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J D Taylor

Publications and source records attributed to J D Taylor.

At least 109 records · Page 6Linked to original sources
PubMed1989

Methods to evaluate the wellbeing of laboratory primates: comparisons of macaques and tamarins.

Three objective behavioral tests are described for the assessment of wellbeing and possible enrichment of laboratory primates. One test, foraging for food in a pickup tray, proved practical for both macaques and tamarins. It provides positive human interaction as well as standardized evaluation of appetite for food and sensory-motor coordination. A puzzle feeder provided more complex foraging which could be performed by macaques, but not by tamarins. A third noninvasive test, used only with macaques, measured daily energy expenditure and sleep-wakefulness cycles as expressed in the diurnal rhythm of homecage activity. Normative data indicate the usefulness of each. Further refinement and validation of new tests and enrichment strategies requires a major research effort. Definitive measures such as those described here, coupled with data on long-term health outcomes, are essential before regulations for primate care can be revised with confidence.

Animal Welfare↗
PubMed1988

Role of tumor cytoskeleton and membrane glycoprotein IRGpIIb/IIIa in platelet adhesion to tumor cell membrane and tumor cell-induced platelet aggregation.

Components of the tumor cell cytoskeleton (i.e., microtubules, microfilaments, and intermediate filaments) have been reported to affect metastatic ability, since disruption of these components leads to a decrease in metastasis. One mechanism of metastasis which has not been previously considered is the decreased interaction of tumor cells with platelets. We present evidence that disruption of the tumor cell cytoskeleton decreases the ability of tumor cells to aggregate homologous platelets. This effect is dependent upon the disruption of microfilaments/intermediate filaments but not disruption of microtubules. In addition, tumor cell platelet interactions require the lateral mobility of specific receptors (i.e., clustering) on the tumor cell plasma membrane. A membrane glycoprotein immunologically related to the platelet glycoprotein IIb/IIIa complex was identified on Walker 256 carcinosarcoma cells using specific polyclonal and monoclonal antibodies and Northern blot analysis using complementary DNA probes for IIb and IIIa. Mobility of this receptor is dependent upon tumor cell microfilaments/intermediate filaments, but not microtubules. Furthermore, treatment of tumor cells with specific antibodies to the platelet glycoprotein IIb/IIIa complex inhibits tumor cell-platelet interaction at the macroscopic level (i.e., aggregation) and at the ultrastructural level (i.e., platelet adhesion to the tumor cell surface). These results suggest that this immunologically related glycoprotein IIb/IIIa is a receptor for platelet binding to the tumor cell surface, an event which precedes overt platelet aggregation and is dependent upon an intact tumor cell microfilament and intermediate filament network. Therefore, the decreased metastasis observed by others following disruption of the tumor cell cytoskeleton may be due, in part, to a decreased tumor cell-platelet interaction.

Animals↗
PubMed1988

Dioctanoylglycerol and phorbol esters regulate transcription of c-myc in human promyelocytic leukemia cells.

Treatment of human promyelocytic leukemia cells (HL-60) with phorbol 12-myristate 13-acetate or phorbol 12,13-dibutyrate (PDBu) caused a rapid decrease in transcription of the c-myc protooncogene. In the continuous presence of PMA or PDBu, the rate of transcription of c-myc decreased to 20% of control within 2 h and was maintained at 20-30% of the control level for the ensuing 24 h. Cell-permeable sn-1,2-dioctanoylglycerol (diC8), a diacylglycerol analogue, also caused a rapid decrease in c-myc transcription. The decrease in the transcription of c-myc induced by diC8 or PDBu was reversible; prolonged exposure of the cells to either agent for periods greater than 2 h was necessary to maintain the transcription of c-myc below the control rate. With both PDBu and diC8, there was a close correlation between the concentration dependence for binding to the phorbol ester receptor and the concentration dependence for inhibition of c-myc transcription. The decrease in transcription of c-myc induced by PDBu or diC8 appeared to be due to a block of elongation of the nascent mRNA beyond exon 1. The results of this study suggest that prolonged stimulation of protein kinase C (Ca2+/phospholipid-dependent enzyme) is required for persistent inhibition of transcription of c-myc in HL-60 cells.

