In vivo and in vitro antiproliferative effects of antisense interleukin 10 oligonucleotides.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
M He
Publications and source records attributed to M He.
Anti-anti-idiotypic (Ab3) antibodies that bind progesterone-11alpha-bovine serum albumin differ in their combining sites from antibodies raised directly against the antigen.
Polyclonal rabbit anti-idiotypic (Ab2) antibodies raised against the antiprogesterone mAb DB3 (Ab1) were used to induce an Ab3 antiprogesterone response in BALB/c mice. While the affinity of Ab3 sera for progesterone was 10-50-times lower than that of DB3, their steroid-binding specificity showed considerable similarity to DB3. Two immunoglobulin M (IgM) Ab3 monoclonal antibodies (mAbs), 1A4 and 3B11, were obtained, both of which bound progesterone conjugated to bovine serum albumin (progesterone-BSA). 1A4 also bound free progesterone, although with low affinity and very broad cross-reactivity. Like DB3, 1A4 is encoded by a heavy-chain variable region (VH) gene segment from the small VGAM3.8 family, a restriction that is characteristic of antibodies raised against progesterone-11alpha-BSA. In contrast, 3B11 binds progesterone-11alpha-BSA but not free progesterone and is encoded by an unrelated VH gene from the J558 family. The light chain variable region (VL) of 1A4 lacks the intradomain disulphide bridge owing to replacement of CysL23 by Tyr. Both the 1A4 and 3B11 heavy chains have extremely short complementarity determining region (CDR) H3 loops, comprising three and four amino acids, respectively. Modelling of the combining site of 1A4 from the X-ray crystallographic structure of DB3 indicates that the short H3 loop is a major factor in the loss of affinity and specificity for steroid.
Amino Acid Sequence↗
Region-specific enhancement of basal extracellular and cocaine-evoked dopamine levels following constitutive deletion of the Serotonin(1B) receptor.
The behavioral effects of cocaine are enhanced following constitutive deletion of the serotonin(1B) receptor. The neural substrates mediating the enhanced response to cocaine are unknown. The present studies determined whether basal dopamine dynamics or cocaine-evoked dopamine levels are altered in projection areas of mesostriatal or mesoaccumbens dopamine neurons following serotonin(1B) receptor deletion. Male wild-type and serotonin(1B) knockout mice were implanted with microdialysis guide cannulas aimed at the dorsal striatum or nucleus accumbens. The zero net flux method of quantitative microdialysis was used to quantify basal extracellular dopamine concentrations (DA(ext)) and the extraction fraction of dopamine (E(d)), which provides an index of dopamine uptake. Conventional microdialysis techniques were used to quantify cocaine (0, 5.0, and 20.0 mg/kg)-evoked dopamine overflow. Basal DA(ext) and E(d) did not differ in striatum of wild-type and knockout mice. Similarly, cocaine-stimulated dopamine overflow did not differ between genotype. The basal E(d) did not differ in the nucleus accumbens of wild-type and knockout mice. However, DA(ext) was significantly elevated in the nucleus accumbens of knockout mice. Cocaine-evoked dopamine overflow (nM) was also enhanced in the nucleus accumbens of knockout mice. However, the cocaine-induced increase in dopamine levels, relative to basal values, did not differ between genotype. These data demonstrate that deletion of the serotonin(1B) receptor is associated with increases in basal DA(ext) in the nucleus accumbens. This increase is not associated with an alteration in E(d), suggesting increased basal dopamine release in these animals. It is hypothesized that these alterations in presynaptic neuronal activity are a compensatory response to constitutive deletion of the serotonin(1B) receptor and may contribute to the enhanced behavioral effects of psychostimulants observed in knockout mice.
Animals↗
Structural modeling and site-directed mutagenesis of the actinorhodin beta-ketoacyl-acyl carrier protein synthase.
A three-dimensional model of the Streptomyces coelicolor actinorhodin beta-ketoacyl synthase (Act KS) was constructed based on the X-ray crystal structure of the related Escherichia coli fatty acid synthase condensing enzyme beta-ketoacyl synthase II, revealing a similar catalytic active site organization in these two enzymes. The model was assessed by site-directed mutagenesis of five conserved amino acid residues in Act KS that are in close proximity to the Cys169 active site. Three substitutions completely abrogated polyketide biosynthesis, while two replacements resulted in significant reduction in polyketide production. (3)H-cerulenin labeling of the various Act KS mutant proteins demonstrated that none of the amino acid replacements affected the formation of the active site nucleophile.
