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Biomedical subjects

N Li

Publications and source records attributed to N Li.

At least 343 records · Page 19Linked to original sources
PubMed1995

A study of growth kinetics of the flocs from Schizosaccharomyces pombe.

Inducing yeast cells to self-flocculate could be considered a cell immobilization method. The growth kinetics of the flocs from Schizosaccharomyces pombe was studied in an experimental suspended-bed bioreactor with starch hydrolysate obtained by two-stage enzymatic hydrolysis. It was discovered that a limited oxygen supply was necessary during continuous ethanol fermentation with yeast flocs. The oxygen supplied was a kind of limited substrate effecting on the floc growth. Further, a kinetic model describing this floc growth was proposed.

Cell Division↗
PubMed1995

Dopaminergic (4aR,10bS)-cis- and (4aS,10bS)-trans-octahydrobenzo[F]quinolines have similar pharmacophores.

The structures and absolute configurations of two N-phenethyl substituted cis- and trans-octahydrobenzo[f]quinolines were determined by X-ray crystallography. The absolute configurations of the enantiomers that have high affinity for dopaminergic receptors were found to be (4aR,10bS) and (4aS,10bS) for the (-)-cis- and (-)-trans-8,9-dihydroxy substituted compounds. This is consistent with previous results for a dopamine agonist pharmacophore. MM2-87 calculations for a cis isomer, which has two alternative chair conformations of the piperidine ring, indicated that the preferred conformer is the same as that observed in the crystal structure. Superposition of the more active cis and trans enantiomers showed that the three dimensional orientations of the phenyl ring and the ammonium group are similar in the two geometrical isomers. The cis isomer, however, has steric bulk out of the plane of the molecule and this appears to result in a loss of agonist efficacy. The addition of the N-phenethyl group to the 7-OH and 7,8-diOH cis compounds, however, appears to be sufficient to restore high affinity for dopaminergic receptors unlike previously synthesized cis compounds. These cis compounds, however, appear to be mixed agonist/antagonists or antagonists on functional assays of dopaminergic activity.

Benzoquinones↗
PubMed1995

[Cloning and analysis of prophage PBSX repressor gene from Bacillus subtilis].

The repressor gene and its allele--a temperature sensitive mutant have been cloned from the defective prophage PBSX of Bacillus subtilis by means of PCR technique. The characterization of these sequences suggest that wild-type and mutant gene have the same open reading frame, which probably encode a repressor protein of 113 amino acids, and the putative promoter region and ribosome binding sites within the sequences have also been identified. The results from complementation experiments demonstrate that repressor encoded by wild-type gene is capable of blocking the temperature-shift to induce PBSX prophage in Bacillus subtilis.

Amino Acid Sequence↗
PubMed1994

A region in Shc distinct from the SH2 domain can bind tyrosine-phosphorylated growth factor receptors.

Shc is a ubiquitously expressed Src homology 2 (SH2) domain protein that can transform fibroblasts and differentiate PC12 cells in a Ras-dependent fashion. Shc binds a variety of tyrosine-phosphorylated growth factor receptors presumably via its carboxyl-terminal SH2 domain. We cloned a fragment of Shc when screening a bacterial expression library with tyrosine-phosphorylated epidermal growth factor (EGF) receptor. Surprisingly, this fragment encodes the amino terminus of Shc, a region that has no significant similarity to an SH2 domain. When expressed as a glutathione S-transferase fusion protein, this amino-terminal domain binds to autophosphorylated EGF receptor, as well as HER2/neu and TrkA receptors. This fragment acts like an SH2 domain in that it does not bind non-phosphorylated EGF receptor or EGF receptor with all tyrosine phosphorylation sites mutated or deleted. Our data define a novel domain in Shc that has the potential to interact with growth factor receptors and other tyrosine-phosphorylated proteins.

3T3 Cells↗
PubMed1994

Childhood cancer incidence in relation to distance from the former nuclear testing site in Semipalatinsk, Kazakhstan.

Rates of childhood cancer between 1981 and 1990 in the 4 administrative zones of Kazakhstan were studied to assess the relationship, if any, with distance from nuclear testing sites. Risk of various cancers among children aged 14 years or younger were estimated in relation to distance from (1) a site where testing in air was performed before 1963, (2) a site where underground testing took place thereafter, and (3) a reservoir, known as "Atom Lake," created by 4 nuclear explosions in 1965. Risk of acute leukaemia rose significantly with increasing proximity of residence to the testing areas, although the absolute value of the risk gradient was relatively small. The relative risk for those living less than 200 km from the air-testing site was 1.76 compared with those living 400 km or more away from the site. Similar relative risks were observed for the underground site and "Atom Lake." There was also some evidence of increased risk of brain tumours in association with proximity to the test sites. In 2 of the 4 zones studied, there was substantial regional variation in acute leukaemia rates which was not attributable to distance from the test site. The findings may be affected by potential confounders, notably urban/rural status and ethnic factors.

