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Biomedical subjects

C Morrow

Publications and source records attributed to C Morrow.

At least 19 recordsLinked to original sources
PubMed2000

Effects of beta-L-3'-azido-3'-deoxythymidine 5'-triphosphate on host and viral DNA polymerases.

We have previously reported that several beta-L-thymidine analogues including beta-L-3'-azido-3'-deoxythymidine (beta-L-AZT), beta-L-3'-fluoro-2',3'-dideoxythymidine (beta-L-FLT) and beta-L-2', 3'-didehydro-2',3'-dideoxythymidine (beta-L-D4T) did not inhibit HIV replication in human peripheral blood mononuclear (PBM) cells whereas their corresponding beta-D-counterparts are known as potent and selective anti-HIV agents [Faraj et al., 1997. Nucleosides and Nucleotides 16, 1287-1290]. In order to gain insight on the lack of antiviral activities of these beta-L-derivatives, in vitro enzymatic steady state studies were conducted in the present study with beta-L-AZT. beta-L-AZT 5'-triphosphate (L-AZTTP) was chemically synthesized and found to moderately inhibit wild-type HIV reverse transcriptase (HIV-1 RT) with a K(i) value of 2 microM; while lacking any inhibitory effect towards human DNA polymerase alpha, beta or gamma. However, the inhibitory effect of L-AZTTP towards HIV-1 RT was very modest (266-fold less potent) when compared to its isomer beta-D-AZT 5'-triphosphate (D-AZTTP) which exhibits a K(i) value of 0.0075 microM and this finding was further confirmed by DNA chain termination assay. These data suggest that the absence of antiviral activity of the parent beta-L-AZT may in part be explained by the poor inhibition of the targeted viral enzyme by L-AZTTP, the active metabolite. Finally, L-AZTTP was found to lack affinity for the mutant RT at position 184 (M184V) demonstrating that this mutation confers resistance not only to beta-L-2',3'-dideoxycytidine analogs as previously reported by our group [Faraj et al., 1994. Antimicrob. Agents Chemother. 38, 2300-2305] but as well as to beta-L-2',3'-dideoxythymidine analogs.

Anti-HIV Agents↗
PubMed1994

Phosphatidic acid promotes phosphoinositide metabolism and DNA synthesis in cultured cortical astrocytes.

The addition of exogenous phosphatidic acid (PA) to cultured cortical astrocytes prelabelled with [3H]inositol resulted in the accumulation of intracellular [3H]inositol phosphates (IP) in a concentration-dependent (EC50 = 20 microM) manner. Analysis of the individual IPs formed following a PA challenge revealed a rapid but transient generation of [3H]inositol trisphosphate (IP3) indicating the involvement of phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown in this response a fact which was confirmed when the recovery of radiolabel in membrane phosphoinositides was assessed. PA's ability to stimulate IP3 accumulation was found to be dependent upon its acyl-chain length. Dioleoyl-PA (C18:1) was equally as effective as PA from egg yolk lecithin in this respect whilst dipalmitoyl-PA (C16:0) was less so and dimyristoyl-PA (C14:0) and dilauroyl-PA (C12:0) were without effect. In subconfluent, serum-deprived cultures, PA was found to increase DNA synthesis following a 48 h exposure period. This effect was observed over the same concentration range used to measure phosphoinositide breakdown and was found to be mediated by the activation of protein kinase C. As with its effect on phosphoinositide metabolism, PA's ability to promote DNA synthesis was correlated with its acyl-chain length. These data show that PA is capable of stimulating both phosphoinositide metabolism and DNA synthesis in cultured astrocytes possibly via the activation of specific membrane receptors. However, the precise relationship between these events remains to be elucidated.

Animals↗
PubMed1993

Use of hypnosis following training in a psychiatry residency and psychology internship program: a brief communication.

Despite growing numbers of internships and residencies offering training in hypnotherapy, no systematic attempt has been made to assess hypnotherapy beliefs and use among former trainees in these settings. This study investigated posttraining hypnotherapy use and effectiveness beliefs in a sample of 77 former psychiatry residents and psychology interns. Over 50% of the study sample had sought additional hypnotherapy training beyond the standard lectures and seminars, and almost 30% had attended external hypnotherapy workshops or presentations. Beliefs in hypnotherapy effectiveness were high, but use of hypnotherapy in clinical practice was very low. Former residents and interns who had received supervised training with patients, who had attended hypnosis workshops, and who had a colleague using hypnotherapy were more likely to use hypnotherapy following training.

Adult↗
PubMed1992

Reduced intracellular drug accumulation in the absence of P-glycoprotein (mdr1) overexpression in mitoxantrone-resistant human MCF-7 breast cancer cells.