3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗
Strain differences in basal and cocaine-evoked dopamine dynamics in mouse striatum.
In vivo microdialysis was used to characterize basal dopamine (DA) dynamics and cocaine-evoked DA levels in the striatum of 129/Sv-ter, C57BL/6J, DBA/2J, and Swiss-Webster mice. Basal dialysate levels of DA did not differ in the four strains tested. Similarly, the no net flux method of quantitative microdialysis revealed no difference in extracellular levels between strains. However, the in vivo extraction fraction of DA was significantly less in 129/Sv-ter (53%) mice compared with C57BL/6J (68%), DBA/2J (69%), and Swiss-Webster (67%) mice, indicating a lower rate of basal DA uptake in the 129/Sv-ter strain. Perfusion of K(+) (60 and 100 mM) through the microdialysis probe significantly increased dialysate DA levels and there was no difference between strains in the magnitude of this effect. The acute administration of cocaine (5-20 mg/kg i.p.) increased DA levels in the four strains tested. Cocaine-evoked DA levels (in nanomoles) were significantly greater in 129/Sv-ter compared with C57BL/6J, DBA/2J, or Swiss-Webster mice after administration of either 5, 10, or 20 mg/kg cocaine. However, the percentage increase in DA did not differ across strains. These data demonstrate that there are strain-related differences in basal DA dynamics in the striatum of the mouse. Basal DA uptake was reduced in striatum of 129/Sv-ter mice compared with C57BL/6J, DBA/2J, or Swiss-Webster mice. In addition, the response of DA levels to cocaine may be enhanced in 129/Sv-ter compared with C57BL/6J, DBA/2J, or Swiss-Webster mice.
Animals↗
[A primary study on distribution and binding forms of arsenic in polluted crop seeds].
The distribution, binding form and processing removal of arsenic in rice and wheat seeds were studied. The result shows that the distribution of arsenic in seed parts was uneven, as concentration in rice seed was embryo > seed capsule > chaff > endosperm, and that in wheat seed was embryo > seed capsule > endosperm. Arsenic was mainly accumulated in endosperm, and mainly in the form of protein-binding. With the removal of chaff, coarse rice bran and fine rice bran in the processing, the content of arsenic decreased by 16.51%, 12.41% and 10.26%, respectively. Similarly, with the removal of coarse wheat bran and fine wheat bran, it decreased by 22.0% and 45.6%, respectively.
Arsenic↗
The prevalence of lactase deficiency and lactose intolerance in Chinese children of different ages.
OBJECTIVE: To determine lactose metabolism and lactase activity in Chinese children of different ages, prevalence of lactase deficiency (LD), and lactose intolerance (LI). METHODS: All 1168 healthy subjects between 3 and 13 years were recruited from schools in four large cities in China. They were screened by a 25 g lactose tolerance test. Some subjects were challenged with 50 g milk powder on different days. Both indicators, the expiratory H2 concentration and intolerance symptoms, were analyzed. RESULTS: LD occurred in 38.5% of children in the 3-5 year age group, and 87% of the 7-8 year and 11-13 year old groups. The age of occurrence for LD may be at 7-8 years among Chinese children. The prevalence of LI among Chinese children was 12.2% at age 3-5 years, 33.1% at age 7-8 years, and 30.5% at age 11-13 years, respectively. CONCLUSION: The results demonstrate that LD is very common in Chinese children from these four cities. LD and LI have a dose dependent response: lactose absorption and symptoms are based on lactase activity. The relationship between breast feeding history (or the history of cow milk intake) and lactase activity among Chinese children has not been established.
Adolescent↗
[Flow cytometric 3-color analysis of circulating activated platelets and its clinical significance in ischemic cerebrovascular diseases].
