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Biomedical subjects

S Hsieh

Publications and source records attributed to S Hsieh.

At least 19 recordsLinked to original sources
PubMed2000

A transcriptional insulator at the imprinted H19/Igf2 locus.

Igf2 and H19 exhibit parent-of-origin-specific monoallelic expression. H19 is expressed from the maternal chromosome and Igf2 from the paternal. The two genes share enhancer elements and monoallelic expression of both genes is dependent on cis-acting sequences upstream of the H19 promoter. In this work we examine the mechanisms by which this region silences the maternal Igf2 allele and we demonstrate that deletion of this region can result in high levels of activation of both H19 and Igf2 from a single chromosome. Moreover, by inserting this cis element between a promoter and its enhancer at a heterologous position, we demonstrate that the sequences carry both insulator activity and the ability to be stably imprinted. We also characterize the insulator in vitro and show that it is neither enhancer nor promoter specific.

Animals↗
PubMed2000

H19 and Igf2 monoallelic expression is regulated in two distinct ways by a shared cis acting regulatory region upstream of H19.

H19 and Igf2 are expressed in a monoallelic fashion from the maternal and paternal chromosomes, respectively. A region upstream of H19 has been shown to regulate such imprinted expression of both genes in cis. We have taken advantage of a loxP/cre recombinase-based strategy to delete this region in mice in a conditional manner to determine the temporal requirement of the upstream region in initiating and maintaining the imprinted expression of H19 and Igf2. Analysis of allele-specific expression of H19 and Igf2 and DNA methylation at the H19 promoter demonstrates that this region controls the monoallelic expression of the two genes in different ways, suggesting that it harbors two functionally distinct regulatory elements. Continued presence of the region is required to silence maternal Igf2 in accordance with its proposed role as an insulator. However, it does not have a direct role in keeping the paternal H19 promoter silenced. Instead, on the paternal chromosome, the upstream element mediates epigenetic modifications of the H19 promoter region during development, leading to transcriptional silencing of H19. Thereafter, its presence is redundant for preventing transcription. Presently, this temporal requirement of the silencing element appears to be a unique cis activity in the mammalian system. However, it is likely that other cis-acting elements, positive and negative, have the ability to effect stable changes in the chromatin structure and are not constantly required to give signals to the transcriptional machinery.

Alleles↗
PubMed2000

The variability of practice hypothesis in motor learning: does it apply to Alzheimer's disease?

Based on Schmidt's (1975) variability of practice hypothesis, this study examined acquisition and transfer of a gross motor skill, namely tossing, in 58 patients with Alzheimer's disease (AD) and 58 healthy older adults under constant, blocked, and random practice conditions. While healthy older adults were able to learn the tossing task equally well under the three practice conditions, only AD patients receiving constant practice showed significant improvements. Tests of intermediate transfer yielded the expected random practice advantage in healthy controls but not AD patients. None of the practice conditions facilitated intermediate transfer in AD patients; however, constant practice did benefit these impaired individuals on tests of near transfer. These results indicate that the variability of practice hypothesis does not extend to AD patients. As motor learning and transfer were clearly a function of constant practice, future attempts to retrain basic activities of daily living in AD patients should emphasize consistency in training.

Aged↗
PubMed2000

Transgenic mice expressing surface markers for IFN-gamma and IL-4 producing cells.

The detection of T(H)1-type and T(H)2-type cells directly in situ would be of great value in the study of T(H) development and function in vivo. Transgenic mice expressing human Thy1 and mouse Thy1.1 under the control of the murine IFN-gamma and IL-4 promoters, respectively, have been generated. The hThy1(+) cells represent (with some temporal lag) most of the IFN-gamma-producing CD4(+) T-cells, while the mThy1.1(+) cells represent only a percentage of IL-4 secreting cells. This may be due to mono-allelic expression of the IFN-gamma and IL-4 genes. Since permeabilization is not required for the detection of the transgenic surface markers, these transgenic mice can facilitate the detection of T(H)1-type and T(H)2-type cells by flow cytometry with surface immunofluorescent staining. These surface markers should permit isolation of viable cells according to their T(H) type for adoptive transfer experiments, and may serve as a model system for tracing the development of T(H)1 and T(H)2-type cells in vivo.