A mitoxantrone-resistant human MCF-7 breast cancer subline (MCF/MX) which is approximately 4000-fold resistant to mitoxantrone was isolated by serial passage of the parental wild-type MCF-7 cells (MCF/WT) in stepwise increasing concentrations of drug. MCF/MX cells were also approximately 10-fold cross-resistant to doxorubicin and etoposide but were not cross-resistant to vinblastine. Intracellular accumulation of radiolabeled mitoxantrone was markedly reduced in MCF/MX cells relative to that in the drug-sensitive MCF/WT cells. This decrease in intracellular drug accumulation into MCF/MX cells was associated with enhanced drug efflux, which was reversed when cells were incubated in the presence of sodium azide and 2, 4-dinitrophenol, suggesting an energy-dependent process. Incubation of MCF/MX cells with verapamil did not affect either the accumulation of mitoxantrone or the level of resistance in these cells. Furthermore, RNase protection and Western blot analyses failed to detect the expression of the mdr1 RNA or P-glycoprotein, a drug efflux pump known to be associated with the development of multidrug resistance in vitro. However, a polyclonal antibody directed against a synthetic peptide corresponding to the putative ATP binding domain of P-glycoprotein reacted with two (M(r) 42,000 and 85,000) membrane proteins from MCF/MX cells which were not found in MCF/WT. Functional assays and Western blot analysis for topoisomerase II revealed no differences in topoisomerase II activity or protein levels in MCF/MX cells. Thus, resistance in this cell line is apparently associated with enhanced drug efflux involving a pathway distinct from the mdr1-encoded multidrug transporter P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Basic fibroblast growth factor in retardation of doxorubicin extravasation injury.

Extravasation of chemotherapeutic agents such as doxorubicin results in significant morbidity and remains a serious clinical problem. No single agent or combination of agents has proven to be completely effective in preventing the chronic avascular ulcerative wound. Basic fibroblast growth factor (bFGF) is one of many angiogenic agents and is strongly mitogenic for vascular endothelial cells in nanogram quantities. In a Sprague-Dawley rat model, bFGF was moderately effective in retarding the development of doxorubicin-induced skin ulceration.

Animals↗
PubMed1992

Massage reduces anxiety in child and adolescent psychiatric patients.

A 30-minute back massage was given daily for a 5-day period to 52 hospitalized depressed and adjustment disorder children and adolescents. Compared with a control group who viewed relaxing videotapes, the massaged subjects were less depressed and anxious and had lower saliva cortisol levels after the massage. In addition, nurses rated the subjects as being less anxious and more cooperative on the last day of the study, and nighttime sleep increased over this period. Finally, urinary cortisol and norepinephrine levels decreased, but only for the depressed subjects.

Adjustment Disorders↗
PubMed1991

Perinatal cocaine effects on neonatal stress behavior and performance on the Brazelton Scale.

Fifty-two newborns were assessed for the effects of maternal cocaine use on their performance on the Brazelton Neonatal Behavior Assessment Scale and on their stress behaviors during the Brazelton as tapped by the Neonatal Stress Scale. The cocaine-exposed newborns experienced more obstetric complications, had smaller head circumferences, showed more limited habituation abilities on the Brazelton Scale, and exhibited more stress behaviors than control newborns.

Birth Weight↗
PubMed1990

Further characterisation of excitatory amino acid receptors coupled to phosphoinositide metabolism in astrocytes.

Excitatory amino acids stimulate phosphoinositide breakdown in astrocytes with the following rank order of effect: quisqualate greater than ibotenate = glutamate greater than kainate greater than N-methyl-D-aspartate. Quisqualate-induced responses were resistant to blockade with a range of receptor antagonists whereas those to glutamate were partially reversed by gamma-D-glutamylaminosulphonic acid and gamma-D-glutamylglycine. These antagonists were, however, more effective against kainate-stimulated phosphoinositide metabolism. These experiments together with those where combinations of agonists were used, suggest that the kainate-induced and, to some extent, the glutamate-induced responses were due to membrane depolarisation and that quisqualate activates a non-ionotropic class of receptor at which glutamate and ibotenate are partial agonists.

Astrocytes↗
PubMed1989

ATP-evoked Ca2+ mobilisation and prostanoid release from astrocytes: P2-purinergic receptors linked to phosphoinositide hydrolysis.