Adolescent↗
PubMed1994

Nonsense mutations in human transcobalamin II deficiency.

Reverse transcription-polymerase chain reaction has been used to amplify, clone and sequence transcobalamin II (TC II) cDNA from fibroblasts of three unrelated TC II deficient patients who had undetectable TC II protein and mRNA in their fibroblasts (Li et al., Biochem. J, 301, 585-590, 1994). One child of a consanguineous marriage contained a single nucleotide deletion at position 258 in both alleles, while the child from unrelated parents revealed a nonsense mutation at position 1206 in one allele and a single nucleotide deletion at position 483 in the other allele. Both the single nucleotide deletion mutations caused a frameshift and introduced a premature termination codon (indirect nonsense mutations). No mutation was detected in TC II cDNA from the third patient. Based on these results we suggest that TC II deficiency due to lack of TC II protein/mRNA in these patients is due to heterogeneous types of nonsense mutations.

Alleles↗
PubMed1994

Polymorphism of human transcobalamin II: substitution of proline and/or glutamine residues by arginine.

The sequence of transcobalamin II (TC II) cDNA amplified from human fibroblast and colon adenocarcinoma (Caco-2) and the electrophoretic mobility of TC II secreted by these cell lines were analyzed to get some insights into the structural basis for the expression of various polymorphic forms of human TC II. Based on relative anodic mobilities of TC II phenotypes expressed in human serum, TC II expressed in the fibroblast cell line studied and Caco-2 cells were assigned as the MX (medium/extremely slow) and S (slow) types, respectively. Nucleotide sequence analysis of TC II cDNA amplified from these cells revealed that residues Arg and Arg, Gln and Arg, and Gln and Pro were present at positions 234 and 259, respectively, in TC II alleles encoding the X, S and M types. Based on these results, we suggest that differences in the anodic mobilities of the various polymorphic forms of TC II such as the X, S and M types are due to charge difference on the protein caused by the replacement of uncharged residues by arginine at positions 234 and/or 259.

Arginine↗
PubMed1994

Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway.

Activation of growth factor receptors results in tyrosine autophosphorylation and recruitment of SH2 domain-containing effectors, including Grb2. Grb2 recruitment mediates activation of the Ras nucleotide exchanger Sos by an unknown mechanism. To examine the role of membrane recruitment, we prepared Sos derivatives containing either myristoylation or farnesylation signals. This resulted in plasma membrane targeting of Sos and stimulation of the Ras signaling pathway, including ERK and AP-1 activities leading to oncogenic transformation. Sos derivatives with nonfunctional myristoylation or farnesylation sequences were inactive. Farnesylation of Sos also activated Ras signaling in yeast. In both mammalian cells and yeast, membrane-targeted Sos derivatives lacking the C-terminal region were considerably more active. Therefore, targeting of Sos to the plasma membrane in the vicinity of Ras appears to be the primary mechanism leading to activation of the Ras pathway. A secondary mechanism could involve relief of the inhibitory effect of the Sos C-terminal region.

3T3 Cells↗
PubMed1994

Expression of transcobalamin II mRNA in human tissues and cultured fibroblasts from normal and transcobalamin II-deficient patients.

Transcobalamin II (TCII) is an important plasma transporter of cobalamin (Cbl; vitamin B12). In the present study, TCII gene expression in human and rat tissues and in the fibroblasts of patients with TCII deficiency was investigated. Northern-blot analyses revealed expression of TCII mRNA in many human and rat tissues. In humans, this was 14-fold higher in the kidney than in liver, whereas in the rat the levels of expression were similar in the kidney and liver. Southern-blot analysis of genomic DNA from several species revealed sequence similarity in TCII across species. Metabolic labelling and ribonuclease protection assay revealed a 43 kDa TCII protein and a fully protected TCII mRNA band in normal fibroblasts but not in fibroblasts from three TCII-deficient patients. Southern-blot analysis of genomic DNA from all these fibroblasts revealed identical restriction patterns on BamHI, HindIII, KpnI, MspI and EcoRI digestion. On the basis of these results, we suggest that TCII is expressed in multiple tissues, and its level of expression in tissues varies within the same and across species. Furthermore, the TCII deficiency characterized in this study is due to the absence of TCII protein which in turn is due to the absence or extremely low levels of its mRNA and not to detectable gross alterations in the gene structure.

