Search PubMed⌕ Search

Biomedical subjects

L Lin

Publications and source records attributed to L Lin.

At least 235 records · Page 13Linked to original sources
PubMed1995

In vivo and in vitro studies on the neurotoxic potential of 6-hydroxydopamine analogs.

In an attempt to determine which physical and biological properties could best be correlated with neurotoxic potential, seven analogs of 1-(2,4,5-trihydroxyphenyl)-2-aminoethane (1), better known as 6-hydroxydopamine, were synthesized and compared to 1 in a variety of ways both in vivo and in vitro. The analogs, in combination with the standard 1, include all eight of the 2,4,5-trisubstituted-phenyl derivatives of phenethylamine and alpha-methylphenethylamine in which the substitution is of the trihydroxy or aminodihydroxy form. Low (60 nmol) and high (300 nmol) intracerebroventricular doses of all analogs produced long-term (7 day) reduction of mouse whole brain norepinephrine (NE) and lesser depletions of dopamine (DA), and effects on serotonin were varied. The analog 1-(5-amino-2,4-dihydroxyphenyl)-2-aminopropane (8) was both more complete and more selective than the standard 1 in depleting NE. Using a histofluorometric glyoxylic acid method and Fink-Heimer silver degeneration stain, it was determined that overt neural degeneration was produced by 8. In vitro, the ease of oxidation of the eight analogs was found to be represented by a formal potential range of -130 to -212 mV vs SCE. However, there was no obvious relationship between ease of oxidation and the extent of monoamine depletion from mouse brain. Using kinetic analysis of synaptosomal accumulation of [3H]NE and [3H]DA, it was found that the standard 1 is more potent in its interaction with the DA uptake site (Ki = 12 +/- 0 microM) than the NE uptake site (Ki = 51 +/- 1 microM). A correlation analysis was used to determine that differences in NE and DA depletion by each analog could not be explained by differences in potency for in vitro uptake blockade. However, there was a correlation between the Ki for [3H]NE uptake blockade and the EC50 for synaptosomal release of preloaded [3H]NE for the eight analogs (R2 = 0.96; for log:log plot, R2 = 0.54), indicating that the results for these two in vitro tests both reflect interaction with the same NE neuronal membrane transport site. A similar correlation between Ki and EC50 was shown for all eight analogs using [3H]DA (R2 = 0.92; for log:log plot, R2 = 0.52), indicating interaction with the same DA neuronal membrane transport site. These findings demonstrate that there is no single property that can account for selectivity of action and/or potency of catecholamine neurotoxins related to 6-hydroxydopamine.

Animals↗
PubMed1995

Inhibitors of protein and RNA synthesis block the cytotoxic effects of non-steroidal antiestrogens.

Non-steroidal antiestrogens such as tamoxifen are known to exert cytotoxic effects against various cell lines in culture. When the antiestrogens are present at sufficiently high concentrations, their cytotoxicity cannot be reversed by estrogens and is demonstrable even with cell lines which lack the estrogen receptor. The mechanism of this cytotoxicity, which is clearly independent of estrogen antagonism, remains unknown. Using two murine cancer cell lines (the K36 leukemia and the EL4 lymphoma cell line), the human breast cancer cell line MCF7, and two non-steroidal antiestrogens (tamoxifen and clomiphene), our laboratory attempted to determine whether the cytotoxic action of non-steroidal antiestrogens was mediated by a mechanism requiring protein or RNA synthesis. In the case of K36 and EL4 cells, inclusion of tamoxifen or clomiphene in the culture medium regularly caused the viable call count to fall below 20-30% of control in 36-48 h. Under these conditions, the addition of inhibitors of protein or RNA synthesis consistently increased viable cell count in a dose-dependent manner. With cultures of K36 cells grown in the presence of 10 microM tamoxifen, for example, the addition of appropriate concentrations of emetine, cycloheximide, puromycin, or actinomycin D increased the percentage of viable cells to 5.0, 2.4, 4.0, and 4.0 times that of control, respectively. Additional experiments revealed that the macromolecular synthesis inhibitors, while effective in inhibiting protein or RNA synthesis to varying degrees, did not affect the cellular uptake of [3H]tamoxifen, suggesting that their ability to protect cells against antiestrogen-induced cell death was not due to an inhibition of cellular uptake of antiestrogens. In the case of MCF7 cells, however, inhibition of protein synthesis did not protect the cells against the cytotoxic effect of tamoxifen. These observations suggest that non-steroidal antiestrogens may exert their cytotoxic effect by at least two different mechanisms; only one of these require de novo protein synthesis. The effect of antiestrogens on K36 and EL4 cells may provide a useful system for the identification of proteins involved in cell death.

