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Biomedical subjects

R Li

Publications and source records attributed to R Li.

At least 469 records · Page 26Linked to original sources
PubMed1994

Construction and characterization of a human chromosome 2-specific BAC library.

We have constructed a human chromosome 2-specific bacterial artificial chromosome (BAC) library using DNA from the somatic cell hybrid GM10826. The average size of the clones is about 63 kb. The coverage and distribution of the library were estimated by screening with known polymorphic genetic markers and fluorescence in situ hybridization (FISH). Twenty-one markers tested positive when DNA pools prepared from approximately one-sixth of the library were screened with 33 known markers. This is consistent with the theoretical calculation of 63% coverage at one genomic equivalent. This suggested that the coverage of the library is approximately 5-6x. FISH analysis with 54 BACs revealed single site hybridization to chromosome 2, and the clones were distributed randomly on the chromosome. We have also performed direct sequencing of the BAC insert ends to generate sequence-tagged sites suitable for mapping and chromosome walking. This is the first reported human chromosome 2-specific BAC library and should provide a resource for physical mapping and disease searching for this chromosome.

Base Sequence↗
PubMed1994

Effect of chronic haloperidol treatment on dopamine-induced inositol phosphate formation in rat brain slices.

The effects of chronic haloperidol administration on the accumulation of inositol phosphates were examined in rat brain slices pre-labeled with [3H]myo-inositol and incubated with various dopaminergic drugs. Rats were treated with haloperidol-decanoate or its vehicle (sesame oil) for two, four or six weeks. Dopamine and the selective D1 agonist, SKF38393, induced a significant increase in lithium-dependent accumulation of [3H]inositol monophosphate (IP1) in the frontal cortex, hippocampus and striatum of vehicle-treated animals, while the selective D2 agonist quinpirole did not show any effect on IP1 accumulation. The actions of dopamine and SKF38393 were blocked by the D1 antagonist, SCH23390, but not by the D2 antagonist, spiperone, in all three brain regions. Haloperidol treatment did not affect basal phosphoinositide turnover in the three brain regions. Four or six weeks of haloperidol treatment significantly decreased dopamine-induced IP1 accumulation in the striatum (by 30% and 25%, respectively), but not in the frontal cortex and the hippocampus. Four weeks of treatment with haloperidol significantly decreased IP1 levels in the striatal slices when measured in the presence of quinpirole. However, the accumulation of IP1 measured in the presence of SKF38393 was not significantly altered after haloperidol treatment. The loss of dopamine-sensitive IP accumulation was not observed in the presence of spiperone after haloperidol treatment. The number, but not the affinity, of [3H]sulpiride binding sites in the striatum was significantly increased (by 34-46%) after chronic haloperidol treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Anti-malarial drug development using models of enzyme structure.

BACKGROUND: The trophozoite stage of the malaria parasite infects red blood cells. During this phase of their life-cycle, the parasites use hemoglobin as their principal source of amino acids, using a cysteine protease to degrade it. We have previously reported a three-dimensional model of this cysteine protease, based on the structures of homologous proteases, and the use of the program DOCK to identify a ligand for the malaria protease. RESULTS: Here we describe the design of improved ligands starting from this lead. Ligand design was based on the predicted configuration of the lead compound docked to the model three-dimensional structure of the protease. The lead compound has an IC50 of 6 microM, and our design/synthesis strategy has resulted in increasingly potent derivatives that block the ability of the parasites to infect and/or mature in red blood cells. The two best derivatives to date have IC50(s) of 450 nM and 150 nM. CONCLUSIONS: A new class of anti-malarial chemotherapeutics has resulted from a computational search that was based on a model of the target protease. Despite the lack of a detailed experimental structure of the target enzyme or the enzyme-inhibitor complex, we have been able to identify compounds with increased potency. These compounds approach the activity of chloroquine (IC50 = 20 nM), but have a distinct mechanism of action. This series of compounds could thus lead to new therapies for chloroquine-resistant malaria.

Animals↗
PubMed1994

Ambiguous pictorial depth cues and perceptions of nonrigid motion in the three-loop figure.

