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C W Lin

Publications and source records attributed to C W Lin.

At least 37 records · Page 2Linked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

Elimination of the slow gating of ClC-0 chloride channel by a point mutation.

The inactivation of the ClC-0 chloride channel is very temperature sensitive and is greatly facilitated by the binding of a zinc ion (Zn2+) from the extracellular side, leading to a Zn2+-induced current inhibition. To further explore the relation of Zn2+ inhibition and the ClC-0 inactivation, we mutated all 12 cysteine amino acids in the channel and assayed the effect of Zn2+ on these mutants. With this approach, we found that C212 appears to be important for the sensitivity of the Zn2+ inhibition. Upon mutating C212 to serine or alanine, the inactivation of the channel in macroscopic current recordings disappears and the channel does not show detectable inactivation events at the single-channel level. At the same time, the channel's sensitivity to Zn2+ inhibition is also greatly reduced. The other two cysteine mutants, C213G and C480S, as well as a previously identified mutant, S123T, also affect the inactivation of the channel to some degree, but the temperature-dependent inactivation process is still present, likewise the high sensitivity of the Zn2+ inhibition. These results further support the assertion that the inhibition of Zn2+ on ClC-0 is indeed due to an effect on the inactivation of the channel. The absence of inactivation in C212S mutants may provide a better defined system to study the fast gating and the ion permeation of ClC-0.

Amino Acid Sequence↗
PubMed1999

De novo CD5+ Burkitt lymphoma/leukemia.

CD5 is a T-cell marker aberrantly expressed in B-cell chronic lymphocytic leukemia and mantle cell lymphoma. Other B-cell neoplasms, including Burkitt lymphoma, are usually CD5-. We report 4 cases of de novo CD5+ Burkitt lymphoma/leukemia in elderly patients, all of whom were in a leukemic phase and had variable lymph node and splenic involvement. The blasts were typically medium sized, with folded nuclei, distinct but not prominent nucleoli, and moderate amounts of somewhat vacuolated basophilic cytoplasm; they were terminal deoxynucleotidyl transferase--negative and surface immunoglobulin--positive. All 4 cases demonstrated c-myc rearrangement, but none had t(14;18), t(11;14), or cyclin D1 overexpression or rearrangement. Only 1 patient achieved complete remission after hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) therapy. One patient responded poorly to hyper-CVAD, and 2 patients died during induction chemotherapy. These rare cases of aggressive lymphoid malignancy with CD5 positivity and molecular features associated with Burkitt lymphoma/leukemia are best classified as Burkitt leukemia. However, the morphologic and immunophenotypic similarity to the blastoid variant of mantle cell lymphoma are diagnostically challenging. The diseases can be distinguished at the genetic level, since Burkitt lymphoma involves the rearrangement of c-myc, and mantle cell lymphoma usually the overexpression or rearrangement of cyclin D1.

Aged↗
PubMed1999

Identification of an activin-follistatin growth modulatory system in the human prostate: secretion and biological activity in primary cultures of prostatic epithelial cells.

PURPOSE: To determine if the activin/follistatin system is present in human prostate tissue and primary cultures of prostatic epithelium and if these growth factors play a role in the control of epithelial cell growth. MATERIALS AND METHODS: Cells derived directly from human prostates were studied to determine: a) if they secrete activin and follistatin, and b) if they are growth inhibited by activin. Primary cell cultures were established from tissues removed from 13 unselected prostate carcinoma patients in order to examine the secretion of activin and follistatin and test the effects of these proteins on cell proliferation. RESULTS: Both primary explant cells and epithelial cells isolated and sub-cultured from explant cultures secreted activin A and follistatin. Treatment of cultured cells with recombinant human activin A resulted in a dose-dependent inhibition of thymidine incorporation, with an IC50 of 0.22 nM. Recombinant follistatin neutralized the inhibitory effects of activin A on cell proliferation whilst adding follistatin alone enhanced thymidine incorporation, suggesting a similar neutralizing effect on the endogenous activin produced by these cells. CONCLUSION: These results demonstrate that cells derived from human prostate tissue secrete activin and follistatin and, as observed in human prostate cancer cell lines, activin inhibited the growth of prostatic epithelial cells. Also consistent with our earlier studies of prostate cancer cell lines, the biological activity of activin was neutralized by follistatin. These observations support the hypothesis that the activin/follistatin system plays an important role in the local regulation of human prostate cell growth.

