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Biomedical subjects

J Hsiao

Publications and source records attributed to J Hsiao.

At least 19 recordsLinked to original sources
PubMed2002

Genome sequencing of a 239-kb region of rice chromosome 10L reveals a high frequency of gene duplication and a large chloroplast DNA insertion.

In this study we describe a 239-kb region on the long arm of rice chromosome 10 that contains a high density (71%) of locally duplicated genes, including 24 copies of a glutathione S-transferase gene. Intriguingly, embedded within this cluster is a large insertion (approximately 33 kb) of rice (Oryza sativa) chloroplast DNA that is derived from two separate regions of the chloroplast genome. We used DNA fiber-based fluorescence in situ hybridization (fiber-FISH) analyses of O. sativa spp. japonica nuclei to confirm that the insertion of organellar DNA was not a cloning artifact. The sequence of the chloroplast insertion is nearly identical (99.7% identity) to the corresponding regions in the published rice chloroplast genome sequence, suggesting that the transfer event occurred recently. PCR amplification and sequence analysis in two subspecies of rice, O. sativa spp. japonica and spp. indica, indicates that the transfer event predated the divergence of these two subspecies. The chloroplast insertion is flanked by a 2.1-kb perfect direct repeat that is unique to this location in the rice genome.

Base Sequence↗
PubMed2000

Anchoring of rice BAC clones to the rice genetic map in silico.

A wealth of molecular resources have been developed for rice genomics, including dense genetic maps, expressed sequence tags (ESTs), yeast artificial chromosome maps, bacterial artificial chromosome (BAC) libraries and BAC end sequence databases. Integration of genetic and physical maps involves labor-intensive empirical experiments. To accelerate the integration of the bacterial clone resources with the genetic map for the International Rice Genome Sequencing Project, we cleaned and filtered the available EST and BAC end sequences for repetitive sequences and then searched all available rice genetic markers with our filtered databases. We identified 418 genetic markers that aligned with at least one BAC end sequence with >95% sequence identity, providing a set of large insert clones with an average separation of 1 Mb that can serve as nucleation points for the sequencing phase of the International Rice Genome Sequencing Project.

Chromosome Mapping↗
PubMed1998

Citron rho-interacting kinase, a novel tissue-specific ser/thr kinase encompassing the Rho-Rac-binding protein Citron.

We have identified a novel serine/threonine kinase belonging to the myotonic dystrophy kinase family. The kinase can be produced in at least two different isoforms: a approximately 240-kDa protein (Citron Rho-interacting kinase, CRIK), in which the kinase domain is followed by the sequence of Citron, a previously identified Rho/Rac binding protein; a approximately 54-kDa protein (CRIK-short kinase (SK)), which consists mostly of the kinase domain. CRIK and CRIK-SK proteins are capable of phosphorylating exogenous substrates as well as of autophosphorylation, when tested by in vitro kinase assays after expression into COS7 cells. CRIK kinase activity is increased severalfold by coexpression of costitutively active Rho, while active Rac has more limited effects. Kinase activity of endogenous CRIK is indicated by in vitro kinase assays after immunoprecipitation with antibodies recognizing the Citron moiety of the protein. When expressed in keratinocytes, full-length CRIK, but not CRIK-SK, localizes into corpuscular cytoplasmic structures and elicits recruitment of actin into these structures. The previously reported Rho-associated kinases ROCK I and II are ubiquitously expressed. In contrast, CRIK exhibits a restricted pattern of expression, suggesting that this kinase may fulfill a more specialized function in specific cell types.

Amino Acid Sequence↗
PubMed1998

Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint.

The Rad53 protein kinase of Saccharomyces cerevisiae is required for checkpoints that prevent cell division in cells with damaged or incompletely replicated DNA. The Rad9 protein was phosphorylated in response to DNA damage, and phosphorylated Rad9 interacted with the COOH-terminal forkhead homology-associated (FHA) domain of Rad53. Inactivation of this domain abolished DNA damage-dependent Rad53 phosphorylation, G2/M cell cycle phase arrest, and increase of RNR3 transcription but did not affect replication inhibition-dependent Rad53 phosphorylation. Thus, Rad53 integrates DNA damage signals by coupling with phosphorylated Rad9. The hitherto uncharacterized FHA domain appears to be a modular protein-binding domain.

