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Biomedical subjects

L Yin

Publications and source records attributed to L Yin.

At least 19 recordsLinked to original sources
PubMed2006

Theory of laser acceleration of light-ion beams from interaction of ultrahigh-intensity lasers with layered targets.

Experiments at the LANL Trident facility demonstrated the production of monoenergetic ion beams from the interaction of an ultraintense laser with a target comprising a heavy ion substrate and thin layer of light ions. An analytic model is obtained that predicts how the mean energy and quality of monoenergetic ion beams and the energy of substrate ions vary with substrate material and light-ion layer composition and thickness. Dimensionless parameters controlling the dynamics are derived and the model is validated with particle-in-cell simulations and experimental data.

Journal Article↗
PubMed2006

Nonlinear development of stimulated Raman scattering from electrostatic modes excited by self-consistent non-Maxwellian velocity distributions.

The parametric coupling involving backward stimulated scattering of a laser and electron beam acoustic modes (BAM) is described as observed in particle-in-cell (PIC) simulations. The BAM modes evolve from Langmuir waves (LW) as the electron velocity distribution is nonlinearly modified to be non-Maxwellian by backward stimulated Raman scattering (BSRS). With a marginal damping rate, BAM can be easily excited and allow an extended chirping in frequency to occur as later SRS pulses encounter modified distributions. Coincident with the emergence of this non-Maxwellian distribution is a rapid increase in BSRS reflectivities with laser intensities. Both the reflectivity scaling with laser intensity and the observed spectral features from PIC simulations are consistent with recent Trident experiments.

Journal Article↗
PubMed2006

Refined techniques for intestinal transplantation in rat.

Intestinal transplantation (IT), unlike other solid-organ transplantations, such as liver, kidney, and heart, has relatively disappointing results in humans. Significant advances have been made during the past 40 years, but rejection, graft-versus-host disease (GVHD), and infection remain the major obstacles to successful IT. These aspects may be studied using a rat model of IT. Without a microscope and traditional suture for vascular reconstruction, we simplified the procedure using a "three cuffs" technique for orthotopic intestinal transplantation (OIT). Technical modifications of our OIT model that induced good results included (1) adopting a "double cuffs" technique on the graft aorta, (2) using a portal cuff anastomosis to reconstitute the natural and physiologic portal graft drainage with the cuff fixed to the recipient first, and (3) administering a large volume of crystalloid or whole blood to maintain blood pressure and reduce ischemic injury to the graft during operation. In our group, the survival rate of recipients was 87.5% (21 of 24 rats), the average volume of bleeding in the recipient operation was less than 1 mL, and the cold ischemic time, 50 +/- 11 minutes.

Animals↗
PubMed2006

On the natural course of oral lichen lesions in a Swedish population-based sample.

OBJECTIVES: The aim was to assess the natural course of oral lichen lesions (OLL) among unselected, non-consulting individuals. SUBJECTS AND METHODS: A cohort of 327 subjects with OLL, confirmed in 1973-1974 during a population-based survey in two Swedish municipalities, was followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 80 drawn from the 194 surviving subjects who still resided in the area in 1993-1995 was invited for interview and oral re-examination. RESULTS: At the end of follow-up, one case of oral cancer was detected, while 0.4 were expected. The overall mortality among subjects with OLL was not significantly different from that in the 15,817 OLL-free subjects who participated in the initial population based survey in 1973-1974. The lesion had disappeared in 14 (39%) of 36 re-examined subjects with white OLLs in 1973-1974, and four (11%) had transformed into red types. In the corresponding group of 19 with red forms initially, five (26%) had become lesion free and four (21%) had switched to white types. Although the cohort size does not permit firm conclusions regarding oral cancer risk, the natural course over up to 30 years appears to be benign in the great majority.

Adolescent↗
PubMed2005

Nonlinear spectral signatures and spatiotemporal behavior of stimulated Raman scattering from single laser speckles.

Simulations are reported of the Thomson scatter spectrum of electrostatic waves (ESWs) excited in single laser hot spots by backward stimulated Raman scattering (BSRS). Under conditions similar those in the recent experiments of Kline et al. [Phys. Rev. Lett. 94, 175003 (2005)], a spectral streak, resulting from the trapping-induced frequency shift of the ESW, is found for high wave-number ESWs, similar to the observations. This shift and parametric frequency matching lead to isolated BSRS pulses. Modes with acoustic dispersion, resulting from the trapping-modified electron velocity distribution, can enhance the frequency range of the streak.

