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Biomedical subjects

A Leung

Publications and source records attributed to A Leung.

At least 109 records · Page 6Linked to original sources

Adhesivity and rigidity of erythrocyte membrane in relation to wheat germ agglutinin binding.

Binding of the plant lectin wheat germ agglutinin (WGA) to erythrocyte membranes causes membrane rigidification. One of our objectives has been to directly measure the effects of WGA binding on membrane rigidity and to relate rigidification to the kinetics and levels of WGA binding. Our other objective has been to measure the strength of adhesion and mechanics of cell separation for erythrocytes bound together by WGA. The erythrocyte membrane rigidity was measured on single cells by micropipette aspiration. The slope of the suction pressure-length data for entry into the pipette provided the measure of the membrane extensional modulus. Data were collected for cells equilibrated with WGA solutions in the range of concentrations of 0.01-10 micrograms/ml. Erythrocyte-erythrocyte adherence properties were studied by micropipette separation of two-cell aggregates. First, a "test" cell was selected from a WGA solution by aspiration into a small micropipette, then transferred to a separate chamber that contained erythrocytes in WGA-free buffer. Here, a second cell was aspirated with another pipette and maneuvered into close proximity of the test cell surface, and adhesive contact was produced. The flaccid cell was separated from the test cell surface in steps at which the force of attachment was derived from the pipette suction pressure and cell geometry. In addition, we measured the time-dependent binding and release of fluorescently labeled WGA to single erythrocytes with a laser microfluorometry system. The results showed that the stiffening of the erythrocyte membrane and binding of fluorescently labeled WGA to the membrane surface followed the same concentration and time dependencies. The threshold concentration for membrane stiffening was at approximately 0.1 microgram/ml where the time course to reach equilibrium was close to 1 h. The maximal stiffening (almost 30-fold over the normal membrane elastic modulus) occurred in concentrations greater than 2 micrograms/ml where the time to reach equilibrium took less than 1 min. The WGA binding also altered the normal elastic membrane behavior into an inelastic, plastic-like response which indicated that mechanical extension of the membrane caused an increase in cross-linking within the surface plane. Similar to the stiffening effect, we observed that the membrane adhesivity of cells equilibrated with WGA solutions greatly increased with concentration greater than 0.1 microgram/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Adhesion↗

Static and dynamic rigidities of normal and sickle erythrocytes. Major influence of cell hemoglobin concentration.

Static and dynamic deformabilities of erythrocytes are important determinants of microcirculatory blood flow. To determine the influence of increased cellular hemoglobin concentration on these properties, we quantitated static and dynamic deformabilities of isolated subpopulations of oxygenated normal and sickle erythrocytes with defined cell densities using micromechanical manipulations of individual cells. The rheological properties measured to characterize static deformability were membrane extensional rigidity and bending rigidity. To characterize dynamic deformability of the cells, we measured the time constants for rapid elastic recovery from extensional and bending deformations. The extensional rigidity of sickle cells increased with increasing cell hemoglobin concentration while that of normal cells was independent of the state of cell hydration. Moreover, sickle cells were found to exhibit inelastic behavior at much lower cell hemoglobin concentrations than normal cells. In contrast, the dynamic rigidity of both normal and sickle cells was increased to the same extent at elevated hemoglobin concentrations. Moreover, this increase in dynamic rigidity with increasing cellular dehydration was much more pronounced than that seen for static rigidity. Both the increased static and dynamic rigidities of the dehydrated sickle cells could be greatly improved by hydrating the cells. This suggests that increased bulk hemoglobin concentration, which is perhaps inordinately increased adjacent to the membrane, plays a major role in regulating the rigidity of sickle cells. In addition, irreversible membrane changes also appear to accompany cell dehydration in vivo, resulting in increased membrane shear rigidity and plastic flow. We expect that the marked increases in rigidity of dehydrated sickle cells observed here may have a major influence on the dynamics of their circulation in the microvasculature.

Anemia, Sickle Cell↗

Complementation analysis in Gaucher disease using single cell microassay techniques. Evidence for a single "Gaucher gene".

Gaucher disease is a lysosomal storage disorder resulting from a deficiency of acid beta-glucosidase. Several clinical forms have been described, including infantile, juvenile, and adult onset variant. We have examined complementation in infantile and adult forms of Gaucher disease by monitoring enzyme activity in multinucleate cells produced by fusing skin fibroblasts from different patients in the presence of polyethylene glycol. beta-Glucosidase activity was monitored in lysates of individual multinucleate cells by a microassay method utilizing methylumbelliferyl-beta-D-glucoside as the substrate (normal: 1.3 +/- 0.12 x 10(-13) mol/h/cell). The microassay was linear with time up to 4 h, for up to 20 mononucleate cells, and for individual multinucleate cells containing up to 12 nuclei. Complementation was examined in 11 fibroblasts strains fused in all pairwise combinations. In no instance was there any clear indication of complementation (at least 10-15% of normal activity to adequately account for experimental variation) although there was an indication of marginal increases in some fusions. On the other hand, the expected 50% activity was obtained in "heterozygous" fusions (normal/mutant) for both types of clinical variants. Our results are consistent with a single gene, presumably the structural gene encoding the enzyme, responsible for at least the infantile and adult variants, and confirm the autosomal recessive nature of the disorder.

