Biomedical subjects

S J Lin

Publications and source records attributed to S J Lin.

At least 109 records · Page 6Linked to original sources

PubMed1998

Henoch-Schönlein purpura in Chinese children and adults.

From 1987 to 1996, we retrospectively analyzed 84 children and 38 adults admitted to Chang Gung Memorial Hospital with the diagnosis of Henoch-Schönlein purpura (HSP). All of the adult patients had skin biopsy finding showing leukocytoclastic vasculitis. Male predominance was noted in children, but not in adults. Preceding infection was noted in 40.5% of children and 31.6% of the adults (P = 0.46). 8.3% of children and 13.2% of adults had medication intake at disease onset (P = 0.62). Children had more frequent abdominal pain than the adults (70.2% vs 28.9%, P < 0.01). Renal involvement was more common and severe in adults, manifested as more frequent hypertension (P < 0.05) and heavy proteinuria (P < 0.01). During acute attack, leukocytosis, thrombocytosis, elevation of serum C-reactive protein levels were more frequently observed in children, while elevated serum IgA and cryoglobulin levels were more common in adults. The overall prognosis was good in both age groups, although two adults developed end stage renal disease. Our study demonstrated the different expression of HSP in Chinese children and adults.

Adult↗

PubMed1997

Metal ion chaperone function of the soluble Cu(I) receptor Atx1.

Reactive and potentially toxic cofactors such as copper ions are imported into eukaryotic cells and incorporated into target proteins by unknown mechanisms. Atx1, a prototypical copper chaperone protein from yeast, has now been shown to act as a soluble cytoplasmic copper(I) receptor that can adopt either a two- or three-coordinate metal center in the active site. Atx1 also associated directly with the Atx1-like cytosolic domains of Ccc2, a vesicular protein defined in genetic studies as a member of the copper-trafficking pathway. The unusual structure and dynamics of Atx1 suggest a copper exchange function for this protein and related domains in the Menkes and Wilson disease proteins.

Amino Acid Sequence↗

PubMed1997

Effects of short-term treatment of nicorandil on exercise-induced myocardial ischemia and abnormal cardiac autonomic activity in microvascular angina.

The underlying mechanisms of myocardial ischemia in microvascular angina may include endothelial dysfunction, abnormal smooth muscle tone, and abnormal autonomic control of coronary microvasculatures. This randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the effect of nicorandil (a nitrate-potassium channel opener) therapy on exercise-induced myocardial ischemia and cardiac autonomic activity in 13 patients with microvascular angina. After a 2-week placebo run-in period, patients were randomly assigned to the first 2-week treatment with nicorandil 5 mg tid or placebo, then crossed over to the second 2-week treatment after a 2-week washout period. Treadmill exercise tests and 24-hour ambulatory electrocardiogram monitoring were performed at the end of each treatment phase. The results showed that both time to 1-mm ST depression and total exercise duration were significantly prolonged with nicorandil treatment compared with placebo (p = 0.026 and 0.036, respectively). Maximum exercise ST depression also tended to be less with nicorandil treatment than with placebo (p = 0.083). Compared with 10 healthy control subjects, study patients had significantly reduced heart rate variability in both low- and high-frequency bands while receiving placebo. Nicorandil treatment did not change the altered heart rate variability in either time domain or spectral analysis. Systemic hemodynamics were also unchanged with nicorandil treatment. Thus, 2-week oral nicorandil therapy moderately improved exercise-induced myocardial ischemia without modifying the already altered cardiac autonomic activity, suggesting that nicorandil might have a direct vasodilatory effect on coronary microvasculatures in patients with microvascular angina.

Administration, Oral↗

PubMed1997

Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis.

