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Biomedical subjects

L He

Publications and source records attributed to L He.

At least 253 records · Page 14Linked to original sources
PubMed1998

Lead-induced alterations in retinal cGMP phosphodiesterase trigger calcium overload, mitochondrial dysfunction and rod photoreceptor apoptosis.

Lead exposure results in the selective apoptotic loss of rods and bipolar cells. During and following developmental lead exposure rod/retinal cGMP phosphodiesterase expression and activity are delayed in onset and decreased, [Ca2+] is elevated, and mitochondrial ATP synthesis is decreased. In vitro studies, using retinas incubated in Ca2+ and/or Pb2+, demonstrate that rods selectively die by apoptosis, retinal mitochondrial ATP synthesis is decreased, mitochondrial cytochrome c is released and caspase activity is increased. These results suggest that lead-induced rod and bipolar cell apoptosis is triggered by Ca2+ and Pb2+ overload due to altered cGMP phosphodiesterase activity and that mitochondrial alterations play a central role in this process.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

4,4,14 alpha-trimethyl 9 beta,19-cyclo-5 alpha-26-homocholesta-24,26-dien-3 beta-ol: a potent mechanism-based inactivator of delta 24(25)- to delta 25(27)-sterol methyl transferase.

The title compound (4A) was synthesized and tested as a mechanism-based inactivator of the sterol methyl transferase (SMT) enzyme from Prototheca wickerhamii. Using cycloartenol as substrate, 4A was found to exhibit time-dependent inactivation kinetics, generating a Ki value of 30 microM and Kinact value of 0.30 min-1.

Cholesterol↗
PubMed1998

[Association of VNTR region of the human serotonin transporter gene with bipolar disorder among the Han Chinese].

OBJECTIVE: The serotonin transporter gene (SERT) plays an important role in the serotonin uptake into neurons. This paper reports a population and association study among the Han Chinese. METHODS: DNA were extracted from peripheral blood samples of 50 patients with bipolar disorder (DSM-IIIR), 170 unrelated healthy Han Chinese individuals and 10 healthy trios for polymerase chain reaction. The VNTR locus was amplified and PCR products were separated on the 2% agrose gel. RESULTS: All the three alleles(9,10 and 12 copies of repeat unit) reported in other studies were observed in this study with frequency 0.0029, 0.0676 and 0.9294, respectively. Four genotypes distributed in Caucasian: 12/12, 12/10, 12/9 and 10/10 were also found in the Han Chinese population. A significant difference in the allele frequency between the Han Chinese and Caucasian populations was found(P 0.000000001). No disequilibrium was observed after checking the Hardy-Weinberg equilibrium (P=0. 9995). The hereditary stability of this locus in accordance with the rules of Mendelian inheritance was demonstrated in the analysis of ten trios. In addition, a significant increase of frequency of the allele 10 in female patients with bipolar disorder was found (P=0. 043). CONCLUSION: The data of association study might indicate a different mechanism of aetiology of bipolar disorder in male and female.

Asian People↗
PubMed1998

Lymphotactin gene-modified bone marrow dendritic cells act as more potent adjuvants for peptide delivery to induce specific antitumor immunity.

