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Biomedical subjects

G Li

Publications and source records attributed to G Li.

At least 289 records · Page 16Linked to original sources

Direct in vivo evidence demonstrating neointimal migration of adventitial fibroblasts after balloon injury of rat carotid arteries.

BACKGROUND: Clinical and experimental evidence suggest that the adventitia participates in the response to endoluminal vascular injury. The current study used a direct approach to test the hypothesis that, after balloon injury of the rat carotid artery, adventitial fibroblasts migrate in a luminal direction and contribute to neointima formation. METHODS AND RESULTS: Primary syngeneic adventitial fibroblasts were stably transduced with retroviral particles coordinating expression of beta-galactosidase (LacZ) and introduced into the adventitia of right carotid arteries of rats immediately after balloon injury. At defined times after injury and fibroblast implantation, rats were euthanized, and arterial tissue was examined for detection of LacZ mRNA (reverse transcription polymerase chain reaction), DNA (polymerase chain reaction), and in situ enzymatic activity. LacZ expression was detected in the media 5 days postinjury and in both media and neointima at 7, 10, and 14 days postinjury. LacZ was undetectable in injured vessels that had not been seeded with transduced fibroblasts and was restricted to the adventitia in seeded vessels that were not injured. CONCLUSIONS: These observations provide direct demonstration of adventitial fibroblast migration into neointima of arteries after endoluminal injury.

Animals↗

Characterization of glucokinase regulatory protein-deficient mice.

The glucokinase regulatory protein (GKRP) inhibits glucokinase competitively with respect to glucose by forming a protein-protein complex with this enzyme. The physiological role of GKRP in controlling hepatic glucokinase activity was addressed using gene targeting to disrupt GKRP gene expression. Heterozygote and homozygote knockout mice have a substantial decrease in hepatic glucokinase expression and enzymatic activity as measured at saturating glucose concentrations when compared with wild-type mice, with no change in basal blood glucose levels. Interestingly, when assayed under conditions to promote the association between glucokinase and GKRP, liver glucokinase activity in wild-type and null mice displayed comparable glucose phosphorylation capacities at physiological glucose concentrations (5 mM). Thus, despite reduced hepatic glucokinase expression levels in the null mice, glucokinase activity in the liver homogenates was maintained at nearly normal levels due to the absence of the inhibitory effects of GKRP. However, following a glucose tolerance test, the homozygote knockout mice show impaired glucose clearance, indicating that they cannot recruit sufficient glucokinase due to the absence of a nuclear reserve. These data suggest both a regulatory and a stabilizing role for GKRP in maintaining adequate glucokinase in the liver. Furthermore, this study provides evidence for the important role GKRP plays in acutely regulating of hepatic glucose metabolism.

Adaptor Proteins, Signal Transducing↗

New C=C bond formation via nonstoichiometric titanium(IV) halide mediated vicinal difunctionalization of alpha,beta-unsaturated acyclic ketones

[reaction: see text] Highly stereoselective vicinal difuctionalization of alpha,beta-unsaturated ketones for the synthesis of multifunctionalized trisubstituted alkenes is described. The new reaction employs titanium(IV) halides (0.5 equiv) as promoters and inexpensive commercial chemicals as starting materials. The reaction can be performed at room temperature in a convenient vial without the protection of inert gases. Good to excellent yields and high Z/E stereoselectivity have been realized in most cases presented (16 examples).

Journal Article↗

Cloning and characterization of the human retinoid X receptor alpha gene: conservation of structure with the mouse homolog.

Retinoid X receptors (RXRs) are members of the steroid/thyroid hormone receptor superfamily which, along with retinoic acid receptors (RARs), mediate the biological effects of retinoids. These effects include the regulation of many aspects of embryonic development, reproductive and visual function, and the maintenance of epithelial homeostasis throughout life. The genes for three distinct retinoid X receptors, RXRalpha, beta, and gamma, have been localized to separate chromosomes. In order to determine the organization of the human RXRalpha gene, we have isolated a clone containing the majority of the gene from a human genomic bacterial artificial chromosome (BAC) library and generated a physical map. The gene spans over 40 kilobases in size and contains at least 10 exons. Comparison with mapped portions of the mouse RXRalpha gene indicates highly conserved intron-exon positioning. These results provide information necessary to generate constructs for targeting the RXRalpha gene in human cell lines, which may eventually lead to an understanding of the function of RXRalpha in human cancer.

Animals↗

GTPase mechanism and function: new insights from systematic mutational analysis of the phosphate-binding loop residue Ala30 of Rab5.

