[Research progress on the effect of zinc on behavior].
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Biomedical subjects
Publications and source records attributed to Y Q Liu.
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Diabetic states are characterized by a raised serum/islet level of long chain fatty acids and a lowered ED50 for glucose-induced insulin secretion. Prolonged culture (> 6 h) of islets with long chain fatty acids replicates the basal insulin hypersecretion. We examined this effect in rat islets cultured for 24 h with 0.25 mM oleate. Insulin secretion at 2.8 mM glucose was doubled in combination with a 60% lowered islet content of glucose-6-phosphate (G6P). Investigation of the lowered G6P showed: (a) increased glucose usage from 0.5 to 100 mM glucose with identical values measured by [2-3H]glucose and [5-3H]glucose, (c) indicating little glucose- 6-phosphatase activity, (b) unchanged low pentose phosphate shunt activity, (c) 50% increased phosphofructokinase (PFK) Vmax, (d) a normal ATP/ADP ratio, and (e) unchanged fructose 2,6 bisphosphate content. Triacsin C, an inhibitor of fatty acyl-CoA synthetase, prevented the increase in PFK activity and the lowered G6P content. These results suggest that long chain acyl-CoA mediates the rise in PFK activity, which in turn lowers the G6P level. We speculate that the inhibition of hexokinase by G6P is thus attenuated, thereby causing the basal insulin hypersecretion.
BW-Sp3 is a BW-5147-derived T cell lymphoma with limited immunogenicity since, despite regression of the majority of subcutaneous tumors, an important fraction of the animals will die from metastases. In the present study, the BW-Sp3 cells were transfected with genes encoding B7-1 or B7-2, known to be involved in the induction of T cell responses. The resulting transfectants exhibited a reduced tumorigenicity and did not cause mortality in the syngeneic recipients. Furthermore, immunization with the B7-1 or B7-2 transfectants resulted in an increased generation of cytotoxic T lymphocytes (CTL) that lysed both the transfectants and the wild-type BW-Sp3 cells. Since the B7 transfectants were completely rejected in syngeneic recipients and induced potent CTL recognizing the wild-type BW-Sp3 cells, these engineered cells were considered as candidates for immunotherapy. Vaccinations with the B7-1 or B7-2 transfectants could completely protect the animals from metastatic disease when subsequently challenged with wild-type BW-Sp3 cells. Furthermore, immunization with the B7 transfectants could prolong the survival time of mice that had been challenged intravenously with BW-Sp3 cells. Surprisingly, however, when these transfectants, as well as the wild-type BW-Sp3 cells, were used for vaccination of tumor-bearing animals, the presence of the subcutaneous BW-Sp3 tumors clearly interfered with the outcome of immunotherapy, resulting in increased malignancy, as reflected by a higher incidence of progressing tumors and a reduced survival rate. Possible implications for immunotherapy in humans are discussed.
Three new triterpenoid saponins, latifolosides F, G, H were isolated from the leaves of Ilex latifolia. Their structures were elucidated on the basis of chemical and spectral evidence. Latifoloside F was determined to be 3-O-[alpha-L-rhamnopyranosyl(1-2)]-[beta-D-glucopyranosyl(1-3)-]- alpha-L-arabinopyranosyl ilexgenin B 28-O-[alpha-L-rhamnopyranosyl(1-2)]-beta-D-glucopyranoside. Latifoloside G was 3-O-[alpha-L-rhamnopyranosyl(1-2)]-[beta-D-glucopyranosyl(1-3)-]- alpha-L-arabinopyranosyl pomolic acid 28-O-[alpha-L-rhamnopyranosyl(1-2)]-beta-D-glucopyranoside. Latifolioside H(3) was 3-O-[alpha-L-rhamnopyranosyl(1-2)]-[beta-D-glucopyranosyl(1-3)-]- alpha-L-arabinopyranosyl siaresinolic acid 28-O-[alpha-L-rhamnopyranosyl(1-2)]-beta-D-glucopyranoside.
