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Biomedical subjects

S Li

Publications and source records attributed to S Li.

At least 829 records · Page 46Linked to original sources

Metallothionein-induced increase in mitochondrial inner membrane permeability.

OBJECTIVE: To elucidate the effect of metallothionein on the permeability of the mitochondrial inner membrane. BACKGROUND: Metallothionein (MT) is a 6-7-kDa protein which is rapidly produced by stressed cells. MT is induced by cytokines and other factors thought to mediate the stress response. The organelle with the highest concentration of MT is the mitochondrion. Therefore we studied the effect of MT on mitochondrial function. We chose to study the effect of MT on mitochondrial inner membrane permeability because of the role of this function in numerous cellular processes. METHODS: Mitochondria were isolated from livers of Sprague-Dawley rats by differential centrifugation and suspended in sucrose-containing buffer. Changes in mitochondrial inner membrane permeability were monitored by following the change in absorbance at 540 nm. All experiments were of a paired design. RESULTS: We found that an increase in inner membrane permeability was induced by physiological metallothionein 1 (MT1) concentrations between 6 and 50 microM. There was no increase in the effect beyond 50 microM. The metals of MT1, zinc, and cadmium alone had no effect at physiological concentrations. The action of MT1 was inhibited by the aliphatic polyamine, spermine, as well as magnesium both at physiological concentrations. Spermine was effective whether added before or after MT1. Metallothionein 2 of different Zn2+ and Cd2+ compositions induced different kinetics of pore opening. CONCLUSIONS: These experiments reveal the possibility that the permeability of the mitochondrial inner membrane is regulated by relative concentrations of MT, spermine, and magnesium. The metal composition of MT could also play a role in this regulation.

Animals↗

Influence of muscle morphometry and moment arms on the moment-generating capacity of human neck muscles.

STUDY DESIGN: The function of neck muscles was quantified by incorporating experimentally measured morphometric parameters into a three-dimensional biomechanical model. OBJECTIVE: To analyze how muscle morphometry and moment arms influence moment-generating capacity of human neck muscles in physiologic ranges of motion. SUMMARY OF BACKGROUND DATA: Previous biomechanical analyses of the head-neck system have used simplified representations of the musculoskeletal anatomy. The force- and moment-generating properties of individual neck muscles have not been reported. METHODS: A computer graphics model was developed that incorporates detailed neck muscle morphometric data into a model of cervical musculoskeletal anatomy and intervertebral kinematics. Moment arms and force-generating capacity of neck muscles were calculated for a range of head positions. RESULTS: With the head in the upright neutral position, the muscles with the largest moment arms and moment-generating capacities are sternocleidomastoid in flexion and lateral bending, semispinalis capitis and splenius capitis in extension, and trapezius in axial rotation. The moment arms of certain neck muscles (e.g., rectus capitis posterior major in axial rotation) change considerably in the physiologic range of motion. Most neck muscles maintain at least 80% of their peak force-generating capacity throughout the range of motion; however, the force-generating capacities of muscles with large moment arms and/or short fascicles (e.g., splenius capitis) vary substantially with head posture. CONCLUSION: These results quantify the contributions of individual neck muscles to moment-generating capacity and demonstrate that variations in force-generating capacity and moment arm throughout the range of motion can alter muscle moment-generating capacities.

Biomechanical Phenomena↗

DBI-1, a novel gene related to the notch family, modulates mitogenic response to insulin-like growth factor 1.

