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Papers by Katherine Liu

Advances in Inorganic Chemistry, 1995

... Biophys. Acta 952,220 (1988). 41. Rosenzweig, AC, Frederick, CA, Lippard, SJ, and Nordlund, P... more ... Biophys. Acta 952,220 (1988). 41. Rosenzweig, AC, Frederick, CA, Lippard, SJ, and Nordlund, P.,Nature (London) 366,537 (1993). 42. DeRose, VJ, Liu, KE, Kurtz, DM, Jr., Hoffman, BM, and Lippard, SJ, J . A m . Chem. SOC. 115,6440 (1993). 43. ...

Advances in Inorganic Chemistry, 1995

... Biophys. Acta 952,220 (1988). 41. Rosenzweig, AC, Frederick, CA, Lippard, SJ, and Nordlund, P... more ... Biophys. Acta 952,220 (1988). 41. Rosenzweig, AC, Frederick, CA, Lippard, SJ, and Nordlund, P.,Nature (London) 366,537 (1993). 42. DeRose, VJ, Liu, KE, Kurtz, DM, Jr., Hoffman, BM, and Lippard, SJ, J . A m . Chem. SOC. 115,6440 (1993). 43. ...

Journal of The American Chemical Society, 1993

Received March 22, 1993 The hydroxylase component of methane monooxygenase (MMO) belongs to a rec... more Received March 22, 1993 The hydroxylase component of methane monooxygenase (MMO) belongs to a recently identified class of non-heme iron carboxylate proteins including hemerythrin, ribonucleotide re-ductase, and purple acid phosphatase, all of which ...

Journal of The American Chemical Society, 1993

Studies of the Hydroxylation of Hydrocarbons by Methane ... Katherine E. Liu,+ Cathy C. Johnson,t... more Studies of the Hydroxylation of Hydrocarbons by Methane ... Katherine E. Liu,+ Cathy C. Johnson,t Martin Newcomb,*,* and Stephen J. Lippard**t Contribution from the Departments of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 021 39, ...

Journal of The American Chemical Society, 1994

Katherine E. Liu,'a Danli Wang,lb Boi Hanh Huynh,*Jb Dale E. Edmondson,lc Athanasios Salifog... more Katherine E. Liu,'a Danli Wang,lb Boi Hanh Huynh,*Jb Dale E. Edmondson,lc Athanasios Salifoglou,la and Stephen J. Lippard'Ja ... Department of Chemistry Massachusetts Institute of Technology Cambridge, Massachusetts 021 39 Departments of Physics and ...

Journal of The American Chemical Society, 1995

The zinc and cobalt forms of the prototypic γ-carbonic anhydrase from Methanosarcina thermophila ... more The zinc and cobalt forms of the prototypic γ-carbonic anhydrase from Methanosarcina thermophila were characterized by extended X-ray absorption fine structure (EXAFS) and the kinetics were investigated using steady-state spectrophotometric and 18 O exchange equilibrium assays. EXAFS results indicate that cobalt isomorphously replaces zinc and that the metals coordinate three histidines and two or three water molecules. The efficiency of either Zn-Cam or Co-Cam for CO 2 hydration (k cat /K m ) was severalfold greater than HCO 3dehydration at physiological pH values, a result consistent with the proposed physiological function for Cam during growth on acetate. For both Zn-and Co-Cam, the steady-state parameter k cat for CO 2 hydration was pH-dependent with a pK a of 6.5-6.8, whereas k cat / K m was dependent on two ionizations with pK a values of 6.7-6.9 and 8.2-8.4. The 18 O exchange assay also identified two ionizable groups in the pH profile of k cat /K m with apparent pK a values of 6.0 and 8.1. The steady-state parameter k cat (CO 2 hydration) is buffer-dependent in a saturable manner at pH 8.2, and the kinetic analysis suggested a ping-pong mechanism in which buffer is the second substrate. The calculated rate constant for intermolecular proton transfer is 3 × 10 7 M -1 s -1 . At saturating buffer concentrations and pH 8.5, k cat is 2.6-fold higher in H 2 O than in D 2 O, suggesting that an intramolecular proton transfer step is at least partially rate-determining. At high pH (pH > 8), k cat /K m is not dependent on buffer and no solvent hydrogen isotope effect was observed, consistent with a zinc hydroxide mechanism. Therefore, at high pH the catalytic mechanism of Cam appears to resemble that of human CAII, despite significant structural differences in the active sites of these two unrelated enzymes.

