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Biomedical subjects

K Liu

Publications and source records attributed to K Liu.

At least 19 recordsLinked to original sources

Prognostic significance of osteopontin in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND AND AIMS: Osteopontin (OPN) is known to be associated with metastasis in many types of cancers. Since OPN is a highly phosphorylated and glycosylated protein, the modification after transcription is very important to its function. In hepatocellular carcinoma (HCC), the elevated expression of OPN at mRNA levels and its relationship with metastasis and poorer prognosis of the patients have been reported. However, the prognostic impact of OPN at protein levels on the patients with hepatitis B virus (HBV)-related HCC after hepatectomy is still limited. PATIENTS AND METHODS: The expression of OPN was examined at protein level by using immunohistochemistry in 72 patients who underwent hepatectomy for HBV-related HCC, and its prognostic significance in disease-free and overall survival of the patients was also analyzed by log-rank test and multivariate Cox regression analyses. RESULTS: Thirty-nine of 72 (54.17%) HBV-related HCC specimens were positive for OPN with cytoplasmic staining. OPN was highly expressed in the specimens with capsular infiltration compared to those without (P<0.05), and also was significantly related with portal vein invasion (P<0.01) and lymph node invasion (P<0.01). The mean disease-free survival (DFS) was only 13.55+/-14.77 months when the HBV-related HCC specimens highly expressed OPN compared to 36.00+/-18.68 months for those with low expression (P<0.001). The overall survival (OS) of the patients was 18.63+/-17.28 months when the HCC over-expressed OPN compared to 42.59+/-16.85 months for HCC with the low expressed OPN (P<0.001). Multivariate analysis showed that OPN over-expression was the strongest independent adverse prognostic factor for both DFS (P=0.01) and OS (P=0.014). CONCLUSIONS: OPN over-expression was closely related to capsular infiltration, venous invasion, lymph node metastasis, and also with worse prognosis, suggesting that OPN might be deemed as a useful molecular marker for predicting the prognosis of HCC.

Adult↗

Coagulation factor VII gene haplotypes, obesity-related traits, and cardiovascular risk in young women.

BACKGROUND: Associations between common F7 haplotypes, plasma factor VII (FVII) levels, and cardiovascular risk have recently been reported in population studies involving predominantly European men. METHODS: We assessed associations between F7 haplotypes and cardiovascular risk in two US population-based studies: a case-control study of these alleles related to a decreased risk of arterial thrombotic outcomes such as myocardial infarction (MI) in young-to-middle-aged women (n = 671), and a cohort study of cardiovascular disease risk factors in young women (n = 1040). RESULTS: The high-expression F7 haplotype B (containing the promoter variant allele -402A) was associated with an increased FVII level among controls, but not with MI risk. Women carrying a> or =1 copy of the low FVII expression level haplotype C (containing the -401T/-323del/-122C and Gln353 alleles) had decreased FVII levels and decreased risk of MI (odds ratio 0.54, 95% CI 0.31-0.93) compared with women homozygous for the most common haplotype A. Haplotype C was also associated with a decreased body mass index (BMI) and an increased high-density lipoprotein (HDL) cholesterol level, but not with MI risk after adjustment for these metabolic risk factors. In a cohort study composed of young US women, individuals homozygous for haplotype C had a lower BMI and lower systolic blood pressure, but the association between the F7 haplotype and HDL cholesterol was not confirmed. CONCLUSION: Common FVII haplotypes may contribute to the risk of MI in women, but the mechanisms appear complex. The association between F7 haplotypes and MI susceptibility may be mediated in part through an influence on atherogenic risk factors such as BMI.

Adolescent↗

Changes in BMI modulate age-associated changes in sex hormone binding globulin and total testosterone, but not bioavailable testosterone in young adult men: the CARDIA Male Hormone Study.

