Long-term outcomes of innovative curricular tracks used in four countries.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to X M Li.
Explore the source record for details and available documents.
Gliosis is commonly observed in the CNS following tissue damage, and it also occurs in aging and in many neurodegenerative diseases. Glial fibrillary acidic protein (GFAP) accumulation is a prominent feature of astrocytic gliosis. An inhibition or delay in GFAP synthesis could mitigate scar formation and thus reduce the formation of a physical barrier. The consequence of this would be to allow neurons and oligodendrocytes to reestablish a functional environment. (-)-Deprenyl, a specific monoamine oxidase (MAO) B inhibitor, has been used as an effective antiparkinsonian drug, and it has been reported to possess neuroprotective and neurorescue properties. Using northern and slot blots to detect GFAP mRNA in C6 glioma cells, we have demonstrated that (-)-deprenyl decreases the abundance of GFAP mRNA in a time- and dose-dependent manner. The effect seems to be specific to MAO B inhibitors because (+)-deprenyl and clorgyline exhibit no effect. This study indicates therefore that (-)-deprenyl may be useful for regulating astrogliosis following CNS injury as well as in some neurodegenerative diseases.
In this study we have attempted to classify a group of North American patients with autoimmune chronic hepatitis into types I, II, and III according to the class of autoantibody present in serum, and determine the prevalence and significance of antibody to hepatitis C virus (anti-HCV). A total of 62 patients (type I, 51; type II, 3; type III, 8) were tested with first-generation enzyme-linked immunosorbent assay (ELISA)-1. Seropositive patients were assessed by second-generation recombinant immunoblot assay (RIBA)-2 and polymerase chain reaction (PCR). Our results demonstrate that 12 (19%) of the 62 patients with autoimmune hepatitis were anti-HCV ELISA-1 positive (type I, 9; type II, 1; type III, 2). Only one patient with type II autoimmune hepatitis was reactive by RIBA-2 and PCR. Eight of the 12 seropositive patients entered remission after corticosteroid therapy and seven of them became seronegative by ELISA-1. The RIBA-2 and PCR reactive patient did not respond to immunosuppressive therapy and remained seropositive. We conclude that there is a low prevalence of anti-HCV antibody in autoimmune hepatitis. Results based only on ELISA-1 anti-HCV testing can be misleading, and second-generation testing is necessary to recognize the presence of HCV infection. The fact that the only RIBA-2 reactive patient had type II autoimmune hepatitis may suggest a role for HCV infection in the pathogenesis of this condition. Nevertheless, corticosteroid therapy remains effective in those patients who are ELISA-1 seropositive, but RIBA-2 and PCR nonreactive.
Depending on the character for the Helicobacter pylori (HP) to decompose the urea by its endogenous urease, we have investigated the possibility to diagnose HP infection by 13C-urea breath test in 55 cases. Also, we compared the diagnostic results from 13C-urea breath test with those from culture, histology, and rapid urease test. The satisfied accuracy for the detection of HP infection with 13C-urea breath test was indicated.
After whole body irradiation with X-ray 5 Gy (radiation condition: 0.31 Gy.min-1, 200 kV, 10 mA, 0.5 mm Cu and 1.0 mm Al), the male rats were given ip panaxatriols 5 mg.d-1 24 h before and after irradiation for 14 d. The results showed that hypothalamic leu-enkephalin (165 +/- 12 vs 131 +/- 14 pg.mg-1), pituitary beta-endorphin (2.3 +/- 0.5 vs 1.6 +/- 0.3 ng.mg-1) contents, and serum testosterone (1.66 +/- 0.15 vs 0.82 +/- 0.23 ng.ml-1) level were decreased, while serum FSH (1.34 +/- 0.10 vs 1.99 +/- 0.10 ng.ml-1) level increased in irradiation group vs normal control. These indices approached to control levels in irradiation + panaxatriols group. These suggest that panaxatriols have protective effects on reproductive endocrine axis and promote their recovering course from the radiation injuries.