Journal of The American Chemical Society, 1996

Despite the steric caveat, hydroxylations of simple alkanes by hepatic P-450 enzymes generally fo... more Despite the steric caveat, hydroxylations of simple alkanes by hepatic P-450 enzymes generally follow the pattern of reactivity observed in hydrogen atom abstraction reactions of the alkanes with alkoxyl radicals. For example, microsomal rat liver P-450 and a purified P-450 ...

Journal of The American Chemical Society, 1997

The tritiated chiral alkanes (S)were oxidized by soluble methane monooxygenase (sMMO) from Methyl... more The tritiated chiral alkanes (S)were oxidized by soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath), and the absolute stereochemistry of the resulting product alcohols was determined in order to probe the mechanism of substrate hydroxylation. When purified hydroxylase, coupling protein, and reductase components were used, the product alcohol displayed 72% retention of stereochemistry at the labeled carbon for the ethane substrates and 77% retention for the butanes labeled at the primary carbon. A putative alkyl radical which would yield these product distributions would have a lifetime of 100 fs, a value too short to correspond to a discrete intermediate. Intramolecular k H /k D ratios of 3.4 and 2.2 were determined for ethane and butane, respectively. When the hydroxylations were performed with purified hydroxylase but only a partially purified cellular extract for the coupling and reductase proteins, different product distributions were observed. These apparently anomalous results could be explained by invoking exchange of hydrogen atoms at the R carbon of the product alcohols. The characteristics of this exchange reaction are discussed. Hydroxylation of [2-3 H]butanes by the latter system yielded ∼90% retention of stereochemistry at the labeled carbon. The implication of these results for the catalytic mechanism of sMMO is discussed. Together with the mechanistic information available from a range of substrate probes, the results are best accounted for by a nonsynchronous concerted process involving attack on the C-H bond by one or more of several pathways discussed in the text. ponent (H) which binds the hydrocarbon substrate and dioxygen, 8 a reductase (R) containing Fe 2 S 2 and FAD cofactors which enable it to accept electrons from NADH and transfer them to the hydroxylase, 10,13 and a regulatory or coupling component, protein B. 14,15 In addition to methane, the sMMO system can oxidize a wide variety of substrates. [16][17][18] X-ray crystallographic studies of the resting, diferric form of the M. capsulatus (Bath) hydroxylase, 19,20 EPR and ENDOR

Journal of The American Chemical Society, 1995

The resonance Raman spectra reported in these three papers have been found to be unreliable and t... more The resonance Raman spectra reported in these three papers have been found to be unreliable and to consist mainly of artifacts. However, the non-Raman data [specifically the IR spectra of the CODH cyanide adduct in the second paper [ ], and the kinetic absorption data for MMO in the third [ ]] are reliable. We are confident that all the samples were properly prepared and contained the reaction intermediates under investigation. However, we have been unable to reproduce the Raman spectra with fresh samples, and judge the published spectra to be artifacts resulting from electronic processing of the data.

Analytical Chemistry, 1989

Page 1. Anal. Chem. 1989, 61, 2599-2602 2599 Electroanalysis of Aromatic Aldehydes with Modified ... more Page 1. Anal. Chem. 1989, 61, 2599-2602 2599 Electroanalysis of Aromatic Aldehydes with Modified Carbon Paste Electrodes Katherine E. Liu and HBctor D. Abruiia* Department of Chemistry, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301 ...