To search for a mammalian homologue of ATX1, a human liver cDNA library was screened and a cDNA clone was isolated, which encodes a protein with 47% amino acid identity to Atx1p including conservation of the MTCXGC copper-binding domain. RNA blot analysis using this cDNA identified an abundant 0.5-kilobase mRNA in all human tissues and cell lines examined. Southern blot analysis using this same clone indicated that the corresponding gene exists as a single copy in the haploid genome, and chromosomal localization by fluorescence in situ hybridization detected this locus at the interface between bands 5q32 and 5q33. Yeast strains lacking copper/zinc superoxide dismutase (SOD1) are sensitive to redox cycling agents and dioxygen and are auxotrophic for lysine when grown in air, and expression of this human ATX1 homologue (HAH1) in these strains restored growth on lysine-deficient media. Yeast strains lacking ATX1 are deficient in high affinity iron uptake and expression of HAH1 in these strains permits growth on iron-depleted media and results in restoration of copper incorporation into newly synthesized Fet3p. These results identify HAH1 as a novel ubiquitously expressed protein, which may play an essential role in antioxidant defense and copper homeostasis in humans.

Amino Acid Sequence↗

PubMed1997

A role for the Saccharomyces cerevisiae ATX1 gene in copper trafficking and iron transport.

The ATX1 gene of Saccharomyces cerevisiae was originally identified as a multi-copy suppressor of oxidative damage in yeast lacking superoxide dismutase. We now provide evidence that Atx1p helps deliver copper to the copper requiring oxidase Fet3p involved in iron uptake. atx1Delta null mutants are iron-deficient and are defective in the high affinity uptake of iron. These defects due to ATX1 inactivation are rescued by copper treatment, and the same has been reported for strains lacking either the cell surface copper transporter, Ctr1p, or the putative copper transporter in the secretory pathway, Ccc2p. Atx1p localizes to the cytosol, and our studies indicate that it functions as a carrier for copper that delivers the metal from the cell surface Ctr1p to Ccc2p and then to Fet3p within the secretory pathway. The iron deficiency of atx1 mutants is augmented by mutations in END3 blocking endocytosis, suggesting that a parallel pathway for intracellular copper trafficking is mediated by endocytosis. As additional evidence for the role of Atx1p in iron metabolism, we find that the gene is induced by the same iron-sensing trans-activator, Aft1p, that regulates CCC2 and FET3.

Biological Transport, Active↗

PubMed1997

Electron microscopic studies of phenotypic modulation of smooth muscle cells in coronary arteries of patients with unstable angina pectoris and postangioplasty restenosis.

BACKGROUND: Proliferation and matrix protein secretion of coronary smooth muscle cells (SMCs) have been suggested as one of the mechanisms responsible for the development of postangioplasty restenosis and an alternative cause of unstable angina. Phenotypic modulation of SMCs may produce a pool of cells potentially responsive to growth stimulation that can synthesize abundant extracellular matrix. This study tested the hypothesis that phenotypic modulation of SMCs occurred during the evolution of postangioplasty restenosis and unstable angina. METHODS AND RESULTS: The SMCs of coronary atherectomy specimens from 24 patients were identified under electron microscope. Volume fractions of synthetic organelles (VFSOs) and other features related to phenotypic modulation of SMCs were measured. The results showed that the VFSO in SMCs from 5 patients with unstable angina (group 2) resembled those from 9 patients with postangioplasty restenosis (group 3; 0.42 +/- 0.13 versus 0.36 +/- 0.10; P = NS), and both were significantly higher than those from 6 patients with stable angina (group 1; 0.21 +/- 0.11). Four patients with restenosis lesions who underwent angioplasty > 6 months ago (group 4) also had a low VFSO in SMCs (0.19 +/- 0.05). This value was significantly less than those in groups 2 and 3 (P < .05) but similar to that in group 1. CONCLUSIONS: The coronary lesions from patients with unstable angina resembled those from patients with postangioplasty restenosis in terms of the phenotypic modulation and VFSO in SMCs. Our findings therefore suggest that after phenotypic modulation, the SMCs may become responsive to growth stimulation, with an ability to massively proliferate and synthesize abundant extracellular matrix. These processes may lead to plaque expansion and eventually to the development of unstable angina and restenosis.

Aged↗

PubMed1997

A carboxy-terminal pro-sequence of aqualysin I prevents proper folding of the protease domain on its secretion by Saccharomyces cerevisiae.