In order to investigate a more efficient effector cell than the classical LAK cell in tumor immunotherapy, anti-tumor activity of lymphokine-induced cytotoxic cell (LICC) was studied. The results showed that LICC had greater cytotoxicity to YAC-1, HL60, P815 and H22 tumor cells in vitro than the control spleen cells. In vivo, LICC revealed a prominent inhibiting effect on the growth of H22 cells. A mixture of LICC and H22 in the ratio of 100: 1 was injected subcutaneously into the subaxillary tissue of Km mice (Group 1). Tumor developed in 8% of the experimental animals within 10 weeks, while all of the control animals inoculated with H22 cells died from tumor in the same period (P < 0.001). In the other groups, H22 cells were injected as in group 1, but the LICC cells were administered through the tail vein (Group 2) or to the abdominal cavity (Group 3) once every week. In group 2, tumor developed in 25% of the experimental mice and 100% of the control mice (P < 0.001). In group 3, there was no significant difference in the frequency of tumor development between the experimental and control animals.
The effect of methylflavonolamine [4'-methyl-7-(2-hydroxy-3-isopropylamino-propoxy)-flavone hydrochloride, MFA], synthesized recently by the Shanghai Institute of Pharmaceutical Industry, on the development of atherosclerosis was studied in male New Zealand white rabbits fed cholesterol for 10 wk. MFA, 7 mg.kg-1 daily ip, did not significantly alter the serum total cholesterol, HDL, and triglyceride levels, but significantly lowered the aortic cholesterol and calcium contents. Atheromatous lesions covered 53.3 +/- 11.8% of the intimal surface of the aorta in the saline group and 11.3 +/- 2.3% in the MFA group (P < 0.01). We conclude that MFA suppresses cholesterol-induced atherosclerosis.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Using an immortalized human glomerular epithelial cell line (E71 A1), we studied the effect of endothelin-1 (ET-1), a potent vasoconstrictor peptide, on the synthesis of urokinase type plasminogen activator (u-PA) and its receptor (u-PAR). The results show that ET-1 had no effect on u-PA synthesis but induced an increase in u-PAR number (2.8 +/- 0.6 x 10(4) vs 1.2 +/- 0.5 x 10(4) sites per cell, p less than 0.001) without change in receptor affinity (280 +/- 80 pM vs 250 +/- 50 pM, NS), maximal effect being observed at 10(-7) M. Time course shows that a plateau was reached after a 24 hour incubation. ET-1 induced-increase in binding capacity was abolished by cycloheximide. ET-1 also induced an increase in u-PAR mRNA level, which was completely blocked by alpha-amanitin (5 micrograms/ml). Cycloheximide (1 microgram/ml) alone induced an increase in u-PAR mRNA level and this effect was enhanced when cycloheximide was combined with ET-1. Our data show that ET-1 can induce an increase in membrane expression of u-PAR through activation of the transcription of the u-PAR gene and de novo protein synthesis.
There are several copies of related sequences on the distal short arm of the human X chromosome and the proximal long arm of the Y chromosome which were originally detected by cross hybridization with a genomic DNA clone, CRI-S232. Recombination between two S232-like sequences flanking the steroid sulfatase locus has been shown to cause frequent deletions in the X chromosome short arm, resulting in steroid sulfatase deficiency. We now report the characterization of several S232-like sequences. Restriction mapping and sequence analysis show that each S232 unit contains 5 kb of unique sequence in addition to two elements, RU1 and RU2, composed of a variable number of tandem repeats. RU1 consists of 30 bp repeating units and its length shows minimal variation between individuals. The RU2 elements in the hypervariable S232 loci on the X chromosome consist of repeating sequences which are highly asymmetric, with about 90% purines and no C's on one strand. The X-derived RU2 elements range from 0.6 kb to over 23 kb among different individuals, accounting entirely for the observed polymorphism at the S232 loci. Although the repeating units of the RU2 elements in the nonpolymorphic S232 loci on the Y chromosome share high sequence homology with those on the X chromosome, they exhibit much higher intrarepeat sequence variation. S232 homologous sequences are found in great apes, old world and new world monkeys. In chimpanzees and gorillas the S232-like sequences are polymorphic in length.
In laboratory cultures of Drosophila melanogaster derived from an African population, the quantities of six out of seven enzymes (G6PD, IDH, GPDH, ME, MDH, PGM and ADH) were higher in Adh-FF homozygotes than they were in Adh-SS. In crosses between Adh-FF and Adh-SS flies, the differences segregated as co-dominant alleles of a single Mendelian gene closely linked, or identical, to the Adh locus. The generality of these associations was suggested by the study of a French population with a very different history and genetic background. The possibility that the associations were caused by artefacts of the immunodiffusion techniques, or to a linked inversion (In(2L)t), was excluded. Possible ways by which the Adh locus may affect the quantities of other enzymes are discussed.
