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Biomedical subjects

S Chiu

Publications and source records attributed to S Chiu.

At least 19 recordsLinked to original sources
PubMed2006

A novel cationic cardiolipin analogue for gene delivery.

The optically active R and S isomers of cationic cardiolipin analogues (CCA) were synthesized and evaluated as a liposome based transfection reagent. Both isomers form stable liposomes with mean diameters of about 120 nm without any additional lipid ingredients. No significant change in particle size distribution profile was observed over one-month storage at room temperature (20-25 degrees C). The gel to liquid crystalline phase transition temperature (Tm) of cationic liposomes comprised of both R and S isomers was approximately 2 degrees C, as measured by differential scanning calorimetry (DSC). Both isomers also formed stable liposomes when combined with DOPE. In vitro transfection efficiency of the CCA/DOPE liposomes complexed to plasmid DNA was evaluated using a luciferase reporter gene. Both liposomes composed of R and S isomers of the cationic cardiolipin displayed higher transfection efficiency than commercially available Lipofectin. Further in vivo studies are warranted.

Animals↗
PubMed2001

Phthalocyanine 4 photodynamic therapy-induced apoptosis of mouse L5178Y-R cells results from a delayed but extensive release of cytochrome c from mitochondria.

Photodynamic therapy (PDT) activates the mitochondrial pathway of apoptosis, for which the release of cytochrome c into the cytosol is considered critical. To further elucidate the role of cytochrome c release in PDT-induced apoptosis, we monitored cytochrome c localization immunocytochemically and related it to nuclear apoptosis of the same cells. When mouse L5178Y-R cells were treated with 300 nM phthalocyanine (Pc) 4 and 0-75 mJ/cm(2) red light, cytochrome c release had a dose response similar to that of clonogenic cell killing, with nearly identical threshold doses. Within individual cells, the release of cytochrome c appeared to be an all-or-none phenomenon. Moreover, it was tightly associated with activation of a caspase-3-like protease and changes in nuclear morphology. Thus, in response to Pc 4-PDT, the release of cytochrome c from mitochondria is a key determinant of apoptotic cell death.

Animals↗
PubMed2001

Human and mouse ABCA1 comparative sequencing and transgenesis studies revealing novel regulatory sequences.

The expression of ABCA1, a major participant in apolipoprotein-mediated cholesterol efflux, is regulated by a variety of factors, including intracellular cholesterol concentration. To identify sequences involved in its regulation, we sequenced and compared approximately 200 kb of mouse and human DNA containing the ABCA1 gene. Furthermore, expression of the human gene containing different 5' ends was examined in transgenic mice. Sequence comparison revealed multiple conserved noncoding sequences. The two most highly conserved noncoding elements (CNS1, 88% identity over 498 bp; CNS2, 81% identity over 214 bp) were also highly conserved in other organisms. Mice containing the human ABCA1 gene, 70 kb of upstream DNA, and 35 kb of downstream DNA expressed the transgene similarly to endogenous Abca1. A second transgene beginning 3' to exon 1 was expressed only in liver, providing strong evidence of an unsuspected liver-specific promoter. The identified conserved noncoding sequences invite further investigation to elucidate ABCA1 regulation.

ATP Binding Cassette Transporter 1↗
PubMed2001

Inverse agonist binding of peripheral benzodiazepine receptors in anxiety disorder.

The binding characteristics of the pBR (peripheral benzodiazepine receptor) inverse agonist, [3H]-Ro 5-4864, were examined in patients diagnosed as generalized anxiety disorder. As compared to normal healthy controls, the anxious subjects demonstrated a statistically significant (p < 0.001) increase in the density of pBR in platelets. The enhanced pBR binding correlated significantly with the severity of global anxiety symptom of the Hamilton Anxiety Rating Scale (HAR-S, p < 0.001). The Psychic component, but not the Somatic component, of the HAR-S, correlated significantly (p < 0.001) with the enhanced pBR binding in platelets. The results provide evidence for the hypothesis of dysregulation of peripheral benzodiazepine receptors in generalized anxiety disorder.

Adult↗
PubMed2001

Septic arthritis of the hip caused by Salmonella typhi.

We describe septic arthritis of the hip in a child with typhoid fever. The aetiological diagnosis was confirmed by a positive Widal test as well as by isolation of Salmonella typhi from joint aspirate. Treatment with ceftriaxone along with surgical drainage was successful.

Arthritis, Infectious↗
PubMed2001

Longitudinal outcome of verbal discourse in children with traumatic brain injury: three-year follow-up.

