PubMed Health⌕ Search

Biomedical subjects

F Qin

Publications and source records attributed to F Qin.

At least 19 recordsLinked to original sources
PubMed2007

Regulation of TRP ion channels by phosphatidylinositol-4,5-bisphosphate.

Phosphatidylinositol-4,5-bisphosphate (PIP2) has emerged as a versatile regulator of TRP ion channels. In many cases, the regulation involves interactions of channel proteins with the lipid itself independent of its hydrolysis products. The functions of the regulation mediated by such interactions are diverse. Some TRP channels absolutely require PIP2 for functioning, while others are inhibited. A change of gating is common to all, endowing the lipid a role for modulation of the sensitivity of the channels to their physiological stimuli. The activation of TRP channels may also influence cellular PIP2 levels via the influx of Ca2+ through these channels. Depletion of PIP2 in the plasma membrane occurs upon activation of TRPV1, TRPM8, and possibly TRPM4/5 in heterologous expression systems, whereas resynthesis of PIP2 requires Ca2+ entry through the TRP/TRPL channels in Drosophila photoreceptors. These developments concerning PIP2 regulation of TRP channels reinforce the significance of the PLC signaling cascade in TRP channel function, and provide further perspectives for understanding the physiological roles of these ubiquitous and often enigmatic channels.

Animals↗
PubMed2001

Antioxidant vitamins attenuate oxidative stress and cardiac dysfunction in tachycardia-induced cardiomyopathy.

OBJECTIVES: We administered antioxidant vitamins to rabbits with pacing-induced cardiomyopathy to assess whether antioxidant therapy retards the progression of congestive heart failure (CHF). BACKGROUND: Although oxidative stress is increased in CHF, whether progression of heart failure could be prevented or reduced by antioxidants is not known. METHODS: Rabbits with chronic cardiac pacing and sham operation were randomized to receive a combination of beta-carotene, ascorbic acid and alpha-tocopherol, alpha-tocopherol alone or placebo over eight weeks. Echocardiography was used to measure cardiac function weekly. Resting hemodynamics and in vivo myocardial beta-adrenergic responsiveness were studied at week 8. Animals were then sacrificed for measuring myocardial beta-receptor density, norepinephrine (NE) uptake-1 site density, sympathetic neuronal marker profiles, tissue-reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and oxidative damage of mitochondrial DNA (mtDNA). RESULTS: Rapid cardiac pacing increased myocardial oxidative stress as evidenced by reduced myocardial GSH/GSSG ratio and increased oxidized mtDNA and produced cardiac dysfunction, beta-adrenergic subsensitivity, beta-receptor downregulation, diminished sympathetic neurotransmitter profiles and reduced NE uptake-1 carrier density. A combination of antioxidant vitamins reduced the myocardial oxidative stress, attenuated cardiac dysfunction and prevented myocardial beta-receptor downregulation and sympathetic nerve terminal dysfunction. Administration of alpha-tocopherol alone produced similar effects, but the effects were less marked than those produced by the three vitamins together. Vitamins produced no effects in sham-operated animals. CONCLUSIONS: Antioxidant vitamins reduced tissue oxidative stress in CHF and attenuated the associated cardiac dysfunction, beta-receptor downregulation and sympathetic nerve terminal abnormalities. The findings suggest that antioxidant therapy may be efficacious in human CHF.

Analysis of Variance↗
PubMed2001

Glucose-dependent insulinotropic peptide is an integrative hormone with osteotropic effects.

Glucose-dependent insulinotropic peptide (GIP) is a gut-derived hormone known to be important in modulating glucose-induced insulin secretion. In addition, GIP receptors are widely distributed and may have effects on multiple other tissues: fat cells, adrenal glands, endothelium and brain. We have demonstrated recently that GIP also has anabolic effects on bone-derived cells. We now demonstrate that GIP administration prevents the bone loss associated with ovariectomy. We propose that GIP plays a unique role in signaling the bone about nutrient availability, indicating the importance of the gut hormones in directing absorbed nutrients to the bone, and suggesting the concept of an 'entero-osseous axis'. Thus, GIP plays an integrative role helping coordinate efficient and targeted nutrient absorption and distribution.

