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Papers by Jim Lin

Research paper thumbnail of Characterization of Cardiomyocyte-Like Cells in Thoracic Blood Vessels

Research paper thumbnail of Autoantibodies against human tropomyosin isoform 5 in ulcerative colitis destroys colonic epithelial cells through antibody and complement-mediated lysis

Introduction. Patients with ulcerative colitis (UC) have IgG1 antibodies in serum and colon again... more Introduction. Patients with ulcerative colitis (UC) have IgG1 antibodies in serum and colon against human tropomyosin isoform 5 (hTM5), a cytoskeletal microfilament protein found intracellularly and on the surface of colonic epithelial cells (EC). These antibodies may be pathogenic in UC.

Research paper thumbnail of Xin Scaffolding Proteins and Arrhythmias

Journal of cardiology & clinical research, Jan 24, 2013

Research paper thumbnail of Chapter 1: roles of caldesmon in cell motility and actin cytoskeleton remodeling

International review of cell and molecular biology

Caldesmon (CaD) is a multimodular protein that regulates contractility and actin cytoskeleton rem... more Caldesmon (CaD) is a multimodular protein that regulates contractility and actin cytoskeleton remodeling in smooth muscle and nonmuscle cells. A single gene (CALD1) encodes high molecular mass CaD (h-CaD) and low molecular mass CaD (l-CaD) by alternative splicings. The h-CaD exclusively expresses in smooth muscle, whereas the l-CaD ubiquitously expresses in all cell types except skeletal muscle. The h-CaD/l-CaD ratio could be a marker for monitoring differentiating and pathological states of smooth muscles. The l-CaD associates with stress fibers and membrane ruffles in nonmuscle cells and with the actin core of podosomes in highly motile/invasive cells. Together with tropomyosin, CaD stabilizes actin filaments and inhibits actin-tropomyosin-activated myosin ATPase activity. This inhibition can be effectively released by Ca(2+)-calmodulin and/or by phosphorylation with various kinases. Through its interactions with a spectrum of actin-binding proteins, CaD modulates dynamics of cort...

Research paper thumbnail of Characterization of cis-regulatory elements and transcription factor binding: gel mobility shift assay

Methods in molecular biology (Clifton, N.J.), 2007

To understand how cardiac gene expression is regulated, the identification and characterization o... more To understand how cardiac gene expression is regulated, the identification and characterization of cis-regulatory elements and their trans-acting factors by gel mobility shift assay (GMSA) or gel retardation assay are essential and common steps. In addition to providing a general protocol for GMSA, this chapter describes some applications of this assay to characterize cardiac-specific and ubiquitous trans-acting factors bound to regulatory elements [novel TCTG(G/C) direct repeat and A/T-rich region] of the rat cardiac troponin T promoter. In GMSA, the specificity of the binding of trans-acting factor to labeled DNA probe should be verified by the addition of unlabeled probe in the reaction mixture. The migratory property of DNA-protein complexes formed by protein extracts prepared from different tissues can be compared to determine the tissue specificity of trans-acting factors. GMSA, coupled with specific antibody to trans-acting factor (antibody supershift assay), is used to ident...

Research paper thumbnail of Monoclonal Antibodies Against Cardiac Myosin Heavy Chain

Hybridoma, 1990

Three mouse IgG monoclonal antibodies (MAbs), named FAl, FA2, and FA3, against cardiac myosin hea... more Three mouse IgG monoclonal antibodies (MAbs), named FAl, FA2, and FA3, against cardiac myosin heavy chain (MHC) with high specificity have been obtained.

Research paper thumbnail of Transcranial Doppler ultrasound in therapeutic hypothermia for children after resuscitation

Resuscitation, 2015

The aim of the present study was to assess the cerebral flow in children receiving therapeutic hy... more The aim of the present study was to assess the cerebral flow in children receiving therapeutic hypothermia after resuscitation. The prognostic value of transcranial Doppler findings was correlated with the clinical outcomes in these children. A retrospective cohort study was conducted at the paediatric intensive care unit of Chang Gung Children's Hospital between January 2011 and December 2012. All children from 1 month to 18 years of age who received therapeutic hypothermia after resuscitation were eligible. Serial transcranial Doppler examinations were performed and the findings were reviewed. Seventeen children met the eligibility criteria for this study. Fourteen patients (82.3%) were asphyxial in aetiology, and 12 (70.5%) of these cases occurred outside of the hospital. Eight patients (47.1%) had a Paediatric Cerebral Performance Score of 1 or 2 at 3 months after the events. Reversal diastolic or undetectable flow patterns during therapeutic hypothermia were associated with unfavourable prognosis. Normal mean flow velocity in the rewarming phase and normal pulsatility index in the hypothermia and rewarming phases were associated with favourable outcome. The transcranial Doppler examinations provided additional information for cerebral perfusion during therapeutic hypothermia, which may in the future be used to guide changes to hypothermia management. Mean cerebral blood flow velocity and pulsatility index by transcranial Doppler sonography can serve as a prognostic factor for children who receive therapeutic hypothermia after resuscitation.