OBJECTIVES: To compare age-associated 8-year changes in total testosterone, calculated bioavailable testosterone and sex hormone binding globulin (SHBG) across five groups of men stratified according to change in body mass index (BMI) (i.e., BMI stable (+/-0.69 kg/m(2)), decreased (-0.7 kg/m(2)), increased minimally (0.7-1.74 kg/m(2)), increased moderately (1.75-3.19 kg/m(2)) and increased most (> or =3.20 kg/m(2))). DESIGN: Eight-year longitudinal cohort study. SUBJECTS: Four hundred and seventy-four black and 695 white men, aged 24-31 years at the time of the first hormone measurement. MEASUREMENTS: Aging-related changes in serum SHBG, total testosterone and bioavailable testosterone. RESULTS: SHBG significantly increased with age for men whose BMI decreased, and there were progressively smaller increases for men whose BMI was stable, or whose BMI increased minimally or moderately (range 1.1-0.3 nM per year, P< or =0.03, respectively). There was no age relationship with SHBG among men whose BMI increased most. Total testosterone did not change with age for men whose BMI decreased, was stable or increased minimally, but for men whose BMI increased moderately and most there was a graded decrease in total testosterone with age (beta=-0.2 and -0.4 nM per year, respectively, P< or =0.005). However, bioavailable testosterone decreased with age to a similar extent across all groups. CONCLUSIONS: These results suggest that changes in BMI during young adulthood modulate age-related changes in SHBG and total testosterone, but not bioavailable testosterone.

Adult↗

Isoflurane preconditioning-induced cardio-protection in patients undergoing coronary artery bypass grafting.

BACKGROUND AND OBJECTIVES: Ischaemic preconditioning is commonly regarded as one of the most powerful protective mechanisms against a subsequent lethal ischaemic injury during coronary artery bypass graft surgery but is not practiced routinely. Experimentally, isoflurane, a commonly used volatile anaesthetic agent, provides myocardial protection through a signal transduction cascade that is remarkably similar to the pathways identified in ischaemic preconditioning. The aim of our study was to investigate whether pre-ischaemic administration of isoflurane exerted protection against prolonged ischaemia with functional recovery and reduced necrosis among patients undergoing coronary artery bypass graft surgery. METHODS: Forty patients scheduled for elective coronary artery bypass graft operations were prospectively randomized into the control or isoflurane groups. In the isoflurane group, isoflurane 2.5 minimum alveolar concentration was administered for 15 min followed by a 5-min washout period before aortic cross-clamping. The control group received a time-matched period of isoflurane-free cardiopulmonary bypass. The conduction of anaesthesia and surgery were standardized in all patients. Haemodynamic data, troponin I release and inotropic support were measured and recorded perioperatively. RESULTS: There were no adverse effects related to isoflurane administration. In the isoflurane group, the mean cardiac index after cardiopulmonary bypass was significantly higher than the pre-bypass value (P < 0.05), whereas no difference was found in the control group. At 15 min after cardiopulmonary bypass and 6 h after surgery, the changes in cardiac index and stroke volume index were significantly higher in the isoflurane group than in the control group (P < 0.05). There was a consistently lower release of troponin I in the isoflurane group compared to the control group. Compared to the controls, the mean troponin I level was significantly reduced in the isoflurane group at 24 h after surgery (P = 0.042). CONCLUSIONS: The present results support the preconditioning effect of isoflurane in patients undergoing coronary artery bypass graft surgery as clinically feasible and providing optimal cardiac protection.

Aged↗

The inhibitory effects of oxytocin on distal colonic contractile activity in rabbits are enhanced by ovarian steroids.

AIMS: To study the effects of oxytocin on isolated rabbit distal colon and the regulation of ovarian steroids by its action. METHODS: Muscle strips parallel to either the circular or the longitudinal fibres were excised and suspended in tissue chambers containing 5 mL Krebs solution (37 degrees C) and bubbled continuously with 95% O(2) and 5% CO(2). The effects of oxytocin on isometric spontaneous contractile responses were recorded. The effects of atosiban, tetrodotoxin, Mg(2+), progesterone and oestradiol on the oxytocin-induced response were also examined. RESULTS: Oxytocin (1, 10 and 100 nmol L(-1)) dose dependently decreased the area under the contraction curve of distal colonic smooth muscle strips. The oxytocin receptor antagonist atosiban blocked the oxytocin (10 nmol L(-1))-caused responses in a dose-dependent manner. Tetrodotoxin (10 micromol L(-1)) had no effect on the oxytocin-induced response. Mg(2+)-free Krebs solution attenuated the oxytocin-induced response, but oestradiol (0.1 micromol L(-1)) or progesterone (0.1 micromol L(-1)) increased the oxytocin-induced response. CONCLUSION: These results suggest that oxytocin inhibits the contractile motility of the distal colon, which is regulated by Mg(2+) and ovarian steroids.

