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Biomedical subjects

G Liu

Publications and source records attributed to G Liu.

At least 415 records · Page 23Linked to original sources

The study of iodine in Chinese total diets.

In this work, China was divided into four area groups according to their geographical positions and dietary habits. All foods were divided into 12 types and the iodine contents in various diets were determined using epithermal neutron activation analysis (NAA). The intakes for China were evaluated. The results indicate that the intakes of iodine in northern areas are slightly higher and in south areas lower than the lowest recommended intake, and the average intake in China is 166 micrograms/person per day, which is within the recommended range. In addition, one province were chosen from each area groups. The dietary intakes of iodine were investigated in different ages and sex using total mixed diet method. Our results indicate that the average iodine intake of four provinces was lower than the recommended value, which suggests that it is necessary to supplement iodine in foods in China.

Adult↗

Efficient adenovirus-mediated ectopic gene expression of human lipoprotein lipase in human hepatic (HepG2) cells.

Gene therapy to deliver and express a corrective lipoprotein lipase (LPL) gene may improve the lipid profile and reduce the morbidity and potential atherogenic risk from hypertriglyceridemia and dyslipoproteinemia in patients with complete or partial LPL deficiency. We have used an E1-/E3- adenoviral vector, with an RSV-driven human LPL cDNA expression cassette (Ad-RSV-LPL), to achieve high ectopic LPL gene expression in the human hepatoma cell line HepG2, an accepted hepatocellular model of lipoprotein metabolism. Ad-RSV-LPL transduction of HepG2 cells with a multiplicity of infection (moi) between 12.5 and 100 yielded dose-dependent increments in LPL mass and activity. Peak levels of LPL protein of 2,032.1 +/- 274.5 ng/10(5) cells per ml (mol 100) correlated with increased activity of 92.7 +/- 22.6 mU/10(5) cells per ml relative to negligible LPL levels in Ad-RSV-LacZ (beta-galactosidase) controls. Exogenous LPL expression over a 5-day period peaked at day 3. Susceptibility to inhibition by 1 M NaCl and an anti-LPL monoclonal antibody confirmed that lipase activity was indeed derived from human LPL. Hydrolysis, by LPL-overexpressing HepG2 cells, of TG carried in very-low-density lipoprotein (VLDL) showed that greater than 50% of the triglycerides (TG) disappeared after 4 hr of incubation. These results were compatible with FPLC evidence of a marked reduction in VLDL-TG. These results provide strong in vitro evidence that adenoviral-mediated ectopic expression of the human LPL gene could render hepatic cells capable of VLDL catabolism and thus support the possibility for in vivo adenoviral vector-mediated liver-targeted LPL gene therapy.

Adenoviridae↗

An unidentified species of Theileria infective for cattle discovered in China.

Infection experiments, morphological observations and transmission experiments were conducted with an unidentified Theileria sp. isolated from a naturally infected ox. The results showed that the protozoa could multiply extensively in a splenectomized ox and the parasitaemia could reach 52.69%. The Theileria sp. was polymorphic: being pear-shaped, circular, elliptical, rod-like, comma-shaped, three-leafed- or cross-shaped and having many other irregular-shapes which were seldom detected. In erythrocytes, the anaplasma-like protozoa grew, producing protoplasm which could extend and clump together, and developed into many polymorphic protozoa. Some of the protozoa propagated themselves by budding. The protozoa could not be transmitted by Haemaphysalis longicornis or Hyalomma detritum. The pathogenicity, vector ticks and life cycle of this protozoan are unknown.

Animals↗

Effect of osteoarthritis in the lumbar spine and hip on bone mineral density and diagnosis of osteoporosis in elderly men and women.