PURPOSE: This study compared changes in discourse ability between two groups of children age 5 to 10 years after brain injury: those with severe traumatic brain injury (TBI) and those with mild/moderate injury over 3-year follow-up testing. MATERIALS AND METHODS: Forty-three children with TBI were recruited from a larger research project examining cognitive and linguistic recovery after injury. Twenty-two of these patients had severe injuries and 21 sustained mild/moderate injuries. All children were presented an ordered sequence of pictures and asked to verbally produce a story/narrative discourse. Each child was then asked to produce a lesson relating to the story. RESULTS: The severe group performed significantly worse than the mild/moderate group when performance across all four discourse domains was considered. Both groups improved across time on selected discourse measures. Qualitative analysis suggested that the severe group showed differential rates of improvement across the individual discourse variables over the 3-year interval. CONCLUSIONS: Severe TBI can have a pernicious effect on discourse abilities in children years after injury compared with children with mild/moderate injuries. The major caveat is that the discourse measures must be sufficiently challenging when used to assess older children and children with milder forms of TBI.

Analysis of Variance↗
PubMed2000

Two double-blinded, randomized, comparative trials of 4 human immunodeficiency virus type 1 (HIV-1) envelope vaccines in HIV-1-infected individuals across a spectrum of disease severity: AIDS Clinical Trials Groups 209 and 214.

The potential role of human immunodeficiency virus type 1 (HIV-1)-specific immune responses in controlling viral replication in vivo has stimulated interest in enhancing virus-specific immunity by vaccinating infected individuals with HIV-1 or its components. These studies were undertaken to define patient populations most likely to respond to vaccination, with the induction of novel HIV-1-specific cellular immune responses, and to compare the safety and immunogenicity of several candidate recombinant HIV-1 envelope vaccines and adjuvants. New lymphoproliferative responses (LPRs) developed in <30% of vaccine recipients. LPRs were elicited primarily in study participants with a CD4 cell count >350 cells/mm(3) and were usually strain restricted. Responders tended to be more likely than nonresponders to have an undetectable level of HIV-1 RNA at baseline (P=.067). Induction of new cellular immune responses by HIV-1 envelope vaccines is a function of the immunologic stage of disease and baseline plasma HIV-1 RNA level and exhibits considerable vaccine strain specificity.

AIDS Vaccines↗
PubMed2000

Surgical validation and implications for transcatheter closure of quantitative echocardiographic evaluation of atrial septal defect.

Accurate evaluation of secundum atrial septal defect (ASD) is important for the success of transcatheter closure. The purpose of this study was (1) to describe a quantitative evaluation by transthoracic (TTE) and transesophageal (TEE) echocardiography of the various morphologic features of ASD that might be important for patient selection for transcatheter closure, and (2) to assess the reliability of these 2 methods by surgical findings. Preoperative TTE and TEE were used to evaluate the ASD of 27 children undergoing surgical closure. Measurements included the diameters of ASD and the atrial septal lengths in the transverse and longitudinal axis, and the width of the superior, inferior, anteroinferior, and posterior septal margins. The shape and location of the ASD and the adequacy of the septal margins for anchoring occluding devices were determined. Echocardiographic data were compared with corresponding surgical measurements. No significant difference occurred in the means of all the parameters measured with the 3 methods, except for the transverse ASD diameter (p <0.05). Good agreement occurred between TTE and TEE and surgical data, except for the transverse ASD diameter, transverse atrial septal length, and the posterior septal margin on TTE. Intraclass correlations between TTE and TEE and surgical measurements of all parameters were good, except for the transverse ASD diameter. The accuracy in determining shape and location of the ASD by TTE and TEE were 100%, whereas that for determining the adequacy of septal margins was 98% and 97%, respectively. In conclusion, TTE and TEE are reliable methods for quantitative evaluation of ASD.

Cardiac Catheterization↗
PubMed2000

A poly(N-isopropylacrylamide-co-N-acryloxysuccinimide-co-2-hydroxyethyl methacrylate) composite hydrogel membrane for urease immobilization to enhance urea hydrolysis rate by temperature swing*