Research paper thumbnail of Psychological Presentations Without Hepatic Involvement in Wilson Disease

Pediatric Neurology, 2006

Wilson disease is an autosomal recessive inborn error of copper metabolism that leads to neurolog... more Wilson disease is an autosomal recessive inborn error of copper metabolism that leads to neurologic symptoms and variable degrees of hepatic damage. The most common characteristic signs clinically are liver disease, psychiatric disease, neurologic disease, or a combination of these. Early recognition by means of clinical signs and an early initiation of therapy using chelators or zinc-salts are essential for a good outcome and prognosis. This report describes a male suffering from Wilson disease who exhibited an unusual presentation that included psychological manifestations without hepatic involvement. He was initially treated for attention-deficit hyperactivity disorder and a seizure disorder until brain imaging established the diagnosis of Wilson disease.

Research paper thumbnail of Therapeutic Hypothermia for Febrile Infection-Related Epilepsy Syndrome in Two Patients

Pediatric Neurology, 2012

Despite advances in critical care, febrile infection-related epilepsy syndrome remains the most i... more Despite advances in critical care, febrile infection-related epilepsy syndrome remains the most important cause of mortality and neurologic deficits during childhood. Only a few therapeutic agents were reported to shorten the acute phase and improve outcomes. Therapeutic hypothermia was reported effective in stabilizing immune activation, brain edema, and seizure activity, to protect the brain from ongoing functional, apoptotic neural, and glial damage and the systemic expansion of the cytokine storm. We present two pediatric cases of febrile infection-related epilepsy syndrome, refractory to conventional medical therapy. Moderate therapeutic hypothermia at 33 C resulted in fast, sustained control of refractory status epilepticus. After 3 months, both patients recovered with a Glasgow Outcome Scale score of 4. Therapeutic hypothermia may play an important role in children with febrile infection-related epilepsy syndrome.

Research paper thumbnail of Inhibition of intracellular granule movement by microinjection of monoclonal antibodies against caldesmon

Cell Motility and the Cytoskeleton, 1991

Monoclonal antibodies, C2, C9, C18, and C21, against chicken gizzard caldesmon (called high molec... more Monoclonal antibodies, C2, C9, C18, and C21, against chicken gizzard caldesmon (called high molecular weight isoform) were shown to crossreact with a low molecular weight isoform of caldesmon in chicken embryo fibroblasts (CEF). These antibodies were used in a microinjection study to investigate the in vivo function of caldesmon in nonmuscle cell motility. Injected cells did not appear to change their morphology significantly; the cells displayed a flat appearance and were able to ruffle and locomote normally. However, in the C21 injected cells, saltatory movements of granules and organelles appeared to be greatly inhibited. This inhibition of granule movement was reversible, so that by 3 hr after injection, granules in injected cells had already recovered to normal speed. The inhibition of granule movement by C21 antibody was also very specific; the average speeds of granule movement in cells injected with C2, C9, or C18 antibody, or with C21 antibody preabsorbed with caldesmon, were not significantly different from that in uninjected cells. In a previous epitope study, we demonstrated that, of the antibodies used in this study, only C21 antibody was able to compete with the binding of caldesmon to Caf +/calmodulin and to F-actin, although both C21 and C2 antibodies recognized the same carboxyl-terminal 10K fragment of gizzard caldesmon : Cell Motil. Cytoskeleton 20:95-1081. The caldesmon distribution in C21 injected cells changed from stress-fiber localization to a more diffuse appearance, when the injection was performed at 10-30 mg/ml of C21 antibody. We have previously shown that a monoclonal anti-tropomyosin antibody exhibited motility-dependent recognition of an epitope, and that microinjection of this antibody specifically inhibited intracellular granule movements of CEF cells : J . Cell Biol. 109:1141. Therefore, it is likely that tropomyosin and caldesmon may both function in intracellular granule movement by regulating the contractile system in response to [Ca++] change inside nonmuscle cells.