Animals↗
PubMed2001

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

Algorithms↗
PubMed2001

Antioxidant vitamins prevent cardiomyocyte apoptosis produced by norepinephrine infusion in ferrets.

BACKGROUND: Norepinephrine (NE) induces apoptosis in cultured neonatal rat myocytes. To determine whether this change occurred in intact animals after chronic subhypertensive doses of NE, and whether the effect was mediated via oxidative stress produced by NE, we measured myocyte apoptosis and apoptotic gene proteins in ferrets receiving chronic NE with and without antioxidant vitamin treatment. METHODS: Ferrets were administered either subcutaneous NE or vehicle and simultaneously assigned to receive antioxidant vitamins (beta-carotene, ascorbic acid and alpha-tocopherol) or vehicle for 4 weeks. Resting hemodynamics and plasma NE were measured at 4 weeks. Animals were then sacrificed for measuring cardiac myocyte size by electron microscopy, and oxidative stress by reduced to oxidized glutathione (GSH/GSSG) ratio and mitochrondrial DNA 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG). Cardiomyocyte apoptosis was detected by both terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and monoclonal antibody to single-stranded DNA (Mab) staining. Western blot analysis was used to measure the expression of the antiapoptotic protein Bcl-2 and apoptotic protein Bax. RESULTS: NE administration produced a 4-fold increase in plasma NE, but had no effect on resting heart rate, heart weight, arterial pressure, left ventricular systolic function or cardiac cell size. NE infusion decreased tissue GSH/GSSG ratio, and increased mtDNA 8-oxo-dG, and TUNEL- and Mab-positive apoptotic cells. These changes were associated with a 27% decrease in Bcl-2 protein, a 42% increase in Bax and a 57% reduction in the ratio of Bcl-2/Bax. All of the changes were prevented by co-administration of antioxidant vitamins. CONCLUSION: NE administration at a dose which produced no significant increase in blood pressure or myocyte hypertrophy caused cardiomyocyte apoptosis in intact animals. This effect was associated with an increase in oxidative stress, up-regulation of Bax protein and down-regulation of Bcl-2 protein. Antioxidant vitamins prevented the changes produced by NE. The findings suggest that NE-induced myocyte apoptosis is mediated by oxidative stress, and that antioxidant vitamins may be beneficial in heart failure in which cardiac NE release is increased.

Animals↗
PubMed2001

Remodeling and suppression of intimal hyperplasia of vascular grafts with a distal arteriovenous fistula in a rat model.

PURPOSE: The purpose of this study was to evaluate the effects of a distal arteriovenous fistula (dAVF) on the morphologic changes occurring in arterial bypass grafts by the use of a novel experimental model. METHODS: Aortofemoral bypass grafts with or without dAVFs were constructed in 36 Sprague-Dawley rats with a microsurgical technique. The bypass graft material consisted of deendothelialized autogenous tail artery (length, 25 mm; inside diameter, 0.5 mm). In 18 rats, dAVFs were constructed at the distal anastomosis. After 6 weeks, flow rates and shear stress were determined, and grafts were then harvested. Luminal, intimal, and medial cross-sectional areas were measured with computer imaging. Desmin, alpha-smooth muscle actin, and von Willebrand factor (vWF) were identified with immunohistochemistry. Endothelialization was evaluated with SEM. RESULTS: All bypass grafts remained patent at the time of graft harvest. Grafts with dAVFs showed increased flow rates (11.5 +/- 0.6 mL/min) compared with grafts without dAVFs (2.1 +/- 0.3 mL/min; P < .01). Shear stress was also increased in the dAVF group (340.9 +/- 23.4 dyne/cm(2) vs 113.7 +/- 12.5 dyne/cm(2); P < .01), with a corresponding suppression of intimal hyperplasia (0.059 +/- 0.011 mm(2) for dAVF grafts vs 0.225 +/- 0.009 mm(2) for non-dAVF grafts; P < .01). Staining for vWF was found in both the reendothelialized flow surface and the neointimal extracellular matrix. Remodeling of the grafts was characterized by a 50% increased luminal area, 70% decreased intimal area, and a 25% decreased medial area when a dAVF was constructed. CONCLUSION: A small animal experimental model of an arterial bypass graft can enable the evaluation of a variety of factors that influence graft patency. Increased blood flow velocity and shear stress induced by a dAVF are associated with a decrease in intimal and medial areas, which may reflect changes in cell proliferation, apoptosis, migration, or matrix deposition. Deposition of vWF was also found both in the endothelium and throughout the hyperplastic intima. These findings suggest that the hemodynamic and morphologic changes associated with dAVF may potentiate graft patency and function.

