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Biomedical subjects

L Lin

Publications and source records attributed to L Lin.

At least 217 records · Page 12Linked to original sources
PubMed1998

[Application of simple OMA system for rapid spectrochemical quantitative analysis to steel sample composition].

In this paper, the experimental method and characteristic of a simple optical multichannel analyzer (OMA) system used for rapid spectrochemical quantitative analysis was introduced. Mangangese and chromium contents in different steel samples were measured. The reliability of experimental results was discussed according to the mathematical statistics theory. Analytical results were compared with those of chemical and ICP analysis.

English Abstract↗
PubMed1998

[Research of eximer laser-excited fast speed spectrochemical analysis].

Experimental method including XeCl eximer Laser-excited, optical multichannel analyzer (OMA) combined with the simultaneous spectrum widen technique was introduced in this paper. We programed data acquisition software and tested alloy-steel sample. The acquisition result of 150nm simultaneous spectrum was showed. The charaterics and significances of our research were discussed.

English Abstract↗
PubMed1998

[A kind of method for measuring absorbance spectrum with dual beam light and one detector].

A kind of method of measuring spectral transmittivity with source compensated is introduced in this paper. It detects simultaneously intensity of source and transmission light with dual light road and one detector by means of the characters of selective frequence amplifing and coherent detection of a lock-in amplifier. The experimental result shows that the method is excellent on overcoming shake of a source and improving signal-to-noise ratio.

English Abstract↗
PubMed1998

Betaseron.

Betaseron, an analogue of human beta-interferon where serine was genetically engineered to substitute for cysteine at position 17, is produced in E. coli. The molecule is a small polypeptide of 165 amino acids with a single disulphide bond, and is non-glycosylated. The site-specific substitution was made to obtain a product that is more stable upon storage. Similar to native IFN-beta, Betaseron is hydrophobic in nature and has been shown to have the same panel of biological activities which includes antiviral activity against a variety of viruses, inhibition of cell growth, activation of natural killer cells, and binding to interferon receptors on the cell surface. Betaseron has been tested in a wide variety of clinical settings since 1983. The pivotal trial for the treatment of relapsing-remitting multiple sclerosis began in 1988. A PLA was filed for this indication in 1992 by Berlex and Chiron, and FDA approval was received in 1993. Betaseron is synthesized in E. coli and deposited as inclusion bodies. The manufacturing process involves solubilization and reduction of the insoluble protein, followed by purification by organic extraction, cystine oxidation and size exclusion chromatographic steps. The purified Betaseron is formulated with human serum albumin to maintain solubility at neutral pH. The complete primary sequence of Betaseron was verified by amino and carboxy-terminal sequence analysis, peptide mapping, amino acid analysis and fragment analysis after chemical cleavages. Overlapping amino acid sequence information confirmed that the amino acid sequence is the same as predicted by the DNA sequence. The amino-terminal methionine of Betaseron is removed after synthesis in E. coli. An intramolecular disulphide bond between Cys 31 and Cys 141 formed during the manufacturing process is routinely confirmed by peptide map analysis. The purity of Betaseron is assessed using a panel of analytical methods including non-reducing and reducing SDS-PAGE and reversed phase HPLC analysis where minor product-related components can be identified. These minor species were characterized with respect to their biological and biochemical properties, and identified using a variety of approaches including construction of additional, beta-interferon analogs. There is significant redundancy in the release testing of Betaseron. The amount of characterization information available on this relatively simple molecule along with the extensive manufacturing experience would suggest that some redundant testing could be eliminated for this well-characterized protein.

Amino Acid Sequence↗
PubMed1997

Identification of the mouse homologue of human discs large and rat SAP97 genes.

The human homologue of the Drosophila discs large (dlg) tumor suppressor gene encodes a 926 amino acid protein, hDlg, which is a member of the MAGUK (Membrane Associated GUanylate Kinase homologues) family of proteins. To facilitate the development of murine model system for functional studies in vivo, the primary structure of the mouse homologue of hDlg has been determined. Dlgh1 encodes a approximately 5.5 kb transcript that is ubiquitously expressed in murine tissues. Mouse mDlg is a 927 amino acid protein that is 95% identical to hDlg and 94% identical to rat synapse associated protein, SAP97. The unusually high conservation of the primary structure of murine and human Dlg proteins across their distinct protein domains suggests a conserved function in vivo.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Human homologue of the Drosophila discs large tumor suppressor binds to p56lck tyrosine kinase and Shaker type Kv1.3 potassium channel in T lymphocytes.