Activins↗
PubMed1999

Pulse oximeter-associated toe injuries in a premature neonate: a case report.

Pulse oximetry is noninvasive and widely used in the intensive care unit and during surgery. Complications associated with the use of pulse oximetry have been reported, including burns, pressure erosion, skin necrosis and digital sensory loss. The causes of these complications may be due to the incompatibilities between the probes and the monitors used from different companies, pressure duration for too long on a single skin site or overheating induced by a short circuit of the probe cable. We report a 940-g premature infant who had severe pulse oximetry-associated injury to the oximetry site. This may have been due to the infant's susceptibility to injury resulting from his critical condition, including low cardiac output, poor peripheral circulation and poor heat dissemination. Our experience shows that, when pulse oximetry is used, especially in critically ill, premature infants, frequent checking of the sensor and the site where the sensor is applied is required to avoid burn injury or pressure erosion of the skin.

Burns↗
PubMed1999

Altered intracellular calcium level in association with neuronal death induced by lithium chloride.

In this study, we examined the effects of lithium chloride (LiCl) on the intracellular calcium levels ([Ca2+]i), and the survival of immature and mature cultured cerebellar granule neurons (CGNs) grown in medium containing high (25 mmol/L) or normal (5 mmol/L) potassium (K+) levels. LiCl dramatically reduced [Ca2+]i in immature CGNs maintained in high K+ (HK) medium and in those switched to serum containing normal K+ (NK) medium for 1 to 2 days. This reduction in [Ca2+]i led to massive neuronal death of immature neurons developed in both HK and NK medium. In mature (cultured 5-8 days in vitro) CGNs, LiCl exhibited potent toxicity when cells were grown in HK medium, and led to increased [Ca2+]i. Exposing mature CGNs to serum deprivation and normal extracellular K+ concentrations decreased [Ca2+]i and induced cell death, while the addition of LiCl in these conditions further decreased [Ca2+]i but prevented cell death. The morphologic features revealed by Nomarski optics further confirmed these effects of LiCl on neuronal survival. Together, these findings indicate that the effects of LiCl on [Ca2+]i and neuronal death, and the association between [Ca2+]i and cell death, depend on the developmental stage of CGNs and the growth conditions to which they are subjected. These findings may help in understanding the mechanism of neurotoxicity of LiCl during therapy.

Animals↗
PubMed1998

Identification and expression of the Na+/H+ exchanger in mammalian cerebrovascular and choroidal tissues: characterization by amiloride-sensitive [3H]MIA binding and RT-PCR analysis.

We report the initial characterization of [3H]5-(N-methyl-N-isobutyl)amiloride (MIA) binding to the Na+/H+ exchanger (NHE) and expression of its gene in mammalian cerebrovascular, choroidal and neocortical tissues. [3H]MIA bound reversibly to particulate fractions of rat, pig and human cerebral microvessels, choroid plexus and cerebral cortex. Scatchard analyses revealed binding to a single amiloride-sensitive site with dissociation constants (Kd) ranging from 20 to 90 nM for the various tissue preparations. The maximal binding capacities (Bmax) were between 2 to 17 pmol/mg protein and were several-fold greater in cerebral microvessels compared to the cerebral cortex. Amiloride, MIA, 5-(N, N-hexamethylene)amiloride (HMA), 5-(N, N-dimethyl)amiloride (DMA) and 5-(N-methyl-N-isopropyl)amiloride (IPA) variably displaced [3H]MIA binding to the microvessels in the following rank order: MIA>HMA>/=IPA>DMA>amiloride. Benzamil, a potent ligand of the Na+/Ca+ transporter was the least sensitive. These binding results were most compatible with the existence of the amiloride-sensitive NHE type 1 in the brain vascular and choroidal tissues. To substantiate this, we utilized reverse transcription polymerase chain reaction (RT-PCR) techniques to search for NHE-1 mRNA. Using primers corresponding to conserved sequences of the human growth factor-activatable NHE gene, RT-PCR revealed strong expression of NHE-1 mRNA in cerebral microvessels, choroid plexus, pial vessels and vascular smooth muscle cells relative to neocortical tissues from several species including rat, pig, cow, monkey and human subjects. Further confirmation of NHE-1 isoform mRNA expression in the cerebrovascular tissues was obtained by HpaII restriction digestion analysis and by subcloning and sequencing of the PCR amplified products. Our study suggests that mammalian cerebrovascular and choroidal tissues contain high amounts of the ubiquitous amiloride-sensitive [3H]MIA binding proteins consistent with the expression of NHE type 1 mRNA.