Actins↗
PubMed2001

[The protective effects of Zn-metallothionein on severely scalded rats inflicted by oxygen free radicals].

OBJECTIVE: To investigate the protective effects of metallothionein (MT) on severely scalded rats inflicted by oxygen free radicals after delayed resuscitation. METHODS: Wistar rats inflicted by 30% TBSA III degree scalding injury were taken as the model. Fifty-Six rats were randomly divided into four groups, i.e. normal control, delayed resuscitation, MT treated and VitC treated groups. The changes in superoxide dismutase (SOD) and malondialdehyde (MDA) contents in plasma and subeschar edematous fluid were determined at 24 and 48 postburn hours with traditional indirect detecting method and electron spin resonance (ESR). Pathomorphological examination was simultaneously carried out for cardiac, hepatic, renal and intestinal samples. Plasma biochemical indices were determined at the same time. RESULTS: In delayed resuscitation group, SOD content decreased and the MDA contents increased in plasma and subeschar fluid obviously, with remarkable changes in the pathomorphology of all the internal organs and the blood biochemical indices. But in MT treating group, SOD content increased (P < 0.05) with decreased content of MDA (P < 0.05) and the pathomorphology and blood biochemical indices improved significantly when compared with those in delayed resuscitation group and VitC treatment group. CONCLUSION: MT treatment might be beneficial in the management of severely scalding rats infliced by oxygen free radicals.

Alanine Transaminase↗
PubMed2000

Alterations by norepinephrine of cardiac sympathetic nerve terminal function and myocardial beta-adrenergic receptor sensitivity in the ferret: normalization by antioxidant vitamins.

BACKGROUND: Chronic excessive norepinephrine (NE) causes cardiac sympathetic nerve terminal abnormalities, myocardial beta-adrenergic receptor downregulation, and beta-adrenergic subsensitivity. The present study was carried out to determine whether these changes could be prevented by antioxidants. METHODS AND RESULTS: Ferrets were administered either NE (1.33 mg/d) or vehicle by use of subcutaneous pellets for 4 weeks. Animals were simultaneously assigned to receive either antioxidant vitamins (beta-carotene, ascorbic acid, and alpha-tocopherol) or placebo pellets. NE increased plasma NE 4- to 5-fold but had no effect on heart rate, heart weight, arterial pressure, or left ventricular systolic function. However, myocardial NE uptake activity and NE uptake-1 site density were reduced, as well as cardiac neuronal NE, tyrosine hydroxylase, and neuropeptide Y. In addition, there was a decrease in myocardial beta-adrenergic receptor density with a selective decrease of the beta(1)-receptor subtype, reduction of the high-affinity site for isoproterenol, decreased basal adenylyl cyclase activity, and the adenylyl cyclase responses to isoproterenol, Gpp(NH)p, and forskolin. All of these changes were prevented by antioxidant vitamins. The effects of NE on myocardial beta-adrenergic receptor density, NE uptake-1 carrier site density, and neuronal NE were also prevented by superoxide dismutase or Trolox C. CONCLUSIONS: The toxic effects of NE on the sympathetic nerve terminals are mediated via the formation of NE-derived oxygen free radicals. Preservation of the neuronal NE reuptake mechanism is functionally important, because the antioxidants also prevented myocardial beta-adrenergic receptor downregulation and postreceptor abnormalities. Thus, antioxidant therapy may be beneficial in heart failure, in which cardiac NE release is increased.