Amino Acid Sequence↗
PubMed1998

Inhibitory function of p21Cip1/WAF1 in differentiation of primary mouse keratinocytes independent of cell cycle control.

The cyclin-dependent kinase inhibitor p21(Cip1/WAF1) has been implicated as an inducer of differentiation. However, although expression of p21 is increased in postmitotic cells immediately adjacent to the proliferative compartment, its expression is decreased in cells further along the differentiation program. Expression of the p21 protein was decreased in terminally differentiated primary keratinocytes of mice, and this occurred by a proteasome-dependent pathway. Forced expression of p21 in these cells inhibited the expression of markers of terminal differentiation at both the protein and messenger RNA levels. These inhibitory effects on differentiation were not observed with a carboxyl-terminal truncation mutant or with the unrelated cyclin-dependent kinase inhibitor p16(INK4a), although all these molecules exerted similar inhibition of cell growth. These findings reveal an inhibitory role of p21 in the late stages of differentiation that does not result from the effects of p21 on the cell cycle.

Acetylcysteine↗
PubMed1996

Velocity-dependent ankle torque in the normal rat.

We evaluated the velocity-dependent ankle torque and associated activity of the ankle extensor muscle stretch reflexes in normal rats. A 287% increase in velocity-dependent ankle torque was observed at the highest velocity tested compared with the lowest velocity. Low velocity torques were minimally altered during general anesthesia that depressed EMG activity by up to 90%. However, velocity-dependent torque during higher velocity ankle rotations (306-612 degrees s-1 correlated with parallel increases in EMG magnitude recorded from the triceps surae muscles. General anesthesia (pentobarbital) abolished 61% of the velocity-dependent ankle torque at 612 degrees s-1. We conclude that ankle torque and ankle extensor muscle activity display velocity enhancement over a broad range. These observations indicate that protocols designed to assess ankle torque in the rat should use instrumentation to produce a broad range of velocities up to at least 600 degrees s-1.

Anesthesia, General↗
PubMed1996

Individual variation in D2 dopamine receptor occupancy in clozapine-treated patients.

OBJECTIVE: The objectives of this study were 1) to pursue the question of clozapine's striatal D2 occupancy in relation to its clinical effectiveness; 2) to investigate the relation between schizophrenic symptoms, clozapine blood levels, and estimated D2 occupancy during clinically stable and unstable conditions; and 3) to examine long-term stability in D2 occupancy. METHOD: Specific binding of the D2 radioligand [123I]benzamide ([123I]IBZM) was studied with single photon emission computed tomography in 13 patients with schizophrenia when they were clinically stable during chronic clozapine treatment, after clozapine dose reduction of > or = 50%, and in a subgroup (N = 7) after restabilization on clozapine regimens. Clozapine's estimated D2 occupancy was based on comparison with values from drug-free normal subjects. RESULTS: A wide range of estimated D2 occupancies (18% to > or = 80%) were associated with sustained, favorable response to clozapine without correlation with residual symptoms. Clozapine blood levels were negatively related to [123I]IBZM specific binding. Acute dose reduction was associated with predicted worsening in positive and negative symptoms and increases in [123I]IBZM specific binding. Independent of clozapine blood level, patients with more symptoms showed lower [123I]IBZM specific binding, consistent with competition of endogenous dopamine for D2 binding sites in patients with greater symptoms. Restabilization on clozapine regimens produced D2 occupancies closely correlated with baseline values. CONCLUSIONS: There was no evidence for a critical degree of D2 occupancy required to sustain clozapine's therapeutic effects across subjects. Simple linear regression was the best-fit model for clozapine's D2 occupancy. Longitudinal follow-up suggests stability over time of D2 occupancy in relation to dose and clinical response within individual patients.

