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S Z Lin

Publications and source records attributed to S Z Lin.

At least 19 recordsLinked to original sources
PubMed2004

The homozygote AA genotype of the alpha1-antichymotrypsin gene may confer protection against early-onset Parkinson's disease in women.

There has been increasing evidence suggesting that inflammatory response maybe involved in the pathogenesis of Parkinson's disease (PD). Alpha1-antichymotrypsin gene (ACT) has been regarded as a susceptibility factor for PD in the past, but the evidence remains controversial. This case-control study was designed to investigate the association of alpha1-antichymotrypsin gene (ACT) polymorphism between 210 Taiwanese patients with clinical definite sporadic PD and 260 controls, matched by age and sex. There were no differences of allelic frequency (A and T) and genotype polymorphism (AA, AT and TT) of the ACT in PD patients from the controls. However, there were significantly fewer early-onset PD (onset age younger than 60 years) or PD women carrying the homozygote AA genotype (ACT-AA) than in controls (p=0.046 and 0.044, respectively). Further analysis revealed that the reduced risk of ACT-AA was particularly significant among PD women with the onset age younger than 60 years (OR=0.796, 95% CI=0.749-0.847, p<0.0001). This study shows that ACT-AA may confer a modest protection against developing early-onset PD in women.

Age of Onset↗
PubMed2003

First human ventral mesencephalon and striatum cografting in a Parkinson patient.

Fetal ventral mesencephalon (VM) transplantation has been reported to improve parkinsonian symptoms. Animal studies show that cografting of striatal tissue increases the survival of dopamine neurons. Whether or not VM and striatum cografting could ameliorate motor dysfunction in a Parkinson's disease (PD) patient was explored in this study. The patient was a 53-year-old male who had presented with symptoms of tremor, rigidity and bradykinesia for 11 years. He had been treated with L-dopa and had progressive deterioration of symptoms even with the daily dosage of L-dopa increased to 900 mg per day. Before transplantation, his PD symptoms were scored with Unified Parkinson's Disease Rating Scale (UPDRS) and video recordings. The influx constant (ki) of the [18F] 6-fluoro-L-dopa uptake in the striatum was measured by positron emission tomography (PET) imaging. The fetal VM and the lateral part of the lateral ganglionic eminence (LGE) were cografted into the right putamen and, one week later, fetal VM alone was transplanted into the left putamen. After the transplantation, the patient's UPDRS score improved from 128 to 62 at 6 months and to 24 at 22 months during the "off" phase. The score of daily living disability improved from 35 to 18 at 6 months and to 10 at 22 months post transplantation. Twenty-two months after grafting, "off" phases were almost absent, and the freezing had totally disappeared. The [18F] 6-fluoro-L-dopa PET studies were performed 1 month before and 21 months after transplantation. The ki for [18F] 6-fluoro-L-dopa was decreased by 15% in the right caudate and 5% in the left caudate, both of which did not have any ventral mesencephalic grafts. However, the ki was increased by 35%, in the left non-cografted putamen, and by 58% in the right cografted putamen. In conclusion, cografting the fetal VM and the LGE in the putamen may improve the motor function of PD patients.

Activities of Daily Living↗
PubMed2001

Methamphetamine potentiates ischemia/reperfusion insults after transient middle cerebral artery ligation.

BACKGROUND AND PURPOSE: Previous studies have indicated that both methamphetamine (MA) and ischemia/reperfusion injuries involve reactive oxygen species formation and activation of apoptotic mechanism. That MA could have a synergistic or additive effect with stroke-induced brain damage is possible. The purpose of the present study was to investigate whether administration of MA in vivo would potentiate ischemic brain injury. METHODS: Adult CD-1 mice were pretreated with MA or saline. Each animal later was anesthetized with chloral hydrate and placed in a stereotaxic frame. A subset of animals received intracerebral administration of glial cell line-derived neurotrophic factor (GDNF). The right middle cerebral artery and bilateral carotids were transiently occluded for 45 minutes. Regional cerebral blood flow was measured by laser Doppler. Animals were sacrificed for triphenyltetrazolium chloride staining and p53 mRNA Northern blot assay after 24 hours of reperfusion. Cortical and striatal GDNF levels were assayed by ELISA. RESULTS: We found that pretreatment with MA increased ischemia-induced cerebral infarction. Ischemia or MA alone enhanced p53 mRNA expression. Moreover, MA potentiated expression of p53 mRNA in the ischemic mouse brain. MA pretreatment decreased GDNF levels in ischemic striatum. Intracerebral administration of GDNF before ischemia reduced MA-facilitated infarction. CONCLUSIONS: Our data indicate that MA exacerbates ischemic insults in brain, perhaps through the inhibition of GDNF-mediated pathways and suggest that MA may antagonize endogenous neuroprotective pathways as part of its mechanism of action.

