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Biomedical subjects

C S Lu

Publications and source records attributed to C S Lu.

At least 19 recordsLinked to original sources
PubMed2006

The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence.

Evidence of LRRK2 haplotypes associated with Parkinson's disease (PD) risk was recently found in the Chinese population from Singapore, and a common LRRK2 missense variant, Gly2385Arg, was independently detected as a putative risk factor for PD in the Chinese population from Taiwan. To test the association between the Gly2385Arg variant in a large case-control sample of Chinese ethnicity from Singapore, and to perform functional studies of the wild type and Gly2385Arg LRRK2 protein in human cell lines. In a case-control study involving 989 Chinese subjects, the frequency of the heterozygous Gly2385Arg genotype was higher in PD compared to controls (7.3 vs. 3.6%, odds ratio = 2.1, 95% CI: 1.1-3.9, P = 0.014); these values yield an estimated population attributable risk (PAR) of approximately 4%. In a multivariate logistic regression analysis with the disease group (PD vs. controls) as the dependent variable and the genotype as an independent factor with adjustments made for the effect of age and gender, the heterozygous Gly2385Arg genotype remained associated with an increased risk of PD compared to wild type genotype (odds ratio = 2.67, 95% CI: 1.43-4.99, P = 0.002). The glycine at position 2385 is a candidate site for N-myristoylation, and the Gly2385Arg variant replaces the hydrophobic glycine with the hydrophilic arginine, and increases the net positive charge of the LRRK2 WD40 domain. In transfection studies, we demonstrated that both the wild type and Gly2385Arg variant LRRK2 protein localize to the cytoplasm and form aggregates. However, under condition of oxidative stress, the Gly2385Arg variant was more toxic and associated with a higher rate of apoptosis. Our study lends support to the contention that the Gly2385Arg is a common risk factor for PD in the Chinese population. Our bioinformatics and in-vitro studies also suggest that the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms.

Aged↗
PubMed2006

UV light induced photodegradation of malachite green on TiO2 nanoparticles.

The photodegradation of malachite green (MG), a cationic triphenylmethane dye, is examined both under different pH values and amounts of TiO(2). After 15W UV-365nm irradiation for 4h, ca. 99.9% of MG was degraded with addition of 0.5gL(-1) TiO(2) to solutions containing 50mgL(-1) of the MG dye. The HPLC-PDA-ESI-MS technique was used to obtain a better understanding on the mechanistic details of this TiO(2)-assisted photodegradation of the MG dye with UV irradiation. Five intermediates of the process were separated, identified, and characterized for the first time. The results indicated that the N-de-methylation degradation of MG dye took place in a stepwise manner to yield mono-, di-, tri-, and tetra-N-de-methylated MG species generated during the processes. Under acidic conditions, the results indicated that the photodegradation mechanism is favorable to cleavage of the whole conjugated chromophore structure of the MG dye. Under basic conditions, the results showed that the photodegradation mechanism is favorable to a formation of a series of N-de-methylated intermediates of the MG dye.

Anti-Infective Agents, Local↗
PubMed2006

Genetic and DAT imaging studies of familial parkinsonism in a Taiwanese cohort.

We here summarize the results of genetic investigations on a series of 82 parkinsonian patients from 60 families in Taiwan. We found 13 parkin patients in 7 families (12%), 2 PINK1 sibs from 1 family, and 1 LRRK2 patient from 1 family with I2012T mutation. We also identified SCA2 in 8 patients from 5 families (8%) and SCA3 in 3 patients from 1 family, all presenting with parkinsonian phenotype. In the available patients with parkin, PINK1, SCA2 and SCA3, the dopamine transporter (DAT) scan revealed that the reduction of uptake was primarily observed in the bilateral putamen, basically sharing a similar pattern with that in idiopathic Parkinson's disease. We concluded that the genetic causes contributed to about 25% of our series of familial parkinsonism. The parkin mutations and SCA2 were the most frequent genetic causes in our series with Chinese ethnicity. The results of DAT scan indicated that bilateral putamen was essentially involved in various genetically-caused familial parkinsonism.

Adult↗
PubMed2004

PARK6-linked autosomal recessive early-onset parkinsonism in Asian populations.

The authors performed linkage analysis in 39 families with autosomal recessive early-onset PD (AR-EOPD) negative for parkin and DJ-1 mutations. Eight families including three Japanese, two Taiwanese, one Turkish, one Israeli, and one Philippine showed evidence of linkage with PARK6 with multipoint log of the odds (lod) score of 9.88 at D1S2732. The results indicate worldwide distribution of PARK6-linked parkinsonism.

