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Biomedical subjects

C W Lin

Publications and source records attributed to C W Lin.

At least 19 recordsLinked to original sources

Synthesis and characterization of non-steroidal ligands for the glucocorticoid receptor: selective quinoline derivatives with prednisolone-equivalent functional activity.

A novel class of functional ligands for the human glucocorticoid receptor is described. Substituents in the C-10 position of the tetracyclic core are essential for glucocorticoid receptor (GR) selectivity versus other steroid receptors. The C-5 position is derivatized with meta-substituted aromatic groups, resulting in analogues with a high affinity for GR (K(i) = 2.4-9.3 nM) and functional activity comparable to prednisolone in reporter gene assays of glucocorticoid-mediated gene transcription. The biological activity of these novel quinolines was also prednisolone-equivalent in whole cell assays of glucocorticoid function, and compound 13 was similar to prednisolone (po ED(50) = 2.8 mpk for 13 vs ED(50) = 1.2 mpk for prednisolone) in a rodent model of asthma (sephadex-induced eosinophil influx).

Animals↗

Preparation of EVAL membranes with smooth and particulate morphologies for neuronal culture.

In this work, the in vitro interaction of cerebellar granule neurons prepared from 7-day-old Wistar rats and poly ethylene-co-vinyl alcohol (EVAL) membranes was investigated. Cells were cultured in smooth and particulate EVAL membranes for up to 7 days. Particulate membranes were prepared by using 1-octanol to precipitate EVAL solutions in DMSO. Such a membrane was microporous characterized by a packed bed of particles. Voids left between the aggregated particles formed a continuous and interconnected porous network. Crystallization of the EVAL polymer induced by 1-octanol is responsible for the formation of particulate morphology. The membrane structure and its relationship with cells were examined by scanning electron microscopy and the MTT assay. It was observed that the particulate membrane was more favorable for the neuron culture than the smooth membrane. Neurons seeded on the particulate membrane were able to regenerate with formation of an extensive neuritic network. Therefore, the particulate structure may spatially mediate cellular response that can promote neuronal cell attachment, differentiation and neuritic growth, indicating that the particulate structure should be useful as a new polymer scaffold for nerve repair.

Animals↗

Neutralizing peptide ligands selected from phage-displayed libraries mimic the conformational epitope on domain III of the Japanese encephalitis virus envelope protein.

The envelope (E) protein of Japanese encephalitis virus (JEV) contains 500 amino acids with six "conserved" disulfide bonds to maintain its conformational structure. Neutralizing epitopes located on the E protein are mostly conformational dependent. In this study, we used phage-displayed 12-residue combinatorial peptide libraries to select high-affinity peptide ligands bound to monoclonal antibody E3.3. The specific peptide ligands presented on ten high-affinity phage clones displayed six different amino acid sequences, all showing a novel cis-proline turn structure. After being superimposed onto the best fit of the three-dimensional structure of JEV E protein, these peptide structures were mapped to a conformational region constituted by three continuous polypeptide segments (E307-E309, E327-E333, E386-E390) in domain III. Synthetic peptide ligands based on one peptide sequence (E18) were further investigated using alanine scanning within the cis-proline turn structure to demonstrate its unique molecular characteristics. Our results showed that three residues forming the novel cis-proline turn structure were all important in eliciting JEV-specific neutralizing antibodies in mice.

Animals↗

Colonoscopic manifestations of primary colorectal lymphoma.

