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Biomedical subjects

L Song

Publications and source records attributed to L Song.

232 records · Page 13Linked to original sources
PubMed1990

Modulation of phosphoinositide metabolism in rat brain slices by excitatory amino acids, arachidonic acid, and GABA.

In rat brain slices the synthesis of [3H]phosphoinositides and the production of [3H]inositol monophosphate (IP1) induced by norepinephrine (NE) were inhibited by glutamate. Calcium concentrations were varied to test if these inhibitory effects of glutamate were mediated by a calcium-dependent process. Although reducing calcium or addition of the calcium antagonist verpamil reduced the inhibitory effects of glutamate, these results were equivocal because reduced calcium directly decreased agonist-induced [3H]phosphoinositide synthesis. The inhibitory effects of glutamate were mimicked by quisqualate in a dose-dependent manner, but none of a variety of excitatory amino acid receptor antagonists modified the inhibition caused by quisqualate. It is suggested that glutamate activates a quisqualate-sensitive receptor (for which an antagonist is not available) and causes inhibition of phosphoinositide hydrolysis mediated in part by a direct or indirect inhibitory effect of calcium on phosphoinositide synthesis. Modulatory effects of arachidonic acid were examined because glutamate and calcium can activate phospholipase A2. Arachidonic acid caused a rapid and dose-dependent inhibition of [3H]phosphoinositide synthesis and of NE-stimulated [3H]IP1 production. A similar inhibition of the response to carbachol also occurred. The inhibition caused by arachidonic acid was unchanged by addition of inhibitors of cyclooxygenase or lipoxygenase. Activation of phospholipase A2 with melittin caused inhibitory effects similar to those of arachidonic acid. Inhibitors of phospholipase A2 were found to impair phosphoinositide metabolism, likely due to their lack of specificity for phospholipase A2. Further studies were carried out in slices that were prelabelled with [3H]inositol in an attempt to separate modulatory effects on [3H]phosphoinositide synthesis and agonist-stimulated [3H]IP1 production. Several excitatory amino acid agonists inhibited NE-stimulated [3H]IP1 production. This inhibitory interaction could be due to impaired synthesis of [3H]phosphoinositides because, even though the slices were prelabeled, addition of unlabelled inositol reduced NE-stimulated [3H]IP1 production, indicating that continuous regeneration of [3H]phosphoinositides is required. In contrast to the inhibitory effects of the excitatory amino acids, gamma-aminobutyric acid (GABA) enhanced the response to NE in cortical and hippocampal slices. GABA also enhanced the response to carbachol in hippocampal and striatal slices and to ibotenic acid in hippocampal slices. Baclofen potentiated the response to NE similarly to the effect of GABA and baclofen partially blocked the inhibitory effect of arachidonic acid but did not alter that of quisqualate.

Amino Acids↗
PubMed1990

[Change of myocardial glucose and free fatty acid metabolism and effect of electroacupuncture on them during experimental myocardial angina].

This study was designed to observe the effect of electroacupuncture applied at "Neiguan" point on myocardial Glucose (GLU) and Free fatty acid (FFA) metabolism of dogs with experimental myocardial angina, experimental myocardial angina model was set up in 20 healthy mongrel dogs with reducing the volume of blood flow of left anterior descending coronary (LAD) and intracoronary administration of bradykinin. The results showed that arterial-venous difference of glucose (GLUa-v) was increased significantly and arterial-venous difference of free fatty acid (FFAa-v) was decreased significantly after experimental myocardial angina. with prolongation of the period of myocardial ischemia and increase of the times of myocardial angina, in control group, GLUa-v was increased lightly and FFAa-v was markedly decreased (P less than 0.05), this showed that FFA uptake of ischemic myocardium was markedly decreased. Electroacupuncture at bilateral "Neiguan" point resulted significant decrease of GLUa-v and slight increase of FFAa-v. There were statistical significance between the two groups (P less than 0.05) in GLUa-v and FFA-v. Aterial blood free fatty acid had not significant change after experimental myocardial angina and electroacupuncture had not marked effect on it. The above results indicated that experimental myocardial angina result in metabolic disorders of myocardial glucose and free fatty acid. Electroacupuncture may reduce glucose uptake and increase free fatty acid uptake of ischemic myocardium. Thus improved metabolic disorder of ischemic myocardium.