Dendritic cells (DC) are regarded as attractive candidates for cancer immunotherapy. Our aim is to improve the therapeutic efficacy of DC-based tumor vaccine by augmenting DC preferential chemotaxis on T cells. Mouse bone marrow-derived DC were transduced with lymphotactin (Lptn) gene by adenovirus vector. The supernatants from Lptn gene-modified DC (Lptn-DC) were capable of attracting CD4+ and CD8+ T cells in a chemotaxis assay, whereas their mock control could not. Lptn expression of Lptn-DC was further confirmed by RT-PCR. Lptn-DC were pulsed with Mut1 peptide and used for vaccination. Immunization with the low dose (1 x 10(4)) of Mut1 peptide-pulsed DC induced weak CTL activity, whereas the same amounts of Mut1 peptide-pulsed Lptn-DC markedly induced specific CTL against 3LL tumor cells. A single immunization with 1 x 10(4) Mut1 peptide-pulsed Lptn-DC could render mice resistant to a 5 x 10(5) 3LL tumor cell challenge completely, but their counterpart could not. The protective immunity induced by Mut1 peptide-pulsed Lptn-DC depends on both CD4+ T cells and CD8+ T cells rather than NK cells in the induction phase and depends on CD8+ T cells rather than CD4+ T cells and NK cells in the effector phase. Moreover, the involvement of CD28/CTLA4 costimulation pathway and IFN-gamma are also necessary. When 3LL tumor-bearing mice were treated with 1 x 10(4) Mut1 peptide-pulsed Lptn-DC, their pulmonary metastases were significantly reduced, whereas the same low dose of Mut1 peptide-pulsed DC had no obvious therapeutic effects. Our data suggest that Lptn-DC are more potent adjuvants for peptide delivery to induce protective and therapeutic antitumor immunity.

Adenoviridae↗
PubMed1998

RIZ1, but not the alternative RIZ2 product of the same gene, is underexpressed in breast cancer, and forced RIZ1 expression causes G2-M cell cycle arrest and/or apoptosis.

The retinoblastoma protein-interacting zinc finger gene RIZ maps to the distal short arm of human chromosome 1 (1p36), a region thought to harbor tumor suppressor genes for a variety of human cancers including breast cancer. The RIZ gene normally produces two protein products of different length, RIZ1 and RIZ2. RIZ2 is generated by an internal promoter and lacks an NH2-terminal motif of RIZ1, the PR domain conserved in a subfamily of zinc finger genes that function as negative regulators of tumorigenesis. We have here studied whether the RIZ gene may play a role in human neoplasia. We found that expression of RIZ1 is commonly decreased or at undetectable levels in breast cancer tissues and cell lines. Decreased RIZ1 expression was also found in other tumor types including neuroblastoma and lung cancer. Remarkably, RIZ2 is normally expressed in all cases examined, suggesting that the abnormality observed for RIZ1 is specific. Forced RIZ1 expression in breast cancer cells caused cell cycle arrest in G2-M and/or programmed cell death. These observations suggest an exclusive negative selection for RIZ1 but not RIZ2 in breast cancer and a role for RIZ1 in tumor suppression.

Alternative Splicing↗
PubMed1998

HIV type 1 Tat protein inhibits interleukin 12 production by human peripheral blood mononuclear cells.

HIV-1 Tat protein, which trans-activates HIV-1 expression, exerts many effects on host immune function. Meanwhile, PBMCs and pulmonary macrophages from HIV-1-infected patients produce only a small amount of IL-12, which plays an essential role in the development of helper T type 1 (Th1) cells, and in the generation of cytotoxic T lymphocytes. We examined the possibility that Tat suppresses IL-12 production by PBMCs from healthy donors. Tat significantly inhibited IL-12 production by human PBMCs stimulated with Staphylococcus aureus Cowan 1 strain (SAC) at concentrations between 5 and 40 ng/ml. Immunoabsorption by using polyclonal antibody to Tat abolished the suppression of the IL-12 production by Tat. Tat at the same concentrations did not affect IL-10, IL-6, or TNF-alpha production. Other HIV-1 proteins (Nef and gp120) did not influence IL-12 production. Tat also suppressed the expression of mRNA encoding the p40 chain of IL-12, whereas it did not affect the expression of mRNA encoding IL-10 and beta-actin. IL-12 production by monocytes, separated from PBMCs by the adhesion method, was also inhibited by Tat. These results suggest that Tat protein is one of the main causes of decreased IL-12 production by PBMCs (mostly by monocytes) from HIV-1-infected individuals.

Amino Acid Sequence↗
PubMed1998

Involvement of de novo ceramide biosynthesis in tumor necrosis factor-alpha/cycloheximide-induced cerebral endothelial cell death.

