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Biomedical subjects

S C Liu

Publications and source records attributed to S C Liu.

At least 145 records · Page 8Linked to original sources

Indomethacin causes a simultaneous decrease of both prolactin binding and fluidity of mouse liver membranes.

Indomethacin suppressed the numbers of prolactin receptors detectable in the liver membranes of both male and female C3H mice. This occurred in a dose-dependent fashion with 7.5 mug/gm body weight injected every 4 hours exerting a maximal effect within 20 hours. While injection of 50 mug prolactin every 4 hr increased the number of prolactin receptors in control animals it could not in the indomethacin-treated animals. Membrane fluidity was estimated by fluorescence polarization techniques using the lipid probe 1, 6-diphenylhexatriene. Indomethacin caused a decrease in membrane fluidity, whereas, exogenous prolactin increased the fluidity of the recipients' liver membranes but again could not overcome these suppressive effects of indomethacin. The data suggest that prolactin induces its own membrane-associated receptor by means of the prostaglandin cascade, perhaps by altering the fluidity of the supporting lipid bilayer.

Animals↗

Psychological depression and 17-year risk of death from cancer.

Psychological depression, measured in 1957-1958 by the Minnesota Multiphasic Personality Inventory at the baseline examination of 2,020 middle-aged employed men, was associated (p less than 0.001) with a twofold increase in odds of death from cancer during 17 years of follow-up. The association did not vary appreciably in magnitude among the early (1958-1962), middle (1963-1968), and later (1969-1974) years of follow-up, persisted after adjustment for age, cigarette smoking, use of alcohol, family history of cancer, and occupational status, and was apparently not specific to any particular site or type of cancer. This result, predicted in advance on the basis of findings by other investigators, is consistent with the hypothesis that psychological depression is related to impairment of mechanisms for preventing the establishment and spread of malignant cells.

Adult↗

DNA repair responses in human skin cells.

Sunlight and some environmental chemical agents produce lesions in the DNA of human skin cells that if unrepaired may interfere with normal functioning of these cells. The most serious outcome of such interactions may be malignancy. It is therefore important to develop an understanding of mechanisms by which the lesions may be repaired or tolerated without deleterious consequences. Our models for the molecular processing of damaged DNA have been derived largely from the study of bacterial systems. Some similarities but significant differences are revealed when human cell responses are tested against these models. It is also of importance to learn DNA repair responses of epidermal keratinocytes for comparison with the more extensive studies that have been carried out with dermal fibroblasts. Our experimental results thus far indicate similarities for the excision-repair of ultraviolet-induced pyrimidine dimers in human keratinocytes and fibroblasts. Both the monoadducts and the interstrand crosslinks produced in DNA by photoactivated 8-methoxypsoralen (PUVA) can be repaired in normal human fibroblasts but not in those from xeroderma pigmentosum patients. The monoadducts, like pyrimidine dimers, are probably the more mutagenic/carcinogenic lesions while the crosslinks are less easily repaired and probably result in more effective blocking of DNA function. It is suggested that a split-dose protocol that maximizes the production of crosslinks while minimizing the yield of monoadducts may be more effective and potentially less carcinogenic than the single ultraviolet exposure regimen in PUVA therapy for psoriasis.

Bacteria↗

Cyclic nucleotide content of passaged keratinocytes in culture during various growth stages.

Human newborn foreskin keratinocytes were maintained in culture in first passage for up to 60 days. An initial lag phase was followed by a growth and a final plateau phase. During this time, cell numbers, the morphologic appearance of both attached and detached cells, DNA, and cyclic nucleotide content were evaluated. Cell cycle analysis during growth phase was performed by flow cytofluorometry. High levels of cAMP and cGMP coincided with the early growth phase, when up to 70% of cells were in S, G2, or M compartments of the cell cycle. Halfway through growth phase, a fall in cyclic nucleotide levels coincided with a drop in mitotic index and increase in G1 cells. Plateau phase was characterized by increased desquamation, a gradual elevation of intracellular cAMP, cGMP, and DNA, and in later stages, an increased proportion of squamous cells in the attached layers. The oldest cultures were mostly squamous with low cyclic nucleotide levels. Results suggest that high cyclic nucleotide content is a feature of cycling, possibly S phase keratinocytes. Onset of differentiation coincides with a small but definite increase in both cAMP and cGMP, which in general vary in the same direction.

