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Biomedical subjects

D Liu

Publications and source records attributed to D Liu.

At least 613 records · Page 34Linked to original sources

Paraquat--a superoxide generator--kills neurons in the rat spinal cord.

Microdialysis was used to administer paraquat into the spinal cord of the anesthetized rat to determine the effects of the in vivo generation of the superoxide anion (O2.-) on neurons. Exposure to paraquat caused blockage of axonal conduction, destruction of the cell bodies of neurons, and a general release of amino acids. Thus, paraquat is quite harmful to neuronal tissue. Similarities between paraquat-induced damage and that previously observed from the hydroxyl radical are consistent with paraquat, causing damage by generation of reactive oxygen species and the widespread belief that generation of O2.- initiates the formation of destructive reactive oxygen species in a wide variety of traumas and other disorders.

Amino Acids↗

Pingyangmycin as a 99mTc carrier in tumor localization.

A simple method of preparation of 99mTc-pingyangmycin (PYM) for clinical use has been established using super-micro-amounts of SnCl2 as a reductant under dark conditions. The labeling efficiency was higher than 96%, and further purification was not necessary. The effect of ascorbic acid on the distribution of 99mTc-PYM had been investigated. Ascorbic acid increased uptake of 99mTc-PYM in the tumor. Tumor uptake increased with increasing concentration of ascorbic acid. Tumor-blood, tumor-liver, tumor-lung ratios at 1.5 h after 99mTc-PYM administration were 5.19 +/- 1.64, 2.71 +/- 0.51 and 4.15 +/- 0.57, respectively. Preliminary clinical trials in nine patients showed that 99mTc-PYM is a potentially useful tracer for tumor detection with good sensitivity and specificity (true positive 7/7, true negative 1/1, and false positive 1/1).

Aged↗

Measurement of the subarachnoid pressure of the optic nerve in human subjects.

PURPOSE: We measured the subarachnoid pressure of the optic nerve in 16 patients scheduled for ocular enucleation or evisceration. METHODS: We measured the subarachnoid pressure of the optic nerve directly with an electronic digital manometer in 16 patients scheduled for enucleation or evisceration for various blinding conditions. The nerve was exposed via a medial orbitotomy, and the subarachnoid pressure of the optic nerve was measured 5 mm posterior to the optic nerve head. The subarachnoid pressure of the optic nerve was also measured in five patients who were placed in the Trendelenburg position (head declined at a 30-degree angle) for three minutes. RESULTS: The subarachnoid pressure of the optic nerve varied from 4 to 14 mm Hg in the 16 patients tested. The mean subarachnoid pressure of the optic nerve was 8.5 mm Hg in the 16 patients tested. An increase of 1 to 2 mm Hg in the subarachnoid pressure was observed in all five patients placed in the Trendelenburg position. CONCLUSIONS: Subarachnoid pressure of the optic nerve can be measured in vivo in humans. The values obtained are consistent with the known physiologic range of intracranial pressure. There was no statistically significant correlation between subarachnoid pressure of the optic nerve and age or cause of blindness. The subarachnoid pressure of the optic nerve varies over a wide range.

Adolescent↗

35Cl nuclear magnetic resonance line broadening shows that eosin-5-maleimide does not block the external anion access channel of band 3.

It has been suggested that Lys-430 of band 3, with which eosin-5-maleimide (EM) reacts, is located in the external channel through which anions gain access to the external transport site, and that EM inhibits anion exchange by blocking this channel. To test this, we have used 35Cl nuclear magnetic resonance (NMR) to measure Cl- binding to the external transport site in control and EM-treated human red blood cells. Intact cells were used rather than ghosts, because in this case all line broadening (LB) results from binding to external sites. In an NMR spectrometer with a 9.4-T magnetic field, red blood cells at 50% concentration (v/v) in 150 mM Cl- medium at 3 degrees C caused 19.0 +/- 1.2 Hz LB. Of this, 7.9 +/- 0.7 Hz was due to Cl- binding to the high affinity band 3 transport sites, because it was prevented by an apparently competitive inhibitor of anion exchange, 4,4'-dinitrostilbene-2,2'-disulfonate (DNDS). The LB was not due to hemoglobin released from the cells, as little LB remained in the supernatant after cells were removed by centrifugation. Saturable Cl- binding remained in EM-treated cells, although the binding was no longer DNDS-sensitive, because EM prevents binding of DNDS. The lower limit for the rate at which Cl- goes from the binding site to the external medium is 2.15 x 10(5) s-1 for control cells and 1.10 x 10(5) s-1 for EM-treated cells, far higher than the Cl- translocation rate at 3 degrees C (about 400 s-1). Thus, EM does not inhibit Cl- exchange by blocking the external access channel. EM may therefore be useful for fixing band 3 in one conformation for studies of Cl- binding to the external transport site.