Research paper thumbnail of Childhood encephalitis: relationship between diffusion abnormalities and clinical outcome

Neuroradiology, 2014

The impact of restricted diffusion on clinical outcome has not been well studied in childhood enc... more The impact of restricted diffusion on clinical outcome has not been well studied in childhood encephalitis. We hypothesized that the patients with lesions with restricted diffusion (LRD) would have worse clinical outcome. We reviewed the MR studies of 83 children with encephalitis for LRD. An MRI scoring system (0-12) based on fluid-attenuated inversion recovery (FLAIR) imaging was created to evaluate the extent of imaging abnormality. Clinical outcome was graded by using Glasgow outcome scale (GOS) (1-5) in 1st and 12th month: 1 for death and five for full recovery. With respect to diffusion, the correlation between imaging score and GOS was assessed. Logistic regression analysis was used to explore the impact of diffusion and imaging score on clinical outcome. The patients were divided into three subgroups regarding imaging score: I, 0-4; II, 5-8; and III, 9-12. LRD was found in 28 patients. Negative significant correlation was found between imaging score and GOS in the group with LRD in both 1st month (R = -0.67, P < 0.001) and 12th month (R = -0.56, P = 0.001). Multivariate logistic regression showed that LRD (P < 0.001) and age (P = 0.026) were significant independent risk factors for unfavorable outcome in 1st month, and both LRD (P = 0.001) and imaging score (P = 0.043) were significant risk factors for unfavorable outcome in 12th month. Patients with LRD have a worse clinical outcome than those without LRD. In patients with LRD, those with a greater extent of abnormality have a poorer outcome.

Research paper thumbnail of Monoclonal Antibodies Against Chicken Tropomyosin Isoforms: Production, Characterization, and Application

Hybridoma, 1985

Eight mouse monoclonal antibodies, CHI, CH106, CH291, CL2, CGI, CG3, CG/32 and CG/36, against chi... more Eight mouse monoclonal antibodies, CHI, CH106, CH291, CL2, CGI, CG3, CG/32 and CG/36, against chicken tropomyosin isoforms have been prepared and characterized. The antigens recognized by these isoform-specific monoclonal antibodies were identified by both solid-phase radioimmunoassay and protein immunoblotting. To some extent, most antibodies showed isoform-specific, but one (CG3) recognized all isoforms of tropomyosin from chicken materials. The effects of monoclonal antibodies on the binding of cardiac tropomyosin to F-actin were investigated. Antibodies CHI, CH106, and CH291 had the ability to interfere with the binding of tropomyosin to F-actin, whereas others appeared to have no effect. Monoclonal antibody CL2 was able to distinguish the skeletal muscle tropomyosin-enriched microfilaments from the fibroblastic tropomyosin-enriched microfilaments of differentiating muscle cells. This antibody will be most useful for studying the córnpartmentalization of microfilaments and microfilament-associated proteins, particularly actin and tropomyosin isoforms during muscle differentiation. Immunofluorescence microscopy with CGI antibody which recognized CEF tropomyosin isoforms 1 and 3 revealed the continuous staining of stress fibers in some populations of CEF cells. On the other hand, both periodic fluorescent staining and continuous staining of stress fibers were observed with CG3 antibody in all CEF cells.

Research paper thumbnail of Pericardial effusion with cardiac tamponade as a cardiac manifestation of duchenne muscular dystrophy

Muscle & Nerve, 2009

Duchenne muscular dystrophy (DMD) is the most common hereditary neuromuscular disease in children... more Duchenne muscular dystrophy (DMD) is the most common hereditary neuromuscular disease in children. It is an X-linked hereditary dystrophinopathy due to the absence of dystrophin. Its onset is often in early childhood and presents with proximal distribution of weakness and a progressive course. Cardiac involvement in DMD is common, and its onset is usually after the age of 10 years. The most common cardiac manifestations are a dilated cardiomyopathy and cardiac arrhythmia. However, pericardial effusion with cardiac tamponade is a very rare cardiac complication of DMD. We report a boy with DMD who initially presented with progressive dyspnea and an enlarged cardiac silhouette on chest radiography who subsequently developed a large pericardial effusion with cardiac tamponade. Early recognition of pericardial effusion with cardiac tamponade is important for institution appropriate therapy.

Research paper thumbnail of Hemorrhagic Stroke Associated with Pulmonary Edema and Catastrophic Cardiac Failure

Pediatrics & Neonatology, 2008

:97−100 Cerebral arteriovenous fistula (AVF) is a vascular malformation that is rare in the pedia... more :97−100 Cerebral arteriovenous fistula (AVF) is a vascular malformation that is rare in the pediatric population. Older children with cerebral AVF tend to present with neurologic problems related to intracranial venous hypertension or intracranial hemorrhage. Cardiac and pulmonary complications following acute neurologic injury such as subarachnoid hemorrhage are common in adults, but are rarely reported in children. However, complications have been reported in cases of enterovirus 71 rhombencephalitis in infants and children and can cause high morbidity and mortality. Here, we report a 14-year-old boy who presented with cardiac failure associated with pulmonary edema following cerebral hemorrhagic stroke due to AVF. After aggressive investigation and management, we intervened before significant hypoxia and hypotension developed, potentially reducing the risk of long-term adverse neurologic consequences in this patient.

