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Biomedical subjects

M Cheung

Publications and source records attributed to M Cheung.

53 records · Page 3Linked to original sources

Brain cellular injury and recovery--horizons for improving medical therapies in stroke and trauma.

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Professor of Medicine. After ischemic and traumatic brain injury, many cells may be rendered dysfunctional but are not irreversibly damaged or disrupted. The brain tissue may become metabolically deranged, and neurons, while still alive, are paralyzed and cannot create an action potential or conduct an electrical impulse. This injured brain tissue is in a precarious state of increased vulnerability. If the milieu of the favorable, they may recover; if it is slightly unfavorable, they may die. There is now evidence that reversibly injured brain tissue will die from an ischemic or hypoxic insult ordinarily tolerated by the normal brain. The major challenge of modern research in stroke and trauma is to define the chemical and metabolic milieu in which the injured brain exists and to define an ideal milieu for healing.

Adult↗

Isolation and characterization of a specific antibody population against human fibrinogen.

A specific antibody population against human fibrinogen was isolated from a rabbit antiserum by affinity chromatography on fibrinogen-bound Sepharose gel. Using a sensitive competitive radioimmunoassay, the antibody population was found to recognize epitopes on native fibrinogen but crossreacted minimally with fibrinogen fragment D and an early plasmin-degraded fibrinogen A alpha-chain product, but not at all with fragment E or fibrinopeptides A and B. Fibrin monomers shared part of these epitopes. The antibody population crossreacted to a small extent with bovine, horse and baboon fibrinogens and not at all with fibrinogens from sheep, rat, pig, goat, guinea pig, dog and rabbit.

Animals↗

Characterization of monoclonal antibodies to carcinoembryonic antigen with increased tumor specificity.

Nine monoclonal antibodies reacting with carcinoembryonic antigen (CEA) were produced after immunization of mice with either purified CEA or a CEA-producing human cell line. Their specificities were assessed by immunohistochemistry on tissue sections of neoplastic and nonneoplastic lesions. These monoclonal antibodies have different patterns of tissue reactivity. Two of them, D14 and B18, were found to have a high degree of specificity for colonic carcinoma and did not react with formalin-fixed paraffin-embedded sections of normal colon with standardized staining conditions. Most cases of noncolonic adenocarcinomas and normal epithelial structures were not stained by these two monoclonal antibodies. The specificity of the monoclonal antibodies was further investigated immunochemically using intact, reduced, and alkylated or chemically fragmented CEA. Liquid phase radioimmunoassays and antibody competition immunoenzymatic assays confirmed that the antibodies recognize different epitopes of CEA. These data support the concept of CEA heterogeneity and the reactivity of the D14 and B18 monoclonal antibodies with colonic adenocarcinomas indicates that they are useful immunohistochemical probes.

Animals↗

Use of 125I-labeled-histamine-cyclosporin C for monitoring serum cyclosporine concentrations in transplantation patients.

We synthesized an 125I-labeled-histamine-cyclosporin C tracer, to obviate the use of tritiated tracer in radioimmunoassay of cyclosporine. With this tracer, the assay results varied linearly with concentration up to at least 800 micrograms/L. The within-assay CV was 6.6% at 39 micrograms/L, 4.2% at 100 micrograms/L, and 7.0% at 300 micrograms/L (n = 15). The between-assay CV was 10.0, 6.4, and 7.8% for the same respective concentrations. Comparison with an assay involving tritiated tracer (x) showed good agreement of results: y = 3.81 + 0.927x (r = 0.975, n = 604). Analytical recovery ranged from 100 to 106%. We also compared another commercially available radioiodinated tracer ("125Iodocyclosporin"; Immunonuclear Corp.). Our tracer appeared to be more specific for cyclosporine, as determined by assaying chromatographic fractions of bile extract from a patient being treated with cyclosporine. Results with use of our tracer compared favorably with those obtained with the tritiated tracer, and our assay has the advantages of gamma counting vs liquid-scintillation counting.

Chromatography, High Pressure Liquid↗

Gastric emptying rate in the elderly: implications for drug therapy.

