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Biomedical subjects

R A Gelman

Publications and source records attributed to R A Gelman.

17 recordsLinked to original sources

Collagen fibril formation in vitro. The role of the nonhelical terminal regions.

We showed previously that fibril formation in vitro from rat tail tendon collagen requires a temperature-dependent initiation (Step 1) following which linear assembly to form thin filaments (Step 2) proceeds as rapidly at 4 degrees C as at 26 degrees C. Step 3, lateral assembly of filaments to form fibrils, is again temperature-dependent. We now find that Step 1 is complete in 6 min at 26 degrees C and the time is independent of collagen concentration in the range 0.08 to 0.39 mg/ml. Collagen treated with pepsin, which removes the nonhelical ends but leaves the triple helix intact, forms fibrils by a similar mechanism. However, Step 1 is altered or absent and early temperature changes produce a complex response consistent with an alternate, counterproductive pathway. Assembly is also much slower, particularly Step 2, and the fibrils formed are abnormal in that native banding is often absent and short tactoidal forms are common. These results suggest that in the assembly of fibrils from normal collagen the nonhelical ends are involved in an early conformational change and critically regulate later steps.

Animals

Serum long-chain alcohol levels in healthy individuals and in patients with breast cancer.

Total long-chain alcohols were analyzed in blood sera from normal individuals and patients with diagnosed breast cancer. Tetra-, hexa- and octadecan-1-ol were the major long-chain alcohols detected in both groups. While the qualitative composition of the serum alcohols was similar in the two groups the average alcohol content of the serum of the breast cancer patients was approximately six times greater than that of the normal group. This difference in serum alcohol levels between the two groups was significant at p less than 0.01.

Adolescent

Mucociliary transference rate and mucus viscoelasticity dependence on dynamic storage and loss modulus.

Various samples of estrous bovine cervical mucus were collected, and their dynamic viscoelastic properties were determined at between 2.7 and 4.4 rad/s. Comparing the loss modulus with the rigidity (storage) modulus for the samples taken, the former was found to increase markedly as the latter increased. Limited exposure of mucus to increased temperatures removed crosslinks, whereas treatment with glutaraldehyde introduced additional ones. In the case of one sample, the number of crosslinks was altered in this way. As the number of crosslinks decreased or increased, the storage modulus decreased or increased, but the loss modulus remained relatively unaffected. The transference (ability to move particle loads) of native and modified samples on the ciliated epithelium of a frog palate depleted of mucus was determined. All data for transference rate correlated against changes in the storage modulus. The rate was maximal for a storage modulus of 1.6 dynes.cm-2 and decreased rather sharply to either side of this value. No such correlation could be found against the loss modulus. In fact, whereas very different values of the loss modulus corresponded to the same storage modulus, the transference rate was the same. Hence, the storage rather than the loss modulus determines transference rate.

Animals

Effects of small amounts of pentadecan-2-one on the growth of Clostridium butyricum.

Primary alcohols occur as trace lipids and are the only long-chain alcohol species present in Clostridium butyricum. Secondary alcohols do not occur physiologically in this microorganism. Exposure of these cells to the methyl ketone, pentadecan-2-one, results in a marked decrease in the primary alcohol content with the secondary alcohol, pentadadecan-2-ol, becoming the major alcohol present. This change in lipid composition is associated with a significant decrease in growth rate that is proportional to the log of the pentadecan 2-one concentration of the incubation medium. When these cells are incubated with pentadecan-2-ol alone, growth is unaffected. Simultaneous exposure of the bacteria to pentadecan-2-one and a mixture of primary alcohols results in a partial relief of the growth inhibition observed with the ketone alone. These observations indicate that pentadecan-2-one inhibits the formation of primary alcohols that are important for normal growth of this bacterium.

Alcohols

Inhibition of growth of Morris hepatomas 7777 and 7800 by corn oil.

