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Biomedical subjects

Y J He

Publications and source records attributed to Y J He.

At least 19 recordsLinked to original sources

Self-trapped spatiotemporal necklace-ring solitons in the Ginzburg-Landau equation.

We consider a class of self-trapped spatiotemporal solitons: spatiotemporal necklace-ring solitons, whose intensities are azimuthally periodically modulated. We reveal numerically that the spatiotemporal necklace-ring solitons carrying zero, integer, and even fractional angular momentum can be self-trapped over a huge propagation distance in the three-dimensional cubic-quintic complex Ginzburg-Landau equation, even in the presence of random perturbations.

Journal Article↗

Cytoplasmic localized ubiquitin ligase cullin 7 binds to p53 and promotes cell growth by antagonizing p53 function.

Cullins are a family of evolutionarily conserved proteins that bind to the small RING finger protein, ROC1, to constitute potentially a large number of distinct E3 ubiquitin ligases. CUL7 mediates an essential function for mouse embryo development and has been linked with cell transformation by its physical association with the SV40 large T antigen. We report here that, like its closely related homolog PARC, CUL7 is localized predominantly in the cytoplasm and binds directly to p53. In contrast to PARC, however, CUL7, even when overexpressed, did not sequester p53 in the cytoplasm. We have identified a sequence in the N-terminal region of CUL7 that is highly conserved in PARC and a sequence spanning the tetramerization domain in p53 that are required for CUL7-p53 binding. CUL7 and MDM2 did not form a detectable tertiary complex with p53. In vitro, CUL7 caused only mono- or di-ubiquitination of p53 under the conditions MDM2 polyubiquitinated p53. Co-expression of CUL7 reduced the transactivating activity of p53. Constitutive ectopic expression of CUL7 increased the rate of cell proliferation and delayed UV-induced G2 accumulation in U2OS cells expressing functional p53, but had no detectable effect in p53-deficient H1299 cells. Deletion of the N-terminal domain of CUL7 or a mutation disrupting p53 binding abolished the ability of CUL7 to increase the rate of U2OS cell proliferation. Our results suggest that CUL7 functions to promote cell growth through, in part, antagonizing the function of p53.

Amino Acid Sequence↗

Effects of Matrine on proliferation and differentiation in K-562 cells.

We investigated the effects of Matrine on proliferation by trypan blue exclusion and differentiation by benzidine staining positive cells in K-562 cells, assayed the telomerase activity using PCR-ELISA assay, analyzed cell cycle by fluorescence-activated cell sorter analysis of the DNA content, and also determined the gene expression level of c-myc, N-ras and p53 by northern blot and dot blot analysis. The results showed that with the addition of 0.1 mg/ml Matrine, cell growth was inhibited significantly by 4 days, benizidine-positive cells rose from 1% to 2% in control cells to 15% in treated cells on day 5; treatment of K-562 cells with 0.1 mg/ml Matrine for 5 days resulted in a marked inhibition in telomerase activity, in a manner that correlated with the extent of differentiation; after exposure to Matrine for 72 h, 64.6% cells were arrested in the G1-phase of the cell cycle, the fraction of cells in S-phase had decreased from 56.9% in control cells to 24.4% in differentiated cells, and the levels of N-ras and p53 mRNA were remarkably increased for 24 and 48 h, respectively, c-myc mRNA expression level declined for 24 h and was inhibited significantly for 48 h. Our study confirmed that Matrine plays a significant effect on the inhibition of proliferation cells and inducing differentiation in K-562 cells.

Alkaloids↗

Earth's orbital chirality and driving force of biomolecular evolution.

In our recent studies, it has been suggested that both symmetry breaking (violation) and biological rhythms could be caused by the natural rhythmic right-handed helical force field produced by the Earth's orbital chirality (EOC) (1--3). In this essay, according to the further theoretical and experimental studies, it was suggested that the natural EOC force field could serve as the diving force of biomolecular evolution via the chiral interactions. In addition, the following suggestions also were pointed out: (1) The EOC force field could cause the origin of non-coding repetitive DNA sequences ('Junk DNA') to increase the genomes stability and complexity; (2) The EOC force field could increase the structural order of biological systems via the biomolecular EOC stabilization energy effects; (3) The biological information could be spontaneously produced by the chiral interactions of the protogenes with the EOC force field.