Astrocyte cultures prelabelled with either [3H]inositol or 45Ca2+ were exposed to ATP and its hydrolysis products. ATP and ADP, but not AMP and adenosine, produced increases in the accumulation of intracellular 3H-labelled inositol phosphates (IP), efflux of 45Ca2+, and release of thromboxane A2 (TXA2). Whereas ATP-stimulated 3H-IP accumulation was unaffected, its ability to promote TXA2 release was markedly reduced by mepacrine, an inhibitor of phospholipase A2 (PLA2). ATP-evoked 3H-IP production was also spared following treatment with the cyclooxygenase inhibitor, indomethacin. We conclude that ATP-induced phosphoinositide (PPI) breakdown and 45 Ca2+ mobilisation occurred in parallel with, if not preceded, the release of TXA2. Following depletion of intracellular Ca2+ with a brief preexposure to ATP in the absence of extracellular Ca2+, the release of TXA2 in response to a subsequent ATP challenge was greatly reduced when compared with control. These results suggest that mobilisation of cytosolic Ca2+ may be the stimulus for PLA2 activation and, thus, TXA2 release. Stimulation of alpha 1-adrenoceptors also caused PPI breakdown and 45 Ca2+ efflux but not TXA2 release. The effects of ATP and noradrenaline (NA) on 3H-IP accumulation were additive, but their combined ability to increase 45Ca2+ efflux was not. Interestingly, in the presence of NA, ATP-stimulated TXA2 release was reduced. Our data provide evidence that functional P2-purinergic receptors are present on astrocytes and that ATP is the first physiologically relevant stimulus found to initiate prostanoid release from these cells.

Adenine Nucleotides↗
PubMed1988

A role for protein kinase C in astrocyte glycogen metabolism.

Astrocytes accumulated 2-[3H]deoxyglucose (2-DG) from the incubation medium and incorporated a proportion of it into glycogen. When cells were exposed to the phorbol ester, phorbol 12-myristate 13-acetate (PMA), or the diacylglycerol analogue, dioctanoylglycerol, there was a 30% reduction in the amount of 3H recovered in the glycogen pool. This effect was abolished in cells which had been depleted of protein kinase C (PKC) by prior exposure to PMA. Activation of adenylate cyclase with forskolin caused an increase (40%) in glycogen labelling indicating enhanced glycogen turnover. However, this effect was potentiated when astrocytes were incubated with forskolin and PMA in combination. We suggest that there is an interaction between PKC and adenylate cyclase in the regulation of astrocyte glycogen metabolism.

Animals↗
PubMed1988

Perforated peptic ulcer.

Peptic ulcer disease has declined significantly since 1950 in industrialized nations. However, the number of patients with perforated and bleeding ulcers has been constant or has declined only slightly, except for older patients, in whom the frequency has increased. In patients with perforated ulcers, operative management is preferable to non-operative treatment. The operative choices are simple closure of the perforation or definitive surgery. Patients who have significant risk factors should undergo simple closure. Closure of the ulcer with parietal cell vagotomy is the author's first choice for definitive operative treatment when this procedure can be performed.

Abdomen, Acute↗
PubMed1988

Effects of extracellular potassium on glycogen stores of astrocytes in vitro.

Astrocyte-enriched and meningeal cell cultures of the rat cerebral cortex were prepared, and their glycogen content was measured after 10-90 min under control (2.5 mM) concentrations of potassium after prefeeding with 20 mM glucose. No net change in glycogen level was noted in either culture over this period. Cell cultures were then exposed to increased concentrations of potassium (5, 10, and 15 mM), and their glycogen content was measured after 10-90 min. Both types of cell culture showed complex and variable changes in glycogen content. In general, increased potassium concentrations caused astrocyte glycogen stores to be reduced at physiological increases of potassium levels (from 2.5 to 5 mM and above), although a period of resynthesis was evident at all potassium concentrations. Meningeal cell glycogen levels were highly variable and only affected by high (10 and 15 mM) levels of potassium. These results are discussed with respect to the theory that changes in the external potassium concentration caused by neuronal activity might act as a signal controlling astrocyte glycogen stores.

Animals↗
PubMed1988

Effects of neurotransmitters on astrocyte glycogen stores in vitro.

We have used receptor binding assays to determine the presence of three neurotransmitter receptors in a crude membrane fraction derived from neonatal rat cortical astrocyte cultures and subsequently determined the effects of transmitter receptor activation on astrocyte glycogen content in vitro. beta-Adrenergic (KD = 88 pM; Bmax = 51 fmol/mg of protein), serotonin (KD = 70 nM; Bmax = 44 pmol/mg of protein), and muscarinic cholinergic receptors (KD = 79 pM; Bmax = 44 fmol/mg of protein) were found to be present on astrocyte membranes using [3H]dihydroalprenolol, [3H]serotonin, and [3H]quinuclidinyl benzilate, respectively, as ligands. Astrocyte cultures exposed to noradrenaline but not specific alpha- and beta-receptor agonists contained 33% less glycogen than controls. Neither serotonin nor carbachol caused alterations in astrocyte glycogen content under normal conditions. Reserpine-treated cultures, however, responded to serotonin with a 28% decrease in glycogen content and contained higher levels of glycogen than non-reserpine-treated controls (a 55% increase). These results show that both noradrenaline and serotonin can evoke astrocyte glycogenolysis and that noradrenergic control of glycogen metabolism is probably exerted through both alpha- and beta-receptors. Neurotransmitter control of astrocyte glycogen turnover may represent a form of neuron-astrocyte signalling in addition to that provided by changes in external potassium concentration.