Amiloride↗
PubMed1998

Induced expression of neuronal membrane attack complex and cell death by Alzheimer's beta-amyloid peptide.

beta-amyloid peptide (A beta) and complement-derived membrane attack complex (MAC) are co-localized in senile plaques of brains from Alzheimer's disease (AD) patients. But the relationship between A beta and complement activation is unclear. We have used human neurotypic cells, differentiated SH-SY5Y, as a model system to examine regulation of neuronal MAC expression and cell death by A beta. We demonstrated that mRNAs (C1q, C2, C3, C4, C5, C6, C7, C8 and C9) and proteins (C1q, C3 and C9) for the major components of the classical complement cascade are present in the SH-SY5Y neurotypic cells, indicating that neuronal cells can synthesize the necessary proteins required for MAC formation. Furthermore, immunocytochemical studies showed the A beta-induced neuronal MAC expression on the SH-SY5Y cells after CD59 was removed by PIPLC or blocked by anti-CD59 antibody. Meanwhile, increased A beta-induced neuronal cell death was observed following treatment with anti-CD59. Taken together, these results suggest that A beta activates neuronal complement cascade to induce MAC, and a deficiency of endogenous complement regulatory proteins, e.g., CD59, may increase the vulnerability of neurons to complement-mediated cytotoxicity.

Alzheimer Disease↗
PubMed1998

Androgen responsiveness of stromal cells of the human prostate: regulation of cell proliferation and keratinocyte growth factor by androgen.

PURPOSE: Growth and development of the prostate are androgen dependent and mainly influenced by stromal-epithelial interaction. It is believed that indirect androgenic activation of paracrine factors like keratinocyte growth factor (KGF) in the prostatic stroma influences the growth of epithelial cells. In this study we investigated the role androgen plays in stromal cell growth and stimulation of KGF in the human prostate. MATERIALS AND METHODS: Stromal cells were derived from explant primary culture of human normal or benign prostatic tissue. The effect of different dihydrotestosterone (DHT) concentrations on cell proliferation was measured using 3[H]thymidine incorporation assay. The effect of DHT on levels of KGF protein was determined by Western blotting. The effect of DHT on levels of KGF gene expression was measured by various cycles of polymerase-chain-reaction (PCR) and multiplex PCR. RESULTS: Characterization of stromal cells showed epithelial cells less than 9.5% in all passages. DHT stimulated human prostate stromal cells in a dose dependent fashion over a concentration range of 0.001-10 nM. Immunocytochemical evaluation of KGF after DHT exposure showed a higher staining intensity. Relative quantitation of Western blotting showed a 1.93-fold increase in KGF protein in the androgen treated stromal cells. At 1 nM DHT conventional and multiplex PCR revealed a significant stimulation of the KGF mRNA expression. CONCLUSIONS: These data show for the first time that androgen stimulates cell proliferation as well as KGF protein and gene expression in human prostate stromal cells. This supports the hypothesis that androgen-induced stromal-derived KGF stimulates prostate epithelial cell growth.

Aged↗
PubMed1998

Ultrasonic tissue characterization for coronary care unit patients with acute myocardial infarction.