To determine in the elderly the effect of osteoarthritis on bone mineral density (BMD) and on diagnosis of osteoporosis, lumbar spine and hip were radiographed and BMD measured by dual-energy X-ray absorptiometry (DXA) in 120 men and 314 women, aged 60-99 years. Prevalence and severity of osteoarthritis were scored on osteophytes, joint space narrowing and bone sclerosis. Ultrasound measurements were also made at the heel to examine whether osteoarthritis at hip or lumbar spine influence bone at this remote site. Osteophytes were the commonest feature, with men having a higher prevalence than women, and lumbar spine having more disease than hip. Lumbar spine osteophytes affected 75% of men and 61.1% of women, and hip osteophytes affected 31.7% of men and 27.4% of women. Stepwise multiple regression analysis using age, weight, height, osteophytes, sclerosis and joint space narrowing indicated that lumbar osteophytes explained 16.6% of variation in lumbar spine BMD in women, and 22.4% in men. Hip osteophytes had a minimal effect on hip BMD, accounting for only 2.2% of variation in women, and none in men. Sclerosis and joint narrowing had little effect on BMD at lumbar spine or hip. Indirect effects of osteoarthritis on BMD were small and inconsistent across genders. Lumbar spine osteophytes in men explained 3.1% of hip BMD variation and 6% of variation in speed of sound at the heel, whereas hip osteophytes in women explained 2.2% of lumbar spine BMD variation. Osteoporosis at the hip, defined as BMD < 2.5 SD of the young normal mean, was present in 33.1% of women and 25.8% of men, whereas, at the lumbar spine it was present in only 24.2% of women and 4.2% of men. However, in women and men free of spinal osteoarthritis, 37.7% of women and 10% of men had osteoporosis. We conclude that lumbar spine osteophytes affect most subjects over the age of 60 years, and contribute substantially to lumbar spine BMD measured in the anteroposterior position by DXA. The effect is largely direct by virtue of osteophytes being included in the BMD measurement. However, a small indirect effect on remote skeletal sites is also present. Diagnosis of osteoporosis and assessment of osteoporotic fracture risk in the elderly should be based on hip BMD and not on anteroposterior lumbar spine, unless spinal osteoarthritis has been excluded.

Aged↗

The lppC gene of Streptococcus equisimilis encodes a lipoprotein that is homologous to the e (P4) outer membrane protein from Haemophilus influenzae.

We report the cloning, sequencing, and analysis of a novel chromosomal gene of Streptococcus equisimilis strain H46A that codes for a membrane lipoprotein, designated LppC. The lppC gene is located 3' adjacent to, and co-oriented with, the unrelated gapC gene that encodes the previously characterized glyceraldehyde-3-phosphate dehydrogenase. Sequencing of lppC revealed an 855-bp open reading frame that predicted a 32.4-kDa polypeptide possessing a potential lipoprotein signal sequence and modification site (VTGC). Signal sequence processing of LppC synthesized in the homologous host or expressed from plasmid pLPP2 in Escherichia coli was sensitive to globomycin, a selective inhibitor of lipoprotein-specific signal peptidase II. Subcellular localization of LppC using polyclonal antibodies raised to the hexahistidyl-tagged protein proved LppC to be tightly associated with the cytoplasmic membrane of S. equisimilis and with the outer membrane of E. coli JM109 (pLPP2). Southern, Northern and Western analyses indicated that lpp was conserved in S. pyogenes, and transcribed independently of gap as monocistronic 0.9-kb mRNA from a sigma 70-like consensus promoter. Database searches found homology of LppC to the hel gene-encoded outer membrane protein e (P4) from Haemophilus influenzae to which it exhibits 58% sequence similarity. However, unlike the hel gene, lppC was unable to complement hemA mutants of E. coli for growth on hemin as sole porphyrin source in aerobic conditions. Furthermore, neither the wild type nor an lppC insertion mutant of S. equisimilis could grow on hemin in iron-limited medium. These results, together with findings indicating that S. equisimilis H46A had no absolute requirement for iron, led us to conclude that lppC, in contrast to hel, is not involved in hemin utilization and has yet to be assigned a function.

Amino Acid Sequence↗

Configurational transitions in Fourier series-represented DNA supercoils.