Research paper thumbnail of Tropomyosin Isoforms in Nonmuscle Cells

International Review of Cytology, 1997

Research paper thumbnail of Xin Scaffolding Proteins and Cardiac Conduction Defects

1st Annual International Conference on Advanced Research: Physiology (ARP 2014), 2014

Research paper thumbnail of Reactive Resonance in a Polyatomic Reaction

Physical Review Letters, 2004

In the course of an extensive investigation aimed at understanding the detailed mechanisms of a p... more In the course of an extensive investigation aimed at understanding the detailed mechanisms of a prototypical polyatomic reaction, several remarkable observations were uncovered. To interpret these findings, we surmise the existence of a reactive resonance in this polyatomic reaction. The reaction of concern is F+CH4-->HF+CH3, and the abnormal attributes were revealed only near the reaction threshold. The discovery of reactive resonance in a polyatomic reaction is more than just an extension from a typical atom+diatom reaction. As shown here, it holds great promise to disentangle the elusive intramolecular vibrational dynamics of transient collision complex in the critical transition-state region.

Research paper thumbnail of Dynamics of reactions between two closed-shell molecules

Physical Chemistry Chemical Physics, 2011

The crossed molecular beam technique has been utilized to investigate a large number of elementar... more The crossed molecular beam technique has been utilized to investigate a large number of elementary reactions. However, most of the studied reactions involve atoms or radicals; reactions between two stable molecular reactants are, in fact, seldom studied with the crossed molecular beam method. In this perspective, reactions between two stable molecules are reviewed and discussed. With crossed molecular beams and vacuum UV photoionization, the nascent products have been unambiguously identified. Consistent pictures of the reaction paths have been constructed based on the experimental data and ab initio calculations. Furthermore, there are intriguing features about the reaction barriers. The F(2) + organosulfur reactions are barrierless, demonstrating the first examples of such interactions between two closed-shell reactants. The barrier of F(2) + alkene reaction decreases with more methyl substitution groups at the C=C double bond, yet the absolute barrier heights from experiment and theory disagree with each other by ~2 kcal mol(-1), leaving an issue to be resolved in the future.

Research paper thumbnail of Thin Filament Changes during In Vivo Rat Heart Development

Pediatric Research, 1991

Developmental differences in myocardial performance are known to exist. It is likely that the pro... more Developmental differences in myocardial performance are known to exist. It is likely that the profile of protein isoforms present on the developing thin filament contributes to these observed differences. We have prepared thin filaments from developing and mature rat hearts by using an immunoprecipitation procedure developed in our laboratory. Analysis of these isolated thin filaments by Western immunoblots and two-dimensional gel electrophoresis demonstrates troponin I and troponin T isoform switching on the developing thin filament. Troponin I isoform switching begins by embryonic d 18 and is complete before the 3rd postnatal wk. Troponin T isoform switching begins between embryonic d 18 and birth and is complete between the 2nd and 3rd postnatal wk. The degree of phosphorylation of tropomyosin in thin filaments appears to be developmentally regulated, decreasing with advancing age. Nonmuscle isoforms of tropomyosin are also detectable in thin filaments from developing and mature rat hearts. These phenomena (troponin isoform switching, the degree of phosphorylation of tropomyosin, and the presence of nonmuscle isoforms of tropomyosin on cardiac thin filaments) likely play a role in the function of immature thin filaments and in the assembly of mature thin filaments. (Pediatr Res 30: 232-238, 1991)

Research paper thumbnail of Therapeutic Hypothermia Associated With Increased Survival After Resuscitation in Children

Pediatric Neurology, 2013

Brain injury after resuscitation is associated with high morbidity and mortality in children. The... more Brain injury after resuscitation is associated with high morbidity and mortality in children. Therapeutic hypothermia has theoretical benefits on brain preservation. It has been shown to be effective in improving neurological outcomes after adult ventricular arrhythmia-induced cardiac arrest and neonatal asphyxia. However, there have only been a few reports about therapeutic hypothermia after pediatric resuscitation. We conducted this retrospective cohort study in a tertiary pediatric intensive care unit between January 2010 and June 2012. All children from 2 months to 18 years of age with resuscitation and a history of at least 3 minutes of chest compressions with survival for 12 hours or more after return of circulation were eligible. Forty-three patients met the eligibility criteria for the study. Forty-two patients (97.6%) were asphyxial in etiology; 29 (67.4%) of them occurred out-of-hospital. Excluding one child with cardiac etiology, the overall survival rate to hospital discharge was 57.1%. Fourteen (33.3%) patients received hypothermia therapy and were cooled to 33 C for 72 hours. The survival rate was higher in the therapeutic hypothermia group (11/14, 78.6%) than in the normothermia group (13/28, 46.4%). In conclusion, therapeutic hypothermia was associated with increased survival rate after pediatric resuscitation.

