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S Chin

Publications and source records attributed to S Chin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Stimulation of active sodium-potassium transport by hydrogen peroxide in cultured rabbit nonpigmented ciliary epithelium.

PURPOSE: Studies were conducted to examine the effect of hydrogen peroxide on active sodium-potassium transport in a cell line derived from nonpigmented ciliary epithelium of the rabbit eye. METHODS: Studies were carried out using a rabbit nonpigmented ciliary epithelium cell line. 86Rb uptake by intact cells was measured in the presence or absence of ouabain. The ouabain-sensitive potassium (86Rb) uptake rate was used as an index of the rate of active sodium-potassium transport. Cell sodium content was measured by atomic absorption spectrophotometry. Na,K-ATPase activity was determined by measuring ATP hydrolysis in the presence or absence of ouabain, using membrane material isolated by centrifugation of cell homogenates. RESULTS: Ouabain-sensitive potassium (86Rb) uptake rate measured in cells that had been preincubated with 200microM hydrogen peroxide for either 30 min or 60 min was increased to 196% and 181% of the control uptake rate, respectively. Lesser concentrations of hydrogen peroxide caused lesser degrees of stimulation. 200microM hydrogen peroxide caused an increase of cell sodium content. Such a change of cell sodium content is likely to be responsible, at least in part, for the observed stimulation of active sodium-potassium transport. However, the response may also be partly dependent on activation of a protein kinase since the serine/threonine protein kinase inhibitors staurosporine (1microM) and H-89 (20microM) were both found to prevent the stimulatory effect of 200microM hydrogen peroxide on ouabain-sensitive potassium (86Rb) uptake. Interestingly, neither H-89 nor staurosporine prevented the elevation of sodium content in cells that received 200microM hydrogen peroxide. CONCLUSIONS: Taken together, these findings suggest a low concentration of hydrogen peroxide causes increased sodium entry into the cell and also activates a protein kinase-dependent mechanism for sodium pump stimulation. The protein kinase-dependent mechanism does not appear to be triggered by an increased rate of sodium entry since staurosporine did not prevent the stimulation of ouabain-sensitive potassium (86Rb) uptake elicited by an increase in sodium permeability caused by amphotericin B.

Animals↗
PubMed1999

Clinical genetics of familial progressive supranuclear palsy.

Recent studies have shown that progressive supranuclear palsy (PSP) could be inherited, but the pattern of inheritance and the spectrum of the clinical findings in relatives are unknown. We here report 12 pedigrees, confirmed by pathology in four probands, with familial PSP. Pathological diagnosis was confirmed according to recently reported internationally agreed criteria. The spectrum of the clinical phenotypes in these families was variable including 34 typical cases of PSP (12 probands plus 22 secondary cases), three patients with postural tremor, three with dementia, one with parkinsonism, two with tremor, dystonia, gaze palsy and tics, and one with gait disturbance. The presence of affected members in at least two generations in eight of the families and the absence of consanguinity suggests autosomal dominant transmission with incomplete penetrance. We conclude that hereditary PSP is more frequent than previously thought and that the scarcity of familial cases may be related to a lack of recognition of the variable phenotypic expression of the disease.

Adult↗
PubMed1999

Laterality in functional brain imaging studies of schizophrenia.

Brain laterality in schizophrenia has been examined through the application of functional neuroimaging methods. These methods have included the 133Xenon technique for measuring cerebral blood flow (CBF); positron emission tomography for assessing rates of glucose metabolism, CBF, and neuroreceptor functioning; single photon emission computerized tomography for studying CBF and neuroreceptors; and functional magnetic resonance imaging for measuring changes attributable to CBF. This article highlights the application of this technology in schizophrenia research, emphasizing more recent studies that have evaluated hemispheric differences. There is evidence for lateralized abnormalities in some studies that have examined this dimension. In general, the results implicate abnormalities in left hemispheric activity. Recent advances in basic and clinical neuroscience provide an opportunity for focused application of functional imaging in neurobiological studies of schizophrenia.

Brain↗
PubMed1999

Type 1 protease resistant prion protein and valine homozygosity at codon 129 of PRNP identify a subtype of sporadic Creutzfeldt-Jakob disease.

