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Biomedical subjects

C Lai

Publications and source records attributed to C Lai.

At least 109 records · Page 6Linked to original sources
PubMed1988

Anti-ischaemic and anti-anginal activity of atenolol, nifedipine and their combination in stable, chronic effort angina.

To assess the anti-anginal and anti-ischaemic activity of the beta-blocker atenolol (ATN) and the calcium antagonist nifedipine (NIFE) and their combination in coronary patients, a double-blind, cross-over, placebo-controlled study was performed. Ten male patients (mean age: 58 +/- 2.9 years) suffering from a stable effort angina were studied. The study lasted 14 weeks: after 2 weeks of wash-out, patients were randomly assigned to ATN (100 mg/day) and placebo-NIFE, or placebo-ATN and NIFE (10 mg three times/day), or ATN (100 mg) plus NIFE (10 mg three times/day) for 4 weeks. Maximal symptom-limited stress tests on a bicycle (10 watt/min) during the wash-out period (on days 10 and 14) and at the end of each treatment period were performed. All treatments significantly increased the work load at 1 mm ST depression, the angina threshold and the total work, and reduced ST depression at the maximal common work and at the maximal work. Also the atenolol-nifedipine combination significantly reduced ST depression at maximal common work and maximal work as compared to ATN and NIFE alone. In conclusion, this study confirms the anti-ischaemic and anti-anginal activity of both atenolol and nifedipine in stable effort angina and shows that their combination is able to increase anti-ischaemic activity.

Angina Pectoris↗
PubMed1987

Two forms of 1B236/myelin-associated glycoprotein, a cell adhesion molecule for postnatal neural development, are produced by alternative splicing.

The structures of two rat brain-specific 1B236 mRNAs, alternative splice products from a single gene regulated differently during postnatal brain development, were deduced from full-length cDNA clones. The 626- and 582-amino acid-long encoded proteins are indistinguishable from two forms of myelin-associated glycoprotein, a cell adhesion molecule involved in axonal-glial and glial-glial interactions in postnatal brain development, particularly in myelination. The two proteins share a single membrane-spanning domain and a glycosylated N terminus but differ in the structures of their C termini. The N terminus consists of five domains related in sequence to each other and to immunoglobulin-like molecules, especially the neural cell adhesion molecule N-CAM, suggesting a common structure for cell adhesion molecules.

Aging↗
PubMed1987

Splice site selection in the proteolipid protein (PLP) gene transcript and primary structure of the DM-20 protein of central nervous system myelin.

Proteolipid protein (PLP) is the major myelin membrane protein of the central nervous system. We have isolated a copy of an alternatively spliced PLP gene transcript from a mouse brain cDNA library that was screened for PLP-related sequences. The encoded 241-amino acid protein differs from PLP by an internal deletion of 35-amino acid residues (116-150) from the major hydrophilic domain. This PLP variant is identical with the DM-20 protein of myelin, previously described as a brain-specific myelin component and known to be related to PLP. We determined the corresponding nucleotide sequence of the rat PLP gene and found that DM-20 mRNA results when a second 5' splice site, located 105 nucleotides within the third exon of the primary PLP transcript, is utilized in precursor mRNA (pre-mRNA) splicing. This demonstrates that alternative 5' splice site selection can determine the protein product of a cellular gene. DM-20 mRNA is expressed in rat brain with approximately 50% abundance relative to PLP mRNA and appears to be developmentally coregulated.

Amino Acid Sequence↗
PubMed1987

Neural protein 1B236/myelin-associated glycoprotein (MAG) defines a subgroup of the immunoglobulin superfamily.

