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Biomedical subjects

S Liu

Publications and source records attributed to S Liu.

At least 757 records · Page 42Linked to original sources
PubMed1996

Extending the chemistry that supports genetic information transfer in vivo: phosphorothioate DNA, phosphorothioate RNA, 2'-O-methyl RNA, and methylphosphonate DNA.

DNA and RNA are the polynucleotides known to carry genetic information in life. Chemical variants of DNA and RNA backbones have been used in structure-function and biosynthesis studies in vitro, and in antisense pharmacology, where their properties of nuclease resistance and enhanced cellular uptake are important. This study addressed the question of whether the base(s) attached to artificial backbones encodes genetic information that can be transferred in vivo. Oligonucleotides containing chemical variants of DNA or RNA were used as primers for site-specific mutagenesis of bacteriophage f1. Progeny phage were scored both genetically and physically for the inheritance of information originally encoded by bases attached to the nonstandard backbones. Four artificial backbone chemistries were tested: phosphorothioate DNA, phosphorothioate RNA, 2'-O-methyl RNA and methylphosphonate DNA. All four were found capable of faithful information transfer from their attached bases when one or three artificial positions were flanked by normal DNA. Among oligonucleotides composed entirely of nonstandard backbones, only phosphorothioate DNA supported genetic information transfer in vivo.

Base Sequence↗
PubMed1996

Reliability of alcohol intake as recalled from 10 years in the past.

The authors assessed the reliability of alcohol intake as recalled from 10 years in the past in a cohort of 2,907 US adults. Participants reported their drinking habits in the First National Health and Nutrition Examination Survey interview during 1971-1975. During a follow-up interview in 1982-1984, they were asked to recall their drinking habits 10 years earlier and to report their current habits. In general, the correlation for recalled alcohol intake versus reported intake at baseline was good (r = 0.7). For all subgroups stratified by race, sex, education, smoking status, and disease status, the age-adjusted correlations for recalled alcohol intake versus baseline intake were equal to or higher than those for current alcohol intake versus baseline intake. The reliability of recall of alcohol intake in the past differs among subgroups with different age and education levels. Recalled alcohol intake was also highly correlated with current alcohol intake; in particular, current heavier drinkers tended to underestimate their previous amount of drinking, an effect that was independent of other factors. These data suggest that although recalled alcohol intake is a better predictor of past intake than are reports of current intake, current drinking habits may be an important influencing factor in the estimation of alcohol intake as recalled from the distant past.

Adult↗
PubMed1996

Axons of Xenopus neural tube respond to reversals of neural tube orientation.

Axonal trajectories of the Kolmer-Agduhr (KA) neurons of Xenopus embryos, were observed after anterior-posterior (A-P) inversions of neural tube grafts to determine whether KA axons follow cell-inherent directional cues, cues from their immediate environment, or rostrocaudal signals from the embryo. KA axons form one of the earliest ascending spinal pathways in Xenopus and are visible in the lateral marginal zone of whole mounts processed for GABA immunoreactivity. Grafts were made at trunk levels at stages 22-24, 3-5 h before the first KA neurons were detectable and prior to axonal out-growth. Embryos were fixed and immunostained 6-36 h later. KA trajectories within and adjacent to reversed grafts were compared to those of nonrotated control grafts and to neural tube lengths comparable in position and in length in unoperated embryos. Most KA axons within rotated grafts followed the graft's orientation. However, others changed direction, taking novel routes, including turning to conform to the orientation of the host embryo. Reorientations were most common near the posterior host/graft interface. Some host KA cells also reoriented, always within a few hundred microns of the graft interface. Taken together, these growth patterns show that most KA axons within the grafts grow normally with respect to the original polarity of the graft neural tube and maintain that direction even into tissue of opposite polarity, suggesting that their routes are mainly determined by cell-intrinsic and/or local tissue factors. However, the reorientation of many other axons, particularly near graft seams, implies that KA axons can respond to local fluctuations in directional or segment identity signals generated in both host and graft after this perturbation.

Animals↗
PubMed1996

Induction of mutagenic DNA damage by chromium (VI) and glutathione.