Animals↗
PubMed2001

Bone morphogenetic protein-6 reduces ischemia-induced brain damage in rats.

BACKGROUND AND PURPOSE: Bone morphogenetic protein-6 (BMP6) and its receptors are expressed in adult and fetal brain. Receptors for BMP6 are upregulated in adult brain after injury, leading to the suggestion that BMP6 is involved in the physiological response to neuronal injury. The purpose of this study was to determine whether there was a neuroprotective effect of BMP6 in vivo and in vitro. METHODS: Lactate dehydrogenase and microtubule-associated protein-2 (MAP-2) activities were used to determine the protective effect of BMP6 against H(2)O(2) in primary cortical cultures. The neuroprotective effects of BMP6 were also studied in chloral hydrate-anesthetized rats. BMP6 or vehicle was injected into right cerebral cortex before transient right middle cerebral artery (MCA) ligation. Animals were killed for triphenyl-tetrazolium chloride staining, caspase-3 immunoreactivity and enzymatic assays, and TUNEL assay. A subgroup of animals were used for locomotor behavioral assays. RESULTS: Application of H(2)O(2) increased lactate dehydrogenase activity and decreased the density of MAP-2(+) neurons in culture. Both responses were attenuated by BMP6 pretreatment. Complementary in vivo studies showed that pretreatment with BMP6 increased motor performance and generated less cerebral infarction induced by MCA ligation/reperfusion in rats. Pretreatment with BMP6 did not alter cerebral blood flow or physiological parameters. There was decreased ischemia-induced caspase-3 immunoreactivity, caspase-3 enzymatic activity, and density of TUNEL-positive cells in ischemic cortex in BMP6-treated animals. CONCLUSIONS: BMP6 reduces ischemia/reperfusion injury, perhaps by attenuating molecular events underlying apoptosis.

Animals↗
PubMed2001

Treatment of intractable generalized dystonia by bilateral posteroventral pallidotomy--one-year results.

BACKGROUND: Recent study has revealed that bilateral posteroventral pallidotomy (PVP) significantly improve dystonic movements and improve motor function of those patients with generalized dystonia (GD). However, there is only a limited number of patients who have been reported so far. METHODS: This study was conducted to evaluate the clinical efficacy of surgical treatment with bilateral PVP on patients with intractable GD. All the studied patients were regularly rated with standardized scales (Burke-Fahn-Marsden Evaluation Scale for Dystonia) for dystonic movement and living disability before and after surgery. RESULTS: There were 18 patients, 8 males and 10 females with an average age of 24.8 years, included in the study. Postoperatively, there were slow, partial, but steady improvements of the dystonic movement and daily living function. Maximal effects were noted at the sixth month and the clinical benefits were sustained one year after the surgical treatment when there were statistically significant improvements in 13% of total dystonia movement score and 9% of the total disability score (p < 0.05). Upon further analysis, improvements of dystonic movements were statistically significant in the regions of mouth (50%), speech/swallowing (19%) and neck (43%), and daily living functions in speech (14%) and eating/swallowing (29%). CONCLUSIONS: Bilateral posteroventral pallidotomy was only partially effective for the treatment of GD, and it produced clinical improvement in the dystonic movement limited to the craniocervical region. We therefore suggest that patients with GD should be carefully selected for the treatment of bilateral posteroventral pallidotomy, despite the surgery having a partially beneficial effect on this kind of movement.

Adolescent↗
PubMed2001

Evaluation of early-stage Parkinson's disease with 99mTc-TRODAT-1 imaging.