p210bcr-abl-Related tyrosine kinase activity has been shown to cause chronic myelogenous leukemia (CML), a disease of bone marrow stem cells. Having previously demonstrated that the aptameric oligonucleotide, ODN-1, could inhibit p210bcr-abl kinase activity, the current study sought to determine if ODN-1 could selectively inhibit the growth of CML cells relative to that of normal bone marrow. ODN-1, when introduced by electroporation into peripheral blood mononuclear cells (PBMC) from patients with CML, decreased the number of committed progenitors (CML CFU-GM) by an average of 67%+/-19% (mean+/-SEM, range 28-98%). Treatment of CML PBMC with ODN-1 was also shown to decrease the number of more primitive cobblestone area-forming cells (CAFC) by 35%-87%. In contrast, there was little suppressive effect by the combination of electroporation and ODN-1 on either CFU-GM or CAFC numbers from normal donor bone marrow. These studies suggest that inhibition of p210bcr-abl protein-tyrosine kinase (PTK) activity by ODN-1 is associated with some degree of selective growth inhibition of p210bcr-abl-transformed cells. p210bcr-abl kinase inhibitory agents may be useful for the ex vivo purging of bone marrow or peripheral blood progenitor/stem cells in the setting of autologous transplantation for CML.
Diabetic states are characterized by a raised serum/islet level of triglycerides and a lowered EC50 (concentration at half-maximal stimulation) for glucose-induced insulin secretion. Culturing islets with long-chain fatty acids (FAs) replicates the basal insulin hypersecretion. In a previous study, we showed that the mechanism involved deinhibition of hexokinase by a 60% decrease in glucose-6-phosphate (G-6-P). The key event was proposed to be an increased phosphofructokinase (PFK) Vmax secondary to an upregulatory effect of the FA metabolite, long-chain acyl-coenzyme A (LC-CoA). We now show another contributory factor, a lowered content of the PFK inhibitor citrate. Citrate synthase Vmax and citrate levels were lowered 45% in rat islets cultured with 250 micromol/l oleate for 24 h. Both effects were reversed by triacsin C, an inhibitor of fatty acyl-CoA synthetase, the enzyme that generates LC-CoA. Culturing islets with high doses of glucose (16.7 mmol/l) for 48 h should also raise cytosolic LC-CoA. As predicted, citrate synthase Vmax was lowered and PFK Vmax was increased, both in a triacsin C-reversible fashion. These results show shared selected functional and biochemical properties in beta-cells of so-called glucotoxicity and lipotoxicity.
Brain function research is one of the most important projects in biological sciences. Learning and memory is one of the most advanced functions in brain. This article reviewed the effects of some neurotransmitters and neuroactive peptides on learning and memory in an attempt to stimulate the research aiming at improving learning and memory.
BACKGROUND: Large-scale partial sequencing of cDNA libraries to generate expressed sequence tags (ESTs) is an effective means of discovering novel genes and characterizing transcription patterns in different tissues. To catalogue the identities and expression levels of genes in the cardiovascular system, we initiated large-scale sequencing and analysis of human cardiac cDNA libraries. METHODS AND RESULTS: Using automated DNA sequencing, we generated 43,285 ESTs from human heart cDNA libraries. An additional 41,619 ESTs were retrieved from public databases, for a total of 84,904 ESTs representing more than 26 million nucleotides of raw cDNA sequence data from 13 independent cardiovascular system-based cDNA libraries. Of these, 55% matched to known genes in the Genbank/EMBL/DDBJ databases, 33% matched only to other ESTs, and 12% did not match to any known sequences (designated cardiovascular system-based ESTs, or CVbESTs). ESTs that matched to known genes were classified according to function, allowing for detection of differences in general transcription patterns between various tissues and developmental stages of the cardiovascular system. In silico Northern analysis of known gene matches identified widely expressed cardiovascular genes as well as genes putatively exhibiting greater tissue specificity or developmental stage specificity. More detailed analysis identified 48 genes potentially overexpressed in cardiac hypertrophy, at least 10 of which were previously documented as differentially expressed. Computer-based chromosomal localizations of 1048 cardiac ESTs were performed to further assist in the search for disease-related genes. CONCLUSIONS: These data represent the most extensive compilation of cardiovascular gene expression information to date. They further demonstrate the untapped potential of genome research for investigating questions related to cardiovascular biology and represent a first-generation genome-based resource for molecular cardiovascular medicine.
