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Biomedical subjects

L A Davidson

Publications and source records attributed to L A Davidson.

69 records · Page 4Linked to original sources

A freeze fracture and thin section study of intestinal cell membranes and intercellular junctions of a nematode, Ascaris.

The microvillar and lumenal plasma membrane P-face of Ascaris intestinal cells is shown to be covered by relatively large (13 nm) particles at a fairly high density (1000/microm2), while the E-face has virtually none. The P-face of the lateral cell membranes, those separating the cells, have fewer and smaller (8 nm) particles. The intestinal cells are also shown to be connected by an apical complex of smooth septate and tricellular junctions similar to those found between some insect midgut cells. A periodic layer of tannic acid staining material is found on the cytoplasmic sides of the smooth septate junction, and when the intercellular space is filled with lanthanum, smoothly curved, 10 nm wide septal walls can be seen. Below the belt of septate junctions are a large number of gap junctions. These have closely packed arrays of particles on the P-face with some particle aggregates adhering to the closely packed pit arrays on the E-face.

Animals↗

Effects of therapeutic drugs on lymphocyte transformation.

1 Over 40 non-steroidal drugs, routinely given on a long term therapeutic basis, were tested in lymphocyte transformation cultures at high therapeutic concentrations, or in serum cultures after short term oral drug administration. Lymphocyte transformation was assessed by measuring thymidine and 2-deoxyuridine incorporation into DNA. 2 When added in vitro, salicylate significantly inhibited thymidine (48%, n = 35) and deoxyuridine incorporation (20%, n = 12). Thymidine incorporation was specifically inhibited by phenylbutazone (39%, n = 6) and chlorpropamide (48%, n = 5). Specific inhibition of deoxyuridine incorporation, indicative of impaired lymphocyte folate metabolism, was obtained following the addition of pyrimethamine (51%, n = 3) and to some extent by carbimazole (30%, n = 2). In serum cultures, pyrimethamine inhibited deoxyuridine incorporation (30%, n = 3) and chloroquine inhibited the incorporation of both thymidine (37%, n = 3) and deoxyuridine (46%, n = 3). 3 Most classes of drugs used long term are unlikely to cause any significant clinical effect, by impairing lymphocyte function. Caution may be warranted when high doses of salicylate, phenylbutazone, chloroquine, pyrimethamine, chloropropamide or combinations of these drugs are prescribed.

Deoxyuridine↗

The influence of culture conditions on the suppression of lymphocyte transformation by salicylate.

Therapeutic concentrations of salicylate enhanced or inhibited human lymphocyte PHA transformation, depending on the conditions of culture. Response to salicylate were influenced by serum and cell concentration, PHA mitogenic activity and concentration. In particular, pre-incubation of the mononuclear cell population, in salicylate-free medium, made lymphocyte transformation more susceptible to inhibition. The results suggest that the inhibitory effect of salicylate on lymphocyte transformation may be mitigated by a factor released form adherent mononuclear cells. The extent to which culture conditions influence the results of this test emphasise its limitations for assessing the effects of drugs on lymphocyte function in vivo.

Blood↗

Studies on the mycolic acids from the walls of Mycobacterium microti.

Mycobacterium microti walls contained three types of mycolic acids, very similar to those found in Mycobacterium tuberculosis. An alpha-mycolate with two cyclopropane rings, a methoxymycolate with one cyclopropane ring and a methoxyl group, and a ketomycolate with one cyclopropane ring and a keto group were partially characterized. The mycolates made up 34% (by weight) of the peptidoglycan-arabinogalactan-mycolate wall skeleton. Young exponential phase cultures and organisms harvested from mouse lungs contained high proportions of ketomycolates; older cultures had roughly equal proportions of keto- and methoxymycolates. The proportion of alpha-mycolates increased slightly with age of culture, but was always less than one-third of the total.

Cell Wall↗

An analysis of spindle ultrastructure during anaphase of micronuclear division in Tetrahymena.

Mitotic micronuclei were isolated from Tetrahymena thermophila and data on spindle ultrastructure were obtained from serial, transverse sections. Comparison of data from nuclei at meta- and early anaphase with data from nuclei at late anaphase showed that during anaphase, sister kinetochores move from the equator to the spindle poles, but kinetochore translocation occurs without any apparent change in either the number or length of kinetochore microtubules. This unprecedented result is ascribed significance with regard to the mechanism of kinetochore transport since there are only a limited number of ways that result could be achieved. The organization of the peripheral sheath changes during anaphase as evidenced by gaps in the sheath at late anaphase. Numerous kinetochore and non-kinetochore microtubules are located in polar regions of the spindle at late anaphase, whereas those regions contained only peripherally arranged microtubules at earlier stages. Tracking of individual kinetochore microtubules in late anaphase nuclei showed that some of them appeared to become incorporated into the peripheral sheath near the pole. At early and late anaphase, crossbridges connect adjacent microtubules throughout the spindle poleward to the kinetochores, as well as in the interzone.