The three-loop figure is a two-dimensional (2-D) pattern that generates (mis)perceptions of nonrigid three-dimensional (3-D) structure when rotated about its centre. Such observations have been described as counterexamples to the principle whereby a moving object is presumed to be rigid, provided that a rigid interpretation is possible (ie the 'rigidity constraint'). In the present investigation we demonstrated that stationary three-loop figures exhibit many of the classic properties of multistable/ambiguous figures, with any one of several possible 3-D configurations being reported at any one instant. Further investigation revealed that perceived nonrigidity during rotation was markedly reduced (and rigidity enhanced) when the figure was modified with static pictorial depth cues (eg shading, interposition). These cues had no effect on the overall proportion of time that observers reported 3-D organisations in stationary versions of the figure, but significantly reduced the frequency of perceptual reorganisation, and increased the duration for reporting a particular organisation. Since each of the perceived 3-D structures in a stationary ambiguous 2-D figure has a unique kinetic counterpart (ie rigid transformation), we attribute the nonrigid structure perceived when the figure rotates to the integration of these otherwise inconsistent kinetic components; and have further illustrated this with modified versions of a Penrose impossible triangle. Under kinetic versions of the classical size/distance invariance hypothesis, the rigidity constraint may be considered to represent a special instance of size/shape constancy, in which case counterexamples involving (mis)perceptions of nonrigid structure are comparable to other well-known exceptions to such principles of minimum object change (eg classical illusions).

Cues↗
PubMed1994

Functional consequences of iron supplementation in iron-deficient female cotton mill workers in Beijing, China.

Eighty iron-deficient, nonpregnant female workers were randomly assigned to ferrous sulphate (60 or 120 mg Fe/d) or placebo treatment for 12 wk. Energy expenditure was estimated during 3 d by heart rate (HR) recording. Production efficiency (PE) was calculated as the ratio of productivity to energy expenditure. In the iron-treated group mean hemoglobin (Hb) increased from 114 to 127 g/L (P < 0.001), mean serum ferritin increased from 9.7 to 30.0 micrograms/L (P < 0.001), and mean free erythrocyte protoporphyrin decreased from 1.01 to 0.49 mumol/L (P < 0.001). Mean HR at work decreased from 95.5 to 91.1 beats/min (P < 0.001), which was inversely correlated with the change in Hb (r = -0.60, P < 0.001). PE increased significantly in the iron-treated group (P < 0.001) and its change paralleled the change in Hb (r = 0.58, P < 0.001). The results show that iron supplementation enabled these women to do the same work at a lower energy cost.

Adult↗
PubMed1994

B-mode-detected carotid artery plaque in a general population. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

BACKGROUND AND PURPOSE: There is little information on the distribution of atherosclerotic lesions of the extracranial carotid artery wall in free-living populations. The purpose of the present study was to describe the prevalence from 1987 through 1989 of extracranial carotid artery plaque and plaque with acoustic attenuation (shadowing) lesions in a general population of white and black adults from four US communities. METHODS: B-mode ultrasound was used to characterize wall lesions in the common and internal carotid arteries and at the carotid artery bifurcation in 14,046 men and women 45 to 64 years old who participated in the Atherosclerosis Risk in Communities Study baseline survey. RESULTS: Thirty-four percent of participants had plaque and 6.4% had plaque with acoustic shadowing. The prevalence of plaque with acoustic shadowing increased steadily with age from 2.5% at ages 45 to 49 to 12.4% at ages 60 to 64. Overall, whites had more plaque with acoustic shadowing lesions than blacks (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.02 to 1.46), and men had more than women (OR, 1.42; 95% CI, 1.22 to 1.63). However, plaque lesions in the common carotid artery were less common among whites than among blacks, and no racial difference was observed in the prevalence of plaque with acoustic shadowing at this segment. CONCLUSIONS: Although these prevalence rates are likely to be underestimated because of the emphasis on arterial boundary visualization of the scanning protocol, they show a large, mostly asymptomatic burden of atherosclerosis in these populations, especially among older individuals. Site-specific frequency rates of plaque varied between blacks and whites. Among those with plaque, however, whites had more lesions with acoustic shadowing attenuation.

Adult↗
PubMed1994

A preliminary analysis of divorce in China.

"With data from the 1982 and 1990 censuses and data of divorce from civil administration departments, it is possible to make a preliminary analysis on changes in the number of divorces and the population of divorcees in China since the 1980s." Aspects considered include regional differentials, sex differences, age patterns, and remarriage.

Age Factors↗
PubMed1994

[Distribution of ABH substances in normal secretor human tissue cells by avidin-biotin complex method].

