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R W Keck

Publications and source records attributed to R W Keck.

At least 37 records · Page 2Linked to original sources
PubMed1988

New photosensitizers for photodynamic therapy: combined effect of metallopurpurin derivatives and light on transplantable bladder tumors.

A series of metallopurpurins was tested for their photodynamic activity against transplantable N-[4-(5-nitro-2-furyl)-2-thiazoyl]formamide-induced urothelial tumors growing in male Fischer CDF (F344/CrlBR) rats. Histological examination of tumors in animals treated with the metallopurpurins and red light (greater than 590 nm, 360 J/cm2) revealed tumor necrosis 24 h after completion of therapy. Control tumors showed no histological change. In 30-day tumor regrowth studies, 70% of animals treated with the metallopurpurin derivative SnET2 were free of tumors while 50% of the animals treated with the free-base purpurin ET2 were free of tumor. Metallopurpurins have intense absorptions in the red region of the visible spectrum, a region with good tissue penetration. The metallopurpurins are easily prepared from the corresponding purpurins with a high degree of purity. This study demonstrates the potential of these photosensitizers for photodynamic cancer therapy.

Animals↗
PubMed1987

Morphological study of the combined effect of purpurin derivatives and light on transplantable rat bladder tumors.

Purpurin derivatives, a group of synthetic photosensitizers, were tested for their photodynamic activity against transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced urothelial tumors growing in male Fischer 344 rats. Histological examination of tumors in animals treated with the purpurin derivatives and red light (greater than 590 nm, 360 joules/cm2) revealed tumor cell necrosis 24 h after completion of therapy. Control tumors showed no histological change. Purpurins have a major absorption peak in the red region (greater than 650 nm) of the visible spectrum, a region with good tissue penetration, and purpurins can be synthesized with a high degree of purity. This study demonstrates the potential of purpurin derivatives as photosensitizers for photodynamic cancer therapy.

Animals↗
PubMed1987

A dose response analysis of purpurin derivatives used as photosensitizers for the photodynamic treatment of transplantable FANFT induced urothelial tumors.

Rats engrafted with transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced urothelial tumors were treated with purpurin derivatives and red light (greater than 590 nm., 360 joules/cm.2). Treated and control tumors were harvested 12 days after treatment and dry weights compared. At doses of 5.0 micrograms./gm. and 2.5 micrograms./gm. body weight, the purpurins designated NT1 and NT2, when combined with light, caused statistically significant (p less than 0.02) tumor regression when compared to light shielded controls. At 1.0 micrograms./gm. body weight, NT1 and light also induced significant tumor regression (p less than 0.02). Purpurins, which have strong absorption bands above 650 nm. and can be synthesized with a high degree of purity, appear to have potential as photosensitizers for photodynamic therapy.

Animals↗
PubMed1986

Photodynamic treatment of transplantable bladder tumors in rodents after pretreatment with chloroaluminum tetrasulfophthalocyanine.

Chloroaluminum tetrasulfophthalocyanine (AlPCS) was used as a photosensitizer for the photodynamic treatment of transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced urothelial tumors. Two groups of six rats each were injected with AlPCS (three micrograms./gm. body weight) and 24 hours after injection underwent photodynamic treatment with red light (greater than 590 nm., 360 joules/cm.2). Tumors examined four hours (Group I) and 24 hours (Group II) after the completion of phototreatment showed extensive hemorrhagic necrosis. Tumors treated with AlPCS alone showed no changes. In two other groups of six rats each, blood flow to tumors treated with AlPCS alone (Group III) and AlPCS plus light (Group IV) was measured using the radioactive microsphere technique. AlPCS plus light resulted in a significant decrease (p less than .05) in tumor blood flow within 10 minutes of completion of phototreatment while AlPCS alone had no effect on tumor blood flow. These findings are similar to those observed when higher doses (10 micrograms./gm. to 20 micrograms./gm. body weight) of hematophorphyrin derivative (HpD) and light were used for phototreatment of FANFT induced tumors. AlPCS is a stable sulfonated derivative of tetraazotetrabenzoporphyrin which absorbs maximally in the red portion of the visible spectrum, a region with good tissue penetration properties. These studies suggest the AlPCS may be a useful new agent for photodynamic therapy of cancer.

Animals↗
PubMed1986

Histological study of the effect of hematoporphyrin derivative photodynamic therapy on the rat jejunum.