BACKGROUND AND STUDY AIMS: Little is known about the colonoscopic manifestation of colorectal lymphoma. This article describes the use of colonoscopy for diagnosis of primary colorectal lymphoma. PATIENTS AND METHODS: We analyzed colonoscopic findings in 13 retrospectively collected cases of primary colorectal lymphoma diagnosed between 1990 and 1999 at our hospital. RESULTS: The primary colorectal tymphomas were distinguished into three colonoscopic types: a) the mucosal type, which included six lymphomas (46%), which were classified into two subtypes, erosive (two lymphomas) and ulcerative (four tymphomas); b) the polypoid type, which included three tymphomas (23%); and c) the massive type, which included four (31%). The proportion of patients with T-cell lineage lymphoma (5 of 12, 42%) was higher than in previous studies. Three cases were diagnosed as enteropathy-associated T-cell (EAT)-like lymphoma: one presenting with multicentric ulcerations, one as a massive type and another as a polypoid type. Of those with B-cell lineage lymphoma (7 of 12, 58%), three presented as massive type, two as polypoid type and two as erosive subtype. CONCLUSIONS: Based on the analysis of colonoscopic records, we have proposed three main types of primary colorectal lymphoma. An unusually high proportion of T-cell lineage lymphomas was noted, but as the number of cases was low, further study is still needed for confirmation.

Adult↗

A new mode of percutaneous upper thoracic phenol sympathicolysis: report of 50 cases.

OBJECTIVE: Our previous study demonstrated that a high concentration of phenol (75-90%) with minimal volume (0.02 ml) can elicit serious degeneration of ganglion cells of the stellate ganglia in cats. Another previous study in our clinical patients demonstrated that approximately 84 to 90% of the upper thoracic (T2-T3) sympathetic trunks can be found under an endoscope on the ventral side of the T2-T3 rib heads. In this report, we present a new mode of dorsal percutaneous thoracic phenol sympathicolysis (PTPS) for the treatment of palmar hyperhidrosis or axillary bromidrosis. METHODS: Fifty patients with palmar hyperhidrosis or axillary bromidrosis were injected with 75% phenol into a total of 98 sides of the T2-T3 or T3-T4 sympathetic trunks and ganglia. The injected volume was 0.6 to 1.2 ml (average, 0.8 ml) for each side. The technique of dorsal percutaneous injection was performed under local anesthesia or local with intravenous general anesthesia and under the guidance of a C-arm fluoroscope. RESULTS: Forty patients (80%) showed satisfactory results, including cessation of sweating. The success rates of PTPS were 83.7% (41 of 49 patients) on the left side and 91.8% (45 of 49 patients) on the right side. The skin temperature of the thumb increased by 5.3 to 5.4 degrees C approximately 1 hour after the phenol injection in patients with satisfactory results, whereas it increased by only 1.3 to 2.7 degrees C in patients who had unsatisfactory results. CONCLUSION: PTPS may be a good alternative to endoscopic sympathectomy to treat palmar hyperhidrosis and axillary bromidrosis. The skin temperature of the thumb is still a useful index to evaluate preliminarily whether PTPS has been successful.

Adolescent↗

Surface characterization and platelet compatibility evaluation of surface-sulfonated chitosan membrane.

The effect of various sulfonated derivatives of chitosan on platelet activation and blood coagulation was examined. The surface properties of artificial biomaterials have been thought as the key factors which mediate the interactions between the biological environment and biomaterial itself. In this study, the sulfonation was directly performed on the chitosan membrane surface. The chitosan membrane was surface-sulfonated by reactions with sulfur-pyridine trioxide complex (SO3/pyridine) in H2O solution and N,N-sulfur-dimethylformamide trioxide complex (SO3/DMF) in DMF. Blood compatibility was evaluated by an in vitro platelet adhesion assay. The surface reaction of SO3/pyridine in aqueous acid medium yields N,O-sulfated chitosan with cationic NH3+ groups. After neutralization, this surface has been shown to induce a low degree of platelet adhesion and activation. When the surface-sulfonation is performed in an aqueous alkaline medium, although the degree of sulfonation is lower than the samples above, the N-sulfated chitosan significantly reduced the adhesion and activation of platelets. For the acidic SO3/DMF reaction system, N,O-sulfated chitosan was obtained with a high extent of sulfonation and cationic NH3+ groups. On this surface fully spread platelets and some platelet aggregates were found instead. This may be attributed to the ionic interactions between the platelets membrane surface and the cationic groups on the modified chitosan membrane.