The distribution and location of ABH substances in 54 various kinds of normal secretor human tissue cell of known ABO type were studied by Avidin-Biotin complex (ABC) method. It was firstly demonstrated that 18 different kinds of tissue cells contained ABH substances, which were as follows: neuron and nerve fiber, astrocyte, oligodendrocyte, ependyma epithelial cells, epithelial cells of soft meninges, epithelial cells of parotid gland duct, taste bud cells of tongue, acinar and epithelial cells of duct of buccal gland, epithelial cells of rectal mucous membrane gland, regenerated liver cells of hepatocirrhosis, basal cells of stratified aquamous epithelium of epiglottis, spermiogenesis and spermatozoa of seminiferous tubules, epithelial cells of tubuli reti, rete testis and tubuli epididymis, both primary and secondary follicles of ovary and decidua cells of endometrium. Some new phenomena were observed as follows: ABH substances in chief cells more than those in parietal cells of gastric gland, locally distributed ABH positive cells in stratum spinosum of stratified squamous epithelium of skin, segmentally distributed ABH positive cells in pseudostratified ciliated columanal epithelium of epiglottis. The ABH substances were located at the infranuclear and/or supranuclear region and/or brush border of the epithelial cells of submaxillary gland, mosaic distributed ABH substances were found in the epithelia of both sweat and submaxillary glandular ducts. A few controversies about distribution of ABH substances were solved. The relationship between H and A, B substances, origin of ABH substances, source of ABH substances in body fluids. Production of ABH substances and cell differentiation, mosaicism and inconsistency of ABH distribution are discussed and compared with other reports.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗
PubMed1994

Coleopterancidal delta-endotoxin and constructing its genomic library.

The composition of crystal proteins and plasmid patterns in five new coleopterancidal strains of Bacillus thuringiensis were investigated. Larvae of Plagiodera versicolora were chosen as a model insect in bioassay. Strain YM-03 had the highest toxicity. Plasmid patterns were detected by rapid agarose gel electrophoresis. It was demonstrated that plasmid patterns of five Bt strains were quite different. The partial amino acid sequences of the N-terminal of crystal protein from YM-03 were analyzed by amino acid analyzer. A genomic library of delta-endotoxin of YM-03 was constructed. The EcoRI fragments (20-30 kb) from the total DNA were ligated with the vector DNA of pLAFRI. Thirteen clones which contained both of pLAFRI and foreign DNA fragments were obtained from 17 recombined plasmids. The frequency of recombinant clones was 76%. Three positive clones, LE392 (pBYM2), LE392 (pBYM3) and LE392 (pBYM4) were detected from 1200 resistant clones by using a synthesized 18bp probe from a coleopterancidal delta-endotoxin gene. It was shown that LE392 (pBYM3) and LE392 (pBYM4) had the same EcoRI digestion patterns and that they all contained coleoptera-specific delta-endotoxin gene but showed a different level of expression.

Amino Acid Sequence↗
PubMed1994

[Preliminary results of three different cannulations for percutaneous transhepatic cholecystic drainage in the interventional gallstone dissolutions].

Three different methods of percutaneous transhepatic gallbladder cathetering drainage were applied in 33 patients undergoing interventional gallstone dissolution. Among them, sheathed needle was used in 6 cases with a success rate of 33%; wire-guided in 16 with a success rate of 50%; and double-sheathed inner needle was successfully used in all the 11 cases. The authors believe that this last method could safely be used in the nonoperative drainage of acute cholecystitis as well as the interventional gallstone dissolutions.

Adolescent↗
PubMed1994

[Pharmacological study on Asparagus officinalis Linn].

Our experiment shows that Asparagus officinalis can increase the clearance rate of charcoal particles and the weight of immune organs in mice, and thus helps to facilitate their antifatigue, anoxia tolerance, analgesia and memory improvement, as well as decrease the contents of lipid peroxide (LPO) in plasma, liver and brain of the animal.

Animals↗
PubMed1994

[Gas chromatographic method with EC detection to determine isosorbide-5-mononitrate (IS-5-MN) in human serum and its pharmacokinetic parameters].