Hematoporphyrin derivative photodynamic therapy is evolving as a local treatment for neoplastic disease. The emphasis of previous research has been on the determination of mechanisms of tumoricidal activity and defining the tumoricidal porphyrin component in hematoporphyrin derivative. The effect of hematoporphyrin derivative photodynamic therapy on normal tissue has received little attention. In the following study we examined the morphological changes of normal rat intestine exposed to hematoporphyrin derivative and light. In this model a segment of rat jejunum was exposed to red light (greater than 590 nm; 360 J/cm2) 24 or 72 h after the i.v. administration of hematoporphyrin derivative (5 or 10 micrograms/g body weight). Control groups received either no treatment, hematoporphyrin derivative only, or light only. Four h after treatment, intestinal segments were removed and examined by light microscopy. Segments treated with hematoporphyrin derivative and light showed extensive sloughing of the mucosa and submucosa with sparing of the muscular and serosal layers. It appears that hematoporphyrin derivative photodynamic therapy is capable of causing mucosal and submucosal damage to normal rat jejunum at these doses of light and hematoporphyrin derivative.

Animals↗
PubMed1985

Solid-phase purification and analysis of dicarboxylic porphyrins extracted from cultured tumor cells.

We describe here a sensitive method for the purification and analysis of porphyrins present in hematoporphyrin derivative. Hematoporphyrin derivative is a solution containing a complex mixture of dicarboxylic porphyrins such as hematoporphyrin IX, monohydroxyethyl monovinyl deuteroporphyrin isomers, and protoporphyrin IX in addition to porphyrin aggregates of variable molecular sizes. This mixture is known for its ability to be selectively retained by tumor cells and for its cytotoxicity in the presence of light. In order to study the mechanisms of hematoporphyrin derivative uptake and its cellular metabolism, extraction methods are required that combine high recoveries with minimum changes of very labile components. Extraction with perchloric acid: methanol mixtures recovered only some 60% of the porphyrins taken up by tumor cells and artifactual fluorescent spots were seen on thin-layer chromatograms. Improved yields were obtained upon extraction with dimethyl sulfoxide or Triton X-100:4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (Hepes) buffer mixture, but the extracts were not suitable for reverse-phase thin-layer chromatography (RTLC). The procedure described here consists of extracting porphyrins from cultured tumor cells with a buffered detergent followed by sequential chromatography on DEAE-cellulose columns and on reverse-phase octadecylsilyl cartridges. Identification of the isolated free dicarboxylic porphyrins is conveniently done by RTLC.

Animals↗
PubMed1985

Hematoporphyrin derivative photochemotherapy of experimental bladder tumors.

Recent studies have shown that disruption of tumor blood flow is a major consequence of hematoporphyrin derivative photochemotherapy. A series of experiments was undertaken on the transplantable N-(4-(5-nitro-2-furyl)-2-thiazolyl)-formamide induced urothelial tumor in Fischer 344 rats to determine a dose response for both hematoporphyrin derivative and light. Tumor blood flow was used as the biologic criteria of response. Hematoporphyrin derivative doses of 10 micrograms./gm. body weight or above were necessary to cause a significant decrease in tumor blood flow when the tumors were illuminated with 360 joules/cm.2 of noncoherent red light (greater than 590 nm.). With a constant hematoporphyrin derivative dose of 20 micrograms./gm. body weight, significantly lower tumor blood flows were observed with fluences of 240 joules/cm.2 and above. In order to correlate dose response to tumor regression, experiments were done in which tumor dry weights were determined 3 weeks after completion of photochemotherapy (360 joules/cm.2). Hematoporphyrin derivative doses of 10 micrograms./gm. body weight or above were necessary to induce tumor regression. These studies support the hypothesis that disruption of tumor blood flow is a tumoricidal mechanism of hematoporphyrin derivative photochemotherapy.

Animals↗
PubMed1985

Localization of hematoporphyrin derivative in injured bladder mucosa. An experimental study.

Hematoporphyrin derivative, a fluorescent mixture of porphyrins, has the putative property of being retained in neoplastic tissue after systemic administration. This preferential retention is the basis for the use of this agent as a tumor localizer and tumor photosensitizer. The retention of hematoporphyrin derivative in non-neoplastic but regenerating urothelium has not been reported. In this study, thermal urothelial injury was induced in Fischer 344 rats. Animals were then injected intravenously with hematoporphyrin derivative at 3 days, 1, 2, 3 and 6 weeks after injury. Photography under ultraviolet illumination was used to detect porphyrin fluorescence in the bladder mucosa. Up to 3 weeks after injury porphyrin fluorescence was detectable in areas of inflammation and hyperplasia around the area of injury. This study suggests that in this experimental model HpD fluorescence is not specific for neoplasia.

Animals↗
PubMed1985

Jejunal blood flow after exposure to light in rats injected with hematoporphyrin derivative.