Adult↗

Familial vanishing limbs: four generations of idiopathic multicentric osteolysis.

A family is described which has exhibited in four generations a bizarre form of arthritis mutilans and osteolysis, the features of which seem to fit most closely with a diagnosis of hereditary multicentric osteolysis, a subgroup of idiopathic multicentric osteolysis. The differential diagnosis of arthritis mutilans associated with osteolysis is discussed; this includes a wide variety of disorders ranging from rheumatoid arthritis to rare conditions such as the Winchester syndrome.

Adult↗

Gonadotropins regulate plasminogen activator production by rat granulosa cells.

The role of FSH in the regulation of plasminogen activator production was studied in granulosa cells obtained from 23- to 25-day-old female rats. Cells cultured without FSH secreted a negligible amount of plasminogen activator. Purified ovine, rat, and human FSH produced dose-dependent increases in plasminogen activator production. This FSH effect was mimicked by analogs of cAMP, prostaglandin E2, and choleratoxin. Purified ovine LH and ovine PRL had no effect on plasminogen activator production by these immature granulosa cells. However, when these granulosa cells were treated in vitro or in vivo with FSH and then exposed to LH or PRL, the cells responded to LH in a dose-dependent manner with increased plasminogen activator production. These cells remained unresponsive to PRL. Similarly to FSH, in vitro pretreatment of the cells with choleratoxin or analogs of cAMP also induced responsiveness to LH with increased plasminogen activator production. This responsiveness to both FSH and LH with increased plasminogen activator production was also observed in granulosa cells obtained from rat preovulatory follicles. These studies demonstrate that: 1) FSH but not LH regulates plasminogen activator production by immature granulosa cells from preantral follicles; 2) Pretreatment of the undifferentiated granulosa cells with FSH, choleratoxin, or cAMP induced granulosa cell responsiveness to LH with increased plasminogen activator production; and 3) Granulosa cells obtained from preovulatory follicles respond to both FSH and LH with increased plasminogen activator secretion. These results suggest that with the LH surge at ovulation, plasminogen activator production in follicles is increased and may be important in follicular rupture.

8-Bromo Cyclic Adenosine Monophosphate↗

Lupus foot.

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Adult↗

Serum immunoreactive somatomedin levels in normal adults, pregnant women at term, children at various ages, and children with constitutionally delayed growth.

Immunoreactive somatomedin (IRSM) levels in term pregnancy material sera (MS) and newborn cord sera (CS) were higher and lower, respectively, than those in normal adults. IRSM levels in MS and CS were not correlated, suggesting that SM dose not cross the placenta. The similar levels of IRSM in arterial and venous CS suggest that the placenta does not produce SM. IRSM levels in CS were higher than those in newborn sera and were correlated with day 1 newborn sera, suggesting that the placenta may regulate fetal serum IRSM levels. Serum IRSM levels in normal children gradually increased from birth to peak levels at puberty. The mean levels of serum IRSM reached peak levels 2 yr earlier in females. Males near pubertal age with constitutionally delayed growth had lower serum IRSM levels than age-matched controls. Diagnostic measurements of serum IRSM in children requires comparison with age- and sex-matched controls. Serum SM levels may only approximately reflect the local concentrations or activities of SM in various tissues.

Adolescent↗

Intracranial pressure telemetry system. I. Hardware development.

Results in the development of intracranial pressure(ICP) telemetry systems are reported. Included are a single-channel ICP system and a two-channel ICP and temperature system. The unit used hybrid-integrated circuits housed in a Kovar flatpack and packaged with polyurethane or Hysol epoxy. Battery and radio frequency (RF) induction power supplies were tested. The two-channel systems used RF power at 3.5 MHz and transmitted signals around 120 MHz. The package measures 3 x 2 x 0.8 cm and weighs 9 g. The pressure range is -20 to +100 mm Hg with accuracy to 1.0 mm Hg. The implant measures absolute pressure and has a baseline stability of better than +/- 2 mm Hg/month. 17 dogs and 4 goats were used for in vivo evaluation. A summary of results is presented. Detailed evaluation is given in section II of this paper.

Animals↗

An implantable micropower command receiver for telemetry battery power switching.

Command receivers that control the functioning of additional implanted circuitry can be useful in many medical telemetry applications. The authors have designed and constructed a thick-film hybrid command receiver system that directly interfaces with the second-generation ICP telemetry system. This command receiver controls telemetry on/off state through enabling/disabling the telemetry pulse generator stage. Lithium battery powering of the implant is made practical through use of this command receiver. An automatic power shutdown feature is incorporated to guard against accidental battery drain. The unit uses two commercial CMOS integrated circuits, a transistor, a resistor and an RF coil.

Electric Power Supplies↗