A composite membrane made of cross-linked poly(N-isopropylacrylamide-co-N-acryloxysuccinimide-co-2-hydroxyethyl methacrylate) (p(NIPAAm-NAS-HEMA)) hydrogel on polyester nonwoven support has been synthesized. The composite membrane shows temperature-responsive properties similar to conventional PNIPAAm hydrogels beads, which reversibly swells below and de-swells above the lower critical solution temperature of PNIPAAm (around 32 to 33 degrees C). Diffusion of urea through the membrane was temperature-dependent with the effective diffusion coefficient at 20 degrees C being 18 times that at 60 degrees C. Urease was immobilized directly to the membrane by forming covalent bonds between its amino groups and the succinimide ester groups of the membrane. Membrane prepared with NIPAAm to NAS molar ratio of 9, and then reacted in pH 7 buffer with 6 mg of urease gave the best immobilized enzyme, where 0.102 mg protein and 5.71 U activity per cm(2) membrane, and 55% relative specific activity could be obtained. There was negligible internal mass transfer resistance for this preparation judging from the calculated effectiveness factor. Urease shows enhanced thermal stability after immobilization with the first-order inactivation rate constant at 70 degrees C decreased to 1/8 of that of free urease. Membrane-immobilized urease could be utilized in a two-compartment membrane reactor with temperature swing to substantially enhance urea hydrolysis rate. The best operating condition of the membrane reactor was with temperature cycling between 60 to 20 degrees C and with temperature change every 10 min, where concentration of product ammonia after 3 h reaction increased 3.8-folds when compared with isothermal operation at 60 degrees C.

Journal Article↗
PubMed2000

Reduced mobilization of CD34+ stem cells in advanced human immunodeficiency virus type 1 disease.

Granulocyte colony-stimulating factor (r-met Hu G-CSF; filgrastim; 10 microgram/kg/day for 7 days) was used to mobilize CD34+stem cells into the peripheral blood of human immunodeficiency virus type 1 (HIV-1)-infected individuals and a group of HIV-1-uninfected donors as a measure of immunologic reserve in HIV-1-infected people. G-CSF mobilized CD34+ cells of HIV-1-infected individuals with cell counts >500 CD4+ cells/mm3, as well as in HIV-1-uninfected donors. In contrast, CD34 cell mobilization was significantly blunted in HIV-1-infected individuals with cell counts <500 CD4+ cells/mm3 (<200 cell days vs. >650 cell days, P<.0005, compared with the >500 CD4+ cell cohort). At least 1.75x10(7) CD34 cells were harvested by leukapheresis from patients in each study cohort. CD34+ cell viability and the ability to differentiate precursor cells into myeloid and erythroid progenitor cells were not affected by HIV-1 infection.

Adult↗
PubMed2000

The role of amino acid neurotransmitters in the regulation of pituitary gonadotropin release in fish.

Both glutamate and gamma-aminobutyric acid (GABA) are involved in pituitary hormone release in fish. Glutamate serves 2 purposes, both as a neurotransmitter and as a precursor for GABA synthesis. Glutamate can be catabolized to GABA by the actions of 2 distinct but related enzymes, glutamate decarboxylase 65 (GAD65) and GAD67. They derive from 2 different genes that likely arose from an early gene duplication prior to the emergence of teleosts more than 400 million years ago. There is good evidence for the involvement of GABA in luteinizing hormone (LH) release in fish. The mechanism of GABA action to stimulate LH release appears to be a combination of effects on GnRH release, potentiation of gonadotropin hormone-releasing hormone (GnRH) action, and in some cases directly at the LH cell. These actions appear to be dependent on such factors as sex or sex steroid levels, and there may also be species differences. Nevertheless, the stimulatory effects of GABA on LH are present in at least 4 fish species. In contrast, convincing data for the inhibitory effects of GABA on LH release have only been observed in 1 fish species. The sites and mechanisms of action of amino acid neurotransmitters on LH release have yet to be fully characterized. Both 130N-methyl-D-aspartic acid (NMDA) and S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptors are likely to have important roles. We suggest that it is a receptor similar to the GABA(A) type which mediates the effects of GABA on LH release in fish, at least partially acting on the GnRH neuron, but likely directly acting at the gonadotroph as well. GABA may also be involved in regulating the release of other pituitary hormones in fish, namely follicle stimulating hormone (FSH = GTH-I), prolactin, and growth hormone. Based on the findings described in this review, a working model for the involvement of glutamate and GABA in the regulation of LH release in teleost fish is proposed.

Animals↗
PubMed1999

Secretory event in intestinal grafts during preservation ischemia.