Adenylyl Cyclases↗
PubMed2000

Rapid upregulation of caspase-3 in rat spinal cord after injury: mRNA, protein, and cellular localization correlates with apoptotic cell death.

Although the precise mechanisms explaining loss of, and failure to regain, function after spinal cord injury are unknown, there is increasing interest in the role of "secondary cell death." One prevalent theme in cell loss in other regions of the CNS involves apoptosis executed by the intracellular caspase proteases. A recent study demonstrated that spinal cord injury rapidly increased the activation of caspase-3. Our previous studies demonstrated peak apoptosis in three of four cellular compartments 3 days after controlled contusion in the rat. We have extended these analyses to include enzyme and substrate studies of caspase subfamilies both in rostral and in caudal adjacent segments compared to the lesion site. Although presumed activation of programmed proenzyme is considered the mechanism for enhanced caspases, our novel analyses were designed to detect upregulation of gene expression. We surveyed traumatically injured spinal cord for caspase family messages with a modified differential mRNA display approach and found that the caspase-3 (CASP3) message was present and upregulated severalfold after injury. Our results clearly demonstrate that cell death in the spinal cord occurs after posttranslational activation of caspases that follow, at least for caspase-3, initial upregulation of CASP3 mRNA levels.

Animals↗
PubMed2000

A direct optimization approach to hidden Markov modeling for single channel kinetics.

Hidden Markov modeling (HMM) provides an effective approach for modeling single channel kinetics. Standard HMM is based on Baum's reestimation. As applied to single channel currents, the algorithm has the inability to optimize the rate constants directly. We present here an alternative approach by considering the problem as a general optimization problem. The quasi-Newton method is used for searching the likelihood surface. The analytical derivatives of the likelihood function are derived, thereby maximizing the efficiency of the optimization. Because the rate constants are optimized directly, the approach has advantages such as the allowance for model constraints and the ability to simultaneously fit multiple data sets obtained at different experimental conditions. Numerical examples are presented to illustrate the performance of the algorithm. Comparisons with Baum's reestimation suggest that the approach has a superior convergence speed when the likelihood surface is poorly defined due to, for example, a low signal-to-noise ratio or the aggregation of multiple states having identical conductances.

Algorithms↗
PubMed2000

Hidden Markov modeling for single channel kinetics with filtering and correlated noise.

Hidden Markov modeling (HMM) can be applied to extract single channel kinetics at signal-to-noise ratios that are too low for conventional analysis. There are two general HMM approaches: traditional Baum's reestimation and direct optimization. The optimization approach has the advantage that it optimizes the rate constants directly. This allows setting constraints on the rate constants, fitting multiple data sets across different experimental conditions, and handling nonstationary channels where the starting probability of the channel depends on the unknown kinetics. We present here an extension of this approach that addresses the additional issues of low-pass filtering and correlated noise. The filtering is modeled using a finite impulse response (FIR) filter applied to the underlying signal, and the noise correlation is accounted for using an autoregressive (AR) process. In addition to correlated background noise, the algorithm allows for excess open channel noise that can be white or correlated. To maximize the efficiency of the algorithm, we derive the analytical derivatives of the likelihood function with respect to all unknown model parameters. The search of the likelihood space is performed using a variable metric method. Extension of the algorithm to data containing multiple channels is described. Examples are presented that demonstrate the applicability and effectiveness of the algorithm. Practical issues such as the selection of appropriate noise AR orders are also discussed through examples.

Algorithms↗
PubMed2000

Regulation of the dual function tissue transglutaminase/Galpha(h) during murine neuromuscular development: gene and enzyme isoform expression.