The insulin-like growth factor 1 (IGF-1) receptor has been found to transform fibroblast cells when overexpressed. The removal of 108 aa from the C-terminus of the IGF-1 receptor abolishes the transforming ability of the receptor without affecting its ability to induce cell growth. The availability of this mutant receptor provides a means to examine the changes in gene expression which take place during transformation, solely in response to an increased number of IGF-1 receptors. Using differential display, we have examined differences in gene expression between cells expressing a wild-type, transforming IGF-1 receptor and cells expressing a C-terminally truncated, nontransforming IGF-1 receptor. We have cloned a novel 6. 3-kb cDNA transcript (DBI-1) which is expressed at much lower levels in cells containing the wild-type IGF-1 receptor. The predicted protein sequence of DBI-1 contains seven EGF-like repeats, which bear >90% sequence identity to the rat Notch 2 protein. The cDNA also contains a potential DEAD box in the C-terminal region. The DBI-1 message is detected at relatively high levels in cardiac tissue and at lower levels in lung, liver, and kidney. Antibodies generated to a unique region of the DBI-1 protein recognize a protein of 88 kDa, which is localized in the nucleus. Overexpression of DBI-1 in cells which contain the wild-type IGF-1 receptor diminishes the mitogenic response to IGF-1.

3T3 Cells↗

Noninvasive in vivo clot dissolution without a thrombolytic drug: recanalization of thrombosed iliofemoral arteries by transcutaneous ultrasound combined with intravenous infusion of microbubbles.

BACKGROUND: Previous in vivo studies have shown that microbubbles not only enhance the effectiveness of thrombolytic agents in the presence of ultrasound but may also augment clot dissolution without thrombolytic drugs. METHODS AND RESULTS: The objective of this study was to examine the efficacy of arterial clot disruption by a noninvasive, nonlytic approach with intravenous administration of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) and transcutaneous delivery of ultrasound alone. Pairs of iliofemoral arteries in 10 rabbits were randomized to receive transcutaneous ultrasound treatment or no ultrasound treatment after an acute artery thrombotic occlusion and intravenous PESDA infusion. Five arteries from 3 additional rabbits served as controls (ultrasound alone). All 10 iliofemoral arteries treated with PESDA + ultrasound were recanalized by angiography after ultrasound treatment. None of the 10 contralateral arteries treated with PESDA alone and none of the 5 arteries treated with ultrasound alone were patent after 1 hour. D-Dimer levels did not change after intravenous PESDA + ultrasound-mediated reperfusion. CONCLUSIONS: In vivo arterial clot dissolution can be achieved with intravenous microbubbles and transcutaneous ultrasound delivery alone. This technique has potential for clinical application in patients with acute arterial and venous thrombotic occlusions.

Animals↗

Mobility of "Unfreezable" and "Freezable" Water in Waxy Corn Starch by (2)H and (1)H NMR.

"Freezable" and "unfreezable" water in waxy corn starch were characterized by thermal analysis, and the mobility in those states was characterized by solid state (2)H and (1)H NMR. Water was found to be isotropically mobile for samples over a range of water contents (6.3-47% by total weight) at room temperature. Mobility increased with increasing water content and temperature. According to (1)H and (2)H NMR data, a large fraction of "unfreezable" (DSC) was relatively mobile comparable to a liquid state even down to -32 degrees C. Some anisotropically immobile D(2)O at low temperatures exhibited a solid state Pake pattern in (2)H NMR spectra, which was similar to that of frozen D(2)O (ice) with a 144 kHz splitting. The decreasing fraction of mobile water with decreasing temperature suggested that only some of the so-called "unfreezable" water could be progressively immobilized as temperature decreased. However, much of the water (>50% of water present) remained very high in mobility, regardless of the relatively rigid starch molecules in the glassy solid state.

Journal Article↗

The carboxyl-terminal domain of insulin-like growth factor-I receptor interacts with the insulin receptor and activates its protein tyrosine kinase.

Receptors for insulin and insulin-like growth factor-I (IR and IGFIR) consisting of the alpha2beta2 structure are protein tyrosine kinases (PTKs). Carboxyl-terminal (CT) domains of their beta subunits are structurally diverse while the PTK domains share the highest homology. Interactions between CT and PTK domains of IR and IGFIR were studied by means of PTK activity, fluorescence energy transfer or surface plasmon resonance using BIAcore. We present evidence that IGFIR CT directly interacts with both IGFIR and IR. Although binding to both receptors, stimulation of PTK activity only occurs with IR but not IGFIR.

Animals↗

Mechanisms of insulin resistance in experimental hyperinsulinemic dogs.