A man was studied with sporadic Creutzfeldt-Jakob disease (sCJD) who had serial cortical syndromes evolving over 15 months without significant ataxia, prominent myoclonus, or periodic complexes on EEG examinations. This clinical phenotype correlated with a predominantly cortical and striatal distribution of lesions and accumulation of protease resistant prion protein with relative sparing of the brainstem or cerebellum. No amyloid plaques were seen and prion protein (PrP) immunohistochemistry only demonstrated very faint granular deposits in the cerebral cortex. Molecular analysis showed homozygosity for valine at codon 129 in the prion protein gene (PRNP) and protease resistant prion protein type 1 deposition. The comparison of molecular and clinicopathological features of the present case with those previously reported in sCJD, indicates that valine homozygosity at codon 129 and type 1 protease resistant prion protein are associated with a distinct phenotypic variant of sCJD. The data also support the view that the PRNP codon 129 polymorphism and the physicochemical properties of the protease resistant prion protein are major determinants of phenotypic variability in sCJD.

Codon↗
PubMed1998

Selective induction of Na,K-ATPase alpha3 subunit mRNA abundance in cardiac myocytes by retinoic acid.

Retinoic acid (RA) is a high affinity ligand for a nuclear receptor which regulates transcription in target cells. Specific effects of RA on cardiac development and myocardial cell hypertrophy have been demonstrated; however, little information exists concerning RA-mediated regulation of cardiac genes. This study was initiated to investigate whether RA regulates Na,K-ATPase subunit gene expression in primary cultures of neonatal rat cardiac myocytes. Northern blot analyses demonstrated that NA, K-ATPase alpha3 subunit mRNA content was stimulated three-fold by RA. The effect of RA on alpha3 subunit gene expression was selective as RA treatment had no effect on either Na,K-ATPase alpha1, alpha2 or beta1 subunit mRNAs. A stimulatory effect of RA on Na,K-ATPase alpha3 gene transcription was not evident in either transient transfection or nuclear run-on studies, suggesting that augmentation of alpha3 mRNA content by RA was due to a post-transcriptional mechanism. Finally, RA diminished the magnitude of the thyroid hormone (T3)-mediated increase in Na,K-ATPase beta1 subunit mRNA, while RA had no effect on the stimulation of alpha3 mRNA content by T3.

Animals↗
PubMed1998

The metabolic effects of preferential reduction of visceral adipose tissue in abdominally obese men.

SETTING: This study was performed on free living subjects attending the body composition laboratory on a monthly basis for a total of six months. SUBJECTS/DESIGN: Thirty-one abdominally obese men (30 0.95) were enrolled in a placebo-controlled randomized double-blind study, using either dexfenfluramine (d-fen) or placebo, whilst also receiving food and fitness counselling. After a two week run-in period they were randomized to either d-fen or placebo for three months. This was followed by a further three months without medication, although food and fitness counselling continued. METHODS: Body composition assessment included anthropometry (weight, height and abdominal circumferences), dual-energy X-ray absorptiometry (DEXA) for total body fat, and intra-abdominal fat measured via magnetic resonance imaging (MRI) at the L3/L4 level. Biochemistry included serum lipids, insulin and glucose. All measurements including blood pressure were performed at baseline, three months and six months. STATISTICAL ANALYSIS: The change within each group in the three months on medication (d-fen or placebo) was assessed by paired t-tests, whilst the difference between the groups at baseline and at three months (measured by percentage change from baseline) was assessed by unpaired t-tests. An analysis of variance was performed over the six months for the d-fen group and the placebo group separately, to determine the overall effect of three months treatment with either d-fen or placebo, three months after medication had ceased. OUTCOMES AT THREE MONTHS: At three months, BMI decreased by -5.8+/-0.8% in the group on d-fen and by -2.7+/-0.8% in the placebo group (P<0.01 d-fen vs placebo). There was also a significant difference in the reduction of the visceral fat area between the groups (-21.0+/-4.0% in the d- fen group vs -6.7+/-2.2% in the placebo group, P<0.01) although there was no significant difference between groups with regard to reduction in subcutaneous fat area. The visceral:subcutaneous fat ratio (V/S ratio) was significantly reduced between groups at three months (-13.3+/-4.9% in the d-fen group vs -0.7+/-3.0% in the placebo group, P=0.03). At three months, the only metabolic parameters to show significant difference between the two groups were total cholesterol and LDL cholesterol. Total cholesterol reduced by -12.4+/-2.0% in the d-fen group compared with -2.3+/-2.1% in the placebo group (P<0.01). LDL cholesterol reduced by -15.6+/-2.6% in the d-fen group compared with -1.2+/-2.8% in the placebo group (P<0.01). OUTCOMES AT SIX MONTHS: In the d-fen group, the reductions in BMI, abdominal circumference and % total body fat (DEXA) were sustained after three months on no medication, whereas all changes in body composition seen in the group on placebo at three months, had reverted at the three month follow-up. Both groups sustained a reduction in the insulin to glucose (I/G) ratio and systolic and diastolic blood pressure for three months after medication was ceased, while those on d-fen initially also maintained a reduction in total and LDL cholesterol.

