Biomedical subjects

C H Lin

Publications and source records attributed to C H Lin.

At least 37 records · Page 2Linked to original sources

PubMed2001

Mechanisms involved in the inhibition of neointimal hyperplasia by abciximab in a rat model of balloon angioplasty.

Monoclonal antibodies raised against beta(3) integrin are able to inhibit the binding of ligands to certain beta(3) integrins such as alpha(IIb)beta(3) (glycoprotein IIb/IIIa complex) and alpha(v)beta(3) (vitronectin receptor) and as such are inhibitors of platelet aggregation and smooth muscle cell (SMC) migration, both of which are involved in neointimal hyperplasia. The present study was designed to explore the detailed mechanisms of abciximab (Reopro), a monoclonal antibody (mAb) raised against alpha(IIb)beta(3) integrin in neointimal hyperplasia. In this study, carotid arteries of Wistar rats were damaged, and neointimal hyperplasia and lumen occlusion was determined at different time points. Abciximab was administered intravenously by an implanted osmotic pump. Abciximab (0.25 mg/kg/day) time-dependently inhibited both neointimal hyperplasia and lumen occlusion after angioplasty in carotid arteries of rats. Furthermore, the electromicrographs highlighted that SMCs were phenotypically different from the typical contractile, spindle-shaped SMCs normally seen in uninjured vessel walls. Platelet-derived growth factor (PDGF)-BB was strongly produced in thrombus formation and neointimal SMCs after angioplasty, while abciximab significantly reduced PDGF-BB expression in vessel lumens and neointimal SMCs after angioplasty. Balloon angioplasty caused a significant increase of nitrate and cyclic GMP as compared with sham-operated rats. Infusion of abciximab (0.25 mg/kg/day) did not significantly change. Furthermore, the plasma level of thromboxane B(2) (TxB(2)) obviously increased after angioplasty, while abciximab markedly suppressed the elevation of plasma TxB(2) concentration. The results indicate that abciximab effectively prevents neointimal hyperplasia, possibly through the following 2 mechanisms: (1) Abciximab binds to alpha(IIb)beta(3) integrin on platelet membranes resulting in inhibition of platelet adhesion, secretion, and aggregation in injured arteries, followed by inhibition of thromboxane A(2) formation and PDGF-BB release from platelets. (2) Abciximab may also bind to alpha(v)beta(3) integrin on SMCs, thus, subsequently inhibiting cell migration and proliferation.

Abciximab↗

PubMed2001

Neurological abnormalities in a knock-in mouse model of Huntington's disease.

Mice representing precise genetic replicas of Huntington's disease (HD) were made using gene targeting to replace the short CAG repeat of the mouse Huntington's disease gene homolog (HDH:) with CAG repeats within the length range found to cause HD in humans. Mice with alleles of approximately 150 units in length exhibit late-onset behavioral and neuroanatomic abnormalities consistent with HD. These symptoms include a motor task deficit, gait abnormalities, reactive gliosis and the formation of neuronal intranuclear inclusions predominating in the striatum. This model differs from previously described HDH: knock-ins by its method of construction, longer repeat length and more severe phenotype. To our knowledge, this is the first knock-in mouse model of HD to show increased glial fibrillary acidic protein immunoreactivity in the striatum, suggesting that these mice have neuronal injury similar to that found early in the course of HD. These mice will serve as useful reagents in experiments designed to reveal the molecular nature of neuronal dysfunction underlying HD.

Alleles↗

PubMed2001

On-line identification of trans- and cis-resveratrol by nonaqueous capillary electrophoresis/fluorescence spectroscopy at 77 K.

This work presents a novel method for the accurate determining trans- and cis-resveratrol (3,5,4'-trihydroxystilbene) by nonaqueous capillary electrophoresis/fluorescence spectroscopy at 77 K. The proposed method permits not only the separation of resveratrol isomers, but also ensures that on-line spectra are readily distinguishable and unambiguously assigned. The experimental results also indicate that the effect of nonaqueous capillary electrophoresis buffer and low-temperature technique increase the detection limit by more than 150-fold.

