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Biomedical subjects

J L Liu

Publications and source records attributed to J L Liu.

At least 37 records · Page 2Linked to original sources
PubMed2001

Liver-derived IGF-I regulates GH secretion at the pituitary level in mice.

We have reported that liver-specific deletion of IGF-I in mice (LI-IGF-I-/-) results in decreased circulating IGF-I and increased GH levels. In the present study, we determined how elimination of hepatic IGF-I modifies the hypothalamic-pituitary GH axis to enhance GH secretion. The pituitary mRNA levels of GH releasing factor (GHRF) receptor and GH secretagogue (GHS) receptor were increased in LI-IGF-I-/- mice, and in line with this, their GH response to ip injections of GHRF and GHS was increased. Expression of mRNA for pituitary somatostatin receptors, hypothalamic GHRF, somatostatin, and neuropeptide Y was not altered in LI-IGF-I-/- mice, whereas hypothalamic IGF-I expression was increased. Changes in hepatic expression of major urinary protein and the PRL receptor in male LI-IGF-I-/- mice indicated an altered GH release pattern most consistent with enhanced GH trough levels. Liver weight was enhanced in LI-IGF-I-/- mice of both genders. In conclusion, loss of liver-derived IGF-I enhances GH release by increasing expression of pituitary GHRF and GHS receptors. The enhanced GH release in turn affects several liver parameters, in line with the existence of a pituitary-liver axis.

Animals↗
PubMed2001

Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity.

Insulin and insulin-like growth factors (IGFs) mediate a variety of signals involved in mammalian development and metabolism. To study the metabolic consequences of IGF-I deficiency, we used the liver IGF-I-deficient (LID) mouse model. The LID mice show a marked reduction (approximately 75%) in circulating IGF-I and elevated growth hormone (GH) levels. Interestingly, LID mice show a fourfold increase in serum insulin levels (2.2 vs. 0.6 ng/ml in control mice) and abnormal glucose clearance after insulin injection. Fasting blood glucose levels and those after a glucose tolerance test were similar between the LID mice and their control littermates. Thus, the high levels of circulating insulin enable the LID mice to maintain normoglycemia in the presence of apparent insulin insensitivity. Insulin-induced autophosphorylation of the insulin receptor and tyrosine phosphorylation of insulin receptor substrate (IRS)-1 were absent in muscle, but were normal in liver and white adipose tissue of the LID mice. In contrast, IGF-I-induced autophosphorylation of its cognate receptor and phosphorylation of IRS-1 were normal in muscle of LID mice. Thus, the insulin insensitivity seen in the LID mice is muscle specific. Recombinant human IGF-I treatment of the LID mice caused a reduction in insulin levels and an increase in insulin sensitivity. Treatment of the LID mice with GH-releasing hormone antagonist, which reduces GH levels, also increased insulin sensitivity. These data provide evidence of the role of circulating IGF-I as an important component of overall insulin action in peripheral tissues.

Animals↗
PubMed2001

Liver-derived IGF-I is of importance for normal carbohydrate and lipid metabolism.

IGF-I is important for postnatal body growth and exhibits insulin-like effects on carbohydrate metabolism. The function of liver-derived IGF-I is still not established, although we previously demonstrated that liver-derived IGF-I is not required for postnatal body growth. Mice whose IGF-I gene in the liver was inactivated at 24 days of age were used to investigate the long-term role of liver-derived IGF-I for carbohydrate and lipid metabolism. Serum levels of leptin in these mice were increased by >100% at 3 months of age, whereas the fat mass of the mice was decreased by 25% at 13 months of age. The mice became markedly hyperinsulinemic and yet normoglycemic, indicating an adequately compensated insulin resistance. Furthermore, they had increased serum levels of cholesterol. We conclude that liver-derived IGF-I is of importance for carbohydrate and lipid metabolism.

Absorptiometry, Photon↗
PubMed2001

The regulation of sympathetic outflow in heart failure. The roles of angiotensin II, nitric oxide, and exercise training.

Sympatho-excitation is a hallmark of the chronic heart failure (CHF) state. It has long been assumed that this sympatho-excitation is mediated by a reduction in sensory input from cardiopulmonary and arterial baroreceptors. However, recent data suggest that these reflexes may only be important in the initiation of the sympatho-excitatory state and may not be necessary for the sustained increase in sympathetic nerve activity (SNA) in CHF. Two humoral factors that can influence SNA are nitric oxide (NO) and angiotensin II (AngII). Animals with CHF exhibit a downregulation in central gene expression for the neuronal isoform of nitric oxide synthase (nNOS). In addition, blockade of AngII receptors in combination with NO donation reduces SNA in animals with CHF, while NO donation alone has no effect on SNA. Chronic exercise training (EX) reduces both plasma AngII and SNA in rabbits with CHF while improving baroreflex function. Blockade of AT1 receptors enhances baroreflex function in non-EX CHF rabbits, but has little effect in EX CHF rabbits. These data suggest that the sympatho-excitatory state that is typical of CHF is, in part, due to changes in AngII and NO. Depressed baroreflex function and the elevated SNA can be improved by EX in animals with CHF.