A new Fourier series representation of supercoiled DNA is employed in Langevin dynamics simulations to study large-scale configurational motions of intermediate-length chains. The polymer is modeled as an ideal elastic rod subject to long-range van der Waals' interactions. The van der Waals' term prevents the self-contact of distant chain segments and also mimics attractive forces thought to stabilize the association of closely spaced charged rods. The finite Fourier series-derived polymer formulation is an alternative to the piecewise B-spline curves used in past work to describe the motion of smoothly deformed supercoiled DNA in terms of a limited number of independent variables. This study focuses on two large-scale configurational events: the interconversion between circular and figure-8 forms at a relatively low level of supercoiling, and the transformation between branched and interwound structures at a higher superhelical density.

Biophysical Phenomena↗

In vitro effects of prostaglandin E2 or indomethacin on the proliferation of lymphokine-activated killer cells and their cytotoxicity against bladder tumor cells in patients with bladder cancer.

PURPOSE: To investigate the combined effects of interleukin-2 (IL-2) with either prostaglandin E2 (PGE2) or indomethacin (IM) on the proliferation and cytolysis of bladder tumor cells by lymphokine-activated killer (LAK) cells in patients with bladder cancer. METHODS: LAK cell proliferation was assayed in the presence of various concentrations of either PGE2 or IM by cell counting. Bladder cancer cell lines BIU-87, EJ and bladder tumor cells (BTC) from the patients were cultured as target cells, and the cytotoxicity of LAK cells was determined by 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, PGE2 in samples of conditioned medium from bladder cancer cells or peripheral blood mononuclear cells (PBMC) as well as plasma from 21 patients with bladder cancer and 20 healthy donors were determined by radioimmunoassay (RIA). RESULTS: The proliferation of LAK cells induced by IL-2 was inhibited by PGE2 (0.05 to 5 ng/mL) in concentration-dependent manner. The enhanced growth of LAK cells was observed at certain concentrations of IM (100-400 ng/mL) from 48 to 96 h. Pretreatment of LAK cells with IM (200 ng/mL) significantly enhanced cytotoxicity against BIU-87, EJ cells, or BTC. More PGE2 was present in conditioned medium from BIU-87 cells than in the conditioned medium from PBMC. CONCLUSIONS: These studies indicate that LAK cell proliferation induced by IL-2 in patients with bladder cancer is inhibited by PGE2 produced by PBMC and bladder cancer cells. This inhibition can be overcome by IM, which may be of use in immunotherapy of bladder cancer.

Carcinoma, Transitional Cell↗

Direct interaction between S-methyl dithiocarbazate and pertechnetate-99m.

Although according to the literature S-methyl dithiocarbazate could not form complex directly with 99mTcO4- in acidic condition, we deduced that the formation of such complex should be possible based on "cavity model" and the knowledge of coordination chemistry, and that acidic condition would favor the process. This deduction had been verified by the preparation of lipophilic complex in strong acidic condition with a radio-chemical yield of 80-95%. The radioactive content accumulated in the myocardium of small white mice with ID%/g of 6.4 at 2 min p.i. and it was washed out gradually.

Animals↗

Structure-based design and combinatorial chemistry yield low nanomolar inhibitors of cathepsin D.