Certain chromium (Cr) compounds are known to be carcinogenic in humans and mutagenic in cell culture. However, the mechanism of Cr mutagenesis is not well understood. It appears that intracellular reduction of Cr by agents such as glutathione plays a role in the induction of DNA damage. We have used a simian virus 40-based shuttle vector to investigate the relationship between chromium-induced DNA damage and Cr mutagenicity. The treatment of the plasmid pZ189 with Cr(VI) plus glutathione (GSH) induced DNA strand breaks and reduced the plasmid biological activity, whereas Cr(III) treatment with or without GSH did not give rise to such DNA damage. When Cr(VI)/GSH- or Cr(III)/GSH-treated pZ189 was replicated in mammalian cells, a dose-dependent increase in mutant frequency was observed with Cr(VI)/GSH-treated pZ189, but not with Cr(III)/GSH-treated plasmid. About 43% of the mutants from Cr(VI)/GSH-treated pZ189 were deletion mutants. The remainder were base substitution mutants, mostly GC-->AT transitions and GC-->TA transversions. This pattern of mutagenesis is similar to that observed with other agents that cause oxidative DNA damage such as ionizing radiation and H2O2. These results support the hypothesis that Cr mutagenesis can be induced by the generation of reactive oxygen intermediates during the reduction of Cr(VI) by glutathione.

Animals↗
PubMed1996

Scales, diagnoses, and child psychopathology: II. Comparing the CBCL and the DISC against external validators.

Using a multimethod multistage screening procedure, the authors interviewed 201 parents and their children with the Diagnostic Interview Schedule for Children (DISC 2.1). In addition, parents completed the Child Behavior Checklist (CBCL) and other survey measures, while their children completed self-report scales. Receiver operating characteristic (ROC) analyses were done to determine optimal cutpoints on the CBCL, referenced to DISC diagnostic "caseness." DISC diagnoses, DISC "stem" symptoms, CBCL scores, and CBCL ROC-outpoints were compared against "external validators," in order to determine the comparative advantages of each approach for assessing child psychopathology. Overall findings suggest that the controversies about "best" assessment strategies may be artificial: When both assessment approaches are compared using similar methods, they are reasonably comparable. However, highly specific diagnostic categories may show fewer relationships with external validators and may therefore need more systematic validational studies.

Adolescent↗
PubMed1996

A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors.

In this study, PGE2 levels in lipopolysaccharide (LPS)-challenged human whole blood and TxB2 levels following blood coagulation were measured as biochemical index for cyclooxygenase (Cox)-2 and Cox-1 activity respectively. Incubation of human mononuclear cells isolated from whole blood with LPS (100 mu g/mL) induced a time-dependent increase in the expression of Cox-2 protein (>100 fold at 24 hr). This is associated with increases in PGE2 production and free arachidonate release in the plasma. Cox-1 protein was detected in the human mononuclear cells at time zero but was not induced by either LPS or PBS. Most non-steroidal anti-inflammatory drugs (NSAIDs) are more potent at inhibiting Cox-1 than Cox-2. Five experimental compounds CGP-28238, Dup-697, NS-398, SC-58125 and L-745,337, have a greater selectivity for Cox-2. Indomethacin at a single oral dose (25 mg) inhibited approximately 90% the whole blood Cox-2 and Cox-1 activities ex vivo in healthy subjects. These results support the use of this assay to assess the biochemical efficacy of selective Cox-2 inhibitors in clinical trials.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Factors accounting for different responses of pulmonary and cerebral vessels to hypoxia.

The roles of sympathicus, sensory neuropeptides (SNP), cyclooxygenase metabolites (COX-M), lipoxygenase metabolites (LOX-M), endothelium derived relaxing factor (EDRF), reactive oxygen (ROS) and potassium channels (PC) in the hypoxic pulmonary vasoconstriction (HPV) and hypoxic cerebral vasodilation (HCVD) were investigated in intact rats, rabbits and dogs. The results showed that during hypoxia, the excitation of sympathicus caused a constriction of both pulmonary and cerebral vessels, while SNP, EDRF and the opening of voltage sensitive PC caused the dilation of both of them; LOX-M mediated HPV and HCVD, COX-M might serve as their modulators; the blockade of ATP sensitive PC induced by hypoxia mediated HPV, but had no effect on HCVD; the reduction of O2-. in the lung might potentiate HPV, however, O2-. remained unchanged in brain during hypoxia. It is suggested that the alterations of LOX-M, ROS and the ATP sensitive PC are the factors accounting for the difference in the response of pulmonary and cerebral vessels to hypoxia.

Animals↗
PubMed1996

Correlated flow cytometric analysis of H-ras p21 and DNA ploidy in acute myelogenous leukemia.

The flow cytometric immunoassay was used to study the correlation between the H-ras oncogene product p21 and the DNA ploidy in 30 de novo cases of acute myelogenous leukemia (AML). The results showed that 17 cases were negative for p21 expression and 13 positive for p21. The patients with positive p21 had higher percentage of bone marrow and peripheral blasts and lower peripheral leukocyte count. The expression of p21 had no influence on the therapeutic effect. Before treatment, DNA diploidy occurred in 18 cases including 13 p21 negative ones, and DNA aneuploidy was revealed in 12 cases including 8 p21 positive ones. Patients with positive p21 or having aneuploidy in complete remission were at risk for early relapse. Our results suggest that p21 may be involved in the process of leukemogenesis and progression in AML.