3T3 Cells↗
PubMed2000

The psychological refractory period in Parkinson's disease.

The Psychological Refractory Period paradigm was used to investigate whether patients with Parkinson's disease showed disproportional deficits in regulating responses to two sequential presented stimuli. The first task required a speeded key-press response to an auditory stimulus, and the second task required a speeded key-press response to a visual stimulus. The stimulus onset asynchrony (SOA) between Task 1 and Task 2 was 50 msec., 150 msec., and 650 msec. According to the bottleneck model, the SOA manipulation should not affect performance on Task 1, but reaction time for Task 2 should increase as the SOA between the two tasks decreased. The increase in reaction time for Task 2 was referred to as the Psychological Refractory Period. In this study, both patients with Parkinson's disease and normal controls showed classical effects. More importantly, although the 22 patients with Parkinison's disease took longer to respond to both Tasks 1 and 2 than the 20 normal controls, the effects of the Psychological Refractory Period for the two groups were of the same magnitude. The results suggest that Parkinson's disease affects only the response-execution stages rather than the response-selection stages, based on the central bottleneck model.

Acoustic Stimulation↗
PubMed1999

Source memory in Parkinson's disease.

Three experiments (ns = 14 per group) are reported which investigated the ability of Parkinson patients to remember the characteristics of conditions under which a memory was acquired. In Exp. 1, subjects were required to indicate for each item in a recognition memory test whether it was spoken by Experimenter 1 or by Experimenter 2 (external-external source memory). In Exp. 2, subjects had to indicate for each item whether it was generated by themselves or by the experimenter (internal-external source memory). In Exp. 3, subjects had to judge whether an item was generated by themselves in saying or in thinking (internal-internal source memory). We found that patients with Parkinson's disease were not impaired in the previous two kinds of source memory (Exp. 1 and 2) but were impaired in internal-internal source memory (Exp. 3) relative to the age-matched control groups. In addition, both groups' performance could be improved when given distinctive cues, i.e., perceptual cues in Exp. 1 and different-domain cues in Exp. 2. These results suggest that the availability of cues was critical for Parkinson's disease in source memory. Finally, the result of Exp. 2 also showed generation effects for patients with Parkinson's disease. The generation effect refers to better memory of information by people when they had to produce it, e.g., producing associates to a word, compared with memory of information given to them.

Adult↗
PubMed1998

Separation and identification of peptides in single neurons by microcolumn liquid chromatography-matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and postsource decay analysis.

Microcolumn liquid chromatography (LC) was interfaced with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for separation and identification of peptides present in single neurons from the brain of the snail Lymnaea stagnalis. The nanoliter microcolumn LC effluent, mixed off-line with nanoliter matrix solution, was deposited onto the sample target every 60 s, producing fractions of approximately 145 nL in volume, which, upon drying, produced spots of approximately 1 mm in size. At the end of the chromatographic separation, fractions from the sample target were scanned by MALDI-TOF-MS. Identification of peptide peaks was achieved on the basis of LC elution order and mass information. Further identification based on sequence information was carried out for a native peptide fractionated by microcolumn LC from a single neuron with the postsource decay technique.

Animals↗
PubMed1998

Quantal corelease of histamine and 5-hydroxytryptamine from mast cells and the effects of prior incubation.

Corelease of histamine and 5-hydroxytryptamine from individual mast cells has been measured with fast-scan cyclic voltammetry using a carbon-fiber electrode placed next to a single cell. Release events, induced by exposure of the cells to the calcium ionophore, A23187, were resolved at the level of individual exocytotic events. Changes in the relative concentrations secreted from individual granules were observed after incubation with 5-hydroxytryptamine, histamine, and tryptophan. In contrast, an alteration in individual cell content after such incubations, analyzed with capillary chromatography, was only found after incubation with 5-hydroxytryptamine. Cells incubated with 5-hydroxytryptamine or its precursor, tryptophan, released more 5-hydroxytryptamine and less histamine per secretory event relative to controls. Coincubation of the cells with pargyline and 5-hydroxytryptamine further reduced the release of histamine. Since cell content of histamine is unchanged, the reduction in its release must be due to its displacement to a nonreleasable compartment induced by 5-hydroxytryptamine granular uptake. Incubation with histamine increased histamine secretion and, surprisingly, also increased 5-hydroxytryptamine release without changing its cell content. This result is consistent with a relaxation of the storage matrix accompanying histamine granular uptake allowing more 5-hydroxytryptamine to be released. These results demonstrate that the intragranular mode of storage as well as granular uptake of biogenic amines affects the stoichiometry of their release.