The ultrasonic integrated backscatter of myocardium changes in infarction and ischemia. On the third day after acute myocardial infarction, 30 patients underwent ultrasonic tissue characterization from the parasternal short-axis view. With a composite parameter, the phase-weighted variation, sensitivity, specificity, and accuracy for diagnosing multivessel coronary artery disease were 84.6%, 52.9% and 66.6%, respectively. Using 67 degrees as the cutoff value for the phase deviation of the backscatter power curve, the recanalization of the infarct-related artery could be detected with a positive predictive value of 77.7% and a negative predictive value of 66.6%. Ultrasonic tissue characterization is a feasible technique for detecting the multivessel coronary artery diseases and the recanalization of infarct-related artery for patients with acute myocardial infarction. The diminished cardiac cycle-dependent variation in integrated backscatter and increased phase deviation can differentiate patent coronary arteries from those coronary arteries with anatomically significant stenoses.

Aged↗
PubMed1998

Tachykinins in propranolol-augmented, hyperpnoea-induced bronchoconstriction in Taida guinea-pigs: effects of dimethylthiourea.

1. The present authors recently found that a marked hyperpnoea-induced bronchoconstriction (HIB) only occurred in guinea-pigs after treatment with propranolol, a non-selective beta-adrenoceptor antagonist. This study investigated tachykinin-dependent and antioxidant-modulated mechanisms for this propranolol-augmented HIB. 2. Guinea-pigs were pre-treated with an antioxidant, dimethylthiourea (DMTU), or saline for 3 days. On the day of study, each animal was given a dose of propranolol (0.5 mg kg(-1)), then the airway function was examined in the anaesthetized-paralysed animal before, during and after hyperpnoea with a dry 95% O2:5% CO2 gas mixture. Tracheal neutral endopeptidase (NEP) activity and plasma substance P (SP) level were measured after functional study. 3. In the presence of propranolol, HIB was augmented, and was found to be associated with decreased NEP activity and an increased plasma SP level. The augmented HIB was attenuated by DMTU. 4. Therefore, the present results suggest that propranolol-augmented HIB is tachykinin-dependent and is modulated by DMTU.

Adrenergic beta-Antagonists↗
PubMed1998

Attenuation of isocapnic hyperpnoea-induced guinea-pig bronchoconstriction by chronic hypoxia.

Chronic hypoxia has been shown to augment the production of antioxidants in rat lungs and to reduce airway hyperreactivity in patients with asthma. This study investigated indirectly whether this increase in antioxidants occurs in guinea-pig lungs and whether the increased antioxidants affect hyperpnoea-induced bronchoconstriction (HIB). Guinea-pigs were divided into four groups: control (n=8); chronic hypoxia (n=7); capsaicin pretreatment (n=7); and capsaicin pretreatment plus chronic hypoxia (n=8). Control animals were not treated. Animals in the hypoxia group were intermittently exposed to an ambient pressure of 380 mmHg for 7 days. A five day pretreatment of capsaicin was used to deplete tachykinins. In the last group, animals were pretreated with capsaicin, followed by a seven day hypoxic exposure. On the day of the study, airway function was examined in the anaesthetized and paralysed animal. Fifteen minutes of hyperpnoea caused marked decreases in the maximal expiratory flow rate at 15% vital capacity, forced expiratory volume in one second, and dynamic respiratory compliance, indicating HIB. This HIB and plasma substance P levels were significantly attenuated by chronic hypoxia, capsaicin pretreatment, and capsaicin pretreatment plus chronic hypoxia. Furthermore, chronic hypoxia attenuated airway constriction induced by xanthine-xanthine oxidase. The results suggest that chronic hypoxia attenuates hyperpnoea-induced bronchoconstriction via a decrease in the oxygen radical-mediated release of tachykinins.

Animals↗
PubMed1998

Helicobacter pylori in gastric biopsies of Taiwanese patients with gastroduodenal diseases.