Animals↗
PubMed1988

Characteristics of phorbol ester- and agonist-induced down-regulation of astrocyte receptors coupled to inositol phospholipid metabolism.

We have examined some of the characteristics of phorbol ester- and agonist-induced down-regulation of astrocyte receptors coupled to phosphoinositide metabolism. Our results show that preincubation of [3H]inositol-labelled astrocyte cultures with phorbol 12-myristate 13-acetate (PMA) resulted in a time- (t 1/2, 1-2 min) and concentration-dependent (IC50, 1 nM) decrease in the accumulation of [3H]inositol phosphates (IP) evoked by muscarinic receptor stimulation. Much longer (30-40 min) preincubation periods with higher concentrations (IC50, 600 microM) were required to elicit the same effect with the receptor agonist carbachol. Following preincubation, agonist-stimulated [3H]IP accumulation recovered with time; in both cases pretreatment levels of inositol lipid metabolism were attained within 2 days. Both phorbol ester and agonist pretreatments were also effective in reversing the carbachol-evoked mobilisation of 45Ca2+ in these cells. However, their effects on phosphoinositide metabolism were found not to be additive. Although neither pretreatment affected the incorporation of [3H]inositol into phosphoinositides, both resulted in a loss of membrane muscarinic receptors as assessed by [3H]N-methylscopolamine binding. In washed membranes prepared from [3H]inositol-labelled cultures, the guanine nucleotide analogue, guanosine 5'-O-thiotriphosphate (GTP-gamma-S), caused a dose-dependent increase in [3H]IP formation. This response was enhanced when carbachol was also included in the incubation medium, although the agonist alone was without effect. Pretreatment with either PMA or carbachol had no effect on GTP-gamma-S-stimulated [3H]IP accumulation but did reduce the ability of carbachol to augment this response. Similar findings were obtained when membranes were exposed directly to PMA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Development of a second clonally discrete Burkitt's lymphoma in a human immunodeficiency virus-positive homosexual patient.

We have studied, at a molecular level, two small non-cleaved cell malignant lymphomas (Burkitt's type) that were separated by a disease-free interval of 3 years in a patient infected with the human immunodeficiency virus (HIV). The late occurrence of the apparent relapse suggested that the second lymphoma might be caused by a separate malignant transformation in a discrete clone of B cells. Although both tumors expressed the same immunologic surface markers (mu k) and carried the same t(8;14) translocation, Southern blot analysis of DNA from each tumor, using specific restriction endonucleases and probes to the c-myc and the immunoglobulin heavy chain loci, demonstrated that the chromosomal breakpoints relevant to the translocations differed between the tumors. This was corroborated by analysis of the immunoglobulin light-chain rearrangements in the two tumors. These observations indicate that the second tumor was not a recurrence of the first but represented the malignant transformation of a different clone of B cells. Thus late relapses of certain malignancies in individuals at high risk may be caused by the malignant transformation of discrete cell clones (i.e., induction of a new tumor).

Acquired Immunodeficiency Syndrome↗
PubMed1987

Phorbol ester stimulation of prostanoid synthesis by cultured astrocytes.

The role of protein kinase C in mediating the synthesis and release of various prostanoids (prostaglandins E2, I2, F2 alpha and thromboxane A2) from astroglial cells derived from neonatal rat cerebrum and maintained in primary culture was investigated using phorbol ester. Phorbol myristate acetate stimulated the release of arachidonic acid from prelabelled cells and all 4 prostanoids in a dose-dependent manner (EC50 = 300 nM). This effect was inhibited by the protein kinase inhibitor 1-(-5-isoquinolinylsulfonyl)-2-methylpiperizine (IC50 = 25 microM) and the phospholipase A2 inhibitor, mepacrine (IC50 = 5 microM). In addition, the stimulatory effect of the phorbol ester was not apparent in cells which had been depleted specifically of protein kinase C. In the presence of the calcium ionophore A23187, phorbol ester-stimulated prostanoid release was enhanced. In the absence of extracellular calcium, there was no prostanoid-stimulation by phorbol ester, but the calcium channel blocker verapamil did not mimic this effect. We conclude that stimulation of protein kinase C by phorbol ester elicits prostanoid synthesis and release by a process that involves calcium influx and the activation of phospholipase A2.

Animals↗