Biocompatible Materials↗

Differential expression of human topoisomerase IIIalpha during the cell cycle progression in HL-60 leukemia cells and human peripheral blood lymphocytes.

Human topoisomerase IIIalpha (huTop IIIalpha) has been demonstrated to belong to type IA subfamily. In this study, we found that huTop IIIalpha expressed constitutively and remained at high levels throughout the cell cycle in HL-60 cells when compared to the cell-cycle-dependent expression of huTop IIIalpha in phytohemagglutinin-activated peripheral blood lymphocytes. During the cell cycle progression, this protein remained accentuated in the nucleolus without significant translocation from the nucleolus to the nucleoplasm. In addition, during the course of granulocytic maturation in DMSO-treated HL-60 cells, huTop IIIalpha levels decreased when cells stopped proliferation and nucleoli diminished in size. However, its level remained unchanged during the course of monocytic maturation of vitamin D(3)-treated HL-60 cells which still retained its proliferative capacity and did not change the size of the nucleolus. The data suggested that huTop IIIalpha is involved in rDNA metabolism, such as rDNA transcription. Its cellular level appeared to be under control during the cell cycle progression of normal lymphocytes, but was found to be deregulated in HL-60 cells which may be associated with the tumor transformed cell phenotypes.

Amino Acid Sequence↗

In vitro and in vivo studies for modified ethyl cyanoacrylate regimens for sclerotherapy.

Cyanoacrylates have known for their ability to polymerize rapidly in the presence of traces of weakly basic moieties such as water. The tissue adhesive, Histoacryl(R) (N-butyl 2-cyanoacrylate), has been reported to control bleeding through endoscopic sclerotherapy. But the commercially available Histoacryl(R) is expensive, and it has the problem like other cyanoacrylates that the glue tends to flow/run away from the point of application, which is inherent to the low viscosity, making precise application difficult. In this study, ethyl cyanoacrylate (ECA), the main constituent of "super glue," was employed instead of Histoacryl(R) due to its lower cost. The aim of the research is to modify the compositions of ECA regimen and evaluate its feasibility for sclerosant application through both in vitro flow circuit model and in vivo animal tests. It was noted that the difference in the relative hardening rate between the in vitro Hepes-Tyrodes buffer flowing model and the in vivo rat model for the ECA and Histoacryl(R) was related to the existence of the blood protein, such as albumin, in the physiological milieu. It was also noticed that the ECA setting rate was greatly increased either in Hepes-Tyrodes buffer or in blood (to a comparable rate as Histoacryl(R) in vivo) by adding a few doses of caffeine, which acts as a polymerization initiator. This would lead to far better injection precision during sclerotherapy. Furthermore, in vivo histological examination for the occluded lumen of the rat's inferior vena cava and a clinical piglet portal vein occlusion experiment have suggested this new sclerosant regimen, caffeine/ECA, is of great promise in endoscopic sclerotherapy.

Animals↗

Expression of cyclin-dependent kinase 6 (cdk6) and frequent loss of CD44 in nasal-nasopharyngeal NK/T-cell lymphomas: comparison with CD56-negative peripheral T-cell lymphomas.