Research paper thumbnail of Characterization of Cardiomyocyte-Like Cells in Thoracic Blood Vessels

Research paper thumbnail of Autoantibodies against human tropomyosin isoform 5 in ulcerative colitis destroys colonic epithelial cells through antibody and complement-mediated lysis

Introduction. Patients with ulcerative colitis (UC) have IgG1 antibodies in serum and colon again... more Introduction. Patients with ulcerative colitis (UC) have IgG1 antibodies in serum and colon against human tropomyosin isoform 5 (hTM5), a cytoskeletal microfilament protein found intracellularly and on the surface of colonic epithelial cells (EC). These antibodies may be pathogenic in UC.

Research paper thumbnail of Xin Scaffolding Proteins and Arrhythmias

Journal of cardiology & clinical research, Jan 24, 2013

Research paper thumbnail of Chapter 1: roles of caldesmon in cell motility and actin cytoskeleton remodeling

International review of cell and molecular biology

Caldesmon (CaD) is a multimodular protein that regulates contractility and actin cytoskeleton rem... more Caldesmon (CaD) is a multimodular protein that regulates contractility and actin cytoskeleton remodeling in smooth muscle and nonmuscle cells. A single gene (CALD1) encodes high molecular mass CaD (h-CaD) and low molecular mass CaD (l-CaD) by alternative splicings. The h-CaD exclusively expresses in smooth muscle, whereas the l-CaD ubiquitously expresses in all cell types except skeletal muscle. The h-CaD/l-CaD ratio could be a marker for monitoring differentiating and pathological states of smooth muscles. The l-CaD associates with stress fibers and membrane ruffles in nonmuscle cells and with the actin core of podosomes in highly motile/invasive cells. Together with tropomyosin, CaD stabilizes actin filaments and inhibits actin-tropomyosin-activated myosin ATPase activity. This inhibition can be effectively released by Ca(2+)-calmodulin and/or by phosphorylation with various kinases. Through its interactions with a spectrum of actin-binding proteins, CaD modulates dynamics of cort...

Research paper thumbnail of Characterization of cis-regulatory elements and transcription factor binding: gel mobility shift assay

Methods in molecular biology (Clifton, N.J.), 2007

To understand how cardiac gene expression is regulated, the identification and characterization o... more To understand how cardiac gene expression is regulated, the identification and characterization of cis-regulatory elements and their trans-acting factors by gel mobility shift assay (GMSA) or gel retardation assay are essential and common steps. In addition to providing a general protocol for GMSA, this chapter describes some applications of this assay to characterize cardiac-specific and ubiquitous trans-acting factors bound to regulatory elements [novel TCTG(G/C) direct repeat and A/T-rich region] of the rat cardiac troponin T promoter. In GMSA, the specificity of the binding of trans-acting factor to labeled DNA probe should be verified by the addition of unlabeled probe in the reaction mixture. The migratory property of DNA-protein complexes formed by protein extracts prepared from different tissues can be compared to determine the tissue specificity of trans-acting factors. GMSA, coupled with specific antibody to trans-acting factor (antibody supershift assay), is used to ident...

Research paper thumbnail of Monoclonal Antibodies Against Cardiac Myosin Heavy Chain

Hybridoma, 1990

Three mouse IgG monoclonal antibodies (MAbs), named FAl, FA2, and FA3, against cardiac myosin hea... more Three mouse IgG monoclonal antibodies (MAbs), named FAl, FA2, and FA3, against cardiac myosin heavy chain (MHC) with high specificity have been obtained.

Research paper thumbnail of Transcranial Doppler ultrasound in therapeutic hypothermia for children after resuscitation

Resuscitation, 2015

The aim of the present study was to assess the cerebral flow in children receiving therapeutic hy... more The aim of the present study was to assess the cerebral flow in children receiving therapeutic hypothermia after resuscitation. The prognostic value of transcranial Doppler findings was correlated with the clinical outcomes in these children. A retrospective cohort study was conducted at the paediatric intensive care unit of Chang Gung Children's Hospital between January 2011 and December 2012. All children from 1 month to 18 years of age who received therapeutic hypothermia after resuscitation were eligible. Serial transcranial Doppler examinations were performed and the findings were reviewed. Seventeen children met the eligibility criteria for this study. Fourteen patients (82.3%) were asphyxial in aetiology, and 12 (70.5%) of these cases occurred outside of the hospital. Eight patients (47.1%) had a Paediatric Cerebral Performance Score of 1 or 2 at 3 months after the events. Reversal diastolic or undetectable flow patterns during therapeutic hypothermia were associated with unfavourable prognosis. Normal mean flow velocity in the rewarming phase and normal pulsatility index in the hypothermia and rewarming phases were associated with favourable outcome. The transcranial Doppler examinations provided additional information for cerebral perfusion during therapeutic hypothermia, which may in the future be used to guide changes to hypothermia management. Mean cerebral blood flow velocity and pulsatility index by transcranial Doppler sonography can serve as a prognostic factor for children who receive therapeutic hypothermia after resuscitation.