Coagulation Factor XIII (F. VIII), a member of the transglutaminase (TGase) superfamily, is activated by thrombin, cross-links fibrin and stabilizes clots. Another member of this family, tissue TGase (tTG), having similar enzymatic activity, is implicated in neural development and synapse stabilization. Our previous studies indicated that synapse formation and maintenance at the neuromuscular junction (NMJ) involved components of the coagulation cascade in development. Others then showed that either F. XIII or tTG were localized at NMJs in a developmentally-regulated fashion. In the current studies, we addressed the temporal course of skeletal muscle tTG gene expression and found maximal expression at birth and continuing into the immediate postnatal period. Subcellular fractionation revealed a relatively constant particulate isoform of TGase activity which predominated in early embryonic muscle development. In contrast, cytosolic TGase specific activity became the major isoform in the postnatal period. The timing of muscle TGase activity correlated well with expression of tTG mRNA and we now present novel data of Tgm 2 gene expression for tTG in skeletal muscle. Confirming and extending the previous studies, TGase becomes localized at NMJs in the early, further ramifying in the late, neonatal period. These data suggest that the early pulse of particulate activity could coincide with the period of myoblast cell death in embryonic muscle. On the other hand, the peak cytosolic TGase activity occurs in the neonatal period, correlating temporally with muscle prothrombin expression during activity-dependent synapse elimination and possibly the source of the enzyme localized to the NMJ extracellular matrix resulting in synaptic stabilization.

Aging↗
PubMed2000

Osteoblast-derived cells express functional glucose-dependent insulinotropic peptide receptors.

Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid peptide synthesized and secreted from endocrine cells in the small intestine. The role of GIP in coupling nutrient intake and insulin secretion, the incretin effect, is well known. We report that GIP receptor messenger RNA and protein are present in normal bone and osteoblast-like cell lines, and that high affinity receptors for GIP can be demonstrated by [125I]GIP binding studies. When applied to osteoblast-like cells (SaOS2), GIP stimulated increases in cellular cAMP content and intracellular calcium, with both responses being dose dependent. Moreover, administration of GIP results in elevated expression of collagen type I messenger RNA as well as an increase in alkaline phosphatase activity. Both of these effects reflect anabolic actions of presumptive osteoblasts. These results provide the first evidence that GIP receptors are present in bone and osteoblast-like cells and that GIP modulates the function of these cells.

Alkaline Phosphatase↗
PubMed2000

The tourniquet revisited as an adjunct to lower limb revascularization.

PURPOSE: The purpose of this study was to evaluate the role and efficacy of the tourniquet in lower limb revascularization. METHODS: During a 3-year period, 195 patients underwent 205 infrainguinal reconstruction operations in the lower extremity. These patients underwent bypass with a tourniquet and inflow occlusion (group 1) or bypass without a tourniquet (group 2). The type of infrainguinal reconstruction, tourniquet ischemia time, blood loss, and complications related to tourniquet use were recorded. A subset of patients underwent serial muscle biopsies. Specimens from calf muscle were taken just (1) before application of the tourniquet, (2) before tourniquet release, and (3) once wound closure was initiated. These biopsy specimens were studied by histochemical staining and also analyzed for phosphorylase enzyme, a marker for subcellular ischemia. RESULTS: One hundred eleven patients underwent 117 infrainguinal reconstruction procedures in which the tourniquet and inflow occlusion were used. These patients were matched against 84 patients who underwent 88 infrainguinal reconstructions without the use of the tourniquet. Complete hemostatic control in group 1 was obtained in 108 of the procedures (92%). Eight percent of the procedures required minor additional techniques to obtain complete hemostasis; in two instances, the tourniquet was removed because it did not provide hemostasis. Mean tourniquet time was less than 1 hour for all reconstruction groups. There were no instances of neurologic deficit, thrombosis of distal vessels, or vascular injury that was related to the use of a tourniquet. A comparison of the two groups revealed no differences with regard to overall blood loss (P =.63) or duration of operation (P = 0.60), observations that reflect the complexity of the cases rather than the use or nonuse of a tourniquet. When tourniquet control was used, we noted a definite decrease in the time for the distal dissection, because total vascular control with extensive dissection was unnecessary. Histochemical analysis with phosphorylase revealed a conversion of tissue with active enzyme activity to a low level with tourniquet use (P <.05). CONCLUSION: The use of a tourniquet for lower limb revascularization is safe and effective and improves visualization of the operative field. Less dissection of the target vessels is required. With a combination of the nonuse of clamps and other occluding devices, we project a decrease in host hyperplastic response that will, in turn, impact favorably on patency rates. The possibility exists that early failure may be prevented by avoiding the application of traumatic forces to diseased and brittle or calcified arteries. In this study, tourniquet time had no impact on overall operative procedural time, although certain phases of the operation were clearly shortened and facilitated, particularly in complex and difficult reconstructions. Histochemical changes found in muscle biopsy specimens did not adversely impact patients clinically, but further investigation is required to elucidate subcellular events.