Age of Onset↗
PubMed2004

Two novel mutations of the glycine receptor gene in a Taiwanese hyperekplexia family.

The authors report a Taiwanese family with autosomal recessive hyperekplexia. Two novel mutations, W96C (from the paternal allele) and R344X (from the maternal allele), which are located in exon 4 and exon 7 of the GLRA1 gene, were identified in this family. A series of electrophysiologic investigations were conducted in one of the probands, and the results suggest that the "startle center" is located subcortically.

Acoustic Stimulation↗
PubMed2002

Environmental risk factors of young onset Parkinson's disease: a case-control study.

While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests certain environmental factors, such as well water drinking, herbicides and pesticides exposure, and neurotoxins, may trigger the chain of oxidative reactions culminating in the death of dopaminergic neurons in substantia nigra to cause parkinsonism. Most studies to date focused on PD with old age onset. However, there is a peculiar group of parkinsonian patients, the young onset Parkinson's disease (YOPD), in whom the age of onset is before 40. It is intriguing to know whether earlier exposure to the putative neurotoxin(s) may contribute to the earlier onset. We therefore conducted this case-control study in which 60 PD patients, 30 YOPD patients and the same number of age- and sex-matched young controls were included. Using logistic regression, we found well water drinking and head injury were risk factors for the development of YOPD. When YOPD patients were compared with PD, we found head injury and exercise were the significant predictors. Keeping all other variables constant, head injury was a risk factor and exercise appeared to be a protective factor. We conclude early exposure to well water drinking and head trauma may trigger and expedite the appearance of parkinsonian features, but such acceleration may be prevented through regular exercise.

Adult↗
PubMed2001

Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome.

CONTEXT: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. OBJECTIVE: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia. DESIGN, SETTING, AND PATIENTS: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000. MAIN OUTCOME MEASURES: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses. RESULTS: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001). CONCLUSION: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.

Aged↗
PubMed2001

Bacterial polysaccharides as vaccines--immunity and chemical characterization.

Studies on protective immunity and biochemical characterization of bacterial capsular polysaccharides have led to significant contributions to understanding of the mechanisms of infectious diseases and development of effective vaccines. Immunity to encapsulated bacteria is related to antibody response to polysaccharide (PS) antigen, interactions with T- and B-lymphocytes, and host defense mechanisms. Meningococcal, pneumococcal and Salmonella vi PSs and Haemophilus type b PS-protein conjugate vaccines have been licensed and provided effective immunity for prevention of these bacterial infections. Capsular PSs are cell-surface polymers consisting of oligosaccharide repeating units. Many PSs are highly polar and hydrophilic and interfere with cell-to-cell interactions with phagocytes. Most pneumococcal PSs are negatively charged and possess acidic components such as D-glucuronic acid and phosphate in phosphodiester bonds. Extensive immunologic cross-reactivity has been observed among bacterial capsular PSs. In infants the antibody responses to most capsular PSs are generally poor. Enhanced immunogenicity of PS antigens can be achieved through PS-protein conjugate vaccines, immunization during a critical period of perinatal development and effective antigen delivery system.

Bacterial Infections↗
PubMed2001

Particle size distribution and anion content at a traffic site in Sha-Lu, Taiwan.

Ambient air particle concentrations were sampled by two total suspended particle (TSP) samplers, PM10/PM2.5 specific sampler and micro-orifice uniform deposit impactor (MOUDI) during July-October 2000 at a traffic sampling site in central Taiwan. The average TSP concentration (194 microg/m3) was about a factor of two higher than that of the fraction <2.5 microm (93.2 microg/m3). The mean level of the fraction <10 microm collected by MOUDI (93.2 microg/m3) was about 1 1/2 times higher than that of the size class <2.5 microm (43.8 microg/m3). Furthermore, this fraction showed a certain correlation with the TSP concentration. The particle size distribution was bimodal in the ambient air at the traffic site. The major peaks appear at particle diameters between 0.56-1.0 and 3.2-5.6 microm. The percentages of anions contained in TSP were 0.24% F-, 13.7% Cl, 0.52% Br, 12.0% NO-, 18.9% NO2-, and 54.6% SO2-. The Cl-, NO2-, and NO3- size distributions were all unimodal and the major peaks appeared at 3.2-5.6 microm. The SO2 size distribution was bimodal, with major peaks at 0.32-0.56 and 3.2-5.6.

Air Pollutants↗
PubMed2001

The optimal imaging time for [99Tcm]TRODAT-1/SPET in normal subjects and patients with Parkinson's disease.