Acupuncture Therapy↗
PubMed1989

[Scanning electron microscopy observations on the vascular casts of the placental chorion in normal pregnancy and pregnancy-induced hypertension].

The method of vascular casting in human placental chorion for scanning electron microscopy (SEM) was described. Through SEM of the placental chorion in five normal pregnant cases and twenty-two pregnancy induce hypertension (PIH), the three-dimensional angioarchitecture of the placental chorion in normal pregnancy and PIH of different clinical classes were clarified. Increasing with the severity of PIH, the capillaries in the placental chorion became more and more attenuated and irregular in diameter, with their branches decreasing in number and the inner wall roughened. These capillary changes were found even in mild PIH. However, the pathological changes in the chorionic capillaries in moderate and severe cases treated beforehand with magnesium sulfate were much less than those in untreated cases.

Adult↗
PubMed1988

Interaction of chloroquine with linear and supercoiled DNAs. Effect on the torsional dynamics, rigidity, and twist energy parameter.

The magnitude and uniformity of the torsion elastic constant (alpha) of linear pBR322 DNA and supercoiled pBR322 DNAs with high-twist (sigma = -0.083) and normal-twist (sigma = -0.48) are measured in 0.1 M NaCl as a function of added chloroquine/base-pair ratio (chl/bp) by studying the fluorescence polarization anisotrophy (FPA) of intercalated ethidium dye. The time-resolved FPA is measured by using a picosecond dye laser for excitation and time-correlated single-photon counting detection. A general theory is developed for the binding of ligands that unwind superhelical DNAs, and the simultaneous binding of two different intercalators is treated in detail. The equilibrium constant (K) for binding chloroquine to linear pBR322 DNA and the number (r) of bound chloroquines per base pair are determined from the relative amplitude ratio of the slow (normally intercalated) and fast (free) components in the decay of the (probe) ethidium fluorescence intensity as a function of chl/bp. For chloroquine binding to supercoiled pBR322 DNAs, the intrinsic binding constant is assumed to be the same as for the linear DNA, but the twist energy parameter ET (N times the free energy to change the linking number from 0 to 1 in units of kBT) is regarded as adjustable. Using the best-fit ET, the binding ratios r are calculated for each chl/bp ratio. Twist energy parameters are also determined for ethidium binding to these supercoiled DNAs by competitive dialysis. For chloroquine binding, we obtain ET = 360 and 460 respectively for the normal-twist and high-twist supercoiled DNAs. For ethidium binding the corresponding values are ET = 280 +/- 70 and 347 +/- 50. Like other dye-binding values, these are substantially lower than those obtained by ligation methods. In the absence of chloroquine, the torsion constants of all three DNAs are virtually identical, alpha = (5.0 +/- 0.4) x 10(-12) dyn.cm. For linear pBR322 DNA, the magnitude and uniformity of alpha remain unaltered by intercalated chloroquine up to r = 0.19. This finding argues that the FPA is not significantly relaxed by diffusion of any kinks or solitons. If alpha d denotes the torsion constant between a dye and a base pair and alpha 0 that between two base pairs, then our data imply that alpha d/alpha 0 lies in the range 0.65-1.64, with a most probable value of 1.0.(ABSTRACT TRUNCATED AT 400 WORDS)

Chloroquine↗
PubMed1986

On the molecular mechanisms of the Schiff base deprotonation during the bacteriorhodopsin photocycle.