Acetates↗

PubMed2001

Additional hydrogen bonds and base-pair kinetics in the symmetrical AMP-DNA aptamer complex.

The solution structure of an adenosine monophosphate (AMP)-DNA aptamer complex has been determined previously [Lin, C. H., and Patel, D. J. (1997) Chem. Biol. 4:817-832]. On a symmetrical aptamer complex containing the same binding loop, but with better resolved spectra, we have identified two additional hydrogen bond-mediated associations in the binding loop. One of these involves a rapidly exchanging G imino proton. The phosphate group of the AMP ligand was identified as the acceptor by comparison with other aptamer complexes. Imino proton exchange measurements also yielded the dissociation constants of the stem and binding loop base pairs. This study shows that nuclear magnetic resonance-based imino proton exchange is a good probe for detection of weak hydrogen-bond associations.

Adenosine Monophosphate↗

PubMed2001

Frequent gain of copy number on the long arm of chromosome 3 in human cervical adenocarcinoma.

We analyzed genomic aberrations in 20 cervical adenocarcinomas by comparative genomic hybridization (CGH). Most tissue samples (85%) showed DNA copy number changes; gains were more common than losses. The most consistent region of chromosomal gain was mapped to chromosome arm 3q, found in 70% of the cases, with a minimal common region of 3q28-ter. Other recurrent amplifications of genetic material were detected on 17q (45%), 1p (30%), 1q (25%), and 11q (20%). High-level copy number increases were found in chromosomal regions 3q27-ter and 9pter-13. DNA losses were seldom observed, occurring primarily in underrepresented regions of chromosome arms 4q, 13q, and 18q. The presence of high-risk human papilloma virus genomes in the cervical adenocarcinoma samples was detected in 90% of the cases. However, there was no correlation between human papilloma virus type and the pattern of genomic changes. This study is the first report of CGH analysis in human cervical adenocarcinoma. Among the major genomic alterations, our results demonstrate the importance of DNA copy increases of chromosome arm 3q in the development of cervical adenocarcinoma and identify other amplified chromosomal regions that are also associated with cervical carcinogenesis.

Adenocarcinoma↗

PubMed2001

An indicator cell assay for detection of human cytomegalovirus based on enhanced green fluorescent protein.

An indicator cell line (ML-UL54-EGFP) for the detection of human cytomegalovirus (HCMV) by a simple and direct method was developed. The stable line was constructed by introducing into mink lung cells an expression cassette that contains the enhanced green fluorescent protein (EGFP) reporter gene under the control of an HCMV-inducible promoter. The promoter was from the upstream region of the HCMV UL54 (pol) gene, an early gene promoter that is activated in the early phase of HCMV infection. Following infection with HCMV for 48 h, the stable line expressed well detectable level of the EGFP as observed under a fluorescence microscope. The sensitivity of the indicator cell assay is at least comparable with that of a plaque assay as assessed with a panel of HCMV strains. There were no detectable fluorescent cells after inoculations with several viruses other than HCMV, indicating high specificity. Analysis with flow cytometry revealed that the induced fluorescence from the infected cells was proportional to the titer of HCMV inoculated, making it possible to quantify HCMV infectious particles. In summary, the EGFP-based indicator cell line is of potential use for rapid detection and quantification of HCMV in clinical specimens.

Animals↗

PubMed2001

A small domain of CBP/p300 binds diverse proteins: solution structure and functional studies.