Research paper thumbnail of Psychological Presentations Without Hepatic Involvement in Wilson Disease

Pediatric Neurology, 2006

Wilson disease is an autosomal recessive inborn error of copper metabolism that leads to neurolog... more Wilson disease is an autosomal recessive inborn error of copper metabolism that leads to neurologic symptoms and variable degrees of hepatic damage. The most common characteristic signs clinically are liver disease, psychiatric disease, neurologic disease, or a combination of these. Early recognition by means of clinical signs and an early initiation of therapy using chelators or zinc-salts are essential for a good outcome and prognosis. This report describes a male suffering from Wilson disease who exhibited an unusual presentation that included psychological manifestations without hepatic involvement. He was initially treated for attention-deficit hyperactivity disorder and a seizure disorder until brain imaging established the diagnosis of Wilson disease.

Research paper thumbnail of Therapeutic Hypothermia for Febrile Infection-Related Epilepsy Syndrome in Two Patients

Pediatric Neurology, 2012

Despite advances in critical care, febrile infection-related epilepsy syndrome remains the most i... more Despite advances in critical care, febrile infection-related epilepsy syndrome remains the most important cause of mortality and neurologic deficits during childhood. Only a few therapeutic agents were reported to shorten the acute phase and improve outcomes. Therapeutic hypothermia was reported effective in stabilizing immune activation, brain edema, and seizure activity, to protect the brain from ongoing functional, apoptotic neural, and glial damage and the systemic expansion of the cytokine storm. We present two pediatric cases of febrile infection-related epilepsy syndrome, refractory to conventional medical therapy. Moderate therapeutic hypothermia at 33 C resulted in fast, sustained control of refractory status epilepticus. After 3 months, both patients recovered with a Glasgow Outcome Scale score of 4. Therapeutic hypothermia may play an important role in children with febrile infection-related epilepsy syndrome.

Research paper thumbnail of Inhibition of intracellular granule movement by microinjection of monoclonal antibodies against caldesmon

Cell Motility and the Cytoskeleton, 1991

Monoclonal antibodies, C2, C9, C18, and C21, against chicken gizzard caldesmon (called high molec... more Monoclonal antibodies, C2, C9, C18, and C21, against chicken gizzard caldesmon (called high molecular weight isoform) were shown to crossreact with a low molecular weight isoform of caldesmon in chicken embryo fibroblasts (CEF). These antibodies were used in a microinjection study to investigate the in vivo function of caldesmon in nonmuscle cell motility. Injected cells did not appear to change their morphology significantly; the cells displayed a flat appearance and were able to ruffle and locomote normally. However, in the C21 injected cells, saltatory movements of granules and organelles appeared to be greatly inhibited. This inhibition of granule movement was reversible, so that by 3 hr after injection, granules in injected cells had already recovered to normal speed. The inhibition of granule movement by C21 antibody was also very specific; the average speeds of granule movement in cells injected with C2, C9, or C18 antibody, or with C21 antibody preabsorbed with caldesmon, were not significantly different from that in uninjected cells. In a previous epitope study, we demonstrated that, of the antibodies used in this study, only C21 antibody was able to compete with the binding of caldesmon to Caf +/calmodulin and to F-actin, although both C21 and C2 antibodies recognized the same carboxyl-terminal 10K fragment of gizzard caldesmon : Cell Motil. Cytoskeleton 20:95-1081. The caldesmon distribution in C21 injected cells changed from stress-fiber localization to a more diffuse appearance, when the injection was performed at 10-30 mg/ml of C21 antibody. We have previously shown that a monoclonal anti-tropomyosin antibody exhibited motility-dependent recognition of an epitope, and that microinjection of this antibody specifically inhibited intracellular granule movements of CEF cells : J . Cell Biol. 109:1141. Therefore, it is likely that tropomyosin and caldesmon may both function in intracellular granule movement by regulating the contractile system in response to [Ca++] change inside nonmuscle cells.