British Journal of Ophthalmology, 2008

To study the effect of posterior capsular opacification (PCO) on vision and visual function in pa... more To study the effect of posterior capsular opacification (PCO) on vision and visual function in patients undergoing cataract surgery in rural China, and to compare this with the effect of refractive error. Patients undergoing cataract surgery in at least one eye by local surgeons in a rural setting between 8 August and 31 December 2005 were examined with slit lamp grading of PCO 10-14 months after surgery. Subjects with any PCO associated with best-corrected visual acuity of 6/7.5 or worse, or with grade 2+ or worse PCO without visual decrement, were offered YAG laser capsulotomy. Vision and self-reported visual function were assessed, and various demographic and clinical factors potentially associated with PCO were recorded. Of 313 patients operated on within the study window, 239 (76%) could be contacted by telephone; study examinations were performed on 176 (74%). Examined subjects had a mean (SD) age of 69.4 (10.5) years, 116 (67%) were female, and 149 (86%) had been blind (presenting visual acuity < or = 6/60) in the operated eye before surgery. PCO of grade 1 or above was present in 34 of 204 operated eyes (16.7%). Those with PCO had significantly worse presenting vision (p = 0.007) but not visual function (p>0.3) than those without PCO. Women had a significantly higher prevalence of PCO (20.9%) than did men (8.6%, p<0.05). Of 19 eyes undergoing capsulotomy with best-corrected visual acuity measured the next day, 13 (68%) improved by one or more lines, and seven (37%) improved by two or more lines. Despite a higher uptake of capsulotomy (95%) as opposed to refraction (35%) in this cohort, the yield in terms of eyes with poor presenting visual acuity (< 6/18) that could be improved was higher for refraction (26% = 9/35) than for capsulotomy (9% = 3/35). The prevalence of PCO and impact on vision and visual function in this cohort was modest 1 year after surgery. However, PCO prevalence increases with time. Follow-up of this cohort is underway to determine the effectiveness of this early intervention in identifying and treating subjects who will eventually experience clinically significant PCO.

Muscle & Nerve, 2012

Amyotrophic lateral sclerosis (ALS), a degenerative disorder of the central nervous system, manif... more Amyotrophic lateral sclerosis (ALS), a degenerative disorder of the central nervous system, manifests as progressive weakening of muscles. The diagnosis and prognosis of ALS are often unclear, so useful biomarkers are needed. Total proteins were extracted from muscle samples from 36 ALS, 17 spinal muscular atrophy (SMA), and 36 normal individuals. The expression levels of 134 proteins and phosphoproteins were assessed using protein pathway array analysis. Seventeen proteins were differentially expressed between ALS and normal muscle, and 9 proteins were differentially expressed between ALS and SMA muscle. The low-level expression of Akt and Factor XIIIB correlates with unfavorable survival, and the risk score calculated based on these proteins predicts the survival of each individual patient. Some proteins could be selected as clinically useful biomarkers. Specifically, Akt and Factor XIIIB were found to be promising biomarkers for estimating prognosis in ALS.

Journal of Epidemiology and Community Health, 2007

Objectives: Following the first case in Hong Kong in 1998, the method of committing suicide by ch... more Objectives: Following the first case in Hong Kong in 1998, the method of committing suicide by charcoal burning has spread to other communities. This aim of this study was to examine the impact of charcoal burning suicides on both overall suicide rates and older-method suicide rates in Hong Kong and urban Taiwan. Design: Trend analysis of the overall and method-specific suicide rates between 1997 and 2002. Comparison of age and gender profiles of those who committed suicide by charcoal burning and other methods of suicide. Setting: Hong Kong and Urban Taiwan. Main results: Suicides by charcoal burning increased rapidly within five years in both Hong Kong and urban Taiwan. This increase was not paralleled by decreases in suicides by older methods and led to an increase of more than 20% in the overall suicide rates. Those in the 24-39 age range were more likely to choose charcoal burning than other methods. Conclusions: The lack of parallel decreases in the suicides rates of older methods with the rise of charcoal burning suicides suggests limited substitution between the methods. The preponderance of the rise in suicide deaths associated with charcoal burning suggests that its invention, followed by wide media dissemination, may have specifically contributed to the increase in suicides in both regions. As a similar increase was found in urban Taiwan as in Hong Kong, charcoal burning suicide should not be viewed as merely a local health problem and has the potential to become a major public health threat in other countries.