Structural and biochemical data indicate the importance of the phosphate-binding loop residues Gly(12) and Gly(13) of Ras both in the GTP hydrolysis reaction and in biological activity, but these two residues are not conserved in other Ras-related GTPases. To gain a better understanding of this region in GTP hydrolysis and GTPase function, we used the Ras-related Rab5 GTPase as a model for comparison, and substituted the Ala(30) residue (the equivalent of Gly(13) of Ras) with all the other 19 amino acids. The resulting mutants were analysed for GTP hydrolysis, GTP binding, GTP dissociation and biological activity. Only the substitution of alanine with proline reduced the GTPase activity by an order of magnitude. This effect is in sharp contrast with the observation that a proline substitution at the neighbouring position (Gly(12) of Ras) has little effect on the GTPase activity. Whereas most other substitutions showed either a small negative effect or no effect on the GTPase activity, the arginine substitution surprisingly stimulated the GTPase activity by 5-fold. Molecular modelling suggests that this built-in arginine mimics the catalytic arginine residues found in trimeric GTPases and GTPase-activating proteins in providing the positive charge to facilitate the GTP hydrolysis reaction. We investigated further the biological activity of the Rab5 mutants in relation to stimulating endocytosis. When expressed in cultured baby hamster kidney cells, both arginine and proline mutants, like wild-type Rab5, stimulated endocytosis. However, the arginine mutant was a more potent stimulator than the proline mutant (3-fold stimulation as against 1.7-fold). The tryptophan mutant, on the other hand, was completely deficient in activity in terms of the stimulation of endocytosis, demonstrating the importance of the phosphate-binding loop in Rab GTPase function.

Alanine↗

Covalent modification regulates ligand binding to receptor complexes in the chemosensory system of Escherichia coli.

In the Escherichia coli chemosensory pathway, receptor modification mediates adaptation to ligand. Evidence is presented that covalent modification influences ligand binding to receptors in complexes with CheW and the kinase CheA. Kinase inhibition was measured with serine receptor complexes in different modification levels; Ki for serine-mediated inhibition increased 10,000-fold from the lowest to the highest level. Without CheA and CheW, ligand binding is unaffected by covalent modification; thus, the influence of covalent modification is mediated only in the receptor complex, a conclusion supported by an analogy to allosteric enzymes and the observation of cooperative kinase inhibition. Also, the finding that a subsaturating serine concentration accelerates active receptor-kinase complex assembly implies that the assembly/disassembly process may also contribute to kinase regulation.

Allosteric Regulation↗

Transition from spirals to defect-mediated turbulence driven by a doppler instability.

A transition from rotating chemical spirals to turbulence is observed in experiments on the Belousov-Zhabotinsky reaction. The transition occurs when the waves near the spiral tip spontaneously break, generating defects. Measurements reveal that this defect-mediated turbulence is caused by the Doppler effect on the traveling waves. The observations are in good accord with numerical simulations and theory.

Doppler Effect↗

[Effect of typical aldehyde pollutants on the DNA damage of spleen lymphocytes of mice].

The DNA damage of spleen lymphocytes induced by three typical aldehyde pollutants was studied in vitro with microgel single cell electrophoresis assay (comet assay). It showed that the comet cells induced by the three chemicals were observed, and the dose-dependent relations were existed. It suggested that the three aldehydes could induce DNA strand breakage.

Acetaldehyde↗

Validation of biomarkers in humans exposed to benzene: urine metabolites.

BACKGROUND: The present study was conducted among Chinese workers employed in glue- and shoe-making factories who had an average daily personal benzene exposure of 31+/-26 ppm (mean+/-SD). The metabolites monitored were S-phenylmercapturic acid (S-PMA), trans, trans-muconic acid (t,t-MA), hydroquinone (HQ), catechol (CAT), 1,2, 4-trihydroxybenzene (benzene triol, BT), and phenol. METHODS: S-PMA, t,t-MA, HQ, CAT, and BT were quantified by HPLC-tandem mass spectrometry. Phenol was measured by GC-MS. RESULTS: Levels of benzene metabolites (except BT) measured in urine samples collected from exposed workers at the end of workshift were significantly higher than those measured in unexposed subjects (P < 0.0001). The large increases in urinary metabolites from before to after work strongly correlated with benzene exposure. Concentrations of these metabolites in urine samples collected from exposed workers before work were also significantly higher than those from unexposed subjects. The half-lives of S-PMA, t,t-MA, HQ, CAT, and phenol were estimated from a time course study to be 12.8, 13.7, 12.7, 15.0, and 16.3 h, respectively. CONCLUSIONS: All metabolites, except BT, are good markers for benzene exposure at the observed levels; however, due to their high background, HQ, CAT, and phenol may not distinguish unexposed subjects from workers exposed to benzene at low ambient levels. S-PMA and t,t-MA are the most sensitive markers for low level benzene exposure.