The transcriptional coactivators CBP and p300 are critical regulators of metazoan gene expression. They associate with many different DNA-bound transcription factors through small, conserved domains. We have identified a compactly folded 46 residue domain in CBP and p300, the IRF-3 binding domain (IBiD), and we have determined its structure by NMR. It has a helical framework containing an apparently flexible polyglutamine loop that participates in ligand binding. Spectroscopic data indicate that induced folding accompanies association of IBiD with its partners, which exhibit no evident sequence similarities. We demonstrate the significance both in vitro and in vivo of interactions between IBiD and a number of diverse partners. Thus, IBiD is an important contributor to signal integration by CBP and p300.

Amino Acid Sequence↗

PubMed2001

Induction of cyclooxygenase-2 protein by lipoteichoic acid from Staphylococcus aureus in human pulmonary epithelial cells: involvement of a nuclear factor-kappa B-dependent pathway.

1. This study investigated the role of protein kinase C (PKC) and transcription factor nuclear factor-kappaB (NF-kappaB) in cyclooxygenase-2 (COX-2) expression caused by lipoteichoic acid (LTA), a cell wall component of the gram-positive bacterium Staphylococcus aureus, in human pulmonary epithelial cell line (A549). 2. LTA caused dose- and time-dependent increases in COX-2 expression and COX activity, and a dose-dependent increase in PGE(2) release in A549 cells. The LTA-induced increases in COX-2 expression and COX activity were markedly inhibited by dexamethasone, actinomycin D or cyclohexamide, but not by polymyxin B, which binds and inactivates endotoxin. 3. The phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and the phosphatidate phosphohydrolase inhibitor (propranolol) reduced the LTA-induced increases in COX-2 expression and COX activity, while phosphatidylinositol-phospholipase C inhibitor (U-73122) had no effect. The PKC inhibitors (Go 6976, Ro 31-8220 and GF 109203X) and NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), also attenuated the LTA-induced increases in COX-2 expression and COX activity. 4. Treatment of A549 cells with LTA caused an increase in PKC activity in the plasma membrane; this stimulatory effect was inhibited by D-609, propranolol, or Go 6976, but not by U-73122. 5. Exposure of A549 cells to LTA caused a translocation of p65 NF-kappaB from the cytosol to the nucleus and a degradation of IkappaB-alpha in the cytosol. Treatment of A549 cells with LTA caused NF-kappaB activation by detecting the formation of NF-kappaB-specific DNA-protein complex in the nucleus; this effect was inhibited by dexamethasone, D-609, propranolol, Go 6976, Ro 31-8220, or PDTC. 6. These results suggest that LTA might activate PC-PLC and phosphatidylcholine-phospholipase D to induce PKC activation, which in turn initiates NF-kappaB activation, and finally induces COX-2 expression and PGE(2) release in human pulmonary epithelial cell line.

Cyclooxygenase 2↗

PubMed2001

Development of a capillary electrophoresis-77 K luminescence detection system for online spectral identification.

We have demonstrated that capillary electrophoresis (CE) can be easily interfaced with 77 K luminescence spectroscopy (LS) for separation and online spectral identification of structurally similar analytes. This novel CE-LS apparatus consists of a regular CE system, instrumentation for LS and a specially designed capillary Dewar. When the separating molecules traverse into the cryostat detection window, liquid nitrogen is added, freezing the separating analyte zones within the capillary. At low temperature, detection limits are improved via signal averaging and the inherent increase in quantum yield at 77 K. We present the first application of the CE-LS system to structural isomers (2,3- and 3,4-methylenedioxymethamphetamine) and stereoisomers (trans- and cis-resveratrol). With this approach, the CE-LS interfacing provides a sensitive, accurate, rapid, simple and economic methodology for analytical chemistry.

Journal Article↗

PubMed2001

Study of anticipation in Chinese families with schizophrenia.