Imaging of dopamine transporters (DATs) in the brain using [99Tcm]TRODAT-1 showed excellent pharmacokinetics for estimation of transporter concentrations. It has been reported that there may be differences in the binding kinetics of DAT radiotracers to DATs between normal subjects and patients with Parkinson's disease (PD). The aim of this study was to determine an optimal time point for (99Tcm]TRODAT-1 brain single photon emission tomography (SPET) acquisition that provides stable target to non-target ratios reflecting the DAT concentration in the brain. Serial [99Tcm]TRODAT-1 brain SPET images 2, 3 and 4 h after intravenous injection of [99Tcm]TRODAT-1 (925 MBq) were performed in five healthy subjects and nine PD patients. Regions of interests were drawn, and caudate/occipital (C/O) and putamen/occipital (P/O) specific to non-specific [99Tcm]TRODAT-1 binding ratios were calculated. The C/O and P/O ratios in healthy subjects showed consistent increases with time, but in PD patients, the C/O and P/O ratios of [99Tcm]TRODAT-1 reached a stable level at 3 h post-injection. There was a statistically significant difference (P < 0.001) between PD and normal subjects at 4 h post-injection for both the C/O and the P/O ratios. In conclusion, we recommend the acquisition of [99Tcm]TRODAT-1 SPET images at 4 h post-injection, as at this time point the C/O and P/O ratios can be used to discriminate between PD patients and healthy subjects.

Aged↗
PubMed2001

The inclusion compound of a new ionizable derivative of beta-cyclodextrin with ferrocenium drug.

A new beta-cyclodextrin (beta-CD) derivative, mono[6-deoxy-6-(2-butenedinitrile-2,3-dimercapto sodium salt)]-beta-CD (6-mnt-beta-CD), and its inclusion compound with a ferrocenium drug, have been prepared and characterized by IR, UV, 13C-NMR spectroscopy, and mass spectrometry, elemental analysis, thermogravimetry, and cyclic voltammetry (CV). The interplay between the side-arm anion of beta-CD and the ferrocenium (guest) in the inclusion compound 6-mnt-beta-CD-/Fc+ has been investigated by 13C-NMR, UV, IR, and thermogravimetric methods. Charge transfer from the anion to the cation in 6-mnt-beta-CD-/Fc+ was then experimentally identified. The interaction between the guest and the host with side-arm in 6-mnt-beta-CD-/Fc+ resulted in smaller positive potential shifts compared to that in the inclusion compound [beta-CD/Fc+]BF4-.

Antineoplastic Agents↗
PubMed2001

Differential diagnosis of Parkinson's disease and vascular parkinsonism by (99m)Tc-TRODAT-1.

UNLABELLED: The aim of this study was to use brain SPECT to differentiate vascular parkinsonism (VP) from Parkinson's disease. METHODS: Fourteen VP patients (age range, 59-87 y; mean age, 70 +/- 7.5 y), 30 Parkinson's disease patients (age range, 54-84 y; mean age, 65 +/- 8.8 y), and 26 healthy (control) individuals (age range, 50-85 y; mean age, 60 +/- 9 y) were examined. A 925-MBq (25 mCi) dose of (99m)Tc-TRODAT-1 was injected intravenously, and brain SPECT images were acquired 4 h after injection. The ratio of specific to nonspecific striatal (99m)Tc-TRODAT-1 binding was measured and compared. RESULTS: After a region-of-interest analysis of the images from VP patients, Parkinson's disease patients, and healthy volunteers was performed to obtain ratios of putamen to occipital and striatal to occipital binding as a measurement of specific binding to the dopamine transporters in these regions of the brain, where dopamine neurons are concentrated, the specific binding in the 14 VP patients was slightly lower than but not statistically different from that of the healthy individuals in both putamen and caudate areas. A significant decrease in uptake of (99m)Tc-TRODAT-1 in the striatum (P<0.01) was found in Parkinson's disease patients. Reduction of the uptake was more pronounced in the contralateral putamen of Parkinson's disease patients than that of VP patients (P<0.001). A significant bilateral striatal asymmetry was also observed in Parkinson's disease patients but not in VP patients (P< 0.01). CONCLUSION: Our findings clearly show that, for VP patients, (99m)Tc-TRODAT-1 SPECT is a reliable method to differentiate VP from Parkinson's disease. Further studies, including those to differentiate Parkinson's disease from arteriosclerotic parkinsonism and patients with both VP and Parkinson's disease, are needed to help rule out the possibility of Parkinson's disease as early as possible.

Aged↗
PubMed2001

Epstein-Barr virus-associated hemophagocytic syndrome masquerading as lymphoma: a case report.

