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Biomedical subjects

K J Clark

Publications and source records attributed to K J Clark.

29 records · Page 2Linked to original sources

In vitro activation of rat brain protein kinase C by polyenoic very-long-chain fatty acids.

A variety of fatty acids including the cis-polyunsaturated very-long-chain fatty acids (VLCFA) (> 22 carbon atoms) common in retina, spermatozoa, and brain were examined for their ability to activate protein kinase C (PKC) purified from rat brain. Arachidonic [20:4(n-6)], eicosapentaenoic [20:5(n-3)], and docosahexaenoic [22:6(n-3)] acids as well as the VLCFA dotriacontatetraenoic [32:4(n-6)] and tetratriacontahexaenoic [34:6(n-3)] were equally capable of activating PKC in vitro with maximal activity being between 25 and 50 microM. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate further enhanced the in vitro activation of PKC when added to the protein kinase assay system with the fatty acids. The fully saturated arachidic acid (20:0) was inactive in both assay systems. The potential significance of the in vitro activation of PKC by the VLCFA is discussed.

Animals↗

Neglected subjects in sex research: a survey of sexologists.

This study surveyed registered diplomates of the American Board of Sexology on neglected areas in sex research. Three rounds of questionnaires were completed by the diplomates as they identified and narrowed the most neglected sexual research questions. Results indicate that among three of the four specialty groups, marital sexual behavior was ranked as the most neglected sex research subject in the literature. In reviewing the individual research questions under each subject, more outcome studies on the treatment of various sexual disorders and dysfunctions were identified and ranked consistently higher than any questions under another subject area. The single exception was among sex educators, where individual research questions concerning sex education received the highest priority. These findings may suggest the need for new directions in sex research.

Counseling↗

Further development of hydrogen bond functions for use in determining energetically favorable binding sites on molecules of known structure. 1. Ligand probe groups with the ability to form two hydrogen bonds.

The directional properties of hydrogen bonds play a major role in determining the specificity of intermolecular interactions. An energy function which takes explicit account of these properties has been developed for use in the determination of energetically favorable ligand binding sites on molecules of known structure by the GRID method (Goodford, P.J.J. Med. Chem. 1985, 28, 849. Boobbyer, D.N.A.; Goodford, P.J.; McWhinnie, P.M.; Wade, R.C.J. Med. Chem. 1989, 32, 1083). In this method, the interaction energy between a target molecule and a small chemical group (a probe), which may be part of a larger ligand, was calculated using an energy function consisting of Lennard-Jones, electrostatic, and hydrogen bond terms. The latter term was a function of the length of the hydrogen bond, its orientation at the hydrogen-bonding atoms, and their chemical nature. We now describe hydrogen bond energy functions which take account of the spatial distribution of the hydrogen bonds made by probes with the ability to form two hydrogen bonds. These functions were designed so as to model the experimentally observed angular dependence of the hydrogen bonds. We also describe the procedure to locate the position and orientation of the probe at which the interaction energy is optimized. The use of this procedure is demonstrated by examples of biological and pharmacological interest which show that it can produce results that are consistent with other theoretical approaches and with experimental observations.

Binding Sites↗

Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas.

The fatty acid composition of erythrocyte total lipids taken from a group of term infants 10 weeks after being fed a commercial infant formula with a high ratio of linoleic acid (18:2n-6) (LA) to alpha-linolenic acid (18:3n-3) (ALA) (19:1; LA, 14%; ALA, 0.7%; group A, n = 10) was compared with the fatty acid composition of erythrocytes from infants fed formulas that contained LA/ALA ratios reduced by either increasing ALA (4:1; LA, 13%; ALA, 3.3%; group B, n = 11) or decreasing LA (3:1; LA, 3.5%; ALA, 1.1%; group C, n = 8). Results were compared with those in an age-controlled group (n = 9) of breast-fed infants. Decreasing the LA/ALA ratio increased n-3 C20 and C22 fatty acid incorporation (formula B = 8.98% +/- 0.65%; formula C = 9.30% +/- 0.95%) relative to formula A (5.97% +/- 0.76%; p less than 0.05). Although docosahexaenoic acid (22:6n-3) (DHA) incorporation was highest in infants fed formulas B and C (4.78% +/- 0.45% and 4.48% +/- 0.49%, respectively) relative to formula A (3.47% +/- 0.46%; p less than 0.05), it did not reach levels found in breast-fed infants (6.55% +/- 1.23%; p less than 0.05). In addition, levels of arachidonic acid (20:4n-6) (AA) were lower in all formula-fed groups (p less than 0.05) relative to those in breast-fed infants. Based on some equations, it is predicted that AA levels in tissues of infants fed lower LA/ALA ratios would be reduced even further. Because both AA and DHA are probably essential for normal neural development of the infant, formulas with LA/ALA ratios below 4:1 are likely to result in fatty acid profiles notably different from those of breast-fed infants.