This study was undertaken to characterize the insulin resistance and the mechanism thereof caused by chronic hyperinsulinemia produced in dogs by surgically diverting the veins of the pancreas from the portal vein to the vena cava. Pancreatic venous diversion (PVD, n = 8) caused a sustained increase in arterial insulin and decrease in portal insulin concentration compared with the control group (n = 6). Hyperinsulinemic euglycemic clamps were conducted 4 wk after surgery. The increase in the glucose disposal rate (GDR) was significantly less in the PVD group (39.0+/-5.0 vs. 27.9+/-3.2 micromol/kg/min, P < 0.01) compared with the control group, but the suppression of hepatic glucose production by insulin was similar for both groups. Muscle insulin receptor tyrosine kinase activity (IR-TKA) increased from 6.2+/-0.4 to 20.3+/-2.7 in the control group, but from 5.8+/-0.5 to only 12.7+/-1.7 fmol P/fmol IR in the PVD group (P < 0.01). With respect to the periphery, the time to half-maximum response (t1/2a) for arterial insulin was the same for both groups, whereas the t1/2a for lymph insulin (30+/-3 vs. 40+/-4 min, P < 0.05) and GDR (29+/-3 vs. 66+/-10 min, P < 0.01) were greater for the PVD group. Chronic hyperinsulinemia led to marked peripheral insulin resistance characterized by decreased insulin-stimulated GDR, and impaired activation of GDR kinetics due, in part, to reduced IR-TKA. Transendothelial insulin transport was impeded and was responsible for one third of the kinetic defect in insulin-resistant animals, while slower intracellular mechanisms of GDR were responsible for the remaining two thirds.

Animals↗

Overexpression of protein kinase C alpha enhances lipopolysaccharide-induced nitric oxide formation in vascular smooth muscle cells.

Our previous studies showed that lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis in cardiovascular tissues is attenuated by protein kinase C (PKC) inhibitors. In the current study, we identify a specific PKC isotype involved in the LPS signal transduction pathway that leads to NO formation in rat vascular smooth muscle cells (VSMC). VSMC were transfected with a mammalian expression vector containing a full length PKCalpha cDNA insert, and a stable transfectant overexpressing PKCalpha was obtained as evidenced by increased expression of PKCalpha mRNA and protein. In response to 100 ng/ml LPS stimulation, the PKCalpha transfectants showed a 1.8-fold increase in PKC activity at 30 min and a twofold increase in NO production over 24 hr compared with cells transfected with control plasmids. The LPS-stimulated increase in NO synthesis in PKCalpha transfectants was blocked by the specific PKCalpha inhibitor Gö 6976. After 6 hr LPS treatment, PKCalpha-transfected and control cells showed equivalent increases in mRNA and protein for the inducible NO synthase. NO synthase activity of the cell extracts assayed in the presence of excess substrate and cofactors was not significantly different between PKCalpha-transfected and control cells after LPS stimulation. However, mRNA levels for GTP cyclohydrolase I, a key enzyme in (6R)-tetrahydro-L-biopterin synthesis, and cationic amino acid transporter-2, involved in L-arginine transport, was enhanced in cells overexpressing PKCalpha compared with control cells. These results suggest that PKCalpha plays an important role in LPS-induced NO formation and that a significant portion of this effect may be by means of enhanced substrate availability to the inducible nitric oxide synthase enzyme.

Amino Acid Transport Systems, Basic↗

Enhanced proliferation of human fibroblasts, in the presence of dexamethasone, is accompanied by changes in p21Waf1/Cip1/Sdi1 and the insulin-like growth factor type 1 receptor.