Cytokines, including tumor necrosis factor-alpha (TNF-alpha), may elicit cytotoxic response through the sphingomyelin-ceramide signal transduction pathway by activation of sphingomyelinases and the subsequent release of ceramide: the universal lipid second messenger. Treatment of bovine cerebral endothelial cells (BCECs) with TNF-alpha for 16 h followed by cycloheximide (CHX) for 6 h resulted in an increase in ceramide accumulation, DNA fragmentation, and cell death. Application of a cell permeable ceramide analogue C2 ceramide, but not the biologically inactive C2 dihydroceramide, also induced DNA laddering and BCEC death in a concentration- and time-dependent manner. TNF-alpha/CHX-mediated ceramide production apparently is not a result of sphingomyelin hydrolysis because sphingomyelin content does not decrease in this death paradigm. In addition, an acidic sphingomyelinase inhibitor, desipramine, had no effect on TNF-alpha/CHX-induced cell death. However, addition of fumonisin B1, a selective ceramide synthase inhibitor, attenuated TNF-alpha/CHX-induced intracellular ceramide elevation and BCEC death. Together, these findings suggest that ceramide plays at least a partial role in this paradigm of BCEC death. Our results show, for the first time, that ceramide derived from de novo synthesis is an alternative mechanism to sphingomyelin hydrolysis in the BCEC death process initiated by TNF-alpha/CHX.

Animals↗
PubMed1998

Ammonia acquisition in enteric bacteria: physiological role of the ammonium/methylammonium transport B (AmtB) protein.

Homologues of the amtB gene of enteric bacteria exist in all three domains of life. Although their products are required for transport of the ammonium analogue methylammonium in washed cells, only in Saccharomyces cerevisiae have they been shown to be necessary for growth at low NH4+ concentrations. We now demonstrate that an amtB strain of Escherichia coli also grows slowly at low NH4+ concentrations in batch culture, but only at pH values below 7. In addition, we find that the growth defect of an S. cerevisiae triple-mutant strain lacking the function of three homologues of the ammonium/methylammonium transport B (AmtB) protein [called methylammonium/ammonium permeases (MEP)] that was observed at pH 6.1 is relieved at pH 7.1. These results provide direct evidence that AmtB participates in acquisition of NH4+/NH3 in bacteria as well as eucarya. Because NH3 is the species limiting at low pH for a given total concentration of NH4+ + NH3, results with both organisms indicate that AmtB/MEP proteins function in acquisition of the uncharged form. We confirmed that accumulation of [14C]methylammonium depends on its conversion to gamma-N-methylglutamine, an energy-requiring reaction catalyzed by glutamine synthetase, and found that at pH 7, constitutive expression of AmtB did not relieve the growth defects of a mutant strain of Salmonella typhimurium that appears to require a high internal concentration of NH4+/NH3. Hence, contrary to previous views, we propose that AmtB/MEP proteins increase the rate of equilibration of the uncharged species, NH3, across the cytoplasmic membrane rather than actively transporting-that is, concentrating-the charged species, NH4+.

Bacterial Proteins↗
PubMed1998

Astrocytic gap junctions remain open during ischemic conditions.

Gap junctions are highly conductive channels that allow the direct transfer of intracellular messengers such as Ca2+ and inositol triphosphate (IP3) between interconnected cells. In brain, astrocytes are coupled extensively by gap junctions. We found here that gap junctions among astrocytes in acutely prepared brain slices as well as in culture remained open during ischemic conditions. Uncoupling first occurred after the terminal loss of plasma membrane integrity. Gap junctions therefore may link ischemic astrocytes in an evolving infarct with the surroundings. The free exchange of intracellular messengers between dying and potentially viable astrocytes might contribute to secondary expansion of ischemic lesions.

Animals↗
PubMed1998

Hypervariable allelic expression patterns of the imprinted IGF2 gene in tumor cells.

