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Biomedical subjects

R D Clark

Publications and source records attributed to R D Clark.

At least 91 records · Page 5Linked to original sources
PubMed1983

Spectrally distinct cytochrome b-563 components in a chloroplast cytochrome b-f complex: Interaction with a hydroxyquinoline N-oxide.

The two heme equivalents of cytochrome b-563 in the photosynthetic cytochrome b-f complex can be distinguished by their rate of reduction with dithionite at 25 degrees C and by their optical absorption spectra at 77 K. The cytochrome b component that is rapidly reduced after addition of dithionite or reduced ferredoxin possesses an alpha band that splits at 77 K into two peaks, at 557 and 561 nm. Prolonged incubation with reductant reveals a second, approximately equimolar cytochrome b component that has at 77 K an unsplit alpha-band maximum at 561 nm. The designations cytochrome b-563(H) and cytochrome b-563(L), respectively, are proposed for the rapidly and more slowly reduced cytochrome b-563 components. Potentiometric titration establishes a midpoint potential, E(m), of -30 mV (electron change n approximately 2) for cytochrome b-563(H) and -150 mV (n = 1) for cytochrome b-563(L) at pH 7.5. The reduction potential of these components is raised by 2-heptyl-4-hydroxyquinoline N-oxide, giving E(m) values of +57 and -34 mV, respectively, with each titration slope approximating n = 2.

Journal Article↗
PubMed1982

Structure-activity relationships for 2-substituted imidazoles as alpha 2-adrenoceptor antagonists.

Several 2-[(1,4-benzodioxan-2-yl)alkyl]imidazoles were prepared and evaluated for their blocking activity and relative selectivity on presynaptic (alpha 2) and postsynaptic (alpha 1) receptors in the isolated rat vas deferens. 1-Ethyl-2-[(1,4-benzodioxan 2-yl)methyl]imidazole (13) was the most selective alpha 2-adrenoceptor antagonist of the series and was, for practical purposes, devoid of alpha 1-adrenoceptor antagonist activity. The lipophilicity of 13 (log D = 2.31) indicated that it would have an excellent chance to enter the central nervous system. Compound 13 was selected for clinical evaluation as an antidepressant agent.

Adrenergic alpha-Antagonists↗
PubMed1981

Synthesis and evaluation of ureido- and vinylureidopenicillins as inhibitors of intraruminal lactic acid production.

A series of 14 vinylureidopenicillins and a series of 9 ureidopenicillins were prepared by reaction of 6-aminopenicillanic acid with vinyl isocyanates and isocyanates. These compounds were evaluated for their potential to protect ruminants against lactic acidosis. The compounds were tested for inhibition of in vitro ruminal lactic and propionic acid production, and six compounds inhibited lactic acid production to less than 10% of control at doses of 0.31 microgram/mL or lower, whereas they did not inhibit propionic acid production at doses greater than 10 micrograms/mL. The most active compounds also were screened for general antibacterial activity and were found to be weakly active against Gram-positive bacteria. The structure--activity relationships are discussed for both series. Triethylammonium 6-[3[2-(4-tert-butylphenyl)vinyl]ureido]penicillanate (4) was chosen for evaluation as an inhibitor of intraruminal lactic acidosis in vivo.

Acidosis↗
PubMed1981

Synthesis and antihypertensive activity of a series of 8-substituted 1-oxa-3,8-diazaspiro[4.5]decan-2-ones.

Forty-three new 1-oxa-3,8-diazaspiro[4,5]decan-2-ones optionally substituted with 2-(3-indolyl)ethyl, 3-(2-methoxyphenoxy)-2-hydroxypropyl, or 2-(1,4-benzodioxan 2-yl)-2-hydroxyethyl at the 8 position were prepared for screening as antihypertensive agents in the spontaneous hypertensive rat. For the 8-[2-(3-indolyl)ethyl] compounds the most active were those substituted in the 4 position, where activity was at maximum with the 4-ethyl compound (1). The 8-[3-(2-methoxyphenoxy)-2-hydroxypropyl] compounds were less active than their 1,4-benzodioxane counterparts, which were tested as mixtures of erythro and threo diastereoisomers. Both the 4-ethyl-8-[2-(1,4-benzodioxan-2-yl)-2-hydroxyethyl]-substituted 38 and (S)-3-methyl-8-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-substituted 42 were designed as mixed alpha- and beta-adrenergic receptor blockers. Bother compounds lowered blood pressure, but they gave no evidence of working as beta-adrenergic blockers. Examination of 8-[2-(3-indolyl)ethyl]-1-oxa-3,8-diazaspiro[4.5]-decan-2-one (8) and 3 methyl-8-[2-(1,4-benzodioxan-2-yl)-2-hydroxyethyl]-1-oxa-3,8-diazaspiro[4,5]decan-2-one (29) in the dog showed them to be alpha-adrenergic blockers. Compound 29 was primarily an alpha 2-adrenoceptor antagonist, while 8 was more skewed toward alpha 1-adrenoceptor antagonism. Tilt-response studies for evaluating the potential for producing orthostatic hypotension showed that both 8 and 29 had little potential for avoiding orthostatic hypotension at therapeutically effective doses.