Animals↗
PubMed1995

Effects of halothane on the nicotinic acetylcholine receptor from Torpedo californica.

To determine whether the binding of anesthetics to key membrane receptors is a plausible mode of action, we modeled the effect of the general anesthetic halothane in the nicotinic acetylcholine receptor membrane system isolated from Torpedo californica. Our results demonstrated that halothane inhibits the binding of [3H]phencyclidine ([3H]PCP) to the acetylcholine receptor. The inhibition was reversible, concentration dependent, and had an equilibrium dissociation constant (Kd) of 2.2% atm halothane at 25 degrees. Double-reciprocal plots of the halothane effects at various phencyclidine (PCP) concentrations imply that, under equilibrium conditions, halothane inhibits [3H]PCP binding competitively. In contrast, results from kinetic studies showed that the rate of PCP dissociation is highly sensitive to halothane with EC50 = 0.8% atm halothane in nitrogen. Several possible interpretations are discussed; however, the basic observation was that the kinetics of [3H]PCP binding to the nicotinic acetylcholine receptor was affected by halothane at low concentrations in this model system.

Animals↗
PubMed1995

A method for probing the topography and interactions of proteins: footprinting of myoglobin.

We describe a procedure for mapping residues on the surface of a protein molecule to its sequence, using a scheme that is analogous to nucleic acid footprinting. The protein is end labeled radioactively and subjected to limited proteolysis, and the products are analyzed by denaturing polyacrylamide gel electrophoresis and autoradiography. The method is tested with the heme protein myoglobin and applied to mapping the (unknown) surface of the molecule lacking the heme group: apomyoglobin. Sites of protein-protein interaction can be identified, as illustrated by footprinting the association between myoglobin and an anti-myoglobin monoclonal antibody.

Adenosine Triphosphate↗
PubMed1995

Arrhythmias after cardioverter-defibrillator implantation: comparison of epicardial and transvenous systems.

Surgery for implantable cardioverter-defibrillators can cause postoperative exacerbation of ventricular and atrial arrhythmias. It is not known whether the techniques of electrode implantation (epicardial vs transvenous) influence the incidence of arrhythmia exacerbation. We reviewed the postoperative course of 229 consecutive patients who received either epicardial (n = 119) or transvenous (n = 110) implantations from 1984 to 1994. Exacerbation of ventricular tachycardia (VT) was defined as an increase in the number of sustained VTs during the postoperative versus the preoperative 2 weeks. Of the entire cohort, 18 patients (8%) developed exacerbation of VT after operation, which was more frequent in patients with epicardial than with transvenous implantations (12% vs 4%, p < 0.03, odds ratio 3.5, 95% confidence interval 1.0 to 13.2). New-onset atrial fibrillation occurred in 15% of patients with epicardial versus 1% of those with transvenous implantations (p = 0.00005, odds ratio 19.4, 95% confidence interval 2.7 to 86.7). These differences persisted after excluding patients with concurrent cardiac surgery. Preoperative occurrence of arrhythmias was the strongest independent predictor for postoperative occurrence (p < 0.01 for VT, p < 0.0001 for atrial fibrillation). Epicardial implantation (p = 0.03) and a history of myocardial infarction (p = 0.04) were independent predictors for postoperative VT exacerbation, whereas epicardial implantation (p < 0.05) and concurrent coronary bypass surgery (p = 0.0001) were independent predictors for postoperative new atrial fibrillation. Perioperative discontinuation of antiarrhythmic drugs did not influence postoperative VT exacerbation. Epicardial implantation was associated with longer length of hospital stay than transvenous implantation (p = 0.0005), independent of age, left ventricular ejection fraction, and concurrent cardiac surgery.

Aged↗
PubMed1995

Perceptions of fear in other children and adolescents: the role of gender and friendship status.

Gender differences in fear were examined in 693 Chinese children and adolescents. Subjects were asked to rate their own fears, the fears of their best friends, and the fears of "other" classmates using the Fear Survey Schedule for Children--Revised (Ollendick, 1983). Consistent with previous investigations in Western and Eastern countries, girls rated themselves as more fearful than boys. In addition, both girls and boys rated their best friends as similar in number, content, and intensity of fears. However, girls rated their classmates as less fearful than themselves or their best friends, while boys rated their classmates as more fearful then themselves or their best friends. Findings are discussed in terms of gender role expectations and similarity-attraction hypotheses.

Adolescent↗
PubMed1995

Medicagenic acid saponins from Aster batangensis.