Journal Article↗
PubMed2005

Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral.

BACKGROUND: Genetic testing for hereditary cancer syndromes contributes to the medical management of patients who may be at increased risk of one or more cancers. BRCA1 and BRCA2 testing for hereditary breast and ovarian cancer is one such widely used test. However, clinical testing methods with high sensitivity for deleterious mutations in these genes also detect many unclassified variants, primarily missense substitutions. METHODS: We developed an extension of the Grantham difference, called A-GVGD, to score missense substitutions against the range of variation present at their position in a multiple sequence alignment. Combining two methods, co-occurrence of unclassified variants with clearly deleterious mutations and A-GVGD, we analysed most of the missense substitutions observed in BRCA1. RESULTS: A-GVGD was able to resolve known neutral and deleterious missense substitutions into distinct sets. Additionally, eight previously unclassified BRCA1 missense substitutions observed in trans with one or more deleterious mutations, and within the cross-species range of variation observed at their position in the protein, are now classified as neutral. DISCUSSION: The methods combined here can classify as neutral about 50% of missense substitutions that have been observed with two or more clearly deleterious mutations. Furthermore, odds ratios estimated for sets of substitutions grouped by A-GVGD scores are consistent with the hypothesis that most unclassified substitutions that are within the cross-species range of variation at their position in BRCA1 are also neutral. For most of these, clinical reclassification will require integrated application of other methods such as pooled family histories, segregation analysis, or validated functional assay.

Amino Acid Sequence↗
PubMed2005

Inhibition of DLX4 promotes apoptosis in choriocarcinoma cell lines.

Homeodomain (HDM) proteins encoded by homeobox (HBX) genes represent a large family of transcriptional factors that control differentiation and development in certain cell types. DLX4 is a member of Distal-less (DLX) family of HBX genes. Recent studies have demonstrated that abnormal expression of DLX4 is present in several types of human tumors, such as breast cancer, leukemia and colon cancer. In the present study, we investigated DLX4 mRNA and protein expression in both normal placental tissues and human choriocarcinoma cell lines. Also, using RNA interference (RNAi) technique, we knocked down the expression of DLX4 and examined apoptosis in JEG-3 cells. Our studies demonstrated that DLX4 RNAi inhibited DLX4 mRNA expression and decreased DLX4 protein mass specifically and effectively, potentially enhancing apoptosis. Moreover, we examined expression of caspase-3 and caspase-8, and found that both caspases were increased after DLX4 knockdown. However, DLX4 RNAi did not influence Bax expression in JEG-3 cells. In conclusion, this study suggests that DLX4 may be involved in the survival of human choriocarcinoma cells, which may be mediated by the inhibition of apoptosis. The detailed mechanism needs further investigation.

Apoptosis↗
PubMed2005

Observation of a transition from fluid to kinetic nonlinearities for langmuir waves driven by stimulated Raman backscatter.

Thomson scattering is used to measure Langmuir waves (LW) driven by stimulated Raman scattering (SRS) in a diffraction limited laser focal spot. For SRS at wave numbers klambda(D) less similar 0.29, where k is the LW number and lambda(D) is the Debye length, multiple waves are detected and are attributed to the Langmuir decay instability (LDI) driven by the primary LW. At klambda(D) greater similar 0.29, a single wave, frequency-broadened spectrum is observed. The transition from the fluid to the kinetic regime is qualitatively consistent with particle-in-cell simulations and crossing of the LDI amplitude threshold above that for LW self-focusing.

Journal Article↗
PubMed2005

Region-specific growth properties and trophic requirements of brain- and spinal cord-derived rat embryonic neural precursor cells.