UNLABELLED: Parkinson's disease is a progressive neurodegenerative disorder characterized by a selective loss of dopamine in the striatum. Problems remain in the accurate diagnosis of Parkinson's disease. A 99mTc-labeled tropane derivative that binds to dopamine transporter with high selectivity is [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)] (TRODAT-1). The purpose of this study was to investigate the potential usefulness of 99mTc-TRODAT-1 imaging in the evaluation of patients with early-stage Parkinson's disease. METHODS: Thirty-four patients with early-stage idiopathic Parkinson's disease were recruited. For all patients, the Parkinson's disease was stage 2 or less as assessed by the Hoehn and Yahr scale. Seventeen age-matched healthy volunteers (8 men, 9 women) served as controls. 99mTc-TRODAT-1 was prepared from a lyophilized kit. Brain SPECT imaging was performed between 165 and 195 min after injection, using a double-head camera equipped with fanbeam collimators. Specific uptake in the striatum and its subregions, including the putamen and caudate nucleus, was calculated and compared with that of the other sides and of healthy volunteers. RESULTS: A continuous reduction in specific striatal uptake of 99mTc-TRODAT-1 with increasing disease severity was found in Parkinson's disease patients (control vs. stage I vs. stage II, 1.98 vs. 1.62 vs. 1.22, respectively, P < 0.01). The changes were magnified by measurement of specific putaminal uptake (control vs. stage I vs. stage II, 1.81 vs. 1.27 vs. 0.94, respectively, P < 0.01). The mean values of specific putaminal uptake contralateral to the more affected limbs were significantly decreased compared with the ipsilateral sides in both stage I and stage II groups (1.02 vs. 1.49 for stage I and 0.73 vs. 1.14 for stage II, P < 0.01). Moreover, a significant loss of putaminal uptake ipsilateral to the symptoms was found in the stage I group compared with the healthy volunteers (1.49 vs. 1.81, P < 0.01). The difference became greater when the posterior putaminal uptakes were compared. No remarkable adverse reactions were found in either healthy volunteers or Parkinson's disease patients during or after imaging. CONCLUSION: For clinical practice, 99mTc-TRODAT-1 may serve as a useful imaging agent for the early detection of Parkinson's disease.

Aged↗
PubMed2000

Vitamin D(3) attenuates cortical infarction induced by middle cerebral arterial ligation in rats.

We have previously reported that intracerebral administration of glial cell line derived neurotrophic factor (GDNF) reduces the extent of middle cerebral arterial (MCA) ligation-induced cortical infarction in rats. Recent studies have shown that application of 1, 25 dihydroxyvitamin D(3) (D3) enhances GDNF mRNA expression in vitro. The purpose of the present study was to investigate if administration of D3 in vivo will protect against ischemic brain injury. Adult male Sprague-Dawley rats were injected daily with D3 or with saline for four or eight days. Animals received a 90-min right MCA ligation on the 4(th) or 8(th) day after anesthesia with chloral hydrate. Animals were sacrificed for tri-phenyl-tetrazolium chloride (TTC) staining 24 h after the onset of reperfusion. A subset of animals receiving eight days of D3 or saline treatment were used for blood gas and cerebral GDNF protein level analysis. We found that pretreatment with D3 for four days did not attenuate the ischemic injury. However, animals receiving eight days of D3 injections showed a significant reduction in the amount of infarction in the cortex. Eight day D3 treatment did not alter blood gases or blood pressure; however, it did increase calcium levels. Pretreatment with D3 significantly increased GDNF levels in the cortex. In conclusion, our data indicate that D3 reduces ischemia-induced brain damage and supports the hypothesis that this effect may be through the up-regulation of GDNF mechanisms in cortex.

Animals↗
PubMed2000

Recombinant adeno-associated virus vector expressing glial cell line-derived neurotrophic factor reduces ischemia-induced damage.