Two new medicagenic acid saponins, named asterbatanoside J and K, were isolated from the roots of Aster batangensis. On the basis of chemical and spectral studies especially 2D NMR including COSY, HETCOR, HMQC, HOHAHA, TOCSY, ROESY and HMBC techniques, their structures were established as 3-O-beta-D-glucopyranosyl-(1--> 6)-beta-D-glucopyranosyl-2 beta, 3 beta-dihydroxy-olean-12-en-23 alpha, 28-dioic acid- 28-O-alpha-L-arabinopyranosyl-(1-->3)-alpha-L- rhamnopyranosyl-(1-->2)-beta-D-fucopyranoside and 3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl- medicagenic acid-28-O-beta-D-xylopyranosyl-(-->4)-[alpha-L- arabinopyranosyl-(1 -->3)-alpha-L-rhamnopyranosyl-(1-->2) -beta-D-fucopyranside, respectively.

Carbohydrate Conformation↗
PubMed1995

A new B18 sequence (B*1802) from Asian individuals.

A new HLA-B18 allele (B*1802) derived from a Thai individual was sequenced. Comparison of this B18 nucleotide sequence with the published B*1801 sequence indicated that this Asian B18 allele has a nucleotide sequence different from that of B*1801. Three nucleotide changes were observed in exon 3, in which two substitutions at codon 97, AGG in B*1801 to AAT in the B*1802, result in an amino acid change from arginine to asparagine. The residue 97Asn has also been described in some B27 subtypes. A silent mutation was also observed at codon 99, TAC in B*1801 to TAT in the B*1802. This sequence has been reported in many class I alleles published so far. Moreover, 18 HLA-B18-positive samples were examined by the PCR-SSO method using specific probes for B*1801 and B*1802. The results demonstrated that three Asian samples possess B*1802 and share HLA-Cw7, DR12, and DQ7.

Alleles↗
PubMed1995

A new HLA-A9 subtype lacking the Bw4 epitope. Ancestral or revertant allele?

The HLA-A9 group has been subdivided into three serologically defined splits, A23, A24, and A2403. We have found a new HLA-A9 split antigen, tentatively called A24AK, in the Japanese population. Sequence analysis of A24AK (officially assigned A*2404) showed that this new allele was different from HLA-A*2402, which codes for the common A24 antigen, by seven nucleotides, and the two alleles could be discriminated by the PCR-SSCP method. These nucleotide substitutions are predicted to result in substitution of six amino acid residues at positions 76, 79, 80, 81, 82, and 83. In all HLA-A9-group alleles described to date, this region is known to code for the Bw4 epitope, which is usually localized on HLA-B molecules. However, the new allele lacks the Bw4 coding sequence. Sequencing results are supported by results showing that the lymphocytes from A24AK-positive individuals did not react with anti-Bw4 antiserum. The nucleotide sequence of A*2404 in this region was identical to that of A*0101, A*2601, A*2602, and several other alleles. These findings suggest several possible paths of evolution of this new allele.

Alleles↗
PubMed1995

Both HLA-B*1301 and B*1302 exist in Asian populations and are associated with different haplotypes.

A B13 split antigen was newly identified with three alloantisera in Japanese, and two B13 split antigens were found in a Thai family. To confirm the variation of B13 and understand the correspondence between the serologic splits and the published B13 alleles, B*1301 and B*1302, we determined the sequences of genes coding for these B13 splits. The common Japanese B13 allele was found to be B*1301, whereas another split antigen was shown to be coded by B*1302. Two B13 variants identified in a Thai individual corresponded to B*1301 and B*1302. Moreover, 57 B13-positive samples from several ethnic groups were examined using the PCR-SSO method. Differing from previous reports, both B*1301 and B*1302 were found in samples from Asian populations. These two alleles were separately associated with different antigens: HLA-B*1301 exhibited a strong association with A2, Cw10, DR12, and DQ7 antigens, whereas HLA-B*1302 was strongly associated with A30, Cw6, DR7, and DQ2 antigens. In addition, applying the PCR-SSCP method, B*1301 and B*1302 could also be simply distinguished from each other.

Alleles↗
PubMed1995

A new HLA-C allele, Cw*1403, associated with HLA-B44 in Japanese.