Intraperitoneal injection of trace amounts of corn oil prior to and following the injection of 40-50 mg of tissue from hepatoma 7777 or 7800 into the thigh of adult male Buffalo rats resulted in a marked decrease in the growth rate of both tumors. Exhaustive extraction of the corn oil with water indicated that the active component was not water soluble. Similar injections of safflower oil or isotonic saline had no effect on tumor growth rate. Analysis of the tissue phospholipid fatty acids revealed that the injected corn oil caused no change in the esterified fatty acids in this lipid fraction.

Animals

Cyanogen bromide fragments of bovine cervical mucus glycoprotein.

Treatment of bovine cervical mucus glycoprotein with cyanogen bromide gives four fractions, with the molecular weights of the three major fractions being 230 000, 130 000, and 35 000. The results indicate that, as for other glycoproteins, there are different regions along the protein core, some of which have a high sugar content and others which contain considerably less carbohydrate; it seems likely that the regions of lower sugar content may be important to intermolecular linkages. The data suggest that the basic unit of the glycoprotein has a molecular weight of 550 000-600 000, with its protein core consisting of approx. 1200 amino acid residues.

Amino Acids

The effect of a strongly-interacting macromolecular probe on the swelling and exclusion properties of loose connective tissue.

Poly(L-lysine), a cationic polypeptide known to undergo specific interactions with acid mucopolysaccharides, is used as a macromolecular probe in an investigation into the structure of loose connective tissue. The polypeptide apparently binds, via an electrostatic mechanism, to the mucopolysaccharide component of the tissue, leading to a reduction in the swelling of the tissue. The polypeptide does not, however, have a deswelling effect on the tissue; the ultimate reduction in swelling is influenced by the absolute amount of polybase which enters the tissue during the swelling process. Dextran 2000 is found to have a dwelling effect on the tissue which is independent of the action of the polypeptide; this is suggestive of a large degree of independence between the collagen network and the mucopolysaccharide-containing matrix. The polypeptide, moreover, causes a reduction in the excluded volume of the tissue.

Arginine

On the role of sialic acid in the rheological properties of mucus.

The importance of sialic acid in the rheological properties of mucus has been investigated. Both bovine cervical mucus, which is a gel, and the structural glycoprotein derived from it were studied before and after treatment with neuraminidase which selectively cleaves terminal sialic acid residues. The storage modulus, viscosity and circular dichroism spectrum were all essentially changed after removal of the sialic acid. These results would indicate that removal of sialic acid does not affect the physical structure of the glycoprotein and it is concluded that sialic acid has no significant role in the rheological properties of cervical mucus.

Animals

Permeability of the blood-brain barrier to long-chain alcohols from plasma.

Cis-9-octadecenyl alcohol was fed as a dietary supplement to adult male rats for 7 and 14 days. At the end of these feeding intervals, lipids were extracted from brain and liver. The neutral lipids were analyzed for free and esterified long-chain alcohols and alkyl and alk-1-enyl glycerols. Total lipid phosphorus, alkyl acyl and alk-1-enyl acyl phosphoglycerides were determined in the phospholipid fraction. A marked change was observed in these lipid types in the liver, but not in the brain. In liver the free and esterified long-chain alcohols increased threefold following feeding of the dietary supplement. Feeding cis-9-octadecenyl alcohol had no effect on the neutral alkoxy lipids of liver but resulted in an approximately three- to eightfold increase in the ionic alkoxy lipids.

Animals

Percutaneous absorption of 7, 10 14C-benzo[a]pyrene and 7, 12 14C-dimethylbenz[a]anthracene in mice.

The percutaneous penetration, tissue distribution and excretion of 14C-labeled benzo[a]pyrene (BP) and dimethylbenz[a]anthracene (DMBA) were studied in mice. Both BP and DMBA rapidly penetrated the skin and were excreted more in the feces than in the urine. The proportion of BP and DMBA absorbed was less with increasing applied dose due to apparent saturation of the uptake process. Uptake from the dorsal skin of the nose was similar to uptake from the dorsal nuchal skin.

9,10-Dimethyl-1,2-benzanthracene