To explore the potential of using the recombinant adeno-associated viral (rAAV) vector, expressing glial cell line-derived neurotrophic factor (GDNF) as the gene therapy for stroke, we injected rAAV vectors expressing GDNF (rAAV-GDNF) into the cortex of rats which had been experiencing transient bilateral common carotid artery ligation and right middle cerebral artery ligation for 90 min. GDNF levels in cortical tissues of rAAV-GDNF-injected animals were significantly higher than in the control animals injected with rAAV-expressing lacZ (rAAV-lacZ), indicating that rAAV can deliver and express the GDNF gene in cortical tissues. Triphenyltetrazolium chloride tissue stain analysis revealed that the rAAV-delivered GDNF gene could rescue the brain tissues from ischemia-induced injury. Cortical tissues which received rAAV-GDNF injections had both significantly smaller total volumes of infarction and smaller areas of infarction on each brain slice than those which were injected with rAAV-lacZ. An in situ labeling analysis demonstrated significantly less apoptotic cells in cortical tissues rescued by rAAV-GDNF, indicating prevention of apoptosis as the mechanism of cortical cell protection. Moreover, immunohistochemistry staining of Neu-N indicated that the rescued brain tissues contained the same number of Neu-N-positive neuronal cells as contralateral undamaged brain tissues. This provides strong evidence that cortical neuronal cells can be rescued by GDNF gene therapy. Indeed, these findings show that the rAAV is a potential delivery vector of GDNF gene for the therapy of stroke.

Adenoviridae↗
PubMed2000

Glial cell line-derived neurotrophic factor receptor alpha1 availability regulates glial cell line-derived neurotrophic factor signaling: evidence from mice carrying one or two mutated alleles.

Glial cell line-derived neurotrophic factor receptor alpha1 (GFRalpha1, also known as GDNFR-alpha) is a glycolipid-anchored membrane protein of the GFRalpha family, which binds glial cell line-derived neurotrophic factor [Jing S. et al. (1996) Cell 85, 1113-1124; Treanor J. J. et al. (1996) Nature 382, 80-83], a survival factor for several populations of central and peripheral neurons, including midbrain dopamine neurons [Lin L. F. et al. (1993) Science 260, 1130-1132], and mediates its ligand-induced cell response via a tyrosine kinase receptor called Ret [Takahashi M. et al. (1988) Oncogene 3, 571-578; Takahashi M. and Cooper G. M. (1987) Molec. Cell Biol. 7, 1378-1385]. In this paper, we show that mice with a null mutation of the GFRalpha1 gene manifest epithelial-mesenchymal interaction deficits in kidney and severe disturbances of intestinal tract development similar to those seen with glial cell line-derived neurotrophic factor or Ret null mutations. There is a marked renal dysgenesis or agenesis and the intrinsic enteric nervous system fails completely to develop. We also show that newborn GFRalpha1-deficient mice display no or minimal changes in dorsal root and sympathetic ganglia. This is in contrast to the deficits reported in these neuronal populations in glial cell line-derived neurotrophic factor and Ret null mutations. Mesencephalic dopaminergic neurons in the substantia nigra and ventral tegmental area appear intact at the time of birth of the mutated mice. Mice homozygous for the GFRalpha1 null mutation die within 24 h of birth because of uremia. Heterozygous animals, however, live to adulthood. There is a significantly reduced neuroprotective effect of glial cell line-derived neurotrophic factor in such heterozygous animals, compared with wild-type littermates, after cerebral ischemia. Taken together with previous data on glial cell line-derived neurotrophic factor and Ret, our results strongly suggest that GFRalpha1 is the essential GFRalpha receptor for signaling in the glial cell line-derived neurotrophic factor-Ret pathway in the kidney and enteric nervous system development, and that GFRalpha2 or GFRalpha3 cannot substitute for the absence of GFRalpha1. Moreover, neuroprotective actions of exogenous glial cell line-derived neurotrophic factor also require full GFRalpha1 receptor expression.

Alleles↗
PubMed2000

Malignant meningioma with rhabdoid transformation.

We report a rare case of recurrent meningioma with malignant change and rhabdoid transformation in a 54-year-old woman who presented with severe headache and progressive weakness of the right extremities. The patient had a history of atypical meningioma and had undergone a craniotomy to remove a tumor nine years earlier. We discuss the distinctive morphologic, immunohistochemical staining and ultrastructural features of a recurrent malignant meningioma. A meningioma with rhabdoid transformation may indicate aggressive biologic and clinical behavior of the tumor.

Female↗
PubMed2000

Antagonistic action of caffeine against LY294002-induced apoptosis in cerebellar granule neurons.