American Journal of Ophthalmology, 2007

Variants in the complement factor H (CFH) gene have been reported to be associated with age-relat... more Variants in the complement factor H (CFH) gene have been reported to be associated with age-related macular degeneration (AMD). We conducted a case-control association study to investigate the association of 6 single nucleotide polymorphisms (SNPs) in CFH with exudative AMD in the Chinese population. We recruited 163 cases and 244 controls, all ethnic Chinese, with complete ophthalmic examination including fundus investigation. Cigarette smoking was recorded. Six SNPs (dbSNP ID: rs3753394, rs800292, rs1061147, rs1061170, rs380390, and rs1329428) in the CFH gene were genotyped by Taqman assays. Y402H (1277 T>C) has low frequencies in our study population, 5.8% in patients and 3.9% in controls. It was not associated with exudative AMD adjusted for age, gender and smoking. Significant associations were detected for AMD with rs3753394 (p=0.003, p(corr)=0.018), rs800292 (p=0.00053, p(corr)=0.0032), and rs1329428 (p=0.00092, p(corr)=0.0028), p(corr) values obtained after adjustment for multicomparison. A haplotype containing these four SNPs (TGTC) was found to confer a significantly increased likelihood of exudative AMD with an odds ratio of 1.68 (95% CI: 1.26-2.23) p=0.0003 (p(corr)=0.0026 after correction by permutation test). Logistic regression analysis detected no interactions between the SNPs and age, gender or smoking. We have found differences in the association between the CFH gene and exudative AMD in Chinese from Caucasians and Japanese. We detected SNP rs3753394 in the CFH promoter carrying a significantly increased risk for exudative AMD.

Bone Marrow Transplantation, 2005

Methotrexate (MTX) is commonly used in the prophylaxis of graft-versus-host disease (GVHD) after ... more Methotrexate (MTX) is commonly used in the prophylaxis of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to evaluate the efficacy and safety of low-dose MTX treatment in patients with GVHD after allo-HSCT, 38 patients with acute GVHD (aGVHD), chronic GVHD (cGVHD) or GVHD post-donor lymphocyte infusion (post-DLI GVHD) after allo-HSCT received intravenous MTX at a dose of 5 or 10 mg every 5-7 days until a complete or partial response was seen, or there was treatment failure or intolerable side effects. The overall response rate was 94.7% (18/19 patients) in patients with aGVHD, 76.2% (16/21 patients) in patients with cGVHD and 2/2 in patients with post-DLI GVHD. The response rate for GVHD involving various organs was 100% in skin, 75% in gut, 55.6% in liver, 75% in mouth and 100% in the eye, among all enrolled patients. Side effects were minor. Short-term, low-dose MTX is a tolerable and an effective regimen for patients with aGVHD, cGVHD or post-DLI GVHD after allo-HSCT.

Advances in Inorganic Chemistry, 1995

... Biophys. Acta 952,220 (1988). 41. Rosenzweig, AC, Frederick, CA, Lippard, SJ, and Nordlund, P... more ... Biophys. Acta 952,220 (1988). 41. Rosenzweig, AC, Frederick, CA, Lippard, SJ, and Nordlund, P.,Nature (London) 366,537 (1993). 42. DeRose, VJ, Liu, KE, Kurtz, DM, Jr., Hoffman, BM, and Lippard, SJ, J . A m . Chem. SOC. 115,6440 (1993). 43. ...

Advances in Inorganic Chemistry, 1995

... Biophys. Acta 952,220 (1988). 41. Rosenzweig, AC, Frederick, CA, Lippard, SJ, and Nordlund, P... more ... Biophys. Acta 952,220 (1988). 41. Rosenzweig, AC, Frederick, CA, Lippard, SJ, and Nordlund, P.,Nature (London) 366,537 (1993). 42. DeRose, VJ, Liu, KE, Kurtz, DM, Jr., Hoffman, BM, and Lippard, SJ, J . A m . Chem. SOC. 115,6440 (1993). 43. ...

Journal of The American Chemical Society, 1993

Received March 22, 1993 The hydroxylase component of methane monooxygenase (MMO) belongs to a rec... more Received March 22, 1993 The hydroxylase component of methane monooxygenase (MMO) belongs to a recently identified class of non-heme iron carboxylate proteins including hemerythrin, ribonucleotide re-ductase, and purple acid phosphatase, all of which ...

Journal of The American Chemical Society, 1993

Studies of the Hydroxylation of Hydrocarbons by Methane ... Katherine E. Liu,+ Cathy C. Johnson,t... more Studies of the Hydroxylation of Hydrocarbons by Methane ... Katherine E. Liu,+ Cathy C. Johnson,t Martin Newcomb,*,* and Stephen J. Lippard**t Contribution from the Departments of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 021 39, ...