Animals↗
PubMed1998

A specific shifting deficit in Parkinson's disease: a reversal shift of consistent stimulus-response mappings.

Two experiments were designed to investigate effects of cueing upon aptitude for shifting by patients with Parkinson's disease. Subjects executed in alternation two different components of a task set over successive items in a list. We compared the costs of shifting when the stimulus ensemble remained constant from trial to trial ("uniform" lists), with the case in which a change of stimulus ensemble cued each shift of task ("mixed" lists). Shift costs with mixed lists were significantly smaller than those with uniform lists (Exp. 1, ns = 12). This suggests that patients with Parkinson's disease can benefit from cues about the stimulus ensemble in performing tasks. Patients' shifting performance was different from that of controls only in a reversal-shift condition of the previously consistent stimulus-response mappings (Exp. 2, ns = 12). This result suggests that patients with Parkinson's disease suffer from a specific but not a general deficit in ability to shift.

Basal Ganglia↗
PubMed1998

Drug abuse treatment and risky sex: evidence for a cumulative treatment effect?

This paper presents evidence regarding the possibility of a cumulative effect of drug-abuse treatment on reducing risky sexual behavior among individuals entering drug-abuse treatment in the United States from 1991-1993 and participating in the Drug Abuse Treatment Outcome Study (DATOS). Analyses were done of the relationship between lifetime treatment exposure and risky sex by drug users during the year before intake into DATOS. Analyses controlled for age, drug-use severity, criminal history, antisocial conduct disorder, and other factors that might have confounded the relationship between treatment exposure and risky sex. Results indicated that users with more lifetime treatment exposure had lower scores for risky sex. This finding is consistent with the hypothesis that successive episodes of treatment may have long-term cumulative effects on drug users' HIV-risk behavior.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Malignant fibrous histocytoma of the heart presenting as right ventricular outflow tract obstruction: a case report.

Primary malignant fibrous histocytoma (MFH) of the heart is extremely rare. Herein, we report the case of a 17-year-old woman with a primary MFH in the right ventricular outflow tract, presenting with increasing dyspnea on exertion. Wide excision of the tumor, including part of the pulmonary artery and pulmonary valve, was performed under cardiopulmonary bypass. Her postoperative recovery was uneventful.

Adolescent↗
PubMed1997

Determination of enzyme activity in single bovine adrenal medullary cells by separation of isotopically labeled catecholamines.

A microcolumn liquid chromatography method for determining norepinephrine (NE), epinephrine (E), and phenylethanolamine N-methyltransferase (PNMT) enzyme activity in single bovine adrenal medullary cells is presented. Single cells were isolated and treated with excess deuterated substrate, D3-NE (0.05 mM) for enzyme reaction. After 6 h, the reaction was quenched and the product, D3-E, was quantified along with endogenous NE and E. Separation and detection of deuterated and protiated NE and E were achieved with microcolumns (110-125 cm long, 25 microns inner diameter) packed with 3 microns octadecylsilane-modified particles and operated with amperometric detection. Of the 33 cells reported, most cells containing predominantly E have enzyme activity while cells containing predominantly NE and cells containing a mixture of both NE and E show no enzyme activity. After incubation with 10 microM hydrocortisone, of the 17 cells reported, most cells containing predominantly E and cells containing a mixture of both NE and E have enzyme activity while cells containing predominantly NE have no enzyme activity. Detection limits for NE and E were 42 and 48 amol, respectively.

Adrenal Medulla↗
PubMed1996

Organization and chromosomal localization of the gene encoding the mouse acid labile subunit of the insulin-like growth factor binding complex.