This study was designed to study the in vivo prevalence and the heterogeneity of H. pylori in patients with gastroduodenal diseases in central Taiwan. H. pylori infection was detected in 74.1% (575/776) of the symptomatic population studied. The prevalence of H. pylori infection increased from 11.1% in those between the ages of one to 20, to 82.9% in those between the ages of 41 and 50, and to 84% in those between the ages of 51 and 60. There was no significant difference in the prevalence of H. pylori infection between men and women. Among different blood types, the prevalence and relative risk of H. pylori infection was significantly higher in blood group O patients (90.3%) than in blood group A (41%), blood group B (27.4%), or blood group AB (62%) patients. Metronidazole resistance was found in 6.7% of the primary isolates. The prevalence of metronidazole-resistant H. pylori strains was higher in women (7.69%) than in men (6.25%), but this difference was not significant. A total of 88% of H. pylori strains were cagA-positive. CagA gene-positive strains were present in 90.1% of duodenal ulcers, 90% of duodenal ulcers combined with gastric ulcer, 85.8% of gastric ulcers, and 69.2% of gastritis patients, and was significantly higher in peptic ulcer disease groups than in the gastritis group. In conclusion, there was a low incidence (6.7%) of metronidazole-resistant H. pylori strains and a high prevalence (88%) of H. pylori cagA-positive strains in central Taiwan. This study also demonstrated a significant in vivo correlation between active H. pylori infection and blood group O-positive patients, and showed a significant association between cagA gene-positive H. pylori strains and the development of peptic ulcers.

ABO Blood-Group System↗
PubMed1998

Serratia marcescens bacteremia: clinical features and antimicrobial susceptibilities of the isolates.

From July 1996 to June 1997, 22 adult patients with Serratia marcescens bacteremia were retrospectively studied at China Medical College Hospital. All patients had severe underlying disease, most commonly diabetes mellitus. Eighteen (82%) patients had nosocomial infection. Clinical syndromes included primary bacteremia (68%), pneumonia (14%), urinary tract infection (9%), suppurative thrombophlebitis (5%) and surgical wound infection (5%). Twelve patients had central venous catheters in place at the onset of bacteremia, but only one case met the definition of catheter-related infection. In 14 (64%) patients, portal of entry of S. marcescens infection was unknown. Five (23%) patients had concurrent polymicrobial bacteremia. The overall mortality rate was 50% (11/22). Seven (32%) of the 22 patients died of S. marcescens bacteremia. All isolates were resistant to ampicillin and cephalothin and susceptible to imipenem. Ninety-five percent of strains were susceptible to moxalactam, 68% to amikacin, 55% to ceftazidime, 45% to aztreonam, 32% to ceftriaxone, 27% to gentamicin, 18% to cefoperazone and cefotaxime, and 9% to piperacillin. MICs of various antibiotics demonstrated that ciprofloxacin and imipenem had good activities against S. marcescens, with MIC90 of 0.19 microg/mL and 1.0 microg/mL, respectively. Due to increasing multidrug resistance, choosing appropriate antimicrobial agents such as moxalactam, imipenem, and ciprofloxacin should be highly recommended for the treatment of S. marcescens infections.

Adolescent↗
PubMed1998

Clinical and microbiologic characteristics of Ochrobactrum anthropi bacteremia.

Ochrobactrum anthropi is an oxidase-positive, nonfermenting, gram-negative bacillus that is an emerging pathogen in immunocompromised patients, particularly in those with indwelling central venous catheters. Reports of clinical manifestation of O. anthropi bacteremia are rare. Herein, we report the clinical and microbiologic characteristics of O. anthropi bacteremia in 15 patients. There were eight males and seven females, whose ages ranged from 1 month to 84 years (mean, 34 years). Ten infections were community acquired. All patients had severe underlying disease and manifested primary O. anthropi bacteremia with no obvious focus. Only three patients had central venous catheters in place at the onset of bacteremia, but none of these showed evidence of catheter-related infection. The mean duration of fever was 4 days (range 0-11) and the mean white blood cell count was 13 x 10(9)/L (range 5.5-28 x 10(9)). All O. anthropi isolates tested were resistant to ampicillin, cephalothin, cefonicid, amoxicillin/clavulanic acid, piperacillin, aztreonam, and ceftazidime, and all were susceptible to gentamicin, amikacin, imipenem, ceftriaxone, and cefoperazone. Most were also susceptible to cefotaxime and moxalactam. Monotherapy with an aminoglycoside or an appropriate beta-lactam (such as cefotaxime or ceftriaxone) yielded good clinical response. None of the 15 patients died directly from O. anthropi bacteremia. Our findings indicate that O. anthropi is often community acquired and can be pathogenic in critically ill or immunocompromised patients with or without indwelling catheters. Although O. anthropi can produce clinically significant infections, the organism seems to be of relatively low virulence.

Adolescent↗