We have reviewed the structure and properties of the neural protein 1B236/MAG. This molecule consists largely of five Ig-like domains separated from its carboxyl terminal tail by a single membrane-spanning region. Two forms of the protein differ in the length and sequence of the carboxyl terminus: these are encoded by alternatively spliced mRNAs that are differentially expressed during postnatal neural development. The Ig-like domains of 1B236/MAG are unusual in having structural similarities to Ig V domains but with short Cys-Cys distances characteristic of C domains. Several other Ig-like molecules exhibit this structural feature, including the cell adhesion molecule N-CAM, which is most closely related in sequence to 1B236/MAG. We have proposed 1B236/MAG as the prototype for this subgroup of the Ig family and offer a model for this type of Ig domain structure. 1B236/MAG probably acts as a cell adhesion molecule to mediate interactions between cells in a fashion similar to that proposed for N-CAM. In particular, 1B236/MAG may be involved in interactions between myelinating oligodendrocytes or Schwann cells and axons or between adjacent layers of myelin membrane during the process of myelin compaction. It is most likely that the homophilic or heterophilic interactions of 1B236/MAG occur through binding to the Ig-like domains. The structure of 1B236/MAG is therefore quite consistent with its proposed function and may serve as the model for this class of cell-cell interaction molecules. One would predict, for example, that the neuron-glia cell adhesion molecule Ng-CAM, also known as NILE or L1 (Bock et al. 1985, Friedlander et al. 1985), which mediates interactions between neurons and glial cells, would have a very similar structure to those of N-CAM and 1B236/MAG. In addition, the carboxyl terminal tails of the 1B236/MAG proteins may also be involved in interactions with cytoskeletal components, during membrane vesicle transport through the glial cytoplasm during myelination or through neuronal axoplasm or cytoplasm. The availability of full-length cDNA clones of 1B236/MAG mRNAs with the ability to express these products in vitro will enable the structure and interactions of 1B236/MAG to be tested in detail.

Amino Acid Sequence↗
PubMed1986

Jimpy mutant mouse: a 74-base deletion in the mRNA for myelin proteolipid protein and evidence for a primary defect in RNA splicing.

The mouse mutant jimpy carries an X chromosome-linked recessive gene defect that affects the formation of myelin in the central nervous system. To understand the molecular basis of the jimpy mutation, we have examined the expression of mRNAs encoding myelin proteolipid protein (PLP). PLP mRNAs were detectable in jimpy brain RNA at 21 days after birth but were severely reduced in abundance compared to wild-type littermates. Nucleotide sequence analysis of cDNA clones for PLP mRNA, isolated from a cDNA library of jimpy brain poly(A)+ RNA, revealed that the PLP mRNA expressed in jimpy contained a deletion of 74 nucleotides with respect to the wild-type sequence. This deletion causes a frameshift in the open reading frame resulting in an altered carboxyl terminus for jimpy PLP. Probes specific for the deleted sequence, however, hybridize with equal efficiency to genomic DNA from jimpy and wild-type littermates, suggesting that the defect in the jimpy PLP mRNA is generated by aberrant RNA processing rather than by deletion of genomic sequences. We conclude that a mutation in the gene for PLP that leads to an incorrectly spliced RNA transcript is the primary defect of this genetic disorder.

Amino Acid Sequence↗
PubMed1986

Structural characterization of a heterogeneous family of rat brain mRNAs.

A large heterogeneous family of RNAs derived from a single rat gene contains members that differ from each other at one or more of three positions. Their 5' ends are nested and transcription can begin at 22 or more sites covering 265 nucleotides. Many of the 5' ends are detectable only in brain RNAs, and even 5' ends common with other tissues appear with different absolute and relative abundances in brain RNA. The central portions of the RNAs are of two forms, differing only by the presence or absence of 17 nucleotides; these forms are probably produced by alternative splicing. Polyadenylation occurs at either of two sites. This complicated family of 88 RNAs encodes two novel putative proteins that differ at their C termini.

Animals↗
PubMed1986

Phenylarsine oxide inhibits agonist-induced changes in photolabeling but not agonist-induced desensitization of the beta-adrenergic receptor.