Animals↗
PubMed1994

Deletion of the carboxyl-terminal region of 1-aminocyclopropane-1-carboxylic acid synthase, a key protein in the biosynthesis of ethylene, results in catalytically hyperactive, monomeric enzyme.

1-Aminocyclopropane-1-carboxylic acid (ACC) synthase is a key enzyme regulating biosynthesis of the plant hormone ethylene. The expression of an enzymatically active, wound-inducible tomato (Lycopersicon esculentum L. cv Pik-Red) ACC synthase (485 amino acids long) in a heterologous Escherichia coli system allowed us to study the importance of hypervariable COOH terminus in enzymatic activity and protein conformation. We constructed several deletion mutants of the gene, expressed these in E. coli, purified the protein products to apparent homogeneity, and analyzed both conformation and enzyme kinetic parameters of the wild-type and truncated ACC syntheses. Deletion of the COOH terminus through Arg429 results in complete inactivation of the enzyme. Deletion of 46-52 amino acids from the COOH terminus results in an enzyme that has nine times higher affinity for the substrate S-adenosylmethionine than the wild-type enzyme. The highly efficient, truncated ACC synthase was found to be a monomer of 52 +/- 1.8 kDa as determined by gel filtration, whereas the wild-type ACC synthase, analyzed under similar conditions, is a dimer. These results demonstrate that the non-conserved COOH terminus of ACC synthase affects its enzymatic function as well as dimerization.

Amino Acid Sequence↗
PubMed1994

Copper complexation by 3-hydroxypyridin-4-one iron chelators: structural and iron competition studies.

Clinical trials of 1,2-dimethyl-3-hydroxypyridine-4-one (1) as an orally available iron chelator are presently underway in several centers. Discrepant reports of toxicity in human and animal studies have stimulated debate on the role of iron status and the availability of iron for chelation relative to other essential elements like copper in determining the clinical effects of 1. Therefore, we investigated the ability of 1, its 1,2-diethyl analog 2, and their iron chelates to complex copper. Both compounds formed tetracoordinate 2:1 Cu(II) complexes which X-ray structure analysis showed to be planar and coordinated through the oxygen atoms of the hydroxy ketone functionality. Potentiometric analysis revealed that these complexes dominated at physiological pH, although between pH 6 and 7 approximately equal amounts of the mono and bis complexes of Cu with 1 were present at equilibrium. Comparing the stepwise formation constants deduced from the stability constants of these complexes (log beta 2 = 21.7 +/- 0.8 (1) and 20.2 +/- 2.0 (2)) with those of their Fe(III) complexes (Motekaitis,R.J.;Martell,A.E.Inorg.Chim.Acta 1991, 183,71-80) leads to a prediction of insignificant copper complexation when equimolar iron is present and dissociation products are thermodynamically unimportant. However, displacement of Fe3+ occurred from both complexes with stoichiometric amounts of Cu2+, implicating the participation of metal hydrolysis products in the equilibria. We conclude that Cu(II) complexes of the 3-hydroxypyridin-4-one chelators are stable under physiological conditions and that copper can effect displacement of iron by these agents under circumstances where hydrolysis of the metals is important.

Antithyroid Agents↗
PubMed1994

Prevalence of coronary heart disease indicated by electrocardiogram abnormalities and risk factors in developing countries.

A cross-sectional population survey was carried out in 15 population groups (ethnicity includes Melanesian, Polynesian, Micronesian, Asian Indian and Chinese) in 9 developing countries: Fiji, Nauru, Kiribati, Cook Island, Niue, Western Samoa, New Caledonia, Mauritius and China (Beijing) in 1978-1987. The total sample included 4594 men and 4988 women aged 35-59 years. The aim of study is to report the prevalence of coronary heart disease (CHD) as indicated by ECG Minnesota coding, and risk factor levels and to describe the individual and ecological relationship between CHD prevalence and CHD risk factors among different ethnic groups in developing countries. Mauritians had the highest prevalence of CHD of these countries. Total serum cholesterol concentration and the prevalence of CHD were higher in Mauritius Chinese than in Beijing Chinese. Mean total cholesterol was lower than or equal to 5.2 mmol/l (200 mg/dl) in all population groups, except in Mauritians. Hypertensive subjects in most populations had a low cholesterol concentration. The prevalence of hypertension varied from 7 to 35% and mean body mass index (BMI) from 22.9 to 37.0 kg/m2. Smoking was more common in men (36-82%) than women (0.8-65%). Multiple logistic regression analysis using individuals as a unit of analysis showed that cholesterol and systolic blood pressure were significant independent predictors of CHD prevalence. When fasting or 2 hr post-load blood glucose was included in the model total cholesterol was no longer significant in men but remained significant in women. Ecological analysis using populations as units of analysis showed that the combination of several CHD risk factors could explain about 90% of the interpopulations variance of the CHD prevalence in women. The best models were those where 2 hr post-load glucose was included. Our study has demonstrated that the total cholesterol concentration of the population was consistent with the prevalence of CHD in the population. A considerable proportion of the variation in CHD prevalence across populations in developing countries can be explained by well-known risk factors. These data support the concept that retaining traditional balanced dietary habits and limiting salt intake together with avoiding smoking use are important activities for the prevention of cardiovascular disease (CVD) in developing countries.