The IGF2 gene, which encodes a growth factor, is subject to genomic imprinting. The frequently observed loss of IGF2 imprinting in a variety of tumors has been suggested to contribute to neoplasia. Since these reports have not documented the imprinting status of IGF2 at the cellular level, it cannot be excluded that the imprinting status might vary within the tumor. The possibility that loss of IGF2 imprinting in neoplastic cells reflects random imprinting patterns, was therefore addressed. We show here that individual cell populations of the JEG-3 choriocarcinoma cell line display heterogenous imprinting patterns of both IGF2 and H19. In addition, a lack of correlation between IGF2 and H19 imprinting status suggests that any regional parental imprint has been functionally lost. This notion is reinforced by the observation that JEG-3 cell subclones display a range of promoter-specific IGF2 allele usage. Moreover, we observed that the imprinting status of H19 and IGF2 were differentially modulated in JEG-3-derived tumors generated in nude mice. The results suggest that allele-specific expression of IGF2 operates in the absence of a parental imprint. Finally, our observations urge caution with respect to the general interpretation of biallelic expression as 'loss of imprinting'.

Alleles↗
PubMed1998

Evaluation of the macrocyclic antibiotic avoparcin as a new chiral selector for HPLC.

Avoparcin is a macrocyclic glycopeptide antibiotic structurally related to vancomycin, teicoplanin, and ristocetin A. When attached to 5-microns spherical silica gel, the avoparcin proved to be an effective chiral stationary phase (CSP) that could be used in the reversed-phase, normal-phase, and polar-organic modes. The avoparcin CSP was complimentary to the other macrocyclic glycopeptide CSPs in that it could resolve some racemates that the others could not, and vice versa. Some important compounds resolved on the avoparcin CSP include verapamil, thyroxine, mephenytoin, and 2-imidazolidone-4-carboxylic acid. The use of this CSP and the optimization of separations on it are discussed. Avoparcin appears to be a useful addition to this family of CSPs.

Anti-Bacterial Agents↗
PubMed1998

Chemoattractive effect on the effector cells of the supernatants from melanoma cells transfected with the interleukin-2 (IL-2), IL-4 or IL-6 gene.

By using the Boyden chamber system, the chemoattractive activity of the supernatants from the B16 melanoma cells transfected with the interleukin-2 (IL-2), IL-4 or IL-6 gene was investigated. We found that supernatants from IL-2- or IL-6-gene-transfected B16 melanoma cells showed chemoattractive activity on natural killer (NK) cells, CD4+ T cells and CD8+ T cells, while the supernatants from IL-4-gene-transfected B16 melanoma cells showed chemotactic activity on macrophages but not on NK cells and T cells. Further, the chemoattractive activity of the supernatants from cytokine-gene-transfected B16 cells might be the direct effects of the cytokine that they have been engineered to secrete. These results indicate that reduced tumorigenicity and increased immunogenicity of cytokine-gene-transfected B16 cells may be attributed to the direct recruitment of immune effector cells by the secreted cytokine, which plays an important role in the induction of the local antitumor immunity.

Animals↗
PubMed1998

Mode-actions of the Na(+)-Ca2+ exchanger: from genes to mechanisms to a new strategy in brain disorders.

Mode-actions of the Na(+)-Ca2+ exchanger from genes to mechanisms to a new strategy for brain disorders were comparatively studied in oxidative stress. In transfected Chinese hamster ovary (CHO) cells steadily expressing the Na(+)-Ca2+ exchanger's gene, Ca(2+)-efflux via an active mode of the Na(+)-Ca2+ exchanger was elicited by hydrogen peroxide (H2O2) after preincubation of the cell with a Ca(2+)-free medium, whereas Ca(2+)-influx via a reverse mode of the Na(+)-Ca2+ exchanger was dramatically evoked by H2O2 after preincubation of the cell with a Ca2+ medium, as a prelude to neuronal death. According to [45Ca2+] uptake of transfected CHO cells at given time intervals or extracellular Na+[Na+]o gradients, hyperbola, logarithmic and sigmoid curve equations of the Na(+)-Ca2+ exchanger's mode-actions were respectively defined in the absence and the presence of H2O2. The Na(+)-Ca2+ exchanger's conformational transition in oxidative stress was dominated by adenosine triphosphate (ATP)-dependent cytoskeletal redox modification, cation-pi interactions and secondary Ca2+ activation. These mechanisms were used to generate an intracellulary distributed tetra-cluster (named VISA931) for rescuing G-protein agonist-sensitive signal transduction and cortico-cerebral somatosensory evoke potential (SEP) from oxidation via activating forward operation of the Na(+)-Ca2+ exchanger, the beta-adrenergic and the P2-purinergic receptors, blocking Ca2+ influx and catalyzing the dismutation of superoxide anions (O2-.) to H2O2. In conclusion, knowledge-based drug design is a new strategy for developing promising candidates of neuroprotective agents.