Adipose Tissue↗
PubMed1998

Partial inhibition of Na,K-ATPase activity in cultured rabbit non-pigmented ciliary epithelium following an episode of cytoplasmic ATP depletion.

Ouabain-sensitive ATP hydrolysis (Na,K-ATPase activity) was measured in digitonin-permeabilized monolayers of cultured cells derived from rabbit non-pigmented ciliary epithelium. Diminished Na,K-ATPase activity was observed in cells that had been pre-treated 10 min with the protein kinase C activator, PDBu, as well as in cells that had been cooled to 4 degrees C for 4 h then rewarmed to 37 degrees C for 30 min (cool-rewarm manoeuvre). In the intact cells, ouabain binding was not decreased either by PDBu treatment or the cool-rewarm manoeuvre. However, both PDBu and the cool-rewarm manoeuvre increased the rate of ouabain-sensitive potassium (86Rb) uptake measured in intact cells. Cell ATP content was diminished in PDBu-treated cells and cells subjected to the cool-rewarm manoeuvre. We suggest that an episode of ATP depletion might initiate a mechanism which causes lasting, partial inhibition of Na,K-ATPase activity. In keeping with this suggestion, diminished Na,K-ATPase activity was observed in cells that had been pre-treated 20 min with the metabolic inhibitors CCCP or rotenone and in cells pre-treated 2.5 h in dextrose-free medium. This study illustrates that Na,K-ATPase activity measured in the permeabilized cell is a complex parameter which is not necessarily a reliable indicator of sodium pump responses in the intact cell.

Adenosine Triphosphate↗
PubMed1998

Characterization of a negative thyroid hormone response element in the rat sodium, potassium-adenosine triphosphatase alpha3 gene promoter.

The thyroid hormone L-T3 elicits either a stimulatory or an inhibitory effect on expression of the Na,K-adenosine triphosphatase alpha3-subunit gene in primary cultures of neonatal rat cardiac myocytes. The present study was undertaken to characterize a negative thyroid hormone response element present within the rat Na,K-adenosine triphosphatase alpha3-subunit gene proximal promoter. Transient transfection assays indicated that the DNA-binding domain of thyroid hormone receptor was essential for mediating repression of alpha3 gene transcription by thyroid hormone. This negative effect of thyroid hormone was enhanced in the presence of cotransfected retinoid X receptor and its ligand 9-cis-retinoic acid. Inhibition of alpha3 chimeric gene expression by thyroid hormone was dependent on the initial cell plating density. The negative thyroid hormone response element was localized to a region between nucleotides -68 to -6 of the alpha3 gene. Electrophoretic mobility shift assays showed that thyroid hormone receptor binds in a synergistic manner as a heterodimer with retinoid X receptor to two sites at positions -62 to -41 and -39 to -17 of the alpha3 gene promoter. The upstream and downstream heterodimer binding sites coexist with CAAT and TATA elements, respectively.

Animals↗
PubMed1998

Ocular tilt reaction with vertical eye movement palsy caused by localized unilateral midbrain lesion.

A 60-year-old man developed diplopia and experienced difficulty moving his eyes. Vertical movement of each eye, including vestibulo-ocular reflex and smooth pursuit, was extremely limited. Horizontal eye movements were normal. His head position was tilted toward his left. There was 10 prism diopters of exotropia and 10 prism diopters of right hypertropia. Fundus photographs revealed a clockwise torsion of both eyes. These signs indicate leftward ocular tilt reaction. Magnetic resonance imaging showed a small area of an increased signal intensity localized in the midbrain dorsomedial to the red nucleus on the right side. Based on recent experimental evidence, it may be assumed that the unilateral lesion involving the right interstitial nucleus of Cajal most probably caused leftward ocular tilt reaction in our patient.

Cerebral Hemorrhage↗
PubMed1997

Virucidal treatment of blood protein products with UVC radiation.