Using optical flash photolysis and time-resolved Raman methods, we examined intermediates formed during the photocycle of bacteriorhodopsin (bR), as well as the bR color change, as a function of pH (in the 7.0-1.5 region) and as a function of the number of bound Ca(2+) ions. It is found that at a pH just below 3 or with less than two bound Ca(2+) per bR, the deprotonation (the L(550) --> M(412)) step ceases, yet the K(610) and L(550) analogues are still formed as in native bR. The lack of deprotonation in the photocycle of both acid blue and deionized blue bR and the similarity of their Raman spectra as well as of their K(610) and L(550) analogues strongly suggest that both blue samples have nearly the same retinal active site. It is suggested that in both blue species, bound cations are removed via a proton-cation exchange equilibrium, either on the cation exchange column for the deionized sample or in solution for the acid blue sample. The proton-cation exchange equilibrium is found to quantitatively account for the pH dependence of the purple-to-blue color change. The different mechanisms responsible for the large reduction ( approximately 11 units) of the pK(a) value of the protonated Schiff base (PSB) during the photocycle are discussed. The absence of the L(550) --> M(412) deprotonation process in both blue species is discussed in terms of the previously proposed cation model for the deprotonation of the PSB during the photocycle of native bR. The extent of the deprotonation and the blue-to-purple color change are found to follow the same dependence on either the pH or the amount of cations added to deionized blue bR. This observed correlation is briefly discussed.

Journal Article↗
PubMedDate not supplied

Intramolecular interference effects in dynamic light scattering: rigid double spirals and superhelical DNAs.

A theory is developed for dynamic light scattering (DLS) from rigid double spirals by treating an invisible rigid cylinder with two helical scattering stripes on opposite sides of its cylindrical surface. The exact initial, or first cumulant, diffusion coefficient Dapp (K) is obtained in terms of the translational diffusion coefficients (D parallel and D perpendicular) parallel and perpendicular to the symmetry axis, the rotational diffusion coefficients (DR parallel and DR perpendicular) around the symmetry and transverse axes, the length (L) and radius (b) of the cylindrical surface bearing the stripes, and the pitch (p). Interference effects, namely geometrical antiresonances, between strands, produce deep minima in the static structure factor S (K) and corresponding prominent peaks in Dapp (K). These peaks in Dapp (K) depend sensitively on the rotational dynamics around the symmetry axis, and nearly vanish when DR parallel = 0. Some results for single spirals are also presented. A simpler model in which scattering points are attached at opposite ends of an otherwise invisible thin rigid rod is also treated, and shown to exhibit modest minima in S (K) and corresponding maxima in Dapp (K). Confining this rod to a plane containing K enhances the amplitudes of the oscillations in S (K) and Dapp (K), as expected. Rigid double spirals are employed as crude models for interwound supercoiled DNAs in order to assess the possible occurrence of interference effects. Although native supercoiled DNAs exhibit a cylinder diameter that is much too small to exhibit geometrical antiresonances in the presently accessible range of K2, nearly relaxed supercoiled DNAs are predicted to exhibit their first maximum in Dapp (K) just inside this range. Previously reported data for the effect of Escherichia coli single-strand binding (ssb) protein on the DLS of supercoiled pBR322 DNA cannot be mimicked by a gradual homogeneous reduction of superhelix density with increasing ssb, but instead can be mimicked by inhomogeneous all-or-none binding in which uncomplexed native DNAs and nearly relaxed saturated ssb/DNA complexes coexist in varying proportions. Experimental Dapp (K) and S (K) data for a sample of relaxed pUC8 dimers display, respectively, a broad maximum and a corresponding minimum, in qualitative agreement with rough theoretical predictions.

DNA Topoisomerases, Type I↗
PubMedDate not supplied

Impaired phosphoinositide hydrolysis in Alzheimer's disease brain.

