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Biomedical subjects

L Han

Publications and source records attributed to L Han.

At least 19 recordsLinked to original sources
PubMed2006

Rapid eye movement sleep deprivation selectively impairs recall of fear extinction in hippocampus-independent tasks in rats.

Previous studies have shown that rapid eye movement (REM) sleep deprivation (RSD) exerts a detrimental effect on some memory tasks. However, whether post-learning RSD impairs memory for fear extinction, an important model of inhibitory learning, remains to be elucidated. The present study examined the effects of post-extinction RSD from 0 to 6 h and 6 to 12 h on recall of fear extinction tested 24 h after extinction training. We found that RSD from 0 to 6 h significantly increased freezing when recall of extinction of cued fear was tested in the context in which rats received extinction training whereas RSD from 6 to 12 h had no effect (experiments 1 and 2, two hippocampus-independent memory tasks). RSD at either time point had no effect on freezing when recall of extinction of cued fear was tested in the context different from that in which extinction training occurred (experiment 3, a hippocampus-dependent memory task). Additionally, we observed no effect of RSD at either time point on freezing during recall test for extinction of contextual fear (experiment 4, a hippocampus-dependent memory task). These results suggest that the effects of post-extinction RSD on memory for fear extinction are complex. RSD impairs recall of fear extinction in hippocampus-independent tasks, but does not affect recall of fear extinction in hippocampus-dependent tasks. Our findings extend previous research on the effects of RSD on learning and memory and support the notion that REM sleep is involved in memory process of certain tasks.

Acoustic Stimulation↗
PubMed2006

Mutagenesis in mice of nuclear hormone receptor binding sites in the Igf2/H19 imprinting control region.

The H19/Igf2 imprinting control region (ICR) is a DNA methylation-dependent chromatin insulator in somatic cells. The hypomethylated maternally inherited ICR binds the insulator protein CTCF at four sites, and blocks activity of the proximal Igf2 promoter by insulating it from the shared distal enhancers. The hypermethylated paternally inherited ICR lacks CTCF binding and insulator activity, but induces methylation-silencing of the paternal H19 promoter. The paternal-specific methylation of the ICR is established in the male germ cells, while the ICR emerges from the female germ line in an unmethylated form. Despite several attempts to find cis-regulatory elements, it is still unknown what determines these male and female germ cell-specific epigenetic modifications. We recently proposed that five in vivo footprints spanning fifteen half nuclear hormone receptor (NHR) binding sites within the ICR might be involved, and here we report on the effects of mutagenizing all of these half sites in mice. No effect was obtained--in the female and male germ lines the mutant ICR remained hypomethylated and hypermethylated, respectively. The ICR imprinting mechanism remains undefined.

Animals↗
PubMed2005

Classical genotropic versus kinase-initiated regulation of gene transcription by the estrogen receptor alpha.

Elucidation of kinase-initiated routes by which the estrogen receptors alpha and beta (ERalpha and ERbeta) control gene transcription, along with evidence of distinct biologic outcomes in response to ligands that can selectively activate nongenotropic signaling of the ERs or the androgen receptor, suggest that the ERs control a range of genes wider than that regulated by their direct association with DNA. To ascertain the extent and significance of nongenotropic ER-mediated transcription, we employed transduced HeLa cells expressing wild-type ERalpha or the ligand binding domain of ERalpha localized to the cell membrane (E-Mem), the OB-6 osteoblastic cell line, MCF-7 breast carcinoma cells and uteri from mice treated with 17beta-estradiol (E(2)), or the nongenotropic signaling activator 4-estren-3alpha,17beta-diol (estren). E(2) and estren induced ERK1/2 and Akt phosphorylation in ERalpha or E-Mem stably transfected HeLa cells; however, the phosphorylation kinetics differed between the two cell lines. In all four models, nongenotropic ER actions regulated a population of genes distinct from those regulated by genotropic ER actions. Specifically, the expression of Wnt2, Frizzled10, Egr-1, and c-Fos was strongly up-regulated in E-Mem-containing HeLa cells treated with E(2) or estren, or in ERalpha-containing HeLa cells treated with estren. Up-regulation of Frizzled10 by estren was reproduced in MCF-7 cells. Egr-1 was up-regulated by both estren and E(2); but complement 3, only by E(2) in the uteri. Estren had no effect on complement 3, cathepsin D, progesterone receptor, bcl-2, and cyclin D1 in MCF-7 cells, whereas E(2) up-regulated all these estrogen response element or activating protein-1-containing genes. These results support an extensive divergence in gene expression depending on the mode of ER activation.

Animals↗
PubMed2005

Effects of Si-Jun-Zi decoction polysaccharides on cell migration and gene expression in wounded rat intestinal epithelial cells.