BACKGROUND: The identification of potent small molecule ligands to receptors and enzymes is one of the major goals of chemical and biological research. Two powerful new tools that can be used in these efforts are combinatorial chemistry and structure-based design. Here we address how to join these methods in a design protocol that produces libraries of compounds that are directed against specific macromolecular targets. The aspartyl class of proteases, which is involved in numerous biological processes, was chosen to demonstrate this effective procedure. RESULTS: Using cathepsin D, a prototypical aspartyl protease, a number of low nanomolar inhibitors were rapidly identified. Although cathepsin D is implicated in a number of therapeutically relevant processes, potent nonpeptide inhibitors have not been reported previously. The libraries, synthesized on solid support, displayed nonpeptide functionality about the (hydroxyethyl)amine isostere. The (hydroxyethyl)amine isostere, which targets the aspartyl protease class, is a stable mimetic of the tetrahedral intermediate of amide hydrolysis. Structure-based design, using the crystal structure of cathepsin D complexed with the peptide-based natural product pepstatin, was used to select the building blocks for the library synthesis. The library yielded a 'hit rate' of 6-7% at 1 microM inhibitor concentrations, with the most potent compound having a Ki value of 73 nM. More potent, nonpeptide inhibitors (Ki = 9-15 nM) of cathepsin D were rapidly identified by synthesizing and screening a small second generation library. CONCLUSIONS: The success of these studies clearly demonstrates the power of coupling the complementary methods of combinatorial chemistry and structure-based design. We anticipate that the general approaches described here will be successful for other members of the aspartyl protease class and for many other enzyme classes.

Amides↗

Structural factor analyses for medically unexplained somatic symptoms of somatization disorder in the Epidemiologic Catchment Area study.

BACKGROUND: Assess the latent structure of the DSM-III somatization symptoms and the stability of symptom patterns over time. METHODS: Cross-sectional and longitudinal covariation of symptoms of somatization disorder were investigated using structural equation models in a population-based data set from the Epidemiologic Catchment Area study. RESULTS: Medically unexplained physical complaints were discovered to cluster into three separate factors, consistent with the DSM-IV definition of somatization disorder, but one dominant general factor was defined, consistent with the DSM-III conceptualization. Individual symptom prevalences and factor structures were different for men and women. The factor structures remained stable at 1 year follow-up. Variations in the threshold of number of somatization symptoms required for diagnosis affected prevalence, sex ratio and temporal stability of the diagnosis. CONCLUSIONS: These population-based results support dimensional models of somatization. Implications for changing the threshold of the categorical diagnosis of somatization disorder and providing better care for these patients are given.

Adult↗

Fusion of phospholipid vesicles induced by the ribosome inactivating protein saporin.

The single chain ribosome-inactivating protein Saporin-S6 (SO-6) induces the fusion of acid phospholipid vesicles. The extent of fusion was measured by resonance energy transfer assay between the N-(7-nitro-2-1,3-benzoxadiazol-4-yl)-dimyristoylphosphatidyl lithanolamine (NBD-PE)(donor) and N-(lissamine rhodamine B sulphonyl)-diacylphoshaidylethanolamine (Rh-PE) (acceptor) incorporated in the vesicle. The saturated lipid/protein molar ratio is approx. 100:1. The time course of fusion of vesicles induced by the protein showed that the process was completed within 10 minutes, and the size of the particles in the medium was enlarged which conforms the occurrence of the fusion occurring. The fusion is temperature dependent and the liquid-crystalline state lipid is more apt to fuse than the gel phase lipid. The effect of SO-6 is also dependent on ionic strength and pH, high salt concentration and basic pH may abolish fusion, which suggests that both electrostatic and hydrophobic components may be involved in the process.

Hydrogen-Ion Concentration↗

Expression and function of the leucine zipper protein Par-4 in apoptosis.

The prostate apoptosis response-4 (par-4) gene was identified by differential screening for genes that are upregulated when prostate cancer cells are induced to undergo apoptosis. The par-4 gene is induced by apoptotic signals but not by growth-arresting, necrotic, or growth-stimulatory signals. The deduced amino acid sequence of par-4 predicts a protein with a leucine zipper domain at its carboxy terminus. We have recently shown that the Par-4 protein binds, via its leucine zipper domain, to the zinc finger domain of Wilms' tumor protein WT1 (R. W. Johnstone et al., Mol. Cell. Biol. 16:6945-6956, 1996). In experiments aimed at determining the functional role of par-4 in apoptosis, an antisense par-4 oligomer abrogated par-4 expression and activator-driven apoptosis in rat prostate cancer cell line AT-3, suggesting that par-4 is required for apoptosis in these cells. Consistent with a functional role for par-4 in apoptosis, ectopic overexpression of par-4 in prostate cancer cell line PC-3 and melanoma cell line A375-C6 conferred supersensitivity to apoptotic stimuli. Transfection studies with deletion mutants of Par-4 revealed that full-length Par-4, but not mutants that lacked the leucine zipper domain of Par-4, conferred enhanced sensitivity to apoptotic stimuli. Most importantly, ectopic coexpression of the leucine zipper domain of Par-4 inhibited the ability of Par-4 to enhance apoptosis. Finally, ectopic expression of WT1 attenuated apoptosis, and coexpression of Par-4 but not a leucine zipperless mutant of Par-4 rescued the cells from the antiapoptotic effect of WT1. These findings suggest that the leucine zipper domain is required for the Par-4 protein to function in apoptosis.