Earth, Planet↗

17-beta estradiol can reduce secondary ischemic damage and mortality of subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a unique disorder commonly occurring when an aneurysm ruptures, leading to bleeding and clot formation, with a higher incidence in females. To evaluate the influence of 17-beta estradiol (E2) in the outcome of subarachnoid hemorrhage, SAH was induced by endovascular puncture of the intracranial segment of internal carotid artery in 15 intact females (INT), 19 ovariectomized females (OVX), and 13 ovariectomized female rats with E2 replacement (OVX + E2). Cerebral blood flow was recorded before and after SAH. All animals were decapitated immediately after death or 24 hours after SAH for clot area analysis. Brains were sliced and stained with 2,3,5-triphenyltetrazolium chloride (TTC) for secondary ischemic lesion analysis. The cortical cerebral blood flow (CBF), which was measured by a laser-Doppler flowmeter, decreased to 29.6%+/-17.7%, 22.8%+/-8.3%, and 43.5%+/-22.9% on the ipsilateral side (P = 0.01), and decreased to 63.4%+/-14.1%, 57.4%+/-11.0%, and 66.6%+/-17.9% on the contralateral side (P = 0.26) in INT, OVX, and OVX + E2, respectively. The subcortical CBF, which were measured by the H2 clearance method, were 7.77+/-12.03, 7.80+/-8.65, and 20.58+/-8.96 mL 100 g(-1) min(-1) on the ipsilateral side (P < 0.01), and 21.53+/-2.94, 25.13+/-3.01, and 25.30+/-3.23 mL 100 g(-1) min(-1) on the contralateral side in INT, OVX, and OVX + E2, respectively. The mortality was 53.3%, 68.4%, and 15.4% in INT, OVX, and OVX + E2, respectively (P = 0.01), whereas no significant difference in clot area was noted among the groups. The secondary ischemic lesion volume was 9.3%+/-8.4%, 24.3%+/-16.3%. and 7.0%+/-6.4% in INT, OVX, and OVX + E2, respectively (P < 0.01). This study demonstrated that E2 can reduce the mortality and secondary ischemic damage in a SAH model without affecting the clot volume.

Animals↗

Leptin resistance is associated with hypothalamic leptin receptor mRNA and protein downregulation.

It is well known that leptin plays a predominant role in body weight regulation. Leptin receptors are especially abundant in the hypothalamus, where the majority of leptin's biologic activity occurs. In instances where leptin has no or limited activity, it is easy to implicate leptin resistance and speculate as to the multiple levels where resistance may occur. We hypothesize that leptin resistance is associated with hypothalamic leptin receptor downregulation. Rats were randomly divided into 3 groups receiving phosphate-buffered saline (PBS) or low- or high-dose leptin continually over a 28-day period. Body weight and food intake were measured daily. Long-term leptin treatment resulted in a dose-dependent decrease in body weight for the duration of the study. It also resulted in a dose-dependent decrease in food intake, but only for the first half of the study. A test of leptin resistance was performed at week 3 demonstrating the development of resistance to the anorectic effects of leptin in both treatment groups. The results of the resistance test together with the food intake data suggest that resistance to the appetite-regulating effects of leptin developed during the final 2 weeks of the study. In addition, we show a downregulation of leptin receptor mRNA and protein in the hypothalamus, which may be one of the mechanisms by which the food-intake effects of leptin were lost.

Animals↗

Effect of earth's orbital chirality on elementary particles and unification of chiral asymmetries in life on different levels.

Life is chirally asymmetric at all scales from microscopic elementary particles to molecular and macroscopic levels. How these chiral asymmetries in life on different levels are unified remains unanswered. It has been demonstrated that both the biomolecular homochirality and biological rhythms can be caused by the right-handed helical force-field of the Earth's orbital chirality (EOC). Similar to the helical biomolecules (1), it is here suggested that the right-handed EOC force-field could make the right-handed elementary particles more stable than their left-handed enantiomers to result in the symmetry violation of elementary particles, and the EOC could also cause the macroscopic predominant selection of right-handed asymmetries of living objects (e.g. the helical seashells and plants). Our studies indicated that the weak force in weak interaction may only be a form of the EOC force-field at the microscopic particle level, and the chiral asymmetries in life on various levels could be unified by the natural right-handed EOC force-field. Moreover, the chiral and quantum effects, time, mass, rhythms and relativity could also be unified by the interaction of the EOC force-field with chiral motions and structures under certain conditions.

Circadian Rhythm↗

Periodicity of Earth's orbital chirality and possible mechanism of biological rhythms.

Biological rhythms are ubiquitous in living systems from prokaryote to eukaryote on the Earth. So far, the origin of biological rhythms is still a problem. It is suggested here that the periodicity of the Earth's orbital chirality (EOC) could give rise to the periodicity of the chiral helical biomolecular stability and activity, and then generate the biological rhythms in terrestrial living systems. Our experimental results strongly support the theory that the periodic chiral helical EOC force-field should be the power behind the origin of biological rhythms.