Journal of The American Chemical Society, 1994

Katherine E. Liu,'a Danli Wang,lb Boi Hanh Huynh,*Jb Dale E. Edmondson,lc Athanasios Salifog... more Katherine E. Liu,'a Danli Wang,lb Boi Hanh Huynh,*Jb Dale E. Edmondson,lc Athanasios Salifoglou,la and Stephen J. Lippard'Ja ... Department of Chemistry Massachusetts Institute of Technology Cambridge, Massachusetts 021 39 Departments of Physics and ...

Journal of The American Chemical Society, 1995

The zinc and cobalt forms of the prototypic γ-carbonic anhydrase from Methanosarcina thermophila ... more The zinc and cobalt forms of the prototypic γ-carbonic anhydrase from Methanosarcina thermophila were characterized by extended X-ray absorption fine structure (EXAFS) and the kinetics were investigated using steady-state spectrophotometric and 18 O exchange equilibrium assays. EXAFS results indicate that cobalt isomorphously replaces zinc and that the metals coordinate three histidines and two or three water molecules. The efficiency of either Zn-Cam or Co-Cam for CO 2 hydration (k cat /K m ) was severalfold greater than HCO 3dehydration at physiological pH values, a result consistent with the proposed physiological function for Cam during growth on acetate. For both Zn-and Co-Cam, the steady-state parameter k cat for CO 2 hydration was pH-dependent with a pK a of 6.5-6.8, whereas k cat / K m was dependent on two ionizations with pK a values of 6.7-6.9 and 8.2-8.4. The 18 O exchange assay also identified two ionizable groups in the pH profile of k cat /K m with apparent pK a values of 6.0 and 8.1. The steady-state parameter k cat (CO 2 hydration) is buffer-dependent in a saturable manner at pH 8.2, and the kinetic analysis suggested a ping-pong mechanism in which buffer is the second substrate. The calculated rate constant for intermolecular proton transfer is 3 × 10 7 M -1 s -1 . At saturating buffer concentrations and pH 8.5, k cat is 2.6-fold higher in H 2 O than in D 2 O, suggesting that an intramolecular proton transfer step is at least partially rate-determining. At high pH (pH > 8), k cat /K m is not dependent on buffer and no solvent hydrogen isotope effect was observed, consistent with a zinc hydroxide mechanism. Therefore, at high pH the catalytic mechanism of Cam appears to resemble that of human CAII, despite significant structural differences in the active sites of these two unrelated enzymes.

Journal of The American Chemical Society, 1996

Despite the steric caveat, hydroxylations of simple alkanes by hepatic P-450 enzymes generally fo... more Despite the steric caveat, hydroxylations of simple alkanes by hepatic P-450 enzymes generally follow the pattern of reactivity observed in hydrogen atom abstraction reactions of the alkanes with alkoxyl radicals. For example, microsomal rat liver P-450 and a purified P-450 ...

Journal of The American Chemical Society, 1997

The tritiated chiral alkanes (S)were oxidized by soluble methane monooxygenase (sMMO) from Methyl... more The tritiated chiral alkanes (S)were oxidized by soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath), and the absolute stereochemistry of the resulting product alcohols was determined in order to probe the mechanism of substrate hydroxylation. When purified hydroxylase, coupling protein, and reductase components were used, the product alcohol displayed 72% retention of stereochemistry at the labeled carbon for the ethane substrates and 77% retention for the butanes labeled at the primary carbon. A putative alkyl radical which would yield these product distributions would have a lifetime of 100 fs, a value too short to correspond to a discrete intermediate. Intramolecular k H /k D ratios of 3.4 and 2.2 were determined for ethane and butane, respectively. When the hydroxylations were performed with purified hydroxylase but only a partially purified cellular extract for the coupling and reductase proteins, different product distributions were observed. These apparently anomalous results could be explained by invoking exchange of hydrogen atoms at the R carbon of the product alcohols. The characteristics of this exchange reaction are discussed. Hydroxylation of [2-3 H]butanes by the latter system yielded ∼90% retention of stereochemistry at the labeled carbon. The implication of these results for the catalytic mechanism of sMMO is discussed. Together with the mechanistic information available from a range of substrate probes, the results are best accounted for by a nonsynchronous concerted process involving attack on the C-H bond by one or more of several pathways discussed in the text. ponent (H) which binds the hydrocarbon substrate and dioxygen, 8 a reductase (R) containing Fe 2 S 2 and FAD cofactors which enable it to accept electrons from NADH and transfer them to the hydroxylase, 10,13 and a regulatory or coupling component, protein B. 14,15 In addition to methane, the sMMO system can oxidize a wide variety of substrates. [16][17][18] X-ray crystallographic studies of the resting, diferric form of the M. capsulatus (Bath) hydroxylase, 19,20 EPR and ENDOR