DNA, Neoplasm↗
PubMed1996

Construction of eukaryotic expression vector pBlacz and its expression both in vitro and in vivo.

A novel eukaryotic expression vector pBlacZ was constructed, which was transfected into the cell lines of NIH/3T3, COS-1, CHO and the primary culture of murine dermatic fibroblasts in vitro, and also into the murine subcutaneous layer and skeletal muscles of rats in vivo. It was detected that the gene expression vector could encode the E. Coli beta-galactosidase effectively in all these histocytes. The results suggested that pBlacZ, as a novel expression vector, might have certain value of application.

3T3 Cells↗
PubMed1996

Activation and inactivation kinetics of an E-4031-sensitive current from single ferret atrial myocytes.

Ferret atrial myocytes can display an E-4031-sensitive current (IKr) that is similar to that previously described for guinea pig cardiac myocytes. We examined the ferret atrial IKr as the E-4031-sensitive component of current using the amphotericin B perforated patch-clamp technique. Steady-state IKr during depolarizing pulses showed characteristic inward rectification. Activation time constants during a single pulse were voltage dependent, consistent with previous studies. However, for potentials positive to +30 mV, IKr time course became complex and included a brief transient component. We examined the envelope of tails of the drug-sensitive current for activation in the range -10 to +50 mV and found that the tail currents for IKr do not activate with the same time course as the current during the depolarizing pulse. The activation time course determined from tail currents was relatively voltage insensitive over the range +30 to +50 mV (n = 5), but was voltage sensitive for potentials between -10 and +30 mV and appeared to show some sigmoidicity in this range. These data indicate that activation of IKr occurs in at least two steps, one voltage sensitive and one voltage insensitive, the latter of which becomes rate limiting at positive potentials. We also examined the rapid time-dependent inactivation process that mediates rectification at positive potentials. The time constants for this process were only weakly voltage dependent over the range of potentials from -50 to +60 mV. From these data we constructed a simple linear four-state model that reproduces the general features of ferret IKr, including the initial transient at positive potentials and the apparent discrepancy between the currents during the initial depolarizing pulse and the tail current.

Animals↗
PubMed1996

Radioimmunoscintigraphy of gastric adenocarcinomas with 99mTc-chimeric ccM4 antibody.

Fourteen patients with gastric lesions were studied for radioimmunoscintigraphy using the 99mTc-ccM4 chimeric antibody reactive with the human tumor-associated TAG72 antigen. These include 10 gastric adenocarcinomas, 3 gastric ulcers and 1 gastric lymphoma. Each patient received an infusion of 30-40 mCi 99mTc-ccM4 antibody. Gamma camera scans were performed at 12-h postadministration. All patients underwent operation after radioimmunoscintigraphy. All surgical specimens including gastric adenocarcinomas, lymphoma and ulcers were confirmed by histopathological studies. The 99mTc-ccM4 antibody was able to detect 6 out of 10 gastric adenocarcinomas (60%) by scans. Its accuracy was even 5 out of 6 (83%) in a group of patients with well/moderately-differentiated adenocarcinomas. In addition to the primary adenocarcinomatous lesions, the 99mTc-ccM4 antibody was also able to detect metastatic lesions in liver and lymph nodes. The smallest adenocarcinomatous lesion detected by scans was about 1 x 1 x 2 cm3. All four patients with gastric ulcers or lymphoma showed negative scan results. Therefore, the chimeric ccM4 antibody may be useful in radioimmunoscintigraphy of gastric adenocarcinomas, especially the well/moderately-differentiated adenocarcinomas.

Adenocarcinoma↗
PubMed1996

Magnetic resonance imaging of cerebrospinal fluid volume and the influence of body habitus and abdominal pressure.