Animals↗

Preparation and in vitro and in vivo release studies of Huperzine A loaded microspheres for the treatment of Alzheimer's disease.

The purpose of this study was to prepare microspheres containing Huperzine A, which is used for patients suffering from Alzheimer's disease because of its potent anticholineestase activity, and to clarify in vitro and in vivo release characteristics of them. The preparation and in vitro and in vivo release studies of Huperzine A loaded microspheres were described. By spray drying method, Huperzine A was encapsulated successfully in the microspheres which were spherical with a non-porous and smooth surface. In vitro studies showed that the release of Huperzine A from microspheres was depended on the properties of polymers and the release medium. Counter-ionic interaction between the primary amine group of Huperzine A and the carboxylic terminal group of PLG polymers improves the encapsulation of Huperzine A, reducing the initial burst and extending the sustained release. High molecular weight of PLG polymer leads to a negative influence on sustained release of Huperzine A due to less carboxylic terminal groups. Acidic medium also reduces the initial burst and sustained the release due to decreased swelling of the polymeric matrix. In vivo experiment showed, after intramuscular injection, that the plasma concentration of Huperzine A reached the max. at 2 h, then fell rapidly to a stable and near constant level of 0.5 to 2.5 ng/ml within 2 weeks, until the drug was exhausted from the microspheres. It indicates the potential of a 2-week sustained release system of Huperzine A.

Alkaloids↗

Epidural abscess in an obstetric patient with patient-controlled epidural analgesia--a case report.

We present the case of a 37-year-old pregnant woman who underwent a cesarean section due to previous cesarean delivery. Spinal anesthesia was performed at the L2-3 intervertebral space with an epidural catheter inserted at L1-2 for postoperative patient-controlled epidural analgesia. When the epidural catheter was removed on day three, an area of redness round the entry point was noted and the patient complained of low back pain, but was discharged from hospital. Later the same day, she felt backache so severe that she was unable to stand up or bend her body. She called for help and was sent to our emergency room. Physicians noted a small amount of discharge from the insertion site, and the body temperature was elevated to 38 degrees C. An anesthesiologist and an infectious disease specialist were consulted, and an epidural abscess was suspected. Urgent magnetic resonance imaging revealed an epidural abscess at L1-2. After five days of unsuccessful treatment with oxacillin, a 28-day course of vancomycin, followed by two months of oral fusidic acid, resulted in complete remission of the epidural abscess. The patient has remained free of neurologic deficit.

Adult↗

Comparison of Matrigel and gelatin substrata for feeder-free culture of undifferentiated mouse embryonic stem cells for toxicity testing.

Murine embryonic stem (mES) cells have been used to evaluate cytotoxicity and developmental injury following exposure to embryotoxic agents. However, maintaining a homogeneous population of undifferentiated mES cells for this purpose has been complicated by the need for continuous co-culture with murine embryonic fibroblast (mEF) cells or limited passaging on plastic surfaces coated with gelatin. Here, we compare the synthetic basement membrane Matrigel with 0.1% gelatin substratum for feeder-free propagation of undifferentiated mES cells. Biomarkers of pluripotentiality, chromosome number, caspase-3 expression, and cardiomyocyte differentiation were monitored for mES cells cultured on Matrigel or 0.1% gelatin up to passage 7 (P7). Our results suggest that choice of substratum had no significant effect on population doubling time, cell viability, stage-specific embryonic antigen-1 (SSEA-1) expression, or early passage formation of beating cardiomyocytes (all P>or=0.09). In other comparisons, however, Matrigel supported significantly higher synthesis of alkaline phosphatase (7.7x10(-3)+/-0.8 vs 6.6x10(-3)+/-0.8 units/liter/cell, respectively, P=0.012), overall expression of activated caspase-3 following exposure to 5, 10, 50, 100 and 500 parts per billion (ppb) sodium arsenite (P<0.0001), and percent development to beating cardiomyocytes at P7 (P=0.01). Together, our findings suggest that Matrigel shows promise as a substrate for feeder-free propagation of undifferentiated mES cells for embryotoxicity endpoints.