The addition of dexamethasone (dex) to human fibroblast cultures has been found to elicit enhanced proliferation. This enhancement is manifested by an increase in the initial growth rate, saturation density, and proliferative life span of WI-38 fibroblast cultures grown in the presence of dex. We examined the acute effects of dex on a number of growth-related genes in WI-38 cells. Our results show a decrease in the level of the cyclin-dependent kinase inhibitor p21Waf1/Cip1/sdi1 in response to dex. In addition, the level of the insulin-like growth factor type 1 receptor (IGF-1R) is increased in dex-treated cells. These changes are correlated with changes in the activity of the p21waf1/Cip1/Sdi1 and IGF-1R promoters. The results presented in this report suggest that dex may delay growth arrest in response to contact inhibition, as well as during cellular senescence. Thus, dex may act at multiple levels to enhance cellular proliferation in WI-38 cells: first, to decrease the level of an inhibitor of cell-cycle progression, and second, to increase the sensitivity of WI-38 cells to the proliferative effects of IGF-1. These acute effects may cooperate with other, as yet uncharacterized effects, to result in the enhanced proliferation seen in the presence of dex.

Cell Division↗

SAR and B1 field distributions in a heterogeneous human head model within a birdcage coil. Specific energy absorption rate.

Calculations of radiofrequency magnetic (B1) field and specific energy absorption rate (SAR) distributions in a sphere of tissue and a multi-tissue human head model in a 12-element birdcage coil are presented. The coil model is driven in linear and quadrature modes at 63, 175, 200, and 300 MHz. Plots of B1 field magnitude and SAR distributions, average SAR, maximum local SAR, and measures of B1 field homogeneity and signal-to-noise ratio are given. SAR levels for arbitrary pulse sequences can be estimated from the calculated data. Maximum local SAR levels are lower at lower frequencies, in quadrature rather than in linear coils, and in linear fields oriented posterior-to-anterior rather than left-to-right in the head. It should be possible to perform many experiments in the head at frequencies up to 300 MHz without exceeding standard limits for local or average SAR levels.

Color↗

A birdcage coil tuned by RF shielding for application at 9.4 T.

The design and performance of an inductively fed low-pass birdcage radiofrequency (RF) coil for applications at 9.4 T are described where tuning is accomplished by mechanically moving a concentric RF shield about the longitudinal axis of an RF coil. Moving the shield about the RF coil effectively changes the mutual inductance of the system, providing a mechanism for adjusting the resonant frequency. RF shield tuning eliminates adjustable capacitors on the legs of the RF coil, eliminates current imbalances and field distortions, and results in improved B1 field homogeneity and high quality (Q) factors. RF shield tuning and inductive matching provide an isolated resonance structure which is both physically and electrically unattached. Experimental analysis of shield position on both B1 field homogeneity and resonant frequency is provided. Computer simulations of B1 field homogeneity as a function of shield position and shield diameter are also presented. Magnetic resonance microimaging substantiates the usefulness of this design.

Animals↗

Differential activation of mitogen-activated protein kinases by palytoxin and ouabain, two ligands for the Na+,K+-ATPase.

We previously demonstrated that the marine toxin and skin tumor promoter palytoxin activates the stress-activated protein kinase/c-Jun N-terminal kinase (JNK), but not the extracellular signal-regulated kinase (ERK), which is typically activated by mitogenic agents. JNK, ERK, and p38, another stress-activated protein kinase, are members of the mitogen-activated protein (MAP) kinase family of serine/threonine kinases, which coordinate the transmission of various signals through the cell. The Na+,K+-ATPase is the putative palytoxin receptor. Therefore, we hypothesized that the Na+,K+-ATPase inhibitor ouabain might also stimulate signaling pathways that activate MAP kinases. Using HeLa and COS7 cells, we found that, although there are similarities between the protein kinase cascades by which palytoxin and ouabain activate JNK, there are also significant differences between the activation of specific MAP kinases by palytoxin and ouabain. Transient expression of dominant negative mutants indicates that ouabain, like palytoxin, activates JNK through a protein kinase cascade that involves the JNK kinase SEK1 but does not require the GTPase Ras. Palytoxin activates JNK and p38 to a greater extent than ouabain. By contrast, ouabain activates ERK to a greater extent than palytoxin. Ouabain blocked palytoxin-stimulated activation of JNK and p38, but not anisomycin-stimulated activation of these kinases, supporting the conclusion that ouabain and palytoxin bind to the same site on the Na+,K+-ATPase. These results suggest that the Na+,K+-ATPase can differentially mediate the activation of MAP kinases by two diverse ligands, palytoxin and ouabain.