OBJECTIVE: To explore the flow cytometric 3-color analysis of circulating activated platelets (CAP) and its clinical significance in ischemic cerebrovascular diseases. METHODS: The fibrinogen receptor (FIB-R) and P-selectin (CD62P) were used for molecular marker of CAP, which were analyzed by flow cytometric 3-color immunofluorescence. RESULTS: Expression of FIB-R and CD62P on the resting platelet membrane surface was very lower in normal individuals, the median of FIB-R and CD62P positive percent was 1.40% and 0.70% respectively. Platelet can be obviously activated by 0.1 micromol/L ADP, and 10.0 micromol/L ADP leaded to the peak expression of FIB-R and CD62P on the activated platelet membrane surface, FIB-R and CD62P positive percent of 87.8% and 81.34% respectively. That monoclonal antibody of the FIB-R combined with ADP activating platelets was inhibited by synthetic peptide (RGDS). The quantity of CAP with FIB-R expression was markedly higher (P < 0.01) and the amount of CAP with CD62P expression was not significantly higher (P > 0.05) in blood of 112 patients with thrombotic tendency and 120 patients with ischemic cerebrovascular diseases than in healthy individuals. The expression of CAP with FIB-R of in front and behind treatment of acute cerebral infarction continuously decreased (P < 0.05), and the quantity of CAP with FIB-R expression was related negatively to Europe stroke score (ESS) of patients with acute cerebral infarction. CONCLUSION: The FIB-R may be regarded as sensitive and specific molecular marker in detection of CAP. The level of platelet activation in vivo can be reflected accurately by flow cytometric 3-color analysis of CAP, which has an important clinical significance for the study of pathogenesis, estimation of prognosis and supervision of curative effect in ischemic cerebrovascular diseases.
Adenosine Diphosphate↗
Selection of a human anti-progesterone antibody fragment from a transgenic mouse library by ARM ribosome display.
In antibody-ribosome-mRNA complex (ARM) ribosome display, stable complexes of nascent protein, mRNA and ribosomes are produced in a eukaryotic in vitro expression system, through coupled transcription and translation of DNA lacking a 3' stop codon. Selection of the protein simultaneously captures the relevant mRNA, which is recovered as DNA by coupled reverse transcription-polymerase chain reaction (RT-PCR) performed on the intact complexes. Here, we describe the use of ARM display to select a specific human antibody fragment from a transgenic mouse library. The mice carry unrearranged gene segments of the human heavy (H) and kappa light (L) chain loci, while the endogenous murine H and kappa loci are functionally silenced; they respond to immunisation by production of fully human IgM antibodies. A library encoding human single-chain (sc) antibody (V(H)/K) fragments, in which V(H) domains and kappa light chains were combined at random by PCR, was prepared from spleen cells of transgenic mice immunised with progesterone-bovine serum albumin (BSA). Library diversity was demonstrated by sequencing. Progesterone-binding fragments were selected over five cycles of ARM display and the selected DNA cloned and expressed in Escherichia coli. Soluble V(H)/K fragments obtained in periplasmic extracts had the same specificity as ribosome-bound V(H)/K, supporting the view that folding and specificity of the displayed and soluble proteins are equivalent. The affinity of the expressed V(H)/K was approximately 10(-8) M. Sequencing showed that ARM display selected a single V(H)/V(L) combination (V(H)1-2, Vkappa4-1) and rearrangement, with a few mutational differences between clones. Monoclonal antibodies against progesterone-BSA obtained from hybridomas were encoded by the same V(H) and V(L) segments and had similar properties to the fragments obtained in vitro. The combination of ribosome display and transgenic mouse technologies is a rapid means of generating fully human antibody fragments in vitro for expression and further manipulation.
Amino Acid Sequence↗
Structural forms of phenprocoumon and warfarin that are metabolized at the active site of CYP2C9.
Possible reasons for the observed differences in metabolic behavior and drug interaction liability between the structurally similar oral anticoagulants warfarin and phenprocoumon were explored. Incubating (S)-phenprocoumon with human liver microsomes and cDNA-expressed CYP2C9 and determining its metabolism both in the absence and presence of the CYP2C9 inhibitor, sulfaphenazole, confirmed that phenprocoumon is a substrate for CYP2C9. Comparing the metabolic behavior of (S)- and (R)-warfarin, (S)- and (R)-phenprocoumon, and fixed structural mimics of the various tautomeric forms [(S)- and (R)-4-methoxyphenprocoumon, (S)- and (R)-2-methoxyphenprocoumon, (S)- and (R)-4-methoxywarfarin, (S)- and (R)-2-methoxywarfarin, and 9(S)- and 9(R)-cyclocoumarol] available to these two drugs with expressed CYP2C9 provides compelling evidence indicating that the ring closed form of (S)-warfarin and the ring opened anionic form of (S)-phenprocoumon are the major and specific structural forms of the two drugs that interact with the active site of CYP2C9. The conclusion that (S)-warfarin and (S)-phenprocoumon interact with CYP2C9 in very different structural states provides a clear basis for the significant differences observed in their metabolic profiles. Moreover, in accord with a previously established CoMFA model these results are consistent with the hypothesis that the active site of CYP2C9 possesses at least two major substrate binding sites, a pi-stacking site for aromatic rings and an ionic binding site for organic anions. An additional electrostatic binding site also appears to contribute to the orientation of coumarin analogs in the CYP2C9 active site by interacting with the C2-carbonyl group of the coumarin nucleus.