Diglycerides↗
PubMed1988

Regulation of the distribution of carotenoid droplets in goldfish xanthophores and possible implication to secretory processes.

In goldfish xanthophores, the formation of pigment aggregate requires: 1) that a pigment organelle (carotenoid droplet) protein p57 be in the unphosphorylated state; 2) that self-association of pigment organelles occur in a microtubule-independent manner; and 3) that pigment organelles via p57 associate with microtubules. In the fully aggregated state, the pigment organelles are completely stationary. Pigment dispersion is initiated by activation of a cAMP-dependent protein kinase, which phosphorylates p57 and allows pigment dispersion via an active process dependent on F-actin and a cytosolic factor. This factor is not an ATPase, and its function is unknown. However, its abundance in different tissues parallels secretory activity of the tissues, suggesting a similarity between secretion and pigment dispersion in xanthophores. The identity of the motor for pigment dispersion is unclear. Experimental results show that pigment organelles isolated from cells with dispersed pigment have associated actin and ATPase activity comparable to myosin ATPase. This ATPase is probably an organelle protein of relative molecular mass approximately 72,000, and unlikely to be an ion pump. Isolated pigment organelles without associated actin have 5x lower ATPase activity. Whether this organelle ATPase is the motor for pigment dispersion is under investigation. The process of pigment aggregation is poorly understood, with conflicting results for and against the involvement of intermediate filaments.

Actin Cytoskeleton↗
PubMed1988

Cisplatin and nifedipine: synergistic antitumor effects against an inherently cisplatin-resistant tumor.

Resistance to cisplatin is a relative term and is at least partially attributable to its narrow therapeutic index. It is often not possible to successfully treat tumors exhibiting even a small inherent resistance to cisplatin by increasing the dose level of cisplatin, because such therapies may be fatally toxic to a patient. Thus, combination therapy with an agent which enhances cisplatin's antitumor effects with little or no enhancement of cisplatin's toxicities, may be of value in the treatment of human tumors which fail to respond to treatment with cisplatin alone. We recently reported that nifedipine, a dihydropyridine class calcium channel blocker, enhances the antitumor actions of cisplatin against a cisplatin-sensitive murine amelanotic melanoma. We now report that nifedipine enhances cisplatin's antitumor effects against a murine carcinoma (Lewis lung carcinoma) that is inherently resistant to cisplatin.

Animals↗
PubMed1988

Role of tumor cell glycoproteins immunologically related to glycoproteins Ib and IIb/IIIa in tumor cell-platelet and tumor cell-matrix interactions.

A panel of monoclonal and polyclonal antibodies raised against human platelet GpIb or the GpIIb/IIIa complex were used to detect immunologically related molecules on two cell lines derived from human solid tumors. Human cervical carcinoma (MS751) and human colon carcinoma (clone A) expressed molecules immunologically related to platelet GpIb and GpIIb/IIIa complex. These molecules were localized to their plasma membranes by immunofluorescence and immunocytochemistry. The immunologically related GpIb was evenly distributed on the tumor cell membrane with occasional areas of aggregates, whereas the immunologically related GpIIb/IIIa had a pronounced punctate distribution of aggregates in prefixed cells. When MS751 or clone A cells were pretreated with antibodies against platelet GpIb and/or the GpIIb/IIIa complex, their ability to induce platelet aggregation was significantly inhibited. In addition, when tumor cells were pretreated with antibodies against the platelet IIb/IIIa complex, adherence to fibronectin-coated plates was also significantly inhibited. These results suggest a role for these immunologically related tumor cell glycoproteins in tumor cell-host cell (i.e., platelet, endothelial cells) interactions, tumor cell interactions with components of the subendothelial matrix, and subsequent tumor metastasis.

Antibodies, Monoclonal↗
PubMed1988

Separation of high and low metastatic subpopulations from solid tumors by centrifugal elutriation.