Anion Exchange Protein 1, Erythrocyte↗

Long-circulating emulsions (oil-in-water) as carriers for lipophilic drugs.

PURPOSE: Rapid clearance of parenterally administered oil-in-water emulsions from blood by the reticuloendothelial system (RES), mainly macrophages of the liver and spleen, has been one of the major obstacles for delivering lipophilic drugs to cells other than those in the RES. The purpose of this study therefore is to overcome this problem and develop emulsions that will have prolonged blood circulation time. METHODS: A series of amphipathic polyethylene-glycol (PEG) derivatives have been included as co-emulsifier into emulsions composed of Castor oil and phosphatidylcholine. The effect of amphipathic PEG on reducing the RES uptake and prolonging the blood circulation of the emulsion particles has been tested in vivo using mice as an animal model. RESULTS: Inclusion of PEG derivatives such as Tween-80 or dioleoyl N-(monomethoxy-polyethyleneglycol succinyl)phosphotidylethanolamine (PEG-PE) into emulsions composed of Castor oil and phosphatidylcholine decreases the RES uptake and increases blood residence time of the emulsions. The activity of PEG derivatives in prolonging the circulation time of emulsions depends on the PEG chain length (PEG2000 > PEG5000 > PEG1000, Tween-80) and the PEG density on emulsion surface. CONCLUSIONS: Inclusion of amphipathic PEG as emulsifier into oil-in-water emulsions is a very effective method to prolong the blood half life of the emulsions. Emulsions with long circulating half life in blood should be very useful as a delivery vehicle for lipophilic drugs.

Animals↗

Antibody dependent, complement mediated liver uptake of liposomes containing GM1.

PURPOSE: We have previously reported that GM1 exhibits an opposite effect on regulating liposome circulation time in mice and rats (Liu et al. Pharm. Res. Vol. 12:508-512 (1995)). Inclusion of GM1 into liposomes significantly prolongs liposome circulation time in mice, while it dramatically decrease the blood half life and increases liver uptake of liposomes in rats. The purpose of this study was to elucidate the mechanism that underlies this phenomenon. METHODS: Single-pass liver perfusion in vitro and complement mediated liposome lysis assay was used. RESULTS: Serum appeared to play an important role in determining the liver uptake of GM1 liposomes. Specifically, rat serum enhanced the uptake of GM1-containing liposomes by the perfused liver. Such activity was also found in human and bovine serum, but not in mouse serum. Taking human serum as an example, we demonstrated that such serum activity can be blocked by EDTA and EGTA/Mg2+. Antibodies against human IgM and the third component of complement system (C3) also inhibited serum activity. CONCLUSIONS: The presence of naturally occurring anti-GM1 antibodies in rats, through the activation of the classic pathway of complement system, is likely the cause of rapid blood clearance of GM1-liposomes. The third component of complement is likely to serve as the opsonin that is directly involved in mediating liposome clearance.

Animals↗

Monosialoganglioside GM1 shortens the blood circulation time of liposomes in rats.

Inclusion of monosialoganglioside GM1 into liposomes significantly enhances the circulation time of liposomes in mice. Conversely, intravenously injected GM1-containing liposomes were rapidly removed from the blood circulation and accumulated in the liver and spleen in rats. In rats, increasing the GM1 content in liposomes resulted in more rapid clearance from the blood. Increasing the membrane rigidity of liposomes further increased the liver uptake of GM1-containing liposomes. The activity of GM1 in enhancing the liposome uptake by rat liver appears to be mediated by complement components.