Cell Division↗

Altered spectrin dimer-dimer association and instability of erythrocyte membrane skeletons in hereditary pyropoikilocytosis.

Hereditary pyropoikilocytosis (HPP) is a hemolytic anemia characterized by microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of erythrocytes. We have investigated the contribution of abnormal membrane skeletal assembly to these abnormal HPP erythrocyte properties. Skeletons prepared from fresh HPP ghosts with Triton X-100 were considerably more fragile than skeletons from control erythrocytes. Spectrin, the major skeleton component, extracted at 0 degrees C from normal erythrocytes, was present primarily as tetramers and high molecular weight complexes. In contrast, spectrin extracted from HPP erythrocytes under identical conditions contained a significant amount of dimers with a concomitant decrease of tetramers. Furthermore, spectrin dimers from HPP erythrocytes differed from normal spectrin dimers in their failure to reassociate into tetramers both in solution and in the membrane. Presumptive HPP carriers (asymptomatic mothers of the two patients) exhibited a mild but reproducible increase of spectrin dimers in 0 degrees C extracts and a defective reassociation of spectrin dimers of tetramers both in solution and in the membrane. We conclude that in HPP, self-association of spectrin dimers into tetramers is defective, which accounts for the instability of membrane skeletons.

Cytoplasm↗

Effects of dietary essential fatty acids on murine mammary gland development.

Removal of unsaturated fatty acids from the diet of female C3H mice resulted in the gradual onset of essential fatty acid deficiency. Upon reaching the deficient state, alveolar components of the mammary gland began to regress as did the ovarian corpora lutea. An increase in the viscosity of microsomal membranes and a decrease in the number of prolactin binding sites also occurred concomitantly as the deficient state increased in severity. Modification of fats with the diet changes the fluidity of cellular membranes. This appears to alter the functionality of the membrane-associated receptors and their subsequent ability to respond to circulating hormones.

Animals↗

Effect of methylglyoxal bisguanylhydrazone on polyamine biosynthesis, growth, and differentiation of cultured keratinocytes.

The putrescine, spermidine, and spermine content of subcultured human newborn foreskin keratinocytes was determined during growth and early plateau phase and found to be highest during growth. Exposure of the cells to methylglyoxal bis(guanylhydrazone) during growth phase caused a dose-dependent fall in intracellular spermidine and spermine levels and an increase in putrescine levels at higher concentrations. These effects reflect inhibition of S-adenosyl methionine decarboxylase by the drug. At 8 X 10(-6) M the drug reduced incorporation of leucine into protein, lowered or stopped the accumulation of DNA per dish, inhibited mitotic activity, and increased the histidine/leucine incorporation into protein. The last effect is regarded as induction of keratinization. All these effects were reversible if the use of the drug was discontinued after 3 days. Inhibition of the enzymes of polyamine biosynthesis may have value in psoriasis therapy.

Amino Acids↗

Prostaglandin synthesis by murine mammary gland is modified by the state of the estrus cycle.

Mammary glands were excised from female C3H mice at various stages of their estrus cycle. Homogenates incubated at 37 degrees C +/- 10(5) M indomethacin synthesized prostaglandins (PG) E and f2 alpha at rates that varied as a function of the stage at estrus. The rate of PGF2 alpha synthesis was maximal at 1330 pg per mg protein per 2 hr in early diestrus and fell to undetectable levels in early estrus. PGE synthesis exhibited a similar pattern, being maximal at 83 pg per mg protein per 2 hr in early diestrus. These observations suggest that prostaglandins play a role in the cyclic changes observed within the mammary gland.