An allele encoding an HLA-C antigen, tentatively called CX44, associated with HLA-B44 was identified as a new member of the Cw14 group, Cw*1403. The nucleotide sequence of Cw*1403 was closest to that of Cw*1401: five bases were different between the two alleles, in which three bases in Cw*1403 (two in exon 3 and one in exon 4) were the same as those of most HLA-C alleles. Two substitutions from guanine to adenine were found in the new allele, both of which are in exon 2, one at position 134 (61 of exon 2) and the other at position 201 (128 of exon 2). The former nucleotide substitution leads to the substitution of amino acid residue 21 from Arg to His, and the other substitution was synonymous. The former substitution was shared with Cw2, 3, 5, 13, and 15 alleles, and the latter was shared with Cw2, 4, 5, 8, 12, 13, 15 and 16 alleles. The other seven unrelated Japanese samples with CX44 were analyzed by a PCR-SSO method. It was confirmed that all the seven samples have the same substitutions as the sequenced allele, and the allele demonstrates a strong association with A33, B44, DR13, and DQ1, which are known to form a common haplotype in Japanese and Koreans.

Alleles↗
PubMed1995

Plasma mass spectrometry as a detector for chemical speciation studies.

Inductively coupled plasma mass spectrometry (ICP-MS), when coupled with the unique separating power of various chromatographic techniques, allows the detection of various elements at ultra-trace levels. The investigation of various toxic elements of environmental concern coupling relatively recent techniques, such as supercritical fluid chromatography (SFC) and capillary zone electrophoresis (CZE), to ICP-MS, is discussed. Comparisons have been made with detection limits obtained by using the flame ionization detector. The conventional technique of liquid chromatography for the speciation of vanadium, chromium and nickel is also discussed.

Capillary Action↗
PubMed1995

Arsenic speciation using capillary zone electrophoresis with indirect ultraviolet detection.

The toxicological or biological importance of many trace elements in biological and environmental samples depends to a great extent on their quantities as well as their oxidation states and chemical forms. In this work, arsenic species (arsenate, arsenite, dimethylarsinate [DMA], and monomethylarsonate [MMA]) are determined using capillary zone electrophoresis (CZE) with indirect ultraviolet absorption detection. Sodium chromate is used as an electrolyte solution and to provide the chromophore. The effect of the pH of the solution on the separation of species of interest is discussed. The absolute detection limits are 5.2, 3.5, 15.6, and 15.6 pg for arsenate, arsenite, monomethylarsonate, and dimethylarsinate, respectively. A solution extracted from coal fly ash is analyzed using this method. The arsenate concentration is determined to be 5 micrograms/g. Arsenite, monomethylarsonate, and dimethylarsinate are not found. The advantages of using CZE as an efficient and sensitive separation method are discussed.

Arsenicals↗
PubMed1995

The stability and prediction of fears in Chinese children and adolescents: a one-year follow-up.

The stability in number, level, content, and pattern of fears over a one-year period was examined in Chinese children and adolescents aged 7-17. In addition, perceptions of fear in friends and parents as well as perceptions of the controllability and modifiability of fears were explored as predictors of subsequent fear level. Evidence for moderate stability of fears was obtained. However, stability was qualified by age and sex interaction effects. A developmental-cultural hypothesis was put forth to account for those findings. Hierarchical regression analyses revealed that perceptions of fears in friends and parents, along with perceptions of the controllability and modifiability of fears, were predictive of fear level at follow-up. Limitations of the study are noted.

Adolescent↗
PubMed1995

Monoclonal IgM antiphosphatidylserine antibody reacts against cytoskeleton-like structures in cultured human umbilical cord endothelial cells.

PROBLEM: It has been proposed that antibodies against phospholipid-dependent antigens (aPLs), induce recurrent pregnancy loss and thrombosis through modulation of endothelial cell function, yet aPLs have not been conclusively shown to bind with endothelial cells. METHOD: Using indirect immunofluorescence we investigated the anti-endothelial cell reactivity of three monoclonal antibodies that differentiate between the phospholipids cardiolipin (CL) and phosphatidylserine (PS): BA3B5C4 (CL+/PS+); 3SB9b (CL-/PS+); and D11A4 (CL+/PS-). Cultured umbilical cord endothelial cells were prepared without fixation or with cold acetone fixation. RESULTS: None of the aPLs reacted with endothelial cells prepared without fixation. 3SB9B reacted strongly with cytoskeletal-like components in acetone-fixed cells, whereas BA3B5C4 and D11A4 were unreactive. The cytoskeletal-like binding of 3SB9b was completely blocked by a monoclonal antibody against vimentin, whereas antibodies against tubulin or actin were not inhibitory. Lipid extraction of the cells destroyed the 3SB9b reactive antigen without affecting the reactivity of anti-vimentin. CONCLUSION: These results suggest that phospholipid-dependent antigenic determinants are not expressed on the surface of resting endothelial cells but that a PS-dependent antigenic determinant is associated with endothelial cell intermediate filaments.

Animals↗