The anticipation phenomenon is an important aspect in several genetic disorders in which the age at onset (AAO) decreases and the severity of illness increases in successive generations. This phenomenon has been reported in several schizophrenic family studies, and expanded repeat mutations are implicated. In the present study, we investigate the anticipation phenomenon in Chinese schizophrenic families. We compare the AAO between two generations of 38 unilinear schizophrenic families. Intergenerational comparisons show that the AAO was significantly earlier in the offspring generation (mean AAO, 22.2 years) than that in the parental generation (mean AAO, 31.0 years) (P < 0.001). When only including the offspring generation who married, the AAO difference between the two generations was not significant (28.4 years vs 31.0 years, P = 0.151). Our findings suggest that a selection bias in the parental group might greatly impact the study of anticipation in schizophrenia. Other unavoidable biases associated with these analyses are discussed in the text.

Adolescent↗

PubMed2001

Chyloperitoneum: a postoperative complication after repair of tracheoesophageal fistula.

Chyloperitoneum is rare condition that can occur in response to various pathologic process. The authors described a newborn baby who had chyloperitoneum after primary surgical repair of esophageal atresia with tracheoesophageal fistula (Gross type C). This probably resulted from iatrogenic damage of the thoracic duct during ligation of azygous vein resulting in leaking lacteal within the intestinal wall. Biochemical analysis of ascitic fluid, plasma, and milk formula for triglyceride and cholesterol level can differentiate neonatal gastric intestinal perforation.

Chylous Ascites↗

PubMed2001

Effect of antenatal dexamethasone on the expression of endothelial nitric oxide synthase in the lungs of postnatal pups.

Activities of endothelial nitric oxide synthase (eNOS) are developmentally regulated and its presence at birth may play a role in the transition of cardiopulmonary circulation. Antenatal dexamethasone (Dex) therapy accelerates fetal lung maturation. We speculate that Dex therapy may enhance pulmonary eNOS protein expression in the newborn. This article examines whether antenatal Dex therapy affected the expression of eNOS in the lungs of rat pups in the postnatal period. Time-dated pregnant Wistar rats were subjected to 2 doses of Dex (0.8 mg/kg, intramuscularly, daily) or equivalent volume of normal saline at the 18th and 19th gestational day and delivered naturally. The newborn pups were randomly assigned to 4 groups by age: days 1, 3, 5, and 7. After homogenization, abundance of eNOS protein in lungs was determined by Western blot analysis. There were 7 dams in each group. Mean body weights of the pups in the Dex group were lighter than those in the control at birth and remained stunted up to day 7 (5.68+/-0.47 g v 6.34+/-0.47 g, P <.01). However, there were no differences in wet lung weights and lung/body weight ratios between both groups in the study period. Abundance of eNOS protein expression decreased in both the control and Dex groups (P < .01). Pups that received antenatal Dex had 39% more in abundance of eNOS protein expression in lungs when compared to the control on day 1 (P < .05) but there were no differences between both groups from day 3 to 7. We conclude that antenatal Dex therapy enhances the abundance of eNOS protein expression in the lung at birth and could be a factor in improving respiratory functions in infants who received antenatal steroid therapy.

Animals↗

PubMed2001

Mechanisms in the inhibition of neointimal hyperplasia with triflavin in a rat model of balloon angioplasty.