Experiments were performed to determine the effect of hematoporphyrin derivative (HPD) photodynamic therapy on blood flow to normal rat intestine. A segment of rat jejunum was exposed to red (greater than 590 nm) light (200 mW/cm2) 24 h after the i.v. administration of HPD. Blood flow to the light exposed segment was determined using the radioactive microsphere technique while blood flow to an adjacent light shielded segment of intestine served as an internal control. Animals were divided into six groups of six each: Group I, no HPD, no light; Group II, light, no HPD; Group III, HPD (20 micrograms/g body weight), no light; and Group IV, HPD (20 micrograms/g body weight), light. Blood flow in these four groups was determined 10 min after completion of a 30-min exposure to light. Only in Group IV was there a statistically significant decrease (P less than 0.005) in blood flow to the segment treated with HPD and light. In Groups V [HPD (20 micrograms/g body weight), light] and VI [HPD (10 micrograms/g body weight), light] blood flows were determined 24 h after exposure to light. In both of these groups there was also a significant (P less than 0.05) decrease in blood flow in the segment treated with HPD and light. This study demonstrates that normal intestinal blood flow can be disrupted by HPD photodynamic therapy.

Animals↗
PubMed1984

Blood flow in transplantable bladder tumors treated with hematoporphyrin derivative and light.

Following hematoporphyrin derivative (HPD) photochemotherapy, blood flow to transplantable N-[4-(5-nitro-2-furyl)-2-thia-zolyl] formamide-induced urothelial tumors was determined by a radioactive microsphere technique using either 103Ru or 141Ce. Two tumors were implanted s.c. on the abdominal wall of Fischer 344 weanling rats. HPD (10 mg/kg body weight) was administered 24 hr prior to phototherapy (red light, greater than 590 nm; 360 J/sq cm). One of the two tumors was shielded from light exposure and served as an internal control. Blood flows were determined in control animals that received no treatment (Group 1), HPD only (Group 2), or light only (Group 3). In Groups 4 and 5, animals received the combination of HPD and light but differed in the time interval between treatment and blood flow determinations (10 min and 24 hr, respectively). Only blood flow to tumors treated with HPD and light showed a significant decrease (p less than 0.05) when compared with their internal controls both at 10 min (Group 4) and 24 hr (Group 5) after completion of phototherapy. These studies suggest that disruption of tumor blood flow may be an important mechanism of action of this method of cancer therapy.

Animals↗
PubMed1978

Cadmium alteration of root physiology and potassium ion fluxes.

Segments of oat (Avena sativa L.) roots which had been exposed to 1 millimolar CdSO(4) in quarter-strength Hoagland No. 1 solution exhibited decreased respiratory rates, ATP levels, membrane-bound ATPase activity, and reduced K(+) fluxes. Respiration and ATP levels were decreased after a 2-hour treatment with 1 millimolar CdSO(4) to 65 and 75%, respectively, of control rates. A membrane-bound, Mg(2+)-dependent, K(+)-stimulated acid ATPase was rapidly inhibited to 12% of control activity in the presence of 1 millimolar CdSO(4). Potassium uptake into root segments was inhibited to 80% of control values after 30 minutes in the presence of CdSO(4). A 2-hour pretreatment of root segments with CdSO(4) inhibited K(+) uptake to 15% of control values. Cytoplasmic K(+) efflux was inhibited with 1 millimolar CdSO(4).The rates and the degree of Cd(2+) inhibition of the parameters listed above suggest that one of the first sites of Cd(2+) action is the plasmalemma K(+) carrier (ATPase) in oat roots.

Journal Article↗
PubMed1976

Differential Oxygen Response of Photosynthesis in Soybean and Panicum milioides.

The carbon dioxide compensation concentration of Panicum milioides was less than that of soybean over the range of 15 to 35 C. In soybean (Glycine max [L.] Merr. cv. Wayne), the compensation concentration was directly proportional to O(2) concentration. In P. milioides, the compensation concentration was near zero up to 10% O(2) and then increased linearly with higher O(2), although the slope of the response was less than that in soybean. Leaf extracts of P. milioides contained 3-fold higher phosphoenolpyruvate carboxylase activity than soybean leaf extracts. Oxygen inhibition of photosynthesis and carboxy-lation efficiency was less in P. milioides than that observed in soybean. The affinity of P. millioides ribulose-1,5-di-P carboxylase for CO(2) appeared to be slightly greater than that of soybean. The affinity of both enzymes for O(2) was similar. The reduced response of the compensation concentration and photosynthesis to O(2) in P. milioides may be explained by photosynthetic phosphoenolpyruvate carboxylase fixation and by an apparent increased affinity of ribulose-1,5-di-P carboxylase for CO(2).

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PubMed1974

Chloroplast Response to Low Leaf Water Potentials: III. Differing Inhibition of Electron Transport and Photophosphorylation.