Angiotensin II↗
PubMed2001

Quantitative evaluation of hypothermia, hyperthermia, and hemodilution on coagulation.

The purpose of this study was to investigate the effects of temperature change on the coagulation time of blood at two different hematocrit levels by using various coagulation-monitoring devices. The devices used in this study were the Bayer Rapid Point Coag Analyzers, Hemochron Jr. Signature, Hemochron Response, Medtronic ACT II, and Haemoscope Thrombelastograph. One unit of human bank blood was used in this study. The hematocrit level was adjusted to 40% and 20%. A control bath and experimental bath were set up. Control blood was maintained at 37 degrees C and tested every 45 +/- 15 min throughout the experimental period of 6 h to demonstrate the stability of the model. The experimental blood was tested at temperature points of 37, 32, 27, 32, 37, 42, and 37 degrees C. Activated clotting time (ACT) tended to increase when the temperature was initially decreased from 37 to 27 degrees C, which reached a statistically significant level when measured by the Hemochron Response at both the 20% (147 +/- 10.7 to 159.3 +/- 11.0, p < .0332) and 40% hematocrit level (130 +/- 14.9 to 152.1 +/- 19.7, p < .0148). ACT was decreased significantly (p < .05) when the temperature was increased to 42 degrees C as measured by all machines except the Hemochron Jr. Signature at the 20% hematocrit level. ACT was significantly higher (p < .05) at a 20% hematocrit level as compared to that at a 40% hematocrit level on all devices for the majority of temperature points. These data suggested that hypothermia only increased ACT when measured by a macrosample device requiring a milliliter sample (Hemochron Response). However, hemodilution induced anticoagulatory effects and hyperthermia caused an acceleration in coagulation by all devices utilized in this study.

Blood Banks↗
PubMed2001

Effects of ultrafiltration on enoxaparin: an in vitro analysis.

The use of low molecular weight heparins (LMWH) as an anticoagulant in the heparin-resistant patient poses challenges during cardiopulmonary bypass (CPB). The ultrafiltrability of LMWH has not been previously examined. The purpose of this study was to determine the effects of continuous ultrafiltration on the concentraton of a LMWH, enoxaparin. An in vitro analysis was performed using fresh whole human blood and an extracorporeal circuit containing four parallel ultrafiltrators and a cardiotomy reservoir with an integrated heat exchanger. Constant conditions included temperature (37 degrees C), flow (0.20 L-min(-1)) transmembrane pressure (200 mmHg), and hematocrit (25 +/- 2%). Samples were collected at the inlet, outlet, and ultrafiltrate line at one and three min for one control trial and again for each of the four hemoconcentrators following the bolus of enoxaparin. Coagulation measurements included a viscoelastic monitor (TEG), activated clotting time (ACT), activated partial thromboplastin time (aPTT), and quantitative analysis utilizing a membrane-based electrode for potentiometric measurement of polyanionic concentrations of enoxaparin. Enoxaparin concentration, from inlet to outlet, increased from 2.95 +/- 0.64 to 5.89 +/- 0.95 (p < .001) at 1 min and 4.24 +/- 0.49 to 7.89 +/- 0.606 (p < .001) at 3 min. Kinetic clot activity, as assessed by the TEG index, decreased from -3.8 +/- 2.5 vs. -10.5 +/- 6.0; (p < .01) pre- to postultrafiltrator samples after 3 min. ACT and aPTT results demonstrated no significant change. In conclusion, this study demonstrates enoxaparin is concentrated with the use of continuous ultrafiltration. Functional coagulation studies also indicate a concentrating effect, primarily via the TEG.

Anticoagulants↗
PubMed2001

[Effect of ATXII on opening modes of myocyte sodium channel, action potential and QT intervals of ECG].