The effect of the aging process on gastric emptying was studied in 11 elderly subjects (mean age, 77) and in 7 young healthy volunteers (mean age, 26). Gastric emptying rates were assessed by a modified sequential scinti-scanning technique after administration of the nonabsorbable chelated radiopharmaceutical 99mTc-DTPA. The rate of emptying, expressed as half-time (T 1/2e) in minutes, was significantly longer (p less than 0.001) in the elderly subjects (mean apparent T 1/2e = 123.23 min) compared to the young healthy volunteers (mean apparent T 1/2e = 49.69 min). Clinical implications of these findings are discussed, particularly with respect to the rate and extent of drug absorption in elderly persons.

Administration, Oral↗

Gastric emptying rate and the systemic availability of levodopa in the elderly parkinsonian patient.

The gastric emptying rate and systemic availability of levodopa, administered as a single oral dose, was studied in six elderly parkinsonian patients, five elderly nonparkinsonian subjects, and six young healthy volunteers. In both elderly groups, gastric emptying was slowed relative to the young healthy volunteers. The lack of significant differences in the plasma elimination half-life of levodopa among the three groups was accompanied by increased absorption of the drug in the elderly patient groups. These findings are discussed in relation to a possible age-related alteration in the activity of peripheral dopa decarboxylase in the elderly parkinsonian patients.

Administration, Oral↗

Isolation of ribosome containing synaptosome subpopulation with active in vitro protein synthesis.

Subpopulations of synaptosomes harvested from neonatal rat brain cortices revealed a differential ability to synthesize protein in vitro. Incubation of synaptosomes with radiolabeled leucine, followed by continuous sucrose gradient centrifugation produced an asymmetric shift in the radioactivity toward the higher density sucrose fractions. The bulk of the mitochondrial cytochrome c-oxidase activity was also found in these fractions, however, subfractionation studies of osmotically-lysed synaptosomes suggested that the newly-synthesized proteins reside in an osmotically sensitive, non-mitochondrial compartment. The ability of each subpopulation of synaptosomes to synthesize protein in vitro was assessed after their isolation from linear continuous sucrose gradients. There was an enrichment of highly active protein synthesizing particles in the "heavy" subpopulations of neonatal synaptosomes. The inhibitory effects of chloramphenicol and cycloheximide on the protein synthesis in these particles were similar to those of the original synaptosome fraction. Electron microscopic analysis revealed an increase in the numbers of ribosome-containing structures resembling dendritic and axonal growth cones.

Animals↗

Effects of neonatal hypothyroidism on cerebral and cerebellar synaptosome development.

The effect of hypothyroidism on cerebral and cerebellar synaptosome development has been studied. Neonatal hypothyroidism was induced following addition of 0.3% propylthiouracil to the diet of nursing mothers. Maturation profiles of total synaptosome fraction and specific activities of lactate dehydrogenase, Na+K ATPase, cytochrome c oxidase, and protein were obtained from days 6 to 32 on synaptosomes isolated from Ficoll-sucrose gradients. The greatest changes were found in the total activities of enzymes isolated from the cerebellum. Hypothyroidism induced a retardation of LDH and cytochrome c oxidase in cerebellar synaptosomes, but no change in corresponding specific activities. Maximum rates of 14C-leucine incorporation into cerebellar synaptosome protein was found at 16-20 days, after which a rapid decline occurred to adult levels at 32 days. In neonatal hypothyroidism, synthesis was significantly reduced at 8 and 14 days, but reached control levels or above at 21--32 days. In the cerebrum, maximum rates of 14C-leucine incorporation into synaptosome protein were identified at 8--12 days in normal with a rapid drop to adult levels at approximately 20 days. In neonatal hypothyroidism, peak activities were identified at 14 days and increased activities over control were noted at 14, 20 and 30 days. These observations demonstrate the sensitivity of the developing cerebellar synaptic apparatus to neonatal hypothyroidism, with a protraction in the peak levels of synaptosome protein synthesis in cerebrum and cerebellum.

Adenosine Triphosphatases↗

Mitochondrial conformation and swelling-contraction reactivity during early liver regeneration.