To determine whether neural precursor cells have region-specific growth properties, we compared the proliferation, mitogenicity, and differentiation of these cells isolated from the embryonic day 16 rat forebrain and spinal cord. Neural precursor cells isolated from both regions were cultured in growth medium supplemented with epidermal growth factor, basic fibroblast growth factor, or epidermal growth factor+basic fibroblast growth factor. Under all three conditions, both neural precursor cell populations proliferated for multiple passages. While spinal cord-derived neural precursor cells proliferated moderately faster in epidermal growth factor-enriched growth medium, brain-derived cells proliferated much faster in basic fibroblast growth factor-enriched growth medium. When exposed to both epidermal growth factor and basic fibroblast growth factor, the two neural precursor cell populations expanded and proliferated more rapidly than when exposed to a single factor, with brain-derived neural precursor cells expanding significantly faster than spinal cord-derived ones (P<0.0001). Differentiation studies showed that both neural precursor cell populations were multi-potent giving rise to neurons, astrocytes, and oligodendrocytes. However, neuronal differentiation from brain-derived neural precursor cells was greater than spinal cord-derived ones (11.95+/-5.00% vs 1.92+/-1.13%; passage 2). Further, the two neural precursor cell populations differentiated into a similar percentage of oligodendrocytes (brain: 8.66+/-5.85%; spinal cord: 7.69+/-3.91%; passage 2). Immunofluorescence and Western blot studies showed that neural precursor cells derived from both regions expressed receptors for basic fibroblast growth factor and epidermal growth factor. However, brain-derived neural precursor cells expressed higher levels of the two receptors than spinal cord-derived ones in growth medium containing epidermal growth factor+basic fibroblast growth factor. Thus, our results showed that neural precursor cells isolated from the two regions of the CNS have distinct properties and growth requirements. Identifying phenotypic differences between these neural precursor cell populations and their growth requirements should provide new insights into the development of cell therapies for region-specific neurological degenerative diseases.

Animals↗
PubMed2004

Calculating biological behaviors of epigenetic states in the phage lambda life cycle.

The biology and behavior of bacteriophage lambda regulation have been the focus of classical investigations of molecular control of gene expression. Both qualitative and quantitative aspects of this behavior have been systematically characterized experimentally. Complete understanding of the robustness and stability of the genetic circuitry for the lysis-lysogeny switch remains an unsolved puzzle. It is an excellent test case for our understanding of biological behavior of an integrated network based on its physical, chemical, DNA, protein, and functional properties. We have used a new approach to non-linear dynamics to formulate a new mathematical model, performed a theoretical study on the phage lambda life cycle, and solved the crucial part of this puzzle. We find a good quantitative agreement between the theoretical calculation and published experimental observations in the protein number levels, the lysis frequency in the lysogen culture, and the lysogenization frequency for mutants of O(R). We also predict the desired robustness for the lambda genetic switch. We believe that this is the first successful example in the quantitative calculation of robustness and stability of the phage lambda regulatory network, one of the simplest and most well-studied regulatory systems.

Bacteriophage lambda↗
PubMed2004

Robustness, stability and efficiency of phage lambda genetic switch: dynamical structure analysis.

Based on the dynamical structure theory for complex networks recently developed by one of us and on the physical-chemical models for gene regulation, developed by Shea and Ackers in the 1980's, we formulate a direct and concise mathematical framework for the genetic switch controlling phage lambda life cycles, which naturally includes the stochastic effect. The dynamical structure theory states that the dynamics of a complex network is determined by its four elementary components: The dissipation (analogous to degradation), the stochastic force, the driving force determined by a potential, and the transverse force. The potential may be interpreted as a landscape for the phage development in terms of attractive basins, saddle points, peaks and valleys. The dissipation gives rise to the adaptivity of the phage in the landscape defined by the potential: The phage always has the tendency to approach the bottom of the nearby attractive basin. The transverse force tends to keep the network on the equal-potential contour of the landscape. The stochastic fluctuation gives the phage the ability to search around the potential landscape by passing through saddle points. With molecular parameters in our model fixed primarily by the experimental data on wild-type phage and supplemented by data on one mutant, our calculated results on mutants agree quantitatively with the available experimental observations on other mutants for protein number, lysogenization frequency, and a lysis frequency in lysogen culture. The calculation reproduces the observed robustness of the phage lambda genetic switch. This is the first mathematical description that successfully represents such a wide variety of major experimental phenomena. Specifically, we find: (1) The explanation for both the stability and the efficiency of phage lambda genetic switch is the exponential dependence of saddle point crossing rate on potential barrier height, a result of the stochastic motion in a landscape; and (2) The positive feedback of cI repressor gene transcription, enhanced by the CI dimer cooperative binding, is the key to the robustness of the phage lambda genetic switch against mutations and fluctuations in kinetic parameter values.