Animals↗
PubMed1981

Calcified left ventricular thrombus causing repeated retinal arterial emboli: clinical, echocardiographic, and pathologic features.

The clinical, echocardiographic, and pathologic features of a discrete calcified left ventricular thrombus are presented in a young adult man with a two-year history of transient visual field defects leading to eventual loss of vision in his left eye. M-mode and cross-sectional echocardiographic studies suggested a large mass extending across the left ventricle. These findings were confirmed at surgery when a calcified mass pathologically consistent with a calcified thrombus was removed. The pertinent literature on the echocardiographic diagnosis of left ventricular thrombi is reviewed.

Adult↗
PubMed1976

Structural and functional changes in an identified cricket neuron after separation from the soma. I. Structural changes.

The morphological effects of separation from the soma were examined in isolated arborization and isolated axon segments of an identified motor neuron in the Polynesian field cricket, Teleogryllus oceanicus. The identified neuron, the contralateral dorsal longitudinal motor neuron of the metathoracic ganglion (CDLM), possesses an arborization most of which lies contralateral to its soma within the metathoracic ganglion. Midline surgical lesions in the metathoracic ganglion separated CDLM into a distal segment composed of the axon and most of the arborization, and a proximal segment comprised of the remaining arborization, neuritie, and soma. Isolated axonal segments were produced by cutting the nerve root containing the axon of CDLM close to the ganglion. The normal anatomy of CDLM was determined by axonal dye-fills using cobaltous chloride. Morphological changes in the isolated arborization of CDLM were examined by axonal dye-fills at successive time intervals. Changes in the isolated CDLM axon were examined via dissection and histological cross-sections of the distal nerve at graded time intervals. In one example, a remnant of the isolated CDLM arborization survived to 168 days postoperative, a time comparable to the longest previously-reported physiological and morphological survival times of distal axonal segments of invertebrates. In general the isolated arborization does not survive this long. Normally-occurring branches of the arborization can be preserved about 0 to 50 days. After this period branches of the arborization seem to be lost in progressive fashion from smaller to larger, leading to complete loss of the arborization and axon in most cases at 100 or more postoperative days. There is evidence for the presence of supernumerary fibers in the isoalted CDLM arborization between 0 to 63 days postoperative. Such supernumerary fibers indicate an independent capacity for outgrowth of the isolated arborization without connection to the nucleus. The distal axonal segment of CDLM degenerates physiologically and morphologically within 4 to 15 days after peripheral nerve section. This time course is close to that of Wallerian degeneration of vertebrate peripheral nerve axons.

Animals↗
PubMed1976

Structural and functional changes in an identified cricket neuron after separation from the soma. II. Functional changes.

Physiological and behavioural effects of separation from the soma were examined in isolated arborization and isolated axon segments of an identified motor neuron in the Polynesian field cricket, Teleogryllus oceanicus. The identified neuron, the contralateral dorsal longitudinal motor neuron of the metathoracic ganglion (CDLM), has an arborization most of which lies contralateral to its soma within the ganglion. Midline lesions in the ganglion separated CDLM into a distal segment composed of the axon and most of the arborization, and a proximal segment made up of the remaining arborization, neurite and soma. Isolated axonal segments were produced by cutting the nerve containing the CDLM axon. The function of the neuron-muscle system composed of CDLM, its pre-synaptic inputs, and its innervated muscle bundle was examined in contrl and experimentally operated animals. Extracellular recording assessed function in the axon. Electrical or tactil stimulation was used to excite pre-synaptic inputs to the CDLM arborization. Intracellular recording determined changes in post-synaptic potentials and miniature end-plate potentials in the muscle bundle innervated by CDLM. Normal axonal conduction, competence to respond to pre-synaptic input, neuron-muscle transmission, and miniature end-plate potential appearance can remain in the isolated arborization preparation. Physiological viability is longer in the cricket isolated arborization than in other insect distal segments described. Survival times of axonal conduction and the competence of the isolated arborization to respond to pre-synaptic input are roughly correlated with disappearance of the whole distal segment at 100 or more postoperative days. A naturally-occurring breakdown of the metathoracic dorsal longitudinal muscles in Teleogryllus eventually prevents measurements of post-synaptic potentials and miniature end-plate potentials. Normal post-synaptic function mediated by the distal arborization is maintained up to this breakdown, to a maximum of 44 days postoperative. The distal axonal segment of CDLM degenerates physiologically within four days postoperative, a time course approximating that of degeneration in vertebrate peripheral nerve distal axons.

Animals↗