Human homologue of the Drosophila discs large tumor suppressor protein (hDlg) belongs to a newly discovered family of proteins termed MAGUKs that appear to have structural as well as signaling functions. Consistent with the multi-domain organization of MAGUKs, hDlg consists of three copies of the PDZ (PSD-95/Discs large/zO-1) domain, an SH3 motif, and a guanylate kinase-like domain. In addition, the hDlg contains an amino-terminal proline-rich domain that is absent in other MAGUKs. To explore the role of hDlg in cell signaling pathways, we used human T lymphocytes as a model system to investigate interaction of hDlg with known tyrosine kinases. In human T lymphocyte cell lines, binding properties of hDlg were studied by immunoprecipitation, immunoblotting, and immune complex kinase assays. Our results show that protein tyrosine kinase activity is associated with the immunoprecipitates of hDlg. Immunoblotting experiments revealed that the immunoprecipitates of hDlg contain p56lck, a member of the Src family of tyrosine kinases. The specificity of the interaction is demonstrated by the lack of p59fyn tyrosine kinase and phosphotidylinositol 3-kinase in the hDlg immunoprecipitates. Direct interaction between hDlg and p56lck is demonstrated using glutathione S-transferase fusion proteins of hDlg and recombinant p56lck expressed in the baculovirus-infected Sf9 cells. The p56lck binding site was localized within the amino-terminal segment of hDlg containing proline-rich domain. In addition, we show in vivo association of hDlg with Kv1.3 channel, which was expressed in T lymphocytes as an epitope-tagged protein using a vaccinia virus expression system. Taken together, these results provide the first evidence of a direct interaction between hDlg and p56lck tyrosine kinase and suggest a novel function of hDlg in coupling tyrosine kinase and voltage-gated potassium channel in T lymphocytes.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Medial fetal ventral mesencephalon: a preferred source for dopamine neuron grafts.

Currently, fetal tissue transplantation into patients with Parkinson's disease utilizes the entire ventral mesencephalon (VM) as donor tissue. However, the resulting mixture of cell types contains a relatively low proportion of therapeutically relevant dopamine (DA) neurons. We show that differential dissection of a medial region of embryonic day 14 rat VM yields a significantly higher proportion of DA neurons (8-10%) than is found in lateral VM (2%) or whole VM (4-5%). Medial VM also contained a larger number of the specific subpopulation of DA neurons (aldehyde dehydrogenase-positive; AHD) that project to dorsolateral motor region of the striatum. Selective dissection of fetal medial VM selectively enriches DA neurons in cell preparations useful for transplantation in Parkinson's disease.

Aldehyde Dehydrogenase↗
PubMed1997

Large fragment of the probasin promoter targets high levels of transgene expression to the prostate of transgenic mice.

BACKGROUND: Androgen regulation and prostate-specific expression of targeted genes in transgenic mice can be controlled by a small DNA fragment of the probasin (PB) promoter (-426 to +28 base pairs, bp). Although the small PB fragment was sufficient to direct prostate-specific expression, the low levels of transgene expression suggested that important upstream regulatory sequences were missing. METHODS: To enhance transgene expression, a large fragment of the PB promoter (LPB, -11,500 to +28 bp) was isolated, linked to the bacterial chloramphenicol acetyl transferase (CAT) gene, and microinjected into CD1 mouse oocytes to generate transgenic mouse lines. RESULTS: As shown by the immunohistochemical studies, CAT gene expression was restricted to the prostatic epithelial cells in a tissue-specific manner. High levels of CAT gene expression were observed in two of the six LPB-CAT transgenic lines. In Line 1, developmental regulation of LPB-CAT was detected early, from 1 to 4 weeks of age, with the activity of CAT increasing from 3 to 40,936 dpm/min/mg protein. Upon sexual maturation and elevated serum androgen levels (7 weeks of age), a further 18-fold rise in CAT activity occurred. Hormone ablation by castration in mature mice dramatically reduced transgene expression, whereas treatment with androgens returned LPB-CAT expression to precastration levels. In contrast, treatment with glucocorticoids had no significant effect on CAT gene expression. Zinc treatment of the castrated animals also increased LPB-CAT expression three- to four-fold in two prostatic lobes. CONCLUSIONS: This study demonstrates that important regulatory DNA sequences located in the LPB fragment contribute to tissue-specific expression and greatly increase levels of transgene expression induced by androgens and zinc.