Animals↗

Simultaneous determination of copper and zinc in the hair of children by pH gradient construction in a flow-injection system.

A flow-injection method is described for the simultaneous determination of copper and zinc with a single detector using the pH gradient technique. Zincon is used as the colour reagent for the spectrophotometric determination. The linear range for the determination of zinc is 0.4-12 micrograms ml-1 and for copper is 0.1-3.0 micrograms ml-1. About 20-30 samples can be determined in one hour. The proposed method has been applied to the determination of zinc and copper in childrens' hair.

Child↗

Toxicity of organomercury compounds: bioassay results as a basis for risk assessment.

A former mercury plant, where mercury salts and organomercurials for pesticide use were produced, caused soil contamination in high concentrations. Typical organomercurial products included ethylmercury, phenylmercury, methoxyethylmercury and ethoxyethylmercury compounds. Risk assessment of these sites must be carried out before any major clean-up processes can be planned. A sensitive speciation technique for the various organomercury species in environmental matrices is a prerequisite for toxicity investigations. In this connection, a high-performance liquid chromatography-atomic fluorescence spectrometry (HPLC-AFS) technique has been developed to differentiate between and determine the presence of eight organomercury compounds in environmental samples. Using this technique, methylmercury, ethylmercury and phenylmercury and some unknown organomercury species were found in soil samples collected from the sites of an old mercury products producing plant. With regard to risk assessment, it is necessary to assess the toxicity of the organomercurials. As different microbial metabolic pathways react differently to mercury and its compounds, batteries of bioassays are, therefore, useful to evaluate the toxicity of pollutants. To describe the toxicity and genotoxicity of MeHg+, MeOEtHg+, EtHg+, EtOEtHg+ and PhHg+, p-tolymercury chloride, nitromersol and Hg2+ six bioassays were used: resazurin reduction method, Spirillum volutans test, nematode toxicity assay Panagrellus redivivus, Toxi-Chromotest and SOS-Chromotest. A ranking of the toxicity of the organomercurial is shown. The SOS-Chromotest indicated genotoxicity for 5-7 organomercurials.

Animals↗

Determination of manganese in Chinese tea leaves by a catalytic kinetic spectrophotometric method.

The catalytic effect of manganese(II) on the oxidation of Rhodamine B with potassium periodate in the presence of 1,10-phenanthroline in acetic acid-sodium acetate was studied. A catalytic kinetic spectrophotometric method for determination of manganese(II) was developed. Manganese in the range 0.1-5.0 ng ml-1 can be determined, and the detection limit is 0.02 ng ml-1. Manganese in Chinese tea leaves was successfully determined.

Catalysis↗

Welding helmet airborne fume concentrations compared to personal breathing zone sampling.

Metal fume concentrations inside the welding helmet and in the personal breathing zone in 23 experimental welding exposures were studied to explore whether welding helmet use substantially attenuates exposure to airborne metal fume. Observations produced a mean ratio of inside to outside metal fume concentrations of 0.9 +/- S.D. 0.2 with a highly variable effect. Iron fume concentration was inversely correlated with this ratio, representing greater helmet-associated attenuation with heavier exposure (r = -0.70, p < 0.001). In contrast to previous reports, these data suggest that welding helmet use provides marginal and highly variable reductions in fume exposure and cannot substitute for standard respiratory protection.

Adult↗

The neuronal toxic factor in serum of type 1 diabetic patients is a complement-fixing autoantibody.