Several studies have suggested a population-wide decline in the quality of human semen during the past three decades, but the mechanism remains unclear. It was proved that damage to the DNA of germ cells would lead to mutation, and 8-hydroxydeoxyguanosine (8-OHdG), one of the major products of oxidative damage to DNA, may serve as one of the important factors to affect the sperm quality. In the present paper, 67 semen samples were collected to analyze the sperm quality (density, sperm number, motility, normal head, etc.), and 8-OHdG was measured in DNA isolated from the same sperm samples. The results showed that a significant inverse correlation exists between 8-OHdG/dG(deoxyguanosine) and sperm density (r = -0.358, p = 0.004), and between 8-OHdG/dG and sperm number (r = -0.389, p = 0.01). The results indicate that endogenous oxidative DNA damage could affect sperm quality and subsequently increase the risk of genetic defects.
BACKGROUND: The patch test has become the standard method of investigating patients with allergic contact dermatitis. Many countries have developed standard screening allergens to make patch testing more efficient. A series of the Chinese Standard Screening Allergens were studied and modified. OBJECTIVE: This study investigated the frequency of contact allergies in suspected allergic contact dermatitis and tested the practicality of the Chinese Standard Screening Patch Test Allergens. METHODS: A total of 1,135 patients suspected of having allergic contact dermatitis were patch tested. Three hundred twelve (27.5%) were men, and their age ranged from 2 to 75 years old (mean age, 34.3 years), 823 (72.5%) were women, and their age ranged from 2 to 76 years old (mean age, 33.0 years). Nanjing Medical University supplied the Chinese Standard Screening Allergens and Finn-Chamber. All patients were patch tested according to the Chinese Standard Screening Patch Test Allergens with Finn-Chamber the protocol as established by the International Contact Dermatitis Research Group (ICDRG). RESULTS: From the 1,135 patients suspected to have allergic contact dermatitis, 650 (57.3%) had at least one positive reaction. Nineteen (95%) of the Chinese Standard Screening Patch Test Allergens had positive reactions higher than 1%. Of 485 patients with negative reaction to the Standard Allergens, 106 patients were tested with other suspected contactants according to history. Thirty-nine (36.8%) had positive reactions to the contactants they provided. The total positive rate therefore increased by 3.4%. CONCLUSIONS: Our study results indicate that the Chinese Standard Screening Patch Test Allergens are suitable for use in routine clinic in China.
The availability of high quality cDNA libraries is often crucial to the successful identification and characterization of genes. The concepts and potential pitfalls of constructing cDNA libraries are presented. Various applications requiring high quality cDNA libraries are outlined, including large-scale single pass sequencing of cDNA clones to generate expressed sequence tags (ESTs) and differential screening of cDNA libraries. The usefulness of combining such approaches for the discovery of novel disease-related and cardiovascular-based ESTs (CVBest) is discussed.
In order to determine the mechanism for delayed increase in Fructose 2,6-P2 in livers of refed rats, the time course of changes in various metabolites upon refeeding NIH or high sucrose diet was investigated. Kinetics of increase in Fructose 2,6-P2 and Xylulose 5-P were similar but different from hexose 6-P or glycogen in the livers of 48 h starved rats refed with NIH diet. The increase in the Fructose 2,6-P2 level was a result of a combination of changes in Fructose 6-P,2-kinase and Fructose 2,6-bisphosphatase activity ratios, indicating dephosphorylation of the bifunctional enzyme and decreased cAMP. A similar correlation between Fructose 2,6-P2 and Xylulose 5-P and dephosphorylation was observed with refeeding high sucrose diet and also with 16 h starved rats. These kinetic results are consistent with the idea that a specific protein phosphatase 2A, activated by Xylulose 5-P, dephosphorylates Fructose 6-P,2-kinase:Fructose 2,6-bisphosphatase and also decreased protein kinase A activity, resulting in increased hepatic Fructose 2,6-P2.