4-Hydroxycoumarins↗
Observation of Multi-TeV Gamma Rays from the Crab Nebula using the Tibet Air Shower Array.
The Tibet experiment, operating at Yangbajing (4300 m above sea level), is the lowest energy air shower array, and the new high-density array constructed in 1996 is sensitive to gamma-ray air showers at energies as low as 3 TeV. With this new array, the Crab Nebula was observed in multi-TeV gamma-rays and a signal was detected at the 5.5 sigma level. We also obtained the energy spectrum of gamma-rays in the energy region above 3 TeV which partially overlaps those observed with imaging atmospheric Cerenkov telescopes. The Crab spectrum observed in this energy region can be represented by the power-law fit dJ&parl0;E&parr0;&solm0;dE=&parl0;4.61+/-0.90&parr0;x10-12&parl0;E&solm0;3 TeV&parr0;-2.62+/-0.17 cm-2 s-1 TeV-1. This is the first observation of gamma-ray signals from point sources with a conventional air shower array using scintillation detectors.
Journal Article↗
[Effect of exogenous lactase on the absorption of lactose and its intolerance symptoms].
The objective of this study was to evaluate the effects of lactase on lactose malabsorption and its intolerance symptoms, as well as the available way to improve lactose absorption. Healthy adults with a history of lactose intolerance were screened by 25 g lactose tolerance test. The individuals with higher H2 expired and/or lactose intolerance symptoms were selected as the subjects. Subjects were challenged twice with "400 ml low fat milk" and "400 ml low fat milk + 9000Fcc lactase" separately in 3 days interval. The breath H2 concentration and intolerance symptoms were tested in 4 hours after the challenge. The results showed that exogenous lactase can significantly decrease the incidence of lactose malabsorption (the abnormal expiration of H2 decreased from 100% to 48.9%) and milk intolerance symptoms(from 51.1% to 13.3%). The results from this study demonstrate that lactose malabsorption and intolerance symptoms are resulted from the reduced enzyme activities of individuals, and the exogenous lactase can improve lactose absorption and intolerance symptoms. Lactose supplementation may be an available way to increase the dairy consumption and promote health of people.
Adolescent↗
[Study on the incidence of lactose intolerance of children in China].
1168 healthy children of 3-13 years old were selected as subjects from Beijing, Shanghai, Guangzhou and Haerbin. Total subjects were challenged by 25 gram lactose test. The breath hydrogen was determined, the symptoms of lactose intolerance were recorded. The results showed that the incidences of lactase deficiency of children of 3-5, 7-8 and 11-13 years old were 38.5%, 87.6% and 87.8% respectively. The incidences of lactose intolerance were 12.3%, 33.2% and 30.5% respectively. Lactase activity decreasing of Chinese children occurred at the age of 7-8 years old, and the symptom of lactose intolerance depended on lactose dose. But, there still are 39%-41.7% children with lactose maldigestion and 14%-16% children with intolerance symptom, after taking 50 gram milk powder (12 g lactose). The relationship between lactase activity and milk intake was not found.
Adolescent↗
Electron impact mass spectral characteristics and fragmentation pathways of isomeric tetradecadien-1-ols
Characteristics of mass spectra of isomeric tetradecadien-1-ols were investigated by electron impact mass spectrometry, and mass spectral fragmentation pathways were proposed based on collision-induced dissociation experiments and mass-analyzed ion kinetic energy spectrometry. Copyright 1999 John Wiley & Sons, Ltd.
Journal Article↗
A rapid screening and diagnosis on fragile X syndrome by PCR.