Si-Jun-Zi decoction (SJZD), a traditional Chinese herbal prescription, has been used clinically for treating patients with disorders of the digestive system. Previous studies indicated that the polysaccharides of SJZD (SJZPS) are the active components contributing towards its pharmacological effects in improving gastrointestinal function and immunity. However, the protective and restitutive effects on intestinal epithelial cells remain unknown. In the present study, SJZPS were first extracted and chemically characterized. Then their stimulatory and restitutive effects on intestinal epithelial cells (IEC-6 cells) were elicited by different in vitro models including migration of wounded IEC-6 cells and cell proliferation. Results indicated that SJZPS not only protects the cells against the harmful impairment of indomethacin but also enhances re-epithelialization of a wounded monolayer at an optimal dose of 100 mug/ml at 24 h incubation. To elucidate the modulatory effect of SJZPS on wounded IEC-6 cells at the molecular level, an oligonucleotide microarray was employed to study differential gene expression of SJZPS-treated IEC-6 cells and the candidate genes were validated by RT-PCR. There was increased expression of genes coding for ion channels and transporters, which are critical to cell migration and restoration of wounded intestinal cells, suggesting a possible mechanism for re-epithelialization. In conclusion, our data show for the first time that SJZPS can enhance intestinal restitution and protect against indomethacin-induced damage of intestinal epithelial cells. These findings provide new insight into the mechanism of action of a traditional Chinese herbal prescription, SJZD, in intestinal wound restitution.

Animals↗
PubMed2004

Self-administered, standardized regimens for multidrug-resistant tuberculosis in South Korea.

SETTING: National Masan Tuberculosis Hospital, Masan, South Korea, a 430-bed tertiary referral hospital specializing in tuberculosis. OBJECTIVE: To evaluate the treatment outcomes of standardized, empiric regimens for multidrug-resistant tuberculosis (MDR-TB). DESIGN: A retrospective analysis of the hospital records of 142 patients with MDR-TB who had failed short-course chemotherapy. Between 1 January 1998 and 30 June 2000, patients were started on one of two standardized, empiric regimens based on previous treatment history. Drug susceptibility testing of the infecting strain was not used to modify the treatment regimen. Treatment was continued for at least 18 months after conversion to a negative culture. RESULTS: Sixty-three patients (44.1%) were cured and discharged from treatment after at least 18 months of negative cultures; 18 (12.7%) failed treatment, 41 (28.9%) defaulted, four died (2.8%), and 15 (10.6%) were transferred to another institution. One patient is still on treatment. Resistance to ofloxacin was the only risk factor related to poor outcome (death or failure) in univariate or multiple logistic regression analysis. CONCLUSIONS: High levels of resistance to second-line drugs are likely a cause of poor outcome of MDR-TB therapy in Korea. Directly observed therapy and other methods to increase patient compliance should be considered nationwide, as they may improve MDR-TB treatment outcomes.

Adolescent↗
PubMed2003

Synthesis and biocompatibility of porous nano-hydroxyapatite/collagen/alginate composite.

Porous nano-hydroxyapatite/collagen/alginate (nHAC/Alginate) composite containing nHAC and Ca-crosslinked alginate is synthesized biomimetically. This composite shows a significant improvement in mechanical properties over nHAC material. Mechanical test results show that the compressive modulus and yield strength of this composite are in direct proportion to the percentage of Ca-crosslinked alginate in the composite. Primary biocompatibility experiments in vitro including fibroblasts and osteoblasts co-culture with nHAC/alginate composite indicated the high biocompatibility of this composite. Therefore the composite can be a promising candidate of scaffold material for bone tissue engineering.

Journal Article↗
PubMed2002

Reversal of bone loss in mice by nongenotropic signaling of sex steroids.

We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand (4-estren-3alpha,17beta-diol) that reproduces the nongenotropic effects of sex steroids, without affecting classical transcription, increases bone mass and strength in ovariectomized females above the level of the estrogen-replete state and is at least as effective as dihydrotestosterone in orchidectomized males, without affecting reproductive organs. Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis in both women and men [corrected].

Animals↗
PubMed2002

A modified technique for the preparation of SO2 from sulphates and sulphides for sulphur isotope analyses.

A modified technique for the conversion of sulphates and sulphides to SO2 with the mixture of V2O5-SiO2 for sulphur isotopic analyses is described. This technique is more suitable for routine analysis of large number of samples. Modification of the reaction vessel and using manifold inlet system allows to analyse up to 24 samples every day. The modified technique assures the complete yield of SO2, consistent oxygen isotope composition of the SO2 gas and reproducibility of delta34S measurements being within 0.10 per thousand. It is observed, however, oxygen in SO2 produced from sulphides differs in delta18O with respect to that produced from sulphates.

Air Pollutants↗
PubMed2001

A repressor-response regulator gene pair controlling jadomycin B production in Streptomyces venezuelae ISP5230.