Research paper thumbnail of Childhood encephalitis: relationship between diffusion abnormalities and clinical outcome

Neuroradiology, 2014

The impact of restricted diffusion on clinical outcome has not been well studied in childhood enc... more The impact of restricted diffusion on clinical outcome has not been well studied in childhood encephalitis. We hypothesized that the patients with lesions with restricted diffusion (LRD) would have worse clinical outcome. We reviewed the MR studies of 83 children with encephalitis for LRD. An MRI scoring system (0-12) based on fluid-attenuated inversion recovery (FLAIR) imaging was created to evaluate the extent of imaging abnormality. Clinical outcome was graded by using Glasgow outcome scale (GOS) (1-5) in 1st and 12th month: 1 for death and five for full recovery. With respect to diffusion, the correlation between imaging score and GOS was assessed. Logistic regression analysis was used to explore the impact of diffusion and imaging score on clinical outcome. The patients were divided into three subgroups regarding imaging score: I, 0-4; II, 5-8; and III, 9-12. LRD was found in 28 patients. Negative significant correlation was found between imaging score and GOS in the group with LRD in both 1st month (R = -0.67, P < 0.001) and 12th month (R = -0.56, P = 0.001). Multivariate logistic regression showed that LRD (P < 0.001) and age (P = 0.026) were significant independent risk factors for unfavorable outcome in 1st month, and both LRD (P = 0.001) and imaging score (P = 0.043) were significant risk factors for unfavorable outcome in 12th month. Patients with LRD have a worse clinical outcome than those without LRD. In patients with LRD, those with a greater extent of abnormality have a poorer outcome.

Research paper thumbnail of Monoclonal Antibodies Against Chicken Tropomyosin Isoforms: Production, Characterization, and Application

Hybridoma, 1985

Eight mouse monoclonal antibodies, CHI, CH106, CH291, CL2, CGI, CG3, CG/32 and CG/36, against chi... more Eight mouse monoclonal antibodies, CHI, CH106, CH291, CL2, CGI, CG3, CG/32 and CG/36, against chicken tropomyosin isoforms have been prepared and characterized. The antigens recognized by these isoform-specific monoclonal antibodies were identified by both solid-phase radioimmunoassay and protein immunoblotting. To some extent, most antibodies showed isoform-specific, but one (CG3) recognized all isoforms of tropomyosin from chicken materials. The effects of monoclonal antibodies on the binding of cardiac tropomyosin to F-actin were investigated. Antibodies CHI, CH106, and CH291 had the ability to interfere with the binding of tropomyosin to F-actin, whereas others appeared to have no effect. Monoclonal antibody CL2 was able to distinguish the skeletal muscle tropomyosin-enriched microfilaments from the fibroblastic tropomyosin-enriched microfilaments of differentiating muscle cells. This antibody will be most useful for studying the córnpartmentalization of microfilaments and microfilament-associated proteins, particularly actin and tropomyosin isoforms during muscle differentiation. Immunofluorescence microscopy with CGI antibody which recognized CEF tropomyosin isoforms 1 and 3 revealed the continuous staining of stress fibers in some populations of CEF cells. On the other hand, both periodic fluorescent staining and continuous staining of stress fibers were observed with CG3 antibody in all CEF cells.

Research paper thumbnail of Pericardial effusion with cardiac tamponade as a cardiac manifestation of duchenne muscular dystrophy

Muscle & Nerve, 2009

Duchenne muscular dystrophy (DMD) is the most common hereditary neuromuscular disease in children... more Duchenne muscular dystrophy (DMD) is the most common hereditary neuromuscular disease in children. It is an X-linked hereditary dystrophinopathy due to the absence of dystrophin. Its onset is often in early childhood and presents with proximal distribution of weakness and a progressive course. Cardiac involvement in DMD is common, and its onset is usually after the age of 10 years. The most common cardiac manifestations are a dilated cardiomyopathy and cardiac arrhythmia. However, pericardial effusion with cardiac tamponade is a very rare cardiac complication of DMD. We report a boy with DMD who initially presented with progressive dyspnea and an enlarged cardiac silhouette on chest radiography who subsequently developed a large pericardial effusion with cardiac tamponade. Early recognition of pericardial effusion with cardiac tamponade is important for institution appropriate therapy.

Research paper thumbnail of Hemorrhagic Stroke Associated with Pulmonary Edema and Catastrophic Cardiac Failure

Pediatrics & Neonatology, 2008

:97−100 Cerebral arteriovenous fistula (AVF) is a vascular malformation that is rare in the pedia... more :97−100 Cerebral arteriovenous fistula (AVF) is a vascular malformation that is rare in the pediatric population. Older children with cerebral AVF tend to present with neurologic problems related to intracranial venous hypertension or intracranial hemorrhage. Cardiac and pulmonary complications following acute neurologic injury such as subarachnoid hemorrhage are common in adults, but are rarely reported in children. However, complications have been reported in cases of enterovirus 71 rhombencephalitis in infants and children and can cause high morbidity and mortality. Here, we report a 14-year-old boy who presented with cardiac failure associated with pulmonary edema following cerebral hemorrhagic stroke due to AVF. After aggressive investigation and management, we intervened before significant hypoxia and hypotension developed, potentially reducing the risk of long-term adverse neurologic consequences in this patient.