Acetylcysteine↗

Tissues formed during distraction osteogenesis in the rabbit are determined by the distraction rate: localization of the cells that express the mRNAs and the distribution of types I and II collagens.

An experimental model of leg lengthening was used to study the morphology of, the collagenous proteins present, and the collagen genes expressed in the regenerating tissue following 20% lengthening at four different distraction rates. At a distraction rate of 0.3 mm/day (8 weeks distraction), the regenerate consists of intramembranous bone and localized areas of fibrocartilage. At rates of 0.7 (4 weeks) and 1.3 mm/day (2 weeks), the bone that grows from the cut ends of the cortical bone is separated by fibrous tissue and cartilage is present. At 2.7 mm/day (1 week), only fibrous tissue and sparse bone are present. Type I collagen is present in the matrices around the cells expressing its mRNA and similarly, type II collagen is located around the chondrocytes. Type I collagen mRNA is expressed predominantly by the fibroblasts in the fibrous tissue, the bone surface cells and to a reduced extent by the osteocytes. Type II collagen mRNA is expressed by chondrocytes. The results suggest that osteoblasts and chondrocytes within the regenerate originate from the same pool of progenitor cells, and the differentiation of these cells and the expression of types I and II collagen genes are altered by different rates of distraction. These observations suggest that the optimal rate of distraction in the model is 0.7 mm/day.

Animals↗

Characterization of a granulovirus from the cassava hornworm (Erinnyis ello: Sphingidae).

A Colombian isolate of Erinnyis ello granulovirus (EeGV) was characterized by electron microscopy, restriction endonuclease digestion, and SDS-PAGE. Electron microscopy showed the occlusion bodies to have a morphology typical of granuloviruses. The restriction patterns of DNA from EeGV and the granuloviruses of Trichoplusia ni (TnGV) and Pieris rapae (PrGV) show little or no similarity, indicating little relatedness among these viruses. EeGV was estimated to possess a relatively small genome of 90.5 +/- 0.5 kbp. SDS-PAGE analysis compared the occulsion body and enveloped nucleocapsid proteins of EeGV and TnGV, and the polypeptide patterns also showed little similarity between these viruses. These analyses, as well as comparison of our results to those reported for other granuloviruses, indicate that EeGV represents a new granulovirus isolate.

Animals↗

Alcohol use in relation to driving records among injured bicyclists.

To prevent alcohol-related occupational mishaps, employers often conduct background checks on prospective employees for history of driving while intoxicated (DWI) and driving under the influence of alcohol (DUI) to screen out candidates with drinking problems. Few studies, however, have examined the pervasive nature of drinking behavior across activity domains. Based on trauma registry data, we constructed a historical cohort of 120 Maryland residents ages 18 years or older who were injured while riding a bicycle between 1990 and 1997. Driving records for the 120 bicyclists for the 3 years between May 6, 1995 and May 5, 1998 were obtained from the state motor vehicle administration and were analyzed in relation to BAC-positive status at the time of injury. Bicyclists with positive BACs at the time of admission to the trauma center were significantly more likely than those with negative BACs to have a record of license suspension/revocation (52% vs 14%, P < 0.01) and to have DWI/DUI convictions (30% vs 3%, P < 0.01). Despite the modest sample size, this study provides compelling evidence of the pervasive nature of risky drinking between bicycling and driving activities.

Accidents, Traffic↗

Autologous smooth muscle cell transplantation improved heart function in dilated cardiomyopathy.

BACKGROUND: Transplantation of myocytes into scarred myocardium has been shown to inhibit ventricular remodeling and maintain myocardial contractility. However, the effect of cell transplantation on hearts with global rather than regional dysfunction is unknown. Therefore, we evaluated the effect of transplantation of autologous smooth muscle cells on the morphometry and function of dilated cardiomyopathic hearts. METHODS: Smooth muscle cells were isolated from the ductus deferens of 13-week-old BIO 53.58 hamsters with dilated cardiomyopathy, and cultured for 4 weeks before transplantation. Smooth muscle cells (4 x 10(6) cells) or culture medium were injected into 17-week-old animals in the transplantation and control groups (n = 12 each), respectively. Prelabeling of the smooth muscle cells with 5-bromo-2'-deoxyuridine was performed before transplantation in a group of transplanted hamsters. Another group (sham, n = 12) underwent the operation but did not receive an injection either of smooth muscle cells or of culture medium. Four weeks after transplantation, heart function was evaluated in a Langendorff preparation. RESULTS: Musclelike tissue, labeled with 5-bromo-2'-deoxyuridine, was found at the site of transplantation in the cell-transplanted animals. The cell-transplanted hearts were smaller (p < 0.001), and had greater developed pressures and maximum rate of increase of left ventricular pressure (both p < 0.001) than control and sham hearts. Control hamsters injected with culture medium did not differ from sham-operated animals. CONCLUSIONS: Transplantation of autologous smooth muscle cells prevented cardiac dilatation and improved ventricular function in hamsters with dilated cardiomyopathy.