BACKGROUND: Ischemia triggers secretion of proteins from the intestine, including type II secretory phospholipase A2 (sPLA2). This "secretory event" was studied in intestinal grafts during the first few hours of preservation by measuring total protein, sPLA2, and other enzymes in the UW preservation solution over time. The effect of PX-13, a PLA2 inhibitor, was also studied. MATERIALS AND METHODS: Twenty-five centimeter intestinal grafts were harvested from Lewis rats, flushed, and preserved in UW solution +/- PX-13 at 4 degrees C. UW samples from 0 to 48 h (n = 5 each) were analyzed for total protein, sPLA2, lactate dehydrogenase (LDH), N-acetylglucosamine (NAGA), and lysozyme. Nonpreserved grafts were homogenized in PBS as tissue controls. Standard biochemical methods were used for all assays. RESULTS: Total protein increased rapidly by 5 min, continued to rise more slowly until 30 min, and then stabilized. The most significant increase in sPLA2 activity occurred between 90 and 180 min. NAGA increased most markedly between 30 and 180 min, while LDH increased in the first 30 min, although the level of both enzymes was negligible compared to tissue enzyme. Lysozyme levels were minimal at all times. PX-13 decreased sPLA2 activity markedly at all time points. CONCLUSION: Total protein levels increased before sPLA2, suggesting that sPLA2 may be secreted in response to other proteins or enzymes released even earlier during preservation (e.g., cytokines). These elevations do not appear to be caused by cell death. Phospholipase A2 secretion may be blocked, and this may greatly improve the outcome of intestinal preservation.

Acetylglucosamine↗
PubMed1999

Characterization of the analgesic and anti-inflammatory activities of ketorolac and its enantiomers in the rat.

The marked analgesic efficacy of ketorolac in humans, relative to other nonsteroidal anti-inflammatory drugs (NSAIDs), has lead to speculation as to whether additional non-NSAID mechanism(s) contribute to its analgesic actions. To evaluate this possibility, we characterized (R,S)-ketorolac's pharmacological properties in vivo and in vitro using the nonselective cyclooxygenase (COX) inhibitors [indomethacin (INDO) and diclofenac sodium (DS)] as well as the selective COX-2 inhibitor, celecoxib, as references. The potency of racemic (R,S)-ketorolac was similar in tests of acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema formation in rats; ID50 values = 0.24, 0. 29, and 0.08 mg/kg, respectively. (R,S)-ketorolac's actions were stereospecific, with (S)-ketorolac possessing the biological activity of the racemate in the above tests. The analgesic potencies for (R,S)-, (S)-, and (R)-ketorolac, INDO, and DS were highly correlated with their anti-inflammatory potencies, suggesting a common mechanism. (R,S)-ketorolac was significantly more potent than INDO or DS in vivo. Neither difference in relative potency of COX inhibition for (R,S)-ketorolac over INDO and DS nor activity of (S)-ketorolac at a number of other enzymes, channels, or receptors could account for the differences in observed potency. The distribution coefficient for (R,S)-ketorolac was approximately 30-fold less than for DS or INDO, indicating that (R,S)-ketorolac is much less lipophilic than these NSAIDs. Therefore, the physicochemical and pharmacokinetics properties of (R,S)-ketorolac may optimize the concentrations of (S)-ketorolac at its biological target(s), resulting in greater efficacy and potency in vivo.

Acetic Acid↗
PubMed1998

Radioprotection of cellular chromatin by the polyamines spermine and putrescine: preferential action against formation of DNA-protein crosslinks.

Spermine is an efficient radioprotector of plasmid or viral DNA and of viral minichromosomes by a mechanism involving radical scavenging and the induction of compaction and aggregation of DNA. Based on radioprotection of SV40 minichromosomes at a lower spermine concentration than needed for SV40 DNA, Newton et al. (Radiat. Res. 145, 776-780, 1996) proposed that the differential concentration dependence could account for the greater radiosensitivity of open regions of cellular chromatin compared to bulk inactive chromatin at physiological levels of spermine. However, we recently reported that, whereas the effects of spermine on the formation of DNA double-strand breaks (DSBs) in dehistonized V79 cell DNA (nucleoids) were consistent with spermine-induced DNA compaction, spermine provided no radioprotection of native chromatin and only modest radioprotection of histone H1-depleted chromatin (Chiu and Oleinick, Radiat. Res. 148, 188-192, 1997). To further characterize the radioprotection of cellular chromatin by spermine, radiation-induced DNA-protein crosslinks (DPCs) were investigated, because of evidence that these lesions occur preferentially at or near the sites of anchorage of chromosomes to the nuclear matrix. In contrast to the relatively inefficient radioprotection of V79 cell chromatin against the formation of DSBs, low concentrations (<0.1 mM) of spermine or putrescine provided partial radioprotection against the formation of DPCs in both native and H1-depleted chromatin. Whereas all DPCs generated by the irradiation of chromatin, above the level generated in intact cells, could be blocked by 5 mM spermine, less than half could be blocked by 5 mM putrescine. The difference in efficiency of radioprotection of native chromatin by the two polyamines can be accounted for by assuming that the binding of spermine is 10 times as efficient as the binding of putrescine. The results suggest that (a) both spermine and putrescine bind preferentially and with high affinity at matrix-associated sites of formation of DPCs, disrupting the associations between DNA and protein that are essential for formation of DPCs and/or scavenging hydroxyl radicals at these sites; (b) a smaller fraction of the sites are susceptible to putrescine than to spermine; and (c) endogenous spermine is a major radioprotector of cells against the formation of DPCs, either because of specific features of the lesion or because of the site of lesion formation at the nuclear matrix.