Alkaline Phosphatase↗

Disorder-induced microscopic magnetic memory.

Using coherent x-ray speckle metrology, we have measured the influence of disorder on major loop return point memory (RPM) and complementary point memory (CPM) for a series of perpendicular anisotropy Co/Pt multilayer films. In the low disorder limit, the domain structures show no memory with field cycling--no RPM and no CPM. With increasing disorder, we observe the onset and the saturation of both the RPM and the CPM. These results provide the first direct ensemble-sensitive experimental study of the effects of varying disorder on microscopic magnetic memory and are compared against the predictions of existing theories.

Journal Article↗

Low-dose methotrexate for the treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Methotrexate (MTX) is commonly used in the prophylaxis of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to evaluate the efficacy and safety of low-dose MTX treatment in patients with GVHD after allo-HSCT, 38 patients with acute GVHD (aGVHD), chronic GVHD (cGVHD) or GVHD post-donor lymphocyte infusion (post-DLI GVHD) after allo-HSCT received intravenous MTX at a dose of 5 or 10 mg every 5-- days until a complete or partial response was seen, or there was treatment failure or intolerable side effects. The overall response rate was 94.7% (18/19 patients) in patients with aGVHD, 76.2% (16/21 patients) in patients with cGVHD and 2/2 in patients with post-DLI GVHD. The response rate for GVHD involving various organs was 100% in skin, 75% in gut, 55.6% in liver, 75% in mouth and 100% in the eye, among all enrolled patients. Side effects were minor. Short-term, low-dose MTX is a tolerable and an effective regimen for patients with aGVHD, cGVHD or post-DLI GVHD after allo-HSCT.

Acute Disease↗

Signalling functions for sphingolipid long-chain bases in Saccharomyces cerevisiae.

Over the past several years, studies of sphingolipid functions in the baker's yeast Saccharomyces cerevisiae have revealed that the sphingoid LCBs (long-chain bases), dihydrosphingosine and PHS (phytosphingosine), are important signalling molecules or second messengers under heat stress and during non-stressed conditions. LCBs are now recognized as regulators of AGC-type protein kinase (where AGC stands for protein kinases A, G and C) Pkh1 and Pkh2, which are homologues of mammalian phosphoinositide-dependent protein kinase 1. LCBs were previously shown to activate Pkh1 and Pkh2, which then activate the downstream protein kinase Pkc1. We have recently demonstrated that PHS stimulates Pkh1 to activate additional downstream kinases including Ypk1, Ypk2 and Sch9. We have also found that PHS acts downstream of Pkh1 and partially activates Ypk1, Ypk2 and Sch9. These kinases control a wide range of cellular processes including growth, cell wall integrity, stress resistance, endocytosis and aging. As we learn more about the cellular processes controlled by Ypk1, Ypk2 and Sch9, we will have a far greater appreciation of LCBs as second messengers.

Animals↗

Synthesis and evaluation of a new series of peptide-based endothelin receptor antagonists.

Novel peptide-based endothelin (ET) receptor antagonists were designed and synthesized in our laboratory. BQ-485, HIM-CO-Leu-d-Trp-d-Trp-OH, was selected as the leading compound. The primary structures of these new tripeptides were ABO-CO-Leu-d-Trp-d-AA(X)-OH. The introduction of unnatural aromatic amino acids into these tripeptides was useful in the structure-activity relationship studies. Among the 20 tripeptides, 16 of them showed high activities against the contraction of rat aortic smooth muscles induced by ET-1.

Animals↗

Randomized, double-blind study comparing postoperative effects of treatment timing with histamine H-receptor antagonist cimetidine.