Arachidonic Acid↗

Phorbol esters modulate the turnover of both ether- and ester-linked phospholipids in cultured mammalian cells.

The effects of 12-O-tetradecanoylphorbol 13-acetate (TPA) on the metabolism of ester- and ether derivatives of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were studied in HeLa and HEL-37 cells. TPA stimulated the incorporation of [3H]choline into diacyl-, alkylacyl- and alkenylacy/PC in HeLa cells, but inhibited the incorporation of [3H]ethanolamine into the corresponding derivatives of PE. TPA also stimulated the incorporation of [3H]ethanolamine into lysoPE and the release of labelled ethanolamine and phosphoethanolamine from HeLa cells prelabelled with [3H]ethanolamine. All responses to TPA were abolished in HeLa cells preincubated with the phorbol ester and which were deficient in protein kinase C. In HEL-37 cells TPA stimulated label incorporation into both ester- and ether-forms of PE. The marked effects of TPA on ether-lipid metabolism raises the possibility that hydrolysis products of this class of lipid are important in transmembrane signalling pathways.

Animals↗

An anatomy-based coordinate system for the description of the kinematic displacements in the human knee.

The effects and interaction of the anatomical displacements in the human knee are a prerequisite to an accurate assessment and communication of the kinematic data. For the kinematic information to be used to improve diagnosis and treatment, and for better prosthetic design and installation, there must be clear, concise, and universal definitions of the displacements. In general, the displacements are defined as three translations and three rotations. In this paper, anatomic landmarks on the femur and on the tibia are used to define the locations and orientations of the six displacement axes; i.e. three translational and three rotational displacement axes. The most commonly accepted kinematic representation of the knee joint, in the literature, is a special geometry three-cylindric open chain in which the axes of the cylindric joints are defined according to the rotational displacement axes. The sequentially adjacent joint axes are assumed to not only intersect but to intersect at right-angles. The open chain permits a total of six degrees of freedom between a Cartesian reference frame attached to the femur and a Cartesian reference frame attached to the tibia. In this paper, the three rotational axes are shown to be skewed and off-set from each other, therefore, a three-cylindric open chain with skewed joint axes is proposed to measure the six displacements between the two reference frames. The authors believe that the proposed open chain is the most general to date and provides a more realistic representation of the displacements in the knee. To illustrate the significance of the reference frames on the interpretation of measured data, the anterior/posterior drawer is plotted against per cent gait cycle for three existing open chains and the proposed open chain.

Biomechanical Phenomena↗

Phorbol ester induces differential membrane-association of protein kinase C subspecies in human platelets.

Human platelets contained proteins which cross-reacted with antisera specific for brain protein kinase C-alpha and -beta. When platelets were incubated with 12-O-tetradecanoylphorbol-13-acetate there was a rapid accumulation of protein kinase C-alpha in the particulate fraction associated with a loss of this subspecies from the soluble fraction. No particulate accumulation or soluble loss of protein kinase C-beta could be detected when platelets were incubated with the phorbol ester.

Blood Platelets↗

Lithium allergy.

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Coloring Agents↗

Methoxychlor residues in milk of cattle treated with Marlate 50 insecticide as a dermal spray.

Lactating Holstein cattle were treated twice at an interval of 14 days with methoxychlor (Marlate 50 insecticide) as a 0, .25, or .50% dermal spray, with 2 quarts of spray mix applied to each animal. Residues of methoxychlor in whole milk were highest on the 1st or 2nd day after treatment and, when expressed as part per million equivalent in milk fat, were as high as 2.0 and 3.0 ppm in samples from the low and high dosage sprays. Residues in milk dropped rapidly after residues were at most only slightly above the sensitivity limit (.005 ppm in whole milk) of the analytical method. Applicative specifications for Marlate 50 insecticide use on lactating dairy cattle might result in violative methoxychlor residues in milk during the first 1 to 3 days after treatment.

Administration, Topical↗