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Biomedical subjects

L Lam

Publications and source records attributed to L Lam.

12 recordsLinked to original sources
PubMed1992

Glucose transport in human skeletal muscle cells in culture. Stimulation by insulin and metformin.

Primary human muscle cell cultures were established and the regulation of glucose transport was investigated. Primary cultures were allowed to proceed to the stage of myotubes through fusion of myoblasts or were used for clonal selection based on fusion potential. In clonally selected cultures, hexose (2-deoxy-glucose) uptake into myotubes was linear within the time of study and inhibitable by cytochalasin B (IC50 = 400 nM). Cytochalasin B photolabeled a protein(s) of 45,000-50,000 D in a D-glucose-protectable manner, suggesting identity with the glucose transporters. In the myotube stage, the cells expressed both the GLUT1 and GLUT4 glucose transporter protein isoforms at an average molar ratio of 7:1. Preincubation in media of increasing glucose concentrations (range 5-25 mM) progressively decreased the rate of 2-deoxyglucose uptake. Insulin elevated 2-deoxyglucose uptake in a dose-dependent manner, with half maximal stimulation achieved at 3.5 nM. Insulin also stimulated the transport of the nonmetabolizable hexose 3-O-methylglucose, as well as the activity of glycogen synthase, responsible for nonoxidative glucose metabolism. The oral antihyperglycemic drug metformin stimulated the cytochalasin B-sensitive component of both 2-deoxyglucose and 3-O-methylglucose uptake. Maximal stimulation was observed at 8 h of exposure to 50 microM metformin, and this effect was not prevented by incubation with the protein-synthesis inhibitor cycloheximide. The relative effect of metformin was higher in cells incubated in 25 mM glucose than in 5 mM glucose, consistent with its selective action in hyperglycemic conditions in vivo. Metformin (50 microM for 24 h) was more effective than insulin (1 microM for 1 h) in stimulating hexose uptake and the hormone was effective on top of the stimulation caused by the biguanide, suggesting independent mechanisms of action.

Biological Transport↗
PubMed1992

Prevalence of tardive dyskinesia, tardive dystonia, and respiratory dyskinesia among Chinese psychiatric patients in Hong Kong.

OBJECTIVE: Only scanty information on the prevalence of tardive dyskinesia in Chinese patients has been available. This study was undertaken to examine the prevalence of tardive dyskinesia, tardive dystonia, and respiratory dyskinesia in Chinese psychiatric patients in Hong Kong. METHOD: All inpatients of a mental hospital in Hong Kong, except those in the admission and children's wards, were surveyed with the Abnormal Involuntary Movement Scale, and standard research criteria were used to establish the diagnosis of tardive dyskinesia. In addition, patients were screened for tardive dystonia, according to published criteria, and for respiratory dyskinesia by physical examination and laboratory tests. RESULTS: Among the 917 patients surveyed, the prevalence rates were 9.3% for tardive dyskinesia, 0.4% for tardive dystonia, and 1.2% for respiratory dyskinesia. With multivariate analysis, greater age and a lower current dose of antipsychotic, but not the presence of mood disorder, were factors found to be significantly associated with tardive dyskinesia. CONCLUSIONS: The prevalence rates were much lower than those found in Western studies. This may indicate that there is an ethnic difference in the prevalence of these conditions. Prospective cross-cultural studies are necessary to explore this possibility.

Adolescent↗
PubMed1992

Stimulation of hexose transport by metformin in L6 muscle cells in culture.

L6 muscle cells grown in culture to the stage of fused myotubes were incubated with the oral hypoglycemic drug metformin to test the effects of this drug on glucose transport. Metformin increased the initial rate of uptake of 2-deoxyglucose and 3-O-methylglucose. The effect was time dependent, with half-maximal stimulation at 5-6 h and maximal stimulation by about 16 h. The stimulation of hexose uptake was not prevented by cycloheximide. In 15 mM glucose medium, the basal rate of transport was lower than in 5 mM glucose medium. The stimulation of hexose uptake by metformin was comparable in absolute units in both media; hence, relative to basal uptake, stimulation was greater in the high glucose medium than in the low glucose medium. In 5 mM glucose medium, half-maximal stimulation was obtained with 800 microM metformin when tested for 24 h. The stimulation of hexose transport by metformin was only detectable in fused myotubes and not in perfusion myoblasts. No significant changes were observed in glucose transporter levels in total cell membranes from L6 myotubes (measured as D-glucose-protectable binding sites for cytochalasin-B) or in the total levels of the immunoreactive glucose transporter isoforms GLUT4 or GLUT1. It is concluded that metformin stimulates hexose transport into differentiated muscle cells by acting at a posttranslational level. We speculate that this might also constitute the basis for the ability of the drug to lower glycemia in diabetic individuals.

3-O-Methylglucose↗
PubMed1990

The Drosophila neurogenic locus mastermind encodes a nuclear protein unusually rich in amino acid homopolymers.