Adult↗
PubMed1994

Flexural behavior of visible light-cured composites as a function of temperature under water immersion test conditions.

OBJECTIVES: The purpose of this study was to investigate the effect of temperature of the flexural behavior for four visible light-cured hybrid composite materials. METHODS: Light-cured samples were post-cured for 24 h at 37 degrees C in 100% relative humidity prior to testing. Flexural tests were performed at the following water immersion temperatures: 5, 15, 25, 37, 45 and 55 degrees C, as well as in the dry condition which served as control. The following flexural property parameters were obtained as a function of test temperature: flexural strength, sigma fs, flexural modulus, Efs, flexural stress at 0.06% total offset strain, 0.06% (yield stress), and the total displacement at fracture, delta fs. Statistically significant differences (p < 0.01) in flexural parameters were noted for all the materials as a function of test temperature. RESULTS: The yield stress, sigma 0.06% was found to be most sensitive to thermomechanical changes. The results of this study indicate significant softening due to temperature under wet immersion test conditions for all materials. The temperature range at which two of the materials show significant reduction in yield stress compare well with "Wet Tg" values obtained by dynamic thermal mechanical analysis (Culbertson et al., 1990; 1991). SIGNIFICANCE: The effect of damage accumulation on surface or subsurface microstructure due to transient thermomechanical loads needs to be taken into account in the correlation of in vitro and in vivo wear or creep behavior.

Absorption↗
PubMed1993

Effects of clozapine and fluphenazine treatment on responses to m-chlorophenylpiperazine infusions in schizophrenia.

OBJECTIVE: To explore serotonin function in patients with schizophrenia during typical and atypical neuroleptic treatment. We hypothesized that clinically relevant doses of the atypical neuroleptic clozapine would attenuate responses to the serotonin agonist m-chlorophenylpiperazine (m-CPP). DESIGN AND INTERVENTIONS: m-CPP or placebo was administered intravenously over 90 seconds to patients who had been receiving no medications for at least 3 weeks. m-CPP was also administered during treatment with the typical neuroleptic fluphenazine and the atypical neuroleptic clozapine. PATIENTS: Fifteen inpatients (two women and 13 men) who met DSM-III-R criteria for chronic schizophrenia (n = 13) or schizoaffective disorder (n = 2) participated in the study. Mean age (+/- SD) was 33.8 +/- 8.0 years. MAIN OUTCOME MEASURES: Measures of m-CPP effects included plasma cortisol and prolactin, body temperature, and the Brief Psychiatric Rating Scale (BPRS). The final BPRS total score at approximately 12 weeks of treatment was used to assess response to clozapine. RESULTS: m-CPP infusion significantly increased plasma cortisol and prolactin levels in drug-free patients. There was a range of behavioral responses while drug-free, but no statistically significant effects on BPRS total or BPRS factor scores. Clozapine treatment significantly blocked neuroendocrine responses to m-CPP, whereas fluphenazine had no effect. Clozapine also appeared to attenuate behavioral responses. CONCLUSIONS: These results demonstrate that clozapine treatment has potent serotonin antagonist effects in patients with schizophrenia. This may be related to clozapine's therapeutic effects since patients with greater cortisol response to m-CPP while drug-free had a better subsequent response to clozapine.

Adult↗
PubMed1993

Site density of mouse intestinal glucose transporters declines with age.

To evaluate the effect of age on nutrient transport, the absorption rates of D-glucose, D-fructose, L-alanine, L-aspartate, L-leucine, L-lysine, L-proline, folic acid, and nicotinamide were determined in isolated jejunal tissues of young (6.7 mo old) and aged (23.7 and 27.0 mo old) mice (COBS:SFW). D-Glucose and D-fructose uptakes per milligram tissue were approximately 20-120% higher in the proximal jejunum and 15-50% higher in the distal jejunum of young mice. Amino acid and vitamin uptakes per milligram were also higher in young mice, but differences were not statistically significant. The number of Na(+)-D-glucose transporters per milligram tissue as estimated by specific phlorizin binding decreased with age. There was no age-related change in passive L-glucose permeability, in Kd of specific phlorizin binding, in transporter turnover rate, and in the molecular weight of the Na(+)-D-glucose transporter. Thus a reduction in D-glucose transporter site density fully accounts for the age-related decline in D-glucose transport rate per milligram small intestine.