We have isolated from murine solid tumors (B16a) subpopulations of cells possessing high and low metastatic potential. Tumors were dispersed by collagenase treatment. The resulting heterogeneous population of cells (i.e., viable and non-viable tumor cells and host cells) were separated by centrifugal elutriation. Four of the fractions (100, 180, 260, 340) contained tumor cells of high viability (greater than 95%) and high purity (less than 1% host cell contamination). The four fractions were characterized by flow cytometry and found to differ in distribution of cells in G1, S and G2. The cell populations were also found to differ in metastatic potential as determined by their ability to form lung colonies following intravenous injection. The 340 fraction was approximately 5-fold more metastatic than the 100 fraction. We also observed that cells from the 100 fraction failed to induce platelet aggregation whereas cells from the 340 fraction induced significant platelet aggregation. These observations demonstrate that cells of B16a tumors are heterogeneous for phenotypic characteristics (i.e., metastatic potential; platelet aggregation, etc.) and that their ability to induce platelet aggregation is positively correlated with metastatic potential.

Animals↗
PubMed1988

Lipoxygenase products regulate IRGpIIb/IIIa receptor mediated adhesion of tumor cells to endothelial cells, subendothelial matrix and fibronectin.

Tumor cell adhesion to endothelial cells, subendothelial matrix, and fibronectin is stimulated by the lipoxygenase metabolite of arachidonic acid, 12(S)-HETE, but not by 12(R)-HETE, 5-HETE or 15-HETE. Adhesion is also stimulated by the phorbol ester TPA, an effect inhibited by lipoxygenase but not cyclooxygenase inhibitors. TPA and 12(S)-HETE mediated adhesion is due, in part, to an integrin receptor (i.e., IRGpIIb/IIIa) related to the platelet glycoprotein IIb/IIIa complex and is inhibited by specific monoclonal and polyclonal antibodies against platelet IIb/IIIa. TPA and 12(S)-HETE stimulated adhesion is also inhibited by a lipoxygenase product of linoleic acid; i.e., 13-HODE. These results suggest bidirectional control of tumor cell adhesion by lipoxygenase products of arachidonic acid (increase) and linoleic acid (decrease).

Animals↗
PubMed1987

Role of platelet membrane in enhancement of tumor cell adhesion to endothelial cell extracellular matrix.

Tumor cell adhesion to subendothelial matrix in the presence of platelets and plasma has been examined in vitro using an entirely homologous system of rat Walker 256 carcinosarcoma cells, matrix laid down by rat aortic endothelial cells and rat platelets and plasma. In the presence of platelets or platelets plus plasma, tumor cell adhesion was significantly enhanced when compared to adhesion in the absence of platelets. In the presence of plasma alone (0.1%), we observed no significant increase in tumor cell adhesion. In order to determine which platelet factors contribute to the enhancement of tumor cell adhesion by platelets, we subjected washed rat platelets to mechanical lysis or thrombin stimulation followed by centrifugation. The membrane fractions and supernatant fractions containing platelet attachment proteins were compared for their abilities to support tumor cell adhesion to subendothelial matrix. Platelet membranes were also recombined with platelet supernatant fractions to determine if platelet attachment proteins or platelet membranes required the presence of the other to enhance tumor cell adhesion. Platelet supernatant fractions which contained release reaction proteins (confirmed by polyacrylamide gel electrophoresis) did not enhance tumor cell adhesion. Purified thrombospondin, fibronectin, beta-thromboglobulin, platelet derived growth factor, and serotonin had no effect on tumor cell adhesion. Platelet membrane containing fractions affected tumor cell adhesion to subendothelial matrix as follows: (a) platelets formed an adhesive bridge between tumor cells and the subendothelial matrix as demonstrated by scanning electron microscopy; (b) intact platelets and thrombin stimulated platelets were the most effective at facilitating tumor cell adhesion; (c) preparations containing partially lysed platelet ghosts were more effective in supporting tumor cell adhesion to subendothelial matrix than were preparations containing completely lysed platelet membrane fragments; (d) recombination of platelet supernatant fractions with mechanically lysed platelets did not enhance their ability to support adhesion; (e) fixed platelets, either alone or in combination with platelet supernatant fractions, failed to enhance adhesion. These data indicate that platelet enhanced tumor cell adhesion appears to be dependent on platelet membrane factors including receptor mobility, rather than intraplatelet components.

Animals↗
PubMed1987

The role of platelet cyclooxygenase and lipoxygenase pathways in tumor cell induced platelet aggregation.