Lymphomas involving the nasal and nasopharyngeal region mainly include CD56-positive natural killer (NK)/T-cell lymphomas, CD56-negative peripheral T-cell lymphomas (PTL), and B-cell lymphomas. Among these, the CD56-positive lymphoma, presumably of an NK/T-cell nature, is frequently seen in Asian, Mexican, and South American patients. NK cells are proposed to be closer developmentally to T cells than to other lymphoid cells, because bipotential common progenitor cells of NK/T-cell lineage have been isolated. In this study, we collected 47 cases of nasal lymphoma and investigated the phenotypic difference between NK/T-cell lymphoma and PTL by examining the pattern of the developmentally differentially expressed molecules cdk6 (cyclin-dependent kinase 6), CD44, CD117, and by examining the rearrangement of the T-cell receptor gene (TcR-GR). cdk6, an essential regulator of the cell cycle in G1 progression, was over-expressed in a subset of cortical thymocytes, but absent in mature thymocytes. In contrast, CD44, a glycosylated adhesion molecule, was absent in cortical thymocytes, but present in mature thymocytes and peripheral activated T cells. We found both over-expression of nuclear cdk6 (n-cdk6) and frequent absence of CD44 in nasal CD56-positive NK/T-cell lymphomas, in contrast to most nasal CD56-negative PTL, which were CD44-immunoreactive with weak or no expression of n-cdk6. Almost all tested cases of NK/T-cell lymphoma displayed a germ-line configuration of TcR, without evidence of gene rearrangement. Thus, there seems to be a useful distinction between the classical NK/T type of nasal lymphoma (CD56+/n-cdk6+/CD44-/TcR-GR-) and PTL (CD56-/n-cdk6-/CD44+/TcR-GR+) involving the nasal region. The presence of Epstein-Barr virus does not seem to be a good marker for distinguishing between NK/T lymphoma and PTL involving the nasal region.

Adult↗

Genetic analysis and clinical evaluation of vacuolating cytotoxin gene A and cytotoxin-associated gene A in Taiwanese Helicobacter pylori isolates from peptic ulcer patients.

The aims of this study were to investigate the cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene A (vacA) subtype in Taiwanese H. pylori isolates from patients with gastroduodenal diseases and to assess the relationship between genotypes of isolates and clinical features. The vacA s1a allele was found in all isolates and vacA m1 allele was found in 15% of isolates. The cagA gene was found in 82.5% of isolates. The vacA s1a/m2 strains had a significantly higher prevalence rate than vacA s1a/m1 strains in Taiwan (p < 0.05). By aligning and comparing the nucleotide and amino acid sequences of vacA from the Taiwanese isolates, the signal sequence and N-terminal region were found to be highly conserved, but the middle region was found to be highly heterogeneous. Determining the relationship between the genotypes and clinical features, we found that the cagA gene was more closely associated with duodenal ulcer than with gastric ulcer and the vacA s1a/m2 strain was more closely associated with active chronic gastritis and atrophic gastritis than with chronic gastritis. Together, our results indicated that (i) the middle region of vacA gene in Taiwanese isolates was heterogeneous; (ii) s1a/m2 vacA strains had a high prevalence in Taiwanese peptic ulcers; and (iii) the cagA gene was significantly associated with duodenal ulcer.

Acute Disease↗

Cysteine modification of a putative pore residue in ClC-0: implication for the pore stoichiometry of ClC chloride channels.

The ClC channel family consists of chloride channels important for various physiological functions. Two members in this family, ClC-0 and ClC-1, share approximately 50-60% amino acid identity and show similar gating behaviors. Although they both contain two subunits, the number of pores present in the homodimeric channel is controversial. The double-barrel model proposed for ClC-0 was recently challenged by a one-pore model partly based on experiments with ClC-1 exploiting cysteine mutagenesis followed by modification with methanethiosulfonate (MTS) reagents. To investigate the pore stoichiometry of ClC-0 more rigorously, we applied a similar strategy of MTS modification in an inactivation-suppressed mutant (C212S) of ClC-0. Mutation of lysine 165 to cysteine (K165C) rendered the channel nonfunctional, but modification of the introduced cysteine by 2-aminoethyl MTS (MTSEA) recovered functional channels with altered properties of gating-permeation coupling. The fast gate of the MTSEA-modified K165C homodimer responded to external Cl(-) less effectively, so the P(o)-V curve was shifted to a more depolarized potential by approximately 45 mV. The K165C-K165 heterodimer showed double-barrel-like channel activity after MTSEA modification, with the fast-gating behaviors mimicking a combination of those of the mutant and the wild-type pore, as expected for the two-pore model. Without MTSEA modification, the heterodimer showed only one pore, and was easier to inactivate than the two-pore channel. These results showed that K165 is important for both the fast and slow gating of ClC-0. Therefore, the effects of MTS reagents on channel gating need to be carefully considered when interpreting the apparent modification rate.