Aging↗
PubMed1997

Cloning and characterization of the Neisseria meningitidis rfaC gene encoding alpha-1,5 heptosyltransferase I.

We cloned and characterized the Neisseria meningitidis rfaC gene which encodes an enzyme, alpha-1,5 heptosyltransferase I, involved in the synthesis of the deep-core of the lipooligosaccharide. The N. meningitidis rfaC mutant, obtained by an allelic exchange, produced lipooligosaccharide which migrated faster in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the lipooligosaccharide isolated from the wild-type N. meningitidis. The N. meningitidis rfaC mutant was not affected by growth in a rich microbiological medium and did not show any defect in adhesion to epithelial cell lines. Conversely, the rfaC mutant was attenuated in the infant rat model of meningococcemia, thus confirming the importance of intact lipooligosaccharide in the virulence of N. meningitidis.

Amino Acid Sequence↗
PubMed1997

A point mutation in the glucose-dependent insulinotropic peptide receptor confers constitutive activity.

The glucose-dependent insulinotropic peptide receptor (GIP-R) is a member of the secretin and parathyroid hormone (PTH) family of seven transmembrane-spanning receptors. Point mutations of a histidine at the junction between the first intracellular loop and the second membrane-spanning domain and a threonine in the sixth membrane-spanning domain of the human PTH-receptor have been reported to be associated with constitutive activation of the PTH receptor in Jansen-type metaphyseal chondrodysplasia. In this study, we explored whether such mutations in the GIP-R might similarly induce constitutive, ligand-independent activation of the receptor. Single amino acid substitutions in the GIP receptor were made by site-directed mutagenesis and receptor binding and cAMP levels were measured in transfected human embryonal kidney cell line (L293). Mutation of the threonine at position 340 in the sixth transmembrane spanning domain to proline (T340P) led to agonist-independent constitutive activity and exhibited a four-fold increase in basal cAMP level as compared to the wild-type GIP-R. The increase in cAMP level in T340P mutant was proportional to the amount of transfected plasmid and corresponded to the receptor number on the cell surface. Despite its high basal cAMP level, the T340P mutant could be further stimulated by GIP, with maximal cAMP generation comparable to the wild-type receptor. The change of amino acid histidine at position 169 to arginine (H169R), however, behaved like the wild type receptor and did not possess constitutive activity. These results illustrate that a point mutation of threonine to proline at position 340 results in constitutive activation of the GIP receptor, without affecting its sensitivity to agonist stimulation.

Amino Acid Sequence↗
PubMed1997

Comparisons of the effects of enterostatin on food intake and gastric emptying in rats.

The effects of central and peripheral administration of enterostatin (ENT) on food intake and gastric emptying of a non-nutrient liquid meal have been studied in rats. Intraperitoneal and intragastric administration of ENT at a dose of 120 nmol suppressed the intake of a high-fat diet but failed to inhibit gastric emptying in Sprague-Dawley (SD) rats. Intracerebroventricular (i.c.v.) ENT (1 nmol) reduced intake of a high-fate diet in Osborne-Mendel (OM) and SD rats but not in S5B/Pl rats, whereas it decreased gastric emptying in S5B/P1 and SD rats but not in OM rats. The data suggest that although central ENT may reduce gastric emptying rate, this effect is not related to the inhibitory effect of ENT on food intake.

Animals↗
PubMed1997

Termination and suppression of idiopathic left ventricular tachycardia by diltiazem.

Idiopathic left ventricular tachycardia is known to be responsive to verapamil in many cases. However, the role of other calcium-channel blockers, such as diltiazem, in treating this specific type of ventricular tachycardia is unknown. We report a case of idiopathic left ventricular tachycardia in a patient with a structurally normal heart, which was terminated and suppressed in the electrophysiology laboratory by a single dose of diltiazem intravenously, and was subsequently suppressed long-term with sustained-release diltiazem. Our finding suggests that idiopathic left ventricular tachycardia may be managed effectively with diltiazem in both the acute and chronic settings.