Walker 256 carcinosarcoma cells induce the aggregation of rat platelets and concomitant production of eicosanoid metabolites (e.g., 12-hydroxyeicosatetraenoic acid, thromboxane A2). Cyclooxygenase inhibitors, but not lipoxygenase inhibitors, were able to inhibit platelet aggregation induced in vitro by low concentrations of agonists. At high agonist concentrations, neither cyclooxygenase nor lipoxygenase inhibitors affected platelet aggregation; however the combination of both inhibitors resulted in inhibition of aggregation. Also, a low concentration of agonist induced minimal eicosanoid metabolism, whereas a high concentration resulted in increased eicosanoid metabolism. These inhibitors, at the doses tested, did not inhibit protein kinase C activity.

Animals↗
PubMed1987

A new in vitro model for investigation of tumor cell-platelet-endothelial cell interactions and concomitant eicosanoid biosynthesis.

We have developed a new in vitro model system to examine tumor cell-platelet-endothelial cell interactions under dynamic conditions. Using the same model, we can determine endogenous eicosanoid metabolism and alterations in the prostacyclin-thromboxane A2 balance associated with interactions among tumor cells, platelets, and endothelial cells. The model consisted of cloned rat aortic endothelial cells grown on gelatin microcarrier beads under dynamic conditions (i.e., spinner culture). Interactions of these endothelial cells with platelets (heparinized rat platelet rich plasma) and/or tumor cells (rat Walker 256 carcinosarcoma) were assessed in an aggregometer. Gelatin beads alone or microcarrier grown endothelial cells did not elicit spontaneous aggregation of platelet rich plasma over a time period of 30 min. Microcarrier grown endothelial cells inhibited tumor cell induced platelet aggregation in a dose dependent fashion (i.e., depending on endothelial cell number). The ability of microcarrier grown endothelial cells to inhibit tumor cell induced platelet aggregation depended on endogenous production of prostacyclin. This conclusion is based on the following results: an increased number of microcarrier grown endothelial cells caused a prolongation of the aggregation lag time; an increased number of microcarrier grown endothelial cells caused a proportionate increase in 6-keto-prostaglandin F1 alpha concentration; an increased number of microcarrier grown endothelial cells was inversely correlated with thromboxane A2 production by platelets; indomethacin pretreatment of microcarrier grown endothelial cells caused a decrease in prostacyclin production and therefore overcame the associated inhibition of tumor cell induced platelet aggregation; and the inhibition of tumor cell induced platelet aggregation in the presence of endogenous prostacyclin produced by microcarrier grown endothelial cells was the same as that observed in the presence of exogenous prostacyclin. Scanning electron microscopy of aggregometry samples revealed: little or no platelet or tumor cell adhesion to gelatin beads alone, a low basal adhesion of tumor cells to microcarrier grown endothelial cells, and large aggregates of platelets and tumor cells located primarily at gaps in the monolayer of indomethacin treated microcarrier grown endothelial cells. This new in vitro model provides a method for examining the effects of eicosanoid metabolism by endothelial cells on tumor cell-platelet-endothelial cell interactions under dynamic conditions.

Blood Platelets↗
PubMed1987

Purification of Black Moor goldfish melanophores and responses to epinephrine.

Two key modifications of the previously reported method for isolation of goldfish xanthophores allowed the isolation and establishment of primary cultures of terminally differentiated melanophores from the Black Moor goldfish (Carassius auratus). First, pretreatment with 10(-4) M epinephrine causing aggregation of the melanosomes and collapse of the dendrites, prevents damage to the melanophores during tissue dissociation and melanophore isolation. Second, maintenance of these cells in culture was successful only when the culture medium was supplemented with fish serum. The purified melanophores attached, flattened, and were maintained in culture for up to 3 mo. Although the morphology of the cultured melanophores is less dendritic than their in vivo counterparts, the melanophores translocate melanosomes in a normal manner except that they exhibit enhanced sensitivity to epinephrine. This epinephrine-induced pigment aggregation, as well as the redispersion of pigment after the removal of epinephrine, can occur in the presence of ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and absence of Ca2+.

Animals↗
PubMed1987

Inhibition of human tumor cell induced platelet aggregation by antibodies to platelet glycoproteins Ib and IIb/IIIa.