Research paper thumbnail of Tropomyosin Isoforms in Nonmuscle Cells

International Review of Cytology, 1997

Research paper thumbnail of Xin Scaffolding Proteins and Cardiac Conduction Defects

1st Annual International Conference on Advanced Research: Physiology (ARP 2014), 2014

Research paper thumbnail of Reactive Resonance in a Polyatomic Reaction

Physical Review Letters, 2004

In the course of an extensive investigation aimed at understanding the detailed mechanisms of a p... more In the course of an extensive investigation aimed at understanding the detailed mechanisms of a prototypical polyatomic reaction, several remarkable observations were uncovered. To interpret these findings, we surmise the existence of a reactive resonance in this polyatomic reaction. The reaction of concern is F+CH4-->HF+CH3, and the abnormal attributes were revealed only near the reaction threshold. The discovery of reactive resonance in a polyatomic reaction is more than just an extension from a typical atom+diatom reaction. As shown here, it holds great promise to disentangle the elusive intramolecular vibrational dynamics of transient collision complex in the critical transition-state region.

Research paper thumbnail of Dynamics of reactions between two closed-shell molecules

Physical Chemistry Chemical Physics, 2011

The crossed molecular beam technique has been utilized to investigate a large number of elementar... more The crossed molecular beam technique has been utilized to investigate a large number of elementary reactions. However, most of the studied reactions involve atoms or radicals; reactions between two stable molecular reactants are, in fact, seldom studied with the crossed molecular beam method. In this perspective, reactions between two stable molecules are reviewed and discussed. With crossed molecular beams and vacuum UV photoionization, the nascent products have been unambiguously identified. Consistent pictures of the reaction paths have been constructed based on the experimental data and ab initio calculations. Furthermore, there are intriguing features about the reaction barriers. The F(2) + organosulfur reactions are barrierless, demonstrating the first examples of such interactions between two closed-shell reactants. The barrier of F(2) + alkene reaction decreases with more methyl substitution groups at the C=C double bond, yet the absolute barrier heights from experiment and theory disagree with each other by ~2 kcal mol(-1), leaving an issue to be resolved in the future.

Research paper thumbnail of Thin Filament Changes during In Vivo Rat Heart Development

Pediatric Research, 1991

Developmental differences in myocardial performance are known to exist. It is likely that the pro... more Developmental differences in myocardial performance are known to exist. It is likely that the profile of protein isoforms present on the developing thin filament contributes to these observed differences. We have prepared thin filaments from developing and mature rat hearts by using an immunoprecipitation procedure developed in our laboratory. Analysis of these isolated thin filaments by Western immunoblots and two-dimensional gel electrophoresis demonstrates troponin I and troponin T isoform switching on the developing thin filament. Troponin I isoform switching begins by embryonic d 18 and is complete before the 3rd postnatal wk. Troponin T isoform switching begins between embryonic d 18 and birth and is complete between the 2nd and 3rd postnatal wk. The degree of phosphorylation of tropomyosin in thin filaments appears to be developmentally regulated, decreasing with advancing age. Nonmuscle isoforms of tropomyosin are also detectable in thin filaments from developing and mature rat hearts. These phenomena (troponin isoform switching, the degree of phosphorylation of tropomyosin, and the presence of nonmuscle isoforms of tropomyosin on cardiac thin filaments) likely play a role in the function of immature thin filaments and in the assembly of mature thin filaments. (Pediatr Res 30: 232-238, 1991)

Research paper thumbnail of Therapeutic Hypothermia Associated With Increased Survival After Resuscitation in Children

Pediatric Neurology, 2013

Brain injury after resuscitation is associated with high morbidity and mortality in children. The... more Brain injury after resuscitation is associated with high morbidity and mortality in children. Therapeutic hypothermia has theoretical benefits on brain preservation. It has been shown to be effective in improving neurological outcomes after adult ventricular arrhythmia-induced cardiac arrest and neonatal asphyxia. However, there have only been a few reports about therapeutic hypothermia after pediatric resuscitation. We conducted this retrospective cohort study in a tertiary pediatric intensive care unit between January 2010 and June 2012. All children from 2 months to 18 years of age with resuscitation and a history of at least 3 minutes of chest compressions with survival for 12 hours or more after return of circulation were eligible. Forty-three patients met the eligibility criteria for the study. Forty-two patients (97.6%) were asphyxial in etiology; 29 (67.4%) of them occurred out-of-hospital. Excluding one child with cardiac etiology, the overall survival rate to hospital discharge was 57.1%. Fourteen (33.3%) patients received hypothermia therapy and were cooled to 33 C for 72 hours. The survival rate was higher in the therapeutic hypothermia group (11/14, 78.6%) than in the normothermia group (13/28, 46.4%). In conclusion, therapeutic hypothermia was associated with increased survival rate after pediatric resuscitation.