AIM: To study the effect of caffeine on apoptosis induced by inhibition of 1-phosphatidylinositol 3-kinase in cerebellar granule neurons. METHODS: Cerebellar granule neurons culture, agar gel electrophoresis, and stress-activated protein kinase (SAPK)/c-Jun N-terminal protein kinase (JNK) assay kit to measure SAPK/JNK activity. RESULTS: LY294002 evoked apoptosis concentration-dependently in cerebellar granule neurons. But death resulting from LY294002 was prevented by caffeine in a concentration-dependent manner. The survival effect of caffeine was not affected by inhibitors of ryanodine-sensitive Ca2+ release, nor was it inhibited by L-type channel blockers and N-methyl-D-aspartate (NMDA) receptor blocker. In addition, RP-cAMP, H89, and KN62 were not able to inhibit the protective effect of caffeine. Phosphorylation of c-Jun was necessary for the induction of apoptosis induced by LY294002 in cerebellar granule neurons. But caffeine directly inhibited the activation of JNK and decreased phospho-c-Jun in granule neurons. CONCLUSION: Caffeine inhibited the activation of JNK and decreased the phosphorylation of c-Jun to protect granule neurons from LY294002-induced apoptosis.

Animals↗
PubMed2000

[Treatment of diseased middle turbinate in endoscopic sinus surgery].

OBJECTIVE: To study the clinical significance of reservation of the middle turbinate in functional endoscopic sinus surgery (FESS) for sinusitis and/or nasal polyps. METHOD: According to anatomic criteria of the middle turbinate surgery in adult, 32 cases who had sinusitis and/or nasal polyps were treated and followed up. The recovery of middle turbinate contour, postoperative ethmoid cavity and the rate of patency of the maxillary sinus ostium were observed postoperatively. RESULT: 1. After 6 months, the form of middle turbinate returned to normal in 24 cases (75%), adhesions occurred in 8 cases (25%), including the closure of ethmoid sinus cavity in 2 cases. 2. The patency of maxillary sinuses ostium maintained well in 25 cases (78.1%), stenosed in 6 cases (18.8%) and closed in 1 case (3.1%). The diseased middle turbinate can recover to normal contour in most cases, often plastics in FESS. CONCLUSION: Reservation of middle turbinate plays an important role in promoting the clinical cure rate.

Adolescent↗
PubMed2000

[Neuroprotective effect of alpha-dihydroergocryptine depends on activation of nuclear factor kappa B].

AIM: To investigate the relationship between the neuroprotective effect of alpha-dihydroergocryptine (alpha-DHEC) and the activation of nuclear factor Kappa B (NF-Kappa B). METHODS: Adult male rats were subjected to cerebral ischemia induced by middle cerebral artery occlusion (MCAO). DNA binding activity of NF-Kappa B was determined with electrophoretic mobility shift assay (EMSA) in animals subjected to varying durations of cerebral ischemia. Neuroapoptosis induced by ischemic damage was measured by deoxynucleotidy transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry (FCM) analysis. RESULTS: No change was observed in nuclear NF-Kappa B DNA binding in normal animal. A low level of constitutive NF-Kappa B DNA binding was detected in animals subjected to cerebral ischemia of 1 h, and significant increase in the amount of active NF-Kappa B in nuclear extracts was observed after cerebral ischemia of 3 h, 6 h, and 12 h. Peak of NF-Kappa B DNA binding was observed at the time point of 3 h. Animals subjected to cerebral ischemia of 3 h potentially initiates neuroapoptosis and activates NF-Kappa B in nuclear extract. Alpha-DHEC (100 micrograms.kg-1 and 150 micrograms.kg-1) showed significant protective effect on neuroapoptosis-induced by cerebral ischemia of 3 h, and inhibiting NF-Kappa B activation using 100 mg.kg-1 pyrrolidinedithiocarbamate (PDTC) in the continuous presence of alpha-DHEC, the neuroprotective effect of alpha-DHEC was blocked. CONCLUSION: The findings suggest that the neuroprotetive effect of alpha-DHEC may depend on the activation of NF-Kappa B.

Animals↗
PubMed1999

Transplantation of fetal kidney tissue reduces cerebral infarction induced by middle cerebral artery ligation.