Bacteriophage lambda↗
PubMed2003

Expression of tumor necrosis factor alpha (TNFalpha) following transient cerebral ischemia.

It has been considered that tumor necrosis factor alpha (TNFalpha) is participated in the Alzheimer's, and Parkinson's diseases, brain injury and brain ischemia. However, expression of TNFalpha after brain ischemia has not been demonstrated in detail. Therefore we examined the cellular expression of TNFalpha during and after transient middle cerebral artery occlusion (tMCAO) in mice by use of reverse transcriptase-polymerase chain reaction and immunohistochemical technique. TNFalpha mRNA expression was gradually increased in the neocortex of the ipsilateral hemisphere during ischemia and peaked at 1 hour after reperfusion. Then, the mRNA expression decreased and peaked again at 24 hours after reperfusion. TNFalpha-like immunoreactivities were observed in the process such as dendrite of neuron slightly before ischemia, and markedly increased in neurons in addition to the process of the ipsilateral hemisphere at 1 and 24 hours after ischemia. The results suggest that the expression of TNFalpha is up-regulated in the neurons after tMCAO. TNFalpha may induce ischemic neuronal cell death during ischemic insult.

Animals↗
PubMed2003

Evaluation of neuronal cell death after a new global ischemia model in infant mice.

For the first time we set up a new model for global ischemia in the infant mice, and time-dependent changes of the blood-brain barrier (BBB) disruption and neuronal cell death were investigated in detail. Infant C57/B16 mice (postnatal 13 days) were anesthetized with inhalation of sevoflurane in N2O/O2 (70/30%) and were subjected to global ischemia by bilateral common carotid artery occlusion (CCAO) for 25 minutes. Disruption of BBB was noted at 4 hours and increased up to 24 hours after the injection of 2% Evan's Blue in the transient CCAO (tCCAO) model. Evaluation of neuronal cell death was determined with toluidine blue staining. Morphological changes of neurons after tCCAO were clearly observed in the hippocampal CA1 region but were slightly detected in the CA3 region. However, there were no morphological changes in the hippocampal dentate gyrus, the neocortex, the striatum and the hypothalamus. The number of survival neurons in the CA1 was significantly decreased at 2 days and sustained up to 4 days after tCCAO. These data indicate that this method is very useful to induce selective vulnerability in mouse hippocampus, and it provides a reliable ischemic model in infant mice.

Animals↗
PubMed2003

Suppression of oxidative stress after transient focal ischemia in interleukin-1 knock out mice.

Interleukin-1 (IL-1) contributes to ischemic neurodegeneration. However, the mechanisms regulating action of IL-1 are still poorly understood. In order to clarify this central issue, mice that were gene deficient both IL-1alpha and beta (IL-1 KO) and wild-type mice were subjected to 1 hour transient middle cerebral artery occlusion (tMCAO). The concentration of 8-hydroxy deoxyguanosine (8OHdG) which is considered to be a reliable oxidative DNA damage by superoxide anion, in brain and of total nitric oxide (NO) in plasma were determined by use of HPLC. Twenty-four hours after tMCAO, the ratio of 8OHdG to dG in the ipsilateral hemisphere of wild-type mice were 2.24 x 10(-3) and 4.41 x 10(-3) in the neocortex and striatum, respectively. The concentration of 8OHdG in the ipsilateral hemisphere of the wild-type mice was higher than that of the IL-1 KO mice. The concentration of total NO in the plasma of IL-1 KO mice was also lower than that of the wild-type 24 hours after tMCAO. These results strongly suggest that IL-1 is participated in generating reactive oxygen spices and it aggravates and induces the ischemic neuronal cell death.(183 words).

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Proliferation and differentiation of ductular progenitor cells and littoral cells during the regeneration of the rat liver to CCl4/2-AAF injury.