The precursor of aqualysin I, a subtilisin-type protease secreted by Thermus aquaticus, consists of four domains, an N-terminal signal sequence, an N-terminal pro-sequence, a protease domain, and a C-terminal pro-sequence. A non-covalent N-terminal pro-sequence facilitates the production of active aqualsin I, when the C-terminal pro-sequence is deleted. The role of the C-terminal pro-sequence in protein secretion was analyzed using a Saccharomyces cerevisiae expression system. Deletion of the C-terminal pro-sequence resulted in increased secretion of aqualysin I, i.e., about three times as much as that in the case of the wild type. In the case of the wild-type precursor, non-secreted aqualysin I with the C-terminal pro-sequence was retained in the endoplasmic reticulum in an inactive form, suggesting that the C-terminal pro-sequence prevents the protease domain from taking on a properly folded structure, unlike the N-terminal pro-sequence.

Amino Acid Sequence↗

PubMed1997

Novel point mutation within intron 10 of FMR-1 gene causing fragile X syndrome.

The majority of cases involving fragile X syndrome are due to expansion of a (CGG)n trinucleotide repeat at the 5' untranslated region of the FMR-1 gene. Deletion and intragenic loss of function mutations of the FMR-1 gene also have been reported. Here, we report a C to T point mutation at the 14th nucleotide in intron 10 of the FMR-1 gene in three unrelated fragile X patients. However, the (CGG)n repeat of FMR-1 in those patients does not expand. To determine the effect of this mutation on the patients' FMR-1 transcripts, total RNA from peripheral blood cells was reverse transcribed and amplified by polymerase chain reaction (RT-PCR). Direct and subcloned sequencing of the RT-PCR products revealed that the transcripts from the allele with C to T mutation skip exon 10 entirely, resulting in a joining of exons 9 and 11. Deletion of exon 10 results in frame-shift and premature termination of translation, which removes the highly conserved region that encoding the KH2 and RGG box domains of FMRP. Interestingly, a male of the three patients has another G to A substitution in exon 15. However, the intron 10 mutation is sufficient for development of fragile X syndrome.

Adolescent↗

PubMed1997

Human immunodeficiency virus (HIV) type-1 GP120-specific cell-mediated cytotoxicity (CMC) and natural killer (NK) activity in HIV-infected (HIV+) subjects: enhancement with interleukin-2(IL-2), IL-12, and IL-15.

Cell-mediated cytotoxicity (CMC), as mediated by cytophilic antibody to human immunodeficiency virus (HIV) antigens, may be an important defense in HIV-infected (HIV+) patients in response to the virus. In this study the ability of interleukin (IL)-2, IL-12, and IL-15 to enhance natural killer (NK) and gp120-specific CMC of mononuclear cells (MNCs) from HIV+ children and adults was examined. NK activity against K562 cells was deficient in HIV+ patients compared to controls and could be enhanced by IL-2, IL-12, or IL-15, with the combinations of IL-2 + IL-12 and IL-12 + IL-15 producing more cytotoxicity than individual cytokines. Gp120-specific CMC was significantly higher in patients than in controls. It could be increased by IL-2, IL-12, and IL-15 and further by combining IL-2 and IL-12. When an exogenous source of antibody in the form of hyperimmune HIV-specific immunoglobulin (HIVIG) was present, the response of control MNCs was much higher than that of patients, although gp120-specific cytotoxicity of patients' MNCs was significantly enhanced (two- to threefold) by the addition of HIVIG. This increment in cytotoxicity due to HIVIG, however, could not be further augmented by cytokines in controls or patients. Our findings suggest multiple cytokine administration to boost NK cell function, together with passive immunotherapy, might offer a new therapeutic approach to benefit HIV+ patients.

Adolescent↗

PubMed1997

Particle-bound PAH content in ambient air.