Type 1 diabetes is an autoimmune disease resulting in destruction of pancreatic beta cells. Many of the pancreatic beta cell autoantigens are also neuronal cell components. Using adrenergic neuroblastoma cells, we have previously demonstrated that humoral mechanisms may contribute to the development of diabetic neuropathy in Type 1 patients. We hypothesize that the toxic factor in Type 1 diabetic serum is an immunoglobulin. When neuroblastoma cells were exposed to immunoglobulins precipitated from serum of Type 1 diabetes patients with neuropathy, cell growth was significantly inhibited by day 5 (3.8 +/- 2.4 x 10(5) cells) compared to cells cultured with immunoglobulins from control (8.2 +/- 2.3 x 10(5) cells) or Type 2 diabetic serum (7.0 +/- 3.0 x 10(5) cells). The inhibitory effect (3.2 +/- 0.9 x 10(5) cells) could be removed from Type 1 diabetic serum by affinity precipitation with protein A-agarose (8.0 +/- 0.8 x 10(5) cells). Mild heat denaturing of the serum reversed the inhibitory effect (3.8 +/- 0.9 vs 1.4 +/- 1.4 x 10(5) cells), indicating a requirement for complement. Immunofluorescent labelling with anti-IgG secondary antibody of cells exposed to Type 1 diabetic serum indicated recognition of a membrane-bound antigen. The studies in this report support the hypothesis that autoimmune neuronal destruction may contribute to the development of diabetic autonomic neuropathy in patients with Type 1 diabetes.

Adult↗

Transferases of O-antigen biosynthesis in Salmonella enterica: dideoxyhexosyltransferases of groups B and C2 and acetyltransferase of group C2.

The O antigen is a polymer of oligosaccharide units. O antigens differ in their sugar composition and glycosidic linkages, and genes responsible for O-antigen-specific biosynthesis are grouped in the rfb gene cluster. In this study, we identified two abequosyltransferase genes and an acetyltransferase gene in Salmonella enterica groups B and C2 by in vitro assay and identified paratosyl-, tyvelosyl-, and abequosyltransferase genes from S. enterica groups A and D and Yersinia pseudotuberculosis serovar IIA, respectively, by comparison.

Acetyltransferases↗

An upstream control region required for inducible transcription of the mouse H1(zero) histone gene during terminal differentiation.

The replacement linker histone H1 (zero) is associated with terminal differentiation in many mammalian cell types, and its accumulation in chromatin may contribute to transcriptional repression occurring during terminal differentiation. H1 (zero) also accumulates in a variety of cell culture lines undergoing terminal differentiation. During in vitro mouse erythroleukemia cell differentiation, H1 (zero) gene expression is induced very rapidly, prior to the time when the cells actually commit to terminal differentiation. We have used a combination of transfection assays and in vitro DNA-protein interaction studies to identify nuclear protein binding sites in the H1 (zero) promoter that control expression and induction of the H1(zero) gene in mouse erythroleukemia cells. The results indicate that transcription of the H1 (zero) gene is controlled by three elements present in the upstream region of the promoter between positions -305 and -470. Site-directed mutagenesis of each of these elements showed that one of them controls inducibility of the gene in differentiating cells. The other two elements in the upstream control region affect primarily the level of transcription of the gene in undifferentiated and differentiating cells. These two elements share a DNA sequence motif consisting of a (dG)6 tract contained in an eight-base consensus, (A/C)GGGGGG(A/C). Additional copies of this motif are present elsewhere in the H1 (zero) promoter.

Animals↗

Long-term consequences in offspring of diabetes in pregnancy: studies with syngeneic islet-transplanted streptozotocin-diabetic rats.

To study the long-term effects of exposure to maternal hyperglycemia and insulin deficiency in utero, we used the syngeneic islet transplanted streptozotocin-diabetic rat model of diabetes in pregnancy and examined insulin secretion and action in 6-month-old offspring. Female rats were rendered diabetic with streptozotocin and then transplanted with 2500, 750, or 500 islets. Control animals were also studied, and one group whose islet transplants failed remained diabetic. During pregnancy, plasma glucose levels in the diabetic rats and the groups receiving 500 and 750 islets were 24.7 +/- 1.0, 15.3 +/- 1.4, and 7.9 +/- 0.5 mmol/liter, respectively, all significantly greater than the control value (5.6 +/- 0.3 mmol/liter; P < 0.05). The plasma glucose level in the 2500 islet group was 6.2 +/- 0.2 mmol/liter, which was not significantly higher than the control value. When the offspring were studied at 6 months, there was no significant difference between groups in either glucose or insulin levels after iv glucose, although acute insulin secretion tended to be higher in the offspring of the diabetic animals. A study of insulin action with the euglycemic clamp at two insulin levels showed that insulin sensitivity was reduced in the offspring of diabetic animals vs. controls (1.97 +/- 0.24 vs. 7.58 +/- 0.95 mumol/liter x 100/kg/min.pmol/liter; P < 0.05). Insulin sensitivity was also significantly reduced in the 2500, 750, and 500 islet group offspring (4.81 +/- 0.57, 4.82 +/- 0.64, and 4.01 +/- 0.63 mumol/liter x 100/kg/min.pmol/liter; P < 0.05) compared to that in the control. There were no differences in insulin sensitivity between male and female animals. In summary, animals displaying maternal insulin deficiency have offspring who are insulin resistant without any evidence of iv glucose intolerance or diminished insulin secretion.