Cyclic and noncyclic photophosphorylation and electron transport by photosystem 1, photosystem 2, and from water to methyl viologen ("whole chain") were studied in chloroplasts isolated from sunflower (Helianthus annus L. var Russian Mammoth) leaves that had been desiccated to varying degrees. Electron transport showed considerable inhibition at leaf water potentials of -9 bars when the chloroplasts were exposed to an uncoupler in vitro, and it continued to decline in activity as leaf water potentials decreased. Electron transport by photosystem 2 and coupled electron transport by photosystem 1 and the whole chain were unaffected at leaf water potentials of -10 to -11 bars but became progressively inhibited between leaf water potentials of -11 and -17 bars. A low, stable activity remained at leaf water potentials below -17 bars. In contrast, both types of photophosphorylation were unaffected by leaf water potentials of -10 to -11 bars, but then ultimately became zero at leaf water potentials of -17 bars. Although the chloroplasts isolated from the desiccated leaves were coupled at leaf water potentials of -11 to -12 bars, they became progressively uncoupled as leaf water potentials decreased to -17 bars. Abscisic acid and ribonuclease had no effect on chloroplast photophosphorylation. The results are generally consistent with the idea that chloroplast activity begins to decrease at the same leaf water potentials that cause stomatal closure in sunflower leaves and that chloroplast electron transport begins to limit photosynthesis at leaf water potentials below about -11 bars. However, it suggests that, during severe desiccation, the limitation may shift from electron transport to photophosphorylation.

Journal Article↗
PubMed1970

Chloroplast composition and structure differences in a soybean mutant.

A nuclear mutation of Glycine max (soybean) segregates 1:2:1 in regard to chlorophyll content. The heterozygous (LG) leaf blade contains about one-half the pigment content of the wild type (DG) per gram fresh weight. A lethal yellow (LY) type contains about 1 to 2% of the DG leaf pigment values. The chlorophyll a/b ratio in the LG is about 5 compared to about 2 in the DG. Protein/leaf values are lower in the LG and LY types when compared to DG. The LG plastid lamellae contain more protein/chlorophyll, cytochromes/chlorophyll, and quinones/chlorophyll than the DG. P(700)/chlorophyll values are similar in the DG and LG types.The chlorophyll-depleted LG and LY types had less total acyl lipids per leaf weight when compared to the DG type. Similar amounts of sulfolipid and phosphatidyl glycerol per protein residue weight were found in the LG and DG plastids; however, the monogalactosyl and digalactosyl diglycerides were reduced in the LG paralleling the chlorophyll depletion.Thin sections of leaf tissue show similar-sized LG and DG plastids but reduced grana formation in the LG. The LY has very few grana and very small grana compared to either DG or LG. The two characteristic particles revealed in higher plant chloroplasts by freeze-etching are about 15% smaller in the LG compared to the DG plants.

Journal Article↗
PubMed1970

Photochemical characteristics in a soybean mutant.

Chloroplasts were isolated from wild type (DG) and heterozygous mutant (LG) soybean (Glycine max) leaves, and various biochemical functions were compared. Noncyclic electron transport, and its coupled phosphorylation, cyclic phosphorylation and H(+) ion transport in both systems, were 3 to 5 times faster in rate (on a chlorophyll basis) in the mutant plastids. On a chloroplast lamellar protein basis, the mutant plastid rates were 1.5 to 2.5 times the wild type rates.Plastoquinone (PQ) reduction and oxidation (rates and extent) were measured by following absorbance changes at 260 nanometers with the repetitive flash technique. Mutant plastids have about a 2-fold greater apparent first order rate constant for PQ oxidation and a 3- to 5-fold larger pool of rapidly reducible PQ. Plastoquinone oxidation has been identified by other workers as the rate-limiting step in electron transport. Assuming the PQ oxidation is a first order process (d(PQH(2))/dt = k(D)[PQH(2)]t), the observed increase in k(d) for the LG (k(d) (LG) approximately 2k(d) (DG)) and the greater steady state amount of rapidly turning over PQ, [PQH(2)](LG)>[PQH(2)](DG), could account for the 3- to 5-fold greater rates of electron transport and phosphorylation found in the mutant chloroplasts.Light saturation for noncyclic photophosphorylation and photosystem 2 plus 1 electron transport occurred at similar intensities for both LG and DG plastids. Relative quantum requirements extrapolated to zero intensity were similar in the LG and DG, although at finite light intensities the LG had a better relative quantum efficiency.Ammonium chloride concentrations needed to inhibit cyclic photophosphorylation 50% were similar in both LG and DG plastids. Nigericin, poly-l-lysine, and chlorotri-n-butyltin, were needed in concentrations 5 to 10 times greater in the LG to yield 50% inhibition at comparable chlorophyll concentrations.

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