Earth, Planet↗

Effects of sound preconditioning on hearing loss from low or middle-frequency noise exposure.

Objective. To explore prior noise exposures or sound conditioning as a moderator of hearing loss produced by traumatic exposure to low or middle-frequency noise. Method. Two experimental groups of guinea-pigs were conditioned using a 0.5 kHz octave band noise (OBN) at 85 dB, 6 h/d for 4 d. The subjects were allowed to recover for 3 d after conditioning. Then the first group was exposed to a 0.5 kHz OBN at 110 dB for 1 h, the second group was exposed to 1 kHz OBN at 110 dB for 1 h. Two control groups received 0.5 kHz and 1 kHz OBN respectively at 110 dB for 1 h without prior sound conditioning. Result. Hearing threshold shifts recorded at 48 h after the high-level noise exposure in conditioned groups and control groups demonstrated that conditioning provided significant protection on hearing threshold shift from low or middle frequency noise exposure. Histological examination revealed significantly less hair cell loss in the conditioned than in the control groups. In addition, malondialdehyde (MDA) levels in red blood cell (RBC) of conditioned groups were significantly lower as compared with that of the control groups. Conclusion. Low-frequency conditioning provided significant protection not only on hearing threshold shift caused by noise of the same frequency, but also on that caused by middle frequency noise.

Acoustic Stimulation↗

Characterization of the neuroprotective and toxic effects of alpha7 nicotinic receptor activation in PC12 cells.

The alpha7 nicotinic receptor partial agonist DMXB protected differentiated PC12 cells from NGF+ serum deprivation over a concentration range (1-10 microM) that correlated with activation of protein kinase C. Increased toxicity was observed at a higher concentration of DMXB (30 microM) that did not elevate protein kinase C activity, but did increase tyrosine protein kinase activity. Neuroprotection was blocked with the protein kinase C-inhibitor bis-indolemaleimide, while toxicity was attenuated with the tyrosine protein kinase-antagonists herbimycin and genistein. The alpha7-selective antagonist methyllyconitine attenuated both the protective and toxic actions of DMXB, but in temporally distinct manners. Methyllyconitine (1 microM) attenuated toxicity when added 10 s before, but not 10 s after, 30 microM DMXB. In contrast, it blocked neuroprotection when added 10 min post-agonist addition. This temporal difference in receptor-activation that was necessary for protection vs. toxicity reflected the time courses for agonist-induced desensitization of the receptor expressed in Xenopus oocytes. These results indicate that alpha7 nicotinic receptors act through different intracellular transduction processes to protect or kill cells. Further, they suggest that the transduction processes may be differentially activated depending on the amplitude and duration of calcium signals.

Animals↗

Multicentre trial on the efficacy and toxicity of single-dose samarium-153-ethylene diamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases in China.

A multicentre trial was organized in China as part of an international coordinated research project to study the efficacy and toxicity of single-dose samarium-153 ethylene diamine tetramethylene phosphonate (EDTMP) as a palliative treatment for painful skeletal metastases. One hundred and five patients with painful bone metastases from various primaries were treated with 153Sm-EDTMP at a dose of 37 MBq/kg(group I) or 18.5 MBq/kg (group II). The effects were evaluated according to change in daily analgesic consumption, pain score, sum of effect product (SEP), Physician's Global Assessment (PGA), blood counts, and organ function tests conducted regularly for 16 weeks. Fifty-eight of 70 patients in group I and 30 of 35 in group II had a positive response, with SEPs of 22.29+/-14. 47 and 20.13+/-13.90 respectively. Of 72 patients who had been receiving analgesics, 63 reduced their consumption. PGA showed that the Karnofsky score (KS) increased from 58.54+/-25.90 to 71.67+/-26. 53, indicating improved general condition, but the difference was not significant. Among subgroups of patients, only those with breast cancer showed a significant change in the Karnofsky score after treatment. Inter-group differences were found for net change in KS between patients with lung and patients with breast cancer, and between patients with lung and patients with oesophageal cancer. Seventeen patients showed no response. No serious side-effects were noted, except for falls in the white blood cell (nadir 1.5x10(9)/l) and platelet (nadir 6.0x10(10)/l) counts in 44/105 and 34/105 cases, respectively. Ten patients had an abnormal liver function test. Response and side-effects were both independent of dose. In conclusion, 153Sm-EDTMP provided effective palliation in 83.8% of patients with painful bone metastases; the major toxicity was temporary myelosuppression. Further studies are needed to identify better ways of determining the appropriate dose in the individual case and the efficacy of treatment.