Adult↗
PubMed1994

Identification of two mutant alleles of transcobalamin II in an affected family.

Transcobalamin II (TC II) deficiency is a rare autosomal recessive disease leading to cobalamin (Cbl; Vitamin B12) deficiency characterized by failure to thrive, megaloblastic anemia, impaired immunodefence and neurological manifestations. By means of Southern blotting and sequence analysis of TC II cDNA amplified from fibroblasts of an affected child and his parents, we have identified two mutant TC II alleles, one with a gross deletion and the other with a 4 nucleotide deletion. Both the mutations caused TC II mRNA and protein deficiency and hence defective plasma transport of Cbl and the development of Cbl deficiency in the affected child. The present study has identified molecular defects that cause TC II deficiency and lead to intracellular Cbl deficiency in humans.

Alleles↗
PubMed1994

16S ribosomal DNA sequences of anaerobic cocci and proposal of Ruminococcus hansenii comb. nov. and Ruminococcus productus comb. nov.

The 16S ribosomal DNA sequences of representative members of the family Peptococcaceae were determined. The members of the family examined were divided into the following four phylogenetic groups: Peptococcus niger ATCC 27731T (T = type strain), the Sarcina-Peptostreptococcus anaerobius group, the ruminococcus-coprococcus group, and the peptostreptococcus group. Peptococcus niger, the type species of the family, was not related to other members of the family. Peptostreptococcus anaerobius ATCC 27337T, the type strain of the type species of the genus Peptostreptococcus, was closely related to Clostridium sordellii NCIB 10717T (level of sequence similarity, 85%). Sarcina ventriculi GIFU 7886, a spore-forming anaerobic gram-positive coccus, clustered with Clostridium perfringens ATCC 13124T at a similarity value of 91%. Members of the Sarcina-Peptostreptococcus anaerobius group clustered with clostridia at similarity values ranging from 85 to 91%. The type strains of Peptostreptococcus prevotii, Peptostreptococcus asaccharolyticus, Peptostreptococcus micros, and Peptostreptococcus magnus clustered at levels of sequence homology of 84 to 93%. This cluster was not included in the Peptococcus niger group or the Peptostreptococcus anaerobius group. Thus, these members of the genus Peptostreptococcus should be separated from the other members of the genus and also from members of the family Peptococcaceae. The sequence of Peptostreptococcus productus ATCC 27340T was different from the sequences of Peptostreptococcus anaerobius and Peptococcus niger. The sequence of Streptococcus hansenii ATCC 27752T, a strictly anaerobic strain, was different from the sequences of other streptococci; this strain clustered with Peptostreptococcus productus, coprococci, and ruminococci. Several phenotypic characteristics of Streptococcus hansenii ATCC 27752T were similar to characteristics of ruminococci.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaerobiosis↗
PubMed1994

[Overexpression of c-erbB-2 proto-oncogene product in chondrosarcomas].

The c-erbB-2 proto-oncogene plays an important role in the regulation of cellular proliferation and differentiation. Overexpression of c-erbB-2 proto-oncogene product in 40 cases of chondrosarcomas was investigated using ABC immunoperoxidase method. Overexpression of c-erbB-2 product was present in 36/40 (90%) chondrosarcomas and in 1/9 (11%) benign cartilage tumors. Normal cartilage tissue gave negative results. These findings indicate that c-erbB-2 proto-oncogene product has practical value in diagnosing chondrosarcomas. c-erbB-2 positive grading showed a significant inverse correlation with the histopathological grading. Chondrosarcomas with high histological grade and poor differentiation showed a bias toward a decline in expression of c-erbB-2 product. The c-erbB-2 proto-oncogene product may be used as a differentiation marker.

Adult↗