The glucose-stimulated rise in Fru-2,6-P2 in liver results from xylulose 5-P activation of a specific protein phosphatase 2A which dephosphorylates Fru-6-P,2-kinase:Fru-2,6-bisphosphatase (Nishimura, M., and Uyeda, K. (1994) J. Biol. Chem. 269, 26100-26106). In order to determine the role of xylulose 5-P in regulating Fru-2, 6-P2 in liver, the effect of fatty acids, various hexoses, and hormones was examined in perfused rat liver and in intact rats. When 24-h starved rat livers were perfused with acetate, butyrate, or propionate, Fru-2,6-P2 and xylulose 5-P decreased to the same extent and at similar rates. The activity ratios of the kinase and the phosphatase changed in a reciprocal manner, indicating that the phosphorylated form of the enzyme was increased by the fatty acids perfusion. The fatty acids caused the similar changes in the metabolites and the phosphorylation state of the bifunctional enzyme in livers of fed animals. Fructose, galactose, or mannose perfusion in starved rat liver increased both Fru-2,6-P2 and xylulose 5-P and converted the bifunctional enzyme to the dephospho form. Both the Fru-2,6-P2 and xylulose 5-P levels in rats fed a high fat diet decreased over 50% compared to that in control rats. These results indicated a close correlation between Fru-2,6-P2 and xylulose 5-P levels and the phosphorylation state of fructose 6-P, 2-kinase:fructose 2,6-bisphosphatase. Fatty acid inhibition of glucose metabolism can be explained by a decrease in xylulose 5-P, which lowers xylulose 5-P-activated protein phosphatase 2A activity, resulting in more phosphorylated form of the bifunctional enzyme and consequently lower Fru-2,6-P2.
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From the dried roots of Panax ginseng two new minor dammarane saponins named koryoginsenoside-R1 and -R2 were isolated, along with fourteen known saponins. On the basis of spectral and chemical evidence, the structure of the new saponins were elucidated as 6-O-[trans butenoyl-(1-->6)-beta-D-glucopyranosyl]-20-O-beta-D- glucopyranosyl dammar-24-en-3 beta,6 alpha,12 beta,20(S)-tetrol and 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-20-O-[beta-D- glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] dammar-22-en-3 beta,12 beta, 20(S),- 25-tetrol, respectively.
16S rRNA gene, a highly conservative gene in molecular evolution, was labeled with digoxigenin-11-dUTP by PCR. Using it as a probe, we investigated the 16S rRNA gene restriction patterns (16S rRNA GRP) of S. typhi after their chromosomes were digested with Pst I. Results show that the Pst I 16S rRNA GRP appears obvious polymorphism in strains of distinctive sources. The fragments containing 16S rRNA gene are sized 7.0-26.5kb in 16S rRNA GRP of Pst I. 119 strains can be divided into 38 ribotypes. Most of the strains causing outbreaks from Dalian in 1990 and strains isolated during the pandemic from Yili, Xinjiang in 1991 have the same ribotype; some ribotypes contain epidemic strains which are from different geographic areas; some strains from sporadic cases have their unique ribotypes. We also find the 16S rRNA GRP with Pst I of S. typhimurium rather different from that of S. typhi. Data from further analysis of Pst I ribotypes by mean-linkage clustering method show that pandemic strains, outbreak strains and epidemic strains cluster at 0.55 in genetic distance; nonepidemic strains and strains from sporadic cases gather to form another cluster at 0.70 in genetic distance. Ribotype of strain 251, which was isolated forman asymptomatic carrier is different from the two clusters. The ribotype of S. typhimurium is apparently far distant, comparing with that of S. typhi.
A protein having a high-affinity binding site for [3H]mepyramine (MBP) was purified to homogeneity from rat liver membranes. The purified MBP has a single type of binding site for [3H]mepyramine with Kd value of 18.5 nM, and its molecular weight was determined to be 56,000 by SDS polyacrylamide gel electrophoresis. Amino acid sequences of twelve tryptic peptides derived from MBP are highly homologous with those of rat debrisoquine 4-hydroxylase (cytochrome P450 2D1) and other rat P450 2D subfamily members. In immunoblotting analysis, an antibody against rat P450 2D1 stained a band corresponding to MBP with Mr of 56,000; its migration position was clearly different from that of rat P450 2D1. Substrates and inhibitors of debrisoquine 4-hydroxylase potently displace [3H]-mepyramine binding to MBP. Quinine and quinidine showed 400 and 80 times, respectively, higher affinity for MBP than for debrisoquine 4-hydroxylase. These results suggest that MBP is a novel P450 2D family member.