Restoration of centrolobular injury induced by carbon tetrachloride (CCl4), when hepatocyte proliferation is inhibited by treatment with N-2-acetylaminofluorene (AAF), is accomplished by proliferation of ductular progenitor cells, that arise intraportally and extend into the liver lobule. This pattern contrasts to the restitutive proliferation of hepatocytes when AAF is not administered, and the proliferation of non-ductular periportal oval cells follows periportal necrosis induced by allyl alcohol. The expanding ducts stain for alphafetoprotein (AFP), OV-6, pan-cytokeratin (CKPan), and laminin. The neoductular proliferation is accompanied by fibronectin-positive Kupffer cells and desmin-positive stellate (Ito) cells, which may play critical roles not only in controlling proliferation and differentiation of ductular progenitor cells, but also in reestablishing hepatic cord structure. When AAF is discontinued 7 days after injury, clusters of small hepatocytes appear next to the neoductules. Some of these small hepatocytes, as well as some larger hepatocytes adjacent to the ducts, stain for AFP and for carbamoylphosphate synthetase I (CPS-I), suggesting that the ductular progenitor cells may differentiate into hepatocytes when AAF is withdrawn. The restitutive process is facilitated by clearing of the central necrotic zone by infiltrating macrophages and co-migration of mature hepatocytes, with Kupffer cells and stellate cells, into the necrotic zone.

2-Acetylaminofluorene↗
PubMed2001

Pre-emptive targeting of the epitope spreading cascade with genetically modified regulatory T cells during autoimmune demyelinating disease.

Epitope spreading or endogenous self-priming has been implicated in mediating the progression of autoimmune disease. In the present study we created an immune-deviated, epitope spreading response in SWXJ mice after the onset of experimental autoimmune encephalomyelitis, a prototypic autoimmune animal model widely used in multiple sclerosis research. We established an immunoregulatory spreading repertoire by transferring T cells genetically modified to produce high levels of IL-10 in response to a dominant epitope spreading determinant. Installation of a Th2/Tr1-like spreading repertoire resulted in a marked and prolonged inhibition of disease progression and demyelination characterized by 1) bystander inhibition of the recall response to the priming immunogen, and 2) a Th1-->Tr1 immune-deviated spreading response involving a shift in the source of IL-10 production from the transferred regulatory population to the host-derived, endogenously primed repertoire. Thus, our data provide a rationale for cell-based therapeutic intervention in multiple sclerosis by showing that pre-emptive targeting of the epitope spreading cascade with regulatory T cells effectively induces an immune-deviated spreading response capable of inhibiting ongoing inflammatory autoreactivity and disease progression.

Adoptive Transfer↗
PubMed2001

Butyrate suppression of colonocyte NF-kappa B activation and cellular proteasome activity.

Butyrate is derived from the microbial metabolism of dietary fiber in the colon where it plays an important role in linking colonocyte turnover and differentiation to luminal content. In addition, butyrate appears to have both anti-inflammatory and cancer chemopreventive activities. Using confocal microscopy and cell fractionation studies, butyrate pretreatment of a human colon cell line (HT-29 cells) inhibited the tumor necrosis factor-alpha (TNF-alpha)-induced nuclear translocation of the proinflammatory transcription factor NF-kappaB. Butyrate inhibited NF-kappaB DNA binding within 30 min of TNF-alpha stimulation, consistent with an inhibition of nuclear translocation. IkappaB.NF-kappaB complexes extracted from butyrate-treated cells were relatively resistant to in vitro dissociation by deoxycholate, suggesting a change in cellular IkappaB composition. Butyrate treatment increased p100 expression, an IkappaB that was not degraded upon TNF-alpha treatment. Butyrate also reduced the extent of TNF-alpha-induced IkappaB-alpha degradation and enhanced the presence of ubiquitin-conjugated IkappaB-alpha. The suppression of IkappaB-alpha degradation corresponded with a reduction in cellular proteasome activity as determined by in vitro proteasome assays and the increased presence of ubiquitin-conjugated proteins. The butyrate suppression of IkappaB-alpha degradation and proteasome activity may derive from its ability to inhibit histone deacetylases since the specific deacetylase inhibitor trichostatin A had similar effects. These results suggest a potential mechanism for the anti-inflammatory activity of butyrate and demonstrate the interplay between short chain fatty acids and cellular proteasome activity.

Active Transport, Cell Nucleus↗