A simple, sensitive and precise capillary GC-ECD method was developed for the determination of isosorbide-5-mononitrate in human serum. Pharmacokinetic parameters of the drug was obtained from the human serum level-time curve measured. Serum samples were extracted with a mixture of ethyl ether-ethyl acetate (4:1), the upper phase was collected and evaporated to about 100 microliters under a gentle nitrogen stream. Isosorbide dinitrate was used as internal standard. With a human serum sample size of 200 microliters, the detection limit of IS-5-MN was found to be about 5 ng/ml, and the absolute recovery from 74% to 85%. The within-day and between-day relative standard deviation were less than 7% and 9%, respectively. This method was applied to the pharmacokinetic studies of IS-5-MN tablets from two different sources. Two sets of t1/2 (Ke), Tmax and AUC values obtained from 8 volunteers were tested statistically and no significant difference was found.

Chromatography, Gas↗
PubMed1994

Modulation of human myelopoiesis by human gangliosides.

Cell surface gangliosides are potent modulators of cellular proliferation. We hypothesize that gangliosides shed by tumor cells modulate hematopoiesis and contribute to human tumor-associated suppression of hematopoiesis. To test this hypothesis, we determined the effects on myeloid colony formation by human bone marrow mononuclear cells of total gangliosides isolated from human brain and of seven highly purified individual ganglioside species (GM1, GM2, GD1a, GD1b, GD2, GD3, and GT1b). Total human brain gangliosides and certain individual species, GD1a, GD1b, and GT1b, significantly inhibited myeloid colony formation (number as well as size). The most complex molecules, GD1a, GD1b, and GT1b, were the most inhibitory, suggesting that the degree of inhibition is related to ganglioside structural complexity. To extend these findings, we also investigated certain tumor-derived (neuroblastoma) gangliosides, which we found inhibited both myeloid colony formation and 3H-thymidine incorporation by human bone marrow mononuclear cells. These data suggest a role for gangliosides, which are shed by proliferating cells, in the regulation of human hematopoiesis and may explain the bone marrow hypoplasia observed in association with many human malignancies.

Bone Marrow↗
PubMed1993

Enhancer activity of light-responsive regulatory elements in the untranslated leader regions of cyanobacterial psbA genes.

Three psbA genes encoding the D1 protein of the photosystem II reaction center are differentially expressed under different light intensities in the cyanobacterium Synechococcus sp. strain PCC 7942. Two of the three psbA genes, psbAII and psbAIII, are induced rapidly when light intensity is increased from 125 x 10(-6) mol.m-2.s-1 to 750 x 10(-6) mol.m-2.s-1. A recombinational cloning vector that carries a transcriptional lacZ reporter gene was used to characterize the controlling elements responsible for light induction. At least three distinct cis elements are present in the regulatory regions of pbsAII and psbAIII: basal promoters, comparable to Escherichia coli sigma 70 promoters in position and sequence, confer constitutive expression of the genes under both low and high light intensities; negative elements upstream of the promoters down-regulate the expression of the corresponding gene; and sequences downstream of the promoters that correspond to the untranslated leader regions of the mRNAs (+1 to +41 in psbAII and +1 to +39 in psbAIII) are responsible for increased expression under high light. When these light-responsive elements were combined with an E. coli promoter (conII) in different positions and orientations, the expression of the lacZ gene was induced 4- to 11-fold. The induction of gene expression under high light by these enhancers was position independent but orientation dependent. When the elements were combined with the conII promoter in the correct orientation, they also conferred a small but reproducible level of light-responsive expression on this E. coli promoter.

Bacterial Proteins↗
PubMed1993

The mitotic feedback control gene MAD2 encodes the alpha-subunit of a prenyltransferase.

The mad2-1 mutation inactivates the cell-cycle feedback control that prevents budding yeast cells from leaving mitosis until spindle assembly is complete. The gene product of MAD2 shows significant sequence similarity to the alpha-subunit of prenyltransferases. Here we isolate a new temperature-sensitive mad2 mutant, mad2-2ts, and find that Mad2p is required for the membrane association of Ypt1p and Sec4p, two prenylated small GTP-binding proteins involved in protein trafficking. Extracts from mad2-2ts mutant cells fail to geranylgeranylate a number of substrates at the non-permissive temperature. mad2-2ts is synthetically lethal with bet2-1, a mutation in the gene that encodes for the beta-subunit of the Ypt1p and Sec4p geranylgeranyl transferase. Therefore MAD2 and BET2 gene products may physically interact to form a geranylgeranyl transferase complex. In addition, the difference between the phenotypes of mad2-1 and mad2-2ts suggests that MAD2 has distinct roles in protein transport and the mitotic feedback control.

Calcium-Binding Proteins↗