Single sodium channel currents were recorded by patch clamp technique in isolated guinea-pig ventricular myocytes, and action potentials of papillary muscle and ECG were conventionally measured. Sea anemone toxin (ATXII), a high affinity toxin to sodium channel, was used to change the sodium channel dynamics. Changes in the duration of action potentials and the QT interval of ECG depending on the channel modes were studied in order to provide hints to an understanding of pathogenesis of the long QT syndrome (a genetic disease). With the binding of ATXII to the sodium channel, the occurrence frequency and the open time constant of the "long opening" mode of single Na channels increased significantly, whereas the action potential durations, APD50 and APD90, were prolonged by 23% and 27% respectively. Following application of ATXII, on the other hand, the QT interval and the QTc, a rectified QT interval, increased by 18.6% and 18.9% respectively. The results suggest that the dynamics or modes of Na channel play an important role in determining the action potential duration and the QT interval of ECG. The dynamical changes in Na channels induced by genetic mutation may be partially responsible for the long QT syndrome.

Action Potentials↗
PubMed2001

Refrigeration of donor cells in preparation for bovine somatic nuclear transfer.

In mammals, preparation of donor cells for somatic nuclear transfer is very important because the character of the donor cell directly affects the efficiency and outcome of transfer. The protocols used most commonly for donor preparation are (i) disaggregating cells from fresh tissue 1-2 h before micromanipulation or (ii) trypsinizing cultured cells temporarily, after special treatments for 3-8 days (for example, serum starvation). In this study, a new simple protocol was designed, whereby the donor cells (cumulus cells) used in bovine somatic nuclear transfer were refrigerated. In brief, cultured cells at 80-100% confluency were detached using trypsin, washed by centrifugation, aliquoted into different vials and refrigerated at 4 degrees C. The density of viable cells was decreased after day 1 of refrigeration; however, the rate of decrease tended to slow down with increasing duration of refrigeration. Cells refrigerated for 15 days were seeded at a density of 5 x 10(4) ml(-1) and reached 70% confluency after day 2 of culture. Most cells had the normal number of chromosomes (2n = 60). Cells chilled at 4 degrees C for different durations were removed from refrigeration and immediately subjected to micromanipulation. The in vitro development of reconstructed embryos (fusion rates, cleavage rates, morula and blastocyst rates) indicated that there were no significant differences among treatment groups regardless of the duration of refrigeration (0-2 weeks) of the donor cells. Reconstructed embryos were transferred into the uteri of recipient cows. No significant differences were observed in established early pregnancies between embryos derived from the non-refrigerated donor cells and those derived from refrigerated donor cells. This study indicates that refrigeration of donor cells for 1-2 weeks is a feasible protocol for preparing donor cells for bovine somatic nuclear transfer, and does not compromise development in vitro and early development in vivo.

Animals↗
PubMed2001

The effect of volume replacement on serum protein concentration during cardiopulmonary bypass.

Although controversy exists concerning the optimal total protein and colloid osmotic pressure that should be maintained during cardiopulmonary bypass (CPB), the primary volume expanders remain albumin and 6% hetastarch. The purpose of this study was to quantify the effect of adding boluses of volume replacement agents under various conditions to total serum protein values during CPB. A standard CPB circuit was utilized in eight 45-kg swine that had a priming volume (physiologic saline solution) of 2309 +/- 245 mL. Volumetric alterations occurred throughout the CPB period by the addition of combinations of physiologic saline solution, 6% hetastarch or 5% swine albumin. Pre- and postadministration samples were assayed for total serum protein, total protein, and albumin throughout the CPB period and at pre- and postvolume administration times. There was a significant decline in total serum protein with the initiation of CPB (6.14 +/- 0.49 g/dL vs. 3.40 +/- 0.43 g/dL, p < .0001). Addition of 12.5 g of swine albumin (N = 5) to two different swine increased total serum protein significantly when compared to adding 500 mL of 6% hetastarch (N = 6) (swine albumin 12.4 +/- 6.3% vs. hetastarch 3.3 +/- 2.1%, p < .005). A reduction in total serum protein occurred after hemodilution with varying amount of physiologic saline solution: 250-450 mL (7.4 +/- 4.5%), 451-650 mL (9.6 +/- 5.6%), and 651-1050 mL (19.4 +/- 4.0%). In summary, knowledge of total serum protein concentration and estimated circulating blood volume can be used to guide albumin and hetastarch administration following hemodilution.

Albumins↗
PubMed2000

Chronic exercise reduces sympathetic nerve activity in rabbits with pacing-induced heart failure: A role for angiotensin II.