In the human lymphocyte, desensitization of the beta-adrenergic receptor-adenylate cyclase complex is associated with sequestration of the receptor as well as a change in photolabeling of beta-receptor proteins. Thus, desensitization of the lymphocyte beta-adrenergic receptor-adenylate cyclase system is associated with a selective reduction in the photoaffinity labeling of an Mr approximately equal to 55,000 beta-adrenergic receptor-binding site as compared to an Mr approximately equal to 68,000 beta-adrenergic receptor-binding moiety. In order to examine the relationship between sequestration and reduction in labeling of the Mr approximately equal to 55,000 peptide, we have studied the effect of phenylarsine oxide (an inhibitor of beta-receptor sequestration in astrocytoma cells) on agonist-induced desensitization of the beta-adrenergic receptor-adenylate cyclase system in circulating lymphocytes. Incubation of cells with phenylarsine oxide prior to exposure to agonists did not block the consequent reduction in isoproterenol-stimulated adenylate cyclase activity. However, sequestration of the receptor, as assessed by a decrease in accessibility of beta-adrenergic receptors on intact cells to hydrophilic receptor ligands, is blocked by phenylarsine oxide. Thus, the agonist-induced reduction in binding of the hydrophilic beta-adrenergic receptor ligand CGP-12177 was blocked by phenylarsine oxide (without phenylarsine oxide, 57 +/- 6% of control, with phenylarsine oxide, 97 +/- 3% of control). Photolabeling studies with [125I]iodocyanopindolol diazirine revealed that phenylarsine oxide pretreatment also blocked the selective loss in labeling of the Mr approximately equal to 55,000 beta-adrenergic receptor protein. These data suggest that agonist-induced alterations in the photolabeling pattern of the lymphocyte beta-adrenergic receptor that occur with desensitization closely parallel the apparent sequestration of beta-adrenergic receptors but can be dissociated from the initial desensitization phenomenon.

Adenylyl Cyclases↗
PubMed1986

Brain-specific gene expression.

The brain of an adult rat expresses approximately 30,000 different brain-specific mRNAs. To investigate their encoded proteins, we have selected cDNA clones corresponding to mRNAs expressed exclusively in rat brain, determined their nucleotide sequences and generated antisera against synthetic peptides mimicking short regions of the deduced protein sequences. The clone plB236 encodes a protein that defines a widely distributed neuronal system and may be the precursor for a family of novel neuropeptides. A second clone, plB208, encodes rat brain proteolipid protein, the major protein component of central nervous system myelin. These studies have also identified an 82 nucleotide genetic element called an ID (identifier) sequence that may be involved in the regulation of transcription of brain-specific genes.

Amino Acid Sequence↗
PubMed1985

Nucleotide sequences of two mRNAs for rat brain myelin proteolipid protein.

The 3200 and 1600 nucleotide mRNAs encoding rat brain proteolipid protein (PLP), the major protein component of central nervous system myelin, are heterogeneous at their 5' ends, differ in their 3' polyadenylation sites, and are transcribed from a single gene. The mRNAs, which first appear postnatally, encode identical 277 amino acid proteins that are 99% identical to the bovine protein sequence. Thus, PLP has been highly conserved during mammalian evolution. A single amino-terminal methionine is removed post-translationally, indicating that PLP does not require a signal peptide sequence for insertion into the myelin membrane. Mouse and monkey utilize the 3200 but not the 1600 nucleotide mRNA, suggesting that there is no functional necessity for two sizes of rat PLP mRNAs.

Amino Acid Sequence↗
PubMed1985

Effects of L-carnitine on exercise tolerance in chronic stable angina: a multicenter, double-blind, randomized, placebo controlled crossover study.

L-carnitine was studied in forty-four men with stable chronic angina in a multicenter, double-blind, randomized, placebo controlled crossover trial. A cycloergometer exercise test was performed after a 10-day wash-out with placebo and at the end of each 4-week treatment period with either L-carnitine (1 g twice daily) or placebo. The mean (+/- SD) exercise work load showed an increase after L-carnitine compared to placebo (102.73 +/- 22.23 and 97.05 +/- 22.77 watts respectively, p = 0.001), as did the watts to onset of angina (95.7 +/- 24.07 and 87.44 +/- 24.67, p = 0.000). On the contrary, the ST segment depression was reduced by L-carnitine compared to placebo both at the maximum work load (1.40 +/- 0.90 and 1.69 +/- 0.82 mm, p = 0.05) and at the maximum work load common to L-carnitine and placebo (1.24 +/- 0.90 and 1.66 +/- 0.79 mm, p = 0.005). 22.7% of the patients became free of angina with L-carnitine and 9.1% with placebo. Resting and exercise blood pressure, heart-rate and double product were unaffected by L-carnitine. 1 patient decided to discontinue the trial because of gastric pyrosis while taking the active drug. The results of this study show that treatment with L-carnitine increases exercise tolerance and reduces ECG indices of ischemia in stable effort-induced angina.

Angina Pectoris↗