The authors, and others, have recently reported that intracerebral administration of glial cell line-derived neurotrophic factor (GDNF) or osteogenic protein-1 protects against ischemia-induced injury in the cerebral cortex of adult rats. Because these trophic factors are highly expressed in the fetal, but not adult, kidney cortex, the possibility that transplantation of fetal kidney tissue could serve as a cellular reservoir for such molecules and protect against ischemic injury in cerebral cortex was examined. Fetal kidneys obtained from rat embryos at gestational day 16, and adult kidney cortex, were dissected and cut into small pieces. Adult male Sprague-Dawley rats were anesthetized with chloral hydrate and placed in a stereotactic apparatus. Kidney tissues were transplanted into three cortical areas adjacent to the right middle cerebral artery (MCA). Thirty minutes after grafting, the right MCA was transiently ligated for 90 minutes. Twenty-four hours after the onset of reperfusion, animals were evaluated behaviorally. It was found that the stroke animals that received adult kidney transplantation developed motor imbalance. However, animals that received fetal kidney grafts showed significant behavioral improvement. Animals were later sacrificed and brains were removed for triphenyltetrazolium chloride staining, Pax-2 immunostaining, and GDNF mRNA expression. It was noted that transplantation of fetal kidney but not adult kidney tissue greatly reduced the volume of infarction in the cerebral cortex. Fetal kidney grafts showed Pax-2 immunoreactivity and GDNF mRNA in the host cerebral cortex. In contrast, GDNF mRNA expression was not found in the adult kidney grafts. Taken together, our data indicate that fetal kidney transplantation reduces ischemia/reperfusion-induced cortical infarction and behavioral deficits in adult rats, and that such tissue grafts could serve as an unique cellular reservoir for trophic factor application to the brain.

Animals↗
PubMed1999

Absence of G209A and G88C mutations in the alpha-synuclein gene of Parkinson's disease in a Chinese population.

A G209A mutation in the alpha-synuclein gene was recently discovered in a large Italian kindred and three unrelated Greek kindreds with autosomal dominant Parkinson's disease (PD). Subsequently, another mutation in the gene (G88C) was also identified in a German family with autosomal PD. These results indicate that the alpha-synuclein gene may have an important role in the pathogenesis of PD. This study was designed to screen the existence of both mutations of the alpha-synuclein gene among 100 Chinese patients with PD, including 80 with sporadic and 20 with familial PD. Results showed that none of our patients, both sporadic and familial PD, had either of the two mutations of this gene. We therefore conclude that although of great interest, these two mutations are not relevant for the pathogenesis of PD in a Han Chinese population.

Aged↗
PubMed1999

Osteogenic protein-1 protects against cerebral infarction induced by MCA ligation in adult rats.

BACKGROUND AND PURPOSE: Osteogenic protein-1 (OP1) not only possesses trophic activity on bone tissue but also influences neuronal survival and differentiation in vitro. Specific receptors for OP1 are present in brain and spinal cord and can be upregulated during cerebral contusion. OP1 is a member of the transforming growth factor-beta superfamily, several of whose members possess neuroprotective activity. In this study, the neuroprotective effect of OP1 in cerebral ischemia was evaluated in adult animals. METHODS: Adult male Sprague-Dawley rats were anesthetized with chloral hydrate. OP1 or vehicle was administered intracortically or intracerebroventricularly to the rats. Thirty minutes, 24 hours, or 72 hours after OP1 injection, the right middle cerebral artery (MCA) was ligated for 90 minutes. Twenty-four hours after reperfusion, animals were tested for motor behavior. The animals were subsequently anesthetized with urethane and perfused intracardially with saline. Brain tissue was removed, sliced, and incubated with 2% triphenyltetrazolium chloride to localize the area of infarction. RESULTS: Only animals pretreated with OP1 24 hours before MCA ligation showed a reduction in motor impairment. OP1, given 30 minutes or 72 hours before MCA ligation, did not reduce cortical infarction. In contrast, pretreatment with OP1 24 hours before MCA ligation significantly attenuated the volume of infarction in the cortex, in agreement with the behavioral findings. CONCLUSIONS: Intracerebral administration of OP1 24 hours before MCA ligation reduces ischemia-induced injury in the cerebral cortex.

Animals↗