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Biomedical subjects

R L Clark

Publications and source records attributed to R L Clark.

At least 127 records · Page 7Linked to original sources

Morphogenesis in dictyostelium: an orbital hypothesis.

Free-living amoebae of Dictyostelium discoideum aggregate when deprived food, guided by the intercellular transmission of signals of adenosine 3',5'-monophosphate. A succession of multicellular forms is then constructed, each with a circular cross section in every plane normal to its central axis. Amoebae are in constant circular and helical motion around the circumference of these structures. A theory is proposed wherein the sustained progagation of waves of cyclic adenosine 3',5'-monophosphate secretion in cellular loops determines their circumference and thereby organizes morphogenesis in this organism.

Cell Aggregation↗

Systemic cancer and the metastatic process.

Various known and presumed characteristics of malignant cells that permit metastasis and factors that contribute to the establishment of secondary tumor foci are reviewed. The potential for therapeutic control with and the limitations of chemotherapy are discussed briefly.

Animals↗

Neuronal, non-neuronal and hybrid forms of enolase in brain: structural, immunological and functional comparisons.

Three forms of the glycolytic enzyme, enolase [2-phospho-D-glycerate hydrolase (E.C. No. 4.2.1.11)] have been prepared from rat whole brain extract. The most acidic enolase form is neuron specific enolase (NSE) which had previously been designated neuron specific protein (NSP). The least acidic form designated non-neuronal enolase (NNE) has been purified and compared structurally, immunologically and functionally to NSE. NNE is a dimer of 86,500 M.W. consistint of two very similar subunits. The data establish that NNE is larger than NSE which has been shown to be composed of two apparently identical 39,000 molecular weight subunits (78,000). NNE is less acidic than NSE having a pI of 5.9 compared to the value of 4.7 for NSE. Structural and immunological analysis establishes that the NNE subunit is distinct from the NSE subunit, and are therfore products of two separate genes. The structural designation of NSE is (gammagamma) and that of NNE (alpha' alpha'). NSE is strictly localized in neurons indicating that the gene coding for the gamma subunit is only expressed in neuronal cells. The intermediate brain enolase form has been partially purified; structural and immunological evidence indicate that it is a hybrid molecule consisting of one NNE subunit and one NSE subunit (alpha'gamma).

Amino Acid Sequence↗

Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.

In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the pain thresholds of both the inflamed and normal foot were elevated. This is not commonly observed with nonsteroidal antiinflammatory agents. The most active compounds were 1,3-dihydro-3[3,4-(methylenedioxy)phenyl]imidazo[4,5-b]pyridin-2-one (I-15) and its N-allyl (I-21) and N-isopropyl (I-121) derivatives. In the triazole series the 3-(2-fluoro- and 2,4-difluorophenyl)triazolo[4,5-b]pyridines (T-1 and T-8) were the best. The imidazole compounds were somewhat superior in analgesic activity to codeine and d-propoxyphene without showing any narcotic characteristics. Some of the compounds also possessed activity against carrageenan-induced foot edema in the rat, so these compounds represent a new class of nonnarcotic analgesic antiinflammatories, capable of producing a greater degree of analgesia than that obtainable with other nonsteroidal antiinflammatory agents.

Animals↗

Microradiographic demonstration of pyelolymphatic backflow in the porcine kidney.

Pyelolymphatic backflow occurs when intrapelvic pressure rises acutely. Although peripelvic and hilar lymphatics have occasionally been demonstrated during intravenous urography and retrograde pyelography, the patterns of intrarenal microlymphatic filling have not previously been studied radiographically in multipapillary kidneys. Microradiography was performed after retrograde ureteral injections of barium sulfate suspension in recently excised pig kidneys. Contrast filled the ducts of Bellini and extended in a retrograde fashion as far as the distal convoluted tubules. Intrarenal cortical and corticomedullary microlymphatics, as well as veins, filled following forniceal rupture and interstitial extravasation. These anatomic studies suggest that the renal lymphatics may function as an alternate pathway of drainage of an acutely obstructed kidney.

Animals↗

Microradiographic studies of renal lymphatics.

Cortical and medullary lymphatics have been observed during micro-angiographic studies of canine renal allograft rejection and retrograde ureteral injection in normal pigs. Lymphatic filling results from microvascular damage in the canine model and forniceal rupture in the pig. Renal lymphatics function as an alternate route for drainage during altered physiological states.

Animals↗

Investigations on metabolic modulation of p-aminohippurate accumulation by rabbit renal cortical slices.

Preparation and incubation of renal cortical slices from adult, female, New Zealand white rabbit depleted tissue citrate concentration. Acetate (10.0 mM) in the incubation significantly increased slice citrate concentration and p-aminohippurate (PAH) accumulation. Physiological concentrations of citrate increased PAH accumulation and final medium pH. increasing concentrations of citrate produced a biphasic effect on PAH accumulation. These data suggested that citrate may act as an intracellular modulator of organic anion transport. This hypothesis was tested with other stimulators of PAH accumulation. Physiological concentrations of alpha-ketoglutarate or succinate increased slice accumulation of PAH. Higher concentrations of either substrate significantly inhibited PAH accumulation. Final medium pH increased with increased medium concentration of both substrates. alpha-Ketoglutarate (0.5 mM) increased PAH accumulation but had no effect on slice citrate concentration. Glucose did not alter either PAH accumulation or slice citrate concentration. Slices incubated without substrate were depleted of citrate but not of alpha-ketoglutarate. Acetate (1.0 mM) significantly increased slice concentration of both alpha-ketoglutarate and citrate. These data suggested that organic anion transport could be modulated by several metabolic intermediates acting through similar but separate mechanisms.

Acetates↗

Acoustical holography: physical parameters and potential clinical applications.

Acoustical holography achieves real-time imaging of bodily structures through ultrasound. The fundamentals of acoustical holography and a description of a prototype unit undergoing trials at the authors' institution are presented. Physical parameters and means of calibrating the acoustic beam are discussed, and results of preliminary experimental and clinical studies reviewed. Acoustical holography has the potential for providing complementary diagnostic information which, after further technical developments, may furnish clinically useful information.

Accident Prevention↗