A second regulatory gene (jadR(1)) is located immediately upstream of the putative repressor gene (jadR(2)) in the jad cluster for biosynthesis of the antibiotic jadomycin B in Streptomyces venezuelae ISP5230. It encodes a 234-amino acid polypeptide with a sequence resembling those of response regulator proteins in two-component control systems. Features in the conserved C-terminal domain of JadR(1) place the protein in the OmpR-PhoB subfamily of response regulators. In mutants where jadR(1) was deleted or disrupted, jadomycin B was not produced, implying that the gene has an essential role in biosynthesis of the antibiotic. Cloning jadR(1) from S. venezuelae in pJV73A, and introducing additional copies of the gene into the wild-type parent by plasmid transformation gave unstable strains with pJV73A integrated into the chromosome. The transformants initially showed increased production of jadomycin B but gave lower titers as excess copies of jadR(1) were lost; mature cultures stabilized with a wild-type level of antibiotic production. The mutant from which jadR(1) had been deleted could not be transformed with pJV73A. Altering the composition of jadR genes in the chromosome by integration of vectors carrying intact and disrupted copies of jadR(1) and jadR(2) provided evidence that the two genes form a regulatory pair different in function from previously reported two-component systems controlling antibiotic biosynthesis in streptomycetes.

Alleles↗
PubMed2001

Core-shell nanostructured nanoparticle films as chemically sensitive interfaces.

This paper reports the results of an investigation of vapor molecule sorption at different types of nanostructured nanoparticle films. Core-shell nanoparticles of two different core sizes, AU2-nm and Au5-nm, and molecular linkers of two different binding properties, 1,9-nonanedithiol and 11-mercaptoundecanoic acid, are utilized as building blocks for constructing chemically sensitive interfaces. The work couples measurements of two different transducers, interdigitated microelectrodes and quartz crystal microbalance, to determine the correlation of the electronic resistance change and the mass loading with vapor sorption. The responses to vapor sorption at these nanostructured interfaces are demonstrated to be dependent on the core size of nanoparticles and the chemical nature of linking molecules. The difference of molecular interactions of vapor molecules at the nanostructured interface is shown to have a significant impact on the response profile and sensitivity. For the tested vapor molecules, while there are small differences for the sorption of nonpolar and hydrophobic vapor molecules, there are striking differences for the sorption of polar and hydrophilic vapor molecules at these nanostructured interfacial materials. The implication of the findings to the delineation of design parameters for constructing core-shell nanoparticle assemblies as chemically sensitive interfacial materials is also discussed.

Journal Article↗
PubMed2001

Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients.

BACKGROUND: Use of anticholinergic (ACH) medications is a biologically plausible and potentially modifiable risk factor of delirium, but research findings are conflicting regarding its association with delirium. OBJECTIVES: To evaluate the longitudinal association between use of ACH medications and severity of delirium symptoms and to determine whether this association is modified by the presence of dementia. PATIENTS AND METHODS: A total of 278 medical inpatients 65 years and older with diagnosed incident or prevalent delirium were followed up with repeated assessments using the Delirium Index for up to 3 weeks. Exposure to ACH and other medications was measured daily. The association between change in medication exposure in the 24 hours preceding a Delirium Index assessment was assessed using a mixed linear regression model. RESULTS: During follow-up (mean +/- SD, 12.3 +/- 7.0 days), 47 medications with potential ACH effect were used in the population (mean, 1.4 medications per patient per day). Increase in delirium severity was significantly associated with several measures of ACH medication exposure on the previous day, adjusting for dementia, baseline delirium severity, length of follow-up, and number of non-ACH medications taken. Dementia did not modify the association between ACH medication use and delirium severity. CONCLUSION: Exposure to ACH medications is independently and specifically associated with a subsequent increase in delirium symptom severity in elderly medical inpatients with diagnosed delirium.

Aged↗
PubMed2001

Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity.

The relationship of the classical receptors and their transcriptional activity to nongenotropic effects of steroid hormones is unknown. We demonstrate herein a novel paradigm of sex steroid action on osteoblasts, osteocytes, embryonic fibroblasts, and HeLa cells involving activation of a Src/Shc/ERK signaling pathway and attenuating apoptosis. This action is mediated by the ligand binding domain and eliminated by nuclear targeting of the receptor protein; ERalpha, ERbeta, or AR can transmit it with similar efficiency irrespective of whether the ligand is an estrogen or an androgen. This antiapoptotic action can be dissociated from the transcriptional activity of the receptor with synthetic ligands, providing proof of principle for the development of function-specific-as opposed to tissue-selective-and gender-neutral pharmacotherapeutics.

Androgens↗
PubMed2001

Rare adult acute lymphocytic leukemia with CD56 expression in the ECOG experience shows unexpected phenotypic and genotypic heterogeneity.