Aged↗
PubMed1999

1,25-dihydroxyvitamin D3 induces phospholipase D-1 expression in primary mouse epidermal keratinocytes.

The hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) elicits the programmed pattern of differentiation in epidermal keratinocytes. Based on data indicating a potential role of phospholipase D (PLD) in mediating keratinocyte differentiation, we investigated the effect of 1,25(OH)2D3 on PLD expression. A 24-h exposure to 1, 25(OH)2D3 stimulated PLD-1, but not PLD-2, mRNA expression. This 1, 25(OH)2D3-enhanced expression was accompanied by increased total PLD and PLD-1 activity. Time course studies indicated that 1,25(OH)2D3 induced PLD-1 expression by 8 h, with a maximal increase at 20-24 h. Exposure to 1,25(OH)2D3 inhibited proliferation over the same time period with similar kinetics. Expression of the early (spinous) differentiation marker keratin 1 decreased in response to 1, 25(OH)2D3 over 12-24 h. Treatment with 1,25(OH)2D3 enhanced the activity of transglutaminase, a late (granular) differentiation marker, by 12 h with a maximal increase after 24 h. In situ hybridization studies demonstrated that the highest levels of PLD-1 expression are in the more differentiated (spinous and granular) layers of the epidermis, with little expression in basal keratinocytes. Our results suggest a role for PLD expression/activity during keratinocyte differentiation.

Animals↗
PubMed1999

[Effects of metallothionein (MT) on burned skin of rats].

OBJECTIVE: To elucidate the relationship between skin viability and lipid peroxidation after deep partial thickness burn injury. METHODS: Deep partial thickness burn was produced. Metallothionin (MT) in different concentrations (0.5 x 10(-6) mol/L, 1 x 10(-5) mol/L) was topically applied. Oxygen consumption, succinate dehydrogenase(SDH), Schiff's base contents and healing time of wound were determined in 24 Wistar rats. Specimens were harvested at 8, 24, and 48-hour postburn. RESULTS: Oxygen consumption and SDH value decreased and Schiff's base value increased after burn injury. With the application of MT, oxygen consumption and SDH value of burned skin were significantly higher compared with control group, and Schiff's base value was significantly lower (P < 0.05 or P < 0.01). The mean healing time of burned wound was two days less in two MT protection groups. CONCLUSION: MT may be beneficial in improving postburn skin viability by attenuating lipid peroxidation of burned tissue.

Animals↗
PubMed1999

[Changes of serum elastase, alpha 1-antitrypsin, procollagen III peptide and malonaldehyde in smokers with and without chronic obstructive pulmonary diseases].

OBJECTIVE: Serum elastase, alpha(1)-antitrypsin (alpha(1)-AT), procollagen III peptide (PIIIP) and malonaldehyde (MDA) were studied in smokers with and without chronic obstructive pulmonary disease (COPD) to explore the roles of these factors in COPD induced by smoking. METHODS: A design of 154-pair case-control study was used. alpha(1)-AT, MDA and PIIIP were determined with colorimetric method, fluo-spectrophotometric method and radio-immunological assay, respectively, in non-smoker control and smokers with and without COPD. RESULTS: Serum PIIIP content was increased in smokers and alpha(1)-AT decreased significantly in patients with COPD. CONCLUSION: Decreased alpha(1)-AT may be a susceptible factor in the development of COPD caused by smoking.

Adult↗