Journal of The American Chemical Society, 1995

The resonance Raman spectra reported in these three papers have been found to be unreliable and t... more The resonance Raman spectra reported in these three papers have been found to be unreliable and to consist mainly of artifacts. However, the non-Raman data [specifically the IR spectra of the CODH cyanide adduct in the second paper [ ], and the kinetic absorption data for MMO in the third [ ]] are reliable. We are confident that all the samples were properly prepared and contained the reaction intermediates under investigation. However, we have been unable to reproduce the Raman spectra with fresh samples, and judge the published spectra to be artifacts resulting from electronic processing of the data.

Analytical Chemistry, 1989

Page 1. Anal. Chem. 1989, 61, 2599-2602 2599 Electroanalysis of Aromatic Aldehydes with Modified ... more Page 1. Anal. Chem. 1989, 61, 2599-2602 2599 Electroanalysis of Aromatic Aldehydes with Modified Carbon Paste Electrodes Katherine E. Liu and HBctor D. Abruiia* Department of Chemistry, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301 ...

British Journal of Ophthalmology, 2008

To study the effect of posterior capsular opacification (PCO) on vision and visual function in pa... more To study the effect of posterior capsular opacification (PCO) on vision and visual function in patients undergoing cataract surgery in rural China, and to compare this with the effect of refractive error. Patients undergoing cataract surgery in at least one eye by local surgeons in a rural setting between 8 August and 31 December 2005 were examined with slit lamp grading of PCO 10-14 months after surgery. Subjects with any PCO associated with best-corrected visual acuity of 6/7.5 or worse, or with grade 2+ or worse PCO without visual decrement, were offered YAG laser capsulotomy. Vision and self-reported visual function were assessed, and various demographic and clinical factors potentially associated with PCO were recorded. Of 313 patients operated on within the study window, 239 (76%) could be contacted by telephone; study examinations were performed on 176 (74%). Examined subjects had a mean (SD) age of 69.4 (10.5) years, 116 (67%) were female, and 149 (86%) had been blind (presenting visual acuity < or = 6/60) in the operated eye before surgery. PCO of grade 1 or above was present in 34 of 204 operated eyes (16.7%). Those with PCO had significantly worse presenting vision (p = 0.007) but not visual function (p>0.3) than those without PCO. Women had a significantly higher prevalence of PCO (20.9%) than did men (8.6%, p<0.05). Of 19 eyes undergoing capsulotomy with best-corrected visual acuity measured the next day, 13 (68%) improved by one or more lines, and seven (37%) improved by two or more lines. Despite a higher uptake of capsulotomy (95%) as opposed to refraction (35%) in this cohort, the yield in terms of eyes with poor presenting visual acuity (< 6/18) that could be improved was higher for refraction (26% = 9/35) than for capsulotomy (9% = 3/35). The prevalence of PCO and impact on vision and visual function in this cohort was modest 1 year after surgery. However, PCO prevalence increases with time. Follow-up of this cohort is underway to determine the effectiveness of this early intervention in identifying and treating subjects who will eventually experience clinically significant PCO.

Muscle & Nerve, 2012

Amyotrophic lateral sclerosis (ALS), a degenerative disorder of the central nervous system, manif... more Amyotrophic lateral sclerosis (ALS), a degenerative disorder of the central nervous system, manifests as progressive weakening of muscles. The diagnosis and prognosis of ALS are often unclear, so useful biomarkers are needed. Total proteins were extracted from muscle samples from 36 ALS, 17 spinal muscular atrophy (SMA), and 36 normal individuals. The expression levels of 134 proteins and phosphoproteins were assessed using protein pathway array analysis. Seventeen proteins were differentially expressed between ALS and normal muscle, and 9 proteins were differentially expressed between ALS and SMA muscle. The low-level expression of Akt and Factor XIIIB correlates with unfavorable survival, and the risk score calculated based on these proteins predicts the survival of each individual patient. Some proteins could be selected as clinically useful biomarkers. Specifically, Akt and Factor XIIIB were found to be promising biomarkers for estimating prognosis in ALS.