Virus-associated hemophagocytic syndrome (VAHS) is a non-neoplastic, generalized histiocytic proliferation with prominent hemophagocytosis associated with a systemic viral infection. Although Epstein-Barr virus (EBV) is one candidate virus for this association, thorough serologic and molecular biologic studies to determine the presence of the viral infection have been lacking in many reports. Whereas elevated liver function tests are common findings in patients with VAHS, exudative ascites and abdominal lymphadenopathy are rare. We describe a case of EBV-AHS masquerading as lymphoma in which treatment with intravenous immunoglobulins was associated with complete clinical remission at 2 years and 6 months after the onset. Regardless of the exact mechanism responsible for ascites formation in VAHS, this case adds support to the possible involvement of EBV in patients with abdominal lymphadenopathy and ascites.

Child, Preschool↗
PubMed2001

Posteroventral pallidotomy for advanced Parkinson's disease.

BACKGROUND: Provoked by the limitations and late complications of levodopa therapy, the advances in stereotactic surgery, and better understanding of the pathophysiology of the basal ganglia, the role of pallidotomy in the treatment of advanced Parkinson's disease (PD) has been revived. METHODS: We included 11 patients with advanced PD, who had a good response to levodopa but had late complications of motor fluctuation and severe dyskinesia. The internal globus pallidus was identified with computed tomography prior to posteroventral pallidotomy and it was reaffirmed by microelectrode recording during surgery. Clinical evaluations were carried out in both the "on" and "off" motor periods at baseline and at 1 week, 3 months, 6 months and 1 year postoperatively. Repeated measures ANOVA followed by multiple comparisons were used for statistical analysis. RESULTS: Dyskinesia improved bilaterally but only significantly in the contralateral limbs. This benefit was sustained up to 1 year. Parkinsonism, particularly contralateral tremor and rigidity, improved in the "off" motor period but not in the "on" motor period. The average Unified Parkinson's Disease Rating Scale motor score was reduced 36% at 3 months and 26% at 1 year in the "off" motor period. Both of the mean Hoehn and Yahr staging and Schwab and England activities of daily living score improved in "off" motor period. Improvement in parkinsonism, however, did not reach a significant level. Mild dysarthria and unstable gait were observed temporarily in 2 patients. Mild weakness in the contralateral limbs was found in 1 patient. CONCLUSIONS: Unilateral pallidotomy guided by microelectrode recording is helpful for severe levodopa-induced dyskinesia in advanced PD. Contralateral parkinsonian disabilities also improve in the "off" motor period.

Adult↗
PubMed2000

Immunohistochemical study of the distribution of endogenous biotin and biotin-binding enzymes in ductal structures of salivary gland tumours.

To clarify the pathologic value of endogenous biotin in the salivary gland, we examined in a series of neoplasms of the salivary gland by immunohistochemical staining the distribution of endogenous biotin and of biotin-binding enzymes, namely, acetyl CoA carboxylase (AC), which is a cytosolic enzyme, and pyruvate carboxylase (PC), which is a mitochondrial enzyme. In pleomorphic adenoma, we found biotin and PC in ductal epithelial elements, while AC was found mainly in myoepithelial elements. Carcinoma ex pleomorphic adenoma, adenocarcinoma and mucoepidermoid carcinoma were frequently immunopositive for biotin, PC and AC, while adenoid cystic carcinoma was rarely immunopositive for biotin, PC or AC. These results indicate that endogenous biotin might be associated with the mitochondrial enzyme, which is present at high levels in ductal cells of the salivary gland. However, the neoplastic cells in adenoid cystic carcinoma seemed to have an unusual expression of biotin and related enzymes.

Acetyl-CoA Carboxylase↗
PubMed2000

The inclusion compounds of beta-cyclodextrin with 4-substituted benzoic acid and benzaldehyde drugs studied by proton nuclear magnetic resonance spectroscopy.

Inclusion compounds of some 4-substituted benzoic acid and benzaldehyde drugs with beta-cyclodextrin were prepared and characterized by IR spectroscopy, powder X-ray diffraction, thermogravimetry, and 1H-NMR spectroscopy. The thermal stability and chemical stability of these drugs were strikingly improved after inclusion. The effect of inclusion on the chemical-shifts of protons H-3 and H-5 in the NMR spectroscopy is discussed. Using the relative shift theory, the preferred inclusion mode was proposed. The center of the aromatic ring of the drug molecule was considered to be located in the cavity 1.2 A inside from the H-5 plane of beta-cyclodextrin.

Algorithms↗