Analgesics, Non-Narcotic↗

Spectroscopic comparison of different DNA structures formed by oligonucleotides.

Six different nucleic acid structures including duplex, triplex and quadruplex are formed by oligonucleotides. Their structural properties are studied in detail by four spectroscopic techniques, i.e. CD, UV, NMR and fluorescence. Results are: CD Spectra: The common characteristics is a negative band at 240 nm, and the spectra are different from each other in the range 260-300 nm. Many factors such as chain direction, sugar puckering, orientation of the glycosyl bond, base stacking and sequence can effect their conformation and then show diversity and complexity in the spectra. UV Spectra: The UV spectra of all forms are quite similar, all of them exhibit a sharp positive peak around 210 nm and a broad positive band in the region of 240-280 nm. Although the bands are different in absorbance, the spectra are not characteristic enough to distinguish these forms. In addition, their thermal denaturation is also observed by UV spectrum, different melting curves and points are shown and some thermodynamic information is provided. NMR Spectra: Since the G residues in the six samples all participate in hydrogen bond, the imino proton can not exchange with the solvent freely so as to allow an observable resonance to arise. The resonance number and chemical shift will vary with the change in base-pairing number and mode as well as the whole geometry of its molecule. Fluorescence Spectra: The interaction mechanisms between EB and these structures are different. B type duplex and triplex adopt an intercalative mode in which the efficiency of energy transfer is relatively high and the fluorescence of EB can not be quenched easily. While for the parallel duplex, outside binding is predominant in which energy transfer can hardly happen and most of its fluorescence can be quenched. As for the quadruplex, groove binding is possible, so the efficiency of energy transfer is higher than that in outside binding, but lower than that in intercalative binding, and fluorescence is quenched partly.

Circular Dichroism↗

Effect of chiral helical force field on molecular helical enantiomers and possible origin of biomolecular homochirality.

Biomolecular homochirality means that the amino acids in proteins, and sugars in nucleic acids, occur in one form: amino acids in L-form and sugars in D-form. So far, the reason why these molecules have such uniform chirality is not known. In this paper, it is suggested that a net natural chiral right-handed helical force field, produced by the Earth's orbital chirality (EOC), could affect the stability of molecular helical enantiomers and make the right-handed helical enantiomers more stable than their left-handed enantiomers, so terrestrial biological systems must select both right-handed helical nucleic acids based on D-sugars, and proteins based on L-amino acids. In given conditions, the maximum energy difference between biomolecular helical enantiomers (deltaEmax=/Eleft-Eright/) caused by the EOC may be calculated theoretically to be in the order: B-DNA > A-RNA > A-DNA >> alpha-protein > beta-protein. Our experimental results strongly supported the hypothesis that the EOC could cause the spontaneous selection and amplification of right-handed helical enantiomers and could be the origin of homochirality on the Earth.

Amino Acids↗

Formation and characteristics of an unusual lambda-DNA species.

An unusual DNA species, termed as DNA species A, has been isolated and purified from thermal-denatured lambda-DNA Hind III by Sephadex G-200 gel filtration. Our studies indicate that DNA species A is resistant to DNase I digestion and has a higher melting point. The new DNA species showed a lower absorbency at 260 nm, and a lower fluorescence quantum yield after interaction with ethidium bromide (EB) than native double-stranded lambda-DNA. CD spectrum of DNA species A consists of a broad positive band centered at 245 nm and a weak negative band at 220 nm. transmission electron microscope (TEM) visualizations showed that their lengths of DNA species A fell mainly in three regions (300-500 nm, 750-1000 nm and 1500 nm) that corresponded to three fluorescence bands in the EB-stained gels. Their apparent width and height were 65-75 nm and 2.2 nm respectively as observed by images of atomic force microscope (AFM).

Circular Dichroism↗

Homolog-scanning mutagenesis reveals poliovirus receptor residues important for virus binding and replication.