BACKGROUND: The purpose of this study was to evaluate the effect of timing of preoperative, postoperative, and placebo administration of the H(2)-antagonist cimetidine on postoperative pain management and the incidence of side-effects. METHODS: One hundred and twenty ASA I to II patients, undergoing major gynaecological abdominal surgery, were randomly divided into three groups, and received a standardized general anaesthesia. The patients in the preoperative ('Pre') group received an intravenous infusion of cimetidine 4 mg kg(-1) prior to anaesthesia induction; the postoperative ('Post') group received the same volume of normal saline. Postoperatively, the patients in the Post group received an intravenous infusion of cimetidine 4 mg kg(-1); the patients in the Pre group received the same volume of normal saline. The Control group received the same volume of normal saline prior to anaesthesia induction and after the end of operation. Postoperatively, all patients were treated with a patient-controlled intravenous analgesia system, which was programmed to deliver 1 mg of morphine on demand for three consecutive days. RESULTS: Pain intensity, morphine consumption, sedation score, and side-effects were recorded and evaluated. We found no difference among the three groups with respect to pain intensities, morphine usage, sedation scores, and the incidence of nausea, vomiting, pruritus, or dizziness. CONCLUSIONS: Our results suggested that neither preoperative nor postoperative administration of cimetidine 4 mg kg(-1) provided a pre-emptive or preventive analgesic advantage for postoperative pain or morphine consumption, and that the use of cimetidine failed to reduce the incidence of nausea or vomiting.

Adult↗

Role of beta-blockade in anaesthesia and postoperative pain management after hysterectomy.

BACKGROUND: Perioperative use of beta-blockers has been advocated as a strategy to prevent cardiac sequelae. This study evaluated the influence of perioperative esmolol administration upon anaesthesia and postoperative pain management amongst patients undergoing hysterectomy. METHODS: Ninety-seven ASA I-II patients, undergoing abdominal total hysterectomy, were randomly divided into one of two groups. Patients in the Esmolol group received an i.v. loading dose of esmolol 0.5 mg kg(-1) followed by infusion of 0.05 mg kg(-1) min(-1) before anaesthesia induction. The infusion was documented at the completion of surgery. The Control group received a volume of normal saline. After surgery, all patients were treated with patient-controlled i.v. analgesia (PCA), which was programmed to deliver 1 mg of morphine on demand for 3 consecutive days. Pain intensity on movement and at rest, sedation score, and side effects were recorded. RESULTS: The two groups were comparable with respect to their characteristics. Patients in the esmolol group received significantly lower end-tidal isoflurane concentrations (1.0 (0.3) vs 1.4 (0.5)%, respectively; P<0.001) and fentanyl (0.9 (0.2) vs 1.2 (0.5) microg kg(-1), respectively; P=0.006) during anaesthesia. They also showed a reduced heart rate and arterial pressure response to tracheal intubation, skin incision, and tracheal extubation. The Esmolol group consumed less PCA morphine in 3 days (37.3 (8.4) vs 54.7 (11.2) mg, respectively; P=0.005). Pain intensity and medication side effects were similar in the two groups. CONCLUSION: The results suggest that perioperative esmolol administration during anaesthesia reduces the intraoperative use of inhalation anaesthetic and fentanyl, decreases haemodynamic responses, and reduced morphine consumption for the first 3 postoperative days.

Adrenergic beta-Antagonists↗

Molecular characterization of HMW glutenin subunit allele 1Bx14: further insights in to the evolution of Glu-B1-1 alleles in wheat and related species.

1Bx14 is a member of the high molecular weight (HMW) glutenin subunits specified by wheat Glu-B1-1 alleles. In this work, we found that the full-length amino acid sequence of 1Bx14 and 1Bx20, the last two of the three cysteine residues, which are conserved in 1Bx7, 1Bx17 and homologous 1Ax and 1Dx subunits, were replaced by tyrosine residues. In the 5' flanking regions (-900 to -1,200 bp relative to the start codon), a novel miniature inverted-repeat transposable element insertion was present in 1Bx12 and 1Bx20 but not 1Bx7 and 1Bx17. 1Bx14 and 1Bx20 like alleles were readily found in tetraploid wheat subspecies but not several S genome containing Aegilops species. Phylogenetic analysis showed that the four molecularly characterized Glu-B1-1 alleles (1Bx7, 1Bx14, 1Bx17, 1Bx20) could be divided into two allelic lineages. The lineage represented by 1Bx7 and 1Bx17 was more ancient than the one represented by 1Bx14 and 1Bx20. Combined, our data establish that 1Bx14 and 1Bx20 represent a novel subclass of Glu-B1-1 alleles. Based on current knowledge, potential mechanism involved in the differentiation of two Glu-B1-1 lineages is discussed.