RGD-containing peptides are able to inhibit the binding of ligands to certain beta3 integrins, such as alpha(IIb)beta3 and alpha(v)beta3, both of which are involved in neointimal hyperplasia. The present study was designed to elucidate the detailed mechanisms involved in the inhibition of neointimal hyperplasia with triflavin in a rat model of balloon angioplasty. Triflavin (0.25 mg x kg(-1) x d(-1)), an RGD-containing disintegrin, time dependently inhibited both neointimal hyperplasia and lumen occlusion after angioplasty in carotid arteries of rats. Furthermore, electron micrographs highlighted that SMCs were phenotypically different from the typical contractile, spindle-shaped SMCs normally seen in uninjured vessel walls. PDGF-BB was strongly produced in thrombus formation and neointimal SMCs after angioplasty, and triflavin significantly reduced PDGF-BB expression in vessel lumens and neointimal SMCs after angioplasty. Balloon angioplasty caused a significant increase of nitrate and cyclic guanosine monophosphate levels compared with levels found in sham-operated rats, and these were not significantly changed with infusion of triflavin (0.25 mg x kg(-1) x d(-1)). Furthermore, the plasma level of TXB2 obviously increased after angioplasty, and triflavin markedly suppressed the elevation of plasma TXB2 concentration. The results indicate that triflavin effectively prevents neointimal hyperplasia, possibly through the following 2 mechanisms. First, triflavin binds to alpha(IIb)beta3 integrin on platelet membranes, resulting in inhibition of platelet adhesion, secretion, and aggregation in injured arteries, followed by inhibition of TXA2 formation and PDGF-BB release from platelets. Second, triflavin may also bind to alpha(v)beta3 integrin on SMCs, thus subsequently inhibiting cell migration and proliferation. These results provide new insights into the mechanisms of neointimal hyperplasia and have significant implications for disintegrin therapy for the treatment of restenosis and atherosclerosis.

Angioplasty, Balloon↗

PubMed2001

The outcome of failed free flaps in head and neck and extremity reconstruction: what is next in the reconstructive ladder?

The indications for free flaps have been more or less clarified; however, the course of reconstruction after the failure of a free flap remains undetermined. Is it better to insist on one's initial choice, or should surgeons downgrade their reconstructive goals? To establish a preliminary guideline, this study was designed to retrospectively analyze the outcome of failed free-tissue transfers performed in the authors hospital. Over the past 8 years (1990 through 1997), 3361 head and neck and extremity reconstructions were performed by free-tissue transfers, excluding toe transplantations. Among these reconstructions, 1235 flaps (36.7 percent) were transferred to the head and neck region, and 2126 flaps (63.3 percent) to the extremities. A total of 101 failures (3.0 percent total plus the partial failure rate) were encountered. Forty-two failures occurred in the head and neck region, and 59 in the extremities. Evaluation of the cases revealed that one of three following approaches to handling the failure was taken: (1) a second free-tissue transfer; (2) a regional flap transfer; or (3) conservative management with debridement, wound care, and subsequent closure by secondary intention, whether by local flaps or skin grafting. In the head and neck region, 17 second free flaps (40 percent) and 15 regional flaps (36 percent) were transferred to salvage the reconstruction, whereas conservative management was undertaken in the remaining 10 cases (24 percent). In the extremities, 37 failures were treated conservatively (63 percent) in addition to 17 second free flaps (29 percent) and three regional flaps (5 percent) used to salvage the failed reconstruction. Two cases underwent amputation (3 percent). The average time elapsed between the failure and second free-tissue transfer was 12 days (range, 2 to 60 days) in the head and neck region and 18 days (range, 2 to 56 days) in the extremities. In a total of 34 second free-tissue transfers at both localizations, there were only three failures (9 percent). However, in the head and neck region, seven of the regional flaps transferred (47 percent) and four cases that were conservatively treated (40 percent) either failed or developed complications that lengthened the reconstruction period because of additional procedures. Six other free-tissue transfers had to be performed to manage these complicated cases. Conservative management was quite successful in the extremities; most patients' wounds healed, although more than one skin-graft procedure was required in 10 patients (27 percent). In conclusion, a second free-tissue transfer is, in general, a relatively more reliable and more effective procedure for the treatment of flap failure in the head and neck region, as well as failed vascularized bone flaps in the reconstruction of the extremities. Conservative treatment may be a simple and valid alternative to second (free) flaps for soft-tissue coverage in extremities with partial and even total losses.

Extremities↗

PubMed2001

Microsurgical tissue transplantation or replantation in patients with psychoneurological impairment.