Aging↗
PubMed1992

Effect of lithium chloride on ornithine decarboxylase activity in rat adrenal.

The effects of lithium chloride on ornithine decarboxylase (ODC) activity were compared in the adrenal and kidney of control (saline treated) and prolactin-treated rats. ODC activity was decreased in kidney of both groups of animals, the magnitude of the effect of lithium in the hormone-treated group varying with the time of administering the lithium relative to prolactin. The response in the adrenal was quite different. Following treatment with LiCl, there was a gradual increase in ODC activity from a low of 10-35 pmol CO2 x 30 min-1.mg protein-1 in control animals to values 20- to 30-fold greater at 5 h. In rats treated simultaneously with LiCl and prolactin, ODC activity was greater at 5 h than that observed in animals receiving either compound alone, indicating that their effects were additive. When LiCl was given 4 h after prolactin, i.e., 1 h before sacrifice, ODC activity decreased to a very low level at 5 h, as in other tissues. The increase in ODC activity in the adrenal following LiCl is of the same magnitude as the changes observed in tissues stimulated to undergo alterations in proliferation, differentiation, or metabolic or membrane activity by hormones and other external stimuli.

Adrenal Glands↗
PubMed1990

Methodology of microdialysis of neostriatum in hemiparkinsonian nonhuman primates.

In vivo biochemical microdialysis in primate brain would greatly expand our understanding of functional neuronal systems. This work describes our efforts to establish a microdialysis system in primate brain. Seven anesthetized rhesus monkeys underwent magnetic resonance imaging (MRI) with the head fixed in a compatible stereotaxic frame. This allowed stereotaxic localization of the caudate nucleus and putamen. Guide cannulae were implanted and fixed to the skull. Microdialysis probes made from polyethylene and fused silica were inserted into the caudate and putamen through the guide cannulae and perfused at the rate of 1.3 microliters/min. The putamens were approached horizontally, while the caudate nuclei were reached via a 30 degrees-45 degrees angle from the vertical. Postdialysis MRI and histologic evaluation proved that all probes accurately arrived at the predetermined region. Our data show that MRI guided stereotaxis allows accurate placement of dialysis probes and that implantation of guide cannulae is a reliable and convenient way to perform repeated brain microdialysis procedures.

Animals↗
PubMed1990

In vivo changes of catecholamines in hemiparkinsonian monkeys measured by microdialysis.

In monkeys, unilateral intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a useful model of hemiparkinsonism. To evaluate MPTP-induced neurochemical changes in vivo, brain microdialysis was employed to measure extracellular levels of dopamine and its metabolites in the neostriatum of normal and hemiparkinsonian rhesus monkeys (Macaca mulatta). The microdialysis probes were implanted bilaterally into the caudate nucleus and putamen at coordinates determined from magnetic resonance imaging. Dopamine and its metabolites were depleted in the MPTP-lesioned side versus the unlesioned side in hemiparkinsonian monkeys. Tyrosine hydroxylase immunocytochemistry revealed a complete unilateral denervation in the caudate nucleus and putamen and a total loss of tyrosine hydroxylase-immunoreactive cells in the substantia nigra pars compacta in those monkeys. Baseline levels of amines in the neostriatum in normal monkeys were not significantly different from those in the normal (non-MPTP-treated) side in hemiparkinsonian monkeys. These data demonstrate that brain microdialysis is a valuable tool for measuring in vivo neurochemical changes in nonhuman primate brains.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Inhibition of hormone-stimulated ornithine decarboxylase activity by lithium chloride.