Journal of Epidemiology and Community Health, 2007

Objectives: Following the first case in Hong Kong in 1998, the method of committing suicide by ch... more Objectives: Following the first case in Hong Kong in 1998, the method of committing suicide by charcoal burning has spread to other communities. This aim of this study was to examine the impact of charcoal burning suicides on both overall suicide rates and older-method suicide rates in Hong Kong and urban Taiwan. Design: Trend analysis of the overall and method-specific suicide rates between 1997 and 2002. Comparison of age and gender profiles of those who committed suicide by charcoal burning and other methods of suicide. Setting: Hong Kong and Urban Taiwan. Main results: Suicides by charcoal burning increased rapidly within five years in both Hong Kong and urban Taiwan. This increase was not paralleled by decreases in suicides by older methods and led to an increase of more than 20% in the overall suicide rates. Those in the 24-39 age range were more likely to choose charcoal burning than other methods. Conclusions: The lack of parallel decreases in the suicides rates of older methods with the rise of charcoal burning suicides suggests limited substitution between the methods. The preponderance of the rise in suicide deaths associated with charcoal burning suggests that its invention, followed by wide media dissemination, may have specifically contributed to the increase in suicides in both regions. As a similar increase was found in urban Taiwan as in Hong Kong, charcoal burning suicide should not be viewed as merely a local health problem and has the potential to become a major public health threat in other countries.

American Journal of Ophthalmology, 2007

Variants in the complement factor H (CFH) gene have been reported to be associated with age-relat... more Variants in the complement factor H (CFH) gene have been reported to be associated with age-related macular degeneration (AMD). We conducted a case-control association study to investigate the association of 6 single nucleotide polymorphisms (SNPs) in CFH with exudative AMD in the Chinese population. We recruited 163 cases and 244 controls, all ethnic Chinese, with complete ophthalmic examination including fundus investigation. Cigarette smoking was recorded. Six SNPs (dbSNP ID: rs3753394, rs800292, rs1061147, rs1061170, rs380390, and rs1329428) in the CFH gene were genotyped by Taqman assays. Y402H (1277 T>C) has low frequencies in our study population, 5.8% in patients and 3.9% in controls. It was not associated with exudative AMD adjusted for age, gender and smoking. Significant associations were detected for AMD with rs3753394 (p=0.003, p(corr)=0.018), rs800292 (p=0.00053, p(corr)=0.0032), and rs1329428 (p=0.00092, p(corr)=0.0028), p(corr) values obtained after adjustment for multicomparison. A haplotype containing these four SNPs (TGTC) was found to confer a significantly increased likelihood of exudative AMD with an odds ratio of 1.68 (95% CI: 1.26-2.23) p=0.0003 (p(corr)=0.0026 after correction by permutation test). Logistic regression analysis detected no interactions between the SNPs and age, gender or smoking. We have found differences in the association between the CFH gene and exudative AMD in Chinese from Caucasians and Japanese. We detected SNP rs3753394 in the CFH promoter carrying a significantly increased risk for exudative AMD.

Bone Marrow Transplantation, 2005

Methotrexate (MTX) is commonly used in the prophylaxis of graft-versus-host disease (GVHD) after ... more Methotrexate (MTX) is commonly used in the prophylaxis of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to evaluate the efficacy and safety of low-dose MTX treatment in patients with GVHD after allo-HSCT, 38 patients with acute GVHD (aGVHD), chronic GVHD (cGVHD) or GVHD post-donor lymphocyte infusion (post-DLI GVHD) after allo-HSCT received intravenous MTX at a dose of 5 or 10 mg every 5-7 days until a complete or partial response was seen, or there was treatment failure or intolerable side effects. The overall response rate was 94.7% (18/19 patients) in patients with aGVHD, 76.2% (16/21 patients) in patients with cGVHD and 2/2 in patients with post-DLI GVHD. The response rate for GVHD involving various organs was 100% in skin, 75% in gut, 55.6% in liver, 75% in mouth and 100% in the eye, among all enrolled patients. Side effects were minor. Short-term, low-dose MTX is a tolerable and an effective regimen for patients with aGVHD, cGVHD or post-DLI GVHD after allo-HSCT.