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Biomedical subjects

J D Taylor

Publications and source records attributed to J D Taylor.

At least 127 records · Page 7Linked to original sources

Inhibition by prostacyclin of the tumor cell-induced platelet release reaction and platelet aggregation.

Prostacyclin was examined for its inhibitory effects on the tumor cell-induced platelet release reaction. Prostacyclin inhibited in a dose-dependent manner tumor cell-induced release of platelet dense granules and alpha-granules concomitant with an inhibition of platelet aggregation. Release was determined by assay of biochemical markers (serotonin for dense granules and beta-thromboglobulin for alpha-granules). A tenfold higher concentration of prostacyclin was required to inhibit completely serotonin release as compared to the concentration required for beta-thromboglobulin release. Correlative ultrastructural studies demonstrated that prostacyclin at doses of over 10 ng/ml inhibited the ultrastructural changes associated with tumor cell-induced platelet shape change and platelet granule release. Platelet aggregates exhibited the retention of granule reservoirs that could potentially be involved in long-term release of biologically active substances.

Animals↗

Bile peritonitis and hemobilia after percutaneous liver biopsy: endoscopic retrograde cholangiopancreatography demonstration of bile leak.

A 29-yr-old woman developed portal hypertension secondary to congenital intrahepatic multiple microhamartomata. Percutaneous liver biopsy was complicated by both bile peritonitis and hemobilia. Endoscopic retrograde cholangiopancreatography was used to demonstrate the bile leak. Abdominal paracentesis failed to control the leak, which was managed by surgery. Endoscopic drainage by nasobiliary intubation with suction might have avoided surgery.

Adult↗

Regulation of pigment organelle translocation. I. Phosphorylation of the organelle-associated protein p57.

Treatment of goldfish xanthophores with adrenocorticotropin (ACTH) or cyclic AMP (cAMP) induces the centrifugal movement of their pigment organelles from the center of the cells. Using purified xanthophores pulse labeled with 32Pi, we have shown that the dispersion of the organelles is accompanied by the phosphorylation of a pair of polypeptides, termed p57. After fractionation on sucrose gradients, nearly all of the p57 is found associated with the pigment organelles. The phosphorylation induced by ACTH or cAMP apparently occurs at multiple sites on p57. The minimal effective doses of ACTH or cAMP required to induce full pigment dispersion also fully stimulate the phosphorylation of p57. Increased phosphorylation of p57 is detectable within a minute after stimulating the cells and appears to be near completion during the early phases of pigment dispersion. Upon withdrawal of ACTH, these events are reversed; the pigment organelles reaggregate toward the center of the cells and p57 is dephosphorylated. Again, dephosphorylation commences soon after ACTH is withdrawn and is complete before the organelles have completely reaggregated. These results suggest a novel mechanism for governing the movement of these organelles which acts on the organelles themselves through the phosphorylation and dephosphorylation of p57.

Adrenocorticotropic Hormone↗

Regulation of pigment organelle translocation. II. Participation of a cAMP-dependent protein kinase.

In intact goldfish xanthophores, the phosphorylation of a pigment organelle (carotenoid droplet) protein, p57, appears to play an important role in adrenocorticotropin (ACTH)- or cAMP-induced pigment organelle dispersion while the dephosphorylation of this protein upon withdrawal of ACTH or cAMP is implicated in pigment aggregation. In this paper, we report the cAMP-dependent phosphorylation of this protein in cell-free extracts of xanthophores as determined by the incorporation of 32P from [gamma-32P]ATP. As is the case in intact cells, p57 is the predominant protein phosphorylated in the presence of cAMP. The cAMP-dependent protein kinase which phosphorylates p57 is not bound to the isolated organelles but is found in the soluble portion of the cell extracts. Hence, the phosphorylation of p57 requires the carotenoid droplets bearing the substrate, soluble extract containing the kinase, cAMP (half-maximal activation at 0.5 microM), and Mg2+ (optimal at 5 mM or higher). The presence of protein phosphatase(s) in these extracts was shown indirectly by the stimulation of phosphorylation by fluoride. The phosphorylation of p57 does not appear to require a cell-specific kinase as soluble extracts of goldfish dermal nonpigment cells also phosphorylate p57 associated with isolated carotenoid droplets. Furthermore, using a constant amount of carotenoid droplets, a linear relationship was demonstrated between the rate of p57 phosphorylation and the amount of extract present in the assays. These results suggest that p57 is phosphorylated directly by a cAMP-dependent protein kinase and that the activity of this enzyme is important in regulating the intracellular movement of the pigment organelles of the xanthophore.