Studies of mitochondrial respiratory control and swelling contraction activity during early cell regeneration after partial hepatectomy have revealed a selective defect in the rate of substrate-supported, phosphate-induced mitochondrial swelling. Swelling profiles induced by Fe(2-) or Cu(2-) revealed no differences between sham-operated and partially hepatectomized mice, which suggests no defects in -SH group composition or ability to form lipid peroxides. The specific activity of mitochondrial cytochrome c oxidase was unchanged. There was no significant mitochondrial swelling in situ as determined from mitocrit and mitochondrial protein ratios. A significant decline in respiratory control and efficiency of oxidative phosphorylation was found in mitochondria from animals 8 and 24 hours after partial hepatectomy, partially reversed by bovine serum albumin. No significant change in ADP:O ratio was noted and the decrease in RCI was due primarily to a significant decline in state 3 respiration rate. In situ electron microscopic studies of mitochondria failed to reveal significant abnormalities during early cell regeneration apart from decrease in numbers of matrix granules, focal matrix rarefaction and predominance of round forms. Electron microscopic studies of mitochondria after in vitro phosphate-induced swelling experiments showed no differences between sham and partially hepatectomized animals, but revealed two distinct populations of mitochondria, the predominant form (type III) showing distortion, matrix lucency and outer membrane rupture. ATP induced a diminished reversal in light scattering in partially hepatectomized mitochondria even when examined at 20 minutes, manifested as an increase in numbers of orthodox mitochondrial forms at the expense of the swollen type III forms. The pathogenesis of the impaired respiratory control and phosphate-induced swelling is unknown, but analogous observations have been found in mitochondria harvested from cells in which abnormal accumulations of free fatty acids have been demonstrated.

Adenosine Triphosphate↗

Physiologic and supraphysiologic increases in lipoprotein lipids and apoproteins in late pregnancy and postpartum. Possible markers for the diagnosis of "prelipemia".

A supraphysiologic (greater than 95th percentile) rise in plasma lipids in pregnancy may serve as a marker for "prelipemia" in the same way that gestational diabetes is a marker for prediabetes. To qualify as prelipemic, subjects with an abnormal lipid rise antepartum must return to normal postpartum but may have other identifying characteristics. This paper describes the antepartum-postpartum changes of lipoprotein lipids and apoproteins at 34 to 38 weeks of gestation and 6 and 20 weeks postpartum in 23 subjects with physiologic and six subjects with supraphysiologic plasma lipid increases during pregnancy. These results are compared to measurements in 23 nonpregnant controls matched for weight, age, and race. In subjects with a physiologic antepartum lipid rise, postpartum total triglyceride and very low density lipoprotein (VLDL) lipids (cholesterol and triglyceride) and apo B returned to baseline within 6 weeks. In contrast, low density lipoprotein (LDL) showed a slow postpartum decline in lipids and apo B with elevations remaining at 20 weeks postpartum. High density lipoprotein (HDL) cholesterol concentrations, elevated in pregnancy, remained elevated at 6 weeks postpartum, but fell to baseline by 20 weeks postpartum. HDL triglyceride and apo A-l concentrations, both elevated in pregnancy, returned to baseline by 6 weeks postpartum. A supraphysiologic triglyceride rise in pregnancy was associated with a slower return of total triglycerides and VLDL to baseline, reduced HDL cholesterol ante- and postpartum, atypical changes in LDL cholesterol during pregnancy and postpartum, and evidence of hyperlipidemia among family members. Two subjects with hypercholesterolemia in the nonpregnant state showed no marked exaggeration of total or LDL cholesterol concentrations in pregnancy. The data support the hypothesis that a supraphysiologic rise in plasma triglyceride concentrations in late pregnancy may serve as a marker of prelipemia. Proof of the hypothesis requires further investigation and longer follow-up.

Adult↗

Comparison of plasma lipoproteins and apoproteins in Chinese and American non-insulin-dependent diabetic subjects and controls.

Plasma lipoproteins and apoproteins were compared among Chinese and American controls and non-insulin-dependent diabetic (NIDDM) subjects in the same laboratory. Apoprotein AI concentrations in Chinese subjects, both NIDDM subjects and controls (men, 147 and 158 mg/dl, respectively), were significantly higher than those in American subjects (men, 104 and 124 mg/dl, respectively). Apoprotein AII concentrations, however, were comparable between Chinese and American subjects. Chinese NIDDM subjects had lower high-density lipoprotein cholesterol (HDLC), higher low-density lipoprotein cholesterol (LDLC), and higher apoprotein B levels than Chinese controls. Chinese subjects with NIDDM had HDLC and LDLC levels similar to those of American controls but trends of higher HDLC and lower LDLC compared with American subjects with NIDDM. These differences may in part explain the relatively higher incidence of atherosclerotic vascular disease in Americans.

Apolipoproteins↗