Anaphase↗

Enoyl coenzyme A reduction by bovine mammary fatty acid synthetase. Specificity and other characteristics.

The NADPH-dependent enoyl coenzyme A reductase activity of bovine mammary fatty acid synthetase has been characterized with regard to substrate specificity and the product formed. A relatively high specificity for an unsubstituted, four-carbon, 2,3-enoyl chain in trans configuration is obtained. Reduction of trans-crotonyl-CoA results in butyrate, 50% of which is coenzyme A-bound. The reaction is subject to product inhibition, specifically by butyryl-CoA and NADP. Free coenzyme A, on the other hand, is an activator. The pH profile, susceptibility to inhibition by -SH reagents, the results of the relative activities obtained with substrate analogues and homologues, and the ready use of crotonyl-CoA as a primer in fatty acid synthesis are consistent with a mechanism in which the crotonyl group is transferred to an -SH group, is reduced, and then is either transferred back to CoA or hydrolyzed.

Acyl Coenzyme A↗

An analysis of spindle ultrastructure during prometaphase and metaphase of micronuclear division in Tetrahymena.

Mitotic micronuclei were isolated from Tetrahymena thermophila in a medium containing hexylene glycol and their ultrastructure was analyzed using thin section techniques. The two stages selected for analysis were early prometaphase and metaphase. A comparison of data from these two stages revealed several differences in nuclear morphology. Metaphase nuclei were longer, they contained more microtubules, and the distribution of microtubules at metaphase was different from that at early prometaphase. Increases in microtubules, which are a unique class of microtubules that can be distinguished from other classes on the basis of their close association to the nuclear membrane. Growth of peripheral sheath microtubules is thought to be significant because it could be the mechanical basis of nuclear elongation. Crossbridges were observed throughout the spindle between all classes of microtubules, but the exact function of these elements remains to be determined.

Animals↗

Effect of low temperature on growth, viability, and synthesis of mycolic acids of Mycobacterium tuberculosis strain H37Ra.

Cultures of Mycobacterium tuberculosis strain H37Ra were grownto early logarithmic phase at 37 degrees C and were incubated at 16 degrees, 20 degrees, and 25 degrees C. The decrease in this ability was more rapid at 20 degrees C than at 16 degrees C. Low-temperature incubation caused decreases in the ratios of mycolic acids and monounsaturated C16-19 fatty acids relative to the total of fatty acids synthesized. It also caused an increase in the ratio of saturated C24-26 fatty acids relative to the total of fatty acids synthesized. These ratios were based on the incorporation of radiolabel from 14C-acetate into fatty acids. These results showed that when M. tuberculosis H37Ra was incubated at low temperatures, it did not adapt by increasing the ratio of unsaturated to saturated fatty acids synthesized. The ability of the cells to synthesize mycolic acids was sharply decreased. These changes may lead to the loss of viability of M. tuberculosos H37Ra. Mycolic acid synthesis is similarly affected by exposure of cells to isoniazid, an antimycobacterial drug.

Chromatography, Thin Layer↗

Ultrastructure of the membrane attachment sites of the extrusomes of Ciliophrys marina and Heterophrys marina (Actinopoda).

The actinopods Ciliophrys marina and Heterophrys marina both have membrane bounded extrusomes attached to their cellular and axopodial membranes. The extrusomes of C. marina, the muciferous bodies, are fairly simple in structure and contain a homogeneous osmiophilic substance. Their attachment site is characterized by a rectangular array of freeze fracture particles in the cell membrane. The extrusomes of H. marina, the conicysts, are more complex and contain a two-part osmiophilic body. The attachment site of conicysts is characterized by a rosette of 8 freeze fracture particles very similar to the 9-particle rosette found at the mucocyst attachment sites in Tetrahymena. Furthermore, intracytoplasmic bridges connect the conicyst and cell membrane faces, and a specialized fibrillar structure is found on the cell membrane in the region of conicyst attachment. The various possible roles for such particle arrays are discussed and their presence in virtually all extrusomes is predicted.

Animals↗