Adrenocorticotropic Hormone↗

Sequences of four mouse histone H3 genes: implications for evolution of mouse histone genes.

The sequences of four histone H3 genes coding for the replication variant proteins H3.1 and H3.2 have been determined. Three of these genes, two coding for H3.1 proteins and one for an H3.2 protein, are located on chromosome 13 and expressed at low levels. The fourth gene, encoding an H3.2 protein, is located on chromosome 3 and expressed at a high level. The coding regions of the three genes on chromosome 13 are more similar to each other than to the H3 gene on chromosome 3, and equally divergent from it, suggesting that either gene duplication or gene conversion has occurred since the genes were dispersed onto two chromosomes. A 14-base sequence including the CCAAT sequence and located 5' to the genes on chromosome 13 has been conserved. The histone H3 gene on chromosome 3 has multiple potential binding sites for the Sp1 transcription factor. The coding regions show greater than 95% conservation among the four genes. This is due to the strict pattern of codon usage and the presence of two long (greater than 60 base) regions of completely conserved nucleic acid sequence. These conserved regions in the coding sequence may have an important functional role at the mRNA or DNA level.

Amino Acid Sequence↗

A system for assessing toxicity of chemicals by continuous monitoring of homecage behaviors.

A noninvasive system is described for continuous recording of behaviors in the home cages of rats. Commercially available mesh cages were used so as to conform with housing conditions in most toxicological studies. A minicomputer controlled environmental lighting and recorded eating, drinking, rearing, and horizontal activity. The system's sensitivity was comparable to more complex systems. Validity was demonstrated through manipulation of environmental lighting, food deprivation, and the effects of amphetamine, scopolamine, ethanol, methylscopolamine, triethyltin, and trimethyltin. Advantages over other systems are practicality, economy, the simultaneous analyses of several naturalistic behaviors of individual rats, and the quantification of diurnal rhythms.

Amphetamine↗

Cisplatin and nifedipine: synergistic cytotoxicity against murine solid tumors and their metastases.

Calcium channel blockers of 3 chemical classes and calmodulin antagonists have recently been shown to enhance the cytotoxicity of conventional cancer chemotherapeutic agents. We tested the ability of nifedipine, a dihydropyridine class calcium channel blocker, to enhance the cytotoxicity of cisplatin, the current chemotherapeutic of choice against human head and neck tumors and testicular carcinoma. Both in vitro and in vivo, combination therapy with nifedipine and cisplatin resulted in synergistic inhibition of tumor cell proliferation, primary tumor growth and appearance of spontaneous pulmonary metastases. This combination also significantly increased the survival of mice bearing cisplatin-resistant tumors. This is the first indication that calcium channel blockers can enhance the cytotoxicity of cisplatin as well as the first demonstration that calcium channel blockers can enhance cytotoxicity of chemo-therapeutic agent against a solid tumor and its metastases.

Animals↗

Intermediate filaments with novel protein composition from certain goldfish cells.

Using the conditions for vimentin filament recycling, intermediate filaments (approximately 10 nm) were prepared from the cytoskeleton of a goldfish tumor cell line (erythrophoroma or xanthophoroma). 2-D analysis showed unusual protein composition, with four proteins of molecular weights of 60, 45, 56 and 51 kilodaltons in ratios of approximately 4:4:1:1. These correspond to four of the major cytoskeletal proteins of both the tumor cells and normal xanthophores.

Animals↗

Effects of toluene inhalation on behavior and expired carbon dioxide in macaque monkeys.

Cynomolgus macaque monkeys received head-only exposure to 0, 100, 200, 500, 1000, 2000, 3000, and 4500 ppm toluene for 50 min while simultaneously tested for delayed matching-to-sample behavior, a test of cognitive functions. Response time increased and accuracy of matching decreased at 2000 ppm or more of toluene, indicating an attentional deficit but not specific memory effects. Behavioral indices exhibited monotonic concentration-related changes. Expired carbon dioxide (CO2), the most sensitive index, displayed an inverted U-shaped concentration-effect curve, which increased at 100 ppm (the TLV) and decreased at 4500 ppm toluene. Changes in expired CO2 provide new evidence of physiological changes at very low levels of toluene. These changes may indicate combined behavioral, respiratory, sensory, and metabolic effects. No behavioral measure exhibited either cumulative effects or tolerance to 4500 ppm during two 3-day exposures. However, both response time and expired CO2 exhibited an acute, within-session tolerance. The results indicate that brief inhalation exposure to toluene impairs cognitive and motor abilities at concentrations below those causing overt signs, such as ataxia and intention tremoring.