Amino Acid Sequence↗

Correction of hypertriglyceridemia and impaired fat tolerance in lipoprotein lipase-deficient mice by adenovirus-mediated expression of human lipoprotein lipase.

Humans homozygous or heterozygous for mutations in the lipoprotein lipase (LPL) gene demonstrate significant disturbances in plasma lipoproteins, including raised triglyceride (TG) and reduced HDL cholesterol levels. In this study we explored the feasibility of adenovirus-mediated gene replacement therapy for LPL deficiency. A total of 5 x 10(9) plaque-forming units (pfu) of an E1/E3-deleted adenovirus expressing either human LPL (Ad-LPL) or the bacterial beta-galactosidase gene (Ad-LacZ) as a control were administered to mice heterozygous for targeted disruption in the LPL gene (n = 57). Peak expression of total postheparin plasma LPL activity was observed at day 7 in Ad-LPL mice versus Ad-LacZ controls (834 +/- 133 vs 313 +/- 89 mU/mL, P < .01), and correlated with human-specific LPL activity (522 +/- 219 mU/mL) and mass (9214 +/- 782 ng/mL), a change that was significant to 14 and 42 days, respectively. At day 7, plasma TGs were significantly reduced relative to Ad-LacZ mice (0.17 +/- 0.07 vs 1.90 +/- 0.89 mmol/L, P < .01) but returned to endogenous levels by day 42. Ectopic liver expression of human LPL was confirmed by in situ hybridization analysis and from raised LPL activity and mass in liver homogenates. Analysis of plasma lipoprotein composition revealed a marked decrease in VLDL-derived TGs. Severely impaired oral and intravenous fat-load tolerance in LPL-deficient mice was subsequently corrected after Ad-LPL administration and closely paralleled that observed in wild-type mice. These findings suggest that liver-targeted adenovirus-mediated LPL gene transfer offers an effective means for transient correction of altered lipoprotein metabolism and impaired fat tolerance due to LPL deficiency.

Adenoviridae↗

Bimodal effects of angiotensin II on migration of human and rat smooth muscle cells. Direct stimulation and indirect inhibition via transforming growth factor-beta 1.

Angiotensin II may be an important mediator of neointima formation in vascular disease. This study was designed to examine the mechanisms involved in angiotensin II-stimulated migration of human and rat aortic vascular smooth muscle cells (VSMCs). VSMCs were seeded in one corner of Nunc four-well culture chambers; angiotensin II within filter paper was glued onto the wall of the opposite side. After 48 hours of incubation in serum-free medium containing growth-arresting factor, migrated cells were counted using a light microscope. Angiotensin II (2 x 10(-11) to 2 x 10(-8) mol/L) increased migration of VSMCs in a concentration-dependent manner. Interestingly, at higher concentrations of angiotensin II (up to 2 x 10(-6) mol/L), migration was reduced to levels comparable with control levels. Losartan, an AT1 receptor antagonist, prevented migration, while PD123319, an AT2 receptor antagonist, had no significant inhibitory effect. Transforming growth factor-beta 1 (TGF-beta 1; 0.01 to 10.0 pg/mL) inhibited migration induced by angiotensin II (2 x 10(-8) mol/L) in a concentration-dependent manner. A neutralizing TGF-beta antibody unmasked migratory effects of high concentrations of angiotensin II. Furthermore, angiotensin II (10(-6) mol/L) upregulated TGF-beta 1 mRNA levels fivefold in rat and fourfold in human VSMCs; this effect was prevented by losartan but not by PD123319. Thus, the effects of angiotensin II on migration of VSMCs are bimodal, ie, both migratory and antimigratory pathways are activated. Autocrine release of TGF-beta 1 induced by angiotensin II exerts an antimigratory effect in rat and human VSMCs. The AT1 receptor is involved in regulation of both pathways.