Animals↗

An adaptive 3-D discrete cosine transform coder for medical image compression.

In this communication, a new three-dimensional (3-D) discrete cosine transform (DCT) coder for medical images is presented. In the proposed method, a segmentation technique based on the local energy magnitude is used to segment subblocks of the image into different energy levels. Then, those subblocks with the same energy level are gathered to form a 3-D cuboid. Finally, 3-D DCT is employed to compress the 3-D cuboid individually. Simulation results show that the reconstructed images achieve a bit rate lower than 0.25 bit per pixel even when the compression ratios are higher than 35. As compared with the results by JPEG and other strategies, it is found that the proposed method achieves better qualities of decoded images than by JPEG and the other strategies.

Biomedical Engineering↗

Astrocytes modulate thapsigargin-induced changes in calcium concentration and neuronal survival.

When mature cerebellar granule neurons (CGN) grown in high K+ (25 mM K+, HK)-serum containing medium are subjected to the HK/serum deprivation, they are destined for neuronal death. In this study, we attempted to elucidate the roles of endoplasmic reticular (ER) Ca2+-store and co-cultured astrocytes in HK/serum deprivation induced neuronal death. Thapsigargin (TG), an inhibitor of ER Ca2+-ATPase was simultaneously applied with normal K+ (5 mM K+, NK) serum free medium, and its effects on neuronal death in either astrocyte-poor or astrocyterich culture were examined. By means of the fura-2 microfluorimetric technique, we monitored the changes of the intracellular Ca2+ concentration, [Ca2+]i, associated with neuronal death under various treatments. The results obtained showed that in astrocyte-poor cultures of mature CGN (10 days in vitro, DIV), the basal level of [Ca2+]i markedly decreased from 184 +/- 5 to 89.7 +/- 5 nM 24 h after HK/serum deprivation. Although treatment with TG slightly increased the [Ca2+]i to 117.6 +/- 4 nM, the survival rate of the neurons was even worse; it was reduced from 49 +/- 4% to 28 +/- 2%. In the astrocyte-rich cultures, HK/serum deprivation also caused a profound reduction of neuronal [Ca2+]i, from 166 +/- 3 to 90.2 +/- 6 nM, accompanied by even more serious neuronal death (95.5 +/- 1%). On the other hand, treatment with TG in astrocyterich cultures further lowered the [Ca2+]i to 65 +/- 2 nM but markedly improved the neuronal survival rate from 4.5 +/- 1% to 60 +/- 2% in a concentration-dependent manner. The strong implication of these findings is that ER Ca2+-store and astrocytes participate in modulating the responses of neurons to stress stimulation.

Animals↗

Immunolocalization of the keratinocyte growth factor in benign and neoplastic human prostate and its relation to androgen receptor.

BACKGROUND: Growth and development of the prostate are androgen-dependent. Keratinocyte growth factor (KGF), widely expressed by mesenchymal cells, is thought to act like an andromedin between stroma and epithelium of the prostate. Since KGF has recently emerged as an autocrine mediator in prostate cancer, we investigated the role KGF plays in the human prostate and its relationship to androgen receptor (AR). METHODS: Normal (n = 13), benign hyperplastic (n = 5), and neoplastic (n = 14) human prostate tissues as well as cultured epithelial and stromal cells were analyzed using polymerase chain reaction (PCR), Western blot analysis, and immunohistochemistry. RESULTS: Reverse transcriptase polymerase chain reaction and Western blotting showed KGF expression in stromal cultured cells of the normal prostate but not in epithelial cells. Using immunohistochemistry, KGF was found to be localized in fibroblasts and smooth muscle cells, independent of prostate disease. There was KGF expression in epithelial cells of BPH and prostate cancer. Human androgen receptor was uniformly expressed in the same secretory glandular cells that were positive for KGF in BPH and prostate cancer. CONCLUSIONS: Our results provide evidence that KGF is a stromal-derived mediator, recently shown to act in a paracrine manner in normal prostate but now detected in epithelial cells in prostate cancer and BPH. These findings support the hypothesis that KGF might act as an autocrine factor in prostate cancer and BPH.