The effect of Alzheimer's disease (AD) on the activity of the phosphoinositide second messenger system was studied by measuring the hydrolysis of [3H]phosphatidylinositol (PI) by membranes from postmortem human prefrontal cortex. The activity of phospholipase C was similar in AD and control tissue. Activation with GTP gamma S and with carbachol demonstrated less [3H]PI hydrolysis in AD than control membranes. The concentration of Gq/11, the G-proteins most likely functional in phosphoinositide metabolism, was unchanged in AD compared with controls, indicating that function of the receptor-G-protein complex rather than the G-protein concentration was the site of the impairment in AD. These results indicate that postsynaptic muscarinic receptor responses are impaired in AD, a finding that may explain, in part, the limited therapeutic responses achieved by administration of cholinomimetics to patients with AD. Also, this assay provides a means to identify cholinomimetics that are most effective in activating muscarinic receptor-coupled phosphoinositide hydrolysis in human brain, agents which should have the greatest potential for providing therapeutic responses in AD.

Aged↗
PubMedDate not supplied

Age-related effects in T cell activation and proliferation.

Age-associated thymic involution manifests its effects in a variety of ways that are related to a loss of T cell function. These include the appearance of a non-functional subset of T cells that increase in representation with age. Moreover there is a loss of T cell proliferative ability, a decline in the synthesis and release of interleukin-2 (IL-2), a decline in the ability of the T cell to express the IL-2 receptor, and a loss of control activity. This loss of control is demonstrated by the age-related appearance of autoantibodies and an increase in the elaboration of inflammatory cytokines such as TNF, IFN, IL-6, and TGF. A major part of the basis for the loss of T cell function is an inability of the T cell to respond to activation signals that are transmitted through the membrane binding of specific stimulatory signals. Transduction events, differentiation signals, and a loss of control mechanisms are all parts of a complicated picture of age-related immune deficiencies.

Adult↗
PubMedDate not supplied

Cholinergic activation of phosphoinositide signaling is impaired in Alzheimer's disease brain.

The function of the phosphoinositide signal transduction system was compared in membranes from Alzheimer's disease (AD) and control postmortem brain. [3H]Phosphatidylinositol hydrolysis was concentration-dependently stimulated by GTP[S] and this was 40% lower than controls in AD prefrontal cortical membranes. Carbachol induced a response greater than that of GTP[S] alone, and this response was impaired in AD by 45%. Differential analysis of the receptor-coupled and G-protein contributions to the responses indicated that the G-protein deficit in AD had a predominant influence on the lowered responses to cholinergic agonists. Similar deficits were observed in AD in the responses to five additional cholinergic agonists, including acetylcholine with three different acetylcholinesterase inhibitors. Deficits in stimulated phosphoinositide hydrolysis were regionally selective and these deficits did not correlate directly with reductions in choline acetyltransferase activity in AD tissues. These data demonstrate that in AD there is a brain region-selective, large impairment of cholinergic agonist-induced signal transduction mediated by the phosphoinositide system, which we speculate may impact on amyloid precursor protein processing.

Aged↗
PubMedDate not supplied

Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy.

A considerable amount of retrospective data is available that describes putative mesenchymal stem cells (MSCs). However, there is still very little knowledge available that documents the properties of a MSC in its native environment. Although the precise identity of MSCs remains a challenge, further understanding of their biological properties will be greatly advanced by analyzing the mechanisms that govern their self-renewal and differentiation potential. This review begins with the current state of knowledge on the biology of MSCs, specifically with respect to their existence in the adult organism and postulation of their biological niche. While MSCs are considered suitable candidates for cell-based strategies owing to their intrinsic capacity to self-renew and differentiate, there is currently little information available regarding the molecular mechanisms that govern their stem cell potential. We propose here a model for the regulation of MSC differentiation, and recent findings regarding the regulation of MSC differentiation are discussed. Current research efforts focused on elucidating the mechanisms regulating MSC differentiation should facilitate the design of optimal in vitro culture conditions to enhance their clinical utility cell and gene therapy.