The virus safety of blood derivatives continues to be of concern, especially with respect to nonenveloped and/or heat-stable viruses. Previously, we demonstrated that treatment of whole plasma, AHF concentrate or fibrinogen with short wavelength ultraviolet light (UVC) results in the inactivation of > or = 10(6) infectious doses (ID) of encephalomyocarditis virus (EMCV), hepatitis A virus (HAV) and porcine parvovirus (PPV), each of which is nonenveloped. Protein recovery was enhanced greatly by inclusion of the flavonoid, rutin, added prior to UVC exposure to quench reactive oxygen species. We now report on the treatment of albumin and intravenous immune globulin (IVIG) isolated by a previously described, integrated chromatographic method. Albumin was treated with either 0.1 or 0.2 J/cm2 UVC in the presence of 0.8 or 1.6 mM rutin; IVIG was treated with either 0.05 or 0.1 J/cm2 UVC in the presence of 0.5 or 1.0 mM rutin. Our results show that > or = 10(6.9) ID of EMCV and PPV were inactivated under each of the conditions studied except the treatment of albumin with 0.1 J/cm2 UVC in the presence of 1.6 mM rutin where 10(4.3) ID of EMCV and > or = 10(6.9) ID of PPV were killed. It appears that the sensitivity of PPV to UVC exceeds that of EMCV and that virus kill with UVC is higher in IVIG than in albumin. In the absence of rutin, UVC increased the extent of aggregation of both albumin and IVIG by two- to three-fold. With rutin present, the increase in albumin aggregation was reduced, and it was virtually eliminated by subsequent processing on Sephacryl S-200, a step in the existing procedure designed to remove aggregates. The increase in aggregation of IVIG appeared to be eliminated on inclusion of either 0.5 mM or 1 mM rutin. We conclude that both albumin and IVIG can be treated with UVC to inactivate > or = 10(6) ID of nonenveloped viruses. The inclusion of rutin during treatment helps protect against protein aggregation.

Blood Proteins↗
PubMed1997

[Progressive supranuclear palsy with macular degeneration--report of three cases].

Three cases of progressive supranuclear palsy (PSP) with decreased visual acuity were reported. Case 1 was a 50-year-old man, case 2 a 60-year old woman, and case 3 a 66-year-old woman. They all had vertical gaze palsy and unexplained falls, and were diagnosed as PSP by NINDS-SPSP clinical criteria. All cases had symptoms of difficulty in vision; therefore, detailed ophthalmological tests were performed. Ophthalmoscopic findings of macula revealed atrophy in case 1 and 2, and brownish discoloration in case 3. Fluorescein fundus angiography done in case 1 showed abnormal staining at the macula. Multifocal electroretinography performed in case 3 showed absence of big response in the macula. These results indicated macular degeneration. None of three cases had cataract. And visual evoked potentials of case 2 and 3 showed prolonged P100 latency. From these results, we suspected that decreased visual acuity of our cases were due to macular degeneration and difficulty to catch the object at the fovea because of gaze palsy. There had been no reports of macular degeneration with PSP, but we might have overlooked these findings, because of dementia, gaze palsy, and apraxia of lid opening. The possibility of macular degeneration is raised as a part of neurological signs is PSP.

Aged↗
PubMed1996

Simple-spike activity of floccular Purkinje cells responding to sinusoidal vertical rotation and optokinetic stimuli in alert cats.

To understand how the cerebellar flocculus is involved in the processing of semicircular canal signals in the vertical vestibulo-ocular reflex (VOR), we analyzed the simple-spike activity of floccular Purkinje (P) cells that was modulated by sinusoidal pitch rotation, and then analyzed their activity during presentation of sinusoidal vertical optokinetic stimuli in alert, head-fixed cats. The great majority of P cells also responded to optokinetic stimuli with peak discharge near peak stimulus velocity. Eighty percent of P cells that responded to both pitch and optokinetic stimuli showed increased activity when the directions of the resultant eye movements were the same. During rapid modification of the VOR induced by visual pattern movement, modulation amplitudes of the cells tested increased together with the eye velocity increase. Maximal activation directions of these cells studied during vertical rotation in many planes were near the vertical canal planes, similar to those in our previous studies. The remaining 20% of P cells showed increased discharge for the same direction of stimulus movement. These results suggest that the activity of the majority of pitch-responding P cells contains, at least partly, a vertical eye velocity component during presentation of vestibular or optokinetic stimuli in addition to canal inputs during pitch rotation.