Animals↗

Functional analysis of estrogen-responsive elements in chinook salmon (Oncorhynchus tschawytscha) gonadotropin II beta subunit gene.

The salmon gonadotropin II gene regulates ovulation and spawning. Analysis of the 5' flanking sequence of the hormone-specific beta-subunit of salmon gonadotropin II (sGTHII beta) gene reveals the presence of several presumptive estrogen-responsive elements (ERE). The participation of ERE in the control of sGTHII beta gene transcription was examined by the transient expression of sGTHII beta gene promoter-chloramphenicol acetyltransferase chimeric DNA constructs in HeLa cells, with the cotransfection of a rainbow trout estrogen receptor expression vector. Three ERE have been identified: the proximal ERE [pERE, at -267 base pair (bp) from the transcription start site], the distal ERE (dERE, at -2698 bp, three GGTCA motifs each separated by exactly 31 bp), and the half-ERE (1/2ERE, at -157 bp as a GGTCA motif), respectively. The pERE (TGTCAATCTGACC) represents a novel but less effective variation of the consensus ERE (cERE). The dERE is a unique estrogen-induced enhancer. It requires the participation of the pERE to be functional and the enhancer activity of pERE and dERE is promoter specific. The contribution of 1/2ERE is minor and is not cell-type specific. The activation of the ERE in the sGTHII beta gene and the synergistic cooperation between the dERE and pERE by estradiol-17 beta is dose dependent. DNA sequences in the vicinity of the ERE decreases their hormone responsiveness and the synergism between dERE and pERE. These negative regions may contribute to the quiescent endocrine state of the sGTHII beta gene during the regressive phase of the reproductive cycle in teleost.

Animals↗

Defects in insulin secretion and action in women with a history of gestational diabetes.

Gestational diabetes mellitus (GDM) is associated with defects in insulin secretion and insulin action, and women with a history of GDM carry a high risk for the development of non-insulin-dependent diabetes mellitus (NIDDM). Assessment of subjects with a history of GDM who are currently normoglycemic should help elucidate some of the underlying defects in insulin secretion or action in the evolution of NIDDM. We have studied 14 women with normal oral glucose tolerance who had a history of GDM. They were compared with a group of control subjects who were matched for both body mass index (BMI) and waist-to-hip ratio (WHR). All subjects underwent tests for the determination of oral glucose tolerance, ultradian oscillations in insulin secretion during a 28-h glucose infusion, insulin secretion in response to intravenous glucose, glucose disappearance after intravenous glucose (Kg), and insulin sensitivity (SI) as measured by the Bergman minimal model method. The BMI in the post-GDM women was similar to that in the control subjects (24.9 +/- 1.2 vs. 25.4 +/- 1.4 kg/m2, respectively), as was the WHR ratio (0.80 +/- 0.01 vs. 0.76 +/- 0.01, respectively). The post-GDM women were slightly older (35.2 +/- 0.9 vs. 32.1 +/- 1.4 years, P = 0.04). The fasting plasma glucose levels were significantly higher in the post-GDM group than in the control group (4.9 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, respectively, P < 0.001) and remained higher at each of the subsequent determinations during the oral glucose tolerance test, although none had a result indicative of either diabetes or impaired glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity Cycles↗