BACKGROUND: Chronic exercise (EX) improves the quality of life and increases the survival of patients with chronic heart failure (CHF). Because sympathetic nerve activity is elevated in the CHF state, it is possible that EX is beneficial in this disease due to a decrease in sympathetic outflow. METHODS AND RESULTS: We evaluated arterial baroreflex function and resting renal sympathetic nerve activity (RSNA) in EX normal and CHF rabbits before and after angiotensin II type 1 (AT(1)) receptor blockade. Four groups of rabbits were studied: a normal non-EX group, a normal EX group, a CHF non-EX group, and a CHF EX group. EX lowered resting RSNA in rabbits with CHF but not in normal rabbits. In addition, EX increased arterial baroreflex sensitivity in the CHF group (heart rate slope: CHF 1. 7+/-0.3 bpm/mm Hg, EX CHF 4.9+/-0.3 bpm/mm Hg; P:<0.01; RSNA slope: CHF 2.2+/-0.2%max/mm Hg, EX CHF 5.7+/-0.4%max/mm Hg; P:<0.01. AT(1) receptor blockade enhanced baroreflex sensitivity in the non-EX CHF rabbits but had no effect in EX CHF rabbits. Concomitant with this effect, EX lowered the elevated plasma angiotensin II concentration in the CHF group. A significant positive correlation was observed between sympathetic nerve activity and plasma angiotensin II. CONCLUSIONS: These data strongly suggest that EX reduces the sympathoexcitatory state in the setting of CHF. Enhanced arterial baroreflex sensitivity may contribute to this reduction. In addition, EX lowers plasma angiotensin II concentration in CHF. These data further suggest that the lowering of angiotensin II may contribute to the decrease in sympathetic nerve activity after EX in the CHF state.

Angiotensin II↗
PubMed2000

Effect of telophase enucleation on bovine somatic nuclear transfer.

Telophase enucleation has been proven to be an efficient method for preparing recipient cytoplasts in bovine embryonic nuclear transfer (2, 11). This research was designed to study in vitro development of bovine oocytes containing transferred somatic cell nuclei, reconstructed by using enucleated in vitro-matured oocytes 32 h of age at telophase II stage as recipient cytoplasts, compared with those 24 h of age at metaphase II stage. Two protocols for donor cell injection were adopted, i.e., subzonal injection (SUZI) and intracytoplasmic injection (ICI). Bovine oviduct epithelial cells (BOECs) and bovine cumulus cells (BCCs) from an adult cow were used as nuclear donors for these experiments. In SUZI groups, the fusion rate of donor cells, both BOECs and BCCs, with MII enucleated oocytes were higher than those with TII enucleated oocytes (54% vs. 41% and 53% vs. 39%, respectively; P<0.05), but the development rates to morula plus blastocyst stage in MII groups were lower than those in TII groups (22% vs. 39% and 21% vs. 41%, respectively; P<0.05). In ICI groups, about 26% of enucleated MII oocytes injected with BOECs or BCCs cleaved and only small parts of them developed to blastocyst stage (4% and 3%, respectively; P>0.05). When BOECs or BCCs were intracytoplasmically injected into oocytes enucleated at TII stage, no blastocyst was formed in either donor cell group and no cleavage occurred in BOEC group. Our data demonstrated that telophase enucleation is beneficial to early embryo development when bovine somatic nuclei are transferred by subzonal injection. However, it is harmful when donor cells are directly injected into the cytoplast of the enucleated oocytes.

Animals↗
PubMed2000

Effect of long term fluoride exposure on lipid composition in rat liver.

Chronic fluorosis can severely damage many systems of human body, but its pathogenesis is unclear. Normal composition and structure of cellular membrane lipids are a basic factor to maintain cell function. In this investigation, cellular membrane lipids of the liver were analysed after a long term fluoride treatment for rats and the results are discussed in order to give an explanation for the pathogenesis of this disease. Wistar rats were supplied with drinking water containing either 30 or 100 ppm fluoride (NaF) for seven months. Contents of phospholipid and neutral lipid in rat liver were analyzed by high-performance liquid chromatography, and fatty acid composition from individual phospholipids was measured by gas chromatography. Results showed that the total liver phospholipid content decreased in the rats treated with high dose of fluoride due to a lower content of phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidylserine (PS). Among the fatty acid compositions of PE and PC in the livers of fluoride poisoned animals, the proportion of polyunsaturated fatty acids (20:4 and 22:6) decreased, whereas saturated fatty acids (16:0 and 18:0) increased. No changes could be detected in the amounts of liver cholesterol and dolichol. Total ubiquinone contents in rat liver were reduced by 11% in the group treated with 30 ppm fluoride and by 42% in the group treated with 100 ppm fluoride. In the subclasses of ubiquinone, both ubiquinone-9 and ubiquinoine-10 amounts decreased after fluoride treatment. These modifications of membrane lipids might be induced by oxidative stress, which might be an important factor in the pathogenesis of chronic fluorosis.