Earlier work has suggested the existence of saturable and highly specific binding sites for [3H]2-phenylethylamine in rat forebrain membranes. Since monoamine oxidase (MAO) was not inhibited during the assay, the [3H]2-phenylethylamine binding may have been affected by an interaction between 2-phenylethylamine and the enzyme. This is an investigation of [3H]2-phenylethylamine binding to rat forebrain membranes in the presence of two MAO inhibitors, (-)-deprenyl and pargyline. The results show that the high affinity specific binding of [3H]2-phenylethylamine to rat forebrain membranes is inhibited by pretreatment of the membrane with the MAO inhibitors and in vivo injection of the MAO inhibitors in a concentration-dependent manner. In the presence of higher concentrations of MAO inhibitors, the specific binding of [3H]2-phenylethylamine is completely blocked, suggesting that the binding sites reported earlier represent binding to MAO-B.
The majority of patients with steroid sulfatase deficiency have a deletion of the entire STS gene located on the distal short arm of the human X chromosome; however, two patients with partial gene deletions have been identified. We now report the sequences at the breakpoints of a deletion of the 3' end of the STS gene. The deletion starts within intron 7 of the gene and extends over 150 kb downstream toward the centromere. Analysis of sequences flanking the deletion breakpoints revealed 3 bp of homology. The 3' flanking sequence provides a new probe for isolation of YAC clones and for studying patients with deletions in this region of the X chromosome.
Northern blot hybridization was performed to detect aromatic L-amino acid decarboxylase (AADC) mRNA in primary cultures of astrocytes and C6 glioma cells. The cDNA probe for rat AADC was generated by reverse transcription from rat adrenal gland total RNA and was amplified by the polymerase chain reaction method. AADC mRNA from cultured astrocytes and C6 glioma cells was present as a single band, 2.2 kbp in size, that comigrated with the RNA from rat kidney. Western immunoblot showed a single protein band at 52 kDa for AADC enzyme protein. These findings demonstrate that AADC is expressed in rat glial cells.
The effect of some selective monoamine oxidase (MAO) inhibitors on aromatic L-amino acid decarboxylase (AADC) gene expression in PC12 cells has been examined. Irreversible MAO B inhibitors [(-)-deprenyl, pargyline, and MDL 72,974A] stimulated AADC gene expression, whereas a selective irreversible MAO A inhibitor (clorgyline) and a reversible MAO B inhibitor (Ro 19-6327) had no effect. Because there is no apparent MAO B activity in PC12 cells, it is postulated that there is a novel site of action for these MAO B inhibitors and that the pharmacological profile of this site matches that of neuroprotective MAO B inhibitors. Finally, it is suggested that the stimulation of AADC gene expression may be relevant to the antiparkinsonian effects of MAO B inhibitors.
Evidence has been presented that behavioral actions of NT, inducing its neuroleptic-like action, can be explained on the basis of NT-D2 intramembrane receptor-receptor interactions in the basal ganglia, unrelated to the coexistence phenomenon, leading to reduced affinity and transduction of the D2 agonist binding site. By reducing selectively D2 receptor transduction at the pre- and postsynaptic level, the NT receptor appears capable of switching the DA synapses towards a D1 receptor-mediated transduction, illustrating how receptor-receptor interactions can increase the functional plasticity of central synapses (FIG. 12).
The effect of carboxyethylgermanium sesquioxide (Ge-132) on cultured neonatal rat myocytes and isoproterenol injured myocytes was studied. The results showed that Ge-132 (0.01 mmol.L-1 and 1 mmol.L-1) increased the incorporation of both [3H]-TdR and [14C]-UR, reduced the membrane lipid fluidity and inhibited the release of the cytoplasmic enzyme lactate dehydrogenase (LDH). Exposure of the myocytes to isoproterenol 0.5 mmol.L-1 for 6 hours resulted in 5-fold release of LDH compared with the control. All myocytes ceased beating. Ultrastructurally, severe sarcolemmal and mitochondrial damage was evident. When the cells were pretreated with Ge-132 before the addition of isoproterenol, the increased LDH release was inhibited significantly, and preservation of beat and ultrastructure of myocytes was observed. In addition, the activity of superoxide dismutase (SOD) was elevated by Ge-132. All the effects of Ge-132 were dose-related. The results indicate that Ge-132 may improve the metabolism of cultured neonatal rat myocytes and protect myocytes from isoproterenol-induced injury.