Aluminum Compounds↗
PubMed1998

Interaction of the Na(+)-Ca2+ exchanger with small molecules on cell Ca2+ signaling.

Interactions of the Na(+)-Ca2+ exchanger with small molecules on cell Ca2+ signaling were elucidated in Chinese hamster ovary (CHO) C1 cells, which transfected a control vector without any expression of the Na(+)-Ca2+ exchanger's gene while CHO CK1.4 cells transfected an expression vector encoding the bovine cardiac Na(+)-Ca2+ exchanger's cDNA, treated with lithium- or sodium-buffer medium respectively, by using L16(2)15 multifactorial orthogonal statistics and fura-2 fluorescence real-time imaging. In contrast to controls of Li(+)-treated C1 cells, the store-dependent Ca(2+)-influx (SDCI) was enhanced by either the Na(+)-Ca2+ exchanger, Na(+), 1-¿(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl¿-1H-imidazole HCl (SK&F96365) or ouabain, and by interactions of the Na(+)-Ca2+ exchanger with either Na+, SK&F96365 or both SK&F96365 and ouabain; and ATP-induced Ca2+ release (AICR) was activated by SK&F96365 or Na+ alone, interactions of the Na(+)-Ca2+ exchanger with SK&F96365 or Na+, and an interaction between SK&F96365 and ouabain. The dramatic interaction of the Na(+)-Ca2+ exchanger with small molecules indicates that cell Ca2+ signaling is generated by inositol triphosphate (InsP3)-dependent pathways, allosteric effects of the G-protein coupled P2y&2u purinoceptor and multi-site recognition. Our findings provide meaningful clues for designing new strategies of cardiocerebral vascular oxidative diseases.

Adenosine Triphosphate↗
PubMed1998

Simulation model of mammographic calcifications based on the American College of Radiology Breast Imaging Reporting and Data System, or BIRADS.

RATIONALE AND OBJECTIVES: The authors developed and evaluated a method for the simulation of calcification clusters based on the guidelines of the Breast Imaging Reporting and Data System of the American College of Radiology. They aimed to reproduce accurately the relative and absolute size, shape, location, number, and intensity of real calcifications associated with both benign and malignant disease. MATERIALS AND METHODS: Thirty calcification clusters were simulated by using the proposed model and were superimposed on real, negative mammograms digitized at 30 microns and 16 bits per pixel. The accuracy of the simulation was evaluated by three radiologists in a blinded study. RESULTS: No statistically significant difference was observed in the observers' evaluation of the simulated clusters and the real clusters. The observers' classification of the cluster types seemed to be a good approximation of the intended types from the simulation design. CONCLUSION: This model can provide simulated calcification clusters with well-defined morphologic, distributional, and contrast characteristics for a variety of applications in digital mammography.

Breast Neoplasms↗
PubMed1998

The Platelet Function Analyzer (PFA-100): a novel in-vitro system for evaluation of primary haemostasis in children.

The PFA-100 system provides an in-vitro method of assessing primary platelet-related haemostasis by measuring the time (the closure time, or CT) taken for a platelet plug to occlude a microscopic aperture cut into a membrane coated with collagen and either epinephrine or ADP. We used the system to establish normal ranges for CTs in healthy children, adults and neonates. Mean CTs of healthy children were independent of the needle gauge used (21G or 23CG) for blood sampling; they were very similar to the mean CTs of healthy adults, but longer than mean CTs of healthy neonates. Although children with haemophilia had normal CTs, the PFA-100 system was found to be potentially useful in screening for von Willebrand disease in children.

Adolescent↗