Ambient air samples from a traffic intersection, an urban site and a petrochemical-industrial site (PCI) were collected by using several dry deposition plates, two Microorifice uniform deposited impactors (MOUDIs), one Noll Rotary Impactor (NRI) and several PS-1 (General Metal Work) samplers from March 1994 to June 1995 in southern Taiwan, to characterize the atmospheric particle-bound PAH content of these three areas. Twenty-one individual polycyclic aromatic hydrocarbons (PAHs) were analyzed primarily by using a gas chromatograph/mass spectrometer (GC/MS). In general, the sub-micron particles have a higher PAH content. This is due to the fact that soot from combustion sources consists primarily of fine particles and has a high PAH content. In addition, a smaller particle has a higher specific surface area and therefore may contain more organic carbon, which allows for more PAH adsorption. For a particle size range between 0.31 and 3.2 microm, both Urban/Traffic and PCI/Traffic ratios of particle-bound total-PAH content have the lowest values, ranging from 0.25 to 0.28 (mean = 0.26) and from 0.07 to 0.13 (mean = 0.10), respectively. This indicates that, during the accumulation process, the PAH mass shifted from a particle phase to a gas phase, or the particles aggregated with lower PAH-content particles, resulting in a reduction in particle-bound PAH content. By using the particle size distribution data, the dry deposition model in this study can provide a good prediction for the PAH content of dry deposition materials. In general, lower molecular weight PAHs had a larger fraction of dry deposition flux contributed by the gas phase; for 2-ring PAH (50.4, 46.3 and 28.4%), 3-ring PAHs (15.2, 15.4 and 11.7%) and 4-ring PAHs (13.0, 3.60 and 5.01%) for the traffic intersection, urban and PCI sites, respectively. For higher molecular weight PAHs-5-ring, 6-ring and 7-ring PAHs-their cumulation fraction (F%) of dry deposition flux contributed by the gas phase was lower than 3.26%. At the traffic intersection, urban and PCI sites, the mass median diameter of dry deposition materials (MMD(F)) of individual PAHs was between 25.3 and 49.6 microm, between 27.6 and 43.9 microm, and between 19.1 and 41.9 microm, respectively. This is due to the fact that PAH dry-deposition primarily resulted from gravitational settling of the coarse particulates (> 10 microm).

Journal Article↗

PubMed1997

Perioperative low molecular weight heparin for infrageniculate bypass.

PURPOSE: Recent studies suggest that subcutaneous low molecular weight heparin (LMWH) is a safe, effective alternative to intravenous heparin (IVH) for deep venous thrombosis. LMWH may also be a safe, effective alternative to IVH when necessary for lower extremity bypass procedures performed with polytetrafluoroethylene (PTFE) grafts. The purpose of this study was to compare subcutaneous LMWH with IVH for perioperative anticoagulation in patients who underwent infrageniculate bypass procedures with PTFE grafts. METHODS: Of 361 lower extremity bypass operations performed at a single center over a 32-month period, 76 were to the tibial or below-knee levels using PTFE grafts for limb salvage. Seven patients were excluded because of absolute indications for perioperative IVH (ventricular thrombus in 1 patient, prosthetic valve in 2, cardiac dysrhythmia in 2, and documented hypercoagulable syndrome in 2), leaving 68 patients (35 women; mean age, 69.8 years) with 69 bypass procedures for study. Grafts completed in the past 16 months were treated with LMWH (28 grafts; Oct. 1994 to Jan. 1996) and were compared with 41 consecutive control grafts from the previous 16-month interval (Apr. 1993 to Oct. 1994) who received IVH. There were similar percentages of composite bypasses (IVH, 50%; LMWH, 46%), patients with tissue loss or gangrene (IVH, 56%; LMWH, 61%), and patients with prior ipsilateral bypass (IVH, 57%; LMWH, 56%) in each group. Age, sex, and atherosclerotic risk factors were also similar between the two groups. RESULTS: Morbidity rates (IVH, 19%; LMWH, 11%) and mortality rates (IVH, 2.5%; LMWH, 4%) were not significantly different. There were no significant differences in the number of grafts that failed before discharge (IVH, 1; LMWH, 0) or percentage of hemorrhagic complications (IVH, 15%; LMWH, 7%). The mean number of postoperative hospital days (IVH, 9.5; LMWH, 7.2; p < 0.009) and coagulation monitoring studies (IVH, 22; LMWH, 8.4; p < 0.0001) were significantly decreased in patients who were anticoagulated with LMWH. The mean number of days before conversion to oral anticoagulation (IVH, 7.3; LMWH, 8.0) did not differ significantly. CONCLUSIONS: When perioperative anticoagulation is deemed necessary, LMWH provides a safe, effective alternative to IVH for infrageniculate PTFE bypass grafting procedures. LMWH may reduce the number of postoperative hospital days and coagulation studies by allowing discharge before therapeutic anticoagulation with warfarin.