Polymerase chain reaction (PCR) technique combined with direct detection by silver staining on denaturing DNA sequencing gel was used to analyze the (CGG)n repeats within the FMR1 gene on 169 suspected patients with mental retardation and 33 kindreds of 6 fragile X families. The results showed that: (1) No PCR products were detected in 3 males in the suspected group. (2) In the fragile X family studies, the 5 male probands failed to show any PCR products. (3) Diplex PCR with the primers flanking the FRAXE locus was used to serve as an internal control for the 8 above-mentioned males and only normal products of the FRAXE locus were detected, indicating that the possibility of false negative results of the FRAXA locus could be eliminated. These findings suggested that analysis of (CGG)n repeat within the FMR1 gene by PCR technique could efficiently detect premutation carriers and that negative PCR products in mentally retarded males might highly imply the diagnosis of fragile X syndrome after the false negative results have been excluded by diplex PCR. This PCR assay is suitable for the screening and diagnosis of fragile X syndrome in a large number of populations due to its rapidity, simplicity, stability and reliability.
Alleles↗
The comprehensive evaluation on four indices of drug resistance in acute myeloid leukemia.
To study sensitivity of drug resistance indexes and resistance manner in acute myeloid leukemia (AML), MTT drug sensitivity, growth types of CFU-L in vitro, Bcl-2 antigen and Bcl-2/Bax ratio and intracellular fluorescence intensity of daunorubicin (DNR) were determined. In 62 cases of AML, the positive coincidence rate was 73% with MTT test and the negative coincidence rate was 70%. In 3 commonly used drugs, if one drug showed sensitivity, the coincidence remission rate reached 71%. In 51 cases of AML, there were 31 patients in the group of complete remission (CR), in which CFU-L of 29 patients showed independent growth. CFU-L of 2 patients showed no growth. However, there were 20 patients in the group of non-remission (NR), in which CFU-L of 14 patients showed independent growth. CFU-L of 6 patients showed non-growth pattern. Statistical analysis showed significant difference (P < 0.05). In 32 cases of AML, the expression rate of Bcl-2 was 59.55% +/- 19.56% in drug-sensitive group, and one was 77.36% +/- 11.91% in drug-resistant group, respectively (P < 0.05). At the same time, the ratio of Bcl-2/Bax was 7.50 +/- 5.04 in drug-sensitive group and one was 14.32 +/- 8.99 in drug-resistant group, respectively (P < 0.05). In 15 case of clinically drug-resistant AML, the fluorescence histogram of DNR showed left-shift of main peak (LSMP) in 12 patients. They were diagnosed as classical drug resistance. Meanwhile, 1 patient showed right-shift of main peak (RSMP) in 3 patients. They were diagnosed as re-growth drug resistance. It is concluded that MTT and CFU-L might be used for prediction of drug sensitivity or resistance when patients were on treatment. Bcl-2 and ratio of Bcl-2/Bax might be associated with the prognosis. DNR histogram could be employed for identify the pattern drug resistance. The strength and weakness of these techniques were discussed.
Adult↗
The use of microdialysis in the mouse: conventional versus quantitative techniques.
Explore the source record for details and available documents.
Animals↗
A survey of blindness and cataract surgery in Doumen County, China.
PURPOSE: To assess blindness prevalence and that caused specifically by cataract in rural southern China. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 5342 persons older than 50 years of age. METHODS: Visual acuity and eye examinations were performed in the summer of 1997 in a random sample of villages in Doumen County. Differences in blindness prevalence associated with age, gender, and education were explored using logistic regression. The survey was preceded by a pilot study in which operational methods were refined and quality assurance measures were performed. MAIN OUTCOME MEASURES: Distance visual acuity and lens status. RESULTS: Bilateral blindness (presenting visual acuity < 0.10) was found in 4.37% (95% confidence interval, 3.67%-5.06%). Blindness was associated with increasing age (P < 0.001) and with the lack of education (P < 0.01). Cataract was the principal cause of blindness in at least one eye in 61.5% of blind people, with refractive error responsible for another 10%. An estimated 40% of the cataract blind were operated on; surgical coverage was lowest among the elderly, women, and those without schooling, although not at statistically significant levels. CONCLUSIONS: Despite the increased attention given to eye care in Doumen County, blindness remains a major public health problem. Cataract surgery is reaching fewer than half of those who could benefit from it.
Aged↗