Poliovirus initiates infection of primate cells by binding to the poliovirus receptor, Pvr. Mouse cells do not bind poliovirus but express a Pvr homolog, Mph, that does not function as a poliovirus receptor. Previous work has shown that the first immunoglobulin-like domain of the Pvr protein contains the virus binding site. To further identify sequences of Pvr important for its interaction with poliovirus, stable cell lines expressing mutated Pvr molecules were examined for their abilities to bind virus and support virus replication. Substitution of the amino-terminal domain of Mph with that of Pvr yields a molecule that can function as a poliovirus receptor. Cells expressing this chimeric receptor have normal binding affinity for poliovirus, yet the kinetics of virus replication are delayed. Results of virus alteration assays indicate that this chimeric receptor is defective in converting native virus to 135S altered particles. This defect is not observed with cells expressing receptor recombinants that include Pvr domains 1 and 2. Because altered particles are believed to be an intermediate in poliovirus entry, these findings suggest that Pvr domains 2 and 3 participate in early stages of infection. Additional mutants were made by substituting variant Mph residues for the corresponding residues in Pvr. The results were interpreted by using a model of Pvr predicted from the known structures of other immunoglobulin-like V-type domains. Analysis of stable cell lines expressing the mutant proteins revealed that virus binding is influenced by mutations in the predicted C'-C" loop, the C" beta-strand, the C"-D loop, and the D-E loop. Mutations in homologous regions of the immunoglobulin-like CD4 molecule alter its interaction with gp120 of human immunodeficiency virus type 1. Cells expressing Pvr mutations on the predicted C" edge do not develop cytopathic effect during poliovirus infection, suggesting that poliovirus-induced cytopathic effect may be induced by the virus-receptor interaction.

Amino Acid Sequence↗

Isolation and characterization of an early T-helper/inducer cell line with a unique pattern of surface phenotype, constitutive cytokine secretion and myc oncogene expression.

The cell line AG-F was isolated from the marrow of a neuroblastoma patient undergoing myeloablative treatment and autologous bone marrow rescue. A year later, the patient developed a Hodgkin's type lymphoma. AG-F cell line demonstrated an unusual phenotype, lacking surface CD2 and CD3, but expressing high levels of CD4, CD5, CD7, CD29, and CD45RO. Markers associated with Hodgkin's lymphoma cells, CD15 and CD30, were also positive. AG-F cells grow in suspension in clusters of 50-200 cells, with a doubling time of 9 h. They can also grow in serum-free medium and form tumors in nude mice. AG-F cells have amplified N-myc and c-myc and high levels of the corresponding mRNA transcripts. Cytogenetic analysis revealed a DNA index by flow cytometry of near tetraploid cells and a karyotype of 85-87 chromosomes, with consistent abnormalities in chromosomes 1, 5, and 9. Gene rearrangement studies revealed rearrangement of the beta gene of the T-cell receptor. AG-F cells secrete high levels of IL-6, IL-8, IL-10, and GM-CSF. Cell adherence and formation of long processes could be induced by fibronectin and were enhanced by exposure to PMA. Cells exposed to phorbol myristate acetate (PMA) had increased expression of CD11a, CD11b, CD18, CD45RO, and HLA-DR, whereas expression of CD15 and CD30 was markedly decreased. Similarly, the level of c-myc and N-myc oncoproteins and the levels of the cytoskeletal proteins, actin, tubulin, and vimentin markedly decreased early after PMA-induced differentiation.

Antigens, CD↗

Expression of N-myc, c-myc, and MDR-1 proteins in newly established neuroblastoma cell lines: a study by immunofluorescence staining and flow cytometry.

A methodology for rapid isolation of neuroblastoma cells from marrow with metastatic neuroblastoma cells was developed using a cocktail of five antibodies and magnetic microspheres coated with secondary antibodies. Cells bound to microspheres were released by brief exposure to chymopapain, followed by repeated culture of released cells in serum-supplemented Dulbecco's modified Eagle's medium and selection for adherent cells. Using this methodology, over 35 primary cell lines were obtained free of contaminating normal cells. Detailed analyses of over 14 cell lines revealed gross differences in cell phenotype, size, morphology development of neurite processes, and doubling time (40 to 80 h). All cell lines expressed the M(r) 145,000 neurofilament, and a few expressed the M(r) 200,000 neurofilament, with very little or no expression of the M(r) 68,000 neurofilament. Eight % of all cells lines had near-diploid DNA content. High expression of the MDR-1 protein was detected in six of the 22 cell lines tested. Great heterogeneity was observed in the expression of N-myc oncoprotein, with ten of 13 patients overexpressing the protein. c-myc oncoprotein was also expressed in all cell lines; however, the level of expression was 4- to 10-fold lower than the N-myc oncoprotein. Localization studies of c-myc and N-myc oncoproteins on the level of light microscopy and electron microscopy revealed exclusive nuclear localization of c-myc, whereas N-myc was localized to the nucleus and to the cytoplasm.

ATP Binding Cassette Transporter, Subfamily B, Mem↗