Expression of CD56, a marker of natural killer (NK) cells, in acute lymphocytic leukemia (ALL) is rare and, to date, has been described only in non-B lineage ALL. Among 194 patients with CD56 analysis on the ongoing Eastern Cooperative Oncology Group (ECOG) ALL trial, E2993, 6 cases of CD56+ ALL were found (3.1%) with a median of 95% of blast cells expressing CD56, compared with a median of 1% of blast cells in CD56- ALL (P = 0.0001). FAB-L2 characteristics dominated, without granulation. Blast cells from four CD56+ patients expressed T-cell antigens at variable levels of maturation. A clonal rearrangement of the T-cell receptor beta (TCRbeta) gene was detected only in one patient. TCRbeta variable gene usage studies in this and one other CD56+ ALL patient demonstrated a significantly perturbed usage pattern in both patients when compared with control lymphocytes. The two remaining cases typed as early pre-B ALL (CD19+, CD10+), with one case co-expressing CD7. Cytogenetically, 4 patients were normal, 1 complex abnormal, and 1 Philadelphia chromosome positive. Epstein-Barr virus (EBV) sequences were detected in one T- and both B-lymphoid cases. Our data suggest that CD56 is expressed at a precursor stage common to the T- and the B-cell lineage.

Adult↗
PubMed2001

Fluorescent imaging and analysis with Typhoon 8600.

Current technologies in laser-based imaging systems for life science applications offer highly sensitive and quantitative detection of multiple labels. Typhoon 8600 variable mode imager is capable of fluorescence, storage phosphor, and chemiluminescence detection of gels and blots. The system delivers sensitive fluorescent detection of nucleic acids and proteins in both agarose and polyacrylamide gel formats. Detection and discrimination of multicolor fluorescent signals in fragment analysis, electromobility shift assays, Western blotting and other applications enhance the speed and accuracy of analysis.

DNA↗
PubMed2001

Interleukin 4 content in chronic lymphocytic leukaemia (CLL) B cells and blood CD8+ T cells from B-CLL patients: impact on clonal B-cell apoptosis.

B-chronic lymphocytic leukaemia (CLL) clonal B cells are characterized by resistance to apoptosis. We evaluated clonal B cells and blood T cells for interleukin 4 (IL-4) content as IL-4 is able to increase CLL cell resistance to apoptosis. The content of IL-4 in CD8+ T cells of CLL patients (n = 9) ranged from 37% to 63% of the total CD8+ T cells (mean level of 49% +/- 3.4) compared with a range of 5-10% for control CD8+ T cells. Clonal B cells positive for cytoplasmic IL-4 ranged from 1% to 97% (mean value 57.8 +/- 6.9%). CD8+ T cells and clonal B cells secreted detectable levels of IL-4, but only clonal CLL B cells (n = 4) secreted IL-4 in association with increasing cell numbers. Fludarabine (F-ara-AMP, 0.1-100 micromol/ml) was able to downregulate the IL-4 content of CD8+ T cells, but not clonal B-cell IL-4. Culture supernatant from CLL CD8+ T cells decreased the spontaneous apoptotic rate of clonal B cells that was reversed with anti-IL-4 and soluble IL-4 receptor. These findings show that IL-4 is present in the microenvironment of B-CLL. In addition, use of agents that can interfere with IL-4 presentation to clonal B cells can be effective in increasing clonal B-cell apoptosis.

Antineoplastic Agents↗
PubMed2001

Environmental risk factors for delirium in hospitalized older people.

OBJECTIVES: To evaluate the relationship of environmental risk factors in hospitals to changes over time in delirium symptom severity scores. DESIGN: Observational prospective clinical study with repeated measurements, several times during the first week of hospitalization and then weekly during hospitalization. SETTING: University-affiliated general community hospital. PARTICIPANTS: Four hundred forty-four patients age 65 and older admitted to the medical wards: 326 with delirium and 118 without delirium. Patients with prior cognitive impairment were oversampled. MEASUREMENTS: The severity of delirium symptoms was measured with the Delirium Index, a scale developed and validated by our group, based on the Confusion Assessment Method. Potential environmental risk factors assessed included isolation, hospital unit, room changes, levels of sensory stimulation, aids to orientation, and presence of medical (e.g., intravenous) or physical restraints. RESULTS: Controlling for initial severity of delirium and patient characteristics, variables significantly related to an increase in delirium severity scores included hospital unit (intensive care or long-term care unit), number of room changes, absence of a clock or watch, absence of reading glasses, presence of a family member, and presence of medical or physical restraints. CONCLUSION: The associations of intensive care and medical and physical restraints with severity of delirium symptoms may be due to uncontrolled confounding by indication. However, the other factors identified suggest potentially modifiable risk factors for symptoms of delirium in hospitalized older people.

Aged↗