Effects of Li+ on hormone-stimulated ornithine decarboxylase (ODC) activity were determined in kidney and liver of rats treated with dexamethasone or prolactin (PRL) and also in cultured, PRL-stimulated Nb2 lymphoma cells. In both systems, LiCl led to rapid and marked decreases in ODC activity. The inhibitory effect of Li+ in exponentially growing Nb2 lymphoma cell cultures, measured at 45 min, was dose-dependent, ranging from 10% at 0.1 mM LiCl to 95% at 10 mM LiCl. Surprisingly, on continued incubation with 10 mM LiCl, the lymphoma cells partially overcame the inhibition, showing ODC activities which reached a maximal value of ca 50% of the control at 4.5 h. The inhibition by Li+ could not be reduced by adding myo-inositol to the culture medium. LiCl did not inhibit ODC activity when added to cell-free extracts of rat tissues and Nb2 lymphoma cells indicating it did not act directly on the enzyme; however, there is evidence that, in intact cells, Li+ enhances the rate of inactivation of the enzyme.

Animals↗
PubMed1989

Isolation of a novel morphinan 3-O-diglucuronide metabolite from dog urine.

Following oral administration of the narcotic antagonist nalmefene [17-(cyclopropylmethyl)-4,5 alpha-epoxy-6-methylenemorphinan-3,14-diol] labeled with 14C to the dog, approximately 50% of the dose was excreted in the urine as a highly polar water-soluble conjugate. Although this major metabolite could be hydrolyzed with beta-glucuronidase to yield nalmefene, the intact conjugate was chromatographically more polar on reversed-phase high-performance liquid chromatography (HPLC) than authentic nalmefene 3-O-glucuronide. Milligram quantities of the metabolite were subsequently isolated and subjected to fast atom bombardment (FAB) mass spectral and nuclear magnetic resonance (NMR) analyses. The conjugate was identified as nalmefene 3-O-beta-diglucuronide with a 1,2-beta linkage between the two glucuronic acids. It is unlikely that this novel form of conjugate is unique to nalmefene and it is probably a metabolite of other morphinans and/or similar drugs in the dog. Nalmefene 3-O-diglucuronide is not a metabolite of nalmefene in man.

Animals↗
PubMed1989

The effects of intravenous clomipramine on neurohormones in normal subjects.

The neuroendocrine effects of iv administration of clomipramine (CMI), a serotonin reuptake inhibitor, were studied in normal subjects. Under double blind, placebo-controlled conditions, single 10- and 20-mg doses of CMI were administered. Ten milligrams of CMI led to significant increases in plasma PRL and cortisol concentrations; plasma ACTH increased slightly but not significantly. In contrast, plasma GH, melatonin, and norepinephrine concentrations did not increase. Plasma PRL, ACTH, and cortisol levels increased significantly after 20 mg CMI; again, there were no significant changes in plasma GH, melatonin, or norepinephrine concentrations. All subjects tolerated the 10-mg dose well, but the 20-mg dose caused nausea in three of six subjects. Desmethylclomipramine, a metabolite that inhibits reuptake of norepinephrine, was not detectable in plasma after either CMI dose. These results support the hypothesis that serotonin is involved in the regulation of PRL, cortisol, and ACTH in humans.

Adrenocorticotropic Hormone↗
PubMed1988

Pharmacokinetics of a new inotropic catecholamine in dog plasma using solid phase extraction technology.

The pharmacokinetics of a new inotropic catecholamine, N-[2-(3,4-dihydroxyphenyl)-ethyl]-1-methyl-3-(3-carbomylphenyl)-pr opylamine HCL (KM-13), was studied following i.v. injection of 50 and 100 micrograms/kg doses to dogs. KM-13 was extracted from plasma using Bond-Elut CN columns and quantitated by HPLC with electro-chemical detection. The plasma concentration--time profile of KM-13 following an i.v. bolus was best fitted with a bi-exponential equation and the terminal elimination phase had a half life of about 20 min. The analytical method, with a limit of sensitivity of 2 ng/ml, would appear to have general applicability in studying the pharmacokinetics of synthetic catecholamines.

Animals↗