Aged↗

PubMed1997

Increase of the protease activity of aqualysin I, a thermostable serine protease, by replacing Asn219 near the catalytic residue Ser222.

Functional role of Asn219 of aqualysin I, a thermostable serine protease from Thermus aquaticus, was investigated by using site-directed mutagenesis. Replacement of Asn219 with serine increased the catalytic efficiency (kcat/Km) for synthetic peptide substrates about twice as much as that of the wild type, while threonine replacement caused a slight decrease in the efficiency. Such replacements resulted in a significant change of kcat rather than Km, indicating that the side chain in the vicinity of the catalytic residue Ser222 affects the catalytic rate constant.

Asparagine↗

PubMed1997

Molecular cloning and expression of a fungal immunomodulatory protein, FIP-fve, from Flammulina velutipes.

FIP-fve, a fungal immunomodulatory protein, was isolated from the fruiting bodies of the edible mushroom, Flammulina velutipes. FIP-fve was shown to stimulate blast-forming activity of human peripheral blood lymphocytes and gene expression of interleukin-2, interferon-gamma and tumor necrosis factor-alpha. Repeated administration of FIP-fve to mice inhibits the Arthur and systemic anaphylaxis reactions. FIP-fve cDNA was cloned and sequenced, and the amino acid sequence of FIP-fve deduced from the nucleotide sequence is identical to that previously determined by protein sequencing. FIP-fve cDNA was amplified by polymerase chain reaction, ligated into the expression vector, pGEX-2T, and expressed in Escherichia coli as a fusion protein of glutathione S-transferase (GST) and FIP-fve. The GST-FIP-fve fusion protein was soluble, and the yield of recombinant FIP-fve was about 5 mg/L of induced culture. The recombinant FIP-fve was obtained by cleaving the GST-FIP-fve fusion protein with thrombin and purifing to homogeneity. The recombinant FIP-fve had about 50% of the immunomodulatory activity of the native FIP-fve.

Animals↗

PubMed1997

Syndrome X: pathophysiology and clinical management.

The term "syndrome X" is now widely used to specify a group of patients with anginal chest pain, ischemia-like electrocardiogram, normal coronary angiograms, and no evidence of coronary spasm. Though chest pain and exercise-induced myocardial ischemia may both be present in patients with syndrome X and those with coronary artery disease, the underlying pathogenesis of these two disease entities is different. In patients with syndrome X, the causes of angina and myocardial ischemia are multifarious while coronary angiograms are normal. Coronary microvascular function has been shown to be impaired in these patients. However, the presentation of myocardial ischemia may be varied and even subclinical, suggesting dynamic characteristics and regional distribution of coronary microvascular insufficiency in them. Recently, there is increasing evidence that chest pain may develop without detectable myocardial ischemia and has been attributed to abnormal pain perception in at least some of the patients. Thus, there is a heterogeneous group of patients with syndrome X. The rational patient management should be related to individual clinical presentation and depend upon the proper identification of the underlying mechanisms of anginal chest pain or myocardial ischemia or both in these patients.

Chest Pain↗

PubMed1996

Local alcohol delivery may reduce phenotype conversion of smooth muscle cells and neointimal formation in rabbit iliac arteries after balloon injury.