Tumor cell induced platelet aggregation was shown to be inhibited in a dose dependent manner by preincubation of human platelets with antibodies to platelet glycoprotein Ib and the IIb/IIIa complex. Combination of antibody to Ib and antibody to the IIb/IIIa complex at concentrations which produced half maximal inhibition of platelet aggregation alone caused complete inhibition of tumor cell induced platelet aggregation. Antibodies to platelet glycoproteins Ib and the IIb/IIIa complex also inhibited platelet synthesis of thromboxane A2, but not synthesis of 12-hydroxyeicosatrienoic acid. Inhibition of tumor cell induced platelet aggregation with antibodies against platelet glycoproteins suggests a role for these glycoproteins in tumor cell-platelet interactions and possibly platelet facilitated tumor cell metastasis.

Antibodies↗
PubMed1987

Tumor cell-platelet-endothelial cell interactions and prostaglandin metabolism.

We have proposed that tumor cell induction of platelet aggregation facilitates tumor cell attachment to endothelium and that this attachment is limited by endogenous PGI2. We have developed an in vitro model to study tumor cell-platelet-endothelial cell interactions in which endothelial cells are grown on microcarrier beads. Untreated endothelial cells inhibit tumor cell-induced platelet aggregation, as well as tumor cell attachment to endothelial cells. Inhibition of endothelial cell PGI2 production by indomethacin obviates this inhibition.

Animals↗
PubMed1987

Inhibition of tumor cell induced platelet aggregation by prostacyclin and carbacyclin: an ultrastructural study.

Prostacyclin and its synthetic analog carbacyclin were compared as to their abilities to inhibit tumor cell-platelet interactions. Aggregation of rat platelets was induced in vitro by homologous rat Walker 256 carcinosarcoma cells. The extent of cellular interactions was examined ultrastructurally. The ultrastructural data presented here indicate that the tumor cell-platelet interactions began with individual platelets which initiated platelet chain formation in focal association with tumor cell surfaces. By mid-phase aggregation large homotypic platelet aggregates had formed with tumor cells positioned on the external surfaces of the emboli. Tumor cell-platelet interactions became progressively more extensive as tumor cells became enmeshed with growing platelet aggregates. Prostacyclin and carbacyclin inhibited tumor cell platelet interactions in a dose-dependent manner. Carbacyclin inhibition of tumor cell induced platelet aggregation was longer in duration but carbacyclin was 10-fold less effective than was prostacyclin. We report here that prostacyclin and carbacyclin inhibit both aggregation and the ultrastructural changes associated with tumor cell-platelet interactions.

Animals↗
PubMed1987

Platelet enhancement of tumor cell adhesion to subendothelial matrix: role of platelet cytoskeleton and platelet membrane.

Platelet involvement during tumor cell adhesion to subendothelial matrix was examined in vitro. Platelets were subjected to thrombin stimulation and mechanical lysis and examined for their effects on tumor cell adhesion. These treatments altered the platelet ultrastructure and cytoskeletal integrity. Untreated washed rat platelets (WRP) exhibited extensive adhesion to and spreading on substrates and substantially enhanced tumor cell adhesion to the same substrates (i.e., 250% greater than tumor cells without platelets). Thrombin prestimulation of platelets limited platelet adhesion and spreading and platelet facilitation of tumor cell adhesion. Complete mechanical lysis disrupted both the platelet membrane and the cytoskeleton and eliminated the ability of platelets to adhere or to enhance tumor cell adhesion. Partially lysed platelets resembled membrane ghosts and facilitated tumor cell adhesion by a mechanism independent of spreading and cytoskeletal rearrangement. Fractionation studies indicated that platelet cytoskeletal components played a role in the adhesion process. Pretreatment of WRP with cytochalasin A or B dose dependently inhibited microfilament-mediated platelet spreading and platelet-enhanced tumor cell adhesion. Colchicine and vinblastine induced microtubule depolymerization, but they had no observable effect on platelet spreading or platelet-enhanced tumor cell adhesion. It was concluded that platelet-enhanced tumor cell adhesion to subendothelial matrix depends on an intact platelet cytoskeleton and on a platelet membrane component(s) and is mediated by surface contact between platelets and tumor cells. Furthermore, platelet-mediated tumor cell adhesion to subendothelial matrix may involve two mechanisms: one dependent on, and one independent of, platelet spreading and cytoskeletal rearrangement.

Animals↗