Antibody Specificity↗

trans-2,6-,3,6- and 4,6-diaza-5,6,6a,7,8,12b-hexahydro-benzo[c]phenanthrene-10,11- diols as dopamine agonists.

The title compounds were synthesized by replacing the thiophene moiety of A-86929(2a) with variously substituted pyridines. Dopamine D-1 and D-2 binding and adenylate cyclase assays indicate that 4,6-diaza compounds 15 are potent and selective full D1 agonists when R1 is H or a small substituent and R2 = H, with D1 binding affinity and adenylate cyclase functional potency equivalent to that of A-86929(2a).

Dopamine Agonists↗

Roles of thapsigargin-sensitive Ca2+ stores in the survival of developing cultured neurons.

The roles of the intracellular calcium pool involved in regulating the Ca2+ profile and the neuronal survival rate during development were studied by using thapsigargin (TG), a specific inhibitor of endoplasmic reticulum (ER) Ca2+-ATPase in cultured cerebellar granule neurons. Measuring the neuronal [Ca2+]i directly in the culture medium, we found a bell-shaped curve for [Ca2+]i versus cultured days in cerebellar granule neurons maintained in medium containing serum and 25 mM K+. The progressive increase in [Ca2+]i of the immature granule neurons (1-4 days in vitro) was abolished by TG, which resulted in massive neuronal apoptosis. When the [K+] was lowered from 25 to 5 mM, neither the progressively increasing [Ca2+]i nor the survival of immature granule neurons was significantly changed over 24-h incubation. Similarly, TG caused a dramatic decrease in the [Ca2+]i and survival rate of these immature neurons when switched to 5 mM K+ medium. Following maturation, the granule neurons became less sensitive to TG for both [Ca2+]i and neuronal survival. However, TG can protect mature granule neurons from the detrimental effect of switching to a 5 mM K+ serum-free medium by decreasing [Ca2+]i to an even lower level than in the respective TG-free group. Based on these findings, we propose that during the immature stage, TG-sensitive ER Ca2+-ATPase plays a pivotal role in the progressive increase of [Ca2+]i, which is essential for the growth and maturation of cultured granule neurons.

Animals↗

Endemic burkholderia cepacia bacteraemia: clinical features and antimicrobial susceptibilities of isolates.

Burkholderia cepacia has emerged as a nosocomial pathogen, causing numerous outbreaks, particularly among cystic fibrosis (CF) patients. Reports of clinical features of endemic B. cepacia bacteraemia in non-CF patients are rare. Twenty-five patients with B. cepacia bacteraemia were matched with 25 controls with nosocomial Escherichia coli bacteraemia at China Medical College Hospital, Taichung, Taiwan, over a period of 3 y. Case-patients included 16 men and 9 women, from 13 to 75 y. All had severe underlying diseases, most commonly malignancy (44%). Twenty-four patients (96%) had nosocomial infections. Five patients (20%) had polymicrobial bacteraemia. Our controls included 11 men and 14 women, age range 18-80 y. The most common underlying disease was malignancy (44%). Multivariate analysis revealed that indwelling central venous catheter was the significant risk factor predisposing to B. cepacia bacteraemia (p= 0.025). Eleven case-patients met the definition of catheter-related bloodstream infection. Fifteen patients (60%) received appropriate antimicrobial therapy after notification of positive blood cultures and susceptibility patterns. The overall case-fatality rate was 12% (3/25), only 1 of whom died of B. cepacia bacteraemia. There was no statistically significant difference in overall mortality rate between case-patients and controls. All isolates were susceptible to ceftazidime, piperacillin and minocycline and 84% of the isolates were susceptible to imipenem. B. cepacia should be considered a potential pathogen in hospitalized patients with severe underlying diseases, particularly those with indwelling central venous catheters.

Adolescent↗