Animals↗

Hyperglycemia, hyperlipemia, and periodic paralysis: a case report of new side effects of clozapine.

1. This case report of a Chinese male schizophrenic patient describes new side effects that have not been documented previously for patients treated with clozapine. At certain doses of clozapine, the patient showed direct adverse reactions, which include a combination of hyperglycemia, hyperlipemia, and periodic paralysis. 2. In a four-year study of this patient who had no previous episodes of diabetes in his or his family history, the authors found that these symptoms disappeared upon withdrawal of clozapine and relapsed with re-treatment of the drug. This study indicates that hyperglycemia, hyperlipemia, and periodic paralysis may need to be monitored on patients treated with clozapine.

Adult↗

Phenoloxidase, a marker enzyme for differentiation of the neural ectoderm and the epidermal ectoderm during embryonic development of amphioxus Branchiostoma belcheri tsingtaunese.

The development of phenoloxidase during amphioxus embryogenesis was spectrophotometrically and histochemically studied for the first time in the present study. It was found that (1) PO activity initially appeared in the general ectoderm including the neural ectoderm and the epidermal ectoderm at the early neurula stage but not in the mesoderm or the endoderm, and (2) PO activity disappeared in the neural plate cells but remained unchanged in the epidermal cells when the neural plate was morphologically quite distinct from the rest of the ectoderm. It is apparent that PO could serve as a marker enzyme for differentiation of the neural ectoderm from the epidermal ectoderm during embryonic development of amphioxus.

Animals↗

Dynamics of intercellular communication during melanoma development.

Melanoma development involves processes determined collectively by various microenvironmental factors, among which intercellular communication has drawn increased attention. Cell-cell crosstalk mediated by cadherins and connexins results in coordinated regulation of cell growth, differentiation, apoptosis and migration. Abnormal expression of adhesion receptors and dysregulated intercellular communication appears to drive tumor development and progression.

Animals↗

Polymorphism of the ABO blood group genes in Han, Kazak and Uygur populations in the Silk Route of northwestern China.

Genetic polymorphism in the ABO blood group gene of Han, Kazak and Uygur populations inhabiting the most northwestern part of China was investigated using polymerase chain reaction-based techniques. The present study enrolled 43 healthy unrelated Han, 37 Kazak and 59 Uygur volunteers. The allele in A1 blood group is distinguished A0101 and A0102 in difference of nucleotide position 467. The A0101 allele is more frequent in Caucasian and the A0102 allele is characteristic in Mongoloid. It must be notable that A0201 in the A2 group (with a single base deletion at nucleotides 1059 to 1061) which was characteristic of Caucasian was observed in Kazak and Uygur populations but not in Han. Further, 00201 (with no nucleotide deletion at 261 and three nucleotide differences), which is frequent in different races including Caucasian except for Mongoloid, was detected also in Kazak and Uygur populations. The frequencies of B0101 in Kazak, Uygur and Han were comparable to those of other Asian populations but higher than those of Caucasian populations. Collectively, these results reveal that the allele frequencies of Kazak and Uygur at the ABO blood group locus are an intermediate between those of Mongoloid and Caucasian, suggesting the admixed feature of Kazak and Uygur with Mongoloid and Caucasian.

ABO Blood-Group System↗

Photoelectron spectroscopy of ammonia via a fast predissociative state

We report a study on resonance enhanced multiphoton ionization photoelectron spectroscopy (REMPI-PES) involving the fast predissociative A state of ammonia, using nano- and femtosecond lasers. The multiphoton scheme involves (1 + 1), (2 + 2), (2 + 2) + 1 and (2 + 2) + 2 photon processes. We have found a progression of stretching vibrations v1 in the PE spectrum when pumping NH3 A v2 = 0, 1 and 3 as intermediate states. The stretching vibration intensity distributions in the photoelectron spectrum are calculated by using the Chebychev method of the wavepacket propagation. The femtosecond spectrum shows a similar feature to the nanosecond spectrum. However, high laser power also causes band broadening and shifting effect as well as above threshold multiphoton ionization.

Journal Article↗