Alleles↗

Combined effects of Matrigel and growth factors on maintaining undifferentiated murine embryonic stem cells for embryotoxicity testing.

Undifferentiated, murine embryonic stem (mES) cells have shown promise as a substrate for identifying embryotoxic chemicals and for studying mechanisms of early developmental injury. However, long-term maintenance of mES cells in an undifferentiated state is problematic. The present study evaluates the combination of Matrigel matrix and three growth factors for this purpose. Biomarkers of mES cell pluripotency, apoptosis, chromosome number and cardiomyocyte differentiation were monitored over 119 population doublings. D3 mES cells retained undifferentiated characteristics, including sustained expression of alkaline phosphatase and stage specific embryonic antigen-1 (SSEA-1) and continued transcription of Pou5f1 (Oct-4). Cell viability remained at > or=95% and population-doubling times averaged 14.3 h over 10 weeks of observation. Caspase-3 activation, a marker of cellular death by apoptosis, was measured in early- and late-passage mES cells. Early-passage cells showed dose-responsive caspase-3 activation following exposure to sodium arsenite, whereas caspase-3 activation of late-passage cells dropped to background levels at toxicant dosages above 50 ppb. Aneuploidy and impaired differentiation into beating cardiomyocytes were noted for late-passage mES cells. Matrigel, combined with growth factors, may sustain undifferentiated mES cells. However, aneuploidy, reduced caspase-3 activation, and inability to differentiate suggests further modifications to the culture system may be needed for long-term propagation of cells for embryotoxicity endpoints.

Aneuploidy↗

The effect of promethazine on postoperative pain: a comparison of preoperative, postoperative, and placebo administration in patients following total abdominal hysterectomy.

BACKGROUND: Histamine receptors are involved in the development of inflammatory pain and hyperalgesia, and the use of antihistamines is advocated as an alternative for pain therapy and treatment of postoperative nausea and vomiting. We investigated the influence of timing of promethazine administration on postoperative pain outcomes. METHODS: Ninety female patients undergoing total abdominal hysterectomy were randomly divided into three groups. All individuals received infusions of promethazine and normal saline before anaesthesia induction, and postoperatively the Pre group received promethazine 0.1 mg kg(-1) before anaesthesia and saline postoperatively, and the Post group received saline before anaesthesia and promethazine 0.1 mg kg(-1) postoperatively, while the Control group received two equivalent volumes of saline. Patients were treated using patient-controlled intravenous analgesia (PCA). The primary endpoint was pain intensity and morphine consumption. The secondary endpoint was postoperative nausea and vomiting. RESULTS: Postoperative morphine usage was significantly lower in the Pre group (24.1 +/- 3.9 mg) relative to the Post (30.0 +/- 4.6 mg) and Control groups (32.1 +/- 4.8 mg) during the first 24 h postoperatively (P<0.05). The number and incidence of patients suffering from postoperative nausea in the first 24 h was six (21%), seven (23%), and 15 (47%) in the Pre, Post, and Control groups, respectively (P<0.05). The number and incidence of patients vomiting in the first 24 h was three (10%), two (7%), and 10 (32%) in the Pre, Post, and Control groups, respectively (P<0.05). The number of patients asking for rescue antiemetic in the first 24 h was one (3%), two (7%), and seven (22%) in the Pre, Post, and Control groups, respectively (P<0.05). CONCLUSIONS: Our results suggest that preoperative administration of promethazine 0.1 mg kg(-1) reduces postoperative morphine consumption compared with postoperative and placebo administration, and that use of promethazine reduces PONV and the number of patients asking for rescue antiemetic in the first 24 h after surgery when compared with placebo.

Adult↗