Animals↗

Requirement of essential fatty acids in the diet for development of the mouse mammary gland.

The ductal system of mammary glands in C3H mice that were started on diets deficient in essential fatty acid(s) (EFA) 1--2 weeks after weaning developed at a normal rate. The alveolar structures, however, began to disappear in the mice after 17 weeks on the EFA-deficient regimen. Injection sc of linoleic acid prevented the atrophic process. Alveoli were also absent in the glands of multiparous mice that were maintained for 32 weeks on the EFA-deficient diet. When the EFA-deficient regimen was started in females during midpregnancy and maintained continuously thereafter, both ductal and alveolar structures failed to develop in the mammary glands of the offspring. Linoleic acid appears to be required for development of ductal and alveolar structures during growth of the mammary gland and also for maintenance of the alveolar structures in the adult mammary gland.

Animals↗

Red cell membrane skeleton: structure-function relationships.

This papaer reviews our present understanding of ultrastructure, organization, and functional characteristics of the erythrocyte membrane cytoskeleton. This two-dimensional fibrillar network of submembrane proteins can be visualized after extraction of lipids and integral membrane proteins by Triton X-100. Current data suggest that the major structural components of the cytoskeleton are heterodimers of double-stranded spectrin that form tetramers by head-to-head associations. The tetramers may be connected into a fibrillar meshwork by oligomers of actin. The control of membrane integrity by this network is illustrated by examples of two hemolyotic anemias characterized by marked membrane instability and vesiculation: 1) hereditary spherocytic anemia of the house mouse associated with spectrin deficiency and 2) hereditary pyropoikilocytosis, a hemolytic anemia in man characterized by thermal instability of the membrane and the presence of abnormal spectrin, which exhibits an increased propensity to thermal denaturation. Stabilization of the cytoskeletal network by covalent cross-links between the nearest cytoskeletal and integral membrane proteins results in a decrease of membrane deformability and a fixation of erythrocytes in their abnormal shape. Such cross-linkings include: 1) transamidative cross-links produced by introduction of Ca2+ (>0.5 mM) into fresh erythrocytes, and 2) intermolecular disulfide couplings, which are formed after extensive oxidation of fresh erythrocytes or after mild oxidation of ATP-depleted, but not fresh, erythrocytes. The significance of these cross-links in stabilization of shape of abnormal erythrocytes such as schistocytes remains to be determined. We conclude that spectrin and actin form a fibrillar submembrane network that plays an important role in control of membrane integrity, erythrocyte deformability, and stabilization of cells in abnormal shapes.

Actins↗

Cross-linkings between spectrin and band 3 in human erythroycte membranes.

A specific structural association between spectrin component 1 and band 3 in human erythrocyte membrane has been demonstrated by covalent cross-linkings, specific labeling, and the technique of two-dimensional gel electrophoresis. A complex of 330,000 daltons, representing 1 + 3, was produced in mildly oxidized membranes at physiologic pH and isotonic conditions but not at hypotonic conditions ( less than 10 mM KCl or NaCl). The yield of this complex decreased dramatically as the monovalent cation concentration decreased from 90 mM to 30 mM. The presence of Mg++ or Ca++ (2 mM) at low ionic strength promoted 1 + 3 cross-linking in an amount similar to that produced at isotonic conditions. The specific segment of band 3 involved in the cross-linking was also investigated by means of chymotrypsin digestion of band 3 in the intact red cells. The results showed the cross-links between spectrin component 1 and the 55,000-dalton fragment of band 3 at physiologic pH and isotonic conditions. This is consistent with the idea that band 3 is anchored on or contacted with the submembrane meshwork at the cytoplasmic membrane surface.

Electrophoresis, Polyacrylamide Gel↗