Angiotensin II↗

Patient preferences for oral versus intravenous palliative chemotherapy.

PURPOSE: To assess patient preference for oral versus intravenous (i.v.) palliative chemotherapy (CT). A strong preference would be an important quality-of-life issue. PATIENTS AND METHODS: A structured interviewer-administered scenario-based questionnaire evaluated incurable cancer patients who would be likely to receive palliative CT in the future. Using probability trade-offs, the preference for route of administration was evaluated against diminishing treatment response. RESULTS: Of 103 assessable patients, 92 preferred oral CT, 10 preferred i.v. CT, and one had no preference. Patient preferences were not associated with age, sex, site of primary cancer, or previous CT experiences. Major reasons for preferring oral CT were convenience, problems with i.v. access or needles, and a better CT-taking environment (outside of the clinic). Regardless of initial preference, 70% of patients were not willing to accept a lower response rate and 74% were not willing to accept a shorter duration of response to retain their initial preference. Although 99% of patients had a preference, 39% wanted the specific treatment decision made primarily by their physicians, 38% primarily by themselves, and 22% shared equally. CONCLUSION: Patients with incurable cancer have a clear preference for oral CT, but are generally not willing to sacrifice efficacy for their preference. Almost 40% of patients did not want to make final treatment decisions themselves.

Administration, Oral↗

[Hemodynamic response to exercise in patients with chronic obstructive pulmonary disease (COPD)].

OBJECTIVE: The present study was undertaken to assess the cardiopulmonary response during the initial period of exercise. METHODS: Eight patients with COPD and 10 normal subjects were investigated during exercise (35W) in room air and oxygen breathing for 15 minutes, respectively. Pulmonary arterial mean pressure (mPAP), cardiac output (CO) and mixed venous oxygen saturation (SvO2) were measured by Swan-Ganz catheter during exercise. RESULTS: Compared with normal controls, mPAP in COPD patients was increased and SvO2 decreased markedly both in room air and oxygen breathing during exercise. And CO increased relative slowly than that of normal controls. Furthermore, in patients with COPD, the time to reach their steady state in mPAP and SvO2 during exercise were delayed compared with normal controls. Moreover, we found that the time to reach their steady state in mPAP and SvO2 were shortened when the patients were given oxygen breathing during exercise. CONCLUSIONS: The results indicate that the measurement of initial changes in mPAP and SvO2 during exercise have important clinical significance for evaluating the cardiopulmonary response in patients with COPD.

Blood Pressure↗

[Surgical handling of primary hepatic carcinoma with severe cirrhosis and portal hypertension].

Four hundred and ninety eight cases of primary hepatic carcinoma (PHC) were discovered complicating with cirrhosis in 608 PHC cases during 1974-1994. 63 cases of them were with severe cirrhosis and portal hypertension (10.4%). Laparotomy indication was evaluated according to Child's grade and image data such as BUS and CT etc. Operative extension should be limited as segment or wedge hepatectomy or semi-hepatic artery chemo-embolization. Splenic artery ligation plus venous ligalion of cardiac region of stomach were applied to portal hypertension and hypersplenism. Frusemide, antacid and insulin were used in the perioperation period. Three-year survival rate was 57%. It is considered that splenic artery ligation instead of splenectomy is the first choice for preventing and treating hypersplenism and digestive tract bleeding in PHC with severe cirrhosis.

Adult↗