BACKGROUND: Although the cerebrospinal fluid (CSF) is the pathway of anesthetic delivery and the diluent for neuraxially administered drugs, little is known about its volume, including variability among individuals, longitudinal distribution, or influence of body habitus. Models made to investigate subarachnoid anesthetic distribution lack valid dimensions. CSF volume was measured in volunteers, and the effect of obesity and abdominal compression on CSF volume was evaluated using magnetic resonance imaging. METHODS: Low thoracic and lumbosacral axial magnetic resonance images of 25 healthy volunteers were obtained at 8-mm intervals by fast spin-echo sequence, which highlights CSF. A repeat image series was performed in 15 subjects during external abdominal compression. In two subjects, images were obtained without compression for the entire vertebral column. Dural sac and spinal cord areas were determined in a blinded fashion for each image using video/digital analysis. Area of the sac minus area of the cord constituted area of CSF and roots ("CSF/root"); this area multiplied by 8 mm resulted in CSF/root volume per section. RESULTS: There is great interindividual variability in CSF/root volume. From the T11-T12 disc to the sacral terminus of the dural sac, the mean volume for all subjects is 49.9 +/- 12.1 ml (mean +/- SD; range 28.0-81.1 ml). This volume was significantly less in relatively obese subjects (42.9 +/- 9.5 ml) than in nonobese subjects (53.5 +/- 12.9 ml). Abdominal compression decreased CSF/root volume by 3.6 +/- 3.2 ml. Sections through intervertebral foramina showed the biggest decrease with abdominal compression, with a lesser change in sections with veins and no change in the absence of these anatomic features. Total vertebral CSF/root volume in two subjects was 94.84 and 120.01 ml, respectively. CONCLUSIONS: CSF volume is widely variable between individuals. The decreased CSF volume that results from increased abdominal pressure, such as with obesity or pregnancy, may produce more extensive neuraxial blockade through diminished dilution of anesthetic. The mechanism by which increased abdominal pressure decreases CSF volume is probably inward movement of soft tissue in the intervertebral foramen, which displaces CSF.

Abdomen↗
PubMed1996

Neuronal damage following intraspinal injection of a nitric oxide synthase inhibitor in the rat.

Intraspinal microinjection of the nonspecific nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) was used to determine if inhibition of NOS results in morphological changes in the rat spinal cord. Following spinal injections of 100-750 mM L-NAME (pH 7.0), 1.0-500 mM L-NAME (pH 2.5-5.4), or L-NAME + L-arginine, quantitative analysis of morphological changes revealed a positive dose-response relationship between L-NAME and neuronal loss. This effect was blocked by L-arginine and was inversely related to spinal levels of NOS enzyme activity. Results of this study have shown the importance of basal NOS activity in maintaining the structural integrity of spinal neurons. It is proposed that the effects of L-NAME on nitric oxide (NO) production leads to decreased blood flow, secondary to vasoconstriction, and a hypoxic-ischemic reaction in spinal tissue. The results suggest that a potential contributing factor to neuronal damage in pathological conditions such as spinal cord injury may be the decreased production of nitric oxide.

Animals↗
PubMed1996

Changes in average blood pressure and incidence of high blood pressure 1983-1984 to 1987-1988 in four population cohorts in the People's Republic of China. The PRC-USA Cardiovascular and Cardiopulmonary Epidemiology Research Group.

OBJECTIVE: To assess comparative changes in systolic and diastolic blood pressure and incidence of high blood pressure over 4 years, and factors related to these changes, in northern and southern, urban and rural adults in the People's Republic of China. SETTING: This is a prospective study of populations surveyed by standardized methods in 1983-1984 and 1987-1988 in north China, Beijing area steel mill workers and farmers, and south China, Guangzhou area shipyard workers and farmers. SUBJECTS: The subjects were 8805 men and women aged 35-54 years at baseline (1983-1984), of whom 7338 were non-hypertensive (systolic blood pressure < 140, diastolic blood pressure < 90 mmHg, not being administered antihypertensive drugs). MAIN OUTCOME MEASURES: The main outcome measures were 4-year changes in systolic and diastolic blood pressures and the 4-year incidence of high blood pressure in persons not hypertensive at baseline. RESULTS: At baseline, the average systolic and diastolic blood pressures were higher for Beijing than for Guangzhou cohorts. At resurvey the average systolic blood pressure had increased for seven of eight sex-city-setting cohorts (all but Guangzhou urban men). The Beijing urban cohorts had the greatest increases (men 6.2 mmHg, women 4.9 mmHg, slopes of 1.6 and 1.2 mmHg/year). The incidence of high blood pressure was higher for Beijing than for Guangzhou cohorts in all four comparisons (men and women, urban and rural). Beijing men, urban and rural, had the highest incidence rates (about 21%). In multiple logistic analyses by sex, variables significantly related to 4-year high blood pressure incidence were city, baseline systolic blood pressure and body mass index, change in weight, and, for men, baseline alcohol use and heart rate. CONCLUSION: Modifiable lifestyle traits, previously shown to be related to blood pressure and high blood pressure in cross-sectional studies, also relate to the incidence of hypertension.

Adult↗