Animals↗

Inhibition by dihydropyridine class calcium channel blockers of tumor cell-platelet-endothelial cell interactions in vitro and metastasis in vivo.

Three calcium channel blockers of the dihydropyridine class were tested in vitro for their effects on tumor cell-platelet-endothelial cell interactions and in vivo for antimetastatic properties. Felodipine, nimodipine and nifedipine inhibited tumor cell-induced platelet aggregation in vitro in a dose-dependent manner. These compounds also inhibited platelet-enhanced tumor cell adhesion to endothelial cells in vitro. Lung colony formation ("experimental" metastasis) and spontaneous pulmonary metastasis were inhibited by felodipine, nimodipine and nifedipine. From the present studies on three calcium channel blockers of the dihydropyridine class we hypothesize that calcium channel blockers may represent a new generic class of antimetastatic agents.

Animals↗

Purification and characterization of platelet aggregating activity from tumor cells: copurification with procoagulant activity.

The platelet aggregating component from murine 15091A mammary adenocarcinoma cells was purified by solubilization of activity with CHAPS (3-[(3-cholidamidopropyl)-dimethylammonio]-1-propane sulfonate), fractionation with ammonium sulfate, ion exchange chromatography on DEAE cellulose, and hydrophobic interaction chromatography on dodecyl agarose. A purification of 90-100 fold over the initial cell homogenate was achieved. SDS-PAGE of the purified material resulted in a single major band with a molecular weight of 51,000 +/- 2,000. Procoagulant activity was found to copurify with platelet aggregating activity. Reconstitution with phospholipids was necessary to obtain platelet aggregating activity and procoagulant activity. Trypsin abolished both platelet aggregating and procoagulant activities. The irreversible proteinase inhibitors phenylmethylsulfonyl fluoride, N alpha-p-tosyl-L-lysine chloromethyl ketone, iodoacetamide or phenanthroline had no effect on platelet aggregating or procoagulant activities. Platelet aggregation induced by this material was inhibited by low concentrations of the specific irreversible thrombin inhibitors, dansylarginine N-(3-ethyl-1, 5-pentanediyl) amide and D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. This is the first report of copurification of tumor cell platelet aggregating and coagulating activities.

Animals↗

Unusual responses of cultured Fundulus heteroclitus melanophores to epinephrine and ions, paradox of K+ versus Na+.

Fundulus heteroclitus melanophores were successfully cultured and maintained in culture for up to 2 months. Compared to other teleost melanophores in the fin, scale, or split fin preparation, the cultured melanophores show unusual responses to both epinephrine and ion solutions. First, they aggregated their melanosomes in response to concentrations of epinephrine as low as 10(-12) M. Second, the melanophores in a 6-day, or older, culture aggregated their melanosomes in response to both sodium and potassium ion solutions. This is in contrast to 4-day-old cultures (and reports of noncultured melanophores) where melanosomes are aggregated in response to potassium but dispersed in sodium ion solutions.

Adrenocorticotropic Hormone↗

The accuracy of "pull-through" pressure measurements and papaverine testing.

Intra-arterial pressure measurements have been made in a group of vascular patients using two different methods. The pull-through method, without systemic pressure monitoring, is compared with a technique employing simultaneous radial and femoral arterial puncture. In both techniques, pressures are measured at resting flow and during papaverine induced hyperaemia.

Angioplasty, Balloon↗

Femoral herniae in children.

A series of 12 femoral herniae in children is presented. Nine were misdiagnosed, eight as inguinal hernia. Nine were reducible. The sex incidence, M:F was 7:5 and nine presented between the ages of 8 and 10 years. One presented as intestinal obstruction due to a Richter's hernia and two had had a previous ipsilateral inguinal hernia repaired. All but one were repaired by herniorrhaphy.

Child↗