Acrylamides↗

Biodegradation of tricalcium phosphate ceramics by osteoclasts.

Biodegradation of tricalcium phosphate (TCP) ceramics was observed through mixed culture of osteoclasts and TCP discs in vitro in this study. Osteoclasts were isolated from newborn SD rat's marrow of long bone and cultured on TCP discs. The culture terminated at the 48th h and 96th h respectively. Under an inverted microscope, the osteoclasts imparted round or oval body with multinuclear and many thin processes. These cells were positively stained for tartrate-resistance acid phosphatase (TRAP). Scanning electron microscope showed that many resorption lacunae on TCP disc surface and their diameters were smaller than 20 microns. Osteoclasts were located in the lacunae. At the 96th h, the resorption lacunae become larger and osteoclasts showed degeneration. It is suggested that osteoclasts possess ability to re-absorb TCP ceramics under in vitro culturing condition.

Animals↗

The bacterial inhibitory ability and in vivo drug release pattern of a new drug delivery system: ciprofloxacine/tricalcium phosphate delivery capsule.

The bacterial inhibitory ability of a new drug delivery system (DDS): Ciprofloxacine/tricalcium phosphate delivery capsule (CTDC), its in vivo drug release pattern, and the influence of ultrasonic irradiation on its drug release were investigated. It was found that CTDC had a strong and sustained inhibitory ability to some common pathogens of bone and joint infections, such as staphylococcus aureus, escherichia coli and pseudomonas aeruginosa. In vivo drug-release study in animals demonstrated a high concentration of ciprofloxacine in the bone tissue surrounding CTDC which was placed in the greater trochanter of the rabbit and continued to release ciprofloxacine for at least 5 weeks and the blood level of ciprofloxacine was low. In vivo study also showed ultrasonic irradiation could increase the amount of ciprofloxacine released from CTDC, which may be an economical, effecient and safe new method to achieve the control of drug release from DDS.

Animals↗

Demographic and psychosocial predictors of fruit and vegetable intakes differ: implications for dietary interventions.

OBJECTIVE: The National Cancer Institute (Rockville, Md) has launched a nationwide initiative--5 A Day for Better Health--to encourage consumption of fruits and vegetables. Because the tastes and culinary uses of fruits and vegetables differ, however, it is not known whether a general 5-A-Day message is an effective intervention strategy. This study examined whether there are differences between the demographic and psychosocial correlates of fruit and vegetable intakes. DESIGN: Data are from the Washington State Cancer Risk Behavior Survey (1995-1996), a cross-sectional, random-digit-dial telephone survey representative of the adult population of Washington State. SUBJECTS/SETTING: Interviews were completed with 1,450 adults. Data were collected about demographic characteristics, health status, health-related behavior, fruit and vegetable intakes, and the following diet-related psychosocial factors: beliefs, motives, barriers, attitudes, and stages of dietary change. STATISTICAL ANALYSES: Multivariate linear regression analysis was used to test whether the associations of demographic characteristics and psychosocial factors with fruit intake differed from associations with vegetable intake. RESULTS: In general, health status, health-related behavior, and psychosocial factors were more strongly associated with fruit intakes than vegetable intakes. For example, regular exercisers consumed 0.44 more daily servings of fruits and 0.36 more servings of vegetables than nonexercisers. Compared with those in the preaction stage of dietary change, adults in the maintenance stage consumed 0.99 more daily servings of fruits and 0.68 more servings of vegetables. Intrinsic motivations for eating a healthful diet (eg, to feel better) were strongly associated with both fruit and vegetable intakes, and these associations were stronger for fruit. Extrinsic motivations were not associated with either fruit or vegetable intakes. APPLICATIONS: Dietary interventions based on a general 5-A-Day message may be more effective in increasing fruit intakes than vegetable intakes. Targeted interventions that focus specifically on vegetables are probably necessary. Intrinsic motives for eating a healthful diet should be key components of interventions to increase fruit and vegetable intakes.