Cell Differentiation↗
PubMedDate not supplied

Modulation of in vitro biomarkers of the carcinogenic process by chemopreventive agents.

A structurally diverse group of chemopreventive agents was evaluated using in vitro biomarkers of the carcinogenesis process. With cultured human bronchial epithelial (BEAS-2B) cells, sulfur-containing compounds such as 1.2-dithiole-3-thione and sulforaphane, and phenolic compounds such as caffeic acid phenethyl ester and genistein, showed potent inhibition of benzo(a)pyrene [B(a)P] metabolite-DNA binding. Phenolic compounds also demonstrated strong antioxidant activity. Most of the test compounds did not inhibit 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity with cultured mouse epidermal ME 308 cells, with the exception of sulfur-containing compounds, 1,2-dithiole-3-thione and sulforaphane, and a selenium compound, 1,4-phenylenebis (methylene)selenocyanate. With cultured Hepa 1c1c7 cells, sulforaphane and 1,2-dithiole-3-thione mediated strong induction of quinone reductase, and genistein and ursolic acid were moderate inducers. Chalcone, 1,4-phenylenebis (methylene)selenocyanate and caffeic acid phenethyl ester induced HL-60 cell differentiation. Interestingly, sulforaphane and caffeic acid phenethyl ester inhibited the total metabolism of benzo(a)pyrene with cultured BEAS-2B cells, and the distribution pattern of water-soluble metabolites was altered in comparison with the control groups. These data are suggestive of pleiotropic mechanisms that should prove beneficial when considering the chemopreventive activity of these substances. As a result, of the group of 25 agents tested, four were judged as superior cancer chemopreventive agents: caffeic acid phenethyl ester, 1,2-dithiole-3-thione, genistein, and sulforaphane.

Animals↗
PubMedDate not supplied

A study on occupational exposure to petrochemicals and smoking on seminal quality.

A cross-sectional study of 68 petrochemical workers (23 had never smoked [E/NS], 45 were current smokers [E/S]) and 130 subjects with no known history of exposure to petrochemicals (49 had never smoked [NE/NS], 81 were current smokers [NE/S]) was conducted to assess the effect of occupational exposure to petrochemicals and smoking on semen quality. In-person interviews revealed occupational history, smoking habit, and lifestyle. Semen parameters such as volume, viability, sperm forward progression rate, sperm density, and total sperm count were determined for all subjects. The results show that the E/NS workers had a lower sperm forward progression rate (P < .05) compared with controls (NE/NS). Individuals in the NE/S group showed a significant inverse relationship between years smoked and sperm density (r = -.24, P < .05). The data also revealed that cigarette smokers who had worked in a petrochemical plant had significantly poorer quality semen, including sperm density, total sperm count, and forward progression rate, compared with the control (NE/NS) group (P < .01). Furthermore, there was a significant inverse correlation between combined exposure and smoking years, and sperm density (r = -.28, P < .05). These findings suggest that occupational exposure to petrochemical compounds may aggravate the adverse effect that smoking has on semen quality.

Adult↗
PubMedDate not supplied

The integrated patient information system.

The complexity and potential impact of today's health care crisis requires a comprehensive approach to problem analysis and innovative thinking in developing solution strategies. Patient care, by its information-intensive nature, involves extensive information processing for decision-making, and requires the support of an effective and efficient information system. Therefore, information Technology must play a critical part in developing any solution strategy. Blue Chip, as an industry leader in leveraging information Technology to create innovative business processes, took the challenge and found a solution to the problem of comprehensive patient information processing. Through the generous support of the Agency for Health Care Policy and Research, a branch of the US Public Health Service, the company completed research and development under two Small Business Innovative Research grants. After 3 years of intensive study, design, and development, Blue Chip created an integrated Patient information System called Care-Centric.

Computer Communication Networks↗