Sometimes patients with a psychoneurological impairment present with a traumatic injury that requires either microsurgical replantation or free-tissue transfer. We reviewed 38 patients undergoing 40 microvascular operations; the patients included 26 patients with psychological impairment (group 1), 3 with mental disability (group 2), and 9 with an acquired head injury and consciousness disturbance (Glasgow Coma Scale score < or =14) (group 3). Patients with a psychological impairment, especially those with a self-inflicted injury, are often uncooperative and do not recognize the necessity of restorative procedures. A multidisciplinary approach by the trauma surgeon, plastic surgeon, psychiatrist, and neurosurgeon, with coordinated assistance from the physician, nurse, therapist, and family, is required for treatment. In our study the success rate of replantation was 77.8 percent (14 of 18); for free tissue transfer the success rate was 95.5 percent (21 of 22). The overall success rate of microsurgical procedures (87.5 percent, 35 of 40) was similar to that in the population at large. Patients with psychological impairment tend to be lost during follow-up; therefore, their functional results may be poorer than expected. Nonetheless, patients with psychological impairment should not be deprived of the benefits of restorative surgery.

Adult↗

PubMed2001

Traction avulsion amputation of the major upper limb: a proposed new classification, guidelines for acute management, and strategies for secondary reconstruction.

Major replantation of a traction avulsion amputation is undertaken with the goal of not only the reestablishment of circulation, but also functional outcome. This type of amputation is characterized by different levels of soft-tissue divisions involving crushing, traction, and avulsion injuries to various structures. Between 1985 and 1998, 27 cases were referred for secondary reconstruction following amputation of the upper extremity involving both arm and forearm. Replantation was performed by at least 12 qualified plastic surgeons using different approaches and management, resulting in different outcomes. Initial replantation management significantly affects the later reconstruction. For comparing studies and prognostic implications, the authors propose a new classification according to the level of injury to muscles and innervated nerves: type I, amputation at or close to the musculotendinous aponeurosis with muscles remaining essentially intact; type II, amputation within the muscle bellies but with the proximal muscles still innervated; type III, amputation involving the motor nerve or neuromuscular junction, thereby causing total loss of muscle function; and type IV, amputation through the joint; i.e., disarticulation of the elbow or shoulder joint. Some patients required further reconstruction for functional restoration after replantation, but some did not. Through this retrospective study based on the proposed classification system, prospective guidelines for the management of different types of traction avulsion amputation are provided, including the value of replantation, length of bone shortening, primary or delayed muscle or nerve repair, necessity of fasciotomy, timing for using free tissue transfer for wound coverage, and the role of functioning free muscle transplantation for late reconstruction. The final functional outcome can also be anticipated prospectively through this classification system.

Adolescent↗

PubMed2001

Genetic variants of the serotonin system and weight change during clozapine treatment.

Clozapine-induced weight gain may impair health and affect patient compliance. The aim of this study is to investigate the relationship between the genetic variants of the serotonin system and clozapine-induced body weight change (BWC). Ninety-three treatment-resistant schizophrenic patients were weighed monthly for 4 months during clozapine treatment. At the conclusion of treatment, patients had gained an average of 2.4 kg body weight, with BWC ranging from -17.5 to +12.9 kg. The levels of the serotonin transporter variants, serotonin 2A, serotonin 2C and serotonin 6, demonstrated no statistically significant relationship to BWC. Patients with a lower initial body mass index demonstrated a greater weight gain associated with clozapine treatment. Further exploration of the neurotransmitters implicated in the antipsychotic-induced BWC is important in order to reduce the morbidity and noncompliance associated with weight gain.

Adolescent↗

PubMed2001

Association analysis for dopamine D2 receptor Taq1 polymorphism with P300 event-related potential for normal young females.

P300 has been demonstrated abnormal for a variety of neuropsychiatric disorders, and heritability has been proposed. We analyzed the event-related potentials for three DRD2 genotype groups in 134 normal young females. The results demonstrate that there is no association for DRD2 genotype and P300 components. Our negative findings in normal subjects suggest association demonstrated for P300 latency and the DRD2 allele may be disease dependent.

Adult↗