venopuncture as temporary vascular access to reduce complications. METHODS: We have demonstrated hemodialysis via direct puncture of peripheral veins of the antecubital fossa (cephalic vein in the process of arterial inflow to dialyzer and venous outflow from dialyzer to basilic vein) as temporary vascular access for these patients. RESULTS: Renal function of case 1 and case 2 progress to normal status after several sessions of dialytic therapy as well as quit hemodialysis, and case 3 successfully shifts to peritoneal dialysis following four sessions of dialytic therapy. CONCLUSIONS: We recommend this short-term access contribute a important additional new choice in selected patients with acute, reversible renal failure, obstructive uropathy, initiation of peritoneal dialysis, patients on peritoneal dialysis with peritonitis, or under plasmapheresis therapy.

Acute Kidney Injury↗

PubMed2000

Alteration of cytokine production in follicular cystic ovaries induced in mice by neonatal estradiol injection.

PROBLEM: Neonatal estradiol injections in mice lead to follicular cystic ovaries that are similar to ovaries in patients with polycystic ovarian syndrome (PCOS). The present study examined ovarian cytokine production following neonatal estradiol injection. METHOD OF STUDY: Female (C3H,HeJ x 129/HeJ)F1 mice were injected daily with 20 microg 17beta-estradiol from 0-3 days postpartum. At intervals, animals were sacrificed to determine ovarian architecture, circulating levels of estradiol, ovarian and peritoneal macrophage cytokine production, and ovarian P450 aromatase enzyme mRNA levels. RESULTS: Similar to PCOS, our results show that neonatally estradiol-injected mice have lower levels of circulating estrogen that are correlated with decreased mRNA levels of P450 aromatase enzyme. Our data also show that follicular cystic ovaries have increased tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production. This increase in TNF-alpha and IL-6 production is also observed in peritoneal macrophages of estradiol-injected mice. CONCLUSION: The present study showed that neonatal estrogen injection in mice has an overall systemic effect on cytokine production. We speculate that increased cytokine production may alter certain important steps in follicular maturation, ultimately contributing to ovarian dysfunction.

Animals↗

PubMed2000

Organ system failures predict prognosis in critically ill patients with acute renal failure requiring dialysis.

BACKGROUND: Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill patients with acute renal failure is still high. Previous efforts to predict the outcome in this population have been limited by small sample sizes. In addition, data obtained decades ago may not apply today owing to changes in the case mix. We have attempted to determine whether organ system failures can be used to predict prognosis. METHODS: The medical records of 100 consecutive intensive care unit patients with acute renal failure who required dialysis from January 1997 through December 1998 were evaluated by a blinded reviewer. RESULTS: Of the 100 patients studied, 65 were men and 35 were women. The mean age of survivors and non-survivors was 59.4 +/- 20.3 years and 58.3 +/- 20.0 years, respectively. The overall mortality rate was 71%. There were no significant differences between survivors and non-survivors in age, gender, or indication for dialysis. The cause of death in the majority of patients was related to organ system failure, and they carried mortality rates exceeding 83% with the coexistence of four or more failed organs. CONCLUSION: The mortality rate for intensive care unit patients with acute renal failure continues to be high. Multiple organ system failure occurs frequently and is the major cause of death. The mortality rate increases as the number of failed organs increases.

Acute Kidney Injury↗

PubMed2000

Importance of valine at position 152 for the substrate transport and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane binding of dopamine transporter.

Human and bovine dopamine transporters (DAT) demonstrate discrete functional differences in dopamine (DA), 1-methyl-4-phenylpyridium (MPP(+)) transport, and cocaine analog binding. In a previous study, the functional analyses on the chimeras of human and bovine DAT have revealed that the region from residues 133 through 186 (encompassing the third transmembrane domain) is responsible for the substrate transport and cocaine analog binding. The present study has been carried out to determine the specific amino acid(s) conferring DAT functions by interchanging the amino acid residues in the corresponding region between human and bovine DAT. As described previously, the DA, MPP(+) transport, and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT) binding almost disappeared in chimera hb3 in which the region from residues 133 through 186 of bovine DAT was substituted into human DAT. Replacement of isoleucine, residue 152 of chimera hb3 (bovine DAT sequence), with valine, the human DAT residue at the identical position, remarkably restored the substrate transport and CFT binding to 76% to 98% of the human DAT values. Similarly, substitution of isoleucine for valine at position 152 in the human DAT reduced the substrate transport and CFT binding by 57% to 97%. Among other amino acids tested at position 152 of the chimera hb3, only alanine resulted in small but significant increases in the DAT functions ranging from 16 to 34%. Thus, valine at position 152 plays a crucial role for molecular mechanisms underlying the interactions of DA, MPP(+), and CFT with human DAT.

Amino Acid Sequence↗

PubMed2000

Peripheral venopuncture as temporary vascular access in rhabdomyolysis-induced acute renal failure related to frog leaps: case report.

Rhabdomyolysis, or acute muscle destruction, may be accompanied by myoglobinemia, myoglobinuria, and an elevated serum creatine kinase level. The disorder has many potential causes, the most common one in otherwise healthy people being severe exercise. Rhabdomyolysis has many complications, but the most important one is acute renal failure. We describe a man with rhabdomyolysis-induced acute renal failure occurring after frog leaps. During 3 dialytic sessions, we practiced direct puncture of peripheral veins of the antecubital fossa as temporary vascular access for this patient. His renal function improved, after which he was discharged with a smooth clinical course.

Acute Disease↗