Adult↗
PubMed1997

Sequence-based association analysis of HLA class I and II alleles in Japanese supports conservation of common haplotypes.

Alleles of HLA-A, B, C, DRB1, DQB1, and DPB1 loci were fully determined in 117 healthy Japanese. A*2402, A*3303, A*1101, A*0201, B*4403, B*5201, Cw*0102, Cw*1403, Cw*0304, Cw*0702, Cw*0801, and Cw*1202 showed frequencies of over 10%. Multi-locus haplotype frequencies were estimated by the maximum likelihood method. Strength of association between C and B loci was comparable with that between DRB1 and DQB1 loci. Alleles unidentified by a serological method and having very similar nucleotide sequences (A2: A*0201, A*0206, A*0207, B61: B*4002, B*4006) were carried by different haplotypes. Several frequent five-locus haplotypes were identified including A*3303-Cw*1403-B*4403-DRB1(*)1302-DQB1(*)0604, and A*2402-Cw*1202-B*5201-DRB1(*)1502-DQB1(*)0601. These sequence-based haplotypes corresponded to serology-based common haplotypes which have already been described in Japanese. These findings indicate that common HLA haplotypes consist of particular sets of HLA alleles and that these haplotypes have been conserved through recent human evolution.

Alleles↗
PubMed1997

Chronic ICV enterostatin preferentially reduced fat intake and lowered body weight.

The pancreatic peptide enterostatin will acutely reduce fat intake in rats provided a choice of diets. Chronic ICV infusions of enterostatin suppress the intake of high fat diet. However, the effects of chronic ICV enterostatin on diet choice has not previously been studied. To investigate this, enterostatin (0.5 microgram/h) or artificial cerebrospinal fluid (CSF) was infused for 9 days into the lateral ventricle of rats adapted to a two-choice high-fat (HF) and low-fat (LF) diet regime. Enterostatin reduced intake of HF diet with the maximum depression at day 4, but there was no compensatory increase in LF intake. The body weight of enterostatin-infused rats declined. This was associated with a reduction in fat pad and liver weights compared to the CSF-infused control rats. Serum triglycerides and insulin were decreased and corticosterone was elevated in enterostatin-infused rats. The data show that enterostatin will chronically reduce fat intake and body weight and suggest that enterostatin may attenuate the appetite for fat.

Animals↗
PubMed1997

Enterostatin actions in the amygdala and PVN to suppress feeding in the rat.

The pentapeptide enterostatin (ENT) inhibits feeding after injection into the cerebral ventricles. To localize the central sites of action of ENT, the peptide (0.01 to 3.3 nM) was microinjected into several brain regions and the intake of a high fat diet was measured. The results show that ENT injection in the paraventricular nucleus (PVN) or the amygdala (AMYG) produced a bi-phasic dose related feeding response, low doses of ENT inhibited feeding while higher dose had no effect. The effective dose to inhibit feeding in the AMYG was 10 fold lower than that in the PVN. No changes in food intake were observed after ENT injection into the ventromedial hypothalamus and nucleus tractus solitarius. The data provide further support that there are targets in the CNS for ENT and suggest that central ENT function is site specific.

Adaptation, Physiological↗
PubMed1997

Japanese population does not manifest significant association between low NK activity and HLA-B(C) locus homozygosity.

It was reported previously that natural killer (NK) activity is controlled by the HLA-B(C) region and that individuals homozygous for HLA-B(C) or homozygous for the NKB complementation groups, which are mapped to the HLA-B(C) region, have fewer circulating NK cells and lower NK activity than do individuals heterozygous for these alleles. Those studies had used subjects in the United States. In the present study, we investigated the NK activity, NK subpopulation, and HLA types of 65 healthy Japanese individuals in Japan, most of whom have a quite different HLA-B(C) type than did subjects in the earlier study. Among 13 individuals having low NK activity, only two were HLA-B(C) homozygous and the rest were heterozygous. No obvious relation between low NK activity and specific HLA-B(C) allele was found. Seven of the nine HLA-B(C) homozygotes had medium or high NK activity. No significant differences were detected in either the NK activity or in the NK subset frequencies (circulating NK cell number) between HLA-B(C) homozygous and heterozygous individuals. These results indicate that HLA-B(C) homozygosity does not always induce low NK activity and that other factors also may influence NK activities.

Adult↗