After birth, most of insulin-like growth factor I and II (IGFs) circulate as a ternary complex formed by the association of IGF binding protein 3-IGF complexes with a serum protein called acid-labile subunit (ALS). ALS retains the IGF binding protein-3-IGF complexes in the vascular compartment and extends the t1/2 of IGFs in the circulation. Synthesis of ALS occurs mainly in liver after birth and is stimulated by growth hormone. To study the basis for this regulation, we cloned and characterized the mouse ALS gene. Comparison of genomic and cDNA sequences indicated that the gene is composed of two exons separated by a 1126-bp intron. Exon 1 encodes the first 5 amino acids of the signal peptide and contributes the first nucleotide of codon 6. Exon 2 contributes the last 2 nt of codon 6 and encodes the remaining 17 amino acids of the signal peptide as well as the 580 amino acids of the mature protein. The polyadenylylation signal, ATTAAA, is located 241 bp from the termination codon. The cDNA and genomic DNA diverge 16 bp downstream from this signal. Transcription initiation was mapped to 11 sites over a 140-bp TATA-less region. The DNA fragment extending from nt -805 to -11 (ATG, +1) directed basal and growth hormone-regulated expression of a luciferase reporter plasmid in the rat liver cell line H4-II-E. Finally, the ALS gene was mapped to mouse chromosome 17 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1996

Preparation and evaluation of slurry-packed liquid chromatography microcolumns with inner diameters from 12 to 33 microns.

Fused silica capillary liquid chromatography columns with inner diameters between 12 and 33 microns were slurry packed with 5 microns octadecylsilane-modified silica particles. Column efficiencies and van Deemter coefficients were compared. A linear decrease of the A term as column diameter was decreased was the most significant contributor to a lower overall plate height at the optimum velocity.

Chemical Phenomena↗
PubMed1996

Visuospatial orienting of attention in Parkinson's disease.

Orienting attention to visual stimuli was studied in 13 patients with Parkinson's disease whose responses were compared to those of a matched control group using a cued reaction-time task which measured cost and benefit effects of orienting of attention. Both groups were screened to exclude dementia, psychiatric disease, and other neurological abnormalities. Although Parkinson patients showed overall slow mean reaction time, responses showed a pattern of cost and benefit effects similar to that of the control group. The results suggested that Parkinson patients are not impaired on visuospatial orienting of attention on this task.

Aged↗
PubMed1996

Precued shifting of attention between cognitive sets in Parkinson patients.

The precueing paradigm developed by Posner has been used to examine visuospatial shifting of attention. In the current study, we modified such a paradigm so that it could be studied in nonvisuospatial domains and its component processes of disengagement, movement, and engagement could be analyzed in a similar fashion to the visuospatial domains. 14 patients with Parkinson's disease and 14 normal controls matched for age, sex, handedness, and years of education served as subjects. The speed of shifting attention was measured using the cost and benefit analysis. Analyses showed an over-all slowness in reaction time of patients with Parkinson's disease compared to the control group but without a concomitant slowness to engage, shift, and disengage their attention.

Aged↗
PubMed1995

Electrochemical detection of histamine and 5-hydroxytryptamine at isolated mast cells.

The electrochemical oxidation of histamine has been investigated as an analytical tool. In a physiological buffer, histamine is oxidized at carbon fiber microelectrodes at potentials close to the background in a chemically irreversible process. Cylindrical carbon fiber electrodes were used as amperometric detectors for histamine separated with a reversed-phase capillary column, and detection limits of 240 amol were achieved. Electrodes with beveled tips were used as real-time sensors by monitoring with repetitive cyclic voltammograms at a scan rate of 800 V/s with a 16.7-ms repetition rate, and detection limits of 1.4 microM were achieved. Both techniques were used to probe histamine and 5-hydroxytryptamine (5-HT) stored in rat peritoneal mast cells. The content in single cells was measured by capillary HPLC, and both substances were found in single cells. Although the analysis revealed a large cell-to-cell variation in the amount of histamine and 5-HT, the average amount was 150 and 4 fmol of histamine and 5-HT, respectively. Release of histamine and 5-HT was measured with the electrode placed 1 microm from the cell surface. Release was observed as a series of sharp concentration spikes, consistent with corelease of the two substances from individual vesicles following exocytosis.

Animals↗