Local delivery of pharmacological agents into the vessel wall has been extensively studied to prevent restenosis after coronary angioplasty. Alcohol solution was found to affect cellular responses to growth stimulation. This study was carried out to examine the effect of local delivery of alcohol solution on intimal proliferation following balloon injury. New Zealand white rabbits of 2-3 kg underwent balloon denudation of bilateral iliac arteries. Following denudation, 2 ml 10% or 15% alcohol solution was infused into one iliac arterial wall using a Wolinsky porous balloon catheter. The other iliac artery of the same animal received local delivery of normal saline and was used as the control. The animals were killed at 2 weeks. The neointimal areas of alcohol treated vascular segments were significantly less than those of control segments in both 10% (n = 10) and 15% (n = 11) groups (65 +/- 16 versus 113 +/- 20 x 10(3) microns2 in 10% group, P < 0.0001; 48 +/- 15 versus 107 +/- 10 x 10(3) microns2 in 15% group, P = 0.002). In order to determine the effect of alcohol solution on smooth muscle cell proliferation, a method of quantifying phenotypic conversion of smooth muscle cells was chosen. This consists of a measurement of volume fraction of the synthetic organelles (VFSO) of vascular smooth muscle cell profiles (SMC) using transmission electron micrographs taken in the animals killed at day 8. The VFSO of SMC of the control sites were significantly greater than those of paired 10% alcohol treated arteries in both intima (0.39 +/- 0.02 versus 0.21 +/- 0.01, P < 0.0001) and media (0.33 +/- 0.03 versus 0.19 +/- 0.02, P < 0.0001). Similar findings were noted in the 15% alcohol treated group. It is concluded that intramural alcohol delivery using porous balloon catheter is effective in reducing neointimal proliferation in rabbit iliac arteries after balloon injury. The mechanisms of action may involve direct inhibition of cellular responses to growth stimulation.

Angioplasty, Balloon↗

PubMed1996

Transient induction of apoptosis in serum-starved glioma cells by insulin and IGF-1.

Insulin has a wide variety of biological effects. One of them is a mitogen-like activity whereby cell proliferation is stimulated. In this study we found a heretofore unreported insulin-elicited transient apoptosis of glioma cells. When serum-starved glioma cells were fed with a fresh regular medium, in the 6- to 12-h post-starvation period, the growth rate as determined by cell number was significantly suppressed by insulin, although cell cycle progression and DNA synthesis were actually accelerated. Increase in apoptosis in those growth-retarded cultures was demonstrable by Hoechst staining, detection of histone-associated DNA fragment, and in situ cell death detection. Apoptosis occurred among cells in all stages of cell cycle. After 24 h post-starvation, insulin increased the total cell number like a typical growth-promoting mitogen. In this regard, IGF-1, but not EGF nor TGF-beta 1, behaved like insulin.

Apoptosis↗

PubMed1996

Determination of gentiopicroside, mangiferin, palmatine, berberine, baicalin, wogonin and glycyrrhizin in the traditional Chinese medicinal preparation sann-joong-kuey-jian-tang by high-performance liquid chromatography.

High-performance liquid chromatography was employed to determine the contents of several marker substances such as gentiopicroside, mangiferin, palmatine, berberine, baicalin, wogonin and glycyrrhizin in Sann-Joong-Kuey-Jian-Tang. The separation was performed on a Cosmosil 5C18-AR column by gradient elution with 0.03% (v/v) phosphoric acid-acetonitrile (0 min, 90:10; 10 min, 87:13; 17-27 min, 77:23; 40 min, 62:38; 50 min, 55:45) as the mobile phase at a flow-rate of 1.0 ml/min, with detection at 254 nm. n-Propylparaben was used as the internal standard and seven regression equations revealed linear relationships between the peak-area ratios (marker substances/internal standard) and concentrations. The repeatability and reproducibility (relative standard deviation) of the method were in the ranges 0.02-1.78% and 1.44-4.95%, respectively.

Berberine↗

PubMed1996

Long Y-associated (GATA)n alleles were observed in a few ethnic groups in Asia.

A Y-associated polymorphic locus, DYS19, was analyzed in a few ethnic groups in Asia and compared with that in Caucasians and Negroes. The locus contains 4-nucleotide repeats, (GATA)n, and the length of the repeated segments can be determined by the polymerase chain reaction (PCR). The predominant allele was 202 bp followed by 198 bp in all the 3 Asian populations examined. Long repeats that were rare in other populations were found more frequently in these Asian populations.

Alleles↗