Animals↗
PubMed1997

Radioprotection against the formation of DNA double-strand breaks in cellular DNA but not native cellular chromatin by the polyamine spermine.

The complexing of histones with DNA and the resulting condensation of chromatin protect mammalian cell DNA from radiation-induced strand breakage. In recent studies of SV40 DNA and minichromosomes, marked radioprotection was afforded by spermine through polyamine-induced compaction and aggregation (Newton et al., Radiat. Res. 145, 776-780, 1996). To evaluate the contribution of polyamines to the radioprotection of cellular chromatin, intact V79 cells, nuclei (native chromatin) and chromatin that was partially or completely stripped of histones were treated with spermine or putrescine and gamma-irradiated while embedded in agarose plugs, and induction of double-strand breaks was determined by pulsed-field gel electrophoresis. In the absence of added spermine, the order of radiosensitivity was: dehistonized chromatin (DNA loops anchored to the nuclear matrix) > chromatin depleted of histone H1 > chromatin partially depleted of histone H1 > native chromatin > intact cells. Spermine at concentrations below 1 mM was without effect on strand breakage in any of the preparations, except for limited radioprotection of H1-depleted chromatin. Increasing radioprotection with increasing concentration (1-10 mM) was provided to dehistonized chromatin by spermine but not by putrescine, a polyamine that does not compact DNA or chromatin. Significant radioprotection by spermine was also found for H1-depleted relaxed chromatin at concentrations > or = 1 mM. In contrast, no radioprotection by spermine (up to 10 mM) was observed for any of the chromatin preparations containing all histones. These observations support the hypothesis proposed by Newton et al. that spermine protects DNA against radiation damage via polyamine-induced compaction and aggregation. With removal of histone H1, the exposed chromatin develops the ability to be protected by spermine. However, the absence of radioprotection of native chromatin by spermine is consistent with a role for histones as the major radioprotectors of cellular DNA and the differential radiosensitivity of decondensed compared to condensed cellular chromatin resulting from the effects of factors other than polyamines.

Animals↗
PubMed1996

Prolactin receptor gene expression in specific hypothalamic nuclei increases with age.

Increasing prolactin levels or increasing responsiveness to prolactin may contribute to reproductive aging by influencing the secretory patterns of hypothalamic GnRH, pituitary gonadotropins, and/or ovarian steroids. Some studies have documented changes in the levels of prolactin in peripheral plasma. The goal of this study was to determine whether prolactin receptor mRNA levels in the brain change with aging, which may lead to increasing responsiveness to prolactin. Young (2-4 months) and middle-aged (9-11 months), demonstrating 3 consecutive estrous cycles, and old (16-19 months) and very old (20-21 months) rats, exhibiting repeated pseudopregnancies, were bilaterally ovariectomized. They were implanted with Silastic capsules containing estradiol-17 beta one week later, and killed 2 days after capsule implantation. Changes in prolactin receptor gene expression were assessed using in situ hybridization. The level of prolactin receptor mRNA in choroid plexus, periventricular area of the preoptic nucleus, and arcuate nucleus increased significantly by the time the animals were old. In the lateral ventromedial nucleus, prolactin receptor gene expression did not change significantly during aging, even in the oldest group of rats. These findings suggest that changes in the prolactin receptor gene may influence the ability of prolactin to exert effects and may allow older animals to be more responsive to prolactin than young rats.

Aging↗
PubMed1994

Crystallization and preliminary X-ray diffraction study of the flavoenzyme 2,4-pentadienoyl-CoA reductase from Clostridium aminovalericum.

The tetrameric flavoenzyme 2,4-pentadienoyl-CoA reductase has been crystallized from solutions containing polyethylene glycol as precipitant. The crystals grow in the monoclinic space group C2 with unit-cell dimensions a = 160.2, b = 120.2, c = 95.3 A, beta = 99.0 degrees. The packing parameter V(M) is 2.3 A(3) Da(-1) (Matthews parameter) for four monomers per asymmetric unit. Complete data sets to about 2.9 A resolution have been collected.

Journal Article↗