The neurogenic loci of Drosophila are required for proper partitioning of ectodermal cells into epidermal versus neural lineages. The loci appear to encode components of a developmental pathway involving cellular communication. In an effort to understand the role of the neurogenic locus mastermind in these processes, we have characterized its expression and sequence. The locus produces a number of transcripts that accumulate ubiquitously during early embryogenesis but more specifically in the central nervous system during later stages. Sequence analysis of a major cDNA product predicts an unusual protein containing an abundance of amino acid homopolymers and charge clusters typical of regulatory molecules. Nearly half of the mass of the predicted protein derives from only three amino acids: glutamine, glycine, and asparagine. Immunohistochemical studies of the protein in cell culture and early embryos show that the protein accumulates predominantly in the nucleus.

Amino Acid Sequence↗
PubMed1986

Myosin isoenzyme distribution in overloaded human atrial tissue.

Using nondenaturing polyacrylamide gel electrophoresis, we have identified two distinct myosin isoenzymes in human atrial tissue that correspond to the V1 and V3 isomyosins found in rat ventricular tissue. Normal left and right atrial appendages have approximately 50% V3. When the left atrium was exposed to hemodynamic overload secondary to mitral stenosis, the percent V3 increased to 77 +/- 10% (n = 10); exposure to hemodynamic overload secondary to mitral regurgitation caused an increase to 70 +/- 14% (n = 6). Changes in the isoenzyme pattern were seen in the right atria of patients with mitral stenosis and markedly elevated pulmonary arterial pressures compared with control subjects and patients with mitral stenosis without severe pulmonary hypertension. Several clinical variables were examined to determine which factors might influence isoenzyme expression. Age, sex, the presence of atrial fibrillation, and pulmonary capillary wedge pressure did not predict the isoenzyme pattern. However, patients with mitral valvular disease and only slightly enlarged left atria tended to have a higher percent V3 than those with massively enlarged atria. These data confirm that human atrial tissue, like rat ventricular tissue, can alter its isomyosin composition in response to a hemodynamic load. The data further suggest that the isoenzyme shift is an early adaptation to the imposed load.

Adult↗
PubMed1979

Correlation between structure and function of heparin.

We have fractionated crude porcine heparin to obtain highly active as well as relatively inactive species of molecular weight approximately 7000 with specific anticoagulant activities of 360 and 12 units/mg, respectively. Nitrous acid degradation of both of these polymers yielded a tetrasaccharide fraction, 1beta, that contained equimolar amounts of iduronic and glucuronic acids, possessed an internal N-acetylated glucosamine, and carried anhydromannitol at the reducing end position. The 1beta tetrasaccharide derived from the highly active heparin, 1betaa, was recovered in a yield of 1.1 mol/7000 daltons. Our analyses indicate that at least 95% of the 1betaa is a single structure that consists of the following unique monosaccharide sequence: L-iduronic acid --> N-acetylated D-glucosamine-6-sulfate --> D-glucuronic acid --> N-sulfate D-glucosamine-6-sulfate. The 1beta tetrasaccharide fraction from relatively inactive mucopolysaccharide, 1betai, was recovered in a yield of 0.3 mol/7000 daltons and was a mixture of several components. Only 8.5% of the 1betai tetrasaccharide fraction exhibited the same uronic acid placement and sulfate group position found in 1betaa. Thus, 2.6% of relatively inactive mucopolysaccharide molecules contain the unique tetrasaccharide sequence found within each molecule of highly active heparin. Given the correlation between abundance of this unique 1betaa tetrasaccharide sequence and biologic potency, we suggest that this structure represents the critical site responsible for anticoagulant activity.

Animals↗
PubMed1979

Rectal aspirin--absorption and antipyretic effect.

Rectal acetylsalicylic acid was given to 14 children who had undergone open heart surgery. The effect on their temperatures was similar whether 15--30 or 30--50 mg/kg was given. Either dose was more effective than no treatment. The greatest fall in temperature occurred after 4 or 5 hours. Rectal aspirin in a triglyceride base is effective in lowering postoperative temperature. It should also be of use in treating other fevers. A dose of 20--25 mg/kg is suggested.

Adolescent↗
PubMed1978

Structure-function relationships of heparin species.

We have fractionated porcine heparin species of low molecular weight, with an average specific anticoagulant activity of 96 units/mg by affinity chromotography. Highly active and relatively inactive preparations of similar size were obtained with specific anticoagulant activities of 360 and 4 units/mg, respectively. The highly active heparin fraction possesses 1.1 additional residues of glucuronic acid and 1.5 fewer residues of N-sulfated glucosamine per molecule compared to the relatively inactive species. This decrease in N-sulfated glucosamine appears to be secondary to a corresponding increase in N-acetylated glucosamine. This form also contains a tetrasaccharide sequence with a N-sulfated glucosamine at its reducing end as well as equivalent amounts of glucuronic acid and iduronic acid. Furthermore, the internal glucosamine residue of this sequence appears to be N-acetylated. Sufficient amounts of this tetrasaccharide sequence are present within the highly active preparation such that each molecule may be endowed with this structure. The relatively inactive product contains a significantly decreased quantity of this tetrasaccharide sequence such that only [unk]20% of these molecules may possess this structure. The mean distance between nonsulfated uronic acid residues of the highly active species is smaller than that separating similar residues of the relatively inactive product. In addition, a larger number of the nonsulfated uronic acid residues of the highly active material appears either to be present in a restricted region of the molecule separated only by glucosamine residues or to be located at penultimate positions within the polysaccharide chain.

Animals↗