Adult↗

Aerosol cyclosporine prevents acute allograft rejection in experimental lung transplantation.

BACKGROUND: The incidence of acute rejection and the morbidity of systemic cyclosporine (INN: cyclosporine) after lung transplantation is significant. Experimental evidence suggests that the allograft locally modulates the immune mechanisms of acute rejection. The purpose of this study was to determine whether aerosolized cyclosporine would prevent acute cellular rejection, achieve effective graft concentrations with low systemic drug delivery, and locally affect production of the inflammatory cytokines involved in acute rejection. METHODS: Unilateral orthotopic left lung transplantation was performed in 64 rats (ACI to Lewis), which were divided into eight groups (each group, n = 8): group A, no treatment; groups B to D, aerosol cyclosporine 1 to 3 mg/kg per day, respectively; group E to H, systemic cyclosporine 2, 5, 10, and 15 mg/kg per day, respectively. After the animals were killed on postoperative day 2, 4, or 6, the transplanted lung, native lung, spleen, and blood were collected. Histologic studies, high-pressure liquid chromatography for trough cyclosporine concentrations, and reverse-transcriptase polymerase chain reaction for cytokine gene expression were performed. RESULTS: Untreated animals showed grade 4 rejection by postoperative day 6. Aerosol cyclosporine prevented acute rejection in a dose-dependent fashion, with group D animals (3 mg/kg per day) showing minimal grade 1 changes. Among animals receiving systemic cyclosporine, only group H (15 mg/kg per day) controlled (grade 1) rejection. However, aerosol cyclosporine, at an 80% lower dose, achieved significantly lower concentrations of cyclosporine in the graft (12,349 vs 28,714 ng/mg, p = 0.002004) and blood (725 vs 3306 ng/ml, p = 0.000378). Group F (systemic 5 mg/kg per day) had higher cyclosporine concentrations in the blood than group D (p = 0.004572) and similar tissue concentrations (p = 0.115180), yet had grade 2 rejection. Reverse-transcriptase polymerase chain reaction demonstrated equivalent suppression of inducible nitric oxide synthase but a 20- to 25-fold higher expression of interleukin-6, interleukin-10, and interferon-gamma in group D versus group H recipient allografts. CONCLUSION: Local delivery of cyclosporine by aerosol inhalation dose-dependently prevented acute pulmonary allograft rejection. Effective graft levels and low systemic drug delivery required significantly lower doses than systemic therapy alone. The gene expression of proinflammatory cytokines involved in allograft rejection was suppressed by aerosol cyclosporine therapy.

Administration, Inhalation↗

Bovine adrenals and hypothalamus are a major source of proscillaridin A- and ouabain-immunoreactivities.

Besides an isomer of the cardenolide ouabain, a material with a similar HPLC retention time as ouabain but cross-reactivating with antibodies against the bufadienolide proscillaridin A and inhibiting the sodium pump is known to circulate in human blood plasma (B. SICH et al., Hypertension 27, 1073-1078 (1996).). The concentrations of both substances are known to correlate with the blood pressure. It was the intention of this work to localize tissues that contain the highest concentrations of the proscillaridin A immunoreactive material, to correlate its concentration with that of ouabain and to get information whether the concentration of this material simply reflects the number of sodium pumps of the tissue extracted. Specific antibodies for each cardiotonic steroid were used to test the tissue concentration. This report shows that in bovine tissues the distribution pattern of proscillaridin A and ouabain immunoreactivities are similar and that hypothalamus and adrenals show the highest concentrations. The cross-reactive material did not reflect the number of sodium pumps per g of wet weight tissue as measured by [3H]ouabain binding. Therefore, it is unlikely that the tissue concentrations in both immunoreactivities reflects the tissue capacity of sodium pumps labeled with cardiotonic steroids via the blood plasma. The study rather favors the concept that two different types of inhibitors of the sodium pump exist within both tissues.

Adrenal Glands↗