Animals↗
PubMed1996

Cross axis vestibulo-ocular reflex induced by pursuit training in alert monkeys.

We examined the effect of conflicting vestibular and smooth pursuit information on the vestibulo-ocular reflex (VOR) in alert monkeys. Sinusoidal whole body rotation was applied either in the pitch or yaw plane while presenting a target spot that moved orthogonally to the rotation plane. The monkeys were rewarded for tracking the spot and eye movements induced by rotation alone were examined every 15-30 min in complete darkness. Orthogonal eye movement responses to rotation were not observed before training but appeared after about 30 min of training. The gains (eye/chair) of the orthogonal component increased up to 0.2 after 1-2 h and were largest at the training frequency and approximately in phase with the stimulus; phase advanced at lower frequencies and lagged at higher frequencies. Amplitude tuning was also demonstrated when examined using different amplitudes at a constant frequency after training. Two hours of training to fixate an earth-stationary spot projected onto a patterned visual background that moved orthogonally to the rotation plane during rotation, did not induce a cross axis response. These results indicate that pursuit training during VOR is effective in inducing cross-axis eye movement responses that are tuned to the metrics of the training stimulus.

Adaptation, Physiological↗
PubMed1996

Further evidence for the specific involvement of the flocculus in the vertical vestibulo-ocular reflex (VOR).

We examined the simple-spike activity of floccular Purkinje (P) cells during sinusoidal pitch rotation and vertical optokinetic stimuli in alert, head-fixed cats. The great majority of pitch-responding P cells also responded to optokinetic stimuli with increased activity when the directions of the resultant eye movements were the same. During rapid modification of the VOR induced by visual pattern movement, modulation amplitudes of the cells tested increased together with the eye velocity increase. Maximal activation directions of these cells studied during vertical rotation in many planes were near the vertical canal planes. These results suggest that the activity of the majority of pitch-responding P cells contains a vertical eye velocity component during vestibular or optokinetic stimuli in addition to canal inputs during pitch rotation.

Animals↗
PubMed1996

Negative regulation of the rat Na-K-ATPase alpha 3-subunit gene promoter by thyroid hormone.

Na-K-ATPase alpha 3-subunit mRNA levels are both positively and negatively controlled by thyroid hormone [3,5,3'triiodothyronine (T3)] in primary cultures of neonatal rat cardiac myocytes. In this study, transient transfection analysis indicated that two regions of the rat alpha 3 gene between nucleotides -116 and -6 and -6 and +80 conferred T3-mediated inhibition of reporter gene expression. Electrophoretic mobility shift assays showed specific binding of T3 receptor monomers and T3 receptor-retinoid X receptor heterodimers at each alpha 3 gene negative T3-response region. The alpha 3 gene region from -116 to -6 base pairs also mediates repression in response to retinoic acid (RA) and binds RA receptor. In the absence of ligand, reporter gene expression driven by the -116 to -6-base pair region is repressed with cotransfection of T3 receptor, whereas it is unaffected by overexpression of RA receptor. These data demonstrate that the proximal promoter of the rat Na-K-ATPase alpha 3 gene contains sequence motifs that mediate repression of alpha 3 gene transcription in response to either T3 or RA in neonatal rat cardiac myocytes.

Animals↗
PubMed1996

PET and MRI of the thalamus in never-medicated patients with schizophrenia.

OBJECTIVE: This study reports the first paired measurements of glucose metabolism and size of thalamic regions in never-medicated schizophrenic patients using coregistered magnetic resonance imaging (MRI) templates. METHOD: Positron emission tomography with [18F]fluorodeoxyglucose and matching MRI scans were obtained in 20 never-medicated patients with schizophrenia and 15 normal volunteers. Methods for thalamic edge finding, statistical testing of shape differences with chi-square maps, and MRI localization of major thalamic subregions were developed. RESULTS: Patients with schizophrenia showed a diminished metabolic rate in the right thalamus, with a loss of the normal pattern of right greater than left asymmetry. Division into anterior/posterior segments revealed that the left anterior and right posterior showed the decrease. Differences were greater for metabolism in the weighted thalamic area (ratexarea) than for rate per unit area, a finding consistent with reported greater decreases in total neuron number than of neuron density in the thalami of schizophrenic patients. The area of the thalamus was smaller in the patients than in the volunteers, and this difference was greatest in the left anterior region. CONCLUSIONS: The reduced thalamic activity observed in this study lends further support to the concept of deficits in sensory filtering in schizophrenia.

Adult↗