Animals↗
PubMed2000

Mother's willingness to pay for her own and her child's health: a contingent valuation study in Taiwan.

We use the contingent valuation (CV) method to estimate mothers' willingness to pay (WTP) to protect themselves and their children from suffering a minor illness-a cold-in Taiwan. WTP is specified as a hedonic function of the duration and severity of the cold (measured alternatively by symptoms experienced and the Quality of Well-Being (QWB) index) and of respondents' socioeconomic characteristics. The average mother is willing to pay more to protect her child than herself from suffering a cold. Median WTP to avoid the average mother's and child's colds are US$37 and US$57, respectively. Adjusting for the greater duration and severity of the average mother's cold suggests that WTP to prevent comparable illnesses is approximately twice as large for the child as for the mother. We also find that mother's WTP is about 20% greater to prevent a son's than a daughter's illness.

Adult↗
PubMed2000

The growth hormone/insulin-like growth factor-I system: implications for organ growth and development.

Growth hormone (GH) and insulin-like growth factors (IGFs) are essential for normal growth and development during embryonic stages as well as postnatally. While GH has little effect on these processes prenatally, the IGFs are important during these stages. On the other hand the GH-IGF-I axis is important for pubertal growth. To determine whether postnatal growth and development are dependent on circulating or locally produced IGF-I, we deleted the IGF-I gene in the liver using the cre/LoxP system used for tissue-specific gene deletion. These animals demonstrated approximately 75%-80% reduction in circulating IGF-I and an approximate fourfold increase in circulating GH. Despite the marked reductions in circulating IGF-I, growth and development was apparently normal. Thus the original somatomedin hypothesis needs to be re-evaluated in the light of these new findings.

Animals↗
PubMed2000

Misleading funnel plot for detection of bias in meta-analysis.

Publication and other forms of selection biases pose a threat to the validity of meta-analysis. Funnel plots are usually used to detect such biases; asymmetrical plots are interpreted to suggest that biases are present. Using 198 published meta-analyses, we demonstrate that the shape of a funnel plot is largely determined by the arbitrary choice of the method to construct the plot. When a different definition of precision and/or effect measure were used, the conclusion about the shape of the plot was altered in 37 (86%) of the 43 meta-analyses with an asymmetrical plot suggesting selection bias. In the absence of a consensus on how the plot should be constructed, asymmetrical funnel plots should be interpreted cautiously. These findings also suggest that the discrepancies between large trials and corresponding meta-analyses and heterogeneity in meta-analyses may also be determined by how they are evaluated.

Data Interpretation, Statistical↗
PubMed2000

Angiotensin II--nitric oxide interactions in the control of sympathetic outflow in heart failure.

Activation of the sympathetic nervous system is a compensatory mechanism which initially provides support for the circulation in the face of a falling cardiac output. It has been recognized for some time that chronic elevation of sympathetic outflow with the consequent increase in plasma norepinephrine, is counterproductive to improving cardiac function. Indeed, therapeutic targeting to block excessive sympathetic activation in heart failure is becoming a more accepted modality. The mechanism(s) by which sympathetic excitation occurs in the heart failure state are not completely understood. Components of abnormal cardiovascular reflex regulation most likely contribute to this sympatho-excitation. However, central mechanisms which relate to the elaboration of angiotensin II (Ang II) and nitric oxide (NO) may also play an important role. Ang II has been shown to be a sympatho-excitatory peptide in the central nervous system while NO is sympatho-inhibitory. Recent studies have demonstrated that blockade of Ang II receptors of the AT(1) subtype augments arterial baroreflex control of sympathetic nerve activity in the heart failure state, thereby predisposing to a reduction in sympathetic tone. Ang II and NO interact to regulate sympathetic outflow. Blockade of NO production in normal conscious rabbits was only capable of increasing sympathetic outflow when accompanied by a background infusion of Ang II. Conversely, providing a source of NO to rabbits with heart failure reduced sympathetic nerve activity when accompanied by blockade of AT(1) receptors. Chronic heart failure is also associated with a decrease in NO synthesis in the brain as indicated by a reduction in the mRNA for the neuronal isoform (nNOS). Chronic blockade of Ang II receptors can up regulate nNOS expression. In addition, exercise training of rabbits with developing heart failure has been shown to reduce sympathetic tone, decrease plasma Ang II, improve arterial baroreflex function and increase nNOS expression in the central nervous system. This review summarizes a large number of studies which have concentrated on the mechanisms of sympatho-excitation in heart failure. It now seems clear that one mechanism which is important in regulating sympathetic outflow in this disease state depends upon a central interaction between Ang II and NO at the cellular and nuclear levels.

Angiotensin II↗